Upwelling as a stressor event during embryonic development: Consequences for encapsulated and early juvenile stages of the marine gastropod Acanthina monodon.

Upwelling phenomena alter the physical and chemical parameters of the sea's subsurface waters, producing low levels of temperature, pH and dissolved oxygen, which can seriously impact the early developmental stages of marine organisms. To understand how upwelling can affect the encapsulated development of the gastropod Acanthina monodon, capsules containing embryos at different stages of development (initial, intermediate and advanced) were exposed to upwelling conditions (pH = 7.6; O2 = 3 mg L-1; T° = 9 °C) for a period of 7 days. Effects of treatment were determined by estimating parameters such as time to hatching, number of hatchlings per capsule, percentage of individuals with incomplete development, and shell parameters such as shell shape and size, shell strength, and the percentage of the organic/inorganic content. We found no significant impacts on hatching time, number of hatchlings per capsule, or percentage of incomplete development in either the presence or absence of upwelling, regardless of developmental stage. On the other hand, latent effects on encapsulated stages of A. monodon were detected in embryos that had been exposed to upwelling stress in the initial embryonic stage. The juveniles from this treatment hatched at smaller sizes and with higher organic content in their shells, resulting in a higher resistance to cracking 30 days after hatching, due to greater elasticity. Geometric morphometric analysis showed that exposure to upwelling condition induced a change in the morphology of shell growth in all post-hatching juveniles (0-30 days), regardless of embryonic developmental stage at the time of exposure. Thus, more elongated shells (siphonal canal and posterior region) and more globular shells were observed in newly hatched juveniles that had been exposed to the upwelling condition. The neutral or even positive upwelling exposure results suggests that exposure to upwelling events during the encapsulated embryonic phase of A. monodon development might not have major impacts on the future juvenile stages. However, this should be taken with caution in consideration of the increased frequency and intensity of upwelling events predicted for the coming decades.

UV-R mitigation strategies in encapsulated embryos of the intertidal gastropod Acanthina monodon: A way to compensate for lack of parental care.

Intracapsular embryonic development in the intertidal zone exposes embryos to various stress sources characteristic of this environment, including UV-R. They require defensive mechanisms to mitigate its adverse effects. The presence of total carotenoids (TC), and mycosporine-like amino acids (MAAs) was studied in adults, in encapsulated embryos, and in the egg capsule walls of the intertidal gastropod Acanthina monodon. Oxygen consumption rates (OCR) were determined in encapsulated and excapsulated embryos exposed to photosynthetically active radiation (PAR) and PAR + UV-A + UV-B to understand if the capsule wall is a protective structure for encapsulated embryos. The results showed the presence of TC in adult pedal and gonad tissues, and in all encapsulated stages. MAAs were not detected. The physical structure of the capsule wall retained most wavelengths, being particularly efficient in the UV-B range. Excapsulated embryos exposed to PAR + UV-A + UV-B radiation increased its OCR compared to encapsulated embryos, indicating the protective character of the capsule wall.

Low-dose radiotherapy to the lungs using an interventional radiology C-arm fluoroscope: Monte Carlo treatment planning and dose measurements in a postmortem subject.

Objective.The goal of this study was to use Monte Carlo (MC) simulations and measurements to investigate the dosimetric suitability of an interventional radiology (IR) c-arm fluoroscope to deliver low-dose radiotherapy to the lungs.Approach.A previously-validated MC model of an IR fluoroscope was used to calculate the dose distributions in a COVID-19-infected patient, 20 non-infected patients of varying sizes, and a postmortem subject. Dose distributions for PA, AP/PA, 3-field and 4-field treatments irradiating 95% of the lungs to a 0.5 Gy dose were calculated. An algorithm was created to calculate skin entrance dose as a function of patient thickness for treatment planning purposes. Treatments were experimentally validated in a postmortem subject by using implanted dosimeters to capture organ doses.Main results.Mean doses to the left/right lungs for the COVID-19 CT data were 1.2/1.3 Gy, 0.8/0.9 Gy, 0.8/0.8 Gy and 0.6/0.6 Gy for the PA, AP/PA, 3-field, and 4-field configurations, respectively. Skin dose toxicity was the highest probability for the PA and lowest for the 4-field configuration. Dose to the heart slightly exceeded the ICRP tolerance; all other organ doses were below published tolerances. The AP/PA configuration provided the best fit for entrance skin dose as a function of patient thickness (R2 = 0.8). The average dose difference between simulation and measurement in the postmortem subject was 5%.Significance.An IR fluoroscope should be capable of delivering low-dose radiotherapy to the lungs with tolerable collateral dose to nearby organs.

Monte Carlo simulations and phantom validation of low-dose radiotherapy to the lungs using an interventional radiology C-arm fluoroscope.

PURPOSE: To use MC simulations and phantom measurements to investigate the dosimetry of a kilovoltage x-ray beam from an IR fluoroscope to deliver low-dose (0.3-1.0 Gy) radiotherapy to the lungs. MATERIALS AND METHODS: PENELOPE was used to model a 125 kV, 5.94 mm Al HVL x-ray beam produced by a fluoroscope. The model was validated through depth-dose, in-plane/cross-plane profiles and absorbed dose at 2.5-, 5.1-, 10.2- and 15.2-cm depths against the measured beam in an acrylic phantom. CT images of an anthropomorphic phantom thorax/lungs were used to simulate 0.5 Gy dose distributions for PA, AP/PA, 3-field and 4-field treatments. DVHs were generated to assess the dose to the lungs and nearby organs. Gafchromic film was used to measure doses in the phantom exposed to PA and 4-field treatments, and compared to the MC simulations. RESULTS: Depth-dose and profile results were within 3.2% and 7.8% of the MC data uncertainty, respectively, while dose gamma analysis ranged from 0.7 to 1.0. Mean dose to the lungs were 1.1-, 0.8-, 0.9-, and 0.8- Gy for the PA, AP/PA, 3-field, and 4-field after isodose normalization to cover âˆ¼ 95% of each lung volume. Skin dose toxicity was highest for the PA and lowest for the 4-field, and both arrangements successfully delivered the treatment on the phantom. However, the dose distribution for the PA was highly non-uniform and produced skin doses up to 4 Gy. The dose distribution for the 4-field produced a uniform 0.6 Gy dose throughout the lungs, with a maximum dose of 0.73 Gy. The average percent difference between experimental and Monte Carlo values were -0.1% (range -3% to +4%) for the PA treatment and 0.3% (range -10.3% to +15.2%) for the 4-field treatment. CONCLUSION: A 125 kV x-ray beam from an IR fluoroscope delivered through two or more fields can deliver an effective low-dose radiotherapy treatment to the lungs. The 4-field arrangement not only provides an effective treatment, but also significant dose sparing to healthy organs, including skin, compared to the PA treatment. Use of fluoroscopy appears to be a viable alternative to megavoltage radiation therapy equipment for delivering low-dose radiotherapy to the lungs.

Embryonic shell shape as an early indicator of pollution in marine gastropods.

Gastropods shell shape has been proposed as a good indicator of environmental changes while geometric morphometric (GM) is a powerful tool to detect such changes. Shell shape pattern in adults of the marine gastropod Buccinanops deformis was proved to be correlated with imposex incidence and maritime traffic in populations of Patagonia. We explore through GM the shell shape variation of B. deformis intracapsular embryos in pre-hatching stages of development, in two populations with contrasting maritime traffic and imposex incidence. Embryonic shell shape from polluted and unpolluted areas was significantly different in apex, lateral, aperture and siphonal channel. The same shell shape pattern was observed previously in B. deformis adult specimens. Our results demonstrate that the embryonic shell shape is an early biomarker that could be used as a tool to detect the response to environmental pollution studying abundant egg capsules laid in the field but protecting reproductive adults.

Guía de práctica clínica de melanoma de la Academia Española de Dermatología y Venereología / Clinical Practice Guideline on Melanoma From the Spanish Academy of Dermatology and Venereology (AEDV)

El diagnóstico y tratamiento del melanoma en atención especializada es un campo en el que se han producido numerosos cambios. El objetivo de esta guía es ofrecer a los dermatólogos españoles una referencia para resolver las dudas clínicas más frecuentes basándose en la evidencia actual. Para la realización de esta guía se escogió a miembros del Grupo Español de Dermato-Oncología y Cirugía con experiencia en el tratamiento de estos tumores y con interés en participar en la elaboración de la guía. Se hizo una adaptación de las guías de práctica clínica existentes mediante el método ADAPTE: inicialmente se resumió el proceso de atención y se elaboraron las preguntas clínicas relevantes. Se seleccionaron las guías mejor puntuadas mediante el instrumento AGREE II, realizando la búsqueda de las respuestas en dichas guías y elaborando las recomendaciones. Finalmente se sometió la guía a revisión externa. La guía se estructuró a partir de 21 preguntas clínicas que fueron seleccionadas por su relevancia, dado que se centran en aspectos que pueden plantear decisiones difíciles en el manejo del melanoma, y se han respondido empleando la evidencia obtenida de las mejores guías existentes. Entre las limitaciones de esta guía merece reseñarse que la evidencia es escasa para responder a algunas preguntas. En algunos aspectos el cambio es rápido y exige una actualización frecuente de la guía. Esta guía responde a preguntas habituales sobre el manejo del melanoma en la práctica clínica diaria, sirviendo a los dermatólogos como referencia en la toma de decisiones, siempre teniendo presente los recursos y preferencias del paciente

Specialist approaches to the diagnosis and treatment of melanoma have undergone many changes. This guideline aims to provide Spanish dermatologists with evidence-based information for resolving the most common doubts that arise in clinical practice. Members of the Spanish Oncologic Dermatology and Surgery Group (GEDOC) with experience treating melanoma were invited to participate in drafting the guideline. The group developed a new guideline on the basis of existing ones, using the ADAPTE collaboration process, first summarizing the care process and posing relevant clinical questions, then selecting guidelines with the best scores according to the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. Finally, the group searched the selected guidelines for answers to the clinical questions, drafted recommendations, and sent them for external review. The guideline is structured around 21 clinical questions chosen for their relevance to issues that make clinical decisions about the management of melanoma difficult. Evidence from existing guidelines was used to answer the questions. A limitation of this guide derives from the scarce evidence available for answering some questions. Moreover, some areas are changing rapidly, so recommendations must be updated often. The present guideline offers answers to clinical questions about the routine management of melanoma in clinical practice and provides dermatologists with a reference to guide decisions, taking into consideration the resources available and patient preferences

Clinical Practice Guideline on Melanoma From the Spanish Academy of Dermatology and Venereology (AEDV). / Guía de práctica clínica de melanoma de la Academia Española de Dermatología y Venereología.

Specialist approaches to the diagnosis and treatment of melanoma have undergone many changes. This guideline aims to provide Spanish dermatologists with evidence-based information for resolving the most common doubts that arise in clinical practice. Members of the Spanish Oncologic Dermatology and Surgery Group (GEDOC) with experience treating melanoma were invited to participate in drafting the guideline. The group developed a new guideline on the basis of existing ones, using the ADAPTE collaboration process, first summarizing the care process and posing relevant clinical questions, then selecting guidelines with the best scores according to the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. Finally, the group searched the selected guidelines for answers to the clinical questions, drafted recommendations, and sent them for external review. The guideline is structured around 21 clinical questions chosen for their relevance to issues that make clinical decisions about the management of melanoma difficult. Evidence from existing guidelines was used to answer the questions. A limitation of this guide derives from the scarce evidence available for answering some questions. Moreover, some areas are changing rapidly, so recommendations must be updated often. The present guideline offers answers to clinical questions about the routine management of melanoma in clinical practice and provides dermatologists with a reference to guide decisions, taking into consideration the resources available and patient preferences.

Cost-benefit analysis of funding smoking cessation before surgery.

BACKGROUND: Smoking at the time of surgery is associated with postoperative complications. Quitting smoking before surgery is linked to fewer complications during the hospital stay. This work analysed whether a smoking cessation intervention before surgery is economically worthwhile when funded by the National Health System (NHS) in Spain. METHODS: The economic analysis considered costs and benefits of the intervention to the NHS for the year 2016. The population who would benefit comprised adult smokers who were ready to quit and for whom surgery requiring admission to hospital was planned. The intervention, a combination of medical counselling and use of a smoking cessation drug which should occur 12 weeks before surgery, considered one attempt only to quit smoking. Benefits were costs avoided by averting postoperative complications if cessation was successful. The analysis compared the net economic outcome (benefit minus cost of intervention) and the return on investment, for intervention funded by the NHS versus the current situation without funding. RESULTS: Smoking cessation increased by 21·7 per cent with funding; the rate was 32·5 per cent when funded versus 10·7 per cent without funding, producing 9611 extra quitters. The cost per averted smoker was €1753 with a benefit of €503, achieving a net economic benefit of €4·8 million per year. Given the annual cost of the intervention (€17·4 million, of which €5·6 million (32·5 per cent) represents drugs), the return on investment was 28·7 per cent annually, equivalent to €1·29 per €1 of investment. CONCLUSION: From the perspective of the Spanish NHS, the benefit of funding smoking cessation before surgery, in terms of healthcare cost savings, appears to greatly outweigh the costs.

ANTECEDENTES: Ser fumador activo hasta el momento de la cirugía se asocia con complicaciones postoperatorias. Se ha descrito una disminución de las complicaciones durante la hospitalización al abandonar el hábito de fumar antes de la cirugía. Este trabajo analizó si una intervención preoperatoria para dejar de fumar es económicamente beneficiosa cuando se financia por el Sistema Nacional de Salud (SNS) en España. MÉTODOS: En el análisis económico se consideraron tantos los costes como los beneficios de la intervención para el SNS, en euros, correspondientes al año 2016. La población que se beneficiaría eran fumadores adultos dispuestos a dejar de fumar, en los que se programase una intervención quirúrgica con hospitalización. La intervención, una combinación de asesoramiento médico y tratamiento farmacológico para dejar de fumar, se llevó a cabo a las 12 semanas antes de la cirugía, considerando únicamente un intento para dejar de fumar. Los beneficios fueron los costes evitados por una reducción en la tasa de complicaciones postoperatorias en los casos en los que se hubiese conseguido la eliminación del hábito. El análisis comparó el resultado económico neto (beneficio menos coste de la intervención) y el retorno de la inversión (return on investment, ROI), cuando la intervención era financiada por el SNS en comparación con la situación actual sin financiamiento público. RESULTADOS: La tasa de abandono del hábito tabáquico aumentó en un 21,8%; 32,5% cuando se financiaba frente al 10,7% sin financiación, consiguiendo un extra de 9.611 personas que dejaron de fumar. El coste por fumador rescatado fue de €1753 con un beneficio de €503, por lo que el beneficio económico neto conseguido fue de €4,8 millones por año. Dado que el coste anual de la intervención (€17,4 millones, de los cuales €5,6 millones corresponden a fármacos (32%)), el ROI anual fue del 28,7% con un beneficio de €1,29 por cada €1 de inversión. CONCLUSIÓN: Desde la perspectiva del SNS español, los beneficios de financiar el abandono del hábito de fumar en el preoperatorio de los pacientes, en términos de ahorro de costes parecen ser muy superiores a los costes de la intervención.

Carcinoma basocelular cutáneo: diagnóstico y tratamiento en atención especializada dermatológica. Guía de Práctica Clínica de la AEDV / Diagnosis and Treatment of Basal Cell Carcinoma in Specialized Dermatology Units: A Clinical Practice Guideline

ANTECEDENTES Y OBJETIVO: El carcinoma basocelular supone el cáncer de piel más frecuente en la población. Hay una gran variabilidad en su manejo y las diferentes guías extranjeras que existen son difícilmente aplicables en nuestro medio. El objetivo de la presente guía es servir de referencia a los dermatólogos españoles para mejorar el manejo de este tumor basándose en la evidencia actual. MATERIALES Y MÉTODOS: Se escogió a miembros del Grupo Español de Dermato-Oncología y Cirugía (GEDOC) con experiencia en el tratamiento de estos tumores y con interés en participar en la elaboración de la guía. Se hizo una adaptación de las guías de práctica clínica existentes mediante el método ADAPTE, se resumió el proceso de atención, y se elaboraron las preguntas clínicas relevantes. Se seleccionaron las guías mejor puntuadas mediante el instrumento AGREE II, realizando la búsqueda de las respuestas en dichas guías y elaborando posteriormente las recomendaciones. Finalmente se sometió la guía a revisión externa. RESULTADOS: Las guías con mejor puntuación fueron las de la British Association of Dermatologits (BAD), del National Comprehensive Cancer Network (NCCN), del European Dermatology Forum (EDF) y de la European Academy of Dermatology and Venereology (EADV). Se obtuvieron en total 11 preguntas clínicas, contestadas a partir de estas guías. CONCLUSIONES: Esta guía responde a preguntas habituales sobre el manejo del carcinoma basocelular en la práctica clínica diaria y sirve a los dermatólogos como referencia en la toma de decisiones, siempre teniendo en cuenta los recursos y las preferencias del paciente

BACKGROUND AND OBJECTIVE: Basal cell carcinoma (BCC) is the most common skin cancer in the general population. BCC is managed in a variety of ways, and available international guidelines are difficult to put into practice in Spain. This guideline aims to improve the management of BCC based on current evidence and provide a point of reference for Spanish dermatologists. MATERIAL AND METHODS: Members of the Spanish Oncologic Dermatology and Surgery Group (GEDOC) with experience treating BCC were invited to participate in drafting this guideline. The drafters used the ADAPTE collaboration process to develop the new guideline based on existing ones, first summarizing the care pathway and posing relevant clinical questions. They then searched for guidelines, assessed them with the AGREEII (Appraisal of Guidelines for Research and Evaluation) tool, and searched the selected guidelines for answers to the clinical questions. Finally, the recommendations were drafted and submitted for external review. RESULTS: The highest-scoring guidelines were from the Association of Dermatologists, the National Comprehensive Cancer Network, the European Dermatology Forum, and the European Academy of Dermatology and Venereology. A total of 11 clinical questions were answered. CONCLUSIONS: This new guideline answers the working group's clinical questions about the routine management of BCC in Spain. It provides dermatologists with a tool they can use for decision-making while taking into consideration the resources available and patient preferences

Diagnosis and Treatment of Basal Cell Carcinoma in Specialized Dermatology Units: A Clinical Practice Guideline. / Carcinoma basocelular cutáneo: diagnóstico y tratamiento en atención especializada dermatológica. Guía de Práctica Clínica de la AEDV.

BACKGROUND AND OBJECTIVE: Basal cell carcinoma (BCC) is the most common skin cancer in the general population. BCC is managed in a variety of ways, and available international guidelines are difficult to put into practice in Spain. This guideline aims to improve the management of BCC based on current evidence and provide a point of reference for Spanish dermatologists. MATERIAL AND METHODS: Members of the Spanish Oncologic Dermatology and Surgery Group (GEDOC) with experience treating BCC were invited to participate in drafting this guideline. The drafters used the ADAPTE collaboration process to develop the new guideline based on existing ones, first summarizing the care pathway and posing relevant clinical questions. They then searched for guidelines, assessed them with the AGREEII (Appraisal of Guidelines for Research and Evaluation) tool, and searched the selected guidelines for answers to the clinical questions. Finally, the recommendations were drafted and submitted for external review. RESULTS: The highest-scoring guidelines were from the Association of Dermatologists, the National Comprehensive Cancer Network, the European Dermatology Forum, and the European Academy of Dermatology and Venereology. A total of 11 clinical questions were answered. CONCLUSIONS: This new guideline answers the working group's clinical questions about the routine management of BCC in Spain. It provides dermatologists with a tool they can use for decision-making while taking into consideration the resources available and patient preferences.

Tratamiento no quirúrgico de las uñas encarnadas con infiltración local de triamcinolona / Nonsurgical Treatment of Ingrown Nails With Local Triamcinolone Injections

No disponible

Comparison of PCR-based methods for the diagnosis of cutaneous leishmaniasis in two different epidemiological scenarios: Spain and Morocco.

BACKGROUND: Cutaneous leishmaniasis (CL) is a disfiguring and stigmatising disease occurring in more than 70 countries across the world including Spain and Morocco. The use of sensitive tests that can differentiate Leishmania species is advised. OBJECTIVE: To evaluate the influence of the epidemiological scenario on the reliability of the PCR techniques and contribute to the selection of the most efficient one for CL diagnosis. METHODS: The sensitivities of parasitological methods and four PCRs were compared in cutaneous samples from 77 patients from Spanish (PSH) and Moroccan hospitals (PMH). Exudates and fresh or paraffin-embedded tissue biopsies were used. RESULTS: None of the PCRs used in this study allowed the diagnosis of all CL cases, showing also some drawbacks. Lmj4/Uni21-PCR displayed the best sensitivity with PMH, but it did not provide positive results in PSH with CL confirmed by other PCRs. Conversely, JW13/JW14-PCR and L. infantum-PCR-ELISA displayed good sensitivities with PSH that were not achieved with PMH. Nested-ITS-1-PCR did not show enough sensitivity with paraffin-embedded tissue biopsies. False-negative results were obtained in 19% of PSH due to unspecific hybridizations of ITS-1 primers with human chromosome1. CONCLUSIONS: PCR should be routinely used in patients with cutaneous lesions compatible with CL and furthermore, the combination of two PCR techniques is advisable. The selection of these PCRs will be influenced by the epidemiological scenario: In areas where L. infantum is endemic, the use of the PCR-ELISA joint with JW13/JW14-PCR seems an appropriate choice, whereas in areas such as Morocco, Lmj4/Uni21 and ITS-1 provide satisfactory results.

Phlebotomus langeroni Nitzulescu (Diptera, Psychodidae) a new vector for Leishmania infantum in Europe.

Burrows of the wild rabbit, Oryctolagus cuniculus, a lagomorph that has been recently suggested as a Leishmania infantum reservoir, constitute an unspoilt biotope in phlebotomine studies in Europe. We hypothesize that Phlebotomus langeroni, a proven vector of L. infantum in North Africa, is associated with rabbits and may have been overlooked in Europe. Sandfly captures were carried out with CDC light traps in an L. infantum endemic area of southern Spain with a high density of lagomorphs and a large numbers of burrows. The stable, permanent, and highly abundant presence of P. langeroni was assessed. After morphological identification, this sandfly species was characterized by comparing it with P. perniciosus and other P. langeroni populations from North Africa through molecular techniques. P. langeroni had not been found in southern Spain to date, despite being a highly investigated area, except for this particular biotope. Its activity period turned out to begin in mid-July, ending in late October, accounting for a maximum activity during this month. This study shows that P. langeroni is associated with the existence of rabbit burrows and has been overlooked in Europe. L. infantum DNA was found in almost half of the female specimens (47.6%) captured inside a biotope where wild rabbits are infected as well.

Effectiveness of the sesquiterpene (-)-α-bisabolol in dogs with naturally acquired canine leishmaniosis: an exploratory clinical trial.

The use of natural products is a promising approach for treating visceral leishmaniosis. (-)-α-Bisabolol is a sesquiterpene that have been proved active in vivo on Leishmania infantum-infected mice without showing toxicity. A single-centre, parallel-group, randomized, exploratory study was designed to assess its efficacy in a canine leishmaniosis model involving naturally infected dogs. In this clinical trial, 12 dogs were allocated into two groups and were treated with either meglumine antimoniate (100 mg/kg) through subcutaneous route or (-)-α-bisabolol (30 mg/kg) through oral route for two treatment series of 30 days, separated by a 30-day interval. A 4-month follow-up period was established as well. Parasite loads in bone marrow, lymph node and blood were estimated through quantitative PCR. Antibody titres were determined through immunofluorescence antibody test and cytokine expression values were estimated through real-time reverse transcription-PCR. Treatment safety was assessed through the evaluation of weight, gastrointestinal alterations and hematological and biochemical parameters in blood. Analyses were performed before and after treatment, and after a 4-months follow-up period. Treatment with the sesquiterpene was effective at decreasing parasite loads and increasing gamma-interferon expression level. Dogs treated with (-)-α-bisabolol did not show any toxicity sign. These results were better than those obtained using the reference drug, meglumine antimoniate. The natural compound seemed to induce a Th1 immune response that led to parasitological and clinical improvement without showing any safety issue, suggesting a high potential for the treatment of canine and human visceral leishmaniosis.

Cutaneous leishmaniasis by Leishmania infantum: behind granulomatous lesions of unknown aetiology.

BACKGROUND: Cutaneous leishmaniasis (CL) is underestimated in Spain as in other European countries due to the polymorphism of its clinical manifestations and histopathological features discouraging doctors from suspecting leishmaniasis. Mucosal manifestations (ML) are misdiagnosed due to the fact that they often mimic cancer. OBJECTIVES: Given that leishmaniasis may be masked as different granulomatous diseases in Leishmania infantum endemic areas, the aim of this study was to verify this misdiagnosing and contributes to the improvement of CL/ML diagnosis. METHODS: A retrospective study involving formalin-fixed paraffin-embedded tissue biopsies with histopathological features of granulomatous lesions of unknown origin (GLUO) detected in 17 patients. This study included 13 patients with CL that was used as positive controls, nine patients with other confirmed diseases used as negative controls and seven patients with histological features suggestive of CL or ML without confirmation. Molecular analysis was blindly performed using two different PCR techniques. RESULTS: The PCR detected 15 CL cases in which the diagnosis was neither clinically nor histologically suspected. Leishmaniasis was confirmed in seven suspected patients in whom the classical techniques failed to detect the parasite. L. infantum was identified in all cases. A systematic review of CL cases in GLUO patients from European countries identified 45 reported cases. CONCLUSIONS: In L. infantum endemic areas, a high percentage of GLUO are due to Leishmania infection. The main consequences are delayed diagnosis and underestimation of the real incidence. PCR performed on paraffin-embedded tissue proved to be a reliable tool for diagnosis of CL/ML and must be performed routinely in any granulomatous dermatitis, even when the morphological features are no stereotypical of leishmaniasis.

Nasal airflow simulations suggest convergent adaptation in Neanderthals and modern humans.

Both modern humans (MHs) and Neanderthals successfully settled across western Eurasian cold-climate landscapes. Among the many adaptations considered as essential to survival in such landscapes, changes in the nasal morphology and/or function aimed to humidify and warm the air before it reaches the lungs are of key importance. Unfortunately, the lack of soft-tissue evidence in the fossil record turns difficult any comparative study of respiratory performance. Here, we reconstruct the internal nasal cavity of a Neanderthal plus two representatives of climatically divergent MH populations (southwestern Europeans and northeastern Asians). The reconstruction includes mucosa distribution enabling a realistic simulation of the breathing cycle in different climatic conditions via computational fluid dynamics. Striking across-specimens differences in fluid residence times affecting humidification and warming performance at the anterior tract were found under cold/dry climate simulations. Specifically, the Asian model achieves a rapid air conditioning, followed by the Neanderthals, whereas the European model attains a proper conditioning only around the medium-posterior tract. In addition, quantitative-genetic evolutionary analyses of nasal morphology provided signals of stabilizing selection for MH populations, with the removal of Arctic populations turning covariation patterns compatible with evolution by genetic drift. Both results indicate that, departing from important craniofacial differences existing among Neanderthals and MHs, an advantageous species-specific respiratory performance in cold climates may have occurred in both species. Fluid dynamics and evolutionary biology independently provided evidence of nasal evolution, suggesting that adaptive explanations regarding complex functional phenotypes require interdisciplinary approaches aimed to quantify both performance and evolutionary signals on covariation patterns.