Clinical Obstacles Research Articles

Diabetes-related quality of life in six European countries measured with the DOQ-30

Background The quantification of diabetes-related quality of life (DR-QoL) is an essential step in making Type 2 Diabetes (T2DM) self-management arrangements. The European General Practitioners Research Network (EGPRN) initiated the EUROBSTACLE study to develop a broadly conceptualised DR-QoL instrument for diverse cultural and ethnic groups; high and low-income countries. In 2016 the Diabetes Obstacles Questionnaire-30 (DOQ-30) was introduced. Objectives The research aimed to study obstacles a patient with diabetes (PWD) may face in everyday life. First, we assessed how descriptive and clinical characteristics and the residential country were associated with the obstacles. Secondly, we calculated the proportion of respondents who expressed obstacles. Methods Data were collected in 2009 in a cross-sectional survey in Belgium, France, Estonia, Serbia, Slovenia, and Turkey. Multiple linear regressions were computed to detect associations between descriptive and clinical characteristics, residential country, and obstacles. Percentages of respondents who perceived obstacles were calculated. Results We found that although descriptive and clinical characteristics varied to quite a great extent, they were weakly associated with the perception of obstacles. The residential country was most often associated with the existence of some obstacle. The highest percent (48%) of all respondents perceived ‘Uncertainty about Insulin Use’ as an obstacle. Conclusion Descriptive and clinical characteristics were weakly associated with perceived obstacles. However, the residential country plays an essential role in the decline of the QoL of PWDs. Education of both PWDs and healthcare professionals (HCPs) plays an essential role in countering the fear of insulin.

Safety of continuous 12-hour delivery of antimicrobial doses of inhaled nitric oxide during ex vivo lung perfusion

IntroductionHigh-dose nitric oxide (NO) has been shown effective against a variety of micro-organisms in vitro, including common bacteria found in donor organs. However, clinical obstacles related to its implementation in vivo are the formation of methemoglobin and the accumulation of toxic nitrogen compounds. Ex vivo lung perfusion (EVLP) is a platform that allows for organ maintenance with an acellular perfusion solution, thus overcoming these limitations. The present study explores the safety of continuous high-dose inhaled (iNO) during EVLP for an extended period of 12 hours. MethodsLungs procured from Yorkshire pigs were randomized into control (standard ventilation) and treatment (standard ventilation + 200 ppm iNO) groups, then perfused with an acellular solution for 12 hours (n = 4/group). Lung physiology and biological markers were evaluated. ResultsAfter 12 hours of either standard EVLP or EVLP + 200 ppm iNO, we did not notice any significant physiologic difference between the groups: pulmonary oxygenation (P = .586), peak airway pressures (P = .998), and dynamic (P = .997) and static (P = .908) lung compliances. In addition, no significant differences were seen among proinflammatory cytokines measured in perfusate and lung tissue. Importantly, most common toxic compounds were kept at safe levels throughout the treatment course. ConclusionsHigh-dose inhaled NO delivered continuously over 12 hours appears to be safe without inducing any significant pulmonary inflammation or deterioration in lung function. These findings support further efficacy studies to explore the use of iNO for the treatment of infections in donor lungs during EVLP.

Hypoxia-Induced Photogenic Radicals by Eosin Y for Efficient Phototherapy of Hypoxic Tumors.

The current reported photosensitizers generally show a decreased reactive oxygen species (ROS) generation property under hypoxia conditions, which is the main reason for the clinical failure of photodynamic therapy (PDT) in treatment of solid tumors. Herein, for the first time, hypoxia-induced photogenic radicals by eosin Y (Eos) were reported for efficient phototherapy of hypoxic tumors. More importantly, Eos shows a higher ROS and radical production efficiency under hypoxia conditions than under normoxia conditions. The photogenic radicals were captured by electron paramagnetic resonance and further verified by ROS and radical probe. Introducing CoCl2 as a hypoxia inducer, the photoinduced therapy of the hypoxia cancer cell model and tumor-bearing mice indicated that bovine serum albumin-Eos in hypoxic tumor sites can produce even higher tumor toxicity, thereby crossing the clinical obstacles of hypoxic tumor therapy. This non-oxygen-dependent PDT may open up an avenue for fighting with hypoxia.

Antipsychotic Polypharmacy.

Physicians who treat patients with schizophrenia frequently encounter complex clinical situations not fully addressed by published treatment guidelines. Some of these situations lead to antipsychotic polypharmacy, often prescribed when clinical and social obstacles prevent access to clozapine and patients have had suboptimal responses to nonclozapine monotherapy. We offer our perspective on the place of antipsychotic polypharmacy in the current treatment guidelines for patients with schizophrenia. We summarize data on the prevalence of antipsychotic polypharmacy and describe common clinical situations in which this practice is encountered, along with the pharmacological underpinnings of this practice. We briefly review evidence on common risks of antipsychotic polypharmacy and describe the limited evidence for the possible benefits of such practice. Moreover, we take a look at alternative antipsychotic augmentation strategies that address all domains of psychosis.

Molecular Heterogeneity and Immunosuppressive Microenvironment in Glioblastoma.

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, with a poor prognosis, despite surgical resection combined with radio- and chemotherapy. The major clinical obstacles contributing to poor GBM prognosis are late diagnosis, diffuse infiltration, pseudo-palisading necrosis, microvascular proliferation, and resistance to conventional therapy. These challenges are further compounded by extensive inter- and intra-tumor heterogeneity and the dynamic plasticity of GBM cells. The complex heterogeneous nature of GBM cells is facilitated by the local inflammatory tumor microenvironment, which mostly induces tumor aggressiveness and drug resistance. An immunosuppressive tumor microenvironment of GBM provides multiple pathways for tumor immune evasion. Infiltrating immune cells, mostly tumor-associated macrophages, comprise much of the non-neoplastic population in GBM. Further understanding of the immune microenvironment of GBM is essential to make advances in the development of immunotherapeutics. Recently, whole-genome sequencing, epigenomics and transcriptional profiling have significantly helped improve the prognostic and therapeutic outcomes of GBM patients. Here, we discuss recent genomic advances, the role of innate and adaptive immune mechanisms, and the presence of an established immunosuppressive GBM microenvironment that suppresses and/or prevents the anti-tumor host response.

Establishing a digital health platform in an academic medical center supporting rural communities.

The University of Arkansas for Medical Sciences (UAMS), like many rural states, faces clinical and research obstacles to which digital innovation is seen as a promising solution. To implement digital technology, a mobile health interest group was established to lay the foundation for an enterprise-wide digital health innovation platform. To create a foundation, an interprofessional team was established, and a series of formal networking events was conducted. Three online digital health training models were developed, and a full-day regional conference was held featuring nationally recognized speakers and panel discussions with clinicians, researchers, and patient advocates involved in digital health programs at UAMS. Finally, an institution-wide survey exploring the interest in and knowledge of digital health technologies was distributed. The networking events averaged 35-45 attendees. About 100 individuals attended the regional conference with positive feedback from participants. To evaluate mHealth knowledge at the institution, a survey was completed by 257 UAMS clinicians, researchers, and staff. It revealed that there are opportunities to increase training, communication, and collaboration for digital health implementation. The inclusion of the mobile health working group in the newly formed Institute for Digital Health and Innovation provides a nexus for healthcare providers and researches to facilitate translational research.

Multifunctional Polymeric Nanoplatforms for Brain Diseases Diagnosis, Therapy and Theranostics.

The blood–brain barrier (BBB) acts as a barrier to prevent the central nervous system (CNS) from damage by substances that originate from the blood circulation. The BBB limits drug penetration into the brain and is one of the major clinical obstacles to the treatment of CNS diseases. Nanotechnology-based delivery systems have been tested for overcoming this barrier and releasing related drugs into the brain matrix. In this review, nanoparticles (NPs) from simple to developed delivery systems are discussed for the delivery of a drug to the brain. This review particularly focuses on polymeric nanomaterials that have been used for CNS treatment. Polymeric NPs such as polylactide (PLA), poly (D, L-lactide-co-glycolide) (PLGA), poly (ε-caprolactone) (PCL), poly (alkyl cyanoacrylate) (PACA), human serum albumin (HSA), gelatin, and chitosan are discussed in detail.

Modeling pediatric medulloblastoma.

Mouse models of medulloblastoma have proven to be instrumental in understanding disease mechanisms, particularly the role of epigenetic and molecular drivers, and establishing appropriate preclinical pipelines. To date, our research community has developed murine models for all four groups of medulloblastoma, each of which will be critical for the identification and development of new therapeutic approaches. Approaches to modeling medulloblastoma range from genetic engineering with CRISPR/Cas9 or in utero electroporation, to orthotopic and patient‐derived orthotopic xenograft systems. Each approach or model presents unique advantages that have ultimately contributed to an appreciation of medulloblastoma heterogeneity and the clinical obstacles that exist for this patient population.

Using Virtual Reality Exposure Therapy to Enhance Treatment of Anxiety Disorders: Identifying Areas of Clinical Adoption and Potential Obstacles.

Despite strong evidence of effectiveness, exposure therapy is an underutilized treatment for anxiety disorders at a time when effective treatment for anxiety is greatly needed. The significant worldwide prevalence and negative impact of anxiety are documented and highlight the importance of increasing therapist and patient use of effective treatment. Obstacles to the use of exposure therapy are explored and steps to lessen these obstacles are proposed. In particular, virtual reality (VR) technology is discussed as a way to increase the availability of exposure therapy. Incorporating VR in therapy can increase the ease, acceptability, and effectiveness of treatment for anxiety. VR exposure therapy (VRET) permits individualized, gradual, controlled, immersive exposure that is easy for therapists to implement and often more acceptable to patients than in vivo or imaginal exposure. VR is presented as a scalable tool that can augment access to and effectiveness of exposure therapy thus improving treatment of anxiety disorders. VR also has the potential to help with assessment and with therapist training standardization. The authors advocate for providing continuing education in VRET to practicing clinicians and including training in exposure therapy and VRET in training programs. Ongoing development of VR applications for clinical use is encouraged, especially when developed in collaboration with software developers, clinical users, therapists who are experienced in VRET, and researchers.

Stanniocalcin 2 (STC2) expression promotes post-radiation survival, migration and invasion of nasopharyngeal carcinoma cells.

Background: Stanniocalcin 2 (STC2) expression is upregulated under multiple stress conditions including hypoxia, nutrient starvation and radiation. Overexpression of STC2 correlates with tumor progression and poor prognosis.Purpose: We previously demonstrated that overexpression of STC2 in nasopharyngeal carcinomas (NPC) positively correlates with radiation resistance and tumor metastasis, two major clinical obstacles to the improvement of NPC management. However, it remains elusive whether STC2 expression is a critical contributing factor for post-radiation survival and metastasis of NPC cells.Materials and methods: Using the radiation resistant CNE2 cell line as a model, we examined the importance of STC2 expression for post-radiation survival, migration and invasion. Here, we report the establishment of STC2 knockout lines (CNE2-STC2-KO) using the CRISPR/Cas9-based genome editing technique.Results: Compared with the parental line, STC2-KO cells showed similar proliferation and morphology in normal culture conditions, and loss of STC2 did not compromise the cell tumorigenicity in nude mice model. However, STC2-KO lines demonstrated increased sensitivity to X-radiation under either normoxic or hypoxic conditions. Particularly, upon X-radiation, parental CNE2 cells only slightly whereas STC2-KO cells remarkably decreased the migration and invasion ability. Cell cycle analysis revealed that loss of STC2 accumulated cells in G1 and G2/M phases but decreased S-population.Conclusion: These data indicate that the expression of STC2, which can be stimulated by metabolic or therapeutic stresses, is one important factor to promote survival and metastasis of post-radiation NPC cells. Therefore, targeting STC2 or relative downstream pathways may provide novel strategies to overcome radiation resistance and metastasis of NPC.

Clinical benefit of EGFR-TKIs plus radiotherapy for treating EGFR-mutated metastatic non-small cell lung cancer.

e20694 Background: Despite the high response rate and prolonged OS of patients with EGFR mutations treated with gefitinib or erlotinib, there are still major clinical obstacles. The local control rate is still low, only 19.4%–58%, with first-line treatment using EGFR-targeted therapy. The aim of this study is to provide scientific evidence to support the clinical benefits of EGFR-TKI combined with radiotherapy compared to EGFR-TKI alone. Methods: From February 2015 to May 2017, a total of 103 patients with stage IV EGFR-mutated NSCLC treated at Sichuan Cancer Hospital & Institute were analysed retrospectively. 50 patients were treated with EGFR-TKIs (gefitinib or erlotinib) plus radiotherapy (Group TKI-RT) and 53 patients received EGFR-TKIs alone (Group TKI). Tumour response, survival and toxicities were compared between the two groups. Results: Median follow up time was 11.7 months (range: 2.8–36.3 months). The overall response rate (ORR) and disease control rate (DCR) in Group TKI-RT vs. Group TKI were 62% vs. 37.7% (P = 0.014) and 88% vs. 75.5% (P = 0.101), respectively. The median progression-free survival (PFS) and median overall survival (OS) in Group TKI-RT were superior to those of Group TKI (18.87 months vs. 12.80 months, P = 0.035 and 23.10 months vs. 18.30 months, P = 0.011). OS rates in Group TKI-RT and Group TKI were 56.0% vs. 35.8% at 1-year (P = 0.04) and 16.0% vs. 3.8% at 2-year (P = 0.036). Multivariate Cox model found that TKI-RT related to significantly better OS (hazard ratio = 0.209; 95% CI, 0.066 to 0.661; P = 0.008) than TKI alone. Adverse events did not differ significantly between the two groups. Conclusions: Compared with EGFR-TKIs alone, EGFR-TKIs combined with radiotherapy was well tolerated and showed benefit in tumour response and survival for EGFR mutation-positive metastatic NSCLC patients.

Using an Electronic Tablet to Assess Patients' Home Environment by Videoconferencing Prior to Hospital Discharge: Protocol for a Mixed-Methods Feasibility and Comparative Study.

BackgroundOccupational therapists working in hospitals are usually involved in discharge planning to assess patients’ safety and autonomy upon returning home. However, their assessment is usually done at the hospital due to organizational and financial constraints. The lack of visual data about the patients’ home may thus reduce the appropriateness and applicability of the support recommended upon discharge. Although various technological tools such as mobile devices (mobile health) are promising methods for home-based distance assessment, their application in hospital settings may raise several feasibility issues. To our knowledge, their usefulness and added value compared to standard procedure have not been addressed yet in previous studies. Moreover, several feasibility issues need to be explored.ObjectiveThis paper aims to (1) document the clinical feasibility of using an electronic tablet to assess the patient's home environment by mobile videoconferencing and (2) explore the added value of using mobile videoconferencing, compared to the standard procedure.MethodsA feasibility and comparative study using a mixed-methods (convergent) design is currently undergoing. Six occupational therapists will assess the home environment of their patients in the hospital setting: they will first perform a semistructured interview (a) and then use mobile videoconferencing (b) to compare “a versus a+b.” Interviews with occupational therapists and patients and their caregivers will further explore the advantages and disadvantages of mobile videoconferencing. Two valid tools are used (the Canadian Measure of Occupational Performance and the telehealth responsivity questionnaire). Direct and indirect time is also collected.ResultsThe project was funded in the spring of 2016 and authorized by the ethics committee in February 2017. Enrollment started in April 2017. Five triads (n=4 occupational therapists, n=5 clients, n=5 caregivers) have been recruited until now. The experiment is expected to be completed by April 2019 and analysis of the results by June 2019.ConclusionsMobile videoconferencing may be a familiar and easy solution for visualizing environmental barriers in the home by caregivers and clinicians, thus providing a promising and inexpensive option to promote a safe return home upon hospital discharge, but clinical feasibility and obstacles to the use of mobile videoconferencing must be understood.International Registered Report Identifier (IRRID)DERR1-10.2196/11674

Challenges in the Clinical Environment: The Saudi Student Nurses’ Experience

Previous studies showed that student nurses faced difficulties in clinical practice; thus, this study examined the clinical challenges encountered by Saudi nationals and the implications to learning outcomes using the descriptive cross-sectional approach. The study was conducted in nursing college in a university in Riyadh, Saudi Arabia. The survey questionnaires were completed by 220 conveniently selected student nurses who were enrolled in Bachelor’s Degree in Nursing from the academic level 5 to 8. Data analysis was done through the Statistical Package for the Social Sciences version 23. Clinical evaluation was perceived as the most common challenge, whereas competency development as the least. Significant associations were found between age and evaluation, academic level and competency development, and grade point average and learning outcomes. Nursing competency development significantly varied with civil status and stream of study. Students in the Regular Nursing Program faced more challenges in achieving learning outcomes then their counterparts. Overall, the challenges were perceived as occasional. Resolving clinical obstacles is crucial in helping student nurses achieve positive learning outcomes.

Stress Induced Overexpression of Stanniocalcin 2 (STC2) Plays Key Role in Radiation Resistance and Metastasis of Nasopharyngeal Carcinomas

Stanniocalcin2 (STC2) expression is up-regulated by multiple stress conditions including hypoxia, nutrient depletion and radiation, and overexpression of STC2 correlates with tumor progression and poor prognosis. Particularly, it has been demonstrated that overexpression of STC2 in nasopharyngeal carcinomas (NPC) positively correlates with radiation resistance and metastasis, two major clinical obstacles to further improvement of NPC management. However, a contributing role of STC2 overexpression in radiation resistance and metastasis of NPC has not been established. We hypothesize that stress-induced overexpression of STC2 plays a key role in radiation resistance and metastasis of NPC. This study has two objectives: 1) to define the importance of STC2 overexpression in radiation resistance in NPC; and 2) to determine if targeting STC2 can be explored as a strategy to sensitize NPC to radiation. Radiation resistant CNE2 cell line was used as a model system. CRISPR/Cas9-based genome editing was used to create STC2 knockout lines (CNE2-STC2-KO). The genomic status of KO lines was confirmed by T7E1 assays. The STC2 mRNA and protein levels of parental and KO cell lines were examined using quantitative reverse transcription polymerase chain reaction (PCR) and Western blotting analysis, respectively. NPC cells were radiated with an ELEKTA accelerator (6MVx, Sweden) at distance of 100 cm at 285cGy/min. Cell survival was assayed by flow cytometric analysis, TrypanBlue staining and clonogenic analysis. Cell cycle distribution was analyzed by flow cytometry, and invasion and migration abilities were gauged with Transwell/MatriGel-based assays. SPSS 17.0 was used for statistical analysis, and p<0.05 was set as significant. CRISP/Cas9 construct was made and transfected into CNE2 cells to create CNE2-KO lines. The KO lines were verified at genomic, mRNA and protein levels. Compared with the parental radiation resistant CNE2 line, the STC2-KO lines show increased radiation sensitivity under either normoxic or hypoxic stress. In response to radiation, STC2-KO cells manifest decreased invasion and migration ability. Cell cycle analyses reveal that loss of STC2 significantly increases NPC cells at G2/M phase post radiation, consistent with an enhanced cytotoxicity. These data demonstrate that elevated expression of STC2 under various stress conditions promotes NPC resistance to radiation, facilitates cell survival and metastasis. Targeting STC2 function may provide a novel strategy to effectively overcome radiation resistance and to prevent metastasis of NPC.

Micro-RNA Expression Profiling in Malaysian Triple-Negative Breast Cancer Patients: Impact on Recurrence Prediction

Background: Triple negative breast cancer (TNBC) is characterized by its biologic aggressiveness, worse prognosis and lack of therapeutic targets. Due to high probability of tumor recurrence and also due to lack of available targeted therapies, TNBC patients are treated with standard chemotherapy using TAC [taxane (T), adriamycin (A) and cytoxan (C)] chemotherapy regimen. However, TNBC patients present significant interindividual differences of treatment efficacy. Drug resistance and recurrence remains major clinical obstacles to successful treatment in many TNBC patients. This warrants the need for early identification of TNBC patients who are likely to be chemosensitive and those who have high recurrence risk. TNBC may have specific molecular features that could be possible targets for new biologic targeted drugs. microRNAs (miRNAs) which are aberrantly expressed in tumors, can target and modulate key genes involved in TNBC chemotherapy. Aberrant microRNA expression is strongly implicated in anticancer drug resistance phenotype and hence, miRNAs appear to be promising candidates for response and recurrence prediction. Aim: To investigate the expression profile of few candidate miRNAs (miR-21, miR-27b, miR-34a, miR-182, miR-200c and miR-451) in tumourous and nontumourous tissues in Malaysian TNBC patients and their utility as predictive markers of recurrence in TNBC patients. Methods: Malaysian TNBC patients who had undergone TAC chemotherapy regimen at Hospital Universiti Sains Malaysia were identified and the clinicopathological variables were recorded. Total RNA from cancerous and adjacent noncancerous tissues of FFPE samples from 41 patients were isolated, transcribed and preamplified. The expression of selected miRNAs (miR-21, miR-27b, miR-34a, miR-182, miR-200c and miR-451) were quantified using quantitative real-time PCR (qRT-PCR). The miRNAs expression was categorized into two groups based on upregulation and downregulation. The disease outcome of the patients were evaluated after completion of chemotherapy. Disease-free survival (DFS) analysis using Kaplan-Meier method followed by univariate and multivariate Cox's regression analysis were performed to investigate the impact of these candidate miRNAs on recurrence prediction. Results: The relative expressions of miR-27b and miR-451 were found to be significantly lower in cancerous as compared with normal adjacent tissues of TNBC patients. Multivariate Cox's regression analysis demonstrated that medullary and metaplastic tumor subtypes and positive axillary lymph nodes significantly increased the risk of recurrence in TNBC patients. Downregulated expression of miR-21 and upregulated expression of miR-182 were found to be associated with risk of recurrence in TNBC patients. Conclusion: Tumor subtypes, positive axillary lymph nodes as well as expression profiles of miR-21 and miR-182 could be useful as predictive biomarkers of recurrence in TNBC patients.

Micro-RNA Expression Profiling in Malaysian Triple-Negative Breast Cancer Patients: Impact on Recurrence Prediction

Background: Triple negative breast cancer (TNBC) is characterized by its biologic aggressiveness, worse prognosis and lack of therapeutic targets. Due to high probability of tumor recurrence and also due to lack of available targeted therapies, TNBC patients are treated with standard chemotherapy using TAC [taxane (T), adriamycin (A) and cytoxan (C)] chemotherapy regimen. However, TNBC patients present significant interindividual differences of treatment efficacy. Drug resistance and recurrence remains major clinical obstacles to successful treatment in many TNBC patients. This warrants the need for early identification of TNBC patients who are likely to be chemosensitive and those who have high recurrence risk. TNBC may have specific molecular features that could be possible targets for new biologic targeted drugs. microRNAs (miRNAs) which are aberrantly expressed in tumors, can target and modulate key genes involved in TNBC chemotherapy. Aberrant microRNA expression is strongly implicated in anticancer drug resistance phenotype and hence, miRNAs appear to be promising candidates for response and recurrence prediction. Aim: To investigate the expression profile of few candidate miRNAs (miR-21, miR-27b, miR-34a, miR-182, miR-200c and miR-451) in tumourous and nontumourous tissues in Malaysian TNBC patients and their utility as predictive markers of recurrence in TNBC patients. Methods: Malaysian TNBC patients who had undergone TAC chemotherapy regimen at Hospital Universiti Sains Malaysia were identified and the clinicopathological variables were recorded. Total RNA from cancerous and adjacent noncancerous tissues of FFPE samples from 41 patients were isolated, transcribed and preamplified. The expression of selected miRNAs (miR-21, miR-27b, miR-34a, miR-182, miR-200c and miR-451) were quantified using quantitative real-time PCR (qRT-PCR). The miRNAs expression was categorized into two groups based on upregulation and downregulation. The disease outcome of the patients were evaluated after completion of chemotherapy. Disease-free survival (DFS) analysis using Kaplan-Meier method followed by univariate and multivariate Cox's regression analysis were performed to investigate the impact of these candidate miRNAs on recurrence prediction. Results: The relative expressions of miR-27b and miR-451 were found to be significantly lower in cancerous as compared with normal adjacent tissues of TNBC patients. Multivariate Cox's regression analysis demonstrated that medullary and metaplastic tumor subtypes and positive axillary lymph nodes significantly increased the risk of recurrence in TNBC patients. Downregulated expression of miR-21 and upregulated expression of miR-182 were found to be associated with risk of recurrence in TNBC patients. Conclusion: Tumor subtypes, positive axillary lymph nodes as well as expression profiles of miR-21 and miR-182 could be useful as predictive biomarkers of recurrence in TNBC patients.

Predictores culturales y psicológicos de la búsqueda de ayuda psicológica en estudiantes universitarios

La prevalencia de problemas de salud mental en estudiantes universitarios chilenos, junto con el bajo porcentaje de búsqueda de ayuda psicológica, son preocupantes. Al respecto, se han señalado obstaculizadores culturales, psicológicos y clínicos que inciden en el proceso de búsqueda de ayuda psicológica, sin que exista claridad de cómo impactan en este grupo particular. En la presente investigación se identificaron los factores predictores de la intención de búsqueda de ayuda psicológica en una muestra de 99 estudiantes universitarios de la Universidad Católica de Temuco. Los resultados señalan que los mejores predictores para la intención de búsqueda de ayuda psicológica son las creencias culturales positivas que estos jóvenes sostienen en relación a la psicoterapia y las expectativas que tienen respecto de ésta. Dichos hallazgos ponen de manifiesto que factores culturales como las creencias socialmente compartidas sobre la psicoterapia y factores psicológicos como las expectativas, juegan un rol significativo, lo cual es un insumo relevante a la hora de planificar intervenciones destinadas a aumentar los niveles de búsqueda de ayuda psicológica en este grupo.

Triclosan Is an Aminoglycoside Adjuvant for Eradication of Pseudomonas aeruginosa Biofilms.

One of the most important clinical obstacles in cystic fibrosis (CF) treatment is antibiotic treatment failure due to biofilms produced by Pseudomonas aeruginosa The ability of this pathogen to survive eradication by tobramycin and pathoadapt into a hyperbiofilm state leading to chronic infections is key to its success. Retrospective studies have demonstrated that preventing this pathoadaptation by improving eradication is essential to extend the lives of CF patients. To identify adjuvants that enhance tobramycin eradication of P. aeruginosa, we performed a high-throughput screen of 6,080 compounds from four drug-repurposing libraries. We identified that the Food and Drug Administration (FDA)-approved compound triclosan, in combination with tobramycin, resulted in a 100-fold reduction of viable cells within biofilms at 6 h, but neither compound alone had significant antimicrobial activity against biofilms. This synergistic treatment significantly accelerated the killing of biofilms compared to that with tobramycin treatment alone, and the combination was effective against 6/7 CF clinical isolates compared to tobramycin treatment alone, including a tobramycin-resistant strain. Further, triclosan and tobramycin killed persister cells, causing a 100-fold reduction by 8 h and complete eradication by 24 h. Triclosan also enhances tobramycin killing of multiple Burkholderia cenocepacia and Staphylococcus aureus clinical isolates grown as biofilms. Additionally, triclosan showed synergy with other aminoglycosides, such as gentamicin or streptomycin. Triclosan is a well-tolerated aminoglycoside adjuvant shown to be safe for human use that could improve the treatment of biofilm-based infections.

Clinical and Genomic Insights from Metastatic Cancers.

Most cancer patients who succumb to their disease die from metastatic, or recurrent, cancer. The growth in our knowledge of the genomic underpinnings of cancer has been exponential due to the study of cancer genomes over the past 10 years with next-generation sequencing (NGS) and advanced computational analytics. However, most of these large-scale discovery studies have focused on primary, treatment-naive cancers, as these are commonly diagnosed by use of tumor material from a needle biopsy or resection sample. Hence, the remaining cancer sample can be used for DNA and/or RNA isolation in the primary diagnostic setting. One reason for the relative paucity of metastatic cancer samples is because their surgical removal is not curative, and hence surgery is not performed either to biopsy or remove (“resect”) the tumor. Metastases may develop coincidentally in several different body sites, which makes a surgical intervention implausible as well. Another reason that cancer metastases are not biopsied is because obtaining a biopsy specimen may pose risks to the patient, such as the risk of pneumothorax during needle biopsy of a lung metastasis. Also, the patient may not opt for the biopsy due to the attendant risks, even if insurance will cover the cost of the procedure. Despite these clinical obstacles to studying the genomics of metastatic cancers, a recent study by Robinson et al. has explored 500 metastatic lesions obtained from cancer patients with over 30 different primary cancer diagnoses (1). Using integrative analysis methods, they combined DNA and RNA data from NGS-based clinical assays of the 500 metastatic cancers to derive several types of molecular characterizations. While similar integrative analytical approaches have been performed as “pan-cancer” analyses from primary cancer genomics data sets, such as those from The Cancer Genome Atlas (2), the results of their application to metastatic cancers from patients who …

Kaempferol inhibits angiogenic ability by targeting VEGF receptor-2 and downregulating the PI3K/AKT, MEK and ERK pathways in VEGF-stimulated human umbilical vein endothelial cells.

Anti-angiogenesis is one of the most general clinical obstacles in cancer chemotherapy. Kaempferol is a flavonoid phytochemical found in many fruits and vegetables. Our previous study revealed that kaempferol triggered apoptosis in human umbilical vein endothelial cells (HUVECs) by ROS‑mediated p53/ATM/death receptor signaling. However, the anti‑angiogenic potential of kaempferol remains unclear and its underlying mechanism warranted further exploration in VEGF‑stimulated HUVECs. In the present study, kaempferol significantly reduced VEGF‑stimulated HUVEC viability. Kaempferol treatment also inhibited cell migration, invasion, and tube formation in VEGF‑stimulated HUVECs. VEGF receptor‑2 (VEGFR‑2), and its downstream signaling cascades (such as AKT, mTOR and MEK1/2‑ERK1/2) were reduced as determined by western blotting and kinase activity assay in VEGF‑stimulated HUVECs after treatment with kaempferol. The present study revealed that kaempferol may possess angiogenic inhibition through regulation of VEGF/VEGFR‑2 and its downstream signaling cascades (PI3K/AKT, MEK and ERK) in VEGF-stimulated endothelial cells.