Nanotechnology-based techniques for hair follicle regeneration.

The hair follicle (HF) is a multicellular complex structure of the skin that contains a reservoir of multipotent stem cells. Traditional hair repair methods such as drug therapies, hair transplantation, and stem cell therapy have limitations. Advances in nanotechnology offer new approaches for HF regeneration, including controlled drug release and HF-specific targeting. Until recently, embryogenesis was thought to be the only mechanism for forming hair follicles. However, in recent years, the phenomenon of wound-induced hair neogenesis (WIHN) or de novo HF regeneration has gained attention as it can occur under certain conditions in wound beds. This review covers HF-specific targeting strategies, with particular emphasis on currently used nanotechnology-based strategies for both hair loss-related diseases and HF regeneration. HF regeneration is discussed in several modalities: modulation of the hair cycle, stimulation of progenitor cells and signaling pathways, tissue engineering, WIHN, and gene therapy. The HF has been identified as an ideal target for nanotechnology-based strategies for hair regeneration. However, some regulatory challenges may delay the development of HF regeneration nanotechnology based-strategies, which will be lastly discussed.

Association between Migraine and Cryptogenic Ischemic Stroke in Young Adults.

OBJECTIVE: To assess the association between migraine and cryptogenic ischemic stroke (CIS) in young adults, with subgroup analyses stratified by sex and presence of patent foramen ovale (PFO). METHODS: We prospectively enrolled 347 consecutive patients aged 18 to 49 years with a recent CIS and 347 age- and sex-matched (±5 years) stroke-free controls. Any migraine and migraine with (MA) and migraine without aura (MO) were identified by a screener, which we validated against a headache neurologist. We used conditional logistic regression adjusting for age, education, hypertension, diabetes, waist-to-hip ratio, physical inactivity, current smoking, heavy drinking, and oral estrogen use to assess independent association between migraine and CIS. The effect of PFO on the association between migraine and CIS was analyzed with logistic regression in a subgroup investigated with transcranial Doppler bubble screen. RESULTS: The screener performance was excellent (Cohen kappa > 0.75) in patients and controls. Compared with nonmigraineurs, any migraine (odds ratio [OR] = 2.48, 95% confidence interval [CI] = 1.63-3.76) and MA (OR = 3.50, 95% CI = 2.19-5.61) were associated with CIS, whereas MO was not. The association emerged in both women (OR = 2.97 for any migraine, 95% CI = 1.61-5.47; OR = 4.32 for MA, 95% CI = 2.16-8.65) and men (OR = 2.47 for any migraine, 95% CI = 1.32-4.61; OR = 3.61 for MA, 95% CI = 1.75-7.45). Specifically for MA, the association with CIS remained significant irrespective of PFO. MA prevalence increased with increasing magnitude of the right-to-left shunt in patients with PFO. INTERPRETATION: MA has a strong association with CIS in young patients, independent of vascular risk factors and presence of PFO. ANN NEUROL 2021;89:242-253.

Development of red-light cleavable PEG-PLA nanoparticles as delivery systems for cancer therapy.

The development of targeted delivery systems can improve the selectivity of cancer drugs. Additionally, a system that promotes the controlled delivery of the drug triggered by an external stimulus in the exact target tissue is highly desirable. Regarding the light stimulus, the NIR window (650-950 nm) is the most suitable due to its higher capacity of penetration in human tissues and less harmful effects on normal cells. In this work, new red-light-responsive nanoparticles for doxorubicin delivery were developed. The nanoparticles were based on cleavable di-block copolymers of poly(ethylene glycol) (PEG) and poly(lactic acid) (PLA) linked by a red-light sensitive segment (1,2-bis(2-hydroxyethylthio)ethylene, BHETE). The PEG-BHETE-PLA copolymers were synthesized under mild conditions and exhibited a narrow polydispersity. The nanoparticles presented a size between 53 and 133 nm, with a doxorubicin loading capacity between 1.2 and 4.4 wt%. Release study of the encapsulated doxorubicin confirms the light-triggered nanoparticle disassembly process. In vitro cytotoxicity tests in MCF7 cell line, for the light-triggered nanoparticles, showed a decrease in cancer cells' viability higher than 25% compared to non-irradiated cells. Due to the promising results obtained with the light-sensitive PEG-BHETE-PLA nanoparticles, these materials have great potential to be used in drug delivery systems for cancer therapy.

The influence of poly(ester amide) on the structural and functional features of 3D additive manufactured poly(ε-caprolactone) scaffolds.

The current research reports for the first time the use of blends of poly(ε-caprolactone) (PCL) and poly(ester amide) (PEA) for the fabrication of 3D additive manufactured scaffolds. Tailor made PEA was synthesized to afford fully miscible blends of PCL and PEA using different percentages (5, 10, 15 and 20% w/w). Stability, characteristic temperatures and material's compatibility were studied through thermal analyses (i.e., TGA, DSC). Even though DMTA and static compression tests demonstrated the possibility to improve the storage modulus, Young's modulus and maximum stress by increasing the amount of PEA, a decrease of hardness was found beyond a threshold concentration of PEA as the lowest values were achieved for PCL/PEA (20% w/w) scaffolds (from 0.39 ±â€¯0.03 GPa to 0.21 ±â€¯0.02 GPa in the analysed load range). The scaffolds presented a controlled morphology and a fully interconnected network of internal channels. The water contact angle measurements showed a clear increase of hydrophilicity resulting from the addition of PEA. This result was further corroborated with the improved adhesion and proliferation of human mesenchymal stem cells (hMSCs). The presence of PEA also influenced the cell morphology. Better cell spreading and a much higher and homogenous number of cells were observed for PCL/PEA scaffolds when compared to PCL ones.

Bioabsorbable polymers in cancer therapy: latest developments.

Cancer is a devastating disease, being responsible for 13 % of all deaths worldwide. One of the main challenges in treating cancer concerns the fact that anti-cancer drugs are not highly specific for the cancer cells and the "death" of healthy cells in the course of chemotherapy treatment is inevitable. In this sense, the use of drug delivery systems (DDS) can be seen as a powerful tool to minimize or overcome this very important issue. DDS can be designed to target specific tissues in order to mitigate side effects. Bioabsorbable polymers, due to their inherent characteristics, and because they can be synthesized in a variety of forms, are materials whose importance in the DDS for cancer therapy has risen significantly in the last years. This review intends to give an overview about the latest developments in the use of bioabsorbable polymers as DDS in cancer therapy, with special focus on nanoparticles, micelles, and implants.

Macrophage polarization following chitosan implantation.

Macrophages are a key cell in the host response to implants and can be polarized into different phenotypes capable of inducing both detrimental and beneficial outcomes in tissue repair and remodeling, being important in tissue engineering and regenerative medicine. The objective of this study was to evaluate the macrophage response to 3D porous chitosan (Ch) scaffolds with different degrees of acetylation (DA, 5% and 15%). The M1/M2 phenotypic polarization profile of macrophages was investigated in vivo using a rodent air-pouch model. Our results show that the DA affects the macrophage response. Ch scaffolds with DA 5% induced the adhesion of lower numbers of inflammatory cells, being the M2 the predominant phenotypic profile among the adherent macrophages. In the inflammatory exudates F4/80(+)/CD206(+) cells (M2 macrophages) appeared in higher numbers then F4/80(+)/CCR7(+) cells (M1 macrophages), in addition, lower levels of pro-inflammatory cytokines together with higher levels of anti-inflammatory cytokines were found. Ch scaffolds with DA 15% showed opposite results, since M1 were the predominant macrophages both adherent to the scaffold and in the exudates, together with high levels of pro-inflammatory cytokines. In conclusion, Ch scaffolds with DA 5% induced a benign M2 anti-inflammatory macrophage response, whereas Ch scaffolds with DA 15% caused a macrophage M1 pro-inflammatory response.

Mucoepidermoid carcinoma of the bulbar conjunctiva - an interventional case report.

PURPOSE: Mucoepidermoid carcinoma is a rare variant of squamous cell carcinoma of the conjunctiva. It appears more frequently in the elderly, it is more aggressive than squamous cell carcinoma, and it has a higher recurrence rate and higher incidence of intraocular and orbital invasion. METHODS: We report a case of a 74-year-old man who presented to the Emergency Department with a one month history of painful red left eye. RESULTS: The patient presented with visual acuity was 10/10 in both eyes and a conjunctiva tumor on the bulbar conjunctiva of left eye. The UBM revealed a thickening of the conjunctiva-sclera complex with no signs of intraocular invasion. A biopsy was performed and the diagnosis was of mucoepidermoid carcinoma. Two local excisions with adjuvant cryotherapy and mitomycin C aplication were carried out in a period of 6 months. After 9 months of follow-up there has not been any sign of recurrence. CONCLUSIONS: The early diagnosis and treatment of carcinoma is essential not only to prevent the intraocular spread and preserve visual function but also to prevent local or systemic recurrence and dissemination.

Monitoring coral reefs, seagrasses and mangroves in Costa Rica (CARICOMP)

The coral reefs, seagrasses and mangroves from the Costa Rican Caribbean coast have been monitored since 1999 using the CARICOMP protocol. Live coral cover at Meager Shoal reef bank (7 to 10m depth) at the Parque Nacional Cahuita (National Park), increased from 13.3% in 1999, to 28.2% in 2003, but decreased during the next 5 years to around 17.5%. Algal cover increased significantly since 2003 from 36.6% to 61.3% in 2008. The density of Diadema antillarum oscillated between 2 and 7ind/m2, while Echinometra viridis decreased significantly from 20 to 0.6ind/m2. Compared to other CARICOMP sites, live coral cover, fish diversity and density, and sea urchin density were low, and algal cover was intermediate. The seagrass site, also in the Parque Nacional Cahuita, is dominated by Thalassia testudinum and showed an intermediate productivity (2.7±1.15 g/m2/d) and biomass (822.8±391.84 g/m2) compared to other CARICOMP sites. Coral reefs and seagrasses at the Parque Nacional Cahuita continue to be impacted by high sediment loads from terrestrial origin. The mangrove forest at Gandoca, within the Refugio Nacional de Vida Silvestre Gandoca-Manzanillo (National Wildlife Refuge), surrounds a lagoon and it is dominated by the red mangrove, Rhizophora mangle. Productivity and flower production peak was in July. Biomass (14kg/m2) and density (9.0±0.58 trees/100m2) in Gandoca were relatively low compared to other CARICOMP sites, while productivity in July in Costa Rica (4g/m2/d) was intermediate, similar to most CARICOMP sites. This mangrove is expanding and has low human impact thus far. Management actions should be taken to protect and preserve these important coastal ecosystems. Rev. Biol. Trop. 58 (Suppl. 3): 1-22. Epub 2010 October 01.

Los arrecifes coralinos, pastos marinos y manglares de la costa Caribe de Costa Rica han sido monitoreados desde 1999 siguiendo el protocolo de CARICOMP. La cobertura de coral vivo en el arrecife de Meager Shoal (7 a 10m de profundidad) en el Parque Nacional Cahuita, aumentó de 13.3% en 1999, a 28.2% en 2003, pero después bajó, por los siguientes 5 años, a aproximadamente 17.5%; la cobertura de algas aumentó significativamente de 36.6% en 2003 a 61.3% en 2008. La densidad de Diadema antillarum osciló entre 2 y 7 ind/m2 mientras que Echinometra viridis decreció significativamente de 20 a 0.6 ind/m2. Comparado con otros sitios CARICOMP, la cobertura de coral vivo, diversidad y densidad de peces, y densidades de erizos de mar fueron bajas y la cobertura algal intermedia. El sitio de pastos marinos, también en el Parque Nacional Cahuita, está dominado por Thalassia testudinum y tiene una productividad (2.7±1.15g/m2/d) y biomasa (822.8±391.84g/m2) intermedia comparado a otros sitios CARICOMP. Los arrecifes coralinos y pastos marinos en el Parque Nacional Cahuita continúan siendo impactados por sedimentos terrígenos. El bosque de manglar en Laguna Gandoca, dentro del Refugio Nacional de Vida Silvestre Gandoca-Manzanillo, está bordeado por una laguna y predomina el mangle rojo, Rhizophora mangle. El pico de productividad y producción de flores fue en julio. La biomasa (14 kg/m2) y densidad (9.0±0.58 árboles/100 m2) en Gandoca fueron relativamente bajas comparadas con otros sitios CARICOMP, mientras que la productividad en julio en Costa Rica (4g/m2/d) fue intermedia, similar a la mayoría de los sitios CARICOMP. Este manglar se está expandiendo y tiene muy poco impacto humano hasta ahora. Se deben tomar acciones de manejo para proteger y preservar estos importantes ecosistemas costeros.

Status and conservation of coral reefs in Costa Rica

Costa Rica has coral communities and reefs on the Caribbean coast and on the Pacific along the coast and off-shore islands. The Southern section of the Caribbean coast has fringing and patch reefs, carbonate banks, and an incipient algal ridge. The Pacific coast has coral communities, reefs and isolated coral colonies. Coral reefs have been seriously impacted in the last 30 years, mainly by sediments (Caribbean coast and some Pacific reefs) and by El Niño warming events (both coasts). Monitoring is being carried out at three sites on each coast. Both coasts suffered significant reductions in live coral cover in the 1980’s, but coral cover is now increasing in most sites. The government of Costa Rica is aware of the importance of coral reefs and marine environments in general, and in recent years decrees have been implemented (or are in the process of approval) to protect them, but limited resources endanger their proper management and conservation, including proper outreach to reef users and the general public. Rev. Biol. Trop. 58 (Suppl. 1): 33-50. Epub 2010 May 01.

Costa Rica tiene comunidades coralinas y arrecifes en la costa Caribe y del lado Pacífico a lo largo de la costa y en islas mar afuera). Arrecifes de franja y de parche, bancos carbonatados y una cresta de algas coralinas incipiente están presentes en la sección sur de la costa Caribe. Comunidades coralinas, arrecifes y colonias de coral aisladas se encuentran a lo largo de todo el Pacífico de Costa Rica. Los arrecifes coralinos han sido impactados seriamente en los últimos 30 años, principalmente por sedimentos en el Caribe y algunos arrecifes del Pacífico, y por el calentamiento durante el Fenómeno de El Niño-Oscilación Sureña en el Pacífico. Tres sitios en el Caribe y otros tres en el Pacífico están siendo monitoreados. Después de reducciones significativas en la cobertura de coral vivo en la década de 1980, tanto en el Caribe como en el Pacífico, la mayoría de los arrecifes se está recuperando. El gobierno de Costa Rica es consciente de la importancia de los arrecifes coralinos y de otros ecosistemas marinos, y en años recientes han implementado (o están en proceso de aprobación) varios decretos para la protección de los arrecifes. Pero, hay limitación de fondos y personal para su adecuado manejo y protección. Se necesita más divulgación de información sobre los arrecifes coralinos al público en general y usuarios de los mismos; de nuevo, la limitación de fondos restringe lo que se puede hacer.

Drug delivery systems: Advanced technologies potentially applicable in personalized treatments.

Advanced drug delivery systems (DDS) present indubitable benefits for drug administration. Over the past three decades, new approaches have been suggested for the development of novel carriers for drug delivery. In this review, we describe general concepts and emerging research in this field based on multidisciplinary approaches aimed at creating personalized treatment for a broad range of highly prevalent diseases (e.g., cancer and diabetes). This review is composed of two parts. The first part provides an overview on currently available drug delivery technologies including a brief history on the development of these systems and some of the research strategies applied. The second part provides information about the most advanced drug delivery devices using stimuli-responsive polymers. Their synthesis using controlled-living radical polymerization strategy is described. In a near future it is predictable the appearance of new effective tailor-made DDS, resulting from knowledge of different interdisciplinary sciences, in a perspective of creating personalized medical solutions.

Monitoreo de pastos marinos en Perezoso, Cahuita, Costa Rica (sitio CARICOMP) / Seagrass monitoring at Perezoso, Cahuita, Costa Rica (CARICOMP site)

The seagrass of Perezoso (Cahuita National Park, Caribbean coast of Costa Rica) was monitored using the CARICOMP protocol. Productivity (2.7 +/- 1.15 g/m2/d; n=74) was intermediate, compared to other Caribbean sites. Total biomass was intermediate to high (750-1500 g/m2) at most CARICOMP sites (Colombia, Cuba, Mexico, Puerto Rico and Venezuela) including Costa Rica (822.8 +/- 391.84 g/m2; n=32). Turnover rates were high (5.5 +/- 1.36%; n=74) compared to what was found in March and August at other sites. Shoot densities average 725 shoots/m2, in the Caribbean region, while in Costa Rica the value was higher (1184 +/- 335.5 shoots/m2). Average leaf length and width in the entire region were 14.4 cm and 10.6 mm, respectively, similar to what we found, but leaf area index average 3.4 m2 m(-2), higher than what was found in Costa Rica (0.92 m2 m(-2)). At Cahuita, seagrass productivity was significantly lower in March 2005 compared with the previous six years, and biomass has decreased with time. Seagrass productivity and biomass are being affected by the maximum temperatures, which increased by almost 10 degrees C from 1999 to 2005, and show a high negative correlation. Turnover rate and temperature were not correlated. Recreational boating, swimming and nutrient loading from deforested lands in the coast, the upstream rivers and local pollution are potential sources of impact to the seagrass beds at Cahuita.