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1.
Eur Rev Med Pharmacol Sci ; 28(6): 2464-2482, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38567607

RESUMO

OBJECTIVE: Vitiligo is a common systemic, idiopathic autoimmune disease. The aim of this study was to analyze the frequency of variants of the superoxide dismutase 1 (SOD1) gene (50 bp Ins/Del, rs4817415, rs2070424, rs1041740, rs17880135) and circulating plasma protein levels through in-silico analysis. PATIENTS AND METHODS: Blood samples were collected from adult patients of both sexes with a clinical diagnosis of vitiligo. ELISA tests for SOD and analysis of gene variants by qPCR were compared to a disease-free reference group. RESULTS: The population analyzed was young people between 29 and 37 years old, with a higher percentage of women. The population was found in the Hardy-Weinberg equilibrium (HWE). The 50 bp Ins/Del, rs4817415, and rs2070424 variants showed no significant difference between groups (p > 0.05). Although, in the dominant model, the CT and CTTT genotypes of the rs1041740 and rs17880135 variants showed an association with susceptibility to vitiligo compared to the control. Plasma SOD levels showed significant differences between the groups, and when stratified according to the genotypes of each variant, there was a significant difference, except with the rs17880135 variant. The haplotypes InsCGTC and InsAGCC are shown to be risk factors for susceptibility to vitiligo. The in-silico analysis demonstrated that the rs4817415, rs2070424, rs1041740, and rs17880135 variants of the SOD1 gene participate in the modification of selected regulatory elements for differentiating the protein, transcription factors, and long non-coding RNA. CONCLUSIONS: Information regarding the pathogenesis of vitiligo helps recognize risk factors and identify the relationship of diagnostic markers of cell damage inherent to the disease. This will help improve aspects of prevention and the choice of treatment alternatives appropriate to each case.


Assuntos
Vitiligo , Masculino , Adulto , Humanos , Feminino , Adolescente , Superóxido Dismutase-1/genética , Vitiligo/genética , Genótipo , Fatores de Risco , Proteínas Sanguíneas/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único
2.
Rev. esp. anestesiol. reanim ; 71(4): 304-316, abril 2024. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-232126

RESUMO

La evidencia sobre la gestión del dolor postoperatorio presenta un grado de calidad bajo o insuficiente. El Grupo de Trabajo del Dolor Agudo SEDAR ha elaborado este documento-guía para aplicar la mejor evidencia científica disponible a la práctica clínica habitual, individualizándolo en función de factores propios del paciente y del procedimiento, y englobando las distintas opciones organizativas del control de dolor.El documento profundiza y actualiza conceptos y requisitos mínimos necesarios para una analgesia óptima postoperatoria, el abordaje multidisciplinar y la gestión del dolor agudo postoperatorio. Se definen y se describen líneas estratégicas y los distintos modelos de gestión. Se establece un plan de actuación general perioperatoria basado en la colaboración con los servicios quirúrgicos implicados, en la revisión conjunta de la evidencia y en la elaboración de protocolos por procedimiento. Finalmente, se presenta un plan de seguimiento y los indicadores mínimos necesarios para un control de calidad del dolor postoperatorio. (AU)


The evidence on postoperative pain management is of low or insufficient quality. The SEDAR Acute Pain Working Group has prepared this guideline-document to apply the best available scientific evidence to clinical practice, individualizing it based on factors specific to the patient and the procedure, and encompassing different organizational options, attempting to individualize it based on specific factors of the patient and the procedure, and encompassing the different organizational options for pain control.The document updates concepts and minimum requirements necessary for optimal postoperative analgesia, a multidisciplinary approach and the management of acute postoperative pain. Strategic lines and different management models are defined. A general perioperative action plan is established based on collaboration with the surgical departments involved, on the joint review of the evidence and on preparation of protocols by the procedure. Finally, a follow-up plan and a series of minimum indicators necessary for quality control of postoperative pain are presented. (AU)


Assuntos
Humanos , Ciências da Saúde , Dor Pós-Operatória , Dor Aguda , Cirurgia Geral , Cuidados Médicos
3.
Public Health ; 230: 163-171, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38555685

RESUMO

OBJECTIVES: Immunisation against preventable diseases as meningitis is crucial from a public health perspective to face challenges posed by these infections. Nurses hold a great responsibility for these programs, which highlights the importance of understanding their preferences and needs to improve the success of campaigns. This study aimed to investigate nurses' preferences regarding Meningococcus A, C, W, and Y (MenACWY) conjugate vaccines commercialised in Spain. STUDY DESIGN: A national-level discrete choice experiment (DCE) was conducted. METHODS: A literature review and a focus group informed the DCE design. Six attributes were included: pharmaceutical form, coadministration evidence, shelf-life, package contents, single-doses per package, and package volume. Conditional logit models quantified preferences and relative importance (RI). RESULTS: Thirty experienced primary care nurses participated in this study. Evidence of coadministration with other vaccines was the most important attribute (RI = 43.78%), followed by package size (RI = 22.17%), pharmaceutical form (RI = 19.07%), and package content (RI = 11.80%). There was a preference for evidence of coadministration with routine vaccines (odds ratio [OR] = 2.579, 95% confidence interval [95%CI] = 2.210-3.002), smaller volumes (OR = 1.494, 95%CI = 1.264-1.767), liquid formulations (OR = 1.283, 95%CI = 1.108-1.486) and package contents including only vial/s (OR = 1.283, 95%CI = 1.108-1.486). No statistical evidence was found for the remaining attributes. CONCLUSIONS: Evidence of coadministration with routine vaccines, easy-to-store packages, and fully liquid formulations were drivers of nurses' preferences regarding MenACWY conjugate vaccines. These findings provide valuable insights for decision-makers to optimize current campaigns.


Assuntos
Vacinas Meningocócicas , Neisseria meningitidis , Enfermeiras e Enfermeiros , Humanos , Espanha , Vacinas Conjugadas , Comportamento de Escolha , Preparações Farmacêuticas
4.
Neurología (Barc., Ed. impr.) ; 39(2): 127-134, Mar. 2024. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-230867

RESUMO

Introducción La enfermedad de Huntington (EH) es un trastorno neurodegenerativo y hereditario. Gracias al diagnóstico predictivo se han descrito características clínicas incipientes en la fase prodrómica. Objetivo Comparar la ejecución en tareas cognitivas de portadores (PEH) del gen de la huntingtina y no portadores (NPEH) y observar la variabilidad en la ejecución, dependiendo de la carga de la enfermedad y cercanía a la etapa manifiesta (edad de inicio de los síntomas). Método Los 146 participantes de un Programa de Diagnóstico Predictivo de EH (PDP-EH) fueron divididos en PEH (41,1%) y NPEH (58,9%). Mediante fórmulas matemáticas se obtuvo la carga de enfermedad y cercanía a la etapa manifiesta en el grupo PEH y se correlacionó con la ejecución neuropsicológica. Resultados Se observaron diferencias significativas entre los grupos con las pruebas Mini-Mental State Examination (MMSE), Stroop-B, SDMT y fluidez fonológica. En el grupo PEH se observaron correlaciones entre la carga de enfermedad con la MMSE, Stroop-B y SDMT. El grupo «Cerca» de la etapa manifiesta es el que obtuvo la puntuación más baja en las pruebas MMSE, Stroop-B, Stroop-C, SDMT y fluidez verbal semántica. De acuerdo al MANCOVA, el efecto MMSE evidencia diferencias estadísticamente significativas entre carga de la enfermedad y la cercanía de inicio de los síntomas. Conclusiones Se observa un nivel menor de desempeño en el grupo PEH con probabilidad de inicio cercano de la fase manifiesta en pruebas que evalúan la velocidad de procesamiento y atención. La disfunción cognitiva prefrontal se altera de manera precoz varios años antes del diagnóstico motor de la EH. (AU)


Introduction Huntington disease (HD) is a hereditary neurodegenerative disorder. Thanks to predictive diagnosis, incipient clinical characteristics have been described in the prodromal phase. Objective To compare performance in cognitive tasks of carriers (HDC) and non-carriers (non-HDC) of the huntingtin gene and to analyse the variability in performance as a function of disease burden and proximity to the manifest stage (age of symptom onset). Method A sample of 146 participants in a predictive diagnosis of HD programme were divided into the HDC (41.1%) and non-HDC groups (58.9%). Mathematical formulae were used to calculate disease burden and proximity to the manifest stage in the HDC group; these parameters were correlated with neuropsychological performance. Results Significant differences were observed between groups in performance on the Mini-Mental State Examination (MMSE), Stroop-B, Symbol-Digit Modalities Test (SDMT), and phonological fluency. In the HDC group, correlations were observed between disease burden and performance on the MMSE, Stroop-B, and SDMT. The group of patients close to the manifest stage scored lowest on the MMSE, Stroop-B, Stroop-C, SDMT, and semantic verbal fluency. According to the multivariate analysis of covariance, the MMSE effect shows statistically significant differences in disease burden and proximity to onset of symptoms. Conclusions Members of the HDC group close to the manifest phase performed more poorly on tests assessing information processing speed and attention. Prefrontal cognitive dysfunction appears early, several years before the motor diagnosis of HD. (AU)


Assuntos
Humanos , Doença de Huntington , Efeitos Psicossociais da Doença , Neuropsicologia , Disfunção Cognitiva
5.
Rehabilitación (Madr., Ed. impr.) ; 58(1): [100816], Ene-Mar, 2024. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-229692

RESUMO

Introducción y objetivo: La hipoterapia (HPOT) y los simuladores de hipoterapia (SHPOT) se utilizan en niños con parálisis cerebral para lograr su máxima funcionalidad e independencia. El objetivo es conocer si la HPOT y los SHPOT producen los mismos efectos beneficiosos sobre el equilibrio, la función motora gruesa y el control postural en menores de 18 años con parálisis cerebral. Materiales y métodos: Se utilizaron como palabras clave: hippotherapy, equine-assisted therapy y cerebral palsy. Las bases de datos utilizadas fueron: PeDro, Scopus, LILACS, ScienceDirect, Cochrane Library, Web of Science y CINAHL Complete (Ebsco). Fueron incluidos ensayos clínicos aleatorizados que estudiaran el efecto de la HPOT y/o los SHPOT sobre las variables mencionadas. Resultados: Cuatro estudios evaluaron el equilibrio, 4 la función motora gruesa y 2 el control postural. La HPOT y los SHPOT produjeron beneficios en todos ellos. Conclusiones: Ambas intervenciones producen mejoras sobre las variables estudiadas, aunque aumentan con la HPOT posiblemente debido a una mayor estimulación sensorial.(AU)


Introduction and objective: Hippotherapy (HPOT) and hippotherapy simulators (SHPOT) are used in children with cerebral palsy to achieve their maximum functionality and independence. The aim is to find out if HPOT and SHPOT produce the same effects on balance, gross motor function, and postural control in children under 18 years old with cerebral palsy. Materials and methods: The keywords used were: hippotherapy, equine-assisted therapy and cerebral palsy. The databases used were PeDro, Scopus, LILACS, ScienceDirect, Cochrane Library, Web of Science and CINAHL Complete (Ebsco). Studies were included if they were randomized clinical trials that studied the effect of HPOT and/or SHPOT on the variables mentioned in these patients. Results: Four studies assessed balance, 4 studied gross motor function, and 2 investigated postural control. Both HPOT and SHPOT produced benefits in all of them. Conclusions: According to the studied variables both interventions produce similar improvements. Although, they increase with HPOT possibly due to greater sensory stimulation.(AU)


Assuntos
Humanos , Masculino , Feminino , Criança , Terapia Assistida por Cavalos , Paralisia Cerebral/reabilitação , Equilíbrio Postural , Destreza Motora , Reabilitação
7.
Semergen ; 50(6): 102197, 2024 Mar 12.
Artigo em Espanhol | MEDLINE | ID: mdl-38479203

RESUMO

OBJECTIVES: To know the needs and lack of information on health issues of Maghrebi women. SUBJECTS, MATERIAL AND METHOD: Design: Qualitative study technique nominal group (TGN). SUBJECTS: 14 North African women from Association for Solidarity and Rapprochement of Cultures (ASAC) from the rural clinic of La Aljorra who knew and understood Spanish, older age, and lived in the town for more than 3 years. Material and method TGN asks: «What daily health issues for you and your family worry you the most and do you need answers?¼ Individual reflection and list that were discussed among them, joining the group consensus. Subsequently, they were prioritized individually and a definitive list of their prioritized health needs was made. RESULTS: Thirty-six percent of the ASAC associates attended. At first, 17 topics were written on health needs for which they wanted a response. The final topics chosen and grouped by them were 6: 1) Contraceptive methods; 2) Relationship problems; 3) Thyroid; 4) How to cure the sciatic nerve?; 5) Anemia and 6) Stress. 70% related to the area of sexuality. CONCLUSIONS: 1) Qualitative research is an adequate consensus method to obtain information on little-known topics and directly from the person involved; 2) The Moroccan migrant woman considers information about sexuality and couple relationships very important; 3) Another pathology unknown to them and emerging in the area is thyroid; 4) Stress and its repercussions; 5) Sciatica and its consequences are also important when being agricultural workers.

8.
Eur Rev Med Pharmacol Sci ; 28(3): 1163-1177, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38375721

RESUMO

OBJECTIVE: The aim of the study was to analyze the association between the superoxide dismutase 2 (SOD2) gene variants rs2758346, rs5746094, and rs2758331 and breast cancer (BC) in the Mexican population as well as to perform in silico assessments of the variants' potential impact. PATIENTS AND METHODS: We performed in silico analysis and analyzed 489 healthy women and 467 BC patients using TaqMan assays and Real-Time PCR. RESULTS: The TT genotype, the T allele of the rs2758346 variant, and the CC genotype of both rs5746094 and rs2758331 were identified as BC risk factors (p < 0.05). The TT and CTTT genotype of the rs2758346 variant stratified by the presence of ki-67 (> 20%), TCCC, and estrogen receptor (ER)-positive of the rs5746094 variant, and the CC and CT genotypes of rs2758331 stratified by menopause status and non-chemotherapy response were risk factors. The TTC and TTA haplotypes are risk factors for BC. In silico analysis revealed that the rs2758346, rs5746094, and rs2758331 variants could influence SOD2 gene regulation by transcription factors and circulating RNAs (circRNAs). CONCLUSIONS: The rs2758346, rs5746094, and rs2758331 variants of the SOD2 gene were associated with BC risk and could influence SOD2 regulation by transcription factors and circRNAs.


Assuntos
Neoplasias da Mama , Superóxido Dismutase , Feminino , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Polimorfismo de Nucleotídeo Único , Fatores de Risco , RNA Circular , Superóxido Dismutase/genética , Fatores de Transcrição/genética
10.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38325567

RESUMO

INTRODUCTION: Controversy exists in the literature about the best treatment for type III acromioclavicular dislocations. The aim of this study is to compare functional results between surgical and conservative treatment in type III acromioclavicular joint dislocations. MATERIAL AND METHOD: We retrospectively evaluated the records of 30 patients from our area with acute type III acromioclavicular dislocations that were treated from January 1st, 2016 to December 31st, 2020. Fifteen patients were treated surgically and 15 conservatively. Follow-up mean time was 37.93 months in operative group and 35.73 months in non-operative group. Results obtained on the Constant score was the main variable analysed and results obtained on the Oxford score and the Visual Analogue Scale for pain were the secondary variables. Epidemiological variables were analysed, as well as range of mobility in injured shoulder and subjective and radiological variables (distance between the superior border of the acromion and the superior border of the clavicle's distal end and presence of osteoarthritis in the acromioclavicular joint). RESULTS: Functional evaluation scores did not show differences between the two groups (Constant: operative 82/non-operative 86.38, p 0.412; Oxford: operative 42/non-operative 44.80, p 0.126) nor did Visual Analogue Scale (operative 1/non-operative 0.20, p 0.345). Subjective evaluation of the injured shoulder was excellent or good in 80% of the patients in both groups. Measurement of the distance between the superior border of the acromion and the superior border of the clavicle's distal end were significantly higher in non-operative group (operative 8.95/non-operative 14.21, p 0.008). CONCLUSIONS: Although radiographic results were better in the surgical treatment group, functional evaluation scores did not show significant differences between the two groups. These results do not support the routine use of surgical treatment for grade III acromioclavicular dislocations.

11.
Rev Esp Anestesiol Reanim (Engl Ed) ; 71(2): 125-128, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38242357

RESUMO

Tubeless anaesthesia has become widespread in videothoracoscopic surgery, even in major procedures such as lobectomies. There are several advantages in avoiding general anaesthesia and one-lung mechanical ventilation, such as faster recovery and shorter hospital stays. However, hypoxaemia and hypercapnia are the most reported causes of conversion to general anaesthesia. High Flow Oxygen Therapy (HFOT) generates flow-dependent positive end-expiratory pressure, improves oxygenation and also carbon dioxide washout by flow-dependent dead space flushing. For this reason, intraoperative HFOT may reduce the rate of conversion to general anaesthesia. We report our experience with intraoperative HFOT in a 71-year-old female with lung adenocarcinoma undergoing VATS upper left lobectomy.


Assuntos
Pulmão , Oxigenoterapia , Feminino , Humanos , Idoso , Oxigenoterapia/métodos , Anestesia Geral , Cirurgia Torácica Vídeoassistida/métodos , Oxigênio
12.
Rev Esp Anestesiol Reanim (Engl Ed) ; 71(2): 112-124, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38244774

RESUMO

Septic shock is a highly lethal and prevalent disease. Progressive circulatory dysfunction leads to tissue hypoperfusion and hypoxia, eventually evolving to multiorgan dysfunction and death. Prompt resuscitation may revert these pathogenic mechanisms, restoring oxygen delivery and organ function. High heterogeneity exists among the determinants of circulatory dysfunction in septic shock, and current algorithms provide a stepwise and standardized approach to conduct resuscitation. This review provides the pathophysiological and clinical rationale behind ANDROMEDA-SHOCK-2, an ongoing multicenter randomized controlled trial that aims to compare a personalized resuscitation strategy based on clinical phenotyping and peripheral perfusion assessment, versus standard of care, in early septic shock resuscitation.


Assuntos
Choque Séptico , Humanos , Choque Séptico/terapia , Hidratação , Ressuscitação , Algoritmos , Estudos Multicêntricos como Assunto
13.
Neurologia (Engl Ed) ; 39(2): 127-134, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38272259

RESUMO

INTRODUCTION: Huntington disease (HD) is a hereditary neurodegenerative disorder. Thanks to predictive diagnosis, incipient clinical characteristics have been described in the prodromal phase. OBJECTIVE: To compare performance in cognitive tasks of carriers (HDC) and non-carriers (non-HDC) of the huntingtin gene and to analyse the variability in performance as a function of disease burden and proximity to the manifest stage (age of symptom onset). METHOD: A sample of 146 participants in a predictive diagnosis of HD programme were divided into the HDC (41.1%) and non-HDC groups (58.9%). Mathematical formulae were used to calculate disease burden and proximity to the manifest stage in the HDC group; these parameters were correlated with neuropsychological performance. RESULTS: Significant differences were observed between groups in performance on the Mini-Mental State Examination (MMSE), Stroop-B, Symbol-Digit Modalities Test (SDMT), and phonological fluency. In the HDC group, correlations were observed between disease burden and performance on the MMSE, Stroop-B, and SDMT. The group of patients close to the manifest stage scored lowest on the MMSE, Stroop-B, Stroop-C, SDMT, and semantic verbal fluency. According to the multivariate analysis of covariance, the MMSE effect shows statistically significant differences in disease burden and proximity to onset of symptoms. CONCLUSIONS: Members of the HDC group close to the manifest phase performed more poorly on tests assessing information processing speed and attention. Prefrontal cognitive dysfunction appears early, several years before the motor diagnosis of HD.


Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Doença de Huntington , Humanos , Doença de Huntington/genética , Cognição , Efeitos Psicossociais da Doença
14.
Rehabilitacion (Madr) ; 58(1): 100816, 2024.
Artigo em Espanhol | MEDLINE | ID: mdl-37862777

RESUMO

INTRODUCTION AND OBJECTIVE: Hippotherapy (HPOT) and hippotherapy simulators (SHPOT) are used in children with cerebral palsy to achieve their maximum functionality and independence. The aim is to find out if HPOT and SHPOT produce the same effects on balance, gross motor function, and postural control in children under 18 years old with cerebral palsy. MATERIALS AND METHODS: The keywords used were: hippotherapy, equine-assisted therapy and cerebral palsy. The databases used were PeDro, Scopus, LILACS, ScienceDirect, Cochrane Library, Web of Science and CINAHL Complete (Ebsco). Studies were included if they were randomized clinical trials that studied the effect of HPOT and/or SHPOT on the variables mentioned in these patients. RESULTS: Four studies assessed balance, 4 studied gross motor function, and 2 investigated postural control. Both HPOT and SHPOT produced benefits in all of them. CONCLUSIONS: According to the studied variables both interventions produce similar improvements. Although, they increase with HPOT possibly due to greater sensory stimulation.


Assuntos
Paralisia Cerebral , Terapia Assistida por Cavalos , Criança , Animais , Cavalos , Humanos , Adolescente , Paralisia Cerebral/terapia , Equilíbrio Postural/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Hernia ; 28(1): 33-42, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37776406

RESUMO

BACKGROUND: To date, there is limited data on the association of active smoking and 30-day wound events following inguinal hernia repair (IHR) with mesh. We aimed to determine if active smoking at the time of IHR with mesh was associated with worse 30-days wound events and additional morbidity outcomes using the Abdominal Core Health Quality Collaborative (ACHQC) database. METHODS: All adult patients undergoing elective, IHR with mesh who had 30-day follow-up data available were identified within the ACHQC database. Smokers were defined as having used nicotine within the 30 days prior to surgery. A 1:1 propensity score matched analysis was performed comparing smokers to non-smokers, controlling for factors previously shown to be associated with postoperative wound events. The effect of smoking on 30-day wound events and additional morbidity outcomes following IHR with mesh was investigated using Chi-square or Fisher's exact test for categorical data and Wilcoxon ranked test for continuous data. RESULTS: A total of 17,543 patients met inclusion criteria; 1855 (11%) were active smokers at the time of minimally invasive IHR with mesh. A total of 3694 patients were used for the matched analysis. There were no statistically significant differences between the non-smokers and smokers with respect to the incidence of surgical site infection (p = 0.10), surgical site occurrences (p = 0.22), or surgical site occurrences requiring procedural intervention (p = 0.64). Non-smokers were significantly more likely to be readmitted to the hospital and had significantly less improvement in all pain domains following IHR with mesh. CONCLUSIONS: Active smoking at the time of IHR with mesh is not associated with worse 30-day wound or additional morbidity and mortality outcomes. Based on these results, preoperative smoking cessation for all patients undergoing IHR may not reduce 30-day morbidity.


Assuntos
Hérnia Inguinal , Adulto , Humanos , Hérnia Inguinal/cirurgia , Fumar/efeitos adversos , Fumar/epidemiologia , Telas Cirúrgicas/efeitos adversos , Herniorrafia/efeitos adversos , Herniorrafia/métodos , Incidência
17.
Chemosphere ; 349: 140949, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38096990

RESUMO

Most research on pharmaceutical presence in the environment to date has focused on smaller scale assessments of freshwater and riverine systems, relying mainly on assays of water samples, while studies in marine ecosystems and of exposed biota are sparse. This study investigated the pharmaceutical burden in bonefish (Albula vulpes), an important recreational and artisanal fishery, to quantify pharmaceutical exposure throughout the Caribbean Basin. We sampled 74 bonefish from five regions, and analyzed them for 102 pharmaceuticals. We assessed the influence of sampling region on the number of pharmaceuticals, pharmaceutical assemblage, and risk of pharmacological effects. To evaluate the risk of pharmacological effects at the scale of the individual, we proposed a metric based on the human therapeutic plasma concentration (HTPC), comparing measured concentrations to a threshold of 1/3 the HTPC for each pharmaceutical. Every bonefish had at least one pharmaceutical, with an average of 4.9 and a maximum of 16 pharmaceuticals in one individual. At least one pharmaceutical was detected in exceedance of the 1/3 HTPC threshold in 39% of bonefish, with an average of 0.6 and a maximum of 11 pharmaceuticals exceeding in a Key West individual. The number of pharmaceuticals (49 detected in total) differed across regions, but the risk of pharmacological effects did not (23 pharmaceuticals exceeded the 1/3 HTPC threshold). The most common pharmaceuticals were venlafaxine (43 bonefish), atenolol (36), naloxone (27), codeine (27), and trimethoprim (24). Findings suggest that pharmaceutical detections and concentration may be independent, emphasizing the need to monitor risk to biota regardless of exposure diversity, and to focus on risk quantified at the individual level. This study supports the widespread presence of pharmaceuticals in marine systems and shows the utility of applying the HTPC to assess the potential for pharmacological effects, and thus quantify impact of exposure at large spatial scales.


Assuntos
Ecossistema , Poluentes Químicos da Água , Humanos , Animais , Peixes , Região do Caribe , Biota , Preparações Farmacêuticas , Poluentes Químicos da Água/toxicidade , Monitoramento Ambiental
19.
bioRxiv ; 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38045341

RESUMO

Here we report the discovery of MED6-189, a new analogue of the kalihinol family of isocyanoterpene (ICT) natural products. MED6-189 is effective against drug-sensitive and -resistant P. falciparum strains blocking both intraerythrocytic asexual replication and sexual differentiation. This compound was also effective against P. knowlesi and P. cynomolgi. In vivo efficacy studies using a humanized mouse model of malaria confirms strong efficacy of the compound in animals with no apparent hemolytic activity or apparent toxicity. Complementary chemical biology, molecular biology, genomics and cell biological analyses revealed that MED6-189 primarily targets the parasite apicoplast and acts by inhibiting lipid biogenesis and cellular trafficking. Genetic analyses in P. falciparum revealed that a mutation in PfSec13, which encodes a component of the parasite secretory machinery, reduced susceptibility to the drug. The high potency of MED6-189 in vitro and in vivo, its broad range of efficacy, excellent therapeutic profile, and unique mode of action make it an excellent addition to the antimalarial drug pipeline.

20.
Rev. chil. infectol ; 40(6)dic. 2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1530005

RESUMO

Introducción: El uso de tigeciclina ha ido en aumento en los últimos años, debido al incremento de la resistencia bacteriana y la escasez de alternativas terapéuticas. Objetivo: Caracterizar y evaluar las prescripciones de tigeciclina en pacientes internados en un hospital universitario, durante los años 2017 y 2018. Metodología: Estudio observacional retrospectivo, donde se caracterizaron los pacientes, las terapias, la microbiología asociada, los desenlaces clínicos y las reacciones adversas asociadas a los tratamientos con tigeciclina. Se determinó la proporción de prescripciones apropiadas por un comité de expertos y el consumo de tigeciclina medido en DDD/100 camas-día. Resultados: Se caracterizaron 89 pacientes, de los cuales 67 (75,3%) cumplieron los criterios de selección. El 53,7% de los pacientes eran hombres, con una edad promedio de 60 ± 15 años. El principal motivo de hospitalización fue quirúrgico (65,7%). El 67,1% de los tratamientos con tigeciclina se inició en una Unidad de Paciente Critico y el foco de infección predominante fue abdominal (64,3%). El 50% de las terapias con tigeciclina fueron dirigidas según la microbiología identificada. En 65,7% de los casos se usó tigeciclina como monoterapia en la dosis habitual (62,9%). Náuseas (8,6%), diarrea (7,1%) y vómitos (4,3%) fueron los efectos adversos más reportados. El 84,3% de los tratamientos se consideraron apropiados. El año 2017 se consumió 0,4 DDD/100 camas-día y 0,6 DDD/100 camas/día el 2018, siendo la UCI el servicio que presentó el mayor uso en ambos años. Discusión: Tigeciclina fue utilizada principalmente en monoterapia para el tratamiento de infecciones intraabdominales en pacientes hospitalizados, por motivos quirúrgicos, en una unidad de paciente crítico, en las dosis habituales recomendadas de 100 mg como dosis de carga seguida de 50 mg cada 12 hs IV. En 50% de los casos, la terapia fue dirigida según microbiología. Los eventos adversos más habituales fueron los gastrointestinales. Conclusión: La mayoría de las terapias prescritas fueron consideradas apropiadas por el comité de expertos.


Background: The use of tigecycline has been increasing in recent years, due to increase in bacterial resistance and the scarcity of therapeutics alternatives. Aim: To characterize and evaluate the tigecycline prescriptions of patients hospitalized in a university hospital, during the years 2017 and 2018. Methods: A retrospective observational study was carried out, where the patients, the therapies, the associated microbiology, the clinical outcomes and the adverse reactions associated with tigecycline were characterized. The proportion of appropriate prescriptions was determined by committee of experts and the consumption of tigecycline measure in DDD/100 bed-days. Results: 89 patients who used tigecycline were characterized, of which 67 (75.3%) met the selection criteria. 53.7% of the patients were male, with a mean age of 60 +/- 15 years The main reason for hospitalization was surgical (65.7%). 67.1% of the treatments with tigecycline were started in a critical patient unit and the predominant focus of the infection was the abdomen (64.3%). 50% of the therapies with tigecycline were ordered according to the identified microbiology. In 65.7% of the cases, tigecyclin was used as monotherapy at the usual dose (62.9%). Nausea (8.6%), diarrhea (7.1%) and vomiting (4.3%) were the most reported adverse events. 84.3% of the treatments were considered appropriate. In 2017, 0.4 DDD/100 bed/days were consumed and 0.6 DDD/100 bed/days in 2018, with de ICU being the service that presented the highest use in both years. Discussion: Tigecycline was mainly used as monotherapy for the treatment of intra-abdominal infections in patients hospitalized for surgical reasons in a critical patient unit at the usual doses of 100 mg loading followed by 50 mg every 12 hours IV. In 50% of the case the therapy was directed according to microbiology. The most common adverse events were gastrointestinal. Conclusion: Most of the prescribed therapies were considered appropriate by the expert committee.

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