Critical Design Strategies Supporting Optimized Drug Release from Polymer-Drug Conjugates.

The importance of an adequate linking moiety design that allows controlled drug(s) release at the desired site of action is extensively studied for polymer-drug conjugates (PDCs). Redox-responsive self-immolative linkers bearing disulfide moieties (SS-SIL) represent a powerful strategy for intracellular drug delivery; however, the influence of drug structural features and linker-associated spacers on release kinetics remains relatively unexplored. The influence of drug/spacer chemical structure and the chemical group available for conjugation on drug release and the biological effect of resultant PDCs is evaluated. A "design of experiments" tool is implemented to develop a liquid chromatography-mass spectrometry method to perform the comprehensive characterization required for this systematic study. The obtained fit-for-purpose analytical protocol enables the quantification of low drug concentrations in drug release studies and the elucidation of metabolite presence. and provides the first data that clarifies how drug structural features influence the drug release from SS-SIL and demonstrates the non-universal nature of the SS-SIL. The importance of rigorous linker characterization in understanding structure-function correlations between linkers, drug chemical functionalities, and in vitro release kinetics from a rationally-designed polymer-drug nanoconjugate, a critical strategic crafting methodology that should remain under consideration when using a reductive environment as an endogenous drug release trigger.

A circuit for secretion-coupled cellular autonomy in multicellular eukaryotic cells.

Cancers represent complex autonomous systems, displaying self-sufficiency in growth signaling. Autonomous growth is fueled by a cancer cell's ability to "secrete-and-sense" growth factors (GFs): a poorly understood phenomenon. Using an integrated computational and experimental approach, here we dissect the impact of a feedback-coupled GTPase circuit within the secretory pathway that imparts secretion-coupled autonomy. The circuit is assembled when the Ras-superfamily monomeric GTPase Arf1, and the heterotrimeric GTPase Giαßγ and their corresponding GAPs and GEFs are coupled by GIV/Girdin, a protein that is known to fuel aggressive traits in diverse cancers. One forward and two key negative feedback loops within the circuit create closed-loop control, allow the two GTPases to coregulate each other, and convert the expected switch-like behavior of Arf1-dependent secretion into an unexpected dose-response alignment behavior of sensing and secretion. Such behavior translates into cell survival that is self-sustained by stimulus-proportionate secretion. Proteomic studies and protein-protein interaction network analyses pinpoint GFs (e.g., the epidermal GF) as key stimuli for such self-sustenance. Findings highlight how the enhanced coupling of two biological switches in cancer cells is critical for multiscale feedback control to achieve secretion-coupled autonomy of growth factors.

Multi-response deconvolution of auditory evoked potentials in a reduced representation space.

The estimation of auditory evoked potentials requires deconvolution when the duration of the responses to be recovered exceeds the inter-stimulus interval. Based on least squares deconvolution, in this article we extend the procedure to the case of a multi-response convolutional model, that is, a model in which different categories of stimulus are expected to evoke different responses. The computational cost of the multi-response deconvolution significantly increases with the number of responses to be deconvolved, which restricts its applicability in practical situations. In order to alleviate this restriction, we propose to perform the multi-response deconvolution in a reduced representation space associated with a latency-dependent filtering of auditory responses, which provides a significant dimensionality reduction. We demonstrate the practical viability of the multi-response deconvolution with auditory responses evoked by clicks presented at different levels and categorized according to their stimulation level. The multi-response deconvolution applied in a reduced representation space provides the least squares estimation of the responses with a reasonable computational load. matlab/Octave code implementing the proposed procedure is included as supplementary material.

Receptor tyrosine kinases activate heterotrimeric G proteins via phosphorylation within the interdomain cleft of Gαi.

The molecular mechanisms by which receptor tyrosine kinases (RTKs) and heterotrimeric G proteins, two major signaling hubs in eukaryotes, independently relay signals across the plasma membrane have been extensively characterized. How these hubs cross-talk has been a long-standing question, but answers remain elusive. Using linear ion-trap mass spectrometry in combination with biochemical, cellular, and computational approaches, we unravel a mechanism of activation of heterotrimeric G proteins by RTKs and chart the key steps that mediate such activation. Upon growth factor stimulation, the guanine-nucleotide exchange modulator dissociates Gαi•ßγ trimers, scaffolds monomeric Gαi with RTKs, and facilitates the phosphorylation on two tyrosines located within the interdomain cleft of Gαi. Phosphorylation triggers the activation of Gαi and inhibits second messengers (cAMP). Tumor-associated mutants reveal how constitutive activation of this pathway impacts cell's decision to "go" vs. "grow." These insights define a tyrosine-based G protein signaling paradigm and reveal its importance in eukaryotes.

Point-of-Care Echocardiography: A Useful Tool for Assessing Complex Arrhythmias in the Pediatric Intensive Care Unit.

OBJECTIVE: To demonstrate that the analysis of the atrioventricular, intraventricular, and interventricular asynchrony by point-of-care ultrasound (POCUS) could be an alternative tool for assessing complex arrhythmias in pediatric patients with congenital heart diseases, mainly when an epicardial register or electrophysiology study is not available. DESIGN: Descriptive, retrospective case series study. SETTING: The pediatric intensive care unit of a university-affiliated tertiary hospital in Spain. PATIENTS: The authors included 12 patients with congenital heart disease younger than 18 years admitted to the authors' pediatric intensive care unit (PICU) from January 2018 to December 2019, with complex arrhythmias after surgery, managed by performing a bedside echocardiography when an electrophysiology test or epicardial auriculogram was unavailable. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors included a total of 14 complex arrhythmias in 12 postsurgical patients in whom a comprehensive transthoracic electrocardiogram was not conclusive. The presence of atrioventricular, intraventricular, or interventricular asynchrony was assessed in standard echo views by performing M-mode and Doppler mitral inflow analysis, checking the heart motion. The final POCUS diagnoses were atrial flutter (n = 5), postsurgical atrioventricular block (n = 4), asynchrony induced by pacemaker (n = 2), junctional ectopic tachycardia (n = 1), nodal rhythm plus ventricular extrasystole (n = 1), and supraventricular tachycardia (n = 1). In all patients, regardless of the type of arrhythmia, detecting motion asynchrony was crucial for making the correct diagnosis. Offline cardiologist analysis of the POCUS scans showed full agreement. CONCLUSIONS: POCUS is a useful tool for initial diagnosis and management of complex arrhythmias in the PICU, mainly when epicardial auriculogram or electrophysiology studies are unavailable.

GIV/Girdin activates Gαi and inhibits Gαs via the same motif.

We previously showed that guanine nucleotide-binding (G) protein α subunit (Gα)-interacting vesicle-associated protein (GIV), a guanine-nucleotide exchange factor (GEF), transactivates Gα activity-inhibiting polypeptide 1 (Gαi) proteins in response to growth factors, such as EGF, using a short C-terminal motif. Subsequent work demonstrated that GIV also binds Gαs and that inactive Gαs promotes maturation of endosomes and shuts down mitogenic MAPK-ERK1/2 signals from endosomes. However, the mechanism and consequences of dual coupling of GIV to two G proteins, Gαi and Gαs, remained unknown. Here we report that GIV is a bifunctional modulator of G proteins; it serves as a guanine nucleotide dissociation inhibitor (GDI) for Gαs using the same motif that allows it to serve as a GEF for Gαi. Upon EGF stimulation, GIV modulates Gαi and Gαs sequentially: first, a key phosphomodification favors the assembly of GIV-Gαi complexes and activates GIV's GEF function; then a second phosphomodification terminates GIV's GEF function, triggers the assembly of GIV-Gαs complexes, and activates GIV's GDI function. By comparing WT and GIV mutants, we demonstrate that GIV inhibits Gαs activity in cells responding to EGF. Consequently, the cAMP→PKA→cAMP response element-binding protein signaling axis is inhibited, the transit time of EGF receptor through early endosomes are accelerated, mitogenic MAPK-ERK1/2 signals are rapidly terminated, and proliferation is suppressed. These insights define a paradigm in G-protein signaling in which a pleiotropically acting modulator uses the same motif both to activate and to inhibit G proteins. Our findings also illuminate how such modulation of two opposing Gα proteins integrates downstream signals and cellular responses.

Cyclin-dependent kinase 5 activates guanine nucleotide exchange factor GIV/Girdin to orchestrate migration-proliferation dichotomy.

Signals propagated by receptor tyrosine kinases (RTKs) can drive cell migration and proliferation, two cellular processes that do not occur simultaneously--a phenomenon called "migration-proliferation dichotomy." We previously showed that epidermal growth factor (EGF) signaling is skewed to favor migration over proliferation via noncanonical transactivation of Gαi proteins by the guanine exchange factor (GEF) GIV. However, what turns on GIV-GEF downstream of growth factor RTKs remained unknown. Here we reveal the molecular mechanism by which phosphorylation of GIV by cyclin-dependent kinase 5 (CDK5) triggers GIV's ability to bind and activate Gαi in response to growth factors and modulate downstream signals to establish a dichotomy between migration and proliferation. We show that CDK5 binds and phosphorylates GIV at Ser1674 near its GEF motif. When Ser1674 is phosphorylated, GIV activates Gαi and enhances promigratory Akt signals. Phosphorylated GIV also binds Gαs and enhances endosomal maturation, which shortens the transit time of EGFR through early endosomes, thereby limiting mitogenic MAPK signals. Consequently, this phosphoevent triggers cells to preferentially migrate during wound healing and transmigration of cancer cells. When Ser1674 cannot be phosphorylated, GIV cannot bind either Gαi or Gαs, Akt signaling is suppressed, mitogenic signals are enhanced due to delayed transit time of EGFR through early endosomes, and cells preferentially proliferate. These results illuminate how GIV-GEF is turned on upon receptor activation, adds GIV to the repertoire of CDK5 substrates, and defines a mechanism by which this unusual CDK orchestrates migration-proliferation dichotomy during cancer invasion, wound healing, and development.

Therapeutic effects of cell-permeant peptides that activate G proteins downstream of growth factors.

In eukaryotes, receptor tyrosine kinases (RTKs) and trimeric G proteins are two major signaling hubs. Signal transduction via trimeric G proteins has long been believed to be triggered exclusively by G protein-coupled receptors (GPCRs). This paradigm has recently been challenged by several studies on a multimodular signal transducer, Gα-Interacting Vesicle associated protein (GIV/Girdin). We recently demonstrated that GIV's C terminus (CT) serves as a platform for dynamic association of ligand-activated RTKs with Gαi, and for noncanonical transactivation of G proteins. However, exogenous manipulation of this platform has remained beyond reach. Here we developed cell-permeable GIV-CT peptides by fusing a TAT-peptide transduction domain (TAT-PTD) to the minimal modular elements of GIV that are necessary and sufficient for activation of Gi downstream of RTKs, and used them to engineer signaling networks and alter cell behavior. In the presence of an intact GEF motif, TAT-GIV-CT peptides enhanced diverse processes in which GIV's GEF function has previously been implicated, e.g., 2D cell migration after scratch-wounding, invasion of cancer cells, and finally, myofibroblast activation and collagen production. Furthermore, topical application of TAT-GIV-CT peptides enhanced the complex, multireceptor-driven process of wound repair in mice in a GEF-dependent manner. Thus, TAT-GIV peptides provide a novel and versatile tool to manipulate Gαi activation downstream of growth factors in a diverse array of pathophysiologic conditions.

Is a second recombinant human thyrotropin stimulation test useful? The value of postsurgical undetectable stimulated thyroglobulin level at the time of remnant ablation on clinical outcome.

OBJECTIVE: The management of patients with differentiated thyroid cancer (DTC) has changed in recent years, and monitoring depends on the risk of persistent/recurrent disease. The objective was to assess the prognostic value of a single stimulated thyroglobulin (Tg) measured at the time of the first radioiodine therapy (Stim-Tg1), and the utility of a second stimulated Tg measurement performed 6-12 months later (Stim-Tg2). We also examined the role of neck ultrasound (US) in the early diagnosis of recurrence. DESIGN: This was a retrospective observational cohort study conducted in a tertiary referral hospital. Of 213 evaluated patients with DTC, 169 were finally included. METHODS: Measurement of Stim-Tg1, Stim-Tg2 and neck US. RESULTS: Stim-Tg1 was undetectable in 71 of 169 patients (42%). All of them (71/71) continued to have negative Stim-Tg2. Seventy of 71 had an excellent response to the first treatment. Sixty-eight of 71 had no evidence of disease after an average follow-up of 7·2 years. In patients with detectable Stim-Tg1 (98/169; 58%), Stim-Tg2 became negative in 40. The negative predictive value (NPV) of Stim-Tg1 was 0·96. The optimal Stim-Tg1 cut-off level for identifying persistence was 3·65 ng/ml. Recurrence was detected in 14 patients. Neck US was useful for identifying local recurrence (13/14; 92·85%). CONCLUSIONS: Stim-Tg1 is a reliable marker with a high NPV. A second stimulation test should be avoided in patients with negative Stim-Tg1. In patients with biochemical persistence, Stim-Tg2 is useful for confirming/ruling out final status. Neck US plays a valuable role in the early diagnosis of recurrence.

Wireless Ultrasound-Guided Axillary Vein Cannulation for the Implantation of Cardiovascular Implantable Electric Devices.

INTRODUCTION: Ultrasound guidance for vascular cannulation seems safer and more effective than an anatomical landmark approach, though it has not gained widespread support partly due to workflow interference of wired probes. A wireless ultrasound transducer (WUST) may overcome this issue. We report the effectiveness, time consumption, and safety of the first-in-human experience in axillary vein cannulation guided with a novel WUST for the implantation of cardiovascular implantable electric devices (CIEDs). METHODS AND RESULTS: After a one-month training period, we routinely performed WUST-guided puncture to all first implants, prospectively registering data from the first 50 patients. We analyzed the time needed for preparing the WUST and for achieving each vein cannulation, and the rate of unsuccessful or accidental arterial punctures and complications. WUST-guided axillary vein access was successful in 49 out of 50 patients, totaling 86 cannulated veins. Median WUST preparation time was 55 [44-62] seconds and median time needed for each venous cannulation was 56 [36-71] seconds. A total of 84.9% of the veins were cannulated at the first attempt. There were 7 unsuccessful puncture attempts and 1 accidental arterial puncture. No pneumothorax, hemothorax, or nervous injury occurred in the 49 successfully cannulated patients. The unsuccessful one (distal subclavian occlusion) developed a minor local subcutaneous emphysema with no confirmed radiologic pneumothorax, not requiring intervention. During a follow-up of 2.5 ± 1.1 months, a patient developed a pocket infection, with no other significant complications. CONCLUSION: Ultrasound-guided axillary vein cannulation using a wireless transducer for the implantation of CIEDs is a feasible, fast, and safe method.

Protein kinase C-theta (PKCθ) phosphorylates and inhibits the guanine exchange factor, GIV/Girdin.

Gα-interacting, vesicle-associated protein (GIV/Girdin) is a multidomain signal transducer that enhances PI3K-Akt signals downstream of both G-protein-coupled receptors and growth factor receptor tyrosine kinases during diverse biological processes and cancer metastasis. Mechanistically, GIV serves as a non-receptor guanine nucleotide exchange factor (GEF) that enhances PI3K signals by activating trimeric G proteins, Gαi1/2/3. Site-directed mutations in GIV's GEF motif disrupt its ability to bind or activate Gi and abrogate PI3K-Akt signals; however, nothing is known about how GIV's GEF function is regulated. Here we report that PKCθ, a novel protein kinase C, down-regulates GIV's GEF function by phosphorylating Ser(S)1689 located within GIV's GEF motif. We demonstrate that PKCθ specifically binds and phosphorylates GIV at S1689, and this phosphoevent abolishes GIV's ability to bind and activate Gαi. HeLa cells stably expressing the phosphomimetic mutant of GIV, GIV-S1689→D, are phenotypically identical to those expressing the GEF-deficient F1685A mutant: Actin stress fibers are decreased and cell migration is inhibited whereas cell proliferation is triggered, and Akt (a.k.a. protein kinase B, PKB) activation is impaired downstream of both the lysophosphatidic acid receptor, a G-protein-coupled receptor, and the insulin receptor, a receptor tyrosine kinase. These findings indicate that phosphorylation of GIV by PKCθ inhibits GIV's GEF function and generates a unique negative feedback loop for downregulating the GIV-Gi axis of prometastatic signaling downstream of multiple ligand-activated receptors. This phosphoevent constitutes the only regulatory pathway described for terminating signaling by any of the growing family of nonreceptor GEFs that modulate G-protein activity.

GIV/girdin binds exocyst subunit-Exo70 and regulates exocytosis of GLUT4 storage vesicles.

Insulin resistance (IR) is a metabolic disorder characterized by impaired glucose uptake in response to insulin. The current paradigm for insulin signaling centers upon the insulin receptor (InsR) and its substrate IRS1; the latter is believed to be the chief conduit for post-receptor signaling. We recently demonstrated that GIV, a Guanidine Exchange Factor (GEF) for the trimeric G protein, Gαi, is a major hierarchical conduit for the metabolic insulin response. By virtue of its ability to directly bind the InsR, IRS1 and PI3K, GIV enhances the InsR-IRS1-Akt-AS160 (RabGAP) signaling cascade and cellular glucose uptake via its GEF function. Phosphoinhibition of GIV-GEF by the fatty-acid/PKCθ pathway inhibits the cascade and impairs glucose uptake. Here we show that GIV directly and constitutively binds the exocyst complex subunit Exo-70 and also associates with GLUT4-storage vesicles (GSVs) exclusively upon insulin stimulation. Without GIV or its GEF function, membrane association of Exo-70 as well as exocytosis of GSVs in response to insulin are impaired. Thus, GIV is an essential component within the insulin signaling cascade that couples upstream signal transducers within the InsR and G-Protein signaling cascade to downstream vesicular trafficking events within the exocytic pathway. These findings suggest a role of GIV in coordinating key signaling and trafficking events of metabolic insulin response.

The Arabic psychosocial impact of assistive devices scale: Development, translation, and evaluation.

This paper describes the development, translation, and early evaluation of the Arabic Psychosocial Impact of Assistive Devices Scale (AR-PIADS), an outcome measure instrument for the subjective impact of Assistive Technology on a person with a disabilities' quality of life. Developing the AR = PIADS instrument involved forward and backward translation by two independent teams of bilingual, Arabic-English speakers (n = 5) and a quality and usability review by a panel of people with disabilities (n = 18). The emergent version was evaluated with a group of experienced Arabic-speaking Assistive Technology users (n = 67) for its psychometric properties. Initial results demonstrate a favorable comparison for 16 of the 26 questionnaire items with scores recorded for the original, English language version. Internal consistency, measured using Cronbach's alpha, yielded a range of 0.97-0.99 for AR-PIADS while the new instrument's reliability was assessed using an intraclass correlation coefficient resulting in scores within the range of 0.86-0.97 for the overall instrument. Despite these positive results however, the translation process did highlight a number of challenges with language and cultural interpretation of the translated instrument. This suggests that further work is warranted to explore its utility in service provision.

Impact of Hypnotherapy on Fear, Pain, and the Birth Experience: A Systematic Review.

In recent times, research has been conducted on the use of hypnosis during childbirth preparation and its effects on pain, fear, and overall childbirth experience. The main objective of this study was to analyze the published scientific literature on the use of hypnotherapy during childbirth preparation and the outcomes achieved during labor. A systematic literature review was conducted following the PRISMA 2020 protocol, with a search performed on the PubMed, Cinahl, Scopus, and WOS databases. Studies meeting inclusion criteria, including randomized controlled trials (RCTs), were evaluated for methodological quality using the PEDro scale. The searches yielded a total of 84 results, from which 7 RCTs of high scientific quality were selected. Each article examined the impact of a hypnosis intervention during pregnancy and the results obtained during labor. The analysis covered the use of epidural anesthesia, pharmacological analgesia during labor, self-reported pain, labor duration, type of delivery, fear of childbirth, and childbirth experience. The results demonstrated benefits in reducing fear and pain during labor, along with an enhancement in the overall childbirth experience. Hypnotherapy can be a valuable resource for reducing fear and pain during labor and improving the lived childbirth experience.

Subjective identification and ablation of drivers improves rhythm control in patients with persistent atrial fibrillation. The CHAOS-AF study.

INTRODUCTION AND OBJECTIVES: The optimal approach for persistent atrial fibrillation (AF) ablation remains unknown. In patients with persistent AF, we compared an ablation strategy based on pulmonary vein isolation (PVI) plus ablation of drivers (PVI+D), with a conventional PVI-only approach performed in a 1:1 propensity score-matched cohort. METHODS: Drivers were subjectively identified using conventional high-density mapping catheters (IntellaMap ORION, PentaRay NAV or Advisor HD Grid), without dedicated software, as fractionated continuous or quasicontinuous electrograms on 1 to 2 adjacent bipoles, which were ablated first; and as sites with spatiotemporal dispersion (the entire cycle length comprised within the mapping catheter) plus noncontinuous fractionation, which were only targeted in patients without fractionated continuous electrograms, or without AF conversion after ablation of fractionated continuous electrograms. Ablation included PVI plus focal or linear ablation targeting drivers. RESULTS: A total of 50 patients were included in each group (61±10 years, 25% women). Fractionated continuous electrograms were found and ablated in 21 patients from the PVI+D group (42%), leading to AF conversion in 7 patients. In the remaining 43 patients, 143 sites with spatiotemporal dispersion plus noncontinuous fractionation were targeted. Globally, AF conversion was achieved in 21 patients (42%). The PVI+D group showed lower atrial arrhythmia recurrences at 1 year of follow-up (30.6% vs 48%; P=.048) and at the last follow-up (46% vs 72%; P=.013), and less progression to permanent AF (10% vs 40%; P=.001). CONCLUSIONS: Subjective identification and ablation of drivers, added to PVI, increased 1-year freedom from atrial arrhythmia and decreased long-term recurrences and progression to permanent AF.

Depression, Anxiety, and Stress Among Emerging Adult Undergraduates: A Longitudinal and Two-Cohort Study.

Mental disorders constitute one of the population's principal health problems, especially among undergraduates. This quantitative study compared levels of depression, anxiety, and stress in a sample of emerging adult university undergraduates from a gender perspective (1) during the initial and intermediate years of emerging adulthood and (2) in two different cohorts. A total of 383 Spanish emerging adult university undergraduates were monitored longitudinally (2015-2018) and two cohorts were compared (2015-2020). Participants completed the validated Spanish version of the Depression Anxiety Stress Scale-21. Mean-level and rank-order stability was found across the two waves of the longitudinal study in relation to levels of depression, anxiety, and stress. Significant differences were found between the two cohorts, indicating higher levels of psychological distress in 2020 than in 2015. Women were found to have higher levels of psychological distress, particularly stress, than men in both waves and cohorts. Results are discussed in relation to the negative effects of the COVID-19 health crisis on the emotional health of emerging adults. The present study highlights the need to establish measures designed to improve the mental health of emerging adults, which was more severely affected by the COVID-19 crisis than by the aftermath of the 2008 financial crisis. It also underscores the need to develop interventions designed to alleviate the greater degree of stress suffered by women.

Unlocking the Mitochondria for Nanomedicine-based Treatments: Overcoming Biological Barriers, Improving Designs, and Selecting Verification Techniques.

Enhanced targeting approaches will support the treatment of diseases associated with dysfunctional mitochondria, which play critical roles in energy generation and cell survival. Obstacles to mitochondria-specific targeting include the presence of distinct biological barriers and the need to pass through (or avoid) various cell internalization mechanisms. A range of studies have reported the design of mitochondrially-targeted nanomedicines that navigate the complex routes required to influence mitochondrial function; nonetheless, a significant journey lies ahead before mitochondrially-targeted nanomedicines become suitable for clinical use. Moving swiftly forward will require safety studies, in vivo assays confirming effectiveness, and methodologies to validate mitochondria-targeted nanomedicines' subcellular location/activity. From a nanomedicine standpoint, we describe the biological routes involved (from administration to arrival within the mitochondria), the features influencing rational design, and the techniques used to identify/validate successful targeting. Overall, rationally-designed mitochondria-targeted-based nanomedicines hold great promise for precise subcellular therapeutic delivery.

Importance Assigned to Breastfeeding by Spanish Pregnant Women and Associated Factors: A Survey-Based Multivariate Linear Correlation Study.

Breastfeeding education, across all disciplines, is often inconsistent and lacking in expertise and confidence. However, recommendations from health professionals, the sociocultural environment, and previous knowledge and experiences significantly influence women's decision to breastfeed. This study aimed to identify factors that promote the assignment of greater importance to breastfeeding and associated practical benefits. This retrospective cross-sectional study included 276 participants who completed a self-administered questionnaire. Descriptive and bivariate analyses were performed, and multivariate linear models were applied to identify factors influencing the importance assigned to breastfeeding. Most participants were married or in a relationship, were native Spaniards, had secondary or higher education, and had an average age of 32.6 years. Seventy percent met the physical activity recommendations, and 91% felt comfortable with their body image during pregnancy. The importance assigned to breastfeeding was high across various aspects, except for postpartum weight loss and body image. Group prenatal care was only significantly associated with the importance assigned to the breastfeeding technique (how to breastfeed). The obesogenic environment and the importance assigned to nutritional aspects and physical activity also turned out to be predictors, although not for all models. In our region, the educational strategy of antenatal care groups could contain gaps regarding the mother's health, which should be addressed in the future to improve results regarding the initiation and continuation of breastfeeding.

Ultrasound Muscle Evaluation for Predicting the Prognosis of Patients with Head and Neck Cancer: A Large-Scale and Multicenter Prospective Study.

Head and neck cancer (HNC) is a prevalent and aggressive form of cancer with high mortality rates and significant implications for nutritional status. Accurate assessment of malnutrition in patients with HNC is crucial for optimizing treatment outcomes and improving survival rates. This study aimed to evaluate the use of ultrasound techniques for predicting nutritional status, malnutrition, and cancer outcomes in patients with HNC. A total of 494 patients with HNC were included in this cross-sectional observational study. Various tools and body composition measurements, including muscle mass and adipose tissue ultrasound evaluations, were implemented. Using regression models, we mainly found that high levels of RF-CSA (rectus femoris cross-sectional area) were associated with a decreased risk of malnutrition (as defined with GLIM criteria (OR = 0.81, 95% CI: 0.68-0.98); as defined with PG-SGA (OR = 0.78, 95% CI: 0.62-0.98)) and sarcopenia (OR = 0.64, 95% CI: 0.49-0.82) after being adjusted for age, sex, and BMI. To predict the importance of muscle mass ultrasound variables on the risk of mortality, a nomogram, a random forest, and decision tree models were conducted. RF-CSA was the most important variable under the random forest model. The obtained C-index for the nomogram was 0.704, and the Brier score was 16.8. With an RF-CSA < 2.7 (AUC of 0.653 (0.59-0.77)) as a split, the decision tree model classified up to 68% of patients as possessing a high probability of survival. According to the cut-off value of 2.7 cm2, patients with a low RF-CSA value lower than 2.7 cm2 had worse survival rates (p < 0.001). The findings of this study highlight the importance of implementing ultrasound tools, for accurate diagnoses and monitoring of malnutrition in patients with HNC. Adipose tissue ultrasound measurements were only weakly associated with malnutrition and not with sarcopenia, indicating that muscle mass is a more important indicator of overall health and nutritional status. These results have the potential to improve survival rates and quality of life by enabling early intervention and personalized nutritional management.

Prognostic value of bioelectrical impedance analysis in head and neck cancer patients undergoing radiotherapy: a VALOR® study.

Introduction: Bioelectrical impedance analysis (BIA) serves as a method to estimate body composition. Parameters such as phase angle (PA), standardized phase angle (SPA), body mass cell (BCM), BCM index (BCMI), and fat-free mass (FFM) might significantly impact the prognosis of head and neck cancer (HNC) patients. The present study aimed to investigate whether bioelectrical parameters can be used to predict survival in the HNC population and establish the optimal cutoff points for predictive accuracy. Methods: A multicenter observational study was performed across 12 tertiary hospitals in Andalusia (a region from the south of Spain). A total of 494 patients diagnosed with HNC between 2020 and 2022 at different stages were included in this study, with a minimum follow-up period of 12 months. The BIA assessment was carried out during the first 2 weeks of radical radiotherapy treatment with chemotherapy or other systemic treatments. A multivariate logistic regression analysis of overall survival, complications, hospital admission, and palliative care and its relationship with BIA nutritional assessment was performed. Results: Significant prognostic factors identified in the multivariable analysis encompassed phase angle (PA), standardized phase angle (SPA), body cell mass (BCM), and BCM index (BCMI). Lower PA and BCM values were significantly associated with adverse clinical outcomes. A BCM threshold above 17 kg/m2 was the most significant predictor for predicting survival within the overall HNC population. The PA values of <5.1° in male and <4.8° in female patients showed the best predictive potential for mortality. Increased PA (as a continuous variable) demonstrated a significantly reduced risk for mortality (OR, 0.64; 95% CI, 0.43-0.94; p < 0.05) and a decreased likelihood of hospital admission (OR, 0.75; 95% CI, 0.52-1.07; p < 0.05). Higher BCM correlated with a lower risk of mortality (OR, 0.88; 95% CI, 0.80-0.96; p < 0.01) and a diminished probability of hospital admission (OR, 0.91; 95% CI, 0.83-0.99; p < 0.05). Conclusion: BIA is a crucial tool in the nutritional assessment of HNC patients. BCM and PA are the main bioelectrical parameters used to predict clinical outcomes in this population. Future studies are needed to validate BIA variables in a large cohort to ensure whether early intensification of nutritional treatment would improve survival.