Genomic advances in the study of the mosquito vector during avian malaria infection.

Invertebrate host­parasite associations are one of the keystones in order to understand vector-borne diseases. The study of these specific interactions provides information not only about how the vector is affected by the parasite at the gene-expression level, but might also reveal mosquito strategies for blocking the transmission of the parasites. A very well-known vector for human malaria is Anopheles gambiae. This mosquito species has been the main focus for genomics studies determining essential key genes and pathways over the course of a malaria infection. However, to-date there is an important knowledge gap concerning other non-mammophilic mosquito species, for example some species from the Culex genera which may transmit avian malaria but also zoonotic pathogens such as West Nile virus. From an evolutionary perspective, these 2 mosquito genera diverged 170 million years ago, hence allowing studies in both species determining evolutionary conserved genes essential during malaria infections, which in turn might help to find key genes for blocking malaria cycle inside the mosquito. Here, we extensively review the current knowledge on key genes and pathways expressed in Anopheles over the course of malaria infections and highlight the importance of conducting genomic investigations for detecting pathways in Culex mosquitoes linked to infection of avian malaria. By pooling this information, we underline the need to increase genomic studies in mosquito­parasite associations, such as the one in Culex­Plasmodium, that can provide a better understanding of the infection dynamics in wildlife and reduce the negative impact on ecosystems.

Implications of migratory and exotic birds and the mosquito community on West Nile virus transmission.

BACKGROUND: Vector-borne diseases like West Nile virus (WNV) pose a global health challenge, with rising incidence and distribution. Culex mosquitoes are crucial WNV vectors. Avian species composition and bird community diversity, along with vector communities, influence WNV transmission patterns. However, limited knowledge exists on their impact in southwestern Spain, an area with active WNV circulation in wild birds, mosquitoes, and humans. METHODS: To address this, we conducted a comprehensive study investigating the contributions of migratory and exotic bird species to WNV transmission and the influence of mosquito community composition. RESULTS: Analysing 1194 serum samples from 44 avian species, we detected WNV antibodies in 32 samples from 11 species, four for the first time in Europe. Migratory birds had higher WNV exposure likelihood than native and exotic species, and higher phylogenetic diversity in bird communities correlated with lower exposure rates. Moreover, in 5859 female mosquitoes belonging to 12 species, we identified WNV competent vectors like Cx. pipiens s.l. and the Univittatus subgroup. Birds with WNV antibodies were positively associated with competent vector abundance, but negatively with overall mosquito species richness. CONCLUSIONS: These findings highlight the complex interactions between bird species, their phylogenetics, and mosquito vectors in WNV transmission. Understanding these dynamics will help to implement effective disease control strategies in southwestern Spain.

Evaluation of Propiophenone, 4-Methylacetophenone and 2',4'-Dimethylacetophenone as Phytotoxic Compounds of Labdanum Oil from Cistus ladanifer L.

This is the first study to evaluate the phytotoxic activity of three phenolic compounds present in the essential oil of the labdanum of Cistus ladanifer, an allelopathic species of the Mediterranean ecosystem. Propiophenone, 4'-methylacetophenone, and 2',4'-dimethylacetophenone slightly inhibit total germination and radicle growth of Lactuca sativa, and they strongly delay germination and reduce hypocotyl size. On the other hand, the inhibition effect of these compounds on Allium cepa was stronger on total germination than on germination rate, and radicle length compared to hypocotyl size. The position and number of methyl groups will affect the efficacy of the derivative. 2',4'-dimethylacetophenone was the most phytotoxic compound. The activity of the compounds depended on their concentration and presented hormetic effects. In L. sativa, on paper, propiophenone presented greater inhibition of hypocotyl size at greater concentrations, with IC50 = 0.1 mM, whereas 4'-methylacetophenone obtained IC50 = 0.4 mM for germination rate. When the mixture of the three compounds was applied, in L. sativa, on paper, the inhibition effect on total germination and the germination rate was significantly greater compared to the effect of the compounds when they were applied separately; moreover, the mixture inhibited radicle growth, whereas propiophenone and 4'-methylacetophenone did not exert such effect when applied separately. The activity of the pure compounds and that of the mixture also changed based on the substrate used. When the trial was conducted in soil, the separate compounds delayed the germination of the A. cepa to a greater extent compared to the trial on paper, although they stimulated seedling growth. In soil, L. sativa against 4'-methylacetophenone also showed the opposite effect at low concentrations (0.1 mM), with stimulation of germination rate, whereas propiophenone and 4'-methylacetophenone presented a slightly increased effect.

Influence of chronic kidney disease and its severity on the efficacy of semaglutide in type 2 diabetes patients: a multicenter real-world study.

Objectives: Semaglutide is a glucagon-like peptide 1 receptor agonist that improves glycemic control and achieves weight loss in type 2 diabetes (T2D) patients. Subcutaneous (s.c.) semaglutide at 1 mg once weekly (OW) is safe in T2D patients with chronic kidney disease (CKD). Whether or not CKD and its severity influence treatment response remains undetermined. Method: This is an observational, ambispective, multicenter, nationwide, real-world study designed to compare safety/efficacy of OW s.c. 1 mg semaglutide in T2D patients with or without CKD. The influence of CKD severity was also addressed. Patients were followed up for 12 months. Primary end-points were glycosylated hemoglobin (HbA1c), weight, and renal outcomes. Secondary end-points included insulin resistance, atherogenic and hepatic steatosis indexes, and changes in antihyperglycemic medications. Results: A total of 296 and 190 T2D patients without or with CKD, respectively, were recruited. Baseline CKD risk was moderate, high, or very high in 82, 53, and 45 patients, respectively. Treatment reduced HbA1c by 0.90%-1.20%. Relevant differences were seen neither between non-CKD and CKD patients nor among CKD subgroups. Notable weight losses were achieved in both non-CKD and CKD patients. The median reduction was higher in the former at 6 months (5.90 kg vs. 4.50 kg, P = 0.008) and at end of study (6.90 kg vs. 5.00 kg, P = 0.087). A trend toward slightly lower weight losses as CKD severity increased was observed. CKD markers improved across all CKD subgroups. Relevant differences were not observed for other variables, either between non-CKD and CKD patients, or among CKD subgroups. Safety concerns were not reported. Conclusion: The safety/efficacy of OW s.c. semaglutide to improve glycemic control and weight in T2D patients with CKD is not notably lower than that in T2D patients without renal failure. CKD severity barely influences treatment response. OW s.c. semaglutide can be useful to manage T2D patients with CKD in daily clinical practice.

Unravelling the mosquito-haemosporidian parasite-bird host network in the southwestern Iberian Peninsula: insights into malaria infections, mosquito community and feeding preferences.

BAKGROUND: Vector-borne diseases affecting humans, wildlife and livestock have significantly increased their incidence and distribution in the last decades. Because the interaction among vectors-parasite-vertebrate hosts plays a key role driving vector-borne disease transmission, the analyses of the diversity and structure of vector-parasite networks and host-feeding preference may help to assess disease risk. Also, the study of seasonal variations in the structure and composition of vector and parasite communities may elucidate the current patterns of parasite persistence and spread as well as facilitate prediction of how climate variations may impact vector-borne disease transmission. Avian malaria and related haemosporidian parasites constitute an exceptional model to understand the ecology and evolution of vector-borne diseases. However, the characterization of vector-haemosporidian parasite-bird host assemblages is largely unknown in many regions. METHODS: Here, we analyzed 5859 female mosquitoes captured from May to November in five localities from southwestern Spain to explore the composition and seasonal variation of the vector-parasite-vertebrate host network. RESULTS: We showed a gradual increase in mosquito abundance, peaking in July. A total of 16 different haemosporidian lineages were found infecting 13 mosquito species. Of these assemblages, more than 70% of these vector-parasite associations have not been described in previous studies. Moreover, three Haemoproteus lineages were reported for the first time in this study. The prevalence of avian malaria infections in mosquitoes varied significantly across the months, reaching a maximum in November. Mosquito blood-feeding preference was higher for mammals (62.5%), whereas 37.5% of vectors fed on birds, suggesting opportunistic feeding behavior. CONCLUSION: These outcomes improve our understanding of disease transmission risk and help tovector control strategies.

Efficacy of Dapagliflozin in Southern Europe Across the Spectrum of Characteristics of Type 2 Diabetes: An International Real-World Analysis.

Purpose: To extend a prior real-world analysis (DARWIN-T2D) of patients with type 2 diabetes initiating dapagliflozin in Italy, Greece, and Spain by evaluating changes in glycemic and extra-glycemic endpoints after initiation of dapagliflozin. Patients and Methods: The association among demographic/clinical characteristics and the change in glycemic and extraglycemic effectiveness endpoints during the observation period was assayed using a mixed effects model. Results: A total of 1438 (860 males; 59.8%) patients were evaluated; patients were followed for a mean of 5.6 months. At baseline, 93.4% and 61.9% of patients were on concomitant metformin and insulin, respectively. A significant mean decrease in HbA1c from 8.7% to 7.5% was observed. The mixed model used also revealed several associations between different glycemic and laboratory parameters and patient characteristics at baseline; insulin use was significantly associated with lower HbA1c. Patients with BMI ≥30 kg/m2 experienced greater weight loss than those with BMI <30 kg/m2. A consistent glucose-lowering effect of dapagliflozin was seen in all subgroups of patients, including those with stage 2 renal impairment and cardiovascular disease. Conclusion: The present analysis confirms the efficacy of dapagliflozin in diversified real-world settings with broadly similar effects on HbA1c across countries and baseline characteristics.

Effectiveness and safety of dapagliflozin in real-life patients: data from the DAPA-RWE Spanish multicentre study.

BACKGROUND: This study aims to evaluate dapagliflozin in patients with type 2 diabetes (T2D) in clinical practice in Spain. METHODS: This is a retrospective study including adults with T2D under stable antidiabetic therapy, with either dapagliflozin or sitagliptin ≥6 months, before inclusion. Data about the effectiveness and safety of dapagliflozin are presented. RESULTS: A total of 594 patients (61.8±9.9 years, 21.7% cardiovascular disease) were included. After 6 months, HbA1c, weight, blood pressure, urine albumin-to-creatinine ratio and uric acid significantly decreased (1.63%, 2.88 kg, 4.82/2.70 mmHg, -17.38 mg/g and -0.30 mg/dL, respectively), whereas glomerular filtration rate and haematocrit significantly increased (3.72 mL/min/1.73 m2 and 1.8%, respectively). No cases of hypoglycaemia, diabetic ketoacidosis, Fournier gangrene, fractures or amputations were reported. CONCLUSION: Thus, dapagliflozin provides a comprehensive cardiometabolic protection in patients with T2D.

DAPA-RWE: a retrospective multicenter study comparing dapagliflozin and sitagliptin in patients with Type 2 diabetes treated under routine clinical practice in Spain.

Background: Weight reduction and glycemic control are key goals during Type 2 diabetes management. However, there are few country-specific, real-world data on cotransporter 2 inhibitors. Materials & methods: DAPA-RWE was a retrospective, multicenter study comparing the efficacy of dapagliflozin versus sitagliptin in Type 2 diabetes patients in Spain. Results: The study population comprised 1046 patients (594 with dapagliflozin, 452 with sitagliptin). Age was 61.8 ± 10.0 and 66.2 ± 11.4 years and glycosylated hemoglobin (HbA1c) 8.9 and 8.8%, respectively. The main end point (reduction in weight and HbA1c) was reached by 24.4 and 56.1% of patients, respectively; p < 0.05. This was confirmed with a propensity score matching analysis balanced for obesity-related variables at baseline. Conclusion: DAPA-RWE confirmed dapagliflozin to be more effective than sitagliptin in reducing HbA1c and weight.

¿Tratamos igual el cáncer de mama en mujeres mayores de 70 años? / Do women with breast cancer older than 70 years receive equal treatment to younger women?

OBJETIVO: Determinar si las pacientes de más de 70 años con diagnóstico de cáncer de mama reciben un infratratamiento en comparación a las mujeres de menos de 70 años. PACIENTES Y MÉTODOS: Se han incluido 140 pacientes con diagnóstico de cáncer de mama en los años 2012 y 2013 en el Servicio de Patología Mamaria del Hospital Universitario Parc Taulí (Sabadell, Barcelona). Las pacientes se han clasificado en función de su edad en el momento del diagnóstico: <70 años (grupo A, n=70) y ≥70 años (grupo B, n=70). Entre ambos grupos se ha comparado si existen diferencias en el modo de presentación, el tipo y grado histológico, el estadio anatómico, el inmunofenotipo, la técnica quirúrgica utilizada en la mama y axila, así como el tratamiento adyuvante recibido. RESULTADOS: Las pacientes añosas presentan tumores de mayor tamaño y en estadios más avanzados en el momento del diagnóstico. También presentan una menor tasa de cirugía en la mama (grupo A: 98,6% vs. grupo B: 78,6%), axila (grupo A: 98,6% vs. grupo B: 69,1%), menor ampliación en caso de márgenes afectos (grupo A: 100% vs. grupo B: 55%) y mayor uso de la hormonoterapia como tratamiento primario (grupo A: 0% vs. grupo B: 17,1%). CONCLUSIONES: Hemos realizado un infratratamiento a igual estadificación en las pacientes añosas, especialmente a partir de los 85 años. En este subgrupo poblacional existe una mayor comorbilidad que ha sido un factor clave a la hora de indicar la opción terapéutica. Consideramos que las pacientes añosas deben recibir un asesoramiento geriátrico integral y multidisciplinar

OBJECTIVE: The aim of this study was to determine if patients older than 70 years with breast cancer received inferior treatment compared with women younger than 70 years. PATIENTS AND METHODS: The study population consisted of 140 patients with primary breast cancer treated at Parc Taulí Hospital (Sabadell, Barcelona) between 2012 and 2013. Patients were classified based on their age at diagnosis: <70 years (group A, n=70) and ≥70 years (group B, n=70). Age groups were compared to determine the presence of possible differences in the mode of presentation, tumoral grade and histology, anatomical stage, immunophenotype, the breast and axillary surgical technique used, and adjuvant therapy. RESULTS: Older patients had larger tumours in more advanced stages at the time of diagnosis. These patients were less likely to undergo breast surgery (group A: 98.6% and group B: 78.6%) and axillary surgery (group A: 98.6% and group B: 69.1%), underwent lower amplification of the affected margins (group A: 100% and group B: 55%) and were more likely to receive primary endocrine treatment (group A: 0% and group B: 17.4%). CONCLUSION: Elderly patients were under-treated compared with younger patients with the same tumoral stage, especially those older than 85 years. This subgroup has major comorbidity, which is a key factor in indicating the therapeutic option. We believe that elderly patients should receive multidisciplinary and comprehensive geriatric counselling

Cribado prenatal no invasivo de aneuploidías mediante análisis de ADN fetal en sangre materna / Non-invasive prenatal screening for aneuploidy through analysis of cell-free fetal DNA from maternal blood

El objetivo de este trabajo es analizar la sensibilidad y la especificidad en gestaciones únicas del análisis de cell free DNA (cfDNA) en sangre materna para el diagnóstico de las principales trisomías fetales (t21,t18 y t13), así como comparar los resultados con los obtenidos mediante el cribado combinado bioquímico ecográfico (CC); 582 gestaciones de más de 10 semanas fueron estudiadas. Todos los resultados con alto riesgo fueron confirmados mediante determinación prenatal del cariotipo o tras el nacimiento. Se realizó seguimiento posnatal en todos los casos, excepto en 5 gestaciones en las que no pudo ser confirmado el cariotipo por pérdida fetal tardía o aborto y renuncia de los padres a su estudio. El análisis de cfDNA fue posible tras la primera determinación en 97.1% de las muestras. En 3 (0,5%) no se obtuvo resultado tras 2 o incluso 3 extracciones; 14 fetos presentaron alto riesgo de t21 en sangre materna que fue confirmado en todos los casos; 3 fetos con alto riesgo de t18 en el estudio no invasivo fueron también confirmados tras el estudio del cariotipo fetal. No hubo falsos positivos ni negativos en la muestra analizada. La sensibilidad del CC fue del 87,5% para una tasa del 6,7% de falsos positivos. El análisis de cfDNA en sangre materna permite con alta sensibilidad y especificidad establecer el riesgo de las principales trisomías fetales. Los resultados obtenidos son probablemente superiores a los del CC. El número de procedimientos invasivos en la población de estudio se redujo de forma muy significativa (AU)

The aim of this study was to assess the sensitivity and specificity of cell-free (cfDNA) screening for diagnosis of the main fetal trisomies (t21,t18 y t13) and to compare its efficiency with that of first-trimester combined screening (FTS). A total of 582 samples were analyzed from singleton pregnancies above 10 weeks of gestation. All abnormal results were confirmed either with a prenatal invasive procedure or by neonatal karyotyping. Postnatal follow-up was also carried out in all but 5 low-risk pregnancies in which the karyotype could not be confirmed due to late fetal loss or miscarriage or parental refusal. cfDNA determination provided a risk score at the first attempt in 97.1% of the samples. Only 3 cases failed after 2 or 3 redraws (0.5%). High-risk results were provided by the Harmony test in 14 cases for t21 and in 3 for t18. No false positive results were observed. No false negative results were obtained in any of the 557 cases with a result of low-risk and postnatal follow-up. The sensitivity of FTS was 87.5%, with a false positive rate of 6.7%. cfDNA analysis in maternal blood has high sensitivity and specificity in establishing the risk of the main fetal trisomies. The results are probably superior to those obtained with FTS. The number of invasive procedures in the study population was significantly reduced (AU)