Soft and stretchable conductors with high electrical conductivity and tissue‐like mechanical properties are crucial for both on‐skin and implantable electronic devices. Liquid metal‐based conductors ...hold great promise due to their metallic conductivity and minimal stiffness. However, the surface oxidation of liquid metal particles in polymeric matrices poses a challenge in forming a continuous pathway for highly conductive elastic composites. Here, it is reported a printable composite material based on liquid metal and conducting polymer that undergoes a self‐assembly process, achieving high conductivity (2089 S cm−1) in the bottom surface while maintaining an insulated top surface, high stretchability (>800%), and a modulus akin to human skin tissue. This material is further applied to fabricate skin‐interfaced strain sensors and electromyogram sensors through 3D printing.
A novel printable, flexible material composed of conducting polymer and liquid metal, which is capable of self‐assembly upon printing, producing asymmetric highly conductive stretchable conductors for human interface.
Abstract Reactive oxygen species (ROS) are important in regulating normal cell physiological functions, but when produced in excess lead to the augmented pathogenesis of various diseases. Among ...these, ischemia reperfusion injury, Alzheimer’s disease and rheumatoid arthritis are particularly important. Since ROS can be counteracted by a variety of antioxidants, natural and synthetic antioxidants have been developed. However, due to the ubiquitous production of ROS in living systems, poor in vivo efficiency of these agents and lack of target specificity, the current clinical modalities to treat oxidative stress damage are limited. Advances in the developing field of nanomedicine have yielded nanoparticles that can prolong antioxidant activity, and target specificity of these agents. This article reviews recent advances in antioxidant nanoparticles and their applications to manage oxidative stress-mediated diseases. From the Clinical Editor Production of reactive oxygen species (ROS) is a purely physiological process in many disease conditions. However, excessive and uncontrolled production will lead to oxidative stress and further tissue damage. Advances in nanomedicine have provided many novel strategies to try to combat and counteract ROS. In this review article, the authors comprehensively highlighted the current status and future developments in using nanotechnology for providing novel therapeutic options in this field.
Objective
Rheumatoid arthritis synovial fibroblasts (RASFs) are crucial mediators of synovial inflammation and joint destruction. However, their intrinsic immunoregulatory mechanisms under chronic ...inflammation remain unclear. Thus, the present study was undertaken to understand the role of a newly identified GTPase, guanylate binding protein 5 (GBP‐5), in RA pathogenesis.
Methods
The expression of GBP1–GBP7 transcripts was evaluated using quantitative reverse transcription–polymerase chain reaction in RA synovial tissue or synovial tissue unaffected by RA. Our investigation on transient small interfering RNA (siRNA) knockdown and lentiviral overexpression in human RASFs examined the regulatory role of GBP‐5 on proinflammatory cytokine signaling pathways. Unbiased whole transcriptome RNA sequencing analysis was used to assess the impact of GBP‐5 on RASF molecular functions. These findings were confirmed using a rat model of adjuvant‐induced arthritis (AIA) in vivo.
Results
Among different GBPs evaluated, GBP‐5 was selectively up‐regulated in RA synovial tissue (P < 0.05; n = 4) and in the joints of rats with AIA (P < 0.05; n = 6) and was significantly induced in human RASFs by interleukin‐1β (IL‐1β), tumor necrosis factor (TNF), and/or interferon‐γ (IFNγ) (P < 0.05; n = 3). Bioinformatics analysis of RNA sequencing data identified cytokine–cytokine receptor signaling as a major function altered by GBP‐5, with IL‐6 signaling as a primary target. Knockdown of GBP‐5 amplified IL‐1β–induced IL‐6, IL‐8, and epithelial neutrophil–activating peptide 78/CXCL5 production by 44%, 54%, 45%, respectively, and matrix metalloproteinase 1 (MMP‐1) production by several‐fold—effects that reversed with exogenously delivered GBP‐5. Lack of GBP‐5 increased IFNγ‐induced proliferation and migration of human RASFs. GBP‐5 knockdown in vivo using intraarticular siRNA exacerbated disease onset, severity, synovitis, and bone destruction in rat AIA.
Conclusion
Expressed by RASFs in response to cytokine stimulation, GBP‐5 has potential to restore cellular homeostasis and blunt inflammation and tissue destruction in RA.
Syndecans (SDCs) are a family of heparan sulfate proteoglycans (HSPGs) glycoproteins ubiquitously expressed on the cell surfaces and extracellular matrix of all mammalian tissues. There are four ...mammalian syndecans, SDC‐1 thorough 4, which play a critical role in cell adhesion, migration, proliferation, differentiation, and angiogenesis through independent and growth factor mediated signaling. An altered expression of SDCs is often observed in autoimmune disorders, cancer, HIV infection, and many other pathological conditions. SDCs modulate disease progression by interacting with a diverse array of ligands, receptors, and other proteins, including extracellular matrix, glycoproteins, integrins, morphogens, and various growth factors and chemokines, along with their receptors and kinases. Specifically, SDCs present on cell surface can bind directly to chemokines to enhance their binding to receptors, downstream signaling, and migration. Alternatively, SDCs can be cleaved and shed to mediate negative regulation of chemokine and growth factor signaling pathways and ligand sequestration. Importantly, SDC shedding may be a biomarker of inflammation, especially in chronic inflammatory diseases. While the current therapies for cancer and several autoimmune disorders have revolutionized treatment outcomes, understanding the pathophysiological role of SDCs and the use of HSPG mimetic or antagonists on cytokine signaling networks may uncover potentially novel targeted therapeutic approaches. This review mainly summarizes the current findings on the role of individual SDCs in disease processes, mechanisms through which SDCs mediate their biological functions, and the possibility of targeting SDCs as future potential therapeutic approaches.
Syndecans (SDCs) are a family of heparan sulfate proteoglycans (HSPGs) glycoproteins that have emerged as important mediators in autoimmune disorders, cancer, HIV infection, and many other pathological conditions. SDCs modulate disease progression by interacting with a diverse array of ligands, receptors, and other proteins, including extracellular matrix, glycoproteins, integrins, morphogens, and various growth factors and chemokines, along with their receptors and kinases. This review mainly summarizes the current findings on the role of individual SDCs in disease processes, mechanisms through which SDCs mediate their biological functions, and the possibility of targeting SDCs as future potential therapeutic approaches.
Many infants with possible serious bacterial infections (PSBI) do not receive inpatient treatment because hospital care may not be affordable, accessible, or acceptable for families. In 2015, WHO ...issued guidelines for managing PSBI in young infants (0-59 days) with simpler antibiotic regimens when hospital care is not feasible. Bangladesh adopted WHO's guidelines for implementation in outpatient primary health centers. We report results of an implementation research study that assessed caregiver acceptability of the guidelines in three rural sub-districts of Bangladesh during early implementation (October 2015-August 2016).
We included 19 outpatient primary health centers involved in the initial rollout of the infection management guidelines. We extracted data for all PSBI cases (N = 192) from facility registers to identify gaps in referral feasibility, simplified antibiotic treatment, and follow-up. Focus group discussions (FGD) and in-depth interviews (IDI) were conducted with both caregivers (6 FGDs; 23 IDIs) and providers (2 FGDs; 28 IDIs) to assess caregiver acceptability of the guidelines.
Referral to the hospital was not feasible for many families (83.3%; N = 160/192) and acceptance varied by infection severity. Barriers to referral feasibility included economic and household factors, and previous experiences with poor quality of care at the sub-district hospital. Conversely, providers and caregivers indicated high acceptability of simplified antibiotic treatment. 80% (N = 96/120) of infants with clinical severe infection for whom referral was not feasible returned to the facility for the second antibiotic injection. Some providers reported developing local solutions-including engaging informal providers in treatment of the infant-to address organizational barriers and promote treatment compliance. Follow-up of young infants receiving simplified treatment is critical, but only 67.4% (N = 87/129) of infants received fourth day follow-up. Some providers' reported deviations from the guidelines that shifted responsibility of follow-up to the caregiver, which may have contributed to lapses.
Caregivers' perception of trust and communication with providers were influential in caregiver acceptability of care. Few caregivers accepted referral to the sub-district hospital, suggesting low acceptability of this option. When referral was not feasible, many caregivers reported satisfaction with simplified antibiotic treatment. Local solutions described by providers require further examination in this context to assess the safety and potential value of these strategies in outpatient treatment. Our findings suggest strengthening providers' interpersonal skills could improve caregiver acceptability of the guidelines.
In this work we present a single scale wavelet-Galerkin method (WGM) for obtaining the linear dynamic response of single degree of freedom (SDOF) and multi-degree of freedom (MDOF) systems, the ...equation of motion is discretized using a polynomial extrapolation-based time stepping scheme. The aim of the study is to investigate the accuracy of the dynamic response resulting from the application of the proposed method and to explore the Daubechies wavelet types that can be used for unconditional stability. In our work we solve only for the scaling function coefficients of the displacement response, the scaling function coefficients of the velocity and the acceleration responses are obtained from the solved scaling function coefficients of the displacement function and the pertaining connection coefficients. The classical central differences method (CCDM) is used to generate consistent values of the velocity and the acceleration response to replace the distorted ones at the edges of the time interval. Stability analysis shows that the method using D6 wavelets is unconditionally stable for the practical range of the product of the time step and the frequency of vibration. An application of a SDOF system with initial conditions shows that for D6 wavelets the calculated responses at an adequate approximation level correspond well with those obtained using Newmark’s average acceleration method (AAM). The method is also applied to a MDOF system without performing a modal analysis, the resulting dynamic response is found to be accurate enough to be compared to that of the mode superposition method used by the STAAD pro program.
The purpose of this study is to assess the prevalence and associated factors of physical and sexual intimate partner violence (IPV) among married women of reproductive age in a rural population in ...northeast Bangladesh. In addition, we examined women's sharing and disclosure of violence experience with others.
This cross-sectional study uses data from a household survey of 3966 women conducted in 2014 in the Sylhet District of Bangladesh. Interviews were completed in respondent's homes by trained local female interviewers.
Twenty-nine percent (28.8%, 95% CI 27.4-30.3%) of the women reported ever experiencing physical or sexual IPV by their spouse; 13.2% (95% CI 12.1-14.3%) reported physical or sexual IPV in the past year. Of the 13.2%, 10.1% (95% CI 9.2-11.1%) reported experiencing physical IPV and 4.6% (95% CI 4.0-5.3%) reported sexual IPV. In a combined model, the adjusted odds of having experienced physical or sexual IPV in the past year were higher for women who were raised in households with history of IPV (AOR = 4.35, 95% CI 3.26-5.80); women with no formal education (AOR = 1.76, 95% CI 1.30-2.37); women whose husbands had no formal education (AOR = 1.63, 95% CI 1.22-2.17); Muslim (AOR = 1.63, 95% CI 1.03-2.57); women younger than age 30 (AOR = 1.53, 95% CI 1.11-2.12); and women who were members of an NGO or microcredit financial organization (AOR = 1.38, 95% CI 1.04-1.82). Wealth, parity, number of household members, and pregnancy status (pregnant, postpartum, neither pregnant nor postpartum) were not associated with physical or sexual IPV after adjusting for other factors. Data on disclosure was available for women who reported experiencing physical violence in the last year; only 31.8% of victims told someone about the violence they had experienced and 1% reported to police, clerics, health workers, or a counselor altogether.
In rural northeast Bangladesh, a high proportion of women of reproductive age experience physical or sexual IPV. Women do not often speak of these experiences, especially to anyone outside of family. Interventions aimed at preventing future IPV and addressing current IPV should focus on women who witnessed IPV in childhood, as well as younger women and less educated couples.
This study was registered as a Clinical Trial (Identifier: NCT01702402). https://clinicaltrials.gov/ct2/show/NCT01702402.
Regulated on activation, normal T expressed, and secreted (RANTES)/CC ligand 5 (CCL5) participates in rheumatoid arthritis (RA) pathogenesis by facilitating leukocyte infiltration, however, its other ...pathological functions are not fully defined in RA. In the present study, we evaluated the effect of RANTES/CCL5 on tissue degrading enzymes matrix metalloproteinase-1 (MMP-1) and MMP-13 expression and its contribution to the progressive joint damage by RA synovial fibroblasts (RASFs). Our results showed that RANTES/CCL5 dose dependently induced MMP-1 and MMP-13 expression in monolayers and three-dimensional (3D) micromass of human RASFs, which correlated with an increase in collagenase activity. This activation by RANTES/CCL5 was observed in RASF, but not in osteoarthritis SFs (OASFs). Evaluation of the signaling events showed that RANTES/CCL5 selectively activated PKCδ, JNK, and ERK proteins to induce MMP expression in human RASFs. Pretreatment with a functional antagonist (Met-RANTES) or heparinase III an enzyme that selectively digests heparan sulfate proteoglycans (HSPGs) completely abrogated RANTES/CCL5-induced MMP-1 and MMP-13 expression. Interestingly, the inhibition of RANTES/CCL5 using small-interfering RNA approach reduced the ability of interleukin-1β (IL-1β) to induce MMP-1 and MMP-13 expression, asserting its mediatory role in tissue remodeling. In the inhibitor study, only the selective inhibition of HSPGs or PKCδ, ERK, and JNK markedly inhibited RANTES/CCL5-induced MMP-1 and MMP-13 production. Circular dichroism spectroscopy results demonstrated the degradation of collagen triple-helical structure upon exposure to the conditioned media from RANTES/CCL5 stimulated RASFs, which was reverted by a broad-spectrum MMP inhibitor (GM6001). These findings suggest that RANTES/CCL5 not only upregulates MMP-1 and MMP-13 expression by partly utilizing HSPGs and/or PKCδ-JNK/ERK pathways but also mediates IL-1β-induced MMP-1 and MMP-13 expression.
Neonatal infections remain a leading cause of newborn deaths globally. In 2015, WHO issued guidelines for managing possible serious bacterial infection (PSBI) in young infants (0-59 days) using ...simplified antibiotic regimens when compliance with hospital referral is not feasible. Bangladesh was one of the first countries to adopt WHO's guidelines for implementation. We report results of an implementation research study that assessed facility readiness and provider performance in three rural sub-districts of Bangladesh during August 2015-August 2016.
This study took place in 19 primary health centers. Facility readiness was assessed using checklists completed by study staff at three time points. To assess provider performance, we extracted data for all infection cases from facility registers and compared providers' diagnosis and treatment against the guidelines. We plotted classification and dosage errors across the study period and superimposed a locally weighted smoothed (LOWESS) curve to analyze changes in performance over time. Focus group discussions (N = 2) and in-depth interviews (N = 28) with providers were conducted to identify barriers and facilitators for facility readiness and provider performance.
At baseline, none of the facilities had adequate supply of antibiotics. During the 10-month period, 606 sick infants with signs of infection presented at the study facilities. Classification errors were identified in 14.9% (N = 90/606) of records. For infants receiving the first dose(s) of antibiotic treatment (N = 551), dosage errors were identified in 22.9% (N = 126/551) of the records. Distribution of errors varied by facility (35.7% IQR: 24.7-57.4%) and infection severity. Errors were highest at the beginning of the study period and decreased over time. Qualitative data suggest errors in early implementation were due to changes in providers' assessment and treatment practices, including confusion about classifying an infant with multiple signs of infection, and some providers' concerns about the efficacy of simplified antibiotic regimens.
Strategies to monitor early performance and targeted supports are important for enhancing implementation fidelity when introducing complex guidelines in new settings. Future research should examine providers' assessment of effectiveness of simplified treatment and address misconceptions about superiority of broader spectrum antibiotics for treating community-acquired neonatal infections in this context.
Women experience high rates of depression, particularly during pregnancy and the postpartum periods. Using population-based data from Bangladesh and Pakistan, we estimated the burden of antenatal ...depression, its risk factors, and its effect on preterm birth.
The study uses the following data: maternal depression measured between 24 and 28 weeks of gestation using the 9-question Patient Health Questionnaire (PHQ-9); data on pregnancy including an ultrasound before 19 weeks of gestation; data on pregnancy outcomes; and data on woman's age, education, parity, weight, height, history of previous illness, prior miscarriage, stillbirth, husband's education, and household socioeconomic data collected during early pregnancy. Using PHQ-9 cutoff score of ≥12, women were categorized into none to mild depression or moderate to moderately severe depression. Using ultrasound data, preterm birth was defined as babies born <37 weeks of gestation. To identify risk ratios (RR) for antenatal depression, unadjusted and adjusted RR and 95% confidence intervals (CI) were calculated using log- binomial model. Log-binomial models were also used for determining the effect of antenatal depression on preterm birth adjusting for potential confounders. Data were analyzed using Stata version 16 (StataCorp LP).
About 6% of the women reported moderate to moderately severe depressive symptoms during the antenatal period. A parity of ≥2 and the highest household wealth status were associated with an increased risk of depression. The overall incidence of preterm birth was 13.4%. Maternal antenatal depression was significantly associated with the risk of preterm birth (ARR, 95% CI: 1.34, 1.02-1.74).
The increased risk of preterm birth in women with antenatal depression in conjunction with other significant risk factors suggests that depression likely occurs within a constellation of other risk factors. Thus, to effectively address the burden of preterm birth, programs require developing and providing integrated care addressing multiple risk factors.
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