Pharmacological Treatments and Therapeutic Targets in Muscle Dystrophies Generated by Alterations in Dystrophin-Associated Proteins.

Muscular dystrophies (MDs) are a heterogeneous group of diseases of genetic origin characterized by progressive skeletal muscle degeneration and weakness. There are several types of MDs, varying in terms of age of onset, severity, and pattern of the affected muscles. However, all of them worsen over time, and many patients will eventually lose their ability to walk. In addition to skeletal muscle effects, patients with MDs may present cardiac and respiratory disorders, generating complications that could lead to death. Interdisciplinary management is required to improve the surveillance and quality of life of patients with an MD. At present, pharmacological therapy is only available for Duchene muscular dystrophy (DMD)-the most common type of MD-and is mainly based on the use of corticosteroids. Other MDs caused by alterations in dystrophin-associated proteins (DAPs) are less frequent but represent an important group within these diseases. Pharmacological alternatives with clinical potential in patients with MDs and other proteins associated with dystrophin have been scarcely explored. This review focuses on drugs and molecules that have shown beneficial effects, mainly in experimental models involving alterations in DAPs. The mechanisms associated with the effects leading to promising results regarding the recovery or maintenance of muscle strength and reduction in fibrosis in the less-common MDs (i.e., with respect to DMD) are explored, and other therapeutic targets that could contribute to maintaining the homeostasis of muscle fibers, involving different pathways, such as calcium regulation, hypertrophy, and maintenance of satellite cell function, are also examined. It is possible that some of the drugs explored here could be used to affordably improve the muscular function of patients until a definitive treatment for MDs is developed.

Evaluation of rapid antiretroviral initiation strategy in a cohort of newly diagnosed people living with HIV in Panama, 2018-2019.

Antiretroviral therapy (ART) has been adopted as a form of HIV treatment and prevention. This study assesses rapid ART initiation using clinical outcomes such as viral load (VL) and CD4+ T lymphocytes count. Over the course of one year, the progress of newly diagnosed people living with HIV who started ART early in a hospital in Panama City was followed. The evaluation of early initiation of ART in achieving viral suppression (VL <200 copies/ml) was analyzed using descriptive statistics. Additionally, the cost difference between early (first 7 days) and late initiation of ART was evaluated from the perspective of the service provider. In total, 209 people were followed up during the study; 85% were male, 70% started ART on same day from hospital arrival, 80% had suppressed viral load at 6 months, and the median count of CD4 increased from 285 (IQR: 166-429) to 509 (IQR: 373-696) over 12 months. Starting ART early led to a 42% increase for the provider in terms of staffing costs; however, the clients had the opportunity to decrease absenteeism in daily activities. The results reveal that early initiation of ART generates clinical and economic benefits for the person in treatment.

trans-Di-chlorido-bis-(secnidazole-κN 3)copper(II).

The use of acetic acid (HOAc) in a reaction between CuCl2·2H2O and secnid-azole, an active pharmaceutical ingredient useful in the treatment against a variety of anaerobic Gram-positive and Gram-negative bacteria, affords the title complex, [CuCl2(C7H11N3O3)2]. This compound was previously synthesized using ethanol as solvent, although its crystal structure was not reported [Betanzos-Lara et al. (2013 ▸). Inorg. Chim. Acta, 397, 94-100]. In the mol-ecular complex, the Cu2+ cation is situated at an inversion centre and displays a square-planar coordination environment. There is a hydrogen-bonded framework based on inter-molecular O-H⋯Cl inter-actions, characterized by H⋯Cl separations of 2.28 (4) Šand O-H⋯Cl angles of 175 (3)°. The resulting supra-molecular network is based on R2 2 (18) ring motifs, forming chains in the [010] direction.

Chlorido-(2-{(2-hy-droxy-eth-yl)[tris-(hy-droxy-meth-yl)meth-yl]amino}-ethano-lato-κ5 N,O,O',O'',O''')copper(II).

The title complex, [Cu(C8H18NO5)Cl] or [Cu(H4bis-tris-)Cl], was obtained starting from the previously reported [Cu(H5bis-tris-)Cl]Cl compound. The deprotonation of the amino-polyol ligand H5bis-tris {[bis-(2-hy-droxy-eth-yl)amino]-tris-(hy-droxy-meth-yl)methane, C8H19NO5} promotes the formation of a very strong O-H⋯O inter-molecular hydrogen bond, characterized by an H⋯O separation of 1.553 (19) Šand an O-H⋯O angle of 178 (4)°. The remaining hy-droxy groups are also engaged in hydrogen bonds, forming R 2 2(8), R 4 4(16), R 4 4(20) and R 4 4(22) ring motifs, which stabilize the triperiodic supra-molecular network.

The NDV-MLS as an Immunotherapeutic Strategy for Breast Cancer: Proof of Concept in Female Companion Dogs with Spontaneous Mammary Cancer.

The absence of tumor-infiltrating lymphocytes negatively impacts the response to chemotherapy and prognosis in all subtypes of breast cancer. Therapies that stimulate a proinflammatory environment may help improve the response to standard treatments and also to immunotherapies such as checkpoint inhibitors. Newcastle disease virus (NDV) shows oncolytic activity, as well as immune modulating potential, in the treatment of breast cancer in vitro and in vivo; however, its potential to enhance tumor-infiltrating immune cells in breast cancer has yet to be evaluated. Since spontaneous canine mammary tumors represent a translational model of human breast cancer, we conducted this proof-of-concept study, which could provide a rationale for further investigating NDV-MLS as immunotherapy for mammary cancer. Six female companion dogs with spontaneous mammary cancer received a single intravenous and intratumoral injection of oncolytic NDV-MLS. Immune cell infiltrates were evaluated by histology and immunohistochemistry in the stromal, intratumoral, and peritumoral compartments on day 6 after viral administration. Increasing numbers of immune cells were documented post-viral treatment, mainly in the peritumoral compartment, where plasma cells and CD3+ and CD3-/CD79- lymphocytes predominated. Viral administration was well tolerated, with no significant adverse events. These findings support additional research on the use of NDV-MLS immunotherapy for mammary cancer.

Chagasin from Trypanosoma cruzi as a molecular scaffold to express epitopes of TSA-1 as soluble recombinant chimeras.

Trypanosoma cruzi is the causative agent of Chagas disease, a global public health problem. New therapeutic drugs and biologics are needed. The TSA-1 recombinant protein of T. cruzi is one such promising antigen for developing a therapeutic vaccine. However, it is overexpressed in E. coli as inclusion bodies, requiring an additional refolding step. As an alternative, in this study, we propose the endogenous cysteine protease inhibitor chagasin as a molecular scaffold to generate chimeric proteins. These proteins will contain combinations of two of the five conserved epitopes (E1 to E5) of TSA-1 in the L4 and L6 chagasin loops. Twenty chimeras (Q1-Q20) were designed, and their solubility was predicted using bioinformatics tools. Nine chimeras with different degrees of solubility were selected and expressed in E. coli BL21 (DE3). Western blot assays with anti-6x-His and anti-chagasin antibodies confirmed the expression of soluble recombinant chimeras. Both theoretically and experimentally, the Q12 (E5-E3) chimera was the most soluble, and the Q20 (E4-E5) the most insoluble protein. Q4 (E5-E1) and Q8 (E5-E2) chimeras were classified as proteins with medium solubility that exhibited the highest yield in the soluble fraction. Notably, Q4 has a yield of 239 mg/L, well above the yield of recombinant chagasin (16.5 mg/L) expressed in a soluble form. The expression of the Q4 chimera was scaled up to a 7 L fermenter obtaining a yield of 490 mg/L. These data show that chagasin can serve as a molecular scaffold for the expression of TSA-1 epitopes in the form of soluble chimeras.

Etnobotánica de los barrios antiguos de Guadalajara, Jalisco, México: el uso de plantas medicinales / Ethnobotany of the old neighborhoods from Guadalajara, Jalisco, Mexico: the use of medicinal plants

Medicinal plants have been used by various cultures since pre - Hispanic times in Mexico. In this study, the use of medicinal plants in the old neighborhoods of Guadalajara, Jalisco, Mexico is described. 137 species, 130 genera and 68 families were recorded. 34% of the species belong to Asteraceae, Lamiaceae, Malvaceae and Fabaceae families. The neighborhoods of Mexicaltzingo and San Juan de Dios are the most related to the knowledge and use of medicinal plants, while El Santuario is the least similar to the rest. The diversity of uses of medicinal plants according to the Shannon index is high (between 3.0 and 4.92). The Use Value Index showed that Matricaria chamomilla L. was the species that obtained the highest valu e (0.28), followed by Gnaphalium americanum Mill. (0.23). The age group between 51 and 85 years old has greater knowledge about medicinal plants and their uses.

Las plantas medicinales han sido utilizadas por diversas culturas desde tiempos prehispánicos en México. En este estudio, se describe el uso de plantas medicinales en los barrios antiguos de Guadalajara, Jalisco, México. Se registraron 137 especies, 130 géneros y 68 familias. El 34% de las especies pertenece a las familias Asteraceae, Lamiaceae, Malvaceae y Fabaceae. Los barrios de Mexicaltzingo y San Juan de Dios son los más parecidos en cuanto al conocimiento y uso de pl antas medicinales, mientras que El Santuario es el menos afín al resto. La diversidad de usos de las plantas medicinales de acuerdo con el índice de Shannon es alta (entre 3.0 y 4.92). El Índice de Valor de Uso mostró que Matricaria chamomilla L. fue la es pecie que obtuvo el máximo valor (0.28), seguida de Gnaphalium americanum Mill. (0.23). El grupo de entre 51 - 85 de edad posee mayor conocimiento sobre las plantas medicinales y sus usos.

Breast MRI in patients with implantable loop recorder: initial experience.

OBJECTIVES: To investigate the feasibility of breast MRI exams and guided biopsies in patients with an implantable loop recorder (ILR) as well as the impact ILRs may have on image interpretation. MATERIALS AND METHODS: This retrospective study examined breast MRIs of patients with ILR, from April 2008 to September 2022. Radiological reports and electronic medical records were reviewed for demographic characteristics, safety concerns, and imaging findings. MR images were analyzed and compared statistically for artifact quantification on the various pulse sequences. RESULTS: Overall, 40/82,778 (0.049%) MRIs during the study period included ILR. All MRIs were completed without early termination. No patient-related or device-related adverse events occurred. ILRs were most commonly located in the left lower-inner quadrant (64.6%). The main artifact was a signal intensity (SI) void in a dipole formation in the ILR bed with or without areas of peripheral high SI. Artifacts appeared greatest in the cranio-caudal axis (p < 0.001), followed by the anterior-posterior axis (p < 0.001), and then the right-left axis. High peripheral rim-like SI artifacts appeared on the post-contrast and subtracted T1-weighted images, mimicking suspicious enhancement. Artifacts were most prominent on diffusion-weighted (p < 0.001), followed by T2-weighted and T1-weighted images. In eight patients, suspicious findings were found on MRI, resulting in four additional malignant lesions. Of six patients with left breast cancer, the tumor was completely visible in five cases and partially obscured in one. CONCLUSION: Breast MRI is feasible and safe among patients with ILR and may provide a significant diagnostic value, albeit with localized, characteristic artifacts. CLINICAL RELEVANCE STATEMENT: Indicated breast MRI exams and guided biopsies can be safely performed in patients with implantable loop recorder. Nevertheless, radiologists should be aware of associated limitations including limited assessment of the inner left breast and pseudo-enhancement artifacts. KEY POINTS: • Breast MRI in patients with an implantable loop recorder is an infrequent, feasible, and safe procedure. • Despite limited breast visualization of the implantable loop recorder bed and characteristic artifacts, MRI depicted additional lesions in 8/40 (20%) of cases, half of which were malignant. • Breast MRI in patients with an implantable loop recorder should be performed when indicated, taking into consideration typical associated artifacts.

A monster into the heart: an unusual presentation of cardiac leiomyosarcoma.

BACKGROUND: Malignant primary cardiac tumors are infrequent and can lead to an unfavorable prognosis if not identified and treated promptly. Early detection and prompt treatment of malignant primary cardiac tumors are crucial for a better prognosis. This article presents a case of primary cardiac leiomyosarcoma and reviews the literature on this topic. CASE PRESENTATION: Female patient that developed recurrent pericardial effusion and hemodynamic instability caused by a cardiac tumor, later identified as leiomyosarcoma. Multidisciplinary treatment was administered to the patient. CONCLUSIONS: The initial approach to this type of pathology should include multimodality imaging to establish a prompt diagnosis leading to complete standard treatment, to minimize risks to the patient's heart function which may include resection with complete margins of the neoplasm, otherwise the prognosis may be poor.

[Quality of life and caregiver burden in caregivers with patients with complications from type 2 diabetes mellitus]. / Calidad de vida y sobrecarga del cuidador en cuidadores con pacientes con complicaciones por la diabetes mellitus tipo 2.

Background: Chronic diseases with partial dependence, including type 2 diabetes mellitus, modify the way of life of the patient and his family, who adopt the role of caregiver having to reorganize, rethink their expectations and adapt their goals and objectives to the situation, this may generate a deterioration of the quality of life and an overload syndrome. Objective: To identify the relationship between quality of life and caregiver overload in caregivers with patients with complications from type 2 diabetes mellitus assigned to the Family Medicine Unit No. 7. Material and methods: Cross-sectional study, carried out with 138 caregivers with a patient with complications from type 2 diabetes mellitus. The sociodemographic profile instruments, the SF-36 health questionnaire, and the Zarit scale were used for data collection. The analysis was carried out through descriptive statistics and Spearman's correlation test, with a significance level of p≤0.05. Results: It was identified that the health-related quality of life in caregivers with patients with complications from type 2 diabetes mellitus evaluated with the SF-36 questionnaire had a mean value of 74.8; with a score in the physical and mental components of 63.9 and 38.1 respectively. The best qualified dimensions were social function (84.9) and physical function, on the other hand, vitality obtained a lower qualification. It was observed that 5.05% of the caregivers present light overload and 5.05% intense overload. When performing the correlation between the global rating of the Zarit scale with the 8 dimensions of the SF-36 health questionnaire in caregivers of patients with complications of type 2 diabetes mellitus, a moderate negative correlation was observed between the dimensions of mental health, physical function, emotional role and vitality, as well as a weak negative correlation between the dimensions of social role and physical role. Conclusions: The results show an inverse correlation between the caregiver's burden and the quality-of-life dimensions, that is, if one decreases, the other increases; It is important to carry out health promotion activities in this population to prevent caregiver overload.

Introducción: las enfermedades crónicas con parcial dependencia, incluyendo la diabetes mellitus tipo2, modifican el modo de vida del paciente y de su familia, quienes adoptan el rol de cuidador, por lo que tienen que reorganizarse, replantear sus expectativas y adecuar sus metas y objeticos a la situación, generando un deterioro de la calidad de vida y un síndrome de sobrecarga. Objetivo: identificar la relación entre calidad de vida y sobrecarga del cuidador en cuidadores con pacientes con complicaciones por la diabetes mellitus tipo 2 adscritos a la Unidad de Medicina Familiar No. 7. Material y métodos: estudio transversal, realizado con 138 cuidadores con paciente con complicaciones por la diabetes mellitus tipo 2. Para la recolección de los datos, fueron utilizados los instrumentos de perfil sociodemográfico, el cuestionario de salud SF-36 y la escala de Zarit. El análisis se realizó por medio de estadística descriptiva y de la prueba de correlación de Spearman, con un nivel de significancia de p ≤ 0.05. Resultados: se identificó que la calidad de vida relacionada con la salud en los cuidadores con pacientes con complicaciones por la diabetes mellitus tipo 2 evaluada con el cuestionario SF-36 tuvo un valor medio de 74,8; con una puntuación en los componentes físico y mental de 63,9 y de 38,1 respectivamente. Las dimensiones mejor calificadas fueron la función social y física, en cambio, la vitalidad obtuvo menor calificación. Se observó que el 5,05% de los cuidadores presentan sobrecarga ligera y el 5,05% sobrecarga intensa. Al realizar la correlación entre la calificación global de la escala de Zarit con las 8 dimensiones del cuestionario de salud SF-36 en cuidadores de pacientes con complicaciones por la diabetes mellitus tipo 2, se observó una correlación moderada negativa entre las dimensiones de salud mental, la función física, el rol emocional y la vitalidad, así como una correlación negativa débil entre las dimensiones de función social y el rol físico. Conclusiones: los resultados muestran una correlación inversa entre la sobrecarga del cuidador y las dimensiones de calidad de vida, es decir, si disminuye una aumenta la otra; es importante realizar actividades de promoción a la salud en esta población para prevenir la sobrecarga del cuidador.

NLRP3 Inflammasome Involved with Viral Replication in Cytopathic NADL BVDV Infection and IFI16 Inflammasome Connected with IL-1ß Release in Non-Cytopathic NY-1 BVDV Infection in Bovine Macrophages.

Inflammasomes are multiprotein complexes that play a role in the processing of proinflammatory cytokines such as interleukin 1 beta (IL-1ß). The secretion of IL-1ß in bovine macrophages infected with the bovine viral diarrhea virus (BVDV) cytopathic strain NADL (NADLcp-BVDV) is caspase 1-dependent. In the present study, we found that in macrophages infected with NADL, the NLRP3 inflammasome participated in the maturation of IL-1ß as the level decreased from 4629.3 pg/mL to 897.0 pg/mL after treatment with cytokine release inhibitory drug 3 (CRID3). Furthermore, NLRP3 activation has implications regarding viral replication, as there was a decrease in the viral titer until 1 log of a supernatant of macrophages that were inhibited with CRID3 remained. In the case of the non-cytopathic BVDV strain NY-1 (NY-1 ncpBVDV), IL-1ß secretion is not affected by NLRP3, but could be related to the IFI16 inflammasome; we found a colocalization of IFI16 with ASC using confocal microscopy in infected macrophages with the NY-1 ncp-BVDV biotype. To relate IFI16 activation to IL-1ß release, we used ODN TTAGGG (A151), a competitive inhibitor of IFI16; the results show a decrease in its level from 248 pg/mL to 128.3 pg/mL. Additionally, we evaluated the caspase 1 activation downstream of IFI16 and found a decrease in the IL-1ß from 252.9 pg/mL to 63.5 pg/mL when caspase 1 was inhibited with Y-VAD. Our results provide an improved understanding of the mechanisms involved in the viral replication, inflammation and pathogenesis of bovine viral diarrhea.

Expression and localization of vascular endothelial growth factor and its receptors in the pig uterus during peri-implantation and determination of the in vitro effect of the angiogenesis inhibitor SU5416 on VEGF system expression.

The aim of this work was to determine endometrial mRNA expression and uterine protein localization of vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2 during the estrous cycle and peri-implantation period in sows. Uterine tissues were collected from pregnant sows on days 12, 14, 16, and 18 after artificial insemination and from non-pregnant animals on days 2 and 12 of the estrous cycle (day 0 = day of estrus). Using immunohistochemistry, a positive signal for VEGF and its receptor VEGFR2 was found in uterine luminal epithelial cells, endometrial glands, stroma, blood vessels, and myometrium. A VEGFR1 signal was only found in endometrial and myometrial blood vessels and stroma. By day 18 of gestation, the mRNA expression levels of VEGF, VEGFR1, and VEGFR2 were higher than those observed on days 2 and 12 of the estrous cycle and on days 12, 14, and 16 of gestation. Then, a primary culture of sow endometrial epithelial cells was established to define the potential of the selective inhibition of VEGFR2 after treatment with inhibitor SU5416 and determine its effects on the expression pattern of the VEGF system. The endometrial epithelial cells treated with SU5416 showed a dose-dependent decrease in VEGFR1 and VEGFR2 mRNA expression. The present study provides additional evidence on the importance of the VEGF system during peri-implantation, as well as on the specific inhibitory activity of SU5416 in epithelial cells, which, as demonstrated, express the protein and mRNA of VEGF and its receptors VEGFR1 and VEGFR2.

Pancreatic tumors exhibit myeloid-driven amino acid stress and upregulate arginine biosynthesis.

Nutrient stress in the tumor microenvironment requires cancer cells to adopt adaptive metabolic programs for survival and proliferation. Therefore, knowledge of microenvironmental nutrient levels and how cancer cells cope with such nutrition is critical to understand the metabolism underpinning cancer cell biology. Previously, we performed quantitative metabolomics of the interstitial fluid (the local perfusate) of murine pancreatic ductal adenocarcinoma (PDAC) tumors to comprehensively characterize nutrient availability in the microenvironment of these tumors. Here, we develop Tumor Interstitial Fluid Medium (TIFM), a cell culture medium that contains nutrient levels representative of the PDAC microenvironment, enabling us to study PDAC metabolism ex vivo under physiological nutrient conditions. We show that PDAC cells cultured in TIFM adopt a cellular state closer to that of PDAC cells present in tumors compared to standard culture models. Further, using the TIFM model, we found arginine biosynthesis is active in PDAC and allows PDAC cells to maintain levels of this amino acid despite microenvironmental arginine depletion. We also show that myeloid derived arginase activity is largely responsible for the low levels of arginine in PDAC tumors. Altogether, these data indicate that nutrient availability in tumors is an important determinant of cancer cell metabolism and behavior, and cell culture models that incorporate physiological nutrient availability have improved fidelity to in vivo systems and enable the discovery of novel cancer metabolic phenotypes.

Etiopathogenesis of chronic kidney disease-associated pruritus: putting the pieces of the puzzle together.

Defined as the unpleasant sensation that causes the desire to scratch, pruritus is the most common skin symptom associated with uremia and appears in almost half of patients with advanced chronic kidney disease (CKD). Beyond its direct impact on quality of life, CKD-associated pruritus (CKD-aP) is an independent predictor of mortality that also has a synergistic effect with other quality of life-related symptoms, such as insomnia, depression, and anxiety. Although different mechanisms have been proposed to explain the origin of Pa-ERC, its etiopathogenesis is still not fully understood. Since new therapeutic targets have been identified and several clinical trials have recently shown promising results, our current understanding of the interrelationships has expanded significantly and the pathophysiological mechanisms underlying CKD-aP are now considered to be multifactorial. The potential triggers of pruritus in patients with CKD are discussed in this review, including hypotheses about skin xerosis, accumulation of uremic toxins, dysregulation of the immune system and systemic inflammation, uremic neuropathy, and imbalances in the endogenous opioid system. Other non-uremic causes of pruritus are also discussed, with the aim of guiding the physicians to apply an adequate aetiopathogenic approach to CKD-aP in their day-to-day clinical practice.

Validation of portable electronic equipment (Accutrend® Plus) to determine glucose, total cholesterol, and triglycerides in rats (Rattus) and dogs (Canis lupus familiaris).

Objective: This study aimed to validate the analytical precision of the Accutrend® Plus portable electronic equipment (PE) to determine glucose (GLU), total cholesterol (TC), and triglycerides (TG) in rats and dogs using the conventional laboratory method (CM) as a reference. Materials and Methods: To determine the analytical accuracy of the Accutrend® Plus in the measurement of GLU, CT, and TG. The EP-9-A2 guide (Clinical and Laboratory Standards Institute), Bland-Altman graphical analysis, and Lin's correlation coefficient of concordance (CCC) were implemented. Results: The average differences (p > 0.05) between PE and CM for GLU, TC, and TG were 2.21, 1.20, and 0.72 mg·dl-1, respectively, in rats and 1.06, 4.30, and 2.41 mg·dl-1, respectively, in dogs (p > 0.05). Both methods showed a linear relationship with Pearson's correlation coefficients > 0.96 and R 2 > 0.97 for the three biochemical indicators evaluated in both species. The GLU, TC, and TG values obtained by the PE were substantial, as evident from Lin's CCC > 0.96. Conclusion: The PE Accutrend® Plus is potent for monitoring GLU, TC, and TG in rats and dogs because of its precision and ability to facilitate measurement by reducing stress in animals during sampling.

Differences in Longevity and Temperature-Driven Extrinsic Incubation Period Correlate with Varying Dengue Risk in the Arizona-Sonora Desert Region.

Dengue transmission is determined by a complex set of interactions between the environment, Aedes aegypti mosquitoes, dengue viruses, and humans. Emergence in new geographic areas can be unpredictable, with some regions having established mosquito populations for decades without locally acquired transmission. Key factors such as mosquito longevity, temperature-driven extrinsic incubation period (EIP), and vector-human contact can strongly influence the potential for disease transmission. To assess how these factors interact at the edge of the geographical range of dengue virus transmission, we conducted mosquito sampling in multiple urban areas located throughout the Arizona-Sonora desert region during the summer rainy seasons from 2013 to 2015. Mosquito population age structure, reflecting mosquito survivorship, was measured using a combination of parity analysis and relative gene expression of an age-related gene, SCP-1. Bloodmeal analysis was conducted on field collected blood-fed mosquitoes. Site-specific temperature was used to estimate the EIP, and this predicted EIP combined with mosquito age were combined to estimate the abundance of "potential" vectors (i.e., mosquitoes old enough to survive the EIP). Comparisons were made across cities by month and year. The dengue endemic cities Hermosillo and Ciudad Obregon, both in the state of Sonora, Mexico, had higher abundance of potential vectors than non-endemic Nogales, Sonora, Mexico. Interestingly, Tucson, Arizona consistently had a higher estimated abundance of potential vectors than dengue endemic regions of Sonora, Mexico. There were no observed city-level differences in species composition of blood meals. Combined, these data offer insights into the critical factors required for dengue transmission at the ecological edge of the mosquito's range. However, further research is needed to integrate an understanding of how social and additional environmental factors constrain and enhance dengue transmission in emerging regions.

Perception of Spanish nephrologists on an old unsolved problem: Pruritus associated with chronic kidney disease (CKD-aP).

INTRODUCTION: Pruritus associated with chronic kidney disease is defined as the sensation of itching, in people with chronic kidney disease, in a one area or all over the body that causes the need to scratch, after having ruled out other dermatological or systemic causes. It is an old and known problem whose prevalence has been able to decrease with the improvement of dialytic techniques but which still persists and is underdiagnosed. OBJECTIVES: The objective of this study was to analyse the current perception of nephrologists about this problem that influences the quality of life of people with chronic kidney disease through a survey. RESULTS: 135 nephrologists, most of them engaged in haemodialysis, participated. 86% considered that pruritus associated with chronic kidney disease is still a problem today that affects the quality of life. Most nephrologists believe that the main pathophysiological cause is uremic toxins (60%) and only 16% believe that it is due to the dysregulation of the opioid system/endorphins-dynorphins. Only 16% comment that the prevalence of pruritus in their centre is greater than 20%. 40% believe that the diagnosis is made because it is manifested by the patient and only 27% because it is asked by the doctor. Moreover, it is not usual to use scales to measure it or the codification in the medical records. The main treatment used is antihistamines (96%), followed by moisturizers/anaesthetics (93%) and modification of the dialysis regimen (70%). CONCLUSIONS: Pruritus associated with chronic kidney disease is still a current problem, it is underdiagnosed, not codified and with a lack of indicated, effective and safe treatments. Nephrologists do not know its real prevalence and the different pathophysiological mechanisms involved in its development. Many therapeutic options are used with very variable results, ignoring their efficacy and applicability at the present time. The new emerging kappa-opioid-receptor agonist agents offer us an opportunity to reevaluate this age-old problem and improve the quality of life for our patients with chronic kidney disease.