Utility of the backscattered ultrasonic A-mode signal for the quantitative grading of beef.
A feasibility study applicable to the IN VITRO differentiation of marbling in beef was conducted using signatures extracted from the A-mode backscattered ultrasonic signals. The energy and threshold count of these RF signals correlated well with the percentage of fat in beef sample determined by either extraction chemical test. As the value of n increases from 1 to 3 in the model for the amplitude attenuation in soft tissue, a(f) = aofn, the media of these values of n correspond from linear to nonlinear dependence of frequency in attenuation. This is observed to be analogous to beef with low to high marbling. The regressed gradient of the spectral differences between a reference spectrum from the sample with low percentage of fat and the spectra of other samples of increasing percentage of fat reveal an increase in gradient as the marbling increases. This phenomena is attributed to the change in the center frequency and the spectral bandwidth of a medium with changing physical scatterers' characteristic. These signatures, the energy, the threshold count and the gradient are then used to back predict the percentage of fat (marbling level).


Glibenclamide inhibits islet carnitine palmitoyltransferase 1 activity, leading to PKC-dependent insulin exocytosis.
Hypoglycemic sulfonylureas such as glibenclamide have been widely used to treat type 2 diabetic patients for 40 yr, but controversy remains about their mode of action. The widely held view is that they promote rapid insulin exocytosis by binding to and blocking pancreatic beta-cell ATP-dependent K+ (KATP) channels in the plasma membrane. This event stimulates Ca2+ influx and sets in motion the exocytotic release of insulin. However, recent reports show that >90% of glibenclamide-binding sites are localized intracellularly and that the drug can stimulate insulin release independently of changes in KATP channels and cytoplasmic free Ca2+. Also, glibenclamide specifically and progressively accumulates in islets in association with secretory granules and mitochondria and causes long-lasting insulin secretion. It has been proposed that nutrient insulin secretagogues stimulate insulin release by increasing formation of malonyl-CoA, which, by blocking carnitine palmitoyltransferase 1 (CPT-1), switches fatty acid (FA) catabolism to synthesis of PKC-activating lipids. We show that glibenclamide dose-dependently inhibits beta-cell CPT-1 activity, consequently suppressing FA oxidation to the same extent as glucose in cultured fetal rat islets. This is associated with enhanced diacylglycerol (DAG) formation, PKC activation, and KATP-independent glibenclamide-stimulated insulin exocytosis. The fat oxidation inhibitor etomoxir stimulated KATP-independent insulin secretion to the same extent as glibenclamide, and the action of both drugs was not additive. We propose a mechanism in which inhibition of CPT-1 activity by glibenclamide switches beta-cell FA metabolism to DAG synthesis and subsequent PKC-dependent and KATP-independent insulin exocytosis. We suggest that chronic CPT inhibition, through the progressive islet accumulation of glibenclamide, may explain the prolonged stimulation of insulin secretion in some diabetic patients even after drug removal that contributes to the sustained hypoglycemia of the sulfonylurea.


The effect of inspiratory muscle training on respiratory variables in a patient with ankylosing spondylitis: A case report.
Ankylosing Spondylitis (AS) presents with both musculoskeletal and cardiorespiratory pathophysiological manifestations. Inspiratory muscle training (IMT) may be a useful intervention to address deficits in respiratory and functional status. A 25-year-old male with AS initially sought treatment for low back and right hip pain, but 7 weeks of IMT was also provided due to abnormal respiratory performance. At baseline, the patient presented with a resting respiratory rate (RR) of 14.5 breaths/minute, tidal volume (TV) of 0.76 L, minute ventilation (VE) of 10.87 L/min, and end tidal CO2 (PetCO2) of 30.56 mmHg. Baseline exercise test results revealed a VO2max of 44 ml/kg/min and VE to CO2 output (VE/VCO2) slope of 30. Baseline MIP, SMIP, and MEP were 54 cm H2O, 507 PTU, and 87 cm H2O, respectively, and increased to 176 cm H2O, 807 PTU, and 151 cm H2O, respectively, after IMT. The VO2max increased to 51 ml/kg/min with decreases in the VE/VCO2 slope (29), resting RR (12 breaths/minute), resting TV (0.52 L), and resting VE (6.83 L/min) after IMT. Improvements during postural challenges were also observed. This case demonstrates the clinical utility of respiratory gas analysis and respiratory performance measures to identify functional deficits and manage a patient with AS. The improvements in respiratory performance at rest, during postural challenges, and during maximal exercise after a relatively short period of IMT highlights the role IMT may have to improve functional status in patients with AS. Further investigation of IMT in patients with AS is warranted.


Virtual Knowledge Brokering: Describing the Roles and Strategies Used by Knowledge Brokers in a Pediatric Physiotherapy Virtual Community of Practice.
Knowledge transfer in pediatric rehabilitation is challenging and requires active, multifaceted strategies. The use of knowledge brokers (KBs) is one such strategy noted to promote clinician behavior change. The success of using KBs to transfer knowledge relies on their ability to adapt to ever-changing clinical contexts. In addition, with the rapid growth of online platforms as knowledge transfer forums, KBs must become effective in virtual environments. Although the role of KBs has been studied in various clinical contexts, their emerging role in specific online environments designed to support evidence-based behavior change has not yet been described. Our objective is to describe the roles of, and strategies used by, four KBs involved in a virtual community of practice to guide and inform future online KB interventions. A descriptive design guided this study and a thematic content analysis process was used to analyze online KB postings. The Promoting Action on Research in Health Sciences knowledge transfer framework and online andragogical learning theories assisted in the coding. A thematic map was created illustrating the links between KBs' strategies and emerging roles in the virtual environment. We analyzed 95 posts and identified three roles: 1) context architect: promoting a respectful learning environment, 2) knowledge sharing promoter: building capacity, and 3) linkage creator: connecting research-to-practice. Strategies used by KBs reflected invitational, constructivism, and connectivism approaches, with roles and strategies changing over time. This study increases our understanding of the actions of KBs in virtual contexts to foster uptake of research evidence in pediatric physiotherapy. Our results provide valuable information about the knowledge and skills required by individuals to fulfill this role in virtual environments.


Heparin priming of EUS-FNA needles does not adversely affect tissue cytology or immunohistochemical staining.
Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) or biopsy (FNB) is an indispensable diagnostic tool. Improvements in needling technique have led to increasing tissue yields. Blood clogging of the needle can cause difficulties with specimen handling and stylet passage, which improves when the needle is primed with heparin before use. However, the effect of heparin on cytology, histology or immunochemistry (IHC) of FNA and FNB specimens is unknown. The goal of the study was to evaluate heparin priming on cytologic/histologic appearance, IHC staining, ease of stylet passage, and specimen bloodiness. This was a retrospective study of patients undergoing EUS-FNA/FNB. Needle sizes were 25 gauge (g), 22 g, and 19 g. Heparin priming of the needle was done and the stylet replaced ("dry heparin") or suction attached without replacing the stylet ("wet heparin"). Smears and cellblocks were examined by pathologists, and IHC staining were done as needed. Specimen bloodiness was compared with matched controls. Adequate tissue yields were obtained in all samples (37 heparin, 36 no heparin). Heparin priming did not exhibit negative effects on cytologic or histologic interpretation of the specimens, nor IHC. There was no difference in cellblock bloodiness between the heparin primed needle specimens and the non-heparin control group. . Heparin priming of EUS-FNA or FNB needles does not negatively affect cytologic or histologic interpretation, nor interfere with IHC. In addition, heparin priming does not increase specimen bloodiness. When the "wet suction" technique is used for EUS-FNA, heparin priming can be used instead of saline priming of the EUS needle.


An Analysis of Mental State Verb and Complex Syntax Use in Children Who Are Deaf and Hard of Hearing.
Children who are deaf and hard of hearing (DHH) have documented deficits with complex syntax and vocabulary knowledge. Mental state verbs (MSVs) are necessary for some kinds of complex syntax use and communicate abstract concepts needed for academic language. The purpose of this study was to examine the frequency, diversity, and syntactic context of MSV use in children who are DHH compared to children with typical hearing (CTH). Seventy-three preschool children (23 with cochlear implants, 22 with hearing aids, and 28 with typical hearing) completed a structured language sample as part of a larger assessment battery. Samples were analyzed and compared across groups for use of MSVs, diversity in MSV use, and syntactical context for MSVs. Children who are DHH used significantly fewer MSV in complex syntax, a smaller diversity of MSV, and significantly fewer MSV in obligatory contexts compared to CTH. Results for the cochlear implants and hearing aid groups were not significantly different from one another despite differing levels of hearing loss. Children who are DHH demonstrate significant differences in the rate, diversity, and complexity of MSV use compared to peers with typical hearing. https://doi.org/10.23641/asha.24091860.


Community-Engaged Strategies to Increase Diversity of Participants in Health Education Research.
Minorities have historically been underrepresented in health-related research. Several strategies have been recommended to increase the participation of minorities in health-related research. However, most of the recommendations and guidelines apply to research in clinical or laboratory contexts. One of the more prominent methods to enhance minority participation in health-related research that has recently come to the fore is the use of community-engaged strategies. The purpose of this article is to summarize community-engaged outreach efforts that can be translated into useable strategies for health education research teams seeking to diversify the pool of research participants. Also, we provide a succinct overview of the various components of a research endeavor that may influence minority participation in health-related research. Finally, we analyze how health education specialists and SOPHE (Society of Public Health Education) can play a leading role in helping enhance minority participation in health-related research.


[Rare thyroid tumors: spindle-cell epithelial tumor and thyroid carcinoma with thymus-like differentiation].
The paper describes 2 cases of spindle-cell epithelial thyroid tumors (SETTLE) and carcinoma showing thymus-like differentiation (CASTLE). They are rare types of thyroid tumors and must be distinguished from medullary carcinoma, anaplastic carcinoma, synovial sarcoma and malignant teratoma. The presented cases show both common and unusual features as compared with the previously described tumors. CASTLE probably arises from ectopic thymus tissue. The further examination is needed to highlight the histogenesis of SETTLE, and to collect additional data on its aggressiveness and clinical outcome.


Metabolomic analysis identifies dysregulation of lipid metabolism in the immune clearance phase of chronic hepatitis B patients.
There is an accelerated progression of liver necroinflammation and fibrosis in the liver during the immune clearance (IC) phase of Chronic hepatitis B virus (HBV) infection, which are critical indicators of antiviral treatment for chronic hepatitis B (CHB) infection. This study applied serum metabolomics to identify the potential metabolite biomarkers for differential diagnosis between the CHB immune tolerance (IT) and Immune clearance (IC) phases. A liquid chromatography-mass spectrometry (LC-MS)-based approach was applied to evaluate and compared the serum metabolic profiles of 28 patients in IT phase and 33 patients in IC phase and appropriate statistical methods with MetaboAnalystR 2.0 R package to analyze those metabolites. The differential metabolites between IT and TC groups were classified and the top altered classification were lipids and lipid-like molecules and fatty acyls, clearly indicating that there were differences in the lipid metabolomic profile of HBV-infected patients with IT vs. IR phase. We identified the top 10 potential metabolite biomarkers for differential diagnosis between IT and IR. There were four lipid metabolites among them and the AUC of two of them, octadecadienoyl-sn-glycero-3-phosphocholine and 3-Cycloheptene-l-acetic acid, were 0.983 and 0.933. octadecadienoyl-sn-glycero-3-phosphocholine is Diacylglycerol (18:2n6/18:0) and 3-Cycloheptene-l-acetic acid is hydroxy fatty acids, both of which were associated with lipid metabolism. This study not only provides the potential metabolic biomarkers but also insight into the mechanism of CHB progression during IT clearance phase.


Nurses have a leading role in weaning patients from mechanical ventilation (WMV) given their constant presence and their continuous monitoring. To promote proper WMV, nurses must exercise autonomy and be involved in decision-making. However, in certain care contexts, there is little involvement of nurses. The purpose of this text is to establish the characteristics of the concept of autonomous decision-making applied to nursing during WMV. An analysis of this concept was carried out according to the evolutionary method of Rodgers. The identification of the attributes, antecedents, and consequences made it possible to note ambiguity in the definition of this concept. Nurses use autonomous decision-making for the execution of assigned tasks and when they make decisions according to a pre-prescribed decision-making algorithm. Significant foundations for the decision-making autonomy of critical care nurses during WMV emerged from this analysis : scope of practice, in-depth knowledge of the patient, and commitment to the success of WMV. Participation in interdependent decision-making allows nurses to bring the patient's perspective into decisions. Avenues of reflection have also emerged, including decisions based on evidence to provide new avenues for autonomous decision-making.


The potential geographical distribution and phenology of Bemisia tabaci Middle East/Asia Minor 1, considering irrigation and glasshouse production.
The Bemisia tabaci species complex is one of the most important pests of open field and protected cropping globally. Within this complex, one species (Middle East Asia Minor 1, B. tabaci MEAM1, formerly biotype B) has been especially problematic, invading widely and spreading a large variety of plant pathogens, and developing broad spectrum pesticide resistance. Here, we fit a CLIMEX model to the distribution records of B. tabaci MEAM1, using experimental observations to calibrate its temperature responses. In fitting the model, we consider the effects of irrigation and glasshouses in extending its potential range. The validated niche model estimates its potential distribution as being considerably broader than its present known distribution, especially in the Americas, Africa and Asia. The potential distribution of the fitted model encompasses the known distribution of B. tabaci sensu lato, highlighting the magnitude of the threat posed globally by this invasive pest species complex and the viruses it vectors to open field and protected agriculture.


Formation of DNA:RNA hybrid G-quadruplexes of two G-quartet layers in transcription: expansion of the prevalence and diversity of G-quadruplexes in genomes.
G-quadruplexes are implicated in important cellular processes. Previous studies mostly focused on intramolecular G-quadruplexes of three or more G-quartets. Those composed of two G-quartets were only shown to form in single-stranded oligonucleotides. On the basis of electrophoresis, DMS footprinting, fluorescence labeling, and photo-cross-linking, we detected the formation of DNA:RNA hybrid G-quadruplexes (HQs) of two G-quartets during the transcription of DNA duplexes. These HQs have a lifetime on the minute scale and are stabilized by a stabilizing ligand. They are far shorter-lived than the HQs of three G-quartets, which last for hours. The occurrence of putative formation motifs of such HQs shows a transcription-dependent strand-biased selection, thus supporting their formation and function in genomes. They are present in almost all human genes in large amounts. We speculate that the two-G-quartet HQs may be a distinct type of G-quadruplexes that may play a role in timely responsive processes and for purposes of fine-tuning.


Retargeting sleeping beauty transposon insertions by engineered zinc finger DNA-binding domains.
The Sleeping Beauty (SB) transposon is a nonviral, integrating vector system with proven efficacy in preclinical animal models, and thus holds promise for future clinical applications. However, SB has a close-to-random insertion profile that could lead to genotoxic effects, thereby presenting a potential safety issue. We evaluated zinc finger (ZF) DNA-binding domains (DBDs) for their abilities to introduce a bias into SB's insertion profile. E2C, that binds a unique site in the erbB-2 gene, mediated locus-specific transposon insertions at low frequencies. A novel ZF targeting LINE1 repeats, ZF-B, showed specific binding to an 18-bp site represented by ~12,000 copies in the human genome. We mapped SB insertions using linear-amplification (LAM)-PCR and Illumina sequencing. Targeted insertions with ZF-B peaked at approximately fourfold enrichment of transposition around ZF-B binding sites yielding ~45% overall frequency of insertion into LINE1. A decrease in the ZF-B dataset with respect to transposon insertions in genes was found, suggesting that LINE1 repeats act as a sponge that "soak up" a fraction of SB insertions and thereby redirect them away from genes. Improvements in ZF technology and a careful choice of targeted genomic regions may improve the safety profile of SB for future clinical applications.


Novel RB1 germline mutation in a healthy man.
Retinoblastoma (Rb) most frequently presents as a unilateral sporadic disease up to 40% of cases, however, arise from a monoallelic germline pathogenic variant. Only 10% of the germline mutations are inherited, and high penetrance is seen in up to 90% of these cases. As an effort to optimize counseling and screening, mutations are classified according to inheritance patterns. However, RB1 spectrum is highly heterogeneous, and information for unaffected carriers remains scarce. The Mexican family of a 5-month-old patient diagnosed with Rb was studied. The family consisted of five individuals (father, mother, and three siblings). Genetic testing using a next-generation sequencing assay targeting RB1 with oligonucleotide baits designed to capture its exons and 20 bases flanking intronic sequences was performed in every family member. Clinical history and a complete ophthalmological examination (best-corrected visual acuity, slit-lamp biomicroscopy, macular optical coherence tomography, fundus autofluorescence, optical coherence tomography angiography, and electrophysiological studies) were performed in members testing positive to RB1 mutation. The father and her five-month-old daughter tested positive for a non-synonymous RB1 mutation c.459del (p.Lys154Serfs*21). The girl presented with bilateral retinoblastoma, successfully treated with cryotherapy and intravenous chemotherapy. The father had no relevant findings on imaging studies or ophthalmologic evaluation. This report describes a rare case of a novel low-penetrance RB1 germline mutation. Long-term follow-up of the father will include periodic evaluation of the eyes and orbits, and surveillance for systemic sarcoma and secondary malignancies. Implications for unaffected individuals need to be further studied.


Circular RNA circNELL2 Acts as the Sponge of miR-127-5p to Promote Esophageal Squamous Cell Carcinoma Progression.
Owing to its involvement in both the initiation and progression of various cancers, aberrant circular RNA (circRNA) expression has been researched extensively in the recent times. In the present study, we aim to investigate the effect of a novel circRNA has_circ_0025933 (circNELL2) in the progression of esophageal squamous cell carcinoma (ESCC). Sanger sequencing and the detection of circNELL2 level after RNase R or actinomycin D treatment were performed to identify the existence of cirNELL2 in ESCC cells. WST, EDU staining and colony-formation assay were used to assess the proliferation while transwell assay was used to evaluate the migration of ESCC cells. Luciferase assay, RNA pull down and the FISH assay were performed to verify the interaction between circNELL2 and miR-127-5p as well as miR-127-5p and CDC6. Xenograft model was carried out to evaluate the effect of circNELL2 in vivo. circNELL2 was proved to exist in ESCC cells. The up-regulated expression of circNELL2 in the clinical ESCC specimens was also verified. Next, function studies suggested that circNELL2 knockdown inhibited the proliferation of ESCC cells in vitro and in vivo, while circNELL2 overexpression promotes that of ESCC cells. Besides, this study mechanically predicted and verified the target miR of circNELL2, which is miR-127-5p. It was found that miR-127-5p was capable of reversing the effect of circNELL2 on ESCC cells. Moreover, miR-127-5p was also found to target CDC6 to participate in the regulation of cell phenotype. circNELL2 promoted the progression of ESCC cells via sponging miR-127-5p, and it has the potential to serve as a novel prognostic and therapeutic target for ESCC.


Summary of the experiences, knowledge, medical management, and family communication of monoallelic MUTYH carriers.
Germline genetic testing for inherited cancer risk is increasingly being performed with multigene panel testing with MUTYH often included on colorectal cancer- and polyposis-focused panels, as well as on broader pan-cancer panels. With up to 1%-2% of the general population being monoallelic MUTYH carriers, pathogenic/likely pathogenic (P/LP) variants in MUTYH are one of the most common findings on multigene cancer panels. However, little is known about patient experience and understanding of monoallelic MUTYH P/LP variants, nor whether such findings influence medical management recommendations and familial communication, which this study aims to better understand. Monoallelic P/LP MUTYH carriers were recruited from the Prospective Registry of Multiplex Testing (PROMPT) and completed a cross-sectional self-report survey on sociodemographic characteristics, medical and family history, experiences with MUTYH genetic testing, genetics and MUTYH knowledge, perceived cancer risk, and familial communication. Of 115 eligible PROMPT participants, 49 (43%) completed the survey who were primarily female (94%), white (96%), had a history of cancer (61%), and a median age of 51.4 years. Most participants (61%) reported satisfaction with how their healthcare provider managed their genetic test result and care, and 65% of survey participants reported their provider recommended colonoscopy based on their genetic test results. Participants' responses also reflected variable levels of knowledge regarding cancer risks and screening recommendations for MUTYH carriers. The majority (98%) of participants shared their genetic test results with at least some of their relatives; however, only 13% of eligible relatives reportedly underwent cascade testing. Taken together, this study provides needed insight into the overall experiences of monoallelic MUTYH carriers and highlights numerous areas for improvement in clinician education, communication, and management of these individuals.


Chemotactic factor binding by metastatic tumour cells: evidence for a formyl-peptide receptor on a non-myelogenous cell.
Analysis of fMet-Leu-[3H]Phe binding to Walker 256 carcinosarcoma cells demonstrated both saturable and reversible binding, and indicated the presence of a single population of binding sites having an equilibrium dissociation constant: KD = 15.7 +/- 3.3 X 10(-9) M, and with 2425 +/- 204 binding sites per cell. The specificity of the binding site was investigated by competitive inhibition of fMet-Leu-[3H]Phe binding studies using 10 oligoformyl peptides. These results demonstrated an order of peptide reactivity with marked similarity in specificity to the leucocyte binding sites for the formyl-peptides. The most active peptides also had potent agonist activity as determined by their ability to increase the cells' adherence response to nylon-wool fibres. In addition, a competitive antagonist of the formyl-peptide receptor, tert-butoxy-Phe-Leu-Phe-Leu-Phe, completely abolished the adherence response induced by fMet-Leu-Phe, but had no inhibitory effect on the adherence response caused by the tumour-promoting agent, phorbol myristate acetate. These data demonstrate that formyl-peptide receptors may be more common than we have anticipated and may be found on cells not derived from the myeloid series. Furthermore, these studies advance our understanding of stimulus-coupled responses in tumour cells.


Yokukansan, a Traditional Japanese Medicine, Enhances the L-DOPA-Induced Rotational Response in 6-Hydroxydopamine-Lesioned Rats: Possible Inhibition of COMT.
The aim of the present study was to investigate the effects of the traditional Japanese medicine yokukansan (YKS) on the function of dopamine (DA) in the rat nigrostriatal system. Unilateral 6-hydroxydopamine lesions were produced in the rat nigrostriatal system. Despite a marked loss in the striatal immunoreactivity of tyrosine hydroxylase on the lesion side, striatal serotonin (5-HT) immunoreactivity was not affected. Treatment using L-3,4-dihydroxyphenylalanine (L-DOPA) in conjunction with benserazide for 15 d induced abnormal involuntary movements (AIMs) such as locomotive (rotational response), axial, forelimb, and orolingual movements in the lesioned rats. The L-DOPA-induced locomotive and axial, but not forelimb and orolingual, AIMs were significantly increased and prolonged by the pre-administration of YKS. We next investigated the effects of YKS on the production of DA from L-DOPA in 5-HT synthetic RIN 14B cells. RIN 14B cells produced DA and its metabolite, 3-methoxytyramine (3-MT), following L-DOPA treatment. YKS significantly augmented DA production and inhibited its metabolism to 3-MT in a manner similar to the catechol-O-methyltransferase (COMT) inhibitor entacapone. YKS and some alkaloids (corynoxeine: CX, geissoschizine methyl ether: GM) in Uncaria hook, a constituent herb of YKS, also inhibited COMT activity, indicating that the augmenting effect of YKS on L-DOPA-induced DA production in 5-HT synthetic cells was due to the inhibition of COMT by CX and GM. Our results suggest that YKS facilitates the DA supplemental effect of L-DOPA, and that COMT inhibition by CX and GM contributes, at least in part, to the effects of YKS.


A chemical switch for inhibitor-sensitive alleles of any protein kinase.
Protein kinases have proved to be largely resistant to the design of highly specific inhibitors, even with the aid of combinatorial chemistry. The lack of these reagents has complicated efforts to assign specific signalling roles to individual kinases. Here we describe a chemical genetic strategy for sensitizing protein kinases to cell-permeable molecules that do not inhibit wild-type kinases. From two inhibitor scaffolds, we have identified potent and selective inhibitors for sensitized kinases from five distinct subfamilies. Tyrosine and serine/threonine kinases are equally amenable to this approach. We have analysed a budding yeast strain carrying an inhibitor-sensitive form of the cyclin-dependent kinase Cdc28 (CDK1) in place of the wild-type protein. Specific inhibition of Cdc28 in vivo caused a pre-mitotic cell-cycle arrest that is distinct from the G1 arrest typically observed in temperature-sensitive cdc28 mutants. The mutation that confers inhibitor-sensitivity is easily identifiable from primary sequence alignments. Thus, this approach can be used to systematically generate conditional alleles of protein kinases, allowing for rapid functional characterization of members of this important gene family.


Brief review: hypertension in pregnancy : a manifestation of the insulin resistance syndrome?
Pregnancy-induced hypertension (PIH), which includes both gestational hypertension and preeclampsia, is a common and morbid pregnancy complication for which the pathogenesis remains unclear. Emerging evidence suggests that insulin resistance, which has been linked to essential hypertension, may play a role in PIH. Conditions associated with increased insulin resistance, including gestational diabetes, polycystic ovary syndrome, and obesity, may predispose to hypertensive pregnancy. Furthermore, metabolic abnormalities linked to the insulin resistance syndrome are also observed in women with PIH to a greater degree than in normotensive pregnant women: These include glucose intolerance, hyperinsulinemia, hyperlipidemia, and high levels of plasminogen activator inhibitor-1, leptin, and tumor necrosis factor-alpha. These observations suggest the possibility that insulin resistance may be involved in the pathogenesis of PIH and that approaches that improve insulin sensitivity might have benefit in the prevention or treatment of this syndrome, although this requires further study.


Are the behavioral symptoms of Alzheimer's disease directly associated with neurodegeneration?
Behavioral and psychological symptoms of dementia (BPSD) are commonly observed over the course of Alzheimer's disease (AD). However, it is unclear whether BPSD are part of AD neuropathology or rather represent a psychological reaction to cognitive disabilities. Using voxel-based-morphometry (VBM), we aimed to clarify this issue by investigating patients with AD at different clinical stages. Twenty-seven patients with AD (12 early [ADe] and 15 moderate [ADm]), 19 with amnestic mild cognitive impairment (a-MCI), and 23 healthy controls underwent MRI scanning at 3T. Assessment of BPSD was done in each patient using the Neuropsychiatric Inventory-12 (NPI-12). VBM was used to investigate changes in grey matter (GM) atrophy across groups, and associations between regional GM volumes and occurrence and severity of BPSD in patients. Mood disorders, anxiety, and agitation were present in both a-MCI and AD, while psychotic symptoms were observed mainly in AD. As expected, VBM showed only limited areas of GM atrophy in a-MCI patients, with a progressive extension in ADe and ADm patients (PFWE-corrected-values < 0.05). Disinhibition was strongly associated with GM volume in bilateral cingulate and right middle frontal gyri, while delusions were associated with GM volume in right hippocampus (PFWE-corrected-values < 0.05). This study confirms that BPSD are present since the earliest AD stages. Interesting associations were found in regions traditionally implicated by AD neuropathology. This suggests that BPSD are likely to represent clinical features of AD and should be regarded for their diagnostic and prognostic value.


A Self-Paced Regularization Framework for Multilabel Learning.
In this brief, we propose a novel multilabel learning framework, called multilabel self-paced learning, in an attempt to incorporate the SPL scheme into the regime of multilabel learning. Specifically, we first propose a new multilabel learning formulation by introducing a self-paced function as a regularizer, so as to simultaneously prioritize label learning tasks and instances in each iteration. Considering that different multilabel learning scenarios often need different self-paced schemes during learning, we thus provide a general way to find the desired self-paced functions. To the best of our knowledge, this is the first work to study multilabel learning by jointly taking into consideration the complexities of both training instances and labels. Experimental results on four publicly available data sets suggest the effectiveness of our approach, compared with the state-of-the-art methods.


Leukotriene B4 omega-hydroxylase in human polymorphonuclear leukocytes. Partial purification and identification as a cytochrome P-450.
Human polymorphonuclear leukocytes (PMN) not only synthesize and respond to leukotriene B4 (LTB4), but also catabolize this mediator of inflammation rapidly and specifically by omega-oxidation. To characterize the enzyme(s) responsible for omega-oxidation of LTB4, human PMN were disrupted by sonication and subjected to differential centrifugation to yield membrane, granule, and cytosol fractions (identified by biochemical markers). LTB4 omega-hydroxylase activity was concentrated (together with NADPH cytochrome c reductase activity) only in the membrane fraction (specific activity increased 10-fold as compared to whole sonicates, 41% recovery). Negligible activity was detected in granule or cytosol fractions. LTB4 omega-hydroxylase activity in isolated PMN membranes was linear with respect to duration of incubation and protein concentration, was maximal at pH 7.4, had a Km for LTB4 of 0.6 microM, and was dependent on oxygen and on reduced pyridine nucleotides (apparent Km for NADPH = 0.5 microM; apparent Km for NADH = 223 microM). The LTB4 omega-hydroxylase was inhibited significantly by carbon monoxide, ferricytochrome c, SKF-525A, and Triton X-100, but was not affected by alpha-naphthoflavone, azide, cyanide, catalase, and superoxide dismutase. Finally, isolated PMN membranes exhibited a carbon monoxide difference spectrum with a peak at 452 nm. Thus, we have partially purified the LTB4 omega-hydroxylase in human PMN and identified the enzyme as a membrane-associated, NADPH-dependent cytochrome P-450.


Effect of early versus late or no tracheostomy on mortality and pneumonia of critically ill patients receiving mechanical ventilation: a systematic review and meta-analysis.
Delay of tracheostomy for roughly 2 weeks after translaryngeal intubation of critically ill patients is the presently recommended practice and is supported by findings from large trials. However, these trials were suboptimally powered to detect small but clinically important effects on mortality. We aimed to assess the benefit of early versus late or no tracheostomy on mortality and pneumonia in critically ill patients who need mechanical ventilation. We systematically searched PubMed, CINAHL, Embase, Web of Science, DOAJ, the Cochrane Library, references of relevant articles, scientific conference proceedings, and grey literature up to Aug 31, 2013, to identify randomised controlled trials comparing early tracheostomy (done within 1 week after translaryngeal intubation) with late (done any time after the first week of mechanical ventilation) or no tracheostomy and reporting on mortality or incidence of pneumonia in critically ill patients under mechanical ventilation. Our primary outcomes were all-cause mortality during the stay in the intensive-care unit and incidence of ventilator-associated pneumonia. Mortality during the stay in the intensive-care unit was a composite endpoint of definite intensive-care-unit mortality, presumed intensive-care-unit mortality, and 28-day mortality. We calculated pooled odds ratios (OR), pooled risk ratios (RR), and 95% CIs with a random-effects model. All but complications analyses were done on an intention-to-treat basis. Analyses of 13 trials (2434 patients, 648 deaths) showed that all-cause mortality in the intensive-care unit was not significantly lower in patients assigned to the early versus the late or no tracheostomy group (OR 0·80, 95% CI 0·59-1·09; p=0·16). This result persisted when we considered only trials with a low risk of bias (511 deaths; OR 0·80, 95% CI 0·59-1·09; p=0·16; eight trials with 1934 patients). Incidence of ventilator-associated pneumonia was lower in mechanically ventilated patients assigned to the early versus the late or no tracheostomy group (691 cases; OR 0·60, 95% CI 0·41-0·90; p=0·01; 13 trials with 1599 patients). There was no evidence of a difference between the compared groups for 1-year mortality (788 deaths; RR 0·93, 95% CI 0·85-1·02; p=0·14; three trials with 1529 patients). The synthesised evidence suggests that early tracheostomy is not associated with lower mortality in the intensive-care unit than late or no tracheostomy. However, early, compared with late or no, tracheostomy might be associated with a lower incidence of pneumonia; a finding that could question the present practice of delaying tracheostomy beyond the first week after translaryngeal intubation in mechanically ventilated patients. Nevertheless, the scarcity of a beneficial effect on long-term mortality and the potential complications associated with tracheostomy need careful consideration; thus, further studies focusing on long-term outcomes are warranted. None.


All-optical switching of 40 Gb/s packets by MMI-BLD optical label memory.
We demonstrated all-optical label storing and switching for 40 Gb/s optical packets by using all-optical signal processing of multimode interference bistable laser diode optical flip-flops. The stored optical labels in the optical flip-flop controlled an all-optical switch to forward the injected optical packets. The 40 Gb/s optical packets were successfully switched in the all-optical scheme with 11-dB extinction ratio. Error-free operation for the output packets from the switch was also obtained with 1.3-dB power penalty. The presented all-optical packet switching has the advantages of ultrafast switching and transparency of data rate and format, suitable for the future optical networks.


Space phobia: syndrome or agoraphobic variant?
Four elderly women had intense fears of falling when there was no visible support at hand or on seeing space cues while driving. Two patients had cervical spondylosis. The mean age at onset of the fear was 54--thirty years later than that for agoraphobia. Fear of public places and of heights was not prominent, nor was depersonalisation or depression. These "space phobias" might be a hitherto unrecognised syndrome or an unusual variant of agoraphobia. The visuospatial reflexes involved might illuminate the pathogenesis of certain fears.


The LXR agonist T0901317 promotes the reverse cholesterol transport from macrophages by increasing plasma efflux potential.
The liver X receptors (LXRs) have been shown to affect lipoprotein plasma profile, lipid metabolism, and reverse cholesterol transport (RCT). In the present study, we investigated whether a short-term administration of the synthetic LXR agonist T0901317 (T0) to mice may affect RCT by modulating the capacity of plasma to promote cellular lipid efflux. Consistent with previous data, the pharmacological treatment of mice caused a significant increase of macrophage-derived [3H]cholesterol content in plasma, liver, and feces and resulted in improved capacity of plasma to promote cellular cholesterol release through passive diffusion and scavenger receptor class B type I (SR-BI)-mediated mechanisms. Differently, plasma from treated mice possessed similar or reduced capacity to drive lipid efflux via ABCA1. Consistent with these data, the analysis of plasma HDL fractions revealed that T0 caused the formation of larger, lipid-enriched particles. These results suggest that T0 promotes in vivo RCT from macrophages at least in part by inducing an enrichment of those HDL subclasses that increase plasma capacity to promote cholesterol efflux by passive diffusion and SR-BI-mediated mechanisms.


TGF-β Signaling in Lung Health and Disease.
Transforming growth factor (TGF)-β is an evolutionarily conserved pleiotropic factor that regulates a myriad of biological processes including development, tissue regeneration, immune responses, and tumorigenesis. TGF-β is necessary for lung organogenesis and homeostasis as evidenced by genetically engineered mouse models. TGF-β is crucial for epithelial-mesenchymal interactions during lung branching morphogenesis and alveolarization. Expression and activation of the three TGF-β ligand isoforms in the lungs are temporally and spatially regulated by multiple mechanisms. The lungs are structurally exposed to extrinsic stimuli and pathogens, and are susceptible to inflammation, allergic reactions, and carcinogenesis. Upregulation of TGF-β ligands is observed in major pulmonary diseases, including pulmonary fibrosis, emphysema, bronchial asthma, and lung cancer. TGF-β regulates multiple cellular processes such as growth suppression of epithelial cells, alveolar epithelial cell differentiation, fibroblast activation, and extracellular matrix organization. These effects are closely associated with tissue remodeling in pulmonary fibrosis and emphysema. TGF-β is also central to T cell homeostasis and is deeply involved in asthmatic airway inflammation. TGF-β is the most potent inducer of epithelial-mesenchymal transition in non-small cell lung cancer cells and is pivotal to the development of tumor-promoting microenvironment in the lung cancer tissue. This review summarizes and integrates the current knowledge of TGF-β signaling relevant to lung health and disease.


Antibiotics exposure and risk of inflammatory bowel disease: a systematic review.
The aim of this study was to critically assess all available evidence suggesting an association between antibiotic exposure and new onset of inflammatory bowel disease (IBD). This systematic review was conducted according to the PRISMA statement and eligible studies were identified through search of PubMed, Embase and the Cochrane Library. Data on patient demographics, antibiotic exposure and confounding factors were analyzed. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of eligible studies. A total of 15 observational studies (10 case control and five cohort) including 8748 patients diagnosed with IBD were systematically reviewed. Antibiotic exposure was mostly associated with Crohn's disease but not with ulcerative colitis. In particular, penicillin's, cephalosporins, metronidazole and fluoroquinolones were most commonly associated with the onset of Crohn's disease. The impact of tetracycline-family antibiotics on the pathogenesis of IBD was not clear. There may be an association between antibiotic exposure and the development of IBD; especially Crohn's disease. Even though, clinicians should be cautious when prescribing certain antibiotic regimens to patients with a strong family history of IBD, it should be emphasized that available data are not granular enough to reach any definitive conclusions.


Pressure distribution in unsteady sink and source flows.
Basic flow generated in a viscous incompressible fluid by a "point" sink (source) of mass is revised. In practice, such flow can be modeled by sucking (pushing) fluid from a thin tube with a small porous sphere at one end. Intuitively, by sucking (pushing) fluid, one creates low (high) pressure near the origin and a positive (negative) radial pressure gradient drives the fluid to (from) the origin. A simple analysis, however, shows that the pressure distribution for both steady flows is the same. Then a question arises: How does the fluid "know" in what direction to flow? To explain this "paradox" an unsteady flow is considered and the pressure terms responsible for the flow direction are derived.


A cell-based high-throughput screen validates the plasmodial surface anion channel as an antimalarial target.
The plasmodial surface anion channel (PSAC) is an unusual small-conductance ion channel induced on erythrocytes infected with plasmodia, including parasites responsible for human malaria. Although broadly available inhibitors produce microscopic clearance of parasite cultures at high concentrations and suggest that PSAC is an antimalarial target, they have low affinity for the channel and may interfere with other parasite activities. To address these concerns, we developed a miniaturized assay for PSAC activity and carried out a high-throughput inhibitor screen. Approximately 70,000 compounds from synthetic and natural product libraries were screened, revealing inhibitors from multiple structural classes including two novel and potent heterocyclic scaffolds. Single-channel patch-clamp studies indicated that these compounds act directly on PSAC, further implicating a proposed role in transport of diverse solutes. A statistically significant correlation between channel inhibition and in vitro parasite killing by a family of compounds provided chemical validation of PSAC as a drug target. These new inhibitors should be important research tools and may be starting points for much-needed antimalarial drugs.


Dexmedetomidine-Associated Hyperthermia: A Series of 9 Cases and a Review of the Literature.
Dexmedetomidine, an α2-adrenergic agonist, can be used to perform mild to moderate sedation in critically ill patients. In this case series, 9 cardiovascular intensive care unit patients with hyperthermia during dexmedetomidine administration, suggestive of drug fever, are presented. Hyperthermia (>38.5°C) occurred 6 (4-10) hours (median [interquartile range]) after dexmedetomidine initiation at a dose of 1.0 (0.8-1.3) μg/kg/h and was resolved 3 (1-8) hours after discontinuation of dexmedetomidine. All patients were screened for infectious and noninfectious causes of hyperthermia, and the findings were analyzed by 2 adverse drug reaction (ADR) assessment methods-the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) Causality Assessment and the Naranjo ADR scale. This resulted in a "probable" ADR in all 9 patients (WHO) and a "probable" and "possible" ADR in 1 and 8 patients (Naranjo), respectively. This case series supports published case reports, suggesting that dexmedetomidine administration may be associated with the occurrence of clinically relevant hyperthermia. The underlying mechanisms and risk factors are uncertain and require further research.


Decrease of plasma sulfur amino acids in essential hypertension.
In order to evaluate the correlation between sulfur amino acids (derived mainly form animal protein in the diet) and blood pressure, free amino acids, including sulfur amino acids such as taurine and methionine, were determined in the plasma and cerebrospinal fluid (CSF) of twelve normotensive subjects and twelve patients with essential hypertension under nutritional control after at least 10 days of standard hospital diet (total calorie and protein content: 2100-2300 Cal per day and 78-83 g per day, respectively). The results obtained were as follows: plasma taurine, serine, methionine and threonine were significantly lower in patients with essential hypertension than in normotensive patients. The levels of plasma taurine, serine, methionine and total sulfur amino acids in individuals correlated inversely to systolic blood pressure. No difference was observed in the CSF levels of free amino acids in normotensive and hypertensive patients. As taurine, methionine and serine are involved in the metabolism of sulfur amino acids, these observations support the view that the decrease in plasma sulfur amino acids may be a factor contributing to elevated blood pressure.


From the selfish gene to selfish metabolism: revisiting the central dogma.
The standard representation of the Central Dogma (CD) of Molecular Biology conspicuously ignores metabolism. However, both the metabolites and the biochemical fluxes behind any biological phenomenon are encrypted in the DNA sequence. Metabolism constrains and even changes the information flow when the DNA-encoded instructions conflict with the homeostasis of the biochemical network. Inspection of adaptive virulence programs and emergence of xenobiotic-biodegradation pathways in environmental bacteria suggest that their main evolutionary drive is the expansion of their metabolic networks towards new chemical landscapes rather than perpetuation and spreading of their DNA sequences. Faulty enzymatic reactions on suboptimal substrates often produce reactive oxygen species (ROS), a process that fosters DNA diversification and ultimately couples catabolism of the new chemicals to growth. All this calls for a revision of the CD in which metabolism (rather than DNA) has the leading role.


A population-based study of visual impairment among pre-school children in Beijing: the Beijing study of visual impairment in children.
To evaluate the prevalence and causes of visual impairment among Chinese children aged 3 to 6 years in Beijing. Population-based prevalence survey. Presenting and pinhole visual acuity were tested using picture optotypes or, in children with pinhole vision < 6/18, a Snellen tumbling E chart. Comprehensive eye examinations and cycloplegic refraction were carried out for children with pinhole vision < 6/18 in the better-seeing eye. All examinations were completed on 17,699 children aged 3 to 6 years (95.3% of sample). Subjects with bilateral correctable low vision (presenting vision < 6/18 correctable to >or= 6/18) numbered 57 (0.322%; 95% confidence interval [CI], 0.237% to 0.403%), while 14 (0.079%; 95% CI, 0.038% to 0.120%) had bilateral uncorrectable low vision (best-corrected vision of < 6/18 and >or= 3/60), and 5 subjects (0.028%; 95% CI, 0.004% to 0.054%) were bilaterally blind (best-corrected acuity < 3/60). The etiology of 76 cases of visual impairment included: refractive error in 57 children (75%), hereditary factors (microphthalmos, congenital cataract, congenital motor nystagmus, albinism, and optic nerve disease) in 13 children (17.1 %), amblyopia in 3 children (3.95%), and cortical blindness in 1 child (1.3%). The cause of visual impairment could not be established in 2 (2.63%) children. The prevalence of visual impairment did not differ by gender, but correctable low vision was significantly (P < .0001) more common among urban as compared with rural children. The leading causes of visual impairment among Chinese preschool-aged children are refractive error and hereditary eye diseases. A higher prevalence of refractive error is already present among urban as compared with rural children in this preschool population.


Analysis of tracheal secretions for rhinovirus during natural colds.
Rhinoviruses (RV) cause 50% of common colds and are frequently isolated from children and adults hospitalized for asthma exacerbations. Although colds may trigger severe coughing and wheezing, it is not known whether these symptoms are a result of lower airway infection with RV. Previous efforts to address this question by sampling lower airway secretions during experimental RV infections have been complicated by the possibility of contamination of the bronchoscope with nasopharyngeal cells and secretions. To further test the hypothesis that RV infections involve the lower airways, tracheal and nasal secretions were obtained from 23 pediatric tracheostomy patients, including seven with cold symptoms and 16 asymptomatic controls. RV was detected by reverse-transcription polymerase chain reaction from the nasal and tracheal secretions of three of the seven children with cold symptoms. In the 16 well children, RV was not detected in any samples of nasal secretions, but was isolated from four samples of tracheal secretions. These results demonstrate the presence of RV in the lower airways of children with tracheostomies during community-acquired colds, without the possibility of nasal contamination. In addition, these findings suggest that children with tracheostomies carry subclinical viral infections in their tracheas, rather than their noses.


Spontaneous pneumothorax resulting from congenital cystic adenomatoid malformation in a pre-term infant: case report and literature review.
In the literature there are only three reported cases of spontaneous pneumothorax resulting from congenital cystic adenomatoid malformation in children under 1 year and for whom any resuscitative efforts were made. We present here a fourth case of a pre-term baby girl who was in perfect health, until she suffered a spontaneous pneumothorax as the initial manifestation of congenital cystic adenomatoid malformation of the lung at 10 weeks of age. Atypical segmentectomy with the use of stapling devices was successful. The characteristics of this particular manifestation are discussed.


A robust estimation of the effects of motorcycle autonomous emergency braking (MAEB) based on in-depth crashes in Australia.
Autonomous emergency braking (AEB) is a safety system that detects imminent forward collisions and reacts by slowing down the host vehicle without any action from the driver. AEB effectiveness in avoiding and mitigating real-world crashes has recently been demonstrated. Research suggests that a translation of AEB to powered 2-wheelers could also be beneficial. Previous studies have estimated the effects of a motorcycle AEB system (MAEB) via computer simulations. Though effects of MAEB were computed for motorcycle crashes derived from in-depth crash investigation, there may be some inaccuracies due to limitations of postcrash investigation (e.g., inaccuracies in preimpact velocity of the motorcycle). Furthermore, ideal MAEB technology was assumed, which may lead to overestimation of the benefits. This study sought to evaluate the sensitivity of the simulations to variations in reconstructed crash cases and the capacity of the MAEB system in order to provide a more robust estimation of MAEB effects. First, a comprehensive classification of accidents was used to identify scenarios in which MAEB was likely to apply, and representative crash cases from those available for this study were populated for each crash scenario. Second, 100 variant cases were generated by randomly varying a set of simulation parameters with given normal distributions around the baseline values. Variants reflected uncertainties in the original data. Third, the effects of MAEB were estimated in terms of the difference in the impact speed of the host motorcycle with and without the system via computer simulations of each variant case. Simulations were repeated assuming both an idealized and a realistic MAEB system. For each crash case, the results in the baseline case and in the variants were compared. A total of 36 crash cases representing 11 common crash scenarios were selected from 3 Australian in-depth data sets: 12 cases from New South Wales, 13 cases from Victoria, and 11 cases from South Australia. The reduction in impact speed elicited by MAEB in the baseline cases ranged from 2.8 to 10.0 km/h. The baseline cases over- or underestimated the mean impact speed reduction of the variant cases by up to 20%. Constraints imposed by simulating more realistic capabilities for an MAEB system produced a decrease in the estimated impact speed reduction of up to 14% (mean 5%) compared to an idealized system. The small difference between the baseline and variant case results demonstrates that the potential effects of MAEB computed from the cases described in in-depth crash reports are typically a good approximation, despite limitations of postcrash investigation. Furthermore, given that MAEB intervenes very close to the point of impact, limitations of the currently available technologies were not found to have a dramatic influence on the effects of the system.


Functional engineering of human iPSC-derived parasympathetic neurons enhances responsiveness to gastrointestinal hormones.
Food-derived biological signals are transmitted to the brain via peripheral nerves through the paracrine activity of gastrointestinal (GI) hormones. The signal transduction circuit of the brain-gut axis has been analyzed in animals; however, species-related differences and animal welfare concerns necessitate investigation using in vitro human experimental models. Here, we focused on the receptors of five GI hormones (CCK, GLP1, GLP2, PYY, and serotonin (5-HT)), and established human induced pluripotent stem cell (iPSC) lines that functionally expressed each receptor. Compared to the original iPSCs, iPSCs expressing one of the receptors did not show any differences in global mRNA expression, genomic stability, or differentiation capacities of the three germ layers. We induced parasympathetic neurons from these established iPSC lines to assess vagus nerve activity. We generated GI hormone receptor-expressing neurons (CCKAR, GLP1R, and NPY2R-neuron) and tested their responsiveness to each ligand using Ca2+ imaging and microelectrode array recording. GI hormone receptor-expressing neurons (GLP2R and HTR3A) were generated directly by gene induction into iPSC-derived peripheral nerve progenitors. These receptor-expressing neurons promise to contribute to a better understanding of how the body responds to GI hormones via the brain-gut axis, aid in drug development, and offer an alternative to animal studies.


Factors contributing to whether or not people with obesity undergo bariatric surgery.
Bariatric surgery has been suggested as a safe and effective way to treat obesity by facilitating weight loss, but factors that predict the likelihood of bariatric surgery are unknown. The objective of this study was to describe factors associated with individuals with obesity that influence their decision to undergo bariatric surgery. The study design was a cross-sectional study and participants were recruited via a survey link posted on the Obesity Action Coalition website. Demographic data, medical data, weight loss program data, and reports of personal experiences were gathered via an online survey. A multivariate logistic regression model was conducted to examine predictors associated with bariatric surgery (N = 4192). Participants who took phentermine (OR=2.983), Phentermine-topiramate (Qsymia) (OR=2.863), Naltrexone-bupropion (Contrave) (OR=3.246), or Liraglutide (Saxenda) (OR=2.144) had a higher likelihood of undergoing bariatric surgery for weight loss. Participants with type 2 diabetes (OR=1.728), post-traumatic stress disorder (PTSD) (OR=1.489), or COVID-19 (OR=3.852) had a higher likelihood of undergoing bariatric surgery while sleep apnea (OR=0.760) was associated with a lower likelihood of receiving surgery. Those who used MyFitnessPal™ (OR=2.232), Noom™ (OR=1.400), Jenny Craig™ (OR=1.533), or Keto (OR=1.664) for weight loss had a higher likelihood of obtaining bariatric surgery. Personal trauma experiences of sexual abuse (OR=1.982) and physical abuse (OR=1.490) were more associated with participants who underwent surgery. A variety of characteristics were associated with decisions to undergo bariatric surgery. These findings may help to determine ways to support individuals who are considering bariatric surgery.


Analysis of the contribution of dydrogesterone to bone turnover changes in postmenopausal women commencing hormone replacement therapy.
Although gestagens have been reported to influence bone metabolism, whether these contribute to the beneficial effects of hormone replacement therapy (HRT) on the skeleton of postmenopausal women is currently unclear. To address this question, we compared changes in bone turnover markers after commencing HRT in 26 postmenopausal women randomized to receive 8 weeks of treatment with 2 mg estradiol daily or 2 mg estradiol plus 10 mg dydrogesterone daily. Serum and second morning void urine samples were obtained at baseline (twice) and after 1, 2, 4, and 8 weeks. Serum estradiol was measured by RIA, urinary total deoxypyridinoline (DPD) excretion by high pressure liquid chromatography, and serum osteocalcin and C-terminal procollagen peptide by enzyme-linked immunosorbent assay. The increase in serum estradiol after treatment with estradiol alone was slightly, but significantly, greater than that in the combination group (P = 0.04). Although estradiol suppressed urinary DPD excretion to a greater extent when given alone (P = 0.02), osteocalcin levels were significantly higher in this group than in women receiving combination therapy (P = 0.04). To assess the effect of dydrogesterone on the balance between formation and resorption in more detail, we subsequently compared the ratio between formation and resorption markers in the two treatment groups. We found that osteocalcin/DPD and C-terminal procollagen peptide/DPD ratios were significantly higher in women treated with estradiol alone (P < 0.0001 and P = 0.002, respectively), suggesting that dydrogesterone may reduce formation relative to resorption. These results suggest that gestagens may reduce estrogen's beneficial effects on the skeleton of postmenopausal women, as assessed over the first 8 weeks of replacement therapy.


A haematological study of patients receiving long-term treatment with trimethoprim and sulphonamide.
The haematological effects of long-term treatment for three months with a combination of trimethoprim and sulphamethoxazole were studied in 10 cases of chronic bronchitis. Trimethoprim selectively inhibits dihydrofolate reductase in bacteria but not in man. Only minor effects on folate metabolism were observed in nine cases, causing no clinical concern. Some degree of thrombocytopenia occurred in the tenth case which improved when folinic acid was given.


Royal College of Physicians Intercollegiate Stroke Working Party evidence-based guidelines for the secondary prevention of stroke through nutritional or dietary modification.
Each year, 15 million people worldwide and 110,000 people in England have a stroke. Having a stroke increases the risk of having another. There are a number of additional known risk factors that can be modified by diet. The present study aimed to systematically review key nutrients and diets and their role in secondary prevention, as well as provide evidence-based guidelines for use in clinical practice. The work was conducted as part of the process to develop the 4th edition of the Royal College of Physicians' (RCP) National Clinical Guideline (NCG) for Stroke. Questions were generated by the research team, in consultation with the Virtual Stroke Group, an online professional interest group, and the RCP Intercollegiate Stroke Working Party Guideline Development Group. Nine questions covering several individual nutrients and diet combinations were defined and searches conducted up until 31 October 2011 using five electronic databases (Embase, Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library and Web of Science). All included studies were assessed for quality and risk of bias using van Tulder criteria for randomised controlled trials (RCTs) and Quality of Reporting of Meta-analyses (QUORUM) criteria for systematic reviews. Of 4287 abstracts were identified, 79 papers were reviewed and 29 systematic reviews and RCTs were included to provide evidence for the secondary prevention components of the guidelines. For each question, evidence statements, recommendations and practical considerations were developed. This systematic review process has resulted in the development of evidence-based guidelines for use in clinical practice and has identified areas for further research.


The long-term changes in liver DNA and total protein contents following low level sarin exposure in rats.
1. The changes in contents of DNA and total protein in the liver of the rats exposed to low level sarin by inhalation at 3, 6 and 12 months following the exposure were studied. The influence of sarin on the DNA and protein metabolism in liver was determined by the measurements of incorporation of tritiated thymidine into DNA, the concentration of DNA and total protein. 2. Our results show that not only symptomatic level 3 but also asymptomatic levels 1 and 2 of sarin are able to significantly decrease the incorporation of radiolabelled thymidine without changing total concentrations of DNA as well as protein at three months following sarin exposure. On the other hand, the significant decrease in total contents of DNA and protein in liver without the changes in the incorporation of tritiated thymidine was determined in liver six months following sarin exposure. Practically no significant changes in the metabolism of DNA and protein were observed at 12 months following sarin exposure. 3. Thus, not only clinically manifested intoxication but also low-level, asymptomatic exposure to nerve agents such as sarin is able to influence the metabolism of nucleic acids as well as proteins even several months following the exposure.


Central modules of the vaccinia virus complement control protein are not in extensive contact.
The 28.6 kDa vaccinia virus complement control protein (VCP) is an inhibitor of the complement system and has therapeutic potential. It is composed of four domains or modules and is a homologue of complement receptor 1 (CR1) and other mammalian regulators of complement activation. A key aspect to structure-function relationships in these proteins is the extent of intramolecular module-module interactions, since these dictate the overall shape and flexibility of the molecules. A protein fragment (VCP approximately 2,3) encompassing modules 2 and 3 of VCP was over-expressed in Pichia pastoris. Ultracentrifugation showed that VCP approximately 2,3 is highly asymmetric with an axial ratio of 5.3:1, which is consistent with an end-to-end arrangement of the two modules. NMR spectroscopy, differential scanning calorimetry, CD and intrinsic tryptophan fluorescence were used to monitor unfolding of VCP approximately 2,3. Experiments performed over a range of temperatures and concentrations of guanidinium chloride revealed that module 2 unfolds under milder conditions than, and independently of, module 3. Unfolding of module 2 is not associated with extensive changes in amide (15)N and (1)H chemical shifts of module 3, implying that the modules do not form an extensive intermodular interface. Results obtained in this work for VCP approximately 2,3 are compared with those obtained in a study of CR1 modules 15-17 [Kirkitadze, Krych, Uhrin, Dryden, Smith, Cooper, Wang, Hauhart, Atkinson and Barlow (1999) Biochemistry 38, 7019-7031].


Hyperbaric oxygen induces a cytoprotective and angiogenic response in human microvascular endothelial cells.
A genome-wide microarray analysis of gene expression was carried out on human microvascular endothelial cells (HMEC-1) exposed to hyperbaric oxygen treatment (HBOT) under conditions that approximated clinical settings. Highly up-regulated genes included immediate early transcription factors (FOS, FOSB, and JUNB) and metallothioneins. Six molecular chaperones were also up-regulated immediately following HBOT, and all of these have been implicated in protein damage control. Pathway analysis programs identified the Nrf-2-mediated oxidative stress response as one of the primary responders to HBOT. Several of the microarray changes in the Nrf2 pathway and a molecular chaperone were validated using quantitative PCR. For all of the genes tested (Nrf2, HMOX1, HSPA1A, M1A, ACTC1, and FOS), HBOT elicited large responses, whereas changes were minimal following treatment with 100% O(2) in the absence of elevated pressure. The increased expression of immediate early and cytoprotective genes corresponded with an HBOT-induced increase in cell proliferation and oxidative stress resistance. In addition, HBOT treatment enhanced endothelial tube formation on Matrigel plates, with particularly dramatic effects observed following two daily HBO treatments. Understanding how HBOT influences gene expression changes in endothelial cells may be beneficial for improving current HBOT-based wound-healing protocols. These data also point to other potential HBOT applications where stimulating protection and repair of the endothelium would be beneficial, such as patient preconditioning prior to major surgery.


A comparative, qualitative and quantitative antimicrobial efficacies of mouthrinses containing chlorhexidine gluconate and essential oils.
A project was launched to evaluate and compare antimicrobial efficacy of Hexidine and Listerine over placebo in 10 day human experimental gingivitis study. A rigid study schedule for subject compliance spanning well over 3 months was sorted out and volunteers recruited for study rinsed all the 3 assigned mouthrinses containing (a) chlorhexidine gluconate, (b) "essential oils" and (c) flavoured distilled water one after the other at certain prefixed intervals. After 10 days of assigned mouthrinse regimen, where the assigned mouthrinse was the only method practiced by the volunteers for oral hygiene, Supragingival Plaque was quantitatively and qualitatively assayed. Qualitatively supragingival plaque was assayed by Gram staining (Direct smear and Thioglycollate Broth) and growth characteristics i.e; Aerobic, Microaerophilic and Anaerobic growth was noted. Quantitatively plaque was assayed by calculating total microbial load per tooth by preparing Mafarland Nephelometer standard and Spectrophotometric analysis. It is concluded that Hexidine and Listerine exert similar antimicrobial efficacy in 10 days experimental gingivitis study. Hexidine and Listerine exert their antimicrobial influence through reduction of total Aerobes and Anaerobes reducing total microbial load per tooth by 58% and 53% respectively as compared to placebo.


Gustave Roussy Immune Score and Royal Marsden Hospital Prognostic Score Are Prognostic Markers for Extensive Disease of Small Cell Lung Cancer.
The Royal Marsden Hospital prognostic score (RMH score) and the Gustave Roussy immune score (GRIm-score) were developed in order to select more suitable patient for phase I trials. Lactate dehydrogenase (LDH) and serum albumin concentration are common risk factors to these two systems. As the third risk factor, the RMH score and the GRIm-score adopt number of metastatic sites and neutrophil-to-lymphocyte ratio (NLR), respectively. We aimed to investigate whether these two systems are also useful for extensive disease of small cell lung cancer (ED-SCLC). We retrospectively collected 128 patients who had initiated platinum-based chemotherapy at our hospital between September 2007 and March 2018. We divided our patients into low (score 0 - 1) and high (2 - 3) score groups, and compared overall survival (OS) and progression-free survival (PFS) between them. Multivariate Cox proportional hazard analyses found prognostic factors of survival times. Regarding GRIm-score, OS was significantly shorter in high score group than in low score group (median 6.1 vs. 11.4 months, P < 0.01), while no significant difference was observed in PFS (median 4.7 vs. 5.0 months, P = 0.12). Both OS (median 6.9 vs. 12.4 months, P < 0.01) and PFS (median 4.4 vs. 5.4 months, P = 0.01) were significantly shorter in high RMH score group than in low group. Multivariate analyses detected both high GRIm-score (hazard ratio (HR) 1.80, 95% confidence interval (CI) 1.20 - 2.72, P < 0.01) and high RMH score (HR 1.93, 95% CI 1.27 - 2.92, P < 0.01) as independent worse prognostic factors of OS, and then only high RMH score (HR 1.53, 95% CI 1.04 - 2.25, P = 0.03) as independent worse prognostic factor of PFS. Both RMH score and GRIm-score are useful as independent prognostic factors of OS in ED-SCLC. However, only RMH score is an independent prognostic factor of PFS.


biojs-io-biom, a BioJS component for handling data in Biological Observation Matrix (BIOM) format.
The Biological Observation Matrix (BIOM) format is widely used to store data from high-throughput studies. It aims at increasing interoperability of bioinformatic tools that process this data. However, due to multiple versions and implementation details, working with this format can be tricky. Currently, libraries in Python, R and Perl are available, whilst such for JavaScript are lacking. Here, we present a BioJS component for parsing BIOM data in all format versions. It supports import, modification, and export via a unified interface. This module aims to facilitate the development of web applications that use BIOM data. Finally, we demonstrate its usefulness by two applications that already use this component. Availability: https://github.com/molbiodiv/biojs-io-biom, https://dx.doi.org/10.5281/zenodo.218277.


Dental treatment on a German warship during a three-month deployment.
Despite routine dental screenings and treatments before military deployments, dental emergencies may arise due to acute infections, trauma or failed restorations. The purpose of this study is to evaluate the dental service during a three-month deployment on a German warship. A retrospective analysis of dental attendances and treatments in a German naval task group of three ships with an average total of 650 soldiers. Diagnosis, treatments performed, percentage of emergencies, routine procedures and numbers of appointments were recorded. Out of 650 soldiers, there were 71 patients (10.92%) with a mean age of 25.1 ±5 .3 years. Out of 136 treatments, 17.65% were for emergency treatment, which is equivalent to 3.69% of all servicemen of the task group. Combining the reasons for dental emergencies, 95.84% were caused by caries. The pre-screening of sailors before an overseas deployment is necessary to avoid severe dental treatments. Caries remains the main cause for dental emergencies, and medical doctors should be trained to treat caries lesions if a dentist is not on board.


Halogenated indigo dyes: a likely source of 1,3,6,8-tetrabromocarbazole and some other halogenated carbazoles in the environment.
In recent years, a number of halogenated carbazoles have been detected in environmental samples. These emerging contaminants have been shown to be persistent and possess dioxin-like toxicological potential. The goal of this research was to examine the literature to determine likely anthropogenic origin(s) of halogenated carbazoles in the environment. The scientific literature indicated a number of pathways by which 1,3,6,8-tetrabromocarbazole could form in the manufacture of 5,5',7,7'-tetrabromoindigo. The U.S. production history of 5,5',7,7'-tetrabromoindigo correlates well with the concentration rise, decline, and disappearance of 1,3,6,8-tetrabromocarbazole in dated Lake Michigan sediments. Additionally, other halogenated carbazoles that have been found in environmental sediments can be explained by the production of other halogenated indigo dyes. 1,8-dibromo-3,6-dichlorocarbazole can be accounted for by the manufacture of 7,7'-dibromo-5,5'-dichloroindigo, while 1,3,6,8-tetrachlorocarbazole was found at relatively high concentration near the outfall of a U.S. manufacturer of 5,5',7,7'-tetrachloroindigo. Carbazoles containing an iodo-substituent can be explained by the use of iodine as a catalyst in the manufacture of halogenated indigo dyes. 3,6-Dichlorocarbazole measured in soils and dibromocarbazoles measured in more recently deposited sediments are not easily rationalized on the basis of an indigo related source and may be related to other anthropogenic sources or natural origins.


Recent results on A-ring modification of 1alpha,25-dihydroxyvitamin D3: design and synthesis of VDR-agonists and antagonists with high biological activity.
The structure-activity relationships of 1alpha,25-dihydroxyvitamin D3 on simultaneous modification at both C2alpha and CD-ring side chain, including 20-epimerization, double side chain (gemini), and vitamin D receptor (VDR) antagonists TEI-9647 and TEI-9648 lactone rings, and also on simultaneous modifications at both C2 and C10 positions, i.e., C2 modified active 19-norvitamin D3, have been studied in our laboratory to find new seeds of B-seco-steroidal medicine for treating bone diseases, psoriasis, secondary hyperparathyroidism, and certain kinds of cancers. We developed an efficient and systematic route to the 2alpha-substituted 1alpha,25-dihydroxyvitamin D3 analogs, i.e., VDR-agonists (20-epi-2-4, double side chain 13a-c, 19-nor 15a-c) and antagonists (36a-c, 37a-c). The A-ring precursors (11a-o) for these analogs were synthesized from D-glucose as a chiral template. In the 19-nor series, we used radical coupling reaction for preparing the A-ring parts from (-)-quinic acid, and the resulting 2-substituted A-ring moiety was coupled with 25-hydroxy Grundmann's ketone utilizing Julia olefination to connect between the C5 and C6 positions. We also synthesized the highly potent VDR-antagonists by introducing the 2alpha-functional group to the TEI-9647 and TEI-9648 skeletons.


Intraoperative tramadol reduces shivering but not pain after remifentanil-isoflurane general anaesthesia. A placebo-controlled, double-blind trial.
Postoperative shivering and pain are frequent problems in patients recovering from anaesthesia with particularly high incidences being observed after remifentanil-isoflurane-based general anaesthesia. The opioid tramadol is generally effective in preventing shivering and treating pain, but its effects are not characterized after remifentanil-based general anaesthesia. This randomized, placebo-controlled, double-blind study evaluated the effects of intraoperative intravenous tramadol on postoperative shivering and pain after remifentanil-based general anaesthesia. After Ethics Committee approval, 60 patients scheduled for lumbar disc surgery were included. Surgery was performed under general anaesthesia (remifentanil, isoflurane). Patients were randomly assigned to receive 2 mg kg(-1) tramadol in 30 mL 0.9% saline infused intravenously (n = 30) or 30 mL saline (n = 30) 45-30 min before skin closure. The following parameters were assessed every 10 min for 2 h: shivering, pain, postoperative nausea and vomiting, sedation, heart rate, non-invasive blood pressure and peripheral oxygen saturation. The primary outcome variable was the incidence of shivering during the first 2 postoperative hours. Secondary variables were: shivering intensity, pain, postoperative nausea and vomiting, sedation, heart rate, non-invasive blood pressure and peripheral oxygen saturation. Shivering was less frequent in patients treated with tramadol (20% vs. 70%, P = 0.0009) and was of lower intensity (severe shivering: 10% vs. 46.7%, P = 0.003). Pain scores were similar between the groups and all other secondary outcome variables failed to reveal significant differences. Compared with placebo, intraoperative intravenous administration of 2 mg kg(-1) tramadol reduces the incidence and extent of postoperative shivering without alterations in pain perception after lumbar disc surgery under remifentanil-isoflurane-based general anaesthesia.


Kinetics of induction of DNA damage and lacZ gene mutations in stomach mucosa of mice treated with beta-propiolactone and N-methyl-N'-nitro-N-nitrosoguanidine, using single-cell gel electrophoresis and MutaMouse models.
beta-Propiolactone (BPL) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) are two direct alkylating agents that induce multiple genetic lesions and tumors in the rodent stomach. We measured the kinetics of the induction of DNA damage by using the single-cell gel electrophoresis assay (SCGE) and the induction of gene mutations by using the MutaMouse model in the glandular stomach mucosa of mice exposed to a single oral administration of BPL or MNNG. The aims were to determine the optimal sampling time and to investigate the cause-effect relationship between DNA damage and gene mutations. The induction of comets, evaluated in individual cells with the tail moment, was analyzed 1, 2, 4, 24, and 72 hr after a single oral administration of 25 mg/kg BPL or 20 mg/kg MNNG. The effects of both compounds were most intense at the earlier sampling times (1-2 hr), tailing off 4 hr after treatment and becoming undetectable at 72 hr. The lacZ mutant frequency (MF) was measured 3, 7, 14, 28, and 50 days after a single oral administration of 150 mg/kg BPL or 100 mg/kg MNNG, and 3 and 14 days after a single administration of 25 mg/kg BPL or 20 mg/kg MNNG. The MF was strongly enhanced at the highest doses and all sampling times, the most marked effects being observed 14 days (11.1-fold) and 28 days (19.0-fold) after BPL and MNNG administration, respectively. At the lowest doses, only a small increase in MF ( approximately 2.5- to 3.5-fold) was found at both sampling times. Primary DNA damage detected with SCGE shortly after treatment (1-2 hr) was rapidly (3 days) transformed into stable gene mutations that remained detectable for 50 days. These results illustrate the ability and complementarity of the SCGE and MutaMouse models to assess the genotoxicity of direct alkylating agents in the mouse gastric mucosa in vivo.


Cerium-carbon dative interactions supported by carbodiphosphorane.
A set of complexes containing dative interactions between a rare-earth metal and carbon are reported. Complex 2, Br3Ce(CDP)(THF), with a Ce←C bond was synthesized by the reaction of CeBr3 with a carbon(0) ligand, carbodiphosphorane (CDP). More significantly, a trivalent cerium complex 3, [BrCe(CDP)2](BPh4)2, with two σ dative interactions C→Ce←C was also isolated, which represents an unusual example of two dative interactions formed with the same atom in a molecule. Furthermore, π donation by the second lone-pair electrons of the CDP ligand is rather weak. Single-crystal X-ray diffraction shows that the Ce-C bond lengths in these complexes are comparable with those in cerium(iii)-carbene species. Density functional theory calculations support the dative interaction formation in these complexes and the strength of σ-donation in 3 is stronger than that in 2.


Biodegradable balloon-expandable self-locking polycaprolactone stents as buckling explants for the treatment of retinal detachment: an in vitro and in vivo study.
The purpose of this report was to develop biodegradable balloon-expandable self-locking poly(ε-caprolactone) (PCL) stents for the treatment of retinal detachment. To create the biodegradable stents, polycaprolactone components were first fabricated by a laboratory-scale microinjection molding machine. The components were then assembled into mesh-like stents of 6 and 8 mm in diameter. A special geometry of the components was designed to self-lock the assembled stents after being expanded by balloons. Characterization of the biodegradable PCL stents was carried out. PCL stents exhibited comparable mechanical properties with that of silicone sponge. Neither significant amount of collapse pressure reduction nor weight loss of the stents was observed after being submerged in phosphate buffered saline for 30 days. In addition, the stents were also implanted in the episcleral space of 10 New Zealand white rabbits. The stents were placed in radial direction and left unsutured after balloon expansion. The stents achieved an efficient buckling effect in echographic and fundus photographic examinations. The ocular pressure was significantly elevated after stent implantation and gradually normalized after the second week. The computed tomography studies verified the hypothesis of minimal migration of the PCL stents. The in vivo result suggests that balloon-expandable biodegradable stents can potentially serve as an ideal indenting biomaterial in retinal detachment surgery.


Nurse relationships and work group disruption.
As nursing administrators and managers respond to healthcare reform pressures with downsizing, rightsizing, and work group reorganization, they need to pay attention to and support the nursing work group relationships. A study of 908 registered nurses (RNs) in a variety of nursing work environments in four hospitals indicates that interpersonal relationships are an important part of job satisfaction, that there is a relationship between some types of work group disruption and RN satisfaction with interpersonal relationships, and that there is a relationship between work group disruption and RN perceptions of patient safety/quality of care.


Oridonin attenuates the release of pro-inflammatory cytokines in lipopolysaccharide-induced RAW264.7 cells and acute lung injury.
Acute lung injury (ALI) is a life-threatening inflammatory disease owing to the lack of specific and effective therapies. Oridonin (Ori) is an active diterpenoid isolated from Rabdosiarubescens (R.rubescens) that has been shown to possess a broadspectrum pharmacological properties including anti-inflammatory, antitumour, antioxidative and neuroregulatory effects. However, its potential protective mechanism in ALI is not well characterized. In this study, we demonstrated that Ori reduces the mortality of mice with ALI induced by a high dose of lipopolysaccharide (LPS), which suggests that Ori has a protective effect on LPS induced ALI. Next, our results confirmed that Ori improves LPS-induced localized pulmonary pathology and decreased the concentration of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in the serum. Nuclear factor-kappa B (NF-κB) is capable of regulating the transcription of pro-inflammatory factors. Interestingly, our results showed that Ori inhibits the expression of TLR4/MyD88 and phosphorylation of NF-κB p65 in lung tissues. To confirm this, we further validated the possible regulatory anti-inflammatory mechanisms of Ori in vitro. LPS-induced RAW264.7 cells, which are widely used as an inflammation model to evaluate the potential protective effect of drugs in vitro, were chosen for this study. Similar results were observed, that is, pre-treatment with Ori, markedly inhibited the nuclear translocation and phosphorylation of NF-κB p65 induced by LPS and subsequently decreased the release of pro-inflammatory cytokines that were increased by LPS. Overall, these results demonstrated that Ori exerts a therapeutic effect on ALI by inhibiting the release of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, through the TLR4/MyD88/NF-κB axis.


Preventing suicide in prison: a collaborative responsibility of administrative, custodial, and clinical staff.
Suicide is a sentinel event in prison, and preventive efforts reflect the adequacy and comprehensiveness of mental health, psychiatric, custodial, and administrative services in a correctional system. This article reviews the literature on suicide in prison during the past three decades and identifies the pattern and occurrence of risk factors. These risk factors are classified as demographic, institutional, and clinical. Based on this review, the author outlines specific administrative, custodial, and clinical steps and procedures that form the basis of a comprehensive suicide-prevention program that can be implemented in small and large systems. The author recognizes the limitations of staff availability, the budget constraints, and the ineffectiveness of efforts to prevent suicides that occur without any warning. Ultimately, a prevention program is the collective responsibility of administrative, custodial, and clinical staff.


Health benefits of walnut polyphenols: An exploration beyond their lipid profile.
Walnuts are commonly found in our diet and have been recognized for their nutritious properties for a long time. Traditionally, walnuts have been known for their lipid profile, which has been linked to a wide array of biological properties and health-promoting effects. In addition to essential fatty acids, walnuts contain a variety of other bioactive compounds, such as vitamin E and polyphenols. Among common foods and beverages, walnuts represent one of the most important sources of polyphenols, hence their effect over human health warrants attention. The main polyphenol in walnuts is pedunculagin, an ellagitannin. After consumption, ellagitannins are hydrolyzed to release ellagic acid, which is converted by gut microflora to urolithin A and other derivatives such as urolithins B, C, and D. Ellagitannins possess well known antioxidant and anti-inflammatory bioactivity, and several studies have assessed the potential role of ellagitannins against disease initiation and progression, including cancer, cardiovascular, and neurodegenerative diseases. The purpose of this review is to summarize current available information relating to the potential effect of walnut polyphenols in health maintenance and disease prevention.


Epigenetic regulation by long noncoding RNAs.
Recent studies show that transcription of the mammalian genome is not only pervasive but also enormously complex. It is estimated that an average of 10 transcription units, the vast majority of which make long noncoding RNAs (lncRNAs), may overlap each traditional coding gene. These lncRNAs include not only antisense, intronic, and intergenic transcripts but also pseudogenes and retrotransposons. Do they universally have function, or are they merely transcriptional by-products of conventional coding genes? A glimpse into the molecular biology of multiple emerging lncRNA systems reveals the "Wild West" landscape of their functions and mechanisms and the key problems to solve in the years ahead toward understanding these intriguing macromolecules.


Arcobacter lacus sp. nov. and Arcobacter caeni sp. nov., two novel species isolated from reclaimed water.
Two strains (RW43-9T and RW17-10T) recovered from secondary treated wastewater from the Wastewater Treatment Plant (WWTP) in Reus (Spain) were characterized by a polyphasic taxonomic study, showing evidence that they represented two novel Arcobacter species. Based on the 16S rRNA gene for strain RW43-9T, the closest relative was Arcobacter butzleri LMG 10828T (99.9 % similarity), while for strain RW17-10T it was Arcobacter venerupis CECT 7836T (99.4 %). Additionally, multilocus phylogenetic analysis of five concatenated housekeeping genes (atpA, gyrA, gyrB, hsp60 and rpoB) showed that the two strains formed separate branches that are different from known Arcobacter species. Whole genome sequences of the two strains (RW43-9T and RW17-10T) were obtained and they were compared with those of the type strains of their nearest species. Using average nucleotide identity and in silico DNA-DNA hybridization gave values that were below 96 and 70 %, respectively. These results clearly confirm that they represent novel species. Additionally, the phenotypic characterization of the strains allowed their differentiation from other species. Therefore, the strains are proposed as representing two novel species with the names Arcobacter lacus sp. nov. (type strain RW43-9T=CECT 8994T=LMG 29062T) and Arcobacter caeni sp. nov. (type strain RW17-10T=CECT 9140T=LMG 29151T).


Genome sequence and annotation of the B3 mycobacteriophage Phayeta.
Mycobacteriophage Phayeta was extracted from soil near Myrtle Beach, South Carolina using Mycobacterium smegmatis as a host. Annotation of the 68,700 base-pair circularly permuted genome identified 104 predicted protein-encoding genes, 34 of which have functional assignments.


[Chemical-nutritional characterization of the moss Spagnum magellanicum].
The goal of the present study was to know the chemical characteristics of the moss Sphagnum magellanicum (S.M.) growing in the southern part of Chile, spreading approximately. in a geographic area of 500.000 Has. Very few antecedents are reported in the literature concerning the functional properties of this resource, with the exception of the water absorption and holding capacity. Many of the industrial or agricultural uses of this moss are strongly related with this characteristic. Looking for other alternatives of utilization, it has been planned its incorporation to staple foods as a source of dietary fiber. But first it is necessary to know its chemical characteristics Representative samples of this material were submitted to different chemical analysis such as proximal analysis, fractional fiber analysis and anti nutrient factors.. Results of those analysis show the high amount of dietary fiber founded in this resource (77%), higher than reported data for other traditional fiber sources such as lupin bran, rice hull, barley hull, oat bran, etc. Finally it is important emphasize the absence of antinutrient factor in this moss, that could make feasible its use for human nutrition.


The Five Ds of Outpatient Antibiotic Stewardship for Urinary Tract Infections.
Urinary tract infections (UTI) are one of the most common indications for antibiotic prescriptions in the outpatient setting. Given rising rates of antibiotic resistance among uropathogens, antibiotic stewardship is critically needed to improve outpatient antibiotic use, including in outpatient clinics (primary care and specialty clinics) and emergency departments. Outpatient clinics are in general a neglected practice area in antibiotic stewardship programs, yet most antibiotic use in the United States is in the outpatient setting. This article provides a comprehensive review of antibiotic stewardship strategies for outpatient UTI in the adult population, with a focus on the "five Ds" of stewardship for UTI, including right diagnosis, right drug, right dose, right duration, and de-escalation. Stewardship interventions that have shown success for improving prescribing for outpatient UTI are discussed, including diagnostic stewardship strategies, such as reflex urine cultures, computerized decision support systems, and modified reporting of urine culture results. Among the many challenges to achieving stewardship for UTI in the outpatient setting, some of the most important are diagnostic uncertainty, increasing antibiotic resistance, limitations of guidelines, and time constraints of stewardship personnel and front-line providers. This article presents a stewardship framework, built on current evidence and expert opinion, that clinicians can use to guide their own outpatient management of UTI.


Atrial natriuretic peptide in patent ductus arteriosus.
Plasma concentrations of atrial natriuretic peptide (ANP) were measured in nine infants (age 4 days-9 months) before and after closure of patent ductus arteriosus. Initially all patients had marked distention of the left atrium as indicated by a left atrium to aortic root ratio greater than or equal to 1.3 on echocardiography. After closure of the ductus, operative in six and pharmacological in three patients, left atrial size normalized (left atrium to aortic root ratio less than 1.3) in all patients, except in one treated surgically. Before closure the plasma concentration of ANP was 86-2224 pg/ml and after closure 44-1400 pg/ml. There was a significant correlation between the size of left atrium and plasma concentration of ANP (r = 0.56; p = 0.01). Our results suggest that in infants with patent ductus arteriosus the left atrium is the main source of ANP. The secretory rate of ANP decreases immediately after restoring left atrial size by closure of the ductus.


Elevated plasma levels of Mac-2 binding protein predict poor cardiovascular outcomes in patients with acute coronary syndrome.
Mac-2 binding protein (M2BP) is an inflammatory glycoprotein associated with carotid atherosclerosis and all-cause mortality in patients with suspected coronary artery diseases. We aimed to explore the potential association of plasma M2BP levels with unstable plaque morphology and cardiovascular outcomes in patients with acute coronary syndrome (ACS). We compared plasma M2BP levels among three groups: 216 patients with ACS, 82 patients with stable angina pectoris, and 50 controls. Angiographic analyses of complex lesions were carried out in patients with ACS and they were followed up prospectively for 12 months for the occurrence of major adverse cardiovascular outcomes (MACEs). Patients with ACS showed significantly higher plasma levels of M2BP than patients with stable angina pectoris (P<0.001) and controls (P<0.001). M2BP levels correlated positively with the presence (P<0.001) and extent (P=0.005) of complex lesions. During follow-up, 45 (20.8%) cases of MACEs occurred. Survival analysis indicated that high M2BP levels were associated with a poor prognosis (log-rank P=0.008). After Cox multivariate adjustment, plasma M2BP levels remained an independent predictor of MACEs either as a continuous variable (hazard ratio: 1.178, 95% confidence interval: 1.093-1.270, P<0.001) or as a categorical variable (hazard ratio: 2.783, 95% confidence interval: 1.433-5.404, P=0.002). Plasma M2BP levels might be predictive of unstable plaque and were associated independently with poor cardiovascular outcomes in patients with ACS.


Adolescents' face mask usage and contact transmission in novel Coronavirus.
The global outbreak of coronavirus has become an international public health threat. Prevention is of paramount importance to contain its spread. This study observes face mask wearing behavior and contact transmission problems in Taiwan. Teachers track student status in class. In addition to measuring body temperature and regular disinfection, classrooms require ventilation wear mask, provide alcohol spray and avoid sharing the microphone. Both questionnaire surveys and experimental were utilized. A total of 160 adults residing in Taiwan participated in the survey. The dye simulated the possible virus area on the mask surface during usage. Subjects were required to complete a questionnaire and simulate the spread of contact transmission when using a computer. Eighty-one % of respondents reported consistent use of surgical masks several times a day. They reported taking their masks off in relatively safe areas. Most people reported using one mask per day and storing the masks in their pockets. As a result, masks surface become a contamination source. In the contact experiment, ten adults were requested to don and doff a surgical mask while doing a word processing task. The extended contamination areas were recorded and identified by image analysis. The results show an average contamination area of the workspace is significant 530 cm2. When the hand touches the surface of the mask, it may spread the virus to the subsequent contact area.