Maternal and child health intervention to promote behaviour change: a population-level cluster-randomised controlled trial in Honduras.

OBJECTIVES: To assess the efficacy of a sustained educational intervention to affect diverse outcomes across the pregnancy and infancy timeline. SETTING: A multi-arm cluster-randomised controlled trial in 99 villages in Honduras' Copán region, involving 16 301 people in 5633 households from October 2015 to December 2019. PARTICIPANTS: Residents aged 12 and older were eligible. A photographic census involved 93% of the population, with 13 881 and 10 263 individuals completing baseline and endline surveys, respectively. INTERVENTION: 22-month household-based counselling intervention aiming to improve practices, knowledge and attitudes related to maternal, neonatal and child health. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were prenatal/postnatal care behaviours, facility births, exclusive breast feeding, parental involvement, treatment of diarrhoea and respiratory illness, reproductive health, and gender/reproductive norms. Secondary outcomes were knowledge and attitudes related to the primary outcomes. RESULTS: Parents targeted for the intervention were 16.4% (95% CI 3.1%-29.8%, p=0.016) more likely to have their newborn's health checked in a health facility within 3 days of birth; 19.6% (95% CI 4.2%-35.1%, p=0.013) more likely to not wrap a fajero around the umbilical cord in the first week after birth; and 8.9% (95% CI 0.3%-17.5%, p=0.043) more likely to report that the mother breast fed immediately after birth. Changes in knowledge and attitudes related to these primary outcomes were also observed. We found no significant effect on various other practices. CONCLUSION: A sustained counselling intervention delivered in the home setting by community health workers can meaningfully change practices, knowledge and attitudes related to proper newborn care following birth, including professional care-seeking, umbilical cord care and breast feeding. TRIAL REGISTRATION NUMBER: NCT02694679.

3D printed polylactic acid-based nanocomposite scaffold stuffed with microporous simvastatin-loaded polyelectrolyte for craniofacial reconstruction.

Critical sized craniofacial defects are among the most challenging bone defects to repair, due to the anatomical complexity and aesthetic importance. In this study, a polylactic acid/hardystonite-graphene oxide (PLA/HTGO) scaffold was fabricated through 3D printing. In order to upgrade the 3D printed scaffold to a highly porous scaffold, its channels were filled with pectin-quaternized chitosan (Pec-QCs) polyelectrolyte solution containing 0 or 20 mg/mL of simvastatin (Sim) and then freeze-dried. These scaffolds were named FD and FD-Sim, respectively. Also, similar PLA/HTGO scaffolds were prepared and dip coated with Pec-QCs solution containing 0 or 20 mg/mL of Sim and were named DC and DC-Sim, respectively. The formation of macro/microporous structure was confirmed by morphological investigations. The release of Sim from DC-Sim and FD-Sim scaffolds after 28 days was measured as 77.40 ± 5.25 and 86.02 ± 3.63 %, respectively. Cytocompatibility assessments showed that MG-63 cells had the highest proliferation, attachment and spread on the Sim containing scaffolds, especially FD-Sim. In vivo studies on a rat calvarial defect model revealed that an almost complete recovery occurred in the group treated with FD-Sim scaffold after 8 weeks and the defect was filled with newly formed bone. The results of this study acknowledge that the FD-Sim scaffold can be a perfect candidate for calvarial defect repair.

Mupirocin loaded core-shell pluronic-pectin-keratin nanofibers improve human keratinocytes behavior, angiogenic activity and wound healing.

In the current study, a core-shell nanofibrous wound dressing based on Pluronic-F127 (F127) containing 2 wt% mupirocin (Mup) core and pectin (Pec)-keratin (Kr) shell was fabricated through coaxial electrospinning technique, and the blended nanofibers were also fabricated from the same materials. The fiber diameter and specific surface area of the blended nanofibers were about 101.56 nm and 20.16 m2/g, while for core-shell nanofibers they were about 97.32 nm and 25.26 m2/g, respectively. The resultant blended and core-shell nanofibers experienced a degradation of 27.65 % and 32.28 % during 7 days, respectively. The drug release profile of core-shell nanofibers revealed a sustained release of Mup over 7 days (87.66 %), while the blended F127-Pec-Kr-Mup nanofibers had a burst release within the first few hours (89.38 % up to 48 h) and a cumulative release of 91.36 % after 7 days. Due to the controlled release of Mup, the core-shell structure significantly improved the human keratinocytes behavior, angiogenic potential and wound healing in a rat model compared to the blended structure. In conclusion, the F127-Mup/Pec-Kr core-shell nanofibrous wound dressing appears to be a promising candidate for the prevention of infection, and can potentially accelerate the recovery and healing of chronic and ischemic wounds.

Xylazine in the drug supply: Emerging threats and lessons learned in areas with high levels of adulteration.

BACKGROUND: Xylazine, a sedative analgesic drug approved as an animal tranquilizer but not for human use, has become an adulterant in the illicit opioid marketplace in North America. Recently declared an emerging health threat in the U.S., the prevalence of xylazine in overdose deaths increased 5.5-fold between 2019 and 2021. More information is needed about the impact of xylazine on opioid users and harm reduction service providers. METHODS: The impact of xylazine adulteration was triangulated through examination of (1) opioid overdose fatalities in Connecticut between 2017 and 2021 reported by the Office of the Chief Medical Examiner data, (2) a convenience survey of people in Connecticut who use drugs (PWUD) regarding their knowledge of and attitude about the local illicit drug supply, and (3) semi-structured interviews of harm reduction service providers in Connecticut and Philadelphia in response to prompts on the impacts of and responses to xylazine adulteration. RESULTS: The presence of fentanyl or its analogues in fatal opioid overdoses was a statistically significant predictor of xylazine presence [OR = 25.0, 95%CI (10.7,81.1)] as was being Hispanic [OR = 1.36, 95%CI (1.03,1.77)]. A survey of people who used drugs revealed that 43% (n = 286) were concerned that the drug supply was always unpredictable. Three-quarters of respondents were aware of xylazine and two-thirds would use a xylazine test strip if one was available. Respondents who identified as White, Hispanic were most likely to be aware of xylazine, to have used a fentanyl test strip, and to be interested in a xylazine test strip. Respondents who injected drugs were 3.6-fold more likely than those who did not inject to endorse an interest in a xylazine test strip. Harm reduction service providers were cognizant of a range of problems surrounding the use and injection of xylazine. Although they reported implementing practices to better respond to xylazine harms, they recognized the absence of solutions to many of the problems encountered. CONCLUSION: The prevalence of xylazine has expanded, especially in combination with fentanyl. Harm reduction education efforts with fidelity to best practices have emerged, but the harms persist and community prevention needs are largely unmet.

Mass gatherings for political expression had no discernible association with the local course of the COVID-19 pandemic in the USA in 2020 and 2021.

Epidemic disease can spread during mass gatherings. We assessed the impact of a type of mass gathering about which comprehensive data were available on the local-area trajectory of the COVID-19 epidemic. Here we examined five types of political event in 2020 and 2021: the US primary elections, the US Senate special election in Georgia, the gubernatorial elections in New Jersey and Virginia, Donald Trump's political rallies and the Black Lives Matter protests. Our study period encompassed over 700 such mass gatherings during multiple phases of the pandemic. We used data from the 48 contiguous states, representing 3,108 counties, and we implemented a novel extension of a recently developed non-parametric, generalized difference-in-difference estimator with a (high-quality) matching procedure for panel data to estimate the average effect of the gatherings on local mortality and other outcomes. There were no statistically significant increases in cases, deaths or a measure of epidemic transmissibility (Rt) in a 40-day period following large-scale political activities. We estimated small and statistically non-significant effects, corresponding to an average difference of -0.0567 deaths (95% CI = -0.319, 0.162) and 8.275 cases (95% CI = -1.383, 20.7) on each day for counties that held mass gatherings for political expression compared to matched control counties. In sum, there is no statistical evidence of a material increase in local COVID-19 deaths, cases or transmissibility after mass gatherings for political expression during the first 2 years of the pandemic in the USA. This may relate to the specific manner in which such activities are typically conducted.

Algorithms for seeding social networks can enhance the adoption of a public health intervention in urban India.

Targeting structurally influential individuals within social networks can enhance adoption of health interventions within populations. We tested the effectiveness of two algorithms to improve social contagion that do not require knowledge of the whole network structure. We mapped the social interactions of 2,491 women in 50 residential buildings (chawls) in Mumbai, India. The buildings, which are social units, were randomized to (1) targeting 20% of the women at random, (2) targeting friends of such randomly chosen women, (3) targeting pairs of people composed of randomly chosen women and a friend, or (4) no targeting. Both targeting algorithms, friendship nomination and pair targeting, enhanced adoption of a public health intervention related to the use of iron-fortified salt for anemia. In particular, the targeting of pairs of friends, which is relatively easily implementable in field settings, enhanced adoption of novel practices through both social influence and social reinforcement.

Development of a Psychometric Tool to Measure Community Solidarity Among Sexual Minorities: Evidence From a Pay-it-Forward Randomized Controlled Trial.

BACKGROUND: Community solidarity is increasingly important in public health. However, few studies have examined solidarity in relation to health outcomes. The purpose of this study was to develop a psychometric tool to measure solidarity among Chinese men who have sex with men (MSM) and assess whether community solidarity relates to differences in sexually transmitted infection testing. METHODS: We used data from the pay-it-forward randomized controlled trial of 301 men from Beijing and Guangzhou, China. Men who have sex with men were randomized into pay-it-forward (participants receive free gonorrhea/chlamydia testing as gifts and choose to donate toward subsequent MSM's tests), pay-what you-want, and standard payment arms. After testing decision, participants completed a cross-sectional questionnaire to assess community solidarity. Factor analysis was conducted to identify dimensions of solidarity. The solidarity factors were compared across study arms and assessed against gonorrhea/chlamydia test uptake in multivariable logistic regression. RESULTS: Two hundred eighty-eight participants responded to the survey. We identified 3 latent community solidarity factors: engagement, social network support, and sense of belonging. Several items related to belonging were significantly greater among participants in the pay-it-forward scenario compared with those assigned to other scenarios. Higher sense of belonging was associated with higher odds of gonorrhea and chlamydia test uptake. CONCLUSIONS: Community solidarity among MSM in China can be characterized by 3 factors: engagement, social network support, and sense of belonging. Sense of belonging was higher in the pay-it-forward intervention arm and may be associated with the uptake of gonorrhea/chlamydia test. Future studies are warranted to confirm the psychometric structure of community solidarity and further investigate behavioral mechanisms of pay it forward.

Chemotherapeutic effects of Apigenin in breast cancer: Preclinical evidence and molecular mechanisms; enhanced bioavailability by nanoparticles.

This review highlights using nanotechnology in increasing the bioavailability of AP (Apigenin) to enhance its therapeutic efficacy in breast cancer treatment. Breast cancer is one of the most leading causes of cancer death in women both in developed and developing countries. According to several epidemiological and clinical trial studies that indicate progestin-stimulated breast cancer in post-menopausal women; it is necessary to determine compounds to suppress or attenuate the tumor-promoting effects of progestins in breast cells. For this purpose, using the natural anti-progestins, including AP compared with the chemical ones could be significantly effective due to the lack of toxicities and contradiction effects. However, AP is categorized as a Class II drug of Biopharmaceutical Classification System with low solubility in water which limited its therapeutic effects. Therefore, nanotechnology due to the presentation of remarkable properties has overcome this limitation through enhanced the solubility and bioavailability of AP. In this regard, various nanocarriers such as nanocrystals, micelles, liposomes, PLGA, etc., have highlighted the significantly increased bioavailability and therapeutic efficacy of AP. Therefore, we will focus on the anticancer effects of AP in breast cancers, including involved mechanisms, the chemistry of AP and its bioavailability, finally different nanostructure systems to enhance the bioavailability of AP.

Stem Cell Differentiation into Cardiomyocytes: Current Methods and Emerging Approaches.

Cardiovascular diseases (CVDs) are globally known to be important causes of mortality and disabilities. Common treatment strategies for CVDs, such as pharmacological therapeutics impose serious challenges due to the failure of treatments for myocardial necrosis. By contrast, stem cells (SCs) based therapies are seen to be promising approaches to CVDs treatment. In such approaches, cardiomyocytes are differentiated from SCs. To fulfill SCs complete potential, the method should be appointed to generate cardiomyocytes with more mature structure and well-functioning operations. For heart repairing applications, a greatly scalable and medical-grade cardiomyocyte generation must be used. Nonetheless, there are some challenges such as immune rejection, arrhythmogenesis, tumorigenesis, and graft cell death potential. Herein, we discuss the types of potential SCs, and commonly used methods including embryoid bodies related techniques, co-culture, mechanical stimulation, and electrical stimulation and their applications, advantages and limitations in this field. An estimated 17.9 million people died from CVDs in 2019, representing 32 % of all global deaths. Of these deaths, 85 % were due to heart attack and stroke.

Characterizing the social support and functioning of a low-threshold medication for opioid use disorder treatment cohort at intake.

BACKGROUND: Despite the growing morbidity and mortality rates associated with opioid use disorder, a large gap still exists between treatment need and capacity. Low-threshold clinics utilizing medication for opioid use disorder (MOUD) treatment can increase treatment access but are understudied, and little is known about how patient demographic characteristics are associated with their social support and functioning in these settings. METHODS: We used multivariate regression to estimate associations between demographic characteristics and self-reported social support or functioning indicators among patients receiving MOUD in a low-threshold clinic using several validated instruments administered at intake: Behavior and Symptom Identification Scale, Brief Pain Inventory, and Life Events Checklist for DSM-5. Patients initiating MOUD treatment between April 1 and December 31, 2017, with complete surveys were included (N=582). RESULTS: Patients were primarily male (62%), aged 34 or older (53%), non-Hispanic White (79%), separated or not married (86%), and unemployed (64%). Over 20% did not live in a house or apartment in the past month. Women were more likely to "get along" with people outside their family or in social situations and to identify their partner as their source of support. Women, non-White, and older patients were at higher risk of social functioning-disrupting events (physical/sexual assaults or experiencing chronic pain), while employment and housing were protective against exposure to these trauma-related events. However, employment and housing also decreased the odds of talking with others about substance use. The aforementioned results were obtained from multivariate logistic regression models and were significant to p<0.05. CONCLUSIONS: Variation in support and functioning by demographic characteristics suggests that treatment facilities may benefit from adopting strategies that take baseline disparities in support and functioning into account.

Emerging treatment strategies in wound care.

Wound healing is a complex process in tissue regeneration through which the body responds to the dissipated cells as a result of any kind of severe injury. Diabetic and non-healing wounds are considered an unmet clinical need. Currently, different strategic approaches are widely used in the treatment of acute and chronic wounds which include, but are not limited to, tissue transplantation, cell therapy and wound dressings, and the use of an instrument. A large number of literatures have been published on this topic; however, the most effective clinical treatment remains a challenge. The wound dressing involves the use of a scaffold, usually using biomaterials for the delivery of medication, autologous stem cells, or growth factors from the blood. Antibacterial and anti-inflammatory drugs are also used to stop the infection as well as accelerate wound healing. With an increase in the ageing population leading to diabetes and associated cutaneous wounds, there is a great need to improve the current treatment strategies. This research critically reviews the current advancement in the therapeutic and clinical approaches for wound healing and tissue regeneration. The results of recent clinical trials suggest that the use of modern dressings and skin substitutes is the easiest, most accessible, and most cost-effective way to treat chronic wounds with advances in materials science such as graphene as 3D scaffold and biomolecules hold significant promise. The annual market value for successful wound treatment exceeds over $50 billion US dollars, and this will encourage industries as well as academics to investigate the application of emerging smart materials for modern dressings and skin substitutes for wound therapy.

Characterizing super-spreaders using population-level weighted social networks in rural communities.

Sociocentric network maps of entire populations, when combined with data on the nature of constituent dyadic relationships, offer the dual promise of advancing understanding of the relevance of networks for disease transmission and of improving epidemic forecasts. Here, using detailed sociocentric data collected over 4 years in a population of 24 702 people in 176 villages in Honduras, along with diarrhoeal and respiratory disease prevalence, we create a social-network-powered transmission model and identify super-spreading nodes as well as the nodes most vulnerable to infection, using agent-based Monte Carlo network simulations. We predict the extent of outbreaks for communicable diseases based on detailed social interaction patterns. Evidence from three waves of population-level surveys of diarrhoeal and respiratory illness indicates a meaningful positive correlation with the computed super-spreading capability and relative vulnerability of individual nodes. Previous research has identified super-spreaders through retrospective contact tracing or simulated networks. By contrast, our simulations predict that a node's super-spreading capability and its vulnerability in real communities are significantly affected by their connections, the nature of the interaction across these connections, individual characteristics (e.g. age and sex) that affect a person's ability to disperse a pathogen, and also the intrinsic characteristics of the pathogen (e.g. infectious period and latency). This article is part of the theme issue 'Data science approach to infectious disease surveillance'.

A Bayesian Method for Material Identification of Composite Plates via Dispersion Curves.

Ultrasonic guided waves offer a convenient and practical approach to structural health monitoring and non-destructive evaluation. A key property of guided waves is the fully defined relationship between central frequency and propagation characteristics (phase velocity, group velocity and wavenumber)-which is described using dispersion curves. For many guided wave-based strategies, accurate dispersion curve information is invaluable, such as group velocity for localisation. From experimental observations of dispersion curves, a system identification procedure can be used to determine the governing material properties. As well as returning an estimated value, it is useful to determine the distribution of these properties based on measured data. A method of simulating samples from these distributions is to use the iterative Markov-Chain Monte Carlo (MCMC) procedure, which allows for freedom in the shape of the posterior. In this work, a scanning-laser Doppler vibrometer is used to record the propagation of Lamb waves in a unidirectional-glass-fibre composite plate, and dispersion curve data for various propagation angles are extracted. Using these measured dispersion curve data, the MCMC sampling procedure is performed to provide a Bayesian approach to determining the dispersion curve information for an arbitrary plate. The distribution of the material properties at each angle is discussed, including the inferred confidence in the predicted parameters. The percentage errors of the estimated values for the parameters were 10-15 points larger when using the most likely estimates, as opposed to calculating from the posterior distributions, highlighting the advantages of using a probabilistic approach.

Blocking and being blocked on gay dating apps among MSM attending a sexual health clinic: an observational study.

BACKGROUND: There are limited studies on blocking and men who have sex with men (MSM) health outcomes. We need such data in China, to better understand the relationship between Chinese MSM gay app use and health outcomes, thus providing insight on risky sexual behaviors and HIV transmission among Chinese MSM - one of the world's largest MSM communities. Blocking someone is when users select a function on an app to prevent another user from contacting them and being blocked is when someone is prevented from contacting another user. We studied the correlates of blocking on the world's largest gay dating app among Chinese MSM (N = 208). METHODS: We conducted a cross-sectional survey as part of an HIV testing intervention in Guangzhou, China, May-December 2019. Using logistic regression models, we estimated the correlates of blocking (e.g. sociodemographic characteristics, sexual behavior, HIV testing history, social network data). RESULTS: MSM had a mean age of 27.9 years (SD = 7.1) and median of one sexual partner in the last 3 months. About 62% had blocked someone in their lifetime and 46% had been blocked in their lifetime. Each additional male partner was associated with an 87% (aOR = 1.87, 95%CI = 1.03, 3.40) increased chance of being blocked. Reporting a versatile sexual role was related with a 90% (aOR = 0.10, 95%CI = 0.02, 0.45) decreased likelihood of blocking behavior and an 86% (aOR = 0.14, 95%CI = 0.04, 0.46) reduced chance of being blocked. CONCLUSIONS: Number of male partners may be associated with blocking behavior, with implications for the design of online sexual health interventions.

The role of social network support in treatment outcomes for medication for opioid use disorder: A systematic review.

BACKGROUND: Social connections can lead to contagion of healthy behaviors. Successful treatment of patients with opioid use disorder may lay in rebuilding social networks. Strong social networks of support can reinforce the benefits of medication treatments that are the current standard of care and the most effective tool physicians have to fight the opioid epidemic. METHODS: The research team conducted a systematic review of electronic research databases, specialist journals and grey literature up to August 2020 to identify randomized controlled trials of social network support in patient populations receiving medication for opioid use disorder (MOUD). The research team placed the studies into a framework of dynamic social networks, examining the role of networks before MOUD treatment is initiated, during the treatment, and in the long-term following the treatment. The research team analyzed the results across three sources of social network support: partner relationships, family, and peer networks. RESULTS: Of 5193 articles screened, eight studies were identified as meeting inclusion criteria. Five studies indicated that social network support had a statistically significant effect on improved MOUD treatment outcomes. We find the strongest support for the positive impact of family social network support. CONCLUSIONS: Social networks significantly shape effectiveness of opioid use disorder treatments. While negative social ties reinforce addiction, positive social support networks can amplify the benefits of medication treatments. Targeted interventions to improve treatment outcomes can be designed and added to MOUD treatment with their effects evaluated in improving patients' odds of recovery from opioid use disorder and reversing the rising trend in opioid deaths.

Induced Pluripotent Stem Cells (iPSCs) Provide a Potentially Unlimited T Cell Source for CAR-T Cell Development and Off-the-Shelf Products.

Chimeric antigen receptor T (CAR-T) cell therapy has been increasingly conducted for cancer patients in clinical settings. Progress in this therapeutic approach is hampered by the lack of a solid manufacturing process, T lymphocytes, and tumor-specific antigens. T cell source used in CAR-T cell therapy is derived predominantly from the patient's own T lymphocytes, which makes this approach impracticable to patients with progressive diseases and T leukemia. The generation of autologous CAR-T cells is time-consuming due to the lack of readily available T lymphocytes and is not applicable for third-party patients. Pluripotent stem cells, such as human induced pluripotent stem cells (hiPSCs), can provide an unlimited T cell source for CAR-T cell development with the potential of generating off-the-shelf T cell products. T-iPSCs (iPSC-derived T cells) are phenotypically defined, expandable, and as functional as physiological T cells. The combination of iPSC and CAR technologies provides an exciting opportunity to oncology and greatly facilitates cell-based therapy for cancer patients. However, T-iPSCs, in combination with CARs, are at the early stage of development and need further pre-clinical and clinical studies. This review will critically discuss the progress made in iPSC-derived T cells and provides a roadmap for the development of CAR iPSC-derived T cells and off-the-shelf T-iPSCs.

Hydrogels as Emerging Materials for Cornea Wound Healing.

Hydrogel biomaterials have many favorable characteristics including tuneable mechanical behavior, cytocompatibility, optical properties suitable for regeneration and restoration of the damaged cornea tissue. The cornea is a tissue susceptible to various injuries and traumas with a complicated healing cascade, in which conserving its transparency and integrity is critical. Accordingly, the hydrogels' known properties along with the stimulation of nerve and cell regeneration make them ideal scaffold for corneal tissue engineering. Hydrogels have been used extensively in clinical applications for the repair and replacement of diseased organs. The development and optimizing of novel hydrogels to repair/replace corneal injuries have been the main focus of researches within the last decade. This research aims to critically review in vitro, preclinical, as well as clinical trial studies related to corneal wound healing using hydrogels in the past 10 years, as this is considered as an emerging technology for corneal treatment. Several unique modifications of hydrogels with smart behaviors have undergone early phase clinical trials and showed promising outcomes. Financially, this considers a multibillion dollars industry and with huge interest from medical devices as well as pharmaceutical industries with several products may emerge within the next five years.