Impact of active and stable psoriasis on health-related quality of life: the PSO-LIFE study.
The aim of this study was to assess the impact of psoriasis on health-related quality of life (HRQOL) using different questionnaires. Prospective observational study of patients with plaque psoriasis of at least 6 months' duration stratified by active and stable disease. The patients were evaluated at baseline, 7 days, and 12 weeks. At the 3 visits, the investigators recorded sociodemographic and clinical data and the patients completed the following HRQOL questionnaires: the Dermatology Life Quality Index (DLQI), the Psoriasis Disability Index (PDI), and psoriasis quality of life questionnaire (PSO-LIFE). In total, 304 patients (182 with active psoriasis and 122 with stable psoriasis) were evaluated. The mean (SD) age was 45.3 (14.5) years, and 56.3% of the group were men. At baseline, the mean (SD) psoriasis and area severity index (PASI) score was 17.0 (7.4) in patients with active disease and 5.6 (5.3) in those with stable disease; a reduction was seen in PASI scores during the evaluation period (P<.01). The mean (SD) score on the PSO-LIFE questionnaire increased significantly from 57.4 (20.4) to 72.2 (19.6) in patients with active psoriasis and from 76.4 (20.6) to 82.3 (18.3) in those with stable disease (P<0.01 in both groups). The difference in standardized mean scores between the 2 groups was 0.79 for the DLQI, 0.62 for the PDI, and 0.85 for the PSO-LIFE questionnaire. The impact of psoriasis on HRQOL as assessed by the PSO-LIFE questionnaire was greater in patients with lesions in visible areas than in those with less visible lesions (P<.01). Changes in PSO-LIFE and PASI scores were moderately and significantly correlated (r=-0.4). The impact of psoriasis on HRQOL is higher in patients with active disease. The PSO-LIFE questionnaire showed a greater tendency to discriminate between active and stable psoriasis than either the DLQI or the PDI. PSO-LIFE scores correlated significantly with lesion site and disease severity as measured by PASI.


DNA-damage-induced differentiation in hematopoietic stem cells.
Aging of hematopoietic stem cells (HSCs) is accompanied by diminished functional potential. Wang et al. now provide evidence for an HSC-specific differentiation checkpoint mediated by the transcription factor BATF, which limits self-renewal of HSCs in response to the accumulation of DNA damage.


Body appreciation in adult women: relationships with age and body satisfaction.
The major aim of the present study was to investigate the effect of age on positive body image (operationalized as body appreciation) across the female lifespan. A secondary aim was to examine the effect of age on the relationship between positive body image and body satisfaction. Participants were 158 women aged between 18 and 75 years who completed questionnaire measures of body appreciation and body dissatisfaction-satisfaction. A significant positive linear relationship was found between age and body appreciation; that is, older women had higher levels of body appreciation than their younger counterparts. Although body appreciation was positively correlated with body dissatisfaction-satisfaction across all age groups, the association was weaker for older women. The results contribute to a richer picture of women's body image across the lifespan, as well as confirming positive body image as something beyond the mere absence of body dissatisfaction.


A dynamic binaural harmonic-cancellation model to predict speech intelligibility against a harmonic masker varying in intonation, temporal envelope, and location.
The aim of this study was to extend the harmonic-cancellation model proposed by Prud'homme et al. [J. Acoust. Soc. Am. 148 (2020) 3246--3254] to predict speech intelligibility against a harmonic masker, so that it takes into account binaural hearing, amplitude modulations in the masker and variations in masker fundamental frequency (F0) over time. This was done by segmenting the masker signal into time frames and combining the previous long-term harmonic-cancellation model with the binaural model proposed by Vicente and Lavandier [Hear. Res. 390 (2020) 107937]. The new model was tested on the data from two experiments involving harmonic complex maskers that varied in spatial location, temporal envelope and F0 contour. The interactions between the associated effects were accounted for in the model by varying the time frame duration and excluding the binaural unmasking computation when harmonic cancellation is active. Across both experiments, the correlation between data and model predictions was over 0.96, and the mean and largest absolute prediction errors were lower than 0.6 and 1.5 dB, respectively.


La-Ca/Fe-LDH-coupled electrochemical enhancement of organophosphorus removal in water: Organophosphorus oxidation improves removal efficiency.
Metal ions or metal (hydrogen) oxides are widely used as active sites in the construction of phosphate-adsorbing materials in water, but the removal of soluble organophosphorus from water remains technically difficult. Herein, synchronous organophosphorus oxidation and adsorption removal were achieved using electrochemically coupled metal-hydroxide nanomaterials. La-Ca/Fe-layered double hydroxide (LDH) composites prepared using the impregnation method removed both phytic acid (inositol hexaphosphate, IHP) and hydroxy ethylidene diphosphonic acid (HEDP) acid under an applied electric field. The solution properties and electrical parameters were optimized under the following conditions: organophosphorus solution pH = 7.0, organophosphorus concentration = 100 mg L-1, material dosage = 0.1 g, voltage = 15 V, and plate spacing = 0.3 cm. The electrochemically coupled LDH accelerates the removal of organophosphorus. The IHP and HEDP removal rates were 74.9% and 47%, respectively in only 20 min, 50% and 30% higher, respectively, than that of La-Ca/Fe-LDH alone. The removal rate in actual wastewater reached 98% in only 5 min. Meanwhile, the good magnetic properties of electrochemically coupled LDH allow easy separation. The LDH adsorbent was characterized using scanning electron microscopy with energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction analysis. It exhibits a stable structure under electric field conditions, and its adsorption mechanism mainly includes ion exchange, electrostatic attraction, and ligand exchange. This new approach for enhancing the adsorption capacity of LDH has broad application prospects in organophosphorus removal from water.


Lost in translation? Information quality in pediatric pre-hospital medical emergencies with a language barrier in Germany.
In pediatric medical emergencies, paramedics and emergency physicians must often rely on the information of third parties, often caregivers, to gather information. Failing to obtain relevant information may lead to misinterpretation of symptoms and subsequent errors in decision making and clinical treatment. Thus, children and/or caregivers with limited proficiency of the locally spoken language may be at risk for medical errors. This study analyzes logs of rescue missions to determine whether paramedics could obtain essential information from German-speaking and foreign-language children and their caregivers. We conducted a secondary data analysis based on retrospective data on pediatric patients of four emergency medical services (EMS) stations in Northern Germany. We defined language discordance with communication difficulties as main exposure. We used documentation quality as outcome defined as existing information on (a) pre-existing conditions, (b) current medication, and (c) events prior to the medical emergency. Statistical analyses include descriptive statistics, simple regression and multivariable regression. As multivariable regression model, a logistic regression was applied with documentation quality as dependent variable and language discordance with communication difficulties as independent variable adjusted for age, sex and Glasgow Coma Scale (GCS). Data from 1,430 pediatric rescue missions were analyzed with 3.1% (n = 45) having a language discordance with communication difficulties. Patients in the pediatric foreign-language group were younger compared to German-speaking patients. Thorough documentation was more frequent in German-speaking patients than in patients in the foreign-language group. Pre-existing conditions and events prior to the medical emergency were considerably more often documented in German-speaking than for foreign-language patients. Documentation of medication did not differ between these groups. The adjustment of sex, age and GCS in the multivariable analysis did not change the results. Language barriers are hindering paramedics to obtain relevant information in pediatric pre-hospital emergencies. This jeopardizes the safe provision of paramedic care to children who themselves or their caregivers are not fluent in German language. Further research should focus on feasible ways to overcome language barriers in pre-hospital emergencies. This is a retrospective secondary data analysis of a study that was registered at the German Clinical Trials Register (No. DRKS00016719), 08/02/2019.


Overview of significant examples of electrochemical sensor arrays designed for detection of nitric oxide and relevant species in a biological environment.
Ultramicroelectrode sensor arrays in which each electrode, or groups of electrodes, are individually addressable are of particular interest for detection of several species concomitantly, by using specific sensing chemistry for each analyte, or for mapping of one analyte to achieve spatio-temporal analysis. Microfabrication technology, for example photolitography, is usually used for fabrication of these arrays. The most widespread geometries produced by photolithography are thin-film microdisc electrode arrays with different electrode distributions (square, hexagonal, or random). In this paper we review different electrochemical sensor arrays developed to monitor, in vivo, NO levels produced by cultured cells or sliced tissues. Simultaneous detection of NO and analytes interacting with or released at the same time as NO is also discussed.


Augmentation index association with reactive hyperemia as assessed by peripheral arterial tonometry in hypertension.
Augmentation pressure has emerged as a surrogate marker for cardiovascular disease, and endothelial dysfunction has been proposed as related factor. However, the relationship between augmentation pressure and digital endothelial function has not yet been well defined. We investigated the relationship between augmentation pressure and digital reactive hyperemia (RH) in patients with hypertension using peripheral arterial tonometry (PAT), which is regarded as being representative of endothelial function. One hundred hypertensive patients (64 males; mean age, 49 ± 12 years) without a history of taking antihypertensive medication were enrolled in this study. The mean augmentation pressure and augmentation index (AIx) normalized for a heart rate of 75 beats/min (AIx75) were 15 ± 8 mm Hg and 26 ± 11%, respectively. The mean RH-PAT index and log transformed PAT ratio were 2.24 ± 0.55 and 0.62 ± 0.30. There was an inverse relationship between the RH-PAT index and age, male sex, and body mass index. The log transformed PAT ratio also showed inverse relationship with age and male sex. The RH-PAT index and the log transformed PAT ratio showed no relationship with augmentation pressure or AIx75. In a multiple linear regression analysis, age, height, and central systolic BP demonstrated an independent association with augmentation pressure and AIx75. In patients with hypertension, the RH-PAT index determined using PAT was not associated with augmentation pressure or AIx75. Digital vascular function may be a less important factor for pressure augmentation in patients with hypertension.


Overlap of hospital use and social care in older people in England.
To link pseudonymous health and social care use data in order to determine what proportion of older people access hospital and social care services. Retrospective analysis of linked, pseudonymous, routine service use data of people aged 75 and over (n = 133,055) drawn from the operational systems of four primary care trusts and their corresponding local authorities in England. Fourteen percent of older people received local authority-funded social care in one year, 59% accessed NHS hospital care and 10% accessed both types of service. Most people using social care also used a hospital service (71%). This was a higher proportion than for people who did not use social care services (57%, P < 0.001). However, the use of hospitals varied by type of social care such that the residents of care homes had fewer admissions to hospital, fewer Accident and Emergency attendances and fewer outpatient visits than people receiving high intensity home care. Using routine data from large populations, we have demonstrated interactions in the use of hospital care and social care for older people. Residents of care homes tend to use hospitals less frequently than people receiving home care. More detailed work is required to explain this phenomenon.


Intracerebral and intracerebellar neurilemoma.
Neurilemomas (schwannomas) within the brain substance and not associated with a peripheral nerve are rare. We have presented two such cases, one with a prominent angiomatous component. Neither patient had neurofibromatosis. Both patients had headache and focal neurologic signs, and surgical excision was curative in both cases.


Transporter-mediated L-glutamate elimination from cerebrospinal fluid: possible involvement of excitatory amino acid transporters expressed in ependymal cells and choroid plexus epithelial cells.
L-Glutamate (L-Glu) is the major excitatory neurotransmitter in the CNS, and its level in cerebrospinal fluid (CSF) is reported to be increased in neuroexcitatory diseases such as epilepsy. Since L-Glu concentration in the CSF is reported to be lower than that in plasma, it has been proposed that some mechanisms of L-Glu clearance from the CSF operate in the brain. The purpose of this study was to elucidate the major pathway of L-Glu elimination from rat CSF and the transporters responsible. Protein expression and localization of excitatory amino acid transporters were examined by immunohistochemical analysis using specific antibodies. In vivo elimination of L-Glu from rat CSF was evaluated by intracerebroventricular administration. An L-Glu uptake study by using primary-cultured rat ependymal cells and isolated rat choroid plexus was performed to characterize L-Glu transport mechanisms. An immunohistochemical analysis has shown that excitatory amino acid transporter (EAAT) 1 and EAAT3, which are D-aspartate-sensitive and kainate-insensitive L-Glu transporters, are localized on the CSF-side of rat ependymal cells and choroid plexus epithelial cells, respectively. In contrast, the kainate-sensitive L-Glu transporter, EAAT2, is not expressed in these cells. In vivo L-Glu elimination clearance from the rat CSF (189 μL/(min · rat)) was 23-fold higher than the CSF bulk flow rate, indicating that facilitative process(es) are involved in L-Glu elimination from the CSF. The in vivo [(3)H]L-Glu elimination from the CSF was significantly inhibited by unlabeled L-Glu and D-aspartate, but not kainate. Moreover, unlabeled L-Glu and D-aspartate inhibited [(3)H]L-Glu uptake by rat ependymal cells and choroid plexus epithelial cells, whereas kainate had little effect. It is suggested that EAAT1 in ependymal cells and EAAT3 in choroid plexus epithelial cells participate in L-Glu elimination from the CSF.


Energy-efficient removal of carbamazepine in solution by electrocoagulation-electrofenton using a novel P-rGO cathode.
In this study, carbamazepine (CBZ) decay in solution has been studied by coupling electrocoagulation with electro-Fenton (EC-EF) with a novel P-rGO/carbon felt (CF) cathode, aiming to accelerate the in-situ generation of •OH, instead of adding Fe2+ and H2O2. Firstly, the fabricated P-rGO and its derived cathode were characterized by XRD, SEM, AFM, XPS and electrochemical test (EIS, CV and LSV). Secondly, it was confirmed that the performance in removal efficiency and electric energy consumption (EEC) by EC-EF (kobs=0.124 min-1, EEC=43.98 kWh/kg CBZ) was better than EF (kobs=0.069 min-1, EEC=61.04 kWh/kg CBZ). Then, P-rGO/CF (kobs=0.248 min-1, EEC=29.47 kWh/kg CBZ, CE=61.04%) showed the best performance in EC-EF, among all studied heteroatom-doped graphene/CF. This superior performance may be associated with its largest layer spacing and richest C=C, which can promote the electron transfer rate and conductivity of the cathode. Thus, more H2O2 and •OH could be produced to degrade CBZ, and almost 100% CBZ was removed with kobs being 0.337 min-1 and the EEC was only 24.18 kWh/kg CBZ, under the optimal conditions (P-rGO loading was 6.0 mg/cm2, the current density was 10.0 mA/cm2, the gap between electrode was 2.0 cm). Additionally, no matter the influent is acidic, neutral or alkaline, no additional pH adjustment is required for the effluent of EC-EF. At last, an inconsecutive empirical kinetic model was firstly established to predict the effect of operating parameters on CBZ removal.


Availability of nitrogen and phosphorus in the nival zone of the Alps.
In high-alpine soils the maximum temperature is low even during the growing season, and hence mineralisation of nutrients is reduced. The aim of this study was to investigate what sources of nitrogen and phosphorus are available for vascular plants in the alpine nival zone to support growth. Using acetylene reduction assays levels of nitrogenase activity were assessed in sealed pots containing nival zone soil and plants at an altitude above 3000 m, and in bacterial isolates of soil and rhizosphere in the laboratory. Nitrogenase activity could not be detected in bacterial isolates or in the soil containing no plants. Small quantities of ethylen (<87 nmol·h-1 per pot) were detected in pots with Cerastium uniflorum and Poa laxa. This activity must be attributable to rhizosphere bacteria since no evidence for the presence of cyanobacteria could be obtained.Other sources of nitrogen for the plants were detected in the form of ammonium and nitrate in soil water and in snow melt water. These solutions also contained extractable phosphorus in quantities normally considered to be sufficient for growth. Analyses of the internal concentration of nitrogen and phosphorus also suggested that these elements were present in adequate amounts in these plants. It was considered that soil and snow melt water together may provide sufficient nitrogen and phosphorus to support the extremely small annual growth increment of nival zone plants.


Inferior petrosal sinus route microcatheterization study and embolization for primary orbital varix.
Primary orbital varix is a rare lesion but difficult to treat. Our main aim was to demonstrate the varices and their central venous communication and to explore the feasibility of embolization of these lesions. In four patients with clinical suspicion of varix, in whom MRI showed retro-global vascular channels, microcatheter digital subtraction angiography (DSA) of the varices was performed using femoral venous access. Embolization was carried out in two patients. In all four patients orbital varices could be accessed with a microcatheter through inferior petrosal sinus and ophthalmic vein (superior or inferior) route. Microcatheter angiography showed opacification of varices and demonstrated their central venous communication. Two patients were treated with coil embolization. Complete resolution of symptoms was seen in one patient and partial relief in the other. The study presents microcatheterization of orbital varices via the inferior petrosal sinus-cavernous sinus-ophthalmic vein route with injections into distal ophthalmic veins for demonstration of these variceal sacs and their central venous connection. Coiling to disconnect the venous communication should be the primary goal of embolization.


Urinary polyamine levels in patients with psoriasis.
Polyamine contents in 24 h urine of 16 psoriatic patients and seven healthy individuals are measured. The average values of putrescine and spermine showed slight increase in the psoriatic group, while those of spermidine were unchanged. When psoriatic patients are divided into three groups according to the extent of their skin lesion, the putrescine level is found to be higher in the group more severely affected.


[The parenteral administration of essential amino acids in patients on periodic hemodialysis treatment. A pilot study].
In an attempt to improve the nutritional status of seven hemodialysed patients, 500 ml of a 5.5% nephrological essential amino acid solution (EAA) were administered during each dialysis session for 2 months. At the end of this treatment, a significant increase in albuminemia was found (p < 0.05). These results are an encouragement to continue this therapy, especially if it is kept in mind that the half-life of albumin is much shorter than the period of EAA administration.


Chronic disseminated cryptococcosis without meningeal involvement in a severely immunosuppressed HIV-infected patient successfully treated with fluconazole.
A 43-year-old female with advanced HIV infection presented with two chronic skin lesions. Cutaneous cryptococcosis was confirmed and pulmonary cryptococcosis was suspected. The patient was neurologically asymptomatic and the cerebrospinal fluid cryptococcal antigen lateral flow assay was negative. She received oral fluconazole and had resolution of the skin lesions and significant improvement of the lung lesions. We report a person with AIDS with chronic disseminated cryptococcosis without meningeal involvement successfully treated with oral fluconazole.


Correction to: Influence of Cystic Fibrosis‑Related Diabetes on Mental Health in Adults: A Single‑Center Study.
The original version of this article unfortunately contained a mistake in one of the co-author name Prof. Don Hayes Jr. During production process, "Jr." was missed to add after the author name. The author name is corrected with this correction. The original article has been corrected.


The roles of Qishen granules recipes, Qingre Jiedu, Wenyang Yiqi and Huo Xue, in the treatment of heart failure.
Recipes (Qingre Jiedu (QJ), Wenyang Yiqi (WYYQ) and Huo Xue (HX)) in Qishen granules (QSG) are believed to synergistically exert cardio-protective effects. However, the underlying pattern of each decomposed recipe in QSG and their synergistic effects in the treatment of heart failure (HF) are not clear. The purpose of this study is to explore the biological contributions of decomposed recipes to therapeutic effects of QSG and reveal the pharmacological mechanism of QSG in treating HF. The therapeutic effects of QSG or its recipes on heart failure were examined in wet-lab at both transcription and phenotypic level using HF Sprague-Dawley rats. Sequencing and transcriptome analyses were performed using in silico approaches including identification of differentially expressed genes, pathway enrichment and protein-protein interaction network studies. Specially, an optimized in silico quantitative pathway analysis that maximally extracted gene expression information was developed to reveal differentially expressed pathways (DEPs) among various groups, and is publicly available as R package QPA on GitHub (https://github.com/github-gs/QPA). Finally, the HF-related genes predicted using DEP approach were validated by quantitative real-time polymerase chain reaction and western blot. Multiple key genes and the associated signaling pathways were shown to be highly relevant for the therapeutic effect of QSG. Decreased expression of Spp1 gene required for inflammatory signaling and profibrotic signaling were observed in failing hearts treated with QJ, WYYQ and HX. Decreased expression of Cx3cr1 gene required for inflammatory signaling was observed in failing hearts treated with WYYQ and HX. Decreased expression of Myc gene required for oxidative stress and Fgfr2 gene required for profibrotic signaling were observed in failing hearts treated with HX and WYYQ, respectively. Increased expression of Adcy1 gene required for cAMP-PKA signaling cascade was observed in failing hearts treated with WYYQ and HX. Our study suggests that QJ, WYYQ and HX recipes in QSG achieve synergistic and complementary therapeutic effects through alleviating inflammatory responses, attenuating ventricular remodeling and enhancing myocardial energy supply.


Regulation of antibiotic resistance in bacteria: the chloramphenicol acetyltransferase system.
The evaluations of antibiotic resistance has been a subject of interest to workers in several disciplines. Our current understanding of the molecular biology of plasmids, phages, and transposable elements provides a basis for appreciating the range of mechanisms likely to be involved in the horizontal spread of resistance determinants through microbial ecosystems. Rather less can be imagined with confidence about the origins of the genes or the constraints and selection pressures operating at the level of protein structure. The CAT system illustrates the extent of variation possible for an accessory gene product which is required infrequently and which is encoded by multicopy and promiscuous vectors which can cross taxonomic boundaries. Still less is known with certainty about the evolution of genetic control of the expression of antibiotic resistance. While there are sound reasons for looking in detail at prokaryotic antibiotic-producing organisms such as Streptomyces to find the progenitors of present resistance mechanisms (44, 45), it seems likely that controls of expression have been acquired during the "passage" of selectable markers through more distant bacterial genera. The CAT system is illustrative of the variety we may expect to find in control strategies used by microbial systems generally. It might indeed be a surprise to find an expression mechanism operating in the CAT system (or for any other family of resistance genes) which was not illustrative of a general strategy exploited by essential genes specifying biosynthetic or degradative functions. There may be some truth in referring to the cat structural gene as a "cartridge" for the isolation and manipulation of promoter functions. It would seem that nature has been at it for some time.


Negative attentional set in the attentional blink: control is not lost.
The attentional blink (AB) refers to the finding that performance on the second of two targets (T1 and T2) in a rapidly presented stimulus stream is impaired when the targets are presented within 200-500 ms. This study investigates whether a negative attentional set, a form of top-down control, has an additional detrimental effect, and whether its influence is modulated by task demands. A negative attentional set was elicited through presentation of a pre-T1 distractor (D1), which belonged to the same category as T2. The presence of D1 impaired T2 performance, and this negative effect was generally larger inside than outside the AB. Moreover, this D1 effect remained constant or was augmented when the demand on T1 processing was enhanced. These findings demonstrate that a negative attentional set is maintained even though the central system is engaged in the in-depth processing of T1 during the AB.


The Effect of Optogenetic Inhibition of the Anterior Cingulate Cortex in Neuropathic Pain Following Sciatic Nerve Injury.
Cortical disinhibition is the underlying pathological alteration contributing to neuropathic pain associated with peripheral nerve injury. Nerve injury resulting in disinhibition of the anterior cingulate cortex has been reported. However, the effect of optogenetic inhibition of the anterior cingulate cortex (ACC) on the sensory component of nerve injury-induced neuropathic pain has not been well studied. To investigate the feasibility of optogenetic ACC modulation, we injected an optogenetic virus or a null virus into the ACC of a nerve injury-induced neuropathic pain model. The unilateral ACC was modulated, and the optogenetic effect was measured by mechanical and thermal sensitivity tests. The assessment was performed in "pre-light off," "stimulation-yellow light on," and "post-light off" states. Optogenetic inhibition of the ACC in injury models revealed improved mechanical and thermal latencies with profound pain-relieving effects against nerve injury-induced neuropathic pain. The sensory thalamic discharge in electrophysiological in vivo recordings was also altered during laser stimulation. This finding indicates that hyperactivity of the ACC in nerve injury increases output to the spinothalamic tract through direct or indirect pathways. The direct photoinhibition of ACC neurons could play a vital role in restoring equilibrium and provide novel insight into techniques that can assuage peripheral nerve injury-induced neuropathic pain.


Arthroscopic Repair of the Acetabular Labrum Using an Anchor-First Modified Toggle Suture Technique.
The goal of acetabular labral repair is to restore stable contact between the labrum and acetabular rim while maintaining the anatomic suction seal. One of the challenges of labral repair is achieving proper in-round repair, so that the labrum contacts the femoral head in the native position. This technique article presents a repair method that allows for enhanced inversion of the labrum to assist with anatomic repair. Our modified toggle suture technique utilizes an anchor-first method and has various distinct technical advantages. We present an efficient and vendor-agnostic technique that allows for straight or curved guides. Similarly, the anchors may be all-suture or hard-anchor designs that accommodate suture sliding. This technique also utilizes a self-retaining hand-tied knot construct to facilitate preventing knots from migrating toward the femoral head or joint space.


In silico Designing of Novel Inhibitors for Triple Inhibition of Aldose Reductase, Aldose Reductase Like Protein 1, and Aldehyde Reductase.
Cancer is a well-known and well-studied disease. There are environmental as well as genetic factors that trigger cancer. All forms of cancer are associated with the deregulation of genes and proteins. Aldose reductase, Aldose Reductase like protein 1 and Aldehyde Reductase are homologous proteins that are overexpressed in different types of cancer. They are NADPHdependent oxidoreductases. The active site is conserved, thus there is very less substrate specificity among those proteins. In this study, novel molecules targeting the three proteins are designed. LigBuilder V2 software is used to design novel molecules. Molecular docking is performed to study the binding affinity of each ligand towards the targets. Molecular Dynamics Simulation was done to check the stability of protein-ligand complexes in an aqueous environment. Six novel molecules have been designed. The six molecules studied are found to have better in silico affinity than tolrestat (known inhibitor). The designed molecules are predicted to be orally active. Finally, Molecular Dynamics Simulation showed that the protein-ligand complexes are stable in an aqueous environment. New molecules targeting Aldose reductase, Aldose Reductase like protein 1 and Aldehyde Reductase have been designed.


The suppressor of Hairy-wing binding region is required for gypsy mutagenesis.
We undertook a deletional analysis of the gypsy retrotransposon in order to determine which sequences of the element are required for its mutagenic effect. We show that a phenotype indistinguishable from that of y2 flies can be generated by transforming y- flies with a construct containing the yellow gene and a gypsy element located at the same insertion site in yellow as found in y2 flies. When flies are transformed with similar constructs in which increasing amounts of the 5' transcribed untranslated region of gypsy have been removed, either a partial y2 revertant or a completely revertant phenotype is obtained. These results yield direct proof that the region of gypsy to which the su(Hw) protein binds is required for the generation of mutant phenotypes by this retrotransposon.


Four Core Concepts in Psychiatric Diagnosis.
In the present article, we aimed at describing the diagnostic process in Psychiatry through a phenomenological perspective. We have identified 4 core concepts which may represent the joints of a phenomenologically oriented diagnosis. The "tightrope walking" attitude refers to the psychiatrist's ability to swing between 2 different and sometimes contrasting tendencies (e.g., engagement and disengagement). The "holistic experience" includes all those intuitive, nonverbal, and pre-thematic elements that emerge in the early stages of the clinical encounter as an emanation of the atmospheric quality of the intersubjective space. The "co-construction of symptoms" regards the hermeneutic process behind psychiatric symptoms, involving both the patient as a self-interpreting agent and the clinician as a translator of his/her experience. Finally, by the "evolving typification" we mean that the closer the relationship becomes with the patient, the more specific and nuanced becomes the typification behind psychiatric diagnosis. Each of these concepts will be accompanied by an extract from a clinical case deriving from one of the authors' most recent clinical experiences.


Systematic metareview of prediction studies demonstrates stable trends in bias and low PROBAST inter-rater agreement.
To (1) explore trends of risk of bias (ROB) in prediction research over time following key methodological publications, using the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and (2) assess the inter-rater agreement of the PROBAST. PubMed and Web of Science were searched for reviews with extractable PROBAST scores on domain and signaling question (SQ) level. ROB trends were visually correlated with yearly citations of key publications. Inter-rater agreement was assessed using Cohen's Kappa. One hundred and thirty nine systematic reviews were included, of which 85 reviews (containing 2,477 single studies) on domain level and 54 reviews (containing 2,458 single studies) on SQ level. High ROB was prevalent, especially in the Analysis domain, and overall trends of ROB remained relatively stable over time. The inter-rater agreement was low, both on domain (Kappa 0.04-0.26) and SQ level (Kappa -0.14 to 0.49). Prediction model studies are at high ROB and time trends in ROB as assessed with the PROBAST remain relatively stable. These results might be explained by key publications having no influence on ROB or recency of key publications. Moreover, the trend may suffer from the low inter-rater agreement and ceiling effect of the PROBAST. The inter-rater agreement could potentially be improved by altering the PROBAST or providing training on how to apply the PROBAST.


Improved De Novo Draft Genome Sequence of the Nocavionin-Producing Type Strain Nocardia terpenica IFM 0706 and Comparative Genomics with the Closely Related Strain Nocardia terpenica IFM 0406.
We report an improved de novo draft genome sequence of the human-pathogenic strain Nocardia terpenica IFM 0706T The resequencing unveiled that the genome size is larger than anticipated, reducing significantly the number of contigs and building a basis for comparison with the closely related strain N. terpenica IFM 0406.


Inconsistent response patterns and the prediction of child maltreatment.
Inconsistent response patterns have been used with other measures to screen for child maltreatment. To date the inconsistency (IC) scale, a validity scale on the Child Abuse Potential (CAP) Inventory, has not been used as a screening criterion for physical child abuse. The present study examined the responses of 89 physical child abusers and 108 comparison subjects to determine if the CAP Inventory IC scale has any utility in the screening for physical child abuse. While results indicated the CAP Inventory IC scale scores were significantly higher for the physical child abuse group, a series of discriminant analyses indicated that the IC scale did not account for any meaningful variance after variance related to child abuse factors was removed. Further, the results indicated that dependence on the IC scale alone for physical child abuse screening purposes could be expected to produce excessive false positive and false negative classifications.


Conventional Non-Fluorescent Polymers: Unconventional Security Inks for Data Storage and Multidimensional Photonic Cryptography.
Traditional security inks relying on fluorescent/phosphorescent molecules are facing increasing risks of forgery or tampering due to their simple readout scheme (i.e., UV-light irradiation) and the advancement of counterfeiting technologies. In this work, a multidimensional data-encryption method based on non-fluorescent polymers via a "lock-key" mechanism is developed. The non-fluorescent invisible polymer inks serve as the "lock" for data-encryption, while the anti-rigidochromic fluorophores that can distinctively light up the polymer inks with programed emissions are "keys" for decryption. The emission of decrypted data is prescribed by polymer chemical structure, molecular weight, topology, copolymer sequence, and phase structure, and shows distinct intensity, wavelength, and chirality compared with the intrinsic emission of fluorophores. Therefore, the data is triply encrypted and naturally gains a high-security level, e.g., only one out of 20 000 keys can access the only correct readout from 40 000 000 possible outputs in a three-polymers-based data-encryption matrix. Note that fluorophores lacking anti-rigidochrimism cannot selectively light up the inks and fail in data-decryption. Further, the diverse topologies, less well-defined structures, and random-coiled shapes of polymers make it impossible for them to be imitated. This work offers a new design for security inks and boosts data security levels beyond the reach of conventional fluorescent inks.


Wnt11 functions in gastrulation by controlling cell cohesion through Rab5c and E-cadherin.
Wnt11 plays a central role in tissue morphogenesis during vertebrate gastrulation, but the molecular and cellular mechanisms by which Wnt11 exerts its effects remain poorly understood. Here, we show that Wnt11 functions during zebrafish gastrulation by regulating the cohesion of mesodermal and endodermal (mesendodermal) progenitor cells. Importantly, we demonstrate that Wnt11 activity in this process is mediated by the GTPase Rab5, a key regulator of early endocytosis, as blocking Rab5c activity in wild-type embryos phenocopies slb/wnt11 mutants, and enhancing Rab5c activity in slb/wnt11 mutant embryos rescues the mutant phenotype. In addition, we find that Wnt11 and Rab5c control the endocytosis of E-cadherin and are required in mesendodermal cells for E-cadherin-mediated cell cohesion. Together, our results suggest that Wnt11 controls tissue morphogenesis by modulating E-cadherin-mediated cell cohesion through Rab5c, a novel mechanism of Wnt signaling in gastrulation.


Effects of cumulus cells removal after 6 h co-incubation of gametes on the outcomes of human IVF.
To investigate the effects of cumulus cells removal after 6 h co-incubation of gametes on the fertilization, polyspermy, multinucleation and clinical pregnancy rates in human IVF. A total of 1,200 IVF-ET cycles undergoing 6 h co-incubation of gametes in 2009 were included in this study. Inclusion criteria were: female age <38 years, first IVF treatment, with bi-ovary and normal ovarian response, e.g., 4 ~ 20 oocytes could be obtained. A 6 h period of co-incubation was applied in all IVF cycles. According to the history of infertility, cumulus cells were mechanically removed either 6 h post-insemination or 20 h post-insemination. For couples with primary infertility, or unexplained infertility, or mild oligospermia or asthenospermia, the cumulus cells were removed at 6 h of insemination for the polar body observation (6 h group, n = 565). Of these, 80 cycles received early rescue ICSI due to fertilization failure or low fertilization rate at 6 h of insemination. For couples with secondary infertility and normal semen analysis, the cumulus cells were removed at 20 h of insemination as routine (20 h group, n = 635). Of these, three cycles received late rescue ICSI due to fertilization failure at 20 h of insemination. Normal fertilization, polyspermy (≥3PN), multinucleation and clinical pregnancy rates were compared between the two groups (rescue ICSI cycles were not included in the comparison in both groups). Significant difference (P < 0.05) was observed between the groups regarding polyspermy rates (7.48% in 6 h group and 9.22% in 20 h group). No difference was observed between the groups regarding normal fertilization rates (2PN rate) (64.89% in 6 h group and 65.74% in 20 h group). No difference was observed between the groups regarding multinucleation and clinical pregnancy rates (11.01% and 65.15% in 6 h group, 10.75% and 66.93% in 20 h group, respectively). The clinical pregnancy rate was 51.43% in cycles receiving early rescue ICSI, while no clinical pregnancy was obtained in cycles receiving late rescue ICSI. The present results indicate that cumulus cells removal at 6 h of insemination is a relatively safe operation, which yielded comparable normal fertilization rate, multinucleation and clinical pregnancy rates compared with 20 h group. This protocol may be beneficial for early obsevation of fertilization failure and make early rescue ICSI possible.


N-(aminobutyl)-N-(ethylisoluminol) functionalized Fe-based metal-organic frameworks with intrinsic mimic peroxidase activity for sensitive electrochemiluminescence mucin1 determination.
Herein, N-(4-aminobutyl)-N-(ethylisoluminol) functionalized Fe-based metal-organic frameworks (ABEI/MIL-101(Fe)) with intrinsic mimic peroxidase activity was synthesized and utilized as highly efficient ECL indicator to construct sensitive immunosensor for mucin1 (MUC1) detection. Firstly, compared with the traditional method for ABEI immobilization, the proposed strategy could successfully achieve the highly efficient ABEI immobilization as ABEI coupled 2-aminoterephhalic acid was used as organic bridge ligand. Moreover, the ABEI/MIL-101(Fe) containing the same luminescent group as luminol could emit strong light when using hydrogen peroxide (H2O2) as a co-reactant. It is worth noting that the ECL signal of ABEI/MIL-101(Fe) could be greatly heightened due to the intrinsic mimic peroxidase activity of ABEI/MIL-101(Fe) that could accelerate the decomposition of H2O2 and produce considerable numbers of reactive oxygen radicals to participate in the ECL reaction of ABEI. The fabricated ECL immunosensor displayed a low detection limit of 1.6 fg mL-1 for MUC1, indicating that the synthesized ABEI/MIL-101(Fe) with intrinsic mimic peroxidase activity may be applied to realize ultrasensitive detection of other biomarkers in early diagnosis.


NYESO-1/LAGE-1s and PRAME are targets for antigen specific T cells in chondrosarcoma following treatment with 5-Aza-2-deoxycitabine.
Chondrosarcoma has no proven systemic option in the metastatic setting. The development of a non-cross-resistant strategy, such as cellular immunotherapy using antigen-specific T cells would be highly desirable. NY-ESO-1 and PRAME are members of the Cancer Testis Antigen (CTA) family that have been identified as promising targets for T cell therapy. LAGE-1 is a cancer testis antigen 90% homologous to NY-ESO-1, sharing the 157-165 A*0201 NY-ESO-1 epitope with its transcript variant, LAGE-1s. A number of CTA's have been induced using 5-Aza-2-Deoxycitabine (5-Aza-dC) in other cancers. We sought to evaluate the feasibility of targeting chondrosarcoma tumors using NY-ESO-1/LAGE-1s and PRAME specific T cells using 5-Aza-dC to induce antigen expression. We used 11 flash frozen tumors from the University of Washington tumor bank to test for the expression of NY-ESO-1, PRAME, LAGE-1s and LAGE-1L in chondrosarcoma tumors. Using four chondrosarcoma cell lines we tested the expression of these CTA's with and without 5-Aza-dC treatments. Finally, using NY-ESO-1/LAGE-1s and PRAME specific effectors that we generated from sarcoma patients, we evaluated the ability of these T cells to lyse A*0201 expressing chondrosarcoma cell lines in vitro both with and without 5-Aza-dC treatment. A minority (36%) of chondrosarcoma tumors expressed either NY-ESO-1 or LAGE-1s at >10% of our reference value and none expressed PRAME at that level. However, in all four of the chondrosarcoma cell lines tested, NY-ESO-1 and PRAME expression could be induced following treatment with 5-Aza-dC including in cell lines where expression was absent or barely detectable. Furthermore, NY-ESO-1/LAGE-1s and PRAME specific CD8+ effector T cells were able to specifically recognize and lyse A*0201 expressing chondrosarcoma cell lines following 5-Aza-dC treatment. These data suggest that adoptive immunotherapy in combination with 5-Aza-dC may be a potential strategy to treat unresectable or metastatic chondrosarcoma patients where no proven systemic therapies exist.


Recognition of Schizophrenia with Regularized Support Vector Machine and Sequential Region of Interest Selection using Structural Magnetic Resonance Imaging.
Structural brain abnormalities in schizophrenia have been well characterized with the application of univariate methods to magnetic resonance imaging (MRI) data. However, these traditional techniques lack sensitivity and predictive value at the individual level. Machine-learning approaches have emerged as potential diagnostic and prognostic tools. We used an anatomically and spatially regularized support vector machine (SVM) framework to categorize schizophrenia and healthy individuals based on whole-brain gray matter densities estimated using voxel-based morphometry from structural MRI scans. The regularized SVM model yielded recognition accuracy of 86.6% in the training set of 127 individuals and validation accuracy of 83.5% in an independent set of 85 individuals. A sequential region-of-interest (ROI) selection step was adopted for feature selection, improving recognition accuracy to 92.0% in the training set and 89.4% in the validation set. The combined model achieved 96.6% sensitivity and 74.1% specificity. Seven ROIs were identified as the optimal discriminatory subset: the occipital fusiform gyrus, middle frontal gyrus, pars opercularis of the inferior frontal gyrus, anterior superior temporal gyrus, superior frontal gyrus, left thalamus and left lateral ventricle. These findings demonstrate the utility of spatial and anatomical priors in SVM for neuroimaging analyses in conjunction with sequential ROI selection in the recognition of schizophrenia.


Spatial dynamics in fluctuating vole populations.
Patterns and consistency of distribution, spatial and temporal components, and the extent of spatial density-dependence were compared between semi-cyclic and cyclic populations of the vole species Clethrionomys glareolus and Microtus agrestis in south-central and north Sweden. Cyclic populations were less clumped and only C. glareolus showed a consistency in distribution between years. Spatial variation contributed little to the distributions in cyclic populations while the spatial and temporal variations were of the same magnitude in the semi-cyclic populations. The latter populations could be subdivided into areas with different spatial and temporal components. The spatial density-dependence increased from increase to decline years in C. glareolus but not in M. agrestis, which differed conspicuously between reregions in population development. The data imply that spatial dynamics should be considered as much as temporal ones for non-cyclic populations, that the same regulating or limiting factors may be at work in both spatial and temporal components and that, in addition, social behaviour may be important in explaining spatial dynamics. However, the latter effects may be fairly species-specific.


The morphology and biomechanical characteristics of subcutaneously implanted tissue-engineered human septal cartilage.
The purpose of the study was to examine the morphology and biomechanical characteristics of in vivo cultured tissue-engineered human septal cartilage as a prospective autogenous transplant material for subcutaneous implantation in reconstructive procedures. Chondrocytes were enzymatically isolated from human septal cartilage biopsies. The cell number was expanded in monolayer culture. Chondrocytes were then fixed on a non-woven poly-lactide-poly-glycolide (PGLA) polymer scaffold by means of fibrin glue. The PGLA-polymer construct was implanted subcutaneously on the back of athymic mice and allowed to mature for 6 or 12 weeks. After killing the mice, the formed cartilage was tested on a material testing machine with a highly standardized reproducible setting. Biomechanical testing consisted of an indentation test, which revealed the failure load and compressive modulus of the neocartilage. The failure load shows the upper limit of supported stress. The compressive modulus is a measure of the templates' stiffness. After testing, the templates were histologically stained. Native human septal cartilage served as a control group. Histological and macroscopic examination showed cartilage formation of a hyaline-like morphology. Histological staining revealed the synthesis of abundant mucopolysaccharid matrix. The biomechanical characteristics of neocartilage proved to be of no statistical difference compared to native human septal cartilage. The failure load and compressive modulus were initially somewhat lower and reached the control group's results after 12 weeks in-vivo. Summarizing, tissue engineered nasal cartilage matches typical mechanical characteristics of native hyaline cartilage. Its elasticity and failure load are of sufficient quality to meet the clinical requirements for reconstructive surgery.


The dichotomy between low frequency and delta waves in human sleep: A reappraisal.
We present the results of an analysis of the low frequency (LF) (0.25-1Hz) and delta (1-4Hz) waves during human sleep. Our objective was to investigate whether LF and delta waves should be considered as separate entities. The slow-wave electroencephalogram (EEG) activity of 2 sets of 10 young, healthy volunteers was analysed utilising the rarely-used Lomb-Scargle periodogram. This method has advantages over the more commonly-used Fast Fourier Transform analysis. During the night, the frequencies of the most powerful waves are concentrated in the 0.5-2Hz range and show a continuous tendency to shift towards slower frequencies during sleep. When considering the frequency dynamics of slow-wave activity below 3Hz, the unifying theory of LF and delta waves is more parsimonious than the idea that there is a different origin and regulation for the two sub-bands. The unifying theory of LF and delta waves is the simplest explanation for the slow-wave activity of the EEG below 3Hz. This finding is important for the clinical use of slow-wave activity.


Contrast-enhanced multiphase dynamic ultrasonography for the characterization of liver tumors.
The purpose of the study was to introduce our protocol for contrast-enhanced multiphase dynamic ultrasonography (US) and examine the effectiveness of this method for characterizing liver tumors. The subjects were 142 patients with liver tumors. The final diagnoses were 58 hepatocellular carcinomas (HCCs), 4 cholangiocellular carcinomas (CCCs), 14 metastases, 29 hemangiomas, 6 cases of focal nodular hyperplasia (FNH), and 31 other benign lesions. The contrast agent used was Levovist. A wide-band pulse inversion harmonic imaging mode was employed. Multiphase dynamic US was achieved by changing the sound transmission interval automatically from 0.3 s to 15.0 s according to a preset menu. Early arterial-phase images were observed at the short interval, and an equilibrium-phase image was observed at the longest interval. After a series of vascular images, a postvascular liver parenchymal image was obtained. Based on previously published criteria, the most compatible diagnosis was noted. The accuracy of this multiphase dynamic US technique for diagnosing focal liver lesions was examined by comparing our results with the final diagnosis based on a prospective study. The overall accuracy of all 142 cases was 93.7%. The sensitivity, specificity, and positive predictive value were, respectively, 100%, 92.9%, and 90.6% for HCC; 88.9%, 97.6%, and 84.2% for metastasis or CCC; 89.7%, 100%, and 100% for hemangioma; and 83.3%, 100%, and 100% for FNH. Contrast-enhanced multiphase dynamic US is a highly accurate, safe diagnostic tool for characterizing liver tumors.


Protosemiosis: agency with reduced representation capacity.
Life has semiotic nature; and as life forms differ in their complexity, functionality, and adaptability, we assume that forms of semiosis also vary accordingly. Here we propose a criterion to distinguish between the primitive kind of semiosis, which we call "protosemiosis" (following Prodi) from the advanced kind of semiosis, or "eusemiosis". In protosemiosis, agents associate signs directly with actions without considering objects, whereas in eusemiosis, agents associate signs with objects and only then possibly with actions. Protosemiosis started from the origin of life, and eusemiosis started when evolving agents acquired the ability to track and classify objects. Eusemiosis is qualitatively different from protosemiosis because it can not be reduced to a small number of specific signaling pathways. Proto-signs can be classified into proto-icons that signal via single specific interaction, proto-indexes that combine several functions, and proto-symbols that are processed by a universal subagent equipped with a set of heritable adapters. Prefix "proto" is used here to characterize signs at the protosemiotic level. Although objects are not recognized by protosemiotic agents, they can be reliably reconstructed by human observers. In summary, protosemiosis is a primitive kind of semiosis that supports "know-how" without "know-what". Without studying protosemiosis, the biosemiotics theory would be incomplete.


Rational design and synthesis of Oreoch-2 analogues as efficient broad-spectrum antimicrobial peptides.
In recent years, bacterial resistance has risen sharply, which seriously endangers public health due to the abuse of antibiotics and the lack of new antibiotics. Therefore, there is an urgent need for new antimicrobial agents to combat multidrug-resistant (MDR) bacterial infections. In this paper, six Oreoch-2 analogues were rationally designed and efficiently synthesized by using the truncation strategy with Oreoch-2 as the lead compound. Evaluation of these analogues against a panel of Gram-positive and Gram-negative bacteria including MDR strains was performed. Among them, ZN-5 and ZN-6 were identified to be broad-spectrum effective analogues, which were superior to their parent peptide Oreoch-2. In addition, ZN-5 and ZN-6 had good stability to the physiological environment, and much higher selectivity to bacterial cells than to mammalian cells. Time-kill kinetics and transmission electron microscope (TEM) studies suggested that these analogues were typical bactericidal agents and quickly eliminated bacteria in a bactericidal mode by disrupting bacterial cell membrane. Moreover, ZN-5 and ZN-6 could inhibit biofilm formation of Staphylococcus aureus ATCC25923. Compared with their parent peptide Oreoch-2, ZN-5 and ZN-6 not only possessed shortened peptide chains, but also showed slightly improved antibacterial activity and greatly reduced hemolysis. This indicates that they are ideal lead compounds of antimicrobial peptides, which can be developed as substitutes for traditional antibiotics.


Enhanced osteogenic activity of poly ether ether ketone using calcium plasma immersion ion implantation.
As a promising implantable material, poly ether ether ketone (PEEK) possesses similar elastic modulus to that of cortical bones yet suffers from bio-inertness and poor osteogenic properties, which limits its application as orthopedic implants. In this work, calcium is introduced onto PEEK surface using calcium plasma immersion ion implantation (Ca-PIII). The results obtained from scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) confirm the modified layer with varying contents of calcium are formed on PEEK surfaces. Water contact angle measurements reveal the increasing hydrophobicity of both Ca-PIII treated surfaces. In vitro cell adhesion, viability assay, alkaline phosphatase activity and collagen secretion analyses disclose improved the adhesion, proliferation, and osteo-differentiation of rat bone mesenchymal stem cells (bMSCs) on Ca-PIII treated surfaces. The obtained results indicate that PEEK surface with enhanced osteogenic activity can be produced by calcium incorporation.


Patient autonomy, informed consent, and the reality of critical care.
The realities of serious illness and critical care environments often complicate our efforts to evaluate treatment refusal according to the doctrine of informed consent. However, health professionals must strive to use informed consent as the ultimate standard for both treatment and nontreatment decisions, by making continual efforts to communicate with patients, share information, and enhance their sense of autonomy and control.


Induction, prevention and mechanisms of contrast media-induced acute renal failure.
This study describes the development of an experimental model of reversible acute renal failure following infusion of contrast media radiographic dye. Experiments were also performed to investigate possible methods of prevention as well as examine single nephron mechanisms involved in the pathogenesis of the renal failure. Acute renal failure was consistently produced by indomethacin treatment (18 mg/kg) and an intravenous infusion of contrast media (7 ml/kg) into New Zealand rabbits that had been on a low sodium diet for one week. Glomerular filtration rate (GFR), measured by daily creatinine clearance in unanesthetized animals, was significantly decreased (P less than 0.001) 24, 48, and 72 hours following infusion of the contrast dye. Two weeks after induction of acute renal failure, GFR had returned to control. GFR was unchanged during the same time period when the sodium deprived rabbits were given either indomethacin or contrast media alone. Chronic administration of DOCA (1 mg/kg s.c.) and saline drinking water which increased sodium and solute excretions and decreased plasma renin activity also prevented the decrease in GFR. However, acute infusion of either saline or mannitol, which transiently increased sodium and solute excretions and decreased plasma renin activity, did not protect against the development of acute renal failure. Light microscopy revealed no glomerular or tubular changes and no visible obstruction. Micropuncture experiments were performed on three additional groups of anesthetized rabbits: control, acute renal failure, and recovery. Recovery rabbits were allowed a two week period after renal failure before they were micropunctured.(ABSTRACT TRUNCATED AT 250 WORDS)


The use of metformin in women with polycystic ovary syndrome: an updated review.
Polycystic ovary syndrome (PCOS) is a major cause of female infertility, being present in up to 20% of women of childbearing age. Insulin resistance (IR) plays an important role in the pathophysiology of PCOS; therefore, its treatment may benefit women with the syndrome. The main drug used for IR management is metformin (MT). We aim to review the literature on the use of metformin in women with PCOS. Using the terms "metformin" and "polycystic ovary syndrome," we conducted a search the PubMed, EMBASE, and Google Scholar databases. The research was restricted to articles published in English. Initially, only published meta-analyses were included, in the absence of meta-analyzes, RCT and well-designed prospective studies were used. Metformin increases success rates and decreases complication rates when used as an adjunctive medication for ovulation induction during low complexity assisted reproduction treatments and during ovarian stimulation for in vitro fertilization in women with PCOS. Evidence about the effect of metformin on fetal and obstetric complication rates is conflicting. Metformin is associated with high incidence of gastrointestinal symptoms; however, serious adverse effects are rare and there is no evidence of teratogenicity. For women with PCOS, metformin is a good adjunctive medication for ovulation induction/stimulation for high and low complexity assisted reproduction therapies. The adverse effects are mostly mild, and there is no risk of teratogenicity, but the risk of long-term complications for the offspring is not yet defined. High heterogeneity of the studies limits extrapolation of findings, and further research is needed to determine which women will benefit most from the medication.


Bioaccumulation and public health implications of trace metals in edible tissues of the crustaceans Scylla serrata and Penaeus monodon from the Tanzanian coast.
The coastal population in East Africa is growing rapidly but sewage treatment and recycling facilities in major cities and towns are poorly developed. Since estuarine mangroves are the main hotspots for pollutants, there is a potential for contaminants to accumulate in edible fauna and threaten public health. This study analysed trace metals in muscle tissues of the giant mud crabs (Scylla serrata) and the giant tiger prawns (Penaeus monodon) from the Tanzanian coast, in order to determine the extent of bioaccumulation and public health risks. A total of 180 samples of muscle tissues of S. serrata and 80 of P. monodon were collected from nine sites along the coast. Both species showed high levels of trace metals in the wet season and significant bioaccumulation of As, Cu and Zn. Due to their burrowing and feeding habits, mud crabs were more contaminated compared to tiger prawns sampled from the same sites. Apart from that, the measured levels of Cd, Cr and Pb did not exceed maximum limits for human consumption. Based on the current trend of fish consumption in Tanzania (7.7 kg/person/year), the measured elements (As, Cd, Co, Cu, Mn, Pb and Zn) are not likely to present health risks to shellfish consumers. Nevertheless, potential risks of As and Cu cannot be ruled out if the average per capita consumption is exceeded. This calls for strengthened waste management systems and pollution control measures.


Prevalence of psilocybin use in vaping and associated factors: a study among amphetamine-type stimulants (ATS) use disorder in Malaysia.
The emergence of New Psychoactive Substances (NPS), including synthetic psilocybin, has raised concern among health experts due to the numerous health and socioeconomic consequences. The current trend is shifting to the hazardous use of synthetic psilocybin in vaping, and little is known about the prevalence of use, specifically among amphetamine-type stimulants (ATS) users. Interviewer-administered questionnaires were conducted in drug detention centers between March and October 2022. The study was conducted using ASSIST 3.0 and obtained information on the respondents' socio-demographic characteristics and clinical profiles. N = 355 ATS users were enrolled in this study. The results show a high prevalence of psilocybin vaping among ATS users (182/355, 53.1%). Most of the respondents were males (85.1%) and unmarried (69.3%), with a mean age of 29.2 (SD = 7.3). Across all respondents, five factors were associated with psilocybin vaping: tobacco smoking, aOR =5.790 (95% CI: 1.723, 8.183); cannabis uses, aOR= 9.152 (95% CI: 2.693, 10.396); and alcohol use, aOR= 3.137 (95% CI: 1.461, 5.817). Respondents of the Malay race had higher odds of being involved in psilocybin vaping compared to other races, with aOR= 1.638 (0.043, 2.459). Meanwhile, a reduction in age by 1.9 will increase the likelihood of involvement in psilocybin vaping with aOR = 1.897 (95% CI: 0.857, 1.938). Psilocybin in vaping is growing among ATS users and across all populations. Unfortunately, knowledge regarding the long-term effects on health is limited. Further studies should highlight the harmful effects of psilocybin and the potential risk of psilocybin vaping among the younger population.


Postnatal disappearance of the pregnancy-associated reduced sensitivity of plasma cortisol to feedback inhibition.
We recently observed that the characteristic insensitivity of the pituitary-adrenal system in women to feedback inhibition during pregnancy persists for at least four days postnatally. We therefore examined women during the first five weeks after delivery to assess when the sensitivity of plasma cortisol to glucocorticoid inhibition returns to normal. Dexamethasone (DEXA, 1 mg) was ingested at 11 pm by normal healthy women, once between the 3rd and 27th postnatal days, and again on day 35. Blood plasma was collected at 4 pm on the following day for cortisol assay. Plasma cortisol levels (nmol/L, mean +/- sem [n]) after DEXA in the first two weeks (216 +/- 28, [47]) were higher (p less than 0.001) than in nonmedicated nonpregnant women (47.4 +/- 8.9 [12]) and were normal by the 35th day after delivery (41.7 +/- 4.8 [74]). A negative association was found between post-DEXA cortisol and time after delivery in the first 4 post-partum weeks (r = -0.46, p less than 0.001). The study confirms that insensitivity of plasma cortisol to feedback inhibition persists beyond normal pregnancy in a significant proportion of healthy women for two to three weeks, and is absent by the 5th postnatal week.


Adherence to ursodeoxycholic acid therapy in patients with cholestatic and autoimmune liver disease.
Ursodeoxycholic acid (UDCA) is used for treatment of cholestatic liver diseases and may improve long-term outcome. Although treatment with this hydrophilic bile acid is virtually without side effects, medication adherence might be suboptimal due to patient misconceptions, compromising clinical outcome. Our aim was to evaluate adherence to UDCA in relation to patient beliefs about medicine and to identify potential predictors of poor adherence. Prospective open-label study recruiting patients in treatment with UDCA from April 2016 to March 2017. Adherence was assessed both by the Sensemedic dispenser and by patient-reported adherence, during 12 weeks. Good adherence was defined as ≥ 80% intake. Quality of life (by SF-36) and beliefs about medicine (by BMQ) were also assessed. A total of 75 patients were enrolled (32% primary biliary cholangitis, 31% autoimmune hepatitis, 29% primary sclerosing cholangitis and 8% other conditions). Average adherence according to the medication dispenser was 92 ± 16% (range: 17-100). Eighty-nine percent of the patients exhibited good adherence and 11% poor adherence. According to the BMQ, 42% of all patients were accepting, 50% ambivalent, 8% indifferent and 0% skeptical to UDCA treatment. Poor adherence was associated with young age (P = 0.029) and male gender (P = 0.021). Despite the excellent safety profile of UDCA, still a significant number of patients are poorly adherent. Young age and male sex are associated with poor adherence. Efforts should be made to identify patients with poor adherence and to improve their compliance to therapy.


Streptococcal pyrogenic exotoxin B causes mitochondria damage to polymorphonuclear cells preventing phagocytosis of group A streptococcus.
The streptococcal pyrogenic exotoxin B (SpeB) is known to be involved in group A streptococcus (GAS) survival in blood, but the detailed mechanism is not clear. For clarification of this issue, speB isogenic mutants of strains M6 and M49 were constructed by using an integrational plasmid and confirmed by Southern blot analysis. The resistance to phagocytosis of wild-type strains and their speB isogenic mutants was analyzed. The results demonstrated a five-fold increase in phagocytosis of speB mutants compared to that of wild-type strains in whole blood, but no significant difference in plasma. To further clarify whether this effect is due to a functional SpeB protein, recombinant SpeB (r-SpeB) and a SpeB mutant protein lacking proteinase activity (r-C192S) were purified and incubated with a speB mutant in whole blood. The results showed a two- to threefold increase in resistance to phagocytosis when the M6 speB mutant was incubated with r-SpeB, but not with r-C192S. Incubation with the wild-type strain, speB mutant, or the r-SpeB protein did not affect the total cell number of polymorphonuclear (PMN) cells in whole blood under laboratory conditions. However, the PMN cells' mitochondria showed decreasing dehydrogenase activity and loss of membrane potential after r-SpeB treatment. These data indicate that SpeB could cause the mitochondria damage to the PMN cells, preventing immune clearance at an early infectious stage.


Increasing the safety of blind gastric tube placement in pediatric patients: the design and testing of a procedure using a carbon dioxide detection device.
The accidental placement of feeding tubes into the airway is a rare but serious complication of blind feeding tube placement in pediatrics. A method using a colorimetric carbon dioxide detector has been tested as a means of decreasing the risk of inadvertent airway placement of gastric tubes in adults, but to date, a similar study has not been accomplished in pediatric patients. This study sought to evaluate the efficacy of a procedure using the colorimetric device during blind gastric tube placement in children. The results demonstrated that the study procedure using the device is effective in detecting inadvertent tube placement into the lung in the pediatric population.


Managing Vascular Tumors-Open Approaches.
The most common vascular tumors encountered by the otolaryngologist are rare chromaffin cell tumors termed paragangliomas. Within the head and neck region, they commonly arise from the carotid body, vagus nerve (glomus vagale), and jugular vein (glomus jugulare). Other vascular head and neck tumors include sinonasal malignancies, because of proximity to or involvement of the pterygoid plexus as well as the rich vascularity of the sinonasal mucosa; juvenile nasopharyngeal angiofibroma, a vascular tumor of male adolescents; unusual vascular tumors such as hemangiopericytoma; and metastatic renal cell cancer, which has a proclivity for an unusually rich blood supply.


Predation by Patiria miniata (Asteroidea) on bryozoans: Prey diversity may depend on the mechanism of succession.
In environments where frequent disturbances interrupt the successional process there will usually be many patches of habitat at intermediate stages of succession. It is then relevant to consider the factors which control local diversity during succession. In offshore kelp forests across the whole Southern Californian Bight settlement panels were rapidly colonised by two species of cyclostome bryozoans (Tubulipora tuba and T. pacifica); but cheilostome bryozoans eventually became dominant during succession because they were able to grow over Tubulipora spp. When abundant, Tubulipora spp. were apparently able to reduce the number of colonies, and hence the number of species, of cheilostome bryozoans settling on the panels. Thus the rapid colonisers may delay the process of succession and reduce the diversity of bryozoans during succession. In field and laboratory experiments we found that the asteroid Patiria miniata preys on Tubulipora spp. but not on cheilostome bryozoans. The predator speeds up the successional process and increases bryozoan diversity by reducing the cover of Tubulipora spp. Other ways in which predators may influence diversity during succession are discussed. The effect of predation may depend on the abundance of the prey and the mechanism of succession.


Comparison study between mesoporous silica nanoscale microsphere and active carbon used as the matrix of shape-stabilized phase change material.
Mesoporous silica nanoscale microsphere (MSNM), with a special morphology, high porosity, large pore volume and specific surface area, was successfully prepared and used as the matrix material of lauric acid (LA) to prepare a favorable shape-stabilized phase change material (LA/MSNM). The porous network structure of MSNM is effective to prevent the leakage and enhance the thermal stability of LA/MSNM. For comparison, shape-stabilized phase change material of LA/AC, which contained commercially purchased active carbon (AC) and LA, was prepared by the same method. Characterizations of LA/MSNM and LA/AC, such as chemical properties, structure, thermal properties and crystallization properties were studied. The mechanisms of interaction between LA molecules and MSNM or AC were explicated. The results of TGA test showed that the LA/MSNM and LA/AC had superior thermal stability, and however, the melting and solidification enthalpies of LA/MSNM were much higher than that of LA/AC, which was attributed that the loading capacity of MSNM was better than that of LA/AC. All of the study results demonstrated that the mesoporous silica nanoscale microspheres of MSNM synthesized in this study possessed the potential for practical applications as a suitable supporter of organic phase change materials.


Experience of road and other trauma by the opiate dependent patient: a survey report.
Trauma plays an important role in the experience of many patients with substance use disorder, but is relatively under-studied particularly in Australia. The present survey examined the lifetime prevalence of various forms of trauma including driving careers in the context of relevant medical conditions. A survey was undertaken in a family medicine practice with a special interest in addiction medicine in Brisbane, Australia. Of 350 patients surveyed, 220 were substance dependent, and 130 were general medical patients. Addicted patients were younger (mean +/- S.D. 33.72 +/- 8.14 vs. 44.24 +/- 16.91 years, P < 0.0001) and had shorter driving histories (15.96 +/- 8.50 vs. 25.54 +/- 15.03 years, P < 0.0001). They had less driving related medical problems (vision, spectacle use, diabetes) but more fractures, surgical operations, dental trauma and assaults. Addicted patients also had significantly worse driving histories on most parameters measured including percent with driving suspensions (O.R. = 7.70, C.I. 4.38-13.63), duration of suspensions (1.71 +/- 3.60 vs. 0.11 +/- 0.31 years, P < 0.0001), number of motor vehicle collisions (2.00 +/- 3.30 vs. 1.10 +/- 1.32, P = 0.01), numbers of cars repaired (1.73 +/- 3.59 vs. 1.08 +/- 1.60, P = 0.042), rear end collisions (O.R. = 1.90, CI 1.13-3.25), running away after car crashes (O.R. = 26.37, CI 4.31-1077.48), other people hospitalized (O.R. = 2.00, C.I. 0.93-4.37, P = 0.037) and people killed (17 vs. 0 P = 0.0005). Upon multivariate analysis group membership was shown to be a significant determinant of both cars repaired and cars hit when controlled for length of driving history. Hence use of all types of drugs (O.R. = 10.07, C.I. 8.80-14.72) was more common in addicted patients as were general (O.R. = 3.64, C.I. 2.99-4.80) and road (O.R.= 2.73, C.I. 2.36-3.15) trauma. This study shows that despite shorter driving histories, addicted patients have worse driving careers and general trauma experience than the comparison group which is not explained by associated medical conditions. Trauma is relevant to addiction management at both the patient and policy levels. Substance dependence policies which focus largely on prevention of virus transmission likely have too narrow a public health focus, and tend to engender an unrealistically simplistic and trivialized view of the addiction syndrome. Reduction of drug driving and drug related trauma likely require policies which reduce drug use per se, and are not limited to harm reduction measures alone.


The role of the C-terminal domain in collagenase and stromelysin specificity.
Recombinant human interstitial collagenase, an N-terminal truncated form, delta 243-450 collagenase, recombinant human stromelysin-1, and an N-terminal truncated form, delta 248-460 stromelysin, have been stably expressed in myeloma cells and purified. The truncated enzymes were similar in properties to their wild-type counterparts with respect to activation requirements and the ability to degrade casein, gelatin, and a peptide substrate, but truncated collagenase failed to cleave native collagen. Removal of the C-terminal domain from collagenase also modified its interaction with tissue inhibitor of metalloproteinases-1. Hybrid enzymes consisting of N-terminal (1-242) collagenase.C-terminal (248-460) stromelysin and N-terminal (1-233) stromelysin.C-terminal (229-450) collagenase, representing an exchange of the complete catalytic and C-terminal domains of the two enzymes, were expressed in a transient system using Chinese hamster ovary cells and purified. Both proteins showed similar activity to their N-terminal parent and neither was able to degrade collagen. Analysis of the ability of the different forms of recombinant enzyme to bind to collagen by ELISA showed that both pro and active stromelysin and N-terminal collagenase.C-terminal stromelysin bound to collagen equally well. In contrast, only the active forms of collagenase and N-terminal stromelysin.C-terminal collagenase bound well to collagen, as compared with their pro forms.


The apple columnar gene candidate MdCoL and the AP2/ERF factor MdDREB2 positively regulate ABA biosynthesis by activating the expression of MdNCED6/9.
MdCoL, which encodes a putative 2OG-Fe(II) oxygenase, is a strong candidate gene for control of the columnar growth phenotype in apple. However, the mechanism by which MdCoL produces the columnar trait is unclear. Here, we show that MdCoL influences abscisic acid (ABA) biosynthesis through its interactions with the MdDREB2 transcription factor. Expression analyses and transgenic tobacco studies have confirmed that MdCoL is likely a candidate for control of the columnar phenotype. Furthermore, the ABA level in columnar apple trees is significantly higher than that in standard apple trees. A protein interaction experiment has showed that MdCoL interacts with MdDREB2. Transient expression and electrophoretic mobility shift assays have demonstrated that MdDREB2 binds directly to the DRE motif in the MdNCED6 and MdNCED9 (MdNCED6/9) gene promoters, thereby activating the transcription of these ABA biosynthesis genes. In addition, a higher ABA content has been detected following co-overexpression of MdCoL-MdDREB2 when compared with the overexpression of MdCoL or MdDREB2 alone. Taken together, our results indicate that an interaction between MdCoL and MdDREB2 promotes the expression of MdNCED6/9 and increases ABA levels, a phenomenon that may underlie the columnar growth phenotype in apple.


Prevalence and histologic significance of cervical human papillomavirus DNA detected in women at low and high risk for cervical neoplasia.
To determine and compare the prevalence and histologic significance of human papillomavirus (HPV) nucleic acids in cervical specimens from women at low (routine hysterectomy) and high (suspicion of cervical neoplasia) risk for cervical neoplasia. Cervical brushings were taken from the cervices of hysterectomy and conization or loop electrical excision specimens and analyzed for HPV nucleic acids by polymerase chain reaction and restriction fragment length polymorphism analysis. Histopathology was confirmed by review of reports or, for HPV-positive results, re-review of the histopathology. Statistical analysis used Student t test or Fisher exact test. Four hundred seventeen and 43 low- and high-risk cervices, respectively, were studied. Statistically significant differences were observed in the index of HPV positivity between the low- and high-risk groups (1.7 versus 42%, P < .001) and the proportion of HPV being cancer-associated HPV types (14 versus 78%, P = .005). None of the 417 cervices from low-risk women contained HPV 16. In the high-risk group, histologically confirmed cervical intraepithelial neoplasia lesion was statistically more likely to be associated with HPV (59 versus 13%, P = .005). Cervices from routine, low-risk hysterectomies in predominately middle-aged women have an extremely low index of cancer-associated HPVs. Considering the strong association of HPV with histologically proven disease, prospective studies exploring the relationship of cancer-associated HPVs to neoplasia in middle-aged women merit consideration.


Hepatic oxidative stress, up-regulation of pro-inflammatory cytokines, apoptotic and oncogenic markers following 2-methoxyethanol administrations in rats.
2-methoxyethanol (2-ME) is an organic solvent widely used in the manufacture of brake fluids, paints, resins, varnish, nail polish, acetate cellulose, wood coloring, and as a plasticizer in plastics manufacturing. We therefore, investigated its effect on the liver, in a time-course study in male Wistar rats. Animals were orally administered 50 mg/kg body weight of 2-ME for a period of 7, 14, and 21 days. Following 7 days of administration of 2-ME, there was a significant increase in the level of Bax, c-Myc, K-Ras, TNF-α, IL-1β, IL-6, MDA and GPx activity, while the levels of Bcl-2, NO and GSH were significantly reduced compared with control. At the end of 14 days exposure, Bcl-2, and GSH levels, as well as GST activity, were significantly decreased, while levels of Bax, c-Myc, K-Ras, caspase-3, TNF-α, IL-1β, IL-6, MDA and NO were significantly increased compared with control. After 21 days of 2-ME administration, Bcl-2, IL-10, and GSH levels, as well as SOD and GST activities, were significantly decreased, while levels of Bax, c-Myc, K-Ras, caspase-3, p53, TNF-α, IL-1β, IL-6, MDA and NO were significantly increased compared with control. Lastly, liver histopathology confirmed and corroborated the biochemical findings reported above. We therefore, advised that exposures to 2-ME should be strictly avoided as it could trigger hepatic damage through the disorganization of the antioxidant system, up-regulation of inflammatory, apoptotic, and oncogenic markers in rats.


The role of beliefs in the relationship between health problems and posttraumatic stress in adolescent and young adult cancer survivors.
In addition to the potential for ongoing health concerns, adolescent and young adult (AYA) childhood cancer survivors frequently report posttraumatic stress symptoms (PTSS). The current study examines whether beliefs about health moderate the relationship between the number of health problems and PTSS 2 months later in 140 survivors. Beliefs, as measured by scales of the Health Competence Beliefs Inventory (HCBI), negatively related to PTSS while health problems positively related to PTSS. Three scales of the HCBI-health perceptions, satisfaction with healthcare and cognitive competence--were significant moderators. The relationship between health problems and PTSS was stronger in the presence of less adaptive beliefs. These beliefs represent potentially malleable intervention targets for reducing PTSS in childhood cancer survivors.


Madelung disease: manifestations of CT and MR imaging.
The purpose of the present study was to assess the head and neck imaging features of Madelung disease on computerized tomography (CT) and magnetic resonance imaging (MRI), delineate the effects of the fatty deposits on underlying structures, and tabulate the anatomic sites where the neck fat was deposited. Sixteen Chinese patients with Madelung disease in our hospital were reviewed. The CT manifestations of the 16 cases and the MRI manifestations of 1 case were analyzed retrospectively. The imaging features of the fatty distribution in the head and neck area were studied. Cross-sectional CT showed that the excess fat was symmetric and unencapsulated, mainly deposited at the anterior or posterior subcutaneous tissue of the neck, was deep under the sternocleidomastoid and trapezius muscles, was situated in the posterior cervical triangle, and was around the salivary glands. It was also found to be situated in supraclavicular fossa, around the paraspinal muscles and larynx, and so on. The accumulated fat at superficial sites was situated at the napex and/or at the anterior neck, forming small or large fatty masses to protrude backwards locally or sometimes at submentum; the markedly thickened neck might appear tubby or oval in anteroposterior diameter. The accumulated fat at deep sites compressed adjacent muscles, salivary glands, and great vessels and caused them to shift and deform. The distinctive appearance was that marked thickening of fat caused sternocleidomastoid muscles and submaxillary glands to shift forward obviously, like a bird spreading its wings. The density of the abnormally proliferated fat was equal to that of normal fat. In MRI, the distribution of the excess fat was equal to that seen with CT. The signal intensity of the excess fat was equal to that of normal fat. Besides the accumulation of the neck fat tissue, CT and MRI did not show other abnormal soft tissue masses. The use of CT and MRI can accurately show the excess fat based on density of CT and signal intensity of MRI. The density and signal intensity of the excess fat are equal to those of normal fat. The excess fat, mainly deposited at the anterior or posterior subcutaneous tissue of the neck, was deep under the sternocleidomastoid and trapezius muscles, was situated in the posterior cervical triangle, and was around the salivary gland, and so on. CT and MRI can also show compression, shift, and deformation of surrounding salivary glands, great vessels, and muscles caused by the excess fat. The CT and MRI can accurately diagnose the disease and exclude other soft tissue tumors.


Supraventricular arrhythmia: a complication of 5-fluorouracil therapy.
5-Fluorouracil is an S-phase-specific, synthetic pyrimidine antimetabolite, which is used as a cytostatic agent for a variety of malignant lesions, either singly or in multidrug regimens. Gastrointestinal toxicity and myelosuppression are the most common adverse reactions, but, of late, clinical cardiotoxicity has been reported in both prospective and retrospective studies. We present our experience of clinical cardiotoxicity in five patients.


Profiles of mRNA expression for prolactin, growth hormone, and somatolactin in Japanese eels, Anguilla japonica: The effect of salinity, silvering and seasonal change.
For understanding the functions of the growth hormone (GH)/prolactin (PRL)/somatolactin (SL) family of hormones, we examined pituitary mRNA expression of these hormones in anguillid eels in relation to salinity difference, silvering, and seasonal change. Female Japanese eels (Anguilla japonica) were collected in the brackish Hamana Lake and its freshwater rivers from July to December. To clarify the effect of salinity, the habitat use history of the eels were determined using otolith microchemistry. Expression levels of mRNA of each hormone were determined using real time PCR. Although GH and PRL have been known to be osmoregulatory hormones, there were no consistent differences in expression levels of these hormones between different salinity habitats. In contrast, SL mRNA expression was higher in eels from freshwater rivers than from the brackish lake. GH mRNA expression clearly decreased during silvering, whereas PRL and SL mRNA expression did not change. We also showed that PRL mRNA and SL mRNA decreased in the brackish lake and PRL mRNA increased in freshwater rivers from autumn to early winter. These findings provide basic knowledge for a further understanding of the role of these hormones.


The actions of the peptides, neuropeptide Y and peptide YY, on the vascular and capsular smooth muscle of the isolated, blood-perfused spleen of the dog.
The two peptides, neuropeptide Y (NPY) and peptide YY (PYY) were compared for potency on the vascular and extravascular smooth muscle of the isolated, blood-perfused spleen of the dog. The only vascular response to both NPY and PYY was vasoconstriction; the maximum effect was to arrest splenic arterial blood flow completely. On a molar basis both NPY and PYY were significantly more potent (P less than 0.01) as splenic arterial vasoconstrictors than the transmitter noradrenaline (NA). PYY was approximately 7 times more potent as a vasoconstrictor than NPY. In contrast to their potency on the vascular smooth muscle, NPY and PYY were significantly (P less than 0.01) less potent than NA in causing contraction of the splenic capsule. The two peptides were equipotent in eliciting this contraction.


Structural characterisation and degradation of Mg-Li thin films for biodegradable implants.
Freestanding thin films of Mg-Li (magnesium-lithium) alloys with a Li mass fraction between 1.6% (m/m) and 9.5% (m/m) were prepared and studied with respect to their structure and degradation properties. With increasing Li content, the microstructure deviates from hexagonal Mg-Li with strict columnar growth and preferred orientation, and additional cubic Mg-Li and Li2CO3 occur. The corrosion rate was measured in Hanks' balanced salt solution by potentiodynamic polarisation and weight loss measurements to investigate biodegradation. Influences of the orientation, phase and protective layer formation lead to an increase in corrosion from 1.6 to 5.5% (m/m) from 0.13 ± 0.03 to 0.67 ± 0.29 mm/year when measured by potentiodynamic polarisation but a similar corrosion rate for 9.5% (m/m) and 3% (m/m) of Li of 0.27 ± 0.07 mm/year and 0.26 ± 0.05 mm/year.


Further characterization of pigment-producing Malassezia strains.
Reference as well as field strains of Malassezia furfur (30), M. sympodialis (49), M. globosa (52), M. obtusa (one), M. restricta (one), M. slooffiae (seven), and M. pachydermatis (373) were investigated for their ability to produce pigment and fluorochromes when tryptophan (Trp) is offered as the main nitrogen source. Only the M. furfur strains produced pigment on a pigment-inducing medium (p-medium). Remarkably, the optical activity of Trp was not significant for pigment synthesis. Other nitrogen sources that are structurally similar to Trp (gramine, tryptamine, serotonin) did not induce pigment formation. All lipophilic non-furfur species failed to grow and to form pigment on this agar. However, growth of all lipid-dependent species was achieved on a modified Dixon agar in which peptone had been substituted by an equal amount of l-Trp. Here, too, the M. furfur colonies were characterized by rapidly developing dark brown halos. Furthermore, about 11% of the M. pachydermatis strains tested produced pigment formation on the p-medium, which was enhanced by addition of d-glucose. In contrast to M. furfur, pigment formation occurred after a markedly longer incubation time (4 weeks unlike 3-5 days) with a lower yield and limited color spectrum (thin layer chromatography, TLC). The UV filter pityriacitrine recently described for M. furfur was also demonstrated for M. pachydermatis by extraction, high-performance liquid chromatography (HPLC) analysis with co-elution and mass spectroscopy. The phenotypic feature of pigment formation in some strains of M. pachydermatis may confirm recent molecular-genetic findings suggesting a relationship between some strains of M. pachydermatis and M. furfur.


Mature green waste compost enhances growth and nitrogen uptake in wheat (Triticum aestivum L.) and oilseed rape (Brassica napus L.) through the action of water-extractable factors.
A series of field and pot trials were carried out to determine the effects of growing wheat and oilseed rape in soils supplemented with green waste composts and provided with additional fertilisers. It was shown consistently that the response of wheat and rape to compost and fertiliser applied together was greater than the responses to the individual additives, but only when very stable compost was used (>10 months processing). Experiments with 15N-labelled fertiliser showed that wheat was able to utilise the applied N more efficiently when cultivated in the stable compost. The enhanced growth was also demonstrated in hydroponic culture of oilseed rape with water extracts of green waste compost in the presence of compound fertiliser. However the effect was rapidly lost at higher dilutions of compost extract (>3). It was concluded that water-extractable growth promoters are present in stable green waste compost, but these only have measurable activity at high concentrations. The identity of the growth promoting factors remains to be found, but the literature suggests that water-extractable humic substances or cytokinins may be involved.


Temporo-mesial extraventricular neurocytoma and cortical dysplasia in focal temporal lobe epilepsy.
We describe a 17-year-old boy with a left extraventricular temporo-mesial neurocytoma associated with cortical dysplasia causing focal pharmacoresistant temporal lobe epilepsy. He presented with a long history of medically refractory, temporal complex partial seizures. MRI showed a left temporo-mesial lesion suspect to be a low-grade tumor. Based on the pre-operative non-invasive neurophysiological studies, the patient underwent a left tailored temporal antero-mesial resection. Histopathological examination showed an extraventricular neurocytoma associated with architectural dysplasia (Type 1a) of the temporal pole. The patient was seizure-free at 2 years follow-up. Extraventricular neurocytomas must be considered in the differential diagnosis of the plethora of low-grade tumors associated with focal epilepsy that typically involve the temporal lobe, and are frequently associated with focal cortical dysplasia.


III. NIH Toolbox Cognition Battery (CB): measuring episodic memory.
One of the most significant domains of cognition is episodic memory, which allows for rapid acquisition and long-term storage of new information. For purposes of the NIH Toolbox, we devised a new test of episodic memory. The nonverbal NIH Toolbox Picture Sequence Memory Test (TPSMT) requires participants to reproduce the order of an arbitrarily ordered sequence of pictures presented on a computer. To adjust for ability, sequence length varies from 6 to 15 pictures. Multiple trials are administered to increase reliability. Pediatric data from the validation study revealed the TPSMT to be sensitive to age-related changes. The task also has high test-retest reliability and promising construct validity. Steps to further increase the sensitivity of the instrument to individual and age-related variability are described.


16,16-Dimethyl prostaglandin E2 delays collagen formation in nutritional injury in rat liver.
Chronic nutritional injury was induced in rats by a high-fat, lipotrope-deficient diet. The hepatoprotective effect of 16,16-dimethyl prostaglandin E2 on the deposition of collagen and fat was assessed by histological evaluation and measurement of hydroxyproline. Dose-response studies established that optimal protection was achieved by the twice daily administration of 16,16-dimethyl prostaglandin E2 at 100 micrograms per kg (subcutaneous) or 250 micrograms per kg (oral). 16,16-Dimethyl prostaglandin E2 and a crystalline analog [(p-acetamidobenzamido)phenyl ester of 16,16-dimethyl prostaglandin E2 significantly delayed both the deposition of collagen and the increase in hepatic hydroxyproline content. There was an excellent correlation between the histological assessment of collagen and the biochemical measurement of hydroxyproline. These data provide a rationale for the evaluation of prostaglandins in the treatment of human liver disease.


The leafhopper genus Atkinsoniella Distant (Hemiptera: Cicadellidae: Cicadellinae) with descriptions of two new species from China.
Two new species in the genus Atkinsoniella from China, Atkinsoniella longiuscula, and A. valida spp. nov. are described and illustrated. A checklist of the known species worldwide is provided.


Blood transfusion during aneurysm surgery.
Increasing costs and concerns about blood supply safety have led to a reevaluation of blood transfusion practices. This study was undertaken to examine blood use during aneurysm surgery. We performed a retrospective analysis of hospital records including operative, anesthetic, and nursing notes, computed tomographic scans, and four-vessel angiographic films of 547 patients undergoing surgery for ruptured and unruptured cerebral aneurysms at Harborview Medical Center in Seattle. During the review period, the transfusion threshold was not altered. A total of 134 patients (24.5%) received an intraoperative blood transfusion (median number of units, 2; range, 1-17). Preoperative factors associated with intraoperative blood use included older patient age (P < 0.001), lower hematocrit level on admission (P = 0.007), ruptured rather than unruptured aneurysm (P = 0.004), severe intraventricular hemorrhage (P = 0.03), and larger aneurysm size (P = 0.004). Factors not associated with intraoperative blood transfusion included past medical history (including cardiac or pulmonary disease), admission clinical grade after aneurysm rupture, findings such as hydrocephalus on computed tomographic scanning, and aneurysm location and aneurysm neck-to-fundus ratio. Also associated with blood transfusion during surgery were intraoperative aneurysm rupture (P < 0.0001), intracerebral hematoma evacuation (P = 0.02), and obliteration of multiple aneurysms (P = 0.002). Among patients who received an intraoperative transfusion, those who experienced an aneurysm rupture required an average of 3.6 +/- 0.35 units, whereas patients who did not have a rupture required 1.9 +/- 0.12 units (P = 0.001). Postoperatively, a total of 244 patients (44.6%), including 77 who received blood intraoperatively, required a blood transfusion (median number of units, 2; range, 1-31). Postoperative blood transfusion was associated with the treatment of patients with subarachnoid hemorrhage (P < 0.0001), particularly among poor-grade patients who developed medical complications. Blood transfusion can be expected in one in five patients undergoing aneurysm surgery. Reducing intraoperative rupture may reduce the need for blood products.