Microbial electrolysis cell scale-up for combined wastewater treatment and hydrogen production.
This study demonstrates microbial electrolysis cell (MEC) scale-up from a 50mL to a 10L cell. Initially, a 50mL membraneless MEC with a gas diffusion cathode was operated on synthetic wastewater at different organic loads. It was concluded that process scale-up might be best accomplished using a "reactor-in-series" concept. Consequently, 855mL and 10L MECs were built and operated. By optimizing the hydraulic retention time (HRT) of the 855mL MEC and individually controlling the applied voltages of three anodic compartments with a real-time optimization algorithm, a COD removal of 5.7g L(R)(-1)d(-1) and a hydrogen production of 1.0-2.6L L(R)(-1)d(-1) was achieved. Furthermore, a two MECs in series 10L setup was constructed and operated on municipal wastewater. This test showed a COD removal rate of 0.5g L(R)(-1)d(-1), a removal efficiency of 60-76%, and an energy consumption of 0.9Whperg of COD removed.


Chemoprevention with a tea from hawthorn (Crataegus oxyacantha) leaves and flowers attenuates colitis in rats by reducing inflammation and oxidative stress.
The purpose of the study was to determine the effects of a tea from the leaves and flowers of Crataegus oxyacantha in rats with colitis. Colitis was induced by administration of 2,4,6-trinitrobenzene sulfonic acid. Hawthorn tea (HT) (100 mg/kg) was given via gavage for 21 days and the mesalamine drug (100 mg/kg) was administrated during the period of disease onset. HT was rich in total phenolic compounds (16.5%), flavonoids (1.8%), and proanthocyanidins (1.5%); vitexin-2-O-rhamnoside was the main compound detected. Mesalamine and the HT diminished the length of the lesions formed in the colon, in addition to reducing the levels of myeloperoxidase and interleukin-1β. Mesalamine was able to significantly reverse the body weight loss, while HT improved the activity of glutathione reductase and catalase. Histological scoring was not changed by the interventions, but it was highly correlated with the necrotic area. HT given at 100 mg/kg can be effective against colitis.


Aminopyrazine CB1 receptor inverse agonists.
A series of 5,6-diaryl-2-amino-pyrazines were prepared and found to have antagonist-like properties at the CB1 receptor. Subsequent SAR studies optimized both receptor potency and drug-like properties including solubility and Cytochrome-P450 inhibition potential. Optimized compounds were demonstrated to be inverse agonists and compared in vivo with rimonabant for their ability to inhibit food intake, to occupy central CB1 receptors and to influence hormonal markers associated with obesity.


Recombination of baculovirus DNA following lipofection of insect larvae.
By injection of a liposomal complex containing baculovirus DNA directly into the hemocoel of insect larvae a polyhedrosis disease was induced. After cotransfection of insect larvae with circular viral DNA and transfer vector DNA recombinant viruses were generated with a frequency of about 2%, similar to what is obtained in vitro using insect cell cultures. Based on these results an alternative strategy for the generation of recombinants can be derived for baculoviruses for which susceptible cell lines are not readily available. This strategy involves the injection of baculovirus DNA into susceptible larvae followed by in vivo cloning.


Semantic fluency in primary school-age children with vision impairment.
Semantic fluency is potentially a useful tool for vocabulary assessment in children with vision impairment because it contains no visual test stimuli. It is not known whether in the primary school years children with vision impairment perform more poorly on semantic fluency tasks compared to their sighted peers. We compared semantic fluency performance of two groups of 5- to 11-year-old British English speaking children-one group with vision impairment and one without. We also investigated within-group differences in performance, based on severity of vision impairment. We administered one category (animals) to children with vision impairment (n = 45) and sighted children (n = 30). Participants had one minute to respond. Responses were coded for accuracy, error type, clusters, and switches. Correct responses increased with age within each group. Groups did not differ significantly on any outcome measure. Severity of vision impairment did not impact task performance. Results suggested that semantic fluency performance-at least for the category animals-is not different in children with vision impairment compared to sighted children. Findings also suggest that semantic fluency could be a suitable addition to the tools that speech-language pathologists use to assess language abilities in children with vision impairment.


[Experimental study on effect of bushen shengjing decoction on kidney yang and testicular dysfunction in rats].
To explore the therapeutical mechanism of Bushen Shengjing Decoction (BSSJD) in treating infertility. Fed Wistar male rats with adenine 30 mg/100 g.d continuously for 30 days. The rats manifested the symptom which was similar to the human Kidney Yang Deficiency, the genitality dropped, the function of sperm-producing in the testis was disturbed, the contents of luteinizing hormone (LH), testosterone (T) and compound F (F) in blood were all lower than rats of normal group, P < 0.01. The model rats took the BSSJD 3 ml/100 g.d (each ml contains crude drugs 2 g) continuously for 10 days, interval for three days, then medicated again and total medication of BSSJD was 30 days. The symptom of Kidney Yang Deficiency in rats was improved obviously, the genitality, sperm quality and function of sperm producing in testis were all enhanced obviously, so did the hormone level of LH, T, F in blood. Comparing to untreated control group, the difference was significant (P < 0.05). BSSJD has the function of reinforcing Yang and replenishing essence and regulate the endocrinological function.


Adsorption kinetic of myoglobin on mica and silica - Role of electrostatic interactions.
Adsorption kinetics of myoglobin molecules on mica and silica was studied using the atomic force microscopy (AFM), the colloid enhancement and the quartz microbalance (QCM) methods. Measurements were carried out for the NaCl concentration of 0.01 and 0.15 M as a function of pH comprising pH 7.4 stabilized by the PBS buffer. The electrophoretic mobility measurements enabled to derive the molecules zeta potential as a function of pH. The isoelectric point appearing at pH 5, is lower than that predicted from the theoretical calculations of the nominal dissociation charge. The AFM investigations confirmed that myoglobin molecules irreversibly adsorb at pH 3.5 yielding well-defined layers of single molecules. These layers were characterized using the colloid enhancement method involving polymer microparticles for pH range 3-9. The microparticle deposition kinetics was adequately interpreted in terms of a hybrid random sequential adsorption model. It is confirmed that the myoglobin layers exhibit a negligible zeta potential at pH equal to 5 in accordance with the electrophoretic mobility measurements. Analogous adsorption kinetic measurements were performed for the silica substrate using QCM and AFM. It is observed that myoglobin molecules irreversibly adsorb at pH 3.5 forming stable layers of single molecules. On the other hand, its adsorption kinetics at larger pHs was much slower exhibiting a poorly defined maximum coverage. This was attributed to aggregation of the myoglobin solutions due to their vanishing charge. The kinetic QCM runs were adequately interpreted in terms of a theoretical model combining the Smoluchowski aggregation theory with the convective diffusion mass transfer theory.


The impact of converting to an electronic health record on organizational culture and quality improvement.
Implementing an information technology system can impact more than just quality of care and patient outcomes. The purpose of this 4-year, observational research project is to examine changes in organizational culture, quality improvement (QI) maturity, and quality of care following adoption of a single, electronic health record (EHR) system within an integrated healthcare network. The primary outcome measure, the Culture and Quality Questionnaire (CQQ), assesses the perceived culture of an organization and the degree of CQI maturity in seven quality management areas. Baseline surveys were distributed prior to conversion to the EHR. Subsequent data collection occurred at 12 months post "go live" and will occur at 24 and 36 months after the first hospital "go live". Secondary data were abstracted from routinely collected patient satisfaction measures and standard quality indicators. Contrary to expectation, our findings from the Baseline and 12-month follow-up data suggest that employees perceived the organizational culture as becoming more, rather than less, hierarchical. We also hypothesized that quality indicators would show improvement due to enhanced information flow and ease of information retrieval. This hypothesis was not supported by 1-year results. However, follow-up data from years two and three may provide different results.


[Bilateral sphenoid sinus mucocele presenting as abducens nerve palsy: case report].
Mucocele is a rare, benign, cystic tumor affecting primarily adults. It arises within the sphenoid sinus and invades the orbit through bony destruction. The most frequent locations are frontal and fronto-ethmoidal; sphenoidal forms are rarer, and bilaterality is exceptionally rare. Ophthalmological signs with the risk of blindness required emergency treatment. The authors report a case of bilateral sphenoid mucocele presenting as an isolated abducens nerve palsy, the etiological investigation confirmed the diagnosis of sphenoid mucocele, and the treatment consisted of a surgical marsupialization through an endonasal endoscopic approach.


Worlds apart: a comparison between physical activities among youth in Glasgow, Scotland and Dunedin, New Zealand.
Against the background of increasing concern about levels of physical activity among young people, this paper reports the results of a cross-national comparison between two longitudinal studies of young people in Glasgow, Scotland and Dunedin, New Zealand, which used similar methods of assessment at 15 and 18 years of age. The comparison revealed that, on average, young people in Dunedin participated in a greater range of activities, encompassing both organised sports and informal activities such as cycling, and with greater frequency than those in Glasgow at both ages, but particularly so at age 18. The difference was especially marked for females, among whom one in three in Glasgow reported no physical activity at all at age 18. By contrast, in both sexes among those who did participate, much less difference in levels of involvement was observed between the two locations. Of 35 activities, only in respect of soccer, and only for males, did participation and involvement in Glasgow exceed that of Dunedin. Neither climatic factors, natural features of the environment, socio-economic composition, nor different proportions in single-sex/co-educational schooling explain the difference in levels of participation between the two locations. Participation rates in selected physical activities do, however, reflect different opportunity structures in Dunedin and Glasgow, with an advantage accruing to the former in respect of both school and post-school provision. Cultural factors, which underpin such differences, also appear to have an additional influence on participation, most notably in relation to the gender gap in physical activities, much bigger in Glasgow than Dunedin. To redress these differences requires an increase in levels of participation generally, particularly among females, which depends as much on a shift in values about physical activity as on the provision of better resources.


Shifting from a thermal-constrained to water-constrained ecosystem over the Tibetan Plateau.
Understanding the seasonality of vegetation growth is important for maintaining sustainable development of grassland livestock systems over the Tibetan Plateau (TP). Current knowledge of changes in the seasonality of TP grasslands is restricted to spring and autumn phenology, with little known about the date of peak vegetation growth, the most relevant quantity for grassland productivity. We investigate the shifts of the date of peak vegetation growth and its climatic controls for the alpine grasslands over the TP during 2001-2020 using a framework based on the law of minimum, which is based on the assumption that peak vegetation growth would be consistent with the peak timing of the most limiting climatic resource. The date of peak vegetation growth over the TP advanced by 0.81 days decade-1 during 2001-2020. This spring-ward shift mainly occurs in the semi-humid eastern TP, where the peak growth date tracks the advancing peak precipitation, and shifted towards the timing of peak temperature. The advancing peak growth over the eastern TP significantly stimulated the ecosystem production by 1.99 gCm-2 year-1 day-1 during 2001-2020, while this positive effect weakened from 3.02 gCm-2 year-1 day-1 during 2000s to 1.25 gCm-2 year-1 day-1 during 2010s. Our results highlighted the importance of water availability in vegetation growth over the TP, and indicated that the TP grassland is moving towards a tipping point of transition from thermal-constrained to water-constrained ecosystem under the rapid warming climate.


Effect of metal cations on antimicrobial activity and compartmentalization of silver in Shewanella oneidensis MR-1 upon exposure to silver ions.
Silver is an antimicrobial agent that is used extensively in consumer products, such as fabrics and humidifiers. Silver ion (Ag+) uptake in bacteria represents a crucial phase of antimicrobial activity. However, the uptake mechanism of Ag+ in bacteria remains largely unknown. The genus Shewanella drives many geochemical processes of nutrients and pollutants in soils. In the present study, Ag+ uptake by Shewanella oneidensis MR-1 was first investigated in a laboratory in defined anaerobic, oligotrophic, and inorganic media with or without cations (potassium ions [K+], magnesium ions [Mg2+], and zinc ions [Zn2+]). Our results revealed variations in antimicrobial activity of Ag+ in the presence of Mg2+ and Zn2+. First, Mg2+ significantly decreased antimicrobial activity of Ag+ in S. oneidensis MR-1 by inhibiting cellular Ag+ uptake when compared with K+. The results were consistent with that of Co2+ (Mg2+ channel blocker) decreased Ag+ uptake by S. oneidensis MR-1. Moreover, Mg2+ promoted riboflavin secretion and facilitated the formation of metallic Ag nanoparticles on bacterial surfaces, which was beneficial for extracellular electron transfer and consequently reduced antibacterial activity of Ag+. Second, Zn2+ increased the antimicrobial activity of Ag+ in S. oneidensis MR-1, although the effect on Ag+ uptake was minimal. A synergistic interaction between Zn2+ and Ag+ led to an increase in dead cells and decreased ferrihydrite reduction capacity. The findings suggest that Mg2+ could reduce the environmental risk of Ag+ to soil bacteria, while Zn2+ should be of particular concern due to its synergistic antimicrobial effect on bacteria.


Differential screen and treatment of sternocleidomastoid syndrome versus eagle syndrome: a case report.
Differential screening is a complex process in chronic pain conditions. There is significant uncertainty that surrounds the pathophysiology of many chronic pain syndromes that may lead to misdiagnosis and treatment failures. Such differential screening is even more challenging where there is regional overlapping from surrounding tissues. This case report chronicles the differential screening and treatment of a patient with sternocleidomastoid syndrome (SCMS) originally diagnosed as Eagle's syndrome (ES). A 55-year-old woman, referred to a physical therapist (PT) by an ear, nose and throat (ENT) physician with the diagnosis of ES. The patient complained of yearlong left-sided otalgia, blurred vision, excessive lacrimation, dysphagia, hyperesthesia on the left side of the face, unilateral temporal headaches, and both left mandibular and anterior neck pain. The PT examination revealed the patient did not exhibit hallmark findings for clinical confirmation of ES and instead demonstrated multiple signs consistent with SCMS. Manual therapy techniques and therapeutic exercises resolved the patient's year-long chronic symptoms within 6 sessions.


The evolution of selector gene function: Expression dynamics and regulatory interactions of tiptop/teashirt across Arthropoda.
The transcription factors spineless (ss) and tiptop/teashirt (tio/tsh) have been shown to be selectors of distal appendage identity in an insect, but it is unknown how they regulate one another. Here, we examined the regulatory relationships between these two determinants in the milkweed bug Oncopeltus faciatus, using maternal RNA interference (RNAi). We show that Ofas-ss RNAi embryos bear distally transformed antennal buds with heterogeneous Ofas-tio/tsh expression domains comparable to wild type legs. In the reciprocal experiment, Ofas-tio/tsh RNAi embryos bear distally transformed walking limb buds with ectopic expression of Ofas-ss in the distal leg primordia. These data suggest that Ofas-ss is required for the maintenance of Ofas-tio/tsh expression in the distal antenna, whereas Ofas-tio/tsh represses Ofas-ss in the leg primordia. To assess whether expression boundaries of tio/tsh are associated with the trunk region more generally, we surveyed the expression of one myriapod and two chelicerate tio/tsh homologs. Our expression survey suggests that tio/tsh could play a role in specifying distal appendage identity across Arthropoda, but Hox regulation of tio/tsh homologs has been evolutionarily labile.


Comparison of corticosterone responses to acute stressors: chronic jugular vein versus trunk blood samples in mice.
A commonly used method for obtaining blood samples from mice is decapitation. However, there is an obvious need for repeated blood sampling in mice under stress-free conditions. Here, we describe a simple technique to repeatedly collect blood samples from conscious, freely moving mice through a chronically implanted jugular vein catheter. Furthermore, we compare plasma corticosterone (CORT) concentrations in samples obtained through the catheter 1 day after surgery with samples taken from trunk blood obtained under basal or acute stress conditions. CORT concentrations in repeated 100-μl venous blood samples were found to be similar to trunk blood samples both under basal conditions and after stressor exposure collected at identical time points (at 5, 15, and 60 min). Using both techniques, we demonstrate a progressive increase in CORT levels until 15 min after termination of stressor exposure and a decrease towards baseline values 60 min later. Anxiety-related behavior, as assessed on the elevated plus maze 3-4 days after surgery, did not differ between catheterized and non-catheterized mice. Our results provide evidence for application of jugular vein catheterization as a technique for repeated blood sampling in conscious laboratory mice. Use of this technique will greatly reduce the number of animals required for experiments involving endocrine endpoints.


Development and validation of novel risk prediction models of breast cancer based on stanniocalcin-1 level.
The function of stanniocalcin-1 (STC-1) in the oncogenesis and progression of tumors has been extensively studied. The purpose of this study was to investigate the relationship between secreted STC-1 and prognosis in patients with breast cancer (BC) and to determine whether STC-1 could be a key prognostic factor in BC. The STC-1 level was measured by ELISA and clinical data from 1210 female patients with BC were used to develop and validate nomograms. We then verified the models through the plotting of ROC curves and calibration curves, calculating the C-index, and performing decision curve analyses (DCA). The level of STC-1 in the peripheral plasma was significantly correlated with the T stage, N stage, clinical stage, grade, hormone receptors, HER-2 status, and tumor subtype. Cox regression analyses revealed that estrogen receptor(ER) status, N stage, and STC-1 level were risk factors for overall survival (OS), whereas T stage, N stage, and STC-1 level were independent prognostic factors for distant disease-free survival (DDFS) and disease-free survival (DFS). Both the ROC curve and the C-index confirmed the high resolution of these models, while the DCA identified the feasibility of their practical application. In addition, the calibration curves indicated good consistency between the predicted and actual survival rates. Nomograms were created based on STC-1 levels for 3-, 5-, and 7-year OS, DDFS, and DFS of patients with BC respectively. As a key prognostic factor for BC, peripheral blood STC-1 level can be used clinically as a liquid biopsy indicator.


Power in Practice: Moments of Reflection.
Power in practice reveals itself in many ways. There are many definitions of power but in nursing care it could be said that the power is within the patient. Nurses facilitate patients power by engaging them in dialogical engagements. This helps patients to decide how to utilize the power of living their quality.


Antecedents of inflammation biomarkers in preterm newborns on days 21 and 28.
Most studies of systemic inflammation in very preterm newborns focus on assessments made during the first two weeks. The purpose of this study was to identify some of the antecedents of systemic inflammation evident during postnatal weeks three and four. We measured the protein concentrations in blood spots collected on postnatal days 21 (N = 176) and 28 (N = 157) from infants born before the 28th week of gestation and sought correlates of measurements in the top quartile. Odds ratios of elevated concentrations were calculated for the most obvious correlates. Infants born for maternal and foetal indications were more likely than their peers to have top quartile concentrations of IL-beta, IL-8, TNF-alpha and ICAM-1 on both days 21 and 28. Similarly, infants whose birthweight Z-score was <-2 or between -1 and -2 were also more likely than their peers to have elevated concentrations of these proteins. Markers of systemic inflammation in the very preterm newborn during the third and fourth postnatal weeks are most strongly associated with maternal and foetal indications for (very preterm) delivery and their common correlate/consequence, foetal growth restriction.


Pleural metastasis of malignant thymoma. A pitfall in the CT-diagnosis of pleural mesothelioma.
We report two cases with metastatic thymomas mimicking the CT feature of pleural mesothelioma.


Clinical Characteristics and Prognosis of Gastric Cancer Patients with BRCA 1/2 Germline Mutations: Report of Ten Cases and a Literature Review.
The prognosis of gastric cancer (GC) is poor with a median overall survival (OS) of less than 12 months in advanced-stage disease. The search for distinct genetic subgroups of GC patients and predictive biomarkers is ongoing. While BRCA1 or BRCA2 germline mutations (gBRCAm) have potential therapeutic implications in ovarian, breast and pancreatic cancers, their significance in GC patients has not been established. A retrospective multi-center data analysis of GC patients with gBRCAm was conducted, detailing the clinical characteristics and disease course in this unique subset of patients. Ten GC patients with gBRCAm were identified, six of them with metastatic disease. The median OS of all ten GC patients was 47.5 (13-192) months. Median OS for patients diagnosed with operable disease was 55.5 (13-192) months and of the patients with metastatic disease (calculated from metastatic disease diagnosis) 32 (15-52) months with an exceptional 1-, 2- and 3-year survival rate of 100%, 83.3% and 50%, respectively. These preliminary data suggest that gBRCAm in GC patients are associated with a favorable prognosis. Furthermore, gBRCAm might be a predictive biomarker to DNA-damaging agents response in GC patients, similarly to its established role in other malignancies. Further research is needed to confirm our findings.


Condensing osteitis of the clavicle: case report and review of the literature.
Osteitis condensans of the clavicle is a benign, often painful disorder of unknown etiology manifested by bony sclerosis of the clavicular head with an uninvolved sternoclavicular joint. The case presented demonstrates the characteristic scintigraphic findings of osteitis condensans of the clavicle. A review of the published pathologically proven cases reveals this disorder to have distinctive clinical and radiological features that allow differentiation from infection, neoplasia, and arthritides in most instances. The frequent observation, as in this case, of devitalized bone and marrow fibrosis with remodeling of cancellous bone suggests that osteonecrosis may play an important role in the pathogenesis of this disorder.


Decarbonylation of benzaldehydes by dual photoorgano-cobalt catalysis.
We report a mild alternative to thermally-driven noble-metal catalyzed decarbonylation protocols for the defunctionalization of benzaldehydes in short reaction times. Our cooperative photocatalytic system involves thioxanthone as an inexpensive HAT-agent and a cobalt complex required for selective C(sp2)-C(sp2) bond cleavage. The generated acyl and phenyl intermediates are postulated to be stabilized as cobalt complexes.


Treatment of resistant hypertension.
Although the true prevalence of resistant hypertension is not known, it is likely that this condition will become increasingly common, driven by an aging population, obesity, nonadherence trends, and effects of target-organ disease. Current approaches focus on two goals: evaluation and correction of contributing causes, then selection of an effective drug regimen. Lifestyle factors contribute to resistance, particularly high sodium intake and weight gain. Secondary causes should be considered and corrected if feasible. Recent efforts have focused on the development of clinical pathways to guide treatment, based on plasma renin activity, aldosterone production, or hemodynamic measurements. The components of drug combinations beyond the second agent remain empiric. Although volume expansion plays a key role in drug resistance, clinical assessment of volume status is often difficult, frustrating efforts to achieve blood pressure control. Determination of the most effective approaches will require clinical trials using combination therapy.


Clinical and Radiologic Predictors of a Pathologic Complete Response to Neoadjuvant Chemotherapy (NACT) in Patients Undergoing Cytoreductive Surgery for Colorectal Peritoneal Metastases: Results of a Prospective Multi-center Study.
Patients undergoing cytoreductive surgery for colorectal peritoneal metastases who have a pathologic complete response (pCR) to neoadjuvant chemotherapy experience a significantly longer survival than those with residual disease. This response is known only after surgery. This study aimed to examine clinical and radiologic predictors of a pCR. From July 2018 to December 2019, the study prospectively enrolled 120 patients. The clinical and radiologic findings were compared between patients with and without a pCR. A protocol for pathologic evaluation was followed. A pCR was observed in 34 patients (28.3%). Receiver operating characteristic (ROC) curves showed that patients with a surgical Peritoneal Cancer Index (sPCI) of 3 or lower had an 80% probability of experiencing a pCR, and that patients with a radiologic PCI (rPCI) of 2 or lower had a 70% probability of experiencing a pCR. A pCR was correctly predicted for 47% of the patients by imaging and for 44.4% of the patients by surgical evaluation. The site of primary tumor, the timing of peritoneal metastasis (PM), histology, tumor marker positivity, and mutations in known poor prognostic genes (KRAS) did not differ between the patients with and those without pCR. The primary tumor showed residual disease in 23.5% and regional nodes in 26.4% of the patients with pCR. The rPCI and sPCI concurred with a pCR in less than 50% of the patients. The patients with a lower PCI had greater concordance. An sPCI of 3 or lower was predictive of a pCR in 80% of the patients. The impact of KRAS mutations on pCR should be evaluated in a larger series. The predictors of pCR and response to systemic chemotherapy should be incorporated in prognostic scores used to select patients for surgery.


Conservative treatment of endometriosis externa: the effects of methyltestosterone therapy.
Twenty-four women with documented endometriosis externa were treated with methyltestosterone. Twenty-one of these patients desired fertility and three conceived (one after methyltestosterone therapy alone, two after conservative operation followed by methyltestosterone treatment). Ten patients later required surgical therapy for recurrence of pain, although all but one patient had initial relief of pain (3 to 6 months after therapy). These results of therapy are contrasted to those of similar studies in the literature in which methyltestosterone and other agents were used.


The impact of hissy fits in primary care.
Hissy fits are experienced by physicians and patients alike, yet their full impact has never been studied before. Specially trained researchers observed hissy fits at a clinic over 12 months. They interviewed perpetrators, victims and witnesses and recorded their comments because they had to. Hissy fits were common at the clinic and sometimes escalated to riots. Seasonal variations were endured. Nobody likes this behaviour. Efforts should be made to counsel hissy fitters in channeling their angst in other, more positive ways.


Determination of cimetidine in human plasma by free capillary zone electrophoresis.
The separation of cimetidine from the metabolites cimetidine amide and cimetidine sulfoxide, endogenous creatinine and the internal standard ranitidine was achieved by capillary electrophoresis in less than 5 min. All compounds were well separated from cimetidine, including possible plasma ingredients, as the UV spectra of cimetidine standard and cimetidine from the plasma extract match. Plasma levels of cimetidine were determined in the range 250-3000 ng/ml in plasma and higher concentrations were determined by dilution of the sample with blank plasma.


Combination therapies for combating antimicrobial resistance.
New drug development strategies are needed to combat antimicrobial resistance. The object of this perspective is to highlight one such strategy: treating infections with sets of drugs rather than individual drugs. We will highlight three categories of combination therapy: those that inhibit targets in different pathways; those that inhibit distinct nodes in the same pathway; and those that inhibit the very same target in different ways. We will then consider examples of naturally occurring combination therapies produced by micro-organisms, and conclude by discussing key opportunities and challenges for making more widespread use of drug combinations.


Anisotropy of Unstably Stratified Near-Surface Turbulence.
Classic Monin-Obukov similarity scaling states that in a stationary, horizontally homogeneous flow, in the absence of subsidence, turbulence is dictated by the balance between shear production and buoyancy production/destruction, whose ratio is characterized by a single universal scaling parameter. An evident breakdown in scaling is observed though, through large scatter in traditional scaling relations for the horizontal velocity variances under unstable stratification, or more generally in complex flow conditions. This breakdown suggests the existence of processes other than local shear and buoyancy that modulate near-surface turbulence. Recent studies on the role of anisotropy in similarity scaling have shown that anisotropy, even if calculated locally, may encode the information about these missing processes. We therefore examine the possible processes that govern the degree of anisotropy in convective conditions. We first use the reduced turbulence-kinetic-energy budget to show that anisotropy in convective conditions cannot be uniquely described by a balance of buoyancy and shear production and dissipation, but that other terms in the budget play an important role. Subsequently, we identify a ratio of local time scales that acts as a proxy for the anisotropic state of convective turbulence. This ratio can be used to formulate a new non-dimensional group. Results show that building on this approach the role of anisotropy in scaling relations over complex terrain can be placed into a more generalized framework.


Nitroglycerin Plus Whole Intracranial Radiation Therapy for Brain Metastases in Patients With Non-Small Cell Lung Cancer: A Randomized, Open-Label, Phase 2 Clinical Trial.
Hypoxia has been associated with chemoradioresistance secondary to vascular endothelial growth factor receptor induced by hypoxia-induced factor (HIF). Nitroglycerin (NTG) can reduce HIF-1 in tissues, and this may have antiangiogenic, proapoptotic, and antiefflux effects. Particularly, epidermal growth factor-mutated (EGFRm) tumor cell lines have been shown to overexpress both vascular endothelial growth factor and HIF. In this phase 2 study, we evaluated the effect of transdermal NTG plus whole brain radiation therapy (WBRT) in patients with non-small cell lung cancer (NSCLC) with brain metastases (BM). This was an open-label, phase 2 clinical trial with 96 patients with NSCLC and BM. Patients were randomized 1:1 to receive NTG plus WBRT (30 Gy in 10 fractions) or WBRT alone. The primary endpoint was intracranial objective response rate (iORR) evaluated 3 months posttreatment. NTG was administered using a transdermal 36-mg patch from Monday through Friday throughout WBRT administration (10 days). The protocol was retrospectively registered at ClinicalTrials.gov (NCT04338867). Fifty patients were allocated to the control group, and 46 were allocated to the experimental group (NTG); among these, 26 (52%) had EGFRm in the control group and 21 (45.7%) had EGFRm in the NTG arm. In terms of the iORR, patients in the NTG group had a significantly higher response compared with controls (56.5% [n = 26/46 evaluable patients] vs 32.7% [n = 16/49 evaluable patients]; relative risk, 1.73; 95% confidence interval [CI], 1.08-2.78; P = .024). Additionally, patients who received NTG + WBRT had an independently prolonged intracranial progression-free survival (ICPFS) compared with those who received WBRT alone (27.7 vs 9.6; hazard ratio [HR], 0.5; 95% CI, 0.2-0.9; P = .020); this positively affected overall progression-free survival among patients who received systemic therapy (n = 88; HR, 0.5; 95% CI, 0.2-0.9; P = .043). The benefit of ICPFS (HR, 0.4; 95% CI, 0.2-0.9; P = .030) was significant in the EGFRm patient subgroup. No differences were observed in overall survival. A significantly higher rate of vomiting presented in the NTG arm of the study (P = .016). The concurrent administration of NTG and radiation therapy improves iORR and ICPFS among patients with NSCLC with BM. The benefit in ICPFS is significant in the EGFRm patient subgroup.


Detection of immunoglobulin M antibody to hepatitis A virus in Alaska residents without other evidence of hepatitis.
During a 38-month period, 13 of 41 persons with test results positive for IgM antibody to hepatitis A virus did not meet the case definition for hepatitis A or have a clear indication for testing, which suggests that test results were falsely positive. No single testing platform or kit was used. Health care providers should restrict serologic testing for hepatitis A to patients with clinical or epidemiologic indications.


Long-term administration of a substance P antagonist, (D-Pro2, D-Trp7,9)-SP, abolishes the response to ocular trauma.
The long-term effect of ocular administration of a substance P (SP) antagonist, (D-Pro2, D-Trp7,9)-SP, was studied in the rabbit. After 2-3 months of topical administration of the antagonist twice daily, a mild trauma was applied in the form of infrared irradiation of the iris. The control eye responded with disruption of the blood-aqueous barrier, the eye treated with the antagonist did not. Two days after termination of treatment, the response to ocular injury was still reduced. Another 2 days later, ocular injury evoked a normal response, which shows that the protection was reversible. No adverse reaction to the SP antagonist was noted.


Post-authorisation study of eslicarbazepine as treatment for drug-resistant epilepsy: preliminary results.
Eslicarbazepine acetate (ESL) is a new antiepileptic drug (AED) and an analogue to carbamazepine (CBZ) and oxcarbazepine (OXC). In this study, we evaluate initial therapeutic response to ESL and events in the change from CBZ and OXC. We evaluated 61 patients with a broad spectrum of drug-resistant epilepsies in a cross-sectional study. The switch from CBZ and OXC to ESL was carried out in a single night at ratios of 1:1.3 and 1:1mg respectively. The most common form of epilepsy was temporal lobe epilepsy (62.3%). The most common aetiology was mesial temporal sclerosis (26.2%). Mean follow-up time was 4.7±3.2 months. In 40 patients with a minimum follow-up period of 3 months, monthly median seizure frequency dropped by 63.6% (P<.001) and a reduction of 80% or more was recorded in 30%. Adverse events (AEs) occurred in 54%; all appeared during the titration phase. They were more frequent at doses in excess of 800mg (73.9% vs. 47.4%; P=.042). The most common AE was dizziness (34.4%), which was commonly associated with VPA, LTG and/or LCS consumption (19.2% vs. 45.7%; P=.031). The retention rate at 3 months was 75.4%. A total of 25 patients replaced CBZ or OXC treatment with ESL; any AEs were transient (69.2% for CBZ and 33% for OXC; P=.073). At 3 months after the treatment change, median seizure frequency had decreased by 20% (P<.075). ESL is effective in the treatment of focal epilepsies and its early retention rate is > 70%. AEs occurred during the titration phase and corresponded to associated AEDs. A rapid change from CBZ and OXC to ESL treatment can be safely performed.


Left Ventricular Diastolic Dysfunction in Ischemic Stroke: Functional and Vascular Outcomes.
Left ventricular (LV) diastolic dysfunction, developed in relation to myocardial dysfunction and remodeling, is documented in 15%-25% of the population. However, its role in functional recovery and recurrent vascular events after acute ischemic stroke has not been thoroughly investigated. In this retrospective observational study, we identified 2,827 ischemic stroke cases with adequate echocardiographic evaluations to assess LV diastolic dysfunction within 1 month after the index stroke. The peak transmitral filling velocity/mean mitral annular velocity during early diastole (E/e') was used to estimate LV diastolic dysfunction. We divided patients into 3 groups according to E/e' as follows: <8, 8-15, and ≥15. Recurrent vascular events and functional recovery were prospectively collected at 3 months and 1 year. Among included patients, E/e' was 10.6±6.4: E/e' <8 in 993 (35%), 8-15 in 1,444 (51%), and ≥15 in 378 (13%) cases. Functional dependency or death (modified Rankin Scale score ≥2) and composite vascular events were documented in 1,298 (46%) and 187 (7%) patients, respectively, at 3 months. In multivariable analyses, ischemic stroke cases with E/e' ≥15 had increased odds of functional dependence or death at 3 months (adjusted OR [95% CI]: 1.73 [1.27-2.35]) or 1 year (1.47 [1.06-2.06]) and vascular events within 1 year (1.65 [1.08-2.51]). Subgroups with normal ejection fraction or sinus rhythm exhibited a similar overall pattern and direction. LV diastolic dysfunction was associated with poor functional outcomes and composite vascular events up to 1 year.


[Prostatic rhabdomyosarcoma in adults].
To report on two adult patients with prostatic embryonal rhabdomyosarcoma. The literature is briefly reviewed and the clinical, diagnostic and therapeutic aspects of this unusual variety of prostate cancer are discussed. Two patients, aged 27 and 34 years, with prostatic embryonal rhabdomyosarcoma are presented. Both cases showed tumor dissemination at the time of diagnosis. Both patients received chemotherapy. A 60% reduction in tumor volume was achieved in one patient, who subsequently underwent rescue surgery and, in spite of a recurrence, is still alive 3 years after the diagnosis. The other patient showed no response to chemotherapy. He refused rescue surgery and was lost to follow-up. Embryonal rhabdomyosarcoma of the prostate in the adult is an unusual and aggressive tumor, of rapid growth and progression. Early diagnosis and treatment without delay by radical surgery and chemotherapy are essential to improve the prognosis of this disease.


Chromosome abnormalities in chronic lymphocytic leukemia revealed by TPA as a mitogen.
Bone marrow and peripheral blood cultures of chronic lymphocytic leukemia patients were mitogenically stimulated with TPA (12-O-tetradecanylphorbol-13-acetate). Clonal cytogenetic abnormalities were detected in frequencies varying from 15% to 100%, in five of the six patients studied. Parallel studies with pokeweek mitogen showed a much lower level of stimulation and only two abnormal clones were detected. The chromosome abnormalities described in this study are similar to those reported in CLL by other authors, particularly with respect to trisomy 12 and deletion 11q. A significant frequency of hypodiploidy and chromosome deletion was also detected in this study, and further studies are underway to determine the significance of these findings.


Relation of antianginal efficacy of nifedipine to degree of coronary arterial narrowing and to presence of coronary collateral vessels.
Thirty-six patients with chronic stable angina pectoris or with stable and vasospastic components of angina pectoris were classified by coronary arteriographic findings into 4 groups. Patients in group A had a single stenotic coronary artery; patients in groups B, C and D had occluded arteries, but these arteries had been collateralized to varying degrees, and an epicardial coronary steal phenomenon was possible. All patients underwent multiple exercise tests before and after randomized, double-blind, crossover treatment with 20 mg of nifedipine, 20 mg of isosorbide dinitrate, a combination of both, and placebo. Maximal and mean ST-segment depression, occurrence of angina pectoris and heart rate were evaluated. After nifedipine treatment, mean ischemic ST-segment depression was reduced 21% in group A (p less than 0.05), but was not significantly altered in the other groups (group B, 2% decrease; group C, 10% increase; group D, 3% decrease). However, isosorbide dinitrate reduced ST-segment depression significantly in all groups (group A, 29%, p less than 0.001; group B, 18%, p less than 0.01; group C, 19%, p less than 0.05; group D, 33%, p less than 0.05). The combination with nifedipine did not further improve the effect of isosorbide dinitrate. Maximal ST-segment depression and angina pectoris paralleled the changes in mean ST depression during the different medications. Heart rate at rest was not significantly changed after nifedipine treatment in any group, but increased significantly after isosorbide dinitrate treatment in groups B and C (group B, 12%, p less than 0.01; group C, 9%, p less than 0.05); heart rate during exercise did not differ significantly in any group or after any form of medication from placebo.


[The Value of Serum HMGB1 and sRAGE in the Diagnosis, Efficacy Monitoring and Prognosis of Newly Diagnosed Multiple Myeloma].
To evaluate the value of high mobility group protein B1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in the diagnosis, efficacy monitoring and prognosis of newly diagnosed multiple myeloma (MM) patients. Fifty newly diagnosed MM patients before and after chemotherapy and 50 hematological outpatients from October 2018 to May 2020 were selected. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum HMGB1 and sRAGE levels of the patients. ROC was used to further analyze the efficacy of serum HMGB1 and sRAGE levels on the diagnosis of MM. At the same time, the serum levels of HMGB1 and sRAGE before and after chemotherapy were compared, and their values in the evaluation of curative effect of MM patients were analyzed. According to the mean values of serum HMGB1 and sRAGE, all the patients were divided into different groups, the clinical characteristics and survival status of the patients were compared. Before treatment the serum HMGB1 level of the patients in MM group was higher than that in control group, while sRAGE level was lower (t=11.363,6.127, P<0.001). The AUC of serum HMGB1 and sRAGE in the MM patients was 0.955 and 0.811, respectively. After 3 courses of chemotherapy, HMGB1 level of the patients in CR group was lower than before chemotherapy, while in PD group was higher, as well as sRAGE level of the patients in PR group (P<0.05). There were significant differences in R-ISS stage, HGB, CRP, ESR, CD56, CD117, D13S319 deletion between HMGB1 high expression group and HMGB1 low expression group (χ2=3.920, 6.522, 6.65, 4.16, 3.945, 6.65, 4.16, P<0.05), while there were significant differences in ISS stage, CRP and CD56 between sRAGE low expression group (28 cases) and sRAGE high expression group (22 cases) (χ2=4.565, 4.711, 5.547, P<0.05). Kaplan-Meier survival analysis showed that the patients in HMGB1 low expression group had better survival condition, for PFS Tlow>Thigh (χ2=9.470, P<0.05), and for OS Tlow>Thigh (χ2=7.808, P<0.05); there was no difference in the survival of sRAGE high expression group and low expression group, for PFS Tlow<Thigh (χ2=1.661, P>0.05), and for OS Tlow<Thigh (χ2=2.048, P>0.05). Cox analysis showed that LDH and HMGB1 were the factors affecting the prognosis of the patients, and both of them affected PFS (HR=2.771, 95% CI: 1.002-7.662, P=0.049; HR=6.022, 95% CI: 1.689-21.470, P=0.006), while HMGB1 also affected OS (HR=4.275, 95% CI: 1.183-15.451, P=0.027). The serum HMGB1 and sRAGE have certain auxiliary value for the diagnosis and curative effect monitoring of newly diagnosed MM patients, and serum HMGB1 is expected to be an auxiliary detection index for the prognosis of MM.


Hospital-associated infections in obstetrics and gynecology. Effects of surveillance.
To determine whether continuous surveillance of hospital-associated infections with regular feed-back to the staff reduces the infection rate in obstetrics and gynecology. Two infection control nurses surveyed all patients over a 2-year period for infections and potential risk factors. After an initial 9-month period (period A), quarterly information to all doctors and nurses was introduced for the rest of the study (period B). A department of obstetrics and gynecology at a Swedish university hospital. All patients undergoing surgery, excluding vacuum aspiration abortions and dilatation and curettage. 2,334 patients were surveyed. In period A, 14.2% of all operations were followed by an infection, compared with 9.5% in period B (p less than 0.001). For purulent wound infections and for endometritis, a significantly reduced rate was noted from period A to B. Several risk factors for infection were significantly more common in period B than in period A. Cesarean sections and hysterectomies were the most common operations also having among the highest infection rates. For both of these operations, infection rates were significantly reduced from period A to period B (from 15.1% to 9.0% and from 15.7% to 10.7%, respectively). The average length of hospitalization was 6 days longer for an infected than for an uninfected patient. Surveillance of hospital-associated infections including regular feed-back to the staff was accompanied by a significant reduction in infection rates. A quality surveillance program for departments of obstetrics and gynecology therefore seems to benefit from including such surveillance. Surveillance could possibly be limited to only a few common operations with high infection rates.


Same but different? A qualitative analysis of the influence of COVID-19 on law enforcement and organized crime in Germany.
Criminological research on COVID-19 and its repercussions on crimes, criminals and law enforcement agencies is still in its infancy. This paper fills that void with regard to the influence of COVID-19 on organized crime and the work of law enforcement agencies' investigations of organized crime in Germany by presenting empirical findings from a nationwide qualitative interview study. Through the methodological combination of Grounded Theory and Situational Analysis, we find three central narratives (us vs. them, nationalization vs. internationalization, conservatism vs. innovation) that were provided by law enforcement personnel in terms of the way in which COVID-19 influenced both organized crime groups and their work in the investigation thereof. Following a reflexive approach, the implications of COVID-19 on the research process itself are also discussed.


Colorectal liver metastases: hepatic pedicle clamping during hepatectomy reduces the incidence of tumor recurrence in selected patients. Case-matched analysis.
Hepatic pedicle clamping (HPC) during Liver Resection (LR) is a vascular procedure designed to prevent bleeding from the liver during hepatectomy. Outgrowth of pre-existing colorectal micrometastases may occur 5-6 times faster in occluded liver lobes than in non-occluded lobes. We conducted a case-matched analysis at our Institution to assess the effects of HPC on overall and recurrence-free survival in highly selected patients, who underwent LR due to Colorectal liver metastases (CLM). From January 2002 to December 2010, 120 patients operated for CLM were included into this case-matched study. Patients were allocated to two groups: Group-A patients who underwent HPC during LR; Group-B patients who underwent LR without HPC. HPC during liver resection was associated with better overall patient 5-year survival (47.2% in Group-A and 32.1% in Group-B) (P-value = 0.06), and significantly better 5-year recurrence-free survival (49.9% in Group-A vs 18.3% in Group-B) (P-value = 0.010) The Cox regression model identified the following risk factors for worse prognosis in terms of shorter recurrence-free survival and higher incidence of tumor recurrence: no HPC (Group-B) (P-value = 0.032) and positive lymph nodes at the time of LR (P-value = 0.018). Lack of HPC in selected patients who underwent LR for CLM results to be a strong independent risk factor for higher patient exposure to tumor recurrence. We suggest that hepatic hilum clamping should be seriously taken into consideration in this patient setting. A case-matched study was performed in 120 patients undergoing liver resection due to colorectal liver metastases, comparing patients who received intermittent hepatic pedicle clamping (HPC) with those who did not. The 5-year overall survival rate was similar, but the 5-year recurrence-free rate was significantly higher with no HPC (p = 0.012).


Sensitive, nonradioactive assay of phosphorylase kinase through measurement of enhanced phosphorylase activity towards fluorogenic dextrin.
Glycogen phosphorylase (GP) exists in two interconvertible forms, GPa (phosphorylated form, high activity) and GPb (nonphosphorylated form, low activity). Phosphorylase kinase (PhK) catalyses the phosphorylation of GPb and plays a key role in the cascade system for regulating glycogen metabolism. In this study, we developed a highly sensitive and nonradioactive assay for PhK activity by measuring the enhanced GP activity towards a pyridylaminated maltohexaose. The enhanced GP activity (ΔA) was calculated by the following formula: ΔA = A(+) - A(0), where A(+) and A(0) represent the GP activities of the PhK-treated and PhK-nontreated samples, respectively. Using a high-performance liquid chromatograph equipped with a fluorescence spectrophotometer, the product of GP activity could be isolated and quantified at 10 fmol. This method does not require the use of any radioactive compounds and only 1 µg of GPb per sample was needed to obtain A(+) and A(0) values. The remarkable reduction in GPb concentration enabled us to discuss an interesting new role for glycogen in PhK activity.


Prognostic Value of a Modified Albumin-Bilirubin Score Designed for Patients with Esophageal Squamous Cell Carcinoma After Radical Resection.
The albumin-bilirubin (ALBI) score was originally developed to assess the severity of liver dysfunction in patients with hepatocellular carcinoma and has subsequently been used as a prognostic marker for that disease. Here, we examined the value of the preoperative ALBI score as a prognostic marker for patients with esophageal squamous cell carcinoma (ESCC) after radical esophagectomy. We retrospectively analyzed data from 449 patients who underwent curative resection for ESCC. The ALBI score was calculated as (log10 serum bilirubin [μmol/l] × 0.66) + (serum albumin [g/l] × - 0.0852). Receiver operating characteristic curve analysis was used to define a preoperative modified ALBI (mALBI) score for patient stratification. Of the 449 ESCC patients, 232 and 217 were assigned to mALBI Grade 1 or Grade 2 groups based on preoperative ALBI scores of ≤ - 3.33 or > - 3.33, respectively. Preoperative mALBI grade was significantly associated with age, excessive alcohol consumption, squamous cell carcinoma antigen level, and clinical disease stage. The mALBI Grade 2 group had significantly shorter disease-specific and recurrence-free survival than the mALBI Grade 1 group. Multivariate analysis demonstrated that mALBI Grade 2 was an independent prognostic factor for disease-specific survival (hazard ratio 1.86, 95% confidence interval 1.18-2.93, P = 0.0074). In most subgroup analyses, mALBI Grade 2 was associated with a greater risk of disease-specific death. mALBI grade serves as a simple and useful prognostic marker for disease-specific survival in patients with ESCC after radical esophagectomy.


Effects of therapy with a free-standing robotic exoskeleton on motor function and other health indicators in people with severe mobility impairment due to chronic stroke: A quasi-controlled study.
Robotic exoskeletons facilitate therapy in upright postures. This study aimed to evaluate potential health-related effects of this therapy for people with severe mobility impairment due to chronic stroke. This quasi-controlled trial with 12 weeks of twice weekly therapy in a free-standing exoskeleton, and 12 weeks follow up, included people dependent for mobility, with stroke at least 3 months prior. The primary outcome was lower limb motor function. A battery of secondary outcomes was evaluated. Nine participants were enrolled. There was no change in motor function. There was a significant between phase difference in level of independence with activities of daily living (median post-intervention change = 5, IQR = 0, 10, p = 0.01), and grip strength (affected limb) (median post-intervention change = 1, IQR = 0, 2, p = 0.03). A significant difference was found for quadriceps strength (affected limb) (median change in wait phase = 4, IQR = 2, 7.5, p = 0.01). Participants consistently reported positive perceptions of the therapy. Therapy with a free-standing exoskeleton is acceptable to participants and can facilitate improvements in level of independence and grip strength. Restrictions regarding eligibility to use the device, may reduce the clinical application of this therapy for people with stroke.


Effect of side dominance on myoelectric manifestations of muscle fatigue in the human upper trapezius muscle.
The purpose of this study was to investigate whether differences in the peripheral and control properties of the neuromuscular system due to long-term preferential use, related to side dominance, affect postural muscles, such as the upper trapezius. Therefore, fatigability properties of the upper trapezius muscles of the dominant and non-dominant side were assessed. Surface EMG signals were detected from the upper trapezius muscles of both sides of nine right- and five left-handed subjects with adhesive linear electrode arrays consisting of eight contact points. Static constant force contractions with the arms 90 degrees abducted were performed by the subjects while holding hand loads of 0 kg, 0.5 kg, and 1 kg. Surface EMG spectral and amplitude variables were computed from the recorded signals. EMG spectral variable rate of change (indicating fatigue) showed a statistically significant difference between the two sides, with the dominant side less fatigable than the non-dominant one. The observed differences held for both the right- and left-handed subject group. A possible explanation for the results is that long preferential use of one side with respect to the other leads to changes in muscle fiber membrane and control properties, in agreement with previous results on limb muscles.


Fine population structure analysis method for genomes of many.
Fine population structure can be examined through the clustering of individuals into subpopulations. The clustering of individuals in large sequence datasets into subpopulations makes the calculation of subpopulation specific allele frequency possible, which may shed light on selection of candidate variants for rare diseases. However, as the magnitude of the data increases, computational burden becomes a challenge in fine population structure analysis. To address this issue, we propose fine population structure analysis (FIPSA), which is an individual-based non-parametric method for dissecting fine population structure. FIPSA maximizes the likelihood ratio of the contingency table of the allele counts multiplied by the group. We demonstrated that its speed and accuracy were superior to existing non-parametric methods when the simulated sample size was up to 5,000 individuals. When applied to real data, the method showed high resolution on the Human Genome Diversity Project (HGDP) East Asian dataset. FIPSA was independently validated on 11,257 human genomes. The group assignment given by FIPSA was 99.1% similar to those assigned based on supervised learning. Thus, FIPSA provides high resolution and is compatible with a real dataset of more than ten thousand individuals.


A one pot one step combined radical and ring-opening route for the dual functionalization of starch in aqueous medium.
Starch based materials are attractive bio-based alternative to fully synthetic polymers. Native starch has however limited thermoprocessability and properties and must be modified. In order to improve the properties of starch-graft-poly(butyl-acrylate-co-styrene) copolymers via a process as green as possible, we report herein a new method for the dual functionalization of the polysaccharide via a one pot one step reaction in aqueous medium combining free radical polymerizations and ring-opening chemistry. Poly(butyl acrylate) or poly(butyl acrylate-co-styrene) (ca. 60 000 g/mol) and oligo(ε-caprolactone) were grafted on starch with a grafting percentage up to 75 %. The copolymers show two glass transition temperatures: one around 55-60 °C related to starch and a second attributed to the grafted vinyl polymers, from -46 °C to 20 °C depending on butyl acrylate/styrene ratio. The resulting dual functionalized materials exhibit excellent mechanical properties, with elongation at break in the range 20-210 %, while single functionalized starch shows less than 5 %.


Ritonavir-based highly active antiretroviral therapy in human immunodeficiency virus type 1-infected infants younger than 24 months of age.
Few data are available regarding clinical outcomes or dosing requirements for the protease inhibitor ritonavir in human immunodeficiency virus (HIV)-infected children younger than under 24 months of age. This prospective, multicenter phase I/II open label treatment trial used ritonavir, zidovudine and lamivudine to treat protease inhibitor-naive, HIV-infected infants between the ages of 4 weeks and 24 months. Two sequential dosing cohorts were treated with 350 or 450 mg/m(2) ritonavir every 12 hours; this report includes results of pharmacokinetics, safety, tolerability and efficacy through 104 weeks of follow-up of all subjects. Fifty HIV-infected children were treated. By week 16, 36 had achieved HIV-1 RNA <400 copies/mL (72% intent-to-treat, 84% as-treated analysis); by week 104, 18 maintained durable viral suppression (36% intent-to-treat, 46% as-treated). Poor medication adherence by caregiver report contributed to virologic failure. Few subjects experienced treatment-limiting toxicity: emesis or ritonavir refusal in 6 (12%); and severe but reversible anemia or elevated serum hepatic transaminases in 1 (4%) each. Apparent oral clearance was higher and the median predose concentrations were substantially lower than those found in adults. Median z scores for weight and height for age/gender were below normal at baseline but improved by week 104. A combination regimen of ritonavir, zidovudine and lamivudine was generally safe and produced sustained viral suppression in more than one-third of infants who initiated therapy before 2 years of age. Improved palatability of liquid preparations of protease inhibitors, supporting infrastructure and behavioral approaches to improve medication adherence with antiretrovirals will likely be necessary to further improve efficacy.


Cost-Effectiveness of Treating Early to Moderate Stage Knee Osteoarthritis with Intra-articular Hyaluronic Acid Compared to Conservative Interventions.
Evidence has demonstrated greater benefit of intra-articular hyaluronic acid (IA-HA) within earlier stages of knee osteoarthritis (OA) rather than waiting for patients to have progressed to later stages of disease progression. High molecular weight (HMW) HA has also been shown to be more effective than low molecular weight (LMW) HA products in mild to moderate knee OA, providing an important distinction to make within the class of IA-HA therapies. The purpose of this study is to evaluate the cost-effectiveness of treating patients with knee OA with HMW HA compared to LMW and conservative treatment, while taking into account disease stage. Decision analytic models were created for early/moderate, as well as late stage knee OA. Models for late stage knee OA were created by assuming a range of response rates to IA-HA treatments from 10% to 50%. These models included conservative treatment using physical therapy/exercise, braces/orthosis, and medications such as non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics. The models compared the cost per quality adjusted life year (QALY) gained for these treatments to the use of either LMW or HMW HA. Incremental cost-effectiveness ratios (ICERs) were calculated for each treatment in relation to HMW HA. When evaluating treatment in early to moderate knee OA, HMW HA was dominant over LMW HA and physical therapy/exercise, as it was less expensive and provided greater benefit. HMW HA was cost-effective versus braces/orthosis and NSAID/analgesic medications based on a willingness to pay threshold of $50,000. In the model of 50% response rate to IA-HA for late stage OA, HMW HA remained cost-effective in comparison to physical therapy/exercise and braces/orthosis at a willingness to pay threshold of $50,000; but not NSAID/analgesic medications. In the worst-case scenario of a 10% responder rate to IA-HA, HMW HA was no longer cost-effective in any circumstance. IA-HA, particularly HMW formulations, demonstrate cost-effectiveness when compared to conservative treatment options and LMW HA in patients with early/mid stage knee OA. The cost-effectiveness of HMW HA in patients with later stage knee OA was not as apparent, particularly because of the uncertainty in the proportion of patients with late stage OA who have a meaningful improvement after receiving IA-HA. This cost-effectiveness finding supports the use of IA-HA in patients with early and moderate knee OA, as the benefits of IA-HA are apparent within the patient population with mild to moderate knee OA. The findings of this study suggest that there is a potential cost savings benefit as a result of utilizing HMW HA in earlier stages of knee OA as opposed to later stages. Ferring Pharmaceuticals Inc.


Kinetics and mechanisms of the oxidation of myoglobin by Fe(III) and Cu(II) complexes.
Two distinct mechanisms by which sperm whale myoglobin reduces, respectively, complexes of Fe(III) and Cu(II) and, in turn, is oxidized to metmyoglobin have been characterized. For both mechanisms, deoxymyoglobin is the active reductant. An outer sphere electron transfer, probably at the edge of the heme, is involved for Fe(III)NTA (NTA is nitrilotriacetic acid). This pathway does not involve ionic binding of the Fe(III) complex to the protein. The most reactive species of Fe(III)NTA is uncharged. No inhibition is observed with Ni(II) or Zn(II). An outer sphere site specific electron transfer is operative for reduction of Cu(II) complexes. The site has been characterized using NMR spectroscopy and involves one or more histidines. There is an initial binding of the Cu(II) chelate. The ternary complex of chelator-Cu(II)-deoxymyoglobin is a mandatory intermediate. Ni(II) and Zn(II) compete with Cu(II) for the binding site. A scheme for the participation of either or both of these mechanisms in reduction reactions of heme proteins is proposed. Both the overall redox potential, delta E0, and the stability constant for the ternary complex, K, govern the pathway and the reaction rate.


Entrapment in micellar assemblies switches the excimer population of potential therapeutic luminophore azapodophyllotoxin.
Azapodophyllotoxin is a new class of anti-tumor agent with brilliant therapeutic activity and understanding its physicochemical nature in bio-mimetic microenvironments may provide substantial importance in context of its intercellular localization, efficacy as well as delivery. The present work epitomizes environment-sensitive fluorescence modulation of a prodigy, 4-(2-Hydroxyethyl)-10-phenyl-3,4,6,7,8,10- hexahydro-1H-cyclopenta[g]furo[3,4-b]quinoline-1-one (HPFQ) from the class of anti-cancer agent Azapodophyllotoxin, in differently charged model bio-mimetic micellar microenvironment of cationic CTAB, anionic SDS and neutral Triton X-100 using UV-visible absorption, steady state fluorescence, time-resolved fluorescence and fluorescence anisotropy studies. As a distinct phenomenon, anticancer HPFQ exhibits prolific fluorescence in solvents of varying polarity, originating from a mixed contribution of locally excited, charge transfer and excimer emission. A dramatic modulation in the photophysics of HPFQ has been observed in two types of surfactant consortiums: pre-micellar and post-micellar at physiological and anoxic pH. On photo-excitation, anti-cancer HPFQ exists in monomer-excimer equilibrium with varying ratios in different polarity regions. The marked enhancement in fluorescence intensity of HPFQ in post-micellar region of the surfactant under study probably arises due to regeneration of the monomer from its excimer. This reoccurrence reduces the possibility of Förster resonance energy transfer (FRET) from monomer to excimer, which essentially increases the desired emission intensity. Localization of HPFQ in micellar systems highly depends on polarity gradient inside the micelle, electrostatic, hydrophobic and intermolecular hydrogen bonding interactions. Further corroboration with the polarity sensitive experiments in dioxane-water mixture indicates towards spatial localization of the probe molecule in the stern layer of cationic CTAB, sheer surface of neutral TX100 and outer Gouy-Chapman layer in anionic SDS micelles. A molecular binary logic gate correlates the dominance of micellization over the polarity factor, which enhances the fluorescence response of HPFQ. The enhancement of the emissive potential of anti-cancer HPFQ in biomimetic environments by switching its excimer population may have an immense importance to achieve the status of a dual therapeutic and imaging agent altogether in progressive biomedical research.


T-2 toxin inhibits osteoblastic differentiation and mineralization involving mutual regulation between Wnt signaling pathway and autophagy.
Mycotoxins are most frequent contaminants in environment and agricultural production globally. The T-2 toxin of Fusarium species is the most toxic type of A trichothecene mycotoxins. T-2 toxin can accumulate in bone and cause bone development disorders. Osteoblast is the functional cell responsible for bone formation. Whereas, the mechanism of T-2 toxin toxicity on osteoblast remains unknown. In present study, MC3T3-E1 cells were treated with 0, 2, 4, and 8 nM T-2 toxin for 24h to explore the effect of T-2 toxin on the differentiation and mineralization of osteoblasts. Subsequently, autophagy and Wnt intervention agents were used to explore the roles of autophagy and Wnt signaling pathway in T-2 toxin-induced osteoblastic differentiation and mineralization disorders, respectively. The results showed that 2 nM of T-2 toxin had no significant effect on cell vitality, but 4 and 8 nM of T-2 significantly inhibited cell viability. All doses of T-2 toxin inhibited both osteoblastic differentiation and mineralization, as assessed by alkaline phosphatase staining, Alizarin red S staining, and protein expressions of osteogenic proteins. In addition, the activation of Wnt signaling pathway mitigated T-2 toxin-induced osteoblast impairment, while the inhibition of autophagy exacerbated it. Our results also indicated that there was a positive feedback loop between the Wnt signaling pathway and autophagy.


Mechanical properties of freely suspended semiconducting graphene-like layers based on MoS2.
We fabricate freely suspended nanosheets of molybdenum disulphide (MoS2) which are characterized by quantitative optical microscopy and high-resolution friction force microscopy. We study the elastic deformation of freely suspended nanosheets of MoS2 using an atomic force microscope. The Young's modulus and the initial pre-tension of the nanosheets are determined by performing a nanoscopic version of a bending test experiment. MoS2 sheets show high elasticity and an extremely high Young's modulus (0.30 TPa, 50% larger than steel). These results make them a potential alternative to graphene in applications requiring flexible semiconductor materials.PACS, 73.61.Le, other inorganic semiconductors, 68.65.Ac, multilayers, 62.20.de, elastic moduli, 81.40.Jj, elasticity and anelasticity, stress-strain relations.


Transcriptome changes during osteogenesis of porcine mesenchymal stem cells derived from different types of synovial membranes and genetic background.
Synovial membrane mesenchymal stem cells (SMSCs) often serve as in vitro model for bone disease, but the molecular mechanisms driving osteogenesis in SMSCs from different donor cells of various sources and breeds remain unclear. In this study, porcine SMSCs isolated from adipose synovium (FP) and fibrous synovium (FS) of Angeln Saddleback (AS) and German Landrace (DL) were used to discover the signaling network change after osteogenic induction. During osteogenic differentiation, mineral deposition was first observed at day 14 and further increased until day 21. Transcriptional changes between day 1 and day 21 were enriched in several signaling pathways, including Wnt, PI3K-Akt, and TGF-beta pathway. Certain pathways related to osteogenesis, including osteoblast differentiation, regulation of bone mineralization, and BMP signaling pathway, were enriched at late time points, as confirmed by the osteogenic markers ALPL, COL1A1, and NANOG. A fraction of differentially expressed genes (DEGs) were found between FP and FS, while DEGs between AS and DL increased during the differentiation phase until day 7 and then decreased from day 14 to day 21. These genes are involved in several important signaling pathways, including TGF-beta, Wnt, and lipid-related signaling pathways, suggesting that SMSCs from these two breeds have different osteogenic capabilities.


Comparison of subcutaneous and conjunctival routes of Rev 1 vaccination for the prophylaxis of Brucella ovis infection in rams.
The serological response and protection conferred against Brucella ovis by the Rev 1 vaccine was evaluated in both adult (experiment 1) and young rams (experiment 2) vaccinated either subcutaneously or conjunctivally. In experiment 1 the Rev 1 vaccine protected 55.5 per cent and 100 per cent, respectively, of subcutaneously and conjunctivally vaccinated rams against three consecutive challenges that infected 100 per cent of unvaccinated controls. In experiment 2, Rev 1 protected 100 per cent of rams vaccinated subcutaneously and 70 per cent of those vaccinated conjunctivally against a challenge dose able to infect all the unvaccinated controls. The serological response after vaccination was significantly lower in rams vaccinated conjunctivally than in those vaccinated subcutaneously.


A case of malignant melanoma: disease progression correlated with serum levels of 5-S-Cysteinyldopa (5-S-CD) and intercellular adhesion molecule-1 (ICAM-1).
A 36-year-old Japanese female, in whom malignant melanoma was detected from symptoms of brain metastasis, died 7 months later. The serum levels of 5-S-Cysteinyldopa (5-S-CD) and intercellular adhesion molecule-1 (ICAM-1) correlated with the disease progression. These values may be useful markers of disease progression for malignant melanoma, because the material is easily, frequently, and non-invasively obtained at regular intervals.


Infrared spectroscopy: a potential tool in huanglongbing and citrus variegated chlorosis diagnosis.
Huanglongbing (HLB) and citrus variegated chlorosis (CVC) are serious threats to citrus production and have caused considerable economic losses worldwide, especially in Brazil, which is one of the biggest citrus producers in the world. Neither disease has a cure nor an efficient means of control. They are also generally confused with each other in the field since they share similar initial symptoms, e.g., yellowing blotchy leaves. The most efficient tool for detecting these diseases is by polymerase chain reaction (PCR). However, PCR is expensive, is not high throughput, and is subject to cross reaction and contamination. In this report, a diagnostic method is proposed for detecting HLB and CVC diseases in leaves of sweet orange trees using attenuated total reflectance Fourier transform infrared spectroscopy and the induced classifier via partial least-squares regression. Four different leaf types were considered: healthy, CVC-symptomatic, HLB-symptomatic, and HLB-asymptomatic. The results show a success rate of 93.8% in correctly identifying these different leaf types. In order to understand which compounds are responsible for the spectral differences between the leaf types, samples of carbohydrates starch, sucrose, and glucose, flavonoids hesperidin and naringin, and coumarin umbelliferone were also analyzed. The concentration of these compounds in leaves may vary due to biotic stresses.


Switch of anti-VEGF agents is an option for nonresponders in the treatment of AMD.
Although anti-VEGF therapy of exudative AMD with bevacizumab and ranibizumab proved efficacious in the majority of patients, CNV activity does not respond to continued treatment after repeated injections in a considerable amount of patients. These are referred to as nonresponders. A change of the drug to bevacizumab or ranibizumab could possibly offer an alternative option for the treatment of nonresponding exudative AMD. A total of 138 nonresponders who switched therapy from bevacizumab to ranibizumab (n=114) or vice versa (n=24) were included in a retrospective study. Visual acuity (VA) and foveal thickness before and after the switch of therapy were compared. By means of linear regression analysis, we analyzed possible prognostic factors associated with a favorable outcome for visual acuity. Linear regression analysis revealed a statistically significant benefit for nonresponders when treatment was changed to a different anti-VEGF drug (bevacizumab or ranibizumab). VA at the time of the switch was positively correlated with a beneficial development of VA after changing the drug. There was no significant correlation with age, macular thickness, number of injections before the switch, or the development of VA under treatment before the switch. Both patients switching to Avastin and Lucentis benefitted without statistically significant differences. An exchange of bevacizumab with ranibizumab or vice versa should be considered in nonresponders in the treatment of exudative AMD. Further prognostic factors may help to identify patients who might benefit from a switch. These factors should be investigated in further studies.


Determination of neotame in non-alcoholic beverage by capillary zone electrophoresis.
Neotame (NEO) is a new artificial sweetener approved as a food additive in many countries. The present method for the determination of NEO in various foodstuffs is high-performance liquid chromatography (HPLC). There are no reports on the determination of NEO in foods by capillary zone electrophoresis (CZE). Therefore a simple and rapid method to determine NEO is desired for quality control. A CZE method combined with solid phase extraction was developed for the determination of NEO in non-alcoholic beverage. The optimum separation conditions obtained were 20 mmol L(-1) sodium borate buffer, pH 8, 25 kV applied voltage, 5 s hydrodynamic injection at 30 mbar and ultraviolet detection at 191 nm. The calibration curve showed good linearity (R(2) = 1.000) in the range 0.5-100 µg mL(-1) , and the limit of detection was 0.118 µg mL(-1) . The method was successfully applied to the determination of NEO in two kinds of beverage with migration time less than 5 min, relative standard deviation (n = 3) less than 2% and recoveries ranging from 90 to 95%. The proposed CZE method has the advantages of shorter analysis time and lower cost compared with HPLC, indicating that it may be a good alternative to the HPLC method.


Short- and long-term discontinuation patterns of commonly prescribed antihypertensive drugs among a Chinese population: cohort study.
This retrospective cohort study compared cumulative incidences of antihypertensive drug discontinuation at 8 and 48 weeks in two public primary care clinics in Hong Kong, including 2531 patients who newly received a first-ever antihypertensive monotherapy during the period 1990-2002. from clinical patient records, thiazide diuretics had significantly lower discontinuation rates (0.00%) as compared to all other drug classes at 8 weeks in both young males ( range: 5.4-10.8% in other classes, P <0.001), while at 48 weeks calcium channel blockers (CCBs) showed the highest discontinuation rate (23.0%, 955 CI 17.0%, 29.0%) significantly different from beta-blockers (14.4%, 95% CI 10.9%, 17.9%, P=0.011) and thiazide diuretics ( 13.1 %, 95% CI 8.6%, 17.6%, P=0.010) in young females ( overall P= 0.041). This finding highlights cautions of higher rates of discontinuing CCBs in the long term, and the lower short-term discontinuation rates of thiazides than other drug classes, which strengthens the recommendations from international authorities such as the British Hypertension Society as a best first-line drug for Chinese patients.


Proton-detected scalar coupling based assignment strategies in MAS solid-state NMR spectroscopy applied to perdeuterated proteins.
Assignment of proteins in MAS (magic angle spinning) solid-state NMR relies so far on correlations among heteronuclei. This strategy is based on well dispersed resonances in the (15)N dimension. In many complex cases like membrane proteins or amyloid fibrils, an additional frequency dimension is desirable in order to spread the amide resonances. We show here that proton detected HNCO, HNCA, and HNCACB type experiments can successfully be implemented in the solid-state. Coherences are sufficiently long lived to allow pulse schemes of a duration greater than 70 ms before incrementation of the first indirect dimension. The achieved resolution is comparable to the resolution obtained in solution-state NMR experiments. We demonstrate the experiments using a triply labeled sample of the SH3 domain of chicken alpha-spectrin, which was re-crystallized in H(2)O/D(2)O using a ratio of 1/9. We employ paramagnetic relaxation enhancement (PRE) using EDTA chelated Cu(II) to enable rapid data acquisition.


The mTOR (mammalian target of rapamycin) kinase maintains integrity of mTOR complex 2.
In higher eukaryotes, growth factors promote anabolic processes and stimulate cell growth, proliferation, and survival by activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway. Deregulation of PI3K/Akt signaling is linked to human diseases, including cancer and metabolic disorders. The PI3K-dependent signaling kinase complex mTORC2 (mammalian target of rapamycin complex 2) has been defined as the regulatory Ser-473 kinase of Akt. The regulation of mTORC2 remains very poorly characterized. We have reconstituted mTORC2 by its assembly in vitro or by co-expression its four essential components (rictor, SIN1, mTOR, mLST8). We show that the functional mTOR kinase domain is required for the mTORC2 activity as the Ser-473 kinase of Akt. We also found that mTOR by phosphorylation of SIN1 prevents its lysosomal degradation. Thus, the kinase domain of mTOR is required for the functional activity of mTORC2, and it controls integrity of mTORC2 by maintaining the protein stability of SIN1.


HPLC-MS/MS method validation for the detection of carbadox and olaquindox in poultry and swine feedingstuffs.
Carbadox (CBX) and olaquindox (OLA) were used in poultry and swine feed for growth promotion, to improve feed efficiency and increase the rate of weight gain. However, the use of these agents in feedingstuffs was prohibited because of concerns about their toxicity. Regulatory laboratories are required to have suitably validated analytical methods to ensure compliance with the ban. A quantitative and confirmatory method for determining the presence of CBX and OLA in poultry and swine feed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed, optimized, and validated. The analytes extraction was performed with a mixture of water and acetonitrile (1:1v/v) and cleanup with hexane and C18 (dispersive phase). The method was evaluated by the following parameters: specificity, linearity, matrix effect, decision limits (CCα), detection capability (CCβ), accuracy, precision, limits of detection (LoD), limits of quantification (LoQ) and measurement uncertainty. The validated method presented a broad linear study range and no significant matrix effect. The limit of detection (LoD) was defined at 9 μg kg(-1) for CBX and 80 μg kg(-1) for OLA, and the limit of quantification (LoQ) was defined at 12 μg kg(-1) and 110 μg kg(-1) for CBX and OLA, respectively. The accuracy of the method was adequate for CBX and OLA. The recovery values found in the repeatability conditions were 99.41% for CBX and 104.62% for OLA. Under intralaboratory reproducibility conditions, the values were 98.63% for CBX and 95.07% for OLA. It was concluded that the performance parameters demonstrated total method adequacy for the detection and quantification of CBX and OLA in poultry and swine feedingstuffs.


Synergistic therapeutic effects of Duzhong Jiangya Tablets and amlodipine besylate combination in spontaneously hypertensive rats using 1 H-NMR- and MS-based metabolomics.
Duzhong Jiangya Tablet (DJT) composed of Eucommia ulmoides Oliv. and several other traditional Chinese medicines is a Chinese herbal compound, which is clinically used to treat hypertension. The aim of this study was to evaluate the antihypertensive effect of DJT and amlodipine besylate (AB) on the synergistic treatment of spontaneously hypertensive rats (SHRs), and to explore its antihypertensive mechanism. The synergistic therapeutic effect of DJT in combination with AB on SHR was studied using two metabolomics methods based on mass spectrum (MS) and nuclear magnetic resonance. Metabolomics analysis of plasma, urine, liver, and kidney and the combination of orthogonal partial least squares discriminant analysis was performed to expose potential biomarkers. Then, the overall metabolic characteristics and related abnormal metabolic pathways in hypertensive rats were constructed. Blood pressure measurements showed that DJT combined with AB has better effects in treating hypertension than it being alone. A total of 30 biomarkers were identified, indicating that hypertension disrupted the balance of multiple metabolic pathways in the body, and that combined administration restored metabolite levels better than their administration alone. The changes of biomarkers revealed the synergistic therapeutic mechanism of DJT combined with AB, which provided a reference for the combination of Chinese and Western medicines.


A legacy for rheumatology from Sir William Osler.
"Of the altruistic instincts, veneration is not the most developed at the present day; but I hold strongly with the statement that it is a sign of a dry age when the great men of the past are held in light esteem".


The prioritisation of motivationally salient stimuli in hemi-spatial neglect may be underpinned by goal-relevance: A meta-analytic review.
Damage to regions underpinning attention can result in hemi-spatial neglect, characterised by inattention to stimuli presented in contralesional space. Motivationally salient stimuli (e.g. reward/threat) are, however, resilient to neglect and more likely to be detected compared to neutral stimuli. Prominent theories of attention suggest that the motivational detection advantage in neglect is underpinned by a goal-independent 'emotional attention' system. However, measures of stimulus awareness previously used often present the stimuli as part of the goal-relevant target set. Previous findings may therefore be more consistent with top-down attentional selection, which is preserved in some cases of neglect. Using multilevel and Bayesian meta-analytic approaches to individual case and group data, the evidence for a motivational detection advantage in neglect, and conditions when it emerges, were examined and conceptual claims reviewed. Cumulative evidence suggested that in perceptually simple conditions, when a single stimulus appeared, there was no evidence of a motivational detection advantage (Individual: k = 36; log OR = .02, 95%CI [-.44,.47]; Group: k = 2, dz = .24, 95%CI [-.26, .74]). Conversely, under more perceptually demanding conditions, with multiple goal-relevant stimuli, motivationally salient stimuli were detected more than neutral stimuli in the contralesion side of space (Individual: k = 37, log OR = 1.04, 95%CI [.74, 1.34]; Group: k = 7, dz = .81, 95%CI [.27, 1.35]). Across investigations the detection advantage occurred when the motivationally salient stimulus was a target, and under perceptually demanding conditions when goal-irrelevant motivationally salient stimuli are usually suppressed. The current evidence therefore does not strongly support a goal-independent mechanism, and a top-down account remains plausible. This account can be contextualised within existing models of neglect, whereby perceptual load induces suppression of contralesional space when ipsilesional space is prioritised. Target stimuli may, however, still be detected under reduced perceptual capacity due to their goal-relevance, which may be selectively enhanced by motivational salience.


[Selective occlusion of the hepatic artery and portal vein in hepatic rupture due to severe pre-eclampsia].
A case of hepatic rupture in 32 years old woman with severe preeclampsia is presented. She was definitively treated by right hepatic arterial occlusion and right porta branch occlusion. There were no postoperative complications, and the patient is still alive. This is the first case report of right hepatic arterial occlusion and right porta branch in severe preeclampsia.


Ln18Li8Rh5O39 (Ln = La, Pr): a mixed-metal oxide with a charge-ordered arrangement of Rh3+ and Rh4+.
Polycrystalline samples of Ln18Li8Rh5O39 (Ln = La, Pr) have been synthesized by the ceramic method and characterized by X-ray and neutron diffraction. The compounds crystallize in the cubic space group Pmn, with a0 approximately 12.1 Angstroms. The unit cell contains four intersecting 111 chains, each comprised of an alternating sequence of face-sharing RhO6 octahedra and LiO6 trigonal prisms. The octahedra located at the points of intersection contain Rh4+, whereas the remainder contain Rh3+; the compounds thus contain a charge-ordered arrangement of the two cations. The polyhedral chains are enclosed in tunnels formed by the Ln-O sublattice. The magnetic properties of the two new compounds are discussed briefly: both are paramagnetic over the temperature range 5 < TK < 300.


Various potentially toxic element tolerances in different rice genotypes correlate with distinct physiological responses and alterations in DNA methylation.
Potentially toxic elements (PTEs) are harmful to plant growth and reduce crop productivity. In this work, we studied three rice genotypes (T-35, RZ-1, and RZ-2) to quantify the diverse PTE effects and tolerances by examining morphology, physiology, and DNA methylation patterns. Morphological results showed that T-35 exhibits the highest tolerance to all studied PTE stressors (Cu, Cd, Cr). Physiological responses under PTE stresses confirmed earlier findings, where T-35 showed a higher potassium (K+) content and more peroxidase (POD) accumulation in the roots than the other two rice genotypes. The differences in PTE tolerance levels observed among the three rice genotypes were also associated with variations in the heavy metal transportation (HMT) gene expression level. Moreover, methylation-sensitive blotting analysis of the selected genes showed that the DNA methylation changes occurring due to PTE treatments are mainly CHG hypomethylation in T-35 but hypermethylation in RZ-1 and RZ-2. Our results demonstrate a tight relationship among physiological response, expression levels of the HMT genes, and DNA methylation pattern under PTEs stresses. It is also indicated that plants use generic mechanisms to tolerate stresses; however, different genotypes employ different combinations of such tactics to confer tolerance, which results in diverse PTE stress tolerances. These findings shed light on the PTE stresses tolerance mechanism and help direct future breeding activities in rice.


Immune response in probiotic-fed New Zealand black-footed abalone (Haliotis iris) under Vibrio splendidus challenge.
Vibriosis disease is a major constraint for sustainable molluscan aquaculture. Development of strategies to enhance disease resistance during grow out would greatly reduce stock mortality and boost production yields. In this study, New Zealand black-footed abalone (Haliotis iris) were fed a commercial diet enhanced with multi-strain probiotics (Exiguobacterium JHEb1, Vibrio JH1 and Enterococcus JHLDc) for four months, then challenged with an injection of pathogenic Vibrio splendidus. Host immune responses in haemocytes were characterized using flow cytometry by measuring total haemocyte counts (THC) and viability, degree of apoptosis, and production of reactive oxygen species (ROS) 48 h post-challenge. Probiotic-fed abalone had significantly higher survival rates compared to control animals after the bacterial challenge. Infected probiotic-fed abalone also had significantly higher haemocyte viabilities, slightly lower proportions of haemocytes undergoing early apoptosis, and lower proportions of ROS-producing haemocytes compared to infected control-fed abalone. In addition, metabolite profiles of muscle tissues generated via gas chromatography-mass spectrometry (GC-MS) delivered complimentary evidence to support a perturbed ROS-regulatory system in infected abalone through changes in key metabolites associated with glutathione biosynthesis. The results of this study provide valuable information to assist in farm management practices, leading to enhance production and sustainability of the New Zealand abalone aquaculture industry.


Echocardiography and magnetic resonance imaging in cardiac amyloidosis.
Cardiac amyloidosis is an uncommon cause of heart failure. Based on an observation of immunocytic cardiac amyloidosis with a fatal course, the diagnostic modalities are reviewed with special emphasis on echocardiographic findings. The possible role of magnetic resonance imaging is discussed.


Major gastrointestinal haemorrhage as a complication of cholecystoduodenal fistula in gallstone disease. Report of three cases.
Three patients with cholecystoduodenal fistulae due to gallstone penetration, resulting in major gastrointestinal haemorrhage are presented. Diagnosis and treatment of this condition are discussed.


A meaningful life is worth living: meaning in life as a suicide resiliency factor.
Given the high rate of suicide worldwide, it is imperative to find factors that can confer resiliency to suicide. The goal of the present study was to examine the search for and the presence of meaning in life as possible resilience factors. We hypothesized that the presence of, but not the search for, meaning in life would predict decreased suicidal ideation over an eight-week time period and decreased lifetime odds of a suicide attempt. We also examined a subsidiary hypothesis that the presence of, but not the search for, meaning in life would mediate the relationship between the two variables associated with the interpersonal psychological theory of suicide (i.e., perceived burdensomeness and thwarted belongingness) and suicidal ideation. Our results were generally in support of our hypothesis: presence of meaning in life predicted decreased suicidal ideation over time and lower lifetime odds of a suicide attempt. Surprisingly, search for meaning in life also predicted decreased suicidal ideation over time. Finally, the search for, but not presence of, meaning in life mediated the relationship between the interpersonal psychological theory variables and suicidal ideation. These findings suggest that interventions that target meaning in life may be useful to attenuate suicide risk in individuals.


Complete decongestive physiotherapy and the Lerner Lymphedema Services Academy of Lymphatic Studies (the Lerner School).
Lymphedema is more common than most physicians realize. It is also an incurable, life long condition that has never been treated effectively in the past in our country. The author describes complete decongestive physiotherapy (CDP) and his contribution to making it available all across the United States. This was done by establishing a network of outpatient CDP clinics where patients can be treated effectively and a training school, the Lerner Lymphedema Services Academy of Lymphatic Studies (the Lerner School), where physicians and therapists can be trained in all facets of the lymphedema problem and where the CDP method with all of its components is taught. The superiority of CDP to pneumatic pumps and to surgical procedures used to treat lymphedema is discussed. A description of the Lerner School's philosophy and curriculum is included.


[Interstitial pregnancy: experience at Rouen's hospital].
Presenting our experience concerning interstitial pregnancies (IP) surgical management and to evaluate our patients' subsequent long-term fertility. Twenty patients underwent surgical treatment of IP in our department over 15 years. In this retrospective study, we present symptoms that led to diagnosis, treatments, fertility and obstetrical outcome. Mean gestational age at diagnosis was 8SA, with a median BHCG rate of 7411 IU/L, and a patient mean age of 30 years. Ninety percent of patients had at least one risk factor for ectopic pregnancy. Pain or bleeding were the most common symptoms at admission, 4 patients were admitted in an hypovolemic shock status. Location of the interstitial ectopic pregnancy was discovered during surgery in 45 % of cases. Six patients had a large hemoperitoneum bigger than 1L, 5 patients had an IP of uterine stump after salpingectomy for a previous ectopic pregnancy. The most used surgical technique was in 60 % of cases the excision by Endo GIA stapling(®) with salpingectomy. Regarding fertility, 12 patients wished pregnancy in the aftermath of the intervention, 10 had at least one pregnancy, among them there is an ectopic contralateral ampullary pregnancy, and a contralateral recurrence of interstitial pregnancy. Four patients were delivered by cesarean section and 4 patients were delivered vaginally, some several times. No uterine rupture occured. Interstitial pregnancy is a rare ectopic pregnancy. Its diagnosis is difficult and may involve maternal life-threatening and fertility. In subsequent pregnancies, the clinician has to be careful concerning the risks of interstitial pregnancy recurrence and uterine rupture.


High-intensity focused ultrasound (HIFU) treatment for uterine fibroids: a meta-analysis.
High-intensity focused ultrasound (HIFU) is a non-invasive uterine-preserving treatment alternative to hysterectomy for women with fibroids. We performed this meta-analysis to evaluate the efficacy of HIFU in the treatment of women with symptomatic fibroids comparing it to other approaches including medical treatment with mifepristone (Mife), traditional surgery with myomectomy or hysterectomy (MYC/HRM), and radiofrequency ablation (RF). 16 studies with 1725 women were included. The pooled data of HIFU comparing it to other methods in terms of complete or partial response rate (CR/PR) was not significantly better, but in subgroup analysis, the response rate was significantly higher than Mife, significantly lower than RF and comparable to MYC/HRM, respectively. For the endpoints of safety, the superiority of HIFU compared to MYC/HMR or Mife was found to be significant in terms of pain/discomfort, fever, transfusion, genital tract, gastrointestinal tract, and anesthesia-related complications, while no superiority was identified for skin burn, urinary tract, and nervous system complications. These results suggest that HIFU treatment of uterine leiomyomas leads to clinical improvement with few significant clinical complications and adverse events.