Microglial cells have been implicated in neuroinflammation-mediated injury in the brain, including neurodevelopmental disorders such as cerebral palsy (CP) and autism. Pro-inflammatory activation of microglial cells results in the impairment of their neuroprotective functions, leading to an exaggerated, ongoing immune dysregulation that can persist long after the initial insult. We have previously shown that dendrimer-mediated delivery of an anti-inflammatory agent can attenuate inflammation in a rabbit model of maternal inflammation-induced CP and significantly improve the motor phenotype, due to the ability of the dendrimer to selectively localize in activated microglia. To elucidate the interactions between dendrimers and microglia, we created an organotypic whole-hemisphere brain slice culture model from newborn rabbits with and without exposure to inflammation in utero. We then used this model to analyze the dynamics of microglial migration and their interactions with dendrimers in the presence of neuroinflammation. Microglial cells in animals with CP had an amoeboid morphology and impaired cell migration, demonstrated by decreased migration distance and velocity when compared to cells in healthy, age-matched controls. However, this decreased migration was associated with a greater, more rapid dendrimer uptake compared to microglial cells from healthy controls. This study demonstrates that maternal intrauterine inflammation is associated with impaired microglial function and movement in the newborn brain. This microglial impairment may play a role in the development of ongoing brain injury and CP in the offspring. Increased uptake of dendrimers by the “impaired” microglia can be exploited to deliver drugs specifically to these cells and modulate their functions. Host tissue and target cell characteristics are important aspects to be considered in the design and evaluation of targeted dendrimer-based nanotherapeutics for improved and sustained efficacy. This ex vivo model also provides a rapid screening tool for evaluation of the effects of various therapies on microglial function.
Exclusive breastfeeding has been endorsed as the healthiest feeding choice for newborns. This study aims to assess impact of expecting mothers' knowledge and attitude toward intention to breastfeed exclusively. Utilizing mobile health (mHealth) as educational tool can offer a widely distributed and affordable platform to promote exclusive breastfeeding. This study aims to assess impact of expecting mothers' knowledge, attitude and beliefs on decision to breastfeed exclusively. Furthermore, it purposes mobile health (mHealth) as educational tool offering a widely distributed, affordable and accessible platform to promote exclusive breastfeeding. The study was conducted in prenatal clinics' waiting areas to interview expecting mothers utilizing a translated version of Infant Feeding Practices Survey II (IFPS II, CDC). After completing the survey, an educational video was shown utilizing a tablet and the question was re-asked about intention toward breastfeeding exclusively. Most expecting mothers indicated having some awareness about breastfeeding (67%) but only 46.1% intended to initiate exclusive breastfeeding early in life prior to the intervention. Moreover, only 53.7% believed breastfeeding is the best nutritional choice. Actually, 39.5% of participants considered breastfeeding equal to formula. Most working mothers complained of lack of workplace support to breastfeed. Also, they were not comfortable breastfeeding in front of others except spouse. Additionally, most participants found nurses and media as poor information resources. Resources utilizing social media and Internet were found useful. After watching the educational video, the majority expressed positive intention to breastfeed exclusively (80.8%). Positive intentions were associated with advance maternal age, prior breastfeeding knowledge and willingness to hear experts' opinions. Saudi women have limited knowledge about exclusive breastfeeding and early initiation. They feel unprepared, unsupported, lack resources and socially challenged. An educational material utilizing mHealth can alter intentions to breastfeed exclusively.
Polyamidoamine (PAMAM) dendrimers are multifunctional nanoparticles with tunable physicochemical features, making them promising candidates for targeted drug delivery in the central nervous system (CNS). Systemically administered dendrimers have been shown to localize in activated glial cells, which mediate neuroinflammation in the CNS. These dendrimers delivered drugs specifically to activated microglia, producing significant neurological improvements in multiple brain injury models, including in a neonatal rabbit model of cerebral palsy. To gain further insight into the mechanism of dendrimer cell uptake, we utilized an in vitro model of primary glial cells isolated from newborn rabbits to assess the differences in hydroxyl-terminated generation 4 PAMAM dendrimer (D4-OH) uptake by activated and non-activated glial cells. We used fluorescently-labelled D4-OH (D-Cy5) as a tool for investigating the mechanism of dendrimer uptake. D4-OH PAMAM dendrimer uptake was determined by fluorescence quantification using confocal microscopy and flow cytometry. Our results indicate that although microglial cells in the mixed cell population demonstrate early uptake of dendrimers in this in vitro system, activated microglia take up more dendrimer compared to resting microglia. Astrocytes showed delayed and limited uptake. We also illustrated the differences in mechanism of uptake between resting and activated microglia using different pathway inhibitors. Both resting and activated microglia primarily employed endocytotic pathways, which are enhanced in activated microglial cells. Additionally, we demonstrated that hydroxyl terminated dendrimers are taken up by primary microglia using other mechanisms including pinocytosis, caveolae, and aquaporin channels for dendrimer uptake.
13 March 2024 in Journal of Epidemiology and Global Health
Objectives: Caring for children in low- and middle-income countries (LMIC) can be challenging. This review article aims to explore role of telemedicine in supporting pediatric care in LMIC. Methodology: A narrative review of existing English and Spanish literature was conducted to assess role of telemedicine to support pediatric care in LMIC. Results: Beside medical education and direct pediatric care, telemedicine can provide sub-specialties consultations without extra burden on families. Additionally, telemedicine can help in lowering under-5 mortality by supporting neonatal care, infectious illnesses, and non-communicable diseases (NCDs). Telemedicine can be a gate for universal coverage for all children at a lower cost. For over a decade, it has been implemented successfully and sustained in a few LMIC. However, challenges in implementing telemedicine are enormous. Still, opportunities arise by using simpler technology, low-width band internet, smartphones, instant messaging applications and solar energy. COVID-19 pandemic facilitated acceptance and applicability of telemedicine worldwide including LMIC. Nevertheless, governments must regulate telemedicine by issuing policies and ensuring employment of local experts when possible to meet local resources and cultural competency. Conclusion: Telemedicine has proven successful in improving pediatrics care. Many LMIC should take advantage of this innovation to promote equity and access to high quality pediatric care.
Child maltreatment is not included in Saudi medical schools and pediatric residency curriculums, which might limit knowledge and spread misconceptions. Additionally, physicians might have different attitudes regarding reporting child abuse and neglect. In this study, we hypothesize that medical students and pediatric trainees have limited knowledge, oblivious attitude and misbeliefs regarding child maltreatment in comparison to experienced pediatricians. But, medical students and trainees might hold higher motives and willingness to learn about child maltreatment and their consequences. A self reported questionnaire was distributed after a pilot study to include pediatricians, pediatrics trainees and medical students in all main areas of pediatrics services: pediatrics wards, pediatrics outpatient clinics, critical care and pediatrics emergency. In disregard to their level of training, medical students and physicians believed that child maltreatment happens within the kingdom and is common. They were familiar with the child maltreatment definition, although only one third thought it is subject to culture sensitivity. However, experienced physicians were more knowledgeable especially about neglect. Moreover, female participants were more likely to report despite being more skeptical of readiness of Saudi law system to deal with cases of maltreatment. In general, knowledge about reporting was clearly deficit at all levels. Fortunately, all participants requested and were enthusiastic to receive further training. Saudi medical students, pediatrics trainees and pediatricians have good basic knowledge, positive attitude and willingness to learn more to provide a safe environment for children in Saudi Arabia. However, knowledge in regards to reporting child maltreatment is a major observed defect. Still, further education and training are needed to combat CAN in Saudi Arabia.
5 October 2016 in PLOS Neglected Tropical Diseases
Plasmodium vivax is the most prevalent cause of human malaria in the world and can lead to severe disease with high potential for relapse. Its genetic and geographic diversities make it challenging to control. P. vivax is understudied and to achieve control of malaria in endemic areas, a rapid, accurate, and simple diagnostic tool is necessary. In this pilot study, we found that a colorimetric system using AuNPs and MSP10 DNA detection in urine can provide fast, easy, and inexpensive identification of P. vivax. The test exhibited promising sensitivity (84%), high specificity (97%), and only mild cross-reactivity with P. falciparum (21%). It is simple to use, with a visible color change that negates the need for a spectrometer, making it suitable for use in austere conditions. Using urine eliminates the need for finger-prick, increasing both the safety profile and patient acceptance of this model. To control malaria, there is an urgent need for applying innovative diagnostics and new technologies. Nanoparticles can augment detection of malaria at lower parasite levels while providing fast and simple methodology. Novel use of MSP10 and gold nanoparticles to identify Plasmodium vivax’s DNA in urine can be utilized as screening tool with global application potentials. The proposed test could impact the control of the most common species of malaria in low resource settings as it could present a simple, fast, cheap and easy to interpret test. Furthermore, utilizing urine instead of blood eliminates the need for finger-prick which would increase safety profile and likely increase participation rate in mass screening programs.