Healthcare Workers’ (HCWs) attitudes towards mandatory influenza vaccination: A systematic review and meta-analysis

Influenza is a disease responsible for thousands of deaths every year. Although healthcare workers (HCWs) represent a way of contagion for patients, vaccination coverage among them is low. Mandatory vaccination has been proposed, but controversies remain. This systematic review and meta-analysis aimed to assess the acceptance of mandatory vaccination by HCWs, and to investigate associated characteristics. MEDLINE, Scopus, Embase, PsycInfo, CINAHL and Web of Science were used to search for studies assessing the topic. PRISMA statements were followed. Of the 13,457 univocal records found, 52 studies were included in the systematic review and 40 in the meta-analysis. The pooled proportion of HCWs accepting the policy was of 61% (95% CI: 53%- 68%) but with great heterogeneity between continents (from 54% in Europe to 69% in Asia) and in different professionals (from 40% in nurses to 80% in students). Vaccinated HCWs agreed more frequently with mandatory vaccination than non-vaccinated ones. More studies that consider mandatory vaccination acceptance as the main outcome are needed, but the results of this study confirm that in some settings the majority of HCWs favour mandatory vaccination. This, combined with effects that a flu epidemic could have if overlapped to pandemics with similar symptoms, requires renewed considerations on mandatory vaccination.     

Iso-electric focusing of aqueous humour IgG in multiple sclerosis

Samples of aqueous fluid were obtained from 35 controls who were people undergoing routine cataract surgery. Similar samples were taken from seven patients with clinically definite multiple sclerosis (MS) and a previous history of optic neuritis, either at cataract surgery or as an elective procedure. Oligoclonal bands were found in only one subject who suffered from the MS-uveitis syndrome.     

Blood retinol and β-carotene levels in rural Guatemalan preschool children

Plasma retinol and -carotene levels were measured in 502 preschool Guatemalan children from five rural hamlets. Their ages ranged from 6 to 78 months (mean: 42.9±19.2 months); 45% males and 55% females. The mean retinol value in the whole group was 0.9±0.4 µmol/1 (range: 0.1 to 8.4 µmol/1). There was no significant difference between sexes in retinol mean values nor in the incidence of retinol values less than 0.7 µmol/1 (22% in males, 18% in females). When grouped by age and community, significant low retinol mean values were found in two hamlets in the youngest age group (12 to 23 months) as compared to the other age-groups (p<0.05). In the other two hamlets, there were no significant differences among retinol means by age-group. The highest prevalence of deficient retinol values by age-group was in the 12 to 23 months group (40%), and decreased as age increased. The mean value for -carotene in the whole group was 0.13±0.18 µmol/1 (range: 0.01 to 2.23 µmol/1). There were no significant differences in -carotene means between sexes in the whole group. Stratifying the -carotene data by age-groups and community, values were significantly higher in the 48–59 months and 72–83 months groups, as compared with the other age groups in two of the communities (p<0.05). Significant differences across communities for -carotene were found only in the 12 to 23 months group.     

Two-year follow-up of laser in situ keratomileusis for hyperopia

PURPOSE: To evaluate excimer laser in situ keratomileusis (LASIK) for hyperopia and its predictability. METHODS: We performed a retrospective study of 100 eyes that had LASIK for hyperopia to assess predictability and long-term stability of refractive results. The Chiron Automated Corneal Shaper was used to create the flap and the Keracor 117CT Chiron-Technolas excimer laser with the plano-scan program was used to ablate all corneas. RESULTS: Mean baseline spherical equivalent manifest refraction was +4.50 +/- 1.73 D (range, +1.25 to +8.50 D). Six months after LASIK, mean manifest spherical equivalent refraction was +0.72 +/- 1.87 D (range, -1.75 to +2.50 D), at 1 year, +0.88 +/- 1.73 D (range, -1.25 to +2.50 D), and at 2 years, +0.85 +/- 1.74 D (range, -0.50 to +2.75 D). Two years after LASIK, 45 eyes (74%) were within +/-1.00 D of intended correction and within +/-1.00 D of emmetropia. Uncorrected visual acuity was 20/40 or better in 50 eyes (82%) at 2 years; 29 eyes (37%) saw 20/20 or better. Undercorrection occurred more frequently in eyes with preoperative keratometric power of more than 45.00 D, when ablation zones less than 6 mm were used and when higher amounts of hyperopic correction were required. CONCLUSION: LASIK with the Keracor 117CT excimer laser appears to be an effective and safe procedure to correct hyperopia. Preoperative keratometric power, amount of hyperopia, and ablation zone diameter affect the efficacy and long-term stability of the procedure.     

Phase II study of intravenous adenosine 5''-triphosphate in patients with previously untreated stage IIIB and Stage IV non-small cell lung cancer

Fifteen patients with Stage IIIB or IV non-small cell lung cancer gave informed consent to receive three or more 96-hour infusions of ATP at a dose of 50 mcg/kg/min or higher to determine whether ATP has antineoplastic activity against this tumor type and to better define the spectrum of toxicity for ATP given as a single agent. There were no objective complete or partial responses observed. The median survival of the overall group was 187 days and the median time to tumor progression was 113 days. The major toxic side effects were chest pain and dyspnea, leading to the cessation of treatment in 5 patients. We conclude that ATP at this dose and schedule of administration is an inactive agent in patients with advanced non-small cell lung cancer.     

Differential scanning calorimetry differences in micronized and unmicronized nimesulide uptake processes in biomembrane models.

Nimesulide release from micronized and unmicronized drug particles was tested at pH 7.4 by measuring the transfer to dimyristoylphosphatidylcholine liposomes (multilamellar and unilamellar vesicles), chosen as a biomembrane model. The perturbing effect of increasing molar fractions of pure nimesulide on the thermotropic behaviour of dimyristoylphosphatidylcholine liposomes was investigated by differential scanning calorimetry. In order to study the drug dissolution process by its uptake into void liposomes, measurements were carried out on suspensions of blank liposomes added to weighed amounts of free powdered nimesulide (micronized and unmicronized). The amount of drug transferred was quantified by comparing the effect caused by the dissolved and released drug to that caused by the free drug that had been previously molecularly dissolved in the liposomes. The calorimetric results show that the dissolution rate depends on the nimesulide form (micronized or unmicronized), and that the transfer to the void liposomes is quicker when the drug is in a micronized form. The uptake was faster when unilamellar vesicles were used instead of multilamellar vesicles because of the greater lipid surface. The calorimetric technique could represent an alternative 'in vitro' method that can be applied to the study of the dissolution kinetics directly at the site of drug uptake, mimicking a biological system.     

Intravenous RNA interference gene therapy targeting the human epidermal growth factor receptor prolongs survival in intracranial brain cancer.

PURPOSE: The human epidermal growth factor receptor (EGFR) plays an oncogenic role in solid cancer, including brain cancer. The present study was designed to prolong survival in mice with intracranial human brain cancer with the weekly i.v. injection of nonviral gene therapy causing RNA interference (RNAi) of EGFR gene expression. EXPERIMENTAL DESIGN: Human U87 gliomas were implanted in the brain of adult scid mice, and weekly i.v. gene therapy was started at day 5 after implantation of 500000 cells. An expression plasmid encoding a short hairpin RNA directed at nucleotides 2529-2557 within the human EGFR mRNA was encapsulated in pegylated immunoliposomes. The pegylated immunoliposome was targeted to brain cancer with 2 receptor-specific monoclonal antibodies (MAb), the murine 83-14 MAb to the human insulin receptor and the rat 8D3 MAb to the mouse transferrin receptor. RESULTS: In cultured glioma cells, the delivery of the RNAi expression plasmid resulted in a 95% suppression of EGFR function, based on measurement of thymidine incorporation or intracellular calcium signaling. Weekly i.v. RNAi gene therapy caused reduced tumor expression of immunoreactive EGFR and an 88% increase in survival time of mice with advanced intracranial brain cancer. CONCLUSIONS: Weekly i.v. nonviral RNAi gene therapy directed against the human EGFR is a new therapeutic approach to silencing oncogenic genes in solid cancers. This is enabled with a nonviral gene transfer technology that delivers liposome-encapsulated plasmid DNA across cellular barriers with receptor-specific targeting ligands.     

Therapeutic targeting of the survivin pathway in cancer: initiation of mitochondrial apoptosis and suppression of tumor-associated angiogenesis.

PURPOSE: Molecular antagonists of the inhibitor of apoptosis protein survivin have shown promise as novel anticancer strategies for triggering tumor cell apoptosis, dysregulating mitotic progression, and inhibiting tumor growth in preclinical models. However, how survivin couples to the cell death machinery has remained elusive, and the relevant cellular targets of survivin antagonists have not been completely elucidated. Experimental Design: Human umbilical vein and dermal microvascular endothelial cells were infected with replication-deficient adenoviruses encoding survivin (pAd-Survivin), green fluorescent protein (pAd-GFP), or a phosphorylation-defective survivin Thr(34)-->Ala (pAd-T34A) dominant negative mutant. The effect of wild-type or mutant survivin was investigated on capillary network stability, endothelial cell viability, and caspase activation in vitro and on kinetics of tumor growth and development of angiogenesis in a breast cancer xenograft model in vivo. The cell death pathway initiated by survivin targeting was mapped with respect to cytochrome c release, changes in mitochondrial transmembrane potential, and apoptosome requirements using mouse embryonic fibroblasts deficient in Apaf-1 or caspase-9. RESULTS: Adenoviral transduction of endothelial cells with pAd-Survivin inhibited growth factor deprivation- or ceramide-induced apoptosis, reduced caspase-3 and -7 generation, and stabilized three-dimensional capillary networks in vitro. Conversely, expression of pAd-T34A caused apoptosis in umbilical vein and dermal microvascular endothelial cells and resulted in caspase-3 activity. Cell death induced by survivin targeting exhibited the hallmarks of mitochondrial-dependent apoptosis with release of cytochrome c and loss of mitochondrial transmembrane potential and was suppressed in Apaf-1 or caspase-9 knockout mouse embryonic fibroblasts. When injected in human breast cancer xenografts, pAd-T34A inhibited growth of established tumors and triggered tumor cell apoptosis in vivo. This was associated with a approximately 60% reduction in tumor-derived blood vessels by quantitative morphometry of CD31-stained tumor areas, and appearance of endothelial cell apoptosis by internucleosomal DNA fragmentation in vivo. CONCLUSIONS: Survivin functions as a novel upstream regulator of mitochondrial-dependent apoptosis, and molecular targeting of this pathway results in anticancer activity via a dual mechanism of induction of tumor cell apoptosis and suppression of angiogenesis.