DosePatch: physics-inspired cropping layout for patch-based Monte Carlo simulations to provide fast and accurate internal dosimetry.

BACKGROUND: Dosimetry-based personalized therapy was shown to have clinical benefits e.g. in liver selective internal radiation therapy (SIRT). Yet, there is no consensus about its introduction into clinical practice, mainly as Monte Carlo simulations (gold standard for dosimetry) involve massive computation time. We addressed the problem of computation time and tested a patch-based approach for Monte Carlo simulations for internal dosimetry to improve parallelization. We introduce a physics-inspired cropping layout for patch-based MC dosimetry, and compare it to cropping layouts of the literature as well as dosimetry using organ-S-values, and dose kernels, taking whole-body Monte Carlo simulations as ground truth. This was evaluated in five patients receiving Yttrium-90 liver SIRT. RESULTS: The patch-based Monte Carlo approach yielded the closest results to the ground truth, making it a valid alternative to the conventional approach. Our physics-inspired cropping layout and mosaicking scheme yielded a voxel-wise error of < 2% compared to whole-body Monte Carlo in soft tissue, while requiring only ≈  10% of the time. CONCLUSIONS: This work demonstrates the feasibility and accuracy of physics-inspired cropping layouts for patch-based Monte Carlo simulations.

TRPV4-Expressing Tissue-Resident Macrophages Regulate the Function of Collecting Lymphatic Vessels via Thromboxane A2 Receptors in Lymphatic Muscle Cells.

Rationale: TRPV4 channels are critical regulators of blood vascular function and have been shown to be dysregulated in many disease conditions in association with inflammation and tissue fibrosis. These are key features in the pathophysiology of lymphatic system diseases, including lymphedema and lipedema; however, the role of TRPV4 channels in the lymphatic system remains largely unexplored. TRPV4 channels are calcium permeable, non-selective cation channels that are activated by diverse stimuli, including shear stress, stretch, temperature, and cell metabolites, which may regulate lymphatic contractile function. Objective: To characterize the expression of TRPV4 channels in collecting lymphatic vessels and to determine the extent to which these channels regulate the contractile function of lymphatics. Methods and Results: Pressure myography on intact, isolated, and cannulated lymphatic vessels showed that pharmacological activation of TRPV4 channels with GSK1016790A (GSK101) led to contractile dysregulation. The response to GSK101 was multiphasic and included, 1) initial robust constriction that was sustained for ≥1 minute and in some instances remained for ≥4 minutes; and 2) subsequent vasodilation and partial or complete inhibition of lymphatic contractions associated with release of nitric oxide. The functional response to activation of TRPV4 channels displayed differences across lymphatics from four anatomical regions, but these differences were consistent across different species (mouse, rat, and non-human primate). Importantly, similar responses were observed following activation of TRPV4 channels in arterioles. The initial and sustained constriction was prevented with the COX inhibitor, indomethacin. We generated a controlled and spatially defined single-cell RNA sequencing (scRNAseq) dataset from intact and microdissected collecting lymphatic vessels. Our data uncovered a subset of macrophages displaying the highest expression of Trpv4 compared to other cell types within and surrounding the lymphatic vessel wall. These macrophages displayed a transcriptomic profile consistent with that of tissue-resident macrophages (TRMs), including differential expression of Lyve1 , Cd163 , Folr2 , Mrc1 , Ccl8 , Apoe , Cd209f , Cd209d , and Cd209g ; and at least half of these macrophages also expressed Timd4. This subset of macrophages also highly expressed Txa2s , which encodes the thromboxane A2 (TXA2) synthase. Inhibition of TXA2 receptors (TXA2Rs) prevented TRPV4-mediated contractile dysregulation. TXA2R activation on LMCs caused an increase in mobilization of calcium from intracellular stores through Ip3 receptors which promoted store operated calcium entry and vasoconstriction. Conclusions: Clinical studies have linked cancer-related lymphedema with an increased infiltration of macrophages. While these macrophages have known anti-inflammatory and pro-lymphangiogenic roles, as well as promote tissue repair, our results point to detrimental effects to the pumping capacity of collecting lymphatic vessels mediated by activation of TRPV4 channels in macrophages. Pharmacological targeting of TRPV4 channels in LYVE1-expressing macrophages or pharmacological targeting of TXA2Rs may offer novel therapeutic strategies to improve lymphatic pumping function and lymph transport in lymphedema.

A three-gene expression score for predicting clinical benefit to anti-PD-1 blockade in advanced renal cell carcinoma.

In the advanced renal cell carcinoma (RCC) scenario, there are no consistent biomarkers to predict the clinical benefit patients derived from immune checkpoint blockade (ICB). Taking this into consideration, herein, we conducted a retrospective study in order to develop and validate a gene expression score for predicting clinical benefit to the anti-PD-1 antibody nivolumab in the context of patients diagnosed with advanced clear cell RCC enrolled in the CheckMate-009, CheckMate-010, and CheckMate-025 clinical trials. First, a three-gene expression score (3GES) with prognostic value for overall survival integrating HMGA1, NUP62, and ARHGAP42 transcripts was developed in a cohort of patients treated with nivolumab. Its prognostic value was then validated in the TCGA-KIRC cohort. Second, the predictive value for nivolumab was confirmed in a set of patients from the CheckMate-025 phase 3 clinical trial. Lastly, we explored the correlation of our 3GES with different clinical, molecular, and immune tumor characteristics. If the results of this study are definitively validated in other retrospective and large-scale, prospective studies, the 3GES will represent a valuable tool for guiding the design of ICB-based clinical trials in the aRCC scenario in the near future.

RET Fusion Testing in Patients With NSCLC: The RETING Study.

Introduction: RET inhibitors with impressive overall response rates are now available for patients with NSCLC, yet the identification of RET fusions remains a difficult challenge. Most guidelines encourage the upfront use of next-generation sequencing (NGS), or alternatively, fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR) when NGS is not possible or available. Taken together, the suboptimal performance of single-analyte assays to detect RET fusions, although consistent with the notion of encouraging universal NGS, is currently widening some of the clinical practice gaps in the implementation of predictive biomarkers in patients with advanced NSCLC. Methods: This situation prompted us to evaluate several RET assays in a large multicenter cohort of RET fusion-positive NSCLC (n = 38) to obtain real-world data. In addition to RNA-based NGS (the criterion standard method), all positive specimens underwent break-apart RET FISH with two different assays and were also tested by an RT-PCR assay. Results: The most common RET partners were KIF5B (78.9%), followed by CCDC6 (15.8%). The two RET NGS-positive but FISH-negative samples contained a KIF5B(15)-RET(12) fusion. The three RET fusions not identified with RT-PCR were AKAP13(35)-RET(12), KIF5B(24)-RET(9) and KIF5B(24)-RET(11). All three false-negative RT-PCR cases were FISH-positive, exhibited a typical break-apart pattern, and contained a very high number of positive tumor cells with both FISH assays. Signet ring cells, psammoma bodies, and pleomorphic features were frequently observed (in 34.2%, 39.5%, and 39.5% of tumors, respectively). Conclusions: In-depth knowledge of the advantages and disadvantages of the different RET testing methodologies could help clinical and molecular tumor boards implement and maintain sensible algorithms for the rapid and effective detection of RET fusions in patients with NSCLC. The likelihood of RET false-negative results with both FISH and RT-PCR reinforces the need for upfront NGS in patients with NSCLC.

Oral infectivity through carnivorism in murine model of Trypanosoma cruzi infection.

Introduction: Oral transmission of T. cruzi is probably the most frequent transmission mechanism in wild animals. This observation led to the hypothesis that consuming raw or undercooked meat from animals infected with T. cruzi may be responsible for transmitting the infection. Therefore, the general objective of this study was to investigate host-pathogen interactions between the parasite and gastric mucosa and the role of meat consumption from infected animals in the oral transmission of T. cruzi. Methods: Cell infectivity assays were performed on AGS cells in the presence or absence of mucin, and the roles of pepsin and acidic pH were determined. Moreover, groups of five female Balb/c mice were fed with muscle tissue obtained from mice in the acute phase of infection by the clone H510 C8C3hvir of T. cruzi, and the infection of the fed mice was monitored by a parasitemia curve. Similarly, we assessed the infective capacity of T. cruzi trypomastigotes and amastigotes by infecting groups of five mice Balb/c females, which were infected orally using a nasogastric probe, and the infection was monitored by a parasitemia curve. Finally, different trypomastigote and amastigote inoculums were used to determine their infective capacities. Adhesion assays of T. cruzi proteins to AGS stomach cells were performed, and the adhered proteins were detected by western blotting using monoclonal or polyclonal antibodies and by LC-MS/MS and bioinformatics analysis. Results: Trypomastigote migration in the presence of mucin was reduced by approximately 30%, whereas in the presence of mucin and pepsin at pH 3.5, only a small proportion of parasites were able to migrate (∼6%). Similarly, the ability of TCTs to infect AGS cells in the presence of mucin is reduced by approximately 20%. In all cases, 60-100% of the animals were fed meat from mice infected in the acute phase or infected with trypomastigotes or amastigotes developed high parasitemia, and 80% died around day 40 post-infection. The adhesion assay showed that cruzipain is a molecule of trypomastigotes and amastigotes that binds to AGS cells. LC-MS/MS and bioinformatics analysis, also confirmed that transialidase, cysteine proteinases, and gp63 may be involved in TCTs attachment or invasion of human stomach cells because they can potentially interact with different proteins in the human stomach mucosa. In addition, several human gastric mucins have cysteine protease cleavage sites. Discussion: Then, under our experimental conditions, consuming meat from infected animals in the acute phase allows the T. cruzi infection. Similarly, trypomastigotes and amastigotes could infect mice when administered orally, whereas cysteinyl proteinases and trans-sialidase appear to be relevant molecules in this infective process.

The Role of Physical Exercise in Chronic Musculoskeletal Pain: Best Medicine-A Narrative Review.

The aim of this paper is to provide a narrative review of the effects of physical exercise in the treatment of chronic musculoskeletal pain. Physical inactivity and sedentary behavior are associated with chronic musculoskeletal pain and can aggravate it. For the management of musculoskeletal pain, physical exercise is an effective, cheap, and safe therapeutic option, given that it does not produce the adverse effects of pharmacological treatments or invasive techniques. In addition to its analgesic capacity, physical exercise has an effect on other pain-related areas, such as sleep quality, activities of daily living, quality of life, physical function, and emotion. In general, even during periods of acute pain, maintaining a minimum level of physical activity can be beneficial. Programs that combine several of the various exercise modalities (aerobic, strengthening, flexibility, and balance), known as multicomponent exercise, can be more effective and better adapted to clinical conditions. For chronic pain, the greatest benefits typically occur with programs performed at light-to-moderate intensity and at a frequency of two to three times per week for at least 4 weeks. Exercise programs should be tailored to the specific needs of each patient based on clinical guidelines and World Health Organization recommendations. Given that adherence to physical exercise is a major problem, it is important to empower patients and facilitate lifestyle change. There is strong evidence of the analgesic effect of physical exercise in multiple pathologies, such as in osteoarthritis, chronic low back pain, rheumatoid arthritis, and fibromyalgia.

Examining the Forearm Intersection through Palpation and Ultrasonography.

BACKGROUND: Forearm intersection syndrome causes pain, swelling, and a rub at the dorsal distal forearm where the first extensor compartment muscles intersect with the second compartment tendons. Although primary care settings tend to treat mild cases, high-performance athletes may suffer from severe symptoms that require surgery. This proof-of-concept study aims to help detect the anatomical substrate of forearm intersection syndrome using palpation and ultrasonography when available. METHODS: Five individuals were studied using independent palpation and ultrasonography to identify the first dorsal compartment muscles and the second dorsal compartment tendons. The distances between the dorsal (Lister's) tubercle of the radius and the ulnar and radial edges of the first dorsal compartment muscles were measured to determine the location and extent of the muscle-tendon intersection. The palpatory and ultrasonographic measurements were compared using descriptive statistics and the paired t-test. RESULTS: The mean distances from the dorsal tubercle of the radius to the ulnar and radial borders of the first dorsal compartment muscles were 4.0 cm (SE 0.42) and 7.7 cm (SE 0.56), respectively, based on palpation. By ultrasonography, the corresponding distances were 3.5 cm (SD 1.05, SE 0.47) and 7.0 cm (SD 1.41, SE 0.63). Both methods showed a similar overlap length. However, ultrasonography revealed a shorter distance between the dorsal tubercle of the radius and the ulnar border of the first compartment than palpation (p = 0.0249). CONCLUSIONS: Our findings indicate that a basic knowledge of anatomy should help health professionals diagnose forearm intersection syndrome through palpation and, if available, ultrasonography.

Epidemiological characterization of ischemic heart disease at different altitudes: A nationwide population-based analysis from 2011 to 2021 in Ecuador.

BACKGROUND: Cardiovascular diseases, including ischemic heart disease, are the leading cause of premature death and disability worldwide. While traditional risk factors such as smoking, obesity, and diabetes have been thoroughly investigated, non-traditional risk factors like high-altitude exposure remain underexplored. This study aims to examine the incidence and mortality rates of ischemic heart disease over the past decade in Ecuador, a country with a diverse altitude profile spanning from 0 to 4,300 meters. METHODS: We conducted a geographic distribution analysis of ischemic heart disease in Ecuador, utilizing hospital discharge and mortality data from the National Institute of Census and Statistics for the years 2011-2021. Altitude exposure was categorized according to two distinct classifications: the traditional division into low (< 2,500 m) and high (> 2,500 m) altitudes, as well as the classification proposed by the International Society of Mountain Medicine, which delineates low (< 1,500 m), moderate (1,500-2,500 m), high (2,500-3,500 m), and very high (3,500-5,800 m) altitudes. FINDINGS: From 2011-2021, we analyzed 49,765 IHD-related hospital admissions and 62,620 deaths. Men had an age-adjusted incidence rate of 55.08/100,000 and a mortality rate of 47.2/100,000, compared to 20.77/100,000 and 34.8/100,000 in women. Incidence and mortality surged in 2020 by 83% in men and 75% in women. Altitudinal stratification revealed higher IHD rates at lower altitudes (<2500 m), averaging 61.65 and 121.8 per 100,000 for incidence and mortality, which declined to 25.9 and 38.5 at elevations >2500 m. Men had more pronounced rates across altitudes, exhibiting 138.7% and 150.0% higher incidence at low and high altitudes respectively, and mortality rates increased by 48.3% at low altitudes and 23.2% at high altitudes relative to women. CONCLUSION: Ecuador bears a significant burden of ischemic heart disease (IHD), with men being more affected than women in terms of incidence. However, women have a higher percentage of mortality post-hospital admission. Regarding elevation, our analysis, using two different altitude cutoff points, reveals higher mortality rates in low-altitude regions compared to high-altitude areas, suggesting a potential protective effect of high elevation on IHD risk. Nevertheless, a definitive dose-response relationship between high altitude and reduced IHD risk could not be conclusively established.

An Unexpected Cause of Abdominal Discomfort: Non-pancreatic Mesenteric Pseudocyst.

Mesenteric cysts (MCs), rare entities of embryologic origin, predominantly affect the small bowel's mesentery. The clinical manifestations of MCs often lack specificity, which complicates diagnosis. Given their rarity, detailed reporting of MC cases is essential to enhance understanding and improve treatment strategies. We present a case of a 45-year-old male who presented to the emergency department with a one-month history of abdominal pain in the umbilical region, postprandial fullness, progressive decrease in food intake, 12 kg weight loss, and increased abdominal girth. Computed tomography (CT) imaging revealed a well-defined mass in the jejunoileal area. During the exploratory laparotomy, we identified and excised a fibrotic mass on the mesentery of the ileal jejunum, which was not adherent to the intestines. We discharged the patient with no complications following an uneventful four-day observational period. Histopathological examination, including immunohistochemical staining, confirmed the lesion as a non-pancreatic mesenteric pseudocyst. On the follow-up visit, the patient reported no complications. This case report underscores the solitary, multilocular nature of the jejunoileal MC, distinct for its serosanguineous fluid content. In conclusion, this case highlights the diagnostic challenge of MCs and illustrates the potential for successful management with a timely and multidisciplinary approach.

Third National Registry of Cardiac Rehabilitation Programs in Mexico (RENAPREC III-2022) / Tercer Registro Nacional de Programas de Rehabilitación Cardiaca en México (RENAPREC III-2022)

Abstract Introduction: In Mexico, cardiac rehabilitation (CR) as an interdisciplinary intervention with therapeutic impact in patients with heart disease is growing. There is the need to know actual conditions of CR in our country. Objectives: The objective of this National Registry is to follow-up those existing and new CR units in Mexico through the comparison between the two previous registries, RENAPREC-2009 and RENAPREC II-2015 studies. This is a descriptive study focused on diverse CR activities such as assistance training, and certification of health professionals, barriers, reference, population attended, interdisciplinarity, permanence over time, growth prospects, regulations, post-pandemic condition, integrative characteristics, and scientific research. Results: Data were collected from 45 CR centers in the 32 states, 75.5% are private practice units, 67% are new, 33% were part of RENAPREC II-2015, and 17 have continued since 2009. With a better distribution of CR units along the territory, the median reference of candidates for CR programs is 9% with a significant reduction into tiempo of enrollment to Phase II admission (19 ± 11 days). Regarding to previous registries, the coverance of Phases I, II, and III is 71%, 100%, and 93%, respectively; and a coverance increases in evaluation, risk stratification, and prescription, more comprehensive attendance and prevention strategies. Conclusions: CR in Mexico has grown in the past 7 years. Even there is still low reference and heterogeneity in specific processes, there are strengths such as interdisciplinarity, scientific professionalization of specialists, national diversification, and an official society that are consolidated over time.

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XRCC1 R194W and R399Q Polymorphisms and Colorectal Cancer Risk in a Northeastern Mexican Population.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Its etiopathogenesis is complex, mainly influenced by genetic instability caused by the accumulation of mutations. The XRCC1 gene, which is involved in DNA repair, has been associated with CRC through the R194W (C194T) and R399Q (G399A) polymorphisms, but the results are inconsistent. Here, we analyzed the association of these polymorphisms with sporadic CRC in a northeastern Mexican population, including 155 male CRC patients and 155 male controls. Genotyping was performed using the RFLP method. An association with CRC was found for the 399A allele (G vs A; OR = 1.48 (1.03-2.13), P=0.034) and for the 399AA genotype in a codominant model (AA vs GG; OR = 3.11 (1.06-9.10), P=0.031). In contrast, there were no significant differences between CRC patients and controls for the C194T polymorphism (C vs T; OR = 0.82 (0.52-1.31), P=0.41). These results are consistent with many similar studies, but further research is needed to verify whether the XRCC1 R194W and R399Q polymorphisms play a role in CRC etiology. The functional significance of these polymorphisms is unclear, but some studies suggest that they influence DNA repair capacity and, thus, cancer risk.

Comorbilidades relacionadas con la severidad de la COVID-19 en adultos. Hospital San Vicente de Paúl. 2021

Fundamento: el estudio de las características clínicas de las personas contagiadas por COVID-19 ha evidenciado que factores como la edad avanzada, sexo masculino y la presencia de comorbilidades están asociados a la variabilidad clínica de esta enfermedad. Objetivo: determinar las comorbilidades relacionadas con la severidad de la COVID-19. Métodos: investigación realizada en el Hospital San Vicente de Paúl, que incluyó 200 pacientes ingresados por COVID-19. La recolección de información se realizó a través de las historias clínicas y se categorizó el grado de severidad de COVID-19. Se empleó el Chi cuadrado de Pearson con un nivel de significación del 95 %, p≤ 0,005 y la prueba Odds Ratio para estimación de riesgo. Resultados: el 53 % de los pacientes pertenece al sexo masculino y el 61,5 % presentó al menos una comorbilidad; la hipertensión arterial fue la más reportada (35 %); el 70 % predominó con una enfermedad grave y el 2,5 % falleció. Además, la enfermedad pulmonar obstructiva crónica se asoció a mayor riesgo de desarrollar una enfermedad leve a moderada de COVID-19. Conclusiones: el estudio propició realizar un seguimiento acerca de la asociación entre comorbolidades conforme avanzaba la pandemia y utilizar la información como factor pronóstico para orientar la intervención temprana y un abordaje terapéutico adecuado.

Foundation: the study of the clinical characteristics of people infected with COVID-19 has shown that factors such as advanced age, male gender and the presence of comorbidities are associated with the clinical variability of this disease. Objective: to determine the comorbidities related to the severity of COVID-19 infections. Methods: research carried out at the San Vicente de Paul Hospital, which includes 200 patients admitted for COVID-19. The collection of information was carried out through the medical records and the degree of severity of COVID-19 was categorized. Pearson's Chi square was used with a significance level of 95%, p≤ 0.005 and the Odds Ratio test for risk estimation. Results: 53% of the patients belong to the male sex and 61.5% presented at least one comorbidity, and arterial hypertension was the most reported (35%); 70% predominated with a serious disease and 2.5% died. Furthermore, chronic obstructive pulmonary disease was associated with an increased risk of developing mild to moderate illness from COVID-19. Conclusions: the study favors monitoring the association between comorbidities as the pandemic progressed and using the information as a prognostic factor to guide early intervention and an appropriate therapeutic approach.

ChatGPT: oportunidades y riesgos en la asistencia, docencia e investigación médica / ChatGPT: opportunities and risks in the fields of medical care, teaching, and research

Resumen ChatGPT es un asistente virtual con inteligencia artificial que utiliza lenguaje natural para comunicarse, es decir, mantiene conversaciones como las que se tendrían con otro humano. Puede aplicarse en educación a todos los niveles, que incluye la educación médica, tanto para la formación, la investigación, la escritura de artículos científicos, la atención clínica y la medicina personalizada. Puede modificar la interacción entre médicos y pacientes para mejorar los estándares de calidad de la atención médica y la seguridad, por ejemplo, al sugerir medidas preventivas en un paciente que en ocasiones no son consideradas por el médico por múltiples causas. Los usos potenciales del ChatGPT en la educación médica, como una herramienta de ayuda en la redacción de artículos científicos, un asistente en la atención para pacientes y médicos para una práctica más personalizada, son algunas de las aplicaciones que se analizan en este artículo. Los aspectos éticos, originalidad, contenido inapropiado o incorrecto, citas incorrectas, ciberseguridad, alucinaciones y plagio son ejemplos de las situaciones a tomar en cuenta al usar las herramientas basadas en inteligencia artificial en medicina.

Abstract ChatGPT is a virtual assistant with artificial intelligence (AI) that uses natural language to communicate, i.e., it holds conversations as those that would take place with another human being. It can be applied at all educational levels, including medical education, where it can impact medical training, research, the writing of scientific articles, clinical care, and personalized medicine. It can modify interactions between physicians and patients and thus improve the standards of healthcare quality and safety, for example, by suggesting preventive measures in a patient that sometimes are not considered by the physician for multiple reasons. ChatGPT potential uses in medical education, as a tool to support the writing of scientific articles, as a medical care assistant for patients and doctors for a more personalized medical approach, are some of the applications discussed in this article. Ethical aspects, originality, inappropriate or incorrect content, incorrect citations, cybersecurity, hallucinations, and plagiarism are some examples of situations to be considered when using AI-based tools in medicine.

Three decades targeting falcipains to develop antiplasmodial agents: what have we learned and what can be done next?

Malaria is a devastating infectious disease that affects large swathes of human populations across the planet's tropical regions. It is caused by parasites of the genus Plasmodium, with Plasmodium falciparum being responsible for the most lethal form of the disease. During the intraerythrocytic stage in the human hosts, malaria parasites multiply and degrade hemoglobin (Hb) using a battery of proteases, which include two cysteine proteases, falcipains 2 and 3 (FP-2 and FP-3). Due to their role as major hemoglobinases, FP-2 and FP-3 have been targeted in studies aiming to discover new antimalarials and numerous inhibitors with activity against these enzymes, and parasites in culture have been identified. Nonetheless, cross-inhibition of human cysteine cathepsins remains a serious hurdle to overcome for these compounds to be used clinically. In this article, we have reviewed key functional and structural properties of FP-2/3 and described different compound series reported as inhibitors of these proteases during decades of active research in the field. Special attention is also paid to the wide range of computer-aided drug design (CADD) techniques successfully applied to discover new active compounds. Finally, we provide guidelines that, in our understanding, will help advance the rational discovery of new FP-2/3 inhibitors.

Spontaneous Subcapsular Renal Hematoma as Cause of Hypovolemic Shock in a Chronic Hemodialysis Patient.

Subcapsular renal hematomas may appear spontaneously in patients in chronic hemodialysis, though other causes as neoplasms, vasculitis, and infections should be excluded. Patients may present with abdominal pain and hemorrhagic shock; hence, early diagnosis is vital. Nephrectomy or renal artery embolization are suitable treatment options.

Effects of Smoking Marijuana on the Respiratory System: A Systematic Review.

BACKGROUND: The prevalence of marijuana use and its derivatives has surged over the past century, largely due to increasing legalization globally. Despite arguments advocating its benefits, marijuana smoking exposes the lungs to harmful combustion byproducts, leading to various respiratory issues such as asthma, pneumonia, emphysema, and chronic obstructive pulmonary disease. METHODS: We embarked on an extensive literature search, utilizing PubMed/Medline, Scopus, Web of Science, and Google Scholar databases, identifying 200 studies. After the elimination of duplicates, and meticulous review of abstracts and full texts, 55 studies were included in our analysis. RESULTS: Current literature demonstrates that marijuana use negatively impacts lung function, triggering symptoms like chronic cough, sputum production, and wheezing, and diminishing FEV1/FVC ratio in spirometry tests. Moreover, prolonged or chronic marijuana use augments the risk of respiratory function impairment. While the carcinogenic effects of marijuana are still contested, a weak correlation between marijuana use and lung cancer has been observed in some studies. Additionally, instances of other pathologies linked to marijuana use have been reported, including the development of COPD, pulmonary bullae, spontaneous pneumothorax, pleuritic pain, chronic pulmonary aspergillosis, hemoptysis, and pulmonary Langerhans cell histiocytosis. CONCLUSIONS: The evidence underscores that marijuana use is detrimental to respiratory health. In light of the escalating trend of marijuana use, particularly among the youth, it is imperative to advocate public health messages discouraging its consumption.

From waste to food and bioinsecticides: An innovative system integrating Tenebrio molitor bioconversion and pyrolysis bio-oil production.

To achieve a waste-free clean production, the present study aimed to valorize an underused agroindustrial byproduct (rice bran) by mealworms bioconversion and produce bio-oil from pyrolysis of insect excreta (frass) as bioinsecticide. To reach the first goal, the suitability of rice bran (RB) versus standard diet, wheat bran (WB), was examined by determining feed conversion, growth performance, and nutritional profile of T. molitor larvae. RB diet was an appropriate feed substrate for breeding mealworms, as evidenced by their high survival rates, optimal feed conversion parameters, and its capability to support the growth and life cycle of this insect. Besides, RB did not affect soluble larval protein content but modified crude fat content and fatty acid profile. In order to address the second aim, egested frass from RB and WB were subjected to pyrolysis to obtain bio-oils. The main compound was acetic acid (≈37%) followed by 1,6-anhydro-ß-d-glucopyranose (from 16 to 25%), as measured by GC-MS analysis. Nitrogen-containing chemicals accounted for ≈10%. Frass bio-oils could represent a novel source of bioinsecticides due to their bioeffectiveness in insect pests of economic importance (Plodia interpunctella and Tribolium castaneum) and medical interest (Culex pipiens pipiens). For P. interpunctella adults, frass bio-oils produced insecticidal activity by fumigant and contact exposure whereas for T. castaneum adults, just fumigant. By a miniaturized model that simulates semireal storage conditions, it was seen that, on T. castaneum, frass RB bio-oil generated higher repellent effect than frass WB. Finally, bio-oils proved to have larvicidal activity against Cx. p. pipiens.

La medicina y el metaverso: aplicaciones actuales y futuro / Medicine and the metaverse: current applications and future

Resumen Las innovadoras tecnologías del metaverso y el chat GPT4 (basado en inteligencia artificial) están presentes en el discurso cotidiano de la sociedad; recientemente se han introducido en la práctica médica y están provocando importantes cambios. En cuanto al metaverso ("después del universo"), diversas escuelas y facultades de medicina del mundo comienzan a utilizarlo como una estrategia innovadora dirigida a la enseñanza de materias como anatomía, histología, oftalmología y simulación en mundos paralelos (virtuales) para el aprendizaje y supervisión de cirugías, así como para otras aplicaciones en educación médica y en la relación médico-paciente. Si bien debe tomarse en cuenta como un área de oportunidad para la transformación de la medicina, es importante considerar las diversas limitaciones y riesgos del metaverso en la práctica médica, la formación de estudiantes y la relación del médico con los problemas de salud a los que se enfrenta en su práctica.

Abstract Innovative technologies such as the metaverse and chat GPT-4 (based on artificial intelligence) are present in the daily discourse of society; recently, they have been introduced into medical practice and are bringing about important changes. In the case of the metaverse ("beyond the universe"), various medical schools and departments around the world are beginning to use it as an innovative strategy for teaching subjects such as anatomy, histology, ophthalmology, and simulation in parallel (virtual) worlds for learning and supervision of surgeries, as well as for other applications in medical education and in the doctor-patient relationship. Although it should be regarded as an area of opportunity for the transformation of medicine, it is important to consider the various limitations and risks of the metaverse in medical practice, student training, and physicians' relationship with the health problems they have to deal with in their practice.