Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 170
Filtrar
2.
Epilepsia ; 2021 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-33464599

RESUMEN

OBJECTIVE: There is a growing recognition of immune-mediated causes in patients with focal drug-resistant epilepsy (DRE); however, they are not systematically assessed in the pre-surgical diagnostic workup. Early diagnosis and initiation of immunotherapy is associated with a favorable outcome in immune-mediated seizures. Patients with refractory focal epilepsy with neuronal antibodies (Abs) tend to have a worse surgical prognosis when compared to other etiologies. METHODS: We studied the prevalence of serum Abs in patients ≥18 years of age with DRE of unknown cause before surgery. We proposed and calculated a clinical APES (Antibody Prevalence in Epilepsy before Surgery) score for each subject, which was modified based on Dubey's previously published APE2 score. RESULTS`: A total of 335 patients were screened and 86 subjects were included in final analysis. The mean age at the time of recruitment was 44.84 ± 14.86 years, with age at seizure onset 30.89 ± 19.88 years. There were no significant differences among baseline clinical features between retrospective and prospective sub-cohorts. The prevalence of at least one positive Ab was 33.72%, and central nervous system (CNS)-specific Abs was 8.14%. APES score ≥4 showed slightly better overall prediction (area under the curve [AUC]: 0.84 vs 0.74) and higher sensitivity (100% vs 71.4%), with slightly lower but similar specificity (44.3% vs 49.4%), when compared to APE2 score ≥4. For subjects who had available positron emission tomography (PET) results and all components of APES score (n = 60), the sensitivity of APES score ≥4 yielded a similar prediction potential with an AUC of 0.80. SIGNIFICANCE: Our findings provide persuasive evidence that a subset of patients with focal DRE have potentially immune-mediated causes. We propose an APES score to help identify patients who may benefit from a workup for immune etiologies during the pre-surgical evaluation for focal refractory epilepsy with unknown cause.

3.
Breast J ; 2020 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-33270304

RESUMEN

INTRODUCTION: Lobular neoplasia is a term encompassing both atypical lobular hyperplasia and lobular carcinoma in situ. These pathological findings are of uncertain malignant potential and predispose to a higher lifetime risk of breast cancer. Debate surrounds the management of such lesions, with the rationale for diagnostic excision based on the possibility of upgrading to malignancy. In this study, we report the upgrade rate of these lesions and risk of subsequent development of breast cancer. METHODS: This is a retrospective review of a prospectively maintained data base of all biopsies of breast screening-detected abnormalities in a single Irish breast-screening unit. We included all patients with lobular neoplasia on core needle biopsy who underwent diagnostic excision from 2005 to 2012. We excluded those who had concurrent high-risk lesions on biopsy. End points included upgrade rate and subsequent diagnosis of malignancy on follow-up. RESULTS: During the study period, 66 patients met criteria for inclusion, with a mean age of 53.74 years. Upgrade rate following excision was 13.64% (n = 9/66). Of those not upgraded, 7.02% (n = 4/57) were subsequently diagnosed with malignancy. Median time to diagnosis was 59.61 months (range = 10.5-124.4). CONCLUSION: There is a significant rate of upgrade following diagnostic excision of lobular neoplasia, supporting the practice of diagnostic excision. There is an increased lifetime risk of breast cancer for women with a diagnosis of lobular neoplasia, with many of these cancers occurring outside the standard five-year monitoring period, suggesting a potential benefit in extending surveillance.

4.
Regul Toxicol Pharmacol ; 119: 104823, 2020 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-33212192

RESUMEN

Nerve agent exposure is generally treated by an antidote formulation composed of a muscarinic antagonist, atropine sulfate (ATR), and a reactivator of acetylcholinesterase (AChE) such as pralidoxime, obidoxime (OBI), methoxime, trimedoxime or HI-6 and an anticonvulsant. Organophosphates (OPs) irreversibly inhibit AChE, the enzyme responsible for termination of acetylcholine signal transduction. Inhibition of AChE leads to overstimulation of the central and peripheral nervous system with convulsive seizures, respiratory distress and death as result. The present study evaluated the efficacy and pharmacokinetics (PK) of ATR/OBI following exposure to two different VX dose levels. The PK of ATR and OBI administered either as a single drug, combined treatment but separately injected, or administered as the ATR/OBI co-formulation, was determined in plasma of naïve guinea pigs and found to be similar for all formulations. Following subcutaneous VX exposure, ATR/OBI-treated animals showed significant improvement in survival rate and progression of clinical signs compared to untreated animals. Moreover, AChE activity after VX exposure in both blood and brain tissue was significantly higher in ATR/OBI-treated animals compared to vehicle-treated control. In conclusion, ATR/OBI has been proven to be efficacious against exposure to VX and there were no PK interactions between ATR and OBI when administered as a co-formulation.

5.
Toxicol Lett ; 332: 36-41, 2020 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-32629075

RESUMEN

The study examined the degradation of riot control agents (RCAs): 2-chloroacetophenone (CN), 2-chlorobenzalmalononitrile (CS), and capsaicin, using the Reactive Skin Decontamination Lotion Kit (RSDL®) lotion and evaluated the the direct liquid phase reactivity of the RSDL lotion component with each RCA. RSDL lotion was mixed with the selected RCAs at different molar ratios. Reactivity of the active ingredient potassium 2,3-butanedione monoximate (KBDO) with the RCA was observed for one hour. Samples of 10 µL were taken and quenched, analyzed for residual RCA using LC-MS. CN, was degraded at molar ratios of two and above in less than 2 min. At a molar ratio of 1:1 KBDO:CN, ∼90 % of CN was degraded within 2 min, the remaining 10 % residual CN was observed for one hour without any change. CS, degradation of more than 68 % of CS was achieved at 20:1 M ratio of KBDO:CS within 1 h of reaction time. For capsaicin, no degradation was observed regardless of the higher molar ratios of up to 20:1 and longer reaction times of up to one hour. This study provides evaluation of neutralizing action of the RSDL lotion without assessment of the physical removal component by the RSDL Kit.


Asunto(s)
Capsaicina/química , Clorobencenos/química , Descontaminación/métodos , Irritantes/química , Fármacos del Sistema Sensorial/química , Crema para la Piel/química , Gases Lacrimógenos/química , omegacloroacetofenona/química , Calibración , Capsaicina/análisis , Clorobencenos/análisis , Cromatografía Líquida de Alta Presión , Humanos , Irritantes/análisis , Fármacos del Sistema Sensorial/análisis , Piel , Gases Lacrimógenos/análisis , omegacloroacetofenona/análisis
6.
J Orthop Sports Phys Ther ; 50(6): 345, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32476581

RESUMEN

A 33-year-old man was referred to physical therapy by his primary care physician for low back pain that had been present for 7 months. The neurologic screen with mixed upper and lower motor neuron signs was of concern for spinal cord involvement. The primary care physician was contacted and magnetic resonance imaging ordered. Facet arthrosis and epidural lipomatosis were present, resulting in thoracic and lumbar spinal stenosis. J Orthop Sports Phys Ther 2020;50(6):345. doi:10.2519/jospt.2020.9059.

7.
J Oral Facial Pain Headache ; 34(2): 174-186, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32255583

RESUMEN

AIMS: To test for the possible antinociceptive effect of nifedipine in rodent models of acute and chronic neuropathic orofacial pain and the possible involvement of TRP- and NMDA-related processes in this effect. METHODS: Acute nociceptive behavior was induced by administering formalin, cinnamaldehyde, glutamate, capsaicin, or acidified saline to the upper lip or hypertonic saline to the cornea of Swiss mice. Acute nociceptive behavior was also induced by formalin injected into the TMJ or mustard oil injected into the masseter muscle of Wistar rats. The chronic pain model involved infraorbital nerve transection (IONX) in Wistar rats to induce mechanical hypersensitivity, which was assessed with von Frey hair stimulation of the upper lip. The effects of pretreatment with nifedipine or vehicle (control) were tested on the nociceptive behaviors. Docking experiments were also performed. Statistical analysis included one-way ANOVA followed by Tukey post hoc test and two-way ANOVA followed by Bonferroni post hoc test (statistical significance P < .05). RESULTS: Nifedipine produced significant antinociceptive effects in all of the acute nociceptive behaviors except that induced by capsaicin. The antinociceptive effects were attenuated by NMDA, TRPA1, or TRPM3 receptor antagonists. The IONX animals developed facial mechanical hypersensitivity, which was significantly reduced by nifedipine. The docking experiments suggested that nifedipine may interact with TRPM3 and NMDA receptors. CONCLUSION: The present study has provided novel findings in a variety of acute and chronic orofacial pain models showing that nifedipine, a selective inhibitor of L-type Ca2+ channels, can suppress orofacial nociceptive behavior through NMDA, TRPA1, and TRPM3 receptor systems.


Asunto(s)
Roedores , Canales Catiónicos TRPM , Analgésicos , Animales , Dolor Facial , Ratones , N-Metilaspartato , Nifedipino , Ratas , Ratas Wistar , Canal Catiónico TRPA1
8.
Cancer Treat Rev ; 85: 101975, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32050108

RESUMEN

The mechanisms of melanoma metastasis have been the subject of extensive research for decades. Improved diagnostic and therapeutic strategies are of increasing importance for the treatment of melanoma due to its high burden of mortality in the advanced stages of the disease. Intercellular communication is a critical event for the progression of cancer. Collective evidence suggests that exosomes, small extracellular membrane vesicles released by the cells, are important facilitators of intercellular communication between the cells and the surrounding environment. Although the emerging field of exosomes is rapidly gaining traction in the scientific community, there is limited knowledge regarding the role of exosomes in melanoma. This review discusses the multifaceted role of melanoma-derived exosomes in promoting the process of metastasis by modulating the invasive and angiogenic capacity of malignant cells. The future implications of exosome research and the therapeutic potential of exosomes are also discussed.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Exosomas/metabolismo , Melanoma/patología , Neoplasias Cutáneas/patología , Microambiente Tumoral/fisiología , Comunicación Celular , Progresión de la Enfermedad , Humanos , Melanoma/metabolismo , Invasividad Neoplásica/patología , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neovascularización Patológica/patología , Sensibilidad y Especificidad , Neoplasias Cutáneas/metabolismo
9.
Chem Biol Interact ; 318: 108980, 2020 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-32044340

RESUMEN

In this study, we assessed the efficacy of the Reactive Skin Decontamination Lotion (RSDL®) Kit against parathion and aldicarb pesticide dermal exposure in a guinea pig model. The pesticides inhibit acetylcholinesterase (AChE) leading to signs and symptoms of hyperactivity of organs due to accumulation of acetylcholine. The RSDL Kit has been shown to physically remove and chemically degrade chemical warfare agents. Degradation occurs from a nucleophilic substitution reaction between an active ingredient in the RSDL lotion, potassium 2,3-butanedione monoximate (KBDO), with susceptible sites in these compounds. In the present study, guinea pigs dermally exposed to parathion and aldicarb were decontaminated with RSDL to mitigate the toxic effects of the pesticides. It is observed that animals exposed to 749 mg/kg of parathion (n = 3) died within 24 h without RSDL decontamination; however, RSDL-treated animals (n = 3) showed only mild signs of neurotoxicity. The RSDL-treated animals had an AChE inhibition of 0-58% while the untreated animals had up to 86% inhibition. Similarly, RSDL has been demostrated to prevent aldicarb neurotoxicity effects. The percent inhibition of AChE activity during the 24 h post challenge of 9 mg aldicarb/kg of animal weight ranged from 25% to 61% with severe signs of intoxication while only up to 5% with mild or no signs of intoxication in the case of RSDL-decontaminated animals. Generally, it has been shown that the toxic effects of the organophosphate and carbamate pesticides can be prevented via decontamination using the RSDL Kit.


Asunto(s)
Aldicarb/toxicidad , Descontaminación/métodos , Insecticidas/toxicidad , Paratión/toxicidad , Aldicarb/química , Animales , Cobayas , Insecticidas/química , Paratión/química , Cuidados de la Piel/métodos , Crema para la Piel
10.
Breast J ; 26(4): 705-710, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31612568

RESUMEN

In many centers internationally, current standard of care is to excise all papillomas of the breast, despite recently reported low rates of upgrade to malignancy on final excision. The objective of this study was to determine the upgrade rate to malignancy in patients with papilloma without atypia. A retrospective review of a prospectively maintained database of all cases of benign intraductal papilloma in a tertiary referral symptomatic breast unit between July 2008 and July 2018 was performed. Patients with evidence of malignancy or atypia on core biopsy and those with a history of breast cancer or genetic mutations predisposing to breast cancer were excluded. One hundred and seventy-three cases of benign papilloma diagnosed on core biopsy were identified. Following exclusions, the final cohort comprised of 138 patients. Mean age at presentation was 51. Mean follow-up time was 9.6 months. The most common symptom was a lump (40%). Of the 124 patients who underwent excision, three had ductal carcinoma in situ and there were no cases of invasive disease, giving an upgrade rate to malignancy of 2.4%. Upgrade to other high-risk lesions (atypical lobular and ductal hyperplasia and lobular carcinoma in situ) was demonstrated in 15 cases (12.1%). Benign papilloma was confirmed in 100 cases (81.5%), and 6 (4.8%) had no residual papilloma found on final excision. Twelve patients (8.7%) were managed conservatively. Of those, one later went on to develop malignancy. Patients with a diagnosis of benign papilloma without atypia on core biopsy have a low risk of upgrade to malignancy on final pathology, suggesting that observation may be a safe alternative to surgical excision. Further research is warranted to determine which patients can be safely managed conservatively.

11.
J Dairy Sci ; 103(2): 1894-1899, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31785873

RESUMEN

Pooling colostrum is commonly practiced on Irish dairy farms. Pooling can result in dilution when colostrums with high and low IgG concentrations are mixed, thereby predisposing calves to failure of passive immunity. The objectives of this study were to compare IgG concentrations in colostrum from individual cows with colostrum pooled from several cows, and assess serum IgG concentrations, morbidity, and mortality among calves fed colostrum from their own dam, from a different cow, or pooled from several cows. We hypothesized that pooling colostrum reduces IgG concentration due to dilution compared with colostrum from individual cows, and that calves fed pooled colostrum achieve lower serum IgG concentrations than calves fed colostrum from individual cows. Calves were randomly assigned to 1 of 3 groups: (1) fed colostrum from their own dam (n = 20); (2) fed colostrum from a different dam (n = 20); or (3) fed pooled colostrum (n = 18). A sample of colostrum fed to each calf was collected. Serum samples were collected from calves at birth (0 h) and at 24 h after colostrum feeding. Colostrum and serum IgG concentrations were measured by radial immunodiffusion. Calves were weighed at birth and at weaning, and the health status of each calf was assessed twice daily. Health assessment was based on general demeanor, rectal temperature, fecal consistency, respiratory rate, and the presence of cough, nasal, or ocular discharge. Colostrum and serum IgG concentrations, and weaning weights were compared using ANOVA. Associations between group and morbidity or mortality rates were compared using χ2 or Fisher's exact tests. Median and 95% confidence intervals (95% CI) of IgG concentrations of colostrum were 99.4 (81.8-111.5), 95.2 (84.1-107.2), and 100.7 (90.5-104.4) g/L for own dam, different dam, and pooled groups, respectively. We did not find any differences in colostrum IgG concentrations among the colostrum sources. Median (95% CI) serum IgG concentrations at 24 h were 52.0 (45.6-65.9), 55.7 (51.2-65.9), and 53.1 (46.2-63.7) g/L for calves that received colostrum from own dam, different dam, and pooled, respectively. All calves achieved adequate passive immunity. Serum IgG concentrations at 24 h, weaning weights, and proportions of morbidity and mortality were not different among the 3 groups. Our results suggest that on dairy farms where median colostrum IgG concentrations are high and colostrum management is optimal, pooling has a minimal effect on passive immunity and subsequent calf health.


Asunto(s)
Bovinos/inmunología , Calostro/inmunología , Inmunización Pasiva/veterinaria , Inmunoglobulina G/sangre , Animales , Animales Recién Nacidos , Bovinos/fisiología , Estudios de Cohortes , Industria Lechera , Femenino , Estado de Salud , Inmunodifusión/veterinaria , Morbilidad , Mortalidad , Embarazo , Estudios Prospectivos , Distribución Aleatoria , Destete
12.
J Dairy Sci ; 102(8): 7459-7463, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31202644

RESUMEN

Transition milk is a source of immunoglobulin G (IgG) and could potentially be used to provide calves with passive immunity, when the IgG concentration is ≥50 g/L. Assessment of IgG concentrations in transition milk would be required before feeding and could be conducted using cow-side tests such as refractometers. Currently, limited information is available on the ability of refractometers to assess transition milk quality. We hypothesized that digital refractometry could be used to provide an accurate cow-side assessment of IgG concentrations in colostrum and transition milk, and IgG concentration in colostrum and one or more transition milking in an Irish herd is >50 g/L. The objectives of this study were to determine the IgG concentrations in colostrum and first, second, third, fourth, and fifth transition milk, and determine the utility of a digital refractometer in assessing quality of colostrum and transition milk produced by cows in a pasture-based dairy production system. A convenient sample of 75 dairy cows were enrolled. Colostrum and transition milk IgG concentrations were determined by radial immunodiffusion and refractometry. Sensitivity and specificity of the refractometer were determined and cut-off points that maximized sensitivity and specificity were determined using receiver operating characteristic curves. Median (range) IgG concentrations in colostrum and first, second, third, fourth, and fifth milking were 99.6, 43.5, 12.5, 5.3, 1.9, and 1.8 g/L, respectively. The sensitivity (0.8-1) of digital refractometry in identifying samples with low IgG concentrations in colostrum, first, second, and third transition milk was acceptable. In contrast, digital refractometry was not useful for assessing IgG concentrations in the fourth and fifth milking due to low IgG concentrations.


Asunto(s)
Calostro/inmunología , Inmunoglobulina G/análisis , Refractometría/veterinaria , Animales , Bovinos , Femenino , Inmunodifusión/veterinaria , Leche , Embarazo , Curva ROC , Refractometría/instrumentación , Sensibilidad y Especificidad
13.
Subst Use Misuse ; 54(6): 1044-1049, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30648460

RESUMEN

BACKGROUND: While there is evidence for socioeconomic inequalities in some adolescent substance use behaviors, there is limited information on how socioeconomic inequalities compare across European countries and over time. OBJECTIVES: To compare socioeconomic inequalities in problematic adolescent substance use (regular smoking, heavy episodic drinking, and cannabis use) across 24 European countries at two time points. METHODS: We use the European School Survey Project on Alcohol and Other Drugs (ESPAD) to examine socioeconomic inequalities in problematic adolescent substance use across 24 European countries in 2007 (n = 73,877) and 2011 (n = 71,060) using within country logistic regressions. Socioeconomic inequalities are measured using a relative index of inequality based on highest level of parental education relative to country of residence within survey year. Countries are ranked according to socioeconomic differentials. RESULTS: In 2007, lower socioeconomic status (SES) adolescents had significantly higher odds of heavy episodic drinking in 10 countries, regular smoking in 12 countries, and recent cannabis use in 1 country. In 2011, the number of countries were 11, 15, and 0, respectively. In 2007, lower SES adolescents had a significantly lower odds of heavy episodic drinking in one country, regular smoking in one country, and cannabis use in four countries. In 2011, the number of countries were two, one, and six, respectively. There was little evidence for changes in socioeconomic inequalities over time. CONCLUSIONS: There are large country level differences in socioeconomic inequalities in adolescent substance use.


Asunto(s)
Conducta del Adolescente , Factores Socioeconómicos , Trastornos Relacionados con Sustancias/epidemiología , Adolescente , Europa (Continente)/epidemiología , Femenino , Humanos , Masculino , Encuestas y Cuestionarios
14.
Sociol Health Illn ; 41(4): 658-672, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30582176

RESUMEN

While previous sociological research on oral health has identified the relevance of personal relationships, there is more scope to analyse the mouth through a lens of connectedness. Recent qualitative interviews with 43 older people (65+) in England and Scotland found that participants constructed relational narratives to make sense of their oral health practices. By drawing on ideas of family practices, family display and personal life, we illustrate how the mouth can be understood relationally. Participants presented their own embodied experiences as connected to the actions of their parents. Narratives also reflected how, as parents and grandparents themselves, participants tried to shape the experiences of others. In this way, oral health practices were conceptualised as being about family. This can be seen in self-narratives that demonstrated how participants located themselves as embedded in webs of ongoing relationships. We highlight the importance of narrated practices of thinking and feeling, whereby participants imagined doing oral health, and indeed family, in different ways. We thereby demonstrate how oral health practices are constituted through family connectedness and at the same time how these practices contribute to the constitution of family. Policy should therefore pay attention to family relations when promoting improvements in oral health practices.


Asunto(s)
Odontólogos , Relaciones Familiares , Miedo/psicología , Narración , Salud Bucal , Padres/psicología , Anciano , Femenino , Humanos , Masculino , Investigación Cualitativa , Apoyo Social , Reino Unido
15.
J Invest Surg ; 32(5): 393-401, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29420097

RESUMEN

Purpose/Aim: Powdered hemostats have been widely adopted for their ease-of-use; however, their efficacy has been limited resulting in applications restricted to low-level bleeds. This study investigates the use of bovine-derived gelatin particles (BGP) as a standalone hemostatic powder and compare BGP to commercially available microporous polysaccharide hemospheres (MPH). Materials and Methods: The powders were investigated for their hemostatic efficacy in a heparinized pre-clinical bleeding model limited to grade 1 and 2 bleeds on a validated intraoperative bleeding scale, which represents the accepted, clinical use of hemostatic powders. Results: At 10 minutes, the hemostatic success of lesions treated with BGP were 78% while MPH were 22%. The odds ratio for hemostatic success of BGP relative to MPH was 15.18 (95% CI: 7.37, 31.27). The 95% lower limit of the odds ratio was greater than 1. This indicates that BGP are superior to MPH (p < 0.001). The median time to hemostasis for BGP was 1.6 minutes and MPH was 14.5 minutes. The ratio for time to hemostasis of MPH relative to BGP was 9.23 (95% CI: 6.99, 12.19). This indicates that BGP achieve significantly faster time to hemostasis (p < 0.001). Conclusions: Characterization of tissue explant ultrastructure, particle size, and swelling revealed differences in the materials. BGP, in addition to absorbing fluid and concentrating clotting factors and platelets, integrate into the clot and stabilize the fibrin matrix. BGP have advantages over MPH in terms of speed and efficacy. BGP are a favorable biomaterial for further research that greatly improve the limited efficacy of powdered hemostats.


Asunto(s)
Materiales Biocompatibles/administración & dosificación , Pérdida de Sangre Quirúrgica/prevención & control , Gelatina/administración & dosificación , Hemostasis Quirúrgica/métodos , Polisacáridos/administración & dosificación , Animales , Materiales Biocompatibles/química , Modelos Animales de Enfermedad , Gelatina/química , Humanos , Hígado/cirugía , Masculino , Microscopía Electrónica de Rastreo , Modelos Animales , Tamaño de la Partícula , Polisacáridos/química , Polisacáridos/ultraestructura , Porosidad , Polvos , Sus scrofa
17.
Ann Epidemiol ; 28(5): 281-288, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29530388

RESUMEN

Mounting epidemiological evidence supports the occurrence of a mild herald pandemic wave in the spring and summer of 1918 in North America and Europe, several months before the devastating autumn outbreak that killed an estimated 2% of the global population. These epidemiological findings corroborate the anecdotal observations of contemporary clinicians who reported widespread influenza outbreaks in spring and summer 1918, with sporadic occurrence of unusually severe clinical manifestations in young adults. Initially seen as controversial, these findings were eventually confirmed by retrospective identification of influenza specimens collected from U.S. soldiers who died from acute respiratory infections in May-August 1918. Other studies found that having an episode of influenza illness during the spring herald wave was highly protective in the severe autumn wave. Here, we conduct a systematic review of the clinical, epidemiological, and virological evidence supporting the global occurrence of mild herald waves of the 1918 pandemic and place these historic observations in the context of pandemic preparedness. Taken together, historic experience with the 1918 and subsequent pandemics shows that increased severity in second and later pandemic waves may be the rule rather than the exception. Thus, a sustained pandemic response in the first years following a future pandemic is critical; conversely, multiwave pandemic patterns allow for more time to rollout vaccines and antivirals.


Asunto(s)
Brotes de Enfermedades , Gripe Humana/epidemiología , Pandemias/historia , Brotes de Enfermedades/historia , Femenino , Historia del Siglo XX , Humanos , Gripe Humana/mortalidad , Gripe Humana/transmisión , Masculino , América del Norte/epidemiología , Estaciones del Año , Adulto Joven
18.
Pediatr Transplant ; 22(3): e13121, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29392867

RESUMEN

Reports for pediatric kidney transplant recipients suggested better outcomes for ODN compared to LDN. Contemporary outcomes stratified by donor type and center volume have not been evaluated in a national dataset. UNOS data (2000-2014) were analyzed for pediatric living donor kidney transplant recipients. The primary outcome was GF; secondary outcomes were DGF, rejection, and patient survival. Live donor nephrectomies for pediatric recipients decreased 30% and transitioned from ODN to LDN. GF rates did not differ for ODN vs LDN (P = .24). GF was lowest at high volume centers (P < .01). Donor operative approach did not contribute to GF. LDN was associated with less rejection than ODN (OR 0.66, CI 0.5-0.87, P < .01). Analysis of the 0- to 5-yr recipient group showed no effect of ODN vs LDN on GF or rejection. For the contemporary era, there was no association between DGF and LDN in the 0- to 5-yr group (OR 1.12, CI 0.67-1.89, P = .67). Outcomes of kidney transplants in pediatric recipients following LDN have improved since its introduction and LDN should be the approach for live donor nephrectomy regardless of recipient age. The association between case volume and improved outcomes highlights future challenges in organ transplantation.


Asunto(s)
Hospitales de Alto Volumen , Hospitales de Bajo Volumen , Trasplante de Riñón , Laparoscopía , Nefrectomía/métodos , Adolescente , Adulto , Niño , Preescolar , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Lactante , Recién Nacido , Trasplante de Riñón/mortalidad , Masculino , Evaluación de Resultado en la Atención de Salud , Análisis de Supervivencia
19.
Nat Commun ; 9(1): 131, 2018 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-29317627

RESUMEN

Magnetic resonance imaging (MRI) is a widely used biomedical imaging modality that derives much of its contrast from microscale magnetic field patterns in tissues. However, the connection between these patterns and the appearance of macroscale MR images has not been the subject of direct experimental study due to a lack of methods to map microscopic fields in biological samples. Here, we optically probe magnetic fields in mammalian cells and tissues with submicron resolution and nanotesla sensitivity using nitrogen-vacancy diamond magnetometry, and combine these measurements with simulations of nuclear spin precession to predict the corresponding MRI contrast. We demonstrate the utility of this technology in an in vitro model of macrophage iron uptake and histological samples from a mouse model of hepatic iron overload. In addition, we follow magnetic particle endocytosis in live cells. This approach bridges a fundamental gap between an MRI voxel and its microscopic constituents.

20.
Biotechnol J ; 13(1)2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28881095

RESUMEN

Polymeric nanoparticles have been extensively studied as drug delivery vehicles both in vitro and in vivo for the last two decades. In vitro methods to assess drug release profiles usually utilize degradation of nanoparticles in aqueous medium, followed by the measurement of the concentration of the released drug. This method, however, is difficult to use for drugs that are poorly water soluble. In this study, a protocol for measuring drug release kinetic using albumin solution as the medium is described. Albumin is a major blood transport protein, which mediates transport of many lipid soluble compounds including fatty acids, hormones, and bilirubin. The use of a dialysis-based system utilizing albumin dialysate solution allows hydrophobic drug release from a diverse set of drug delivery modalities is demonstrated. The method using liposomes and PLGA nanoparticles as drug carriers, and two model hydrophobic drugs, 17ß-estradiol, and dexamethasone is validated.


Asunto(s)
Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Nanopartículas/química , Albúminas/química , Dexametasona/química , Portadores de Fármacos/uso terapéutico , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Cinética , Lípidos/química , Liposomas/química , Nanopartículas/uso terapéutico , Polímeros/química , Soluciones/química , Agua/química
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA