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Patient-ventilator asynchronies are more usual than we believe in critical care patients, and recognition of such an interaction can be challenging in clinical practice, especially if we don´t have advanced monitoring tools such as esophageal pressure tracing at the bedside. Reverse trigger, early cycling, and work shifting are types of asynchronies that must comply with some characteristics in the interaction between ventilator and patient, that could be difficult to detect only with visual analysis of usual waveforms curves showed in mechanical ventilators even for trained operators. In this sense, esophageal catheter is a very useful tool to correct detection and management, if required, of patient-ventilator interactions. more...

Abstract Background Bipolar disorder (BD) is a severe, chronic mental illness that remains difficult to diagnose due to the lack of specific biomarkers, relying primarily on clinical assessments. Early diagnosis and treatment are essential for improving prognosis and lowering suicide risk. This study aimed to identify biomarkers and therapeutic targets by utilizing olfactory neuroepithelium (ONE) cells from patients with BD and controls. Methods Immunofluorescence of ONE cells, along with proteomic and RNA sequencing analyses, was performed to investigate cytoskeletal changes and pathways involved in cell adhesion, movement, and morphology. Additionally, potential biomarkers were investigated in blood samples to improve clinical accessibility. Results Thus, according to functional assays, ONE cells derived from BD patients exhibited decreased substrate adhesion, reduced cell migration, and morphological changes compared to control cells. In addition, proteomic and RNAseq analyses in ONE cells and peripheral blood mononuclear cells (PBMCs) revealed alterations in pathways such as RhoA/PAK/Integrin and Actin Cytoskeleton Signaling, as well as significant changes in inflammatory and immunological pathways. AUROC analysis identified proteins like PTK2 as potential diagnostic biomarkers, showing altered expression in both ONE cells and PBMCs. PTK2 RNA expression correlated with distinct morphological traits in BD ONE cells. Conclusions In summary, this study identified cytoskeletal alterations, reduced adhesion, and disrupted migration patterns in BD ONE cells, highlighting molecular mechanisms underlying these changes and emphasizing PTK2’s role as a potential diagnostic biomarker for BD. more...

Abstract Objective This study aims to investigate the interrelationship of risk factors for suicidal behaviour and their influence on attempt severity in a sample of adolescents who have recently attempted suicide. For it a network analyse was performed. Method Data from a sample of adolescents from 12 to 17 years of age with documented suicide attempts were collected and analysed in the context of a larger study conducted in Spain called SURVIVE. Several factors were examined including age, sex, depression, trauma, impulsivity, and substance abuse. Graph analysis was performed to identify relationships and centrality measures among these factors. Results A total of 267 participants were enrolled: 233 females and 34 males with a mean age of 15.00 years (SD = 1.52). The results indicate that age and sex do not have a notable relationship with attempt severity in adolescents. Emotional and behavioural difficulties, measured by the Strengths and Difficulties Questionnaire (SDQ), have the greatest influence on other variables. Depression and childhood trauma show varying degrees of association with suicidal behaviour, as does motor impulsivity. Substance use does not appear to be strongly related to suicide attempt severity. The number of suicide attempts is strongly correlated with emotional and behavioural difficulties, depression, and childhood trauma. Lethality of suicide attempts and intensity of suicidal ideation do not show significant associations with the other variables. Conclusion This study identifies significant risk factors for adolescent suicide. Emotional and behavioural symptoms, depression, and childhood trauma are strongly linked to suicidal behaviour. However, age, sex, and substance abuse show minimal correlation. Assessing emotional difficulties and depressive symptoms using specific questionnaires could be crucial in evaluating suicidal behaviour in adolescents. more...

Mechanical ventilation is one of the most widespread and characteristic procedures in intensive care units (ICU). Proper understanding of ventilator waveforms is very helpful in achieving protective ventilation for both the lung and the diaphragm, and in many cases improving patient-ventilator interaction. Ultrasound has taken on great importance in recent years in ICU because it is accessible and non-invasive. Sonographic evaluation of the diaphragm is helpful in assessing its function and can also be useful in detecting and correcting possible asynchronies. Early trigger is a particular kind of asynchrony that occurs when a ventilator insufflation precedes the patient trigger effort. more...

Background: A RCT of a novel intervention to detect antidepressant medication response (the PReDicT Test) took place in five European countries, accompanied by a nested study of its acceptability and implementation presented here. The RCT results indicated no effect of the intervention on depression at 8 weeks (primary outcome), although effects on anxiety at 8 weeks and functioning at 24 weeks were found. Methods: The nested study used mixed methods. The aim was to explore patient experiences of the Test including acceptability and implementation, to inform its use within care. A bespoke survey was completed by trial participants in five countries (n = 778) at week 8. Semi-structured interviews were carried out in two countries soon after week 8 (UK n = 22, Germany n = 20). Quantitative data was analysed descriptively; for qualitative data, thematic analysis was carried out using a framework approach. Results of the two datasets were interrogated together. Outcomes: Survey results showed the intervention was well received, with a majority of participants indicating they would use it again, and it gave them helpful extra information; a small minority indicated the Test made them feel worse. Qualitative data showed the Test had unexpected properties, including: instigating a process of reflection, giving participants feedback on progress and new understanding about their illness, and making participants feel supported and more engaged in treatment. Interpretation: The qualitative and quantitative results are generally consistent. The Test's unexpected properties may explain why the RCT showed little effect, as properties were experienced across both trial arms. Beyond the RCT, the qualitative data sheds light on measurement reactivity, i.e., how measurements of depression can impact patients. more...

Mechanical ventilation is used to improve gas exchange and unload the respiratory muscles allowing for their rest and recovery, which require good synchronization between the patient and the ventilator. Spontaneous respiratory effort is generally preferred because it reduces atelectasis, improves oxygenation, and may prevent disuse diaphragm atrophy. Nevertheless, vigorous spontaneous effort can cause both lung injury and diaphragm injury (myotrauma). These injuries lead to prolonged ventilation, difficult weaning, and increased morbidity and mortality. Normal expiration is passive due to the recoil of the lungs and chest wall. In mechanical ventilation, during expiration the ventilator controls the pressure (ie, the target value is PEEP), therefore, we must look at the flow and volume waveforms to see the physiology and patient-ventilator interactions. In expiration the patient-ventilation interaction is not characterized by timing but by work. Expiratory effort (ie, negative Pmus) will deform the flow waveform in a negative direction (away from baseline). more...

Patient-ventilator asynchronies can occur at any phase throughout the respiratory cycle. Because it has been associated with patient outcomes, it is important to recognize and address these asynchronies. Bedside interpretation of air flow and airway pressure waveforms are helpful for recognizing patient–ventilator asynchronies and optimizing ventilator settings. Patient effort is sensed by either a drop in circuit pressure (pressure trigger) or circuit bias flow (flow trigger). Triggering delay is the time interval between the start of the neural and mechanical inspiration. Triggers must be sensitive enough to recognize patient effort to avoid imposing an additional load but not too sensitive to avoid auto-triggering. Despite improvements in triggering technology, triggering asynchronies continue to occur and are manifest, among others, by delayed triggering. more...

Abstract Background Hospitalized patients with COVID-19 demonstrate a higher risk of developing thromboembolism. Anticoagulation (AC) has been proposed for high-risk patients, even without confirmed thromboembolism. However, benefits and risks of AC are not well assessed due to insufficient clinical data. We performed a retrospective analysis of outcomes from AC in a large population of COVID-19 patients. Methods We retrospectively reviewed 1189 patients hospitalized for COVID-19 between March 5 and May 15, 2020, with primary outcomes of mortality, invasive mechanical ventilation, and major bleeding. Patients who received therapeutic AC for known indications were excluded. Propensity score matching of baseline characteristics and admission parameters was performed to minimize bias between cohorts. Results The analysis cohort included 973 patients. Forty-four patients who received therapeutic AC for confirmed thromboembolic events and atrial fibrillation were excluded. After propensity score matching, 133 patients received empiric therapeutic AC while 215 received low dose prophylactic AC. Overall, there was no difference in the rate of invasive mechanical ventilation (73.7% versus 65.6%, p = 0.133) or mortality (60.2% versus 60.9%, p = 0.885). However, among patients requiring invasive mechanical ventilation, empiric therapeutic AC was an independent predictor of lower mortality (hazard ratio [HR] 0.476, 95% confidence interval [CI] 0.345–0.657, p more...

Purpose: The purpose of the study was to evaluate, as a pilot trial, safety and tolerability of CAM-101 10% and 30% topical ophthalmic fibrinogen-depleted human platelet lysate (FD hPL) solution in patients with dry eye disease (DED) secondary to graft-versus-host disease (GvHD) after 6 weeks of treatment. Design: A phase I/II, pilot, prospective, multicenter, randomized, double-masked clinical trial. Participants: Patients with DED secondary to GvHD. Methods: Sixty-four adult patients were stratified by “symptom severity” (Ocular Surface Disease Index [OSDI], ocular discomfort Visual Analog Scale (VAS), ocular symptom frequency, and use of artificial tears) and then randomized 1:1:1 to CAM-101 (FD hPL) at 10% or 30% concentration or an electrolyte (Plasma-Lyte A) vehicle control, 1 drop in both eyes, 4 times daily, for 42 days. After 42 days, control patients were offered 42 days of open-label treatment with 30% FD hPL. Main Outcome Measures: Primary outcome safety measures were ocular and systemic adverse events and the number of patients in each group with clinically significant change from normal to abnormal in any ocular findings. Secondary outcomes were changes from baseline to day 42 in ocular discomfort, OSDI, fluorescein corneal staining, and lissamine green conjunctival staining relative to the vehicle control. The ocular symptom frequency was assessed on a 100-point VAS. Results: FD hPL 10% and 30% were safe and well tolerated. Relative to the vehicle control, significant decreases from baseline to day 42 were seen in the FD hPL 30% group with regard to ocular discomfort (mean decrease = −18.04; P = 0.018), frequency of burning/stinging (−20.23; P = 0.022), eye discomfort (−32.97; P < 0.001), eye dryness (−21.61; P = 0.020), pain (−15.12; P = 0.044), photophobia (−24.33; P = 0.0125), and grittiness (−20.08; P = 0.0185). Decreases were also seen for itching and foreign body sensation, though not statistically significant. Improvements were seen in tear breakup time (mean increase = 1.30 seconds; P = 0.082) and the investigator’s global evaluation 4-point scale (mean decrease = −0.86; P = 0.026). Corneal fluorescein staining was not improved. The OSDI had a mean decrease of −8.88 compared to the vehicle, although not statistically significant. Conclusions: Fibrinogen-depleted human platelet lysate appears to be well tolerated, with no significant toxicity at concentrations of 10% and 30%. These initial data suggest some efficacy, especially for subjective outcome measures relative to baseline assessments and treatment with the vehicle, but larger studies are needed to confirm these effects. more...

Objective Dynamics of humoral immune responses to SARS-CoV-2 antigens following infection suggest an initial decay of antibody followed by subsequent stabilisation. We aim to understand the longitudinal humoral responses to SARS-CoV-2 nucleocapsid (N) protein and spike (S) protein and to evaluate their correlation to clinical symptoms among healthcare workers (HCWs).Design A prospective longitudinal study.Setting This study was conducted in a New York City public hospital in the South Bronx, New York.Participants HCWs participated in phase 1 (N=500) and were followed up 4 months later in phase 2 (N=178) of the study. They underwent SARS-CoV-2 PCR and serology testing for N and S protein antibodies, in addition to completion of an online survey in both phases. Analysis was performed on the 178 participants who participated in both phases of the study.Primary outcome measure Evaluate longitudinal humoral responses to viral N (qualitative serology testing) and S protein (quantitative Mount Sinai Health System ELISA to detect receptor-binding domain and full-length S reactive antibodies) by measuring rate of decay.Results Anti-N antibody positivity was 27% and anti-S positivity was 28% in phase 1. In phase 1, anti-S titres were higher in symptomatic (6754 (5177–8812)) than in asymptomatic positive subjects (5803 (2825–11 920)). Marginally higher titres (2382 (1494–3797)) were seen in asymptomatic compared with the symptomatic positive subgroup (2198 (1753–2755)) in phase 2. A positive correlation was noted between age (R=0.269, p more...

Abstract Background Lithium is recommended as a first line treatment for bipolar disorders. However, only 30% of patients show an optimal outcome and variability in lithium response and tolerability is poorly understood. It remains difficult for clinicians to reliably predict which patients will benefit without recourse to a lengthy treatment trial. Greater precision in the early identification of individuals who are likely to respond to lithium is a significant unmet clinical need. Structure The H2020-funded Response to Lithium Network (R-LiNK; http://www.r-link.eu.com/) will undertake a prospective cohort study of over 300 individuals with bipolar-I-disorder who have agreed to commence a trial of lithium treatment following a recommendation by their treating clinician. The study aims to examine the early prediction of lithium response, non-response and tolerability by combining systematic clinical syndrome subtyping with examination of multi-modal biomarkers (or biosignatures), including omics, neuroimaging, and actigraphy, etc. Individuals will be followed up for 24 months and an independent panel will assess and classify each participants’ response to lithium according to predefined criteria that consider evidence of relapse, recurrence, remission, changes in illness activity or treatment failure (e.g. stopping lithium; new prescriptions of other mood stabilizers) and exposure to lithium. Novel elements of this study include the recruitment of a large, multinational, clinically representative sample specifically for the purpose of studying candidate biomarkers and biosignatures; the application of lithium-7 magnetic resonance imaging to explore the distribution of lithium in the brain; development of a digital phenotype (using actigraphy and ecological momentary assessment) to monitor daily variability in symptoms; and economic modelling of the cost-effectiveness of introducing biomarker tests for the customisation of lithium treatment into clinical practice. Also, study participants with sub-optimal medication adherence will be offered brief interventions (which can be delivered via a clinician or smartphone app) to enhance treatment engagement and to minimize confounding of lithium non-response with non-adherence. Conclusions The paper outlines the rationale, design and methodology of the first study being undertaken by the newly established R-LiNK collaboration and describes how the project may help to refine the clinical response phenotype and could translate into the personalization of lithium treatment. more...

Introduction: Growth retardation is one of the main complications of chronic kidney disease (CKD) in children and induces a negative impact on quality of life.Materials and Methods: Retrospective analysis of all consecutive patients younger than 18 years old who received a first KT in our center between 2008 and 2018.Results: 95 first KT recipients, median age at KT of 7.83 years. At the time of KT, 65.52% of males and 54.05% females showed normal height. After transplantation, linear growth improved from −1.53 at transplant to −1.37 SDS height at the last visit. We detected a different linear growth pattern according to patient age at KT. Children younger than 3 years old exhibited the most significant growth retardation at baseline and the greatest linear growth over time (−2.29 vs. −1.82 SDS height), whereas catch-up was not observed in older patients. Multivariate analysis showed that use of corticosteroids was negatively related to SDS height at 1 year after transplantation and final SDS height only was positively associated with SDS height at KT. 44.2 and 22.1% patients received rhGH treatment before and after KT. 71.88% patients reached adulthood with normal final height.Conclusions: In our study, pediatric KT recipients exhibited a normal height in more than half of cases at KT and in more than two thirds at the final adult height. Only children younger than 6 years old presented a relevant growth catch-up after KT. Treatment with rhGH was used before and after KT with significant improvement in height. more...

Despite the development of several effective vaccines, SARS-CoV-2 continues to spread, causing serious illness among the unvaccinated. Healthcare professionals are trusted sources of information about vaccination, and therefore understanding the attitudes and beliefs of healthcare professionals regarding the vaccines is of utmost importance. We conducted a survey-based study to understand the factors affecting COVID-19 vaccine attitudes among health care professionals in NYC Health and Hospitals, at a time when the vaccine was new, and received 3759 responses. Machine learning and chi-square analyses were applied to determine the factors most predictive of vaccine hesitancy. Demographic factors, education, role at the hospital, perceptions of the pandemic itself, and location of work and residence were all found to significantly contribute to vaccine attitudes. Location of residence was examined for both borough and neighborhood, and was found to have a significant impact on vaccine receptivity. Interestingly, this borough-level data did not correspond to the number or severity of cases in the respective boroughs, indicating that local social or other influences likely have a substantial impact. Local and demographic factors should be strongly considered when preparing pro-vaccine messages or campaigns. more...

Background: Bladder adenocarcinoma (AC) is a scarce histological variant and there are few studies on its proper management. No previous case reports present the management of a urachal tumor and the incidental finding of bladder adenocarcinoma. Clinical case: We present the case of a young woman with nonspecific symptoms, who presented with a prior history of dysuria, bladder tenesmus, suprapubic pain and urinary urgency for one year, which had been treated as recurrent urinary tract infection. A partial cystectomy plus extended lymphadenectomy was scheduled. We found a bladder tumor with characteristics of a urachal tumor and the pathological report indicated a primary bladder AC. The patient had a complete recovery at one year of follow-up. Conclusions: A patient can present with a tumor with urachal characteristics; however, the pathology report can show primary AC. The decision to perform partial cystectomy was an appropriate option for the location of this tumor, with optimal surgical results. Still, a long-term follow-up is necessary. More specific management guidelines are required for the treatment of AC. more...

Background: To study the extent to which neuropsychiatric symptoms (NPS) influence the cognitive and functional decline in frontotemporal degeneration (FTD) and Alzheimer’s disease (AD).Methods: We assessed the progression of NPS and their influence on cognitive and functional progression in a group of FTD (n = 36) and AD patients (n = 47) at two different stages of the disease (2.5 years). A standardized scale was used to assess NPS—the Columbia University Scale for Psychopathology in Alzheimer’s Disease (CUSPAD)—which tracks different symptoms including depression, psychotic symptoms, as well as sleep and conduct problems. In addition, in a subsample of patients (AD n = 14 and FTD n = 14), we analyzed another group of NPS by using the Neuropsychiatric Inventory (NPI). Cognitive declines were tracked by using the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE), while functionality was tracked by using the Lawton scale and the Barthel Index.Results: The presence of NPS impacts cognitive and functional decline in both groups of patients 2.5 years after disease onset. However, we observed a dissociable profile of the affectation of NPS in each group. In the AD group, results indicate that the progression of depressive symptoms and sleep problems predict cognitive and functional decline. In contrast, the progression of a mixed group of NPS, including conduct problems and delusions, predicts cognitive and functional decline in FTD.Conclusion: The presence of NPS has a critical impact on the prediction of cognitive decline in FTD and AD patients after 2.5 years of disease progression. Our results demonstrate the importance of assessing different types of NPS in neurodegenerative disorders which, in turn, predict disease progression. Future studies should assess the role of NPS in predicting different neurocognitive pathways and in neurodegeneration. more...

Controlled release systems are increasing their presence on the market. However, their use is not generating a great impact on horticultural production, mainly due to their price, which makes crop production more expensive. This work proposes a cheaper alternative for the manufacture of these devices. Thus, an agri-food byproduct (soy protein isolate) and a thermomechanical processing were used to create devices (matrices) that can compete in price with the use of conventional fertilizers (0.50–2.00 €/kg). First, different processing methods were evaluated to obtain the matrix with the most optimal mechanical, functional (zinc and water retention/release, biodegradability) and morphological (zinc distribution) properties for the supply of zinc (micronutrient). This was achieved by incorporating an ethanol immersion step into the processing to remove the plasticizer before its use in horticulture. Finally, the efficiency of these matrices was verified in crops (lettuce and peppers), improving up to 60% the assimilation of zinc by plants that conventional fertilization achieves. In addition, these matrices allow a 33% reduction in the water used during cultivation. This work has opened a new possibility of creating more efficient devices for the incorporation of fertilizers into crops, also having an affordable price for industrial use. more...

Background. Melnick-Needles Syndrome is rare congenital hereditary skeletal dysplasia caused by mutations in the FLNA gene, which codifies the protein filamin A. This condition leads to serious skeletal abnormalities, including the stomatognathic region. Case Presentation. This paper describes the case of a 13-year-old girl diagnosed with Melnick-Needles Syndrome presenting with different forms of skeletal dysplasia, such as cranial hyperostosis, short upper limbs, bowed long bones, metaphyseal thickening, genu valgum (knock-knee), shortened distal phalanges, narrow pelvis and shoulders, rib tapering and irregularities, elongation of the vertebrae, kyphoscoliosis, micrognathia, hypoplastic coronoid processes of the mandible, left stylohyoid ligament suggesting ossification, and dental development anomalies. Conclusion. Knowledge of this rare syndrome on the part of dentists is important due to the fact that this condition involves severe abnormalities of the stomatognathic system that cause an impact on the development of the entire face as well as functional and esthetic impairments. more...

O líquen plano oral (LPO) é uma doença mucocutânea inflamatória crônica relacionada com alterações na imunidade mediada por células T. Diversos medicamentos têm sido utilizados no tratamento desta doença, especialmente nas formas erosivas e ulcerativas, com resultados variados. O objetivo deste trabalho é descrever e discutir um caso clínico de líquen plano oral erosivo tratado com corticóide sistêmico que resultou em Síndrome de Cushing, que se manteve com o uso de corticóide tópico. more...

To determine the vertical and horizontal thickness profiles of the corneal epithelium in vivo using ultra-long scan depth and ultra-high resolution spectral domain optical coherence tomography (SD-OCT).A SD-OCT was developed with an axial resolution of ∼ 3.3 µm in tissue and an extended scan depth. Forty-two eyes of 21 subjects were imaged twice. The entire horizontal and vertical corneal epithelial thickness profiles were evaluated. The coefficient of repeatability (CoR) and intraclass correlation (ICC) of the tests and interobserver variability were analyzed.The full width of the horizontal epithelium was detected, whereas part of the superior epithelium was not shown for the covered super eyelid. The mean central epithelial corneal thickness was 52.0 ± 3.2 µm for the first measurement and 52.3 ± 3.4 µm for the second measurement (P>.05). In the central zone (0-3.0 mm), the paracentral zones (3.0-6.0 mm) and the peripheral zones (6.0-10.0 mm), the mean epithelial thickness ranged from 51 to 53 µm, 52 to 57 µm, and 58 to 72 µm, respectively. There was no difference between the two tests at both meridians and in the right and left eyes (P>.05). The ICCs of the two tests ranged from 0.70 to 0.97 and the CoRs ranged from 2.5 µm to 7.8 µm from the center to the periphery, corresponding to 5.6% to 10.6% (CoR%). The ICCs of the two observers ranged from 0.72 to 0.93 and the CoRs ranged from 4.5 µm to 10.4 µm from the center to the periphery, corresponding to 8.7% to 15.2% (CoR%).This study demonstrated good repeatability of ultra-high resolution and long scan depth SD-OCT to evaluate the entire thickness profiles of the corneal epithelium. The epithelial thickness increases from the center toward the limbus. more...

En este artículo se desarrollan e implementan, los algoritmos de integración numérica, que permiten solucionar problemas de ciencias e ingeniería; tales como el cálculo de áreas, volúmenes, mecánica aplicada, y ecuaciones diferenciales (sistemas dinámicos). Dada la necesidad de contar con resultados de gran precisión, se analiza las diferentes reglas de integración numérica; basadas en los errores que ocurren cuando el integrando es reemplazado por un polinomio de interpolación P(x), conocida como las fórmulas de integración de Newton-Cotes. La regla de la extrapolación de Richardson, puede ser aplicada a cualquier fórmula de cuadratura de Newton-Cotes; o cualquier computación que se encuentra basada en una rejilla de ancho h y un error descrito como una potencia de h. more...

El presente articulo esboza las previsibles líneas futuras del desarrollo de la robótica, en el mundo y en nuestro entorno, con dos objetivos principales: conocer la utilización del robot en operaciones de manufactura y de servicios; analizar las tendencias sobre la arquitectura de los robots, el comportamiento dinámico, la integración sensorial y la programación. more...