Spotlight on hTERT Complex Regulation in Cutaneous T-Cell Lymphomas.

As a major cancer hallmark, there is a sustained interest in understanding the telomerase contribution to carcinogenesis in order to therapeutically target this enzyme. This is particularly relevant in primary cutaneous T-cell lymphomas (CTCL), a malignancy showing telomerase dysregulation with few investigative data available. In CTCL, we examined the mechanisms involved in telomerase transcriptional activation and activity regulation. We analyzed 94 CTCL patients from a Franco-Portuguese cohort, as well as 8 cell lines, in comparison to 101 healthy controls. Our results showed that not only polymorphisms (SNPs) located at the promoter of human telomerase reverse transcriptase (hTERT) gene (rs2735940 and rs2853672) but also an SNP located within the coding region (rs2853676) could influence CTCL occurrence. Furthermore, our results sustained that the post-transcriptional regulation of hTERT contributes to CTCL lymphomagenesis. Indeed, CTCL cells present a different pattern of hTERT spliced transcripts distribution from the controls, mostly marked by an increase in the hTERT ß+ variants proportion. This increase seems to be associated with CTCL development and progression. Through hTERT splicing transcriptome modulation with shRNAs, we observed that the decrease in the α-ß+ transcript induced a decrease in the cell proliferation and tumorigenic capacities of T-MF cells in vitro. Taken together, our data highlight the major role of post-transcriptional mechanisms regulating telomerase non canonical functions in CTCL and suggest a new potential role for the α-ß+ hTERT transcript variant.

Nanomedicine and nanobiotechnology applications of magnetoelectric nanoparticles.

Unlike any other nanoparticles known to date, magnetoelectric nanoparticles (MENPs) can generate relatively strong electric fields locally via the application of magnetic fields and, vice versa, have their magnetization change in response to an electric field from the microenvironment. Hence, MENPs can serve as a wireless two-way interface between man-made devices and physiological systems at the molecular level. With the recent development of room-temperature biocompatible MENPs, a number of novel potential medical applications have emerged. These applications include wireless brain stimulation and mapping/recording of neural activity in real-time, targeted delivery across the blood-brain barrier (BBB), tissue regeneration, high-specificity cancer cures, molecular-level rapid diagnostics, and others. Several independent in vivo studies, using mice and nonhuman primates models, demonstrated the capability to deliver MENPs in the brain across the BBB via intravenous injection or, alternatively, bypassing the BBB via intranasal inhalation of the nanoparticles. Wireless deep brain stimulation with MENPs was demonstrated both in vitro and in vivo in different rodents models by several independent groups. High-specificity cancer treatment methods as well as tissue regeneration approaches with MENPs were proposed and demonstrated in in vitro models. A number of in vitro and in vivo studies were dedicated to understand the underlying mechanisms of MENPs-based high-specificity targeted drug delivery via application of d.c. and a.c. magnetic fields. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Correlation tests between relative light unit and colony forming unit for improving adenosine triphosphate bioluminescence analysis in bacterial consolidation treatments on palaeontological heritage.

In this article bacterial carbonate mineralization treatments are proposed as a novel strategy for decayed fossils and palaeontological heritage conservation; specifically, by means of inoculation of Myxococcus xanthus, a bacterium of proven effectiveness in ornamental stone bioconsolidation. Bioconsolidation treatments can be very effective, stable, nontoxic, environmentally friendly, and chemically compatible with fossil heritage. The method reproduces what nature has been doing for millennia with fossils that have been permineralized by bacterial calcium carbonate precipitation. There is, however, some concern that bacterial inoculation could lead to the growth of undesirable microbiota, which could subsequently damage the fossil substrate. Because of this, the use of bacteria on heritage items must be meticulously monitored and analysis strategies should be carried out to detect bacteria viability during and after treatments. For this purpose, adenosine triphosphate assay is proposed in this article as a fast, affordable, portable, and easy-to-use system for conservators. as ATP assay results are relative and difficult to relate to colony forming unit, this study aims to improve their applicability by examining the correlation between ATP analysis and total viable bacteria count in the specific case of M. xanthus. This research provides reference and correlatable data to obtain an approximate estimation of M. xanthus viable bacterial colonies based on relative light unit data.

An Artificial Intelligence-Based Tool for Data Analysis and Prognosis in Cancer Patients: Results from the Clarify Study.

BACKGROUND: Artificial intelligence (AI) has contributed substantially in recent years to the resolution of different biomedical problems, including cancer. However, AI tools with significant and widespread impact in oncology remain scarce. The goal of this study is to present an AI-based solution tool for cancer patients data analysis that assists clinicians in identifying the clinical factors associated with poor prognosis, relapse and survival, and to develop a prognostic model that stratifies patients by risk. MATERIALS AND METHODS: We used clinical data from 5275 patients diagnosed with non-small cell lung cancer, breast cancer, and non-Hodgkin lymphoma at Hospital Universitario Puerta de Hierro-Majadahonda. Accessible clinical parameters measured with a wearable device and quality of life questionnaires data were also collected. RESULTS: Using an AI-tool, data from 5275 cancer patients were analyzed, integrating clinical data, questionnaires data, and data collected from wearable devices. Descriptive analyses were performed in order to explore the patients' characteristics, survival probabilities were calculated, and a prognostic model identified low and high-risk profile patients. CONCLUSION: Overall, the reconstruction of the population's risk profile for the cancer-specific predictive model was achieved and proved useful in clinical practice using artificial intelligence. It has potential application in clinical settings to improve risk stratification, early detection, and surveillance management of cancer patients.

Association of rhinitis with asthma prevalence and severity.

Asthma and rhinitis often co-exist in the same patient. Although some authors observed a higher prevalence and/or greater severity of asthma in patients with rhinitis, this view is not homogeneous and the debate continues. The aim of our study is to describe the prevalence of rhinitis in children and adolescents and to analyse their relationship with the prevalence of asthma. A multicentre study was conducted using the methodology of the International Study of Asthma and Allergies in Childhood (ISAAC). The target population of the study was all those school children aged 6-7 and 13-14 years from 6 of the main health catchment areas of Galicia (1.9 million inhabitants). The schools required were randomly selected, and all children in the targeted age ranges were included. Multiple logistic regression was used to obtain adjusted prevalence odds ratios (OR) between asthma symptoms of the schoolchildren and rhinitis prevalence. The results were adjusted for parental smoking habits, maternal education level, cat and dog exposure, and obesity. A total of 21,420 valid questionnaires were finally obtained. Rhinitis was associated with a significant increase in the prevalence of asthma in both age groups. The highest OR were 11.375 for exercise induced asthma (EIA) for children with recent rhinoconjunctivitis and 9.807 for children with recent rhinitis in 6-7 years old group. The prevalence OR's are higher in EIA and severe asthmatics. Rhinitis in children and adolescents is associated with a higher prevalence and severity of asthma.

Chronodisruption and Ambulatory Circadian Monitoring in Cancer Patients: Beyond the Body Clock.

PURPOSE OF REVIEW: Circadian rhythms impose daily rhythms a remarkable variety of metabolic and physiological functions, such as cell proliferation, inflammation, and DNA damage response. Accumulating epidemiological and genetic evidence indicates that circadian rhythms' disruption may be linked to cancer. The integration of circadian biology into cancer research may offer new options for increasing cancer treatment effectiveness and would encompass the prevention, diagnosis, and treatment of this disease. RECENT FINDINGS: In recent years, there has been a significant development and use of multi-modal sensors to monitor physical activity, sleep, and circadian rhythms, allowing, for the very first time, scaling accurate sleep monitoring to epidemiological research linking sleep patterns to disease, and wellness applications providing new potential applications. This review highlights the role of circadian clock in tumorigenesis, cancer hallmarks and introduces the state-of-the-art in sleep-monitoring technologies, discussing the eventual application of insights in clinical settings and cancer research.

The Retrochiasmal Optic Pathway: A Link in Jeopardy.

The case of an intraventricular meningioma is presented and the visual complication incurred by its surgical resection is discussed. The importance of selecting the most optimal surgical approach and the basis for that selection are highlighted.

Prognostic Significance of RAS Mutations and P53 Expression in Cutaneous Squamous Cell Carcinomas.

TP53 is considered the most commonly-altered gene in cutaneous squamous cell carcinoma (cSCC). Conversely, RAS mutations have been reported in a low percentage of cSCC. The objective of our study was to evaluate the frequency of p53 expression and RAS mutations in cSCC and correlate them with clinicopathological features and patient outcome. We performed immunohistochemistry for p53 and genetic profiling for RAS mutations in a retrospective series of cSCC. The predictive value of p53 expression, RAS mutations, and clinicopathological parameters was assessed using logistic regression models. The overall frequency of RAS mutations was 9.3% (15/162), and 82.1% of the cases (133/162) had p53 overexpression. RAS mutations rate was 3.2% (1/31) of in situ cSCCs and 10.7% (14/131) of invasive cSCCs. RAS mutations were more frequently associated with an infiltrative than an expansive pattern of invasion (p = 0.046). p53 overexpression was a predictor of recurrence in the univariate analysis. Our results indicate that RAS mutations associate with features of local aggressiveness. Larger studies with more recurrent and metastatic cSCCs are necessary to further address the prognostic significance of p53 overexpression in patients' risk stratification.

Extensive Refractory Perineal Pyoderma Gangrenosum Treated with Infliximab, Fecal Diversion, and Negative-Pressure Wound Therapy.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare and difficult-to-diagnose disease that often associates with inflammatory bowel disease. CASE: We present a case of a 57-year-old female with ulcerative colitis receiving 5-ASA who presented with rapidly progressive ulcers in the right foot and on the inside of the thigh, extending from the left large vaginal lip to the perianal area, compatible with PG. She was initially treated with corticosteroids with no response. After multidisciplinary consultation, it was decided to initiate in-fliximab 5 mg/kg, and to perform ileostomy for fecal diversion and negative-pressure wound therapy. The patient presented with marked improvement of the lesions, being discharged after 2 months and demonstrating almost complete resolution of the lesions within 4 months. CONCLUSION: Due to the rarity of PG, there is no evidence of the optimal management. The role of surgery is controversial as PG lesions can demonstrate pathergy and theoretically could worsen with surgical intervention. In this case it was decided based on the extent of the lesions and the experience in other septic/ulcerative perianal conditions.

INTRODUÇÃO: O pioderma gangrenoso (PG) é uma doença rara e de difícil diagnóstico, que frequentemente se associa à doença inflamatória intestinal. CASO: Apresentamos um caso de uma mulher de 57 anos de idade com colite ulcerosa sob 5-ASA que recorreu ao serviço de urgência pelo aparecimento de úlceras rapidamente progressivas no pé direito e no interior da coxa, estendendo-se desde o grande lábio vaginal esquerdo até à área perianal, compatível com PG. A doente foi inicialmente tratada com corticosteroides, sem resposta. Após consulta multidisciplinar, optou-se por iniciar o infliximab 5 mg/kg, realizar ileostomia para desvio fecal e iniciar terapia de vácuo com pressão negativa. A doente apresentou melhoria marcada das lesões tendo tido alta após 2 meses e demonstrando resolução quase completa das lesões aos 4 meses. CONCLUSÃO: Devido à raridade do PG, não há evidências de qual a abordagem ideal. O papel da cirurgia é controverso, pois as lesões do PG podem demonstrar patergiae teoricamente poderiam piorar com a intervenção cirúrgica. Neste caso, a opção cirúrgica foi tomada com base na extensão das lesões e na experiência em outras condições perianais sépticas/ulcerativas.

Haemodynamic and analgesic control in a perioperative opioid-free approach to bariatric surgery - A case report.

New approaches to bariatric surgery aim to achieve stress-free anaesthesia with sympathetic stability to protect organs and provide sufficient tissue perfusion, analgesia and rapid emergence. Opioid-free and multimodal approaches to anaesthesia provide intra- and post-operative sedation and analgesia, particularly advantageous in morbidly obese patients, but their feasibility and efficacy are still disputed. We describe the case of a female patient proposed for laparoscopic bariatric surgery, conducted under an opioid-free anaesthesia protocol, the haemodynamic, ventilatory and analgesic control, and intra- and post-operative monitoring and complications.

Comparative effectiveness of purpuragenic 595 nm pulsed dye laser versus sequential emission of 595 nm pulsed dye laser and 1,064 nm Nd:YAG laser: a double-blind randomized controlled study.

INTRODUCTION: Erythematotelangiectatic rosacea is a common condition in Caucasians. The most frequently used lasers to treat this condition are pulsed dye laser (PDL) and neodymium:yttrium-aluminum-garnet laser (Nd:YAG). This study compares the treatment efficacy of purpuragenic PDL with that of sequential emission of 595 nm PDL and 1,064 nm Nd:YAG (multiplexed PDL/Nd:YAG). METHODS: We performed a prospective, randomized, and controlled split-face study. Both cheeks were treated, with side randomization to receive treatment with PDL or multiplexed PDL/Nd:YAG. Efficacy was evaluated by spectrophotometric measurement, visual photograph evaluation, the Dermatology Quality of Life Index questionnaire, and a post-treatment questionnaire. RESULTS: Twenty-seven patients completed the study. Treatment was associated with a statistically significant improvement in quality of life (p < 0.001). PDL and multiplexed PDL/Nd:YAG modalities significantly reduced the erythema index (EI; p < 0.05). When comparing the degree of EI reduction, no differences were observed between the two treatment modalities. PDL was associated with a higher degree of pain and a higher percentage of purpura. Multiplexed PDL/Nd:YAG modality was associated with fewer side effects and greater global satisfaction, and 96.3% of the patients would recommend this treatment to a friend. CONCLUSIONS: Both laser modalities are efficacious in the treatment of erythematotelangiectatic rosacea. The multiplexed PDL/Nd:YAG modality was preferred by the patients.

Bullous lupus erythematosus with an erythema gyratum repens-like pattern.

Bullous lupus erythematosus is a rare clinical form of lupus. The diagnosis is challenging and involves the exclusion of other subepidermal bullous dermatoses. We present a 21-year-old woman with erythematosus, polycyclic plaques with vesiculobullae along the periphery, creating an erythema gyratum repens-like pattern on acral regions. The cutaneous biopsy, analytical, and autoimmune studies support the diagnosis of systemic lupus erythematosus. Dapsone and glucocorticosteroids were given with prompt resolution of the lesions within two weeks. To our knowledge this is the first case of bullous lupus erythematosus with this atypical acral presentation.

Daylight photodynamic therapy in 25 patients with actinic keratosis and evaluation of efficacy by confocal microscopy.

BACKGROUND: Daylight photodynamic therapy (PDT) has been reported as having similar efficacy to conventional photodynamic therapy in actinic keratosis treatment. METHODS: 25 patients with actinic keratosis of the scalp and/or face were submitted to a daylight photodynamic therapy session. Adverse reactions were evaluated after one week and efficacy after 3 months. Confocal Microscopy was performed in 6 patients, before and one week after the treatment. Our aim was to compare our results with others studies and analyse the changes occurring in the epidermis and upper dermis with confocal microscopy. RESULTS: 76% of the patients were male. The mean age was 74.2 years. In 51.7% of patients the treatment site was the scalp. Mean cure rate at 3 months was 74%. Aesthetic results were excellent in all patients and only one patient reported mild pain during the 2 h exposure. Confocal Microscopy showed a normalization of the honeycomb pattern in all of the patients. CONCLUSIONS: This therapy has similar results to conventional photodynamic therapy and stands out for less discomfort, fewer adverse effects and better cost-effectiveness. Using confocal microscopy it's possible to in vivo demonstrate the efficacy of this method, with normalization of the honeycomb pattern in the epidermis following succcessful PDT.

TERT promoter mutations are associated with poor prognosis in cutaneous squamous cell carcinoma.

BACKGROUND: Telomerase reverse transcriptase gene (TERT) promoter (TERTp) mutations have been reported as potential predictors of poor prognosis in several cancers, but the prognostic value of TERTp mutations for cutaneous squamous cell carcinoma (cSCC) has not been determined. OBJECTIVE: To evaluate the frequency of TERTp mutations and correlate it with clinicopathologic features and patient outcome. METHODS: We performed genetic profiling of TERTp mutations in a retrospective series of cSCCs. The predictive value of TERTp mutations and clinicopathologic parameters were assessed by using logistic regression models. RESULTS: A total of 152 cSCCs from 122 patients were analyzed for TERTp mutations; the mutation rate was 31.6% (48 of 152), and it was higher in invasive cSCC (42 of 121 [34.7%]) than in in situ cSCC (6 of 31 [19.4%]). Age older than 75 years (odds ratio [OR], 14.84; P = .013] and TERTp mutation (OR, 8.11; P = .002) were independent predictors of local recurrence. TERTp mutation (OR, 15.89; P = .022) was independently associated with higher risk of lymph node metastasis. LIMITATIONS: The restricted number of metastatic cases. CONCLUSION: TERTp mutations may prove to be a molecular biomarker with prognostic significance in invasive cSCC, but larger studies are needed.

Causas de no trombólisis: en pacientes en ventana terapéutica con accidente cerebrovascular isquémico atendidos en Hospital Herminda Martín de Chillán / Causes of non-thrombolysis in patients in therapeutic window with ischemic stroke treated in Hospital Herminda Martín de Chillán

INTRODUCCIÓN: El ataque cerebro vascular (ACV) es una emergencia médica, que ocurre cuando se interrumpe el suministro de sangre al cerebro o cuando existe un sangrado en el cerebro. EL OBJETIVO de esta investigación fue determinar las causas de la no trombolisis en pacientes con ventana terapéutica en accidente cerebral isquémico. MATERIALES Y MÉTODOS: Se realizó un estudio descriptivo con el fin de conocer el argumento de no utilización de tratamiento trombolítico en pacientes dentro de ventana terapéutica en accidente cerebral isquémico que consultaron o fueron derivados al Hospital Clínico Herminda Martín de Chillán, desde octubre de 2017 a marzo de 2018. Se revisaron las fichas clínicas tanto de pacientes egresados vivos como fallecidos. Estas se obtuvieron del Servicio de Neurología, extrayendo la información de Datos de Atención de Urgencias (DAU) y/o ficha clínica. RESULTADOS: Una muestra de 78 pacientes cumplió con los criterios de inclusión del estudio, cuya principal causa de no trombolisis en ventana terapéutica fue presentar un puntaje en la escala de NIHSS menor a 5 puntos, representando el 20,51% del total. DISCUSIÓN: Según la literatura, los principales motivos de exclusión en este grupo de pacientes fueron los ACV con manifestaciones leves (13,1%), mejoría clínica (18,2%) y exclusiones percibidas en el protocolo (13,6%), los cuales coinciden con esta investigación, donde el principal motivo fue un puntaje de NIHSS < 5, manifestando déficit neurológico leve al ingreso. Se recomienda la inclusión del criterio de funcionalidad previa a terapia trombolítica, en este grupo de pacientes. En pacientes en ventana terapéutica con accidente cerebrovascular isquémico atendidos en Hospital Herminda Martín de Chillán.

INTRODUCTION: Vascular brain attack (CVA) is a medical emergency, which occurs when the blood supply to the brain is interrupted or when there is bleeding in the brain. The OBJECTIVE of this research was to determine the causes of non-thrombolysis in patients with therapeutic windows in ischemic stroke. MATERIALS AND METHODS: A descriptive study was carried out in order to know the argument of non-use of thrombolytic treatment in patients with therapeutic window in ischemic stroke who consulted or was referred to the Hospital Clínico Herminda Martín de Chillán Clinical, from October 2017 to March of 2018. The clinical records of both living and deceased patients were reviewed. These were obtained from the Neurology Service, extracting the information from Emergency Care Data (DAU) and / or clinical record. RESULTS: A sample of 78 patients met the inclusion criteria of the study, whose main cause of non-thrombolysis in the therapeutic window was to present a score on the NIHSS scale of less than 5 points, representing 20.51% of the total. DISCUSSION: According to the literature, the main reasons for exclusion in this group of patients were stroke with mild manifestations (13.1%), clinical improvement (18.2%) and perceived exclusions in the protocol (13.6%), which, coincide with this investigation where the main reason was an NIHSS score <5, manifesting mild neurological deficit upon admission. The inclusion of the functionality criterion prior to thrombolytic therapy is recommended in this group of patients.

The genetics of cutaneous squamous cell carcinogenesis.

In this review, the current knowledge of cutaneous squamous cell carcinogenesis (cSCC) is outlined based on an appraisal of the different features of cSCC, with particular emphasis on genetic alterations underlying aetiopathogenesis. When appropriate, diagnostic and/or prognostic biomarkers for cSCC are also considered. This review is intended to aid future investigation into the molecular characterization of cSCC.

Near-total lower lip reconstruction: combined Karapandzic and Bernard-Burrow-Webster flap.

Lip carcinoma is a common cancer of the head and neck region. It more often affects the lower lip (> 90%), and squamous cell carcinoma represents 95% of the cases. The authors present a reconstruction of the lower lip combining two classical flaps: the Karapandzic and Bernard-Burrow-Webster flap. The surgical technique is discussed.

DNA-relay mechanism is sufficient to explain ParA-dependent intracellular transport and patterning of single and multiple cargos.

Spatial ordering of macromolecular components inside cells is important for cellular physiology and replication. In bacteria, ParA/B systems are known to generate various intracellular patterns that underlie the transport and partitioning of low-copy-number cargos such as plasmids. ParA/B systems consist of ParA, an ATPase that dimerizes and binds DNA upon ATP binding, and ParB, a protein that binds the cargo and stimulates ParA ATPase activity. Inside cells, ParA is asymmetrically distributed, forming a propagating wave that is followed by the ParB-rich cargo. These correlated dynamics lead to cargo oscillation or equidistant spacing over the nucleoid depending on whether the cargo is in single or multiple copies. Currently, there is no model that explains how these different spatial patterns arise and relate to each other. Here, we test a simple DNA-relay model that has no imposed asymmetry and that only considers the ParA/ParB biochemistry and the known fluctuating and elastic dynamics of chromosomal loci. Stochastic simulations with experimentally derived parameters demonstrate that this model is sufficient to reproduce the signature patterns of ParA/B systems: the propagating ParA gradient correlated with the cargo dynamics, the single-cargo oscillatory motion, and the multicargo equidistant patterning. Stochasticity of ATP hydrolysis breaks the initial symmetry in ParA distribution, resulting in imbalance of elastic force acting on the cargo. Our results may apply beyond ParA/B systems as they reveal how a minimal system of two players, one binding to DNA and the other modulating this binding, can transform directionally random DNA fluctuations into directed motion and intracellular patterning.