ABSTRACT
The ability to learn and form memories allows animals to adapt their behavior based on previous experiences. Associative learning, the process through which organisms learn about the relationship between two distinct events, has been extensively studied in various animal taxa. However, the existence of associative learning, prior to the emergence of centralized nervous systems in bilaterian animals, remains unclear. Cnidarians such as sea anemones or jellyfish possess a nerve net, which lacks centralization. As the sister group to bilaterians, they are particularly well suited for studying the evolution of nervous system functions. Here, we probe the capacity of the starlet sea anemone Nematostella vectensis to form associative memories by using a classical conditioning approach. We developed a protocol combining light as the conditioned stimulus with an electric shock as the aversive unconditioned stimulus. After repetitive training, animals exhibited a conditioned response to light alone-indicating that they learned the association. In contrast, all control conditions did not form associative memories. Besides shedding light on an aspect of cnidarian behavior, these results root associative learning before the emergence of NS centralization in the metazoan lineage and raise fundamental questions about the origin and evolution of cognition in brainless animals.
Subject(s)
Sea Anemones , Animals , Sea Anemones/physiology , Conditioning, Classical , Nervous SystemABSTRACT
BACKGROUND: Dengue fever remains a significant public health challenge in tropical and subtropical regions, with its transmission dynamics being influenced by both environmental factors and human mobility. The Dominican Republic, a biodiversity hotspot in the Caribbean, has experienced recurrent dengue outbreaks, yet detailed understanding of the virus's transmission pathways and the impact of climatic factors remains limited. This study aims to elucidate the recent transmission dynamics of the dengue virus (DENV) in the Dominican Republic, utilizing a combination of genomic sequencing and epidemiological data analysis, alongside an examination of historical climate patterns. METHODS: We conducted a comprehensive study involving the genomic sequencing of DENV samples collected from patients across different regions of the Dominican Republic over a two-year period. Phylogenetic analyses were performed to identify the circulation of DENV lineages and to trace transmission pathways. Epidemiological data were integrated to analyze trends in dengue incidence and distribution. Additionally, we integrated historical climate data spanning several decades to assess trends in temperature and their potential impact on DENV transmission potential. RESULTS: Our results highlight a previously unknown north-south transmission pathway within the country, with the co-circulation of multiple virus lineages. Additionally, we examine the historical climate data, revealing long-term trends towards higher theoretical potential for dengue transmission due to rising temperatures. CONCLUSION: This multidisciplinary study reveals intricate patterns of dengue virus transmission in the Dominican Republic, characterized by the co-circulation of multiple DENV lineages and a novel transmission pathway. The observed correlation between rising temperatures and increased dengue transmission potential emphasizes the need for integrated climate-informed strategies in dengue control efforts. Our findings offer critical insights for public health authorities in the Dominican Republic and similar settings, guiding resource allocation and the development of preparedness strategies to mitigate the impacts of climate change on dengue transmission.
Subject(s)
Climate , Dengue Virus , Dengue , Phylogeny , Serogroup , Dominican Republic/epidemiology , Dengue/epidemiology , Dengue/transmission , Dengue/virology , Humans , Dengue Virus/genetics , Dengue Virus/classification , Disease OutbreaksABSTRACT
Functional gastrointestinal disorders (FGIDs) are characterized by chronic or recurrent gastrointestinal symptoms (GS) that are not explained by structural or biochemical abnormalities. FGIDs are related to lower quality of life, increased demands on medical resources, and greater somatization and emotional instability. Furthermore, GS appears to be an indicator of dysbiosis in gut-microbiota, affecting the gut-microbiota-brain relationship. To develop and evaluate the psychometric properties of a new instrument called the Gastrointestinal Symptom Severity Scale (GSSS) using a web-based survey in a sample of neurotypical children and adolescents from Spain. Instrument development and validation processes were applied to the GSSS following its administration as part of an online survey. The sample included 1242 neurotypical children and adolescents. The mean age of participants was 13.95 years, with a standard deviation of 1.37 years. Overall, 13.8% suffered infectious diarrhea, 12.6% suffered abdominal pain, 5% suffered dyspepsia and 2.6% suffered gastro-esophageal reflux. A single-factor model produced good fit indices. Furthermore, internal consistency and test-retest reliability outcomes were acceptable. The GSSS was found to have acceptable metric measurement invariance. Significant correlations with other instruments were produced and were of expected direction and magnitude, confirming scale validity for hypothesis testing. Conclusions: The GSSS shows promising psychometric properties for assessing GS in neurotypical Spanish adolescents and children. What is Known: ⢠To the best of our knowledge, instruments assessing the severity of gastrointestinal symptoms in children and adolescents are still too few. What is New: ⢠The GSSS shows promising psychometric properties for assessing GS in neurotypical adolescents and children. The GSSS may help improve understanding of GS involvement in the gut-brain microbiota axis in children and adolescents.
Subject(s)
Gastrointestinal Diseases , Psychometrics , Severity of Illness Index , Humans , Adolescent , Male , Female , Child , Spain , Gastrointestinal Diseases/diagnosis , Reproducibility of Results , Surveys and Questionnaires , Quality of LifeABSTRACT
BACKGROUND: Morton's neuroma (MN) is one of the most frequent neurological pathologies in feet, affecting approximately 4% of the general population. The treatment of MN can be surgical, conservative, and infiltrative, with different substances used in the injections for MN, as steroids, sclerosing solutions, and others. This review aims to evaluate the efficacy of current infiltrative therapy for Morton's neuroma and, additionally, to define adverse effects of this therapy. MATERIAL AND METHODS: A literature search was performed in PubMed, Embase, CINHAL, Epistemonikos, Web of Science (WOS), SPORTSDiscus and Cochrane Library. This search involved the application of all types of infiltrative treatment applicable to MN. The search was limited to original data describing clinical outcomes and pain using the Visual Analogue pain Scale (VAS) or the Johnson Satisfaction Scale, between February and June 2023. RESULTS: Twelve manuscripts were selected (six randomized controlled trials and six longitudinal observational studies) involving 1,438 patients. Capsaicin was reported to produce a VAS score reduction of 51.8%. Corticosteroids also reported a high level of efficacy. Alcohol and Hyaluronic Acid injections are well tolerated, but the effects of their application need further research. There were no serious adverse events. CONCLUSIONS: Corticosteroids, sclerosant injections, hyaluronic acid and capsaicin have been shown to be effective in reducing the pain related to MN.
ABSTRACT
Solution-processed two-dimensional nanoplatelets (NPLs) allowing lateral growth of a shell (crown) by not affecting the pure confinement in the vertical direction provide unprecedented opportunities for designing heterostructures for light-emitting and -harvesting applications. Here, we present a pathway for designing and synthesizing colloidal type-II core/(multi-)crown hetero-NPLs and investigate their optical properties. Stoke's shifted broad photoluminescence (PL) emission and long PL lifetime (â¼few 100 ns) together with our wavefunction calculations confirm the type-II electronic structure in the synthesized CdS/CdSe1-xTex core/crown hetero-NPLs. In addition, we experimentally obtained the band-offsets between CdS, CdTe, and CdSe in these NPLs. These results helped us designing hetero-NPLs with near-unity PL quantum yield in the CdSe/CdSe1-xTex/CdSe/CdS core/multicrown architecture. These core/multicrown hetero-NPLs have two type-II interfaces unlike traditional type-II NPLs having only one and possess a CdS ending layer for passivation and efficient suppression of stacking required for optoelectronic applications. The light-emitting diode (LED) obtained using multicrown hetero-NPLs exhibits a maximum luminance of 36,612 cd/m2 and external quantum efficiency of 9.3%, which outcompetes the previous best results from type-II NPL-based LEDs. These findings may enable designs of future advanced heterostructures of NPLs which are anticipated to show desirable results, especially for LED and lasing platforms.
ABSTRACT
Characterized by their strong 1D confinement and long-lifetime red-shifted emission spectra, colloidal nanoplatelets (NPLs) with type-II electronic structure provide an exciting ground to design complex heterostructures with remarkable properties. This work demonstrates the synthesis and optical characterization of CdSe/CdSeTe/CdTe core/crown/crown NPLs having a step-wise gradient electronic structure and disproportional wavefunction distribution, in which the excitonic properties of the electron and hole can be finely tuned through adjusting the geometry of the intermediate crown. The first crown with staggered configuration gives rise to a series of direct and indirect transition channels that activation/deactivation of each channel is possible through wavefunction engineering. Moreover, these NPLs allow for switching between active channels with temperature, where lattice contraction directly affects the electron-hole (e-h) overlap. Dominated by the indirect transition channels over direct transitions, the lifetime of the NPLs starts to increase at 9 K, indicative of low dark-bright exciton splitting energy. The charge transfer states from the two type-II interfaces promote a large number of indirect transitions, which effectively increase the absorption of low-energy photons critical for nonlinear properties. As a result, these NPLs demonstrate exceptionally high two-photon absorption cross-sections with the highest value of 12.9 × 106 GM and superlinear behavior.
ABSTRACT
COVID-19 affects multiple organs. Clinical data from the Mount Sinai Health System show that substantial numbers of COVID-19 patients without prior heart disease develop cardiac dysfunction. How COVID-19 patients develop cardiac disease is not known. We integrated cell biological and physiological analyses of human cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the presence of interleukins (ILs) with clinical findings related to laboratory values in COVID-19 patients to identify plausible mechanisms of cardiac disease in COVID-19 patients. We infected hiPSC-derived cardiomyocytes from healthy human subjects with SARS-CoV-2 in the absence and presence of IL-6 and IL-1ß. Infection resulted in increased numbers of multinucleated cells. Interleukin treatment and infection resulted in disorganization of myofibrils, extracellular release of troponin I, and reduced and erratic beating. Infection resulted in decreased expression of mRNA encoding key proteins of the cardiomyocyte contractile apparatus. Although interleukins did not increase the extent of infection, they increased the contractile dysfunction associated with viral infection of cardiomyocytes, resulting in cessation of beating. Clinical data from hospitalized patients from the Mount Sinai Health System show that a significant portion of COVID-19 patients without history of heart disease have elevated troponin and interleukin levels. A substantial subset of these patients showed reduced left ventricular function by echocardiography. Our laboratory observations, combined with the clinical data, indicate that direct effects on cardiomyocytes by interleukins and SARS-CoV-2 infection might underlie heart disease in COVID-19 patients. IMPORTANCE SARS-CoV-2 infects multiple organs, including the heart. Analyses of hospitalized patients show that a substantial number without prior indication of heart disease or comorbidities show significant injury to heart tissue, assessed by increased levels of troponin in blood. We studied the cell biological and physiological effects of virus infection of healthy human iPSC-derived cardiomyocytes in culture. Virus infection with interleukins disorganizes myofibrils, increases cell size and the numbers of multinucleated cells, and suppresses the expression of proteins of the contractile apparatus. Viral infection of cardiomyocytes in culture triggers release of troponin similar to elevation in levels of COVID-19 patients with heart disease. Viral infection in the presence of interleukins slows down and desynchronizes the beating of cardiomyocytes in culture. The cell-level physiological changes are similar to decreases in left ventricular ejection seen in imaging of patients' hearts. These observations suggest that direct injury to heart tissue by virus can be one underlying cause of heart disease in COVID-19.
Subject(s)
COVID-19/immunology , Induced Pluripotent Stem Cells , Interleukin-10/immunology , Interleukin-1beta/immunology , Interleukin-6/immunology , Myocytes, Cardiac , Cells, Cultured , Humans , Induced Pluripotent Stem Cells/immunology , Induced Pluripotent Stem Cells/pathology , Induced Pluripotent Stem Cells/virology , Myocytes, Cardiac/immunology , Myocytes, Cardiac/pathology , Myocytes, Cardiac/virologyABSTRACT
The potential to regenerate a damaged body part is expressed to a different extent in animals. Echinoderms, in particular starfish, are known for their outstanding regenerating potential. Differently, humans have restricted abilities to restore organ systems being dependent on limited sources of stem cells. In particular, the potential to regenerate the central nervous system is extremely limited, explaining the lack of natural mechanisms that could overcome the development of neurodegenerative diseases and the occurrence of trauma. Therefore, understanding the molecular and cellular mechanisms of regeneration in starfish could help the development of new therapeutic approaches in humans. In this study, we tackle the problem of starfish central nervous system regeneration by examining the external and internal anatomical and behavioral traits, the dynamics of coelomocyte populations, and neuronal tissue architecture after radial nerve cord (RNC) partial ablation. We noticed that the removal of part of RNC generated several anatomic anomalies and induced behavioral modifications (injured arm could not be used anymore to lead the starfish movement). Those alterations seem to be related to defense mechanisms and protection of the wound. In particular, histology showed that tissue patterns during regeneration resemble those described in holothurians and in starfish arm tip regeneration. Flow cytometry coupled with imaging flow cytometry unveiled a new coelomocyte population during the late phase of the regeneration process. Morphotypes of these and previously characterized coelomocyte populations were described based on IFC data. Further studies of this new coelomocyte population might provide insights on their involvement in radial nerve cord regeneration.
Subject(s)
Radial Nerve , Sea Cucumbers , Animals , Humans , Radial Nerve/physiology , Starfish/physiology , Nerve Regeneration/physiologyABSTRACT
OBJECTIVE: To determine the effect of foot orthoses on pain, disability and foot functionality in patients with Systemic Lupus Erythematosus. DESIGN: Randomized clinical trial. SETTING: University Podiatric Clinical Area. SUBJECTS: Patients with systemic lupus erythematosus. INTERVENTIONS: Patients were randomly assigned to either group A, which received custom-made functional foot orthoses, or group B, which received flat cushioning insoles, for three months. MAIN MEASURES: The primary outcome was foot pain, measured by 11-point numeric pain rating scale. Foot functionality and foot-related disability were evaluated using the foot function index, the Manchester foot pain and disability, at the beginning and at days 90. RESULTS: Sixty-six participants (age 47.3 ± 11.9 years) suffering from foot pain, received either the custom-made foot orthoses (N = 33) or the flat cushioning insoles (N = 33). For the analysis of the data, only participants who had finished the follow-up period (90 days) were included. None statistically significant difference between groups were found. In group A, all variables showed statistically significant differences when comparing the initial and final measurements. Pain showed 6.8 ± 1.6 and 4.2 ± 2.9 in group A, at baseline and at 90 days, respectively, group B showed 6.5 ± 1.5 and 4.7 ± 3.0 at baseline and at 90 days, respectively. CONCLUSION: Both groups showed a reduction in foot pain. This study suggests that not only controlling the foot function, but providing cushioning to the foot, may have positive effects to manage foot pain in patients with systemic lupus erythematosus.
Subject(s)
Foot Orthoses , Lupus Erythematosus, Systemic , Humans , Adult , Middle Aged , Pain Management , Pain , Shoes , Lupus Erythematosus, Systemic/complications , Treatment OutcomeABSTRACT
BACKGROUND: Resilience has been associated with greater adherence to treatment, better outcomes, and improved quality of life (QOL) in people with chronic health conditions. This study aimed to identify sociodemographic, treatment accessibility-related, clinical, and psychological variables associated with resilience in patients with advanced chronic kidney disease (CKD) undergoing long-term hemodialysis (>6 months). METHODS: This was a multicenter, cross-sectional, and correlational study. The instruments used were the Spanish versions of the Connor-Davidson Resilience Scale, the Perceived Stress Scale-10, and the Kidney Disease Quality of Life-36. The participants were categorized as resilient (with a score of ≥49.37 on the Connor-Davidson Resilience Scale) or nonresilient. Binary logistic regression analysis was performed to identify variables with predictive power for the group with the resilient profile. RESULTS: Perceived stress, general QOL, and subcomponents of QOL, such as the physical component and burden of kidney disease, were identified as factors related to the resilient profile. DISCUSSION: Identifying the factors related to resilient adjustment in patients with advanced CKD may assist health caregivers in improving adherence to treatment, treatment outcomes, and QOL.
Subject(s)
Renal Insufficiency, Chronic , Resilience, Psychological , Humans , Quality of Life/psychology , Cross-Sectional Studies , Renal Dialysis , Renal Insufficiency, Chronic/therapy , Renal Insufficiency, Chronic/psychologyABSTRACT
PURPOSE: To analyze the results of a conservative method for treating congenital vertical talus in children with early start and to know in which cases surgical treatment was needed. METHODS: A retrospective analysis of all children diagnosed with idiopathic vertical talus was carried out during the years 2008-2021. Thirty-two children (46 feet) were finally included. Children were treated with serial manipulations, muscle stimulation, and corrective bandages. Age at the time of initiation of treatment, duration of treatment, and correction or not of the deformity without surgical intervention were recorded as variables of interest. The talocalcaneal angle, TAMBA, and ankle range of motion were measured before treatment, after treatment, and at the end of the follow-up period. Statistics decision tree was used to determine which variable best discriminated whether the patient needed surgery. To complement the tree diagram, a two-step cluster analysis was carried out. RESULTS: After treatment, TAMBA and talocalcaneal angle changed from "vertical" to "oblique" category in 45 and 37 feet, respectively. The pathological dorsal flexion of the ankle changed to normal in 37 feet and ankle plantar flexion was normal in 46 feet. These variables showed significant changes between the three measurement moments. The results of the statistics decision tree and cluster analysis indicate that "No surgery" was associated with an age equal to or lower than one week when treatment was started, and with an ankle plantar flexion range of motion lower than 36°. CONCLUSIONS: The beginning of this conservative treatment in the first week of life and having a plantar flexion of the ankle lower than 36° were related to the success of the treatment without surgery.
Subject(s)
Flatfoot , Orthopedic Procedures , Talus , Child , Humans , Infant, Newborn , Follow-Up Studies , Flatfoot/surgery , Retrospective Studies , Talus/surgery , Orthopedic Procedures/methods , Treatment OutcomeABSTRACT
Recombination is an evolutionary strategy to quickly acquire new viral properties inherited from the parental lineages. The systematic survey of the SARS-CoV-2 genome sequences of the Andalusian genomic surveillance strategy has allowed the detection of an unexpectedly high number of co-infections, which constitute the ideal scenario for the emergence of new recombinants. Whole genome sequence of SARS-CoV-2 has been carried out as part of the genomic surveillance programme. Sample sources included the main hospitals in the Andalusia region. In addition to the increase of co-infections and known recombinants, three novel SARS-CoV-2 delta-omicron and omicron-omicron recombinant variants with two break points have been detected. Our observations document an epidemiological scenario in which co-infection and recombination are detected more frequently. Finally, we describe a family case in which co-infection is followed by the detection of a recombinant made from the two co-infecting variants. This increased number of recombinants raises the risk of emergence of recombinant variants with increased transmissibility and pathogenicity.
Subject(s)
COVID-19 , Coinfection , Humans , Coinfection/epidemiology , COVID-19/epidemiology , SARS-CoV-2/genetics , Biological Evolution , GenomicsABSTRACT
OBJECTIVE: To test the effect of a podiatric health education activity on foot self-care and the degree of foot-related disability in a group of people with diabetes mellitus (DM) in the province of Seville. A pretest-posttest quasi-experimental design was used. METHODS: Twenty-nine people with DM participated. The intervention was a podiatric health education activity consisting of a 1-hour informative talk. Foot pain-related disability was measured using the Manchester Foot Pain and Disability Index. The degree of foot self-care was measured with the University of Malaga Foot Self-care questionnaire. RESULTS: One month after the intervention, both parameters had improved significantly. The mean score on the Manchester Foot Pain and Disability Index increased from 59.96 (SD, 8.69) at baseline to 67.39 (SD, 6.99) at 1 month, and the mean score on the University of Malaga Foot Self-care questionnaire improved from 11.65 (SD, 20.07) at baseline to 4.52 (SD, 5.47) after 1 month. CONCLUSIONS: Therapeutic education increases the level of self-care and decreases the degree of foot-related disability in people with DM.
Subject(s)
Diabetes Mellitus , Diabetic Foot , Foot Diseases , Podiatry , Humans , Self Care , Diabetes Mellitus/therapy , Pain , Health Education , Diabetic Foot/therapyABSTRACT
A 76-year-old man presented with dysphagia, epigastric pain and weight loss for the last two months. Heavy sweating was also presented. Past medical conditions included type 2 diabetes. He had no evidence of any immunosupressive disease including HIV infection. Physical examination only revealed low-grade fever. Laboratory data showed leukocytosis. Gastroscopy evidenced a complete esophageal stenosis starting at 30 cm, with a severely friable mucosa of malignant appearance. The results of biopsies were insufficient for diagnosis of malignancy. Computed tomography demonstrated a 10-cm irregular tumor located in the distal and middle thirds of the esophagus, which resulted in narrowing of the lumen. Involving tracheal carina, bronchus, and descending aorta were observed. Perforation signs were also seen. Distant metastases were not found. Empirical treatment with piperacillin/tazobactan was started. A surgical gastrostomy to allows nutritional support was performed. Two other gastroscopies were performed resulting in an inconclusive diagnosis. Finally, flow cytometry performed in samples obtained by endobronchial ultrasound-guided biopsy evidenced prominent clonal B-cell populations consistent with extranodal diffuse large B-cell lymphoma exhibing CD10 expression. A treatment with Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was started. Primary esophageal diffuse large B-cell lymphoma (DLBCL), a variant of non-Hodgkin's lymphoma, accounts for less than 1% of all cases of gastrointestinal lymphomas.
Subject(s)
Diabetes Mellitus, Type 2 , HIV Infections , Lymphoma, Large B-Cell, Diffuse , Male , Humans , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Lymphoma, Large B-Cell, Diffuse/drug therapy , Rituximab , Vincristine/therapeutic use , Cyclophosphamide/therapeutic use , Prednisone/therapeutic use , Doxorubicin/therapeutic useABSTRACT
Bilaterian animals display a wide variety of cell types, organized into defined anatomical structures and organ systems, which are mostly absent in prebilaterian animals. Xenacoelomorpha are an early-branching bilaterian phylum displaying an apparently relatively simple anatomical organization that have greatly diverged from other bilaterian clades. In this study, we use whole-body single-cell transcriptomics on the acoel Isodiametra pulchra to identify and characterize different cell types. Our analysis identifies the existence of ten major cell type categories in acoels all contributing to main biological functions of the organism: metabolism, locomotion and movements, behavior, defense, and development. Interestingly, although most cell clusters express core fate markers shared with other animal clades, we also describe a surprisingly large number of clade-specific marker genes, suggesting the emergence of clade-specific common molecular machineries functioning in distinct cell types. Together, these results provide novel insight into the evolution of bilaterian cell types and open the door to a better understanding of the origins of the bilaterian body plan and their constitutive cell types.
Subject(s)
Transcriptome , Turbellaria/cytology , Animals , Phylogeny , Single-Cell Analysis , Turbellaria/genetics , Turbellaria/metabolismABSTRACT
Helicobacter pylori is a Gram-negative bacterium found on the luminal surface of the gastric mucosa in at least 50% of the world's human population. The protective effect of breastfeeding against H. pylori infection has been extensively reported; however, the mechanisms behind this protection remain poorly understood. Human IgA from colostrum has reactivity against H. pylori antigens. Despite that IgA1 and IgA2 display structural and functional differences, their reactivity against H. pylori had not been previously determined. We attested titers and reactivity of human colostrum-IgA subclasses by ELISA, immunoblot, and flow cytometry. Colostrum samples from healthy mothers had higher titers of IgA; and IgA1 mostly recognized H. pylori antigens. Moreover, we found a correlation between IgA1 reactivity and their neutralizing effect determined by inhibition of cytoskeletal changes in AGS cells infected with H. pylori. In conclusion, colostrum-IgA reduces H. pylori infection of epithelial gastric cells, suggesting an important role in preventing the bacteria establishment during the first months of life. As a whole, these results suggest that IgA1 from human colostrum provides protection that may help in the development of the mucosal immune system of newborn children.
Subject(s)
Antibodies, Bacterial/immunology , Antigens, Bacterial/immunology , Colostrum/immunology , Helicobacter pylori/immunology , Immunoglobulin A, Secretory/immunology , Cytoskeleton , Epithelial Cells , Female , Gastric Mucosa/immunology , Helicobacter Infections/immunology , Humans , PregnancyABSTRACT
The estimated 20-30% of women who develop perimenopausal depression (PMD) are at an increased risk of cardiovascular and all-cause mortality. The therapeutic benefits of estradiol (E2) and symptom-provoking effects of E2-withdrawal (E2-WD) suggest that a greater sensitivity to changes in E2 at the cellular level contribute to PMD. We developed an in vitro model of PMD with lymphoblastoid cell lines (LCLs) derived from participants of a prior E2-WD clinical study. LCLs from women with past PMD (n = 8) or control women (n = 9) were cultured in three experimental conditions: at vehicle baseline, during E2 treatment, and following E2-WD. Transcriptome analysis revealed significant differences in transcript expression in PMD in all experimental conditions, and significant overlap in genes that were changed in PMD regardless of experimental condition. Of these, chemokine CXCL10, previously linked to cardiovascular disease, was upregulated in women with PMD, but most so after E2-WD (p < 1.55 × 10-5). CYP7B1, an enzyme intrinsic to DHEA metabolism, was upregulated in PMD across experimental conditions (F(1,45) = 19.93, p < 0.0001). These transcripts were further validated via qRT-PCR. Gene networks dysregulated in PMD included inflammatory response, early/late E2-response, and cholesterol homeostasis. Our results provide evidence that differential behavioral responsivity to E2-WD in PMD reflects intrinsic differences in cellular gene expression. Genes such as CXCL10, CYP7B1, and corresponding proinflammatory and steroid biosynthetic gene networks, may represent biomarkers and molecular targets for intervention in PMD. Finally, this in vitro model allows for future investigations into the mechanisms of genes and gene networks involved in the vulnerability to, and consequences of, PMD.
Subject(s)
Depression , Perimenopause , Depression/genetics , Estradiol , Female , Gene Expression Profiling , Humans , SteroidsABSTRACT
OBJECTIVES: To show that digital informed consent (DIC) improves the subjective understanding of information and, therefore, informed consent. PATIENTS AND METHODS: A nonblinded randomized controlled trial was performed in 84 patients who had undergone transurethral resection of bladder, transurethral resection of prostate, or ureterorenoscopy between July 2017 and March 2018. The DIC group watched a hyperrealistic simulation on a tablet device before surgery. After surgery and again 30 days later, both groups completed a validated questionnaire that measured subjective understanding, anxiety, and utility of and need for information. RESULTS: The mean ± SD age of the participants was 68.7 ± 11.1 years. Nine of 84 patients (10.7%) did not complete the questionnaire. A total of 42 patients were allocated to the DIC group and 42 to the control group. The mean ± SD score for immediate subjective understanding in the DIC group was 14.5% higher than in the control group (72% ± 17.5% vs 57.5% ± 23.5%, respectively; P = 0.006). There was no statistical difference in anxiety, utility of and need for information relative to delayed subjective understanding. In subgroup analysis, subjective understanding scores were higher, but not significantly so, among patients with low and higher education levels in the DIC group than in the control group (68% ± 18.1% vs 54% ± 22.5% [P = 0.06] and 76% ± 18.3% vs and 66% ± 21.9%, respectively [P = 0.89]). CONCLUSION: Hyperrealistic simulations improved subjective understanding of information and, therefore, informed consent for endourological procedures.
Subject(s)
Transurethral Resection of Prostate , Aged , Comprehension , Humans , Informed Consent , Male , Middle Aged , Surveys and QuestionnairesABSTRACT
INTRODUCTION: In palliative care, the prevention and relief of fatigue are regarded as crucial goals in patients with cancer. METHODS: A systematic review was carried out according to the COnsensus-based Standards for the selection of health status Measurement INstruments methodology. Searches were conducted in Medline (through PubMed), Web of Science, Open Gray, Scielo, Cochrane, CINAHL and EMBASE. All instruments found in each study were assessed using the COnsensus-based Standards for the selection of health status Measurement INstruments checklist and Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS: A total of 5598 articles were identified in the different databases. In total, 57 studies describing 19 instruments were included in this study. The main properties evaluated were internal consistency, cross-cultural validity, hypotheses testing and responsiveness. All studies were evaluated with the Strobe scale with a score greater than 6 points. CONCLUSIONS: According to the quality methodological results, Edmonton Symptom Assessment System, Problems and Needs in Palliative Care Questionnaire, European Organisation for Research and Treatment of Cancer Quality of Life 15-item Questionnaire for Palliative Care and Palliative Care Quality of Life Instrument are the recommended instruments used for assessing cancer-related fatigue in palliative care. PROPESRO registration number: CRD42020206783.
Subject(s)
Hospice and Palliative Care Nursing , Neoplasms , Fatigue/etiology , Fatigue/therapy , Humans , Neoplasms/complications , Neoplasms/therapy , Palliative Care , Psychometrics , Quality of Life , Reproducibility of Results , Surveys and QuestionnairesABSTRACT
Delineating the relationship between human neurodevelopment and the maturation of the hypothalamic-pituitary-gonadal (HPG) axis during puberty is critical for investigating the increase in vulnerability to neuropsychiatric disorders that is well documented during this period. Preclinical research demonstrates a clear association between gonadal production of sex steroids and neurodevelopment; however, identifying similar associations in humans has been complicated by confounding variables (such as age) and the coactivation of two additional endocrine systems (the adrenal androgenic system and the somatotropic growth axis) and requires further elucidation. In this paper, we present the design of, and preliminary observations from, the ongoing NIMH Intramural Longitudinal Study of the Endocrine and Neurobiological Events Accompanying Puberty. The aim of this study is to directly examine how the increase in sex steroid hormone production following activation of the HPG-axis (i.e., gonadarche) impacts neurodevelopment, and, additionally, to determine how gonadal development and maturation is associated with longitudinal changes in brain structure and function in boys and girls. To disentangle the effects of sex steroids from those of age and other endocrine events on brain development, our study design includes 1) selection criteria that establish a well-characterized baseline cohort of healthy 8-year-old children prior to the onset of puberty (e.g., prior to puberty-related sex steroid hormone production); 2) temporally dense longitudinal, repeated-measures sampling of typically developing children at 8-10 month intervals over a 10-year period between the ages of eight and 18; 3) contemporaneous collection of endocrine and other measures of gonadal, adrenal, and growth axis function at each timepoint; and 4) collection of multimodal neuroimaging measures at these same timepoints, including brain structure (gray and white matter volume, cortical thickness and area, white matter integrity, myelination) and function (reward processing, emotional processing, inhibition/impulsivity, working memory, resting-state network connectivity, regional cerebral blood flow). This report of our ongoing longitudinal study 1) provides a comprehensive review of the endocrine events of puberty; 2) details our overall study design; 3) presents our selection criteria for study entry (e.g., well-characterized prepubertal baseline) along with the endocrinological considerations and guiding principles that underlie these criteria; 4) describes our longitudinal outcome measures and how they specifically relate to investigating the effects of gonadal development on brain development; and 5) documents patterns of fMRI activation and resting-state networks from an early, representative subsample of our cohort of prepubertal 8-year-old children.