Changes in glucometric parameters in people living with diabetes users of the free-style libre 2 system before and after the update possibility to real-time glucose readings in real world practice.

In Spain, from October 10th, 2023, the FreeStyle Libre 2 system offers the possibility to automatically changed from isCGM to rtCGM with a system update. Our study aimed to evaluate the glucometric before and after that date. We didn't find significant changes in TIR, however time of use increased and TBR decreased.

Identification and characterization of a new pathologic mutation in a large Leber hereditary optic neuropathy pedigree.

BACKGROUND: Most patients suffering from Leber hereditary optic neuropathy carry one of the three classic pathologic mutations, but not all individuals with these genetic alterations develop the disease. There are different risk factors that modify the penetrance of these mutations. The remaining patients carry one of a set of very rare genetic variants and, it appears that, some of the risk factors that modify the penetrance of the classical pathologic mutations may also affect the phenotype of these other rare mutations. RESULTS: We describe a large family including 95 maternally related individuals, showing 30 patients with Leber hereditary optic neuropathy. The mutation responsible for the phenotype is a novel transition, m.3734A > G, in the mitochondrial gene encoding the ND1 subunit of respiratory complex I. Molecular-genetic, biochemical and cellular studies corroborate the pathogenicity of this genetic change. CONCLUSIONS: With the study of this family, we confirm that, also for this very rare mutation, sex and age are important factors modifying penetrance. Moreover, this pedigree offers an excellent opportunity to search for other genetic or environmental factors that additionally contribute to modify penetrance.

Effect of a nutritional intervention based on an energy-reduced Mediterranean diet on environmental impact.

OBJECTIVE: To estimate the environmental impact of a dietary intervention based on an energy-reduced Mediterranean diet (MedDiet) after one year of follow-up. METHODS: Baseline and 1-year follow-up data were used for 5800 participants aged 55-75 years with metabolic syndrome in the PREDIMED-Plus study. Food intake was estimated through a validated semiquantitative food consumption frequency questionnaire, and adherence to the MedDiet was estimated through the Diet Score. Using the EAT-Lancet Commission tables we assessed the influence of dietary intake on environmental impact (through five indicators: greenhouse gas emissions (GHG), land use, energy used, acidification and potential eutrophication). Using multivariable linear regression models, the association between the intervention and changes in each of the environmental factors was assessed. Mediation analyses were carried out to estimate to what extent changes in each of 2 components of the intervention, namely adherence to the MedDiet and caloric reduction, were responsible for the observed reductions in environmental impact. RESULTS: We observed a significant reduction in the intervention group compared to the control group in acidification levels (-13.3 vs. -9.9 g SO2-eq), eutrophication (-5.4 vs. -4.0 g PO4-eq) and land use (-2.7 vs. -1.8 m2). Adherence to the MedDiet partially mediated the association between intervention and reduction of acidification by 15 %, eutrophication by 10 % and land use by 10 %. Caloric reduction partially mediated the association with the same factors by 55 %, 51 % and 38 % respectively. In addition, adherence to the MedDiet fully mediated the association between intervention and reduction in GHG emissions by 56 % and energy use by 53 %. CONCLUSIONS: A nutritional intervention based on consumption of an energy-reduced MedDiet for one year was associated with an improvement in different environmental quality parameters.

The interplay between emotional and breastfeeding difficulties in first-time mothers.

AIM/BACKGROUND: Both mental maternal health and breastfeeding difficulties impact maternal and infant health. The present study analyses the association between psychosocial and breastfeeding variables and maternal mental health. DESIGN/METHODS: The participants were 107 first-time mothers from Chile. Sociodemographic variables and breastfeeding difficulties were assessed at 6 weeks postpartum. Depression and anxiety symptoms, parental self-efficacy, and perceived social support were measured using validated, self-report questionnaires at 6 weeks and 5 months postpartum. This study is a secondary analysis of an intervention trial. RESULTS: 76% of the women reported having experienced some breastfeeding difficulty in the first postpartum weeks. The number of breastfeeding difficulties was associated with maternal mental health symptoms at 6 weeks postpartum and parental self-efficacy at both assessment times. Women who did not experience breastfeeding difficulties presented significantly fewer depressive (t(102) = 2.5, p = .015) and anxiety symptoms (t(50) = 2.3, p = .028) at 6 weeks postpartum than those who did. Mothers who exclusively breastfed at 5 months postpartum presented significantly higher parental self-efficacy (t(94) = 2.4, p = .044). A higher number of breastfeeding difficulties and low perceived social support contributed to higher depressive symptoms (R2 = .30; F(3,103) = 14.6, p < .001), anxiety symptoms (R2 = .32, F(3.103) = 17.27, p < .001) and lower parental self-efficacy at 6 weeks postpartum (R2 = .39; F(2,103) = 9.4, p < .001). CONCLUSION: Breastfeeding difficulties and social support are associated with fewer mental health symptoms and higher parental self-efficacy during early postpartum in first-time mothers.

Attention-based deep learning framework for automatic fundus image processing to aid in diabetic retinopathy grading.

BACKGROUND AND OBJECTIVE: Early detection and grading of Diabetic Retinopathy (DR) is essential to determine an adequate treatment and prevent severe vision loss. However, the manual analysis of fundus images is time consuming and DR screening programs are challenged by the availability of human graders. Current automatic approaches for DR grading attempt the joint detection of all signs at the same time. However, the classification can be optimized if red lesions and bright lesions are independently processed since the task gets divided and simplified. Furthermore, clinicians would greatly benefit from explainable artificial intelligence (XAI) to support the automatic model predictions, especially when the type of lesion is specified. As a novelty, we propose an end-to-end deep learning framework for automatic DR grading (5 severity degrees) based on separating the attention of the dark structures from the bright structures of the retina. As the main contribution, this approach allowed us to generate independent interpretable attention maps for red lesions, such as microaneurysms and hemorrhages, and bright lesions, such as hard exudates, while using image-level labels only. METHODS: Our approach is based on a novel attention mechanism which focuses separately on the dark and the bright structures of the retina by performing a previous image decomposition. This mechanism can be seen as a XAI approach which generates independent attention maps for red lesions and bright lesions. The framework includes an image quality assessment stage and deep learning-related techniques, such as data augmentation, transfer learning and fine-tuning. We used the architecture Xception as a feature extractor and the focal loss function to deal with data imbalance. RESULTS: The Kaggle DR detection dataset was used for method development and validation. The proposed approach achieved 83.7 % accuracy and a Quadratic Weighted Kappa of 0.78 to classify DR among 5 severity degrees, which outperforms several state-of-the-art approaches. Nevertheless, the main result of this work is the generated attention maps, which reveal the pathological regions on the image distinguishing the red lesions and the bright lesions. These maps provide explainability to the model predictions. CONCLUSIONS: Our results suggest that our framework is effective to automatically grade DR. The separate attention approach has proven useful for optimizing the classification. On top of that, the obtained attention maps facilitate visual interpretation for clinicians. Therefore, the proposed method could be a diagnostic aid for the early detection and grading of DR.

[Design of a nursing assessment instrument during pregnancy monitoring in Primary Health care and the validation of its content]. / Diseño de un instrumento de valoración enfermera para el seguimiento de embarazo en Atención Primaria de salud y la validación de su contenido.

OBJECTIVE: This research aims to develop a nursing assessment tool, based on Gordon's Health Functional Patterns, through a content validation by a committee of experts, applying a Delphi technique. DESIGN: An assessment instrument with 53 items has been designed. SITE: It is carried out within the framework of a doctoral thesis, for its implementation by midwives of Primary Health Care. PARTICIPANTS: The committee was made up of 16 professionals with a hide clinical, teaching and research experience who all participated in the entire validation process. INTERVENTION: It has been assessed as a whole and in each of the items through four rounds of consultations, establishing a positive assessment of more than 60% to accept each item, as well as incorporating the suggestions provided by the committee. The final version had to reach a unanimous consensus. MAIN MEASUREMENTS: All items were accepted with a score higher than 60%. RESULTS: There were no contradictions between the inputs provided by the experts, so all of them were integrated into the final version that has a 100% approval by the committee. CONCLUSION: After this process, a new assessment tool is presented to be applied by primary care midwives in the pregnancy monitoring. The questionnaire has been piloted with 50 pregnant women, determining the most prevalent nursing diagnoses, establishing the workload for the midwife of her implementation of individualized care plans to improve some health indicators of pregnant women.

Dual FGFR-targeting and pH-activatable ruthenium-peptide conjugates for targeted therapy of breast cancer.

Dysregulation of Fibroblast Growth Factor Receptors (FGFRs) signaling has been associated with breast cancer, yet employing FGFR-targeted delivery systems to improve the efficacy of cytotoxic agents is still sparsely exploited. Herein, we report four new bi-functional ruthenium-peptide conjugates (RuPCs) with FGFR-targeting and pH-dependent releasing abilities, envisioning the selective delivery of cytotoxic Ru complexes to FGFR(+)-breast cancer cells, and controlled activation at the acidic tumoral microenvironment. The antiproliferative potential of the RuPCs and free Ru complexes was evaluated in four breast cancer cell lines with different FGFR expression levels (SKBR-3, MDA-MB-134-VI, MCF-7, and MDA-MB-231) and in human dermal fibroblasts (HDF), at pH 6.8 and pH 7.4 aimed at mimicking the tumor microenvironment and normal tissues/bloodstream pHs, respectively. The RuPCs showed higher cytotoxicity in cells with higher level of FGFR expression at acidic pH. Additionally, RuPCs showed up to 6-fold higher activity in the FGFR(+) breast cancer lines compared to the normal cell line. The release profile of Ru complexes from RuPCs corroborates the antiproliferative effects observed. Remarkably, the cytotoxicity and releasing ability of RuPCs were shown to be strongly dependent on the conjugation of the peptide position in the Ru complex. Complementary molecular dynamic simulations and computational calculations were performed to help interpret these findings at the molecular level. In summary, we identified a lead bi-functional RuPC that holds strong potential as a FGFR-targeted chemotherapeutic agent.

Aetiology of non-malaria acute febrile illness fever in children in rural Guinea-Bissau: a prospective cross-sectional investigation.

Background: With growing use of parasitological tests to detect malaria and decreasing incidence of the disease in Africa; it becomes necessary to increase the understanding of causes of non-malaria acute febrile illness (NMAFI) towards providing appropriate case management. This research investigates causes of NMAFI in pediatric out-patients in rural Guinea-Bissau. Methods: Children 0-5 years presenting acute fever (≥38°) or history of fever, negative malaria rapid diagnostic test (mRDT) and no signs of specific disease were recruited at the out-patient clinic of 3 health facilities in Bafatá province during 54 consecutive weeks (dry and rainy season). Medical history was recorded and blood, nasopharyngeal, stool and urine samples were collected and tested for the presence of 38 different potential aetiological causes of fever. Results: Samples from 741 children were analysed, the protocol was successful in determining a probable aetiological cause of acute fever in 544 (73.61%) cases. Respiratory viruses were the most frequently identified pathogens, present in the nasopharynx samples of 435 (58.86%) cases, followed by bacteria detected in 167 (22.60%) samples. Despite presenting negative mRDTs, P. falciparum was identified in samples of 24 (3.25%) patients. Conclusions: This research provides a description of the aetiological causes of NMAFI in West African context. Evidence of viral infections were more commonly found than bacteria or parasites.

Morphological correlates of pyramidal cell axonal myelination in mouse and human neocortex.

The axons of neocortical pyramidal neurons are frequently myelinated. Heterogeneity in the topography of axonal myelination in the cerebral cortex has been attributed to a combination of electrophysiological activity, axonal morphology, and neuronal-glial interactions. Previously, we showed that axonal segment length and caliber are critical local determinants of fast-spiking interneuron myelination. However, the factors that determine the myelination of individual axonal segments along neocortical pyramidal neurons remain largely unexplored. Here, we used structured illumination microscopy to examine the extent to which axonal morphology is predictive of the topography of myelination along neocortical pyramidal neurons. We identified critical thresholds for axonal caliber and interbranch distance that are necessary, but not sufficient, for myelination of pyramidal cell axons in mouse primary somatosensory cortex (S1). Specifically, we found that pyramidal neuron axonal segments with a caliber < 0.24 µm or interbranch distance < 18.10 µm are rarely myelinated. Moreover, we further confirmed that these findings in mice are similar for human neocortical pyramidal cell myelination (caliber < 0.25 µm, interbranch distance < 19.00 µm), suggesting that this mechanism is evolutionarily conserved. Taken together, our findings suggest that axonal morphology is a critical correlate of the topography and cell-type specificity of neocortical myelination.

Sensor-Based Quantification of MDS-UPDRS III Subitems in Parkinson's Disease Using Machine Learning.

Wearable sensors could be beneficial for the continuous quantification of upper limb motor symptoms in people with Parkinson's disease (PD). This work evaluates the use of two inertial measurement units combined with supervised machine learning models to classify and predict a subset of MDS-UPDRS III subitems in PD. We attached the two compact wearable sensors on the dorsal part of each hand of 33 people with PD and 12 controls. Each participant performed six clinical movement tasks in parallel with an assessment of the MDS-UPDRS III. Random forest (RF) models were trained on the sensor data and motor scores. An overall accuracy of 94% was achieved in classifying the movement tasks. When employed for classifying the motor scores, the averaged area under the receiver operating characteristic values ranged from 68% to 92%. Motor scores were additionally predicted using an RF regression model. In a comparative analysis, trained support vector machine models outperformed the RF models for specific tasks. Furthermore, our results surpass the literature in certain cases. The methods developed in this work serve as a base for future studies, where home-based assessments of pharmacological effects on motor function could complement regular clinical assessments.

Improving the 3D Printability and Mechanical Performance of Biorenewable Soybean Oil-Based Photocurable Resins.

The general requirement of replacing petroleum-derived plastics with renewable resources is particularly challenging for new technologies such as the additive manufacturing of photocurable resins. In this work, the influence of mono- and bifunctional reactive diluents on the printability and performance of resins based on acrylated epoxidized soybean oil (AESO) was explored. Polyethylene glycol di(meth)acrylates of different molecular weights were selected as diluents based on the viscosity and mechanical properties of their binary mixtures with AESO. Ternary mixtures containing 60% AESO, polyethylene glycol diacrylate (PEGDA) and polyethyleneglycol dimethacrylate (PEG200DMA) further improved the mechanical properties, water resistance and printability of the resin. Specifically, the terpolymer AESO/PEG575/PEG200DMA 60/20/20 (wt.%) improved the modulus (16% increase), tensile strength (63% increase) and %deformation at the break (21% increase), with respect to pure AESO. The enhancement of the printability provided by the reactive diluents was proven by Jacobs working curves and the improved accuracy of printed patterns. The proposed formulation, with a biorenewable carbon content of 67%, can be used as the matrix of innovative resins with unrestricted applicability in the electronics and biomedical fields. However, much effort must be done to increase the array of bio-based raw materials.

Biallelic loss-of-function variants of ZFTRAF1 cause neurodevelopmental disorder with microcephaly and hypotonia.

PURPOSE: Neurodevelopmental disorders exhibit clinical and genetic heterogeneity, ergo manifest dysfunction in components of diverse cellular pathways; the precise pathomechanism for the majority remains elusive. METHODS: We studied five affected individuals from three unrelated families manifesting global developmental delay, postnatal microcephaly, and hypotonia. We employed exome sequencing and prioritized variants that were subsequently characterized using immunofluorescence, immunoblotting, pulldown assays, and RNA sequencing. RESULTS: We identified biallelic variants in ZFTRAF1, encoding a protein of yet unknown function. Four affected individuals from two unrelated families segregated two homozygous frameshift variants in ZFTRAF1, whereas, in the third family, an intronic splice site variant was detected. We investigated ZFTRAF1 at the cellular level and signified it as a nucleocytoplasmic protein in different human cell lines. ZFTRAF1 was completely absent in the fibroblasts of two affected individuals. We also identified 110 interacting proteins enriched in mRNA processing and autophagy-related pathways. Based on profiling of autophagy markers, patient-derived fibroblasts show irregularities in the protein degradation process. CONCLUSION: Thus, our findings suggest that biallelic variants of ZFTRAF1 cause a severe neurodevelopmental disorder.

Adenosine increases PD-L1 expression in mesenchymal stromal cells derived from cervical cancer through its interaction with A2AR/A2BR and the production of TGF-ß1.

Mesenchymal stromal cells (MSCs) together with malignant cells present in the tumor microenvironment (TME), participate in the suppression of the antitumor immune response through the production of immunosuppressive factors, such as transforming growth factor beta 1 (TGF-ß1). In previous studies, we reported that adenosine (Ado), generated by the adenosinergic activity of cervical cancer (CeCa) cells, induces the production of TGF-ß1 by interacting with A2AR/A2BR. In the present study, we provide evidence that Ado induces the production of TGF-ß1 in MSCs derived from CeCa tumors (CeCa-MSCs) by interacting with both receptors and that TGF-ß1 acts in an autocrine manner to induce the expression of programmed death ligand 1 (PD-L1) in CeCa-MSCs, resulting in an increase in their immunosuppressive capacity on activated CD8+ T lymphocytes. The addition of the antagonists ZM241385 and MRS1754, specific for A2AR and A2BR, respectively, or SB-505124, a selective TGF-ß1 receptor inhibitor, in CeCa-MSC cultures significantly inhibited the expression of PD-L1. Compared with CeCa-MSCs, MSCs derived from normal cervical tissue (NCx-MSCs), used as a control and induced with Ado to express PD-L1, showed a lower response to TGF-ß1 to increase PD-L1 expression. Those results strongly suggest the presence of a feedback mechanism among the adenosinergic pathway, the production of TGF-ß1, and the induction of PD-L1 in CeCa-MSCs to suppress the antitumor response of CD8+ T lymphocytes. The findings of this study suggest that this pathway may have clinical importance as a therapeutic target.

Occipito-Cervico-Dorsal Flap for Neck Reconstruction After Postburn Contractures: A Case Report and Literature Review.

Because the head and neck are one of the most frequent locations of burns, it is of paramount importance that plastic surgeons and plastic surgical nurses understand the most effective surgical methods for treating neck contractures and the reconstructive technique required for each case. We introduce the case of a 42-year-old woman who presented with a severe postburn neck contracture that was reconstructed with a pedicled occipito-cervico-dorsal flap. We closed the donor-site wound primarily and completely covered the defect with good results. In addition to conventional skin grafts, dermal matrices, and microsurgical techniques, using an occipito-cervico-dorsal flap should be considered for reconstructing postburn neck contractures as it offers good aesthetic and functional outcomes, provides enough tissue and pliable skin, and results in minimal donor-site morbidity.

Online xenophobia and mental health among Venezuelan migrant youth in Colombia: The interplay with "in-person" discrimination.

Emerging research provides insights into migration-related cultural stress experiences and mental health among Venezuelan migrants; however, prior studies have not considered the critical distinction between online xenophobia and in-person discrimination. To address this gap, we assess the psychometric properties of an abbreviated version of the Perceived Online Racism Scale (PORS) with Venezuelan migrant youth and examine the interplay between online xenophobia, in-person discrimination, and mental health. Survey data were collected from Venezuelan migrant youth (N = 319; ages 13-17, 49.5% female) in Colombia in April-July 2023. Confirmatory factor analysis (CFA) was used to examine the PORS, and multiple regression was conducted to examine key associations. The CFA showed excellent model fit: χ²(7) = 13.498, p = .061; comparative fit index = .989; Tucker-Lewis index = .977; root-mean-square error of approximation = .055; standardized root-mean-square residual = .026. Controlling for demographic factors, online xenophobia was associated with depressive symptoms (ß = .253, p < .001) and anxiety (ß = .200, p = .001). The online xenophobia-mental health association weakened when controlling for in-person discrimination but remained nevertheless significant (depression: ß = .181, p = .002, anxiety: ß = .135, p = .026). Interaction effects (Online × In-Person) revealed a pattern in which greater exposure to online xenophobia was associated with greater distress, but only at relatively low levels of in-person discrimination. Findings provide new insights regarding (a) the properties of an increasingly relevant measure of cultural stress, (b) how online xenophobia relates to mental health, and (c) the interplay of online and in-person cultural stressors vis-à-vis mental health among Venezuelan migrant youth. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Treatment of Schatzker Type VI Tibia Fractures Using Circular External Fixation: State of the Art, Surgical Technique and Results.

BACKGROUND: Schatzker type VI tibia fractures are usually associated with infection and surgical wound-related problems. Circular external fixation (CEF) has been shown to minimize such complications. METHODS: We pose a retrospective study of patients with Schatzker type VI fractures treated with CEF. RESULTS: Twenty-two (22) patients were included (11M/11F) with a mean age of 60.1 ± 14.9 years. According to the AO/OTA classification, two fractures (9.1%) were A2, three (13.6%) were A3, and seventeen (77.3%) were C3. Three (13.6%) of them were open. The tissue damage observed in the nineteen (86.4%) closed fractures was classified according to Tscherne (four grade I, twelve grade II, and three grade III). The mean ex-fix time was 24.1 ± 5.1 weeks. None of the patients experienced deep infections, nonunion, or malunion. The mean ROM was 111.4 ± 17.8 degrees. Although stability was achieved in all cases, 50% of them suffered osteoarthritic degeneration. Four knees required TKR at a mean of 8.77 ± 5.58 years from trauma. The mean HHS knee score was 84.2 ± 10.3 points (excellent in fifteen (68.2%) cases, good in four (18.2%), and acceptable in three (13.6%)). The mean Rasmussen radiological score was 13.3 ± 3.5 (excellent in three (13.6%) cases, good in fifteen (68.2%), and acceptable in four (18.2%)). The mean SF-12 score was 35.1 ± 10.4 points on the physical scale and 53.0 ± 10.6 points on the mental scale. CONCLUSIONS: CEF has shown itself to be a valid treatment for patients with Schatzker type VI fractures, particularly for those where the fracture is comminuted, severely displaced, open, or associated with severe soft tissue damage.

The impact of cultural stress on family functioning among Puerto Rican displaced families and the effect on mental health.

Hurricane María caused significant devastation on the island of Puerto Rico, impacting thousands of lives. Puerto Rican crisis migrant families faced stress related to displacement and relocation (cultural stress), often exhibited mental health symptoms, and experienced distress at the family level. Although cultural stress has been examined as an individual experience, little work has focused on the experience as a family. To address this gap, we conducted a mixed-methods study designed to examine the predictive effects of cultural stress on family conflict and its mental health implications among Puerto Rican Hurricane María parent and child dyads living on the U.S. mainland. In the quantitative phase of the study, 110 parent-child dyads completed an online survey assessing cultural stress, family dynamics, and mental health. As part of our primary analysis, we estimated a structural equation path model. Findings from the quantitative phase showed a significant positive relationship between family cultural stress and family conflict, as well as individual parent and child mental health symptoms. In the qualitative phase of the study, 35 parent-child dyads participated in individual interviews. Findings from the interviews revealed variations in difficulties related to language, discrimination, and financial burdens, with some participants adapting more quickly and experiencing fewer stressors. Findings also highlight the impact on mental health for both parents and youth, emphasizing the family-level nature of cultural stress, while noting a potential discrepancy between qualitative and quantitative findings in the discussion of family conflict.

The pericapsular nerve group block, a highly selective blockage for intracapsular hip fractures: A case series.

Hip fracture is a very frequent clinical situation in the elderly and frail patient. The Pericapsular Nerve Group (PENG) has emerged as a highly selective block for the intracapsular hip fractures. We describe 44 patients with intracapsular hip fractures who underwent a PENG block in addition to spinal anaesthesia with. The main objective was to assess post-surgical pain control at the recovery room and after 24 h. Also, we considered the need for first of second analgesic rescue during the first 24 h after surgery. Only 10 patients presented mild pain at the recovery room. Up to 30 of them had pain after 24 h. However, 25 of these patients reported having mild pain. Only 9 patients required analgesic rescue for postoperative pain control. In conclusion, PENG block is a locoregional technique that allows good postoperative pain control and low opioid consumption during the postoperative period of intracapsular hip fractures.