The Effect of Omega-3 Fatty Acids on Thromboxane,Brain-Derived Neurotrophic Factor,Homocysteine, and Vitamin D in Depressive Children and Adolescents: Randomized Controlled Trial

In the DEPOXIN project, we have found that a high ratio of omega-6/omega-3 fatty acids (FA) is associated with worsening of depressive symptoms in children and adolescents with depressive disorder (DD) and that the 12-week omega-3 FA supplementation modulates DD symptoms. Here we present our results of the secondary outcomes: the levels of thromboxane (TXB), brain-derived neurotrophic factor (BDNF), homocysteine (HCy) and vitamin D. Fifty-eight patients were randomized into two arms. One group received a fish oil emulsion enriched with omega-3 FA, and the other received a sunflower oil emulsion containing omega-6 FA, for 12 weeks. Depressive symptoms were evaluated, using the Child’s Depressive Inventory (CDI). The patients with DD had elevated TXB levels and decreased vitamin D levels, as compared to healthy controls. Both CDI and omega-6/omega-3 ratio correlated positively with TXB and negatively with BDNF at baseline. Compared to the omega-6 FA group, the supplementation with omega-3 FA for 12 weeks significantly reduced plasma TXB (p = 0.024) and increased BDNF (p = 0.011) levels. No changes in HCy and vitamin D were observed. Our results demonstrate the possible role of TXB and BDNF in the pathophysiology of DD and the benefits of omega-3 FA supplementation. The study was registered with the ISRCTN registry (ISRCTN81655012).     

Investigating the relationship between social care supply and healthcare utilization by older people in England

Since 2010, adult social care spending in England has fallen significantly in real terms whilst demand has risen. Reductions in social care supply may also have impacted demand for NHS services, particularly for those whose care is provided at the interface of the health and care systems. We analyzed a panel dataset of 150 local authorities (councils) to test potential impacts on hospital utilization by people aged 65 and over: emergency admission rates for falls and hip fractures (“front‐door” measures); and extended stays of 7 days or longer; and 21 days or longer (“back‐door” measures). Changes in social care supply were assessed in two ways: gross current expenditure (per capita 65 and over) adjusted by local labor costs and social care workforce (per capita 18 and over). We ran negative binomial models, controlling for deprivation, ethnicity, age, unpaid care, council class, and year effects. To account for potential endogeneity, we ran instrumental variable regressions and dynamic panel models. Sensitivity analysis explored potential effects of funding for integrated care (the Better Care Fund). There was no consistent evidence that councils with higher per capita spend or higher social care staffing rates had lower hospital admission rates or shorter hospital stays.     

Comparison of static and dynamic models of maternal immunization to prevent infant pertussis in Brazil

BackgroundThis paper compares cost-effectiveness results from two models of maternal immunization to prevent pertussis in infants in Brazil, one static, one dynamic, to explore when static models are adequate for public health decisions and when the extra effort required by dynamic models is worthwhile.MethodsWe defined two scenarios to explore key differences between static and dynamic models, herd immunity and time horizon. Scenario 1 evaluates the incremental cost/DALY of maternal acellular pertussis (aP) immunization as routine infant vaccination coverage ranges from low/moderate up to, and above, the threshold at which herd immunity begins to eliminate pertussis. Scenario 2 compares cost-effectiveness estimates over the models’ different time horizons. Maternal vaccine prices of $9.55/dose (base case) and $1/dose were evaluated.ResultsThe dynamic model shows that maternal immunization could be cost-saving as well as life-saving at low levels of infant vaccination coverage. When infant coverage reaches the threshold range (90–95%), it is expensive: the dynamic model estimates that maternal immunization costs $2 million/DALY at infant coverage > 95% and maternal vaccine price of $9.55/dose; at $1/dose, cost/DALY is $200,000. By contrast, the static model estimates costs/DALY only modestly higher at high than at low infant coverage. When the models’ estimates over their different time horizons are compared at infant coverage < 90–95%, their projections fall in the same range.ConclusionsStatic models may serve to explore an intervention’s cost-effectiveness against infectious disease: the direction and principal drivers of change were the same in both models. When, however, an intervention too small to have significant herd immunity effects itself, such as maternal aP immunization, takes place against a background of vaccination in the rest of the population, a dynamic model is crucial to accurate estimates of cost-effectiveness. This finding is particularly important in the context of widely varying routine infant vaccination rates globally.Clinical Trial registryClinical Trial registry name and registration number: Not applicable.     

Small animal jet injection technique results in enhanced immunogenicity of hantavirus DNA vaccines

DNA vaccine evaluation in small animals is hampered by low immunogenicity when the vaccines are delivered using a needle and syringe. To overcome this technical hurdle we tested the possibility that a device developed for human intradermal medicine delivery might be adapted to successfully deliver a DNA vaccine to small animals. Disposable syringe jet injection (DSJI) does not currently exist for small animals. However, a commercialized, human intradermal device used to to administer medicines to the human dermis in a 0.1 mL volume was evaluated in Syrian hamsters. Here, we found that hantavirus DNA vaccines administered to hamsters using DSJI were substantially more immunogenic than the same vaccines delivered by needle/syringe or particle mediated epidermal delivery (gene gun) vaccination. By adjusting how the device was used we could deliver vaccine to either subcutaneous tissues, or through the skin into the muscle. RNA and/or antigen expression was detected in epidermal, subepidermal and fibroblast cells. We directly compared six optimized and non-optimized hantavirus DNA vaccines in hamsters. Optimization, including codon-usage and mRNA stability, did not necessarily result in increased immunogenicity for all vaccines tested; however, optimization of the Andes virus (ANDV) DNA vaccine protected vaccinated hamsters from lethal disease. This is the first time active vaccination with an ANDV DNA vaccine has shown protective efficacy in the hamster model. The adaptation of a human intradermal jet injection device for use as a method of subcutaneous and intramuscular jet injection of DNA vaccines will advance the development of nucleic acid based medical countermeasures for diseases modeled in hamsters.     

The Tikhoff-Linberg procedure for bone tumors of the proximal humerus: the classical “extensive” technique versus a modified “transglenoid” resection

Summary The authors report on two groups of patients (each with 12) with primary bone tumors of the humerus who underwent either a classical Tikhoff-Linberg (T-L) procedure or a modified technique by which the body of the scapula was saved. The latter procedure was an en bloc resection of the glenohumeral joint after an extra-capsular osteotomy of the neck of the scapula, followed by reconstruction with a modular prosthesis. Indications, perioperative differences, and complications of both procedures are discussed. Besides producing better aesthetic and functional results, the modified technique offered the advantages of shorter anesthesia time, less blood loss, and a better anchorage of the prosthesis. The results of this study show that the proposed modification of the T-L procedure is indicated in patients with bone tumors of the proximal humerus in which invasion of the joint capsule is present without macroscopic involvement of the glenoid.Supported in part by Special Project Oncology, National Council for Research, grant no. 87.02810.44     

Tumor cell adhesion to frozen lymph node sections — a correlate of lymphatic metastasis in breast carcinoma models of human and rat origin

Summary The role of tumor cell adhesion in lymphatic metastasis of breast cancer was investigatedin vitro using a rat mammary carcinoma model of four cell lines with different metastatic phenotypes, two human breast cancer cell lines, and cryostast sections of normal rat or human lymph nodes, respectively. A positive correlation was found between the adhesion levels obtained with three metastatic rat mammary cell lines (TMT-081 > MT-100M & TMT-50) and a non-metastatic line MT-W9B, the latter being 3–4 fold less adhesive to the lymph node sections than the metastatic tumors. This selective adhesion was specific, as it was not found with cryostat sections of rat liver and brain. Enzyme assays indicated that cell surface glycoproteins bearing terminal -galactoside residues were involved in the adhesion of the rat tumors.Adhesion of the human breast carcinoma cells Hs578T to sections of human lymph nodes was significantly higher than that of the normal breast epithelial cell line Hs578Bst, and comparable to adhesion of a second breast carcinoma line, MCF-7. Moreover, Hs578T cells isolated from regional lymph nodes of tumor-bearing nude mice were significantly more adhesive to human lymph node sections than the parental line.Adhesion of both human and rat tumors could be partially blocked by the addition of the synthetic peptide GRGDSPK and by antibodies directed to the 1 chain of integrin, suggesting that an integrin receptor may played a role in the adhesion. The results suggest that tumor cell adhesion to cryostat sections of lymph nodes is a correlate of the malignant phenotype in mammary tumors of diverse origins, and could be used to delineate the adhesion factors mediating lymphatic metastasis.     

Periictal diffusion-weighted imaging in a case of lesional epilepsy

PURPOSE: Diffusion-weighted MR imaging (DWI) has been used for the early diagnosis of acute ischemic lesions in humans and in animal models of focal status epilepticus. We hypothesized that DWI may be a sensitive, noninvasive tool for the localization of the epileptogenic area during the periictal period. METHODS: A periictal DWI study was performed on a 35-year-old patient during focal status epilepticus with repetitive prolonged focal motor seizures originating from a lesion in the right frontal lobe. DWI results were analyzed visually and by calculating apparent diffusion coefficient (ADC) maps. RESULTS: On DWI, a single area of signal increase (decrease in ADC) was found in the region of focal electrocorticographic seizures that was mapped intraoperatively. CONCLUSIONS: Ictal/postictal DWI may be a useful technique for seizure localization in patients with lesional epilepsy.