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The aims were to assess the ability of a pressure transducer to measure compressive stress within the annulus fibrosus of degenerated intervertebral discs. Measurements could help to explain the mechanisms of disc failure and low back pain. The methods used were as follows. Thirteen full-depth cores of annulus, 7 mm in diameter, were removed from the middle and outer annuli of two severely degenerated human discs and constrained within a metal cylinder. Then static compressive forces were applied by a plane-ended metal indenter of diameter 6.8 mm, while a strain-gauged pressure transducer, side mounted in a needle of diameter 0.9 mm and calibrated in saline, was pulled through the tissue. The transducer output was converted into stress, and the average measured stress was compared with the nominal applied stress. Measurements were repeated at up to 21 load levels, with the transducer oriented vertically and horizontally. The results showed that the measured and applied stress were linearly related (average r2 = 0.98) with a mean gradient (calibration factor) of 0.98 (vertical stress) and 0.92 (horizontal stress). Gradients ranged between 1.28 and 0.73. Damaged transducers grossly under-recorded 'stress' even though their output remained proportional to applied load. It was concluded that pressure transducers can measure compressive stress inside a degenerated human annulus. The tissue is sufficiently deformable to allow efficient coupling of stress between the matrix and transducer membrane. Damage to the transducer can give misleading results. [ABSTRACT FROM AUTHOR]

Scholars warn that partisan divisions in the mass public threaten the health of American democracy. We conducted a megastudy ( n = 32,059 participants) testing 25 treatments designed by academics and practitioners to reduce Americans' partisan animosity and antidemocratic attitudes. We find that many treatments reduced partisan animosity, most strongly by highlighting relatable sympathetic individuals with different political beliefs or by emphasizing common identities shared by rival partisans. We also identify several treatments that reduced support for undemocratic practices-most strongly by correcting misperceptions of rival partisans' views or highlighting the threat of democratic collapse-which shows that antidemocratic attitudes are not intractable. Taken together, the study's findings identify promising general strategies for reducing partisan division and improving democratic attitudes, shedding theoretical light on challenges facing American democracy.

We conducted a retrospective cohort study in Ontario, Canada between December 1, 2020 and June 31, 2021 to compare the incidence of neurological events (hospitalization or emergency room visit) within six weeks of COVID-19 vaccination in Chinese, South Asian and Other ethnic groups. Compared to Others, the crude rates after the first dose for Bell's palsy, ischemic stroke and intracerebral hemorrhage were lower in Chinese (34, 159 and 48 per 1,000,000 doses) and in South Asians (44, 148 and 32), but similar after adjusting for age, sex and vaccine type. Our findings should help encourage vaccination for all, irrespective of ethnicity.

Vascular permeability is temporarily heightened during inflammation, but excessive inflammation-associated microvascular leakage can be detrimental, as evidenced in the inflamed lung. Formylated peptides regulate vascular leakage indirectly via formylated peptide receptor-1 (FPR1)-mediated recruitment and activation of neutrophils. Here we identify how the GTPase-activating protein ARAP3 protects against formylated peptide-induced microvascular permeability via endothelial cells and neutrophils. In vitro, Arap3 -/- endothelial monolayers were characterised by enhanced formylated peptide-induced permeability due to upregulated endothelial FPR1 and enhanced vascular endothelial cadherin internalisation. In vivo, enhanced inflammation-associated microvascular leakage was observed in Arap3 -/- mice. Leakage of plasma protein into the lungs of Arap3 -/- mice increased within hours of formylated peptide administration. Adoptive transfer experiments indicated this was dependent upon ARAP3 deficiency in both immune and non-immune cells. Bronchoalveolar lavages of formylated peptide-challenged Arap3 -/- mice contained neutrophil extracellular traps (NETs). Pharmacological inhibition of NET formation abrogated excessive microvascular leakage, indicating a critical function of NETs in this context. The observation that Arap3 -/- mice developed more severe influenza suggests these findings are pertinent to pathological situations characterised by abundant formylated peptides. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Concern over democratic erosion has led to a proliferation of proposed interventions to strengthen democratic attitudes in the United States. Resource constraints, however, prevent implementing all proposed interventions. One approach to identify promising interventions entails leveraging domain experts, who have knowledge regarding a given field, to forecast the effectiveness of candidate interventions. We recruit experts who develop general knowledge about a social problem (academics), experts who directly intervene on the problem (practitioners), and nonexperts from the public to forecast the effectiveness of interventions to reduce partisan animosity, support for undemocratic practices, and support for partisan violence. Comparing 14,076 forecasts submitted by 1,181 forecasters against the results of a megaexperiment (n = 32,059) that tested 75 hypothesized effects of interventions, we find that both types of experts outperformed members of the public, though experts differed in how they were accurate. While academics' predictions were more specific (i.e., they identified a larger proportion of ineffective interventions and had fewer false-positive forecasts), practitioners' predictions were more sensitive (i.e., they identified a larger proportion of effective interventions and had fewer false-negative forecasts). Consistent with this, practitioners were better at predicting best-performing interventions, while academics were superior in predicting which interventions performed worst. Our paper highlights the importance of differentiating types of experts and types of accuracy. We conclude by discussing factors that affect whether sensitive or specific forecasters are preferable, such as the relative cost of false positives and negatives and the expected rate of intervention success., Competing Interests: Competing interests statement:The authors declare no competing interest.

Norbin is an adaptor protein that binds numerous G protein-coupled receptors (GPCRs), is highly expressed in neurons, and is essential for a functioning nervous system in rodent models. Yet, beyond its control of neurite outgrowth and synaptic plasticity, few cellular roles of Norbin have been investigated to date. Furthermore, while Norbin is known to regulate the steady-state cell surface levels of several GPCRs, only in one case has the protein been shown to control the agonist-induced receptor internalisation which serves to attenuate GPCR signalling. Here, we generated a Norbin-deficient PC12 cell line which enabled us to study both the cellular functions of Norbin and its roles in GPCR trafficking and signalling. We show that Norbin limits cell size and spreading, and is required for the growth, viability and cell cycle progression of PC12 cells. We also found that Norbin regulates both the steady-state surface level and agonist-induced internalisation of the GPCR sphingosine-1-phosphate receptor 1 (S1PR1) in these cells, suggesting that its role in agonist-dependent GPCR trafficking is more widespread than previously appreciated. Finally, we show that Norbin limits the S1P-stimulated activation of Akt and p38 Mapk, and is required for the activation of Erk in PC12 cells. Together, our findings provide a better understanding of the cellular functions of Norbin and its control of GPCR trafficking., (© 2023. Springer Nature Limited.)

Introduction: Rac-GTPases and their Rac-GEF activators play important roles in neutrophil-mediated host defence. These proteins control the adhesion molecules and cytoskeletal dynamics required for neutrophil recruitment to inflamed and infected organs, and the neutrophil effector responses that kill pathogens., Methods: Here, we used live cell TIRF-FRET imaging in neutrophils from Rac-FRET reporter mice with deficiencies in the Rac-GEFs Dock2, Tiam1 or Prex1/Vav1 to evaluate if these proteins activate spatiotemporally distinct pools of Rac, and to correlate patterns of Rac activity with the neutrophil responses they control., Results: All the GEFs were required for neutrophil adhesion, and Prex1/Vav1 were important during spreading and for the velocity of migration during chemotaxis. However, Dock2 emerged as the prominent regulator of neutrophil responses, as this GEF was required for neutrophil polarisation and random migration, for migration velocity during chemokinesis, for the likelihood to migrate and for the speed of migration and of turning during chemotaxis, as well as for rapid particle engulfment during phagocytosis. We identified characteristic spatiotemporal patterns of Rac activity generated by Dock2 which correlate with the importance of the Rac-GEF in these neutrophil responses. We also demonstrate a requirement for Dock2 in neutrophil recruitment during aseptic peritonitis., Discussion: Collectively, our data provide a first direct comparison of the pools of Rac activity generated by different types of Rac-GEFs, and identify Dock2 as a key regulator of polarisation, migration and phagocytosis in primary neutrophils., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Machin, Johnsson, Massey, Pantarelli, Chetwynd, Chu, Okkenhaug, Segonds-Pichon, Walker, Malliri, Fukui and Welch.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Host defense against bacterial and fungal infections diminishes with age. In humans, impaired neutrophil responses are thought to contribute to this decline. However, it remains unclear whether neutrophil responses are also impaired in old mice. Here, we investigated neutrophil function in old mice, focusing on responses primed by lipopolysaccharide (LPS), an endotoxin released by gram-negative bacteria like E. coli , which signals through toll-like receptor (TLR) 4. We show that old mice have a reduced capacity to clear pathogenic E. coli during septic peritonitis. Neutrophil recruitment was elevated during LPS-induced but not aseptic peritonitis. Neutrophils from old mice showed reduced killing of E. coli . Their reactive oxygen species (ROS) production was impaired upon priming with LPS but not with GM-CSF/TNFα. Phagocytosis and degranulation were reduced in a partially LPS-dependent manner, whereas impairment of NET release in response to S. aureus was independent of LPS. Unexpectedly, chemotaxis was normal, as were Rac1 and Rac2 GTPase activities. LPS-primed activation of Erk and p38 Mapk was defective. PIP 3 production was reduced upon priming with LPS but not with GM-CSF/TNFα, whereas PIP 2 levels were constitutively low. The expression of 5% of neutrophil proteins was dysregulated in old age. Granule proteins, particularly cathepsins and serpins, as well as TLR-pathway proteins and membrane receptors were upregulated, whereas chromatin and RNA regulators were downregulated. The upregulation of CD180 and downregulation of MyD88 likely contribute to the impaired LPS signaling. In summary, all major neutrophil responses except chemotaxis decline with age in mice, particularly upon LPS priming. This LPS/TLR4 pathway dependence resolves previous controversy regarding effects of age on murine neutrophils and confirms that mice are an appropriate model for the decline in human neutrophil function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hornigold, Chu, Chetwynd, Machin, Crossland, Pantarelli, Anderson, Hawkins, Segonds-Pichon, Oxley and Welch.)

Objective: To analyze the prevalence and related factors of suicide ideation among nurses in different levels of hospitals in Shandong Province, and to analyze the relationship between them. Methods: From June to July 2020, 1644 nurses in Shandong Province were surveyed by multi-stage stratified cluster sampling. The suicidal ideation of nurses was investigated by suicidal ideation screening. Social support and mental health were measured by the perceived social support scale (pass) and kessler10 scale respectively. The simple coping style scale (SCSQ) was used to evaluate the coping styles of the subjects when they encountered problems. Logistic regression was used to analyze the influencing factors of suicidal ideation, Amos software was used to establish the path model of suicidal ideation related factors, and the maximum likelihood estimation was used to test the path model coefficient. Results: The incidence of suicidal ideation among nurses in secondary hospitals during their career was 8.44%, and that in tertiary hospitals was 11.66%. There was no significant difference in suicidal ideation among nurses at all levels in secondary hospitals ( P >0.05) . The main factors related to suicidal ideation were unmarried and others ( OR =0.362, 95% CI =0.155, 0.844, P =0.019) , social support ( OR =1.084, 95% CI =1.059, 1.109, P =0.000) and mental health status ( OR =0.921, 95% CI =0.890, 0.953, P =0.000) . The suicide ideation of skilled nurses in tertiary hospitals was higher than that of other levels ( P <0.05) . The related factors of suicide ideation mainly included unmarried and others ( OR =0.369, 95% CI =0.214, 0.636, P =0.000) , night shift ( OR =1.889, 95% CI =10.57, 3.377, P =0.032) , general self-rated social status ( OR =2.377, 95% CI =1.031, 5.483, P =0.042) , physical disease ( OR =2.747, 95% CI =1.601, 4.714) , P =0.000) , Social support ( OR =0.960, 95% CI =1.042, 1.077, P =0.000) and mental health status ( OR =0.942, 95% CI =0.922, 0.963, P =0.000) . Social support and mental health have a direct effect on suicidal ideation. Self-assessment of social status, social support and physical disease can affect suicidal ideation by affecting mental health. Conclusion: It is necessary to pay more attention to the mental health status of nurses at different levels in different hospitals during their career, improve their social support level, and improve their cognition of the practice environment.

Background: Due to lack of data on the epidemiology, cardiac, and neurological complications among Ontario visible minorities (Chinese and South Asians) affected by coronavirus disease (COVID-19), this population-based retrospective study was undertaken to study them systematically., Methods: From January 1, 2020 to September 30, 2020 using the last name algorithm to identify Ontario Chinese and South Asians who were tested positive by PCR for COVID-19, their demographics, cardiac, and neurological complications including hospitalization and emergency visit rates were analyzed compared to the general population., Results: Chinese (N = 1,186) with COVID-19 were found to be older (mean age 50.7 years) compared to the general population (N = 42,547) (mean age 47.6 years) ( p < 0.001), while South Asians (N = 3,459) were younger (age of 42.1 years) ( p < 0.001). The 30-day crude rate for cardiac complications among Chinese was 169/10,000 ( p = 0.069), while for South Asians, it was 64/10,000 ( p = 0.008) and, for the general population, it was 112/10,000. For neurological complications, the 30-day crude rate for Chinese was 160/10,000 ( p < 0.001); South Asians was 40/10,000 ( p = 0.526), and general population was 48/10,000. The 30-day all-cause mortality rate was significantly higher for Chinese at 8.1% vs 5.0% for the general population ( p < 0.001), while it was lower in South Asians at 2.1% ( p < 0.001)., Conclusions: Chinese and South Asians in Ontario affected by COVID-19 during the first wave of the pandemic were found to have a significant difference in their demographics, cardiac, and neurological outcomes.

Background: Although we had previously reported the cardiac and neurologic outcomes of Chinese and South Asian Ontarians in wave 1 of COVID-19, data on subsequent waves of COVID-19 remain unexamined. This is an extension study of this cohort in waves 2 and 3., Methods: We identified adult Ontarians with a positive COVID-19 polymerase chain reaction test from January 1, 2020 to June 30, 2021, and they were classified as being Chinese or South Asian using a validated surname algorithm; we compared their outcomes of mortality, and cardiac and neurologic complications with those of the general population using multivariable logistic regression models., Results: Compared to the general population (n = 439,977), the Chinese population (n = 15,208) was older (mean age 44.2 vs 40.6 years, P < 0.001) and the South Asian population (n = 46,333) was younger (39.2 years, P < 0.001). The Chinese population had a higher 30-day mortality (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.28-1.61) and more hospitalization or emergency department visits (OR, 1.14; 95% CI, 1.09-1.28), with a trend toward a higher incidence of cardiac complications (OR, 1.03; 95% CI, 0.87-1.12) and neurologic complications (OR, 1.23; 95% CI, 0.96-1.58). South Asians had a lower 30-day mortality (OR, 0.88; 95% CI, 0.78-0.98) but a higher incidence of hospitalization or emergency department visits (OR, 1.17; 95% CI, 1.14-1.20) with a trend toward a lower incidence of cardiac complications (OR, 0.76; 95% CI, 0.67-0.87) and neurologic complications (OR, 0.89; 95% CI, 0.73-1.09). There was also a significant difference in these outcomes between wave 1, 2 and 3, with a greater mortality in all groups in waves 2 and 3., Conclusions: Ethnicity continues to be an important determinant of mortality, cardiac and neurologic outcomes, and healthcare use among patients with COVID-19, requiring further studies to understand factors driving these differences., (© 2022 The Authors.)

The development of potential and novel proton exchange membranes (PEMs) is imperative for the further commercialization of PEM fuel cells (PEMFCs). In this work, phosphotungstic acid (PWA) and graphene oxide (GO) were integrated into sulfonated poly(arylene ether) (SPAE) through a solution casting approach to create a potential composite membrane for PEMFC applications. Thermal stability of membranes was observed using thermogravimetric analysis (TGA), and the SPAE/GO/PWA membranes exhibited high thermal stability compared to pristine SPAE membranes, owing to the interaction between SPAEK, GO, and PWA. By using a scanning electron microscope (SEM) and atomic force microscope (AFM), we observed that GO and PWA were evenly distributed throughout the SPAE matrix. The SPAE/GO/PWA composite membrane comprising 0.7 wt% GO and 36 wt% PWA exhibited a maximum proton conductivity of 186.3 mS cm -1 at 90 °C under 100% relative humidity (RH). As a result, SPAE/GO/PWA composite membrane exhibited 193.3 mW cm -2 of the maximum power density at 70 °C under 100% RH in PEMFCs.

Persistent neutrophilic inflammation drives host damage in autoimmune diseases that are characterized by abundant immune complexes. Insoluble immune complexes (iICs) potently activate pro-inflammatory neutrophil effector functions. We and others have shown that iICs also promote resolution of inflammation via stimulation of neutrophil apoptosis. We demonstrate here that iICs trigger FcγRIIa-dependent neutrophil macropinocytosis, leading to the rapid uptake, and subsequent degradation of iICs. We provide evidence that concurrent iIC-induced neutrophil apoptosis is distinct from phagocytosis-induced cell death. First, uptake of iICs occurs by FcγRII-stimulated macropinocytosis, rather than phagocytosis. Second, production of reactive oxygen species, but not iIC-internalization is a pre-requisite for iIC-induced neutrophil apoptosis. Our findings identify a previously unknown mechanism by which neutrophils can remove pro-inflammatory iICs from the circulation. Together iIC clearance and iIC-induced neutrophil apoptosis may act to prevent the potential escalation of neutrophilic inflammation in response to iICs.

Background: Our original pilot study in 2008 demonstrated a poor degree of awareness of heart disease and stroke among Chinese Canadians, warranting an updated survey of their knowledge. We sought to determine the current degree of knowledge of cardiovascular disease, including stroke, among ethnic Chinese residents of Canada., Methods: A 35-question online survey was conducted in the fall of 2017 among 1001 Chinese Canadians (aged ≥ 18 years) in the greater Toronto area (n = 501) and Vancouver (n = 500). Knowledge of heart disease and stroke, such as signs and symptoms of stroke and heart attack, health habits, and initial response to a cardiovascular emergency were assessed., Results: A total of 52.0% of the respondents were female, and 46.3% were aged <45 years. A total of 40.1% spoke Cantonese, and 23.7% spoke Mandarin; 79.5% were immigrants, and 31% had lived in Canada < 10 years. A total of 85% identified at least one heart attack symptom, and 80% identified at least one stroke symptom; 86.2% indicated that they would call 911 if experiencing a heart attack or stroke. Internet use was positively associated with the ability to identify a greater number of heart attack and stroke symptoms, compared to the number among non-Internet users ( P < 0.001). Women were 14% more likely to overlook gender as a risk factor for cardiovascular disease (CVD)., Conclusions: This study found that in 2017, compared to 2008, awareness of symptoms of heart disease and stroke improved among Chinese Canadians residing in Toronto and Vancouver., (© 2021 The Authors.)

Significance: Contamination of diffuse correlation spectroscopy (DCS) measurements of cerebral blood flow (CBF) due to systemic physiology remains a significant challenge in the clinical translation of DCS for neuromonitoring. Tunable, multi-layer Monte Carlo-based (MC) light transport models have the potential to remove extracerebral flow cross-talk in cerebral blood flow index ( CBF i ) estimates. Aim: We explore the effectiveness of MC DCS models in recovering accurate CBF i changes in the presence of strong systemic physiology variations during a hypercapnia maneuver. Approach: Multi-layer slab and head-like realistic (curved) geometries were used to run MC simulations of photon propagation through the head. The simulation data were post-processed into models with variable extracerebral thicknesses and used to fit DCS multi-distance intensity autocorrelation measurements to estimate CBF i timecourses. The results of the MC CBF i values from a set of human subject hypercapnia sessions were compared with CBF i values estimated using a semi-infinite analytical model, as commonly used in the field. Results: Group averages indicate a gradual systemic increase in blood flow following a different temporal profile versus the expected rapid CBF response. Optimized MC models, guided by several intrinsic criteria and a pressure modulation maneuver, were able to more effectively separate CBF i changes from scalp blood flow influence than the analytical fitting, which assumed a homogeneous medium. Three-layer models performed better than two-layer ones; slab and curved models achieved largely similar results, though curved geometries were closer to physiological layer thicknesses. Conclusion: Three-layer, adjustable MC models can be useful in separating distinct changes in scalp and brain blood flow. Pressure modulation, along with reasonable estimates of physiological parameters, can help direct the choice of appropriate layer thicknesses in MC models., (© 2021 The Authors.)

A series of novel blended anion exchange membranes (AEMs) were prepared with hyperbranched brominated poly(arylene ether sulfone) (Br-HB-PAES) and linear chloromethylated poly(phenylene oxide) (CM-PPO). The as-prepared blended membranes were fabricated with different weight ratios of Br-HB-PAES to CM-PPO, and the quaternization reaction for introducing the ionic functional group was performed by triethylamine. The Q-PAES/PPO-XY (quaternized-PAES/PPO-XY) blended membranes promoted the ion channel formation as the strong hydrogen bonds interconnecting the two polymers were maintained, and showed an improved hydroxide conductivity with excellent thermal behavior. In particular, the Q-PAES/PPO-55 membrane showed a very high hydroxide ion conductivity (90.9 mS cm -1 ) compared to the pristine Q-HB-PAES membrane (32.8 mS cm -1 ), a result supported by the morphology of the membrane as determined by the AFM analysis. In addition, the rigid hyperbranched structure showed a suppressed swelling ratio of 17.9-24.9% despite an excessive water uptake of 33.2-50.3% at 90 °C, and demonstrated a remarkable alkaline stability under 2.0 M KOH conditions over 1000 h.

We designed and synthesized a series of sulfonated poly(arylene ether sulfone) (SPES) with different hydrophilic or hydrophobic oligomer ratios using poly-condensation strategy. Afterward, we fabricated the corresponding membranes via a solution-casting approach. We verified the SPES membrane chemical structure using nuclear magnetic resonance ( 1 H NMR) and confirmed the resulting oligomer ratio. Field-emission scanning electron microscope (FE-SEM) and atomic force microscope (AFM) results revealed that we effectively attained phase separation of the SPES membrane along with an increased hydrophilic oligomer ratio. Thermal stability, glass transition temperature (T g ) and membrane elongation increased with the ratio of hydrophilic oligomers. SPES membranes with higher hydrophilic oligomer ratios exhibited superior water uptake, ion-exchange capacity, contact angle and water sorption, while retaining reasonable swelling degree. The proton conductivity results showed that SPES containing higher amounts of hydrophilic oligomers provided a 74.7 mS cm -1 proton conductivity at 90 °C, which is better than other SPES membranes, but slightly lower than that of Nafion-117 membrane. When integrating SPES membranes with proton-exchange membrane fuel cells (PEMFCs) at 60 °C and 80% relative humidity (RH), the PEMFC power density exhibited a similar increment-pattern like proton conductivity pattern.

A technology called self-aligned selective undercut dry etching processing has been demonstrated for fabricating a highly efficient hybrid optical spot size converter (SSC) on a Si-on-insulator (SOI) template. The process was based on a bonded wafer between the upper InP-based multiple quantum well heterostructure and the lower SOI substrate. After defining the mask on the upper InP-based ridge waveguide, C F 4 / O 2 dry reactive ion etching was then used for selective undercut etching of the Si material from the surrounding materials, forming a vertical waveguide coupler of the optical SSC. The lower waveguide, whose dimension is even smaller than the upper one, can thus be vertically self-aligned to the top ridge via an independent processing step. A laterally tapered waveguide ranging from 0.3 to 3 µm in width on the upper InP waveguide was fabricated. The phase-matching condition of the vertical coupler leads to a length of 45 µm and extracts 88% conversion efficiency. The selective undercut etching processing in III-V/SOI material provides a vertical self-alignment scheme for realizing compact and submicron scale heterogeneous integration in a Si photonics template.

Objective: To explore the effects of intervention programs during primipara, using the Information-motivation-behavioral skills model (IMB) intervention model on initial exclusive breastfeeding. Method: 206 women of primiparas who were registered to the top three hospitals were selected in Shandong province, 2018. These women were hospitalized in the obstetrics/gynaecology wards during the later periods. IMB model was used to support the intervention programs at the following stages: antenatal period, 1 day postpartum, 3-4 days postpartum and 42 days postpartum. Questionnaire regarding self-efficacy energy meter, knowledge and behavior related to breastfeeding, were used before and after the intervention programs. Results: Through intervention programs, statistically significant differences in breastfeeding self-efficacy scores between the four stages ( F =150.680, P =0.000) were recorded. Significant differences were also noticed in scores on knowledge of breastfeeding ( F =176.556, P =0.000). Conclusion: The application of IMB intervention model in women at childbearing age seemed to be helpful in improving the effect of primary breastfeeding in women at childbearing age.

Neutrophils are abundant circulating leukocytes that are rapidly recruited to sites of inflammation in an integrin-dependent fashion. Contrasting with the well-characterized regulation of integrin activation, mechanisms regulating integrin inactivation remain largely obscure. Using mouse neutrophils, we demonstrate in this study that the GTPase activating protein ARAP3 is a critical regulator of integrin inactivation; experiments with Chinese hamster ovary cells indicate that this is not restricted to neutrophils. Specifically, ARAP3 acts in a negative feedback loop downstream of PI3K to regulate integrin inactivation. Integrin ligand binding drives the activation of PI3K and of its effectors, including ARAP3, by outside-in signaling. ARAP3, in turn, promotes localized integrin inactivation by negative inside-out signaling. This negative feedback loop reduces integrin-mediated PI3K activity, with ARAP3 effectively switching off its own activator, while promoting turnover of substrate adhesions. In vitro, ARAP3-deficient neutrophils display defective PIP3 polarization, adhesion turnover, and transendothelial migration. In vivo, ARAP3-deficient neutrophils are characterized by a neutrophil-autonomous recruitment defect to sites of inflammation., (Copyright © 2019 The Authors.)

Neutrophils are short-lived, abundant peripheral blood leukocytes that provide a first line of defense against bacterial and fungal infections while also being a key part of the inflammatory response. Chemokines induce neutrophil recruitment to inflammatory sites, where neutrophils perform several diverse functions that are aimed at fighting infections. Neutrophil effector functions are tightly regulated processes that are governed by an array of intracellular signaling pathways and initiated by receptor-ligand binding events. Dysregulated neutrophil activation can result in excessive inflammation and host damage, as is evident in several autoimmune diseases. Rho family small GTPases and agonist-activated phosphoinositide 3-kinases (PI3Ks) represent 2 classes of key regulators of the highly specialized neutrophil. Here we review cross-talk between these important signaling intermediates in the context of neutrophil functions. We include PI3K-dependent activation of Rho family small GTPases and of their guanine nucleotide exchange factors and GTPase activating proteins, as well as Rho GTPase-dependent regulation of PI3K.

Neutrophils are short-lived, terminally differentiated leukocytes that form an essential part of host immunity and play a key role in acute and chronic inflammation. The analysis of these important cells is hindered by the fact that neutrophils are not amenable to culture, transfection, or transduction. Conditionally HoxB8-immortalized mouse hematopoietic progenitors are suitable for in vitro differentiation of a range of myeloid cells, including neutrophils. Integrins and FcγRs are cell surface receptors, the ligation of which is required for a range of neutrophil functions that are important in health and disease. We show here that HoxB8 neutrophils express major neutrophil integrins and FcγRs. They respond to FcγR and integrin stimulation in a manner that is comparable with primary neutrophils, in terms of intracellular signaling. HoxB8 neutrophils also perform a range of FcγR/integrin-dependent neutrophil functions, including, generation of reactive oxygen species, degranulation, and chemotaxis. Our findings suggest that HoxB8 neutrophils represent a faithful experimental model system for the analysis of Fc and integrin receptor-dependent neutrophil functions., (©2018 Society for Leukocyte Biology.)

A series of anion exchange membranes composed of partially fluorinated poly(arylene ether sulfone)s (PAESs) multiblock copolymers bearing quaternary ammonium groups were synthesized with controlled lengths of the hydrophilic precursor and hydrophobic oligomer via direct polycondensation. The chloromethylation and quaternization proceeded well by optimizing the reaction conditions to improve hydroxide conductivity and physical stability, and the fabricated membranes were very flexible and transparent. Atomic force microscope images of quaternized PAES (QN-PAES) membranes showed excellent hydrophilic/hydrophobic phase separation and distinct ion transition channels. An extended architecture of phase separation was observed by increasing the hydrophilic oligomer length, which resulted in significant improvements in the water uptake, ion exchange capacity, and hydroxide conductivity. Furthermore, the open circuit voltage (OCV) of QN-PAES X10Y23 and X10Y13 was found to be above 0.9 V, and the maximum power density of QN-PAES X10Y13 was 131.7 mW cm -2 at 60 °C under 100% RH.

Sulfonated poly(arylene biphenylether sulfone)-poly(arylene ether) (SPABES-PAE) block copolymers by controlling the molar ratio of SPABES and PAE oligomers were successfully synthesized, and the performances of SPABES-PAE (1:2, 1:1, and 2:1) membranes were compared with Nafion 212. The prepared membranes including fluorinated hydrophobic units were stable against heat, nucleophile attack, and physio-chemical durability during the tests. Moreover, the polymers exhibited better solubility in a variety of solvents. The chemical structure of SPABES-PAEs was investigated by ¹H nuclear magnetic resonance (¹H NMR), Fourier transform infrared spectroscopy (FT-IR), and gel permeation chromatography (GPC). The membrane of SPABES-PAEs was fabricated by the solution casting method, and the membranes were very flexible and transparent with a thickness of 70⁻90 μm. The morphology of the membranes was observed using atomic force microscope and the ionic domain size was proved by small angle X-ray scattering (SAXS) measurement. The incorporation of polymers including fluorinated units allowed the membranes to provide unprecedented oxidative and dimensional stabilities, as verified from the results of ex situ durability tests and water uptake capacity, respectively. By the collective efforts, we observed an enhanced water retention capacity, reasonable dimensional stability and high proton conductivity, and the peak power density of the SPABES-PAE (2:1) was 333.29 mW·cm -2 at 60 °C under 100% relative humidity (RH).

Objectives: Midshaft clavicular fractures are increasingly treated operatively rather than nonoperatively. Studies have shown mixed results for both types of treatment. The aim of this study was to compare the early-stage functional status associated with open reduction and internal fixation (ORIF) with plating and that associated with conservative treatment for displaced midshaft clavicular fractures., Materials and Methods: A single-center retrospective review of the results of 120 cases of displaced midshaft clavicular fractures in patients aged 30-65 years old was conducted. The primary outcome was fracture union status at 6 months. Other outcomes were subjective shoulder value (SSV) scores, visual analog scale (VAS) scores, and radiographic shortening at 6 weeks, 3 months, and 6 months. The complication rates in the operative and nonoperative groups were recorded., Results: The delayed union rate at 6-month postoperatively and VAS scores at 6 weeks, 3 months, and 6 months postinjury were significantly higher in the conservative treatment group than in the ORIF group. SSV scores were significantly improved at 6-month postinjury in the ORIF group., Conclusions: This is the first study to discuss the importance of early-stage functional restoration after ORIF with plating for displaced midshaft clavicular fractures. This surgery leads to lower pain complications in the earlier stages of bone healing and lower delayed union rates compared with conservative treatment, in patients aged 30-65 years old., Competing Interests: There are no conflicts of interest.

The series of sulfonated poly(arylene ether ketone) (SPAEK) block copolymers with controlled F-oligomer length bearing pendant diphenyl unit were synthesized via a polycondensation reaction. Sulfonation was verified by 1 H NMR analysis to introduce sulfonic acid group selectively and intensively on the pendant diphenyl unit of polymer backbones. The SPAEK membranes fabricated by the solution casting approach were very transparent and flexible with the thickness of ∼50 μm. These membranes with different F-oligomer lengths were investigated to the physiochemical properties such as water absorption, dimensional stability, ion exchange capacity, and proton conductivity. As a result, the SPAEK membranes (X4.8Y8.8, X7.5Y8.8, and X9.1Y8.8) in accordance to increasing the length of hydrophilic oligomer showed excellent proton conductivity in range of 131-154 mS cm -1 compared to Nafion-115 (131 mS cm -1 ) at 90 °C under 100% relative humidity (RH). Among the SPAEK membranes, proton conductivity of SPAEK X9.1Y8.8 (140.7 mS cm -1 ) is higher than that of Nafion-115 (102 mS cm -1 ) at 90 °C under 80% RH. The atomic force microscopy image demonstrated that number of ion transport channels is increased with increase in the length of hydrophilic oligomer in the main chains, and the morphology is proved to be related to the proton conductivity. The synthesized SPAEK membrane exhibited a maximum power density of 324 mW cm -2 , which is higher than that of Nafion-115 (291 mW cm -2 ) at 60 °C under 100% RH.

Inflammation is a complex biological response that serves to protect the body's tissues following harmful stimuli such as infection, irritation or injury and initiates tissue repair. At the start of an inflammatory response, pro-inflammatory mediators induce changes in the endothelial lining of the blood vessels and in leukocytes. This results in increased vascular permeability and increased expression of adhesion proteins, and promotes adhesion of leukocytes, especially neutrophils to the endothelium. Adhesion is a prerequisite for neutrophil extravasation and chemoattractant-stimulated recruitment to inflammatory sites, where neutrophils phagocytose and kill microbes, release inflammatory mediators and cross-talk with other immune cells to co-ordinate the immune response in preparation for tissue repair. Many signalling proteins are critically involved in the complex signalling processes that underpin the inflammatory response and cross-talk between endothelium and leukocytes. As key regulators of cell-cell and cell-substratum adhesion, small GTPases (guanosine triphosphatases) act as important controls of neutrophil-endothelial cell interactions as well as neutrophil recruitment to sites of inflammation. Here, we summarise key processes that are dependent upon small GTPases in leukocytes during these early inflammatory events. We place a particular focus on the regulation of integrin-dependent events and their control by Rho and Rap family GTPases as well as their regulators during neutrophil adhesion, chemotaxis and recruitment., (© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Purpose: The aim of this study was to investigate the safety and effectiveness of tadalafil 5 mg once daily (quaque die [everyday], QD) among Korean men with benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) in a real-world clinical setting., Materials and Methods: This was a single-country, prospective, observational cohort study in which patients newly prescribed tadalafil 5 mg QD for the treatment of BPH/LUTS were followed-up for 12±2 or 24±2 weeks, or to the last treatment, during post-marketing surveillance. Safety was evaluated in terms of the frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Effectiveness was assessed by changes in the International Prostate Symptom Score (IPSS) from baseline to each endpoint., Results: All patients receiving ≥1 dose of tadalafil 5 mg QD (N=637) were included in the safety population. Two percent of patients (n=13) experienced 15 TEAEs of mild (n=10; 66.7%) or moderate (n=5; 33.3%) severity. No severe TEAEs and no SAEs were reported. Effectiveness evaluations included all patients receiving tadalafil who had both baseline and endpoint observations (12-week, N=265; 24-week, N=44). Compared with baseline, the mean IPSS total score (±standard error) significantly improved by 4.7±0.3 and 6.4±0.7 points at the 12- and 24-week endpoints, respectively (p<0.0001), with significant improvements also observed on the storage, voiding, and quality of life subscores. In total, 69.1% of the patients had a clinically meaningful ≥3-point improvement in the IPSS total score., Conclusions: Tadalafil 5 mg QD was well tolerated and effective in Korean men with BPH/LUTS in a real-world clinical setting., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2018 Korean Society for Sexual Medicine and Andrology.)

Near-field scanning optical microscopy (NSOM) enables observation of light-matter interaction with a spatial resolution far below the diffraction limit without the need for a vacuum environment. However, modern NSOM techniques remain subject to a few fundamental restrictions. For example, concerning the aperture tip (a-tip), the throughput is extremely low, and the lateral resolution is poor; both are limited by the aperture size. Meanwhile, with regard to the scattering tip (s-tip), the signal-to-noise ratio (SNR) appears to be almost zero; consequently, one cannot directly use the measured data. In this work, we present a plasmonic tip (p-tip) developed by tailoring subwavelength annuli so as to couple internal radial illumination to surface plasmon polaritons (SPPs), resulting in an ultrastrong, superfocused spot. Our p-tip supports both a radial symmetric SPP excitation and a Fabry-Pérot resonance, and experimental results indicate an optical resolution of 10 nm, a topographic resolution of 10 nm, a throughput of 3.28%, and an outstanding SNR of up to 18.2 (nearly free of background). The demonstrated p-tip outperforms state-of-the-art NSOM tips and can be readily employed in near-field optics, nanolithography, tip-enhanced Raman spectroscopy, and other applications.

Background: First-generation Chinese Canadians have usually maintained different lifestyles before immigration to North America, and the question of whether Chinese Canadians with type 2 diabetes have a different stroke profile than that of non-Chinese Canadians remains unanswered., Objectives: To determine whether 1) Chinese Canadians who have had a stroke within the last 15 years are more likely to have diabetes than non-Chinese Canadians and 2) to explore differences in stroke profiles between the 2 cohorts., Methods: Age- and sex-matched Chinese Canadians (n=70) and non-Chinese Canadians (n=107) were compared on the basis of stroke type, age at stroke onset, stroke etiology and common risk factors. Classifications for disease were done according to professional guidelines. Statistical analysis was done with Student t test and odds ratios to confirm differences between groups., Results: Chinese Canadians with stroke had a higher frequency of diabetes mellitus than non-Chinese Canadians. Chinese Canadians with diabetes were more likely to have small vessel disease, specifically lacunar stroke. Chinese Canadians at high risk for stroke were more likely to have a poor prognosis than non-Chinese Canadians, with near significance., Conclusion: Chinese Canadians with diabetes who had ischemic strokes were especially susceptible to intracranial small vessel disease compared with non-Chinese Canadians. These results signify that risk factor prevalence and stroke types differ considerably between Chinese Canadians and non-Chinese Canadians residing in Toronto, warranting further study., (Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of breast massage at different time in the early period on maternal lactation after cesarean section. Methods: 80 women delivered by cesarean section were randomly selected from maternity ward of a hospital in Shandong province during Jan. 2013 to Jan. 2015; which were divided into four groups, with 20 patients in each. Three groups received 3 times of breast massage every 24 hoursbeginning from 2, 12 and 24 h after cesarean section, respectively. The control group didn't receive any breast massage. The starting time and status of lactation were observed and recorded after cesarean section. 5 ml venous blood sample was drawn from each patient respectively at 2 h before cesarean, 6, 12, 24, 48 and 72 h after cesarean to test the level of serum prolactin. The lactation status of each group was compared. Results: The P (50) ( P (25)- P (75)) of starting time of lactation of the three massage groups and control group were 3 (2-6) h, 4 (2-8) h, 4 (3-12) h and 4 (2-12) h, respectively, whose differences showed no statistical significance ( H =3.32, P= 0.345).The number of delivered women with adequate lactation 24 hours after cesarean was 10 in the group who received massage beginning from 2 h after cesarean; while the number was only 2 in the control group. The number of delivered women with adequate lactation 48 hours after cesarean was 18 in the group who received massage beginning from 2 h after cesarean; while the number was 8 in the control group. The differences showed statistical significances ( P values were 0.021 and 0.008, respectively). The serum prolactin level in the group of delivered women who received massage from 2 h after cesarean was separately (195.9±78.5), (176.0±96.5), (216.4±110.0), (190.0±56.8) and (184.8±69.6) μg/L at 2, 12, 24, 48 and 72 h after cesarean, which were significantly higher than those in the control group (which were (128.8±40.6), (127.3±66.8), (162.2±58.8), (145.1±64.7) and (141.7±49.3) μg/L, respectively) ( P= 0.007). Conclusion: Breast massage beginning from 2 hours after cesarean section can effectively improve the lactation status of delivered women.

Male infertility is a multifactorial syndrome encompassing a wide variety of disorders. In recent years, several genome-wide single-nucleotide polymorphism (SNP) association studies (GWAS) have been performed on azoospermia and/or oligozoospermia in different populations including two GWAS on nonobstructive azoospermia in China; however, the association of SNPs with idiopathic male infertility, especially asthenozoospermia and oligozoospermia, and their correlation with semen parameters are still not clear. To investigate genetic variants associated with idiopathic male infertility (asthenozoospermia, oligozoospermia, and oligoasthenozoospermia) in Chinese Han people, 20 candidate SNPs were selected from GWAS results and genotyped using the Sequenom MassARRAY assay. A total of 136 subfertile men and 456 healthy fertile men were recruited. rs6476866 in SLC1A1 (P = 1.919E-4, OR = 0.5905, 95% CI: 0.447-0.78) and rs10129954 in DPF3 (P = 0.0023, OR = 2.199, 95% CI: 1.311-3.689) were strongly associated with idiopathic male infertility. In addition, positive associations were observed between asthenozoospermia and rs215702 in LSM5 (P = 0.0016, OR = 1.479, 95% CI: 1.075-2.033) and between oligoasthenozoospermia and rs2477686 in PEX10 (P = 0.0011, OR = 2.935, 95% CI: 1.492-5.775). In addition, six SNPs (rs215702 in LSM5, rs6476866 in SLC1A1, rs10129954 in DPF3, rs1801133 in MTHFR, rs2477686 in PEX10, and rs10841496 in PED3A) were significantly correlated with semen quality alterations. Our results suggest that idiopathic male infertility in different ethnic groups may share the same mechanism or pathway. Cohort expansion and further mechanistic studies on the role of genetic factors that influence spermatogenesis and sperm progressive motility are suggested.

Neutrophils act as a first line of defense against bacterial and fungal infections, but they are also important effectors of acute and chronic inflammation. Genome-wide association studies have established that the gene encoding the protein tyrosine phosphatase nonreceptor 22 (PTPN22) makes an important contribution to susceptibility to autoimmune disease, notably rheumatoid arthritis. Although PTPN22 is most highly expressed in neutrophils, its function in these cells remains poorly characterized. We show in this article that neutrophil effector functions, including adhesion, production of reactive oxygen species, and degranulation induced by immobilized immune complexes, were reduced in Ptpn22 -/- neutrophils. Tyrosine phosphorylation of Lyn and Syk was altered in Ptpn22 -/- neutrophils. On stimulation with immobilized immune complexes, Ptpn22 -/- neutrophils manifested reduced activation of key signaling intermediates. Ptpn22 -/- mice were protected from immune complex-mediated arthritis, induced by the transfer of arthritogenic serum. In contrast, in vivo neutrophil recruitment following thioglycollate-induced peritonitis and in vitro chemotaxis were not affected by lack of PTPN22. Our data suggest an important role for PTPN22-dependent dephosphorylation events, which are required to enable full FcγR-induced activation, pointing to an important role for this molecule in neutrophil function., (Copyright © 2016 The Authors.)

Background: To characterize the utilization of Traditional Chinese Medicine (TCM) among patients with hepatitis C (HC)., Methods: This study examined datasets from the National Health Insurance Research Database in Taiwan. One cohort, including one million patients randomly sampled from the beneficiaries of the National Health Insurance Programme from January 1 to December 31 in 2010, was chosen for this analysis. People who had at least three outpatient or inpatient records and had been diagnosed with hepatitis C virus infection from 2000 to 2010 were defined as patients with HC. Patients with HC who had at least one TCM outpatient clinical record from 2000 to 2010 were defined as TCM users (N = 5,691), whereas patients with no TCM outpatient records were defined as non-TCM users (N = 2,876). The demographic data, treatment modalities and disease distributions of TCM users were analysed., Results: Overall, 66.4 % of the patients with HC had used TCM from 2000 to 2010. Of the TCM users, 54.1 % were female. The utilization rate of TCM increased with age and peaked in the age group of those 40 - 64 years old. Herbal remedies (52.4 %) were the most commonly used agents, followed by combination therapy (46.4 %) and acupuncture alone (1.2 %). Patients who had more extrahepatic diseases and were taking more antiviral agents tended to visit TCM clinics. Jia-Wei-Xiao-Yao-San and Dan-Shen (Salvia miltiorrhiza) were the most commonly used formula and single herb, with 88,124 person-days and 59,252 person-days, respectively., Conclusions: Our nationwide population-based study revealed a high prevalence and specific usage patterns of TCM in patients with HC in Taiwan.

Neutrophils are peripheral blood leukocytes that represent the first line of immune cell defense against bacterial and fungal infections but are also crucial players in the generation of the inflammatory response. Many neutrophil cell surface receptors regulate important cellular processes via activation of agonist-activated PI3Ks. We show here that activation of human neutrophils with insoluble immune complexes drives a previously uncharacterized, PI3K-dependent, non-canonical, pro-apoptotic signaling pathway, FcγR-PI3Kβ/δ-Cdc42-Pak-Mek-Erk. This is a rare demonstration of Ras/Raf-independent activation of Erk and of PI3K-mediated activation of Cdc42. In addition, comparative analysis of immune-complex- and fMLF-induced signaling uncovers key differences in pathways used by human and murine neutrophils. The non-canonical pathway we identify in this study may be important for the resolution of inflammation in chronic inflammatory diseases that rely on immune-complex-driven neutrophil activation., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)