Topologically Protected Photovoltaics in Bi Nanoribbons.

Photovoltaic efficiency in solar cells is hindered by many unwanted effects. Radiative channels (emission of photons) sometimes mediated by nonradiative ones (emission of phonons) are principally responsible for the decrease in exciton population before charge separation can take place. One such mechanism is electron-hole recombination at surfaces or defects where the in-gap edge states serve as the nonradiative channels. In topological insulators (TIs), which are rarely explored from an optoelectronics standpoint, we show that their characteristic surface states constitute a nonradiative decay channel that can be exploited to generate a protected photovoltaic current. Focusing on two-dimensional TIs, and specifically for illustration purposes on a Bi(111) monolayer, we obtain the transition rates from the bulk excitons to the edge states. By breaking the appropriate symmetries of the system, one can induce an edge charge accumulation and edge currents under illumination, demonstrating the potential of TI nanoribbons for photovoltaics.

Repeated intravenous doses of human umbilical cord-derived mesenchymal stromal cells for bronchopulmonary dysplasia: results of a phase 1 clinical trial with 2-year follow-up.

BACKGROUND: Currently, there is a lack of effective treatments or preventive strategies for bronchopulmonary dysplasia (BPD). Pre-clinical studies with mesenchymal stromal cells (MSCs) have yielded encouraging results. The safety of administering repeated intravenous doses of umbilical cord tissue-derived mesenchymal stromal cells (UC-MSCs) has not yet been tested in extremely-low-gestational-age newborns (ELGANs). AIMS: to test the safety and feasibility of administering three sequential intravenous doses of UC-MSCs every 7 days to ELGANs at risk of developing BPD. METHODS: In this phase 1 clinical trial, we recruited ELGANs (birth weight ≤1250 g and ≤28 weeks in gestational age [GA]) who were on invasive mechanical ventilation (IMV) with FiO2 ≥ 0.3 at postnatal days 7-14. Three doses of 5 × 106/kg of UC-MSCs were intravenously administered at weekly intervals. Adverse effects and prematurity-related morbidities were recorded. RESULTS: From April 2019 to July 2020, 10 patients were recruited with a mean GA of 25.2 ± 0.8 weeks and a mean birth weight of 659.8 ± 153.8 g. All patients received three intravenous UC-MSC doses. The first dose was administered at a mean of 16.6 ± 2.9 postnatal days. All patients were diagnosed with BPD. All patients were discharged from the hospital. No deaths or any serious adverse events related to the infusion of UC-MSCs were observed during administration, hospital stays or at 2-year follow-up. CONCLUSIONS: The administration of repeated intravenous infusion of UC-MSCs in ELGANs at a high risk of developing BPD was feasible and safe in the short- and mid-term follow-up.

Risk of Severe Maternal Morbidity Associated with Maternal Comorbidity Burden and Social Vulnerability.

OBJECTIVE: We evaluated the associations of the obstetric comorbidity index (OB-CMI) and social vulnerability index (SVI) with severe maternal morbidity (SMM). STUDY DESIGN: Multicenter retrospective cohort study of all patients who delivered (gestational age > 20 weeks) within a university health system from January 1, 2019, to December 31, 2021. OB-CMI scores were assigned to patients using clinical documentation and diagnosis codes. SVI scores, released by the Centers for Disease Control and Prevention (CDC), were assigned to patients based on census tracts. The primary outcome was SMM, based on the 21 CDC indicators. Mixed-effects logistic regression was used to model the odds of SMM as a function of OB-CMI and SVI while adjusting for maternal race and ethnicity, insurance type, preferred language, and parity. RESULTS: In total, 73,518 deliveries were analyzed. The prevalence of SMM was 4% (n = 2,923). An association between OB-CMI and SMM was observed (p < 0.001), where OB-CMI score categories of 1, 2, 3, and ≥4 were associated with higher odds of SMM compared with an OB-CMI score category of 0. In the adjusted model, there was evidence of an interaction between OB-CMI and maternal race and ethnicity (p = 0.01). After adjusting for potential confounders, including SVI, non-Hispanic Black patients had the highest odds of SMM among patients with an OB-CMI score category of 1 and ≥4 compared with non-Hispanic White patients with an OB-CMI score of 0 (adjusted odds ratio [aOR] 2.76, 95% confidence interval [CI] 2.08-3.66 and aOR 10.07, 95% CI 8.42-12.03, respectively). The association between SVI and SMM was not significant on adjusted analysis. CONCLUSION: OB-CMI was significantly associated with SMM, with higher score categories associated with higher odds of SMM. A significant interaction between OB-CMI and maternal race and ethnicity was identified, revealing racial disparities in the odds of SMM within each higher OB-CMI score category. SVI was not associated with SMM after adjusting for confounders. KEY POINTS: · OB-CMI was significantly associated with SMM.. · Racial disparities were seen within each OB-CMI score group.. · SVI was not associated with SMM on adjusted analysis..

Understanding consumer food choices & promotion of healthy and sustainable Mediterranean diet and lifestyle in children and adolescents through behavioural change actions: the DELICIOUS project.

Over the last decades, the abandonment of traditional dietary patterns, such as the Mediterranean diet, represents an important threat for human health and environmental safeguard. The DELICIOUS project aims to promote healthy lifestyles among children and adolescents by implementing activities and tools to increase the adherence to the Mediterranean Diet with an attention to the environmental impacts of the diet. This study protocol describes the DELICIOUS project as a single-arm, uncontrolled behavioural intervention providing formal and non-formal education activities, development of new snacks and recipe reformulation, web/mobile app development, and physical activities to school children and adolescents in five European countries. The project aims to increase awareness of the nutritional benefits and the sustainability aspects of the Mediterranean Diet and to promote consumers' empowerment through an online platform for sustainable and healthy meal planning in the school canteen.

Nickel(II)-Catalyzed Formal [3+2] Cycloadditions between Indoles and Donor-Acceptor Cyclopropanes.

This article describes the development of a nickel-catalyzed regio- and diastereoselective formal [3+2] cycloaddition between N-substituted indoles and donor-acceptor cyclopropanes to synthesize cyclopenta[b]indoles. Optimized reaction conditions provide the desired nitrogen-containing cycloadducts in up to 93% yield and dr 8.6:1 with complete regioselectivity. The substrate scope showed high tolerance to various substituted indoles and cyclopropanes, resulting in the synthesis of six new cyclopenta[b]indoles and the isolation of five derivatives previously reported in the literature. In addition, a mechanistic proposal for the reaction was studied through online reaction monitoring by ESI-MS, allowing for the identification of the reactive intermediates in the Ni(II) catalyzed process. X-ray crystallography confirmed the structure and relative endo stereochemistry of the products. This method enables the fast and efficient construction of fused indolines from readily accessible starting materials.

Active approach in delivery room and survival of infants born between 22 and 26 gestational weeks are increasing in Spain.

AIM: To describe the trends in the delivery room approach and survival of extremely premature infants over the past two decades. METHODS: Time-series analysis of infants included in the Spanish SEN1500 network from 2004 to 2019. Patients born from 22 + 0 to 26 + 6 weeks were included. The primary outcome was an active approach in the delivery room. Survival and temporal trends were also studied. RESULTS: The study population included 8284 patients. At 22 and 23 weeks, an active approach was followed in 41.4% and 80.8%. A temporal trend toward a more active approach was observed at 23 weeks. Antenatal steroids were administered in 19.6% and 58.1% at 22 and 23 weeks. From 24 weeks, an active approach was applied in nearly all cases throughout the period, and more than 80% of patients received antenatal steroids. The rates of survival after an active approach were 8.7%, 21.6%, 40.6%, 59.9%, and 74.7% at 22, 23, 24, 25, and 26 weeks and significantly increased over the period, except for infants born at 22 weeks. CONCLUSION: Active management and survival of infants born from 23 weeks increased over the period, but the frequency of antenatal steroid administration was lower than the intention to resuscitate.

Evaluation of a whole-exome sequencing pipeline and benchmarking of causal germline variant prioritizers.

Most causal variants of Mendelian diseases are exonic. Whole-exome sequencing (WES) has become the diagnostic gold standard, but causative variant prioritization constitutes a bottleneck. Here we assessed an in-house sample-to-sequence pipeline and benchmarked free prioritization tools for germline causal variants from WES data. WES of 61 unselected patients with a known genetic disease cause was obtained. Variant prioritizations were performed by diverse tools and recorded to obtain a diagnostic yield when the causal variant was present in the first, fifth, and 10th top rankings. A fraction of causal variants was not captured by WES (8.2%) or did not pass the quality control criteria (13.1%). Most of the applications inspected were unavailable or had technical limitations, leaving nine tools for complete evaluation. Exomiser performed best in the top first rankings, while LIRICAL led in the top fifth rankings. Based on the more conservative top 10th rankings, Xrare had the highest diagnostic yield, followed by a three-way tie among Exomiser, LIRICAL, and PhenIX, then followed by AMELIE, TAPES, Phen-Gen,  AIVar, and VarNote-PAT. Xrare, Exomiser, LIRICAL, and PhenIX are the most efficient options for variant prioritization in real patient WES data.

Corticosteroids for COVID-19 symptoms and quality of life at 1 year from admission.

The long-term evolution of COVID-19 is unknown, making it necessary to study the persistence of symptoms over time and their impact on quality of life in people who have had the disease. We analyzed these aspects 1 year after admission for COVID-19 and explored the influence of treatment with systemic corticosteroids during the acute phase of the illness. This observational cohort study took place in a tertiary hospital in March and April 2021 and included people admitted due to infection with SARS-CoV-2 in March, April, or May 2020. We excluded patients who had died, were unreachable or had substantial cognitive impairment. A telephone survey was undertaken to assess the presence of symptoms related to COVID-19 and to administer the SF-36 quality of life questionnaire. Other variables collected were demographic and clinical data along with the treatment received and the evolution over time. We analyzed 76 patients, including 44 who did not receive corticosteroids and 32 who did. Most symptoms were less frequent in the group that received corticosteroids, with statistically significant differences for headache, dysphagia, chest pain, and depression. These patients also showed significantly better outcomes in the SF-36 domains for "bodily pain" and "mental health." Corticosteroids administered in the acute phase of COVID-19 could attenuate the presence of long-term symptoms and improve patients' quality of life.

Lanthanide SMMs Based on Belt Macrocycles: Recent Advances and General Trends.

Enhancement of axial magnetic anisotropy is the central objective to push forward the performance of Single-Molecule Magnet (SMM) complexes. In the case of mononuclear lanthanide complexes, the chemical environment around the paramagnetic ion must be tuned to place strongly interacting ligands along either the axial positions or the equatorial plane, depending on the oblate or prolate preference of the selected lanthanide. One classical strategy to achieve a precise chemical environment for a metal centre is using highly structured, chelating ligands. A natural approach for axial-equatorial control is the employment of macrocycles acting in a belt conformation, providing the equatorial coordination environment, and leaving room for axial ligands. In this review, we present a survey of SMMs based on the macrocycle belt motif. Literature systems are divided in three families (crown ether, Schiff-base and metallacrown) and their general properties in terms of structural stability and SMM performance are briefly discussed.

What Is the Status of Immunotherapy in Neuroendocrine Neoplasms?

PURPOSE OF REVIEW: Immunotherapy has changed the treatment of patients with advanced cancer, with different phase III trials showing durable responses across different histologies. This review focuses on the preclinical and clinical evidence of potential predictive biomarkers of response and efficacy of immunotherapy in neuroendocrine neoplasms (NENs) of gastro-entero-pancreatic origin. RECENT FINDINGS: PD-L1 staining by immunohistochemistry has shown heterogeneous results across different studies in both well-differentiated neuroendocrine tumors (NETs) and poorly-differentiated neuroendocrine carcinomas (NECs). Tumor mutational burden in NENs is low, but seems to be higher in NECs. Immune infiltrate (CD3+ lymphocytes) at the tumor microenvironment (TME) is present in NETs and NECs. However, results from clinical trials with immunotherapy as monotherapy o combinations have shown limited efficacy. Further investigation into new strategies aside from anti-CTLA-4/PD-1/PD-L1 antibodies, validation of predictive biomarkers, and better population selection for clinical trials in NENs are more than needed in the near future.

Time at birth and short-term outcomes among extremely preterm infants in Spain: a multicenter cohort study.

The first hours after birth entail a window of opportunity to decrease morbidity and mortality among extremely preterm infants. The availability of staff and its tiredness vary depending on the timing and day of the week. We hypothesized that these circumstances may impact neonatal outcomes. We have conducted a multicenter cohort study with data obtained from the Spanish neonatal network database SEN1500, where staff doctors are in the house 24/7. The main study exposure was the time of birth; secondary exposures were cumulative work hours from the medical and nurses' shifts and day of the week. The primary outcome was survival to hospital discharge. Secondary outcomes included common preterm infants' in-hospital complications. Univariate and multivariate analysis adjusting for potential confounders was performed. All extremely preterm infants (N = 8798) born between 2011 and 2019 were eligible; 35.7% of them were admitted during the night shift. No differences were found between day and night births regarding survival or morbidity. No differences were found between weekdays and weekends or when considering cumulative worked hours in the shifts. Infants born during the night shift were more likely to be intubated at birth (OR 1.20, CI95% 1.06-1.37), receive surfactant (OR 1.24, CI95% 1.08-1.44), and having anemia requiring transfusion (OR 1.23, CI 95% 1.08-1.42). CONCLUSION: the time of birth did not seem to affect mortality and morbidity of extremely preterm infants. WHAT IS KNOWN: • The first hours after birth in extremely preterm infants are a very valuable opportunity to decrease mortality and morbidity. • Time and day of birth have long been linked to outcomes in preterm infants, with night shifts and weekends classically having higher rates of mortality and morbidity. WHAT IS NEW: • In this study, no differences were found between day and night births regarding survival or major morbidity. • Infants born during the night shift were more likely to be intubated at birth, receive surfactant and having anemia requiring transfusion.

Cytotoxic Effects on Breast Cancer Cell Lines of Chalcones Derived from a Natural Precursor and Their Molecular Docking Analysis.

This study aimed to determine the in vitro cytotoxicity and understand possible cytotoxic mechanisms via an in silico study of eleven chalcones synthesized from two acetophenones. Five were synthesized from a prenylacetophenone isolated from a plant that grows in the Andean region of the Atacama Desert. The cytotoxic activity of all the synthesized chalcones was tested against breast cancer cell lines using an MTT cell proliferation assay. The results suggest that the prenyl group in the A-ring of the methoxy and hydroxyl substituents of the B-ring appear to be crucial for the cytotoxicity of these compounds. The chalcones 12 and 13 showed significant inhibitory effects against growth in MCF-7 cells (IC50 4.19 ± 1.04 µM and IC50 3.30 ± 0.92 µM), ZR-75-1 cells (IC50 9.40 ± 1.74 µM and IC50 8.75 ± 2.01µM), and MDA-MB-231 cells (IC50 6.12 ± 0.84 µM and IC50 18.10 ± 1.65 µM). Moreover, these chalcones showed differential activity between MCF-10F (IC50 95.76 ± 1.52 µM and IC50 95.11 ± 1.97 µM, respectively) and the tumor lines. The in vitro results agree with molecular coupling results, whose affinity energies and binding mode agree with the most active compounds. Thus, compounds 12 and 13 can be considered for further studies and are candidates for developing new antitumor agents. In conclusion, these observations give rise to a new hypothesis for designing chalcones with potential cytotoxicity with high potential for the pharmaceutical industry.

Bayesian genomic models boost prediction accuracy for survival to Streptococcus agalactiae infection in Nile tilapia (Oreochromus nilioticus).

BACKGROUND: Streptococcosis is a major bacterial disease in Nile tilapia that is caused by Streptococcus agalactiae infection, and development of resistant strains of Nile tilapia represents a sustainable approach towards combating this disease. In this study, we performed a controlled disease trial on 120 full-sib families to (i) quantify and characterize the potential of genomic selection for survival to S. agalactiae infection in Nile tilapia, and (ii) identify the best genomic model and the optimal density of single nucleotide polymorphisms (SNPs) for this trait. METHODS: In total, 40 fish per family (15 fish intraperitoneally injected and 25 fish as cohabitants) were used in the challenge test. Mortalities were recorded every 3 h for 35 days. After quality control, genotypes (50,690 SNPs) and phenotypes (0 for dead and 1 for alive) for 2472 cohabitant fish were available. Genetic parameters were obtained using various genomic selection models (genomic best linear unbiased prediction (GBLUP), BayesB, BayesC, BayesR and BayesS) and a traditional pedigree-based model (PBLUP). The pedigree-based analysis used a deep 17-generation pedigree. Prediction accuracy and bias were evaluated using five replicates of tenfold cross-validation. The genomic models were further analyzed using 10 subsets of SNPs at different densities to explore the effect of pruning and SNP density on predictive accuracy. RESULTS: Moderate estimates of heritabilities ranging from 0.15 ± 0.03 to 0.26 ± 0.05 were obtained with the different models. Compared to a pedigree-based model, GBLUP (using all the SNPs) increased prediction accuracy by 15.4%. Furthermore, use of the most appropriate Bayesian genomic selection model and SNP density increased the prediction accuracy up to 71%. The 40 to 50 SNPs with non-zero effects were consistent for all BayesB, BayesC and BayesS models with respect to marker id and/or marker locations. CONCLUSIONS: These results demonstrate the potential of genomic selection for survival to S. agalactiae infection in Nile tilapia. Compared to the PBLUP and GBLUP models, Bayesian genomic models were found to boost the prediction accuracy significantly.

Drug Development in Neuroendocrine Tumors: What Is on the Horizon?

OPINION STATEMENT: Neuroendocrine neoplasms (NENs) constitute a heterogenous group of malignancies. Translational research into NEN cell biology is the cornerstone for drug development strategies in this field. Somatostatin receptor type 2 (SSTR2) expression is the hallmark of well-differentiated neuroendocrine tumors (NETs). Somatostatin analogs and peptide receptor radionuclide therapy (PRRT) form the basis of anti-SSTR2 treatment onto new combination strategies, antibody-drug conjugates and bispecific antibodies. Classical pathways involved in NET development (PI3K-Akt-mTOR and antiangiogenics) are reviewed but new potential targets for NET treatment will be explored. Epigenetic drugs have shown clinical activity in monotherapy and preclinical combination strategies are more than attractive. Immunotherapy has shown opposite results in different NEN settings. Although the NOTCH pathway has been targeted with disappointing results, new strategies are being developed. Finally, after years of solid preclinical evidence on different genetically engineered oncolytic viruses, clinical trials for refractory NET patients are now ongoing.

Real-World Usage of the WavelinQ EndoAVF System.

BACKGROUND: Dependent on existing deep to superficial perforating venous branches, the WavelinQ EndoAVF System is a novel technique used to create an arteriovenous fistula (AVF) between ulnar or radial veins and concomitant arteries for dialysis access. We sought to examine a single center's success rates and short-term follow-up using this device. METHODS: All consecutive patients undergoing placement of a WavelinQ AVF from October 2018 to July 2019 were included. Preoperative/intraoperative variables including demographics, preoperative/postoperative duplex ultrasonography, success rate of procedure, and subsequent endovascular/surgical procedures were obtained. Descriptive statistics and comparison of groups requiring subsequent intervention were performed. RESULTS: Thirty-five patients underwent placement of the WavelinQ AVF, with 32 (91%) patients having at least one documented follow-up. These patients were predominantly male (23/32, 72%) with an average age of 60.2 and 23 of 32 (72%) patients were on dialysis. Initial fistula creation success rate was 100%. Average procedural length was 120 min, fluoroscopy time 9.6 min, and contrast usage 52.2 mL. Eight of 32 (25%) patients had perioperative complications (3 hematomas, 3 contrast extravasations, 1 resolved vessel spasm all resolving spontaneously, and 1 pseudoaneurysm requiring surgical repair). Thirteen of 32 (41%) patients underwent subsequent endovascular interventions to assist with maturation [9/32 (28%) branch coiling, 5/32 (16%) angioplasty/stenting, and 3/32 (9%) access thrombectomy] and 4 of 32 (13%) patients required subsequent surgical interventions (1 pseudoaneurysm repair, 1 revision of fistula, and 2 definitive AVF creation in thrombosed grafts). The majority of accesses (30/32, 94%) were ulnar-ulnar fistulas and overall patency at average follow-up of 73 days was 88% (28/32) with average brachial artery inflow volume of 1,078 cc/min and average cephalic vein (18/32) outflow volume of 447 cc/min. Eleven of 23 (48%) patients on dialysis were successfully using the EndoAVF at follow-up. CONCLUSIONS: The WavelinQ AVF system has a high initial procedural success rate, although a significant portion of patients require subsequent endovascular procedures to aid in maturation. Further work on determining factors predictive of need for reintervention is necessary.

Antagonistic Activity of Lactic Acid Bacteria Against Phytopathogenic Fungi Isolated from Cherry Tomato (Solanum lycopersicum var. cerasiforme).

The postharvest deterioration of cherry tomatoes due to diseases caused by fungi is one of the main causes of the loss of this product. The objective of this study was to determine the antagonistic capacity by evaluating the antifungal power of nine strains of lactic acid bacteria (LAB) in vitro against the phytopathogenic fungi Aspergillus niger, Fusarium sp., and Rhizopus stolonifer isolated from cherry tomatoes (Solanum lycopersicum var. cerasiforme) and to measure the biosurfactant production capacity, its antagonism in vivo, and the production of organic acids. The results showed that seven of the nine strains were able to inhibit at least one of the three fungi isolated in the in vitro assay. In eight of nine strains, biosurfactant production was identified, and the strains Weissella confusa and Lactiplantibacillus plantarum A6 showed the highest antifungal activity in vitro and in vivo against the fungi evaluated, with the identification of organic acid production in both strains. LAB demonstrated the ability to inhibit cherry tomato fungi, thus emerging as an alternative to the use of chemical preservatives in the production of this fruit and being projected as a preservation technology for this type of product through the use of strains or their metabolites.

Experimental validation of genetic selection for resistance against Streptococcus agalactiae via different routes of infection in the commercial Nile tilapia breeding programme.

The objective of this study was to validate the genetic selection for resistance to streptococcosis under experimental challenge conditions in a commercial population of Nile tilapia. Further, effects of using two different routes of infection of Streptococcus agalactiae; intraperitoneal injection (IP) and cohabitation with the shedder fish (cohab), on the genomic parameters, prediction accuracy and response to selection are compared. The comparison was made between two different lines of fish; one selected for S. agalactiae resistance for one generation and randomly mated for two generations (to mimic the multiplication activities occurring in distribution channels and hatcheries); and the other unselected. 1,500 fish, each from these two lines, were used for the experimental challenge test. Survival analysis using Kaplan-Meier estimators and Hazard's ratio was used to quantify differences in mortality between the two lines. Further genomic analysis was performed with 2,684 fish and 35,745 SNPs using both univariate and bivariate GBLUP models. Genetic selection for resistance to S. agalactiae led to the significant (p < .001) reduction in the risk of death by 65% in the selected line, compared to the unselected line. Similarly, the risk of death via cohabitation route of infection significantly (p < .01) decreased by 80%, compared to IP. The genetic correlation between these two routes of infection was ~0.9. Genetic selection changed the impact of the routes of infection, with the change in the distribution of estimated breeding values and the gain of 3.04 ± 1.25 days as selection response (p < .05).

Understanding the Molecular Basis of 5-HT4 Receptor Partial Agonists through 3D-QSAR Studies.

Alzheimer's disease (AD) is a neurodegenerative disorder whose prevalence has an incidence in senior citizens. Unfortunately, current pharmacotherapy only offers symptom relief for patients with side effects such as bradycardia, nausea, and vomiting. Therefore, there is a present need to provide other therapeutic alternatives for treatments for these disorders. The 5-HT4 receptor is an attractive therapeutic target since it has a potential role in central and peripheral nervous system disorders such as AD, irritable bowel syndrome, and gastroparesis. Quantitative structure-activity relationship analysis of a series of 62 active compounds in the 5-HT4 receptor was carried out in the present work. The structure-activity relationship was estimated using three-dimensional quantitative structure-activity relationship (3D-QSAR) techniques based on these structures' field molecular (force and Gaussian field). The best force-field QSAR models achieve a value for the coefficient of determination of the training set of R2training = 0.821, and for the test set R2test = 0.667, while for Gaussian-field QSAR the training and the test were R2training = 0.898 and R2test = 0.695, respectively. The obtained results were validated using a coefficient of correlation of the leave-one-out cross-validation of Q2LOO = 0.804 and Q2LOO = 0.886 for force- and Gaussian-field QSAR, respectively. Based on these results, novel 5-HT4 partial agonists with potential biological activity (pEC50 8.209-9.417 for force-field QSAR and 9.111-9.856 for Gaussian-field QSAR) were designed. In addition, for the new analogues, their absorption, distribution, metabolism, excretion, and toxicity properties were also analyzed. The results show that these new derivatives also have reasonable pharmacokinetics and drug-like properties. Our findings suggest novel routes for the design and development of new 5-HT4 partial agonists.

Pain assessment during eye examination for retinopathy of prematurity screening: Skin conductance versus PIPP-R.

AIM: To assess changes in skin conductance during retinopathy of prematurity screening and to study the correlation between the skin conductance and a validated pain scale. METHODS: Prospective observational study. Fifty-three eye examinations were performed in 32 preterm infant candidates for retinopathy of prematurity screening. Outcome measures were changes in Premature Infant Pain Profile-Revised (PIPP-R) scale and number of skin conductance fluctuations. RESULTS: There was a significant increase from baseline in the number of skin conductance fluctuations and PIPP-R during the procedure. The maximum value of number of skin conductance fluctuations was 0.64 ± 0.44 peaks/sec, and the maximum value of PIPP-R was 10.8 ± 3.3. A correlation between the skin conductance and PIPP-R was not found at any time during the eye examination. Repeated measures correlation analyses showed only a moderate positive correlation between PIPP-R and number of skin conductance fluctuation values. CONCLUSION: There were significant changes in both PIPP-R and number of skin conductance fluctuations during retinopathy of prematurity screening, reaffirming that this procedure is painful and stressful. The number of skin conductance fluctuations and PIPP-R are not significantly correlated, which likely reflects that these parameters evaluate different but complementary aspects of neonatal pain responses.

Interactive Web-Based Resource for Annotation of Genetic Variants Causing Hereditary Angioedema (HADA): Database Development, Implementation, and Validation.

BACKGROUND: Hereditary angioedema is a rare genetic condition caused by C1 esterase inhibitor deficiency, dysfunction, or kinin cascade dysregulation, leading to an increased bradykinin plasma concentration. Hereditary angioedema is a poorly recognized clinical entity and is very often misdiagnosed as a histaminergic angioedema. Despite its genetic nature, first-line genetic screening is not integrated in routine diagnosis. Consequently, a delay in the diagnosis, and inaccurate or incomplete diagnosis and treatment of hereditary angioedema are common. OBJECTIVE: In agreement with recent recommendations from the International Consensus on the Use of Genetics in the Management of Hereditary Angioedema, to facilitate the clinical diagnosis and adapt it to the paradigm of precision medicine and next-generation sequencing-based genetic tests, we aimed to develop a genetic annotation tool, termed Hereditary Angioedema Database Annotation (HADA). METHODS: HADA is built on top of a database of known variants affecting function, including precomputed pathogenic assessment of each variant and a ranked classification according to the current guidelines from the American College of Medical Genetics and Genomics. RESULTS: HADA is provided as a freely accessible, user-friendly web-based interface with versatility for the entry of genetic information. The underlying database can also be incorporated into automated command-line stand-alone annotation tools. CONCLUSIONS: HADA can achieve the rapid detection of variants affecting function for different hereditary angioedema types, and further integrates useful information to reduce the diagnosis odyssey and improve its delay.