In vitro models for neuropathic pain phenotypic screening in brain therapeutics.

The discovery of brain therapeutics faces a significant challenge due to the low translatability of preclinical results into clinical success. To address this gap, several efforts have been made to obtain more translatable neuronal models for phenotypic screening. These models allow the selection of active compounds without predetermined knowledge of drug targets. In this review, we present an overview of various existing models within the field, examining their strengths and limitations, particularly in the context of neuropathic pain research. We illustrate the usefulness of these models through a comparative review in three crucial areas: i) the development of novel phenotypic screening strategies specifically for neuropathic pain, ii) the validation of the models for both primary and secondary screening assays, and iii) the use of the models in target deconvolution processes.

A review of the injuries caused by occupational footwear.

BACKGROUND: Occupational footwear is intended to provide protection against the risks associated with work activities. The choice of footwear is complex due to the welfare, health and safety conditions of workers. AIMS: To identify the injuries and problems caused by occupational footwear through a systematic review of the existing literature. METHODS: A literature search was carried out in the Cumulative Index to Nursing and Allied Health Literature, Dialnet Plus, Pubmed, Scientific Electronic Library Online, Medline, Scopus and Web of Science databases over the period 2000-23, following the PRISMA Declaration guidelines. RESULTS: A total of 27 studies were included in the review. The results indicated that there is a wide variety of injuries caused by occupational footwear: from dermal injuries (e.g. calluses) and injuries to the nail apparatus to inflammatory pathologies such as plantar fasciitis or bursitis. In addition, inappropriate footwear can cause pain in the ankle and foot, knees, hips and lower back. Other results include the discomfort derived from the footwear itself. CONCLUSIONS: Inappropriate footwear can cause injuries to the foot and other related bone structures. Further studies are needed on the detection of foot injuries caused by occupational footwear and the levels of action at this level to improve the worker's health, the adaptability of the footwear to the wearer, and the worker's comfort and adherence to the footwear.

Salivary cortisol levels in patients with potentially malignant oral disorders and oral mucosal cancer: a case-control study.

BACKGROUND: The relationship between salivary cortisol secretion and the presence of cancer in the oral cavity has not been completely clarified. Due to this, we proposed carrying out a study to determine salivary cortisol levels in patients with potentially malignant disorders (PMD), oral squamous cell carcinoma (OSCC) and healthy individuals. MATERIAL AND METHODS: Cross-sectional case-control study, among 80 patients seen at the Faculty of Dentistry of the National University of Rosario, Argentina, between January 2018 and April 2020. 40 cases represented by Leukoplakia, Lichen, Erythroplakia and SCC and 40 controls were included. Smoking habit and alcohol consumption were included. The presence of stress was determined. Morning salivary cortisol levels were measured with the Roche electrochemiluminescence method (Traceability: St by ID-MS). RESULTS: Patients with SCC presented elevated salivary cortisol values. Individuals with stage III tumors showed levels higher than 8.74 ng/ml in all cases. A significant association between cortisol levels and stress was detected in patients in the control group (p<0.005) and in individuals with PMD (p=0.009). This association was not significant in patients with SCC (p=0.999). After applying the logistic regression method, when adjusting odds ratios according to tobacco and alcohol consumption and the presence of stress, the association between cortisol levels and presence of stress was highly significant (p<0.001). The possibility of presenting undetectable cortisol results was 94% lower in patients with stress. CONCLUSIONS: The increase in salivary cortisol levels in patients with PMD and SCC, is related to stress conditions, being able to generate alterations tending to immunosuppression of the cellular microenvironment.

The role of multiparametric magnetic resonance in active surveillance of a low-risk prostate cancer cohort from clinical practice.

INTRODUCTION: Active surveillance (AS) is considered a suitable management practice for those patients with low-risk prostate cancer (PCa). At present, however, the role of multiparametric magnetic resonance imaging (mpMRI) in AS protocols has not yet been clearly established. OUTCOMES: To determine the role of mpMRI and its ability to detect significant prostate cancer (SigPCa) in PCa patients enrolled in AS protocols. MATERIALS AND METHODS: There were 229 patients enrolled in an AS protocol between 2011 and 2020 at Reina Sofía University Hospital. MRI interpretation was based on PIRADS v.1 or v.2/2.1 classification. Demographics, clinical, and analytical data were collected and analyzed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for mpMRI in different scenarios. We defined SigPCa and reclassification/progression as a Gleason score (GS) ≥ 3 + 4, a clinical stage ≥T2b, or an increase in PCa volume. Kaplan-Meier and log-rank tests were used to estimate progression-free survival time. RESULTS: Median age was 69.02 (±7.73) at diagnosis, with a 0.15 (±0.08) PSA density (PSAD). Eighty-six patients were reclassified after confirmatory biopsy, with a suspicious mpMRI an indication for a clear reclassification and risk-predictor factor in disease progression (p < 0.05). During follow-up, 46 patients were changed from AS to active treatment mainly due to disease progression. Ninety patients underwent ≥2mpMRI during follow-up, with a median follow-up of 29 (15-49) months. Thirty-four patients had a baseline suspicious mpMRI (at diagnostic or confirmatory biopsy): 14 patients with a PIRADS 3 and 20 patients with ≥PIRADS 4. From 14 patients with a PIRADS 3 baseline mpMRI, 29% progressed radiologically, with a 50% progression rate versus 10% (1/10 patients) for those with similar or decreased mpMRI risk. Of the 56 patients with a non-suspicious baseline mpMRI (PIRADS < 2), 14 patients (25%) had an increased degree of radiological suspicion, with a detection rate of SigPCa of 29%. The mpMRI NPV during follow-up was 0.91. CONCLUSION: A suspicious mpMRI increases the reclassification and disease progression risk during follow-up and plays an important role in monitoring biopsies. In addition, a high NPV at mpMRI follow-up can help to decrease the need to monitor biopsies during AS.

Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV): Data for the First 5 Years. / Registro de linfomas cutáneos primarios (RELCP) de la AEDV: datos tras 5 años de funcionamiento.

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas (PCL) are uncommon. Observations based on the first year of data from the Spanish Registry of Primary Cutaneous Lymphomas (RELCP, in its Spanish abbreviation) of the Spanish Academy of Dermatology and Venereology (AEDV) were published in February 2018. This report covers RELCP data for the first 5 years. PATIENTS AND METHODS: RELCP data were collected prospectively and included diagnosis, treatments, tests, and the current status of patients. We compiled descriptive statistics of the data registered during the first 5 years. RESULTS: Information on 2020 patients treated at 33 Spanish hospitals had been included in the RELCP by December 2021. Fifty-nine percent of the patients were men; the mean age was 62.2 years. The lymphomas were grouped into 4 large diagnostic categories: mycosis fungoides/Sézary syndrome, 1112 patients (55%); primary B-cell cutaneous lymphoma, 547 patients (27.1%); primary CD30+lymphoproliferative disorders, 222 patients (11%), and other T-cell lymphomas, 116 patients (5.8%). Nearly 75% of the tumors were registered in stage I. After treatment, 43.5% achieved complete remission and 27% were stable at the time of writing. Treatments prescribed were topical corticosteroids (1369 [67.8%]), phototherapy (890 patients [44.1%]), surgery (412 patients [20.4%]), and radiotherapy (384 patients [19%]). CONCLUSION: The characteristics of cutaneous lymphomas in Spain are similar to those reported for other series. The large size of the RELCP registry at 5 years has allowed us to give more precise descriptive statistics than in the first year. This registry facilitates the clinical research of the AEDV's lymphoma interest group, which has already published articles based on the RELCP data.

Making thirsty cities sustainable: A nexus approach for water provisioning in Quito, Ecuador.

In view of accelerated climate change and urban demographics, balancing human and ecosystem needs for water resources is a critical environmental challenge of global significance. Since water, agriculture, health, and energy are inextricably linked, sustainable development goals (SDGs) actions in one policy area commonly have impacts on the others, as well as on the ecosystems that natural resources and human activities ultimately depend upon. Managing urban water supply systems therefore requires a nexus approach that integrates goals across sectors, reduces the risk that SDG actions will undermine one another, and ensures sustainable resource use. We developed a transdisciplinary methodological framework based on a Pareto frontier analysis to define the sustainable solutions of a multi-objective optimization among four competing criteria, water provision, water quality, energy cost, and biodiversity conservation. The study was applied to three mountainous headwater basins in the Ecuadorian Andes, which provide around 30% of Quito's total water supply. We found that an optimized management of water intake structures would meet current consumption needs while reducing the probability of emergence of water pathogens and limiting the impact on aquatic biodiversity by 30% and 9% respectively, without any increase in energy costs for pumping water from other sources. Nonetheless, under future scenarios of climate change and water demand, higher energy consumption, and therefore an increase in operating costs, would be needed to meet urban demand and preserve environmental conditions. Overall, the range of Pareto optimal water supply strategies across the water-health-energy-biodiversity nexus provides valuable information for decision makers and offers support for achieving sustainable management of water resources.

Hemifacial microsomia: treatment alternatives-a systematic review of literature.

OBJECTIVE: To systematically review literature on therapeutic options for treating hemifacial microsomia (HFM), in young patients with growth potential, classifying and comparing the different dentofacial treatment methods. STUDY DESIGN: An independent review of databases (Scopus, Embase, Ovid, Cochrane Library and PubMed) following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA), conducted by four evaluators. The protocol of this study was registered in International prospective register of systematic reviews (PROSPERO), under the number CRD42021293076. RESULTS: Between 1970-2021, a total number of 1137 articles were published of which 27 were included in this study according to the selection criteria: one randomized multicentric trial, two case-control studies, three case series and 21 case reports. CONCLUSIONS: The most common orthopedic treatments provide vertical stimulation of the maxillary process in the affected side. Orthodontic approaches are mainly applied for vertical correction and stabilization of the occlusal plane. Other treatment options include orthognathic surgery, osteogenic distraction, temporomandibular reconstruction and grafting. It is recommended that prospective clinical randomized controlled studies be conducted using homogeneous pediatric groups with long-term follow-up, to establish recommended evidence-based methods for treating each set of hemifacial microsomia symptoms.

Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases.

BACKGROUND: The cutaneous manifestations of COVID-19 disease are poorly characterized. OBJECTIVES: To describe the cutaneous manifestations of COVID-19 disease and to relate them to other clinical findings. METHODS: We carried out a nationwide case collection survey of images and clinical data. Using a consensus we described five clinical patterns. We later described the association of these patterns with patient demographics, the timing in relation to symptoms of the disease, the severity and the prognosis. RESULTS: The lesions may be classified as acral areas of erythema with vesicles or pustules (pseudo-chilblain) (19%), other vesicular eruptions (9%), urticarial lesions (19%), maculopapular eruptions (47%) and livedo or necrosis (6%). Vesicular eruptions appear early in the course of the disease (15% before other symptoms). The pseudo-chilblain pattern frequently appears late in the evolution of the COVID-19 disease (59% after other symptoms), while the rest tend to appear with other symptoms of COVID-19. The severity of COVID-19 shows a gradient from less severe disease in acral lesions to more severe in the latter groups. The results are similar for confirmed and suspected cases, in terms of both clinical and epidemiological findings. Alternative diagnoses are discussed but seem unlikely for the most specific patterns (pseudo-chilblain and vesicular). CONCLUSIONS: We provide a description of the cutaneous manifestations associated with COVID-19 infection. These may help clinicians approach patients with the disease and recognize cases presenting with few symptoms. What is already known about this topic? Previous descriptions of cutaneous manifestations of COVID-19 were case reports and mostly lacked illustrations. What does this study add? We describe a large, representative sample of patients with unexplained skin manifestations and a diagnosis of COVID-19, using a consensus method to define morphological patterns associated with COVID-19. We describe five clinical patterns associated with different patient demographics, timing and prognosis, and provide illustrations of these patterns to allow for easy recognition.

Leptospirosis in an asplenic patient -case report.

BACKGROUND: The presentation of clinical leptospirosis has been historically associated with animal workers, slaughterhouse workers and medical veterinarians. This association has shifted to be related to flooding events and outdoor activities; few cases are related to high-risk factors found in immunosuppressed patients. Scarcely a handful of cases have serological evidence of immune response against Leptospira serovar Bratislava representing serogroup Australis, a serovar associated with poor reproductive performance in swine and horses, and recently with cats. CASE PRESENTATION: Herein, we describe a rare clinical presentation of disseminated Leptospira infection in an immunosuppressed 65-year-old woman. She was admitted to the emergency room with fever, bacteraemia, bilateral uveitis and pulmonary involvement. The patient denied outdoor activities; she only had wide exposure to faeces and urine from cats living in her home. Her medical history included idiopathic thrombocytopenic purpura (ITP) diagnosed at the age of 18. She did not respond to medical treatment, and a splenectomy was performed. At age 60, she was diagnosed with Chronic Myeloid Leukemia (CML), and was treated with a tyrosine kinase inhibitor (TKI) -Imatinib. The patient voluntarily discontinued the treatment for the last 6 months. After extensive workup, no microorganisms were identified by the commonly used stains in microbiology. The diagnosis was performed through dark-field microscopy, microagglutination test (MAT), Leptospira genus-specific PCR, the IS1500 PCR for identification of pathogenic species, and 16S based sequencing for the genus identification. CONCLUSION: Immunosuppressed patients may acquire uncommon infections from ubiquitous microorganisms. In this case, serology evidence of exposure to Leptospira serovar Bratislava by MAT and the presence of the Leptospira genus were identified. It should be on mind for the diagnosis in otherwise healthy patients, and thoroughly search on splenectomised patients exposed to animals. Additionally, this report highlights the usefulness of PCR for diagnosis of this potentially life-threatening illness.