bluuebunny/crossref_metadata_2025 huggingface dataset:
Inner Flow-Induced Buckling of Fiber-Reinforced Polymeric Catenary Risers
Authors: Pavlou Dimitrios G.
Published: April 2020

Production and deep-sea mining risers should have sufficient flexibility to avoid severe loading due to vessel motions. Free hanging catenary is the simplest and cheapest configuration because of the ease of installation and the minimal requirements for subsea infrastructure. The interaction of the inner flow with the moving riser dominates the dynamic stability of the system. In the present work, the motion equation for a long, multilayered, fiber-reinforced polymeric (FRP) flexible riser is formulated, and a numerical method for critical inner flow velocities causing buckling in risers is proposed. Taking into account the motion equation, the physics of the inner flow-induced buckling phenomena is analyzed and a detailed interpretation of the terms of the motion equation is carried out. With the aid of transfer matrices and finite elements, the dynamic buckling modes and the natural frequencies are determined. It is proved that the dynamic stability of the riser is affected by the balance of the elastic flexural restoring force, the centrifugal force of the fluid flow in the curved portions, the Coriolis force of the fluid, the inertial force of the fluid and pipe mass, and the damping due to the effect of the surrounding water.
Acoustic Performance of a Periodically Voided Viscoelastic Medium With Uncertainty in Design Parameters
Authors: Sharma Gyani Shankar , Faverjon Beatrice , Dureisseix David , Skvortsov Alex , MacGillivray Ian , Audoly Christian , Kessissoglou Nicole
Published: April 2020

The effect of uncertainties in material and geometric parameters on the acoustic performance of a viscoelastic coating is investigated. The model of the coating comprises a structure conventionally used in underwater applications, namely a soft elastic matrix embedded with periodic arrangements of voids. To investigate the effect of uncertainties on the acoustic performance of the coating, stochastic models based on the non-intrusive polynomial chaos expansion (PCE) method and Monte Carlo (MC) simulations are developed. The same analytical formulation of the acoustic coating is employed in both stochastic models. In the PCE method, the analytical model is transformed into a computationally efficient surrogate model using stochastic collocation. The effect of uncertainty in an individual geometric or material parameter on the acoustic performance of the coating is investigated by examining the mean, envelopes, and probability distribution of the monopole resonance frequency and sound transmission through the coating. The effect of variation in combinations of geometric and material parameters is then examined. Uncertainty in the geometric parameters is observed to have greater impact on the resonance frequency of the voids and sound transmission through the coating compared to uncertainty in the material properties.
Mechanism of actin N-terminal acetylation
Authors: Rebowski Grzegorz , Boczkowska Malgorzata , Drazic Adrian , Ree Rasmus , Goris Marianne , Arnesen Thomas , Dominguez Roberto
Published: April 2020

NAA80 Nt-acetylates the six actin isoforms by specifically targeting the complex of actin-profilin among all cellular proteins.
Locus coeruleus norepinephrine activity mediates sensory-evoked awakenings from sleep
Authors: Hayat Hanna , Regev Noa , Matosevich Noa , Sales Anna , Paredes-Rodriguez Elena , Krom Aaron J. , Bergman Lottem , Li Yong , Lavigne Marina , Kremer Eric J. , Yizhar Ofer , Pickering Anthony E. , Nir Yuval
Published: April 2020

Do noises wake you up at night? Blame your locus coeruleus.
Force production of human cytoplasmic dynein is limited by its processivity
Authors: Brenner Sibylle , Berger Florian , Rao Lu , Nicholas Matthew P. , Gennerich Arne
Published: April 2020

We present a novel experimental framework allowing for determination of the maximal force generation of weakly processive motors.
Chinese Liquor Fermentation: Identification of Key Flavor-Producing
Lactobacillus
spp. by Quantitative Profiling with Indigenous Internal Standards
Authors: Du Rubing , Wu Qun , Xu Yan
Published: April 2020

In this study, we developed a novel strategy using indigenous internal standards to normalize the high-throughput amplicon sequencing results. We chose two
Lactobacillus
species as indigenous internal standards and characterized the absolute abundance of the bacterial community. Further, we identified
Lactobacillus
as the key flavor producer using quantitative microbiome profiling combined with multivariate statistics and metatranscriptomic analysis. This work developed a novel strategy for absolute quantitative abundance analysis of microbiota and expanded our understanding of the role of
Lactobacillus
in food fermentation.
Role of Endogenous Interleukin-18 in Resolving Wild-Type and AttenuatedSalmonella typhimuriumInfections
Authors: Dybing Jody K. , Walters Nancy , Pascual David W.
Published: April 2020

The stimulation of gamma interferon (IFN-γ) has been shown to be essential in resolving infections by intracellular pathogens. As such, several different cytokines including, interleukin-12 (IL-12) and IL-18, can induce IFN-γ. To resolveSalmonellainfections, the stimulation of IL-12 and IFN-γ are important for mediating its clearance. In this present study, the relevance of IL-18 in protection against oral challenge withSalmonella typhimuriumwas investigated to determine the role of this IFN-γ-promoting cytokine. Rabbit anti-murine IL-18 antisera was generated and administered prior to the oral challenge of BALB/c and IL-12p40-deficient knockout (IL-12KO) mice with a wild-typeS. typhimuriumstrain. The median survival time was reduced by 2 days for the anti-IL-18-treated BALB/c mice, while no significant reduction in survival rate for the anti-IL-18-treated IL-12KO mice was observed compared to vehicle-treated mice. To investigate the contribution of IL-18 to resolvingSalmonellainfections, an attenuatedaro-negative mutant (H647) was orally administered to BALB/c mice. ThisSalmonellainfection induced both IL-12 and IFN-γ in both the Peyer's patches and the spleens. In vehicle-treated mice, Peyer's patch IL-12 peaked by 24 h, while IL-18 levels peaked at 3 days, suggesting sequential support by these cytokines for IFN-γ. Anti-IL-18 treatment exerted its greatest effect upon the mucosal compartment, limiting early IFN-γ production. However, anti-IL-18 treatment had little effect upon splenic IFN-γ levels until late in the response. Infection of IL-12KO mice with H647 strain induced IFN-γ, but it was not supported by IL-18, although IL-18 levels were reduced by this treatment. These results suggest that IL-18 does contribute to the clearance ofS. typhimuriumand that endogenously induced IL-18 could not substitute for IL-12.
Mutants ofEscherichia coliHeat-Labile Toxin Act as Effective Mucosal Adjuvants for Nasal Delivery of an Acellular Pertussis Vaccine: Differential Effects of the Nontoxic AB Complex and Enzyme Activity on Th1 and Th2 Cells
Authors: Ryan Elizabeth J. , McNeela Edel , Murphy Geraldine A. , Stewart Helen , O'hagan Derek , Pizza Mariagrazia , Rappuoli Rino , Mills Kingston H. G.
Published: April 2020

Mucosal delivery of vaccines is dependent on the identification of safe and effective adjuvants that can enhance the immunogenicity of protein antigens administered by nasal or oral routes. In this study we demonstrate that two mutants ofEscherichia coliheat-labile toxin (LT), LTK63, which lacks ADP-ribosylating activity, and LTR72, which has partial enzyme activity, act as potent mucosal adjuvants for the nasal delivery of an acellular pertussis (Pa) vaccine. Both LTK63 and LTR72 enhanced antigen-specific serum immunoglobulin G (IgG), secretory IgA, and local and systemic T-cell responses. Furthermore, using the murine respiratory challenge model for infection withBordetella pertussis, we demonstrated that a nasally delivered diphtheria, tetanus, and acellular pertussis (DTPa) combination vaccine formulated with LTK63 as an adjuvant conferred a high level of protection, equivalent to that generated with a parenterally delivered DTPa vaccine formulated with alum. This study also provides significant new information on the roles of the binding and enzyme components of LT in the modulation of Th1 and Th2 responses. LTK63, which lacks enzyme activity, promoted T-cell responses with a mixed Th1–Th2 profile, but LTR72, which retains partial enzyme activity, and the wild-type toxin, especially at low dose, induced a more polarized Th2-type response and very high IgA and IgG antibody titers. Our findings suggest that the nontoxic AB complex has broad adjuvant activity for T-cell responses and that the ADP-ribosyltransferase activity of the A subunit also appears to modulate cytokine production, but its effect on T-cell subtypes, as well as enhancing, may be selectively suppressive.
Activity of Monosaccharide Lipid A Analogues in Human Monocytic Cells as Agonists or Antagonists of Bacterial Lipopolysaccharide
Authors: Matsuura Motohiro , Kiso Makoto , Hasegawa Akira
Published: April 2020

The lipid A portion of bacterial lipopolysaccharide (LPS) plays a central role in the production of endotoxic mediators. Different responses between human and murine macrophages to lipid A-like structures have been indicated. We investigated a series of structurally related monosaccharide lipid A analogues for their potency to activate human macrophage U937 cells and peripheral blood mononuclear cells for production of tumor necrosis factor-α and interleukin-6 compared with their potency to activate murine macrophage RAW264.7 cells. Two of the analogues were found to have sufficient potency to activate the human cells as well as the murine cells. These analogues comprised-glucosamine, phosphoryl groups, and acyl groups of defined carbon chain lengths (C14and C12) in a ratio of 1:1:3. This ratio of molecular constituents is proportional to that of the complete disaccharide structure of lipid A (2:2:6). Other analogues with two or four C14acyl groups and with three acyl groups but including a C10or a C16acyl group, which are active to murine cells, showed no LPS-agonistic activity, but did show LPS-antagonistic activity, to human cells. An LPS-antagonistic analogue in the murine cells also showed antagonistic activity in human cells. These results reveal that lipid A analogues recognized as being LPS agonists by human macrophages have common structural features in monosaccharide and disaccharide structures which are more strict than those required for recognition by murine macrophages and that broad lipid A-like structures are recognized as being LPS antagonists by human cells but are recognized by murine cells as being either LPS agonists or antagonists.
Induction of Cytokines and Chemokines in Human Monocytes byMycoplasma fermentans-Derived Lipoprotein MALP-2
Authors: Kaufmann A. , Mühlradt P. F. , Gemsa D. , Sprenger H.
Published: April 2020

Bacterial infections are characterized by strong inflammatory reactions. The responsible mediators are often bacterially derived cell wall molecules, such as lipopolysaccharide or lipoteichoic acids, which typically stimulate monocytes and macrophages to release a wide variety of inflammatory cytokines and chemokines. Mycoplasmas, which lack a cell wall, may also stimulate monocytes very efficiently. This study was performed to identify mycoplasma-induced mediators. We investigated the induction of cytokines and chemokines in human monocytes exposed to theMycoplasma fermentans-derived membrane component MALP-2 (macrophage-activating lipopeptide 2) by dose response and kinetic analysis. We found a rapid and strong MALP-2-inducible chemokine and cytokine gene expression which was followed by the release of chemokines and cytokines with peak levels after 12 to 20 h. MALP-2 induced the neutrophil-attracting CXC chemokines interleukin-8 (IL-8) and GRO-α as well as the mononuclear leukocyte-attracting CC chemokines MCP-1, MIP-1α, and MIP-1β. Production of the proinflammatory cytokines tumor necrosis factor alpha and IL-6 started at the same time as chemokine release but required 10- to 100-fold-higher MALP-2 doses. The data show that the mycoplasma-derived lipopeptide MALP-2 represents a potent inducer of chemokines and cytokines which may, by the attraction and activation of neutrophils and mononuclear leukocytes, significantly contribute to the inflammatory response during mycoplasma infection.
Misexpression of the Opaque-Phase-Specific Gene
PEP1
(
SAP1
) in the White Phase of
Candida albicans
Confers Increased Virulence in a Mouse Model of Cutaneous Infection
Authors: Kvaal Christopher , Lachke Salil A. , Srikantha Thyagarajan , Daniels Karla , McCoy James , Soll David R.
Published: April 2020

Candida albicans
WO-1 switches reversibly and at high frequency between a white and an opaque colony-forming phenotype that includes dramatic changes in cell morphology and physiology. A misexpression strategy has been used to investigate the role of the opaque-phase-specific gene
PEP1
(
SAP1
), which encodes a secreted aspartyl proteinase, in the expression of the unique opaque-phase phenotype and phase-specific virulence in two animal models. The
PEP1
(
SAP1
) open reading frame was inserted downstream of the promoter of the white-phase-specific gene
WH11
in the transforming vector pCPW7, and the resulting transformants were demonstrated to misexpress
PEP1
(
SAP1
) in the white phase. Misexpression did not confer any of the unique morphological characteristics of the opaque phase to cells in the white phase and had no effect on the switching process. However, misexpression conferred upon white-phase cells the increased capacity of opaque-phase cells to grow in medium in which protein was the sole nitrogen source. Misexpression of
PEP1
(
SAP1
) had no effect on the virulence of white-phase cells in a systemic mouse model, in which white-phase cells were already more virulent than opaque-phase cells. Misexpression did, however, confer upon white-phase cells the dramatic increase in colonization of skin in a cutaneous mouse model that was exhibited by opaque-phase cells. Misexpression of
PEP1
(
SAP1
) conferred upon white-phase cells two dissociable opaque-phase characteristics: increased adhesion and the capacity to cavitate skin. The addition of pepstatin A to the cutaneous model inhibited the latter, but not the former, suggesting that the latter is effected by released enzyme, while the former is effected by cell-associated enzyme.
Complete Genome Sequence of Temperature-Dependent Pigment-Producing Serratia marcescens ATCC 274
Authors: Yabe Suzuka , Fukushima Jun
Published: April 2020

Serratia marcescens
ATCC 274 produces the red pigment prodigiosin and the biosurfactant serrawettin W1 at 30°C but not at 37°C. A complete, high-quality genome sequence of
S. marcescens
ATCC 274 was obtained and found to comprise a single 5,148,533-bp circular genome with 4,799 genes.
Gastrostomy and quality of life in children with intellectual disability: a qualitative study
Authors: Glasson Emma J , Forbes David , Ravikumara Madhur , Nagarajan Lakshmi , Wilson Andrew , Jacoby Peter , Wong Kingsley , Leonard Helen , Downs Jenny
Published: April 2020

Objective

Children with intellectual disability and marked feeding difficulties may undergo gastrostomy insertion to assist with their nutritional and medication needs. Use has increased recently for younger children, and it is intended to provide long-term support. This study explored the perceived value of gastrostomy for the quality of life (QOL) of children with intellectual disabilities and their families.

Methods

Twenty-one primary caregivers of children with intellectual disability aged 2–18 years participated in semistructured telephone interviews. Data were analysed using directed content analysis, and data were coded to existing QOL domains relevant to children with intellectual disability and their families.

Results

Benefits in each of the child and family QOL domains were represented in the interview data. For children, the impacts of gastrostomy for the physical health domain were predominant, supplemented by experiences of value for emotional well-being, social interactions, leisure activities and independence. For families, gastrostomy was integrated into multiple aspects of QOL relating to family interactions, parenting, resources and supports, health and safety, and advocacy support for disability. Shortcomings related to difficulties with equipment and complications.

Conclusions

Our comprehensive overview of the value of gastrostomy for children with intellectual disability and their families was classified within a QOL framework. Gastrostomy was mainly supportive over long time periods across many QOL domains. Findings will be of use to patient counselling and education and the development of family support resources.
Narrow band imaging in the diagnosis of bladder schistosomiasis
Authors: Jimie Joachim , Lyttle Margaret
Published: April 2020

A 23-year-old man presented to us with multiple episodes of visible haematuria associated with dysuria, but no other symptoms suggestive of infection. His physical examination was completely unremarkable. On detailed evaluation of history, it was noted that he was treated for urinary schistosomiasis as a child in Sudan. A diagnostic flexible cystoscopy, with both white light and narrow band imaging (NBI), was done among other tests as a further diagnostic tool to investigate possible causes. This revealed the characteristic features of bladder schistosomiasis. Urine microscopy forSchistosoma haematobiumeggs was negative, and this could have caused the diagnosis to be missed. He was treated with praziquantel for chronic bladder schistosomiasis. This is the first time that the use of NBI as an adjunct to white light imaging in the diagnosis of bladder schistosomiasis has been reported.
Building HIV healthcare worker capacity through telehealth in Vietnam
Authors: Pollack Todd M , Nhung Vo Thi Tuyet , Vinh Dang Thi Nhat , Hao Duong Thi , Trang Le Thi Thu , Duc Pham Anh , Kinh Nguyen Van , Dung Nguyen Thi Hoai , Dung Duong Lan , Ninh Nguyen Thi , Huyen Ho Thi Thanh , Huy Vo Xuan , Hai Duong Minh , Khanh Truong Huu , Hien Nguyen Thi Thu , Khuong Pham Tram An , Trong Nguyen The , Lam Nguyen Van , Phinh Vu Ngoc , Phuong Do Thi , Duat Nguyen Duc , Liem Nguyen Thanh , Binh Nguyen Thanh , Chi Nguyen K , Yen Le Ngoc , Cosimi Lisa
Published: April 2020

Development of a robust technical assistance system is an essential component of a sustainable HIV response. Vietnam’s National HIV Program is transitioning from a largely donor-funded programme to one primarily supported by domestic resources. Telehealth interventions are increasingly being used for training, mentoring and expert consultation in high-resource settings and hold significant potential for use as a tool to build HIV health worker capacity in low and middle-income countries. We designed, implemented and scaled up a novel HIV telehealth programme for Vietnam, with the goal of building a sustainable training model to support the country’s HIV workforce needs. Over a 4-year period, HIV telehealth programmes were initiated in 17 public institutions with participation of nearly 700 clinical sites across 62 of the 63 provinces in the country. The telehealth programme was used to deliver certificate training courses, provide clinical mentoring and case-based learning, support programme implementation, provide coaching in quality improvement and disseminate new guidelines and policies. Programme evaluation demonstrated improved health worker self-reported competence in HIV care and treatment and high satisfaction among the programme participants. Lessons learnt from Vietnam’s experience with telehealth can inform country programmes looking to develop a sustainable approach to HIV technical assistance and health worker capacity building.
Fluocinolone acetonide (0.19 mg) intravitreal implant reduces treatment burden and improves practice resource utilisation for patients with diabetic macular oedema
Authors: Byun Matthew , Osher James , Riemann Christopher D
Published: April 2020

Objective

Patients with diabetic macular oedema (DME) are known to have significantly greater medical treatment burden than patients with non-DME. Frequent injections and office visits can have a substantial impact on patient adherence and quality of life. This analysis assesses the impact of the 0.19 mg fluocinolone acetonide (FAc) implant (or injection) on treatment burden and practice resource utilisation in patients with DME.

Methods and analysis

This study is a single-centre retrospective chart review of 30 eyes (23 patients) that received a single FAc implant. Data was collected for a 12-month period pre-injection and post-injection of the FAc implant. Primary outcomes included the frequency of injections and ophthalmology office visits. Secondary outcomes included visual acuity (VA), intraocular pressure (IOP) and central subfield thickness (CSFT).

Results

The injection frequency significantly decreased from one injection every 2.6 months pre-injection to one injection every 8.8 months post-injection of the FAc implant (p<0.001). Sixty-three percent of the subjects did not require additional injections post-FAc implant. The mean number of ophthalmology office visits significantly decreased from 12.7 visits pre-FAc to 9.3 visits post-FAc implant (p<0.001). The mean VA (p=0.24) and CSFT (p=0.39) showed a mild numerical improvement that was not statistically significant. Thirty-seven percent of the eyes required additional IOP lowering drops. No eyes required incisional glaucoma surgeries.

Conclusions

The FAc implant significantly decreased the treatment burden and improved practice resource utilisation while maintaining or improving VA and CSFT. IOP events were mostly well-controlled with drops and no eyes required incisional glaucoma surgery.
Opioid stewardship: implementing a proactive, pharmacist-led intervention for patients coprescribed opioids and benzodiazepines at an urban academic primary care centre
Authors: Tilli Tiana , Hunchuck Jonathan , Dewhurst Norman , Kiran Tara
Published: April 2020

In 2017, almost 4000 Canadians died from opioid-related causes. Coadministration of opioids and benzodiazepines is a risk factor for overdose. Few studies have evaluated leveraging pharmacists to address opioid-benzodiazepine coprescribing. Our aim was to develop and test a role for pharmacists as opioid stewards, to reduce opioid and benzodiazepine doses in coprescribed patients. We conducted Plan-Do-Study-Act cycles between November 2017 and May 2018 across two primary care centre clinics. A third clinic acted as a control. Our intervention included a pharmacist: (1) identifying patients through medical record queries; (2) developing care plans; (3) discussing recommendations with physicians and (4) discussing implementing recommendations. We refined the intervention according to patient and physician feedback. At the intervention clinics, the number of patients with pharmacist developed care plans increased from less than 20% at baseline to over 60% postintervention. There was also a fourfold increase in the number of patients with an active opioid taper. At the control clinic, the number of patients with pharmacist developed care plans remained relatively stable at less than 20%. The number of patients with active opioid tapers remained zero. At the intervention clinics, mean daily opioid dose decreased 11% from 50.5 milligrams morphine equivalent (MME) to 44.7 MME. At the control clinic, it increased 15% from 62.3 MME to 71.4 MME. The number of patients with a benzodiazepine taper remained relatively stable at both the intervention and control clinics at less than 20%. At the intervention clinics, mean daily benzodiazepine dose decreased 8% from 9.9 milligrams diazepam equivalent (MDE) to 9.3 MDE. At the control clinic, it decreased 4% from 10.8 MDE to 10.4 MDE. A proactive, pharmacist-led intervention for coprescribed patients increased opioid tapers and decreased opioid and benzodiazepine doses. Future work will help us understand whether sustaining the intervention ultimately reduces rates of opioid-benzodiazepine coprescribing.
Prevalence of harmful diagnostic errors in hospitalised adults: a systematic review and meta-analysis
Authors: Gunderson Craig G , Bilan Victor P , Holleck Jurgen L , Nickerson Phillip , Cherry Benjamin M , Chui Philip , Bastian Lori A , Grimshaw Alyssa A , Rodwin Benjamin A
Published: April 2020

Background

Diagnostic error is commonly defined as a missed, delayed or wrong diagnosis and has been described as among the most important patient safety hazards. Diagnostic errors also account for the largest category of medical malpractice high severity claims and total payouts. Despite a large literature on the incidence of inpatient adverse events, no systematic review has attempted to estimate the prevalence and nature of harmful diagnostic errors in hospitalised patients.

Methods

A systematic literature search was conducted using Medline, Embase, Web of Science and the Cochrane library from database inception through 9 July 2019. We included all studies of hospitalised adult patients that used physician review of case series of admissions and reported the frequency of diagnostic adverse events. Two reviewers independently screened studies for inclusion, extracted study characteristics and assessed risk of bias. Harmful diagnostic error rates were pooled using random-effects meta-analysis.

Results

Twenty-two studies including 80 026 patients and 760 harmful diagnostic errors from consecutive or randomly selected cohorts were pooled. The pooled rate was 0.7% (95% CI 0.5% to 1.1%). Of the 136 diagnostic errors that were described in detail, a wide range of diseases were missed, the most common being malignancy (n=15, 11%) and pulmonary embolism (n=13, 9.6%). In the USA, these estimates correspond to approximately 249 900 harmful diagnostic errors yearly.

Conclusion

Based on physician review, at least 0.7% of adult admissions involve a harmful diagnostic error. A wide range of diseases are missed, including many common diseases. Fourteen diagnoses account for more than half of all diagnostic errors. The finding that a wide range of common diagnoses are missed implies that efforts to improve diagnosis must target the basic processes of diagnosis, including both cognitive and system-related factors.

PROSPERO registration number

CRD42018115186.
Women’s experiences of self-referral to an abortion service: qualitative study
Authors: Low Shin Thong , Chen Zhong Eric , Cameron Sharon
Published: April 2020

Background

Guidelines from the UK recommend that women should be able to self-refer to abortion services. In 2016, a self-referral system was introduced to the abortion service in Edinburgh, Scotland, as an option for women. Women could telephone a dedicated phone line during office hours and speak to an administrative assistant working in the abortion service who provided them the next available appointment to be seen in the service. This study aimed to evaluate a self-referral service to abortion by investigating its impact on women’s experiences of the referral process.

Methodology

21 semistructured interviews of women attending a specialist abortion service in Edinburgh, Scotland, were conducted. Interviews were transcribed verbatim and thematically analysed. The interviews focused on women’s experience of the referral process.

Results

Three main themes arose from the interviews, including reasons for choosing self-referral, experience of self-referral and challenges to using self-referral. Reasons for choosing self-referral were related to convenience, privacy and autonomy. Women found the experience of self-referral to be pleasant, non-judgemental and patient-centred, and self-referral prepared them for the appointment at the specialist abortion service. However, some women felt rushed, and self-referral made them anxious to attend the appointment. Challenges were difficulty with getting through on telephone lines, varying levels of support required for different individuals and awareness about the option of self-referral.

Conclusion

Women valued the option of self-referral. Women felt that the service should be expanded to increase availability,and promoted to women more widely within the community .
Loneliness and self-rated physical health among gay, bisexual and other men who have sex with men in Vancouver, Canada
Authors: Marziali Megan E , Armstrong Heather L , Closson Kalysha , McLinden Taylor , Wang Lu , Barath Justin , Harris Marianne , Roth Eric A , Moore David M , Lachowsky Nathan J , Hogg Robert S , Sang Jordan M , Card Kiffer G
Published: April 2020

Background

Due to stigma and discrimination, gay, bisexual and other men who have sex with men (gbMSM) potentially carry a heightened burden of loneliness. This analysis investigates loneliness among gbMSM and its relationship with self-rated physical health, along with the mediating effect of depression.

Methods

Participants were recruited using respondent-driven sampling into the Momentum Health Study (February 2012–February 2015) with follow-up visits occurring every 6 months till February 2018. Using computer-assisted self-interviews, measures of loneliness were assessed using a 6-item Loneliness Scale for Emotional and Social Loneliness (lonely vs not lonely). Current physical health was self-assessed (poor, fair, good, very good or excellent). A multivariable generalised linear-mixed model with a logit link function was used to examine the relationship between loneliness and self-rated physical health. We further investigated the mediating effect of depressive symptomatology on this relationship via the Hospital Anxiety and Depression Scale.

Results

Of the 770 participants included, we found that 61% (n=471) experienced loneliness at baseline. Of the 674 (88%) who reportedgood/very good/excellentphysical health, 59% (n=391) reported loneliness, compared with 87% (n=80) of those in poor/fair self-rated physical health who reported feeling lonely. After adjustment for confounding, loneliness was associated with poor self-rated physical health (adjusted OR 1.71; 95% CI 1.13 to 2.60). Depressive symptomatology was found to partially mediate this relationship.

CONCLUSION

There may be a need for the integration of social, mental and physical health programming, targeted towards gbMSM, to alleviate the degree of loneliness experienced and its co-occurrence with poor self-rated physical health.
Melanoma-specific bcl-2 promotes a protumoral M2-like phenotype by tumor-associated macrophages
Authors: Di Martile Marta , Farini Valentina , Consonni Francesca Maria , Trisciuoglio Daniela , Desideri Marianna , Valentini Elisabetta , D'Aguanno Simona , Tupone Maria Grazia , Buglioni Simonetta , Ercolani Cristiana , Gallo Enzo , Amadio Bruno , Terrenato Irene , Foddai Maria Laura , Sica Antonio , Del Bufalo Donatella
Published: April 2020

Background

A bidirectional crosstalk between tumor cells and the surrounding microenvironment contributes to tumor progression and response to therapy. Our previous studies have demonstrated that bcl-2 affects melanoma progression and regulates the tumor microenvironment. The aim of this study was to evaluate whether bcl-2 expression in melanoma cells could influence tumor-promoting functions of tumor-associated macrophages, a major constituent of the tumor microenvironment that affects anticancer immunity favoring tumor progression.

Methods

THP-1 monocytic cells, monocyte-derived macrophages and melanoma cells expressing different levels of bcl-2 protein were used. ELISA, qRT-PCR and Western blot analyses were used to evaluate macrophage polarization markers and protein expression levels. Chromatin immunoprecipitation assay was performed to evaluate transcription factor recruitment at specific promoters. Boyden chamber was used for migration experiments. Cytofluorimetric and immunohistochemical analyses were carried out to evaluate infiltrating macrophages and T cells in melanoma specimens from patients or mice.

Results

Higher production of tumor-promoting and chemotactic factors, and M2-polarized activation was observed when macrophages were exposed to culture media from melanoma cells overexpressing bcl-2, while bcl-2 silencing in melanoma cells inhibited the M2 macrophage polarization. In agreement, the number of melanoma-infiltrating macrophages in vivo was increased, in parallel with a greater expression of bcl-2 in tumor cells. Tumor-derived interleukin-1β has been identified as the effector cytokine of bcl-2-dependent macrophage reprogramming, according to reduced tumor growth, decreased number of M2-polarized tumor-associated macrophages and increased number of infiltrating CD4+IFNγ+and CD8+IFNγ+effector T lymphocytes, which we observed in response to in vivo treatment with the IL-1 receptor antagonist kineret. Finally, in tumor specimens from patients with melanoma, high bcl-2 expression correlated with increased infiltration of M2-polarized CD163+macrophages, hence supporting the clinical relevance of the crosstalk between tumor cells and microenvironment.

Conclusions

Taken together, our results show that melanoma-specific bcl-2 controls an IL-1β-driven axis of macrophage diversion that establishes tumor microenvironmental conditions favoring melanoma development. Interfering with this pathway might provide novel therapeutic strategies.
Relation of Ionic Conductivity to Solvent Rotation Times in Dinitrile Plastic Crystal Solvents
Authors: Davidowski Stephen , Young-Gonzales Amanda R. , Richert Ranko , Yarger Jeff , Angell C. Austen
Published: April 2020

In a much-cited paper, Armand and coworkers showed that lithium bistrifluoromethyl sulfonylimide (LiTFSI) and other salts dissolve in the well-known plastic crystal, succinonitrile, (CN-CH2-CH2-CN) to give a highly conducting solid solution which they proposed as a novel approach to lithium electrolyte solid state battery technology. Although succinonitrile has been much studied as a molecular rotator phase, there was no direct reference made to its reorientational motion in their paper. In a previous paper we have shown that the time scale for magnetic fluctuations and reorientational relaxation times in dinitrile solvent mixtures (which can be studied over wide temperature and relaxation time ranges) are in close correspondence. Here we use this finding to study the relation between conductivity relaxation times of the LiTFSI solutions and the reorientation times of the solvent molecules. We find that, while the solvent molecule reorientation times accord well with the conductivity relaxation time, the lithium ion is in an environment that fluctuates more slowly. Unfortunately, this will lead to concentration polarization problems in any electrochemical device application. Ways to avoid this problem while maintaining the plastic crystal advantage are suggested. (184)
Wound healing and fibrosis: a contrasting role for periostin in skin and the oral mucosa
Authors: Nikoloudaki Georgia , Creber Kendal , Hamilton Douglas W.
Published: April 2020

Both skin and oral mucosa are characterized by the presence of keratinized epithelium in direct apposition to an underlying collagen-dense connective tissue. Despite significant overlap in structure and physiological function, skin and the oral mucosa exhibit significantly different healing profiles in response to injury. The oral mucosa has a propensity for rapid restoration of barrier function with minimal underlying fibrosis, but in contrast, skin is associated with slower healing and scar formation. Modulators of cell function, matricellular proteins have been shown to play significant roles in cutaneous healing, but their role in restoration of the oral mucosa is poorly defined. As will be discussed in this review, over the last 12 years our research group has been actively investigating the role of the profibrotic matricellular protein periostin in tissue homeostasis and fibrosis, as well as healing, in both skin and gingiva. In the skin, periostin is highly expressed in fibrotic scars and is upregulated during cutaneous wound repair, where it facilitates myofibroblast differentiation. In contrast, in gingival healing, periostin regulates extracellular matrix synthesis but does not appear to be associated with the transition of mesenchymal cells to a contractile phenotype. The significance of these findings will be discussed, with a focus on periostin as a potential therapeutic to augment healing of soft tissues or suppress fibrosis.
Sympathetic neural recruitment strategies following acute intermittent hypoxia in humans
Authors: Ott Elizabeth P. , Jacob Dain W. , Baker Sarah E. , Holbein Walter W. , Scruggs Zachariah M. , Shoemaker J. Kevin , Limberg Jacqueline K.
Published: April 2020

We examined the effect of acute intermittent hypoxia (IH) on sympathetic neural firing patterns and the role of the carotid chemoreceptors. We hypothesized exposure to acute IH would increase muscle sympathetic nerve activity (MSNA) via an increase in action potential (AP) discharge rates and within-burst firing. We further hypothesized any change in discharge patterns would be attenuated during acute chemoreceptor deactivation (hyperoxia). MSNA (microneurography) was assessed in 17 healthy adults (11 male/6 female; 31 ± 1 yr) during normoxic rest before and after 30 min of experimental IH. Prior to and following IH, participants were exposed to 2 min of 100% oxygen (hyperoxia). AP patterns were studied from the filtered raw MSNA signal using wavelet-based methodology. Compared with baseline, multiunit MSNA burst incidence ( P < 0.01), AP incidence ( P = 0.01), and AP content per burst ( P = 0.01) were increased following IH. There was an increase in the probability of a particular AP cluster firing once ( P < 0.01) and more than once ( P = 0.03) per burst following IH. There was no effect of hyperoxia on multiunit MSNA at baseline or following IH ( P > 0.05); however, hyperoxia following IH attenuated the probability of particular AP clusters firing more than once per burst ( P < 0.01). Acute IH increases MSNA by increasing AP discharge rates and within-burst firing. A portion of the increase in within-burst firing following IH can be attributed to the carotid chemoreceptors. These data advance the mechanistic understanding of sympathetic activation following acute IH in humans.
Support Vector Regression-Based Recursive Ensemble Methodology for Confidence Interval Estimation in Blood Pressure Measurements
Authors: Lee Soojeong , Lee Gangseong
Published: April 2020

The monitors of oscillometry blood pressure measurements are generally utilized to measure blood pressure for many subjects at hospitals, homes, and office, and they are actively studied. These monitors usually provide a single blood pressure point, and they are not able to indicate the confidence interval of the measured quantity. In this paper, we propose a new technique using a recursive ensemble based on a support vector machine to estimate a confidence interval for oscillometry blood pressure measurements. The recursive ensemble is based on a support vector machine that is used to effectively estimate blood pressure and then measure the confidence interval for the systolic blood pressure and diastolic blood pressure. The recursive ensemble methodology provides a lower standard deviation of error, mean error, and mean absolute error for the blood pressure as compared to those of the conventional techniques.
Dynamic Change of Polymer in Rice Analogues and Its Effect on Texture Quality
Authors: Zhang Ke , Tian Yang , Liu Chenglong , Xue Wentong
Published: April 2020

Macromolecules will leach from the inside of rice analogues (RA) to the external environment and form escaping substances (ES) when boiling in water for a long time. Some escaped substances adhere to the surface of cooked rice analogues (CRA) to form an adhesive layer (AL), which has an important impact on the cooking quality of RA. In this study, hydrocolloids and emulsifier were added and formed RA. Physicochemical, structural, and textural properties of ES, AL, and CRA samples were analyzed to study the effect of hydrocolloids on cooking quality of RA. The results showed that SA inhibited the leach of molecules, reduced MW of AL, decreased starch content of ES and AL, decreased shear viscosity of RA, and enhanced hydrogen bonding interactions. Ca2+ increased the dry matter content of CRA and AL, enhanced hydrogen bonding interactions of ES and CRA, and decreased MW of ES. Textural property results showed that the gelatinous properties of RA were enhanced after SA was added. The Ca2+ in the solution increased the adhesiveness of RA, while decreasing their elasticity. This study explained how hydrocolloids affect the texture properties of RA at a molecular level.
Epilepsy Treatment Outcome and Its Predictors among Ambulatory Patients with Epilepsy at Mizan-Tepi University Teaching Hospital, Southwest Ethiopia
Authors: Zewudie Ameha , Mamo Yitagesu , Feyissa Desalegn , Yimam Mohammed , Mekonen Gosaye , Abdela Ahmed
Published: April 2020

Background. Epilepsy is among the most common neurological disorders which is highly treatable with currently available antiepileptic drugs at a reasonable price. In Ethiopia, despite a number of studies revealed high prevalence of epilepsy, little is known on predictors of poorly controlled seizures. Thus, the aim of this study was to assess epilepsy treatment outcome and its predictors among patients with epilepsy on follow-up at the ambulatory care unit of Mizan-Tepi University Teaching Hospital, Southwest Ethiopia. Methods. A hospital-based cross-sectional study involving patient interview and chart review was conducted from March 10 to April 10, 2018. Drug use patterns and sociodemographic data of the study participants were accustomed to descriptive statistics. Backward logistic regression analysis was done to identify predictors of poor seizure control. Statistical significance was considered at p value <0.05. Results. From a total of 143 studied patients with epilepsy, 60.8% had uncontrolled seizures. Monotherapy (79%) was commonly used for the treatment of seizures, of which phenobarbital was the most commonly utilized single anticonvulsant drug (62.9%). The majority (72.7%) of the patients had developed one or more antiepileptic-related adverse effects. Medium medication adherence (adjusted odds ratio (AOR) = 5.4; 95% CI = 1.52–19.23; p=0.009), poor medication adherence (AOR = 8.16; 95% CI = 3.04–21.90; p=0.001), head injury before seizure occurrence (AOR = 4.9; 95% CI = 1.25–19.27; p=0.02), and seizure attacks ≥4 episodes/week before AEDs initiation (AOR = 8.52; % CI = 2.41–13.45; p=0.001) were the predictors of uncontrolled seizure. Conclusions. Based on our findings, more than half of the patients with epilepsy had poorly controlled seizures. Nonadherence to antiepileptic drugs, high frequency of seizure attack before AEDs initiation, and history of a head injury before the occurrence of seizure were predictors of uncontrolled seizure. Patient medication adherence should be increased by the free access of antiepileptic drugs and attention should be given for the patients with a history of head injury and high frequency of seizure attacks before AEDs initiation.
Integrated Care Programs for People with Multimorbidity in European Countries: eHealth Adoption in Health Systems
Authors: Melchiorre Maria Gabriella , Papa Roberta , Quattrini Sabrina , Lamura Giovanni , Barbabella Francesco ,   ICARE4EU Consortium
Published: April 2020

Introduction. eHealth applications have the potential to provide new integrated care services to patients with multimorbidity (MM), also supporting multidisciplinary care. The aim of this paper is to explore how widely eHealth tools have been currently adopted in integrated care programs for (older) people with MM in European countries, including benefits and barriers concerning their adoption, according to some basic health system characteristics. Materials and Methods. In 2014, in the framework of the ICARE4EU project, expert organizations in 24 European countries identified 101 integrated care programs. Managers of the selected programs completed an online questionnaire on several dimensions, including the use of eHealth. We analyzed data from this questionnaire, in addition to qualitative information from six innovative programs which were studied in depth through case study methodology, according to characteristics of national health systems: a national health model (financing system), overall strength of primary care (PC) (structure/service delivery process), and level of (de)centralization of health system (executive powers in a country). Results. 85 programs (out of 101) adopted at least one eHealth tool, and 42 of these targeted explicitly older people. In most cases, Electronic Health Records (EHRs) were used and some benefits emerged like improved care management and integration, although inadequate funding mechanisms represented a major barrier. The analysis by health system characteristics showed a greater adoption of eHealth applications in decentralized countries, in countries with a National Health Service (NHS) model, and in countries with a strong/medium level of PC development. Conclusions. Although in the light of some limitations, findings indicate a relation between implementation of care programs using eHealth tools and basic characteristics of health systems, with decentralization of a health system, NHS model, and strong/medium PC having a key role. However adaptations of European health systems seem necessary, in order to provide a more innovative and integrated care.
Finite-Time Projective Lag Synchronization and Identification between Multiple Weights Markovian Jumping Complex Networks with Stochastic Perturbations
Authors: Xie Qian , Mu Changhui , Wang Tong , Wu Gang , Jia Rong
Published: April 2020

Two nonidentical dimension Markovian jumping complex networks with stochastic perturbations are taken as objects. The network models under two conditions including single weight and double weights are established, respectively, to study the problem of synchronization and identification. A finite-time projection lag synchronization method is proposed and the unknown parameters of the network are identified. First of all, based on Itô’s formula and the stability theory of finite-time, a credible finite-time adaptive controller is presented to guarantee the synchronization of two nonidentical dimension Markovian jumping complex networks with stochastic perturbations under both conditions. Meanwhile, in order to identify the uncertain parameters of the network with stochastic perturbations accurately, some corresponding sufficient conditions are given. Finally, numerical simulations under two working conditions are given to demonstrate the effectiveness and feasibility of the main theory result.