Recommendations for post-rehabilitation care of maxillofacial prostheses

Aim: This study aimed to review the scientific literature to describe the main care and hygiene protocols for different types of maxillofacial prostheses (MFP). Methods: A bibliographic search on the PubMed / Medline database using the following keywords: ["maxillofacial prosthesis" OR "ocular prostheses" OR "palatal obturators"] AND ["Cleaning" OR "disinfection"] AND ["care"] AND ["color stability"] OR ["denture cleansers" OR "cleansing agents"]. Articles addressing materials, cleaning and disinfection protocols, and care related to MFP were included. The following exclusion criteria were applied: no adequate methodology, incompatibility with the area of interest, and unavailability for reading in full. Results: The papers were grouped into the following topics: facial prostheses, ocular prostheses, maxillofacial intraoral prostheses, and retention systems. Conclusion: Despite the MFP changes over time, its degradation decreases upon following the recommendations and post-adaptation care. The guidelines for cleaning and disinfection must be individualized to guarantee the longevity of the prosthesis and the patient health

Adult Colocolic Intussusception: A Rare Case of Intestinal Obstruction.

Intussusception occurs when a part of the intestine slides into its distal adjacent portion and is a surgical emergency. Adult colocolic intussusception is rare, but it is a severe condition and is usually associated with a presence of a tumoral process. We present the case of a frail male patient admitted to our emergency department with abdominal pain, prostration, and dyspnea. The patient was diagnosed with colocolic intussusception and was submitted to a subtotal colectomy and ileostomy. Patients with colocolic intussusception usually present with chronic abdominal pain and signs of intestinal obstruction. Abdominal CT scan facilitates the diagnosis, but most cases are only diagnosed intraoperatively. Given the high probability of colon cancer, the treatment involves an oncological resection of the intestinal segment. Colocolic intussusception is a rare cause of intestinal obstruction in adults where a high suspicion index is of paramount importance, especially considering that most of the diagnoses are made at surgery.

Engineering dual-stimuli responsive poly(vinyl alcohol) nanofibrous membranes for cancer treatment by magnetic hyperthermia.

The development of new cancer treatment options, such as multifunctional devices, allows for a more personalized treatment, avoiding the known severe side effects of conventional options. In this context, on-demand drug delivery systems can actively control the rate of drug release offering a precise control of treatment. Magnetically and thermally controlled drug delivery systems have been explored as on-demand devices to treat chronic diseases and cancer tumors. In the present work, dual-stimuli responsive systems were developed by incorporating Fe3O4 magnetic nanoparticles (NPs) and poly(N-isopropylacrylamide) (PNIPAAm) microgels into electrospun polymeric fibers for application in cancer treatment. First, Fe3O4 NPs with an average diameter of 8 nm were synthesized by chemical precipitation technique and stabilized with dimercaptosuccinic acid (DMSA) or oleic acid (OA). PNIPAAm microgels were synthesized by surfactant-free emulsion polymerization (SFEP). Poly(vinyl alcohol) (PVA) was used as a fiber template originating fibers with an average diameter of 179 ± 14 nm. Stress tests of the membranes showed that incorporating both microgels and Fe3O4 NPs in electrospun fibers increases their Young's modulus. Swelling assays indicate that PVA membranes have a swelling ratio of around 3.4 (g/g) and that the presence of microgels does not affect its swelling ability. However, with the incorporation of Fe3O4 NPs, the swelling ratio of the membranes decreases. Magnetic hyperthermia assays show that a higher concentration of NPs leads to a higher heating ability. The composite membrane with the most promising results is the one incorporated with DMSA-coated NPs, since it shows the highest temperature variation, 5.1 °C. To assess the membranes biocompatibility and ability to promote cell proliferation, indirect and direct contact cell viability assays were performed, as well as cell adhesion assays. Following an extract method viability assay, all membrane designs did not reveal cytotoxic effects on dermal fibroblasts and melanoma cancer cells, after 48 h exposure and support long-term viability. The present work demonstrates the potential of dual-stimuli composite membranes for magnetic hyperthermia and may in the future be used as an alternative cancer treatment particularly in anatomically reachable solid tumors.

Stromal changes in the aged lung induce an emergence from melanoma dormancy.

Disseminated cancer cells from primary tumours can seed in distal tissues, but may take several years to form overt metastases, a phenomenon that is termed tumour dormancy. Despite its importance in metastasis and residual disease, few studies have been able to successfully characterize dormancy within melanoma. Here we show that the aged lung microenvironment facilitates a permissive niche for efficient outgrowth of dormant disseminated cancer cells-in contrast to the aged skin, in which age-related changes suppress melanoma growth but drive dissemination. These microenvironmental complexities can be explained by the phenotype switching model, which argues that melanoma cells switch between a proliferative cell state and a slower-cycling, invasive state1-3. It was previously shown that dermal fibroblasts promote phenotype switching in melanoma during ageing4-8. We now identify WNT5A as an activator of dormancy in melanoma disseminated cancer cells within the lung, which initially enables the efficient dissemination and seeding of melanoma cells in metastatic niches. Age-induced reprogramming of lung fibroblasts increases their secretion of the soluble WNT antagonist sFRP1, which inhibits WNT5A in melanoma cells and thereby enables efficient metastatic outgrowth. We also identify the tyrosine kinase receptors AXL and MER as promoting a dormancy-to-reactivation axis within melanoma cells. Overall, we find that age-induced changes in distal metastatic microenvironments promote the efficient reactivation of dormant melanoma cells in the lung.

Incorporation of Dual-Stimuli Responsive Microgels in Nanofibrous Membranes for Cancer Treatment by Magnetic Hyperthermia.

The delivery of multiple anti-cancer agents holds great promise for better treatments. The present work focuses on developing multifunctional materials for simultaneous and local combinatory treatment: Chemotherapy and hyperthermia. We first produced hybrid microgels (MG), synthesized by surfactant-free emulsion polymerization, consisting of Poly (N-isopropyl acrylamide) (PNIPAAm), chitosan (40 wt.%), and iron oxide nanoparticles (NPs) (5 wt.%) as the inorganic component. PNIPAAm MGs with a hydrodynamic diameter of about 1 µm (in their swollen state) were successfully synthesized. With the incorporation of chitosan and NPs in PNIPAAm MG, a decrease in MG diameter and swelling capacity was observed, without affecting their thermosensitivity. We then sought to produce biocompatible and mechanically robust membranes containing these dual-responsive MG. To achieve this, MG were incorporated in poly (vinyl pyrrolidone) (PVP) fibers through colloidal electrospinning. The presence of NPs in MG decreases the membrane swelling ratio from 10 to values between 6 and 7, and increases the material stiffness, raising its Young modulus from 20 to 35 MPa. Furthermore, magnetic hyperthermia assay shows that PVP-MG-NP composites perform better than any other formulation, with a temperature variation of about 1 °C. The present work demonstrates the potential of using multifunctional colloidal membranes for magnetic hyperthermia and may in the future be used as an alternative treatment for cancer.

Tyrosine Kinase Inhibitors Are Promising Therapeutic Tools for Cats with HER2-Positive Mammary Carcinoma.

Feline mammary carcinoma (FMC) is a common neoplasia in cat, being HER2-positive the most prevalent subtype. In woman's breast cancer, tyrosine kinase inhibitors (TKi) are used as a therapeutic option, by blocking the phosphorylation of the HER2 tyrosine kinase domain. Moreover, clinical trials demonstrated that TKi produce synergistic antiproliferative effects in combination with mTOR inhibitors, overcoming resistance to therapy. Thus, to uncover new chemotherapeutic strategies for cats, the antiproliferative effects of two TKi (lapatinib and neratinib), and their combination with a mTOR inhibitor (rapamycin), were evaluated in FMC cell lines (CAT-M, FMCp and FMCm) and compared with a human breast cancer cell line (SkBR-3). Results revealed that both TKi induced antiproliferative effects in all feline cell lines, by blocking the phosphorylation of EGFR members and its downstream effectors. Furthermore, combined treatments with rapamycin presented synergetic antiproliferative effects. Additionally, the DNA sequence of the her2 TK domain (exons 18 to 20) was determined in 40 FMC tissue samples, and despite several mutations were found none of them were described as inducing resistance to therapy. Altogether, our results demonstrated that TKi and combined protocols may be useful in the treatment of cats with mammary carcinomas, and that TKi-resistant FMC are rare.

Histone Deacetylase Inhibitors and Microtubule Inhibitors Induce Apoptosis in Feline Luminal Mammary Carcinoma Cells.

Feline mammary carcinoma (FMC) is the third most common type of neoplasia in cats, sharing similar epidemiological features with human breast cancer. In humans, histone deacetylases (HDACs) play an important role in the regulation of gene expression, with HDAC inhibitors (HDACis) disrupting gene expression and leading to cell death. In parallel, microtubules inhibitors (MTIs) interfere with the polymerization of microtubules, leading to cell cycle arrest and apoptosis. Although HDACis and MTIs are used in human cancer patients, in cats, data is scarce. In this study, we evaluated the antitumor properties of six HDACis (CI-994, panobinostat, SAHA, SBHA, scriptaid, and trichostatin A) and four MTIs (colchicine, nocodazole, paclitaxel, and vinblastine) using three FMC cell lines (CAT-MT, FMCp, and FMCm), and compared with the human breast cancer cell line (SK-BR-3). HDACis and MTIs exhibited dose-dependent antitumor effects in FMC cell lines, and for all inhibitors, the IC50 values were determined, with one feline cell line showing reduced susceptibility (FMCm). Immunoblot analysis confirmed an increase in the acetylation status of core histone protein HDAC3 and flow cytometry showed that HDACis and MTIs lead to cellular apoptosis. Overall, our study uncovers HDACis and MTIs as promising anti-cancer agents to treat FMCs.

Influence of pesticides in reproductive aspects of Tropidurus torquatus in Minas Gerais, Brazil.

Intense agricultural activity in recent years has resulted in a greater use of pesticides in order to improve productivity. However, these pesticides may contain some pollutant component in their composition. Once present in the environment and/or in excess, they can cause damage to the local flora and fauna. The aim of this study was to evaluate the interference of pesticides in the reproductive aspects of male and female specimens collected in two distinct sampling sites and propose a methodology to investigate pesticide effects associated with the reproduction at a macroscopic level for reptile specimens from zoological collection. The results showed that males located in the area with the use of agricultural pesticides had a lower testicle volume compared with the ones located in the area that did not use pesticides. However, no difference was found regarding the volume of eggs compared at the same stage and the average clutch size of each population. Therefore, the present study indicates the analyzed pesticides might influence the reproduction of the studied males. Despite no evident alterations in egg volume and quantity in the area with pesticide use, our findings suggest further studies on the structure and composition of eggshell and yolk in order to assess the effects of pesticides on their viability.

Multidisciplinary care in Amyotrophic Lateral Sclerosis: a systematic review and meta-analysis.

Multidisciplinary care (MDC) has been the most recommended approach for symptom management in amyotrophic lateral sclerosis (ALS) but there is conflicting evidence about its effectiveness on survival and quality of life (QoL) of ALS patients. We conducted a systematic review to determine the effects of multidisciplinary care compared to general neurological care in survival and quality of life of ALS patients. A comprehensive literature search using Scopus, MEDLINE-PubMed, Cochrane, Web of Science, PEDro, and Science Direct was undertaken. Studies related to multidisciplinary care or general neurological care in ALS patients that assessed survival and quality of life and were published in the period up to and including January 2020 were included. A total of 1192 studies were initially identified, but only 6 were included. All studies that investigated survival showed and advantage of MDC over NC, and this benefit was even greater for bulbar onset patients. A meta-analysis was performed and showed a mean difference of 141.67 (CI 95%, 61.48 to 221.86), indicating that patients who received MDC had longer survival than those who underwent NC (p = 0.0005). Concerning QoL, only one study found better mental health scores related to QoL for patients under MDC. Multidisciplinary care is more effective than general neurology care at improving survival of patients with ALS, but only improves mental health outcomes related to quality of life of these patients.

Paradoxical Role for Wild-Type p53 in Driving Therapy Resistance in Melanoma.

Metastatic melanoma is an aggressive disease, despite recent improvements in therapy. Eradicating all melanoma cells even in drug-sensitive tumors is unsuccessful in patients because a subset of cells can transition to a slow-cycling state, rendering them resistant to most targeted therapy. It is still unclear what pathways define these subpopulations and promote this resistant phenotype. In the current study, we show that Wnt5A, a non-canonical Wnt ligand that drives a metastatic, therapy-resistant phenotype, stabilizes the half-life of p53 and uses p53 to initiate a slow-cycling state following stress (DNA damage, targeted therapy, and aging). Inhibiting p53 blocks the slow-cycling phenotype and sensitizes melanoma cells to BRAF/MEK inhibition. In vivo, this can be accomplished with a single dose of p53 inhibitor at the commencement of BRAF/MEK inhibitor therapy. These data suggest that taking the paradoxical approach of inhibiting rather than activating wild-type p53 may sensitize previously resistant metastatic melanoma cells to therapy.

Inhibition of Gap Junctions Sensitizes Primary Glioblastoma Cells for Temozolomide.

Gap junctions have recently been shown to interconnect glioblastoma cells to a multicellular syncytial network, thereby allowing intercellular communication over long distances as well as enabling glioblastoma cells to form routes for brain microinvasion. Against this backdrop gap junction-targeted therapies might provide for an essential contribution to isolate cancer cells within the brain, thus increasing the tumor cells' vulnerability to the standard chemotherapeutic agent temozolomide. By utilizing INI-0602-a novel gap junction inhibitor optimized for crossing the blood brain barrier-in an oncological setting, the present study was aimed at evaluating the potential of gap junction-targeted therapy on primary human glioblastoma cell populations. Pharmacological inhibition of gap junctions profoundly sensitized primary glioblastoma cells to temozolomide-mediated cell death. On the molecular level, gap junction inhibition was associated with elevated activity of the JNK signaling pathway. With the use of a novel gap junction inhibitor capable of crossing the blood-brain barrier-thus constituting an auspicious drug for clinical applicability-these results may constitute a promising new therapeutic strategy in the field of current translational glioblastoma research.

Age-Related Changes in HAPLN1 Increase Lymphatic Permeability and Affect Routes of Melanoma Metastasis.

Older patients with melanoma have lower rates of sentinel lymph node (LN) metastases yet paradoxically have inferior survival. Patient age correlated with an inability to retain Technetium radiotracer during sentinel LN biopsy in more than 1,000 patients, and high Technetium counts correlated to better survival. We hypothesized that loss of integrity in the lymphatic vasculature due to extracellular matrix (ECM) degradation might play a role. We have implicated HAPLN1 in age-dependent ECM degradation in the dermis. Here, we queried whether HAPLN1 could be altered in the lymphatic ECM. Lymphatic HAPLN1 expression was prognostic of long-term patient survival. Adding recombinant HAPLN1 to aged fibroblast ECMs in vitro reduced endothelial permeability via modulation of VE-cadherin junctions, whereas endothelial permeability was increased following HAPLN1 knockdown in young fibroblasts. In vivo, reconstitution of HAPLN1 in aged mice increased the number of LN metastases, but reduced visceral metastases. These data suggest that age-related changes in ECM can contribute to impaired lymphatics. SIGNIFICANCE: Our studies reveal that changes in the stroma during aging may influence the way tumor cells traffic through the lymphatic vasculature. Aging may dictate the route of metastatic dissemination of tumor cells, and understanding these changes may help to reveal targetable moieties in the aging tumor microenvironment.See related commentary by Marie and Merlino, p. 19.This article is highlighted in the In This Issue feature, p. 1.

Remodeling of the Collagen Matrix in Aging Skin Promotes Melanoma Metastasis and Affects Immune Cell Motility.

Physical changes in skin are among the most visible signs of aging. We found that young dermal fibroblasts secrete high levels of extracellular matrix (ECM) constituents, including proteoglycans, glycoproteins, and cartilage-linking proteins. The most abundantly secreted was HAPLN1, a hyaluronic and proteoglycan link protein. HAPLN1 was lost in aged fibroblasts, resulting in a more aligned ECM that promoted metastasis of melanoma cells. Reconstituting HAPLN1 inhibited metastasis in an aged microenvironment, in 3-D skin reconstruction models, and in vivo. Intriguingly, aged fibroblast-derived matrices had the opposite effect on the migration of T cells, inhibiting their motility. HAPLN1 treatment of aged fibroblasts restored motility of mononuclear immune cells, while impeding that of polymorphonuclear immune cells, which in turn affected regulatory T-cell recruitment. These data suggest that although age-related physical changes in the ECM can promote tumor cell motility, they may adversely affect the motility of some immune cells, resulting in an overall change in the immune microenvironment. Understanding the physical changes in aging skin may provide avenues for more effective therapy for older patients with melanoma. SIGNIFICANCE: These data shed light on the mechanochemical interactions that occur between aged skin, tumor, and immune cell populations, which may affect tumor metastasis and immune cell infiltration, with implications for the efficacy of current therapies for melanoma.See related commentary by Marie and Merlino, p. 19.This article is highlighted in the In This Issue feature, p. 1.

Bad company: Microenvironmentally mediated resistance to targeted therapy in melanoma.

This review will focus on the role of the tumor microenvironment (TME) in the development of drug resistance in melanoma. Resistance to mitogen-activated protein kinase inhibitors (MAPKi) in melanoma is observed months after treatment, a phenomenon that is often attributed to the incredible plasticity of melanoma cells but may also depend on the TME. The TME is unique in its cellular composition-it contains fibroblasts, immune cells, endothelial cells, adipocytes, and among others. In addition, the TME provides "non-homeostatic" levels of oxygen, nutrients (hypoxia and metabolic stress), and extracellular matrix proteins, creating a pro-tumorigenic niche that drives resistance to MAPKi treatment. In this review, we will focus on how changes in the tumor microenvironment regulate MAPKi resistance.

The pubovesical complex-sparing technique on laparoscopic radical prostatectomy.

INTRODUCTION: Preservation of urinary continence is a great challenge in Radical Prostatectomy. In order to improve functional results, Asimakopoulos et al. (2010) described a robot-assisted surgical technique with preservation of the pubovesical complex (PVC). We present a pure laparoscopic execution. PRESENTATION: A 61-year-old male patient with a diagnosis of prostate cancer, with PSA 6.54ng/ml, DRE: T1C and Gleason 6 (3+3) 1/12 fragments. All therapeutic possibilities were discussed, including active surveillance. The patient opted for surgical treatment. A transperitoneal technique was used. We started the dissection on the left side, in the limit between the detrusor and the base of the prostate. The left seminal vesicle was dissected and left neurovascular bundle released by a high anterior dissection. We repeated the same procedure on the right side. The urethra was then divided, prostatic apex was laterally drawn and PVC was released. The bladder neck was divided and an urethrovesical anastomosis was achieved. A pelvic drain was placed. RESULTS: The total operative time was 150 minutes. The estimated blood loss was 300mL. The drain was removed on the 1st postoperative day and the patient was discharged. The Foley catheter was removed after 7 days and the patient remained completely dry. Hystopathology revealed adenocarcinoma Gleason 6, negative margins. PSA after 30 days was <0.04ng/mL, and the patient reported partial penile erection. CONCLUSION: The Pubovesical Complex-Sparing Technique on Laparoscopic Radical Prostatectomy was feasible and safe. Further adequately designed studies are needed to confirm whether this technique enhances early functional outcomes.

Phenotypic heterogeneity of hereditary diffuse gastric cancer: report of a family with early-onset disease.

BACKGROUND AND AIMS: The time course for the development of clinically significant hereditary diffuse gastric cancer (HDGC) is unpredictable. Little is known about the progression from preclinical, indolent lesions to widely invasive, aggressive phenotypes. Gastroendoscopy often fails to detect early lesions, and risk-reducing/prophylactic total gastrectomy (PTG) is the only curative approach. We present an HDGC family with early-onset disease in which clinical and histologic findings provided insight into the understanding of different HDGC phenotypes. METHODS: The proband was diagnosed at age 18 years with widely invasive, metastatic DGC. CDH1 genetic testing identified a pathogenic, germline CDH1 variant (c.1901C>T, p.Ala634Val). Thirty family members were tested, and 15 CDH1 carriers were identified. RESULTS: Six family members had PTG, with negative preoperative workup. The proband's 14-year-old sister is the youngest patient, reported to date, to have PTG after negative preoperative biopsy sampling. Intramucosal HDGC foci were detected in all PTG specimens (1-33). In contrast to the "indolent" phenotype of these foci, the aggressive DGC from the proband showed pleomorphic cells, absent E-cadherin expression, increased proliferation (Ki-67 index), and activation of oncogenic events (p53, pSrc and pStat3 overexpression). All family members had Helicobacter pylori gastritis. Cag-A-positive strains were detected in all specimens, except in the proband's sister. CONCLUSIONS: HDGC is a heterogeneous disease regarding clinical behavior, endoscopic findings, histopathologic features, and immunophenotypic/molecular profile. The presence of bizarre, pleomorphic cells in endoscopic biopsy specimens is suggestive of advanced disease and should prompt clinical intervention. The involvement of a full multidisciplinary team is essential for the management of these patients.

The Comfort app prototype: introducing a web-based application for monitoring comfort in palliative care.

AIM: To introduce a web-based application for monitoring comfort in patients receiving palliative care. METHODS: Multi-phase electronic application development process that concluded with a pilot design to assess the feasibility and acceptability of the developed app (n=7 patients). RESULTS: The app is compatible with Android, iOS and Windows. The results from phases I and II provided the knowledge about monitoring comfort. In phase III, five experts analysed the content of the app. The assessment of comfort comprises 11 self-reported items (pain, tiredness, drowsiness, nausea, lack of appetite, shortness of breath, depression, anxiety, fear of the future, peace and the will to live). In phase IV, a total of 117 messages were retrieved. Participants considered the app simple, easy to use and useful. CONCLUSIONS: This prototype is feasible and user-friendly. Further research is needed to continue the app development, particularly in terms of data protection.

The technological influence on health professionals' care: translation and adaptation of scales / A influência tecnológica no cuidar dos profissionais de saúde: tradução e adaptação de escalas / La influencia tecnológica en el cuidar de los profesionales de salud: traducción y adaptación de escalas

Objectives: in this study, two research tools were validated to study the impact of technological influence on health professionals' care practice. Methods: the following methodological steps were taken: bibliographic review, selection of the scales, translation and cultural adaptation and analysis of psychometric properties. Results: the psychometric properties of the scale were assessed based on its application to a sample of 341 individuals (nurses, physicians, final-year nursing and medical students). The validity, reliability and internal consistency were tested. Two scales were found: Caring Attributes Questionnaire (adapted) with a Cronbach's Alpha coefficient of 0.647 and the Technological Influence Questionnaire (adapted) with an Alpha coefficient of 0.777. Conclusions: the scales are easy to apply and reveal reliable psychometric properties, an additional quality as they permit generalized studies on a theme as important as the impact of technological influence in health care.

Objetivos: este estudo consistiu na validação de dois instrumentos de pesquisa que permitem estudar o impacto da influência tecnológica na prática do cuidar dos profissionais de saúde. Método: foram dados os seguintes passos metodológicos: revisão bibliográfica, seleção das escalas, tradução e adaptação cultural e análise das qualidades psicométricas. Resultados: as propriedades psicométricas da escala foram avaliadas a partir da sua aplicação a uma amostra de 342 indivíduos (enfermeiros, médicos, estudantes finalistas de enfermagem e de medicina). Foram realizados estudos de validade e de fiabilidade e consistência interna. Obtiveram-se duas escalas: Escala dos Atributos do Cuidar (adaptada) com um valor de coeficiente de alpha de Cronbach de 0,647 e o Questionário da Influência Tecnológica (adaptado) com um valor de 0,777. Conclusões: as escalas são de fácil aplicação e revelam propriedades psicométricas confiáveis, sendo uma mais valia na medida em que permitem realizar estudos generalizados sobre um tema tão importante como o impacto da influência tecnológica no cuidar em saúde.

Objetivos: en este estudio fueron validados dos instrumentos de investigación que permiten estudiar el impacto de la influencia tecnológica en la práctica del cuidar de los profesionales de salud. Método: fueron dados los siguientes pasos metodológicos: revisión bibliográfica, selección de las escalas, traducción y adaptación cultural y análisis de las calidades psicométricas. Resultados: las propiedades psicométricas de la escala fueron evaluadas a partir de su aplicación a una muestra de 342 individuos (enfermeros, médicos, estudiantes finalistas de enfermería y de medicina). Fueron llevados a cabo estudios de validez y de fiabilidad y consistencia interna. Fueron encontradas dos escalas: Escala de los Atributos del Cuidar (adaptada) con coeficiente de alfa de Cronbach de 0,647 y el Cuestionario de Influencia Tecnológica (adaptado) con valor de 0,777. Conclusiones: las escalas son de fácil aplicación y revelan propiedades psicométricas confiables, siendo un valor añadido en la medida en que permiten desarrollar estudios generalizados sobre un tema tan importante como el impacto de la influencia tecnológica en el cuidado en salud.