The skinny on skin: The role of skin-aware professionals in skin cancer surveillance.

BACKGROUND: Licensed nonmedical, skin-aware professionals (e.g., hairdressers, massage therapists, etc.) have the potential to identify skin cancer, but baseline knowledge may not be sufficient to accomplish this goal. Following educational intervention, self-efficacy is one of the best surrogate metrics for behavior change. Curricula that increase knowledge and confidence levels can improve screening behaviors, but few have been tested for efficacy in this population AIMS: We assessed whether an online curriculum could reliably improve skin screening knowledge, attitudes, and behaviors of nonmedical professionals PATIENTS/METHODS: Skin-aware professionals were recruited through the Oregon Health Authority and IMPACT Melanoma TM. Participants completed a pre-survey, online training module, post-survey, and one-year follow-up survey. We evaluated participants' indicated levels of concern for suspicious and nonsuspicious lesions relative to "gold standard" physician ratings. We also assessed confidence and self-reported behavior change regarding talking to clients about skin cancer and recommending they see a provider to evaluate suspicious lesions RESULTS: The pre-survey was completed by 9872 skin-aware professionals; 5434 completed the post-survey, and 162 completed the one-year follow-up survey. Participants showed a significant improvement in ability to indicate the correct level of concern for all lesion types in concordance with "gold standard" physician ratings (p < 0.001). Participants reported increased comfort levels in discussing health-related topics with their clients posttraining CONCLUSIONS: Our training module effectively increased skin-aware professionals' knowledge, confidence, and concern for malignant lesions. Skin-aware professionals may serve as a valuable extension of the skin self-exam, but additional studies are needed to evaluate the impact of these curricula long-term, including potential downstream consequences.

Oligodendrocyte-specific expression of PSG8-AS1 suggests a role in myelination with prognostic value in oligodendroglioma.

The segmentally duplicated Pregnancy-specific glycoprotein (PSG) locus on chromosome 19q13 may be one of the most rapidly evolving in the human genome. It comprises ten coding genes (PSG1-9, 11) and one predominantly non-coding gene (PSG10) that are expressed in the placenta and gut, in addition to several poorly characterized long non-coding RNAs. We report that long non-coding RNA PSG8-AS1 has an oligodendrocyte-specific expression pattern and is co-expressed with genes encoding key myelin constituents. PSG8-AS1 exhibits two peaks of expression during human brain development coinciding with the most active periods of oligodendrogenesis and myelination. PSG8-AS1 orthologs were found in the genomes of several primates but significant expression was found only in the human, suggesting a recent evolutionary origin of its proposed role in myelination. Additionally, because co-deletion of chromosomes 1p/19q is a genomic marker of oligodendroglioma, expression of PSG8-AS1 was examined in these tumors. PSG8-AS1 may be a promising diagnostic biomarker for glioma, with prognostic value in oligodendroglioma.

Multifunctionalized Carbon Dots as an Active Nanocarrier for Drug Delivery to the Glioblastoma Cell Line.

Nanoparticle-based nanocarriers represent a viable alternative to conventional direct administration in cancer cells. This advanced approach employs the use of nanotechnology to transport therapeutic agents directly to cancer cells, thereby reducing the risk of damage to healthy cells and enhancing the efficacy of treatment. By approving nanoparticle-based nanocarriers, the potential for targeted, effective treatment is greatly increased. The so-called carbon-based nanoparticles, or carbon dots, have been hydrothermally prepared and initiated by a polymerization process. We synthesized and characterized nanoparticles of 2-acrylamido-2-methylpropanesulfonic acid, which showed biocompatibility with glioblastoma cells, and further, we tested them as a carrier for the drug riluzole. The obtained nanoparticles have been extensively characterized by techniques to obtain the exact composition of their surface by using Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), and nuclear magnetic resonance (NMR) spectroscopy, as well as cryo-transmission electron microscopy. We found that the surface of the synthesized nanoparticles (NPs) is covered mainly by sulfonated, carboxylic, and substituted amide groups. These functional groups make them suitable as carriers for drug delivery in cancer cells. Specifically, we have successfully utilized the NPs as a delivery system for the drug riluzole, which has shown efficacy in treating glioblastoma cancer cells. The effect of nanoparticles as carriers for the riluzole system on glioblastoma cells was studied using live-cell synchrotron-based FTIR microspectroscopy to monitor in situ biochemical changes. After applying nanoparticles as nanocarriers, we have observed changes in all biomacromolecules, including the nucleic acids and protein conformation. These findings provide a strong foundation for further exploration into the development of targeted treatments for glioblastoma.

Efficient and scalable gene delivery method with easily generated cationic carbon dots.

Gene delivery is a complex process with several challenges when attempting to incorporate genetic material efficiently and safely into target cells. Some of the key challenges include not only efficient cellular uptake and endosomal escape to ensure that the genetic material can exert its effect but also minimizing the toxicity of the delivery system, which is vital for safe gene delivery. Of importance, if gene delivery systems are intended for biomedical applications or clinical use, they must be scalable and easy and affordable to manufacture to meet the demand. Here, we show an efficient gene delivery method using a combination of carbon dots coated by PEI through electrostatic binding to easily generate cationic carbon dots. We show a biofunctional approach to generate optimal cationic carbon dots (CCDs) that can be scaled up to meet specific transfection demands. CCDs improve cell viability and increase transfection efficiency four times over the standard of PEI polyplexes. Generated CCDs enabled the challenging transfection protocol to produce retroviral vectors via cell cotransfection of three different plasmids into packing cells, showing not only high efficiency but also functionality of the gene delivery, tested as the capacity to produce infective retroviral particles.

The Accuracy and Absolute Reliability of a Knee Surgery Assistance System Based on ArUco-Type Sensors.

Recent advances allow the use of Augmented Reality (AR) for many medical procedures. AR via optical navigators to aid various knee surgery techniques (e.g., femoral and tibial osteotomies, ligament reconstructions or menisci transplants) is becoming increasingly frequent. Accuracy in these procedures is essential, but evaluations of this technology still need to be made. Our study aimed to evaluate the system's accuracy using an in vitro protocol. We hypothesised that the system's accuracy was equal to or less than 1 mm and 1° for distance and angular measurements, respectively. Our research was an in vitro laboratory with a 316 L steel model. Absolute reliability was assessed according to the Hopkins criteria by seven independent evaluators. Each observer measured the thirty palpation points and the trademarks to acquire direct angular measurements on three occasions separated by at least two weeks. The system's accuracy in assessing distances had a mean error of 1.203 mm and an uncertainty of 2.062, and for the angular values, a mean error of 0.778° and an uncertainty of 1.438. The intraclass correlation coefficient was for all intra-observer and inter-observers, almost perfect or perfect. The mean error for the distance's determination was statistically larger than 1 mm (1.203 mm) but with a trivial effect size. The mean error assessing angular values was statistically less than 1°. Our results are similar to those published by other authors in accuracy analyses of AR systems.

External validation of the Melanoma Institute Australia Sentinel Node Metastasis Risk Prediction Tool using the National Cancer Database.

BACKGROUND: To improve patient selection for sentinel node (SN) biopsy, the Melanoma Institute of Australia (MIA) created a predictive model based on readily available clinicopathologic factors. OBJECTIVES: Validation of the MIA nomogram using the National Cancer Database (NCDB), a nationwide oncology outcomes database for >1500 Commission-accredited cancer programs in the United States. METHODS: A total of 60,165 patients were included in the validation. The probability of SN positivity was calculated for each patient. Using calculated probabilities, a receiver operating characteristic curve was generated to assess the model's discrimination ability. RESULTS: At baseline, the NCDB cohort had different clinicopathologic characteristics compared with the original MIA data set. Despite these differences, the MIA nomogram retained high-predictive accuracy within the NCDB dataset (C-statistic, 0.733 [95% CI, 0.726-0.739]), although calibration weakened for the highest risk decile. LIMITATIONS: The NCDB collects data from hospital registries accredited by the Commission on Cancer. CONCLUSIONS: In conclusion, this study validated the use of the MIA nomogram in a nationwide oncology outcomes database collected from >1500 Commission-accredited cancer programs in the United States, demonstrating the potential for this nomogram to predict SN positivity and reduce the number of negative SN biopsies.

Quality of Life in Women after Deep Endometriosis Surgery: Comparison with Spanish Standardized Values.

The quality of life (QoL) of women who have been surgically treated for endometriosis may be severely impaired. Therefore, QoL can be a determining factor in the recovery of these patients. The aims of this study were to evaluate if the QoL of women surgically treated for deep endometriosis differs from a healthy age-matched population from Catalonia (Spain) and to analyze the QoL of these women considering concomitant events. This is an observational cross-sectional study, where 112 women (between 18 and 48 years old), with endometriosis treated by surgery at Hospital Universitario La Paz (Madrid, Spain), were enrolled to assess the QoL using the second version of the 12-item short form (SF-12) questionnaire. The QoL in these women were tested against a reference population of healthy women using a standardized one-sample comparison method. In addition, the QoL was compared according to the pathophysiology and type of surgery. In women with endometriosis, the physical health component, but not mental health component, was positively correlated with age (r = 0.19; p-Value = 0.048). In addition, physical (20.3 ± 29.2) and social functions (29.7 ± 38.3) and the overall physical health component (37.8 ± 19.4) were significantly lower than the reference population. On the contrary, the body pain (64.1 ± 41.2), emotional role (62.5 ± 42.2), mental health (54.4 ± 26.0), vitality (59.3 ± 31.2), and the overall mental health component (59.4 ± 26.6) had significantly higher scores than the reference. The anatomical compartment of endometriosis, reintervention, bowel nodule resection, and fertility preservation did not show statistical differences in QoL. Women with deep endometriosis had worse physical and social functions, and the overall physical health, compared to the norm in Spanish women. Bodily pain, emotional role, vitality, and the overall mental health improved. These areas could be considered protective factors in this disease. Considering the importance of QoL in adjustments in mental and physical health, it would be necessary to improve these areas of QoL in women surgically treated for deep endometriosis.

Modeling chronic cervical spinal cord injury in aged rats for cell therapy studies.

With an expanding elderly population, an increasing number of older adults will experience spinal cord injury (SCI) and might be candidates for cell-based therapies, yet there is a paucity of research in this age group. The objective of the present study was to analyze how aged rats tolerate behavioral testing, surgical procedures, post-operative complications, intra-spinal cell transplantation and immunosuppression, and to examine the effectiveness of human iPSC-derived Neural Progenitor Cells (IMR90-hiPSC-NPCs) in a model of SCI. We performed behavioral tests in rats before and after inducing cervical hemi-contusions at C4 level with a fourth-generation Ohio State University Injury Device. Four weeks later, we injected IMR90-hiPSC-NPCs in animals that were immunosuppressed by daily cyclosporine injection. Four weeks after injection we analyzed locomotor behavior and mortality, and histologically assessed the survival of transplanted human NPCs. As rats aged, their success at completing behavioral tests decreased. In addition, we observed high mortality rates during behavioral training (41.2%), after cervical injury (63.2%) and after cell injection (50%). Histological analysis revealed that injected cells survived and remained at and around the grafted site and did not cause tumors. No locomotor improvement was observed in animals four weeks after IMR90-hiPSC-NPC transplantation. Our results show that elderly rats are highly vulnerable to interventions, and thus large groups of animals must be initially established to study the potential efficacy of cell-based therapies in age-related chronic myelopathies.

Oromucosal immunomodulation as clinical spectrum mitigating factor in SARS-CoV-2 infection.

Mounting evidence supports the importance of mucosal immunity in the immune response to SARS-CoV-2. Active virus replication in the upper respiratory tract for the first days of infection opens a new perspective in immunological strategies to counteract viral pathogenicity. An effective mucosal innate immune response to SARS-CoV-2 paves the way to an also effective adaptive immune response. A strong local immune response seems to be crucial in the initial contention of the virus by the organism and for triggering the production of the necessary neutralizing antibodies in sera and mucosal secretions. However, if the innate immune response fails to overcome the immune evasion mechanisms displayed by the virus, the infection will progress and the lack of an adaptive immune response will take the patient to an overreactive but ineffective innate immune response. To revert this scenario, an immune strategy based on enhancement of immunity in the first days of infection would be theoretically well come. But serious concerns about cytokine response syndrome prevent us to do so. Fortunately, it is possible to enhance immune system response without causing inflammation through immunomodulation. Immunomodulation of local immune response at the oropharyngeal mucosa could hypothetically activate our mucosal immunity, which could send an early an effective warning to the adaptive immune system. There are studies on immunotherapeutic management of upper respiratory tract infections in children that can place us in the right path to design an immune strategy able to mitigate COVID-19 symptoms and reduce clinical progression.

Neoadjuvant treatment for locally advanced unresectable and borderline resectable pancreatic cancer: oncological outcomes at a single academic centre.

INTRODUCTION: Pancreatic cancer (PC), even in the absence of metastatic disease, has a dismal prognosis. One-third of them are borderline resectable (BRPC) or locally advanced unresectable PC (LAUPC) at diagnosis. There are limited prospective data supporting the best approach on these tumours. Neoadjuvant chemotherapy (ChT) is being increasingly used in this setting. METHODS: This is a retrospective series of consecutive patients staged as BRPC or LAUPC after discussion in the multidisciplinary board (MDB) at an academic centre. All received neoadjuvant ChT, followed by chemoradiation (ChRT) in some cases, and those achieving enough downstaging had a curative-intent surgery. Descriptive data about patient's characteristics, neoadjuvant treatments, toxicities, curative resections, postoperative complications, pathology reports and adjuvant treatment were collected. Overall survival (OS) and progression-free survival was calculated with Kaplan-Meier method and log-rank test. RESULTS: Between August 2011 and July 2019, 49 patients fulfilled the inclusion criteria, and all of them received neoadjuvant ChT. Fluorouracil+folinic acid, irinotecan and oxaliplatin was the most frequently used scheme (77%). The most prevalent grade 3 or 4 toxicities were neutropenia (26.5%), neurotoxicity (12.2%), diarrhoea (8.2%) and nausea (8.2%). 18 patients (36.7%) received ChRT thereafter. In total, 22 patients (44,9%) became potentially resectable and 19 of them had an R0 or R1 pancreatic resection. One was found to be unresectable at surgery and two refused surgery. A vascular resection was required in 7 (35%). No postoperative deaths were observed. Postoperative ChT was given to 12 (66.7%) of resected patients. Median OS of the whole cohort was 24,9 months (95% CI 14.1 to 35.7), with 30.6 months for resected and 13.1 months for non-resected patients, respectively (p<0.001). CONCLUSION: A neoadjuvant approach in BRPC and LAUPC was well tolerated and allowed a curative resection in 38.8% of them with a potential improvement on OS.

Retrieval of germinal zone neural stem cells from the cerebrospinal fluid of premature infants with intraventricular hemorrhage.

Intraventricular hemorrhage is a common cause of morbidity and mortality in premature infants. The rupture of the germinal zone into the ventricles entails loss of neural stem cells and disturbs the normal cytoarchitecture of the region, compromising late neurogliogenesis. Here we demonstrate that neural stem cells can be easily and robustly isolated from the hemorrhagic cerebrospinal fluid obtained during therapeutic neuroendoscopic lavage in preterm infants with severe intraventricular hemorrhage. Our analyses demonstrate that these neural stem cells, although similar to human fetal cell lines, display distinctive hallmarks related to their regional and developmental origin in the germinal zone of the ventral forebrain, the ganglionic eminences that give rise to interneurons and oligodendrocytes. These cells can be expanded, cryopreserved, and differentiated in vitro and in vivo in the brain of nude mice and show no sign of tumoral transformation 6 months after transplantation. This novel class of neural stem cells poses no ethical concerns, as the fluid is usually discarded, and could be useful for the development of an autologous therapy for preterm infants, aiming to restore late neurogliogenesis and attenuate neurocognitive deficits. Furthermore, these cells represent a valuable tool for the study of the final stages of human brain development and germinal zone biology.

Impact of type and severity of postoperative complications on long-term outcomes after colorectal liver metastases resection.

BACKGROUND AND OBJECTIVES: Postoperative complications (POCs) after hepatic resection for colorectal liver metastases (CRLM) adversely affect long-term survival. The aim of this study was to analyze the effect of POC etiology and severity on overall survival (OS) and disease-free survival (DFS). METHODS: A retrospective study of 254 consecutive hepatectomies for CRLM was performed. Univariate and multivariate analyses were performed to determine the effects of demographic, tumor-related and perioperative variables on OS and DFS. A 1:1 propensity score matching (PSM) was then used to compare patients with different POC etiology: infective (Inf-POC), noninfective (Non-inf POC), and no-complications (No-POC). RESULTS: Inf-POC, Non-inf POC, and No-POC patients represented 18.8%, 19.2%, and 62% of the sample, respectively. In univariate and multivariate analyses infectious POC were independent risk factors for decreased OS and DFS. After PSM, Inf-POC group presented decreased OS and DFS when compared with Non-inf POC (5-year OS 31.8% vs 51.6%; P = .05 and 5-year DFS 13.6% vs 31.9%; P = .04) and with No-POC (5-year OS 29.4% vs 58.7%; P = .03 and 5-year DFS 11.8% vs 39.7%; P = .03). There were no differences between Non-inf POC and No-POC patients. POC severity calculated using the Comprehensive Complications Index did not influence OS and DFS before and after PSM. CONCLUSION: The negative oncological impact of POCs after CRLM resection is determined by infective etiology not by severity.

Impact of Postoperative Complications on Survival and Recurrence After Resection of Colorectal Liver Metastases: Systematic Review and Meta-analysis.

OBJECTIVE: To study the effect of postoperative complications (POC) on overall survival (OS) and disease-free survival (DFS) after surgical resection of colorectal liver metastases (CRLM). SUMMARY BACKGROUND DATA: Morbidity rates after liver resection can reach 45%. The negative impact of POC on oncologic outcomes has been reported in various types of cancer, especially colorectal. However, data on the consequences of POC after CRLM resection on long-term survival are scarce. METHODS: Eligible studies examining the association between POC after CRLM resection and OS/DFS were sought using the PubMed and Web of Science databases. A random-effects model was used to calculate pooled effect estimate for OS and DFS hazard ratios (HR), estimating between-study variance with restricted maximum likelihood estimator with Hartung-Knapp adjustment. Subgroup analysis was used to control the effect of POC on OS and DFS for: 1) Method used to define postoperative complications, 2) Exclusion of early postoperative death from survival analysis, 3) Method of data extraction used, and 4) Tumor and treatment characteristics. RESULTS: Forty-one studies were deemed eligible, including 12,817 patients. POC patients had a significant risk of reduced OS compared with no POC group (HR 1.43 [95% CI: 1.3, 1.57], P < 0.0001). POC had also a negative impact on DFS. The HR for reduced DFS was 1.38 [95% CI 1.27, 1.49], P < 0.0001. The negative impact of POC on survival and recurrence was confirmed in subgroup analysis. CONCLUSIONS: Our findings evidence the negative impact of POC on survival and recurrence after CRLM resection.

Borderline resectable pancreatic cancer. Challenges and controversies.

Pancreatic cancer is a dismal disease with an increasing incidence. Despite the majority of patients are not candidates for curative surgery, a subgroup of patients classified as borderline resectable pancreatic cancer can be selected in whom a sequential strategy of neoadjuvant therapy followed by surgery can provide better outcomes. Multidisciplinary approach and surgical pancreatic expertise are essential for successfully treating these patients. However, the lack of consensual definitions and therapies make the results of studies very difficult to interpret and hard to be implemented in some settings. In this article, we review the challenges of borderline resectable pancreatic cancer, the complexity of its management and controversies and point out where further research and international cooperation for a consensus strategy is urgently needed.