RESUMEN
The incidence of frailty and cardiovascular disease (CVD) increases as the population ages. There is a bidirectional relationship between frailty and CVD, and both conditions share several risk factors and underlying biological mechanisms. Frailty has been established as an independent prognostic marker in patients with CVD. Moreover, its presence significantly influences both primary and secondary prevention strategies for adults with CVD while also posing a barrier to the inclusion of these patients in pivotal clinical trials and advanced cardiac interventions. This review discusses the current knowledge base on the relationship between frailty and CVD, how managing CVD risk factors can modify frailty, the influence of frailty on CVD management, and future directions for frailty detection and modification in patients with CVD.
Asunto(s)
Enfermedades Cardiovasculares , Fragilidad , Humanos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Fragilidad/epidemiología , Fragilidad/complicaciones , Fragilidad/diagnóstico , Anciano , Factores de Riesgo , Anciano Frágil , Pronóstico , Medición de Riesgo , Evaluación Geriátrica/métodos , Factores de Riesgo de Enfermedad Cardiaca , IncidenciaRESUMEN
Museum collections are an important source for resolving taxonomic issues and species delimitation. Type specimens as name-bearing specimens, traditionally used in morphology-based taxonomy, are, due to the progress in historical DNA methodology, increasingly used in molecular taxonomic studies. Museum collections are subject to constant deterioration and major disasters. The digitisation of collections offers a partial solution to these problems and makes museum collections more accessible to the wider scientific community. The Extended Specimen Approach (ESA) is a method of digitisation that goes beyond the physical specimen to include the historical information stored in the collection. The collections of the Natural History Museum Vienna represent one of the largest non-university research centres in Europe and, due to their size and numerous type specimens, are frequently used for taxonomic studies by visiting and resident scientists. Recently, a version of ESA was presented in the common catalogue of the Fish and Evertebrata Varia collections and extended to include genetic information on type specimens in a case study of a torpedo ray. Here the case study was extended to a heterogeneous selection of historical type series from different collections with the type locality of Vienna. The goal was to apply the ESA, including genetic data on a selected set of type material: three parasitic worms, three myriapods, two insects, twelve fishes, and one bird species. Five hundred digital items (photographs, X-rays, scans) were produced, and genetic analysis was successful in eleven of the 21 type series. In one case a complete mitochondrial genome was assembled, and in another case ten short fragments (100-230 bp) of the cytochrome oxidase I gene were amplified and sequenced. For five type series, genetic analysis confirmed their taxonomic status as previously recognised synonyms, and for one the analysis supported its status as a distinct species. For two species, genetic information was provided for the first time. This catalogue thus demonstrates the usefulness of ESA in providing digitised data of types that can be easily made available to scientists worldwide for further study.
RESUMEN
BACKGROUND: Previous studies have suggested that firefighters, police officers and civil servants in the education sector, particularly in Western countries, are vulnerable to mental stress and disorders; however, evidence for this association in South Korea is lacking. AIMS: This study aimed to identify whether firefighters, police officers and teachers are at a higher risk for occupational mental health disorders. METHODS: We used workers' compensation claims from civil servants (2009-18). Our target population comprised 46â 209 civil servants (9009 civil servants in administrative and technical positions, 23 107 police officers, 4417 firefighters and 8676 civil servants in the educational sector). Occupational and environmental medicine physicians and medical doctors defined and confirmed mental disorders. We conducted Cox proportional hazards regression analyses to evaluate civil servants' risk of occupational mental health disorders. RESULTS: Compared with the civil servants in administrative and technical positions, civil servants in the education sector (hazard ratio [HR]â =â 2.16; 95% confidence interval [CI]:1.65-2.84) showed a statistically significant increased risk of mental disorders; conversely, firefighters did not (HRâ =â 0.80; 95% CI 0.51-1.27). Police officers had a significantly decreased mental disorder risk compared with civil servants in administrative and technical positions (HRâ =â 0.17; 95% CI 0.11-0.25). CONCLUSIONS: The risk of occupational mental health disorders was higher in civil servants in the education sector but lower in police officers and firefighters than civil servants in administrative and technical positions. Further studies on civil servants' mental health awareness are required to confirm our results.
Asunto(s)
Bomberos , Trastornos Mentales , Enfermedades Profesionales , Policia , Indemnización para Trabajadores , Humanos , República de Corea/epidemiología , Trastornos Mentales/epidemiología , Masculino , Adulto , Femenino , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/psicología , Bomberos/estadística & datos numéricos , Bomberos/psicología , Persona de Mediana Edad , Policia/estadística & datos numéricos , Indemnización para Trabajadores/estadística & datos numéricos , Factores de Riesgo , Modelos de Riesgos ProporcionalesRESUMEN
High hydrostatic pressure stabilized galactose oxidase (GaOx) at 70.0-80.0°C against thermal inactivation. The pseudo-first-order rate constant of inactivation kinact decreased by a factor of 8 at 80°C and by a factor of 44 at 72.5°C. The most pronounced effect of pressure was at the lowest studied temperature of 70.0°C with an activation volume of inactivation ΔV of 78.8 cm3 mol-1. The optimal pressure against thermal inactivation was between 200 and 300 MPa. Unlike other enzymes, as temperature increased the ΔV of inactivation decreased, and as pressure increased the activation energy of inactivation Eai increased. Combining the results for GaOx with earlier research on the pressure-induced stabilization of other enzymes suggests that ΔV of inactivation correlates with the total molar volume of cavities larger than ~100 Å3 in enzyme monomers for enzymes near the optimal pH and whose thermal unfolding is not accompanied by oligomer dissociation.
Asunto(s)
Estabilidad de Enzimas , Galactosa Oxidasa , Presión Hidrostática , Galactosa Oxidasa/química , Galactosa Oxidasa/metabolismo , Calor , TemperaturaRESUMEN
Community treatment of hypertension in sub-Saharan Africa is hampered by gaps at several stages of the care cascade. We compared blood pressure (BP) levels (systolic, diastolic and pulse pressures) in four groups of participants by hypertension and treatment status. We conducted a nationally representative survey of adults 35 years and older using a multistage sampling strategy based on the 2013 Gambia Population and Housing Census. The BP measurements were taken in triplicate 5 min apart, and the average of the last two measurements was used for analysis. Systolic and diastolic BP levels and pulse pressure were compared by hypertension status using mean and 95% confidence intervals (CI). 53.1% of the sample were normotensive with mean systolic BP (SBP) of 119.2 mmHg (95% CI, 118.7-119.6) and diastolic BP (DBP) of 78.1 mmHg (77.8-78.3). Among individuals with hypertension, mean SBP was 148.7 mmHg (147.7-149.7) among those unaware of their hypertension, 152.2 mmHg (151.0-153.5) among treated individuals and was highest in untreated individuals at 159.3 mmHg (157.3-161.2). The findings were similar for DBP levels, being 93.9 mmHg (93.4-94.4) among the unaware, 95.1 mmHg (94.4-95.8) among the treated and highest at 99.1 mmHg (98.1-100.2) in untreated participants. SBP and DBP were higher in men, and SBP was as expected higher in those aged ≥55 years. BP level was similar in urban and rural areas. Our data shows high BP levels among participants with hypertension including those receiving treatment. Efforts to reduce the health burden of hypertension will require inputs at all levels of the care cascade.
Asunto(s)
Antihipertensivos , Presión Sanguínea , Hipertensión , Humanos , Hipertensión/epidemiología , Hipertensión/fisiopatología , Hipertensión/tratamiento farmacológico , Hipertensión/diagnóstico , Gambia/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Presión Sanguínea/fisiología , Adulto , Anciano , Antihipertensivos/uso terapéutico , Determinación de la Presión Sanguínea/métodos , Determinación de la Presión Sanguínea/estadística & datos numéricos , Estudios Transversales , Población Rural/estadística & datos numéricos , PrevalenciaRESUMEN
Although patient-derived xenografts (PDX) are commonly used for preclinical modeling in cancer research, a standard approach to in vivo tumor growth analysis and assessment of antitumor activity is lacking, complicating the comparison of different studies and determination of whether a PDX experiment has produced evidence needed to consider a new therapy promising. We present consensus recommendations for assessment of PDX growth and antitumor activity, providing public access to a suite of tools for in vivo growth analyses. We expect that harmonizing PDX study design and analysis and assessing a suite of analytical tools will enhance information exchange and facilitate identification of promising novel therapies and biomarkers for guiding cancer therapy.
Asunto(s)
Neoplasias , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Animales , Neoplasias/patología , Neoplasias/tratamiento farmacológico , National Cancer Institute (U.S.) , Estados Unidos , Ratones , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , ConsensoRESUMEN
OBJECTIVE: The relationship between assisted reproductive techniques (ART) and the risk of asthma and allergic rhinitis (AR) is controversial. Thus, we aimed to investigate the relationship between ART and the risk of asthma and AR in a nationwide, large-scale birth cohort. PATIENTS AND METHODS: This study utilized the National Health Insurance Service data in South Korea to conduct a nationwide, large-scale, population-based birth cohort. We included all infants born between 2017 and 2018. AR, asthma, food allergies, and atopic dermatitis were defined using the International Classification of Diseases tenth edition codes. Asthma was classified as allergic or non-allergic based on accompanying allergic diseases (AR, food allergy, or atopic dermatitis). Using 1:10 propensity score matching, we compared infants conceived through ART with those conceived naturally (non-ART). After matching, logistic regression was used to compare the hazard ratio for asthma and AR between the two groups. RESULTS: We included 543,178 infants [male infants, 280,194 (51.38%)]. After matching, 8,925 and 74,229 infants were selected for the ART and non-ART groups, respectively. The ART group showed a decreased risk of asthma in the offspring [adjusted hazard ratio (aHR), 0.45; 95% confidence interval (CI), 0.41-0.48]. Similarly, for AR, being conceived by ART was associated with a decreased risk of AR (aHR, 0.25; 95% CI, 0.12-0.37). ART offspring showed a decreased risk of asthma and AR in offspring compared to that observed in non-ART offspring. CONCLUSIONS: Our study offers important insights for clinicians, researchers, and parents regarding the health outcomes of ART-conceived infants and enhances our understanding of ART's impact on respiratory health.
Asunto(s)
Asma , Dermatitis Atópica , Rinitis Alérgica , Lactante , Humanos , Masculino , Estudios de Cohortes , Dermatitis Atópica/epidemiología , Asma/epidemiología , Rinitis Alérgica/epidemiología , Rinitis Alérgica/complicaciones , República de Corea/epidemiología , Técnicas Reproductivas Asistidas/efectos adversosRESUMEN
OBJECTIVE: The aim of the study was to investigate the "Internet + rehabilitation guidance" under the theory of Information-Knowledge-Attitude-Practice (IKAP) in patients with esophageal cancer during the perioperative period and to analyze the influence on the short-term prognosis of patients with esophageal cancer. PATIENTS AND METHODS: From April 2022 to February 2023, 118 patients who underwent radical esophagectomy in the First Hospital of Huai'an Affiliated Hospital of Nanjing Medical University were enrolled using the convenience sampling method. They were divided into the IKAP group (59 cases) and the Control Group (Group C) (59 cases), according to the random number table method. The conventional intervention was performed during the perioperative period, and the IKAP group was also given "Internet + rehabilitation guidance" based on IKAP theory. The first postoperative defecation time, exhaust time, feeding time, discharge time, and postoperative complication rate of the two groups were compared. Meanwhile, blood samples were collected before surgery and 1, 3, 7, and 30 days after surgery (at outpatient review) for the detection of inflammatory factor indexes and nutritional indexes. RESULTS: Patients within the IKAP group showed a shorter first postoperative exhaust and defecation time, eating time, and hospital compared to the control group (p<0.05). Before surgery, there was no significant difference in serum inflammatory factors and nutritional indexes between the two groups (p>0.05). Comparing the levels of serum inflammatory factors in the two groups after surgery, the levels of CRP and IL-6 in the IKAP group were lower than those in the control group on days 1, 3, and 7 after surgery. After 30 days, the serum CRP level was found to be lower than the control group, but no statistical difference with the control level of serum IL-6 (p<0.05) was found. Compared with the serum nutritional index levels in the two groups: 1 d after surgery, the serum HGB, PA, and TRF levels were not different (p>0.05). The serum ALB level in the IKAP group was higher than that in the control group (p<0.05). Postoperative 3 d, 7 d, the serum levels of HGB, ALB, PA, and TRF in the IKAP group were higher than those in the control group (p<0.05). After 30 d, there was no statistical difference in serum HGB levels between the two groups (p<0.05); Serum ALB, PA, and TRF levels in the IKAP group were higher than those in the control group (p<0.05). From preoperative to 30 days after surgery, serum CRP and IL-6 levels in 2 groups were first increased and then decreased, while serum HGB, ALB, PA, and TRF levels were first decreased and then increased. After surgery, the IKAP group showed a greater incidence of complications in patients than in controls (p<0.05). CONCLUSIONS: In patients with esophageal cancer, perioperative "Internet + rehabilitation guidance" based on IKAP theory can effectively shorten the postoperative gastrointestinal function recovery time and rapidly reduce the inflammatory response, improving the nutritional status of the body, thereby reducing the risk of short-term postoperative complications.
Asunto(s)
Neoplasias Esofágicas , Interleucina-6 , Humanos , Pronóstico , Complicaciones Posoperatorias/etiología , Periodo Perioperatorio/efectos adversos , Inflamación/complicaciones , Neoplasias Esofágicas/cirugíaRESUMEN
PURPOSE OF REVIEW: To define, describe, and identify potential solutions for health disparities in the uninsured and underinsured with migraine in the USA. RECENT FINDINGS: Uninsured and underinsured patients with migraine experience health disparities in diagnosis and treatment of migraine. Migraine patients have higher healthcare costs and higher employment disability, which contribute to a higher likelihood of uninsured or underinsured status. Uninsured or underinsured status, combined with factors such as race, socioeconomic status, geographic location, and care location, are correlated with delays in or decreased migraine diagnosis and treatment. Migraine prevalence is increased in the uninsured and underinsured. Potential solutions include advocacy for policy changes that improve access to care, increasing awareness and representation of underrepresented groups, providing resources to patients to reduce costs, and active patient engagement in migraine care. Continued efforts from all stakeholders have the potential to reduce health disparities in uninsured and underinsured patients with migraine, reducing disability and improving quality of life.
Asunto(s)
Pacientes no Asegurados , Trastornos Migrañosos , Humanos , Estados Unidos/epidemiología , Calidad de Vida , Trastornos Migrañosos/diagnóstico , Trastornos Migrañosos/epidemiología , Trastornos Migrañosos/terapia , EmpleoRESUMEN
BACKGROUND: As countries progress through economic and demographic transition, chronic non-communicable diseases (NCDs) overtake a previous burden of infectious diseases. We investigated the prevalence of hypertension, diabetes, obesity, and multimorbidity in older adults in The Gambia. METHODS: We embedded a survey on NCDs into the nationally representative 2019 Gambia National Eye Health Survey of adults aged 35 years or older. We measured anthropometrics, capillary blood glucose, and blood pressure together with sociodemographic information, personal and family health history, and information on smoking and alcohol consumption. Hypertension was defined as systolic blood pressure of 140 mmHg or more, diastolic blood pressure of 90 mmHg or more, or receiving treatment for hypertension. Diabetes was defined as fasting capillary blood glucose of 7 mmol/L or more, random blood glucose of 11·1mmol/L or more, or previous diagnosis or treatment for diabetes. Overweight was defined as BMI of 25-29·9 kg/m2 and obesity as 30 kg/m2 or more. Multimorbidity was defined as the coexistence of two or more conditions. We calculated weighted crude and adjusted estimates for each outcome by sex, residence, and selected sociodemographic factors. FINDINGS: We analysed data from 9188 participants (5039 [54·8%] from urban areas, 6478 [70·5%] women). The prevalence of hypertension was 47·0%; 2259 (49·3%) women, 2052 (44·7%) men. The prevalence increased with age, increasing from 30% in those aged 35-45 years to over 75% in those aged 75 years and older. Overweight and obesity increased the odds of hypertension, and underweight reduced the odds. The prevalence of diabetes was 6·3% (322 [7·0%] women, 255 [5·6%] men), increasing from 3·8% in those aged 35-44 years to 9·1% in those aged 65-75 years, and then declining. Diabetes was much more common among urban residents, especially in women (peaking at 13% by age 65 years). Diabetes was strongly associated with BMI and wealth index. The prevalence of obesity was 12·0% and was notably higher in women than men (880 [20·2%] vs 170 [3·9%]). Multimorbidity was present in 932 (10·7%), and was more common in women than men (694 [15·9] vs 238 [5·5]). The prevalence of smoking was 9·7%; 5 (0·1%) women, 889 (19·3%) men. Alcohol consumption in the past year was negligible. INTERPRETATION: We have documented high levels of NCDs and associated risk factors in Gambian adults. This presents a major stress on the country's fragile health system that requires an urgent, concerted, and targeted mutisectoral strategy. FUNDING: The Queen Elizabeth Diamond Jubilee Trust and Wellcome Trust.
Asunto(s)
Diabetes Mellitus , Hipertensión , Masculino , Femenino , Humanos , Anciano , Adulto , Persona de Mediana Edad , Gambia , Sobrepeso/epidemiología , Prevalencia , Estudios Transversales , Glucemia , Multimorbilidad , Factores de Riesgo , Obesidad/epidemiología , Obesidad/complicaciones , Diabetes Mellitus/epidemiología , Hipertensión/epidemiología , Hipertensión/complicacionesRESUMEN
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with various systemic and ocular complications. This study aimed to investigate the prevalence, risk factors, and clinical characteristics of ocular complications in a cohort of Korean AD patients. METHODS: A retrospective review of medical records was conducted for AD patients who visited the dermatology and ophthalmology clinics at the same institution. Demographic data, clinical characteristics, and types of ocular complications were recorded. Logistic regression analysis was performed to identify factors associated with ocular complications. RESULTS: A total of 212 AD patients were included in the study. The intraocular complications had a prevalence of 1.9%, whereas ocular surface diseases were observed more frequently, with prevalence of 13.2%. Among the ocular complications, blepharitis was the most prevalent, followed by atopic keratoconjunctivitis. Subcapsular cataract, atrophic hole, and retinal detachment were also observed. The head and neck score in the Eczema Area and Severity Index (EASI) emerged as a significant predictor for intraocular complications, independent of age, gender, total EASI score, and family history. No significant association was found between total EASI score and ocular surface disease. CONCLUSION: This study provides insights into the prevalence and risk factors of ocular complications in Korean AD patients. The head and neck score in EASI was identified as a significant predictor for intraocular complications. These findings emphasize the importance of comprehensive evaluation and interdisciplinary care for AD patients, particularly in identifying and managing potential vision-threatening complications.
Asunto(s)
Dermatitis Atópica , Índice de Severidad de la Enfermedad , Humanos , Dermatitis Atópica/epidemiología , Dermatitis Atópica/complicaciones , Masculino , Femenino , República de Corea/epidemiología , Estudios Retrospectivos , Adulto , Prevalencia , Adulto Joven , Persona de Mediana Edad , Adolescente , Factores de Riesgo , Niño , Blefaritis/epidemiología , Blefaritis/etiología , Preescolar , Oftalmopatías/epidemiología , Oftalmopatías/etiología , Catarata/epidemiología , Queratoconjuntivitis/epidemiología , Anciano , Conjuntivitis Alérgica/epidemiología , Conjuntivitis Alérgica/complicacionesRESUMEN
OBJECTIVES: This study examined diagnostic profiles and trauma history among treatment-seeking young adults with positive PTSD screens in public mental health care. METHODS: Screening for trauma history and PTSD symptoms was implemented in a community mental health service system. 266 treatment-seeking young adults (aged 18-35) endorsed trauma exposure with a score of at least 45 on the DSM-IV PTSD Checklist, indicating probable PTSD. RESULTS: Young adults with positive PTSD screens were predominantly female, minority, and diagnosed with mood disorders. Of those with positive screens, only 15% had a chart diagnosis of PTSD; 17.3% (ages 18-24) versus 14.1% (ages 25-35). Variables significantly associated with a decreased likelihood of PTSD detection included a diagnosis of schizophrenia or bipolar disorder, exposure to fewer types of traumatic events, male gender, and white race. CONCLUSION: Routine PTSD screening for young adults receiving public mental health care should be prioritized to address long-term impacts of trauma.
RESUMEN
Exposure to disinfection by-products (DBPs) has been found to induce a range of toxic effects in aquatic organism. Previous studies have consistently demonstrated that a majority of DBPs have the ability to induce in vivo toxicity in aquatic organisms. However, the impact of DBPs on the metabolic processes of Daphnia magna (D. magna) and the underlying molecular toxicity mechanisms are still not well understood. Therefore, we investigated the effects of 14 DBPs on two oxidative stress enzymes and malondialdehyde (MDA) levels in D. magna. Additionally, we employed molecular docking to simulate the toxicity of DBPs to D. magna at the molecular level. This comprehensive analysis allowed us to gain further insights into the toxicity of DBPs on D. magna. The results showed that among the aliphatic DBPs, the more bromine substituents, the lower the toxicity effect, and it's opposite in the aromatic DBPs. In the detection of oxidative stress level, catalase (CAT) enzyme and superoxide dismutase (SOD) enzyme in D. magna under compound stress showed a low increase and decrease with the increase of concentration. The level of MDA showed a positive correlation with the concentration. In the last, molecular docking simulations have shown promise in predicting the toxicity of DBPs and providing insights into their toxic effects to a certain extent, and the docking situation of P53 is slightly different. Hence, it is imperative to further regulate the presence of aromatic DBPs due to their pronounced toxic effects on D. magna, and these simulations can be complemented with actual experiments to enhance our understanding of the toxicity mechanisms of DBPs.
Asunto(s)
Desinfección , Contaminantes Químicos del Agua , Animales , Simulación del Acoplamiento Molecular , Daphnia , Estrés Oxidativo , Oxidación-Reducción , Contaminantes Químicos del Agua/metabolismoRESUMEN
Background: Hypertension is a major public health problem in sub-Saharan Africa with poor treatment coverage and high case-fatality rates. This requires assessment of healthcare performance to identify areas where intervention is most needed. To identify areas where health resources should be most efficiently targeted, we assessed the hypertension care cascade i.e., loss and retention across the various stages of care, in Gambian adults aged 35 years and above. Methods: This study was embedded within the nationally representative 2019 Gambia National Eye Health Survey of adults ≥35 years. We constructed a hypertension care cascade with four categories: prevalence of hypertension (defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, and/or current use of medication prescribed for hypertension); those aware of their diagnosis; those treated; and those with a controlled blood pressure (defined as blood pressure <140/90 mmHg). Analyses were age- and sex-standardised to the population structure of The Gambia. Logistic regression was used to assess the socio-demographic factors associated with prevalence, awareness, treatment and control of hypertension. Findings: Of 9171 participants with data for blood pressure, the prevalence of hypertension was 47.0%. Among people with hypertension, the prevalence of awareness was 54.7%, the prevalence of hypertension treatment was 32.5%, and prevalence of control was 10.0% with little difference between urban and rural residence. The cascade of care performance was better in women. However, there was no difference in achieving blood pressure control between men and women who were receiving treatment. Female sex, older age and higher body mass index were associated with higher hypertension awareness whilst having an occupation compared to being unemployed was associated with higher odds of being treated. Patients in the underweight category had higher odds of achieving blood pressure control. Interpretation: There is a high prevalence of hypertension and low performance of the health care system that impact on the hypertension care cascade among middle-aged and older adults in The Gambia. Addressing the full cascade will be paramount especially in reducing the mounting prevalence and improving diagnosis of patients with hypertension, where the greatest dividends will be gained. Funding: The Queen Elizabeth Diamond Jubilee Trust, Wellcome Trust.
RESUMEN
Crossing the blood-brain barrier in primates is a major obstacle for gene delivery to the brain. Adeno-associated viruses (AAVs) promise robust, non-invasive gene delivery from the bloodstream to the brain. However, unlike in rodents, few neurotropic AAVs efficiently cross the blood-brain barrier in non-human primates. Here we report on AAV.CAP-Mac, an engineered variant identified by screening in adult marmosets and newborn macaques, which has improved delivery efficiency in the brains of multiple non-human primate species: marmoset, rhesus macaque and green monkey. CAP-Mac is neuron biased in infant Old World primates, exhibits broad tropism in adult rhesus macaques and is vasculature biased in adult marmosets. We demonstrate applications of a single, intravenous dose of CAP-Mac to deliver functional GCaMP for ex vivo calcium imaging across multiple brain areas, or a cocktail of fluorescent reporters for Brainbow-like labelling throughout the macaque brain, circumventing the need for germline manipulations in Old World primates. As such, CAP-Mac is shown to have potential for non-invasive systemic gene transfer in the brains of non-human primates.
Asunto(s)
Encéfalo , Callithrix , Humanos , Animales , Recién Nacido , Chlorocebus aethiops , Macaca mulatta/genética , Callithrix/genética , Encéfalo/fisiología , Técnicas de Transferencia de Gen , Neuronas , Vectores Genéticos/genéticaRESUMEN
Opioids are the mainstay of pain management and sedation in critically ill patients, which can lead to the development of physiologic tolerance and dependency. The prevalence of iatrogenic opioid withdrawal syndrome (IWS) is reported as 17-32% in the ICU; however, limited evidence exists for the medical ICU patient population. OBJECTIVES: To identify the and risk factors for IWS in adult patients admitted to critical care medicine services who received greater than or equal to 24 hours of continuous opioid infusion therapy. DESIGN SETTING AND PARTICIPANTS: A prospective, observational study was conducted in a tertiary care hospital in adult medical ICU patients. Ninety-two patients who received greater than or equal to 24 hours of continuous opioid infusions were included in the study. MAIN OUTCOMES AND MEASUREMENTS: Patients were assessed daily after opioid infusion discontinuation using the Clinical Opiate Withdrawal Scale (COWS) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) opioid withdrawal criteria for a maximum of 5 days. The primary outcome was the prevalence of IWS of moderate severity or greater using COWS. Secondary outcomes included the prevalence of IWS diagnosis of any severity based on COWS, the prevalence of IWS diagnosis based on a positive DSM-V score, and the identification of potential risk factors for developing IWS of any severity. RESULTS: Four hundred forty-seven patients received greater than or equal to 24 hours of continuous opioid therapy. Of these, 385 were excluded, leaving 92 patients included in the final analysis. Except for a higher prevalence of psychiatric history in the IWS-positive group, baseline characteristics were similar. Overall, 11 patients (12%) developed IWS of moderate severity or greater, based on COWS. The IWS-positive group also had longer durations of opioid infusions, higher cumulative opioid infusion doses, higher mean daily doses, and higher infusion rates at any given time. The concomitant use of dexmedetomidine (38.3 vs 15.6%, p = 0.014) and benzodiazepines (63.8 vs 37.8%, p = 0.021) during or after the opioid infusion were significantly higher in the IWS-positive group compared with the IWS-negative group. No significant differences were found between the two groups for scheduled or as needed opioids after cessation of the opioid infusion. Continuous opioid infusions greater than or equal to 72 hours and total daily dose greater than or equal to 1,200 µg were found to be independent predictors for the development of iatrogenic opioid withdrawal via logistic regression. CONCLUSIONS AND RELEVANCE: Approximately one in every eight patients receiving continuous infusion opioid for greater than 24 hours while mechanically ventilated in the medical ICU will develop IWS of moderate severity or greater; this increases to one in three patients diagnosed with DSM-V criteria or any level of IWS severity. Patients receiving opioid infusions greater than or equal to 72 hours, or a total daily fentanyl dose of greater than or equal to 1,200 µg (~ 50 µg/hr) are at a higher risk for developing IWS and should be monitored as part of clinical practice when opioid infusions are discontinued.