Enhanced Gene Delivery Triggered by Dual pH/Redox Responsive Host-Guest Dimerization of Cyclooligosaccharide Star Polycations

A robust strategy is reported to build perfectly monodisperse star polycationscombining a trehalose-based cyclooligosaccharide (cyclotrehalan, CT) centralcore onto which oligoethyleneimine radial arms are installed. Thearchitectural perfection of the compounds is demonstrated by a variety ofphysicochemical techniques, including NMR, MS, DLS, TEM, and GPC. Key tothe strategy is the possibility of customizing the cavity size of the macrocyclicplatform to enable/prevent the inclusion of adamantane motifs. Theseproperties can be taken into advantage to implement sequential levels ofstimuli responsiveness by combining computational design, precisionchemistry and programmed host-guest interactions. Specifically, it is shownthat supramolecular dimers implying a trimeric CT-tetraethyleneimine starpolycation and purposely designed bis-adamantane guests are preorganizedto efficiently complex plasmid DNA (pDNA) into transfection-competentnanocomplexes. The stability of the dimer species is responsive to theprotonation state of the cationic clusters, resulting in dissociation at acidicpH. This process facilitates endosomal escape, but reassembling can takeplace in the cytosol then handicapping pDNA nuclear import. By equippingthe ditopic guest with a redox-sensitive disulfide group, recapturingphenomena are prevented, resulting in drastically improved transfectionefficiencies both in vivo and in vitro.Ministerio de Ciencia e Innovación y Agencia Estatal de Investigación, de España-MCIN/AEI/10.13039/501100011033Fondo Europeo de Desarrollo Regional de la Unión Europea-RTI2018-097609-B-C21, RTI2018-097609-B-C22, PID2019-105858RB-I00 y PID2020-118384GB-I00Junta de Andalucía-P20_0016

Most worrysome weeds in Spain

Se presentan los resultados de una encuesta realizada durante el periodo de junio a octubre de 2014, y en la que participaron 315 técnicos de campo de toda España. Los datos están disponibles en Internet y su análisis permite concluir que a) las malas hierbas preocupan tanto como las plagas y enfermedades; b) respecto a los métodos de control, el control químico con herbicidas es el más usado y el considerado más eficaz; se han detectado las malas hierbas más preocupantes en una serie de cultivos, incluyendo el motivo de la preocupación. En cultivos leñosos, destaca “Conyza” por su dificultad de control, en arroz destacan “Echinochloa” y “Cyperus”; en algodón y maíz preocupan “Abutilon”, “Chenopodium”, “Cyperus”, Echinochloa y Sorghum; en cultivos extensivos de secano, la preocupación no está tan concentrada en pocas especies, destacando malas hierbas gramíneas en trigo y cebada junto con Centaurea, que es considerada preocupante adicionalmente en el cultivo del girasol. Finalmente, se seleccionan arvenses de preocupación creciente, entre las que destacan “Abutilon”, “Centaurea”, “Chenopodium” y “Sorghum”.Since June to October 2014, 315 Spanish field advisors participated in a survey. Data is available on internet and results show that a) weeds are as worrying as other pests and diseases; b) chemical control is the most used weed control method and is considered to be the most efficient one; c) knowledge transfer in weed management is largely dependant on herbicide industry; d) most worrying weeds have been identified for several crops, as well as the reasons why they are considered worrysome. In permanent crops, “Conyza” is refered to be by far the worst weed, mainly because it is difficult to control; in rice, the worst weeds are “Echinochloa” and “Cyperus”; in corn and cotton “Abutilon”, “Chenopodium”, “Cyperus”, “Echinochloa” and “Sorghum”; in annual dryland crops weed problems are less focused, being the most worrying weeds annual grasses in wheat and barley, besides “Centaurea”, which is also considered to be a problem in sunflower. Finally, there are weeds of increasing threat like “Abutilon”, “Centaurea”, “Chenopodium” and “Sorghum”

Assessment of the differences in the phenolic composition and color characteristics of new strawberry (Fragaria x ananassa Duch.) cultivars by HPLC–MS and Imaging Tristimulus Colorimetry

The phenolic composition (by HPLC-DAD-MS) and color characteristics (by Imaging Tristimulus Colorimetry) of four strawberry cultivars that have shown good climate adaptation to subtropical area (Nikte, Zamorana, Jacona and Pakal) have been assessed. 24 monomeric phenolics were identified, including 15 anthocyanins, 5 phenolic acids, 1 flavanol and 4 flavonols. Nikte and Zamorana showed the highest phenolic potential mainly due to their higher content of anthocyanins, while Pakal was richer in phenolic acids. Regarding color, Nikte and Zamorana were the more similar cultivars having the lowest values of lightness and hue. On the contrary, the color of Pakal was quite different from all the rest, due to the specific distribution between pelargonidin and cyanidin. The inclusion of both phenolic and colorimetric information in the Linear Discriminant Analysis allowed reaching very good discriminations among cultivar

Trifaceted Mickey Mouse Amphiphiles for Programmable Self-Assembly, DNA Complexation and Organ-Selective Gene Delivery

Instilling segregated cationic and lipophilic domains with an angular disposition in a trehalose-based trifaceted macrocyclic scaffold allows engineering patchy molecular nanoparticles leveraging directional interactions that emulate those controlling self-assembling processes in viral capsids. The resulting trilobular amphiphilic derivatives, featuring a Mickey Mouse architecture, can electrostatically interact with plasmid DNA (pDNA) and further engage in hydrophobic contacts to promote condensation into transfectious nanocomplexes. Notably, the topology and internal structure of the cyclooligosaccharide/pDNA co-assemblies can be molded by fine-tuning the valency and characteristics of the cationic and lipophilic patches, which strongly impacts the transfection efficacy in vitro and in vivo. Outstanding organ selectivities can then be programmed with no need of incorporating a biorecognizable motif in the formulation. The results provide a versatile strategy for the construction of fully synthetic and perfectly monodisperse nonviral gene delivery systems uniquely suited for optimization schemes by making cyclooligosaccharide patchiness the focus.Ministerio de Ciencia, Innovación y Universidades y Agencia Estatal de Investigación de España. RTI2018-097609-B-C21, RTI2018-097609-B-C22 y PID2019-105858RB-I00Universidad de Alcalá de Henares, Madrid. CCG19/CC-03

Quality of life impact of primary treatments for localized prostate cancer patients without hormonal treatment

Purpose Earlier studies evaluating the effect on quality of life (QoL) of localized prostate cancer interventions included patients receiving adjuvant hormone therapy, which could have affected their outcomes. Our objective was to compare the QoL impact of the three most common primary treatments on patients who were not receiving adjuvant hormonal treatment. PATIENTS AND METHODS: This was a prospective study of 435 patients treated with radical prostatectomy, external-beam radiotherapy, or brachytherapy. QoL was assessed before and after treatment with the Short Form-36 and the Expanded Prostate Cancer Index Composite. Differences between groups were tested by analysis of variance. Distribution of outcome at 3 years was examined by stratifying according to baseline status. Generalized estimating equation models were constructed to assess the effect of treatment over time. RESULTS: Compared with the brachytherapy group, the prostatectomy group showed greater deterioration on urinary incontinence and sexual scores but better urinary irritative-obstructive results (-18.22, -13.19, and +6.38, respectively, at 3 years; P < .001). In patients with urinary irritative-obstructive symptoms at baseline, improvement was observed in 64% of those treated with nerve-sparing radical prostatectomy. Higher bowel worsening (-2.87, P = .04) was observed in the external radiotherapy group, with 20% of patients reporting bowel symptoms. CONCLUSION: Radical prostatectomy caused urinary incontinence and sexual dysfunction but improved pre-existing urinary irritative-obstructive symptoms. External radiotherapy and brachytherapy caused urinary irritative-obstructive adverse effects and some sexual dysfunction. External radiotherapy also caused bowel adverse effects. Relevant differences between treatment groups persisted for up to 3 years of follow-up, although the difference in sexual adverse effects between brachytherapy and prostatectomy tended to decline over long-term follow-up. These results provide valuable information for clinical decision making

Tirotropina y su correlación con colesterol y triglicéridos en pacientes sanos y con disfunción tiroidea subclínica

Objective: To correlate the levels of thyrotropin with the levels of cholesterol and serum triglycerides in 250 healthy subjects and patients with subclinical thyroid dysfunction with a minimum fasting of 8 hours. Methodology: Analytical methods: total cholesterol, triglycerides: Enzyme-colorimetric and Thyrotropin: ELISA immunoenzymatic. Results: Thyrotropin was found in healthy subjects 88,68% in men and 89,34% in women, in patients with hyper thyroid dysfunction 1,89% for men and 1,52% for women, as well as hypo 9,43% for men and 9,14% for women. Cholesterol in healthy subjects for men is 49,06% and in women 67,01%; in patients with hyper thyroid dysfunction 50,94% for men and 32,99% for women. Triglycerides in healthy subjects 69,81% in men and 62,44% in women, in patients with hyper thyroid dysfunction 30,19% for men and 37,56% in women. Conclusions: A correlation was found between thyrotropin and cholesterol (p &lt;0,05), this is due to an increase in the number of low-density lipoprotein liver receptors (LDL-col), which accelerates its clearance, was not found correlation between thyrotropin and triglycerides (p&gt; 0,05), cholesterol concentrations are high in subjects with hypothyroidism.Objetivo: Correlacionar los niveles de la Tirotropina con los niveles de Colesterol y Triglicéridos séricos en 250 sujetos sanos y pacientes con disfunción tiroidea subclínica con un ayuno mínimo de 8 horas. Metodología: Métodos analíticos: colesterol total, triglicéridos: Enzimático-colorimétrico y Tirotropina: inmunoenzimático ELISA. Resultados: Se encontró Tirotropina en sujetos sanos 88,68% en hombres y 89,34% en mujeres, en pacientes con disfunción tiroidea hiper 1,89% para hombres y 1,52% para mujeres, así como hipo 9,43% para hombres y 9,14% para mujeres. El colesterol en sujetos sanos para hombres es del 49,06% y en mujeres 67,01%; en pacientes con disfunción tiroidea hiper 50,94% para hombres y 32,99% para mujeres. Los triglicéridos en sujetos sanos 69,81% en hombres y 62,44% en mujeres, en pacientes con disfunción tiroidea hiper 30,19% para hombres y 37,56% en mujeres. Conclusiones: Se encontró correlación entre la tirotropina y colesterol (p&lt;0,05), esto se debe bioquímicamente a un aumento del número de receptores hepáticos de lipoproteína de baja densidad (LDL-col), lo que acelera su depuración, no se encontró correlación entre la tirotropina y los triglicéridos (p&gt;0,05), las concentraciones de colesterol están altas en sujetos con hipotiroidismo

Correction : Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885

The authors wish to make the following corrections to this paper [...]

Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain : Large-Scale Epidemiological Study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery