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1.
Phys Rev Lett ; 132(18): 186901, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38759158

RESUMEN

Electron-electron scattering on the order of a few to tens of femtoseconds plays a crucial role in the ultrafast electron dynamics of conventional metals. When mid-infrared light is used for driving and the period of light field is comparable to the scattering time in metals, unique light-driven states and nonlinear optical responses associated with the scattering process are expected to occur. Here, we use high-harmonics spectroscopy to investigate the effect of electron-electron scattering on the electron dynamics in thin film 2H-NbSe_{2} driven by a mid-infrared field. We observed odd-order high harmonics up to 9th order as well as a broadband emission from hot electrons in the energy range from 1.5 to 4.0 eV. The electron-electron scattering time in 2H-NbSe_{2} was estimated from the broadband emission to be almost the same as the period of the mid-infrared light field. A comparison between experimental results and a numerical calculation reveals that competition and cooperation between the driving and scattering enhances the nonperturbative behavior of high harmonics in metals, causing a highly nonequilibrium electronic state corresponding to several thousand Kelvin.

2.
Exp Dermatol ; 33(3): e15025, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38450766

RESUMEN

Ceramides are major constituents of stratum corneum (SC) intercellular lipids involved in skin barrier function. The ratio of molecular species of ceramides and their correlation with disease severity was examined in patients with atopic dermatitis (AD). Thirty-eight patients with AD and 32 healthy controls (HCs) were assessed for transepidermal water loss, SC collection and clinical assessment. The ceramide content of different molecular species in the samples was quantified using high-performance liquid chromatography coupled with tandem mass spectrometry. Unsaturated acyl chains of both covalently bound and free ceramides [EOS] were higher in AD lesional skin than those in AD non-lesional or normal HC skin. The proportion of unsaturated acyl chains (C30:1, C32:1 and C34:1) was higher than other ceramide molecular species among covalently bound and free ceramides [EOS] in patients with AD. The proportion of unsaturated acyl chains in covalently bound ceramides was positively correlated with transepidermal water loss (r = 0.600) when considering the total number of non-lesional and lesional skin. Additionally, thymus and activation-regulated chemokine (TARC) showed a positive correlation with unsaturated acyl chains proportion in AD non-lesional (r = 0.676) and lesional (r = 0.503) skin. Our study is the first to show the increase in unsaturated acyl chains of both covalently bound and free ceramides [EOS] in lesional and non-lesional skin in AD for each molecular species. This increase is associated with dryness and impaired barrier function, which correlates with TARC levels, a marker for the degree of type 2 inflammation. We speculate that type 2 inflammation exacerbation leads to abnormal epidermal lipid metabolism in the skin of patients with AD.


Asunto(s)
Dermatitis Atópica , Humanos , Inflamación , Gravedad del Paciente , Ceramidas , Agua
3.
4.
Ann Oncol ; 34(3): 262-274, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36535565

RESUMEN

BACKGROUND: Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have a poor prognosis. The phase III KESTREL study evaluated the efficacy of durvalumab [programmed death-ligand 1 (PD-L1) antibody] with or without tremelimumab [cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody], versus the EXTREME regimen in patients with R/M HNSCC. PATIENTS AND METHODS: Patients with HNSCC who had not received prior systemic treatment for R/M disease were randomized (2 : 1 : 1) to receive durvalumab 1500 mg every 4 weeks (Q4W) plus tremelimumab 75 mg Q4W (up to four doses), durvalumab monotherapy 1500 mg Q4W, or the EXTREME regimen (platinum, 5-fluorouracil, and cetuximab) until disease progression. Durvalumab efficacy, with or without tremelimumab, versus the EXTREME regimen in patients with PD-L1-high tumors and in all randomized patients was assessed. Safety was also assessed. RESULTS: Durvalumab and durvalumab plus tremelimumab were not superior to EXTREME for overall survival (OS) in patients with PD-L1-high expression [median, 10.9 and 11.2 versus 10.9 months, respectively; hazard ratio (HR) = 0.96; 95% confidence interval (CI) 0.69-1.32; P = 0.787 and HR = 1.05; 95% CI 0.80-1.39, respectively]. Durvalumab and durvalumab plus tremelimumab prolonged duration of response versus EXTREME (49.3% and 48.1% versus 9.8% of patients remaining in response at 12 months), correlating with long-term OS for responding patients; however, median progression-free survival was longer with EXTREME (2.8 and 2.8 versus 5.4 months). Exploratory analyses suggested that subsequent immunotherapy use by 24.3% of patients in the EXTREME regimen arm contributed to the similar OS outcomes between arms. Grade 3/4 treatment-related adverse events (TRAEs) for durvalumab, durvalumab plus tremelimumab, and EXTREME were 8.9%, 19.1%, and 53.1%, respectively. CONCLUSIONS: In patients with PD-L1-high expression, OS was comparable between durvalumab and the EXTREME regimen. Durvalumab alone, and with tremelimumab, demonstrated durable responses and reduced TRAEs versus the EXTREME regimen in R/M HNSCC.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/etiología , Antígeno B7-H1 , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia , Neoplasias de Cabeza y Cuello/etiología
5.
Curr Osteoporos Rep ; 21(1): 85-94, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36477366

RESUMEN

PURPOSE OF REVIEW: Multicentric carpotarsal osteolysis (MCTO) is an ultra-rare disorder characterized by osteolysis of the carpal and tarsal bones, subtle craniofacial deformities, and nephropathy. The molecular pathways underlying the pathophysiology are not well understood. RECENT FINDINGS: MCTO is caused by heterozygous mutations in MAFB, which encodes the widely expressed transcription factor MafB. All MAFB mutations in patients with MCTO result in replacement of amino acids that cluster in a phosphorylation region of the MafB transactivation domain and account for a presumed gain-of-function for the variant protein. Since 2012, fewer than 60 patients with MCTO have been described with 20 missense mutations in MAFB. The clinical presentations are variable, and a genotype-phenotype correlation is lacking. Osteolysis, via excessive osteoclast activity, has been regarded as the primary mechanism, although anti-resorptive agents demonstrate little therapeutic benefit. This paper appraises current perspectives of MafB protein action, inflammation, and dysfunctional bone formation on the pathogenesis of the skeletal phenotype in MCTO. More research is needed to understand the pathogenesis of MCTO to develop rational therapies.


Asunto(s)
Huesos del Carpo , Osteólisis , Humanos , Osteólisis/genética , Mutación , Mutación Missense , Huesos del Carpo/patología , Fenotipo
6.
Plant Biol (Stuttg) ; 25(1): 54-61, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36164964

RESUMEN

Glycerophosphodiester phosphodiesterase (GDPD; EC 3.1.4.46) is involved in plant phosphate (Pi) utilization and its expression is upregulated under phosphorus (P)-deficient conditions. Although rice was grown under P-sufficient conditions, the transcript levels of specific OsGDPD were upregulated in mature rice leaf blades (LB) in elevated CO2 (eCO2 ) environments. Expression and subcellular localization of GDPD, and contents of Pi, sugar phosphates and carbohydrates were analysed to clarify the physiological function of GDPD in rice under eCO2 . Under eCO2 , expression of specific OsGDPD increased only in mature rice LB in which low Pi concentrations were observed. Moreover, eCO2 -induced OsGDPD2 and OsGDPD3 were localized in the plastid, indicating that GDPD2 and GDPD3 may be related to plastidic functions, such as carbon assimilation. Although rice LB contained more carbohydrates under eCO2 than under ambient CO2 , the phosphoglucose content decreased under eCO2 , suggesting that the need for excess phosphoglucose to synthesize carbohydrates under eCO2 causes a local Pi deficiency. Furthermore, we confirmed that glycerol-3-phosphate produced by the catalysis of GDPD from glycerophosphodiester contributes to carbohydrate accumulation in rice LB. Our findings suggest that local Pi deficiency due to excess carbohydrate accumulation under eCO2 influences GDPD to enhance glycerophosphodiester hydrolysis.


Asunto(s)
Oryza , Oryza/genética , Oryza/metabolismo , Dióxido de Carbono/metabolismo , Hojas de la Planta/metabolismo , Fosfatos/metabolismo , Carbohidratos
7.
Folia Morphol (Warsz) ; 82(3): 551-557, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36000590

RESUMEN

BACKGROUND: The growth of parotid glands is inhibited by liquid diet intake during growing period, while that of submandibular glands is not affected. This study examined how liquid diet intake affects nerve growth in the parotid and submandibular glands of growing rats, because nerves are closely involved in the maintenance of salivary gland structure. MATERIALS AND METHODS: Male Wistar rats were weaned at 21 days of age. Then, rats were fed a pellet diet and a liquid diet in the control group and experimental group, respectively. At 0, 2, 4, or 8 weeks, they were euthanised by isoflurane overdose, and parotid and submandibular glands were removed. The frozen sections were made and immuno-stained with anti-protein gene product 9.5 (PGP 9.5) antibody (general nerve marker), anti-tyrosine hydroxylase (TH) antibody (sympathetic nerve marker), or anti-neuronal nitric oxide synthase (nNOS) antibody (parasympathetic nerve marker). RESULTS: In control parotid glands, scattered punctate or short linear patterns of PGP 9.5-positive sites were observed at week 0. After 2 weeks, PGP 9.5-positive sites, some of which were arranged in long linear patterns, increased in number. There were some TH-positive sites at week 0. After 2 weeks, there were increasing numbers of TH-positive sites, often in long linear patterns. At week 0, there were very few nNOS-positive sites, and nNOS immunoreactivity increased over time. After week 4, they demonstrated linear patterns. In the experimental parotid glands, there were fewer PGP 9.5- and nNOS-positive sites than in control parotid glands at each time point, although TH immunoreactivity was similar between two groups at each time point. In control submandibular glands, few punctate exhibited PGP 9.5-positive site were observed at week 0. At week 4, PGP 9.5 immunoreaction increased and showed linear patterns. TH-positive sites demonstrated punctate or short linear patterns at week 0, and thereafter TH immunoreactivity increased and were arranged in long linear patterns. There were few nNOS-positive sites at week 0, and they gradually increased after week 4. The immunoreactivities of all antibodies in the experimental submandibular glands were similar to those in the control at each time point. CONCLUSIONS: Parasympathetic nerve growth in rat parotid glands was inhibited by liquid diet intake during the growth period, while liquid diet intake did not affect parasympathetic nerve growth nor sympathetic nerve growth in rat submandibular glands.


Asunto(s)
Glándula Parótida , Glándulas Salivales , Ratas , Masculino , Animales , Ratas Wistar , Glándula Submandibular , Dieta
8.
ESMO Open ; 7(4): 100554, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35963179

RESUMEN

INTRODUCTION: This pooled analysis of nine phase I and II trastuzumab deruxtecan (T-DXd) monotherapy studies described drug-related interstitial lung disease (ILD)/pneumonitis in patients treated with T-DXd. METHODS: Patients who received T-DXd across nine studies were included. Investigator-assessed ILD/pneumonitis events were retrospectively reviewed by an independent adjudication committee; events adjudicated as drug-related ILD/pneumonitis are summarized. RESULTS: The analysis included 1150 patients (breast cancer, 44.3%; gastric cancer, 25.6%; lung cancer, 17.7%; colorectal cancer, 9.3%; other cancer, 3.0%). Median treatment duration was 5.8 (range, 0.7-56.3) months, with a median of 4 (range, 1-27) prior lines of therapy. The overall incidence of adjudicated drug-related ILD/pneumonitis was 15.4% (grade 5, 2.2%). Most patients with ILD/pneumonitis experienced low-grade events (grade 1 or 2, 77.4%); 87.0% had their first event within 12 months [median, 5.4 (range, <0.1-46.8) months] of their first dose of T-DXd. Based on data review, adjudicated ILD/pneumonitis onset occurred earlier than identified by investigators for 53.2% of events [median difference in onset date, 43 (range, 1-499) days]. Stepwise Cox regression identified several baseline factors potentially associated with increased risk of adjudicated drug-related ILD/pneumonitis: age <65 years, enrollment in Japan, T-DXd dose >6.4 mg/kg, oxygen saturation <95%, moderate/severe renal impairment, presence of lung comorbidities, and time since initial diagnosis >4 years. CONCLUSIONS: In this pooled analysis of heavily treated patients, the incidence of ILD/pneumonitis was 15.4%, with most being low grade and occurring in the first 12 months of treatment. The benefit-risk of T-DXd treatment is positive; however, some patients may be at increased risk of developing ILD/pneumonitis, and further investigation is needed to confirm ILD/pneumonitis risk factors. Close monitoring and proactive management of ILD/pneumonitis are warranted for all.


Asunto(s)
Enfermedades Pulmonares Intersticiales , Neumonía , Anciano , Camptotecina/análogos & derivados , Humanos , Inmunoconjugados , Estudios Retrospectivos , Trastuzumab
9.
Ann Oncol ; 33(2): 216-226, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34843940

RESUMEN

BACKGROUND: Cancer of unknown primary (CUP) has a poor prognosis. Given the recent approval of immune checkpoint inhibitors for several cancer types, we carried out a multicenter phase II study to assess the efficacy of nivolumab for patients with CUP. PATIENTS AND METHODS: Patients with CUP who were previously treated with at least one line of systemic chemotherapy constituted the principal study population. Previously untreated patients with CUP were also enrolled for exploratory analysis. Nivolumab (240 mg/body) was administered every 2 weeks for up to 52 cycles. The primary endpoint was objective response rate in previously treated patients as determined by blinded independent central review according to RECIST version 1.1. RESULTS: Fifty-six patients with CUP were enrolled in the trial. For the 45 previously treated patients, objective response rate was 22.2% [95% confidence interval (CI), 11.2% to 37.1%], with a median progression-free survival and overall survival of 4.0 months (95% CI, 1.9-5.8 months) and 15.9 months (95% CI, 8.4-21.5 months), respectively. Similar clinical benefits were also observed in the 11 previously untreated patients. Better clinical efficacy of nivolumab was apparent for tumors with a higher programmed death-ligand 1 expression level, for those with a higher tumor mutation burden, and for microsatellite instability-high tumors. In contrast, no differences in efficacy were apparent between tumor subgroups based on estimated tissue of origin. Adverse events were consistent with the known safety profile of nivolumab. No treatment-related death was observed. CONCLUSIONS: Our results demonstrate a clinical benefit of nivolumab for patients with CUP, suggesting that nivolumab is a potential additional therapeutic option for CUP.


Asunto(s)
Neoplasias Primarias Desconocidas , Nivolumab , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Inestabilidad de Microsatélites , Neoplasias Primarias Desconocidas/tratamiento farmacológico , Nivolumab/efectos adversos , Supervivencia sin Progresión , Criterios de Evaluación de Respuesta en Tumores Sólidos
10.
Nat Commun ; 12(1): 4356, 2021 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-34272371

RESUMEN

Thermoelectric effects have been applied to power generators and temperature sensors that convert waste heat into electricity. The effects, however, have been limited to electrons to occur, and inevitably disappear at low temperatures due to electronic entropy quenching. Here, we report thermoelectric generation caused by nuclear spins in a solid: nuclear-spin Seebeck effect. The sample is a magnetically ordered material MnCO3 having a large nuclear spin (I = 5/2) of 55Mn nuclei and strong hyperfine coupling, with a Pt contact. In the system, we observe low-temperature thermoelectric signals down to 100 mK due to nuclear-spin excitation. Our theoretical calculation in which interfacial Korringa process is taken into consideration quantitatively reproduces the results. The nuclear thermoelectric effect demonstrated here offers a way for exploring thermoelectric science and technologies at ultralow temperatures.

12.
J Nutr Health Aging ; 24(8): 878-882, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33009539

RESUMEN

AIM: This is a cross-sectional study of relation between metabolic syndrome and cognitive function in community-dwelling non-demented older adults in Japan. We examine the effect of metabolic syndrome and its components on global cognitive function. We also aim to clarify differences of specific cognitive domains between the subjects with and without metabolic syndrome. METHODS: We studied 2150 subjects aged between 60 and 90 years whose scores on mini mental state examination (MMSE) were over 23 points. We analyzed difference in MMSE scores between the subjects with and without metabolic syndrome. Logistic regression analysis was performed with MMSE score as the dependent variable and metabolic syndrome components as the independent variable adjusted with age. We also examined differences in attention, logical memory, and verbal and category fluency between the subjects with and without metabolic syndrome. RESULTS: MMSE scores were not significantly different between subjects with and without metabolic syndrome. In logistic regression analysis, the score of MMSE was significantly negatively associated with triglycerides in males and significantly negatively associated with abdominal circumference in females. Subjects with metabolic syndrome showed significantly lower performance of attention tasks compared to subjects without metabolic syndrome. CONCLUSIONS: Our results suggest that in community-dwelling non-demented Japanese older adults, attention but not global cognitive function may be impaired by metabolic syndrome. Inverted association between some components of metabolic syndrome and global cognitive function indicate necessity of further studies on the relation between undernutrition and cognitive function.


Asunto(s)
Cognición/fisiología , Síndrome Metabólico/epidemiología , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Vida Independiente , Japón , Masculino
14.
Reprod Biol Endocrinol ; 18(1): 57, 2020 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-32471441

RESUMEN

BACKGROUND: A recently published Position Statement (PS) by the Preimplantation Genetics Diagnosis International Society (PGDIS) regarding utilization of preimplantation genetic testing for aneuploidy (PGT-A) in association with in vitro fertilization (IVF) contained inaccuracies and misrepresentations. Because opinions issued by the PGDIS have since 2016 determined worldwide IVF practice, corrections appear of importance. METHODS: The International Do No Harm Group in IVF (IDNHG-IVF) is a spontaneously coalesced body of international investigators, concerned with increasing utilization of add-ons to IVF. It is responsible for the presented consensus statement, which as a final document was reached after review of the pertinent literature and again revised after the recent publication of the STAR trial and related commentaries. RESULTS: In contrast to the PGDIA-PS, we recommend restrictions to the increasing, and by IVF centers now often even mandated, utilization of PGT-A in IVF cycles. While PGT-A has been proposed as a tool for achieving enhanced singleton livebirth outcomes through embryo selection, continued false-positive rates and increasing evidence for embryonic self-correction downstream from the testing stage, has led IDNHG-IVF to conclude that currently available data are insufficient to impose overreaching recommendations for PGT-A utilization. DISCUSSION: Here presented consensus offers an alternative to the 2019 PGDIS position statement regarding utilization of preimplantation genetic testing for aneuploidy (PGT-A) in association with in vitro fertilization (IVF). Mindful of what appears to offer best outcomes for patients, and in full consideration of patient autonomy, here presented opinion is based on best available evidence, with the goal of improving safety and efficacy of IVF and minimizing wastage of embryos with potential for healthy births. CONCLUSIONS: As the PGDIS never suggested restrictions on clinical utilization of PGT-A in IVF, here presented rebuttal represents an act of self-regulation by parts of the IVF community in attempts to control increasing utilization of different unproven recent add-ons to IVF.


Asunto(s)
Aneuploidia , Transferencia de Embrión/normas , Fertilización In Vitro , Mosaicismo , Diagnóstico Preimplantación/normas , Blastocisto , Reacciones Falso Positivas , Femenino , Humanos , Embarazo
15.
Osteoporos Int ; 31(6): 1089-1095, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32060561

RESUMEN

This study revealed the change in the paravertebral muscles in patients with osteoporotic vertebral fracture. Increased pain is likely to be the driver for reduced activity, reduced activities of daily living, and consequent increase in fat infiltration of the paravertebral muscles, assumed to be secondary to reduced activity level or, conversely, partial immobilization. INTRODUCTION: To reveal the time courses and impact of the paravertebral muscles (PVMs) on the healing process of osteoporotic vertebral fractures and risk factors for PVM decrease. METHODS: Consecutive patients with symptomatic osteoporotic vertebral fractures were enrolled in 11 hospitals. At enrollment and 3- and 6-month follow-up, PVMs, including the multifidus and erector spinae, were examined using magnetic resonance imaging (MRI). The PVM cross-sectional area (CSA) and fat signal fraction (FSF) were measured at L3. Low back pain (LBP), activities of daily living (ADLs), and risk factors for PVM decrease at the 6-month follow-up were investigated. PVM decrease was defined as > 1 standard deviation decrease of the CSA or > 1 standard deviation increase of the FSF. RESULTS: Among 153 patients who completed the 6-month follow-up, 117 (92 women, 79%) had MRI of L3 at enrollment and 3- and 6-month follow-up (mean age at enrollment, 78.5 years). The CSA did not change 6 months from onset (p for trend = 0.634), whereas the FSF significantly increased (p for trend = 0.033). PVM decrease was observed in 30 patients (26%). LBP was more severe, and delayed union was more frequent in patients with PVM decrease (p = 0.021 mixed-effect model and p = 0.029 chi-square test, respectively). The risk factors for PVM decrease were ADL decline at the 3-month follow-up (adjusted odds ratio = 5.35, p = 0.026). CONCLUSION: PVM decrease was significantly related to LBP and delayed union after osteoporotic vertebral fracture onset. ADL decline at the 3-month follow-up was a risk factor for PVM decrease. Therefore, restoring ADLs within 3 months after onset is important.


Asunto(s)
Actividades Cotidianas , Músculos de la Espalda/fisiopatología , Dolor de la Región Lumbar , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Anciano , Femenino , Humanos , Dolor de la Región Lumbar/etiología , Imagen por Resonancia Magnética , Masculino , Fracturas Osteoporóticas/complicaciones , Fracturas Osteoporóticas/fisiopatología , Fracturas de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/fisiopatología
16.
Hum Exp Toxicol ; 39(4): 500-513, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31876189

RESUMEN

Methotrexate (MTX)-induced intestinal mucosal injury in animals has been studied to understand how MTX can cause gastrointestinal disorders, but the pathogenesis of gastrointestinal disorders is still uncertain. We have attempted to reveal how dietary factors influence intestinal toxicity due to MTX. Mice were fed normal chow (NC) or a high-fat high-sucrose diet (HFHSD) before oral administration of MTX. While MTX significantly decreased the survival rates of mice fed HFHSD, the intestinal epithelial injury was detected. MTX excretion in the feces of mice fed HFHSD was reduced. Change of diets between NC and HFHSD influences the survival. The survival rates of the mice fed a high-sucrose diet or control diet were higher than those fed HFHSD. Higher survival rates were observed in mice fed a high-fat high-sucrose diet modified (HFHSD-M) in which casein was replaced by soybean-derived proteins. The survival rates of mice treated with vancomycin were lower than those administered neomycin. Microbiome and metabolome analyses on feces suggest a similarity of the intestinal environments of mice fed NC and HFHSD-M. HFHSD may modify MTX-induced toxicity in intestinal epithelia on account of an altered MTX distribution as a result of change in the intestinal environment.


Asunto(s)
Dieta Alta en Grasa , Microbioma Gastrointestinal/efectos de los fármacos , Enfermedades Intestinales/dietoterapia , Mucosa Intestinal/efectos de los fármacos , Metotrexato/toxicidad , Sacarosa/administración & dosificación , Animales , Dieta Alta en Grasa/métodos , Modelos Animales de Enfermedad , Heces/química , Enfermedades Intestinales/inducido químicamente , Enfermedades Intestinales/microbiología , Enfermedades Intestinales/patología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Masculino , Metaboloma/efectos de los fármacos , Metotrexato/farmacocinética , Ratones Endogámicos C57BL , Análisis de Supervivencia , Distribución Tisular
17.
Vaccine ; 38(5): 979-992, 2020 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-31787412

RESUMEN

After many decades of vaccination, measles epidemiology varies greatly between and within countries. National immunization programs are therefore encouraged to conduct regular situation analyses and to leverage models to adapt interventions to local needs. Here, we review applications of models to develop locally tailored interventions to support control and elimination efforts. In general, statistical and semi-mechanistic transmission models can be used to synthesize information from vaccination coverage, measles incidence, demographic, and/or serological data, offering a means to estimate the spatial and age-specific distribution of measles susceptibility. These estimates complete the picture provided by vaccination coverage alone, by accounting for natural immunity. Dynamic transmission models can then be used to evaluate the relative impact of candidate interventions for measles control and elimination and the expected future epidemiology. In most countries, models predict substantial numbers of susceptible individuals outside the age range of routine vaccination, which affects outbreak risk and necessitates additional intervention to achieve elimination. More effective use of models to inform both vaccination program planning and evaluation requires the development of training to enhance broader understanding of models and where feasible, building capacity for modelling in-country, pipelines for rapid evaluation of model predictions using surveillance data, and clear protocols for incorporating model results into decision-making.


Asunto(s)
Países en Desarrollo , Erradicación de la Enfermedad , Programas de Inmunización , Sarampión , Humanos , Sarampión/epidemiología , Sarampión/prevención & control , Vacuna Antisarampión/administración & dosificación , Modelos Teóricos , Cobertura de Vacunación
18.
J Chem Phys ; 150(13): 134702, 2019 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-30954059

RESUMEN

Nanodiamonds (NDs) hosting nitrogen-vacancy (NV) centers are a promising platform for quantum sensing applications. Sensitivity of the applications using NV centers in NDs is often limited due to the presence of paramagnetic impurity contents near the ND surface. Here, we investigate near-surface paramagnetic impurities in NDs. Using high-frequency (HF) electron paramagnetic resonance spectroscopy, the near-surface paramagnetic impurity within the shell of NDs is probed and its g-value is determined to be 2.0028(3). Furthermore, HF electron-electron double resonance-detected nuclear magnetic resonance spectroscopy and a first principles calculation show that a possible structure of the near-surface impurity is the negatively charged vacancy V-. The identification of the near-surface impurity by the present investigation provides a promising pathway to improve the NV properties in NDs and the NV-based sensing techniques.

19.
Vaccine ; 37(18): 2511-2519, 2019 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-30940486

RESUMEN

INTRODUCTION: Measles elimination depends on the successful deployment of measles containing vaccine. Vaccination programs often depend on a combination of routine and non-routine services, including supplementary immunization activities (SIAs) and vaccination weeks (VWs), that both aim to vaccinate all eligible children regardless of vaccination history or natural infection. Madagascar has used a combination of these activities to improve measles coverage. However, ongoing massive measles outbreak suggests that the country was in a "honeymoon" period and that coverage achieved needs to be re-evaluated. Although healthcare access is expected to vary seasonally in low resources settings, little evidence exists to quantify temporal fluctuations in routine vaccination, and interactions with other immunization activities. METHODS: We used three data sources: national administrative data on measles vaccine delivery from 2013 to 2016, digitized vaccination cards from 49 health centers in 6 health districts, and a survey of health workers. Data were analyzed using linear regressions, analysis of variance, and t-tests. FINDINGS: From 2013 to 2016, the footprint of SIAs and VWs is apparent, with more doses distributed during the relevant timeframes. Routine vaccination decreases in subsequent months, suggesting that additional activities may be interfering with routine services. The majority of missed vaccination opportunities occur during the rainy season. Health facility organization and shortage of vaccine contributed to vaccination gaps. Children born in June were the least likely to be vaccinated on time. DISCUSSION: Evidence that routine vaccination coverage varies over the year and is diminished by other activities suggests that maintaining routine vaccination during SIAs and VWs is a key direction for strengthening immunization programs, ensuring population immunity and avoiding future outbreaks. FUNDING: Wellcome Trust Fund, Burroughs Wellcome Fund, Gates Foundation, National Institutes of Health.


Asunto(s)
Programas de Inmunización , Vacuna Antisarampión/administración & dosificación , Sarampión/prevención & control , Estaciones del Año , Cobertura de Vacunación/estadística & datos numéricos , Preescolar , Brotes de Enfermedades/prevención & control , Femenino , Personal de Salud , Administración de los Servicios de Salud/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Madagascar , Masculino , Encuestas y Cuestionarios , Cobertura de Vacunación/métodos
20.
Hernia ; 23(2): 305-310, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30623260

RESUMEN

PURPOSE: Lateral lymph node dissection (LLND) is performed for advanced lower rectal cancer (ALRC) in Japan. The LLND in laparotomy is performed via the extraperitoneal approach, which is similar to radical retropubic prostatectomy (RRP). Inguinal hernias (IHs) appearing after RRP are common. However, there are few reports about IHs appearing after LLND. METHODS: In part A, we retrospectively investigated 108 patients who underwent LLND for ALRC between January 2004 and December 2014. In part B, we compared 13 patients who underwent IH repair after LLND and 57 patients who underwent IH repair after RRP in the same period. RESULTS: In part A, the incidence of IHs after LLND was 7% (8/108). All eight patients who developed IHs were male, and their median age was 60 years. More than 80% of IHs observed were the unilateral lateral type. In part B, the interval between the previous operation and IH occurrence was 4.9 years on average. Furthermore, 2 out of the 13 patients developed additional IHs occurring on the opposite side within 2 years. CONCLUSIONS: The characteristics associated with developing IHs after LLND were similar to those after RRP. Any pelvic operation via the extraperitoneal approach has a risk of IHs, and surgeons should pay attention to IHs after surgery.


Asunto(s)
Hernia Inguinal/etiología , Escisión del Ganglio Linfático/efectos adversos , Neoplasias del Recto/cirugía , Anciano , Femenino , Hernia Inguinal/epidemiología , Humanos , Incidencia , Japón/epidemiología , Laparotomía/efectos adversos , Masculino , Persona de Mediana Edad , Pelvis/cirugía , Estudios Retrospectivos
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