Binaural columns in the primary field (A1) of cat auditory cortex.
Responses of single neurons and neuron clusters were studied at short intervals along penetrations into the high-frequency (4-25 kHz) representation of A1. The monaural and binaural sensitivities of neurons at best frequency were studied. With the exception of some neurons responsive only to binaural stimulation, the monaural responses of most were classified as contralateral dominant, ipsilateral dominant or equidominant. Binaural interactions of most neurons were classified as summation (binaural response size greater than the monaural response size) or suppression (dominant ear response size greater than the binaural response size). Most neurons arrayed in a column perpendicular to the cortical surface display the same aural dominance and binaural interaction. Summation columns occupy about two-thirds of the area sampled; suppression columns, about one-third. Within most suppression columns, the contralateral ear was dominant. Within summation columns, aural dominance varied. Summation columns appear to be composed of smaller columns differing in aural dominance. The sizes of binaural interaction columns vary considerably; some occupy several square millimeters of cortical surface. At least some binaural interaction columns occupy strips of cortex oriented orthogonal to isofrequency contours.


[Relationship between exercising and physical and cognitive function indicators. Comparison of results with age].
Gerontology research shows the importance of physical exercise for active aging. This study demonstrates the relationship between the practice of aerobic exercise, and physical fitness (muscle strength, respiratory capacity and motor speed) and cognitive performance (memory and visual-perceptual speed) and analyzes whether age is a modulating factor of this relationship. The sample included 690 subjects with an age range of 30-85 years. The level of physical exercise was assessed using self-report form. Two sub-scales were used for the evaluation of cognitive performance: Digit Span Backwards and Digit Symbol (both are sub-scales of the Wechsler Adult Intelligence Scale--WAIS). The physical fitness was assessed using bio-behavioral measurements (strength, lung capacity, speed). To test the combined effect of exercise and age on the two variables (physical fitness and cognitive performance) two separate factorial analysis of variance were performed (procedure--general linear model: Univariate). The most significant result showed that scores on cognitive performance is a function of the intensity of the physical activity (F = 4.8; P < 0.002). With regard to physical fitness, its relationship with physical exercise is also significant (F = 4.10; P<0.007) as well as the interaction between exercise and age (F = 2.2; P<0.001). The intensity in achieving aerobic exercise is associated with physical fitness and cognitive performance. Age has a specific weight in the association between exercise and physical fitness, this effect is higher in the older age groups (65-74 and 75-85 years for 30-49 and 50-64 years). These data suggest the compensatory effect of exercise on decline in old age.


Defining the Patchy Landscape of Esophageal Eosinophilia in Children With Eosinophilic Esophagitis.
Eosinophilic esophagitis (EoE) is a patchy disease of the esophagus with significant variability in intraepithelial eosinophilia. Three biopsies each from distal and proximal esophagus are recommended for identification of active EoE. Recent work suggests 3 biopsy sites are more optimal. We sought to evaluate 2-site vs 3-site esophageal biopsy combinations for utility to identify active EoE. We prospectively obtained 3-site esophageal biopsies based on rigorous endoscopic measurements of the proximal, mid, and distal esophagus and gastroesophageal junction. Biopsies were reviewed by a pathologist, and those with at least 15 eosinophils per high-power field were considered active EoE. The sensitivity of one or more sites to identify active EoE was determined, and endoscopic measurements were correlated to height and age. Five hundred ninety-six endoscopies were performed in 217 patients; of these, 304 endoscopies in 167 patients had active EoE. Among the initial esophagogastroduodenoscopies with active EoE, distal biopsies had greater than 80% sensitivity, whereas mid and proximal biopsies had sensitivity of 65% and 62%, respectively, and distal + proximal biopsies had the highest diagnostic sensitivity for a 2-site combination. Among the 304 endoscopies with active EoE, 9 had focal eosinophilia restricted to the mid esophagus, and 8 were restricted to the proximal esophagus. For patients with multiple endoscopies with active EoE, nearly one fourth had reduced sites with eosinophilia at the second time point. Endoscopic measurements strongly correlated with height and age. This study supports endoscopic measurement-guided 3-site biopsies for optimal disease assessment of active EoE in children.


Zinc Supplementation in Preterm Neonates and Neurological Development, A Randomized Controlled Trial.
To assess the effect of zinc supplementation on neuro-development and growth of preterm neonates. Referral neonatal unit of a teaching hospital. Open-labeled Randomized controlled trial. 100 preterm neonates. Participants randomized to receive oral zinc (study group) or not (controls). Primary: Neuro-development status at 40 weeks post conceptional age and at 3 month corrected age using Amiel-Tison neurologic assessment. Secondary: anthropometry and serum alkaline phosphatase at 3 months corrected age. At 40 weeks post-conceptional age, greater number of zinc supplemented infants demonstrated alertness and attention pattern normal for their age (P=0.02). Higher number of controls showed signs of hyper-excitability at 40 week post-conceptional age (P=0.001) and 3 months corrected age (P=0.003). At 3 month corrected age, mean serum alkaline phosphatase level was significantly higher in the study group compared to controls. Zinc supplementation till 3 month corrected age in preterm breastfed infants improves alertness and attention pattern; and decreases signs of hyperexcitability, and proportion with abnormal reflexes.


Design of vectors for transgene expression: The use of genomic comparative approaches.
The design of transgenes has always been limited by the extent of available information on the endogenous locus whose expression pattern had to be replicated. Those genes whose expression domain had not been entirely documented resulted, usually, in transgenes with an unpredictable expression patterns and suboptimal performance in transgenic animals. The use of genomic comparative approaches, highlighting evolutionary conserved homologous DNA sequences, helps to identify crucial regulatory elements that are associated to a given expression domain. The inclusion of these conserved regulatory sequences in transgenic constructs would normally result in optimal expression levels of transgenes in recipient animals. The use of artificial chromosome-type transgenes usually ensures the inclusion of these preserved regulatory elements that are required for the faithful expression of the gene. These constructs could also contain insulators, a subset of regulatory sequences whose application is being addressed in transgenesis. Therefore, the generation of transgenic animals with genomic-type constructs is the recommended approach to achieve optimal transgene expression, according to the expected pattern of the corresponding endogenous locus.


Ochratoxin A and aflatoxins in dried vine fruits from the Iranian market.
Forty samples of dried vine fruit (raisin, n = 22; currant, n = 18) were collected in 2009-2011 from the Iranian market. Aflatoxins (AFs) and ochratoxin A (OTA) were determined in these samples after immunoaffinity column clean-up by high performance liquid chromatography (HPLC) with fluorescence detection. The limit of quantification (LOQ) for AFs B1. B2, G1, G2, and OTA were 0.62, 0.50, 0.70, 0.40, and 0.42 ng/g, respectively. AFB1 was found in one sample of raisin (0.64 ng/g) and in two samples of currant (0.20 and 0.63 ng/g). AFB2 (0.33 ng/g) and AFG2 (0.49 ng/g) were found in 2 samples of currant. OTA was detected in 3 of the 22 samples of raisin (mean 2.21 ng/g) and in one sample of currant (2.99 ng/g). The results show that in AFs and OTA levels are well below the regulatory limits both of the European Union and of Iran.


General coupled mode theory in non-Hermitian waveguides.
In the presence of loss and gain, the coupled mode equation on describing the mode hybridization of various waveguides or cavities, or cavities coupled to waveguides becomes intrinsically non-Hermitian. In such non-Hermitian waveguides, the standard coupled mode theory fails. We generalize the coupled mode theory with a properly defined inner product based on reaction conservation. We apply our theory to the non-Hermitian parity-time symmetric waveguides, and obtain excellent agreement with results obtained by finite element fullwave simulations. The theory presented here is typically formulated in space to study coupling between waveguides, which can be transformed into time domain by proper reformulation to study coupling between non-Hermitian resonators. Our theory has the strength of studying non-Hermitian optical systems with inclusion of the full vector fields, thus is useful to study and design non-Hermitian devices that support asymmetric and even nonreciprocal light propagations.


Toward a Formyl-to-Phenyl Conversion: An Unexpected Photochemical Fulvene Rearrangement.
Toward a conversion of aldehydes into arenes, we designed a sequence involving the initial reaction of an aldehyde to give a fulvene, followed by photochemical and platinum-catalyzed rearrangements into a Dewar benzene derivative, which finally isomerizes into the targeted arene. While computational studies support the plausibility of this route, we found that fulvene irradiation resulted in an unexpected isomerization into a spiro[2.4]heptadiene. This unusual photorearrangement has been investigated mechanistically and provides access to a variety of spiro[2.4]heptadienes with different substituents.


Up-regulation of receptors for IgA on activated human B lymphocytes.
Expression of receptors for the Fc part of IgA (Fc alpha R) by T lymphocytes was recently shown to be up-regulated after activation by T cell mitogens in the absence of IgA. We describe a similar increase on activated human B lymphocytes. Fc alpha R were determined by labelling with human secretory IgA (0.5 mg/ml) and flow cytometry analysis after staining with fluoresceinated goat anti-IgA or goat anti-secretory component F(ab')2 fragments. B-enriched cell suspensions were prepared from peripheral blood or tonsils and activated by Staphylococcus aureus Cowan I, anti-IgM antibodies or E. coli lipopolysaccharide. All three activators increased the percentage of Fc alpha R positive cells although only the former induced significant DNA synthesis. Finally recombinant interleukin 1 (10 nM) and interleukin 2 (10 IU/ml) but not interleukin 4 (300 units/ml) nor low-molecular-weight B cell growth factor induced an increase of Fc alpha R expression. The data show that Fc alpha R can be up-regulated on human B cells in the absence of exposure to IgA.


Management of recurrent Cushing's disease.
The management of patients with Cushing's disease remains a major challenge. The remission rate for initial transsphenoidal surgery is reported as 69-94% while the recurrence rate following initially successful transsphenoidal surgery is 2-27%. Treatment options for Cushing's disease after failed initial therapy or recurrence include repeat transsphenoidal surgery, radiotherapy, medical therapy and bilateral adrenalectomy. Management options following unsuccessful initial surgery or recurrence are presented and discussed.


Extra intravenous Ustekinumab reinduction is an effective optimization strategy for patients with refractory Crohn's disease.
Ustekinumab (UST) optimization strategies, including shortening intervals and intravenous reinduction, should be administered to patients with partial or loss of respond. Evidence comparing these types of optimization treatments is limited. We evaluated the efficacy and safety of weight-based UST intravenous reinduction in patients with refractory Crohn's disease (CD). This was a single-center retrospective observational study. Optimization strategies were designed for patients showing partial or loss of response to standardized UST therapy. Clinical, biochemical, and endoscopic response and remission rate were determined by Crohn's disease activity index (CDAI), C-reactive protein (CRP) levels, and SES-CD evaluation. UST trough concentrations were detected and adverse events were recorded. A total of 128 patients receiving UST optimization therapies were included, with 105 patients administered shortening intervals of q8w or q4w, and 23 receiving intravenous reinduction followed by subcutaneous q8w or q4w. The follow-up duration for the shortening interval and reinduction cohorts were 15.0 (10.0, 31.0) and 23.0 (13.0, 70.0) weeks, respectively. A significant CDAI delta variation pre-and post-treatment could be found between groups [17.0 (-4.4, 65.9) vs. 69.0(10.7, 151.0), p = 0.013]. the trough concentration of UST increased [2.5 (1.3, 5.3) vs. 1.1 (0.5, 2.3), p = 0.001] after intravenous reinduction. Clinical and endoscopic remission were achieved in 69.6 and 31.8% of patients in the intravenous reinduction cohort, and 62.9 and 22.2% of patients in the shortening interval cohort, respectively. No significant difference was found between groups regarding safety. Intravenous reinduction brought about favorable recapture of clinical and endoscopic remission, and should have significant priority over the strategy of merely shortening drug intervals, which should be launched before switching to other biologics targeting different inflammatory pathways.Clinical Trial Registration: identifier NCT04923100. https://classic.clinicaltrials.gov/ct2/show/NCT04923100?id=04923100&draw=2&rank=1.


Cytochrome P450 (CYP) epoxygenases as potential targets in the management of impaired diabetic wound healing.
Epoxyeicosatrienoic acids (EETs) are the epoxidation products of arachidonic acid catalyzed by cytochrome P450 (CYP) epoxygenases, which possess multiple biological activities. In the present study, we aimed to explore the role and effects of CYP epoxygenases/EETs in wound healing in ob/ob mice. Full-thickness skin dorsal wounds were made on ob/ob mice and C57BL/6 control mice. The mRNA and protein expression of CYP epoxygenases were determined in granulation tissues of wounds. Effects of EETs on wound healing were evaluated. Inflammation and angiogenesis in wounds were also observed. Compared with C57BL/6 mice, the mRNA and protein expression of CYP2C65 and CYP2J6 in the granulation tissues in ob/ob mice were significantly reduced. 11,12-EET treatment significantly improved wound healing in ob/ob mice, whereas 14,15-EEZE, an EET antagonist, showed the opposite effect. 11,12-EET treatment decreased neutrophil and macrophage infiltration to the wound sites, resulting in reduced production of inflammatory cytokines, decreased MMP-9 expression, and increased collagen accumulation in the granulation tissues of ob/ob mice. In addition, 11,12-EET increased angiogenesis in the granulation tissues of wounds in ob/ob mice. These findings indicate that reduced expression of CYP epoxygenases may contribute to impaired diabetic wound healing, and exogenous EETs may improve diabetic wound healing by modulating inflammation and angiogenesis.


[One-stage approach to the anterior and posterior vertebral column in operative treatment of advanced traumatic and neoplastic changes of the thoraco-lumbar spine].
There were presented indications and operative technique of one-stage approach to anterior and posterior part of the thoraco-lumbar spine. Presented technique gave chance to control antero-lateral and posterior aspects of the spine. There were 2 patients with delayed compressions of the vertebral bodies in lumbar part with severe kyphotic deformity. Those deformities were the cause of progression of neural symptoms in a few months after injury. Another 4 patients had the spinal tumours. In one case it was giant-cell tumour which destroyed body and the arch of Th12. In two patients metastases of renal cancer infiltrated L2 and L3. The last one had breast cancer metastasis into Th12. In all patients it was necessary to control anterior and posterior columns of the spine to restore its axis and the shape of spinal canal.


High-resolution phylogenetic analysis of residual bacterial species of fouled membranes after NaOCl cleaning.
Biofouling is one of the major problems during wastewater treatment using membrane bioreactors (MBRs). In this regard, sodium hypochlorite (NaOCl) has been widely used to wash fouled membranes for maintenance and recovery purposes. Advanced chemical and biological characterization was conducted in this work to evaluate the performance of aqueous NaOCl solutions during washing of polyacrylonitrile membranes. Fouled membranes from MBR operations supplemented with artificial wastewater were washed with 0.1% and 0.5% aqueous NaOCl solutions for 5, 10 and 30 min. The changes in organics composition on the membrane surface were directly monitored by an attenuated total reflection Fourier transform infrared (ATR-FT-IR) spectrometer. In addition, high-throughput Illumina sequencing of 16S rRNA genes was applied to detect any residual microorganisms. Results from ATR-FT-IR analysis indicated the complete disappearance of functional groups representing different fouling compounds after at least 30 min of treatment with 0.1% NaOCl. However, the biomolecular survey revealed the presence of residual bacteria even after 30 min of treatment with 0.5% NaOCl solution. Evaluation of microbial diversity of treated samples using Chao1, Shannon and Simpson reciprocal indices showed an increase in evenness while no significant decline in richness was observed. These implied that only the population of dominant species was mainly affected. The high-resolution phylogenetic analysis revealed the presence of numerous operational taxonomic units (OTUs) whose close relatives exhibit halotolerance. Some OTUs related to thermophilic and acid-resistant strains were also identified. Finally, the taxonomic analysis of recycled membranes that were previously washed with NaOCl also showed the presence of numerous halotolerant-related OTUs in the early stage of fouling. This further suggested the possible contribution of such chemical tolerance on their survival against NaOCl washing, which in turn affected their re-fouling potential.


Multidisciplinary care in chronic airway diseases: the Newcastle model.
Chronic airway diseases including asthma and COPD are prevalent and high-burden conditions with the majority of patients successfully managed in the primary care setting. However, for some patients with more complex disease such as difficult-to-treat or severe asthma, or complex COPD, tertiary care is required. This review provides an overview of the successful tertiary care multidisciplinary respiratory service that operates in Newcastle, New South Wales, Australia, which has been integrated into the tertiary care outpatient clinics for almost three decades. The service is multifaceted in terms of the clinical care it provides; it includes an "Inpatient Service", "Asthma Management Service", "Difficult Airways Clinic", "Drug Administration Clinic", "Rapid Access Clinic" and "Pulmonary Rehabilitation", and has an integrated research programme. The core of the multidisciplinary approach to airway diseases is a person-centred model of care, the "Treatable Traits" approach. The staffing of this service comprises consultant physicians, respiratory advanced trainees, respiratory scientists, physiotherapists, speech pathologists, nurse specialists and a nurse consultant. Patients that present to this service undergo an initial assessment and clinical review by team members, synthesis of relevant data, and development of a diagnosis and management plan. Based on this clinical review, specific interventions are determined according to the traits identified. Over time the service has evolved to accommodate the increasing numbers of patients requiring access to the Difficult Airways Clinic assessment and therapies. This has been facilitated by partnering with the Centres of Excellence in Severe Asthma and Treatable Traits to develop educational and practice management tools.


Prognosis and therapeutic response according to the World Health Organization histological classification in advanced thymoma.
The clinical efficacy of the World Health Organization (WHO) classification of thymoma has been reported to be a prognostic factor for patients with thymomas. This study focuses on the relationship between the therapeutic response and the WHO histological classification in patients with advanced thymoma. A retrospective review was performed on 22 patients with Masaoka stage III and IV thymoma treated from 1975 to 2007. There were 1, 1, 7, 3, and 10 patients with WHO histological subtypes A, AB, B1, B2, and B3, respectively. Surgery was performed on 10 patients. There were 2 complete resections, 2 incomplete resections, and 6 exploratory thoracotomies. Of 18 patients with unresectable tumors, 8, 5, and 5 were treated with radiotherapy, chemotherapy, and chemoradiotherapy as the initial therapy, respectively. The response rate in 9 patients with type A-B2 was significantly better than that in 9 patients with type B3 regardless of treatment modality (100% vs 11.1%, P = 0.0001). Only the WHO classification was significantly associated with survival, with type B3 having a worse prognosis than A-B2 (P = 0.01). Type B3 thymoma showed a lower response rate to treatments and thus shorter survival. The WHO classification is a good predictive factor for therapeutic response in advanced thymoma.


Smoking is associated with remodeling of gap junction in the rat heart: smoker's paradox explanation?
In a previous study utilizing the rat model, exposure to tobacco smoke for 5 weeks increased survival after AMI, despite similar age and infarct size between the smokers and nonsmokers, and absence of reperfusion. Thus, this study aimed to analyze the effects of exposure to tobacco smoke on intensity, distribution or phosphorylation of connexin 43 in the rat heart. Wistar rats weighing 100 g were randomly allocated into 2 groups: 1) CONTROL (n = 25); 2) Exposed to tobacco smoke (ETS), n = 23. After 5 weeks, left ventricular morphometric analysis, immunohistochemistry and western blotting for connexin 43 (Cx43) were performed. Collagen volume fraction, cross-sectional areas, and ventricular weight were not statistically different between control and ETS. ETS showed lower stain intensity of Cx43 at intercalated disks ( 2.32 ± 0.19; ETS: 1.73 ± 0.18; p = 0.04). The distribution of CX43 at intercalated disks did not differ between the groups ( 3.73 ± 0.12; ETS: 3.20 ± 0.17; p = 0.18). ETS rats showed higher levels of dephosphorylated form of Cx43 (CONTROL: 0.45 ± 0.11; ETS: 0.90 ± 0.11; p = 0.03). On the other hand, total Cx43 did not differ between control and ETS groups ( 0.75 ± 0.19; ETS: 0.93 ± 0.27; p = 0.58). Exposure to tobacco smoke resulted in cardiac gap junction remodeling, characterized by alterations in the quantity and phosphorylation of the Cx43, in rats hearts. This finding could explain the smoker's paradox observed in some studies.


The Hybrid Approach and Its Variations for Chronic Total Occlusion Percutaneous Coronary Intervention.
Selected patients with coronary chronic total occlusion (CTO) benefit with respect to symptoms, quality of life, ischemia reduction, and potentially longevity among other benefits. CTO lesions tend to be the most technically challenging for practicing interventional cardiologists to deliver a successful and safe result and clinical experience for a given patient. The Hybrid algorithm for CTO percutaneous coronary intervention and the subsequent subalgorithms for focused technical challenges have a standardized process and provide a consistent platform for optimized patient care, medical education, and clinical investigation in patients challenged with total occlusion and complex coronary disease.


A facile approach for preparation of molecularly imprinted polymers layer on the surface of carbon nanotubes.
A convenient imprinting method for the preparation of molecularly imprinted polymers (MIPs) layer on the surface of multiwalled carbon nanotubes (MWCNTs) is described. In this method, 9-vinylanthracene was introduced to the surface of MWCNTs, forming vinyl group functionalized MWCNTs. Then the grafting copolymerization of methacrylic acid and trimethylolpropane trimethacrylate in the presence of theophylline as template molecular led to the formation of MIPs-MWCNTs composite. The formation of continuous and nanoscale MIPs layer (thickness about 10-15 nm) would be due to the homogeneous and high-density vinyl groups on the surface of MWCNTs. The resulting surface-imprinted MWCNTs composite showed high binding capacity and good specific recognition behaviour towards template molecule.


Facts and artifacts in brain electrical activity mapping.
As computerized EEG (CEEG) analysis and display methods become increasingly powerful the user is lured toward increasingly abstract representations of data in which artifacts can easily go unrecognized. The presence of even small amounts of artifact can lead to distortion of CEEG results due to the sensitivity of the analysis methods employed. Several common artifacts are discussed, their distortion of CEEG data illustrated, and remedial measures suggested. Some of these artifacts (EOG, EMG, photomyoclonic, tremor, ECG, 60 Hz, volume conducted cortical activity) are familiar to traditional EEG (aliasing, extrapolation) are unique to CEEG and may be inadvertently introduced by workers not specifically trained in CEEG methods.


Yeast Selenium Exerts an Antioxidant Effect by Regulating the Level of Selenoprotein to Antagonize Cd-Induced Pyroptosis of Chicken Liver.
Cadmium (Cd) exposure can cause multiple organ damage in humans and animals by causing oxidative stress. Organic selenium can antagonize the toxic damage of heavy metals by exerting antioxidant effects. Oxidative stress can activate NLRP3/Caspase1-dependent pyroptosis, but it is not clear whether yeast selenium (Se Y) can antagonize Cd-induced pyroptosis in the chicken liver. In this experiment, we studied the effects of CdCl2 single, Se Y single, and combined exposure on the pyroptosis of chicken liver. The results showed that Cd exposure induced oxidative stress in the chicken liver, and the expression of Sepx1, SelU, SelT, GPx1, GPx4, Dio1, Dio2, Dio3, TrxR1, TrxR2, TrxR3, SelH, SelI, SelO, SelK, SelPb, Selpp, and Sel15 decreased. In addition, NLRP3 inflammasome complex (NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing (ASC), and pro-Caspase1), Cysteinyl aspartate specific proteinase (Caspase1), Interleukin-β (IL-1β), and Interleukin-18 (IL-18) were upregulated. The combined treatment of Se Y and Cd found that the antioxidant level and the expression level of selenoprotein recovered to the Se group, and the liver pyroptosis decreased. Principal component analysis and correlation analysis screened out that selenoprotein O (SelO) is negatively correlated with pyroptosis-related genes. In short, our data shows that Se Y exerts an antioxidant effect by increasing the expression of selenoproteins and antagonizing the pyroptosis of chicken liver induced by Cd. This study provides new ideas for the field of heavy metal toxicology research. And the selected SelO has an important reference significance for follow-up research.


Prevalence and factors associated with undernutrition among children under the age of five years in Benin.
Benin ranks as one of the countries in the world with an alarmingly high prevalence of stunting, wasting, and underweight in children under five years. However, limited studies have examined the factors associated with the prevalence of these undernutrition indicators among children under five years in the country. This study aimed to fill this research gap by examining the prevalence rates and factors associated with stunting, wasting, and underweight among this specific population of interest. This quantitative study utilised data from the most recent Benin Demographic and Health Survey (BDHS) conducted in 2017-18. The survey employed a nationally representative cross-sectional design and utilised a two-stage stratified cluster sampling technique to select participants. The study included a sample of 13,589 children under the age of five years. The main analytical approach employed was binary logistic regression, which was used to explore the associations between undernutrition (the combined outcome variable representing stunting, wasting, and underweight) and various socio-demographic factors. The combined prevalence of stunting, wasting, and underweight among children under five years in Benin during the 2017-18 survey period was 14.95%. Several factors were significantly associated with these indicators of undernutrition, including female gender (AOR = 0.71, 95% CI = 0.59-0.85), birth weight of 4.1 kg and over (AOR = 0.26, 95% CI = 0.14-0.48), multiple births (AOR = 3.22, 95% CI = 2.11-4.91), and a child's experience of diarrhoea (AOR = 1.76, 95% CI = 1.40-2.20). Furthermore, the prevalence of these undernutrition indicators was higher among children whose mothers had lower levels of education (AOR = 0.82, 95% CI = 0.01-0.42) and were unmarried (AOR = 0.67, 95% CI = 0.49-0.93). This present study confirms that undernutrition rates are elevated in Benin and are closely linked to perinatal factors such as birth weights and multiple births, postnatal health conditions including diarrheal episodes, and socio-demographic determinants such as a child's gender, maternal education level, and marital status. Therefore, there is the need to consider specific modifiable factors, such as low birth weight, episodes of child diarrhoea, and maternal education as priority targets for child nutrition interventions in Benin.


Developmental plasticity of respiratory control following intermittent hypoxia.
During development, windows of increased vulnerability to noxious stimulus occur. These critical periods of maturation represent times at which the maturing animal is uniquely susceptible to external perturbations that may alter the ultimate configuration of neural networks and their associated function(s), thereby inducing persistent (mal)adaptive changes. In contrast, when comparable perturbations are applied to adult animals the associated adaptive changes do not typically persist. This principle has been demonstrated in models of respiratory plasticity in developing mammals including exposure to sustained hypoxia, hyperoxia, and pharmacological agents. Recently, intermittent hypoxia (IH) during development has also been implicated as a potent inducer of respiratory plasticity. Altered ventilatory patterning induced by IH is distinct from other stimuli and elicits markedly different responses in the developing mammal as compared to the adult. Furthermore, adaptations to acute IH (AIH) exposure may involve mechanisms that differ from those invoked by chronic IH exposure (CIH). Thus, critical examination of IH exposure paradigms is also an important consideration. Greater understanding of IH-induced ventilatory plasticity, particularly in the developing animal, will undoubtedly increase our understanding of IH related diseases such as sleep disordered breathing, and perhaps provide future directions for intervention strategies.


Antibacterial and antioxidant activities of ethanol extract from Paullinia cupana Mart.
The antibacterial and antioxidant activity of the ethanol extract from Paullinia cupana var. sorbilis Mart. (Sapindaceae) seeds, commonly called guarana, was assessed towards selected bacteria as well as in different antioxidant models. The extract, at a concentration between 16 and 128 microg/ml, showed a significant antibacterial effect expressed as minimum inhibitory concentration (MIC) against both Gram-negative and Gram-positive bacteria. In particular, Pseudomonas aeruginosa (MIC=16 microg/ml), Proteus mirabilis (MIC=32 microg/ml), Proteus vulgaris (MIC=32 microg/ml) and Escherichia coli (MIC=32 microg/ml) were the most inhibited. The antioxidant activity was determined by the malonyldialdehyde (MDA) test, measuring the MDA concentration in 3T3-L1 cells after induced cellular damage using ferric ammonium citrate (FAC). The reduction of lipid peroxidation was 62.5% using a guarana extract with a concentration of 2 microg/ml. This effect was dose/dependent. The ethanol extract from Paullinia cupana seeds was analysed by spectrophotometry to determine the concentration of catechol substances after treatment of the extract with p-aminophenol. The total phenolics content in the ethanol extract was also determined spectrophotometrically according to the Folin-Ciocalteu procedure and calculated as gallic acid equivalents (GAE). The concentration of catechol equivalent was 6.06+/-0.13 mg/g (mean+/-S.D.), while the total phenolic content was 8.43+/-0.21 mg/g (mean+/-S.D.). The correlation index between antioxidant activity and catechol content was 0.96.


High titer L-lactic acid production from corn stover with minimum wastewater generation and techno-economic evaluation based on Aspen plus modeling.
Technological potentials of l-lactic acid production from corn stover feedstock were investigated by experimental and techno-economic studies. An optimal performance with 104.5 g/L in l-lactic acid titer and 71.5% in overall yield from cellulose in corn stover to l-lactic acid using an engineered Pediococcus acidilactici strain were obtained by overcoming several technical barriers. A rigorous Aspen plus model for l-lactic acid production starting from dry dilute acid pretreated and biodetoxified corn stover was developed. The techno-economic analysis shows that the minimum l-lactic acid selling price (MLSP) was $0.523 per kg, which was close to that of the commercial l-lactic acid produced from starch feedstock, and 24% less expensive than that of ethanol from corn stover, even though the xylose utilization was not considered. The study provided a prototype of industrial application and an evaluation model for high titer l-lactic acid production from lignocellulose feedstock.


Reproductive state and motor activity in female ferrets.
The pattern of motor activity in female ferrets (Mustela putorius furo) housed in cages mounted upon rocker platforms was followed under conditions of short-(8 hr) and long-(16 hr) day illumination. A distinct diurnal rhythm was evident that remained unchanged after lesioning of the anterior hypothalamus. The level of activity did not differ between animals kept under short days and long days, between anoestrous and oestrous females, or during the development or waning of oestrus. Ovariectomy did not affect the pattern of activity. These findings are at variance with those of a previous study where wheel-running activity was followed and oestrous females found to be more active than anoestrous ferrets.


Elevated CO2 aggravated polystyrene microplastics effects on the rice-soil system under field conditions.
Polystyrene microplastics (PS) are decomposed very slowly due to their recalcitrance and inevitably interact with the changing climate. How the interaction between PS and increasing CO2 concentration affects the plant-soil system is rarely investigated. Here, a free-air CO2 enrichment system in farm fields was used to study the impacts of PS added to soil at 10 mg kg-1 on rice and soil bacterial communities at different CO2 levels (ambient∼390 ppm and elevated∼590 ppm). Results showed that single PS interfered with Fe, Mn and Zn uptake of rice, and it increased the abundances of bacteria taxa assigned to N turnover and urease activities, leading to altered soil N transformation and availability. Elevated CO2 alone enhanced rice photosynthesis, decreased the abundances of nitrogen-fixation bacteria, and induced co-occurrence patterns between bacteria simplified and decentralized. Combined PS and elevated CO2 significantly decreased rice stomatal conductance and transpiration rate by 56.70% and 29.46%, respectively, and further inhibited elements uptake. Besides, combined exposure significantly disturbed bacterial amino acid metabolism, and stimulated the adaptative responses of resistant bacteria. Overall, this study revealed that increasing CO2 concentrations may exacerbate the impacts of PS on rice performance and soil bacterial communities, providing new insights into the interaction between microplastics and climate change.


Steroid-Associated Side Effects: A Symptom Management Update on Multiple Myeloma Treatment .
One constant and relatively unchanged aspect of treatment of multiple myeloma (MM) is the use of glucocorticosteroids, or steroids, which can cause a wide range of adverse side effects and harm patients' quality of life. . The objective of this study was to provide updated recommendations on the management of steroid-associated side effects in patients with MM. . A study of steroid-associated side effects in MM treatment regimens was reviewed to provide updated recommendations to healthcare professionals. Identifying the side effects of steroids and managing them promptly contribute to the success of steroid-containing regimens for patients with MM.


Exogenous progesterone attenuates the subjective effects of smoked cocaine in women, but not in men.
In a previous study, we showed that the positive subjective effects of cocaine were higher during the follicular phase compared to the luteal phase of the menstrual cycle. The purpose of the present study was to determine if exogenously administered progesterone during the follicular phase in females would attenuate the response to cocaine compared to the normal follicular phase, thus making the response to cocaine similar to the luteal phase. To address the role of sex differences, males were also administered exogenous progesterone during one inpatient stay. In all, 11 female and 10 male non-treatment-seeking cocaine smokers participated. Females had three inpatient stays: one during a normal follicular phase, one during a normal luteal phase, and one during a follicular phase when exogenous progesterone was administered. Males had two inpatient stays: one when exogenous progesterone was administered and the other when placebo was administered. During each inpatient admission, there were four smoked cocaine administration sessions: participants were administered six doses of cocaine (0, 6, 12, or 25 mg cocaine base) at 14 min intervals. Smoked cocaine increased heart rate, blood pressure and several subjective effects such as 'good drug effect' and 'drug quality' cluster scores. Administration of progesterone during the follicular phase in women attenuated the positive subjective effects of cocaine, whereas only minimal changes were observed in men. These results indicate that progesterone modulates the response to cocaine in women and suggests that fluctuations in endogenous progesterone levels account for some of the sex differences observed in humans.


Functional properties of a manganese-activated exo-polygalacturonase produced by a thermotolerant fungus Aspergillus niveus.
A thermotolerant fungus identified as Aspergillus niveus was isolated from decomposing materials and it has produced excellent levels of hydrolytic enzymes that degrade plant cell walls. A. niveus germinated faster at 40 °C, presenting protein levels almost twofold higher than at 25 °C. The crude extract of the A. niveus culture was purified by diethylaminoethyl (DEAE)-cellulose, followed by Biogel P-100 column. Polygalacturonase (PG) is a glycoprotein with 37.7 % carbohydrate, molecular mass of 102.6 kDa, and isoelectric point of 5.4. The optimum temperature and pH were 50 °C and 4.0-6.5, respectively. The enzyme was stable at pH 3.0 to 9.0 for 24 h. The DEAE-cellulose derivative was about sixfold more stable at 60 °C than the free enzyme. Moreover, the monoaminoethyl-N-aminoethyl-agarose derivative was tenfold more stable than the free enzyme. PG was 232 % activated by Mn(2+). The hydrolysis product of sodium polypectate corresponded at monogalacturonic acid, which classifies the enzyme as an exo-PG. The K m, V max, K cat, and K cat/K m values were 6.7 mg/ml, 230 U/mg, 393.3/s, and 58.7 mg/ml/s, respectively. The N-terminal amino acid sequence presented 80 % identity with PglB1, PglA2, and PglA3 putative exo-PG of Aspergillus fumigatus and an exo-PG Neosartorya fischeri.


Calcium Imaging of Non-adherent Cells.
Live-cell imaging can reveal dynamic and multimodal cell signaling by monitoring calcium flux. Spatiotemporal changes in Ca2+ concentrations instigate specific downstream processes and by categorizing these events, we can examine the language cells use to communicate both to themselves and with each other. Thus, calcium imaging is an understandably popular and versatile technique that relies on high-resolution optical data as measured by fluorescence intensity. This is executed with relative ease on adherent cells, as changes in fluorescence intensity can be monitored over time in fixed regions of interest. However, perfusion of non-adherent or mildly adherent cells leads to their mechanical displacement thereby hindering the spatial resolution of fluorescence intensity changes through time. Here we provide details of a simple and cost-effective protocol using gelatin to prevent cell dislodgement during the solution exchanges that occur during recording.


LPS and TNF-α induce expression of sphingosine-1-phosphate receptor-2 in human microvascular endothelial cells.
Sphingosine-1-phosphate (S1P) is a bioactive sophospholipid with various S1P receptor (S1PR) expression profiles in cells of different origin. S1PR1, R3 and - to a lesser extent - R2 were the main receptors expressed in most of endothelial cells (ECs). The balances in the expression and activation of S1PR1, R2 and R3 help to maintain the physiological functions of ECs. Reverse transcription-PCR and Western blotting were used to detect the mRNA transcript level and protein expression of S1PR. Endothelial barrier function was measured by transflux of tracer protein through endothelial monolayer. Human dermal microvascular ECs predominantly expressed S1PR1 and S1PR3. Lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α) significantly upregulated S1PR2 mRNA and protein levels. The application of S1PR2 antagonist JTE-013 decreased the endothelial monolayer hyper-permeability response induced by LPS and TNF-α. Inflammatory mediators LPS and TNF-α induce S1PR2 expression in endothelium, suggesting that S1PR2 up-regulation may be involved in LPS and TNF-α elicited endothelial barrier dysfunction.


Novel MRI-based score for assessment of bone density in operative spine patients.
Good bone quality is key in avoiding a multitude of afflictions, including osteoporotic fragility fractures and poor outcomes after spine surgery. In patients undergoing instrumented spine fusion, bone quality often dictates screw pullout strength, insertional torque, and vertebral body loading properties. While dual-energy X-ray absorptiometry (DEXA) screening is the current method of assessing bone mineral density, the majority of patients do not have DEXA measurements available before undergoing surgical instrumentation. To create a simple magnetic resonance imaging (MRI)-based score to evaluate bone quality and evaluate the degree to which it correlates with conventional DEXA scores. Retrospective cohort. Patients ≥18 years of age undergoing spine surgery for degenerative conditions between 2013 and 2018. Correlation of the vertebral bone quality (VBQ) score with DEXA T-scores, and association between VBQ score and presence of osteopenia/osteoporosis. Using noncontrast T1-weighted MRIs of the lumbar spine, the novel VBQ score was calculated for each patient. DEXA T-scores of the femoral neck and total hip were obtained and were compared with patient VBQ scores using linear regression and Pearson's correlation. Among 68 patients included in this study, 37 were found to have osteopenia/osteoporosis (T-score < -1.0) based on DEXA. A greater VBQ score was significantly associated with the presence of osteopenia/osteoporosis with a predictive accuracy of 81%. VBQ scores correlated moderately with femoral neck T-scores, the lowest overall T-scores of each patient, and correlated fairly with total hip T-scores. This is the first study to correlate the novel VBQ score obtained from MRIs with DEXA T-score. We found this score to be a significant predictor of healthy versus osteopenic/osteoporotic bone with an accuracy of 81%, and found that VBQ score was moderately correlated with femoral neck and overall lowest T-score.


Summary of the development of a signature for detection of residual dust from collapse of the World Trade Center buildings.
The collapse of the World Trade Center (WTC) towers on September 11, 2001, caused lower Manhattan and adjacent areas to be covered in millimeters to centimeters of dust. WTC dust penetrated into indoor spaces, and public health concerns remain regarding exposure to possible residual dust in the affected areas. The goal of the studies outlined in this review was to determine which, if any, components of the bulk WTC dust are sufficiently above typical background dust levels in New York City to develop an analytical method to screen for the component(s). Components of the <150-microm-size fraction of the dust are gypsum, phases compatible with crushed concrete, man-made vitreous fibers (MMVFs), silica, lead, chrysotile asbestos, and other materials. Slag wool was the most common WTC MMVF, whereas soda-lime glass and rock wool were minor to trace constituents. Most background samples also contained gypsum, phases compatible with concrete, and MMVF. However, the proportions of the various MMVF in background samples are typically unlike those characteristic of bulk WTC dust. Results indicate that slag wool can be used as a signature marker to identify areas that contain potential residual WTC dust contamination at concentrations that are less than average background levels for the material.


Subharmonic bifurcation in an S-I-R epidemic model.
An S leads to I leads to R epidemic model with annual oscillation in the contact rate is analyzed for the existence of subharmonic solutions of period two years. We prove that a stable period two solution bifurcates from a period one solution as the amplitude of oscillation in the contact rate exceeds a threshold value. This makes rigorous earlier formal arguments of Z. Grossman, I. Gumowski, and K. Dietz [4].


Acute myocardial and vascular responses to specific angiotensin II antagonism in the spontaneously hypertensive rat.
As the AT1 receptor is the primary angiotensin II receptor in the myocardium and vasculature, we assessed the acute myocardial and vascular response to the AT1 angiotensin II antagonist losartan in the spontaneously hypertensive rat (SHR) to determine the contribution of angiotensin II in this genetic form of hypertension. In a preliminary dose response study, which evaluated losartan at 1.0, 3.0, and 10 mg/kg, 10 mg/kg uniformly lowered blood pressure. In a second group of experiments, 10 mg/kg also completely attenuated the pressor effects of angiotensin II administration. In nine adult SHR, intravenous losartan, 10 mg/kg, was given, with hemodynamics measured immediately and at steady-state intervals to delineate the hemodynamic response to angiotensin II antagonism. Losartan significantly lowered systolic, diastolic, and mean blood pressures, yet heart rate was unchanged. Cardiac function, as assessed by cardiac output and blood flow acceleration, demonstrated only transient increases which were not sustained during steady-state blood pressure reduction. Significant increases of peak blood flow and pulse pressure were sustained throughout the blood pressure response. At immediate and steady-state determinations, system vascular resistance and characteristic aortic impedance were significantly reduced with losartan (both P < .01). In addition, concomitant reduction of the wave reflectance index also occurred, achieving significance at steady state (P < .05). These changes demonstrate that the AT1 angiotensin II receptor contributes to both central and peripheral vasoconstriction in the spontaneously hypertensive rat. Absence of sustained increase of cardiac output and blood flow acceleration are consistent with inhibition of the previously reported positive inotropic effect of angiotensin II.


A critical review of experimental data for the half-lives of the uranium isotopes 238U and 235U.
The existing experimental data for the half-lives of the uranium isotopes 238U and 235U have been scrutinised in detail because of their significant practical importance, in particular for geochronogical use and for the assay of standard samples used for neutron fluence and cross-section measurements. The most accurate measurements by Jaffey et al. (Phys. Rev. C 4 (5) 1889) with 1sigma uncertainties of 0.054% (238U) and 0.068% (235U), are not confirmed by other measurements of comparable accuracy. In this work, we take a critical look at the 238U and 235U half-life measurements in the literature. Although we find that the Jaffey et al. data are concordant with other reliable results, generally much higher uncertainties of the latter cannot prove or disprove the Jaffey et al. results. Therefore, at this time, we do not recommend new half-life values. Instead, we call for new measurements of these two half-lives with accuracies comparable to the work of Jaffey et al.


Implementation of the Surviving Sepsis Campaign one-hour bundle in a short stay unit: A quality improvement project.
To improve timely sepsis care by implementing the 2018 Surviving Sepsis Campaign one-hour interventions. Ten-month prospective quality improvement project. A 38-bed short stay unit within an 800-bed hospital in New York City. Patients admitted to the short stay unit who screened positive for sepsis. A sepsis implementation tool was created from the 2018 Surviving Sepsis Campaign guidelines. Sepsis champions delivered education on sepsis recognition, treatment, and management, and the sepsis implementation tool to the healthcare staff. Time to first lactate, blood cultures × 2, antibiotic administration, length of stay and mortality were tracked weekly for five months. From May 6, 2019 to October 1, 2019, 32 patients were diagnosed with sepsis. Initial lactate and blood cultures were completed on every patient within 1one-hour of sepsis diagnosis. Administration of antibiotics within one-hour reached 100% after week four and was sustained. Use of a registered nurse-initiated sepsis implementation tool in a short stay unit led to the completion of blood cultures, initial lactate, and antibiotic administration within one-hour. Key factors to support this practice improvement were increasing registered nurse, physician and physician assistant sepsis knowledge, registered nurse and physician/physician assistant early collaboration, increased staffing and intravenous access equipment.


Going Beyond Diffusion Tensor Imaging Tractography in Eloquent Glioma Surgery-High-Resolution Fiber Tractography: Q-Ball or Constrained Spherical Deconvolution?
As a result of the resolution of intravoxel fiber crossing, high-resolution fiber tractography (HRFT) provides advantages over conventional diffusion tensor imaging (DTI) for fiber tractography (FT). Nevertheless, neurosurgically applied FT is still predominantly based on DTI. Although the application of HRFT is evolving, there is still a lack of data about which method should be preferred. With this prospectively designed study, we present our initial experience comparing an analytical Q-ball imaging (QBI) approach with constrained spherical deconvolution (CSD) and conventional DTI-FT considering a particularly neurosurgical perspective. For 18 patients with eloquent gliomas in the dominant hemisphere, probabilistic FT based on QBI, CSD, and DTI was performed for the major components of the language-associated pathways using a routine diffusion-weighted sequence. Quantitative analysis evaluated tract density, tract volume (TV), tract length (TL), number of fibers, and tract surface (TS) of the fiber object. Both HRFT models showed a significantly larger mean TV, TL, and TS compared with DTI (for QBI vs. DTI: TV (P = 0.0000), TL (P = 0.0048), and TS (P = 0.0129); for CSD vs. DTI: TV (P = 0.0000), TL (P = 0.0008), and TS (P = 0.0010)). However, results of QBI versus CSD did not differ significantly for these variables: TV (P = 0.1415), TL (P = 0.2837), and TS (P = 0.3692). Bland-Altman analysis supports these findings, suggesting systematically higher values for TV, TL, and TS with HRFT but no relevant differences of either QBI or CSD. Neither tumor volume nor peritumoral edema influenced FT results. Our quantitative analysis showed no significant differences regarding TV, TL, and TS for the HRFT methods; however, it suggested advantages over DTI-FT in terms of the display of marginal and terminal fibers. In our recently established setting, QBI-FT shows greater potential for integration into the clinical workflow.


The prognostic value of urinary cytology after trimodal therapy (TMT) for muscle-invasive bladder cancer.
Urine cytology and cystoscopy are routinely employed during follow-up of patients after trimodal therapy (TMT) for muscle-invasive bladder cancer (MIBC). The significance of positive or equivocal cytology without visible disease recurrence on cystoscopy during follow-up is unknown, and studies informing outcomes in this scenario are lacking. This study aims to investigate the temporal trends of positive/equivocal cytology in the absence of visible disease recurrence and the association with bladder cancer recurrence and survival outcomes. One hundred and twenty-nine patients with available post-TMT cytology data and negative cystoscopy from a single academic institution between 2002 and 2017 with a median follow-up of 3.4 (range 0.1-14.2) years were analyzed. Cytology results, first post-TMT cytology positive/equivocal (CP) and negative (CN), were evaluated for association with disease recurrence and survival. Kaplan. Meier and competing risks methods were used to assess time-to-negative cytology in CP patients with ≥2 interval post-TMT cytology results (n = 33), time-to-recurrence, and disease-specific mortality (DSM) stratified by first post-TMT cytology result. At first follow-up (6-8 weeks post-TMT completion), CP was observed in 41 (32%) and CN in 88 (68%) of patients. With further follow-up of CP patients with ≥2 interval post-TMT cytology results, the probability of developing negative cytology was 57% (95% CI 42, 77) at 6 months post-TMT, and the median time-to-negative cytology was 3.2 months (95% CI 2.99, 5.80). The median time-to-recurrence was reduced in CP patients compared to CN (24.3 vs. 78.1 months, p = 0.1), corresponding with an apparent increase in the cumulative incidence of recurrence rate at 3 years in the CP vs. CN group (62% vs. 42%, p = 0.1). No significant difference was observed in the 3-year DSM rates. On univariable analysis, the hazards of recurrence and DSM for patients with CP were 1.5 (95% CI 0.9, 2.5, p = 0.1) and 2.1 (95% CI 0.9, 4.7, p = 0.07) respectively. This is the first study to investigate the significance of a positive/equivocal cytology without visible disease following TMT for MIBC. Positive cytology is common and does not preclude subsequent negative cytology supporting a watchful waiting approach rather than proceeding immediately to biopsy. However, cytology that remains positive at subsequent follow-up may be associated with adverse recurrence and survival outcomes.


The effect of prostaglandins E1, E2 and F2 alpha and indomethacin on the sensitivity of glycolysis and glycogen synthesis to insulin in stripped soleus muscles of the rat.
Prostaglandins E1 and E2 increased the sensitivity of glycolysis to insulin in the isolated stripped soleus muscle of the rat, but prostaglandin F2 alpha had no effect. Indomethacin, which inhibits prostaglandin formation, markedly decreased the sensitivity of glycolysis to insulin. These findings suggest that prostaglandins of the E series increase the sensitivity of muscle glycolysis to insulin in vivo.


Applicability, limitations and downstream impact of echocardiography utilization based on the Appropriateness Use Criteria for transthoracic and transesophageal echocardiography.
To evaluate impact of echocardiography on patient management based on published transthoracic echocardiography (TTE) Appropriate Use Criteria (AUC). A prospective analysis of 170 consecutive outpatients who underwent TTE over a period of 2 months. Echo studies were classified into appropriate (A), inappropriate (I), or uncertain (U) based on the 2007/2011 AUC. A fourth group of studies which were not addressed by the 2007 AUC and therefore have unclassifiable category (UC) were also included in the analysis. The impact of AUC categorized echo results on patient management were evaluated by review of patient records in the ensuing 2 months. Based on 2007 AUC, 77% (131/170) were A, 9% were I, and 14% were UC category. Echo studies classified as A were more likely to be associated with new and major findings, (P = 0.034) and (P = 0.028) respectively when compared to all other studies. Furthermore, patient care intervention as defined in the study protocol was significantly associated with A studies as opposed to I and UC studies (P = 0.004). A studies were also more likely to have an impact on patient management when compared to other studies (P = 0.022). When studies were re-evaluated based on the 2011 AUC, all prior UC studies were now included in the U group in the new AUC of 2011, and there was no change in A or I study classification. This study demonstrates that the 2007/2011 AUC are helpful in evaluating practice patterns in a majority of outpatients undergoing TTE. Implementing AUC have a direct clinical impact as A studies are significantly more likely to reveal new and major findings, and more likely to result in a patient care intervention based on the echo findings.


NADPH as rate-limiting factor for microsomal metabolism. An alternative and economic NADPH-generating system for microsomal mono-oxygenase in in vitro genotoxicity studies.
The effect of NADPH supply on enzymatic activity and its stability were investigated with respect to the mono-oxygenase activities of 7-ethoxyresorufin O-deethylase (ERD), dinemorphan N-demethylase (DND), aminopyrine N-demethylase (APD), 7-ethoxycoumarin O-deethylase (ECD) and p-nitroanisole O-demethylase (p-NAD) under incubation conditions for the liver microsomal assay (LMA). Experiments with S9 liver fractions of mouse (induced with Na-phenobarbital and beta-naphthoflavone) and rat (induced with Aroclor 1254) were set out at different pre-incubation times with and without exogenous isocitrate dehydrogenase (IC-DH) in the LMA. Such LMA mixtures contain Mn2+, NADP+, DL-isocitrate (IC) and endogenous IC-DH as NADPH-generating machinery. No changes in mono-oxygenase stability and lipid peroxidation (LP) were observed in the presence of exogenous IC-DH. The metabolizing capability at the considered times was the maximal one, as shown by no stability changes after the direct addition of IC-DH to the enzymatic assays. Exogenous IC-DH in the incubation for LMA did not alter the mitotic crossing-over and the mitotic gene conversion of dimethylnitrosamine (DMNA) and AR2MNFN (a nitroimidazo[2,1-b]thiazole) in the tester D7 strain of Saccharomyces cerevisiae. It was concluded that endogenous IC-DH seems to be sufficient to provide a saturating level of NADPH for mono-oxygenase activities during incubations for LMA without additional external NADPH-generating enzyme activity.


Lymphangioma of small bowel in adults: A rare cause of abdominal symptoms.
Lymphangioma is unusual malformation of the lymphatic system and rarely occurred in adults below diaphragm. Lymphangioma in small intestine sometimes caused unspecific symptoms and even bleeding, however, this area was most difficult for endoscopic examination and worth investigation. From 1999 to 2019, we retrospectively collected eighteen adult patients with the pathological diagnosis of lymphangioma from duodenum to terminal ileum. The clinical symptoms, origin site, predisposing factor, pre-operative image surveillance, surgical intervention, histopathological findings, follow-up period, and outcome were reviewed and analyzed. The mean age of diagnosis was 50.11 years old with female predominance. The most common symptoms were abdominal pain (77.78%), palpable mass (27.78%) and intestinal bleeding (16.67%). With the different gross and microscopic findings, the adult intestinal lymphangioma could be classified as "simple", "polyposis", and "cystic cavernous". Intestinal lymphangioma in adults is a rare cause of abdominal discomfort but should be listed in differential diagnosis during daily practice. The morphology and classification may be different from pediatric group, and more large-scale studies are need for thorough investigation.


A new hybrid PM[Formula: see text] volatility forecasting model based on EMD and machine learning algorithms.
In recent years, the frequent occurrence of air pollution incidents has seriously affected people's health and life. Therefore, PM[Formula: see text], as the main pollutant, is an important research object of air pollution at present. Effectively improving the prediction accuracy of PM[Formula: see text] volatility makes the PM[Formula: see text] prediction content perfect, which is an important aspect of PM[Formula: see text] concentration research. The volatility series has an inherent complex function law, which drives the volatility movement. When machine learning algorithms such as LSTM (Long Short-Term Memory Network) and SVM (Support Vector Machine) are used for volatility analysis, a high-order nonlinear form is used to fit the functional law of the volatility series, but the time-frequency information of the volatility has not been utilized. Based on EMD (Empirical Mode Decomposition) technique, GARCH (Generalized AutoRegressive Conditional Heteroskedasticity) model and machine learning algorithms, a new hybrid PM[Formula: see text] volatility prediction model is proposed in this study. This model realizes time-frequency characteristic extraction of volatility series through EMD technology, and integrates residual and historical volatility information through GARCH model. The simulation results of the proposed model are verified by comparing the samples of 54 cities in North China with the benchmark models. The experimental results in Beijing showed that MAE (mean absolute deviation) of hybrid-LSTM decreased from 0.00875 to 0.00718 compared with LSTM, and hybrid-SVM based on the basic model SVM also significantly improved generalization ability, and its IA (index of agreement) improved from 0.846707 to 0.96595, showing the best performance. The experimental results show that the hybrid model is superior to other considered models in terms of prediction accuracy and stability, which verifies that the hybrid system modeling method is suitable for PM[Formula: see text] volatility analysis.


Risk factors for neonatal thyroid dysfunction in pregnancies complicated by Graves' disease.
To determine the factors related to adverse pregnancy outcomes and neonatal thyroid dysfunction in pregnancies complicated by Graves' disease. Thirty-five pregnancies complicated by Graves' disease were divided into two groups: adverse pregnancy outcome (n=15) and no adverse pregnancy outcome (n=20). Adverse pregnancy outcomes included spontaneous abortion, stillbirth, premature delivery, fetal growth restriction, and pregnancy-induced hypertension. The 31 pregnancies resulting in live births were also divided into two groups: neonatal thyroid dysfunction (n=9) and normal neonatal thyroid function (n=22). Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), TSH-receptor antibody (TRAb), the duration of hyperthyroidism in pregnancy, doses of antithyroid medication, and the duration of maternal antithyroid medication throughout pregnancy were compared. There were no significant differences in these factors between pregnancies with an adverse pregnancy outcome and those with no adverse pregnancy outcome. However, serum levels of FT4, TRAb, the duration of hyperthyroidism in pregnancy, the maximum daily dose of antithyroid medication, and the total dose of antithyroid medication were significantly different between pregnancies with neonatal thyroid dysfunction and those with normal neonatal thyroid function. Multivariate logistic regression analysis showed that the FT4 level in mothers was a significant factor related to the development of neonatal thyroid dysfunction (odds ratio 28.84, 95% confidence interval 1.65-503.62, p<0.05). Graves' disease activity in women of childbearing age should be well controlled prior to conception.


Immunological evidence for the presence of hormone-sensitive lipase in rat tissues other than adipose tissue.
A polyclonal rabbit antibody was used to detect hormone-sensitive lipase in rat organs other than white adipose tissue. Inhibition of tissue diacylglycerol lipase activity by the anti-hormone-sensitive lipase, and by NaF, Hg2+ and diisopropyl fluorophosphate, known inhibitors of the hormone-sensitive lipase, demonstrated its presence in the adrenals, ovaries, testes, heart and skeletal muscle, but not in the liver and kidneys. After enrichment by immunoprecipitation an immunoreactive protein, corresponding to the adipose tissue hormone-sensitive lipase 84 kDa subunit, and some additional, higher Mrapp proteins, were detected by Western blotting in the same tissues. The adipose tissue contained greater than 80% of the total hormone-sensitive lipase, with 5-10- and 50-100-fold lower specific activity in the steroid-producing and the muscle tissues, respectively.


Old age and underlying interstitial abnormalities are risk factors for development of ARDS after pleurodesis using limited amount of large particle size talc.
Talc pleurodesis is commonly performed to manage refractory pleural effusion or pneumothorax. It is considered as a safe procedure as long as a limited amount of large particle size talc is used. However, acute respiratory distress syndrome (ARDS) is a rare but serious complication after talc pleurodesis. We sought to determine the risk factors for the development of ARDS after pleurodesis using a limited amount of large particle size talc. We retrospectively reviewed patients who underwent pleurodesis with talc or OK-432 at the University of Tokyo Hospital. Twenty-seven and 35 patients underwent chemical pleurodesis using large particle size talc (4 g or less) or OK-432, respectively. Four of 27 (15%) patients developed ARDS after talc pleurodesis. Patients who developed ARDS were significantly older than those who did not (median 80 vs 66 years, P = 0.02) and had a higher prevalence of underlying interstitial abnormalities on chest computed tomography (CT; 2/4 vs 1/23, P < 0.05). No patient developed ARDS after pleurodesis with OK-432. This is the first case series of ARDS after pleurodesis using a limited amount of large particle size talc. Older age and underlying interstitial abnormalities on chest CT seem to be risk factors for developing ARDS after talc pleurodesis.


Leaf water potentials, fire and the regeneration of mallee eucalypts in semi-arid, south-eastern Australia.
Comparisons of predawn leaf water potential were made between adults, seedlings and coppicing lignotubers of yellow mallee, Eucalyptus incrassata Labill., during a period of severe drought between December 1981 and March 1983. Measurements were made on plants from areas which were one year, four years, and more than twenty years unburnt.Seedlings and coppice regrowth from sites burnt one year previously had significantly higher leaf water potentials than plants from older sites. Little change in water status of long-established plants occurred, despite the drought. There was no difference in the water potentials of plants from sites which were more than four years unburnt. Seedlings of both the one year old and four year old cohorts suffered mortality rates of more than 50% during the summer season towards the end of the drought when leaf water potentials had decreased to -4 MPa.It is suggested that the difference in plant water status, observed between sites which were one year unburnt and older sites, was due to a temporary cessation of the depletion of soil moisture reserves by the vegetation. Fire results in complete defoliation of established vegetation and it is some years before community evapotranspiration returns to pre-fire levels.


Effects of physical exercise in people with epilepsy: A systematic review and meta-analysis.
Studies suggest that physical exercise lead to improvements in the psychosocial dimension, associated comorbidities as well as to a higher quality of life (QoL) in people with epilepsy. However, there is a need to provide evidence-based guidelines for its prescription. Therefore, this review aimed to systematically evaluate and meta-analyze the available data on the potential effects of physical exercise training programs in people with epilepsy. Four electronic databases (MEDLINE/PubMed, PEDro, SPORTDiscuss and Scopus) were searched systematically from their inception until April 2022 for randomized controlled trials (RCTs), comparative studies and non-controlled studies that provided information regarding the effects of physical exercise training programs on people with epilepsy. The studies' methodological quality assessment was performed using the PEDro, the MINORS and the Quality Assessment Tool for Before-After Studies with No Control Group scales. For the meta-analysis, inverse variance or generic inverse variance was use to report mean difference or standardized mean difference for continuous data and their 95% confidence intervals (CI). Heterogeneity was assessed with the Chi-squared test and I2 test. After removing duplicated studies, 82 results were retrieved by the literature search and 14 were eligible for full text search. Finally, 14 studies with a methodological quality ranging from good to low quality met the inclusion criteria. Totally, 331 people with epilepsy were evaluated. Significant changes between preand post-intervention results in the exercise intervention groups were observed for QoL, fitness level, psycho-affective and neurocognitive outcomes. Findings from the meta-analysis indicated that moderate exercise led to a non-significant decrease (p = 0.08, Chi-squared test) in seizure frequency (SMD 0.33 95% CI 0.04; 0.70), while a significant effect of exercise was observed on QoL with a mean improvement of 4.72 percentage points (95% CI 0.58; 8.86, p = 0.03). Improvements on QoL, fitness level, psycho-affective and neurocognitive outcomes can be achieved through exercise training in people with epilepsy. Altogether, the findings suggest that people with epilepsy can benefit from exercising.


Pathology of bilateral pulvinar degeneration following long duration status epilepticus.
To define the neuropathological findings of pulvinar degeneration seen in long duration status epilepticus. We review the clinical, radiologic, neurophysiologic, investigational and neuropathological findings on a 27 year old woman who died after 162 days of prolonged refractory status epilepticus. Continuous EEG monitoring confirmed recurrent uncontrolled seizure activity bilaterally and independently, most frequent in the right fronto-temporal region. Initial MRI of the brain was normal. Repeat study until on day 127 of admission showed advanced changes, with bilateral pulvinar T2/FLAIR hyperintensities. The autopsy revealed sharply defined, grey, soft, granular nodules in each medial pulvinar nucleus. Microscopically these consisted of sharply defined paucicellular areas with loss of neurons and myelin and with numerous macrophages in their centers, surrounded by reactive astrocytes with relatively spared of axons. The spinal cord at cervical and thoracic levels showed symmetric spongy vacuolation in the central part of the dorsal columns and lateral corticospinal tracts, with mild myelin loss, relatively preserved axons. The pathological lesions found in this case in thepulvinar are somewhat similar to the pathologic lesions described in Wernicke's encephalopathy. Those found in the spinal cord of our patient resemble characteristic features of B12 related subacute combined degeneration. Characteristic pulvinar degeneration may be found as an acquired phenomenon in prolonged refractory status epilepticus. We hypothesize that the neuropathological findings result from an excessive focal metabolic demand, secondary to neuronal network over activation in the setting of prolonged, frequent bi-temporal seizures.


Transient effects of chemotherapy for testicular cancer on mouse behaviour.
The treatment of testicular cancer includes unilateral orchiectomy and chemotherapy and is curative for most patients. However, observational studies revealed an association with depression, anxiety and cognitive impairment. It is unclear whether these side effects are caused by chemotherapy, hemicastration or the disease itself. The aim of our study was to analyse the behavioural effects of hemicastration and chemotherapy in adult male mice. The animals were randomly divided into four groups - control, chemotherapy, hemicastration and hemicastration with chemotherapy. After chemotherapy that included three cycles of bleomycin, etoposide, cisplatin mice underwent a battery of behavioural tests. To assess the long-term effects animals were tested also 3 months after the end of treatment. Chemotherapy led to lower locomotor- and exploratory activity, higher anxiety-like behaviour and worse spatial memory immediately after treatment. These behavioural effects were not present three months later. Hemicastration had no effect on most of the observed outcomes. In conclusion, adverse behavioural effects induced by chemotherapy in mice are transient and disappear later in life. Further studies are needed to elucidate the mechanisms responsible for the observed effects.


[The nature of methanol-induced acidification of the medium by products of metabolism of methylotrophic yeasts].
The washed cells of Hansenula polymorpha and Pichia pinus grown on the medium with methanol rapidly acidify the medium during incubation with the mentioned alcohol or formaldehyde. It is found that proton extrusion is coupled with formate anion efflux. Acidification is proved to be energy-dependent process since it is inhibited by respiration poisons, uncouplers of oxidative phosphorylation, and by ATPase inhibitors.


Antimicrobial photodynamic therapy mediated by methylene blue in surfactant vehicle as adjuvant to periodontal treatment. Randomized, controlled, double-blind clinical trial.
Antimicrobial photodymanic therapy mediated by methylene blue has been investigated as an adjunctive to periodontal treatment but the dimerization of photosensitizer molecules reduces the phototoxic effects. Sodium dodecyl sulfate is a surfactant that may control this aggregation. The aim of this study was evaluated the photodynamic effect of methylene blue in sodium dodecyl sulfate in periodontitis. 36 participants with periodontitis were selected and allocated randomly in two group for intervention and other two for control - all of them were treated with scaling and root planing before aPDT. Three periodontal evaluations were done: at the selection time, at the day of intervention and thirty-day after this. Pre-irradiation time was 1 min and 2 min for irradiation. Laser (Therapy XT, DMC, São Carlos, Brazil) with wavelength of 660 nm and 100 mW of power was used. Two photosensitizer solutions with 100 µM methylene blue was used, one of them was in water and other in 0,25% of sodium dodecyl sulfate. Two sites of each participant were selected for the experimental procedures. Microbiological evaluations were performed to quantify microorganisms before and immediately after intervention. Quantitative microbiological evaluation was the primary outcome; morphological aspects of bacterial colony, and clinical probing depth was the secondary one. There was no significant difference between the groups in both bacterial reduction and the clinical parameter evaluated. The effect of methylene blue in surfactant did not cause enough phototoxic effects that could promote reduction of periodontal pocket depth.


Enzalutamide in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer: An Asian Multiregional, Randomized Study.
Enzalutamide significantly improved clinical outcomes compared with placebo in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) with disease progression despite androgen deprivation therapy (ADT) in the PREVAIL study. However, few patients from Asia were enrolled. Our study (NCT02294461) aimed to evaluate the safety and efficacy of enzalutamide in this disease setting in patients in mainland China, Korea, Taiwan, and Hong Kong. In this double-blind, phase III study, patients with asymptomatic/mildly symptomatic metastatic prostate cancer and disease progression despite ADT were randomized to enzalutamide (160 mg/day) or placebo. The primary endpoint was time to prostate-specific antigen (PSA) progression. Secondary endpoints included overall survival, radiographic progression-free survival, time to first skeletal-related event (SRE), time to initiation of cytotoxic chemotherapy, PSA response ≥ 50%, best overall soft-tissue response, and safety. Pre-planned interim analysis was scheduled following approximately 175 PSA-progression events (67% of targeted total of 261 events). An additional 5-year landmark analysis of overall survival, time to antineoplastic therapy, and safety was performed. The double-blind study period was stopped after interim analysis owing to the benefit of enzalutamide over placebo. Overall, 388 patients were randomized (enzalutamide, n = 198; placebo, n = 190). Baseline characteristics were balanced between treatment groups. Enzalutamide significantly reduced risk of PSA progression vs placebo (hazard ratio 0.38; 95% CI 0.27-0.52; P < 0.0001). Median time to PSA progression was 8.31 months with enzalutamide and 2.86 months with placebo. Secondary endpoints, including 5-year overall survival, were significantly improved with enzalutamide, except time to first SRE. Adverse-event incidence was similar between enzalutamide and placebo. Fatigue was the most common drug-related adverse event in both treatment groups. Enzalutamide significantly reduced risk of PSA progression, improved secondary efficacy endpoints, and was well tolerated in chemotherapy-naïve Asian patients with mCRPC with disease progression despite ADT. www. gov NCT02294461.


Study about the combination strategy of Bacillus subtilis wt55 with AiiO-AIO6 to improve the resistance of zebrafish to Aeromonas veronii infection.
Disease problems will seriously restrict the sustainable development of aquaculture, and the environmental-friendly prevention strategies are urgently needed. Probiotics and quorum-quenching enzyme are innovative strategies to control bacterial diseases. Firstly, the bacteriostatic activity of Bacillus subtilis wt55 strain and quenching enzyme AiiO-AIO6 on the growth of Aeromonas veronii were tested in vitro, and the results showed wt55 inhibit the growth of A. veronii, but AiiO-AIO6 did not. Then, the synergistic effects of simple combination of B. subtilis wt55 and AiiO-AIO6 were evaluated next. The results showed this combination could improve the survival rate and significantly reduce the number of invasive A. veronii in gut after challenge compared to the other groups, corresponding to the lower intestinal alkaline phosphatase activity. One of its effect mechanisms is the combination could inhibit the growth of A. veronii in vitro; the other is direct immersion of germ-free zebrafish proved AiiO-AIO6 did not directly regulate the innate immune response of the host, but wt55 did it, and the simple combination group could significantly reduce the expression of nuclear factor kappa-B (NF-κB) and proinflammatory cytokine interleukin-1β (IL-1β), increase the expression of lysozyme gene; and the third is intestinal microbiota also plays a regulatory role: the gut microbiota from combination group could significantly inhibit the expression of IL-1β and NF-κB, and increased the expression of transforming growth factor-β (TGF-β) and lysozyme. Given the effectiveness of this simple combination, a B. subtilis quorum-quenching recombinant expression strain in which AiiO-AIO6 was surface displayed on the spores and secreted by vegetative cells was built. The results showed that the survival rate after challenge was lower than that of the group treated with AiiO-AIO6 or wt55 alone, and the expression of proinflammatory cytokine IL-1β and NF-κB were significantly higher. Our study demonstrated the effectiveness of B. subtilis and AiiO-AIO6 simple combination and established an efficient B. subtilis expression system.


Sonographic features of intra-abdominal abscess caused by spilled stones during laparoscopic cholecystectomy.
Spillage of stones into the abdominal cavity resulting from perforation of the gallbladder is one of the common complications of laparoscopic cholecystectomy. Although many surgeons know that stones left in the abdominal cavity can cause late visceral abscess requiring surgical treatment, the sonographic features of such abscesses have not yet to be thoroughly investigated. We investigated the sonographic features of intra-abdominal abscesses caused by spilled stones after laparoscopic cholecystectomy using Hitachi Model EUB-525 (3.5 MHz) and Aloka Model SSD-5500 (3.75 MHz) ultrasound systems. Two thousand thirty-six laparoscopic cholecystectomy procedures were carried out at this institution from 1990 through 2001. During this period, we encountered seven cases of intra-abdominal abscess. Three of these cases were symptomatic, but abscess, granulation, or both, were found incidentally by ultrasonography in the other four patients during routine annual health examinations. Laparotomy and open drainage of pus and gallstones from the intra-abdominal abscess were necessary in five cases. Ultrasonography revealed a mass in six of the seven patients. The abscesses were located in either the right subphrenic or subhepatic space on the surface of the liver and were sometimes difficult to distinguish from liver tumors. Ultrasound showed the abscesses as oval, low-echoic, solid masses with posterior enhancement. They ranged from 20 to 58 mm in diameter, had clear margins and highly echoic peripheral rims, and showed lateral shadowing. The lesions also contained several highly echoic spots with acoustic shadows that were thought to be the spilled stones. We conclude that visceral abscess should be considered after laparoscopic cholecystectomy, and that careful observation using ultrasonography is required, especially when the gallbladder is perforated and bile and stones have spilled out.


THE ROLE OF LYMPHADENECTOMY IN PROSTATE CANCER PATIENTS.
Prostate cancer is one of the most important men's health issues in developed countries. For patients with prostate cancer a preoperative staging of the disease must be made. Involvement of lymph nodes could be assessed using imaging methods (CT or/and MRI), however, newer methods also exist (PET/CT, PSMA PET/CT). For some patients during radical prostatectomy a pelvic lymphadenectomy is recommended. Pelvic lymphadenectomy is indicated in intermediate- and high-risk group patients and with increased probability of lymph node invasion. The most used prediction tools for preoperative assessment of lymph nodes are Briganti and MSKCC nomograms and Partin tables. Pelvic lymphadenectomy can include different lymph nodes group, but extended lymphadenectomy is the recommended procedure. In 1-20% of patients, the lymph node invasion is present. Pelvic lymphadenectomy is primarily a diagnostic and staging method, and in minority of patients with positive lymph nodes it can be a curative method, too. In other patients with positive lymph nodes adjuvant therapy (radiotherapy and androgen deprivation therapy) can be beneficial.


Impact of transitioning to an active, noninterruptive CYP2C19/proton pump inhibitor alert on prescribing patterns.
To compare rates of prescriber acceptance of interruptive and noninterruptive clinical decision support (CDS) alerts regarding potential diminished therapeutic effectiveness and safety risks associated with proton pump inhibitor (PPI) use in carriers of gene variants affecting cytochrome P450 (CYP) isozyme 2C19 metabolism. A retrospective study was conducted at a large rural health system to examine different approaches to improving CDS alert acceptance while minimizing alert fatigue. Manual reviews were conducted to identify alerts regarding CYP2C19 metabolizer status displayed at the time of PPI ordering over 30-day periods before and after the transition from interruptive to noninterruptive CDS alert functionality. A chi-square test was conducted to analyze prescriber acceptance of CDS recommendations by alert modality and type of treatment modification. Overall, interruptive alerts had an acceptance rate of 18.6% (64/344), compared to 8.4% acceptance (30/357 alerts) for noninterruptive alerts (P ≤ 0.0001). Analysis of acceptance criteria -revealed the noninterruptive alert cohort had higher acceptance, as determined by documented medication dose adjustments, than the interruptive alert cohort (53.3% [16/30] and 4.7% [3/64], respectively). The difference in acceptance rates by CDS modality and treatment modification was statistically significant (P ≤ 0.00001). The predominant indication for PPI use was gastroesophageal reflux disease (GERD) in both cohorts. Interruptive alerts that actively influenced workflow had higher acceptance rates than noninterruptive alerts that served an informational purpose without a direct disruption of workflow. The study results suggest the utilization of noninterruptive alerts may be a beneficial tool for prompting clinicians to alter dosing regimens rather than transition to an alternative agent.


Injurious pecking in organic turkey fattening-effects of husbandry and feeding on injuries and plumage damage of a slow- (Auburn) and a fast-growing (B.U.T.6) genotype.
Injuries and plumage damage (PD) are important indicators of welfare. First priority in turkey fattening is to reduce injurious pecking, which includes aggressive pecking (agonistic behavior) and additionally severe feather pecking (SFP) and cannibalism with their multifactorial reasons. Still, there are few studies available evaluating different genotypes for their welfare status under organic conditions. The aim of this study was to investigate the effects of genotype and husbandry with 100% organic feeding (2 variants with different riboflavin content: V1 and V2) on injuries and PD. During rearing nonbeaktrimmed male turkeys of a slow- (Auburn, n = 256) and fast-growing (B.U.T.6, n = 128) genotype were kept in 2 indoor housing systems (without environmental enrichment (EE) = H1-, n = 144 and with EE = H2+, n = 240). During fattening 13 animals per pen of H2+ were relocated to a free-range system (H3 MS, n = 104). EE included pecking stones, elevated seating platforms and silage feeding. The study included five 4-wk feeding phases. At the end of each phase, injuries and PD were scored to assess animal welfare. Injury scores ranged from 0 (=no damage) to 3 (=severe damage) and PD from 0 to 4. Injurious pecking was observed from the 8th week onward (injuries: 16.5% and PD: 31.4%). Binary logistic regression models showed that both indicators were affected by genotype (each P < 0.001), husbandry (each P < 0.001), feeding (injuries P = 0.004; PD P = 0.003), and age (each P < 0.001). Auburn showed less injuries and PD than B.U.T.6. H1- had the fewest injuries and PD for Auburn animals compared to H2+ or H3 MS. In summary, the use of alternative genotypes (Auburn) in organic fattening improved welfare, but keeping them in free-range systems or in husbandry with EE, does not lead to a reduction of injurious pecking. Therefore, further studies are needed with more and changing enrichment materials, further management measures, changes in housing structure, and even more intensive animal care.


What do people die from? The challenges of measuring disease burden posed by multi-morbidity.
Determining the precise cause of death of an individual has become increasingly difficult as life prolonging treatments mean that many people may die with multiple disorders, any of which, individually or in concert, might have killed them. Yet this problem has been recognised from the very earliest attempts to develop classifications of diseases. This paper traces the evolution of thinking on death certification and disease classification, describing what has been achieved but also identifying what more needs to be done to advance research and inform policy.


Pelvic pain comorbidities associated with quality of life after endometriosis surgery.
After endometriosis surgery, pain can persist or recur in a subset of patients. A possible reason for persistent pain after surgery is central nervous system sensitization and associated pelvic pain comorbidities. Surgery addresses the peripheral component of endometriosis pain pathophysiology (by lesion removal) but may not treat this centralized pain. Therefore, endometriosis patients with pelvic pain comorbidities related to central sensitization may experience worse pain-related outcomes after surgery, such as lower pain-related quality of life. This study aimed to determine whether baseline (preoperative) pelvic pain comorbidities are associated with pain-related quality of life at follow-up after endometriosis surgery. This study used longitudinal prospective registry data from the Endometriosis Pelvic Pain Interdisciplinary Cohort at the BC Women's Centre for Pelvic Pain and Endometriosis. Participants were aged ≤50 years with confirmed or clinically suspected endometriosis, and underwent surgery (fertility-sparing or hysterectomy) for endometriosis pain. Participants completed the pain subscale of the Endometriosis Health Profile-30 quality of life questionnaire preoperatively and at follow-up (1-2 years). Linear regression was performed to measure the individual relationships between 7 pelvic pain comorbidities at baseline and follow-up Endometriosis Health Profile-30 score, controlling for baseline Endometriosis Health Profile-30 and type of surgery received. These baseline (preoperative) pelvic pain comorbidities included abdominal wall pain, pelvic floor myalgia, painful bladder syndrome, irritable bowel syndrome, Patient Health Questionnaire 9 depression score, Generalized Anxiety Disorder 7 score, and Pain Catastrophizing Scale score. Least absolute shrinkage and selection operator regression was then performed to select the most important variables associated with follow-up Endometriosis Health Profile-30 from 17 covariates (including the 7 pelvic pain comorbidities, baseline Endometriosis Health Profile-30 score, type of surgery, and other endometriosis-related factors such as stage and histologic confirmation of endometriosis). Using 1000 bootstrap samples, we estimated the coefficients and confidence intervals of the selected variables and generated a covariate importance rank. The study included 444 participants. The median follow-up time was 18 months. Pain-related quality of life (Endometriosis Health Profile-30) of the study population significantly improved at follow-up after surgery (P<.001). The following pelvic pain comorbidities were associated with lower quality of life (higher Endometriosis Health Profile-30 score) after surgery, controlling for baseline Endometriosis Health Profile-30 score and type of surgery (fertility-sparing vs hysterectomy): abdominal wall pain (P=.013), pelvic floor myalgia (P=.036), painful bladder syndrome (P=.022), Patient Health Questionnaire 9 score (P<.001), Generalized Anxiety Disorder 7 score (P<.001), and Pain Catastrophizing Scale score (P=.007). Irritable bowel syndrome was not significant (P=.70). Of the 17 covariates included for least absolute shrinkage and selection operator regression, 6 remained in the final model (lambda=3.136). These included 3 pelvic pain comorbidities that were associated with higher follow-up Endometriosis Health Profile-30 scores or worse quality of life: abdominal wall pain (β=3.19), pelvic floor myalgia (β=2.44), and Patient Health Questionnaire 9 depression score (β=0.49). The other 3 variables in the final model were baseline Endometriosis Health Profile-30 score, type of surgery, and histologic confirmation of endometriosis. Pelvic pain comorbidities present at baseline before surgery, which may reflect underlying central nervous system sensitization, are associated with lower pain-related quality of life after endometriosis surgery. Particularly important were depression and musculoskeletal/myofascial pain (abdominal wall pain and pelvic floor myalgia). Therefore, these pelvic pain comorbidities should be candidates for a formal prediction model of pain outcomes after endometriosis surgery.


Immunohistochemical localization of voltage-activated calcium channels in the rat oesophagus.
Voltage-activated calcium channels play an important role in the physiology of the enteric nervous system. To determine which types of voltage-activated calcium channels are present in the rat oesophagus, an immunohistochemical study was performed using specific antibodies for the alpha1 subunits of Cav2.1 (P/Q-type), Cav2.2 (N-type), Cav1.2 and Cav1.3 (L-type) calcium channels. All myenteric cell bodies showed Cav2.2 immunoreactivity, whereas labelling for this N-type channel was absent in nerve fibres. Cav1.2 immunoreactivity was found on nerve fibres in the myenteric plexus and on fibres innervating the striated muscle of the rat oesophagus, whereas no labelling was detected on neuronal somata. Immunoreactivity against Cav1.3 was not detected in the myenteric plexus or at the level of the striated muscle. Labelling for Cav2.1 was absent at the level of the myenteric plexus, but present in the striated muscle layer at the level of the motor endplates. Comparison with recent literature data from rat small intestine reveals region-specific distribution patterns of the various subtypes of voltage-activated calcium channels within the enteric nervous system. In addition, the present immunohistochemical data corroborate our physiological data (see accompanying paper), which indicate that the Cav2.2 (N-type) channel is the predominant channel involved in the generation of the calcium-dependent action potential evoked by intrasomatic depolarizing current pulses in all rat oesophageal myenteric neurones.


The selenium state of children. II. Selenium content of serum, whole blood, hair and the activity of erythrocyte glutathione peroxidase in dietetically treated patients with phenylketonuria and maple-syrup-urine disease.
The selenium content of serum, whole blood and hair was measured by neutron activation analysis in dietetically treated patients with phenylketonuria (PKU) and maple-syrup-urine disease (MSUD). Follow-up studies showed a decrease of the serum selenium content and the glutathione peroxidase activity of erythrocytes--a selenoenzyme--from normal values at the beginning of the diet to 20% (selenium) and 50% (gluthione peroxidase) of normal within 10--12 weeks of dietary treatment. In 36 patients the serum selenium content was lower at 6.7--28 X 10(-9) g/ml, independent of the age of the patients (0.5 to 10 years). The selenium content of whole blood was reduced: median = 98 X 10(-9) g/g dry weight; range 75 to 165 X 10(-9) g/g dry weitht (healthy children: median = 381 X 10(-9) g/g dry weight; range 245 to 588 X 10(-9) g/g dry weight). The selenium content of hair was markedly lower in the patients (median = 62 X 10(-9) g/g; range 13--140 X 10(-9) g/g) than in healthy children (median = 429; range 213 to 720 X 10(-9) g/g). The mean glutathione peroxidase activity of erythrocytes was reduced to 4.6 +/- 0.64 U37/g Hb, comparison to normal values (mean = 8.8 +/- 0.88 U37/g Hb).


Proteomic Complexity in Parkinson's Disease: A Redox Signaling Perspective of the Pathophysiology and Progression.
Parkinson's disease (PD) is a prevalent age-related neurodegenerative disorder that results in the progressive impairment of motor and cognitive functions. The majority of PD cases are sporadic, and only 5% of patients are associated with mutations in a few genes, which cause the early onset or familial PD. Environmental toxic substances and the individual genetic susceptibility play a role in sporadic cases, but despite significant efforts to treat and prevent the disease, the pathophysiological mechanisms leading to its onset and progress are not fully understood. In the last decade, genomic and proteomic studies have shown an increasing molecular complexity of sporadic PD, suggesting that a broad spectrum of biochemical pathways underlie its progression. Recent investigations and the literature review suggest the potential role of deregulation of the sensitive-cysteine proteome as a convergent pathogenic mechanism that may contribute to this complexity, opening new therapeutic opportunities.