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1.
Fam Cancer ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38780705

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the Western world. The number of diagnosed cases and the mortality rate are almost equal as the majority of patients present with advanced disease at diagnosis. Between 4 and 10% of pancreatic cancer cases have an apparent hereditary background, known as hereditary pancreatic cancer (HPC) and familial pancreatic cancer (FPC), when the genetic basis is unknown. Surveillance of high-risk individuals (HRI) from these families by imaging aims to detect PDAC at an early stage to improve prognosis. However, the genetic basis is unknown in the majority of HRIs, with only around 10-13% of families carrying known pathogenic germline mutations. The aim of this study was to assess an individual's genetic cancer risk based on sex and personal and family history of cancer. The Best Linear Unbiased Prediction (BLUP) methodology was used to estimate an individual's predicted risk of developing cancer during their lifetime. The model uses different demographic factors in order to estimate heritability. A reliable estimation of heritability for pancreatic cancer of 0.27 on the liability scale, and 0.07 at the observed data scale as obtained, which is different from zero, indicating a polygenic inheritance pattern of PDAC. BLUP was able to correctly discriminate PDAC cases from healthy individuals and those with other cancer types. Thus, providing an additional tool to assess PDAC risk HRI with an assumed genetic predisposition in the absence of known pathogenic germline mutations.

2.
Article in English | MEDLINE | ID: mdl-38668099

ABSTRACT

OBJECTIVES: High driving pressure (DP, ratio of tidal volume (Vt) over respiratory system compliance) is a risk for poor outcomes in patients with pediatric acute respiratory distress syndrome (PARDS). We therefore assessed the time course in level of DP (i.e., 24, 48, and 72 hr) after starting mechanical ventilation (MV), and its association with 28-day mortality. DESIGN: Multicenter, prospective study conducted between February 2018 and December 2022. SETTING: Twelve tertiary care PICUs in Colombia. PATIENTS: One hundred eighty-four intubated children with moderate to severe PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The median (interquartile range [IQR]) age of the PARDS cohort was 11 (IQR 3-24) months. A total of 129 of 184 patients (70.2%) had a pulmonary etiology leading to PARDS, and 31 of 184 patients (16.8%) died. In the first 24 hours after admission, the plateau pressure in the nonsurvivor group, compared with the survivor group, differed (28.24 [IQR 24.14-32.11] vs. 23.18 [IQR 20.72-27.13] cm H2O, p < 0.01). Of note, children with a Vt less than 8 mL/kg of ideal body weight had lower adjusted odds ratio (aOR [95% CI]) of 28-day mortality (aOR 0.69, [95% CI, 0.55-0.87]; p = 0.02). However, we failed to identify an association between DP level and the oxygenation index (aOR 0.58; 95% CI, 0.21-1.58) at each of time point. In a diagnostic exploratory analysis, we found that DP greater than 15 cm H2O at 72 hours was an explanatory variable for mortality, with area under the receiver operating characteristic curve of 0.83 (95% CI, 0.74-0.89); there was also increased hazard for death with hazard ratio 2.5 (95% CI, 1.07-5.92). DP greater than 15 cm H2O at 72 hours was also associated with longer duration of MV (10 [IQR 7-14] vs. 7 [IQR 5-10] d; p = 0.02). CONCLUSIONS: In children with moderate to severe PARDS, a DP greater than 15 cm H2O at 72 hours after the initiation of MV is associated with greater odds of 28-day mortality and a longer duration of MV. DP should be considered a variable worth monitoring during protective ventilation for PARDS.

3.
Article in English | MEDLINE | ID: mdl-38546455

ABSTRACT

OBJECTIVE: To compare the pelvic lymph node involvement and risk of recurrence in patients with human papillomavirus (HPV)-associated endocervical adenocarcinoma stage IA2-IB1 undergoing hysterectomy and/or trachelectomy plus lymphadenectomy, according to Silva's classification system. METHODS: A retrospective cohort study was performed in two Colombian cancer centers. The cases were classified according to the Silva classification system. Clinical, surgical, and histopathological variables were evaluated. Recurrence risk was analyzed by patterns A, B, or C. A logistic regression model was performed for tumor recurrence. The Kaplan-Meier method was used to estimate overall survival and disease-free survival (DFS). A weighted kappa was performed to determine the degree of concordance between pathologists. RESULTS: A total of 100 patients were identified, 33% pattern A, 29% pattern B, and 38% pattern C. The median follow-up time was 42.5 months. No evidence of lymph node involvement was found in patients classified as A and B, while in the C pattern was observed in 15.8% (n = 6) of cases (P < 0.01). There were 7% of cases with recurrent disease, of which 71.5% corresponded to type C pattern. Patients with Silva pattern B and C had 1.22- and 4.46-fold increased risk of relapse, respectively, compared with pattern A. The 5-year DFS values by group were 100%, 96.1%, and 80.3% for patterns A, B, and C, respectively. CONCLUSION: For patients with early-stage HPV-associated endocervical adenocarcinoma, the type C pattern presented more lymph node involvement and risk of recurrence compared to the A and B patterns. The concordance in diagnosis of different Silva's patterns by independents pathologists were good.

4.
Sports (Basel) ; 12(2)2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38393280

ABSTRACT

This cross-sectional observational study aims to determine isokinetic normality data at different speeds, and isometric data of ankle and knee joints, in healthy basketball players aged 15-16 years old. The participants were recruited through non-probabilistic convenience sampling. Sociodemographic, anthropometric, and biomechanical variables were collected. The study involved 42 participants. Right-leg dominance was higher in women (85.7%) than in men (78.6%). Men had a higher weight, height, and body mass index compared to women. Statistically significant differences were observed between sex and height (p < 0.001). Significant differences were found between sexes in knee flexor and extensor strength at different isokinetic speeds (30°, 120°, and 180°/s), except for the maximum peak strength knee flexion at 180°/s in the right leg. In the ankle, the variables inversion, eversion, and work strength values at different isokinetic speeds and full RoM, by sex, were not significantly different, except for the right (p = 0.004) and the left (p = 0.035) ankle full RoM. The study found lower knee extensor strength in women, indicating the need to improve knee flexor/extensor strength in women to match that of men, as seen in other joints. The results can guide the development of preventive and therapeutic interventions for lower limb injuries in basketball players.

5.
Sci Rep ; 14(1): 3354, 2024 02 09.
Article in English | MEDLINE | ID: mdl-38336826

ABSTRACT

Throughout pregnancy, the decidua is predominantly populated by NK lymphocytes expressing Killer immunoglobulin-like receptors (KIR) that recognize human leukocyte antigen-C (HLA-C) ligands from trophoblast cells. This study aims to investigate the association of KIR-HLA-C phenotypes in couples facing infertility, particularly recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF), in comparison to a reference population and fertile controls. This observational, non-interventional retrospective case-control study included patients consecutively referred to our Reproductive Immunology Unit from 2015 to 2019. We analyzed the frequencies of KIR and HLA-C genes. As control groups, we analyzed a reference Spanish population for KIR analysis and 29 fertile controls and their male partners for KIR and HLA-C combinations. We studied 397 consecutively referred women with infertility and their male partners. Among women with unexplained RPL (133 women) and RIF (176 women), the centromeric (cen)AA KIR genotype was significantly more prevalent compared to the reference Spanish population (p = 0.001 and 0.02, respectively). Furthermore, cenAA was associated with a 1.51-fold risk of RPL and a 1.2-fold risk of RIF. Conversely, the presence of BB KIR showed a lower risk of reproductive failure compared to non-BB KIR (OR: 0.12, p < 0.001). Women and their partners with HLA-C1C1/C1C1 were significantly less common in the RPL-Group (p < 0.001) and RIF-Group (p = 0.002) compared to the control group. Moreover, the combination of cenAA/C1C1 in women with C1C1 partners was significantly higher in the control group than in the RPL (p = 0.009) and RIF (p = 0.04) groups, associated with a 5-fold increase in successful pregnancy outcomes. In our cohort, the cenAA KIR haplotype proved to be a more accurate biomarker than the classic AA KIR haplotype for assessing the risk of RPL and RIF, and might be particularly useful to identify women at increased risk among the heterogeneous KIR AB or Bx population. The classification of centromeric KIR haplotypes outperforms classical KIR haplotypes, making it a better indicator of potential maternal-fetal KIR-HLA-C mismatch in patients.


Subject(s)
Abortion, Habitual , Infertility , Pregnancy , Humans , Male , Female , HLA-C Antigens/genetics , Retrospective Studies , Amino Acid Motifs , Case-Control Studies , Abortion, Habitual/genetics , Receptors, KIR/genetics , Infertility/genetics , Biomarkers
6.
Math Biosci Eng ; 21(1): 237-252, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38303421

ABSTRACT

In this work, we propose a mathematical model that describes liver evolution and concentrations of alanine aminotransferase and aspartate aminotransferase in a group of rats damaged with carbon tetrachloride. Carbon tetrachloride was employed to induce cirrhosis. A second groups damaged with carbon tetrachloride was exposed simultaneously a plant extract as hepatoprotective agent. The model reproduces the data obtained in the experiment reported in [Rev. Cub. Plant. Med. 22(1), 2017], and predicts that using the plants extract helps to get a better natural recovery after the treatment. Computer simulations show that the extract reduces the damage velocity but does not avoid it entirely. The present paper is the first report in the literature in which a mathematical model reliably predicts the protective effect of a plant extract mixture in rats with cirrhosis disease. The results reported in this manuscript could be used in the future to help in fighting cirrhotic conditions in humans, though more experimental and mathematical work is required in that case.


Subject(s)
Chemical and Drug Induced Liver Injury , Plant Extracts , Humans , Rats , Animals , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Carbon Tetrachloride/toxicity , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/prevention & control , Chemical and Drug Induced Liver Injury/pathology , Liver/pathology , Liver Cirrhosis/drug therapy , Liver Cirrhosis/pathology , Models, Theoretical
7.
Am J Hosp Palliat Care ; 41(1): 26-37, 2024 Jan.
Article in English | MEDLINE | ID: mdl-36943176

ABSTRACT

BACKGROUND: Communication is one of the central axes around which end-of-life care revolves in the context of palliative care. Communication of bad news is reported as one of the most difficult and stressful tasks by palliative care professionals. Therefore, the aim of this study is to identify aspects related to the communication of bad news in palliative care in Spain. METHODS: Descriptive cross-sectional study. An ad hoc questionnaire was designed and sent by e-mail to all palliative care teams in Spain. RESULTS: Overall, 206 professionals (102 nurses, 88 physicians and 16 psychologists) completed the questionnaire. A total of 60.2% considered their communication of bad news skills to be good or very good. This was related to older age, experience in both the profession and palliative care, and to having received specific postgraduate training (P < .001). Around 42.2% perform communication of bad news with the patient first, which is associated with lower skill (P = .013). About 78.15% of the professionals do not use any specific protocol. CONCLUSION: This study suggests that patients access palliative care with little information about their diagnosis and prognosis. The barriers identified in the communication of bad news are the lack of specific education and training in protocol management, the difficult balance between hope and honesty, the young age of the patient, and the family.


Subject(s)
Palliative Care , Physician-Patient Relations , Humans , Truth Disclosure , Cross-Sectional Studies , Spain , Communication
8.
Plants (Basel) ; 12(24)2023 Dec 10.
Article in English | MEDLINE | ID: mdl-38140446

ABSTRACT

One of the causal agents of bacterial canker is Pseudomonas amygdali pv. morsprunorum-Pam (formerly Pseudomonas syringae pv. morsprunorum). Recently detected in Chile, Pam is known to cause lesions in the aerial parts of the plant, followed by more severe symptoms such as cankers and gummosis in the later stages of the disease. This study presents the design of PCR and LAMP detection methods for the specific and sensitive identification of Pseudomonas amygdali pv. morsprunorum (Pam) from cherry trees. Twelve Pseudomonas isolates were collected, sequenced, and later characterized by Multi-locus Sequence Analysis (MLSA) and Average Nucleotide Identity by blast (ANIb). Three of them (11116B2, S1 Pam, and S2 Pam) were identified as Pseudomonas amygdali pv. morsprunorum and were used to find specific genes through RAST server, by comparing their genome with that of other Pseudomonas, including isolates from other Pam strains. The effector gene HopAU1 was selected for the design of primers to be used for both techniques, evaluating sensitivity and specificity, and the ability to detect Pam directly from plant tissues. While the PCR detection limit was 100 pg of purified bacterial DNA per reaction, the LAMP assays were able to detect up to 1 fg of purified DNA per reaction. Similar results were observed using plant tissues, LAMP being more sensitive than PCR, including when using DNA extracted from infected plant tissues. Both detection methods were tested in the presence of 30 other bacterial genera, with LAMP being more sensitive than PCR.

9.
Plants (Basel) ; 12(21)2023 Oct 29.
Article in English | MEDLINE | ID: mdl-37960074

ABSTRACT

Bacterial canker caused by Pseudomonas syringae pv. syringae (Pss) is responsible for substantial loss to the production of sweet cherry in Chile. To date, the molecular mechanisms of the Pss-sweet cherry interaction and the disease-related genes in the plant are poorly understood. In order to gain insight into these aspects, a transcriptomic analysis of the sweet cherry cultivar 'Lapins' for differentially expressed genes (DEGs) in response to Pss inoculation was conducted. Three Pss strains, A1M3, A1M197, and 11116_b1, were inoculated in young twigs, and RNA was extracted from tissue samples at the inoculation site and distal sections. RNA sequencing and transcriptomic expression analysis revealed that the three strains induced different patterns of responses in local and distal tissues. In the local tissues, A1M3 triggered a much more extensive response than the other two strains, enriching DEGs especially involved in photosynthesis. In the distal tissues, the three strains triggered a comparable extent of responses, among which 11116_b1 induced a group of DEGs involved in defense responses. Furthermore, tissues from various inoculations exhibited an enrichment of DEGs related to carbohydrate metabolism, terpene metabolism, and cell wall biogenesis. This study opened doors to future research on the Pss-sweet cherry interaction, immunity responses, and disease control.

10.
PLoS One ; 18(9): e0291056, 2023.
Article in English | MEDLINE | ID: mdl-37669303

ABSTRACT

The technological transformation and advertising utilized in the footwear industry significantly impact purchasing decisions. The gait properties, barefoot and with shoes, change depending on the footwear structure. The aim of this work is the biomechanical analysis of walking barefoot and with different sports shoes in a controlled group of 12 children between 4 and 6 years old. Kinematic and spatiotemporal variables were analyzed using a BTS motion capture analysis system with the Helen Hayes protocol. Previously, a survey was carried out with 262 families with children between 4 and 6 years old to justify the choice of footwear for this study. No significant differences were found between any of the measured conditions. The kinematic results showed significant differences in the ankle (right sagittal plane p = 0.04, left p < 0.01; right frontal plane p < 0.01, left p < 0.01), knee (right and left sagittal plane p < 0.01) and hip (right sagittal plane p < 0.01, left p = 0.04; right frontal plane p = 0.03). Additionally, the post hoc analysis revealed significant differences between barefoot gait and different footwear. The footwear used for this study and each one's various characteristics are not preponderant in the spatiotemporal and kinematic parameters of the children's gait. Thus, the footwear purchase may be conditioned by its design or composition and other properties may not be relevant.


Subject(s)
Advertising , Ankle Joint , Humans , Child , Child, Preschool , Gait , Industry , Knee Joint
11.
Clin Immunol ; 256: 109796, 2023 11.
Article in English | MEDLINE | ID: mdl-37774905

ABSTRACT

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency characterized by decreased immunoglobulins and recurrent infections. Its aetiology remains unknown, and some patients present with severe non-infectious autoimmune or inflammatory complications with elevated associated morbimortality. Recently, intestinal dysbiosis has been proposed as a driver of immune dysregulation. In this study, we assessed the oral, respiratory, and gastrointestinal microbiota of 41 CVID patients (24 with dysimmune and 17 with infection complications) and 15 healthy volunteers using 16S rRNA gene sequencing to explore associations between microbiome profiles and CVID phenotypes. Profound differences in the composition of the microbiota in saliva, sputum, and stool were detected between dysimmune CVID patients and healthy individuals. Globally, respiratory species diversity and faecal bacterial richness were lower in CVID individuals with immune complications. Although a single species could not be identified as a robust predictor of dysimmunity, a combination of around 5-7 bacterial species in each type of sample could predict this severe phenotype with an accuracy of around 90% in the study population. Our study provides new insights into these previously unexplored but highly interrelated ecological niches among themselves and with patient profiles. Our data suggest that this disease-related systemic dysbiosis could be implicated in the immune dysregulation associated with severe cases of CVID.


Subject(s)
Common Variable Immunodeficiency , Gastrointestinal Microbiome , Humans , Dysbiosis , RNA, Ribosomal, 16S/genetics , Bacteria/genetics
12.
Colomb Med (Cali) ; 54(1): e2005304, 2023.
Article in English | MEDLINE | ID: mdl-37440979

ABSTRACT

Background: Older adults admitted to a hospital for acute illness are at higher risk of hospital-associated functional decline during stays and after discharge. Objective: This study aimed to assess the calibration and discriminative abilities of the Hospital Admission Risk Profile (HARP) and the Identification of Seniors at Risk (ISAR) scales as predictors of hospital-associated functional decline at discharge in a cohort of patients older than age 65 receiving management in an acute geriatric care unit in Colombia. Methods: This study is an external validation of ISAR and HARP prediction models in a cohort of patients over 65 years managed in an acute geriatric care unit. The study included patients with Barthel index measured at admission and discharge. The evaluation discriminate ability and calibration, two fundamental aspects of the scales. Results: Of 833 patients evaluated, 363 (43.6%) presented hospital-associated functional decline at discharge. The HARP underestimated the risk of hospital-associated functional decline for patients in low- and intermediate-risk categories (relation between observed/expected events (ROE) 1.82 and 1.51, respectively). The HARP overestimated the risk of hospital-associated functional decline for patients in the high-risk category (ROE 0.91). The ISAR underestimated the risk of hospital-associated functional decline for patients in low- and high-risk categories (ROE 1.59 and 1.11). Both scales showed poor discriminative ability, with an area under the curve (AUC) between 0.55 and 0.60. Conclusions: This study found that HARP and ISAR scales have limited discriminative ability to predict HAFD at discharge. The HARP and ISAR scales should be used cautiously in the Colombian population since they underestimate the risk of hospital-associated functional decline and have low discriminative ability.


Antecedentes: los adultos mayores ingresados en un hospital por una enfermedad aguda tienen un mayor riesgo de deterioro functional hospitalario durante su estancia y después del alta. Objetivo: este estudio tuvo como objetivo evaluar las capacidades de calibración y discriminación de las escalas Hospital Admission Risk Profile (HARP) e Identification of Seniors at Risk (ISAR) como predictores de deterioro funcional hospitalario al alta en una cohorte de pacientes mayores de 65 años que recibieron manejo en una unidad geriátrica de agudos en Colombia. Métodos: este estudio es una validación externa de los modelos de predicción ISAR y HARP en una cohorte de pacientes mayores de 65 años atendidos en una unidad geriátrica de agudos. El estudio incluyó pacientes con índice de Barthel medido al ingreso y al alta y la evaluación de la capacidad de discriminación y calibración, dos aspectos fundamentales para esta medición. Resultados: de 833 pacientes evaluados, 363 (43.6%) presentaron deterioro funcional hospitalario al momento del alta. La escala HARP subestimó el riesgo de deterioro funcional hospitalario para los pacientes en las categorías de riesgo bajo e intermedio (relación entre eventos observados /esperados (ROE) 1.82 y 1.51, respectivamente). El HARP sobrestimó el riesgo de deterioro funcional hospitalario para pacientes en la categoría de alto riesgo (ROE 0.91). El ISAR subestimó el riesgo de deterioro hospitalario para pacientes en categorías de bajo y alto riesgo (ROE 1.59 y 1.11). Ambas escalas mostraron una pobre capacidad de discriminación, con un área bajo la curva (AUC) entre 0.55 y 0.60. Conclusiones: este estudio encontró que las escalas HARP e ISAR tienen una capacidad de discriminación limitada para predecir deterioro funcional hospitalario al alta. Las escalas HARP e ISAR deben usarse con cautela en la población colombiana ya que subestiman el riesgo de deterioro funcional hospitalario y tienen baja capacidad de discriminación.


Subject(s)
Hospitalization , Hospitals , Humans , Aged , Colombia , Risk Assessment , Activities of Daily Living
13.
Metas enferm ; 26(6): 64-70, Jul. 2023. tab
Article in Spanish | IBECS | ID: ibc-222663

ABSTRACT

Objetivo: analizar la inteligencia emocional percibida en estudiantes de Grado en Enfermería de primer y cuarto curso.Método: se realizó un estudio transversal en estudiantes de primero y cuarto de Grado en Enfermería de la Universidad Pontificia Comillas (Madrid, España). Se utilizó la Escala Rasgo de Metaconocimiento Emocional TMMS-24. Se usó una plataforma online de la propia universidad. Se realizó análisis descriptivo y univariante.Resultados: Participaron 140 estudiantes (70 por curso). El 77,9% (n= 109) fue mujer. El 80% (n= 112) tenía entre 18-25 años. Se encontraron diferencias significativas en la comprensión de las emociones entre los estudiantes de primer y cuarto curso (p< 0,05), teniendo mayor claridad emocional los estudiantes de cuarto. Se registraron diferencias significativas en la variable atención entre hombres y mujeres (p= 0,012), siendo la atención mayor en mujeres. En la variable claridad se observaron diferencias significativas entre hombres y mujeres (p= 0,015), siendo en este caso mayor la comprensión de las emociones por el grupo de hombres.Conclusiones: los estudiantes de Grado en Enfermería necesitan mejorar las capacidades definidas por la inteligencia emocional para alcanzar un buen ajuste psicológico. Las habilidades emocionales son similares en los alumnos de primero y cuarto, excepto en la comprensión emocional. La atención a las emociones es mayor en mujeres que en hombres, mientras que la claridad es mayor en hombres que en mujeres. A pesar de estas diferencias significativas en las variables atención y claridad no se observan hallazgos importantes en la reparación emocional entre hombres y mujeres.(AU)


Objective: to analyse the emotional intelligence perceived in Nursing Degree students in their first and fourth years.Method: a cross-sectional study was conducted with students in the first and fourth year of their Nursing Degree at the Universidad Pontificia Comillas (Madrid, Spain). The Trait-Meta Mood Scale (TMMS-24) was used. The University online platform was used; descriptive and univariate analysis was conducted.Results: the study included 140 students (70 per year); 77.9% (n= 109) were female and 80% (n= 112) were between 18 and 25 years old. Significant differences were found in Emotion Understanding between students in their first and fourth year (p< 0.05), with higher Emotional Clarity in fourth-year students. Significant differences were registered in the Attention variable between men and women (p= 0.012), with higher attention among women. In the Clarity variable, significant differences were observed between men and women (p= 0.015), and in this case, Emotion Understanding was higher in the male group.Conclusions: Nursing Degree students need to improve the skills defined by emotional intelligence in order to reach a good psychological adjustment. Emotional skills were similar between first and fourth year students, except in terms of Emotional Understanding. Emotional Attention was higher in women than in men, while Clarity was higher in men than in women. Regardless of these significant differences in the Attention and Clarity variables, there were no major findings in Emotional Repair between men and women.(AU)


Subject(s)
Humans , Male , Female , Education, Nursing , Students, Nursing , Emotional Intelligence , Emotions , Nursing , Cross-Sectional Studies , Spain , Epidemiology, Descriptive
15.
Cell Death Discov ; 9(1): 113, 2023 Apr 05.
Article in English | MEDLINE | ID: mdl-37019880

ABSTRACT

Spinal Muscular Atrophy (SMA) is a severe genetic neuromuscular disorder that occurs in childhood and is caused by misexpression of the survival motor neuron (SMN) protein. SMN reduction induces spinal cord motoneuron (MN) degeneration, which leads to progressive muscular atrophy and weakness. The link between SMN deficiency and the molecular mechanisms altered in SMA cells remains unclear. Autophagy, deregulation of intracellular survival pathways and ERK hyperphosphorylation may contribute to SMN-reduced MNs collapse, offering a useful strategy to develop new therapies to prevent neurodegeneration in SMA. Using SMA MN in vitro models, the effect of pharmacological inhibition of PI3K/Akt and ERK MAPK pathways on SMN and autophagy markers modulation was studied by western blot analysis and RT-qPCR. Experiments involved primary cultures of mouse SMA spinal cord MNs and differentiated SMA human MNs derived from induced pluripotent stem cells (iPSCs). Inhibition of the PI3K/Akt and the ERK MAPK pathways reduced SMN protein and mRNA levels. Importantly, mTOR phosphorylation, p62, and LC3-II autophagy markers protein level were decreased after ERK MAPK pharmacological inhibition. Furthermore, the intracellular calcium chelator BAPTA prevented ERK hyperphosphorylation in SMA cells. Our results propose a link between intracellular calcium, signaling pathways, and autophagy in SMA MNs, suggesting that ERK hyperphosphorylation may contribute to autophagy deregulation in SMN-reduced MNs.

17.
Colomb. med ; 54(1)mar. 2023.
Article in English | LILACS-Express | LILACS | ID: biblio-1534276

ABSTRACT

Background: Older adults admitted to a hospital for acute illness are at higher risk of hospital-associated functional decline during stays and after discharge. Objective: This study aimed to assess the calibration and discriminative abilities of the Hospital Admission Risk Profile (HARP) and the Identification of Seniors at Risk (ISAR) scales as predictors of hospital-associated functional decline at discharge in a cohort of patients older than age 65 receiving management in an acute geriatric care unit in Colombia. Methods: This study is an external validation of ISAR and HARP prediction models in a cohort of patients over 65 years managed in an acute geriatric care unit. The study included patients with Barthel index measured at admission and discharge. The evaluation discriminate ability and calibration, two fundamental aspects of the scales. Results: Of 833 patients evaluated, 363 (43.6%) presented hospital-associated functional decline at discharge. The HARP underestimated the risk of hospital-associated functional decline for patients in low- and intermediate-risk categories (relation between observed/expected events (ROE) 1.82 and 1.51, respectively). The HARP overestimated the risk of hospital-associated functional decline for patients in the high-risk category (ROE 0.91). The ISAR underestimated the risk of hospital-associated functional decline for patients in low- and high-risk categories (ROE 1.59 and 1.11). Both scales showed poor discriminative ability, with an area under the curve (AUC) between 0.55 and 0.60. Conclusions: This study found that HARP and ISAR scales have limited discriminative ability to predict HAFD at discharge. The HARP and ISAR scales should be used cautiously in the Colombian population since they underestimate the risk of hospital-associated functional decline and have low discriminative ability.


Antecedentes: los adultos mayores ingresados en un hospital por una enfermedad aguda tienen un mayor riesgo de deterioro functional hospitalario durante su estancia y después del alta. Objetivo: este estudio tuvo como objetivo evaluar las capacidades de calibración y discriminación de las escalas Hospital Admission Risk Profile (HARP) e Identification of Seniors at Risk (ISAR) como predictores de deterioro funcional hospitalario al alta en una cohorte de pacientes mayores de 65 años que recibieron manejo en una unidad geriátrica de agudos en Colombia. Métodos: este estudio es una validación externa de los modelos de predicción ISAR y HARP en una cohorte de pacientes mayores de 65 años atendidos en una unidad geriátrica de agudos. El estudio incluyó pacientes con índice de Barthel medido al ingreso y al alta y la evaluación de la capacidad de discriminación y calibración, dos aspectos fundamentales para esta medición. Resultados: de 833 pacientes evaluados, 363 (43.6%) presentaron deterioro funcional hospitalario al momento del alta. La escala HARP subestimó el riesgo de deterioro funcional hospitalario para los pacientes en las categorías de riesgo bajo e intermedio (relación entre eventos observados /esperados (ROE) 1.82 y 1.51, respectivamente). El HARP sobrestimó el riesgo de deterioro funcional hospitalario para pacientes en la categoría de alto riesgo (ROE 0.91). El ISAR subestimó el riesgo de deterioro hospitalario para pacientes en categorías de bajo y alto riesgo (ROE 1.59 y 1.11). Ambas escalas mostraron una pobre capacidad de discriminación, con un área bajo la curva (AUC) entre 0.55 y 0.60. Conclusiones: este estudio encontró que las escalas HARP e ISAR tienen una capacidad de discriminación limitada para predecir deterioro funcional hospitalario al alta. Las escalas HARP e ISAR deben usarse con cautela en la población colombiana ya que subestiman el riesgo de deterioro funcional hospitalario y tienen baja capacidad de discriminación.

18.
Nurse Educ Today ; 124: 105770, 2023 May.
Article in English | MEDLINE | ID: mdl-36848698

ABSTRACT

BACKGROUND: The Law on Euthanasia was approved in Spain and implemented in the health system. Nursing students must position themselves with respect to euthanasia in their work in the near future. OBJECTIVES: To know the attitudes of nursing students towards the legalization of euthanasia, its relationship with end-of-life planning, and the spiritual dimension. DESIGN: A cross-sectional descriptive quantitative study. SETTINGS AND PARTICIPANTS: Study carried out with students of the Nursing Degree at the Universities of Huelva and Almería in Spain from April to July 2021. METHODS: Attitudes towards the final phase of life, Anxiety towards death, and Attitudes towards Euthanasia questionnaires were administered. Descriptive, inferential and logistic regression statistics were calculated to determine the relationship between attitudes towards euthanasia and sociodemographic variables, end-of-life planning, and the spiritual dimension. RESULTS: 285 Nursing students with an average age of 23.58 years (SD = 8.19) participated. The scores on the attitude towards euthanasia were higher than the mean. While 70.5 % of the students were aware about advanced planning, only 2.5 % of them had made advanced plans. In religious practice and the spiritual dimension, the average score was high as they considered these elements to be of great support at the end of life. In terms of anxiety about death, the average score was significantly higher in women. Age, spiritual accompaniment and help, and the frequency with which spiritual beliefs are practiced are predictive factors for the attitude towards euthanasia. CONCLUSIONS: Students have a positive vision of euthanasia while admitting anxiety about death. They emphasize advance planning and greater religious practice as supports for euthanasia. The need for curricular training related to moral deliberation and values that support euthanasia is clear.


Subject(s)
Euthanasia , Students, Nursing , Humans , Female , Young Adult , Adult , Cross-Sectional Studies , Attitude , Surveys and Questionnaires , Death , Attitude of Health Personnel
19.
Cells ; 12(3)2023 01 31.
Article in English | MEDLINE | ID: mdl-36766806

ABSTRACT

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental syndrome characterized by dopaminergic dysfunction. In this study, we aimed to demonstrate that there is a link between dopaminergic deficit and neuroinflammation that underlies ADHD symptoms. We used a validated ADHD mice model involving perinatal 6-OHDA lesions. The animals received abscisic acid (ABA), an anti-inflammatory phytohormone, at a concentration of 20 mg/L (drinking water) for one month. We tested a battery of behavior tests, learning and memory, anxiety, social interactions, and pain thresholds in female and male mice (control and lesioned, with or without ABA treatment). Postmortem, we analyzed microglia morphology and Ape1 expression in specific brain areas related to the descending pain inhibitory pathway. In females, the dopaminergic deficit increased pain sensitivity but not hyperactivity. In contrast, males displayed hyperactivity but showed no increased pain sensitivity. In females, pain sensitivity was associated with inflammatory microglia and lower Ape1 levels in the anterior cingulate cortex (ACC) and posterior insula cortex (IC). In addition, ABA treatment alleviated pain sensitivity concomitant with reduced inflammation and normalized APE1. In males, ABA reduced hyperactivity but had no significant effect on inflammation in these areas. This is the first study proving a sex-dependent association between dopamine dysfunction and inflammation in specific brain areas, hence leading to different behavioral outcomes in a mouse model of ADHD. These findings provide new clues for potential treatments for ADHD.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Pregnancy , Male , Female , Mice , Animals , Attention Deficit Disorder with Hyperactivity/drug therapy , Abscisic Acid/pharmacology , Neuroinflammatory Diseases , Pain Threshold , Disease Models, Animal , Inflammation/drug therapy , Inflammation/metabolism
20.
Med Microbiol Immunol ; 212(1): 93-102, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36595027

ABSTRACT

Measurement of anti-pneumococcal capsular polysaccharides (anti-PnPs) IgG titers is an important tool in the immunologic assessment of patients with suspected immunodeficiency disorders (ID) to reduce the morbi-mortality and minimize severe infections. Retrospectively, we studied the relationship among anti-PnPs IgG response to 3 doses of Prevenar®13, levels of immune system components, leukocyte populations, and clinical data in children with ID. Serum samples were collected at least 4 weeks post vaccination. Subsequently, multi-serotype enzyme-linked immunosorbent assay (ELISA) was performed. Eighty-seven children (under 12 years) were enrolled. Primary immunodeficiency disorder (PID) was the most common disorder (45) followed by possible immunodeficiency disorder (POID) (19), secondary immunodeficiency disorder (SID) (15), and mixed immunodeficiency disorder (MID) (8). The median age was 3 (1.50-5.33) years, 65% of patients were male. Deficient production of anti-PnPs IgG (titer ≤ 50 mg/L) was detected in 47 patients (54%), especially in the MID group, all of them under immunosuppressive therapy. In PCV13 responders, the mean of leukocyte population levels was higher with statistically significance differences in CD4 + /CD8 + T lymphocytes (p = 0.372, p = 0.014) and CD56 + /CD16 + NK (p = 0.016). Patients with previous bone marrow transplantation were the worst PCV13 responders. Pneumococcal IgG antibody titers (post-vaccination) along with clinical and analytical markers represented.


Subject(s)
Antibody Formation , Pneumococcal Vaccines , Child, Preschool , Female , Humans , Male , Antibodies, Bacterial , Heptavalent Pneumococcal Conjugate Vaccine , Immunoglobulin G , Retrospective Studies , Streptococcus pneumoniae , Infant
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