Italian healthcare workers' views on mandatory vaccination

Background  

Mandatory vaccination has contributed to the success of immunisation programmes but voluntary vaccination allows people to be responsible for their own health. There are benefits from both policies and the arguments between them remain subject to debate within and without the scientific community, both nationally and internationally. The aim of this study is to assess the opinions of those who actually work in the Vaccination Service.     

The abdomen of <Emphasis Type="Italic">Drosophila</Emphasis>: does planar cell polarity orient the neurons of mechanosensory bristles?

Background

In the adult abdomen of Drosophila, the shafts of mechanosensory bristles point consistently from anterior to posterior. This is an example of planar cell polarity (PCP); some genes responsible for PCP have been identified. Each adult bristle is made by a clone of four cells, including the neuron that innervates it, but little is known as to how far the formation or positions of these cells depends on PCP. The neurons include a single dendrite and an axon; it is not known whether the orientation of these processes is influenced by PCP.

Results

We describe the development of the abdominal mechanosensory bristles in detail. The division of the precursor cell gives two daughters, one (pIIa) divides to give rise to the bristle shaft and socket cell and the other (pIIb) generates the neuron, the sheath and the fifth cell. Although the bristles and their associated shaft and socket cells are consistently oriented, the positioning and behaviour of the neuron, the sheath and the fifth cell, as well as the orientation of the axons and the dendritic paths, depend on location. For example, in the anterior zone of the segment, the axons grow posteriorly, while in the posterior zone, they grow anteriorly. Manipulating the PCP genes can reverse bristle orientation, change the path taken by the dendrite and the position of the cell body of the neuron. However, the paths taken by the axon are not affected.

Conclusion

PCP genes, such as starry night and dachsous orient the bristles and position the neuronal cell body and affect the shape of the dendrites. However, these PCP genes do not appear to change the paths followed by the sensory axons, which must, therefore, be polarised by other factors.

     

Changes in DNA Damage Repair Gene Expression and Cell Cycle Gene Expression Do Not Explain Radioresistance in Tamoxifen-Resistant Breast Cancer

Tamoxifen-induced radioresistance, reported in vitro, might pose a problem for patients who receive neoadjuvant tamoxifen treatment and subsequently receive radiotherapy after surgery. Previous studies suggested that DNA damage repair or cell cycle genes are involved, and could therefore be targeted to preclude the occurrence of cross-resistance. We aimed to characterize the observed cross-resistance by investigating gene expression of DNA damage repair genes and cell cycle genes in estrogen receptor-positive MCF-7 breast cancer cells that were cultured to tamoxifen resistance. RNA sequencing was performed, and expression of genes characteristic for several DNA damage repair pathways was investigated, as well as expression of genes involved in different phases of the cell cycle. The association of differentially expressed genes with outcome after radiotherapy was assessed in silico in a large breast cancer cohort. None of the DNA damage repair pathways showed differential gene expression in tamoxifen-resistant cells compared to wild-type cells. Two DNA damage repair genes were more than two times upregulated (NEIL1 and EME2), and three DNA damage repair genes were more than two times downregulated (PCNA, BRIP1, and BARD1). However, these were not associated with outcome after radiotherapy in the TCGA breast cancer cohort. Genes involved in G₁, G₁/S, G₂, and G₂/M phases were lower expressed in tamoxifen-resistant cells compared to wild-type cells. Individual genes that were more than two times upregulated (MAPK13) or downregulated (E2F2, CKS2, GINS2, PCNA, MCM5, and EIF5A2) were not associated with response to radiotherapy in the patient cohort investigated. We assessed the expression of DNA damage repair genes and cell cycle genes in tamoxifen-resistant breast cancer cells. Though several genes in both pathways were differentially expressed, these could not explain the cross-resistance for irradiation in these cells, since no association to response to radiotherapy in the TCGA breast cancer cohort was found.     

Muscle uridine diphosphate-hexosamines do not decrease despite correction of hyperglycemia-induced insulin resistance in type 2 diabetes

Animal studies suggest that overactivity of the hexosamine pathway, resulting in increased UDP-hexosamines [UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylgalactosamine (UDP-GalNAc)] is an important mechanism by which hyperglycemia causes insulin resistance. This study was performed to test this hypothesis in patients with type 2 diabetes mellitus (DM). Eight obese patients with uncontrolled DM type 2 and severe insulin resistance were treated with iv insulin for 28 +/- 6 d aimed at euglycemia. Before and after iv insulin treatment, insulin sensitivity was measured using a hyperinsulinemic euglycemic clamp, and a muscle biopsy was taken for measurement of UDP-GlcNAc, UDP-GalNAc, UDP-glucose, and UDP-galactose levels. Also, isoelectric focusing patterns of serum transferrin and the urinary excretion of glycosaminoglycans as measures of final products of the hexosamine pathway were examined. After euglycemia, insulin resistance improved, as demonstrated by an increase in the glucose infusion rate during the clamp from 12.7 +/- 5.6 to 22.4 +/- 8.8 micro mol/kg.min (P < 0.0005) and a decrease in insulin requirement from 1.7 +/- 0.9 to 1.1 +/- 0.6 U/kg.d (P < 0.005), whereas metabolic control improved. Surprisingly, both UDP-GlcNAc, from 8.81 +/- 1.21 to 12.31 +/- 2.52 nmol/g tissue (P < 0.005), and UDP-GalNAc concentrations, from 4.49 +/- 0.85 to 5.89 +/- 1.55 nmol/g tissue (P < 0.05) increased. Isoelectric focusing patterns of serum transferrin and excretion of glycosaminoglycans were similar before and after euglycemia. In conclusion, after amelioration of hyperglycemia- induced insulin resistance, UDP-hexosamines increased in skeletal muscle of patients with type 2 DM. These results do not support the hypothesis that accumulation of products of the hexosamine pathway plays a major role in hyperglycemia-induced insulin resistance.     

Hypoxic regulation and prognostic value of LAMP3 expression in breast cancer

BACKGROUND:

LAMP3 is a newly described hypoxia regulated gene of potential interest in hypoxia‐induced therapy resistance and metastasis. The prognostic value of LAMP3 in breast cancer was investigated.

METHODS:

Expression levels of LAMP3 in breast cancer cell lines and patient tissues were determined by real‐time polymerase chain reaction and in a tissue microarray by immunohistochemistry. Immunofluorescent staining was used to evaluate the distribution of LAMP3 in tumor xenografts relative to pimonidazole. Kaplan‐Meier analysis as well as multivariate Cox regression survival analyses were performed.

RESULTS:

LAMP3 was variably expressed in breast cancer cell lines and induced in an oxygen concentration‐dependent manner. LAMP3 protein expression colocalized with hypoxic areas in breast cancer xenografts. LAMP3 mRNA was higher in breast tumors from patients with node‐positive (P = .019) and/or steroid hormone receptor‐negative tumors (P < .001). Breast cancer patients with high LAMP3 mRNA levels had more locoregional recurrences (P = .032 log‐rank). This was limited to patients treated with lumpectomy and radiotherapy as primary treatment (n = 53, P = .009). No association with metastasis‐free survival was found. In multivariate Cox regression analysis, LAMP3 remained as a statistically independent prognostic factor for locoregional recurrence (hazard ratio, 2.76; 95% confidence interval, 1.01‐7.5; P = .048) after correction for menopausal status, histologic grade, tumor size, nodal status, therapy, and steroid hormone receptor status. LAMP3 protein in breast cancer tissue proved also to be of prognostic relevance.

CONCLUSIONS:

Evidence was provided for an association of LAMP3 with tumor cell hypoxia in breast cancer xenografts. In the current breast cancer cohorts, LAMP3 had independent prognostic value. Cancer 2011;117:3670–3681. © 2011 American Cancer Society.     

In-111-labeled white blood cell uptake in noninfected closed fracture in humans: prospective study

Since indium-111 white blood cell (In-111 WBC) scintigraphy is often used to evaluate for osteomyelitis in bone fractures, it is important to know if noninfected fractures have In-111 WBC uptake. Twenty-seven noninfected closed fracture sites in 19 patients were prospectively evaluated with technetium-99m methylene diphosphonate bone scintigraphy and In-111 WBC scintigraphy. In-111 WBC uptake was present in 41% of the 27 sites. In the 11 positive sites, the In-111 WBC uptake was 1+ (definite but minimal) in 55%, 2+ (moderate) in 36%, and 3+ (marked) in 9%. The visual intensity of the radioactive uptake on In-111 WBC scintigrams relative to that on bone scintigrams was less in 82%, equal in 9%, and greater in 9%. The visual size of the area of uptake on In-111 WBC scintigrams and bone scintigrams was smaller in 36%, equal in 55%, and greater in 9%. Factors that may help distinction of In-111 WBC uptake due to fracture alone from infection associated with fracture are discussed.     

Progressive histopathological changes in pancreatic islets of Zucker Diabetic Fatty rats.

Thus far, histopathological changes in the pancreatic islets of Zucker Diabetic Fatty (ZDF) rats, an animal model of type 2 diabetes mellitus (or non-insulin-dependent diabetes mellitus), have only been studied in male rats and in 18-weeks old rats or younger. In this study, we have examined in both male and female ZDF rats the histopathological changes longitudinally, from 6 to 32 weeks of age. We studied islet architecture and cellular distribution of the various islet hormones both in ZDF and control rats. In the ZDF rats, aging was initially associated with an enlargement of the islets. From 18 weeks onwards, no further enlargement was noted but islet boundaries became increasingly irregular, leading to the appearance of projections of endocrine cells into the surrounding exocrine tissue. At the islet boundaries as well as within the islets progressive fibrosis was observed with increasing amounts of collagen and reticular fibers. In the islets, staining intensity of both insulin and islet amyloid polypeptide (IAPP) increased slightly till 10 weeks of age and thereafter decreased rapidly. In contrast, the staining intensities of glucagon, somatostatin, and pancreatic polypeptide (PP) did not change. Even at the age of 32 weeks, just the beta-cells and not the other endocrine islet cells appear to be affected. In control rats, aging evoked only minor changes. Thus, we observed that during prolonged development of diabetes mellitus in both male and female ZDF rats histopathological changes in the pancreatic islets became progressively more severe, eventually leading to disintegration of the islets.     

Non-Epstein-Barr virus-associated T-cell lymphoma following cardiac transplantation for Barth syndrome

Barth syndrome is a metabolic disease characterized by infantile cardiomyopathy, neutropenia and organic aciduria. We report disease evolution in one of the first affected boys to undergo successful cardiac transplantation. CONCLUSION: Although cardiac status stabilized, he developed disabling skeletal myopathy, protracted lymphopenia and--5 y after transplant--fatal Epstein Barr (EBV)-negative T-cell non-Hodgkin's lymphoma.