Short-chain fatty acids and bile acids in human faeces are associated with the intestinal cholesterol conversion status.
The analysis of human faecal metabolites can provide an insight into metabolic interactions between gut microbiota and the host organism. The creation of metabolic profiles in faeces has received little attention until now, and reference values, especially in the context of dietary and therapeutic interventions, are missing. Exposure to xenobiotics significantly affects the physiology of the microbiome, and microbiota manipulation and short-chain fatty acid administration have been proposed as treatment targets for several diseases. The aim of the present study is to give concomitant concentration ranges of faecal sterol species, bile acids and short-chain fatty acids, based on a large cohort. Sterol species, bile acids and short-chain fatty acids in human faeces from 165 study participants were quantified by LC-MS/MS. For standardization, we refer all values to dry weight of faeces. Based on the individual intestinal sterol conversion, we classified participants into low and high converters according to their coprostanol/cholesterol ratio. Low converters excrete more straight-chain fatty acids and bile acids than high converters; 5th and 95th percentile and median of bile acids and short-chain fatty acids were calculated for both groups. We give concentration ranges for 16 faecal metabolites that can serve as reference values. Patient stratification into high or low sterol converter groups is associated with significant differences in faecal metabolites with biological activities. Such stratification should then allow better assessment of faecal metabolites before therapeutic interventions. This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc.


Diversity of fungal assemblages in roots of Ericaceae in two Mediterranean contrasting ecosystems.
The plants belonging to the Ericaceae family are morphologically diverse and widely distributed groups of plants. They are typically found in soil with naturally poor nutrient status. The objective of the current study was to identify cultivable mycobionts from roots of nine species of Ericaceae (Calluna vulgaris, Erica arborea, Erica australis, Erica umbellate, Erica scoparia, Erica multiflora, Arbutus unedo, Vaccinium myrtillus, and Vaccinium corymbosum). The sequencing approach was used to amplify the Internal Transcribed Spacer (ITS) region. Results from the phylogenetic analysis of ITS sequences stored in the Genbank confirmed that most of strains (78) were ascomycetes, 16 of these were closely related to Phialocephala spp, 12 were closely related to Helotiales spp and 6 belonged to various unidentified ericoid mycorrhizal fungal endophytes. Although the isolation frequencies differ sharply according to regions and ericaceous species, Helotiales was the most frequently encountered order from the diverse assemblage of associated fungi (46.15%), especially associated with C. vulgaris (19.23%) and V. myrtillus (6.41%), mostly present in the Loge (L) and Mellousa region (M). Moreover, multiple correspondence analysis (MCA) showed three distinct groups connecting fungal order to ericaceous species in different regions.


Suicide and severe mental illnesses. Cohort study within the UK general practice research database.
We aimed to evaluate suicide risk across the life-course in severe mental illnesses (SMI) including schizophrenia. Using survival analysis, we compared suicide risk in cohorts of 46,136 people with SMI and 300,426 without. The overall unadjusted hazard ratio (HR) for suicide in SMI was 12.97 (95% CI: 9.75-17.25). The unadjusted HRs differed by age band: 18-30 years: 19.56 (9.76-39.17); 30-50 years: 13.14 (8.64-19.99); 50-70 years: 16.39 (9.15-29.37); 70+: 3.25 (1.33-7.94). In schizophrenia, risk was significantly higher when young but marked risk persisted until age 70. Greatest risk was associated with: increased consultation rates; antidepressant prescriptions and living in less deprived areas.


Disentangled Representation Learning for Recommendation.
There exist complex interactions among a large number of latent factors behind the decision making processes of different individuals, which drive the various user behavior patterns in recommender systems. These factors hidden in those diverse behaviors demonstrate highly entangled patterns, covering from high-level user intentions to low-level individual preferences. Uncovering the disentanglement of these latent factors can benefit in enhanced robustness, interpretability, and controllability during representation learning for recommendation. However, the large degree of entanglement within latent factors poses great challenges for learning representations that disentangle them, and remains largely unexplored in literature. In this paper, we present the SEMantic MACRo-mIcro Disentangled Variational Auto-Encoder (SEM-MacridVAE) model for learning disentangled representations from user behaviors, taking item semantic information into account. Our SEM-MacridVAE model achieves macro disentanglement by inferring the high-level concepts associated with user intentions (e.g., to buy a pair of shoes or a laptop) through a prototype routing mechanism, as well as capturing the individual preferences with respect to different concepts separately. The micro disentanglement is guaranteed through a micro-disentanglement regularizer stemming from an information-theoretic interpretation of VAEs, which forces each dimension of the representations to independently reflect an isolated low-level factor (e.g., the size or the color of a shirt). The semantic information including visual and categorical signals extracted from candidate items is utilized to further boost the recommendation performance of the proposed SEM-MacridVAE model. Empirical experiments demonstrate that our proposed approach is able to achieve significant improvement over the state-of-the-art baselines. We also show that the learned representations are interpretable and controllable, capable of potentially leading to a new paradigm for recommendation where users have fine-grained control over some target aspects of the recommendation candidates.


Prevalence and characterization of methicillin-resistant Staphylococcus aureus among healthy children in a city of Argentina.
Community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a major global problem. Healthy carriers of S. aureus strains have an important role in the dissemination of this bacterium. The aim of this study was to estimate the prevalence of S. aureus and methicillin-resistant S. aureus (MRSA) carriage among healthy children in a city of Buenos Aires province, Argentina, and to determine the potential risk factors for its acquisition. We also described the molecular features of MRSA strains circulating in this population. S. aureus carriage was investigated in all children attending the last year of kindergarten during the 2008 school- year period. Household contacts of MRSA carriers were also screened. Of 316 healthy children, 98 (31.0%) carried S. aureus, including 14 MRSA carriers (4.4%) and 84 methicillin susceptible S. aureus (MSSA) carriers (26.6%). All MRSA isolates carried the SCCmec type IV cassette. Eight of the fourteen isolates were closely related to the clone responsible for most severe community-acquired MRSA infections caused in our country (CAA: PFGE A, SCCmec IV, spa t311, ST5). Two subtypes (A(1) and A(2)) were distinguished in this group by PFGE. Both had agr type II and presented the same virulence determinants, except for PVL coding genes and sea that were only harbored by subtype A(1). Our results, based on the analysis of MRSA isolates recovered in the screening of healthy children, provide evidence of a community reservoir of the major CA-MRSA clone described in Argentina.


Surgical and Functional Outcome after Resection of 64 Petroclival Meningiomas.
Objective: The management of petroclival meningiomas (PCMs) remains notoriously difficult due to their close association with neurovascular structures and their complex anatomy, hence the surgical paradigm change from radical to functional resection in the past. With this study, we aimed to analyze surgical and functional outcomes of a modern consecutive series of patients with PCMs. Methods: We reviewed patient charts and imaging data of 64 consecutive patients from 2006 to 2018 with a PCM resected at our institution and compared surgical and functional outcomes between subgroups stratified by surgical approach. Results: Females comprised 67.2% of patients (n = 43), with a mean age of 55 years (median 56; range 21-84). Follow-up data were available for 68.8% and reached a mean of 42.3 months (range 1-129) with a median of 28.5 months. The mean tumor diameter was 37.3 mm (standard deviation (SD) 15.4; median 37.0). Infiltration of the cavernous sinus was observed in 34 cases (53.1%), and the lesions affected the brain stem in 28 cases (43.8%). Preoperative cranial nerve palsy was observed in 73.4% of cases; trigeminal neuropathy (42.2%), hearing loss (32.8%), and impairment of vision (18.8%) were the most common. A retrosigmoid approach was employed in 47 cases (78.1%), pterional in 10 (15.6%), combined petrosal in 2 (3.1%), and transnasal and subtemporal in 1 (1.6%). Fifteen cases (23.4%) were resected in a two-staged fashion. Gross total resection (GTR) was attempted in 30 (46.9%) cases without cavernous sinus infiltration and was achieved in 21 (70.0%) of these cases. Surgical complications occurred in 13 cases (20.3%), most commonly meningitis (n = 4; 6.3%). Postoperatively, 56 patients (87.5%) developed new cranial nerve palsy, of which 36 (63.6%) had improved or resolved on last follow up. Achieving GTR was not significantly associated with higher rates of surgical complications (chi-square; p = 0.288) or postoperative cranial nerve palsy (chi-square; p = 0.842). Of all cases, 20 (31.3%) underwent postoperative radiation. Tumor progression was observed in 10 patients (15.9%) after a mean 102 months (median 124). Conclusions: Surgical resection remains the mainstay of treatment for PCMs, with perioperative cranial neuropathies exhibiting favorable recovery rates. Most essentially, the preselection of patients with hallmarks of brain stem affection and cavernous sinus infiltration should dictate whether to strive for a functionally oriented strategy in favor of radical resection.


Changes in hypothalamic cholecystokininA and cholecystokininB receptor subtypes and associated neuropeptide expression in response to salt-stress in the rat and mouse.
This study demonstrates cholecystokinin receptor plasticity in response to salt-loading in the rat and mouse hypothalamus. It identifies, for the first time, the cholecystokinin receptor subtypes involved, firstly by receptor autoradiography and secondly by in situ hybridization. Both species showed increases in hypothalamic [125I]Bolton Hunter-cholecystokinin-8 binding. Co-incubation with the specific cholecystokininA and cholecystokininB antagonists, devazepide and CI-988, indicated that in the rat cholecystokininB receptor binding markedly increased, with a small increase in cholecystokininA receptor binding. In the mouse the response was comprised solely of cholecystokininA receptors. In situ hybridization studies were carried out on a range of peptide messenger ribonucleic acids after salt-loading. In the rat large increases in hypothalamic gene expression were detected for oxytocin, vasopressin, corticotrophin-releasing factor and preprocholecystokinin. In the mouse only vasopressin messenger ribonucleic acid increased, whilst hypothalamic oxytocin, preprocholecystokinin and corticotropin-releasing factor remained unchanged. However, corticotrophin-releasing factor messenger ribonucleic acid increased in the mouse amygdala. In situ hybridization was performed using oligonucleotide probes specific for either the cholecystokininA or cholecystokininB receptor messenger ribonucleic acid, and this showed good agreement with the receptor autoradiography. CholecystokininB receptor expression was upregulated in the rat hypothalamus along with a small but significant increase in cholecystokininA receptors. In the mouse only cholecystokininA receptor expression was increased. In addition to these molecular changes rats lost about 25% of their body weight during six days of salt-challenge, whilst mice continued to grow in line with controls. This work demonstrates differential changes in cholecystokinin receptor subtype binding between the rat and the mouse. It represents the first report of differential changes in cholecystokininA and cholecystokininB receptor messenger ribonucleic acids within the brain, and shows that cholecystokinin receptors within the rodent hypothalamus are capable of plastic responses to chronic osmotic stress.


The neuronal nuclear antigen recognized by the human anti-Ri autoantibody is expressed in central but not peripheral nervous system neurons.
Anti-Ri is a human autoantibody that recognizes a neuronal nuclear antigen (Ri). Biotinylated IgG from serum of two patients with high titers of anti-Ri antibodies was used to study the distribution of the Ri antigen in a panel of normal human tissues. the expression of the Ri antigen was evaluated by an avidin-biotin peroxidase technique and confirmed by immunoblotting. The Ri antigen was restricted to the neurons of the central nervous system (CNS) and some pituitary cells. Most neurons in dorsal root, Gasserian and sympathetic ganglia, and myenteric plexus were negative or, a few of them, very weakly positive. The functional implication of the different expression of the Ri antigen between neurons of the central and peripheral nervous system is presently unknown.


Evaluating pointwise reliability of machine learning prediction.
Interest in Machine Learning applications to tackle clinical and biological problems is increasing. This is driven by promising results reported in many research papers, the increasing number of AI-based software products, and by the general interest in Artificial Intelligence to solve complex problems. It is therefore of importance to improve the quality of machine learning output and add safeguards to support their adoption. In addition to regulatory and logistical strategies, a crucial aspect is to detect when a Machine Learning model is not able to generalize to new unseen instances, which may originate from a population distant to that of the training population or from an under-represented subpopulation. As a result, the prediction of the machine learning model for these instances may be often wrong, given that the model is applied outside its "reliable" space of work, leading to a decreasing trust of the final users, such as clinicians. For this reason, when a model is deployed in practice, it would be important to advise users when the model's predictions may be unreliable, especially in high-stakes applications, including those in healthcare. Yet, reliability assessment of each machine learning prediction is still poorly addressed. Here, we review approaches that can support the identification of unreliable predictions, we harmonize the notation and terminology of relevant concepts, and we highlight and extend possible interrelationships and overlap among concepts. We then demonstrate, on simulated and real data for ICU in-hospital death prediction, a possible integrative framework for the identification of reliable and unreliable predictions. To do so, our proposed approach implements two complementary principles, namely the density principle and the local fit principle. The density principle verifies that the instance we want to evaluate is similar to the training set. The local fit principle verifies that the trained model performs well on training subsets that are more similar to the instance under evaluation. Our work can contribute to consolidating work in machine learning especially in medicine.


Public health measures implemented during the SARS outbreak in Singapore, 2003.
The SARS outbreak hit Singapore between March and May 2003. Public health control measures were applied along three fronts; prevention and control within healthcare settings, community and at the borders. Nosocomial spread composed majority of SARS cases in Singapore. To prevent infection within healthcare facilities, cases were centralized in a SARS-designated hospital, a no-visitors rule was applied and movement of patients and healthcare staff were restricted. For triaging purposes, fever clinics were established. A dedicated ambulance service was used to transport possible cases to the SARS-designated hospital. Hospitals were surveyed for fever clusters. The challenge was to identify cases with atypical presentation. Effective and safe discharge criteria were established from the lessons learnt. To prevent community spread, contacts of cases were stringently traced, quarantined in their homes and monitored daily. For prompt identification of a case and to reduce the time between onset of symptoms and isolation, the Infectious Diseases Act was amended. A large wholesale market closure resulted in massive quarantine thereby limiting the spread of infection. A mass education campaign was implemented in order to educate and raise awareness of the public. At all air, sea and land points-of-entry, exit and entry screening took place that resulted in zero importation and exportation of SARS cases after implementation of screening. Coordinated effort of the cross sectional inter-ministerial collaboration and strong coordination by the Task Force and commitment from different professionals made it possible to conquer the disease.


Evaluation of povidone-iodine as vesical irrigant for treatment and prevention of urinary tract infections.
This is a preliminary study evaluating diluted solutions of povidone-iodine (PVP-I) as urinary bladder irrigants for the treatment and prevention of urinary tract infection. Diluted povidone-iodine solutions were used as indwelling catheter irrigants and as instillations into the urinary bladder following intermittent catheterization. The diluted PVP-I solutions had no efficacy in either the treatment or prevention of urinary tract infections when used as indwelling urethral or suprapubic catheter irrigants. There was a suggestion of a slight decrease in the incidence of urinary tract infections during the use of PVP-I in the intermittent catheterization group in this uncontrolled study, but the percentage of positive urine cultures was greater than desired. The absence of any unfavorable data has led us to conclude that the diluted PVP-I caused no undesirable side effects in any of the patients treated with this agent, PVP-I bladder irrigation warrants further investigation in special cases such as lower urinary tract fungal infections.


Prevalence and management of fourth molars: a retrospective study and literature review.
To evaluate the prevalence of fourth molars and determine if there are differences in occurrence with respect to gender, race, laterality, and site. The charts and panoramic radiographs of all patients referred for third molar consultation between November 2008 and October 2010 at Misawa, US Air Base, Japan were reviewed and data collected included age, gender, and race. Inclusion criteria were minimum age of 18 years and no history of prior third molar surgery. If fourth molars were present, their number, location, size, and shape were noted. Patients with fourth molars were compared to patients without fourth molars with respect to gender and race. Percentages were calculated for laterality and site of occurrence as well. If differences were observed in these parameters, the χ(2) test was used to evaluate if the observed differences were statistically significant. Four hundred nine patients met the inclusion criteria and their charts and panoramic radiographs were reviewed. Fourth molars were observed in 2.2% of the patients. Their prevalence was slightly higher in males (2.2%) than in females (2.1%). They were notably more common in black patients (6.4%) than in whites (0.9%) (P < .005) and they presented more often in the maxilla (78%) than in the mandible (22%) but this difference was not statistically significant (P < .09). Most patients (55%) with fourth molars had them unilaterally. The maxillary fourth molars were typically peg-shaped and small, while the mandibular ones resembled miniature mandibular third molars. The prevalence of fourth molars in this population is 2%. They appear to be more common in black patients and tend to occur mostly in the maxilla unilaterally. When present, the decision to remove these supernumerary teeth should be based on a risk/benefit analysis similar to that of third molars.


Modulation of proteoglycan receptor regulates RhoA/CRMP2 pathways and promotes axonal myelination.
The function of the myelinating system is important because a defective myelin sheath results in various nervous disorders, including multiple sclerosis and peripheral neuropathies. The dorsal root entry zone (DREZ) is a transitional area between the central nervous system (CNS) and the peripheral nervous system (PNS) that is generated by two types of cells-oligodendrocytes and Schwann cells (SCs). It is well known that after injury the extracellular matrix, including the CSPG, impairs axonal myelination by activating protein tyrosine phosphatase-σ (PTPσ) in both cells. The Intracellular Sigma Peptide (ISP) is memetic of the PTPσ wedge region. It competitively binds to PTPσ and regulates the downstream signaling of RhoA. In the present study, we aimed to investigate whether the ISP increased myelination in vivo and in vitro. The in vitro assay was meant to further verify the in vivo mechanisms. We observed that ISP administration could increase axonal myelination both in vivo and in vitro. Furthermore, we provide evidence that, in oligodendrocytes and Schwann cells, the myelination-induced effects of ISP application entail an inverse expression of the RhoA/CRMP2 signaling pathway. Overall, our results indicate that the ISP modulation of PTPσ enhances axonal myelination via the RhoA/CRMP2 signaling pathways.


Suppression of IgE antibody response by irradiated reticulum cell sarcoma cells in SJL mice.
A low number of highly irradiated spleen or lymph node cells from reticulum cell sarcoma (RCS)-bearing SJL mice brings about suppression of IgE antibody production in adequately immunized and sublethally irradiated recipients, probably by known proliferative action of RCS cells on the few Ly-1 T cells which escaped from the irradiation.


Relevance of 'adaptive' mutations arising in non-dividing cells of microorganisms to age-related changes in mutant phenotypes of neurons.
Brattleboro rats do not produce vasopressin (VP) because of a germ-line single-base deletion (di) that causes a frame shift downstream from the VP sequences and a loss of a stop codon. The resulting frame-shifted peptide precursor does not enter the secretory pathway in hypothalamic neurons, thereby blocking the neurosecretion of VP and other peptides. Yet, from birth onwards, a subpopulation of neurons in di/di rats slowly accumulates revertant cells with a hemizygous wild-type phenotype. Because the rate of reversion during aging is slowed by vasopressin infusion, it is of interest to consider these phenomena in relation to recent observations on 'adaptive' mutations in single cell bacteria and yeast that enable reversion of mutations that blocked cell division under conditions of nutrient deficits. In considering mechanisms that could produce revertant phenotypes in non-dividing cells of both pro- and eukaryotes, we note the pertinence of transcription-coupled repair and SOS 'error-prone' repair.


Purification and characterization of Mtr4 and TRAMP from S. cerevisiae.
The Ski2-like RNA helicase, Mtr4, plays a central role in nuclear RNA surveillance pathways by delivering targeted substrates to the RNA exosome for processing or degradation. RNA target selection is accomplished by a variety of Mtr4-mediated protein complexes. In S. cerevisiae, the Trf4/5-Air1/2-Mtr4 polyadenylation (TRAMP) complex prepares substrates for exosomal decay through the combined action of polyadenylation and helicase activities. Biophysical and structural studies of Mtr4 and TRAMP require highly purified protein components. Here, we describe robust protocols for obtaining large quantities of pure, active Mtr4 and Trf4-Air2 from S. cerevisiae. The proteins are recombinantly expressed in E. coli and purified using affinity, ion exchange, hydrophobic exchange and size exclusion chromatography. Care is taken to remove nuclease contamination during the prep. Assembly of TRAMP is achieved by combining individually purified Mtr4 and Trf4-Air2. We further describe a strand displacement assay to characterize Mtr4 helicase unwinding activity.


The use of Multi-Sensory Environments with autistic children: Exploring the effect of having control of sensory changes.
Multi-Sensory Environments (also called sensory or Snoezelen® rooms) are rooms that contain equipment which can create light, sound and touch experiences. Multi-Sensory Environments are often used with autistic children, particularly in schools, but there is no evidence for how best to use them. We investigated whether having control over the sensory equipment in the Multi-Sensory Environment affected how a group of 41 (8 female) autistic children aged 4-12 years behaved. We found that when autistic children could control the sensory equipment, they paid more attention and performed fewer repetitive and sensory behaviours. They also used less stereotyped speech, produced fewer vocalisations and showed lower levels of activity. Other behaviours were not affected. Our findings demonstrate that how a Multi-Sensory Environment is used can impact behaviour and that providing control of sensory changes to autistic children may help create better conditions for learning.


Short-term cultivation limiting soil aggregate stability and macronutrient accumulation associated with glomalin-related soil protein in Eucalyptus urophylla × Eucalyptus grandis plantations.
The relationship between glomalin-related soil protein (GRSP) and soil aggregation has been a hot topic of research for its close link to soil stability and quality. However, the short-term cultivation of Eucalyptus poses serious threats to soil stability and nutrient stocks, and the effects of GRSP on soil aggregate stability and macronutrient accumulation remain unclear. The aim is to clarify the potential mechanisms affecting soil aggregate stability and macronutrient accumulation in short-term Eucalyptus plantations. Five Eucalyptus urophylla × Eucalyptus grandis plantations with different cultivation periods (1-5 years) in this study were investigated, and a native evergreen broadleaf forest (0 year) was selected as control. The mean weight diameter index increased in the first 3 years and then significantly decreased during 5 years cultivation of Eucalyptus. Soil organic carbon (SOC) and total nitrogen also decreased after planting Eucalyptus for 3 years, but variation in total phosphorus was not obvious. The relative abundance of Glomeraceae and Claroideoglomeraceae decreased in the 5-year-old Eucalyptus plantations and was positively correlated with GRSP content. In pathway modeling, nutrient-acquisition enzyme activities positively affected GRSP and macronutrient content. Total GRSP (T-GRSP) had higher total effects than easily extractable GRSP on soil aggregate stability, and positively correlated with SOC in macroaggregates. Both T-GRSP and SOC had positive and direct effects on soil aggregate stability. Variance partitioning analysis further explained the contribution of GRSP and SOC to aggregate stability, particularly in >2 and 2-0.25 mm macroaggregates. Our results suggested that GRSP was directly associated with SOC content and soil aggregate stability, and was a potential key factor affecting soil aggregate stability in Eucalyptus plantations. Improving T-GRSP and SOC are efficient approaches for preventing the gradual deterioration of soil aggregate stability. Short-term cultivation should be carefully used in Eucalyptus plantations, and a new cultivation period is needed.


History of Mohs surgery.
Mohs micrographic surgery (MMS) has become the gold standard for treating many forms of primary and recurrent contiguous skin cancers and offers the highest cure rates and maximum tissue conservation compared with other modalities. Developed by Dr Frederic E. Mohs in the 1930s, it was initially called chemosurgery and used zinc chloride paste in a process called fixed tissue technique. Although this technique had high cure rates, it could take days to complete, and it gradually gave way to fresh tissue technique, renamed MMS. Now, MMS is practiced widely as part of a multidisciplinary approach for treating skin cancer.


In vitro antibody affinity maturation targeting germline hotspots.
Affinity-matured antibodies can exhibit increased biological efficacy. Regardless of whether an antibody is isolated from a hybridoma or a human Fv phage library, the antibody affinity for its target may need improvement for therapeutic applications. An increased affinity may allow for a reduced dosage of a therapeutic antibody; toxic side effects may also be reduced. In the immune system, affinity maturation is a process involving somatic hypermutations in B cells. Therefore, germline hotspot residues are most likely to have a major impact on antibody affinity. Here, we describe procedures for germline hotspot mutagenesis with an emphasis on strategies for randomizing hotspots with PCR and phage display, using as an example the anti-CD22 monoclonal antibody.


Resting heart rate in first year survivors of myocardial infarction and long-term mortality: a community study.
To evaluate the long-term prognostic effect of resting heart rate (HR) at index myocardial infarction (MI) and during the first year after MI among 1-year survivors. The community-based cohort consisted of 1571 patients hospitalized with an incident MI from January 1, 1983, through December 31, 2007, in Olmsted County, Minnesota, who were in sinus rhythm at index MI and had HR measurements on electrocardiography at index and during the first year after MI. Outcomes were all-cause and cardiovascular deaths. During a median follow-up of 7.0 years, 627 deaths and 311 cardiovascular deaths occurred. Using patients with HRs of 60/min or less as the referent, this study found that long-term all-cause mortality risk increased progressively with increasing HR at index (hazard ratio, 1.62; 95% CI, 1.25-2.09) and even more with increasing HR during the first year after MI (hazard ratio, 2.16; 95% CI, 1.64-2.84) for patients with HRs greater than 90/min, adjusting for clinical characteristics and β-blocker use. Similar results were observed for cardiovascular mortality (adjusted hazard ratio, 1.66; 95% CI, 1.14-2.42; and adjusted hazard ratio, 1.93; 95% CI, 1.27-2.94; for HR at index and within 1 year after MI, respectively). These data from a large MI community cohort indicate that HR is a strong predictor of long-term all-cause and cardiovascular mortality not only at initial presentation of MI but also during the first year of follow-up.


Impact of inadequate respiratory motion management in SBRT for oligometastatic colorectal cancer.
Stereotactic body radiotherapy (SBRT) in oligometastatic colorectal cancer (CRC) resulted in a disappointing 1-year local control rate of 54% in our experience. We aimed to determine the root cause(s). 47 oligometastatic CRC patients were treated with SBRT by helical tomotherapy to a dose of 40 or 50Gy in 10 fractions, without specific respiratory motion management and PTV-margins of 10-10-12mm in all patients. The local recurrences (LRs) were delineated on diagnostic PET-CT scans and co-registered with initial planning CTs. LRs were classified as in-field or marginal with respect to the initial dose distribution, and predictors for LR were determined. Out of 105 irradiated metastases, LR modeling yielded 15 in-field and 15 marginal failures. Metastases in moving organs (liver and lung) exhibited a local control of 53% at 1-year (95% confidence interval (CI): 38-67%), compared to 79% for lymph nodes (95% CI: 32-95%). The first group exhibited a sixfold increased risk compared to the latter on multivariate analysis (p=0.01). The nature and locations of LR indicated that dose prescription and methodology were both inadequate for liver and lung metastases. This study demonstrates the need for individual respiratory motion management and a biological effective dose of >75Gy.


Assessment of pituitary response to nasal application of synthetic gonadotropin-releasing hormone in men.
An attempt has been made to assess the pituitary response to the nasal application of synthetic gonadotropin-releasing hormone (GnRH) in three oligospermic and two azoospermic men. Intranasal administration of 3 mg of GnRH in aqueous or natural plant gum solution produced a pituitary response pattern similar to that produced by the intramuscular injection of 100 microng, with respect to plasma concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). No technical difficulties or side effects were observed. GnRH in a nasal drop preparation seems to be effective in releasing LH and FSH in men. These findings may have a practical application in those cases where long-term therapy with the hormone is indicated.


A novel variant of dehydrodolichol diphosphate synthase (DHDDS) mutation with adult-onset progressive myoclonus ataxia.
We report a novel variant of DHDDS mutation in a patient with progressive adult-onset myoclonus ataxia. The mutation in our patient was different from previous reports of denovo mutations in DHDDS in 6 patients who showed tremor-like myoclonus and generalized epilepsy.


Genetic variants in glutamate cysteine ligase confer protection against type 2 diabetes.
Oxidative stress contributes to the pathogenesis of type 2 diabetes (T2D). This study investigated whether single nucleotide polymorphisms (SNPs) at genes encoding glutamate cysteine ligase catalytic (rs12524494, rs17883901, rs606548, rs636933, rs648595, rs761142 at GCLC) and modifier (rs2301022, rs3827715, rs7517826, rs41303970 at GCLM) subunits are associated with susceptibility to type 2 diabetes. 2096 unrelated Russian subjects were enrolled for the study. Genotyping was done with the use of the MassArray System. Plasma levels of reactive oxygen species (ROS) and glutathione in the study subjects were analyzed by fluorometric and colorimetric assays, respectively.The present study found, for the first time, an association of SNP rs41303970 in the GCLM gene with a decreased risk of T2D (P = 0.034, Q = 0.17). Minor alleles such as rs12524494-G GCLC gene (P = 0.026, Q = 0.17) and rs3827715-C GCLM gene (P = 0.03, Q = 0.17) were also associated with reduced risk for T2D. Protective effects of variant alleles such as rs12524494-G at GCLC (P = 0.02, Q = 0.26) and rs41303970-A GCLM (P = 0.013, Q = 0.25) against the risk of T2D were seen solely in nonsmokers. As compared with healthy controls, diabetic patients had markedly increased levels of ROS and decreased levels of total GSH in plasma. Interestingly, fasting blood glucose level positively correlated with oxidized glutathione concentration (rs = 0.208, P = 0.01). Three SNPs rs17883901, rs636933, rs648595 at GCLC and one rs2301022 at GCLM were associated with decreased levels of ROS, while SNPs rs7517826, rs41303970 at GCLM were associated with increased levels of total GSH in plasma. Single nucleotide polymorphisms in genes encoding glutamate cysteine ligase subunits confer protection against type 2 diabetes and their effects are mediated through increased levels of glutathione.


Fabrication and Study on Magnetic-Optical Properties of Ni-Doped ZnO Nanorod Arrays.
Zn1-xNixO nanorod arrays were prepared on Si substrates by magnetron sputtering and hydrothermal methods at 100 °C. We studied the effects of doped concentration and hydrothermal growth conditions on the crystal structure, morphology, photoluminescence, and magnetic properties of Zn1-xNixO nanorod arrays. The research results show that the Zn1-xNixO nanorod have the hexagonal wurtzite structure without the appearance of the second phase, and all samples have a highly preferred orientation of a (002) crystal face. The Zn1-xNixO nanorod arrays exhibit obvious room temperature ferromagnetism with saturation magnetization at 4.2 × 10-4 emu/g, the residual magnetization is 1.3 × 10-4 emu/g and the coercive field is 502 Oe, and also excellent luminescent properties with seven times greater luminous intensity than that of ZnO nanorod arrays. The redshift of the ultraviolet emission peak was found by Ni2+ doping. We further explained the source and essence of the magnetic properties of Zn1-xNixO nanorod arrays and deemed that the magnetic moment mainly comes from the hybrid electron exchange of O 2p and Ni 3d state.


Effects of Long-term Thrombin Inhibition (Dabigatran Etexilate) on Spontaneous Thrombolytic Activity during the Progression of Atherosclerosis in ApoE-/--LDLR-/- Double-Knockout Mice.
Atherosclerosis is characterized by a hypercoagulable state, during which coagulation and fibrinolytic factors are activated simultaneously. However, details regarding the thrombolytic pathway in this context remain unknown. Here we investigated how direct long-term inhibition of thrombin influenced spontaneous thrombolytic activity during atherosclerotic progression in apolipoprotein E (ApoE)⁻/⁻-low density lipoprotein receptor (LDLR)⁻/⁻ double-knockout mice. All mice received either standard chow (placebo group) or dabigatran-containing chow for 22 weeks, after which we evaluated them. The amount of atherosclerosis was estimated as the ratio of the atherosclerotic area to the total aortic intimal area. In addition, we used immunohistochemistry to analyze the expression of tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), and endothelial nitric oxide synthase (eNOS) in atherosclerotic regions. To evaluate thrombolysis, we used a He-Ne laser to induce thrombosis in vessels of the cremaster muscle and then measured the thrombus volume over time. The atherosclerotic area was smaller and thrombolytic activity greater in the dabigatran-treated group than in the placebo group. Furthermore, according to the thrombolysis model, spontaneous thrombolytic activity was increased in the dabigatran-treated mice compared with the placebo mice. In support of these results, immunohistochemistry demonstrated decreased expression of PAI-1 and TAFI but increased expression of eNOS in the dabigatran group compared with the placebo group. However, t-PA expression did not differ between groups. Direct long-term inhibition by dabigatran etexilate of thrombin led to an increase in spontaneous thrombolytic activity decreasing the expression of PAI-1 and TAFI.


Effects of ischaemia on vasculature.
The effects of ischaemia on the structure and function of coronary vessels have been evaluated most thoroughly in the open-chest anaesthetised dog. In the beating heart the flow into the capillary bed is controlled by precapillary sphincters in the terminal arterioles. Short periods (up to 20 min) of ischaemia result during reperfusion in vasodilatation which is mediated through increased tissue adenosine levels. Longer periods of ischaemia (60 or more min) result in degenerative vascular changes and no-reflow during reperfusion. Endothelial cells swell, lose their pinocytotic vesicles and form spherical cytoplasmic protrusions into the capillary lumina. Prolonged ischaemia (over 3 hours) causes ruptures in microvascular walls. Such vessels become permeable to large tracers, e.g. carbon particles, and reperfusion results in haemorrhage. Capillaries in ischaemic myocardium are collapsed by compression resulting from intra- and extracellular oedema and contracture of myocytes. Erythrocytes plug collapsed microvessels. However, in vitro observations have shown that no-reflow may result from ischaemia even without erythrocyte plugging. Capillary compression is the main determinant of no-reflow after ischaemia. Degenerative ischaemic changes in vascular walls further contribute to vascular incompetence in vivo.


Long-term results of successful vitrectomy with silicone oil for advanced proliferative vitreoretinopathy.
We have analyzed the six-month, one-year, and two-year follow-up examinations in 47 patients who had silicone oil injection in combination with revision of vitrectomy for intractable retinal detachment and advanced proliferative vitreoretinopathy. A visual acuity of 5/200 or better was attained in 22 eyes at six months (47%), 17 eyes at one year (36%), and 14 eyes at two years (30%). Of eyes that were completely attached posterior to the buckle at six months, 77% remained attached at two years. In those eyes that were attached at six months, corneal decompensation was the most frequent cause of a loss of vision between six months and two years. Silicone oil was removed in 22 eyes (47%).


[The erysipelas as complication of a lymph oedema after therapy of mastocarcinomas (author's transl)].
1812 patients with mastocarcinomas were submitted to a combined therapy (surgery and radiotherapy); 34.2% of them developed an oedema. This inflammation is a complicating factor because it may increase the oedematous tendency. The authors discuss the correlations between a disturbed defluxion and an erysipelas tendency as well as the risks of a chronic stasis. These correlations necessitate an immediate and intensive treatment of the erysipelas.


[A technique for investigating the component of cantharidin blisters by flow cytometry].
Cantharidimide cause blister. The effect of blister on immunoregulation was investigated. Cantharidimide was placed on the skin, 48h later, the blister was analyzed by flow cytometry. The blister contained 1 x 10(6) - 1 x 10(7) cells per ml, most of which were neutrophils, macrophages, dendritic cells (DC), and IL-12 secreted by Thl cells. There are high concent of DC in the blister, which is differential and induce the secretion of Th1, the activation of T cell. The blister modulate the biological response of patients and is helpful for treatment with infective disease.


Airway laser procedures in children and the American Society of Anesthesiologists' Practice Advisory: a survey among pediatric anesthesiologists.
Recognizing the risk of fire during laser procedures involving the airway, the American Society of Anesthesiologists (ASA) developed recommendations designed to promote safe practice and reduce burn injuries. The aim of this study was to identify how reported anesthetic management of airway laser endoscopies in pediatric patients aligns with the ASA Practice Advisory (ASA-PA). An online survey was created in an iterative process, pilot-tested, and distributed using the Society for Pediatric Anesthesia's (SPA) membership email list. Responses were analyzed using descriptive statistics. Responses from 322 respondents were included, 296 (92%) of whom participated in pediatric laser airway procedures. Fifty-nine respondents (20%) reported the use of an inspired fraction of oxygen (FiO2) of 90% or greater during laser activation in patients with a native airway, and 101 (34%) reported not waiting after the reduction of the FiO2 and laser activation in the airway. Sixty-four (36%) of respondents reporting the use of a non-laser-safe tube during laser airway cases did so due to a lack of availability of a laser specific tube or size limitations. Six respondents (2%) reported an airway fire during a laser procedure in a child under their care. Our results indicate that, in general, pediatric anesthesiologists do not adhere to the ASA-PA in several important aspects. Possible explanations might be knowledge deficiencies about the Practice Advisory or a perceived limited clinical applicability in the pediatric setting. Regardless, airway fires during laser airway surgeries in this population do occur, emphasizing the need for safe practice standards for both anesthesiologists and surgeons.


Status and future directions of clinical trials in Alzheimer's disease.
Amyloid-β (Aβ) senile plaques and neurofibrillary tangles of tau are generally recognized as the culprits of Alzheimer's disease (AD) and related dementia. About 25 years ago, the amyloid cascade hypotheses postulated a direct correlation of plaques with the development of AD, and it has been the dominant theory since then. In this period, more than 200 clinical trials focused mainly on targeting components of the Aβ cascade have dramatically failed, some of them in Phase III. With a greater than 99.6% failure rate at a cost of several billion from governments, industry, and private funders, therapeutic strategies targeting amyloid and tau are now under scrutiny. Therefore, it is time to reevaluate alternatives to targeting Aβ and tau as effective therapeutic strategies for AD. The diagnosis of AD is currently based on medical examination of symptoms including tests to assess memory impairment, attention, language, and other thinking skills. This is complemented with brain scans, such as computed tomography, magnetic resonance imaging, or positron emission tomography with the help of imaging probes targeting Aβ or tau deposits. This approach has contributed to the tunnel vision focus on Aβ and tau as the main culprits of AD. However, events upstream of these proteopathies (age-related impaired neuronal bioenergetics, lysosome function, neurotrophic signaling, and neuroinflammation, among others) are almost surely where the development of alternative therapeutic interventions should be targeted. Here, we present the current status of therapeutic candidates targeting diverse mechanisms and strategies including Aβ and tau, proteins involved in Aβ production and trafficking (ApoE, α/β/γ-secretases), neuroinflammation, neurotransmitters, neuroprotective agents antimicrobials, and gene and stem cell therapy. There are currently around 33 compounds in Phase III, 78 in Phase II, and 32 more in Phase I trials. With the current world health crisis of increased dementia in a rapidly aging population, effective AD therapies are desperately needed.


Repeated use of SSRIs potentially associated with an increase on serum CK and CK-MB in patients with major depressive disorder: a retrospective study.
There is a large amount of evidence that selective serotonin reuptake inhibitors (SSRIs) are related to cardiovascular toxicity, which has aroused concern regarding their safety. However, few studies have evaluated the effects of SSRIs on cardiac injury biomarkers, such as creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). The purpose of our study was to determine whether SSRIs elevated CK and CK-MB levels of prior medicated depressive patients (PMDP) compared to first-episode drug-naïve depressive patients (FDDPs). We performed an observational and retrospective study involving 128 patients with major depressive disorder. Patients who had never used any type of antidepressant were designated FDDP; patients who had used only one type of SSRI but were not treated after a recent relapse were designated PMDP. Serum CK and CK-MB levels were measured before and after using SSRIs for a period of time. The duration of current treatment in the FDDP and PMDP groups was 16.200 ± 16.726 weeks and 15.618 ± 16.902 weeks, respectively. After SSRI treatment, levels of serum CK in the PMDP group were significantly higher than in the FDDP group. Univariate ANCOVA results revealed that PMDP was 22.313 times more likely to elevate CK (OR 22.313, 95% CI 9.605-35.022) and 2.615 times more likely to elevate CK-MB (OR 2.615, 95% CI 1.287-3.943) than FDDP. Multivariate ANCOVA revealed an interaction between the group and sex of CK and CK-MB. Further pairwise analysis of the interaction results showed that in female patients, the mean difference (MD) of CK and CK-MB in PMDP was significantly greater than that in FDDP (MD = 33.410, P = 0.000, 95% CI 15.935-50.886; MD = 4.613, P = 0.000, 95% CI 2.846-6.381). Our findings suggest that patients, especially females, who had previously used SSRI antidepressants were more likely to have elevated CK and CK-MB, indicators of myocardial muscle injury. Use of SSRIs should not be assumed to be completely safe and without any cardiovascular risks.


Therapeutic advantage of pretargeted radioimmunotherapy using a recombinant bispecific antibody in a human colon cancer xenograft.
To assess if pretargeting, using a combination of a recombinant bispecific antibody (bsMAb) that binds divalently to carcinoembryonic antigen (CEA) and monovalently to the hapten histamine-succinyl-glycine and a (90)Y-peptide, improves therapeutic efficacy in a human colon cancer-nude mouse xenograft compared with control animals given (90)Y-humanized anti-CEA immunoglobulin G (IgG). Clearance and biodistribution were monitored by whole-body readings and necropsy. Animals were monitored for 34 weeks with a determination of residual disease and renal pathology in survivors. Hematologic toxicity was assessed separately in non-tumor-bearing NIH Swiss mice. Hematologic toxicity was severe at doses of 100 to 200 microCi of (90)Y-IgG, yet mild in the pretargeted animals given 500 or 700 microCi of the (90)Y-peptide. Evidence of end-stage renal disease was found at 900 microCi of the pretargeted (90)Y-peptide whereas animals given 700 microCi showed only mild renal pathology, similar to that seen in control animals given (90)Y-IgG. Biodistribution data indicated that the average amount of tumor radioactivity by a 700-microCi dose of the pretargeted peptide over a 96-hour period was increased 2.5-fold (48 microCi/g) compared with 150 microCi of (90)Y-IgG (18.9 microCi/g). At these doses, survival (i.e., time to progression to 2.5 cm(3)) was significantly improved (P < 0.04) compared with (90)Y-IgG, with ablation of about one third of the tumors, whereas viable tumor was present in all of the (90)Y-IgG-treated animals. Pretargeting increases the amount of radioactivity delivered to colorectal tumors sufficiently to improve the therapeutic index and responses as compared with conventional radioimmunotherapy.


Sorption of Cu, Pb and Cr on Na-montmorillonite: competition and effect of major elements.
The competitive sorption among Cu, Pb and Cr in ternary system on Na-montmorillonite at pH 3.5, 4.5 and 5.5 and at different heavy metal concentrations, and the effect of varying concentrations of Al, Fe, Ca and Mg on the sorption of heavy metals were studied. Competitive sorption of Cu, Pb and Cr in ternary system on montmorillonite followed the sequence of Cr≫Cu>Pb. Moreover, the competition was weakened by the increase of pH while was intensified by the increase of heavy metal concentration. The sorption of heavy metal on montmorillonite was inhibited by the presence of Ca and Mg, while Al and Fe showed different patterns in affecting heavy metal sorption. Aluminum and Fe generally inhibited the sorption of heavy metal when the pH and/or concentration of major elements were relatively low. However, promoting effects on heavy metal sorption by Al and Fe were found at relatively high pH and/or great concentration of major elements. The inhibition of major elements on heavy metal sorption generally followed the order of Al>Fe>Ca⩾Mg, while Fe was more efficient than Al in promoting the sorption of heavy metals. These findings are of fundamental significance for evaluating the mobility of heavy metals in polluted environments.


Clinical Features, Management, and Prognostic Factors of Spontaneous Epidural Spinal Hematoma: Analysis of 24 Cases.
Spontaneous spinal epidural hematoma (SSEH) is a rare neurosurgical emergency. It presents as acute spinal cord compression and usually requires surgical decompression. The patients who will benefit most from decompression surgery are unknown, and the factors associated with prognosis remain controversial. The purpose of our study was to identify the clinical features, treatments, and main factors related to the prognosis of SSEH. We reviewed the records of 24 patients treated for SSEH from September 2010 to January 2016 at West China Hospital. Clinical features, radiologic images, treatment methods, and clinical outcomes were reviewed retrospectively. To ascertain which factors were related to outcomes, statistical analysis was performed. Among 24 patients, 19 presented with severe initial neurologic deficits (American Spinal Injury Association grade A-C) underwent decompressive surgery, and the remaining patients (initial American Spinal Injury Association grade D or E) received conservative treatment. Among the 19 patients in the operation group, seven (36.8%) had good outcomes, whereas 12 (63.2%) had poor outcomes. All patients in the conservative group had good outcomes. SSEH is a rare but serious illness. It is more likely that SSEH arises from a ruptured internal vertebral venous plexus. The initial neurologic status is the determining factor influencing the treatment method and clinical outcome. The number of involved segments cannot be used to decide the treatment method or predict prognosis. Patients with shorter operative intervals appear to have better neurologic recovery.


A 4-year sequential assessment of the Families First Edmonton partnership: challenges to synergy in the implementation stage.
This article assesses the partnership functioning of Families First Edmonton, a multisectored collaborative effort formed to determine the best health and recreation service delivery model for families with low income. Partners' evaluations of the collaborative process are examined across the formation, implementation, and maintenance stages of development. Statistical analyses of questionnaire data reveal a significant decrease in the partnership's capacity to maximize synergy-a main indicator of a successful collaborative process-in the implementation stage of the partnership. Implications for partnership practice are addressed.


Evaluation of the dopaminergic system with positron-emission tomography in alcohol abuse: A systematic review.
Performed a systematic review to evaluated the dopaminergic system in alcohol abuse in a systematic review in humans. A search of the electronic databases was proceeded, on MEDLINE, EMBASE, Cochrane Library, Insight and Gray literature (Google Scholar and the British Library) for studies published until August 2018. A search strategy was developed using the terms: "dopamine" and "ethanol" or ""alcohol"," and "positron-emission tomography" as text words and Medical Subject Headings (i.e., MeSH and EMTREE) and searched. We found 293 studies. After reading titles and abstracts 235 were considered irrelevant, as they did not meet the inclusion criteria. For the reading of the full text, 50 studies were analyzed. Of these 41 were excluded with reasons by study design, patient population, intervention and outcomes. Nine studies were included in our qualitative synthesis. Four studies have resulted in a reduction in availability only at the D2 receptor in different brain regions. Concerning the D3 receptor alone only one study reported this finding and four studies reported a decrease in both receptors. Changes in D2 receptors in several brain regions in human alcoholics were found in a systematic review.


Dead Brood of Apis mellifera Is Removed More Effectively from Small-Cell Combs Than from Standard-Cell Combs.
The efficiency of the hygienic behaviour in bee colonies towards dead brood was assessed in small-cell combs (SMCombs) and in standard-cell combs (STCombs). Each colony had both types of combs in the nest on a permanent basis. Simultaneous keeping of a colony on standard- and small-cell combs is a novel approach to the use of small-cell combs in beekeeping. The number of killed pupae removed within 24 h was the measure of the hygienic behaviour efficiency. Regardless of the year, the brood in the SMCombs was uncapped and removed significantly more efficient (p ≤ 0.01) than in the STCombs (number of non-uncapped cells: in 2020 SMCombs = 3.79, STCombs = 11.62; in 2021 SMCombs = 2.34, STCombs = 5.28 and completely removed cells: in 2020 SMCombs = 87.46, STCombs = 80.04; in 2021 SMCombs = 96.75, STCombs = 92.66). In colonies kept simultaneously on standard- and small-cell combs, the width of the comb cells has a significant effect on the efficiency of removal of dead brood, which is removed more efficient from small-cell combs than from standard-cell combs.


Clinical significance of progranulin correlated with serum soluble Oxford 40 ligand in primary Sjögren's syndrome.
The present study aimed to investigate the association between the expressions of serum progranulin (PGRN) and serum soluble Oxford 40 ligand (sOX40L) and determine their clinical significances in primary Sjögren's syndrome (pSS).The present study included a total of 68 patients with pSS and 50 healthy controls. Demographic data and clinical basic information were collected. Enzyme-linked immunosorbent assay (ELISA) was performed to determine serum levels of PGRN, sOX40L and interleukins. Spearman's correlation coefficient and Mann-Whitney U test were used to determine the correlation between PGRN, and sOX40L and the association between PGRN and sOX40L and disease activity and disease severity.Serum interleukin (IL)-4, IL-6, IL-10, PGRN, and sOX40L levels were significantly higher in pSS patients as compared to the healthy controls. A positive correlation was observed between PGRN and sOX40L. Patients with elevated levels of PGRN or sOX40L exhibited higher disease activity compared to those with lower levels. Patients with III to IV stages of pSS or multiple system damage showed higher serum levels of PGRN and sOX40L.Elevated serum PGRN, and sOX40L levels were relevant with disease activity and severity in patients with pSS.


Influence of red wine polysaccharides on cytochrome P450 enzymes and inflammatory parameters in tumor models.
The soluble fraction of polysaccharides from cabernet franc red wine (SFP) previously showed antitumoral effects by modulating the immune system. The present study tested the hypothesis that the SFP can regulate CYPs in vitro in HepG2 cells and in vivo in Walker-256 tumor-bearing rats. The SFP was used in the following protocols: (i) solid tumor, (ii) liquid tumor, and (iii) chemopreventive solid tumor. The SFP reduced solid tumor growth in both solid tumor protocols but did not inhibit liquid tumor development. The SFP reduced total CYP levels in the solid and liquid tumor protocols and reduced the gene expression of Cyp1a1 and Cyp2e1 in rats and CYP1A2 in HepG2 cells. An increase of N-acetylglucosaminidase activity was observed in all SFP-treated rats, and TNF-α levels increased in the solid tumor protocol in the vehicle, SFP, and vincristine (positive control) groups. The chemopreventive solid tumor protocol did not modify CYP levels in the liver or intestine or N-acetylglucosaminidase and myeloperoxidase activity in the liver. The in vitro digestion and nuclear magnetic resonance analyses suggested that SFP was minimally modified in the gastrointestinal system. In conclusion, SFP inhibited CYPs both in vivo and in vitro, likely as a result of its immunoinflammatory actions.


Different phenotypes of gastric fundic gland polyposis and cancer in patients with familial adenomatous polyposis depending on Helicobacter pylori infection.
A 37-year-old male with tarry stool presented to our hospital. Esophagogastroduodenoscopy revealed advanced gastric cancer, fundic gland polyposis (FGPsis), and negativity for Helicobacter pylori (HP) infection. Computed tomography exhibited multiple liver tumors. Total colonoscopy (TCS) demonstrated 139 tubular adenomas. He was diagnosed as having unresectable gastric cancer and received systemic chemotherapy. His sister and mother had colorectal adenomatous polyposis as revealed by TCS. His sister had FGPsis and was negative for HP infection, whereas his mother had early gastric cancer with HP infection but not FGPsis. Genetic analysis revealed a novel mutation in exon 15 of the APC gene (NM_000038.5: c.7647_7648_delTG) for the patient, his mother, and his sister, whereas no mutation was found for his father who had no gastrointestinal polyps. Therefore, the pedigree was diagnosed as an FAP family with a novel APC germline mutation which had different gastric phenotypes depending on the status of HP infection.


Emotion recognition and mind wandering in adults with attention deficit hyperactivity disorder or autism spectrum disorder.
Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in adults are often undiagnosed and overlap in psychopathology. Here we investigated the transdiagnostic traits of emotion recognition and mind wandering in a sample of 103 adults (43 with ADHD and 14 with ASD). The ability to correctly identify a facial expression of anger, fear, disgust or surprise was no different between the adults with ADHD or ASD and neurotypical (NT) adults. However, adults with ADHD or ASD were on average almost 200 ms slower in making a correct decision, suggesting a larger speed-accuracy trade-off in facial emotion recognition compared to NT adults. General processing speed was associated with excessive mind wandering in adults with ADHD, but not with ASD. The deficits in emotional processing were independent from mind wandering in both adults with ADHD or ASD. Emotional dysregulation and functional impairment scales separated adults with ADHD and ASD from the NT adults, but not from each other. When controlling for self-reported ADHD and ASD symptom severity, mind wandering in ADHD was independent from both ADHD and ASD symptom severity. In ASD, mind wandering was related to ASD but not ADHD symptom severity. Our results suggest that ASD and ADHD share a slower ability to recognize emotions, which is exacerbated by excessive mind wandering in ADHD, and by decreased processing speed in ASD.


Pseudophakic glaucoma.
Pseudophakia by itself does not cause ocular hypertension. Pseudophakic glaucoma should be defined as glaucoma that would not be present in an eye if it were not pseudophakic. Ocular hypertension was noted in 15 (9%) of 166 pseudophakic eyes. Only 5 eyes (3%) had ocular hypertension requiring treatment. Three of these eyes (1.8%) had permanent ocular hypertension resulting in chronic pseudophakic glaucoma. This study shows that pseudophakic glaucoma is no more frequent than aphakic glaucoma. Secondary glaucoma in pseudophakic eyes is not always related to the presence of the lens. Pupillary block glaucoma and UGH syndrome are directly related to the lens. Secondary glaucoma by ghost cells and by pigment-dispersion are also in some cases directly related to the lens.


Upper limb motion analysis in children with hemiplegic cerebral palsy: proximal kinematic changes after distal botulinum toxin or surgical treatments.
The purpose of this study is to describe the kinematic changes in children with cerebral palsy (CP) after treatments performed on the forearm, wrist or thumb, with specific attention to the changes around the trunk, shoulder and elbow kinematics. With the use of a specific kinematic protocol, we first described the upper limb kinematics in a group of 27 hemiplegic patients during two simple daily tasks. Eight of these children were treated with botulinum toxin (Botox(®), Allergan) injection or surgery and were, thereafter, evaluated with another kinematic analysis in order to compare the pre- and post-therapeutic condition. The target muscles were the pronator teres, flexor carpi radialis, flexor carpi ulnaris, flexor digitorum superficialis, flexor pollicis longus and the adductor pollicis. Significant kinematic changes were found after treatment. Patients increased forearm supination (P < 0.05) and wrist extension (P < 0.05) during both tasks. Patients also decreased trunk flexion/extension range of motion (ROM) (P < 0.05), improved elbow ROM (P < 0.05) and improved internal shoulder rotation (P < 0.05). Dynamic shoulder or elbow limitations in children with mild hemiplegia involvement could be related to a compensatory movement strategy and/or co-contractions. As these proximal kinematics anomalies are improved after treatments performed at the forearm, wrist and thumb, they should not be treated first but should be reconsidered after the treatment of more distal problems.


Assessment of trace element compatibility in total parenteral nutrition infusions.
The application of X-ray energy dispersive spectroscopy to detect elements collected from TPN mixtures on membrane filters has been investigated. Many simple total parenteral nutrition mixtures prepared aseptically in large bags can be stored for extended periods. Trace elements are normally excluded from such bags, because not enough is known about their long-term stability and compatibility in total parenteral nutrition mixtures. Assessing the compatibility of many trace elements by conventional methods that rely on detecting concentration changes is extremely difficult. Analysis of precipitates from total parenteral nutrition mixtures confirmed that the proposed method was capable of identifying a number of elements from the mixture in complex precipitates, including calcium, phosphorus, iron, copper and selenium.


An Information Theoretic Interpretation to Deep Neural Networks.
With the unprecedented performance achieved by deep learning, it is commonly believed that deep neural networks (DNNs) attempt to extract informative features for learning tasks. To formalize this intuition, we apply the local information geometric analysis and establish an information-theoretic framework for feature selection, which demonstrates the information-theoretic optimality of DNN features. Moreover, we conduct a quantitative analysis to characterize the impact of network structure on the feature extraction process of DNNs. Our investigation naturally leads to a performance metric for evaluating the effectiveness of extracted features, called the H-score, which illustrates the connection between the practical training process of DNNs and the information-theoretic framework. Finally, we validate our theoretical results by experimental designs on synthesized data and the ImageNet dataset.


Long-term survival after autologous peripheral blood stem cell transplantation in two patients with malignant rhabdoid tumor of the kidney.
A 5-month-old male with stage II malignant rhabdoid tumor of the kidney (MRTK) and a 24-month-old male with stage III MRTK were treated with surgical resection of tumors and chemotherapy of alternating ICE (ifosfamide, carboplatin, and etoposide) and VDC (vincristine, doxorubicin, and cyclophosphamide), followed by high-dose chemotherapy using etoposide, carboplatin, and melphalan with autologous hematopoietic stem cell transplantation (SCT). Two patients have been alive without any evidence of disease for 30 and 37 months after diagnosis, respectively, and require no medication. Consolidation with SCT should be further studies for selected patients with high-risk MRTK.


Two distinct patterns of ankylosing spondylitis in Moroccan patients.
Ankylosing spondylitis (AS) is characterised by a geographic differences in terms of prevalence and clinical expression of the disease. The aim of our study was to describe the actual features of AS in Morocco and we wanted to examine a large population of patients for evidence of phenotypic clustering that could suggest the presence of distinct clinical entities. We investigated 117 patients with a diagnosis of primary AS according to the modified New York criteria. All patients were evaluated according to a standardised data collection form, including demographic variables and disease history with clinical and radiological features. To analyse our data and try to individualise clinical subsets, we applied a two-step cluster analysis using log-likelihood distance measures. Patient's mean age at onset was 25.51 +/- 10.8 year. The mean BASDAI and BASFI score was 33.5 +/- 20.3 and 38.9 +/- 27.5, respectively. Radiographic damage was present in 99.1% of the subjects and radiographic hip involvement in 47.3%. Only 52.6% of patients had been treated with disease modifying antirheumatic drugs. Cluster analysis detected two distinct populations within the data set. Statistically significant differences were found between the two groups particularly concerning activity of the disease, age at onset and the hygienic conditions. Our study revealed that the Moroccan AS was active and severe and suggested that the age at onset and the precarious hygienic level has the greatest capacity to predict activity and severity of the disease.


When the internet is wrong: Children's trust in an inaccurate internet or human source.
Prior studies have shown that children can select and evaluate information based on the previous accuracy of an informant. The current study examines how 5- to 6-year-old kindergarteners (N = 46) and 7- to 8-year-old second-graders (N = 48) in China judge scientific information provided by the internet or a teacher, and how a source's history of inaccuracy influences participants' judgments. When lacking explicit information about previous accuracy, neither younger children nor older children showed differential trust in the internet or a teacher. After observing the internet providing inaccurate information, children in both age groups decreased their trust in statements from the internet. When the teacher was consistently inaccurate, children in both age groups also showed reduced preference for the teacher's statements. These findings demonstrate that 5- to 8-year-old children take into account history of inaccuracy when deciding whether to request or endorse information from the internet or a teacher.


Facilitating deep learning through preprocessing of optical coherence tomography images.
While deep learning has delivered promising results in the field of ophthalmology, the hurdle to complete a deep learning study is high. In this study, we aim to facilitate small scale model trainings by exploring the role of preprocessing to reduce computational burden and accelerate learning. A small subset of a previously published dataset containing optical coherence tomography images of choroidal neovascularization, drusen, diabetic macula edema, and normal macula was modified using Fourier transformation and bandpass filter, producing high frequency images, original images, and low frequency images. Each set of images was trained with the same model, and their performances were compared. Compared to that with the original image dataset, the model trained with the high frequency image dataset achieved an improved final performance and reached maximum performance much earlier (in fewer epochs). The model trained with low frequency images did not achieve a meaningful performance. Appropriate preprocessing of training images can accelerate the training process and can potentially facilitate modeling using artificial intelligence when limited by sample size or computational power.


Examination of hemodynamics in patients in hemorrhagic shock undergoing Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA).
The objective of this study was to investigate the hemodynamic effects of aortic occlusion (AO) during Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) using a sophisticated continuous vital sign (CVS) monitoring tool. Patients admitted between February 2013 and May 2017 at a tertiary center that received REBOA were included. Patients in cardiac arrest before or at the time of REBOA were excluded. Time of AO was documented by time-stamped videography and correlated with CVS data. 28 patients were included, mean (standard deviation) ISS was 38 (11). 18 received Zone 1 (distal thoracic aorta) and 10 received Zone 3 (distal abdominal aorta) AO. Among Zone 1 patients the pre-AO systolic blood pressure (SBP) nadir was 64 (19) mmHg, which increased to a mean of 124 (29) mmHg within 5 min after AO (p < 0.01). Among Zone 3 patients the pre-AO SBP nadir was 75 (19) mmHg, which increased to a mean of 98 (14) mmHg within 5 min after AO (p < 0.01). 72% of Zone 1 patients had episodes during AO where SBP was less than 90 mmHg as compared to 80% of Zone 3 patients (p = 0.51). 100% of Zone 1 patients had periods during AO where SBP was greater than 140 mmHg as compared to 70% Zone 3 patients (p = 0.04). The overall mean decrease in SBP after balloon deflation was 13 (20) mmHg (p < 0.01), with similar decreases among groups (14 (21) mmHg vs 12 (18) mmHg for Zone 1 and 3 patients, respectively (p = 0.85)). Patients undergoing Zone 1 AO were more likely to have an acute change (increase or decrease) in their heart rate immediately after AO as compared to Zone 3 AO (p = 0.048). Significant hemodynamic alterations occur before, during, and after AO. The effects of Zone 1 AO on blood pressure and heart rate appear different than Zone 3 AO. This may have important implications for cardiac or cerebral function and perfusion goals, particularly with concomitant injuries such as cardiac contusion or traumatic brain injury.


Experimental research on the spontaneous combustion of Yangquan coal induced by electrochemical oxidation of pyrite.
The 15# coal seam of Yangmei No.5 Mine, which produces anthracite, which is the least prone to spontaneous combustion, has a serious hidden danger of spontaneous combustion due to the high sulfur content in the coal. Based on the better conductivity of anthracite, we designed an electrolysis experiment to accelerate the electrochemical oxidation of pyrite in coal. Through experiments and analysis of thermodynamic characteristic parameters, it is obtained that the electrochemical oxidation of pyrite and its main products Fe3+ and Fe2+ have a coupled catalytic effect on the spontaneous combustion of high-sulfur coal in Yangquan. Combined with the FTIR test and analysis, it is found that the electrochemical process causes spatial polarization in the coal, so that polar groups such as -OH undergo spatial diversion and increase the activity. Due to the high content of -OH in Yangquan anthracite, the electrochemical process has the greatest effect on promoting -OH oxidation. Fe3+ and Fe2+ act as strong oxidants and free radicals to promote the -CH2- reaction to generate C=O and promote the generation of CO. This research provides a new direction for the exploration of the spontaneous combustion mechanism of high-sulfur anthracite.


Some relevant components of adherence behavior.
Adherence to medical or psychological prescriptions is analyzed as a type of rule and self-rule following behavior. Variables that increase the likelihood of compliance are: (1) the specific motivational condition, usually aversive when treatment or preventive prescription is sought, (2) the medium of contact and context used when receiving the prescription, (3) attentive responses under the control of the prescription, (4) understanding the complexity of the prescription, (5) the specific content of the prescription, (6) verbalization on the willingness to follow the prescription, (7) appropriate abilities for producing the behaviors described in the prescription, (8) physical facilities and appropriate biological conditions for producing the behaviors, (9) verbalization describing the relationship between the adherence response and the immediate and long-term consequences, functioning as a discriminative stimulus and as a reinforcing event, (10) compatibility between daily activities and the behaviors described in the prescription: response cost and self-control behavior when several behaviors are possible and probable. Strategies which facilitate self-control as well as incompatible behavior are suggested.


Scratch-wound assay.
The scratch-wound assay is a simple, reproducible assay commonly used to measure basic cell migration parameters such as speed, persistence, and polarity. Cells are grown to confluence and a thin "wound" introduced by scratching with a pipette tip. Cells at the wound edge polarise and migrate into the wound space. Advantages of this assay are that it does not require the use of specific chemoattractants or gradient chambers and it generates a strong directional migratory response, even in cell types that do not show robust responses in "single cell" migration assays. It is most reliably analysed when performed using time-lapse imaging, which can also yield valuable cell morphology/protein localisation information.


Optimization of coliphage HK022 Integrase activity in human cells.
The Integrase (Int) site-specific recombinase of coliphage HK022 catalyzes integrative and excisive DNA recombination between two attachment (att) sites in human cells without the need to supply the accessory proteins Integration Host Factor (IHF) and Excisionase (Xis). Previous work has shown that under these conditions, reactions in cis, i.e. both att sites are located on the same chromosome, can be detected without selection. However, recombination in trans, i.e. one att site positioned on a chromosome and the other on an episomal vector, was detected only after selection. Here we show that optimization of the int-HK022 gene for human codon usage according to the GeneOptimizer software algorithm, as well as addition of accessory proteins IHF and Xis improve the recombination efficiencies in human cells, such that recombinants in a trans reaction could be detected without selection.


Synergistic extraction of gold from the refractory gold ore via ultrasound and chlorination-oxidation.
A synergistic extraction method for gold from the refractory gold ores via ultrasound and chlorination-oxidation was developed. The effects of solid-liquid ratio, extraction time, ultrasound power, NaClO concentration and NaOH concentration on the extraction rate of gold from the refractory gold ore were investigated. The optimum conditions were as follows: NaClO concentration of 1.5mol/L, NaOH concentration of 1.5mol/L, solid-liquid ratio of 5, ultrasound power of 200W and ultrasound time of 2h. Under the optimal conditions, 68.55% of gold was extracted. However, only 45.8% of gold was extracted after 6h without the ultrasound-assisted extraction. XRD and SEM were used to analyze the influence of ultrasound on the mineral properties and strengthening mechanism. The results showed that the interface layer was peeled, new surface was exposed, reaction resistance was reduced, the liquid-solid reaction was promoted and reaction speed was greatly improved under ultrasound. According to the results of range and variance analysis, the optimum leaching experiment with orthogonal design was almost identical with the optimum experiment of single factor. Among them, the ultrasound power was the most significant factors affecting leaching rate of gold. Compared with other extraction method, the synergistic extraction process decomposed completely sulfide and improved significantly the extraction rate of gold.


Impact of different land uses on polycyclic aromatic hydrocarbon contamination in coastal stream sediments.
PAHs are ubiquitous environmental pollutants that can cause adverse health and ecological effects. In the present study, we examined the impact of land use on the concentration and composition of PAHs in 28 coastal stream sediments on the Island of Oahu, Hawaii. In densely populated urban areas, the concentration range of total PAHs in the stream sediments affected by mixed residential and industrial activities (RI) are 0.40-9.05 ppm, which is significantly higher than the 0.36-4.21 ppm detected in the stream sediments affected predominantly by urban residential land uses (UR). The stream sediments affected by agricultural activities (AG) reported a concentration range of 0.09-2.14 ppm, which is lower than those of the RI and UR stream sediments. The molecular weight of PAH is a factor, as only high molecular weight (HMW) PAHs were significantly affected by land uses (ANOVA P=0.009). Correlation analysis showed that only in the UR stream sediments were significant correlations observed between PAH concentration and two anthropogenic indicators: population density (r=0.57, P=0.027) and vehicle density (r=0.55, P=0.034). The fractional concentrations of PAHs were analyzed by using PCA analysis, which led to the separate clustering of the RI and AG stream sediments and suggest distinct PAH sources between the two land uses. Two PAH source indicators, including Ant/(Ant+Phe) and Fl/(Fl+Py), indicates that PAHs sources in the RI stream sediments are most likely of petroleum origin, while PAHs in the UR and AG stream sediments most likely came from combustion activities. In addition, the concentration and relative potency of carcinogenic PAHs in the coastal stream sediments exhibited similar patterns as the total PAH concentration with respect to land uses.


Ultrastructural changes during adhesion and migration of pre-B lymphoid leukaemia cells within bone marrow stroma.
The ultrastructural changes in leukaemic cells on initial contact with, and during migration into, layers of bone marrow stroma in vitro were examined in a variety of types of acute leukaemia and leukaemic cell lines. Bone marrow fibroblasts (BMF) were grown on polycarbonate microporous membranes, and acute leukaemia cells added to cultures and allowed to adhere to BMF for variable periods of time before fixation. Acute lymphoblastic leukaemia (ALL) blasts showed rapid development of surface membrane microvilli on contact with BMF layers. ALL blasts, and the pre-B ALL cell line NALM-6, showed evidence of movement in to the BMF layer within 15-30 min, with intrusion of extended cytoplasic processes into gaps between BMF cytoplasm. ALL cells were frequently seen within the layers of fibroblasts after 30 min incubation, and had pronounced morphological changes, with pseudopodia and attenuated and elongated microvilli interdigitating with the surface of fibroblasts or with strands of extracellular matrix material. Changes were also noted in the surface membrane of BMF adjacent to ALL cells, with invagination of the cytoplasmic membrane and formation of micropits. In contrast to the migratory behaviour of pre-B ALL cells, migration was not observed with acute myeloid leukaemia cells or other leukaemic cell lines. These cells showed membrane activation, with variable degrees of microvillous formation, and in some cases insertion of pseudopodia into BMF layers, but migration was not observed. Ultrastructural immunogold labelling was carried out to determine the localization of leukaemic adhesion molecules and their ligands on BMF. This demonstrated that beta 1 integrins were largely localized to the contact surfaces of both ALL blasts and fibroblasts, with VCAM-1 expressed only on the surface of BMF. These observations confirm the specificity of migratory behaviour for pre-B leukaemic cells, and indicate that a complex pattern of surface and intracellular events mediate this process, including the expression of beta 1 integrins and VCAM-1 at the sites of insertion of leukaemic cells between fibroblast margins.


Strain-specific effects of crowding on long-term memory formation in Lymnaea.
Crowding of snails is a stress that obstructs long-term memory (LTM) formation following operant conditioning of aerial respiratory behaviour in Lymnaea stagnalis. In previous experiments, snails of the same strain/population were used for both the crowding and the operant conditioning training. However, there are different strains/populations of Lymnaea stagnalis exhibiting different cognitive abilities. We asked whether Lymnaea of one strain/population are able to determine that they are of a different strain/population. We did this by asking if LTM formation would continue to be obstructed if we crowded snails with a different species of pond snail (Helisoma = Planorbella) or with different strains/populations of Lymnaea stagnalis. Using an inbred strain, the W-strain, we crowded the W-strain with seven other Lymnaea strains/populations as well as with Helisoma. The results of a 2-Way ANOVA followed by a Tukey's Post-hoc analysis showed that W-strain snails when crowded with another strain/population of Lymnaea or with Helisoma formed LTM formation. That is, the memory test session statistically met the criteria for LTM formation. Thus, one strain/population of snails determines that another strain/population is different from it. The differentness means that crowding now does not obstruct LTM formation.


Calcium gradient dependent pyrophosphate formation by sarcoplasmic vesicles.
The vesicles of the sarcoplasmic membranes synthesize pyrophosphate from inorganic phosphate. Pyrophosphate synthesis proceeds as long as a calcium gradient is maintained across the vesicular membranes. Pyrophosphate synthesis is inhibited by low concentrations of nucleoside triphosphates.


Phadiatop, Phadiatop Infant and total IgE evaluated in allergic Brazilian children and adolescents.
The clinical history is of importance in the investigation of allergic diseases but does have limitations. Many allergic conditions will be over-diagnosed if anamnesis alone is used for diagnostic criteria. Serum total immunoglobulin E (TIgE) quantification, as well as panels containing allergens prevalent in the studied population, may serve as screening tests and facilitate the diagnosis of allergic disease or its exclusion. We assessed the positivity of two versions of these tests, Phadiatop Europe® (PhEU) and Phadiatop Infant® (PhInf), as well as total IgE (TigE) values in patients with a medical diagnosis of allergic disease and non-allergic individuals. A cross-sectional study performed in eleven Brazilian pediatric allergy centers with patients divided into groups according to the primary condition and a group of assessed control subjects. They were submitted to TIgE measurement and screening tests (PhEu and PhInf). TIgE mean serum levels were significantly higher among allergic patients, especially those with asthma/rhinitis or atopic dermatitis. The positivity of the screening tests, considering the total population, was 63.8% for PhEU and 72.6% for PhInf. These increased when we evaluated only the allergic subjects. The concordance index of the two tests was Kappa=0.7 and higher among those of greater age. In the assessed population, there were significantly higher levels among those with positive screening tests and PhInf showed better performance in the identification of sensitized individuals, regardless of age. This is the first study to evaluate Phadiatop and Phadiatop Infant in the same population.


Benefit and risk of exercise on myocardial function in diabetes.
Regular physical activity promotes cardiorespiratory fitness and has been considered a cornerstone for non-pharmacological treatment of more than 17 million Americans with diabetes mellitus. Physical exercise has been shown to positively affect certain cardiovascular risk factors such as insulin resistance, glucose metabolism, blood pressure and body fat composition, which are closely associated with diabetes and heart disease. With the increasingly sedentary life style in our society, routine daily exercise of moderate intensity is highly recommended to reduce cardiovascular risk, the leading cause of death in diabetic patients. Exercise produces many beneficial effects to the heart function such as reduced incidence of coronary heart disease, attenuated severity of diabetic cardiomyopathy, improved cardiac performance, cardiac reserve and autonomic regulation. Nevertheless, many diabetic patients do not appear to gain much benefit from exercise or may even be at risk of performing physical exercise. This review summarizes the benefit and risk of exercise on diabetic heart function, with a special emphasis on myocardial and autonomic function.


Correction: Sun et al. Ergosterol Isolated from Antrodia camphorata Suppresses LPS-Induced Neuroinflammatory Responses in Microglia Cells and ICR Mice. Molecules 2023, 28, 2406.
The original version of this article unfortunately contains an error in Figures 4B,C,H-J and 5C,D [...].


Hydrogen-Bond Regulation of the Microenvironment of Ni(II)-Porphyrin Bifunctional Electrocatalysts for Efficient Overall Water Splitting.
Accurately regulating the microenvironment around active sites is an important approach for boosting the overall water splitting performance of bifunctional electrocatalysts, which can drive both the oxygen evolution reaction (OER) and the hydrogen evolution reaction (HER) in the same electrolyte. Herein, pseudo-pyridine-substituted Ni(II)-porphyrins (o-NiTPyP, m-NiTPyP, and p-NiTPyP) with pseudo-pyridine N-atoms located at the ortho-, meta-, or para-position are prepared and used as model catalysts for alkaline water splitting. Experimental and theoretical results reveal that the pseudo-pyridine N-atom positions can regulate the microenvironment around the active sites and the adsorption free energy of H-donating substances by affecting the H-bonding interaction and the NNiN bond angles of active sites, and thus those pseudo-pyridine-substituted Ni(II)-porphyrins deliver better electrocatalytic activity than the Ni(II)-tetraphenylporphyrin (NiTPP) without pseudo-pyridine N-atoms. Among them, m-NiTPyP on carbon nanotubes delivers the lowest overpotentials of 267 and 138 mV at 10 mA cm-2 for the OER and HER, respectively. Specifically, m-NiTPyP as bifunctional electrocatalyst in an alkaline electrolyzer requires only 1.62 V to drive efficient overall water splitting at 10 mA cm-2 while remaining durable. This work proposes a new H-bond-regulating approach of the microenvironment of electrocatalysts for effectively boosting the overall water splitting activity and deeply understanding its related mechanism.


A recreational water quality index using chemical, physical and microbiological parameters.
The aim of this paper was to develop a new recreational water quality index (RWQI) as a tool to ensure the health of swimmers and to take practical decisions. RWQI was elaborated with epidemiological data, and we carried out an exhaustive study of the different guidelines for recreational waters proposed by different organisations around the world. Different parameters were chosen, considering, as a priority, the swimmer's contact and the possibility of ingestion of water during the recreational activity. Furthermore, rating curves were established for pH, chemical oxygen demand, nitrate, phosphate, detergents, enterococci, total coliforms, faecal coliforms and Escherichia coli. The index was applied to the data set on water quality of the Potrero de los Funes River (San Luis, Argentina), generated during 2 years (2009-2010). Following the RWQI values classification, most of the Potrero de los Funes water samples fell in the good quality range during the study period.


Fabrication of poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) macroporous microspheres through activators regenerated by electron transfer atom transfer radical polymerization for rapid separation of proteins.
Activators regenerated by electron transfer atom transfer radical polymerization (AGET ATRP) were firstly used in suspension polymerization to prepare macroporous microspheres based on a copolymer of glycidyl methacrylate and ethylene glycol dimethacrylate. Compared to conventional radical polymerization (CRP), the microspheres by AGET ATRP showed more homogeneous structure, larger pores, and higher protein binding capacity. The body of microspheres are formed by the large clusters resulted from the aggregated little particles. The size of the particles in microspheres by AGET ATRP was 10-300 nm which was smaller than that (400-800 nm) of the microspheres by CRP. AGET ATRP gave larger pore size (275 ± 5 nm) and surface area (59.3 ± 1 m2/g) than CRP (234 ± 5 nm, 37.5 ± 1 m2/g). The microspheres were modified with polyethylene imine for anion resins that were evaluated in term of its protein binding capacity. The results indicated that the static (69 ± 0.5 mg/mL) and dynamic binding capacity (61 ± 0.5 mg/mL) of proteins on modified microspheres by AGET ATRP were higher than that (34 ± 0.5 mg/mL and 19 ± 0.5 mg/mL) by CRP. Meanwhile, the proteins binding capacity on the microspheres by AGET ATRP decreased only less than 10% when the flow rate increased 10 times. These macroporous media show a large potential in rapid separation of proteins.


Estrogen metabolism in nonhuman primates. I. In vitro biosynthesis of estrogen glucosiduronates in rhesus monkey liver.
Estrone glucosiduronate, 17beta-estradiol-3-glucosiduronate, 17beta-estradiol-17-glucosiduronate and estriol-16alpha-glucosiduronate have been biosynthesized in substantial yield by incubation of radioactive estrone, 17beta-estradiol, estriol and uridine diphosphoglucosiduronic acid with rhesus monkey liver homogenates. The metabolites were characterized by chromatography on Celite and DEAE-Sephadex, enzyme hydrolysis, derivative formation and crystallization to constant specific activity. The percent conversion to 17beta-estradiol-17-glucosiduronate from 17beta-estradiol ranged between 56-71%; from estrone, the conversion was 49-54%. Other metabolites formed from estradiol were estrone glucosiduronate (12-21%) and 17beta-estradiol-3-glucosiduronate(5-12%). The same metabolites derived from estrone accounted for 18-28% and 10-14% respectively. After estriol incubation, more than 90% of the steroid was converted to estriol-16alpha-glucosiduronate with no detectable estriol-3-glucosiduronate. This report represents the first time that 17beta-estradiol-17-glucosiduronate has been reported as a metabolite in the rhesus monkey and this is the only known species which forms 17beta-estradiol-17-glucosiduronate as the predominant metabolite of either estrone or estradiol in vitro. Rhesus monkey liver is similar to the human and baboon in that it metabolizes estriol exclusively to estriol-16-glucosiduronate.


Breakthrough Bleeding Episodes at Minimum and Improvement in Quality of Life in a Child with Severe Hemophilia A with Inhibitors Treated with Emicizumab: A Case Report from Chile.
BACKGROUND People with hemophilia A have shown osteomuscular complications that have a significant impact on their quality of life (QoL) and on health care costs. Patients with hemophilia A with inhibitors living in developing countries such as Chile face a high disease and treatment burden. Emicizumab, a humanized bispecific monoclonal antibody, is associated with improvements in QoL and reduction in the financial impact of the disease related to treatment. This case report describes the impact of emicizumab on a patient with severe hemophilia A with inhibitors in terms of breakthrough bleeding control, improvements in QoL, and reduced financial impact after a year of treatment, in a country where this medication is not routinely available. CASE REPORT A 10-year-old child with severe hemophilia A with inhibitors had several restrictions in his daily life due to multiple incidences of breakthrough bleeding. He was on episodic treatment with bypassing agents, and in the year prior to treatment with emicizumab he had 18 bleeding episodes. After 1 year on prophylaxis treatment with emicizumab, the patient had only 1 bleeding episode (94.4% of reduction), improved pain control (5-point reduction on the visual analogue scale), a decrease in the Hemophilia Joint Health Score from 39 to 19, the QoL perception increased by 86% on the standardized Haemo-QoL-kids, and a 70% reduction in treatment costs versus the costs of episodic treatment with bypassing agents. CONCLUSIONS After 1 year of treatment with emicizumab, this patient had substantial improvements in the evaluated parameters. Further investigations with emicizumab are needed to assess its possible effects on public health policies.


Musical metaphors: evidence for a spatial grounding of non-literal sentences describing auditory events.
This study investigated whether the spatial terms high and low, when used in sentence contexts implying a non-literal interpretation, trigger similar spatial associations as would have been expected from the literal meaning of the words. In three experiments, participants read sentences describing either a high or a low auditory event (e.g., The soprano sings a high aria vs. The pianist plays a low note). In all Experiments, participants were asked to judge (yes/no) whether the sentences were meaningful by means of up/down (Experiments 1 and 2) or left/right (Experiment 3) key press responses. Contrary to previous studies reporting that metaphorical language understanding differs from literal language understanding with regard to simulation effects, the results show compatibility effects between sentence implied pitch height and response location. The results are in line with grounded models of language comprehension proposing that sensory motor experiences are being elicited when processing literal as well as non-literal sentences.


Aldosterone and the control of lower intestinal Na+ absorption and Cl- secretion in chickens.
There are several ion-transport systems expressed in the lower intestinal segments of chickens, depending on the level of the salt intake. The aim of this study was to test the hypothesis that aldosterone is the sole regulator of all these ion-transport systems, as had been indicated by our previous results. Chickens were long-term adapted to low salt intake, and then switched to a high-salt diet. During the first 5 days of resalination, the birds were injected with aldosterone every 8 hr and then the magnitude and characteristics of the epithelial ion-transport systems in colon and coprodeum were investigated. The results support strongly the hypothesis that aldosterone exerts major control of the amiloride-inhibitable Na(+)-transport system in both colon and coprodeum, as its magnitude was maintained high in spite of the resalination process. Spironolactone counteracted the actions of aldosterone, although not totally. On the other hand, aldosterone is not the sole regulator of the hexose/aminoacid-Na+ cotransport systems in colon, although it can act as their modulator, as the injections did delay the normal increase always seen in these transport systems during resalination. Aldosterone can also modulate the Cl(-)-secretory capacity of colon and coprodeum, but only temporarily.