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The use of nanomedicines to induce immunogenic cell death is a new strategy that aims to increase tumor immunogenicity and thereby prime tumors for further immunotherapies. In this study, we developed a nanoparticle formulation for combinatory chemotherapy and photothermal therapy based only on materials previously used in FDA-approved products and investigated the effect of the combinatory therapy on the growth inhibition and induction of immunogenic cell death in human MDA-MB-231 breast cancer cells. The formulation consists of ~108-nm nanoparticles made of poly(lactic acid)-b-methoxy poly(ethylene glycol) which carry doxorubicin for chemotherapy and indocyanine green for photothermal therapy. A 0.3 mg/mL suspension of NPs increased the medium temperature up to 10 °C upon irradiation with an 808-nm diode laser. In vitro studies showed that combination of laser assisted indocyanine green-mediated photothermal therapy and doxorubicin-mediated chemotherapy effectively eradicated cancer cells and resulted in the highest level of damage-associated molecular pattern presentation (calreticulin, high mobility group box 1, and adenosine triphosphate) compared to the individual treatments alone. These results demonstrate that our nanoparticle-mediated combinatory approach led to the most intense immunogenic cell death when compared to individual chemotherapy or photothermal therapy, making it a potent option for future in vivo studies in combination with cancer immunotherapies., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Polymeric nanoparticles (NPs) have a variety of biomedical, biotechnology, agricultural and environmental applications. As such, a great need has risen for the fabrication of these NPs in large scales. In this study, we used a high throughput fiber reactor for the preparation of poly(lactic- co -glycolic acid) (PLGA) NPs via nanoprecipitation. The fiber reactor provided a high surface area for the controlled interaction of an organic phase containing the PLGA solution with an aqueous phase, containing poly(vinyl alcohol) (PVA) as a stabilizer. This interaction led to the self-assembly of the polymer into the form of NPs. We studied operational parameters to identify the factors that have the greatest influence on the properties of the resulting PLGA NPs. We found that the concentration of the PLGA solution is the factor that has the greatest effect on NP size, polydispersity index (PDI), and production rate. Increasing PLGA concentration increased NP sizes significantly, while at the same time decreasing the PDI value. The second factor that was found to affect NP properties was the concentration of PVA solution, which resulted in increased NP sizes and decreased production rates. Flowrates of the feed streams also affected NP size to a lesser extent, while changing the operational temperature did not change the product's features. In general, the results demonstrate that fiber reactors are a suitable method for the large-scale, continuous preparation of polymeric NPs suitable for biomedical applications.

Background: Accessibility of sexual and reproductive health (SRH) services in many lower-and-middle-income countries (LMICs) and humanitarian settings remains limited, particularly for young people. Young people facing humanitarian crises are also at higher risk for mental health problems, which can further exacerbate poor SRH outcomes. This review aimed to explore, describe and evaluate SRH interventions for young people in LMIC and humanitarian settings to better understand both SRH and psychosocial components of interventions that demonstrate effectiveness for improving SRH outcomes., Methods: We conducted a systematic review of studies examining interventions to improve SRH in young people in LMIC and humanitarian settings following Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) standards for systematic reviews. Peer-reviewed journals and grey literature from January 1, 2000 to December 31, 2018 were included. Two authors performed title, abstract and full-text screening independently. Data was extracted and analyzed using a narrative synthesis approach and the practice-wise clinical coding system., Results: The search yielded 813 results, of which 55 met inclusion criteria for full-text screening and thematic analysis. Primary SRH outcomes of effective interventions included: contraception and condom use skills, HIV/STI prevention/education, SRH knowledge/education, gender-based violence education and sexual self-efficacy. Common psychosocial intervention components included: assertiveness training, communication skills, and problem-solving., Conclusions: Findings suggest that several evidence-based SRH interventions may be effective for young people in humanitarian and LMIC settings. Studies that use double blind designs, include fidelity monitoring, and focus on implementation and sustainability are needed to further contribute to this evidence-base.

Background: Evidence-based mental health interventions have helped address health services gaps, but their reach and societal benefit can be limited in low resource settings. The current study extends an ongoing scale-up study of a cognitive behavioral therapy (CBT)-based intervention, the Youth Readiness Intervention (YRI), among high risk youth in post-conflict Sierra Leone to investigate mechanisms of diffusion and spillover effects of the YRI among peers and caregivers of youth who receive the intervention., Methods: We will recruit and enroll YRI index participants and control index participants (ages 18-30). Index participants will complete a standardized ego-network survey to nominate three peers in their social networks and identify their primary cohabitating caregiver. Identified peers and caregivers who consent to participate will complete a quantitative assessment battery on mental health outcomes, emotion regulation, and daily functioning at baseline and 8-month follow-up. Study outcomes also incorporate common indicators for implementation science, including measures of project context, evaluation, and scaleup. Social network analysis will investigate diffusion of YRI components across peer networks. Linear growth modeling will examine mental health spillover effects among caregivers. Incremental health costs and benefits among YRI participants' caregivers and peers will be assessed through cost-effectiveness and return on investment analysis., Discussion: Assessing implementation research outcomes, including penetration of YRI effects across social networks and cost-effectiveness of the YRI as distinct outcomes, will provide key information about the success of YRI implementation. Lessons learned could inform decisions to increase scale up efforts in Sub-Saharan Africa and other low resource settings.

Marine alkaloid rigidins are cytotoxic compounds known to kill cancer cells at nanomolar concentrations by targeting the microtubule network. Here, a rigidin analogue containing a thioether group was "caged" by coordination of its thioether group to a photosensitive ruthenium complex. In the dark, the coordinated ruthenium fragment prevented the rigidin analogue from inhibiting tubulin polymerization and reduced its toxicity in 2D cancer cell line monolayers, 3D lung cancer tumor spheroids (A549), and a lung cancer tumor xenograft (A549) in nude mice. Photochemical activation of the prodrug upon green light irradiation led to the photosubstitution of the thioether ligand by water, thereby releasing the free rigidin analogue capable of inhibiting the polymerization of tubulin. In cancer cells, such photorelease was accompanied by a drastic reduction of cell growth, not only when the cells were grown in normoxia (21% O 2 ) but also remarkably in hypoxic conditions (1% O 2 ). In vivo , low toxicity was observed at a dose of 1 mg·kg -1 when the compound was injected intraperitoneally, and light activation of the compound in the tumor led to 30% tumor volume reduction, which represents the first demonstration of the safety and efficacy of ruthenium-based photoactivated chemotherapy compounds in a tumor xenograft.

Conducting polymers are of interest due to their unique behavior on exposure to electric fields, which has led to their use in flexible electronics, sensors, and biomaterials. The unique electroactive properties of conducting polymers allow them to be used to prepare biosensors that enable real time, point of care (POC) testing. Potential advantages of these devices include their low cost and low detection limit, ultimately resulting in increased access to treatment. This article presents a review of the characteristics of conducting polymer-based biosensors and the recent advances in their application in the recognition of disease biomarkers.

Self-regulation is developed early in life through family and parenting interactions. There has been considerable debate on how to best conceptualize and enhance self-regulation. Many consider self-regulation as the socio-emotional competencies required for healthy and productive living, including the flexibility to regulate emotions, control anger, maintain calm under pressure, and respond adaptively to a variety of situations. Its enhancement is the focus of many child and family interventions. An important limitation of the self-regulation field is that most empirical and conceptual research comes from high-income countries (HICs). Less is known about the manifestation, measurement and role of self-regulation in many collectivistic, rural, or less-developed contexts such as low- and middle-income countries (LMICs). This position paper aims to present an initial review of the existing literature on self-regulation in LMICs, with a focus on parenting, and to describe challenges in terms of measurement and implementation of self-regulation components into existing interventions for parents, children and adolescents in these settings. We conclude by establishing steps or recommendations for conducting basic research to understand how self-regulation expresses itself in vulnerable and low-resource settings and for incorporating components of self-regulation into services in LMICs.

Our laboratories have been investigating synthetic analogues of marine alkaloid rigidins that possess promising anticancer activities. These analogues, based on the 7-deazahypoxanthine skeleton, are available in one- or two-step synthetic sequences and exert cytotoxicity by disrupting microtubule dynamics in cancer cells. In the present work we extended the available structure-activity relationship (SAR) data to N3- and N9-substituted derivatives. Although N3 substitution results in loss of activity, the N9-substituted compounds retain nanomolar antiproliferative activities and the anti-tubulin mode of action of the original unsubstituted compounds. Furthermore, our results also demonstrate that multidrug-resistance (MDR) proteins do not confer resistance to both N9-unsubstituted and -substituted compounds. It was found that sublines overexpressing ABCG2, ABCC1, and ABCB1 proteins are as responsive to the rigidin analogues as their parental cell lines. Thus, the study reported herein provides further impetus to investigate the rigidin-inspired 7-deazahypoxanthines as promising anticancer agents., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

How rurality relates to women's abortion decision-making in the United States remains largely unexplored in existing literature. The present study relies on qualitative methods to analyze rural women's experiences related to pregnancy decision-making and pathways to abortion services in Central Appalachia. This analysis examines narratives from 31 participants who disclosed experiencing an unwanted pregnancy, including those who continued and terminated a pregnancy. Results suggest that women living in rural communities deal with unwanted pregnancy in three phases: (1) the simultaneous assessment of the acceptability of continuing the pregnancy and the acceptability of terminating the pregnancy, (2) deciding whether to seek services, and (3) navigating a pathway to service. Many participants who experience an unwanted pregnancy ultimately decide not to seek abortion services. When women living in rural communities assess their pregnancy as unacceptable but abortion services do not appear feasible to obtain, they adjust their emotional orientation towards continuing pregnancy, shifting the continuation of pregnancy to be an acceptable outcome. The framework developed via this analysis expands the binary constructs around abortion access - for example, decide to seek an abortion/decide not to seek an abortion, obtain abortion services/do not obtain abortion services - and critically captures the dynamic, often internal, calculations women make around unwanted pregnancy. It captures the experiences of rural women, a gap in the current literature.

Context: Studies of how women's individual characteristics and place of residence are related to variability in gestational age at the time of abortion have not examined county of residence and county-level characteristics. The county level is potentially meaningful, given that county is the smallest geographic unit with policy implications., Methods: Data on 38,611 abortions that took place in North Carolina, Virginia and West Virginia in 2012 were used to study the relationship between gestational age and county-level attributes (e.g., metropolitan status and poverty). Three-level hierarchical linear models captured individuals nested in county of residence, clustered by state of residence, and adjusted for individual characteristics and distance traveled to care., Results: Eight percent of the variation in gestational age at abortion was attributable to county-level characteristics. Residents of counties characterized by persistent poverty obtained abortions 2.3 days later in gestation than those from counties not characterized by that level of economic hardship. Women living in nonmetropolitan counties obtained abortions 1.7 days later than those living in metropolitan counties, even after distance traveled and county-level poverty were controlled for., Conclusion: County of residence is relevant to gestational age at the time of abortion for women in these three states. Evidence that county-level attributes are related to access adds insight to the consequences for women when the landscape of abortion service delivery shifts. Integrating county of residence into research on access to abortion services may be critical to capturing disparities in access., (Copyright © 2018 by the Guttmacher Institute.)

Advances in biosensors and drug delivery are dependent on hydrogels that respond to external stimuli. In this work, we describe the preparation and characterization of photoresponsive hydrogels prepared by cross-linking of di-NHS ester of azobenzoic acid and four-armed, amine-terminated poly(ethylene glycol). The porous structure and composition of the hydrogels were confirmed by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy. The reversible photoisomerization of the azobenzene-containing hydrogel cross-linkers in the gels was confirmed by absorption spectroscopy. Specifically, the photoisomerization of the cross-linkers between their trans and cis configurations was observed by monitoring the absorbance of the hydrogels at the two characteristic peaks of azobenzene (π-π* at 330 nm and n-π* at 435 nm). The effect of photoisomerization on the hydrogel structure was investigated by microscopy. Ultraviolet (UV) irradiation-induced reduction in hydrogel size was observed, which may be a result of the inherently smaller footprint of the cis azobenzene conformation, as well as dipole-dipole interactions between the polar cis azobenzene and the polymer network. The UV-triggered reduction in hydrogel size was accompanied by enhanced release of the near-infrared fluorescent dye Alexa Fluor 750 (AF 750 ). Enhanced release of AF 750 was observed in samples irradiated with UV versus dark control. Together, these data demonstrate the potential of these systems as reversible photoresponsive biomaterials.

Background: Results from studies evaluating the effectiveness of focused psychosocial support interventions in children exposed to traumatic events in humanitarian settings in low-income and middle-income countries have been inconsistent, showing varying results by setting and subgroup (eg, age or gender). We aimed to assess the effectiveness of these interventions, and to explore which children are likely to benefit most., Methods: We did a systematic review and meta-analysis of individual participant data (IPD) from 3143 children recruited to 11 randomised controlled trials of focused psychosocial support interventions versus waiting list. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, PsycArticles, Web of Science, and the main local low-income and middle-income countries (LMICs) databases according to the list of databases relevant to LMIC developed collaboratively by Cochrane and WHO Library, up to November, 2016. We included randomised controlled trials that assessed the effectiveness of focused psychosocial support interventions in children exposed to traumatic events in LMICs, compared with waiting lists (eg, inactive controls). We excluded quasi-randomised trials, studies that did not focus on psychosocial support interventions, and studies that compared two active interventions without control conditions. We requested anonymised data from each trial for each of the prespecified variables for each child who was randomly assigned. The main outcomes considered were continuous scores in post-traumatic stress disorder (PTSD) symptoms, depressive symptoms, and anxiety symptoms assessed with rating scales administered immediately (0-4 weeks) after the intervention. We harmonised all individual items from rating scales using item response theory methods. This study is registered with PROSPERO, number CRD42013006960., Findings: We identified a beneficial effect of focused psychosocial support interventions on PTSD symptoms (standardised mean difference [SMD] -0·33, 95% CI -0·52 to -0·14) that was maintained at follow-up (-0·21, -0·42 to -0·01). We also identified benefits at the endpoint for functional impairment (-0·29, -0·43 to -0·15) and for strengths: coping (-0·22, -0·43 to -0·02), hope (-0·29, -0·48 to -0·09), and social support (-0·27, -0·52 to -0·02). In IPD meta-analyses focused on age, gender, displacement status, region, and household size we found a stronger improvement in PTSD symptoms in children aged 15-18 years (-0·43, -0·63 to -0·23), in non-displaced children (-0·40, -0·52 to -0·27), and in children living in smaller households (<6 members; -0·27, -0·42 to -0·11)., Interpretation: Overall, focused psychosocial interventions are effective in reducing PTSD and functional impairment, and in increasing hope, coping, and social support. Future studies should focus on strengthening interventions for younger children, displaced children, and children living in larger households., Funding: European Commission FP7th Framework Programme for Research (Marie Curie International Outgoing Fellowship) and the National Institute on Aging., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Undergraduate research experiences (UREs) have been proposed as means to increase the retention and engagement of minority-and more specifically Hispanic-college students in science, technology, engineering, and mathematics (STEM) majors. This study explores the impact of student characteristics such as gender, classification, ethnicity, and first-generation status on UREs of STEM students through four specific constructs that current literature deem particularly important: (1) research experiences, (2) mentoring experiences, (3) awareness of research opportunities and activities, and (4) perceptions on research. These constructs are here forth referred to as Experiences, Mentoring, Awareness, and Perceptions. The study was conducted at a Hispanic-serving institution (HSI) in Texas, United States (U.S.), where the overall increase in enrollment has been driven by growth in Hispanic student numbers, reflecting the demographic shift of the state and the nation., Results: Participants were recruited to be part of a STEM open house. Thirty-five students participated in the Undergraduate Research Experiences: Mentoring, Awareness, and Perceptions Survey (URE MAPS). This exploratory case study sought to look at student characteristics such as gender, classification, ethnicity, and first-generation status as predictors of UREs. Results show that classification and ethnicity student characteristics are statistically significant predictors of UREs. Although gender and first-generation status regression analysis did not show statistically significant results, crosstabulations looking at correlation among variables yield interesting results. Seven percent of the female respondents responded that they "somewhat agree" with the statement that research is a lonely activity in comparison with 23% of males. The majority (60%) of all respondents who "strongly agreed" with the statement that "research is only for future scientists" were Hispanic, indicating a need to clarify such misconceptions to encourage Hispanic student participation. Most self-identified first-generation participants, of whom 80% were female, reported awareness of faculty research activities, again pointing out gender as an important factor among students' relationship with their professors. Although less than 23% of students noted current participation in mentorship, most of those did report positive impact of this relationship on their attitude and perspective toward their major., Conclusions: Despite the small sample size and inherent bias in the characteristics of the STEM open house participants, regression analysis informed by crosstabs analysis revealed some important findings. The research suggested higher-than-expected awareness of Latinos and first-generation students of institutional research activities; however, this awareness has not translated in engagement in research activities. The data also indicates the critical need for high-impact UREs and mentorship relationships, as well as for efforts to battle student preconceptions of who can benefit from such experiences. Although this case study focused on LatinX students (LatinX is a gender-neutral term for people of Latin American heritage used in the U.S.) in the U.S., retention of historically underrepresented students in STEM disciplines is a concern shared by many countries around the world. The successful recruitment, retention, and eventual success of students in STEM degrees depend greatly on the type of pathways and support that are offered. UREs might be one of those pathways., Competing Interests: This project 2017150 was approved by the Texas State University Institutional Review Board.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Child development in low and middle income countries (LMIC) is compromised by multiple risk factors. Reducing children's exposure to harmful events is essential for early childhood development (ECD). In particular, preventing violence against children - a highly prevalent risk factor that negatively affects optimal child development - should be an intervention priority. We used the Child Health and Nutrition Initiative (CHNRI) method for the setting of research priorities in integrated Early Childhood Development and violence prevention programs (ECD+). An expert group was identified and invited to systematically list and score research questions. A total of 186 stakeholders were asked to contribute five research questions each, and contributions were received from 81 respondents. These were subsequently evaluated using a set of five criteria: answerability; effectiveness; feasibility and/or affordability; applicability and impact; and equity. Of the 400 questions generated, a composite group of 50 were scored by 55 respondents. The highest scoring research questions related to the training of Community Health Workers (CHW's) to deliver ECD+ interventions effectively and whether ECD+ interventions could be integrated within existing delivery platforms such as HIV, nutrition or mental health platforms. The priority research questions can direct new research initiatives, mainly in focusing on the effectiveness of an ECD+ approach, as well as on service delivery questions. To the best of our knowledge, this is the first systematic exercise of its kind in the field of ECD+. The findings from this research priority setting exercise can help guide donors and other development actors towards funding priorities for important future research related to ECD and violence prevention., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Prior to the current public health emergency following the emergence of chikungunya and Zika Virus Disease in the Americas during 2014 and 2015, multi-country research investigated between 2011 and 2013 the efficacy of novel Aedes aegypti intervention packages through cluster randomised controlled trials in four Latin-American cities: Fortaleza (Brazil); Girardot (Colombia), Acapulco (Mexico) and Salto (Uruguay). Results from the trials led to a scaling up effort of the interventions at city levels. Scaling up refers to deliberate efforts to increase the impact of successfully tested health interventions to benefit more people and foster policy and program development in a sustainable way. The different scenarios represent examples for  a 'vertical approach' and a 'horizontal approach'. This paper presents the analysis of a preliminary process evaluation of the scaling up efforts in the mentioned cites, with a focus on challenges and enabling factors encountered by the research teams, analysing the main social, political, administrative, financial and acceptance factors.

A "risk of harm" protocol to identify youth in need of immediate emergency assistance in a study on mental health and HIV in Rwanda among 680 youth ages 10-17 is described. Cases are presented that describe the experience in using this protocol to ensure safety of participants, with ethical and logistical challenges considered. Among the population of the study, 3.2% were deemed "risk of harm." The most prevalent presenting problem was non-fatal suicidal behavior (91% of risk of harm cases), with 36% having a history of a reported previous attempt. Challenges included: acute food insecurity/significant poverty; lack of support/adequate supervision from family members; family violence; alcohol abuse; and HIV-related stigma. Development of a "risk of harm" protocol and collaboration between study staff, community leadership, health authorities, and health workers are critical to ensuring participants' safety in research among vulnerable populations.

Chlorine and fluorine substituted hydroxyapatites (HA-Cl-F) with different degrees of ion replacement were successfully prepared by the one step mechanochemical activation method. X-ray diffraction (XRD) and FT-IR spectra indicated that substitution of these anions in milled powders resulted in the formation of pure hydroxyapatite phase except for the small observed change in the lattice parameters and unit cell volumes of the resultant hydroxyapatite. Microscopic observations showed that the milled product had a cluster-like structure made up of polygonal and spherical particles with an average particle size of approximately ranged from 20±5 to 70±5nm. The zeta potential of milled samples was performed at three different pH (5, 7.4, and 9). The obtained zeta potential values were negative for all three pH values. Negative zeta potential was described to favor osseointegration, apatite nucleation, and bone regeneration. The bioactivity of samples was investigated on sintered pellets soaked in simulated body fluid (SBF) solution and apatite crystals formed on the surface of the pellets after being incubated for 14days. Zeta potential analysis and bioactivity experiment suggested that HA-Cl-F will lead to the formation of new apatite particles and therefore be a potential implant material., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Docking studies of tubulin-targeting C2-substituted 7-deazahypoxanthine analogues of marine alkaloid rigidins led to the design and synthesis of compounds containing linear C2-substituents. The C2-alkynyl analogue was found to have double- to single-digit nanomolar antiproliferative IC50 values and showed statistically significant tumor size reduction in a colon cancer mouse model at nontoxic concentrations. These results provide impetus and further guidance for the development of these rigidin analogues as anticancer agents.

A method for the synthesis of electroactive polymers is demonstrated, starting with the synthesis of extended conjugation monomers using a three-step process that finishes with Negishi coupling. Negishi coupling is a cross-coupling process in which a chemical precursor is first lithiated, followed by transmetallation with ZnCl2. The resultant organozinc compound can be coupled to a dibrominated aromatic precursor to give the conjugated monomer. Polymer films can be prepared via electropolymerization of the monomer and characterized using cyclic voltammetry and ultraviolet-visible-near infrared (UV-Vis-NIR) spectroscopy. Nanoparticles (NPs) are prepared via emulsion polymerization of the monomer using a two-surfactant system to yield an aqueous dispersion of the polymer NPs. The NPs are characterized using dynamic light scattering, electron microscopy, and UV-Vis-NIR-spectroscopy. Cytocompatibility of NPs is investigated using the cell viability assay. Finally, the NP suspensions are irradiated with a NIR laser to determine their effectiveness as potential materials for photothermal therapy (PTT).

Significant research has focused on investigating the potential of hydrogels in various applications and, in particular, in medicine. Specifically, hydrogels that are biodegradable lend promise to many therapeutic and biosensing applications. Endonucleases are critical for mechanisms of DNA repair. However, they are also known to be overexpressed in cancer and to be present in wounds with bacterial contamination. In this work, we set out to demonstrate the preparation of DNA-enabled hydrogels that could be degraded by nucleases. Specifically, hydrogels were prepared through the reaction of dibenzocyclooctyne-functionalized multi-arm poly(ethylene glycol) with azide-functionalized single-stranded DNA in aqueous solutions via copper-free click chemistry. Through the use of this method, biodegradable hydrogels were formed at room temperature in buffered saline solutions that mimic physiological conditions, avoiding possible harmful effects associated with other polymerization techniques that can be detrimental to cells or other bioactive molecules. The degradation of these DNA-cross-linked hydrogels upon exposure to the model endonucleases Benzonase(®) and DNase I was studied. In addition, the ability of the hydrogels to act as depots for encapsulation and nuclease-controlled release of a model protein was demonstrated. This model has the potential to be tailored and expanded upon for use in a variety of applications where mild hydrogel preparation techniques and controlled material degradation are necessary including in drug delivery and wound healing systems.

Men who have sex with men (MSM) in India are a hidden and largely understudied population, and have an HIV prevalence 17 times higher than that of the general Indian population. Experiences of social marginalization and negative psychosocial conditions occur concurrent to HIV risk among Indian MSM. To better understand the contextual variables driving HIV risk and inform intervention development, five focus groups (n = 46) and nine key informant interviews were conducted with 55 MSM in Chennai in 2010. NVivo software was used to code the transcripts, and data were analyzed using qualitative descriptive analysis methodology. Participants described sources of psychological distress and low self-worth related to gender non-conformity and sexual minority status. These included stigma from society, pressure to marry, lack of familial acceptance, childhood sexual abuse, and the imperative to keep sexual minority status a secret. Participants' personal evaluations revealed that self-acceptance may be an important resilience factor that can shield these psychosocial and HIV risk factors. In promoting health-seeking behavioral changes for Indian MSM at an individual level, our findings point to the potential strength of strategies that focus on self-acceptance of one's sexual minority identity to foster better psychosocial and overall health.

Background and Objective: Nanotechnology offers the possibility of creating multi-functional structures that can provide solutions for biomedical problems. The nanoprobes herein described are an example of such structures, where nano-scaled particles have been designed to provide high specificity and contrast potential for optical detection of cancer. Specifically, enzymatically activated fluorescent nanoprobes (EANPs) were synthesized as cancer-specific contrast agents for optical imaging., Study Design/materials and Methods: EANPs were prepared by nanoprecipitation of blends of poly(lactic acid)-b-poly(ethylene glycol) and poly(lactic-co-glycolic acid)-b-poly(l-lysine). The lysine moieties were then covalently decorated with the near infrared (NIR) fluorescent molecule AlexaFluor-750 (AF750). Close proximity of the fluorescent molecules to each other resulted in fluorescence quenching, which was reversed by enzymatically mediated cleavage of poly(l-lysine) chains. EANPs were characterized by dynamic light scattering and electron microscopy. Enzymatic development of fluorescence was studied in vitro by fluorescence spectroscopy. Biocompatibility and contrast potential of EANPs were studied in cancerous and noncancerous cells. The potential of the nanoprobes as contrast agents for NIR fluorescence imaging was studied in tissue phantoms., Results: Spherical EANPs of ∼100 nm were synthesized via nanoprecipitation of polymer blends. Fluorescence activation of EANPs by treatment with a model protease was demonstrated with up to 15-fold optical signal enhancement within 120 minutes. Studies with MDA-MB-231 breast cancer cells demonstrated the cytocompatibility of EANPs, as well as enhanced fluorescence associated with enzymatic activation. Imaging studies in tissue phantoms confirmed the ability of a simple imaging system based on a laser source and CCD camera to image dilute suspensions of the nanoprobe at depths of up to 4 mm, as well as up to a 13-fold signal-to-background ratio for enzymatically activated EANPs compared to un-activated EANPs at the same concentration., Conclusion: Nanoprecipitation of copolymer blends containing poly(l-lysine) was utilized as a method for preparation of highly functional nanoprobes with high potential as contrast agents for fluorescence based imaging of cancer. Lasers Surg. Med. 47:579-594, 2015. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Introduction: The main preventive measure against dengue virus transmission is often based on actions to control Ae. Aegypti reproduction by targeting water containers of clean and stagnant water. Household water storage has received special attention in prevention strategies but the evidence about the rationale of this human practice is limited. The objective was to identify and describe water storage practices among residents of an urban area in Colombia (Girardot) and its association with reported perceptions, rationales and socio-demographic characteristics with a mixed methods approach., Methods: Knowledge, attitudes and practices and entomological surveys from 1,721 households and 26 semi-structured interviews were conducted among residents of Girardot and technicians of the local vector borne disease program. A multivariate analysis was performed to identify associations between a water storage practice and socio-demographic characteristics, and knowledge, attitudes and practices about dengue and immature forms of the vector, which were then triangulated with qualitative information., Results: Water storage is a cultural practice in Girardot. There are two main reasons for storage: The scarcity concern based on a long history of shortages of water in the region and the perception of high prices in water rates, contrary to what was reported by the local water company. The practice of water storage was associated with being a housewife (Inverse OR: 2.6, 95% CI 1.5 -4.3). The use of stored water depends on the type of container used, while water stored in alberca (Intra household cement basins) is mainly used for domestic cleaning chores, water in plastic containers is used for cooking., Conclusions: It is essential to understand social practices that can increase or reduce the number of breeding sites of Ae. Aegypti. Identification of individuals who store water and the rationale of such storage allow a better understanding of the social dynamics that lead to water accumulation.

Introduction: Dengue is a growing public health problem in urban areas, given that its transmission is associated with the environment, as well as with the behaviour of individuals and communities. The model proposed by Ecohealth to study this problem includes the operation of government policies., Objective: To describe the operation of policies to prevent and control dengue in two Colombian cities., Materials and Methods: A qualitative study was conducted. Data was collected through interviews with officials who worked in the health and education sectors. The contents were processed with the Ethnograph software, using the proposals of the bottom-up model of implementation as analytical categories., Results: A lack of coordination was identified between department and municipal offices, with few developments of the protocol for dengue and severe dengue in terms of community participation, communication strategies and studies of inhabitants´ knowledge, attitudes and practices. The integrated management strategy was limited by the instability of human resources, limited intra-institutional and cross-sectorial coordination and little emphasis on promotion interventions, both at the individual and population levels., Conclusions: Coordination between the departament and the municipality needs to be strengthened in the city of Arauca. Both here and in Armenia administration of human resources and interinstitutional coordination should be improved. Promotion of preventative measures should be strengthened to impact on the determinants of dengue.

A territorial analysis of Aedes aegypti density was conducted in two Colombian cities using an ecosystem and chorematic approach. Entomological and behavioral data (by cluster) and information on the urban context were used to analyze the relationship between territorial structures and dynamics and vector density. The results were represented in graphic (chorematic) models. Arauca showed higher vector density than Armenia. Higher density was related to unplanned urbanization, flood-prone areas, low socioeconomic strata, household water tanks, higher temperature, and recall of control measures for adult mosquitos. Zones with low density indices coincided with diverse socioeconomic, ecological, and behavioral conditions. The study found a relationship between territorial structures and dynamics and vector density in both Arauca and Armenia, where the interaction between ecological and social systems shape areas with high and low A. aegypti density.

The present study aims to: (1) estimate the levels of internalizing symptoms and externalizing behaviors among youth affected by HIV in central Haiti; and (2) examine the risk and protective factors associated with these outcomes to identify potential areas of intervention for HIV-affected youth. Baseline data for 492 youth affected by HIV (ages 10-17) and their 330 caregivers were collected for a pilot study of a psychosocial support intervention. Participants were recruited from a list of HIV-positive patients receiving care at Partners In Health/Zanmi Lasante clinic sites. Internalizing and externalizing behaviors were assessed using the Strengths and Difficulties Questionnaire. Demographic, economic, and social indicators were collected using a structured questionnaire administered by trained social workers. Youth affected by HIV in central Haiti displayed high levels of internalizing and, to a lesser degree, externalizing symptoms. Multivariate regression analysis demonstrated risk factors most strongly associated with internalizing symptoms (socioeconomic status, parental depressive symptoms) and externalizing behaviors (household living arrangements, such as living with a stepparent). Social support had a protective effect on externalizing behaviors for both caregiver (β=-0.03, p=0.01) and self-report (β=-0.05, p<0.0001). High levels of psychological distress were observed in this population, especially with respect to internalizing outcomes. Interventions should address the economic security, mental health, and access to antiretroviral therapy for families affected by HIV, as well as emphasize the importance of building supportive caregiver-child relationships to decrease the psychological symptoms and impact of other life stressors experienced by youth affected by HIV in Haiti and similar resource-limited settings.

Background: The global HIV/AIDS response has advanced in addressing the health and well-being of HIV-positive children. Although attention has been paid to children orphaned by parental AIDS, children who live with HIV-positive caregivers have received less attention. This study compares mental health problems and risk and protective factors in HIV-positive, HIV-affected (due to caregiver HIV), and HIV-unaffected children in Rwanda., Methods: A case-control design assessed mental health, risk, and protective factors among 683 children aged 10 to 17 years at different levels of HIV exposure. A stratified random sampling strategy based on electronic medical records identified all known HIV-positive children in this age range in 2 districts in Rwanda. Lists of all same-age children in villages with an HIV-positive child were then collected and split by HIV status (HIV-positive, HIV-affected, and HIV-unaffected). One child was randomly sampled from the latter 2 groups to compare with each HIV-positive child per village., Results: HIV-affected and HIV-positive children demonstrated higher levels of depression, anxiety, conduct problems, and functional impairment compared with HIV-unaffected children. HIV-affected children had significantly higher odds of depression (1.68: 95% confidence interval [CI] 1.15-2.44), anxiety (1.77: 95% CI 1.14-2.75), and conduct problems (1.59: 95% CI 1.04-2.45) compared with HIV-unaffected children, and rates of these mental health conditions were similar to HIV-positive children. These results remained significant after controlling for contextual variables, there were no significant differences on mental health outcomes groups, reflecting a potential explanatory role of factors such as daily hardships, caregiver depression, and HIV-related stigma [corrected]., Conclusions: The mental health of HIV-affected children requires policy and programmatic responses comparable to HIV-positive children., (Copyright © 2014 by the American Academy of Pediatrics.)

We developed synthetic chemistry to access the marine alkaloid rigidins and over 40 synthetic analogues based on the 7-deazaxanthine, 7-deazaadenine, 7-deazapurine, and 7-deazahypoxanthine skeletons. Analogues based on the 7-deazahypoxanthine skeleton exhibited nanomolar potencies against cell lines representing cancers with dismal prognoses, tumor metastases, and multidrug resistant cells. Studies aimed at elucidating the mode(s) of action of the 7-deazahypoxanthines in cancer cells revealed that they inhibited in vitro tubulin polymerization and disorganized microtubules in live HeLa cells. Experiments evaluating the effects of the 7-deazahypoxanthines on the binding of [(3)H]colchicine to tubulin identified the colchicine site on tubulin as the most likely target for these compounds in cancer cells. Because many microtubule-targeting compounds are successfully used to fight cancer in the clinic, we believe the new chemical class of antitubulin agents represented by the 7-deazahypoxanthine rigidin analogues have significant potential as new anticancer agents.

Overview: The World Health Organization Disability Assessment Schedule for children (WHODAS-Child) is a disability assessment instrument based on the WHO's International Classification of Functioning, Disability and Health for children and youth. It is modified from the original adult version specifically for use with children. The aim of this study was to assess the WHODAS-Child structure and metric properties in a community sample of children with and without reported psychosocial problems in rural Rwanda., Methods: The WHODAS-Child was first translated into Kinyarwanda through a detailed committee translation process and back-translation. Cognitive interviewing was used to assess the comprehension of the translated items. Test-retest reliability was assessed in a group of 64 children. The translated WHODAS-Child was then administered to a final sample of 367 children in southern Kayonza district in rural southeastern Rwanda within a larger psychosocial assessment battery. The latent structure was assessed through confirmatory factor analysis. Reliability was evaluated in terms of internal consistency (Cronbach's alpha) and test-retest reliability (Pearson's correlation coefficient). Construct validity was explored by examining convergence between WHODAS-Child scores and mental disorder status, and divergence of WHODAS-Child scores with protective factors and prosocial behaviors. Concordance between parent and child scores was also assessed., Results: The six-factor structure of the WHODAS-Child was confirmed in a population sample of Rwandan children. Test-retest and inter-rater reliability were high (r = .83 and ICC = .88). WHODAS-Child scores were moderately positively correlated with presence of depression (r = .42, p<.001) and post-traumatic stress disorder (r = .31, p<.001) and moderately negatively correlated with prosocial behaviors (r = .47, p<.001). The Kinyarwanda version of the WHODAS-Child was found to be a reliable and acceptable self-report tool for assessment of functional impairment among children largely referred for psychosocial problems in the study district in rural Rwanda. Further research in low-resource settings and with more general populations is recommended.

Objective: We assessed the validity of the Center for Epidemiological Studies Depression Scale for Children (CES-DC) as a screen for depression in Rwandan children and adolescents. Although the CES-DC is widely used for depression screening in high-income countries, its validity in low-income and culturally diverse settings, including sub-Saharan Africa, is unknown., Method: The CES-DC was selected based on alignment with local expressions of depression-like problems in Rwandan children and adolescents. To examine criterion validity, we compared CES-DC scores to depression diagnoses on a structured diagnostic interview, the Mini International Neuropsychiatric Interview for Children (MINI KID), in a sample of 367 Rwandan children and adolescents aged 10 through 17 years. Caregiver and child or adolescent self-reports endorsing the presence of local depression-like problems agahinda kenshi (persistent sorrow) and kwiheba (severe hopelessness) were also examined for agreement with MINI KID diagnosis., Results: The CES-DC exhibited good internal reliability (α = .86) and test-retest reliability (r = .85). The area under the receiver operating characteristic curve for the CES-DC was 0.825 when compared to MINI KID diagnoses, indicating a strong ability to distinguish between depressed and nondepressed children and adolescents in Rwanda. A cut point of≥30 corresponded with a sensitivity of 81.9% and a specificity of 71.9% in this referred sample. MINI KID diagnosis was well aligned with local expressions of depression-like problems., Conclusion: The CES-DC demonstrates good psychometric properties for clinical screening and evaluation in Rwanda, and should be considered for use in this and other low-resource settings. Population samples are needed to determine a generalizable cut point in nonreferred samples., (Copyright © 2012 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Men who have sex with men (MSM) in India have an HIV seroprevalence 22 times greater than the country's general population and face unique challenges that may hinder the effectiveness of current HIV prevention efforts. To obtain an understanding of the logistical and sociocultural barriers MSM experience while accessing HIV prevention services, focus groups and key informant interviews were conducted with 55 MSM in Chennai, India. Qualitative data were analyzed using descriptive qualitative content analysis. Sixty-five percent of participants identified as kothi (receptive partners), 9% as panthi (insertive partners), 22% as double decker (receptive and insertive), and 4% did not disclose. Themes included: (a) fatigue with current HIV risk reduction messages; (b) increased need for non-judgmental and confidential services; and (c) inclusion of content that acknowledges individual and structural-level determinants of risk such as low self-esteem, depression, and social discrimination. MSM interventions may benefit from approaches that address multilevel psychosocial factors, including skills building and strategies to foster self-acceptance and increased social support.

This paper draws attention to the obligation and opportunity to respond to the mental health impacts of collective sexual violence (CSV) among genocide-rape survivors in post-genocide Rwanda. Qualitative data gathered from CSV survivors who were members of Rwandan women's genocide survivor associations are presented to illustrate how they strive to overcome adversity while seeking access to quality mental health care and using informal community mental health services. The results reveal that a system of high quality, holistic health and mental health care is yet needed to meet Rwandan CSV survivors' complex and serious health and mental health needs. Given that a rural health system, modelled on community-based, comprehensive HIV/AIDS care and treatment, is currently being implemented in Rwanda, we recommend enhancements to this model that would contribute to meeting the mental health care needs of CSV survivors while benefiting the health and mental health system as a whole within Rwanda.

Effective oral delivery of proteins is impeded by steep pH gradients and proteolytic enzymes in the gastrointestinal tract, as well as low absorption of the proteins into the bloodstream because of their size, charge, or solubility. In this work, pH-responsive complexation hydrogels of poly(itaconic acid) (PIA) with poly(ethylene glycol) (PEG) grafts were synthesized for applications in oral drug delivery. These hydrogels were expected to be in collapsed configuration at low pH because of hydrogen bonding between PIA carboxyl groups and PEG, and to swell with increasing pH because of charge repulsion between deprotonated carboxylic acid groups. Hydrogels were prepared by UV-initiated free radical polymerization using tetraethylene glycol as the crosslinking agent and Irgacure 2959 as the initiator. The effect of monomer ratios, crosslinking ratio, and solvent amount on the properties of the hydrogels were investigated. The composition of the hydrogels was confirmed by Fourier transform infrared spectroscopy. Equilibrium swelling studies in the pH range of 1.2-7 revealed that the extent of swelling increased with increasing pH up to a pH of about 6, when no further carboxylic acid deprotonation occurred. Studies in Caco-2 colorectal carcinoma cells confirmed the cytocompatibility of these materials at concentrations of up to 5 mg/mL.

This work evaluates various techniques for the incorporation of poly(ethylene glycol) (PEG) onto biodegradable nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA) or poly(lactic acid) (PLA) with the purpose of providing a functional site for surface conjugation of targeting agents and for improving surface properties. The techniques compared were based on NP preparation with blends of PLGA and poloxamer or with block copolymers of PLGA/PLA with PEG. Blending of PLGA with poloxamer 407 resulted in the incorporation of the latter to up to a 43 wt % content. Direct conjugation of heterofunctional NH2-PEG-COOH to the surface of premade NPs was not highly effective. Preparation of copolymers of PLGA with PEG was determined to be more effective and versatile by polymerization of lactide and glycolide dimers onto the hydroxyl group of heterofunctional OH-PEG-COOH than by conjugation of the premade polymers with carbodiimide chemistry. NPs prepared with these copolymers confirmed the surface localization of PEG and proved to be useful for conjugation of mouse immumoglobulin as a model targeting agent.

Nanoparticle-based drug delivery systems are considered promising for the delivery of imaging agents and drugs for the detection and treatment of illnesses, including cancer. Investigation of nanoparticle interactions with the diseased cells can lead to better designs. In this work, poly(lactic-co-glycolic acid) nanoparticles loaded with rhodamine 6G were prepared by nanoprecipitation with high encapsulation efficiency. In vitro release studies demonstrated that rhodamine escaped from the nanoparticles at a very slow rate at physiological pH, thus making it ideal for imaging studies. At acidic pH this agent was released quickly, suggesting charge interactions between the polymer and rhodamine. Microscopy and flow cytometry studies show higher uptake in MDA-MB-231 breast cancer cells when exposed to rhodamine-loaded nanoparticles than to rhodamine in solution.

The objective of this review is to outline current major cancer targets for nanoparticle systems and give insight into the direction of the field. The major targeting strategies that have been used for the delivery of therapeutic or imaging agents to cancer have been broken into three sections. These sections are angiogenesis-associated targeting, targeting to uncontrolled cell proliferation markers, and tumor cell targeting. The targeting schemes explored for many of the reported nanoparticle systems suggest the great potential of targeted delivery to revolutionize cancer treatment.

Aims: The lack of specificity of chemotherapeutic agents to cancer tissue commonly leads to dose-limiting side effects and poor therapeutic results. Drug delivery systems promise to improve the deficiencies of chemotherapeutic treatment by modifying the biodistribution and pharmacokinetics of the drug in vivo. Here, we report the preparation, characterization and in vitro evaluation of a carrier for the chemotherapeutic drug doxorubicin based on acid-capped poly(lactic-co-glycolic acid) nanoparticles., Methods: Doxorubicin-loaded nanoparticles were prepared by nanoprecipitation with bovine serum albumin as the stabilizer. Nanoparticles were characterized and their interaction with MDA-MB-231 breast cancer cells was examined with confocal microscopy and a toxicological assay., Results: Spherical particles with an average diameter of 230 nm, a zeta-potential of -45 mV and a maximum drug loading of 5 wt% were prepared. Doxorubicin was found to be quickly released at endolysosomal pH of 4.0 but was released at a slower rate at pH 7.4. Nanoparticles were found to deliver the drug into cells quickly and in higher quantity than when presented in solution and were found to result in a therapeutic efficacy comparable to the free drug., Discussion: Nanoprecipitation was found to be a promising method for the preparation of nanoparticles with relatively high doxorubicin loading. The pH-dependent release behavior is discussed to possibly be a result of accelerated degradation of the polymer and decreasing ionic interaction between the drug and the polymer at acidic pH. Additional studies are needed to determine why increased nuclear localization of the drug when delivered in the form of nanoparticles did not result in increased therapeutic efficacy in vitro., Conclusion: Nanoparticles formulated by nanoprecipitation of acid-ended poly(lactic-co-glycolic acid) were found to be able to control the release of doxorubicin in a pH-dependent manner and to effectively deliver high payloads of the drug in an active form to MDA-MB-231 breast cancer cells.

Micro- and nanofabrication techniques have revolutionized the pharmaceutical and medical fields as they offer the possibility for highly reproducible mass-fabrication of systems with complex geometries and functionalities, including novel drug delivery systems and bionsensors. The principal micro- and nanofabrication techniques are described, including photolithography, soft lithography, film deposition, etching, bonding, molecular self assembly, electrically induced nanopatterning, rapid prototyping, and electron, X-ray, colloidal monolayer, and focused ion beam lithography. Application of these techniques for the fabrication of drug delivery and biosensing systems including injectable, implantable, transdermal, and mucoadhesive devices is described.