Medical workforce planning in a changing health context: Comparison between Italy and Europe

An increasing need for healthcare workers as been estimated worldwide. To provide a comprehensive framework of the medical workforce in Italy, we investigated the post-lauream medical workforce training supply and demand. Further, a comparison of the medical workforce between Italy and other European Countries with a similar epidemiological and/or demographic context was performed. The distribution of pre-and post-lauream medical educational providers and post-lauream resources in place in Italy was analyzed among Italian macro-areas in the academic years 2015-2016, 2016-2017 and 2017-2018.Italy and the European countries in study were compared in term of post-lauream funding and number of active physicians by specialization per 1,000 inhabitants. Open access data from official Italian and European institutional sources were used. The most of medical schools were distributed in the North, followed by South, islands and Central Italy, while the highest enrolment rate in the pre-lauream medical education was reported in Central Italy, followed by South & islands and North. The total number of active residency programs increased from 1092 to 1286 in the three considered academic years, while number of post-lauream training contracts decreased from 11.0 to 10.2 per 100,000 inhabitants. A misalignment between contracts assigned to residency programs and grants assigned to general practitioners specific courses was observed. Furthermore, when compared to the EU countries in study, Italy documented the lowest number of post-graduated training positions in 2015, with a rate of 12.1/100,000 inhabitants. Also, an excess of medical specialists (3.06 per 1,000 inhabitants) with a simultaneous shortage of general practitioners (0.89 per 1,000 inhabitants) was reported. On the contrary, Italy documented the highest number of paediatric practitioners. More efforts, including the implementation of adequate tools, are required both at national and regional level in order to provide a medical workforce planning in line with a continuously changing health context

Medical workforce planning in a changing health context: Comparison between Italy and Europe

An increasing need for healthcare workers as been estimated worldwide. To provide a comprehensive framework of the medical workforce in Italy, we investigated the post-lauream medical workforce training supply and demand. Further, a comparison of the medical workforce between Italy and other European Countries with a similar epidemiological and/or demographic context was performed. The distribution of pre-and post-lauream medical educational providers and post-lauream resources in place in Italy was analyzed among Italian macro-areas in the academic years 2015-2016, 2016-2017 and 2017-2018.Italy and the European countries in study were compared in term of post-lauream funding and number of active physicians by specialization per 1,000 inhabitants. Open access data from official Italian and European institutional sources were used. The most of medical schools were distributed in the North, followed by South, islands and Central Italy, while the highest enrolment rate in the pre-lauream medical education was reported in Central Italy, followed by South & islands and North. The total number of active residency programs increased from 1092 to 1286 in the three considered academic years, while number of post-lauream training contracts decreased from 11.0 to 10.2 per 100,000 inhabitants. A misalignment between contracts assigned to residency programs and grants assigned to general practitioners specific courses was observed. Furthermore, when compared to the EU countries in study, Italy documented the lowest number of post-graduated training positions in 2015, with a rate of 12.1/100,000 inhabitants. Also, an excess of medical specialists (3.06 per 1,000 inhabitants) with a simultaneous shortage of general practitioners (0.89 per 1,000 inhabitants) was reported. On the contrary, Italy documented the highest number of paediatric practitioners. More efforts, including the implementation of adequate tools, are required both at national and regional level in order to provide a medical workforce planning in line with a continuously changing health context

Treatment of ovarian cancer with surgery, short-course chemotherapy and whole abdominal radiation

Background The primary aim was to induce a high number of pCR in early (FIGO IC, JIB + C)-and advanced (FIGO ffl—IV)—stage ovarian cancer with a surgery plus 4 cycles of cisplatin and meiphalan (PAMP) regimen. The second objective was to prevent relapse with WAR in patients in remission after chemotherapy. Patients and methods 218 eligible patients were treated after staging laparotomy with cisplatin 80 mg/sqm iv. on day 1 and melphalan 12 mg/sqm i.v. on day 2 q 4 weeks. Response was verified by second-look laparotomy. WAR was carried out with the open field technique on a linear accele rator (daily dose: 1.3 Gy, total dose: 29.9 Gy) in patients with pathological or clinicaJ CR or pathological PR with microscopical residual disease. Results 146/218 patients (67%, 95% CI: 61%-73%) responded to PAMIP: 56 (26%) achieved pCR, 24 (11%), cCR, 56 (26%) pPR and 10 (5%) cPR (c=clinical, p=pathological). Multivariate analyses revealed that in advanced stages (92 cases in remission), the achievement of pCR was the most important factor for longer time to failure (TIF) and survival. Only 5 1/118 (43%) patients in remission received WAR Early-stage patients <=55 years were more likely to have WAR than patients older than 55 years (77% vs. 23%; p= 0.02). Advanced-stage patients with cCR were less likely to be irradiated than patients with pCR or pPR (10% vs. 51%; p= 0.003). Toxicity of PAMP was acceptable with 10% of WHO grade 4 hematologic toxicity. Acute hematological toxicity of WAR caused interruption (3 3%) or incompleteness (3 3%) of irradiation in the majority of patients. Conclusions PAMP is an effective treatment for advanced ovarian cancer with a 67% response rate after 4 cycles. For the majority of patients in remission, WAR as a consolidation treatment was hardly feasible. For these patients new treatment modalities to consolidate remission are neede

A phase I study of PankoMab-GEX, a humanised glyco-optimised monoclonal antibody to a novel tumour-specific MUC1 glycopeptide epitope in patients with advanced carcinomas

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Transport of Proteins into Mitochondria

The mitochondrial ADP/ATP carrier is an integral transmembrane protein of the inner membrane. It is synthesized on cytoplasmic ribosomes. Kinetic data suggested that this protein is transferred into mitochondria in a posttranslational manner. The following results provide further evidence for such a mechanism and provide information on its details. 1. In homologous and heterologous translation systems the newly synthesized ADP/ATP carrier protein is present in the postribosomal supernatant. 2. Analysis by density gradient centrifugation and gel filtration shows, that the ADP/ATP carrier molecules in the postribosomal fraction are present as soluble complexes with apparent molecular weights of about 120000 and 500000 or larger. The carrier binds detergents such as Triton X-100 and deoxycholate forming mixed micelles with molecular weights of about 200000–400000. 3. Incubation of a postribosomal supernatant of a reticulocyte lysate containing newly synthesized ADP/ATP carrier with mitochondria isolated from Neurospora spheroplasts results in efficient transfer of the carrier into mitochondria. About 20–30% of the transferred carrier are resistant to proteinase in whole mitochondria. The authentic mature protein is also largely resistant to proteinase in whole mitochondria and sensitive after lysis of mitochondria with detergent. Integrity of mitochondria is a prerequisite for translocation into proteinase resistant position. 4. The transfer in vitro into a proteinase-resistant form is inhibited by the uncoupler carbonyl-cyanide m-chlorophenylhydrazone but not the proteinase-sensitive binding. These observations suggest that the posttranslational transfer of ADP/ATP carrier occurs via the cytosolic space through a soluble oligomeric precursor form. This precursor is taken up by intact mitochondria into an integral position in the membrane. These findings are considered to be of general importance for the intracellular transfer of insoluble membrane proteins. They support the view that such proteins can exist in a water-soluble form its precursors and upon integration into the membrane undergo a conformational change. Uptake into the membrane may involve the cleavage of an additional sequence in some proteins, but this appears not to be a prerequisite as demonstrated by the ADP/ATP carrier protein

Chaperone-dependent Regulation of Endothelial Nitric-oxide Synthase Intracellular Trafficking by the Co-chaperone/Ubiquitin Ligase CHIP

Endothelial nitric-oxide synthase (eNOS), the enzyme responsible for production of endothelial NO, is under tight and complex regulation. Proper cellular localization of eNOS is critical for optimal coupling of extracellular stimulation with NO production. In addition, the molecular chaperone Hsp90 interacts with eNOS and positively regulates eNOS activity. Hsp90 is modulated by physical interaction with its co-chaperones. CHIP (carboxyl terminus of Hsp70-interacting protein) is such a co-chaperone that remodels the Hsp90 heterocomplex and causes protein degradation of some Hsp90 substrates through the ubiquitin-protein isopeptide ligase activity of CHIP. Here we show that CHIP incorporated into the eNOS.Hsp90 complex and specifically decreased soluble eNOS levels in transiently transfected COS cells. Surprisingly, in contrast to the effects of the Hsp90 inhibitor geldanamycin, which induces eNOS ubiquitylation and its subsequent protein degradation, CHIP did not target eNOS for ubiquitylation and proteasome-dependent degradation. Instead, CHIP partitioned soluble eNOS into an insoluble and inactive cellular compartment, presumably through its co-chaperone activity. This effect seems to be due to displacement of eNOS from the Golgi apparatus, which is otherwise required for trafficking of eNOS to the plasmalemma and subsequent activation. Consistent with observations from overexpression studies, eNOS localization to the membrane and activity were increased in mouse lung endothelial cells lacking CHIP. Taken together, these results demonstrate a novel co-chaperone-dependent mechanism through which eNOS trafficking is regulated and suggest a potentially generalized role for CHIP in protein trafficking through the Golgi compartment

Electrical Hole Transport Properties of an Ambipolar Organic Compound With Zn-Atoms on a Crystalline Silicon Heterostructure

In this paper, we investigate the electrical hole transport properties of an organic/inorganic heterostructure consisting of a thin organic film, that combines hole and electron conducting molecules around a bridging Zn-atom, deposited on top of an n-type crystalline silicon substrate. Current-voltage characteristics and capacitance voltage measurements have been used for the determination of the organic layer dielectric and hole conduction parameters

Uncoupling Caveolae from Intracellular Signaling in Vivo

© 2016 Nature America, Inc. Rationale: Caveolin-1 (Cav-1) negatively regulates endothelial nitric oxide (NO) synthase-derived NO production, and this has been mapped to several residues on Cav-1, including F92. Herein, we reasoned that endothelial expression of an F92ACav-1 transgene would let us decipher the mechanisms and relationships between caveolae structure and intracellular signaling. Objective: This study was designed to separate caveolae formation from its downstream signaling effects. Methods and Results: An endothelial-specific doxycycline-regulated mouse model for the expression of Cav-1-F92A was developed. Blood pressure by telemetry and nitric oxide bioavailability by electron paramagnetic resonance and phosphorylation of vasodilator-stimulated phosphoprotein were determined. Caveolae integrity in the presence of Cav-1-F92A was measured by stabilization of caveolin-2, sucrose gradient, and electron microscopy. Histological analysis of heart and lung, echocardiography, and signaling were performed. Conclusions: This study shows that mutant Cav-1-F92A forms caveolae structures similar to WT but leads to increases in NO bioavailability in vivo, thereby demonstrating that caveolae formation and downstream signaling events occur through independent mechanisms