Experiences of parents with very premature-born children at risk of neurodevelopmental disorders: A qualitative study.

BACKGROUND: Premature birth is a traumatic and stressful situation for parents who are immediately separated from their infant because of the newborn's need for specialized care. The staff of these units are in charge of following the principles of family-centred care and practices for neonates at risk of neurodevelopmental disorders, including providing training to the family during their hospital stay and after being discharged. AIMS: The aim of this study is to explore the perceptions of parents of premature children at risk of neurodevelopmental disorders in regard to care, interventions and assistance provided during the first months of their child's life. STUDY DESIGN: A qualitative descriptive study was carried out through individual interviews. The data analysis was conducted through a thematic analysis. The methodology and results were reported following the standards for preparing qualitative research reports and recommendations. RESULTS: Twenty-one parents of premature children were interviewed. From these interviews, three main themes emerged: (i) parents' perspectives on preterm birth risk communication, (ii) navigating parental support and early interventions in preterm birth and (iii) perceptions of preterm birth protective and challenging factors. CONCLUSIONS: The parents of premature children need to receive better communication about the care and interventions for their child, and it is necessary that health personnel are better trained in terms of management and administration of public resources. Strategies must be implemented that continuously guide parents on the follow-up and care of their premature child not only during their first moments of life but also after being discharged from the hospital. RELEVANCE TO CLINICAL PRACTICE: This study highlights the need to improve care for parents with premature infants at risk, emphasizing the necessity for health care system reforms and support structures, allowing health care professionals to enhance attention and care.

Statistical accuracy of molecular dynamics-based methods for sampling conformational ensembles of disordered proteins.

The characterization of the statistical ensemble of conformations of intrinsically disordered regions (IDRs) is a great challenge both from experimental and computational points of view. In this respect, a number of protocols have been developed using molecular dynamics (MD) simulations to sample the huge conformational space of the molecule. In this work, we consider one of the best methods available, replica exchange solute tempering (REST), as a reference to compare the results obtained using this method with the results obtained using other methods, in terms of experimentally measurable quantities. Along with the methods assessed, we propose here a novel protocol called probabilistic MD chain growth (PMD-CG), which combines the flexible-meccano and hierarchical chain growth methods with the statistical data obtained from tripeptide MD trajectories as the starting point. The system chosen for testing is a 20-residue region from the C-terminal domain of the p53 tumor suppressor protein (p53-CTD). Our results show that PMD-CG provides an ensemble of conformations extremely quickly, after suitable computation of the conformational pool for all peptide triplets of the IDR sequence. The measurable quantities computed on the ensemble of conformations agree well with those based on the REST conformational ensemble.

Anti-HLA serologic response to CD38-targeting desensitization therapy is challenged by peripheral memory B cells in highly sensitized kidney transplant candidates.

High human leukocyte antigen (HLA) sensitization limits access to compatible transplantation. New CD38-targeting agents have been shown to reduce anti-HLA antibodies, although with important interpatient variability. Thus, pretreatment identification of responder and nonresponder (NR) patients is needed for treatment decision-making. We analyzed 26 highly sensitized (HS) patients from 2 desensitization trials using anti-CD38 monoclonal antibodies. Hierarchical clustering identified 3 serologic responder groups: high responders, low responders, and NR. Spectral flow cytometry and functional HLA-specific memory B cell (mBC) assessment were first conducted on peripheral blood mononuclear cells and bone marrow samples from 16 patients treated with isatuximab (NCT04294459). Isatuximab effectively depleted bone marrow plasma cells, peripheral CD38-expressing plasmablasts, plasma cells, transitional B cells, and class-switch mBCs, ultimately reducing frequencies of HLA-specific immunoglobulin G (IgG)-producing mBCs. Multidimensional spectral flow cytometry with partial least squares discriminant analysis revealed that pretreatment abundance of specific circulating mBC phenotypes, especially CD38neg class-switch mBCs, accurately distinguished between high serologic responders and low responders or NR (AUC 0.958, 0.860-1.000, P = .009), who also displayed significantly lower frequencies of HLA-specific IgG-producing mBCs (P < .0001). This phenotypical mBC signature predicting response to therapy was validated in an external HS patient cohort (n = 10) receiving daratumumab (NCT04204980). This study identifies critical circulating mBC subset phenotypes that distinguish HS patients with successful serologic responses to CD38-targeting desensitization therapies, potentially guiding treatment decision-making.

Implications of Domestication in Theobroma cacao L. Seed-Borne Microbial Endophytes Diversity.

The study of plant-microbe interactions is a rapidly growing research field, with increasing attention to the role of seed-borne microbial endophytes in protecting the plant during its development from abiotic and biotic stresses. Recent evidence suggests that seed microbiota is crucial in establishing the plant microbial community, affecting its composition and structure, and influencing plant physiology and ecology. For Theobroma cacao L., the diversity and composition of vertically transmitted microbes have yet to be addressed in detail. We explored the composition and diversity of seed-borne endophytes in cacao pods of commercial genotypes (ICS95, IMC67), recently liberated genotypes from AGROSAVIA (TCS01, TCS19), and landraces from Tumaco (Colombia) (AC9, ROS1, ROS2), to evaluate microbial vertical transmission and establishment in various tissues during plant development. We observed a higher abundance of Pseudomonas and Pantoea genera in the landraces and AGROSAVIA genotypes, while the commercial genotypes presented a higher number of bacteria species but in low abundance. In addition, all the genotypes and plant tissues showed a high percentage of fungi of the genus Penicillium. These results indicate that domestication in cacao has increased bacterial endophyte diversity but has reduced their abundance. We isolated some of these seed-borne endophytes to evaluate their potential as growth promoters and found that Bacillus, Pantoea, and Pseudomonas strains presented high production of indole acetic acid and ACC deaminase activity. Our results suggest that cacao domestication could lead to the loss of essential bacteria for seedling establishment and development. This study improves our understanding of the relationship and interaction between perennial plants and seed-borne microbiota.

Early interventions with parental participation and their implications on the neurodevelopment of premature children: a systematic review and meta-analysis.

The occurrence of preterm birth is correlated with the potential emergence of disabilities in children. Early intervention programs are designed to promote better developmental outcomes. These interventions employ family-centered methodologies, wherein parents are instructed to facilitate neurodevelopment, thereby promoting heightened involvement of the child in their daily activities. The objective of this investigation was to evaluate the efficacy of early family-based interventions on motor, cognitive, and language development. A systematic review and meta-analysis was conducted utilizing the databases PubMed, Medline, PEDro, Scopus, CINAHL Complete, SciELO, and Open Grey. The search terms utilized included NDT (neuro-developmental treatment), Bobath, neurodevelopmental therapy, parents administered, family administered, physical therapy modalities, early intervention (educational), early intervention, premature infant, preterm, and premature. Randomized clinical trials and observational studies written in English or Spanish were taken into consideration. The initial search resulted in 420 articles. After removing duplicates and applying the selection criteria, 12 articles were selected for the systematic review and 5 articles were selected for the meta-analysis. The meta-analysis revealed a significant association between early intervention and enhanced cognitive function (p = 0.01) in this study. Additionally, the meta-analysis indicated improvements resulting from early family-based intervention (p = 0.02) in motor function. Early motor interventions that emphasize parent involvement and education in neurodevelopment show significant outcomes in motor and cognitive areas at 2 years of age in very premature or extremely premature infants. However, inconclusive effects have been found in the language area, which is the least studied domain. Due to the methodological heterogeneity observed, further research is needed to establish conclusive decisions regarding the administration of these interventions and the determination of key evaluation periods.

In-vivo 3-dimensional spine and lower body gait symmetry analysis in healthy individuals.

Background: Numerous research studies have delved into the biomechanics of walking, focusing on the spine and lower extremities. However, understanding the symmetry of walking in individuals without health issues poses a challenge, as those with normal mobility may exhibit uneven movement patterns due to inherent functional differences between their left and right limbs. The goal of this study is to examine the three-dimensional kinematics of gait symmetry in the spine and lower body during both typical and brisk overground walking in healthy individuals. The analysis will utilize statistical methods and symmetry index approaches. Furthermore, the research aims to investigate whether factors such as gender and walking speed influence gait symmetry. Methods: Sixty young adults in good health, comprising 30 males and 30 females, underwent motion capture recordings while engaging in both normal and fast overground walking. The analysis focused on interlimb comparisons and corresponding assessments of side-specific spine and pelvis motions. Results: Statistical Parametric Mapping (SPM) predominantly revealed gait symmetries between corresponding left and right motions in the spine, pelvis, hip, knee, and ankle during both normal and fast overground walking. Notably, both genders exhibited asymmetric pelvis left-right obliquity, with women and men showing an average degree of asymmetry between sides of 0.9 ± 0.1° and 1.5 ± 0.1°, respectively. Furthermore, the analysis suggested that neither sex nor walking speed appeared to exert influence on the 3D kinematic symmetry of the spine, pelvis, and lower body in healthy individuals during gait. While the maximum normalized symmetry index (SInorm) values for the lower thorax, upper lumbar, lower lumbar, pelvis, hip, knee, and ankle displayed significant differences between sexes and walking speeds for specific motions, no interaction between sex and walking speed was observed. Significance: The findings underscore the potential disparities in data interpretations between the two approaches. While SPM discerns temporal variations in movement, these results offer valuable insights that may enhance our comprehension of gait symmetry in healthy individuals, surpassing the limitations of straightforward discrete parameters like the maximum SInorm. The information gleaned from this study could serve as reference indicators for diagnosing and evaluating abnormal gait function.

High-dimensional mass cytometry identified circulating natural killer T-cell subsets associated with protection from cytomegalovirus infection in kidney transplant recipients.

Cytomegalovirus (CMV) infection is associated with poor kidney transplant outcomes. While innate and adaptive immune cells have been implicated in its prevention, an in-depth characterization of the in vivo kinetics of multiple cell subsets and their role in protecting against CMV infection has not been achieved. Here, we performed high-dimensional immune phenotyping by mass cytometry, and functional assays, on 112 serially collected samples from CMV seropositive kidney transplant recipients. Advanced unsupervised deep learning analysis was used to assess immune cell populations that significantly correlated with prevention against CMV infection and anti-viral immune function. Prior to infection, kidney transplant recipients who developed CMV infection showed significantly lower CMV-specific cell-mediated immune (CMI) frequencies than those that did not. A broad diversity of circulating cell subsets within innate and adaptive immune compartments were associated with CMV infection or protective CMV-specific CMI. While percentages of CMV (tetramer-stained)-specific T cells associated with high CMI responses and clinical protection, circulating CD3+CD8midCD56+ NK-T cells overall strongly associated with low CMI and subsequent infection. However, three NK-T cell subsets sharing the CD11b surface marker associated with CMV protection and correlated with strong anti-viral CMI frequencies in vitro. These data were validated in two external independent cohorts of kidney transplant recipients. Thus, we newly describe the kinetics of a novel NK-T cell subset that may have a protective role in post-transplantation CMV infection. Our findings pave the way to more mechanistic studies aimed at understanding the function of these cells in protection against CMV infection.

Expression of Rejection-Associated Transcripts in Early Protocol Renal Transplant Biopsies Is Associated with Tacrolimus Exposure and Graft Outcome.

Subclinical inflammation in protocol biopsies relates to tacrolimus exposure and human leukocyte antigen (HLA) matching. We aimed to characterize transcripts associated with rejection and tacrolimus exposure and the latter's association with transplant outcomes. We tested whether gene expression is associated with rejection using strictly normal protocol biopsies (n = 17) and biopsies with T cell-mediated rejection (TCMR) or antibody-mediated rejection (ABMR) according to Banff criteria (n = 12). Subsequently, we analyzed these transcripts in a set of 4-month protocol biopsies (n = 137) to assess their association with donor and recipient characteristics, the intensity of immunosuppression, and the graft outcome. Differential expression (false discovery rate (FDR) < 0.01, fold (change (FC) > 3) between normal and rejection biopsies yielded a set of 111 genes. In the protocol biopsy cohort (n = 137), 19 out of these 111 genes correlated with tacrolimus trough levels at the time of biopsy (TAC-C0), and unsupervised analysis split this cohort into two clusters. The two clusters differed in donor age and tacrolimus trough levels. Subclinical rejection, including borderline lesions, tended to occur in the same cluster. Logistic regression analysis indicated that TAC-C0 at the time of biopsy (OR: 0.83, 95%CI:0.72-0.06, p = 0.0117) was associated with cluster 2. In a follow-up averaging 70 ± 30 months, this patient group displayed a significant decline in renal function (p = 0.0135). The expression of rejection-associated transcripts in early protocol biopsies is associated with tacrolimus exposure and a faster decline in renal function.

The Property Rights Index (PRIF) can be used worldwide to compare different forest governance systems.

The bundle of forest landowners' rights largely varies from one jurisdiction to another. On a global scale, the diversity of forest management regime and property rights systems is such that finding comprehensive and standardised approaches for governance analysis purposes is a challenging task. This paper explores the use of the Property Rights Index for Forestry (PRIF) as an analytical tool based on five rights domains (access, withdrawal, management, exclusion, and alienation) to assess how regulatory frameworks impact the owners' forest property rights. We show that PRIF is a reliable index for various governance arrangements, considering its ability to score forest owners' freedom to decide in case studies that range from the Amazon area (Brazil), Misiones province (Argentina) and Quebec (Canada) to community-managed Nepalese and Mexican forests. PRIF scores obtained in these diverse governance arrangements confirm that the governance of forests held by entities other than the state is driven by two factors: the owner's ability to exclude the public from the use of his/her own resource and the owner's freedom to decide on the forest management goals. These factors explained 66.44% of the variance in our sample and should be considered as the main potential drivers while implementing any new international or national policy. Despite having a few limitations, the PRIF is a promising governance indicator and has been proven to perform well for various socioeconomic and legal contexts.

Did our cochlear implant program make any difference in the lives of our patients? Achievements of 30 patients with long term follow-up averaging 20 years after cochlear implantation.

BACKGROUND: Cochlear implants are standard of care for the patients with sensorineural hearing loss not benefited from hearing aids. AIMS: Evaluate qualitatively the impact of cochlear implantation in the long-term. MATERIALS-METHODS: Thirty middle-class patients with similar patterns of loss and social environment averaging 20 years post-implantation responded to 52 questions that evaluated psychosocial benefits from cochlear implantation. RESULTS: All completed secondary education and 93% had postgraduate studies. Educational and workwise they are at the same level as their hearing counterparts. All use their cochlear implants and would recommend one to people who need it. They attribute their success to the implant, the rehabilitation program, their family, and a stimulating social environment. Despite their success, most experience difficulties relating with others (socially and at work) due to their hearing condition. They manage but work much harder than their hearing peers to achieve the same. CONCLUSIONS: We made a difference in the lives of these patients, however, there is more to be done. SIGNIFICANCE: Early intervention, rehabilitation, plus family, and stimulating-environment are crucial in children with sensory deficits.

Quantum Dynamics of Oblique Vibrational States in the Hénon-Heiles System.

In this paper, we study the quantum time evolution of oblique nonstationary vibrational states in a Hénon-Heiles oscillator system with two dissociation channels, which models the stretching vibrational motions of triatomic molecules. The oblique nonstationary states we are interested in are the eigenfunctions of the anharmonic zero-order Hamiltonian operator resulting from the transformation to oblique coordinates, which are defined as those coming from nonorthogonal coordinate rotations that express the matrix representation of the second-order Hamiltonian in a block diagonal form characterized by the polyadic quantum number n = n1 + n2. The survival probabilities calculated show that the oblique nonstationary states evolve within their polyadic group with a high degree of coherence up to the dissociation limits on the short time scale. The degree of coherence is certainly much higher than that exhibited by the local nonstationary states extracted from the conventional orthogonal rotation of the original normal coordinates. We also show that energy exchange between the oblique vibrational modes occurs in a much more regular way than the exchange between the local modes.

How to measure human leukocyte antigen-specific B cells.

PURPOSE OF REVIEW: The implementation of highly sensitive immune assays measuring anti-human leukocyte antigen (HLA) antibodies has modified alloimmune risk stratification and diagnosis of rejection. Nonetheless, anti-HLA antibodies represent the downstream effector mechanism of the B-cell response. Better characterizing the cellular components of the humoral immune response (including memory B cells (mBCs) and long-lived plasma cells) could help to further stratify the alloimmune risk stratification and enable discovery of new therapeutic targets. Several tests that characterize HLA-specific mBCs, either functionally or phenotypically, have been developed in the last years, showing promising applications as well as some limitations. RECENT FINDINGS: Functional assays involving ex vivo polyclonal activation of mBC have been refined to allow the detection of HLA-specific mBC capable of producing anti-HLA Abs, using different and complementary detection platforms such as multiplex Fluorospot and single antigen bead assay on culture supernatants. Detection of circulating HLA-specific B cells by flow cytometry remains hindered by the very low frequency of HLA-specific mBC. SUMMARY: Technological refinements have allowed the development of tests detecting HLA-specific mBC. Further evaluation of these assays in clinical trials, both for immune risk stratification and to assess treatment efficacy (desensitization strategies, rescue therapies for ABMR) are now urgently needed.

Portable reduced graphene oxide biosensor for detection of rabies virus in bats using nasopharyngeal swab samples.

Rabies is a lethal zoonotic disease caused by rabies virus (RABV) that affects human health and the economy. RABV is transmitted mainly by bats in Brazil, and surveillance in remote areas is hampered by the difficulty of properly collecting samples during fieldwork and the diagnosis is performed in laboratory conditions. Here, we report a portable electrochemical biosensor based on nucleic acid interactions for RABV detection in nasopharyngeal swab samples. The working electrode of the biosensor is composed of reduced graphene oxide (rGO) thin-film immobilized with cDNA through pi-pi stacking to enhance virus detection and specificity. Sensor performance was determined using RNA, and swab samples from bats. RNA detection shows good selectivity, and quantification presents a highly linear calibration curve (R2 = 0.990) using a concentration range of 0.145-25.39 ng/µL. A LOD of 0.104 ng/µL was reached with a sensitivity of 0.321 µA (ng/µL)-1. RABV detection in nasopharyngeal swab samples showed a good difference of positive sample from negative with a response time in seconds, ultra-fast detection compared to known techniques. Three biosensor groups were identified and named after physic-chemical surface characterization as: GO-1, GO-2, and rGO; with best performance for rGO group due to its sp2 hybridized network. Thus, we have successfully fabricated a promising electrochemical biosensor for fast in-situ detection of the RABV in swab samples, which can be expanded to other enveloped viruses that have RNA.

Multi-Phase Interleaved AC-DC Step-Down Converter with Power Factor Improvement.

This paper presents the converter design of a single-phase non-isolated step-down controlled rectifier for power factor improvement and output voltage regulation. The converter consists of a full-bridge diode rectifier and a DC-DC interleaved buck converter of two or more switching cells that has an LC filter in its input. It is proposed that the interleaved switching cells operate in discontinuous conduction mode and the current through the input LC filter be continuous, avoiding switching frequency components to be injected into the grid. The controller, which has a simple structure and a small number of sensors, allows the system to achieve a high power factor. It also regulates the output voltage to a constant reference. An experimental prototype is built and tested to validate the analysis and proposed design. The closed-loop converter is evaluated both in a steady state and in transient conditions. At steady state, the converter achieves a power factor above 0.9 with a maximum of 45.4% THD at 110.1W. The main contributions of this paper are guidelines for the design of the converter, open-loop analysis, and converter control.

Description of conformational ensembles of disordered proteins by residue-local probabilities.

The study of proteins with intrinsically disordered regions (IDRs) has emerged as an active field of research due to their intriguing nature. Although IDRs lack a well-defined folded structure, they play important functional roles in cells, following biological mechanisms different from those of the traditional structured proteins. Consequently, it has been necessary to re-design experimental and theoretical methods in order to face the challenges introduced by the dynamic nature of IDRs. In this work, we present an accurate and cost-effective method to study the conformational dynamics of IDRs based on the use of residue-local probabilistic expressions that characterize the conformational ensembles obtained from finite-temperature molecular dynamics (MD) simulations. It is shown that the good performance and the high convergence rates achieved with our method are independent of the IDR lengths, since the method takes advantage of the major influence of the identity and conformation of the nearest residue neighbors on the amino-acid conformational preferences to evaluate the IDR conformational ensembles. This allows us to characterize the conformational space of IDRs using a reduced number of probabilities which can be obtained from comparatively short MD simulations or experimental databases. To exemplify the usefulness of our approach, we present an application to directly detect Molecular Recognition Features (MoRFs) in an IDR domain of the protein p53, and to follow the time evolution of the thermodynamic magnitudes of this system during its exploration of the conformational space.

On the clinical relevance of using complete high-resolution HLA typing for an accurate interpretation of posttransplant immune-mediated graft outcomes.

Complete and high-resolution (HR) HLA typing improves the accurate assessment of donor-recipient compatibility and pre-transplant donor-specific antibodies (DSA). However, the value of this information to identify de novo immune-mediated graft events and its impact on outcomes has not been assessed. In 241 donor/recipient kidney transplant pairs, DNA samples were re-evaluated for six-locus (A/B/C/DRB1/DQB1+A1/DPB1) HR HLA typing. De novo anti-HLA antibodies were assessed using solid-phase assays, and dnDSA were classified either (1) as per current clinical practice according to three-locus (A/B/DRB1) low-resolution (LR) typing, estimating donor HLA-C/DQ typing with frequency tables, or (2) according to complete six-locus HR typing. The impact on graft outcomes was compared between groups. According to LR HLA typing, 36 (15%) patients developed dnDSA (LR_dnDSA+). Twenty-nine out of 36 (80%) were confirmed to have dnDSA by HR typing (LR_dnDSA+/HR_dnDSA+), whereas 7 (20%) did not (LR_dnDSA+/HR_dnDSA-). Out of 49 LR_dnDSA specificities, 34 (69%) were confirmed by HR typing whereas 15 (31%) LR specificities were not confirmed. LR_dnDSA+/HR_dnDSA+ patients were at higher risk of ABMR as compared to dnDSA- and LR_dnDSA+/HR_dnDSA- (logRank < 0.001), and higher risk of death-censored graft loss (logRank = 0.001). Both LR_dnDSA+ (HR: 3.51, 95% CI = 1.25-9.85) and LR_dnDSA+/HR_dnDSA+ (HR: 4.09, 95% CI = 1.45-11.54), but not LR_dnDSA+/HR_dnDSA- independently predicted graft loss. The implementation of HR HLA typing improves the characterization of biologically relevant de novo anti-HLA DSA and discriminates patients with poorer graft outcomes.

Humoral Immune Response of BNT162b2 and CoronaVac Vaccinations in Hemodialysis Patients: A Multicenter Prospective Cohort.

The CoronaVac vaccine is the most used anti-SARS-CoV-2 vaccine worldwide. Previous data indicate that this vaccine produces a lower immune response than RNA vaccines such as BNT162b2. End-stage renal disease (ESRD) patients have an increased rate of COVID-19 and a reduced immune response to vaccinations. Currently, there is little data on this population's immune response induced by CoronaVac. Methods: This study involved a prospective cohort of ESRD patients in chronic hemodialysis who received a two-dose immunization scheme of either CoronaVac (Sinovac Biotech) or BNT162b2 vaccines (Pfizer-BioNTech). We measured the plasma levels of anti-SARS-CoV-2 IgG antibodies. We determined antibody titers before immunization, 2 and 4 months after two doses, plus 4 months after a booster dose. Results: We evaluated 208 patients in three hemodialysis centers. The mean age was 62.6 ± 15.6 years, of whom 91 were female (41.75%). Eighty-one patients (38.94%) received the BNT162b2 vaccine and 127 (61.06%) received the CoronaVac vaccine. Patients who received the BNT162b2 vaccine had a higher humoral response compared to those who received the CoronaVac vaccine (4 months after the second dose: BNT162b2: 88.89%, CoronaVac: 51.97%, p < 0.001; 4 months after the booster: BNT162b2: 98.77%, CoronaVac: 86.61%, p < 0.001). Conclusions: Our results suggest that the CoronaVac vaccine induced a lower humoral response than the BNT162b2 vaccine in ESRD patients on hemodialysis.