Search

Osteoporosis is a common skeletal disorder which can severely limit one’s ability to complete daily tasks due to the increased risk of bone fractures, reducing quality of life. Spinal cord injury (SCI) can also result in osteoporosis and sarcopenia. Most individuals experience sarcopenia and osteoporosis due to advancing age; however, individuals with SCI experience more rapid and debilitating levels of muscle and bone loss due to neurogenic factors, musculoskeletal disuse, and cellular/molecular events. Thus, preserving and maintaining bone mass after SCI is crucial to decreasing the risk of fragility and fracture in vulnerable SCI populations. Recent studies have provided an improved understanding of the pathophysiology and risk factors related to musculoskeletal loss after SCI. Pharmacological and non-pharmacological therapies have also provided for the reduction in or elimination of neurogenic bone loss after SCI. This review article will discuss the pathophysiology and risk factors of muscle and bone loss after SCI, including the mechanisms that may lead to muscle and bone loss after SCI. This review will also focus on current and future pharmacological and non-pharmacological therapies for reducing or eliminating neurogenic bone loss following SCI.

Immunotherapy with immune checkpoint inhibitors can induce durable clinical responses in different human malignancies but the number of responding patients remains globally modest. The limited therapeutic efficacy of ICI depends on multiple factors, among which the immune suppressive features of the tumor microenvironment play a key role. For this reason, experimental models that enable dissection of the immune-hostile tumor milieu components are required to unravel how to overcome resistance and obtain full-fledged anti-tumor immunity. Recent evidence supports the usefulness of 3D ex vivo systems in retaining features of tumor microenvironment to elucidate molecular and immunologic mechanisms of response and resistance to immune checkpoint blockade. In this perspective article we discuss the recent advances in patient-derived 3D tumor models and their potential in support of treatment decision making in clinical setting. We will also share our experience with dynamic bioreactor tumor explant culture of samples from melanoma and sarcoma patients as a reliable and promising platform to unravel immune responses to immune checkpoint inhibitors.

Los pilares fundamentales de la ciencia son la investigación científica, la tecnología y la innovación (C+T+I). Sin el desarrollo de cada uno de estos aspectos, los resultados y aportes científicos de un país se ven limitados. En Ecuador la realidad es muy compleja. No solo el financiamiento es escaso, sino que no está alineado a las líneas vigentes de investigación y especialidad de los investigadores, acompañado del incumplimiento de las políticas y ofrecimientos estatales. En este entorno la participación de la mujer podría encontrar limitantes. Aun así, podemos constatar que el nivel e impacto de las publicaciones entre géneros se encuentran balanceadas. Debemos fortalecer a la ciencia en el Ecuador para ubicarnos en los niveles de otros países.

Abstract Background Turner syndrome is a genetic disorder that affects women. It is caused by an absent or incomplete X chromosome, which can be presented in mosaicism or not. There are 12 cases of Turner syndrome patients who present structural alterations in autosomal chromosomes. Case presentation The present case report describes a patient with a reciprocal, maternally inherited translocation between chromosomes 2 and 12 with a mosaicism of X monosomy 45,X,t(2;12)(p13;q24)[95]/46,XX,t(2;12)(p13;q24)[5]. Through genetic mapping arrays, altered genes in the patient were determined within the 23 chromosome pairs. These genes were associated with the patient’s clinical features using a bioinformatics tool. Conclusion To our knowledge, this is the first case in which a translocation (2;12) is reported in a patient with Turner syndrome and confirmed by conventional cytogenetics, FISH and molecular genetics. Clinical features of our patient are closely related with the loss of one X chromosome, however mild intellectual disability can be likely explained by autosomal genes. The presence of familial translocations was a common finding, thus emphasizing the need for familiar testing for further genetic counselling.

Abstract Background Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder characterized by insensitivity to pain, inability to sweat and intellectual disability. CIPA is caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) that encodes the high-affinity receptor of nerve growth factor (NGF). Case presentation Here, we present clinical and molecular findings in a 9-year-old girl with CIPA. The high-altitude indigenous Ecuadorian patient presented several health problems such as anhidrosis, bone fractures, self-mutilation, osteochondroma, intellectual disability and Riga-Fede disease. After the mutational analysis of NTRK1, the patient showed a clearly autosomal recessive inheritance pattern with the pathogenic mutation rs763758904 (Arg602*) and the second missense mutation rs80356677 (Asp674Tyr). Additionally, the genomic analysis showed 69 pathogenic and/or likely pathogenic variants in 46 genes possibly related to phenotypic heterogeneity, including the rs324420 variant in the FAAH gene. The gene ontology enrichment analysis showed 28 mutated genes involved in several biological processes. As a novel contribution, the protein-protein interaction network analysis showed that NTRK1, SPTBN2 and GRM6 interact with several proteins of the pain matrix involved in the response to stimulus and nervous system development. Conclusions This is the first study that associates clinical, genomics and networking analyses in a Native American patient with consanguinity background in order to better understand CIPA pathogenesis.

Abstract Background Anaplastic astrocytoma is a rare disorder in children from 10 to 14 years of age, with an estimated 0.38 new cases per 100,000 people per year worldwide. Panel-based next-generation sequencing opens new possibilities for diagnosis and therapy of rare diseases such as this one. Because it has never been genetically studied in the Ecuadorian population, we chose to genetically characterize an Ecuadorian pediatric patient with anaplastic astrocytoma for the first time. Doing so allows us to provide new insights into anaplastic astrocytoma diagnosis and treatment. Case presentation Our patient was a 13-year-old Mestizo girl with an extensive family history of cancer who was diagnosed with anaplastic astrocytoma. According to ClinVar, SIFT, and PolyPhen, the patient harbored 354 genomic alterations in 100 genes. These variants were mostly implicated in deoxyribonucleic acid (DNA) repair. The top five most altered genes were FANCD2, NF1, FANCA, FANCI, and WRN. Even though TP53 presented only five mutations, the rs11540652 single-nucleotide polymorphism classified as pathogenic was found in the patient and her relatives; interestingly, several reports have related it to Li-Fraumeni syndrome. Furthermore, in silico analysis using the Open Targets Platform revealed two clinical trials for pediatric anaplastic astrocytoma (studying cabozantinib, ribociclib, and everolimus) and 118 drugs that target the patient’s variants, but the studies were not designed specifically to treat pediatric anaplastic astrocytoma. Conclusions Next-generation sequencing allows genomic characterization of rare diseases; for instance, this study unraveled a pathogenic single-nucleotide polymorphism related to Li-Fraumeni syndrome and identified possible new drugs that specifically target the patient’s variants. Molecular tools should be implemented in routine clinical practice for early detection and effective preemptive intervention delivery and treatment.

Abstract Background Since 1969, 49 cases have been presented on ring chromosome 4. All of these cases have been characterized for the loss of genetic material. The genes located in these chromosomal regions are related to the phenotype. Case presentation A 10-year-old Ecuadorian Mestizo girl with ring chromosome 4 was clinically, cytogenetically and molecularly analysed. Clinical examination revealed congenital anomalies, including microcephaly, prominent nose, micrognathia, low set ears, bilateral clinodactyly of the fifth finger, small sacrococcygeal dimple, short stature and mental retardation. Cytogenetic studies showed a mosaic karyotype, mos 46,XX,r(4)(p16.3q35.2)/46,XX, with a ring chromosome 4 from 75 to 79% in three studies conducted over ten years. These results were confirmed by fluorescence in situ hybridization (FISH). Loss of 1.7 Mb and gain of 342 kb in 4p16.3 and loss of 3 Mb in 4q35.2 were identified by high-resolution mapping array. Conclusion Most cases with ring chromosome 4 have deletion of genetic material in terminal regions; however, our case has inv dup del rearrangement in the ring chromosome formation. Heterogeneous clinical features in all cases reviewed are related to the amount of genetic material lost or gained. The application of several techniques can increase our knowledge of ring chromosome 4 and its deviations from typical “ring syndrome.”

Abstract Background Ring chromosome 15 has been associated in previous studies with different clinical characteristic such as cardiac problems, digit and musculoskeletal abnormalities, and mental and motor problems among others. Only 97 clinical cases of ring chromosome 15 syndrome have been reported since 1966 and a common phenotype for these patients has not been established. Case presentation The present case report describes a 15-month-old girl from the Amazon region of Ecuador, of Mestizo ancestry, who after cytogenetic tests showed a 46,XX,r(15) karyotype in more than 70% of metaphases observed. Her parents were healthy and non-related. The pregnancy was complicated and was positive for intrauterine growth retardation. Her birth weight was 1950 g, her length was 43.5 cm, and she had a head circumference of 29.3. In addition to postnatal growth delay, she had scant frontal hair, small eyes, hypertelorism, low-set of ears, flattened nasal bridge, anteverted nostrils, down-turned mouth, three café au lait spots, and delayed dentition. Conclusions Despite the frequency of some phenotypes expressed in the different clinical cases reviewed and the present case, a common phenotype for patients with ring 15 could not be determined and it is restricted to the region of the chromosome lost during the ring formation.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. Epidemiological findings revealed that women with PCOS are prone to develop certain cancer types due to their shared metabolic and endocrine abnormalities. However, the mechanism that relates PCOS and oncogenesis has not been addressed. Herein, in this review article the genomic status, transcriptional and protein profiles of 264 strongly PCOS related genes (PRG) were evaluated in endometrial cancer (EC), ovarian cancer (OV) and breast cancer (BC) exploring oncogenic databases. The genomic alterations of PRG were significantly higher when compared with a set of non-diseases genes in all cancer types. PTEN had the highest number of mutations in EC, TP53, in OC, and FSHR, in BC. Based on clinical data, women older than 50 years and Black or African American females carried the highest ratio of genomic alterations among all cancer types. The most altered signaling pathways were p53 in EC and OC, while Fc epsilon RI in BC. After evaluating PRG in normal and cancer tissue, downregulation of the differentially expressed genes was a common feature. Less than 30 proteins were up and downregulated in all cancer contexts. We identified 36 highly altered genes, among them 10 were shared between the three cancer types analyzed, which are involved in the cell proliferation regulation, response to hormone and to endogenous stimulus. Despite limited PCOS pharmacogenomics studies, 10 SNPs are reported to be associated with drug response. All were missense mutations, except for rs8111699, an intronic variant characterized as a regulatory element and presumably binding site for transcription factors. In conclusion, in silico analysis revealed key genes that might participate in PCOS and oncogenesis, which could aid in early cancer diagnosis. Pharmacogenomics efforts have implicated SNPs in drug response, yet still remain to be found.

Abstract Background Detection of chromosomal abnormalities is crucial in various medical areas; to diagnose birth defects, genetic disorders, and infertility, among other complex phenotypes, in individuals across a wide range of ages. Hence, the present study wants to contribute to the knowledge of type and frequency of chromosomal alterations and polymorphisms in Ecuador. Methods Cytogenetic registers from different Ecuadorian provinces have been merged and analyzed to construct an open‐access national registry of chromosome alterations and polymorphisms. Results Of 28,806 karyotypes analyzed, 6,008 (20.9%) exhibited alterations. Down syndrome was the most frequent autosome alteration (88.28%), followed by Turner syndrome (60.50%), a gonosome aneuploidy. A recurrent high percentage of Down syndrome mosaicism (7.45%) reported here, as well as by previous Ecuadorian preliminary registries, could be associated with geographic location and admixed ancestral composition. Translocations (2.46%) and polymorphisms (7.84%) were not as numerous as autosomopathies (64.33%) and gonosomopathies (25.37%). Complementary to conventional cytogenetics tests, molecular tools have allowed identification of submicroscopic alterations regions or candidate genes which can be possibly implicated in patients' symptoms and phenotypes. Conclusion The Ecuadorian National Registry of Chromosome Alterations and Polymorphisms provides a baseline to better understand chromosomal abnormalities in Ecuador and therefore their clinical management and awareness. This data will guide public policy makers to promote and financially support cytogenetic and genetic testing.

Colorectal cancer (CRC) is a major health problem with an estimated 1. 8 million new cases worldwide. To date, most CRC studies have focused on DNA-related aberrations, leaving post-transcriptional processes under-studied. However, post-transcriptional alterations have been shown to play a significant part in the maintenance of cancer features. RNA binding proteins (RBPs) are uprising as critical regulators of every cancer hallmark, yet little is known regarding the underlying mechanisms and key downstream oncogenic targets. Currently, more than a thousand RBPs have been discovered in humans and only a few have been implicated in the carcinogenic process and even much less in CRC. Identification of cancer-related RBPs is of great interest to better understand CRC biology and potentially unveil new targets for cancer therapy and prognostic biomarkers. In this work, we reviewed all RBPs which have a role in CRC, including their control by microRNAs, xenograft studies and their clinical implications.

Introducción: La enfermedad de Caffey también se ha denominado hiperostosis cortical infantil, caracterizada por la presencia de un episodio en la infancia con neoformación subperióstica en las diáfisis de huesos largos, el maxilar inferior y las clavículas. Casos clínicos: Se evaluó a un recién nacido con hallazgos clínico-radiológicos que comprendieron deformidad angular anterior del antebrazo izquierdo y miembros inferiores. La radiografía simple del nacimiento certificó la hiperostosis cortical con curvatura anterior del radio izquierdo, asociado con importante engrosamiento cortical en la diáfisis de tibias. La radiografía de control a los tres y ocho meses de edad mostró disminución de la hiperostosis cortical. El segundo caso es el de una niña de siete años que ha presentado dos exacerbaciones de hiperostosis cortical. En el examen físico presentó hiperextensibilidad de pabellones auriculares, hipermovilidad de articulaciones pequeñas y manchas de hemosiderina múltiples difusas localizadas en las piernas. El tercer caso correspondió a un lactante menor de un mes y tres días de vida, con radiografía que evidenció la hiperostosis cortical de tibias. Conclusión: La familia con neoformación diafisiaria constituye casos de interés por tratarse de un diagnóstico infrecuente en la edad pediátrica y cuya sospecha clínica puede generarse a partir de un buen examen clínico y estudio del caso índice, complementado con la interpretación de la genealogía asociado con el estudio molecular que lo corrobora.

Testicular cancer (TCa) is the most common cancer among 15- to 34-year-old males. Treatments are highly effective, which help foster approximately 98% 5-year survival rate. There are very few known causal factors of the disease (e.g., cryptorchidism and family history), thus possibly limiting primary prevention methods. Secondary preventative measures, on the other hand, most notably testicular self-examination (TSE), are well-known and are promoted to help prevent late-stage diagnosis of TCa. However, debate ensues as to whether or not TSE provides any benefit. In light of a recent systematic review conducted by these authors assessing the effectiveness of TSE promotion interventions, we propose that the behavior can serve as a tool not just for detection of TCa, but other male-specific urogenital health concerns, including varicoceles, hydroceles, among others. Furthermore, we suggest that TSE can also help foster informed decision-making skills among males with regard to health concerns and treatment options. However, our advocacy is in direct conflict with U.S. Preventive Services Task Force’s influential “D” rating of TSE and others who recommend against performing TSE. This article offers an overview of the dispute over TSE’s purpose and net benefit. We conclude that TSE is a behavior that is beneficial beyond detecting cancer. These proposed “off-label” uses of the procedure make for an effectual means to promote testicular health, self-awareness, and wellness among males. Recommendations for future research and advocacy are presented to the academy.

The phrase “standard of care” is primarily a legal term representing what procedure a reasonable person (i.e., health practitioner) would administer to patients across similar circumstances. One major concern for health practitioners is delivering and advocating for treatments not defined as a standard of care. While providing such treatments may meet certain ethical imperatives, doing so may unwittingly trigger medical malpractice litigation fears from practitioners. Apprehension to deviate, even slightly, from the standard of care may (seem to) put the practitioner at significant risk for litigation, which, in turn, may limit options for treatment and preventive measures recommended by the practitioner. Specific to testicular treatment, certain guidelines exist for cancer, torsion, vasectomy, and scrotal masses, among others. As it relates to screening, practitioner examination is expected for patients presenting with testicular abnormalities. Testicular self-examination (TSE) advocacy, however, is discouraged by the U.S. Preventive Services Task Force, which may prompt a general unwillingness among health practitioners to promote the behavior. Considering the benefits TSE has beyond cancer detection, and the historical support it has received among health practitioners, it is paramount to consider the ethical implications of its official “exclusion” from preventive health and clinical care recommendations (i.e., standard of care). Since good ethics should lead practitioner patient care guidelines, not fear of increased malpractice risks, we recommend the development of a standard of care for counseling males to perform TSE.

The WHO’s “Global Strategy for Women’s, Children’s, and Adolescents’ Health 2016-2030” (GS-WCAH 2016-2030) is a comprehensive plan developed to improve the lives of women, children, and adolescents. Due to the success in the creation, ratification, and advocacy of the GS-WCAH 2016-2030, the clear health outcome disparities between males and females, and the general absence of male health from existing policies and sponsored programs, it is time now to develop a global strategy specifically drafted to improve the lives of men and boys. The following commentary provides three points for why a male-oriented program, like the GS-WCAH 2016-2030, should be created: (a) health outcomes disparities, (b) economic impact of poor male health, and (c) fathers’ role in promoting the health of women, children, and adolescents. Implications for how male health can be incorporated into future projects and priorities are provided, as well as advocacy for overall gender-inclusivity in regard to global public health efforts.

We measured sea turtle hatchling production on 16 sea turtle nesting beaches (219.6 km) in Florida (USA) from 2002 to 2012. A standard protocol was used to sample 19701 loggerhead Caretta caretta, 3809 green turtle Chelonia mydas, and 664 leatherback Dermochelys coriacea nest contents, representing all Florida nesting beaches. We assessed (1) annual variation in hatching (hatched eggs/total eggs) and emergence (emerged hatchlings/total eggs) successes, (2) annual hatchling production, and (3) sources of egg and hatchling mortality. Emergence success rates were extrapolated to all Florida sea turtle nesting beaches using means weighted by each beach’s nesting contribution. Weighted mean emergence success was 51.6% for loggerheads, 50.0% for green turtles, and 38.7% for leatherbacks. These estimates represent survivorship to the time hatchlings emerge from the nest. The estimated annual mean number of hatchlings produced on Florida beaches during the study period was 3528180 loggerheads (SD = 1155701), 568098 green turtles (SD = 327156), and 33014 leatherbacks (SD = 17574). Beach erosion from storms and nest predation by mammals were the principal identified sources of egg and hatchling mortality. Average emergence success ranged from 38.8 to 65.0% between years and 41.8 to 61.7% between study beaches, suggesting that a single sample year or location would not adequately represent a sea turtle population in demographic analyses of multiple year classes. We provide recommendations for analyzing hatching success and present a method of analysis that allows the inclusion of partially depredated nests. These nests are typically excluded because the original clutch size and the number of eggs removed by predators may not be known.

Epidemiologic data suggest men often experience excessive morbidity and early mortality, possibly compromising family and community health over the lifespan. Moreover, the negative financial/economic consequences affected by poor male health outcomes also has been of great concern in the United States and abroad. Early and consistent access to preventative health care may improve health outcomes; however, men are far less likely to access these services. The purpose of this study was to understand what factors preclude men from accessing health care. We surveyed 485 participants using a 58-item online survey built from a conceptual model previously developed by the researchers using hegemonic masculinity theory, the theory of normative contentment, and the health belief model. For men, three items significantly ( p s < .05) predicted whether they had seen a health care provider in the past year: “I/Men do not access healthcare because I do not think there is anything wrong with me,” “My health is only about me,” and “I/Men do not access healthcare because most men in my family do not access healthcare.” Other correlations of practical significance also were noted. Results suggest gender norms and masculine ideals may play a primary role in how men access preventative health care. Future programming targeting males should consider barriers and plan programs that are gender-sensitive in addition to being gender-specific. Clinical implications are discussed.

Testicular cancer is one of the greatest threats to health and wellness among 15- to 40-year old males. A concerted effort in the literature promoting awareness, risk factors, and preventative measures is warranted. There is limited discussion on the validity of interventions aimed at promoting testicular self-examination (TSE) performance; the existing body of evidence offers little discussion on what specific factors motivate performance. To assist in making Healthy People 2020 an all-inclusive success, a comprehensive assessment of existing evidence is necessary to assist in closing this research gap. A systematic review of interventions promoting TSE performance discovered moderate levels of effectiveness among 10 studies promoting the behavior. Concerning methodological quality, nine were of average quality and one was of high quality . In terms of significant TSE reporting between intervention and control/comparison groups, 3 out of 10 did not achieve the statistical causal threshold. Based on our assessment of TSE intervention quality and outcomes pertaining to behavior adoption, a best-practices guideline is presented for researchers in the field to consult as they design their interventions. This guideline aims to improve on internal and external validity of TSE promotion research in order to make them more effective.

We analyzed the consequences of aerial spraying with glyphosate added to a surfactant solution in the northern part of Ecuador. A total of 24 exposed and 21 unexposed control individuals were investigated using the comet assay. The results showed a higher degree of DNA damage in the exposed group (comet length = 35.5 µm) compared to the control group (comet length = 25.94 µm). These results suggest that in the formulation used during aerial spraying glyphosate had a genotoxic effect on the exposed individuals.

Epidemiologic studies and related literature consistently report that males have fewer years of life expectancy than females. Moreover, males experience fewer quality years of life in that they tend to live with greater rates of morbidity such as heart disease, cancer, and diabetes among other conditions. Causal evidence traditionally highlights the role of biology in determining the life course for males. However, emerging literature suggests that social determinants of health play a more central role in male morbidity and mortality, and thus contribute to health inequities between the sexes. The purpose of this article is to explore core concepts of social determinants of health as they pertain to male health inequities and provide a systematic conceptualization of how society has become encultured to view these inequities as “normative.” Strategies to improve male health are discussed using a logic model to illustrate male health advocacy in the face of the social climes of encultured health inequities.