Riluzole-Loaded Nanostructured Lipid Carriers for Hyperproliferative Skin Diseases.

Nanocarriers, and especially nanostructured lipid carriers (NLC), represent one of the most effective systems for topical drug administration. NLCs are biodegradable, biocompatible and provide a prolonged drug release. The glutamate release inhibitor Riluzole (RLZ) is a drug currently used for amyotrophic lateral sclerosis (ALS), with anti-proliferative effects potentially beneficial for diseases with excessive cell turnover. However, RLZ possesses low water solubility and high light-sensibility. We present here optimized NLCs loaded with RLZ (RLZ-NLCs) as a potential topical treatment. RLZ-NLCs were prepared by the hot-pressure homogenization method using active essential oils as liquid lipids, and optimized using the design of experiments approach. RLZ-NLCs were developed obtaining optimal properties for dermal application (mean size below 200 nm, negative surface charge and high RLZ entrapment efficacy). In vitro release study demonstrates that RLZ-NLCs allow the successful delivery of RLZ in a sustained manner. Moreover, RLZ-NLCs are not angiogenic and are able to inhibit keratinocyte cell proliferation. Hence, a NLCs delivery system loading RLZ in combination with natural essential oils constitutes a promising strategy against keratinocyte hyperproliferative conditions.

Novel Strategies against Cancer: Dexibuprofen-Loaded Nanostructured Lipid Carriers.

The aim of this work was to design innovative nanostructured lipid carriers (NLCs) for the delivery of dexibuprofen (DXI) as an antiproliferative therapy against tumoral processes, and overcome its side effects. DXI-NLC samples were prepared with beeswax, Miglyol 812 and Tween 80 using high-pressure homogenization. A two-level factorial design 24 was applied to optimize the formulation, and physicochemical properties such as particle size, zeta potential, polydispersity index and entrapment efficiency were measured. Optimized parameters of DXI-NLCs exhibited a mean particle size of 152.3 nm, a polydispersity index below 0.2, and high DXI entrapment efficiency (higher than 99%). Moreover, DXI-NLCs provided a prolonged drug release, slower than the free DXI. DXI-NLCs were stable for 2 months and their morphology revealed that they possess a spherical shape. In vitro cytotoxicity and anticancer potential studies were performed towards prostate (PC-3) and breast (MDA-MB-468) cancer cell lines. The highest activity of DXI-NLCs was observed towards breast cancer cells, which were effectively inhibited at 3.4 µM. Therefore, DXI-NLCs constitute a promising antiproliferative therapy that has proven to be especially effective against breast cancer.

Development and characterization of cholangioids from normal and diseased human cholangiocytes as an in vitro model to study primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is an incurable, fibroinflammatory biliary disease for which there is no effective pharmacotherapy. We recently reported cholangiocyte senescence as an important phenotype in PSC while others showed that portal macrophages accumulate in PSC. Unfortunately, our ability to explore cholangiocyte senescence and macrophage accumulation has been hampered by limited in vitro models. Thus, our aim was to develop and characterize a three-dimensional (3D) model of normal and diseased bile ducts (cholangioids) starting with normal human cholangiocytes (NHC), senescent NHC (NHC-sen), and cholangiocytes from PSC patients. In 3D culture, NHCs formed spheroids of ~5000 cells with a central lumen of ~150 µm. By confocal microscopy and western blot, cholangioids retained expression of cholangiocyte proteins (cytokeratin 7/19) and markers of epithelial polarity (secretin receptor and GM130). Cholangioids are functionally active, and upon secretin stimulation, luminal size increased by ~80%. Cholangioids exposed to hydrogen peroxide exhibited cellular senescence and the senescence-associated secretory phenotype (SASP; increased IL-6, p21, SA-ß-Gal, yH2A.x and p16 expression). Furthermore, cholangioids derived from NHC-sen or PSC patients were smaller and had slower growth than the controls. When co-cultured with THP-1 macrophages, the number of macrophages associated with NHC-sen or PSC cholangioids was five- to seven-fold greater compared to co-culture with non-senescent NHC. We observed that NHC-sen and PSC cholangioids release greater number of extracellular vesicles (EVs) compared to controls. Moreover, conditioned media from NHC-sen cholangioids resulted in an ~2-fold increase in macrophage migration. In summary, we developed a method to generate normal and diseased cholangioids, characterized them morphologically and functionally, showed that they can be induced to senescence and SASP, and demonstrated both EV release and macrophage attraction. This novel model mimics several features of PSC, and thus will be useful for studying the pathogenesis of PSC and potentially identifying new therapeutic targets.

A Case Report of Pseudomonas Infection in a Patient With Nasal Septum Perforation, Cocaine Use Disorder, and a Perinuclear Anti-neutrophil Cytoplasmic Antibody (p-ANCA)-Positive Assay.

Nasal septum perforation (NSP) occurs secondary to many underlying etiologies, including facial trauma, drug use, malignancy, infection, or autoimmune disease. We present the case of a 39-year-old female with a past medical history of cocaine use disorder who presented with symptoms concerning facial cellulitis unresponsive to antibiotic therapy. Physical exam and subsequent imaging revealed the presence of NSP. The patient underwent a full workup exploring potential etiologies of NSP in the setting of cocaine use disorder, with lab results indicating Pseudomonas aeruginosa and Pseudomonas putida cellulitis as well as a positive perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) assay. This case highlights the importance of maintaining a broad differential diagnosis for the etiology of NSP and avoiding anchoring bias.

Case Report: An Unusual Case of Lemierre's Syndrome Presenting as Influenza B-Induced Myositis Complicated by Streptococcus intermedius Infection.

Lemierre's syndrome (LS) is a rare and severe complication primarily associated with the bacteria Fusobacterium necrophorum and characterized by an oropharyngeal infection leading to bacteremia and septic thrombophlebitis. We present a case of an 89-year-old patient with a history of hypertension who initially presented with type B influenza infection and neck pain. She subsequently developed a neck abscess with thrombosis of the internal jugular vein. We believe this to be the first reported case in the literature of LS secondary to Streptococcus intermedius presenting after infection with type B influenza. As more atypical LS cases emerge, it is becoming increasingly clear that this condition can manifest in a number of ways. This unique case highlights the importance of considering LS as a differential diagnosis for patients of all ages presenting with neck pain and Streptococcus intermedius infection.

Pitfalls in Salivary Gland Cytology.

BACKGROUND: Salivary gland lesions possess diagnostic challenges on fine-needle aspiration (FNA) material. They are relatively uncommon, yet present with a wide spectrum of cytomorphology. Herein, we review common salivary gland neoplasms, their cytomorphologic features, their diagnostic pitfalls, and ancillary studies helpful in achieving an accurate diagnosis. SUMMARY: There are many cytomorphologic overlaps between benign and malignant salivary gland entities. Moreover, metaplasia, cystic changes, and degenerative changes are common findings adding to diagnostic dilemmas. These complicating factors contribute to a minute risk of malignancy in salivary gland lesions that are interpreted as benign on FNA. In rare cases, even malignant salivary gland neoplasms are misinterpreted as benign on aspirated material due to the many cytomorphologic overlaps. For example, benign and malignant neoplasms containing stroma such as myoepithelioma and adenoid cystic carcinoma may be misinterpreted as pleomorphic adenoma. Moreover, diagnosis of salivary gland neoplasms with basal cell features can be confusing on FNA materials; for example, basal cell adenoma can be misinterpreted as adenoid cystic carcinoma. Mucoepidermoid carcinomas have many different appearances on aspirated material due to variable amounts of mucin, degree of nuclear atypia, cellular content, and squamous metaplasia. Acinic cell carcinoma exhibits large cells with abundant cytoplasm on FNA, which can be mistaken for oncocytic cells in oncocytoma or Warthin tumor. Salivary duct carcinoma shows distinct features of malignancy and thus can be mistaken for secondary tumors involving the salivary glands or other malignant salivary gland tumors. The presence of tumor-associated lymphocytes is another underlying cause of misdiagnosis, especially when considering the differential diagnosis of an intraparotid lymph node. Ancillary studies such as immunohistochemistry and molecular studies are gaining more attention to be utilized on FNA cases. PLAG1 immunostaining, CD117, DOG1, mammaglobin, and androgen receptor (AR) are examples of commonly used immunostains in diagnosis of salivary gland lesions. MYB gene fusion, rearrangements of the MAML2 gene, and ERBB2/HER2 are examples of molecular alterations useful in diagnosis of salivary gland neoplasms. In conclusion, the aim of salivary gland cytology is to differentiate benign entities from the malignant ones and to prevent unnecessary aggressive treatments. KEY MESSAGES: The diagnostic pitfalls are enormous in salivary gland cytology. Familiarity with cytomorphology of different entities and their cytomorphologic overlaps, and application of ancillary studies improves the diagnostic yield, patient management and prevents unnecessary aggressive procedures.

In vitro and in vivo studies of ocular topically administered NLC for the treatment of uveal melanoma.

Uveal melanoma is one of the most common and aggressive intraocular malignancies, and, due to its great capability of metastasize, it constitutes the most incident intraocular tumor in adults. However, to date there is no effective treatment since achieving the inner ocular tissues still constitutes one of the greatest challenges in actual medicine, because of the complex structure and barriers. Uncoated and PEGylated nanostructured lipid carriers were developed to achieve physico-chemical properties (mean particle size, homogeneity, zeta potential, pH and osmolality) compatible for the ophthalmic administration of (S)-(-)-MRJF22, a new custom-synthetized prodrug for the potential treatment of uveal melanoma. The colloidal physical stability was investigated at different temperatures by Turbiscan® Ageing Station. Morphology analysis and mucoadhesive studies highlighted the presence of small particles suitable to be topically administered on the ocular surface. In vitro release studies performed using Franz diffusion cells demonstrated that the systems were able to provide a slow and prolonged prodrug release. In vitro cytotoxicity test on Human Corneal Epithelium and Human Uveal Melanoma cell lines and Hen's egg-chorioallantoic membrane test showed a dose-dependent cytotoxic effect of the free prodrug on corneal cells, whose cytocompatibility improved when encapsulated into nanoparticles, as also confirmed by in vivo studies on New Zealand albino rabbits. Antiangiogenic capability and preventive anti-inflammatory properties were also investigated on embryonated eggs and rabbits, respectively. Furthermore, preliminary in vivo biodistribution images of fluorescent nanoparticles after topical instillation in rabbits' eyes, suggested their ability to reach the posterior segment of the eye, as a promising strategy for the treatment of choroidal uveal melanoma.

A Unique Patient Presentation of Disseminated Strongyloidiasis: Unraveling the Clinical Complexity of an Immunocompromised Patient.

Strongyloidiasis is a rare parasitic disease that can remain dormant and asymptomatic in many individuals. However, in cases of immunosuppression, the motility rate of the Strongyloides parasite increases significantly. This case study presents a unique clinical scenario involving an 88-year-old Hispanic male with a disseminated Strongyloidesinfection. The patient's medical history includes coronary artery disease, a history of percutaneous coronary intervention, heart failure with reduced ejection fraction and subsequent recovery of left ventricular function, hypertension, dyslipidemia, mantle cell lymphoma being treated with rituximab every two months since 2019, and chronic anemia. This case emphasizes the importance for physicians to consider strongyloidiasis when faced with a diverse range of symptoms, including syndrome of inappropriate antidiuretic hormone secretion (SIADH), rash, gastrointestinal upset, urinary retention, chronic anemia, and chronic eosinophilia, as these manifestations may share a common origin.

Immunosuppression and Opportunistic Infections: A Rare Case Report of Nocardia Osteomyelitis of the Pelvis.

Patients with a long-standing history of immunosuppression are at significantly increased risk of opportunistic infections. One such group of organisms that may cause these types of infections includes the Nocardia genus, a gram-positive, filamentous rod that demonstrates a branching pattern, is urease-producing and has acid-fast properties. The disease profile of Nocardia varies with manifestations ranging from cutaneous infection to severe pulmonary or central nervous system (CNS) infections, and rarely, osteomyelitis. In this case report, we present an 87-year-old female with persistent left gluteal and lumbar pain, generalized body aches, chills, and fevers diagnosed with Nocardia asiatica osteomyelitis of the pelvis, likely secondary to dissemination from pulmonary cavitary disease in an immunosuppressed host with chronic neutropenia. On magnetic resonance imaging (MRI), the patient was found to have heterogeneous enhancement, central necrosis, and loss of cortical margins of the left iliac wing, alongside a rim-enhancing soft tissue mass from the left iliac bone into the left gluteal soft tissues and left paraspinal musculature representing an abscess. She was promptly treated with surgical irrigation and drainage with surgical wound cultures growing Nocardia asiatica. She received treatment with trimethoprim-sulfamethoxazole antibiotics with symptom improvement and is following up with an infectious disease physician outpatient. Management of osteomyelitis, like in this case, involves long-term antibiotics with the potential need for surgical intervention. There are few reported cases of extrapulmonary Nocardia infections, particularly osteomyelitis, demonstrating the importance of their inclusion in the literature to better serve patients to allow for timely intervention for rare and life-threatening conditions. In immunocompromised hosts, the differential diagnosis should include opportunistic infections and less common pathogens, especially in those with atypical presentations, including gluteal and leg pain.

Biodegradable nanoparticles for the treatment of epilepsy: From current advances to future challenges.

Epilepsy is the second most prevalent neurological disease worldwide. It is mainly characterized by an electrical abnormal activity in different brain regions. The massive entrance of Ca2+ into neurons is the main neurotoxic process that lead to cell death and finally to neurodegeneration. Although there are a huge number of antiseizure medications, there are many patients who do not respond to the treatments and present refractory epilepsy. In this context, nanomedicine constitutes a promising alternative to enhance the central nervous system bioavailability of antiseizure medications. The encapsulation of different chemical compounds at once in a variety of controlled drug delivery systems gives rise to an enhanced drug effectiveness mainly due to their targeting and penetration into the deepest brain region and the protection of the drug chemical structure. Thus, in this review we will explore the recent advances in the development of drugs associated with polymeric and lipid-based nanocarriers as novel tools for the management of epilepsy disorders.

Aspirin, Statins, Non-aspirin NSAIDs, Metformin, and the Risk of Biliary Cancer: A Swedish Population-Based Cohort Study.

BACKGROUND: Chemoprevention for biliary tract cancers (BTC), which comprise intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), and gallbladder cancer, is controversial. We examined associations between low-dose aspirin, statins, NSAIDs, and metformin with BTC risk. METHODS: We used a population-based cohort of 5.7 million persons over age 18 without personal history of cancer (except nonmelanoma skin cancer), receiving at least one commonly prescribed drug between July 1, 2005, and December 31, 2012, from the Swedish Prescribed Drug Registry. Hazard ratios (HR) were calculated using age-scaled multivariable-adjusted Cox models. RESULTS: 2,160 individuals developed BTC. Low-dose aspirin was not associated with BTC risk [HR, 0.93; 95% confidence interval (CI), 0.81-1.07], iCCA (HR, 1.21; 95% CI, 0.93-1.57), eCCA (HR, 0.80; 95% CI, 0.60-1.07), or gallbladder cancer (HR, 0.87; 95% CI, 0.71-1.06). Statins were associated with lower risk of BTC (HR, 0.66; 95% CI, 0.56-0.78), iCCA (HR, 0.69; 95% CI, 0.50-0.95), eCCA (HR 0.54; 95% CI, 0.38-0.76), and gallbladder cancer (HR, 0.72; 95% CI, 0.57-0.91). For all BTC subtypes, combined low-dose aspirin and statins were not associated with lower risk than statins alone. NSAIDs were associated with higher risk of BTC and its subtypes. Metformin was not associated with BTC risk (HR, 0.98; 95% CI, 0.82-1.18), iCCA (HR, 1.06; 95% CI, 0.77-1.48), eCCA (HR, 1.15; 95% CI, 0.82-1.61), or gallbladder cancer (HR, 0.84; 95% CI, 0.63-1.11). CONCLUSIONS: Statins were associated with a decreased risk of BTC and its subtypes. Low-dose aspirin alone was not associated with a decreased risk, and use of both was not associated with further decrease in risk beyond statins alone. IMPACT: Statins were most consistently associated with a decreased risk of BTC and its subtypes.

Lipid Nanoparticles for the Posterior Eye Segment.

This review highlights the application of lipid nanoparticles (Solid Lipid Nanoparticles, Nanostructured Lipid Carriers, or Lipid Drug Conjugates) as effective drug carriers for pathologies affecting the posterior ocular segment. Eye anatomy and the most relevant diseases affecting the posterior segment will be summarized. Moreover, preparation methods and different types and subtypes of lipid nanoparticles will also be reviewed. Lipid nanoparticles used as carriers to deliver drugs to the posterior eye segment as well as their administration routes, pharmaceutical forms and ocular distribution will be discussed emphasizing the different targeting strategies most recently employed for ocular drug delivery.

Metal-Based Nanoparticles as Antimicrobial Agents: An Overview.

Metal-based nanoparticles have been extensively investigated for a set of biomedical applications. According to the World Health Organization, in addition to their reduced size and selectivity for bacteria, metal-based nanoparticles have also proved to be effective against pathogens listed as a priority. Metal-based nanoparticles are known to have non-specific bacterial toxicity mechanisms (they do not bind to a specific receptor in the bacterial cell) which not only makes the development of resistance by bacteria difficult, but also broadens the spectrum of antibacterial activity. As a result, a large majority of metal-based nanoparticles efficacy studies performed so far have shown promising results in both Gram-positive and Gram-negative bacteria. The aim of this review has been a comprehensive discussion of the state of the art on the use of the most relevant types of metal nanoparticles employed as antimicrobial agents. A special emphasis to silver nanoparticles is given, while others (e.g., gold, zinc oxide, copper, and copper oxide nanoparticles) commonly used in antibiotherapy are also reviewed. The novelty of this review relies on the comparative discussion of the different types of metal nanoparticles, their production methods, physicochemical characterization, and pharmacokinetics together with the toxicological risk encountered with the use of different types of nanoparticles as antimicrobial agents. Their added-value in the development of alternative, more effective antibiotics against multi-resistant Gram-negative bacteria has been highlighted.

Prevalence of dengue antibodies in healthy children and adults in different Colombian endemic areas.

OBJECTIVES: Colombia is a dengue hyperendemic country; however, the prevalence of antibodies against dengue in the general population including the inhabitants of rural areas is unknown. This study aimed to determine the prevalence of dengue IgM and IgG antibodies in healthy children and adults in urban and rural areas of seven different endemic regions in Colombia between 2013 and 2015. DESIGN OR METHOD: Blood samples from healthy volunteers (1,318) were processed by serology (by indirect IgG and capture IgM and IgG ELISA) and molecular tests to detect viral RNA and circulating serotypes. RESULTS: The seroprevalence of IgG for dengue were 85% in children and over 90% for adults. In addition to the high IgM positive rate (14.9%) and secondary recent infection marker rate (capture IgG, 16%), 8.4% of the healthy volunteers were positive for dengue virus (DENV) RNA. CONCLUSION: This study confirmed the broad and permanent circulation of DENV in Colombia and the high rates of infection and reinfection suffered by its inhabitants. This information can be used by the health authorities to strengthen vector control and vaccine policies and review the algorithms of diagnosis and disease management in children and adults.

Gallbladder cancer: epidemiology and genetic risk associations.

Gallbladder cancer (GBC) is a form of hepatobiliary malignancy that develops from the mucosal lining of the gallbladder. The early development of gallbladder cancer is usually asymptomatic and gallbladder cancer has a high propensity to metastatic dissemination, thus most patients are diagnosed at intermediate to advanced stages for which there is no curative treatment. Consequently, gallbladder cancer is highly lethal. Though the overall global incidence of gallbladder cancer is low, there is marked geographic variation and ethnic communities in Asia as well as Native American populations in both North and South America are affected disproportionately. This article provides a comprehensive overview of the current epidemiology and risk and protective factors associated with gallbladder cancer development. In addition, the current knowledge on environmental and genetic risk associations for gallbladder cancer and the need for additional large-scale genome wide association studies (GWAS) are discussed.

Factors Associated with Dengue Virus Infection and Reinfection in Asymptomatic Children in Two Colombian Municipalities.

Dengue is the most important arbovirosis in the world. In this study, we assessed the knowledge, attitudes, and practices (KAP) regarding dengue in parents from two small Colombian municipalities in the Cundinamarca Province. Parents and their healthy children from 4 to 14 years of age were included in some public elementary schools. After a medical examination, blood samples were taken for diagnosis of dengue using enzyme-linked immunosorbent assays (capture immunoglobulin M and capture immunoglobulin G [IgG], indirect IgG and detection non-structural viral protein 1) and detection of viral RNA by reverse transcription polymerase chain reaction. In addition, a KAP survey was applied to the children's parents or tutors. The indirect IgG test determined that of the 347 examined children, 87.9% had a previous infection with the dengue virus (DENV), 12.7% of them were positive for viral RNA (asymptomatic infection), and 32.0% presented reinfections. Risk factors evaluation showed that children aged 8 years and older living in the municipalities for more than 7 years were more likely to be infected or reinfected by DENV. In the same way, poor nutrition, lack of water supply, sewer service, or waste disposal services could raise the likelihood of dengue infections. The surveys indicated that parents have unhealthy practices and a low knowledge about the transmission of the disease, which could result in an increase of mosquito breeding sites, allowing sustained dengue transmission.

Conocimientos, habilidades, actitudes y prácticas en telesalud de los profesionales de la salud durante la pandemia de COVID-19

Introducción: La pandemia por el SARS-CoV-2 estableció desafíos para los sistemas de salud en función de dar continuidad a la atención de los pacientes por medio de la rápida adopción de la telesalud. Esto conllevó retos para los profesionales que se enfrentaron a las tecnologías de la información y la comunicación. Objetivos: Identificar conocimientos, habilidades, actitudes y prácticas de los profesionales de la salud que emplearon la telesalud en el ámbito ambulatorio durante la pandemia y analizar los posibles factores relacionados con las barreras que presentan los profesionales para implementar de forma efectiva los servicios de telesalud. Métodos: Estudio descriptivo de corte transversal analítico. Se aplicó una encuesta electrónica a profesionales de salud de tres centros médicos de Colombia. Resultados: Se aplicaron 430 encuestas. La mediana de edad fue de 39 años y el 79 % fueron mujeres. El 57 % no habían sido capacitados en aspectos técnicos, normativos y éticos de la telesalud; el 46 % reportó dificultad para administrar el tiempo; el 81 % manifestó el aumento en su carga laboral. La dificultad para emplear las herramientas tecnológicas se asoció 4,67 veces más a la percepción de alteración de su propio estado de salud; sin embargo, el 92 % manifestó que seguiría usando la telesalud. Conclusiones: La actitud frente al uso de la telesalud fue positiva; el conocimiento, habilidades y entrenamiento en telesalud parece determinar su aceptabilidad. Esta es una primera evaluación que revela los puntos a trabajar en el caso de los profesionales, en función de la permanencia de la telesalud como herramienta para la atención de pacientes.

Introduction: The SARS-CoV-2 pandemic posed challenges for health systems in terms of providing continuity of patient care through the rapid adoption of telehealth. This brought challenges for professionals who dealt with information and communication technologies. Objectives: To identify knowledge, skills, attitudes, and practices of health professionals who used telehealth in the outpatient setting during the pandemic and to analyze possible factors related to the barriers that professionals present to effectively implement telehealth services. Methods: This is a descriptive analytical cross-sectional study. An electronic survey was used on health professionals from three medical centers in Colombia. Results: Four hundred thirty (430) surveys were used. The median age was 39 years and 79% were women. 57% had not been trained in technical, regulatory and ethical aspects of telehealth; 46% reported difficulty managing time; 81% reported an increase in their workload. The difficulty in using technological tools was associated 4.67 times more with the perception of alteration of their own state of health; however, 92% said they would continue to use telehealth. Conclusions: The attitude towards the use of telehealth was positive; knowledge, skills, and training in telehealth seem to determine its acceptability. This is a first evaluation that reveals the points to work on in the case of professionals, based on the permanence of telehealth as a tool for patient care.

Biliary tract cancers: epidemiology, molecular pathogenesis and genetic risk associations.

Biliary tract cancers (BTC) are malignancies that arise from the epithelium of the biliary system and comprise the second most common type of hepatobiliary cancer worldwide. BTC are sub-classified as intrahepatic cholangiocarcinoma (iCCA), perhilar/hilar cholangiocarcinoma (pCCA), distal cholangiocarcinoma (dCCA), and gallbladder carcinoma. Due to the differences in their etiologic risk factors, pathogenesis, and molecular and genetic characteristics, each of these subtypes is considered a separate biological entity. The geographic diversity of risk factors for the subtypes of biliary cancers results in profound differences in the worldwide incidence of each. In this article we provide a review of the current epidemiology of BTC and their associated risk factors. Further, we discuss the available evidence for genetic predisposition to BTC and anticipate the results of planned large-scale, genome-wide association studies (GWAS) exploring the inherited sequence variants conferring risk of BTC. These studies may also potentially of reveal important pathogenic mechanisms of the biliary tract cancer subtypes.

Características de la Anidación de Lepidochelys olivacea (Testudinata: Cheloniidae) entre el 2010 y 2012 en Playa Tortuga Ojochal de Osa, Puntarenas, Costa Rica / Features Lepidochelys olivacea Nesting (Testudinata: Cheloniidae) between 2010 and 2012 in Playa Tortuga Ojochal, Osa, Puntarenas, Costa Rica

Resumen En las playas de arribada de Costa Rica el comportamiento de anidación y otros aspectos de la biología de Lepidochelys olivacea han sido ampliamente estudiados, pero existe poca información acerca de las playas de anidación solitaria en especial del Pacífico Sur. Por este motivo el objetivo del presente estudio es describir los aspectos relevantes del comportamiento de la anidación de L. olivacea en Playa Tortuga, Pacífico Sur de Costa Rica, durante tres temporadas de anidación (2010, 2011, 2012). Se dividió la playa en 14 sectores de 100m cada uno, a partir de esto se realizaron patrullajes todas noches durante los meses de julio a diciembre (2010) y de julio a enero (2011, 2012), con el fin de registrar el comportamiento de anidación de las tortugas y proteger sus nidadas. Las hembras observadas fueron identificadas mediante la aplicación de marcas metálicas en sus aletas posteriores, se registró el número de huevos, el sector de ubicación de las nidadas, la hora, datos biométricos ancho y largo curvo del caparazón (ACC-LCC), también se contabilizaron todas las nidadas efectivas (con o sin tortuga). Se logró marcar 100 hembras de L. olivacea, y se contabilizaron un total de 233 nidadas en Playa Tortuga. Se determinó una frecuencia de anidación de dos veces por temporada con un intervalo de reanidación de 14 a 20 días y para cuatro individuos se registró un período de remigración de un año. Se estimó para las tres temporadas una población total de 117 hembras y se determinó el período de agosto a setiembre como el pico de anidación. Con respecto a la biometría, se obtuvo un valor de LCC promedio de 69.91±1.05cm y un valor de ACC promedio de 70.476+/-1.767cm. Un total de 18 711 huevos fueron colectados y 9 858 neonatos fueron reclutados. Se ha comprobado a partir de las tres temporadas de monitoreo que Playa Tortuga debe de ser considerada como una playa de anidación de L. olivacea, a pesar de que que su población actual de hembras anidantes es reducida en comparación a otras playas del Pacífico Sur. El marcaje es una herramienta útil para la caracterización de la frecuencia e intervalo de reanidación.

Abstract Olive Ridley sea turtle (Lepidochelys olivacea) have been amply studied on Costa Rican beaches that experience mass nestings, "arribadas", both in their nesting behavior and other aspects of their biology; however, very little published information exists about beaches where the Olive Ridley is nesting in solitary form, especially along the Southern Pacific Coast. For this reason, the objective of this study is to describe relevant nesting aspects, such as number of nest per season and nesting sites of L. olivacea on the Tortuga Beach in the South Pacific of Costa Rica, during three nesting seasons (2010, 2011, 2012). The beach was divided into 14 sectors of 100m each. Beach patrols were conducted every night from July to December (2010) and July to January (2011, 2012), with the purpose of observing and recording nesting behavior in the turtles as well as to protect their nests. The females observed were identified by means of metal tags applied to their rear flippers. Other data collected included: number of eggs deposited, nest location, hour, biometric data (width and length taken along the curve of the carapace), and the total of nests laid (found with or without the turtle present). After three seasons, 100 females of Olive Ridley Sea Turtle were successfully marked, and a total of 233 nests were counted. The frequency of re-nesting of an individual during a season was of every 14 to 20 days and four individuals re immigrated to nest again over the period of one year. The total population of nesting females during these three years was estimated at 117. The peak nesting happens in September, more sea turtles visited the beach during this period in all the seasons reported. With respect to biometry, the average value of the LCC was 69.91±1.05cm and the average value of the WCC was 70.476+/-1.767cm. A total of 18 711 eggs were collected and 9 858 were successfully hatched. The Tortuga Beach was proven to be a nesting beach of the species L. olivacea; the population of nesting females on the beach can be considered significantly reduced in comparison with other nesting beaches of the same species along the Southern Pacific Coast of Costa Rica. Furthermore, marking the turtles with metal tags has proven a useful tool towards the characterization of the nesting aspects of the sea turtles, such as the frequency and interval of re-nesting, and other variables such as the re immigration which requires a period of time greater than the time period of the study to date. Rev. Biol. Trop. 63 (Suppl. 1): 339-349. Epub 2015 April 01.