The efficacy, challenges, and facilitators of telemedicine in post-treatment cancer survivorship care: an overview of systematic reviews.

BACKGROUND: Telemedicine services have been increasingly used to facilitate post-treatment cancer survivorship care, including improving access; monitoring health status, health behaviors, and symptom management; enhancing information exchange; and mitigating the costs of care delivery, especially since the COVID-19 pandemic. To inform guidance for the use of telemedicine in the post-COVID era, the aim of this overview of systematic reviews (SRs) was to evaluate the efficacy of, and survivor engagement in, telemedicine interventions in the post-treatment survivorship phase, and to consider implementation barriers and facilitators. METHODS: PubMed, Cochrane CENTRAL, CINAHL, Embase, and Web of Science databases were searched. SRs that examined the use of telemedicine in the post-treatment phase of cancer survivorship, published between January 2010 and April 2021, were included. Efficacy data were synthesized narratively. Implementation barriers and facilitators were synthesized using the Consolidated Framework for Implementation Research. RESULTS: Twenty-nine SRs were included. A substantive body of evidence found telemedicine to benefit the management of psychosocial and physical effects, particularly for improving fatigue and cognitive function. There was a lack of evidence on the use of telemedicine in the prevention and surveillance for recurrences and new cancers as well as management of chronic medical conditions. This overview highlights a range of diverse barriers and facilitators at the patient, health service, and system levels. CONCLUSIONS: This review highlights the benefits of telemedicine in addressing psychosocial and physical effects, but not in other areas of post-treatment cancer survivorship care. This large review provides practical guidance for use of telemedicine in post-treatment survivorship care.

Evidence-based guides in tracheostomy use in critical patients. / Guías basadas en la evidencia para el uso de traqueostomía en el paciente crítico.

OBJECTIVES: Provide evidence based guidelines for tracheostomy in critically ill adult patients and identify areas needing further research. METHODS: A task force composed of representatives of 10 member countries of the Pan-American and Iberic Federation of Societies of Critical and Intensive Therapy Medicine and of the Latin American Critical Care Trial Investigators Network developed recommendations based on the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: The group identified 23 relevant questions among 87 issues that were initially identified. In the initial search, 333 relevant publications were identified of which 226 publications were chosen. The task force generated a total of 19 recommendations: 10 positive (1B=3, 2C=3, 2D=4) and 9 negative (1B=8, 2C=1). A recommendation was not possible in six questions. CONCLUSION: Percutaneous techniques are associated with a lower risk of infections compared to surgical tracheostomy. Early tracheostomy only seems to reduce the duration of ventilator use but not the incidence of pneumonia, the length of stay, or the long-term mortality rate. The evidence does not support the use of routine bronchoscopy guidance or laryngeal masks during the procedure. Finally, proper prior training is as important or even a more significant factor in reducing complications than the technique used.

EGFR inhibitors augment antitumour helper T-cell responses of HER family-specific immunotherapy.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a major cause of cancer-related morbidity and mortality worldwide. Epidermal growth factor receptor (EGFR)-targeted therapy is an attractive strategy alternative to conventional cancer treatments for HNSCC, but its efficacy remains controversial. T-cell-based immunotherapy has been proposed as a novel therapeutic approach to improve the clinical outcome for HNSCC. In this study, we report human epidermal receptor (HER) family epitopes that induced CD4 T-cell responses to HNSCC. The results provide support for a novel strategy to treat HNSCC by combining EGFR-targeted therapy with T-cell-based immunotherapy. METHODS: We evaluated the capacity of predicted CD4 T-cell peptide epitopes from EGFR to induce antitumour immune responses in vitro. In addition, EGFR inhibitors were evaluated for their ability to augment tumour MHC class II expression in HNSCC cell lines and subsequently increase T-cell recognition. RESULTS: Among several predicted peptide epitopes, EGFR875-889 elicited CD4 T-cell responses that were restricted by HLA-DR4, DR15, or DR53 molecules, indicating that the peptide functions as a promiscuous T-cell epitope. The peptide-reactive T cells responded to autologous dendritic cells loaded with EGFR-expressing tumour cell lysates, indicating that these epitopes are naturally processed. In addition, the CD4 T cells were capable of directly recognising and killing HNSCC cells expressing EGFR and the appropriate HLA class II molecule. T cells reactive with the EGFR875-889 epitope could be detected in the blood of HNSCC patients. EGFR875-889-reactive CD4 T cells were also able to recognise several peptide analogues derived from homologous regions of EGFR family members, HER-2, HER-3 and c-MET. Finally, we examined the effects of EGFR tyrosine kinase inhibition or EGFR-blocking antibodies on CD4 T-cell tumour reactivity. Treatment of tumour cells with the EGFR inhibitors enhanced tumour recognition by EGFR875-889-reactive T cells presumably due to the upregulation of HLA-DR expression in the HNSCC cells. CONCLUSION: We identified novel CD4 T-cell EGFR epitopes and amongst these, EGFR875-889 functions as a promiscuous helper T-cell epitope that can elicit effective antitumour T-cell responses against tumours expressing HER family members and c-MET. These observations should facilitate the translation of T-cell-based immunotherapy into the clinic for the treatment of HNSCC and provide a rational basis for EGFR inhibition, immune-targeted combination therapy.

Evaluation of Lama glama semen viscosity with a cone-plate rotational viscometer.

Llama semen is highly viscous. This characteristic is usually evaluated subjectively by measuring the thread formed when carefully pippeting a sample of semen. The aims of this study were (i) to objectively determine and analyse llama semen viscosity, (ii) to compare semen viscosity between ejaculates of the same male as well as between different males, (iii) to study the correlation between viscosity and other semen characteristics and (iv) to evaluate the effect of collagenase on semen viscosity. Semen viscosity was evaluated using a cone-plate Brookfield rotational viscometer. A non Newtonian, pseudoplastic behaviour was observed in the 45 semen samples evaluated. Rheological parameters were determined obtaining the following results (mean ± SD): apparent viscosity at 11.5 s(-1): 46.71 ± 26.8 cpoise and at 115 s(-1): 12.61 ± 4.1 cpoise; structural viscosity (K) (dyne s cm(-2)): 2.18 ± 1.4 and coefficient of consistency (n): 0.45 ± 0.1. Statistical differences were found between different ejaculates of the same male for structural viscosity and apparent viscosity at 11.5 s(-1) (P < 0.01). Correlation was found only between coefficient of consistency (n) and sperm concentration (P < 0.01). Significant differences for coefficient of consistency (n) and viscosity at 115 s(-1) were found between samples incubated with and without collagenase (P < 0.05).

The role of polymorphic HLA-DR beta chain residues in presentation of viral antigens to T cells.

The relative importance of 11 polymorphic positions in the HLA-DR7 beta 1 chain in T cell recognition of foreign antigens was investigated using transfectants expressing mutant DR7 beta 1 chains as APC for five rabies virus-specific T cell clones. The results indicate that multiple amino acids, located in both the beta-strands and alpha-helix of DR7 beta 1 in the model of a class II molecule, are involved in DR7-restricted T cell recognition of these antigens. Many of the substitutions appeared to reduce the affinity of an antigenic peptide for the mutant DR7 molecules but did not prevent binding. The heterogeneity of responses of the three G-specific T cell clones to presentation of the G11.3 peptide by several of the mutant DR7 molecules indicates that the T cell receptor (TCR) of each these clones requires a different view of the G11.3/DR7 complex and raises the possibility that the G11.3 peptide may bind to the DR7 molecule in more than one conformation.

Antibodies to hepatitis B surface antigen potentiate the response of human T lymphocyte clones to the same antigen.

Human t-helper lymphocyte clones specific for hepatitis B virus surface antigen (HBsAg) proliferate on stimulation with HBsAg in vitro. Antibodies specific for HBsAg, but no other antibodies, augment this proliferative response. In the presence of antibodies to HBsAg, the maximum response could be achieved at HBsAg concentrations that were 1 percent of those required in the absence of the antibodies. These findings suggest that antigen-specific antibodies exert regulatory controls on T cells that recognize the same antigens.

Perceptions of aging and ageism among Mexican physicians-in-training.

INTRODUCTION: Attributing negative stereotypes to older adults (ageism) may lead to undertreatment, but little is known about the prevalence of ageism among physicians treating patients with cancer in Ibero-America. We studied stereotypes of aging among Mexican physicians-in-training. MATERIALS AND METHODS: Physicians-in-training attending an oncology meeting answered the "Negative Attributes and Positive Potential in Old Age" survey. Ten questions assessed positive characteristics of aging (PPOA; score 1-4, higher scores represent a positive perception), and four assessed negative characteristics (NAOA; score 1-4, higher score representing a negative perception). Descriptive statistics were used to analyze the questionnaires. Participants completed the "Image-of-Aging" question by writing five words describing older adults and young individuals. Each word was rated from - 5 (negative) to + 5 (positive), and presented as word clouds. RESULTS: One hundred physicians-in-training (median age 28.5) were included. For the PPOA scale, the mean score was 2.9 (SD 0.4), while for the NAOA scale it was 2.1 (SD 0.4). Perceptions of aging were better among women and trainees enrolled in geriatrics and/or oncology-related programs. In the "Image-of-Aging" questions, median rating of words describing older adults was - 2, compared to + 3 for young individuals (p < 0.001). Among words used to describe older adults, the most frequent was "frail/frailty" (n = 45), while "health" (n = 46) was the most frequent for younger individuals. CONCLUSIONS: Mexican physicians-in-training showed mostly negative perceptions of aging, exemplified by the use of negative terms to describe older adults. Creating educational initiatives aimed at decreasing ageism among oncology trainees is necessary across Ibero-America.

Chlorthalidone inhibits the KvLQT1 potassium current in guinea-pig ventricular myocytes and oocytes from Xenopus laevis.

BACKGROUND AND PURPOSE: Chlorthalidone is used for the treatment of hypertension as it produces a lengthening of the cardiac action potential. However, there is no experimental evidence that chlorthalidone has electrophysiological effects on the potassium currents involved in cardiac repolarization. EXPERIMENTAL APPROACH: Ventricular myocytes and oocytes, transfected with human ionic channels that produce IK current, were exposed to different concentrations of chlorthalidone. Action potentials and potassium currents were recorded using a patch clamp technique. To determine which component of the current was affected by chlorthalidone, human channel proteins (hERG, minK and KvLQT1) were used. KEY RESULTS: Chlorthalidone prolonged the ventricular action potential at 50 and 90% by 13 and 14%, respectively. The cardiac potassium currents I(to) and IK(1) were not affected by chlorthalidone at any concentration, whereas the delayed rectifier potassium current, IK, was blocked in a dose-response, voltage-independent fashion. In our preparation, 100 microM chlorthalidone blocked the two components of the delayed rectifier potassium current with the same potency (50.1+/-5% for IK(r) and 54.6+/-6% for IK(s)) (n=7, P<0.05). The chlorthalidone-sensitive current was slow and saturated at potentials greater than +30 mV. In our conditions only the KvLQT1 potassium current was affected by the drug, by 14%. CONCLUSIONS AND IMPLICATIONS: Chlorthalidone was demonstrated to have a direct effect on cardiac ventricular myocytes; it blocked the delayed rectifier potassium current (IK), specifically the KvLQT1 component of the potassium current. These results indicate that it has potential for use as an antiarrhythmic but further studies are needed.

Laser induced breakdown spectroscopy as a tool for discrimination of glass for forensic applications.

Materials analysis and characterization can provide important information as evidence in legal proceedings. The potential of laser induced breakdown spectroscopy (LIBS) for the discrimination of glass fragments for forensic applications is presented here. The proposed method is based on the fact that glass materials can be characterized by their unique spectral fingerprint. Taking advantage of the multielement detection capability and minimal to no sample preparation of LIBS, we compared glass spectra from car windows using linear and rank correlation methods. Linear correlation combined with the use of a spectral mask, which eliminates some high-intensity emission lines from the major elements present in glass, provides effective identification and discrimination at a 95% confidence level.

Biodegradation of agricultural herbicides in sequencing batch reactors under aerobic or anaerobic conditions.

This study investigated the biodegradability of the herbicides isoproturon and 2,4-dichlorophenoxyacetic acid (2,4-D) in sequencing batch reactors (SBRs). Two laboratory-scale (2L liquid volume) SBRs were employed: one reactor performing under aerobic and the other under anaerobic conditions. The aerobic SBR was operated at an ambient temperature (22+/-2 degrees C), while the anaerobic SBR was run in the lower mesophilic range (30+/-2 degrees C). Each bioreactor was seeded with a 3:1 mixture (by weight) of fresh sludge and biomass that had been previously exposed to both herbicides. The effect of herbicide concentration on either treatment process was explored at a hydraulic retention time (HRT) of 48 h, using glucose as a supplemental carbon substrate. Although no isoproturon degradation was observed in either system during the study, complete 2,4-D removal occurred after an acclimation period of approximately 30 d (aerobic SBR) and 70 d (anaerobic SBR). The aerobic reactor achieved complete 2,4-D utilization at feed concentrations up to 500 mg/L. A further increase to 700 mg/L, however, proved to be inhibitory since 2,4-D biodegradation was negligible. On the other hand, the anaerobic SBR was able to degrade 120 mg/L of 2,4-D, which corresponds to 40% of the maximum feed concentration applied. Moreover, glucose was consumed first throughout the experiment in a sequential utilization pattern relating to 2,4-D, with biodegradation of both substrates following closely first-order kinetics.

The Royal Philanthropic Expedition of the Vaccine: a landmark in the history of public health.

In 1979, smallpox officially became the first disease ever to be eradicated by mankind. The global efforts to defeat this dreadful pandemic, however, started almost two centuries before. One of the most important, and sometimes forgotten, events in the fight against smallpox was the Royal Philanthropic Expedition of the Vaccine, commissioned by Charles IV of Spain to physicians Francisco Xavier Balmis y Berenguer and Jose Salvany in 1804. The aim of this expedition was to take the smallpox vaccine, discovered by Jenner, to Spain's territories in the Americas and in the Far East. After several years of vaccination in modern day Puerto Rico, Cuba, Venezuela, Ecuador, Peru, Bolivia, Chile, Mexico and the Philippines, the expedition returned to Europe. To this day, the Balmis and Salvany expedition remains a great example of international cooperation, and a landmark in the history of public health.

In vitro effect of aluminium upon erythrocyte membrane properties.

The link between aluminium (Al(III)) and a range of disorders in organisms (plants and animals including human beings) has been stated in diverse studies. As regards as human beings in particular, there are numerous studies on this metal's toxicity in relation to pathological processes. Only few references to the metal's effect upon cell rheological properties can be found. In this study, we present evidence for alterations in the rheological properties of cells as consequence of the Al(III)'s interaction with human red blood cell membrane. Al(III) could damage membrane functions of the red blood cell by favouring lipid peroxidation reactions due to the presence of Fe(II) as an initiator. The metal's effect on lipid bilayer, and probably on the cytoskeleton as well, would constitute the cause for the impaired erythrocyte rheology.

Cancer and aging in Ibero-America.

Population aging represents a worldwide challenge. In Ibero-America (Spain, Portugal, and the American countries in which the Spanish or Portuguese language are spoken), the number of older adults is growing, leading to an increase in aging-related diseases such as cancer. Older adults already account for half of all cancer cases in Ibero-America, and this proportion will continue to increase. Furthermore, Ibero-American healthcare systems are not adequately prepared to provide care for older adults with cancer, mainly due to a lack of resources and generalized paucity of geriatric training for healthcare providers. Across the region, several clinical initiatives, educational activities and research collaborations have been established to set the foundations of Ibero-American geriatric oncology and to increase the geriatric knowledge among healthcare providers. This article provides an overview of the current landscape of geriatric oncology in Ibero-America, highlighting its critical challenges, opportunities for improvement and collaboration, and future directions.

Nitric oxide increases in the rat retina after continuous illumination.

Continuous illumination (CI) of the retina induces an oxidative stress followed by the degeneration of photoreceptors. This phenomenon may be partially related to the excessive production of nitric oxide (NO). In order to confirm this hypothesis, the aims of this work are to determine NO levels during the illumination of the retina by electron paramagnetic resonance (EPR), and if an increase of NO is found, to characterize the NOS isoform responsible of the increment by using Western blot. Sprague-Dawley rats were continuously illuminated with white light (12,000 lux) for 2, 24, 48 h, 5 and 7 days while control rats were maintained at light/dark cycles of 12/12 h. Using EPR, an increase of NO signal was observed in the light exposed retinas peaking at 24 h of CI. Western blot analysis showed the expression of iNOS in the illuminated retinas with a peak after 24 h of CI, but did not show significant differences of nNOS among illuminated and control retinas. In summary, there is an increase of NO during CI. Further studies will reveal whether this mechanism is responsible for light induced photoreceptor degeneration.

Real world patterns of care in HER2-overexpressing breast cancer: Results of a survey of TEACH clinical trial investigators in 2011.

BACKGROUND: HER2-overexpressing breast cancer (BC) is common among young patients and poses a public health burden. Adjuvant anti-HER2/neu therapy with trastuzumab reduces the risk of recurrence and improves survival. METHODS: A web-based survey was sent to 386 physicians of the "TEACH" trial in 2011 to determine access to HER2/neu testing and treatment patterns for HER2-overexpressing BC. RESULTS: There were 151 responders (39%) from 28 countries. Ninety-seven percent reported HER2/neu expression is routinely measured in their institutions by immunohistochemistry (85%), FISH (80%) and other methods (16%). Twenty percent of responders from Asia reported that the test was not routinely available. Forty-eight percent of participants reported instances when adjuvant HER2-directed therapy was recommended to a patient who eventually did not receive it. Reasons for not receiving trastuzumab was cost (73%, p < 0.0001) in low- and middle-income countries and co-morbidities in high-income countries (43%, p = 0.003). CONCLUSIONS: This survey reflects the availability of HER2/neu testing and anti-HER2/neu therapy among physicians who participated in TEACH. A high proportion of women with HER2-overexpressing BC may not receive standard adjuvant therapy due to unavailability of the test and cost of therapy. Despite having some limitations, such as a possible selection bias of participating physicians, variable definitions of access to healthcare among respondents, and changes in trastuzumab availability since 2011, our results demonstrate that access to care and region of practice impact the implementation of cancer treatments.

Isolation, purification, and characterization of a mouse plasmacytoma cell surface glycoprotein involved in the resistance of the tumor cells to immune destruction.

Cells of a subline of the mouse plasmacytoma LPC-1 are resistant to lysis by cytotoxic T-lymphocytes, probably as a result of the blocking of the major histocompatibility gene complex-encoded cell surface antigens by a trypsin-sensitive glycoprotein of approximately 160 kilodaltons. This glycoprotein (gp 160) was extracted from LPC-1 cells with 1.5 M urea and was further purified by ammonium sulfate precipitation and Sephacryl S-300 gel filtration. The gp 160 consists of a single peptide chain rich in sialic acid residues (10% of total molecular weight) and has an acidic isoelectric point. The amino acid composition of gp 160 is compatible with the linkage of carbohydrates (galactose, glucosamine, and sialic acid) to the protein portion. The apparent weak attachment of gp 160 to the cell membrane could explain the finding that LPC-1 cells easily revert from the resistant to the sensitive to the immune lysis phenotype.

Use of two predictive algorithms of the world wide web for the identification of tumor-reactive T-cell epitopes.

Tumor cells can be effectively recognized and eliminated by CTLs. One approach for the development of CTL-based cancer immunotherapy for solid tumors requires the use of the appropriate immunogenic peptide epitopes that are derived from defined tumor-associated antigens. Because CTL peptide epitopes are restricted to specific MHC alleles, to design immune therapies for the general population it is necessary to identify epitopes for the most commonly found human MHC alleles. The identification of such epitopes has been based on MHC-peptide-binding assays that are costly and labor-intensive. We report here the use of two computer-based prediction algorithms, which are readily available in the public domain (Internet), to identify HL4-B7-restricted CTL epitopes for carcinoembryonic antigen (CEA). These algorithms identified three candidate peptides that we studied for their capacity to induce CTL responses in vitro using lymphocytes from HLA-B7+ normal blood donors. The results show that one of these peptides, CEA9(632) (IPQQHTQVL) was efficient in the induction of primary CTL responses when dendritic cells were used as antigen-presenting cells. These CTLs were efficient in killing tumor cells that express HLA-B7 and produce CEA. The identification of this HLA-B7-restricted CTL epitope will be useful for the design of ethnically unbiased, widely applicable immunotherapies for common solid epithelial tumors expressing CEA. Moreover, our strategy of identifying MHC class I-restricted CTL epitopes without the need of peptide/HLA-binding assays provides a convenient and cost-saving alternative approach to previous methods.

Identification of helper T-cell epitopes that encompass or lie proximal to cytotoxic T-cell epitopes in the gp100 melanoma tumor antigen.

The melanocyte-associated antigen gp100 constitutes one of the most attractive targets for T-cell-based immunotherapy against malignant melanoma. Although several MHC class I-restricted epitopes have been identified for CTLs, thus far, only one MHC class II T helper epitope (restricted by HLA-DR4) has been described in the literature. Using an algorithm to identify promiscuous helper T-cell epitopes, here we describe three additional MHC class II-restricted epitopes from gp100. Whereas one T helper epitope, gp100(175-189), was restricted by the HLA-DR53 and DQw6 alleles, the T-cell responses to two other epitopes, gp100(74-89) and gp100(576-590), were restricted by HLA-DR7. Most interestingly, the newly identified helper T lymphocyte epitopes encompass or lie proximal to previously described CTL epitopes for this tumor-associated antigen. Together with the previously described HLA-DR4-restricted epitope, these T helper epitopes offer coverage for the majority of the human population. Moreover, the use of peptide vaccines containing both CTLs and T helper epitopes could offer therapeutic advantages over current approaches that focus solely on eliciting antitumor CTL responses.