Evaluation of rapid antiretroviral initiation strategy in a cohort of newly diagnosed people living with HIV in Panama, 2018-2019.

Antiretroviral therapy (ART) has been adopted as a form of HIV treatment and prevention. This study assesses rapid ART initiation using clinical outcomes such as viral load (VL) and CD4+ T lymphocytes count. Over the course of one year, the progress of newly diagnosed people living with HIV who started ART early in a hospital in Panama City was followed. The evaluation of early initiation of ART in achieving viral suppression (VL <200 copies/ml) was analyzed using descriptive statistics. Additionally, the cost difference between early (first 7 days) and late initiation of ART was evaluated from the perspective of the service provider. In total, 209 people were followed up during the study; 85% were male, 70% started ART on same day from hospital arrival, 80% had suppressed viral load at 6 months, and the median count of CD4 increased from 285 (IQR: 166-429) to 509 (IQR: 373-696) over 12 months. Starting ART early led to a 42% increase for the provider in terms of staffing costs; however, the clients had the opportunity to decrease absenteeism in daily activities. The results reveal that early initiation of ART generates clinical and economic benefits for the person in treatment.

Genetic ancestry and radical prostatectomy findings in Hispanic/Latino patients.

Background: African ancestry is a known factor associated with the presentation and aggressiveness of prostate cancer (PC). Hispanic/Latino populations exhibit varying degrees of genetic admixture across Latin American countries, leading to diverse levels of African ancestry. However, it remains unclear whether genetic ancestry plays a role in the aggressiveness of PC in Hispanic/Latino patients. We explored the associations between genetic ancestry and the clinicopathological data in Hispanic/Latino PC patients from Colombia. Patients and methods: We estimated the European, Indigenous and African genetic ancestry, of 230 Colombian patients with localized/regionally advanced PC through a validated panel for genotypification of 106 Ancestry Informative Markers. We examined the associations of the genetic ancestry components with the Gleason Grade Groups (GG) and the clinicopathological characteristics. Results: No association was observed between the genetic ancestry with the biochemical recurrence or Gleason GG; however, in a two groups comparison, there were statistically significant differences between GG3 and GG4/GG5 for European ancestry, with a higher mean ancestry proportion in GG4/GG5. A lower risk of being diagnosed at an advanced age was observed for patients with high African ancestry than those with low African ancestry patients (OR: 0.96, CI: 0.92-0.99, p=0.03). Conclusion: Our findings revealed an increased risk of presentation of PC at an earlier age in patients with higher African ancestry compared to patients with lower African ancestry in our Hispanic/Latino patients.

Rescue with echoendoscopy-guided cholecystogastrostomy in a patient with rectal melanoma metastasis. A diagnostic and therapeutic challenge.

We present the case of a 70-year-old woman with a history of transanal resection of rectal melanoma who presented with obstructive jaundice. She underwent complementary tests and was diagnosed with metastasis of melanoma at ampullary level. We consider this to be an interesting case given its unusual nature, as well as its difficult diagnostic and therapeutic management.

The production of activated biochar using Calophyllum inophyllum waste biomass and use as an adsorbent for removal of diuron from the water in batch and fixed bed column.

The Calophyllum inophyllum species annually produces a large volume of cylindrical fruits, which accumulate on the soil because they do not have nutritional value. This study sought to enable the use of this biomass by producing activated biochar with zinc chloride as an activating agent for further application as an adsorbent in batch and fixed bed columns. Different methodologies were used to characterize the precursor and the pyrolyzed material. Morphological changes were observed with the emergence of new spaces. The carbonaceous material had a surface area of 468 m2 g-1, Dp = 2.7 nm, and VT = 3.155 × 10-1 cm3 g-1. Scientific and isothermal studies of the adsorption of the diuron were conducted at the natural pH of the solution and adsorbent dosage of 0.75 g L-1. The kinetic curves showed a good fit to the Avrami fractional order model, with equilibrium reached after 150 min, regardless of the diuron concentration. The Liu heterogeneous surface model well represented the isothermal curves. By raising the temperature, adsorption was encouraged, and at 318 K, the Liu Qmax was reached at 250.1 mg g-1. Based on the Liu equilibrium constant, the nonlinear van't Hoff equation was employed, and the ΔG° were < 0 from 298 to 328 K; the process was exothermic nature (ΔH0 = -46.40 kJ mol-1). Finally, the carbonaceous adsorbent showed good removal performance (63.45%) compared to a mixture containing different herbicides used to control weeds. The stoichiometric column capacity (qeq) was 13.30 and 16.61 mg g-1 for concentrations of 100 and 200 mg L-1, respectively. The length of the mass transfer zone was 5.326 cm (100 mg L-1) and 4.946 cm (200 mg L-1). This makes employing the leftover fruits of the Calophyllum inophyllum species as biomass for creating highly porous adsorbents a very effective and promising option.

Gastrointestinal bleeding due to Heyde's syndrome resolved by transcatheter aortic valve implantation (TAVI).

We introduce the case of an 82-year-old woman with Heyde's syndrome (HS) whose gastrointestinal bleeding was refractory to medical and endoscopic therapy, for which a percutaneous aortic valve implantation (TAVI) was performed. The outcome after TAVI was good, gastrointestinal bleeding ceased and Hb remained stable during follow-up in the following 3 months. Currently, although SH is not an indication for TAVI, it could be an indication for TAVI in patients with recurrent gastrointestinal bleeding or refractory anemia to other therapies, using the percutaneous route in those with high surgical risk.

Determination of ERG(+), EZH2, NKX3.1, and SPINK-1 subtypes to evaluate their association with clonal origin and disease progression in multifocal prostate cancer.

BACKGROUND: The prognostic relevance of prostate cancer (PCa) molecular subtypes remains controversial, given the presence of multiple foci with the possibility of different subtypes in the same patient. AIM: To determine the clonal origin of heterogeneity in PCa and its association with disease progression, SPOP, ERG(+), EZH2, NKX3.1, and SPINK-1 subtypes were analyzed. METHODS: A total of 103 samples from 20 PCa patients were analyzed; foci of adjacent non-tumor prostate tissue, HGPIN, GL3, GL4, GL5, and LN were examined to determine the presence of the TMPRSS2-ERG fusion and ERG, EZH2, NKX3.1, and SPINK-1 expression levels, using RT-PCR. Mutations in exons 6 and 7 of the SPOP gene were determined by sequencing. The presence of subtypes and molecular patterns were identified by combining all subtypes analyzed. To establish the clonal origin of multifocal PCa, molecular concordance between different foci of the same patient was determined. Association of these subtypes with histopathological groups and time to biochemical recurrence (BCR) was assessed. RESULTS: No mutation was found in SPOP in any sample. The ERG(+) subtype was the most frequent. The molecular pattern containing all four PCa subtypes was only detected in 3 samples (4%), all LN, but it was the most frequent (40%) in patients. Molecular discordance was the predominant status (55%) when all analyzed molecular characteristics were considered. It was possible to find all subtypes, starting as a preneoplastic lesion, and all but one LN molecular subtype were ERG(+) and NKX3.1 subtypes. Only the expression of the NKX3.1 gene was significantly different among the histopathological groups. No association was found between BCR time in patients and molecular subtypes or molecular concordance or between clinicopathological characteristics and molecular subtypes of ERG, EZH2, and SPINK-1. CONCLUSION: The predominance of molecular discordance in prostatic foci per patient, which reflects the multifocal origin of PCa foci, highlights the importance of analyzing multiple samples to establish the prognostic and therapeutic relevance of molecular subtypes in a patient. All the subtypes analyzed here are of early onset, starting from preneoplastic lesions. NKX3.1 gene expression is the only molecular characteristic that shows a progression pattern by sample.

Metabolic pathways enriched according to ERG status are associated with biochemical recurrence in Hispanic/Latino patients with prostate cancer.

BACKGROUND: The role of ERG-status molecular subtyping in prognosis of prostate cancer (PCa) is still under debate. In this study, we identified differentially expressed genes (DEGs) according to ERG-status to explore their enriched pathways and implications in prognosis in Hispanic/Latino PCa patients. METHODS: RNA from 78 Hispanic PCa tissues from radical prostatectomies (RP) were used for RNA-sequencing. ERGhigh /ERGlow tumor groups were determined based on the 1.5-fold change median expression in non-tumor samples. DEGs with a False Discovery Rate (FDR) < 0.01 and a fold change >2 were identified between ERGhigh and ERGlow tumors and submitted to enrichment analysis in MetaCore. Survival and association analyses were performed to evaluate biochemical recurrence (BCR)-free survival. RESULTS: The identification of 150 DEGs between ERGhigh and ERGlow tumors revealed clustering of most of the non-BCR cases (60%) into de ERGhigh group and most of the BCR cases (60.8%) in ERGlow group. Kaplan-Meier survival curves showed a worst BCR-free survival for ERGlow patients, and a significant reduced risk of BCR was observed for ERGhigh cases (OR = 0.29 (95%CI, 0.10-0.8)). Enrichment pathway analysis identified metabolic-related pathways, such as the renin-angiotensin system and angiotensin maturation system, the linoleic acid metabolism, and polyamines metabolism in these ERG groups. CONCLUSIONS: ERGlow tumor cases were associated with poor BCR-free survival in our Hispanic/Latino patients, with metabolism-related pathways altered in the BCR progression. IMPACT: Our findings suggest the need to dissect the role of diet, metabolism, and lifestyle as risk factors for more aggressive PCa subtypes.

Band ligation-assisted endoscopic resection of a rectal Abrikossoff's tumor.

A 46-year-old man underwent colonoscopy due to familiar screening for colorectal cancer, revealing an 8-mm rounded lesion in the middle rectum, subepithelial in appearance, with non-specific characteristics. Biopsies were taken, which were inconclusive. The study was completed with a CT scan, which was normal. Given the characteristics of the lesion, smaller than one centimetre, with a low probability of muscle invasion and the possibility of complete resection, band-assisted endoscopic treatment was decided, without first carrying out an endosonographic study.

Severe drug esophagitis in a patient with achalasia.

An 82-year-old female with a history of osteoporosis and achalasia treated with periodic botulinum toxin injections presented a few weeks after the last session, reporting dysphagia and retrosternal pain. An upper gastrointestinal endoscopy revealed mucosal involvement in the middle and lower third of the esophagus in the form of edema, friability, exudate and extensive superficial ulcers, which converged distally and extended around the entire circumference. The cardia was punctiform, but could be passed without difficulty.

Toxicological, enzymatic, and immunochemical characterization of Bothrops asper (Serpentes: Viperidae) reference venom from Panama / Caracterización toxicológica, enzimática e inmunoquímica del veneno de referencia de Bothrops asper (Serpentes: Viperidae) de Panamá

Introduction: It is estimated that 2 000 snakebites occur in Panama every year, 70 % of which are inflicted by Bothrops asper. Objective: To determine the biochemical and toxicologic effects and to assess the immunochemical characteristics of a reference pool of B. asper venom representative of Panama. Methods: The reference venom was prepared as a homogeneous mixture of the venoms obtained from 78 adult snakes collected in four geographic areas of Panama. Enzymatic and toxicological activities were assessed. The electrophoretic pattern was studied by SDS-PAGE. Immunoreactivity of various antivenoms was analyzed by Western blot. Results: B. asper reference venom has lethal, hemorrhagic, myotoxic, edema-forming, coagulant, defibrinating, proteinase and phospholipase A2 activities. SDS-PAGE showed the presence of protein bands with molecular weights ranging from 8 to 70 kDa, with the presence of predominant bands at ≈ 15 kDa and ≈ 30 to 66 kDa, which likely correspond to phospholipases A2 and metalloproteinases, respectively. Immunoblotting showed a high degree of recognition by various antivenoms, especially by antivenoms from Colombia and Costa Rica. Conclusions: Following recommendations by the World Health Organization, this reference venom of B. asper of Panama will become a useful tool for the preclinical evaluation of antivenoms distributed in this country.

Introducción: Se estima que 2 000 mordeduras de serpiente ocurren en Panamá cada año, el 70 % de las cuales son infligidas por Bothrops asper. Objetivo: Determinar los efectos bioquímicos y toxicológicos y evaluar las características inmunoquímicas del veneno de referencia de B. asper representativo de Panamá. Métodos: El veneno de referencia se preparó como una mezcla homogénea de los venenos obtenidos de 78 serpientes adultas recolectadas en cuatro áreas geográficas de Panamá. Se evaluaron las actividades enzimáticas y toxicológicas. El patrón electroforético se estudió mediante SDS-PAGE. La inmunoreactividad de varios antivenenos se analizó mediante transferencia de Western. Resultados: El veneno de referencia de B. asper tiene actividades letales, hemorrágicas, miotóxicas, formadoras de edema, coagulantes, desfibrinante, proteolítica y de fosfolipasa A2. El análisis de SDS-PAGE mostró la presencia de bandas de proteínas con pesos moleculares que varían de 8 a 70 kDa, con la presencia de bandas predominantes a ≈ 15 kDa y ≈ 30 a 66 kDa, que probablemente corresponden a fosfolipasas A2 y metaloproteinasas, respectivamente. La inmunotransferencia mostró un alto grado de reconocimiento por varios antivenenos, especialmente por antivenenos de Colombia y de Costa Rica. Conclusiones: Siguiendo las recomendaciones de la Organización Mundial de la Salud, este veneno de referencia de B. asper de Panamá se convertirá en una herramienta útil para la evaluación preclínica de antivenenos distribuidos en este país.

Parent reported outcomes to measure satisfaction, acceptability, and daily life impact after vaccination with whole-cell and acellular pertussis vaccine in Chile.

AIM: To compare parental satisfaction and impact on daily life among parents of children receiving whole-cell pentavalent + oral polio vaccine (Arm1) with an acellular hexavalent vaccine (Hexaxim; Arm2). METHODS: Self-administered electronic questionnaire at vaccination and one week later in six community health clinics of metropolitan Santiago, Chile, exploring parent-reported outcomes on satisfaction, acceptability, and impact on daily life after immunization. Univariate and multivariate analyses were conducted to determine differences in the responses in both groups (α = 0.05). RESULTS: The study enrolled 800 participants and 65% (222 in Arm1, 296 in Arm2) were included for according-to-protocol analysis. Demographic characteristics were comparable, except for a higher proportion of mothers answering the questionnaire at the 6-month visit. Regardless of the study arm, parental knowledge and perception of the immunization practices were good, and there were no differences in vaccination experiences in the prior 5 years. However, satisfaction with vaccination and intention to vaccinate were statistically significantly higher in Arm2 after the 6-month visit. Also, more parents in Arm2 reported no disruption in several aspects of the everyday activities of the parent, the child, and other children in the household. Parents in Arm2 were more likely to be satisfied with the vaccine received (OR 2.82; 95% CI, 1.22-7.07); return for other vaccine dose (OR 2.62; 95% CI, 1.45-4.84); follow a healthcare professional recommendation (OR 2.24; 95% CI, 1.57-3.21); and, to be confident that the vaccine will not disrupt the family's daily routine (OR 1.89; 95% CI, 1.32-2.71). CONCLUSIONS: Overall, satisfaction, intention for future vaccination, and lower impact on the family daily routine were significantly better in the group receiving the hexavalent vaccine. We also found that health care providers' recommendations to vaccinate and participants' access to health services were important factors favoring immunization.

Safety Evaluation of Parastar® Plus in Dogs and Assessment of Transferable Residue of Fipronil and Cyphenothrin from Dogs to Humans.

Dogs are easily infested with fleas, ticks, and other ectoparasites serving as vectors for transmitting bacterial, viral, and parasitic diseases. Therefore, the use of ectoparasiticides is inevitable and important. The present investigation was undertaken with two specific objectives: one, to evaluate the safety of fipronil and cyphenothrin in dogs after topical application of Parastar® Plus, and two, to determine the transferable residue of these insecticides from dogs to humans. Six healthy, adult dogs (medium length hair, weighing between 20.5 and 27.3 kg) received topical application of Parastar® Plus (2.68 mL; fipronil, 9.8%, and cyphenothrin, 5.2%) on the back between the shoulder blades. At predetermined intervals, dogs were given a full physical exam, and residues of fipronil and cyphenothrin were determined in dog blood and cotton glove extracts using GC/MS. Fipronil and cyphenothrin peaks eluted at 7.453 and 9.913 min, correspondingly, and the compounds were confirmed based on characteristic ions. At no time was fipronil or cyphenothrin residue detected in blood samples. In glove extracts, residues of fipronil and cyphenothrin were maximally present at 24-h posttreatment (43.84 ± 5.69 and 59.26 ± 8.97 ppm, respectively). By 48 h, the residue levels sharply declined (16.89 ± 2.82 and 17.98 ± 2.07 ppm, respectively). The insecticides' residues were detected in insignificant amounts after 1 week (5.69 ± 2.16 and 10.00 ± 1.51 ppm, respectively), and only in trace amounts after 2 weeks. At no time did any dog show side effects, except itching at the site of Parastar® Plus application. The findings suggest that Parastar® Plus was safe for dogs, and transferable residues of fipronil and cyphenothrin were minimal, posing very little or no health concern to pet owners or veterinary personnel. Of course, veterinary personnel, who handle many dogs daily, may require proper protection to avoid cumulative exposure.

Síndrome de apnea hipoapnea obstructiva del sueño en paciente con accidente cerebrovascular isqueémico / Obstructive sleep apnea hypoapnea syndrome in patients with ischemic cerebrovascular accident

El síndrome de apnea hipoapnea obstructiva del sueño es considerado factor de riesgo para accidente cerebrovascular, que es a nivel mundial la segunda causa de muerte y primera de discapacidad. Objetivo: describir la prevalencia de sospecha de SAHOS por escala Epwhort y aumento de circunferencia cervical en pacientes con ACV isquémico en los hospitales de San José e Infantil Universitario de San José, de Bogotá DC, de octubre 2013 a septiembre 30 de 2014. Metodología: estudio descriptivo de corte transversal con población elegida con diagnóstico de ACV isquémico. Resultados: 125 pacientes con edad promedio de 69 años (DE 15.0) y relación hombre/mujer 1:1. Antecedente de SAHOS 1.6% (n: 2). Por Epworth 57% (n: 63/109) tenian sospecha de SAHOS, hombres 60,3%(n: 35). La mediana para Epworth fue 10 (RIQ 7-12). Circunferencia cervical >43 cm en hombres 8,6% (n:5) y en mujeres >40 cm en 28% (n:14). El 30% (19/62) de ACV tenía sospecha de SAHOS por Epworth y circunferencia cervical. Los hombres con Epworth (8-15), tenían circunferencia cervical aumentada 14% (5/35) y las mujeres 51,9% (14/27). La mortalidad intrahospitalaria fue 9,7% (n:12). Conclusión: se encontró que más de la mitad tenía sospecha de SAHOS leve por Epworth. Hubo mayor prevalencia de obesidad cervical en mujeres y una tercera parte tenían sospecha de SAHOS por ambos criterios, lo cual confirma la importancia de explorar de rutina estos indicadores...

Obstructive sleep apnea hypoapnea syndrome is considered a risk factor for cerebrovascular accident which is the second cause of death and leading cause of disability worldwide. Objective: to describe suspicion prevalence of OSAHS estimated by the Epworth score and increase of neck circumference in patients with ischemic CVA at San José and Infantil Universitario de San José hospitals, Bogotá DC, from October 2013 and September 30 2014. Methodology: cross sectional descriptive study including a population diagnosed with ischemic CVA. Results: 125 patients with mean age 69 years (SD 15.0) and male/female ratio of 1:1. History of OSAHS in 1.6% (n: 2). By Epworth score, 57% (n: 63/109) had suspicion of OSAHS, 60.3% (n: 35) corresponded to men. The media for Epworth score was 10 (RIQ 7-12). Neck circumference, >43 cm in men 8.6% (n: 5) and women >40 cm in 28% (n: 14). OSAHS was suspected in 30% of CVAs (19/62) by Epworth score and neck circumference. Men with Epworth score (8-15), had an increased neck circumference 14% (5/35) and women 51.9% (14/27). In-hospital mortality was 9.7% (n: 12). Conclusion: we found that mild SOAHS estimated by Epworth score was suspected in more than half the patients. There was a higher prevalence of neck obesity in women and OSAHS was suspected in one third of them by both criteria, which confirms the importance of routinely exploring these indicators...

Probiotic screening and safety evaluation of Lactobacillus strains from plants, artisanal goat cheese, human stools, and breast milk.

The aim of this study was to select autochthonous strains of Lactobacillus from stools of healthy infants and adults, human milk, artisanal goat cheese, and fruits and vegetables according to their probiotic properties and safety. From 421 strains of Lactobacillus isolated, 102 (24.2%) were shown to be tolerant to gastric pH and bile salts; they were used to determine their anti-Helicobacter pylori (agar diffusion assay), antioxidant (oxygen radical absorption capacity), and anti-inflammatory (inhibition of interleukin-8 release by tumor necrosis factor-α-stimulated HT-29 cells) activities as well as their ability to adhere to intestinal (Caco-2) and gastric (AGS) epithelial cells. Results obtained were compared with three commercial probiotic Lactobacillus rhamnosus GG, L. plantarum 299v, and L. johnsonii NCC533. The five strains most efficient according to these activities were subsequently identified by sequencing their 16S rRNA gene, their susceptibility to antibiotics was determined, and their safety evaluated in mice. One strain of L. plantarum was discarded due to the higher prevalence of liver bacterial translocation observed in the animals fed this strain. In conclusion, four autochthonous strains of L. rhamnosus were finally selected with probiotic properties and safety allowing their eventual use in human studies. These results contribute to increase the diversity of probiotic strains available for the development of nutraceuticals and functional foods.

Identification of Lactobacillus spp. in colostrum from Chilean mothers.

The biodiversity of Lactobacillus spp. in colostrum samples from 116 Chilean mothers was analyzed by PCR and 16S rDNA sequencing. Lactobacilli were isolated in 55.3% of the samples, with concentrations of 3.33 +/- 0.55 (log CFU/ml). The predominant species were L. plantarum (64%), L. fermentum (16%) and L. pentosus (9%). 28% of the isolated strains were resistant to gastric pH and bile salts, suggesting that they could be used as probiotics.

Identification of Lactobacillus spp. in colostrum from Chilean mothers

The biodiversity of Lactobacillus spp. in colostrum samples from 116 Chilean mothers was analyzed by PCR and 16S rDNA sequencing. Lactobacilli were isolated in 55.3% of the samples, with concentrations of 3.33 ± 0.55 (log CFU/ml). The predominant species were L. plantarum (64%), L. fermentum (16%) and L. pentosus (9%). 28% of the isolated strains were resistant to gastric pH and bile salts, suggesting that they could be used as probiotics.

Se analizó la biodiversidad de especies de Lactobacillus en muestras de calostro de 116 madres chilenas mediante PCR y secuenciación del rDNA 16S. Se aislaron lactobacilos en 55,3% de las muestras, con concentraciones de 3,33 ± 0,55 (log UFC / ml). Las especies predominantes fueron L. plantarum (64%), L. fermentum (16%) y L. pentosus (9%). 28% de las cepas aisladas fueron resistentes a pH gástrico y a las sales biliares, lo que sugiere que podrían ser utilizados como probióticos.

Alteración en la regulación de la apoptosis vía Fas/FasL en cáncer gástrico / Alteration of Regulation of Fas/FasL Mediated Apoptosis in Gastric Cancer

El cáncer gástrico es una de las enfermedades neoplásicas de más alta incidencia y mortalidad a nivel mundial: es el segundo tipo de cáncer más frecuente en el mundo y la primera causa mundial de mortalidad por esta enfermedad. Por su parte, la apoptosis es un proceso importante de muerte celular programada que se presenta durante la embriogénesis, la regulación del sistema inmune y el mantenimiento de la homeostasis tisular. La evasión de la apoptosis por diferentes mecanismos es uno de los aspectos moleculares más importantes en el desarrollo de cáncer. En este artículo se presenta una revisión exhaustiva de la evidencia del papel de la apoptosis vía Fas/FasL en el desarrollo de la carcinogénesis gástrica, inclusive desde etapas tempranas, como la aparición de lesiones preneoplásicas. Finalmente, se evidencia que el desarrollo de más estudios permitiría esclarecer mejor el papel de la vía Fas/FasL en la carcinogénesis gástrica, en sus diferentes estadios.

Gastric cancer is an important neoplastic disease in all around the world because its high incidence and mortality. Otherwise, apoptosis is a key process of programmed cell death during embryogenesis, regulation of immune system, and holding the tissue homeostasis. Besides, the escape of apoptosis by different ways is an essential molecular aspect for the development of cancer. In this article we present an exhaustive review of the current evidence of the role of apoptosis through Fas/FasL pathway in the development of gastric carcinogenesis, including since early stages like in appearance of preneoplastic lesions. Finally, we think that a better comprehension of the signaling pathway Fas/ FasL role in the different stages of gastric carcinogenesis could let us know more about the implicated molecular ways and the physiopathological changes in the appearance of this disease.