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1.
International Journal of Clinical Oncology - Immune-checkpoint inhibitors (ICIs) are standard treatments for metastatic non-small cell lung cancer (NSCLC). Patients with poor performance status...  相似文献   
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Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN.  相似文献   
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In low and middle-income countries mammographic breast cancer screening is prohibitively expensive and a cheaper alternative option is to use ultrasound as the primary screening test. In 2009, China launched a breast cancer screening programme for rural women aged 35–64 years with clinical breast examination coupled with ultrasound as the primary tool. Our study aimed to analyse the cost-effectiveness of breast screening compared to no screening among Chinese rural women. We developed a Markov model to estimate the lifetime costs and effects for rural women aged 35 years from a societal perspective. Asymptomatic women in the intervention arm were screened every 3 years before age 64 years. Breast cancer in the non-screening arm can only be diagnosed on presentation of symptoms. Parameter uncertainty was explored using one-way and probabilistic sensitivity analyses. Compared to no screening, breast cancer screening cost $186.7 more and led to a loss of 0.20 quality-adjusted life years (QALYs). Breast screening was more expensive and did harm to health among rural women with an incremental cost-effectiveness ratio (ICER) of $-916/QALY. The sensitivity analysis identified utility loss from false positives as the factor that most influenced the results, but this did not affect the conclusions. In a rural setting with such low breast cancer incidence, screening for asymptomatic disease is not cost-effective with current screening tools. Priority should be given to ensure that symptomatic women have proper access to diagnosis and treatment at an early stage as this will lead to mortality reductions without the usual screening harms.  相似文献   
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Food-grade titanium dioxide (E171) is widely used as a food additive, and it is known that after oral consumption, E171 is translocated into the bloodstream reaching the highest titanium level at 6 h. E171 is accumulated in some organs triggering toxicity, but the effects on the blood parameters after oral consumption have been less studied. Recently, evidence shows that oral exposure to E171 induces behavioral signs of anxiety and depression. The relation between blood alterations and psychiatric disorders has been previously demonstrated. However, the oral exposure to E171 effects on alterations in blood parameters and effects linked to alterations in animal behavior has not been explored. In this short communication, we aimed to investigate the effects of E171 on specific blood parameters (hematocrit, hemoglobin, number of erythrocytes, and leukocytes) and anxiety and compulsive-like behavior in males and females orally exposed to ~5 mg/kg for 4 weeks. The results showed that E171 decreased hematocrit and hemoglobin in male but not in female mice while leukocyte and erythrocyte count remained unaltered. Oral consumption of E171 decreased the levels of anxiety-like behavior in females but not in male mice, while compulsive-like behavior was increased in both male and female mice.  相似文献   
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Introduction

Invasive meningococcal disease (IMD) is a severe disease mainly affecting infants and young children. The most common serogroup causing IMD in Germany is the serogroup type B Neisseria meningitidis (MenB). The aim of the present study is to estimate the economic burden of MenB-related IMD in Germany.

Method

A bottom-up, model-based costing approach has been used to calculate the diagnose- and age-specific yearly lifetime costs of a hypothetical cohort of MenB-related IMD cases. Direct costs contain the treatment cost for the acute phase of the disease, long-term sequelae, costs for rehabilitation, and public health response. Indirect costs are calculated for the human-capital approach and the friction-cost approach considering productivity losses of patients or parents for the acute phase and long-term sequelae. Publicly available databases from the Federal Statistical Office, the SOEP panel data set, literature, and expert opinion were used as data sources. All future costs beyond the reference year of 2015 were discounted at 3%.

Results

The total costs for the hypothetical cohort (343 patients) from a societal perspective are €19.6 million (€57,100/IMD case) using the friction-cost approach and €58.8 million (€171,000/IMD case) using the human-capital approach. Direct costs amount to €18.6 million or €54,300 €/case. Sequelae are responsible for 81% of the direct costs/case.

Discussion

The elevated costs/MenB-related IMD case reflect the severity of the disease. The total costs are sensitive to the productivity-loss estimation approach applied. MenB is an uncommon but severe disease; The costs/case reflect the severity of the disease and is within the same magnitude as for human papilloma virus infections. The available literature on sequelae is due to the uncommonness limited and heterogeneous.  相似文献   
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Purpose:This study assessed the regeneration potential of mesenchymal stem cells (MSC) from adipose tissue associated with platelet-rich plasma (PRP) in bone regeneration.Methods:Thirty Wistar rats (Rattus norvegicus albinos) were divided into five groups (according to the grafting material and time to euthanasia): (1) autograft - 14 days (control), (2) autograft - 28 days (control), (3) MSC + PRP - 14 days, (4) MSC + PRP + papaverine - 14 days and (5) MSC + PRP + papaverine - 28 days. After euthanasia, the graft was removed and histological slides were prepared. They were assessed by a blinded pathologist using a previously published histological scale as parameter.Results:There was some degree of neoformed bone trabeculae (NBT) in 93.3% of the samples, as well as osteoblastic activity (OA). The autograft groups (14 and 28 days) had higher levels in the formation of bone trabeculae. Nonparametric data were analyzed using the Wilcoxon-Mann-Whitney test and proved not to be statistically significant at p < 0.05.Conclusions:Experimental parietal bone reconstruction, combining MSC, PRP and papaverine presented regeneration in all groups with no significant difference among them.Key words: Bone Regeneration, Platelet-Rich Plasma, Tissue Engineering, Rats  相似文献   
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Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and presents together with cirrhosis in most cases. In addition to commonly recognized risk factors for HCC development, such as hepatitis B virus/hepatitis C virus infection, age and alcohol/tobacco consumption, there are nutritional risk factors also related to HCC development including high intake of saturated fats derived from red meat, type of cooking (generation of heterocyclic amines) and contamination of foods with aflatoxins. On the contrary, protective nutritional factors include diets rich in fiber, fruits and vegetables, n-3 polyunsaturated fatty acids and coffee. While the patient is being evaluated for staging and treatment of HCC, special attention should be paid to nutritional support, including proper nutritional assessment and therapy by a multidisciplinary team. It must be considered that these patients usually develop HCC on top of long-lasting cirrhosis, and therefore they could present with severe malnutrition. Cirrhosis-related complications should be properly addressed and considered for nutritional care. In addition to traditional methods, functional testing, phase angle and computed tomography scan derived skeletal muscle index-L3 are among the most useful tools for nutritional assessment. Nutritional therapy should be centered on providing enough energy and protein to manage the increased requirements of both cirrhosis and cancer. Supplementation with branched-chain amino acids is also recommended as it improves response to treatment, nutritional status and survival, and finally physical exercise must be encouraged and adapted to individual needs.  相似文献   
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