[Improving the nutritional care of oncology patients - Validation of a multidisciplinary protocol in the Spanish clinical setting]. / Mejorando la atención nutricional del paciente oncológico: validación de un protocolo multidisciplinar en el entorno clínico español.

INTRODUCTION: malnutrition is a very frequent problem in oncology patients and can have serious repercussions. Adequate nutritional management is cost-effective in terms of health and survival in this population, but it requires multidisciplinary coordination, specific training, and continuous follow-up. OBJECTIVE: to validate the applicability and efficacy of a multidisciplinary nutritional support protocol in oncology patients. METHODS: a multidisciplinary nutritional protocol was developed for oncology patients, with guidelines for screening and assessment of malnutrition, treatment, re-evaluation, and management of side effects, as well as guidance on supplementation and eating patterns. The protocol would be implemented in various clinical centers, collecting data through a structured questionnaire, registering variables before and after implementation. RESULTS: the protocol and its impact were implemented and evaluated in 39 centers. An improvement in nutritional care was observed, evidenced by an earlier initiation of nutritional assessment and an increase in the number of patients receiving adequate care following the protocol implementation. Problems related to inadequate malnutrition coding in the centers, limited resources, and the need for greater interdepartmental collaboration were identified. CONCLUSIONS: the conduct of this study provides insights into how the implementation of a multidisciplinary nutritional support protocol can improve the nutritional care received by patients and informs about the main obstacles to adequate implementation.

Assessing the reduction of viral infectivity in HPV16/18-positive women after one, two, and three doses of Gardasil-9 (RIFT): Study protocol.

Human Papillomavirus (HPV) prophylactic vaccination has proven effective in preventing new infections, but it does not treat existing HPV infections or associated diseases. Hence, there is still an important reservoir of HPV in adults, as vaccination programs are mainly focused on young women. The primary objective of this non-randomized, open-label trial is to evaluate if a 3-dose regimen of Gardasil-9 in HPV16/18-positive women could reduce the infective capacity of their body fluids. We aim to assess if vaccine-induced antibodies could neutralize virions present in the mucosa, thus preventing the release of infective particles and HPV transmission to sexual partners. As our main endpoint, the E1^E4-HaCaT model will be used to assess the infectivity rate of cervical, anal and oral samples, obtained from women before and after vaccination. HPV DNA positivity, virion production, seroconversion, and the presence of antibodies in the exudates, will be evaluated to attribute infectivity reduction to vaccination. Our study will recruit two different cohorts (RIFT-HPV1 and RIFT-HPV2) of non-vaccinated adult women. RIFT-HPV1 will include subjects with an HPV16/18 positive cervical test and no apparent cervical lesions or cervical lesions eligible for conservative treatment. RIFT-HPV2 will include subjects with an HPV16/18 positive anal test and no apparent anal lesions or anal lesions eligible for conservative treatment, as well as women with an HPV16/18 positive cervical test and HPV-associated vulvar lesions. Subjects complying with inclusion criteria for both cohorts will be recruited to the main cohort, RIFT-HPV1. Three doses of Gardasil-9 will be administered intramuscularly at visit 1 (0 months), visit 2 (2 months) and visit 3 (6 months). Even though prophylactic HPV vaccines would not eliminate a pre-existing infection, our results will determine if HPV vaccination could be considered as a new complementary strategy to prevent HPV-associated diseases by reducing viral spread. Trial registration: https://clinicaltrials.gov/ct2/show/NCT05334706.

ERK5 Interacts with Mitochondrial Glutaminase and Regulates Its Expression.

Many of the biological processes of the cell, from its structure to signal transduction, involve protein-protein interactions. On this basis, our aim was to identify cellular proteins that interact with ERK5, a serine/threonine protein kinase with a key role in tumor genesis and progression and a promising therapeutic target in many tumor types. Using affinity chromatography, immunoprecipitation, and mass spectrometry techniques, we unveiled an interaction between ERK5 and the mitochondrial glutaminase GLS in pancreatic tumor cells. Subsequent co-immunoprecipitation and immunofluorescence studies supported this interaction in breast and lung tumor cells as well. Genetic approaches using RNA interference techniques and CRISPR/Cas9 technology demonstrated that the loss of ERK5 function led to increased protein levels of GLS isoforms (KGA/GAC) and a concomitant increase in their activity in tumor cells. It is well known that the tumor cell reprograms its intermediary metabolism to meet its increased metabolic needs. In this sense, mitochondrial GLS is involved in the first step of glutamine catabolism, one of the main energy sources in the context of cancer. Our data suggest that ERK5 contributes to the regulation of tumor cell energy metabolism via glutaminolysis.

Molecular Recognition of Tyrosine-Containing Polypeptides with Pseudopeptidic Cages Unraveled by Fluorescence and NMR Spectroscopies.

The molecular recognition of Tyr-containing peptide copolymers with pseudopeptidic cages has been studied using a combination of fluorescence and NMR spectroscopies. Fluorescence titrations rendered a reasonable estimation of the affinities, despite the presence of dynamic quenching masking the unambiguous detection of the supramolecular complexes. Regarding NMR, the effect of polypeptide (PP) binding on relaxation and diffusion parameters of the cages is much more reliable than the corresponding chemical shift perturbations. To that, purification of the commercial PPs is mandatory to obtain biopolymers with lower polydispersity. Thus, the relaxation/diffusion-filtered 1H spectra of the cages in the absence vs presence of the PPs represent a suitable setup for the fast detection of the noncovalent interactions. Additional key intermolecular NOE cross-peaks supported by molecular models allow the proposal of a structure of the supramolecular species, stabilized by the Tyr encapsulation within the cage cavity and additional attractive polar interactions between the side chains of cage and PP, thus defining a binding epitope with a potential for implementing sequence selectivity. Accordingly, the cages bearing positive/negative residues prefer to bind the peptides having complementary negative/positive side chains close to the target Tyr, suggesting an electrostatic contribution to the interaction. Overall, our results show that both techniques represent a powerful and complementary combination for studying cage-to-PP molecular recognition processes.

UV Radiation Effect in New Materials Developed for the Construction of Beehives.

In recent decades, there has been an increasing focus on the alarming decline in global bee populations, given their critical ecological contributions to natural pollination and biodiversity. This decline, marked by a substantial reduction in bee colonies in forested areas, has serious implications for sustainable beekeeping practices and poses a broader risk to ecological well-being. Addressing these pressing issues requires innovative solutions, one of which involves the development and fabrication of beehives crafted from composite materials that are ecologically compatible with bee biology. Importantly, these materials should also exhibit a high resistance to environmental factors, such as ultraviolet (UV) radiation, in order to maintain their mechanical integrity and longevity. To investigate this, we conducted accelerated UV degradation tests on a variety of composite materials to rapidly assess their susceptibility to UV-induced changes. High-density polyethylene (HDPE) served as the matrix material and was reinforced with natural fibers, specifically fique fibers (Furcraea bedinghausii), banana fibers, and goose feathers. Our findings indicate that UV radiation exposure results in a noticeable reduction in the tensile strength of these materials. For example, wood composites experienced a 48% decline in tensile strength over a 60-day period, a rate of deterioration notably higher than that of other tested composite materials. Conversely, HDPE composites fortified with banana fibers initially demonstrated tensile strengths exceeding 9 MPa and 10 MPa. Although these values gradually decreased over the observation period, the composites still displayed favorable stress-strain characteristics. This research underscores the substantial influence of UV radiation on the longevity and efficacy of beehive materials, which in turn affects the durability of natural wood hives exposed to these environmental factors. The resultant increased maintenance and replacement costs for beekeepers further emphasize the need for judicious material selection in beehive construction and point to the viability of the composite materials examined in this study.

Impact of the Covid-19 pandemic on the management of gynecologic cancer: a Spanish survey. Observational, multicenter study.

BACKGROUND: The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) pandemic changed the distribution of healthcare resources, leading in many cases to the suspension of all non-essential treatments and procedures and representing a challenge for medical professionals. The objective of this study was to evaluate whether clinical protocols in gynecologic oncology care were modified as a result of the pandemic and to assess surgeons' perceptions regarding the management of gynecologic cancers". METHODS: Data were collected through an anonymous and voluntary survey sent via email to healthcare professionals in the field of gynecologic oncology in Spain. RESULTS: A total of 75 gynecologic oncologists completed the online survey. Of these, 93.2% (69) reported working in public hospitals and 62.5% (45) in tertiary care hospitals. 97.3% (71) were affiliated with hospitals treating patients infected with SARS-CoV-2. 85.1% (63) of the respondents expressed concern about the SARS-CoV-2 pandemic and 52.1% (38) indicated that the pandemic impacted the diagnostic and therapeutic quality of care for oncology patients. SARS-CoV-2 nasopharyngeal swab PCR (Polymerase Chain Reaction) testing was always performed before surgical interventions by 97.3% (71), being considered a best practice in triage by 94.4% (68). 87.5% (63) reported no change in the type of surgical approach during the pandemic. 62.5% (45) experienced limitations in accessing special personal protective equipment for SARS-CoV-2. An impact on the follow-up of patients with gynecologic cancers due to the pandemic was reported by 70.4% (50). CONCLUSIONS: Most of the Spanish gynecologic oncologists who responded to our survey reported that the SARS-CoV-2 pandemic had affected their clinical practice. The primary measures implemented were an increase in telemedicine, restricting outpatient visits to high-risk or symptomatic patients and the use of SARS-CoV-2 screening prior to surgery. No major changes in the surgical approach or management of the treatment of ovarian, endometrial or cervical cancer during the pandemic were reported.

Brote dentario precoz. Un acercamiento a la realidad / Early tooth eruption. An approach to reality

Introducción: Las tendencias seglares influyen en el crecimiento y desarrollo general del individuo. El brote dentario no escapa a esta realidad. Existen variables que pueden retardarlo o acelerarlo, dentro de las que se encuentran el sexo y el color de la piel. Objetivos: Determinar la cronología y el orden de brote de los dientes permanentes en niños y adolescentes. Métodos: Se realizó un estudio transversal descriptivo desde mayo de 2017 a noviembre de 2020. El universo constituido por 21383 niños y adolescentes entre 5 y 13 años de edad, de la provincia Holguín, Cuba, que no presentaban pérdida prematura de dientes temporales o extracciones de dientes permanentes, ni enfermedades sistémicas que influyen en el crecimiento y desarrollo. En el procesamiento estadístico se utilizaron las medidas de resúmenes para las variables cuantitativas y el test de comparación de las medias. Resultados: La edad de brote de todos los dientes permanentes resultó adelantada en comparación con las tablas para su valoración clínica. El primer diente en brotar fue el primer molar superior, entre los 5,66 años, y el último el segundo molar maxilar, entre los 10,38 años. Al comparar las medias de brote de los dientes permanentes según el sexo, hubo diferencias altamente significativas en la arcada superior: primer premolar (p = 0,000), arcada inferior: canino (p = 0,009), primer premolar (p = 0,000) y segundo molar (p = 0,012). Se encontraron diferencias altamente significativas entre las medias de brote para el color de la piel en el maxilar: incisivo central (p = 0,004), incisivo lateral (p = 0,000), canino (p = 0,002), mandíbula: incisivo central (p = 0,000), incisivo lateral (p = 0,000) y segundo premolar (p = 0,000). Conclusiones: La cronología de brote de todos los dientes permanentes resultó adelantada. Los dientes permanentes siguieron la secuencia de brote, tal como describe Mayoral. Se encontraron diferencias al comparar las medias de brote según el sexo y color de la piel(AU)

Introduction: Secular tendencies influence the overall growth and development of the individual. Tooth eruption does not escape this reality. There are variables that can delay or accelerate it, among which are sex and skin color. Objectives: To determine the chronology and order of eruption of permanent teeth in children and adolescents. Methods: A descriptive cross-sectional study was conducted from May 2017 to November 2020. The universe constituted by 21383 children and adolescents between 5 and 13 years of age, from Holguín province, Cuba, who did not present premature loss of primary teeth or extractions of permanent teeth, nor systemic diseases that influence growth and development. Statistical processing used summary measures for quantitative variables and the comparison test of the average values. Results: The age of teething of all permanent teeth was advanced in comparison with the tables for clinical assessment. The first tooth was the upper first molar at 5.66 years of age and the last tooth was the maxillary second molar at 10.38 years of age. When comparing the teething averages of the permanent teeth according to gender, there were highly significant differences in the upper arch: first premolar (p = 0.000), lower arch: canine (p = 0.009), first premolar (p = 0.000) and second molar (p = 0.012). Highly significant differences were found between bud means for skin color in maxilla: central incisor (p = 0.004), lateral incisor (p = 0.000), canine (p = 0.002), mandible: central incisor (p = 0.000), lateral incisor (p = 0.000) and second premolar (p = 0.000). Conclusions: The teething chronology of all permanent teeth resulted advanced. The permanent teeth followed the teething sequence as described by Mayoral. Differences were found when comparing the teething averages according to gender and skin color(AU)

Influence of the microbiome on radiotherapy-induced oral mucositis and its management: A comprehensive review.

Radiation-induced mucositis is the most common, debilitating and painful acute toxicity associated with active treatment in head and neck cancer area, severely affecting more than 65% of patients. Oral microbiota significantly changes during cancer therapy and appears to be involved on its pathophysiology. This review aims to present a comprehensive update of new etiopathogenic factors and treatments that may decrease the incidence of mucositis, mainly modifications of dietary interventions to modify microbiome. Despite advances in recent years, its management is mainly symptomatic opioid-based with variable results on different substances analyzed for its prevention. Immunonutrition seems to play a significant role, particularly the supplementation of compounds such as fatty acids, polyphenols or selected probiotics have shown to promote commensal bacteria diversity and reduced incidence of ulcerative mucositis. Modification of the microbiome is a promising preventive treatment for mucositis although its evidence is still scarce. Large studies are needed to demonstrate the efficacy of interventions on microbiome and its clinical impact on radiation-induced mucositis.

[Nutritional, bone and body composition assessment of patients with knee and hip arthroplasty]. / Valoración nutricional, ósea y de composición corporal de pacientes con artroplastia de rodilla y cadera.

Introduction: Introduction: malnutrition, both due to deficiency and excess of nutrients, correlates to the morbidity of the surgical patient. Objectives: to analyze the nutritional status, body composition and bone health of patients undergoing elective knee and hip arthroplasty. Methods: an observational cross-sectional study was carried out evaluating patients undergoing hip and knee replacement surgery from February to September 2019. The Malnutrition Universal Screening Tool (MUST), anthropometry, hand-grip dynamometry, bone densitometry, lumbar spine X-ray and bioimpedance analysis were performed. Results: eighty-six patients (61.6 % women) were evaluated, with a mean age of 69.5 ± 9.5 years. The mean body mass index (BMI) was 31.3 ± 4.5. According to MUST, 21.3 % were at risk of malnutrition; 16.9 % had decreased triceps skinfold with respect to p50 and 20 % had a pathological hand-grip dynamometry. In 91.4 %, vitamin D was < 30 pg/ml. In the bioimpedanciometry, the women presented significantly decreased muscle mass values. Age was correlated with a lower presence of fat-free mass, total and appendicular muscle mass. In those over 65 years of age, 52.6 % of men vs 14.3 % of women had a decreased muscle mass index; 58.5 % had low bone mineral density. We observed vertebral bone collapses in 13.9 %. Conclusion: there is a high prevalence of obesity in patients who are candidates for arthroplasty and this does not exclude the existence of a risk of malnutrition. They may also have decreased muscle mass and strength. Nutritional education and physical exercise recommendations are essential in order to optimize nutritional status for surgery.

Introducción: Introducción: la malnutrición tanto por defecto como por exceso de nutrientes se relaciona con la morbilidad del paciente quirúrgico. Objetivos: analizar el estado nutricional, la composición corporal y la salud ósea de pacientes sometidos a artroplastia electiva de rodilla y cadera Método: se realiza un estudio transversal observacional evaluando pacientes que ingresan para cirugía de prótesis de cadera y rodilla de febrero a septiembre de 2019. Al ingreso, se realizan Malnutrition Universal Screening Tool (MUST), antropometría, dinamometría manual, densitometría ósea, radiografía de columna lumbar y bioimpedanciometría. Resultados: se evaluó a 86 pacientes (61,6 % mujeres), con edad media de 69,5 ± 9,5 años. El índice de masa corporal (IMC) medio fue de 31,3 ± 4,5. Según MUST, el 21,3 % estaba en riesgo de desnutrición. El 16,9 % tenía disminuido el pliegue tricipital respecto al p50 y el 20 % tenía una dinamometría manual patológica. En el 91,4 % la vitamina D fue < 30 pg/ml. En la bioimpedanciometría, las mujeres presentaban valores de masa muscular significativamente disminuidos. La edad se correlacionó con menor presencia de masa libre de grasa, masa muscular total y apendicular. En mayores de 65 años, el 52,6 % de varones vs. 14,3 % de mujeres presentaban un índice de masa muscular disminuido. El 58,5 % tenía densidad mineral ósea baja. Objetivamos aplastamientos vertebrales en el 13,9 %. Conclusiones: existe una alta prevalencia de obesidad en pacientes candidatos a artroplastia y esto no excluye la existencia de riesgo de desnutrición. Además, pueden presentar disminución de masa y fuerza muscular. Es fundamental la educación nutricional y recomendaciones de ejercicio físico de cara a optimizar el estado nutricional para cirugía.

Digital Health Literacy and Person-Centred Care: Co-Creation of a Massive Open Online Course for Women with Breast Cancer.

The diagnosis of breast cancer (BC) can make the affected person vulnerable to suffering the possible consequences of the use of low-quality health information. Massive open online courses (MOOCs) may be a useful and efficient resource to improve digital health literacy and person-centred care in this population. The aim of this study is to co-create a MOOC for women with BC, using a modified design approach based on patients' experience. Co-creation was divided into three sequential phases: exploratory, development and evaluation. Seventeen women in any stage of BC and two healthcare professionals participated. In the exploratory phase, a patient journey map was carried out and empowerment needs related to emotional management strategies and self-care guidelines were identified, as well as information needs related to understanding medical terminology. In the development phase, participants designed the structure and contents of the MOOC through a Moodle platform. A MOOC with five units was developed. In the evaluation phase, participants strongly agreed that their participation was useful for the MOOC's development and participating in the co-creation process made the content more relevant to them (experience in the co-creation); most of the participants positively evaluated the content or interface of the MOOC (acceptability pilot). Educational interventions designed by women with BC is a viable strategy to generate higher-quality, useful resources for this population.

Pseudopeptidic host adaptation in peptide recognition unveiled by ion mobility mass spectrometry.

Complexation of the glutamic-tyrosine-glutamic tripeptide (EYE) with a series of pseudopeptidic cages has been thoroughly investigated using different analytical techniques. The stoichiometry and affinities of the supramolecular host : guest complexes both in aqueous solution and in the gas-phase were obtained from a suitable combination of fluorescence spectroscopy, NMR, and mass spectrometry (MS) methods. The cages bearing basic groups (lysine, ornitine and histidine) display the tightest EYE binding in aqueous media following the order CyHis > CyLys > CyOrn, thus suggesting that Tyr side chain encapsulation is additionally modulated by the identity of the cage side chains and their ability to be engaged in polar interactions with the EYE peptide. Similarly, binding affinities estimated by MS methods clearly point towards a reduced affinity for the Cy cages with acidic pendant groups and a higher affinity of the CyHis cage over CyLys and CyOrn. Ion mobility spectrometry (IMS)-MS, assisted by molecular modelling, has been used to uncover the structural and conformational characteristics of the pseudopeptidic hosts and their supramolecular adducts with the EYE peptide. The cages display a collisional cross-section increase upon EYE inclusion that is associated with the expansion of the binding pocket of the cage cavity, thus constituting a unique example of conformational pseudopeptidic host adaptation to accommodate the inclusion of the guest.

Information needs and research priorities in long-term survivorship of breast cancer: Patients and health professionals' perspectives.

OBJECTIVE: The objective of this work is to identify unmet information needs of long-term-survivors of breast cancer (BC) and future research needs from the perspectives of patients and health care professionals. METHODS: Two online Delphi surveys were conducted. Participants in Survey 1 were patients. Participants in Survey 2 were health care professionals from both primary and secondary care involved in BC care. Both surveys included three successive rounds. The first round aimed to identify research and information needs; the second round aimed to rank the relative importance of those needs; the third round aimed to find consensus. RESULTS: The most important information needs were self-management recommendations of common health problems after treatment and complications of breast reconstruction after 5 years. The most important research priorities were related to interventions and tools to increase information provision by professionals about certain tests, diet, and coordinated action between primary and specialised care during follow-up, and indications and safety issues of pregnancy in survivors. CONCLUSIONS: Two fundamental ideas were identified: (1) Patients request information about self-management common health problems after treatment and breast reconstruction complications. (2) Health care professionals emphasise the need for a standardised approach based on protocols, recommendations, and coordinated actions in the provision of information. IMPLICATIONS FOR CANCER SURVIVORS: Given the increasing number of BC survivors, it is essential to identify information and research needs to improve their care and health outcomes.

Patient experience, satisfaction and shared decision-making in colorectal cancer screening: protocol of the mixed-methods study CyDESA.

INTRODUCTION: Colorectal cancer (CRC) screening programmes can reduce incidence and mortality from this condition if adherence to them is high. As patient experience and satisfaction are key factors in determining adherence to screening programmes, they need to be measured. Furthermore, to promote highly patient-centred healthcare, the perception of patients regarding shared decision-making during CRC screening needs to be known. This study aims to assess the experience, satisfaction and participation in decision-making of participants in a CRC screening programme and of patients diagnosed with CRC through this programme in relation to the diagnostic and therapeutic processes of cancer. METHODS AND ANALYSIS: The CyDESA study is a mixed-methods study with a four phase sequential design. In phase 1, we will conduct a systematic review of patient-reported experience measures (PREMs) for patient experience or satisfaction with CRC screening. In case no located PREM can be applied, in phase 2, we will develop a new PREM. We will use the Delphi methodology to reach consensus among experts and patients and will conduct a pilot test of the developed PREM. Phase 3 is a multicentric cross-sectional study based on self-reported questionnaires that will be conducted at three Spanish hospitals (n=843). The objective is to find out about the experience, satisfaction and participation in decision-making of participants in the CRC screening programme who have had a positive screening test result according to their final screening diagnosis: false positives, colorectal polyps or CRC. Phase 4 is a qualitative phenomenological study based on individual interviews. It will explore the experiences of participants in the CRC screening programme and of those diagnosed with CRC. ETHICS AND DISSEMINATION: Ethics approval by the Ethics Committees of Corporació Sanitària Parc Taulí, Hospital de Sant Pau and Parc de Salut Mar. Findings will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: NCT04610086.

Dynamic Combinatorial Optimization of In Vitro and In Vivo Heparin Antidotes.

Heparin-like macromolecules are widely used in clinics as anticoagulant, antiviral, and anticancer drugs. However, the search of heparin antidotes based on small synthetic molecules to control blood coagulation still remains a challenging task due to the physicochemical properties of this anionic polysaccharide. Here, we use a dynamic combinatorial chemistry approach to optimize heparin binders with submicromolar affinity. The recognition of heparin by the most amplified members of the dynamic library has been studied with different experimental (SPR, fluorescence, NMR) and theoretical approaches, rendering a detailed interaction model. The enzymatic assays with selected library members confirm the correlation between the dynamic covalent screening and the in vitro heparin inhibition. Moreover, both ex vivo and in vivo blood coagulation assays with mice show that the optimized molecules are potent antidotes with potential use as heparin reversal drugs. Overall, these results underscore the power of dynamic combinatorial chemistry targeting complex and elusive biopolymers.

Modulation of Src Kinase Activity by Selective Substrate Recognition with Pseudopeptidic Cages.

The selective recognition of tyrosine residues in peptides is an appealing approach to inhibiting their tyrosine kinase (TK)-mediated phosphorylation. Herein, we describe pseudopeptidic cages that efficiently protect substrates from the action of the Src TK enzyme, precluding the corresponding Tyr phosphorylation. Fluorescence emission titrations show that the most efficient cage inhibitors strongly bind the peptide substrates with a very good correlation between the binding constant and the inhibitory potency. Structural insights and additional control experiments further support the proposed mechanism of selective supramolecular protection of the substrates. Moreover, the approach also works in a completely different kinase-substrate system. These results illustrate the potential of supramolecular complexes for the efficient and selective modulation of TK signaling.

Dynamic Stereoselection of Peptide Helicates and Their Selective Labeling of DNA Replication Foci in Cells*.

Although largely overlooked in peptide engineering, coordination chemistry offers a new set of interactions that opens unexplored design opportunities for developing complex molecular structures. In this context, we report new artificial peptide ligands that fold into chiral helicates in the presence of labile metal ions such as FeII and CoII . Heterochiral ß-turn-promoting sequences encode the stereoselective folding of the peptide ligands and define the physicochemical properties of their corresponding metal complexes. Circular dichroism and NMR spectroscopy in combination with computational methods allowed us to identify and determine the structure of two isochiral ΛΛ-helicates, folded as topological isomers. Finally, in addition to the in-vitro characterization of their selective binding to DNA three-way junctions, cell-microscopy experiments demonstrated that a rhodamine-labeled FeII helicate was internalized and selectively stains DNA replication factories in functional cells.

Information needs and research priorities for fertility preservation in women with breast cancer: patients and experts' perspectives.

OBJECTIVE: To identify the information needs and research priorities that women with breast cancer (BC), their families and BC experts perceive on the fertility preservation. METHODS: We conducted two Delphi-based studies through three online rounds. The first was aimed to identify information and research needs; the second one to assess the importance of those needs and the third one to obtain consensus, defined as an interquartile range ≤2. RESULTS: The participation rate was 76.2% in study 1 and 53.7% in study 2. The most important information needs were the referral protocol, pregnancy options for women with BC, side effects of tamoxifen and menopause as a consequence of treatment. The most important research priorities were the participation of different health professionals to provide oncofertility information, referral protocols and efficacy and safety of FP options. CONCLUSION: Information about fertility preservation in the context of BC and different ways to get pregnant, considering risks and benefits, has emerged as an unmet need for patients and careers. The need for a participatory and coordinated approach to the provision of information on oncofertility has been agreed. Other research needs are described in an attempt to focus future research in the most necessary areas.

Importance of structure-based studies for the design of a novel HIV-1 inhibitor peptide.

Based on the structure of an HIV-1 entry inhibitor peptide two stapled- and a retro-enantio peptides have been designed to provide novel prevention interventions against HIV transmission. The three peptides show greater inhibitory potencies in cellular and mucosal tissue pre-clinical models than the parent sequence and the retro-enantio shows a strengthened proteolytic stability. Since HIV-1 fusion inhibitor peptides need to be embedded in the membrane to properly interact with their viral target, the structural features were determined by NMR spectroscopy in micelles and solved by using restrained molecular dynamics calculations. Both parent and retro-enantio peptides demonstrate a topology compatible with a shared helix-turn-helix conformation and assemble similarly in the membrane maintaining the active conformation needed for its interaction with the viral target site. This study represents a straightforward approach to design new targeted peptides as HIV-1 fusion inhibitors and lead us to define a retro-enantio peptide as a good candidate for pre-exposure prophylaxis against HIV-1.

Targeting redox metabolism: the perfect storm induced by acrylamide poisoning in the brain.

Exposure to acrylamide may lead to different neurotoxic effects in humans and in experimental animals. To gain insights into this poorly understood type of neurotoxicological damage, we used a multi-omic approach to characterize the molecular changes occurring in the zebrafish brain exposed to acrylamide at metabolite, transcript and protein levels. We detected the formation of acrylamide adducts with thiol groups from both metabolites and protein residues, leading to a quasi-complete depletion of glutathione and to the inactivation of different components of the thioredoxin system. We propose that the combined loss-of-function of both redox metabolism-related systems configure a perfect storm that explains many acrylamide neurotoxic effects, like the dysregulation of genes related to microtubules, presynaptic vesicle alteration, and behavioral alterations. We consider that our mechanistical approach may help developing new treatments against the neurotoxic effects of acrylamide and of other neurotoxicants that may share its toxic mode of action.

pH-Dependent Chloride Transport by Pseudopeptidic Cages for the Selective Killing of Cancer Cells in Acidic Microenvironments.

Acidic microenvironments in solid tumors are a hallmark of cancer. Inspired by that, we designed a family of pseudopeptidic cage-like anionophores displaying pH-dependent activity. When protonated, they efficiently bind chloride anions. They also transport chloride through lipid bilayers, with their anionophoric properties improving at acidic pH, suggesting an H+ /Cl- symport mechanism. NMR studies in DPC micelles demonstrate that the cages bind chloride within the lipid phase. The chloride affinity and the chloride-exchange rate with the aqueous bulk solution are improved when the pH is lowered. This increases cytotoxicity towards lung adenocarcinoma cells at the pH of the microenvironment of a solid tumor. These properties depend on the nature of the amino-acid side chains of the cages, which modulate their lipophilicity and interactions with the cell membrane. This paves the way towards using pH as a parameter to control the selectivity of cytotoxic ionophores as anticancer drugs.