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1.
Hum Vaccin Immunother ; 20(1): 2353480, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38757507

RESUMEN

Following the introduction of rotavirus vaccination into the Moroccan National Immunization Program, the prevalence of the disease has decreased by nearly 50%. However, evidence on the economic value of rotavirus vaccinations in Morocco is limited. This health economic analysis evaluated, from both country payer and societal perspectives, the costs and the cost-effectiveness of three rotavirus vaccines using a static, deterministic, population model in children aged < 5 years in Morocco. Included vaccines were HRV (2-dose schedule), HBRV (3-dose schedule) and BRV-PV 1-dose vial (3-dose schedule). One-way and probabilistic sensitivity analyses were conducted to assess the impact of uncertainty in model inputs. The model predicted that vaccination with HRV was estimated to result in fewer rotavirus gastroenteritis events (-194 homecare events, -57 medical visits, -8 hospitalizations) versus the 3-dose vaccines, translating into 7 discounted quality-adjusted life years gained over the model time horizon. HRV was associated with lower costs versus HBRV from both the country payer (-$1.8 M) and societal (-$4.1 M) perspectives, and versus BRV-PV 1-dose vial from the societal perspective (-$187,000), dominating those options in the cost-effectiveness analysis. However, costs of BRV-PV 1-dose vial were lower than HRV from the payer perspective, resulting in an ICER of approximately $328,376 per QALY, above the assumed cost effectiveness threshold of $3,500. Vaccination with a 2-dose schedule of HRV may be a cost-saving option and could lead to better health outcomes for children in Morocco versus 3-dose schedule rotavirus vaccines.


Asunto(s)
Análisis Costo-Beneficio , Infecciones por Rotavirus , Vacunas contra Rotavirus , Humanos , Vacunas contra Rotavirus/economía , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/inmunología , Preescolar , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/economía , Lactante , Marruecos , Femenino , Masculino , Recién Nacido , Vacunación/economía , Gastroenteritis/prevención & control , Gastroenteritis/economía , Gastroenteritis/virología
2.
Ann Surg Oncol ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38700799

RESUMEN

BACKGROUND: Rectal tumors display varying degrees of response to total neoadjuvant therapy (TNT). We evaluated the performance of a convolutional neural network (CNN) in interpreting endoscopic images of either a non-complete response to TNT or local regrowth during watch-and-wait surveillance. METHODS: Endoscopic images from stage II/III rectal cancers treated with TNT from 2012 to 2020 at a single institution were retrospectively reviewed. Images were labelled as Tumor or No Tumor based on endoscopy timing (before, during, or after treatment) and the tumor's endoluminal response. A CNN was trained using ResNet-50 architecture. The area under the curve (AUC) was analyzed during training and for two test sets. The main test set included images of tumors treated with TNT. The other contained images of local regrowth. The model's performance was compared to sixteen surgeons and surgical trainees who evaluated 119 images for evidence of tumor. Fleiss' kappa was calculated by respondent experience level. RESULTS: A total of 2717 images from 288 patients were included; 1407 (51.8%) contained tumor. The AUC was 0.99, 0.98, and 0.92 for training, main test, and local regrowth test sets. The model performed on par with surgeons of all experience levels for the main test set. Interobserver agreement was good ( k = 0.71-0.81). All groups outperformed the model in identifying tumor from images of local regrowth. Interobserver agreement was fair to moderate ( k = 0.24-0.52). CONCLUSIONS: A highly accurate CNN matched the performance of colorectal surgeons in identifying a noncomplete response to TNT. However, the model demonstrated suboptimal accuracy when analyzing images of local regrowth.

3.
Psychol Health Med ; : 1-18, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38712645

RESUMEN

Perceived Social Support (PSS) and Physical Activity (PA) could have an important role in reducing psychological distress in women with problems in the menopausal period. The aim was to analyze the associations between a) Self-Perceived Health (SPH), prevalence of self-reported depression and anxiety, and mental health and its subscales, through the Goldberg General Health Questionnaire (GHQ-12) with b) the Physical Activity Level (PAL) and c) the PSS, through the Duke-UNC-11 functional social support questionnaire in Spanish women with problems in the menopausal period. This document uses data from the Spanish National Health Survey of 2017, focusing on women between 40 and 69 years of age with problems in the menopausal period. Dependency relationships were found between the prevalence of depression and PAL, anxiety and PAL, and SPH with PAL (p < 0.001). Weak inverse correlations were found between PAL and mental health, Coping Success, Self-confidence, and Stress (rho: - 0.214 to - 0.258; p < 0.001). Also, weak and very weak significant inverse correlations were found between PAL and all items of the GHQ-12. Weak inverse correlations were found between PSS scores and mental health, Coping, and Stress (r: -0.201 to - 0.304; p < 0.001). Likewise, weak and very weak inverse correlations, although statistically significant, were found between the PSS scores and the responses to the GHQ-12 items. Very active women with higher PSS have less psychological distress, higher self-esteem, and better prevalence of positive health.

4.
Plants (Basel) ; 13(7)2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38611477

RESUMEN

Landscape changes based on spectral responses allow showing plant cover changes through diversity, composition, and ecological connectivity. The spatial and temporal vegetation dynamics of the Bijagual Massif from 1986 to 2021 were analyzed as a measure of ecological integrity, conservation, and territory. The covers identified were high open forest (Hof), dense grassland of non-wooded mainland (Dgnm), a mosaic of pastures and crops (Mpc), lagoons (Lag), and bare and degraded lands (Bdl). The Bijagual Massif has 8574.1 ha. In 1986, Dgnm occupied 42.6% of the total area, followed by Mpc (32.8%) and Hof (24.5%); by 2000, Mpc and Hof increased (43.7 and 28.1%, respectively), while Dgnm decreased (28%); by 2021, Dgnm was restricted to the northeastern zone and continued to decrease (25.2%), Mpc occupied 52.9%, Hof 21.7% and Bdl 0.1%. Of the three fractions of the connectivity probability index, only dPCintra and dPCflux contribute to ecological connectivity. Hof and Dgnm show patches with biota habitat quality and availability. Between 1986 and 2021, Dgnm lost 1489 ha (41%) and Hof 239.5 ha (11%). Mpc replaced various covers (1722.2 ha; 38%) in 2021. Bijagual has a valuable biodiversity potential limited by Mpc. Territorial planning and sustainable agroecological and ecotourism proposals are required due to the context of the ecosystems.

5.
Biol Res ; 57(1): 17, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38664786

RESUMEN

BACKGROUND: Disseminated neoplasia (DN) is a proliferative cell disorder of the circulatory system of bivalve mollusks. The disease is transmitted between individuals and can also be induced by external chemical agents such as bromodeoxyuridine. In Mya arenaria, we have cloned and characterized an LTR-retrotransposon named Steamer. Steamer mRNA levels and gene copy number correlates with DN and can be used as a marker of the disease. So far, the only mollusk where a retrotransposon expression relates to DN is Mya arenaria. On the other hand, it has been reported that the Chilean blue mussel Mytilus chilensis can also suffers DN. Our aim was to identify retrotransposons in Mytilus chilensis and to study their expression levels in the context of disseminated neoplasia. RESULTS: Here we show that 7.1% of individuals collected in August 2018, from two farming areas, presents morphological characteristics described in DN. Using Steamer sequence to interrogate the transcriptome of M. chilensis we found two putative retrotransposons, named Steamer-like elements (MchSLEs). MchSLEs are present in the genome of M. chilensis and MchSLE1 is indeed an LTR-retrotransposon. Neither expression, nor copy number of the reported MchSLEs correlate with DN status but both are expressed at different levels among individual animals. We also report that in cultured M. chilensis haemocytes MchSLEs1 expression can be induced by bromodeoxyuridine. CONCLUSIONS: We conclude that SLEs present in Mytilus chilensis are differentially expressed among individuals and do not correlate with disseminated neoplasia. Treatment of haemocytes with a stressor like bromodeoxyuridine induces expression of MchSLE1 suggesting that in Mytilus chilensis environmental stressors can induce activation of LTR-retrotransposon.


Asunto(s)
Mytilus , Retroelementos , Animales , Mytilus/genética , Retroelementos/genética , Chile
6.
Cornea ; 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38488642

RESUMEN

PURPOSE: This study addresses the growing concern of Dry Eye Disease (DED), which has become increasingly prevalent due to modern lifestyles characterized by prolonged screen usage, global warming, polypharmacy, and extended life expectancy. METHODS: Grounded in the Dry Eye Workshop II (DEWSII) diagnosis framework, the study focuses on DED as a multifactorial condition affecting the ocular surface's tear film homeostasis. The study evaluates the short-term impact of 5 commercially available ocular lubricants on disrupting the hyperosmolar environment and determine whether these lubricants can offer potential treatment benefits for DED. RESULTS: Conducted on 300 eyes (from 150 patients) with 5 preservative-free lubricants compared to a control group, the study reveals that all lubricants effectively reduced tear film osmolarity within 15 minutes of application. Notably, the control group exhibited an increase in average osmolarity (+0.98 mOsm/L) without lubricant use. Siccafluid demonstrated the most substantial osmolarity reduction after 15 minutes, with an average decrease of 11.54 mOsm/L. Statistical significance was observed for Siccafluid, Optive Fusion unique dose (UD), and Systane Ultra UD, while Hyabak and Freegen preservative free (PF) showed lower significance. CONCLUSIONS: Emphasizing the importance of disrupting the hyperosmolar environment to break the cycle of inflammation, the study concludes that ocular lubricants, at least as an immediate post-application effect, can interrupt this cycle and improve the hyperosmolar environment of the ocular surface.

7.
Mov Disord Clin Pract ; 11(5): 567-570, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38454300

RESUMEN

BACKGROUND: Deficiencies in the thyroid hormone transporter monocarboxylate 8 (MCT8) due to pathogenic variants in the SLC16A2 gene (OMIM 300095) result in a complex phenotype with main endocrine and neurologic symptoms. This rare disorder, named Allan-Herndon-Dudley syndrome (AHDS) (OMIM 300523), is inherited in an X-linked trait. One of the prominent features of AHDS is the presence of movement disorders (MD), which are complex and carry a significant burden of the disease. CASES: Patient 1: male with hypotonia since birth, developmental delay, dystonic posturing at 4 months and at 15 months, and startle reaction developed with sensory stimuli. Patient 2: male, at 2 months, shows hypotonia and developmental delay, paroxysmal episodes triggered by a stimulus with sudden blush, tonic asymmetric posture, and no epileptiform activity. At 10 months, generalized dystonic posturing. Patient 3: typical neurodevelopmental milestones until 6 months; at 24 months, dystonia, startle reaction, and upper motoneuron signs. CONCLUSIONS: We aim to describe our patients diagnosed with AHDS, focusing on MD phenomenology and strengthening the phenotype-genotype correlations for this rare condition.


Asunto(s)
Hipotonía Muscular , Humanos , Masculino , Hipotonía Muscular/genética , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/deficiencia , Atrofia Muscular/genética , Atrofia Muscular/patología , Lactante , Trastornos del Movimiento/genética , Discapacidad Intelectual Ligada al Cromosoma X/genética , Discapacidad Intelectual Ligada al Cromosoma X/diagnóstico , Simportadores/genética , Simportadores/deficiencia , Colombia , Preescolar , Fenotipo , Discapacidades del Desarrollo/genética
8.
Epileptic Disord ; 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38512072

RESUMEN

OBJECTIVE: Variants in the ATP1A2 gene exhibit a wide clinical spectrum, ranging from familial hemiplegic migraine to childhood epilepsies and early infantile developmental epileptic encephalopathy (EIDEE) with movement disorders. This study aims to describe the epileptology of three unpublished cases and summarize epilepsy features of the other 17 published cases with ATP1A2 variants and EIDEE. METHODS: Medical records of three novel patients with pathogenic ATP1A2 variants were retrospectively reviewed. Additionally, the PUBMED, EMBASE, and Cochrane databases were searched until December 2023 for articles on EIDEE with ATP1A2 variants, without language or publication year restrictions. RESULTS: Three female patients, aged 6 months-10 years, were investigated. Epilepsy onset occurred between 5 days and 2 years, accompanied by severe developmental delay, intellectual disability, drug-resistant epilepsy, severe movement disorder, and recurrent status epilepticus. All individuals had pathogenic variants of the ATP1A2 gene (ATP1A2 c.720_721del (p.Ile240MetfsTer9), ATP1A2c.3022C > T (p.Arg1008Trp), ATP1A2 c.1096G > T (p.Gly366Cys), according to ACMG criteria. Memantine was p) rescribed to three patients, one with a reduction in ictal frequency, one with improvement in gait pattern, coordination, and attention span, and another one in alertness without significant side effects. SIGNIFICANCE: This study reinforces the association between ATP1A2 variants and a severe phenotype. All patients had de novo variants, focal motor seizures with impaired awareness as the primary type of seizure; of the 11 EEGs recorded, 10 presented a slow background rhythm, 7 multifocal interictal epileptiform discharges (IED), predominantly temporal IEDs, followed by frontal IED, as well as ten ictal recordings, which showed ictal onset from the same regions mentioned above. Treatment with antiseizure medication was generally ineffective, but memantine showed moderate improvement. Prospective studies are needed to enlarge the phenotype and assess the efficacy of NMDA receptor antagonist therapies in reducing seizure frequency and improving quality of life.

9.
Infect Dis Ther ; 13(4): 761-778, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38493411

RESUMEN

INTRODUCTION: Herpes zoster (HZ) can cause substantial patient morbidity and lead to large healthcare costs. However, the disease burden of HZ in Southeast Asia may be underestimated. This study aimed to estimate the public health burden of HZ and the impact of vaccinating adults aged ≥ 50 years old in five Southeast Asian countries (Indonesia, Malaysia, Philippines, Thailand, and Vietnam), with adjuvanted recombinant zoster vaccine (RZV) compared with no vaccination. METHODS: For each country, we adapted a static multicohort Markov model developed with a 1-year cycle length and lifetime horizon. Demographics were obtained from the World Health Organization, HZ incidence from a worldwide meta-regression reporting Asian-specific values, proportions of postherpetic neuralgia (PHN) and non-PHN complications from local/regional studies, and vaccine efficacy from a long-term follow-up trial. First-dose coverage and second-dose compliance were assumed to be 30% and 70%, respectively. A one-way deterministic sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA) were performed to assess the robustness and uncertainty of inputs for each country. RESULTS: Without RZV, it was estimated that there would be a total of approximately 10 million HZ cases, 2.1 million PHN cases, and 1.4 million non-PHN complications in individuals aged ≥ 50 years included in the model. Introducing RZV under 30% coverage could avoid approximately 2.2 million (22%) HZ cases, almost 500,000 (21%) PHN cases, and around 300,000 (22%) non-PHN complications. OWSA showed that first-dose coverage and initial HZ incidence had the largest impact on the estimated number of HZ cases avoided. The number needed to vaccinate ranged from 15 to 21 to prevent one case of HZ and from 68 to 104 to prevent one case of PHN across each country. CONCLUSIONS: This study demonstrated that there is substantial HZ disease burden in older adults for the five selected countries in Southeast Asia, negatively impacting national healthcare systems. Introducing RZV could potentially reduce this burden. A graphical abstract is available with this article.

10.
Angiol. (Barcelona) ; 76(1): 53-55, ene.-feb. 2024. ilus
Artículo en Español | IBECS | ID: ibc-231200

RESUMEN

Introducción: el síndrome de robo de la subclavia es una entidad poco habitual que se presenta en pacientes con estenosis u oclusión de la arteria subclavia, habitualmente la izquierda, y secundario a ateroesclerosis. Los síntomas derivados de esta entidad son: la isquemia del miembro superior y los síntomas neurológicos. Caso clínico: se presenta un caso de un varón que, tras cinco meses de tratamiento endovascular de úlcera de aorta torácica penetrante, presenta síntomas neurológicos. Se realizó diagnóstico del síndrome a través de eco Doppler y se confirmó con angio RM. Finalmente, y debido a la incapacidad que producían los síntomas, se decidió tratamiento quirúrgico mediante cirugía de bypass carótido subclavio izquierdo. Discusión: el síndrome del robo de la subclavia es una entidad que raramente se presenta asociada a síntomas. Debe tenerse una alta sospecha para diagnosticarlo y tratarlo si es necesario. Aunque la tendencia actual es el tratamiento endovascular, en ocasiones la cirugía de derivación tradicional es la única opción. Siempre que sea posible, debe estudiarse la dominancia de las arterias vertebrales antes de ocluir la arteria subclavia en los procedimientos. (AU)


Introduction: subclavian steal syndrome is a rare entity, occurring in patients with stenosis or occlusion of the subclavian artery, usually the left subclavian artery and secondary to atherosclerosis. The symptoms derived from this entity are: ischemia of the upper limb and neurological symptoms. Case report: we present a case of a man who, after five months of endovascular treatment of penetrating thoracic aortic ulcer, presented neurological symptoms. The syndrome was diagnosed by echo-Doppler and confirmed by MRI angiography. Finally, due to the incapacity caused by the symptoms, surgical treatment was decided by left carotid-subclavian bypass. Discussion: subclavian steal syndrome is an entity rarely presents with symptoms, it must be highly suspected in order to diagnose it and, if necessary, treat it. Although, the current trend is endovascular treatment, sometimes traditional bypass surgery is the only option. Whenever possible, the dominance of the vertebral arteries should be studied before occluding the subclavian artery in the procedures. (AU)


Asunto(s)
Humanos , Masculino , Anciano , Síndrome del Robo de la Subclavia/diagnóstico , Síndrome del Robo de la Subclavia/cirugía , Aorta Torácica/lesiones , Isquemia
11.
Med. U.P.B ; 43(1): 118-119, ene.-jun. 2024.
Artículo en Español | LILACS, COLNAL | ID: biblio-1531529
12.
Healthcare (Basel) ; 12(2)2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38255123

RESUMEN

Over the past few years, organizations around the world have tried to reach different populations with recommendations about physical activity (PA), due to this subject playing an important role in the phases of intention development and in preparation for it. Thus, the knowledge of future educators in the fields of health and PA is of vital importance when improving the levels of the latter in students. The objective of this research is to determine what knowledge future teachers have about health and PA, examining possible disparities according to the gender, age, and level of physical exercise of the participants. In addition, the psychometric properties of the instrument used were explored. A total of 321 Colombian university students from the Faculty of Education between the ages of sixteen and thirty-five participated in this study, providing sociodemographic information by filling out the CUAFYS-A questionnaire. Significant differences were found in the scale items according to sex and self-perception of being physically active. Also, the findings revealed a single-factor structure with nine items that had satisfactory reliability (α = 0.71; CR = 0.72) and excellent goodness-of-fit indices (RMSEA = 0.055 (90% CI (0.3, 0.8), RMSR = 0.02, CFI = 0.935, NNFI = 0.912, CMIN/DF = 1.97). Therefore, strategies and campaigns to promote PA knowledge in prospective teachers should be tailored according to gender and PA levels. Similarly, the CUAFYS-A questionnaire can be considered a valid and reliable instrument to identify the PA knowledge of future educators.

13.
Nutrients ; 16(2)2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38257191

RESUMEN

Aging leads to physiological changes affecting body composition, mediated by lifestyle. However, the effectiveness of organized physical activities (OPAs) in attenuating or delaying these age-related transformations remains an area of limited understanding. The primary objectives of this study were threefold: (I) to comprehensively assess the evolution of body composition in a cohort of Spanish older adults over an 8-year period; (II) to compare this evolution in the different age groups; and (III) to investigate the influence of active engagement in OPAs on these age-related changes. From a sample of 3136 Spanish older adults recruited in 2008, 651 agreed to participate in the 8-year follow-up. Anthropometric and bioelectrical impedance data were included for 507 females (70.3 ± 4.4 years) and 144 males (77.8 ± 4.5 years). Age groups were categorized as follows: youngest (65-69 years), mid (70-74 years), and oldest (≥75 years). The engagement in OPA was recorded before and after the follow-up. A repeated measures ANOVA was performed to evaluate the 8-year changes. Males increased in hip (98.1 ± 9.3 vs. 101.5 ± 10.2 cm) and waist circumferences (101.2 ± 6.6 vs. 103.2 ± 6.1 cm), specifically in the youngest group (p < 0.05). Females decreased in weight (67.6 ± 10.0 vs. 66.6 ± 10.5 kg) and fat mass percentage (39.3 ± 5 vs. 38.8 ± 5.4%) and increased in hip circumference (104.4 ± 9.0 vs. 106.5 ± 9.7 cm); these effects were the most remarkable in the oldest group (all p < 0.05). OPA engagement seemed to slow down fat-free mass loses in males, but not in females (grouped by time, p < 0.05). Body composition changes caused by aging seem to happen earlier in males than in females. Moreover, participating in OPAs does not prevent fat-free mass due to aging.


Asunto(s)
Envejecimiento , Composición Corporal , Anciano , Femenino , Humanos , Masculino , Antropometría , Impedancia Eléctrica , Ejercicio Físico , Anciano de 80 o más Años
14.
Exp Gerontol ; 186: 112363, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38244708

RESUMEN

AIMS: The present study sought to analyze the effects of 6-month multicomponent training (MCT) combined with a 4-month detraining on metabolic syndrome (MetS) profile among older adults with decreased functional capacity. METHODS: This quasi-experimental study included a total of 104 older adults (80.5 ± 6.0 years) and the sample was divided into a training (TRAIN, n = 55) or control group (CON). Harmonized definition was used to diagnose the MetS. Functional capacity, blood biochemical parameters, blood pressure, body composition and anthropometric measurements were assessed 3 times. Analysis of variance for repeated measures and Wilcoxon signed-rank test were used to check the differences within groups. RESULTS: TRAIN decreased diastolic blood pressure (DBP), high-density lipoprotein cholesterol (HDLC) and total fat mass during training period, whereas CON did not show any significant changes. During detraining, TRAIN increased HDLC, systolic blood pressure (SBP), waist circumference (WC) and total fat mass; and decreased glucose and fat free mass, whereas CON increased the concentration of glucose and HDLC. From baseline to post-detraining assessment, CON increased the concentration of triglycerides and the WC, while TRAIN only increased the WC (all p < 0.05). CONCLUSIONS: Exercise can be a key component in the treatment of the MetS, since MCT seems to be effective to decrease DBP and total fat mass. Nevertheless, 4-months of detraining could cause a drop of total fat mass, but no in DBP. To avoid reversibility of the benefits obtained, it could be beneficial to promote continuing exercise programs. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT03831841.


Asunto(s)
Síndrome Metabólico , Humanos , Anciano , Síndrome Metabólico/terapia , Ejercicio Físico/fisiología , Presión Sanguínea , Triglicéridos , HDL-Colesterol , Glucosa
15.
Nature ; 625(7993): 166-174, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38057662

RESUMEN

Myeloid cells are known to suppress antitumour immunity1. However, the molecular drivers of immunosuppressive myeloid cell states are not well defined. Here we used single-cell RNA sequencing of human and mouse non-small cell lung cancer (NSCLC) lesions, and found that in both species the type 2 cytokine interleukin-4 (IL-4) was predicted to be the primary driver of the tumour-infiltrating monocyte-derived macrophage phenotype. Using a panel of conditional knockout mice, we found that only deletion of the IL-4 receptor IL-4Rα in early myeloid progenitors in bone marrow reduced tumour burden, whereas deletion of IL-4Rα in downstream mature myeloid cells had no effect. Mechanistically, IL-4 derived from bone marrow basophils and eosinophils acted on granulocyte-monocyte progenitors to transcriptionally programme the development of immunosuppressive tumour-promoting myeloid cells. Consequentially, depletion of basophils profoundly reduced tumour burden and normalized myelopoiesis. We subsequently initiated a clinical trial of the IL-4Rα blocking antibody dupilumab2-5 given in conjunction with PD-1/PD-L1 checkpoint blockade in patients with relapsed or refractory NSCLC who had progressed on PD-1/PD-L1 blockade alone (ClinicalTrials.gov identifier NCT05013450 ). Dupilumab supplementation reduced circulating monocytes, expanded tumour-infiltrating CD8 T cells, and in one out of six patients, drove a near-complete clinical response two months after treatment. Our study defines a central role for IL-4 in controlling immunosuppressive myelopoiesis in cancer, identifies a novel combination therapy for immune checkpoint blockade in humans, and highlights cancer as a systemic malady that requires therapeutic strategies beyond the primary disease site.


Asunto(s)
Médula Ósea , Carcinogénesis , Interleucina-4 , Mielopoyesis , Transducción de Señal , Animales , Humanos , Ratones , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Médula Ósea/efectos de los fármacos , Médula Ósea/metabolismo , Carcinogénesis/efectos de los fármacos , Carcinogénesis/metabolismo , Carcinogénesis/patología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Inhibidores de Puntos de Control Inmunológico/inmunología , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Interleucina-4/metabolismo , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Linfocitos Infiltrantes de Tumor/inmunología , Monocitos/efectos de los fármacos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Recurrencia , Transducción de Señal/efectos de los fármacos
17.
Biomed Pharmacother ; 170: 116015, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38113629

RESUMEN

Development of therapeutic agents that have fewer adverse effects and have higher efficacy for diseases, such as cancer, metabolic disorders, neurological diseases, infections, cardiovascular diseases, and respiratory diseases, are required. Recent studies have focused on identifying novel sources for pharmaceutical molecules to develop therapies against these diseases. Among the sources for potentially new therapies, animal venom-derived molecules have generated much interest. Various animal venom-derived proteins and peptides have been isolated, identified, synthesized, and tested to develop drugs. Venom-derived peptides have several biomedical properties, such as proapoptotic, cell migration, and autophagy regulation activities in cancer cell models; induction of vasodilation by nitric oxide and regulation of angiotensin II; modification of insulin response by controlling calcium and potassium channels; regulation of pain receptor activity; modulation of immune cell activity; alteration of motor neuron activity; degradation or inhibition of ß-amyloid plaque formation; antibacterial, antifungal, antiviral, and antiprotozoal activities; increase in sperm motility and potentiation of erectile function; reduction of intraocular pressure; anticoagulation, fibrinolytic, and antithrombotic activities; etc. This systematic review compiles these biomedical properties and potential biomedical applications of synthesized animal venom-derived peptides reported in the latest research. In addition, the limitations and areas of opportunity in this research field are discussed so that new studies can be developed based on the data presented.


Asunto(s)
Motilidad Espermática , Ponzoñas , Animales , Masculino , Péptidos/farmacología , Angiotensina II
18.
Infect Dis Ther ; 12(12): 2791-2806, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38095808

RESUMEN

INTRODUCTION: Pertussis, a contagious respiratory disease, is underreported in adults. The study objective was to quantify underestimation of pertussis cases in adults aged ≥ 50 years in five Latin American countries (Argentina, Brazil, Chile, Mexico, Peru). METHODS: A previously published probabilistic model was adapted to adjust the number of pertussis cases reported to national surveillance systems by successive multiplication steps (proportion of pertussis cases seeking healthcare; proportion with a specimen collected; proportion sent for confirmatory testing; proportion positive for pertussis; proportion reported to passive surveillance). The proportions at each step were added in a random effects model to produce a pooled overall proportion, and a final multiplier was calculated as the simple inverse of this proportion. This multiplier was applied to the number of cases reported to surveillance to estimate the number of pertussis cases. Monte Carlo simulation with 10,000 iterations estimated median as well as upper and lower 90% values. Input data were obtained from surveillance systems and published sources. RESULTS: The estimated median underestimation factor for pertussis cases in adults ranged from 104 (90% limits 40, 451) in Chile to 114 (90% limits 39, 419) in Argentina. In all five countries, the largest estimated number of cases was in the group aged 50-59 years. The highest number per 100,000 population was in the group aged ≥ 90 years in most countries. The estimated median underestimation factor for pertussis hospitalizations was 2.3 (90% limits 1.8, 3.3) in Brazil and 2.4 (90% limits 1.8, 3.2) in Chile (data not available for other countries). CONCLUSION: This analysis indicates that the number of pertussis cases in adults aged ≥ 50 years in five Latin American countries is approximately 100 times higher than the number captured in surveillance data. These results could support decision-making in the diagnosis, management, and prevention of pertussis disease in adults.

19.
Cell Tissue Bank ; 2023 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-38141131

RESUMEN

The cornea transplant is considered the most frequently performed type of transplant in the world, with a demand that has been increasing in recent years. An observational descriptive study was conducted, focusing on the ocular tissue extracted from cadaveric donors from January 2019 to December 2021 at the Red Cross Eye Bank in Medellin, Colombia. This is the first epidemiological characterization of corneal donor tissues within the eye banks of our city, where high rates of violence-related deaths explain that tissue donors are mostly young individuals. This, in turn, results in excellent counts of endothelial cells and tissue viability in their microscopic studies. Additionally, there are lower rates of discarded tissues compared to similar studies.

20.
Rev. biol. trop ; 71(1)dic. 2023.
Artículo en Español | LILACS, SaludCR | ID: biblio-1514964

RESUMEN

Introducción: Los páramos de Boyacá cubren el 18.3 % de la superficie de Colombia, y son diversos en flora y fauna, además, registran una alta variabilidad climática, topográfica y de hábitats, que permite que estos ecosistemas sean centros de diversidad en el Neotrópico, y por tanto albergan una alta diversidad de briófitos. Objetivo: Analizar la estructura y composición de las comunidades de briófitos de los complejos de páramos de Boyacá. Métodos: a partir de información de literatura, bases de datos y revisión de herbarios, se evaluó la composición florística y la completitud de muestreo para los complejos de páramos y sustratos. Resultados: Se encontraron 5 132 ejemplares, con 343 especies de musgos que fue el grupo más diverso, 256 hepáticas y dos antocerotes. El análisis de completitud de muestreo es representativo en un 98 %. Además, encontramos que la preferencia de sustratos es el terrícola con 409 especies y el cortícola con 341. La diversidad alfa del orden 0D mostró que Tota-Bijagual-Mamapacha (TBM) es el complejo más diverso con 368 especies, y Pisba (124) el menos diverso; el índice 1D mostró que el complejo (TBM) presentó 178 especies consideradas comunes, y la dominancia de especies (2D) fue mayor en el complejo Iguaque-Merchán con 119 taxa dominantes y en menor número Guantiva-La Rusia (105) y TBM (102). Conclusiones: El análisis de la diversidad beta mostró que el 62 % de la disimilitud en la composición de especies entre los complejos se debe al recambio de especies, igualmente sucede con la divergencia por sustratos que es del 51 %. Los briófitos en los páramos de Boyacá representan el 36.05 % de la diversidad colombiana, y el 2.96 % a nivel mundial.


Introduction: The Boyacá paramos cover 18.3 % of the Colombian surface, and are diverse in flora and fauna, moreover, have a high temperature, topography, and habitats, which allow these ecosystems to be centers of diversity in the Neotropics, and therefore they harbor a high diversity of bryophytes. Objectives: Analyze the structure and composition of the bryophyte communities of the paramos in the Boyacá complexes. Methods: Using literature, databases and herbariums records, the floristic composition, and the completeness of the sampling for the paramo and substrate complexes was evaluated. Results: We analyzed 5 132 specimens, with 343 species of mosses being the most diverse group, 256 liverworts and two hornworts. The sampling completeness analysis is 98 % representative. In addition, we found that the preference of substrates is terrestrial with 409 species and corticolous with 341. Alpha diversity of order 0D showed that Tota-Bijagual-Mamapacha (TBM) is the most diverse complex with 368 species, and Pisba (124) the least diverse; the 1D index showed that the complex (TBM) presented 178 species considered common, and the dominance of species (2D) was higher in the Iguaque-Merchán Complex with 119 dominant taxa and Guantiva-La Russia (105) and TBM (105) to a lesser number. (102). Conclusions: the analysis of beta diversity showed that 62 % of the dissimilarity in the composition of species between the complexes is due to the species turnover, the same happens with the divergence by substrates that is 51 %. Bryophytes in the Boyacá paramos represent 36.05 % of Colombian diversity, and 2.96 % worldwide.


Asunto(s)
Plantas/clasificación , Briófitas/anatomía & histología , Biodiversidad , Colombia
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