Cost-effectiveness profile, organizational implications and patient preferences on the use of exogenous TSH therapy (Thyrogen®) vs. THW in thyroid residue ablation in Italy

BACKGROUND: Radioiodine ablation is an adjuvant procedure used to treat patients with differentiated thyroid cancer. For ablation to be successful, patients must have elevated levels of thyroid stimulating hormone (TSH). This can be achieved by withholding thyroid hormone therapy (endogenous stimulation), or by administration of recombinant human thyroid stimulating hormone (rhTSH; Thyrogen®; exogenous stimulation) to patients in the euthyroid state.AIM: To compare the estimated health benefits, cost and cost-effectiveness of TSH stimulation with and without Thyrogen® in the Italian setting.METHODS: A cost-utility analysis was undertaken to assess the impact of exogenous vs. endogenous TSH stimulation before radioiodine remnant ablation of patients with newly diagnosed, well-differentiated papillary or follicular thyroid cancer who have undergone total or near-total thyroidectomy. A Markov model was developed to simulate treatment costs and health outcomes associated with exogenous and endogenous stimulation in four distinct health states: pre-ablation, ablation, post-ablation, and well/recovery. Treatment was stratified by patients who receive high- and low-activity (30-100 mCi, respectively) in the ablation state. The Italian National Health System perspective was adopted in the base case scenario while the impact of indirect costs was explored in a sensitivity analysis. Costs and quality-adjusted life years (QALY) specific to each health state were estimated, summarized and converted into a corresponding incremental cost-effectiveness ratio (ICER).RESULTS: We calculated a cost-effectiveness ratio of 18,357.18 €/QALY gained whereas the inclusion of indirect cost and accident cost produced reductions of the ICER to € 14,609.51 and € 15,515.26 per QALY, respectively. Finally, all results in the sensitivity analysis are below the lower bound of national and international cost- effective threshold.CONCLUSION: Thyrogen® represents a cost-effective option for patients with differentiated thyroid cancer who underwent total or near-total thyroidectomy in Italy. Our findings are consistent with other cost-utility analyses

Muscularis Macrophages in Healthy and Diseased Gut

Muscularis macrophages are a newly discovered population of macrophages distributed within the smooth muscle layers of the gastrointestinal tract. Muscularis macrophages are emerging as essential cell keepers of homeostatic gastrointestinal function, and when affected, can lead to functional gastrointestinal disorders. In this chapter, we briefly introduce the phenotype, the distribution of muscularis macrophages, and the difference compared with other tissue-resident macrophages. We next describe how they contribute to normal gastrointestinal function by interacting with cells required for gastrointestinal motility, such as enteric neurons. Finally, we highlight the increasing pieces of evidence suggesting the contribution of muscularis macrophages to gastrointestinal function diseases, such as gastrointestinal inflammation, gastroparesis and post operative ileus

OGTA: Open gaze tracker and analyzer a remote low cost system based on off-the-shelf components and open source modular software

Several academic and commercial eye tracking systems have evolved to the point that they can operate without contact with the user. In addition, they also permit free head movement (within reasonable limits) without losing tracking and maintaining a good accuracy (errors below 1 degree). However, there are still several aspects which require further improvement before these systems can be extensively used. These include price, accuracy, robustness, and ease of set-up and use. This work proposes a preliminary version of a remote eye tracking system which starts to deal with some of those critical points. To drastically reduce the costs, the system has been built by assembling low cost off-the-shelf components, and the cross-platform software has been developed based on an open source philosophy. Second, the accuracy in gaze detection has been improved through the Starburst algorithm. Last and importantly, the plug-in organization of the software architecture, which crucially distinguishes the proposed system from similar ones previously proposed in literature. This facilitates the addition of dedicated software modules designed to improve specific features according to the particular application at hand. Here we present the architecture of the system and preliminary results on the functioning and accuracy of the system

Strontium isotope stratigraphy of late Cenozoic fossiliferous marine deposits in North Borneo (Brunei, and Sarawak, Malaysia)

Neogene marine deposits of North Borneo are locally very rich in fossils that provide glimpses into the past biodiversity. However, dating these onshore sediments with biostratigraphy is often hampered by the lack and/or the poor preservation state of index fossils. Therefore, the fossiliferous sites were targeted with strontium isotope stratigraphy (SIS) to obtain higher precision relative dating. Well-preserved macrofossils were screened using a multidisciplinary approach, and 87Sr/86Sr ratios of the most pristine remains were used to date the embedding sediments. Most of the measured ages fall in the expected chronostratigraphic framework established by large scale studies for the region. The oldest, Burdigalian (early Miocene) ages were measured for the Sibuti Formation in Sarawak (17.71 \ub1 0.2My and 16.7 \ub1 0.2My) followed by a Serravallian (middle Miocene) age within the Belait Fm in Brunei (12.1 +1.4/-1.2My). Eight localities from the younger units, the Miri and Seria formations in Brunei, gave a range in age from 10.5 \ub1 1 to 7.0 +0.9/-0.5My (Tortonian-Messinian). Reworked fossil assemblages from Tutong beach were also investigated and the SIS ages of Late Miocene support an origin from the younger part of the Seria Fm. One locality, in Lumapas where limestone crops out in Brunei, gave an unexpected younger age (Tortonian, late Miocene, 10.6 \ub1 1My) compared to estimates projected for its assumed stratigraphic position in the lower Belait Formation (late Burdigalian). These challenging data require more research, yet if the young age is accepted, the stratigraphic situation of the limestone needs further revision

NK-receptors, Substance P, Ano1 expression and the ultrastructural features of the muscle coat are modified in the Cav-1-/- mouse ileum

Caveolin (Cav)-1 is an integral membrane protein of caveolae playing a crucial role in various signal transduction pathways. Caveolae represent the sites for calcium entry and storage especially in smooth muscle cells (SMC) and interstitial cells of Cajal (ICC). Cav-1-/- mice lack caveolae and show abnormalities in pacing and contractile activity of the small intestine. In particular, the absence of caveolae in ICC compromised their ability to maintain frequencies of contraction. Presently, we investigated, by transmission electron microscopy (TEM) and immunohistochemistry, whether the absence of Cav-1 in Cav-1-/- mouse small intestine affects ICC, SMC and neuronal morphology, the expression of NK1 and NK2 receptors, and of Ano1 (also called Dog1 or TMEM16A) an essential molecule for slow wave activity in gastrointestinal muscles. ICC were also labeled with c-Kit and tachykinergic neurons with Substance P (SP). Immunohistochemical results showed that in Cav-1-/- mice: i) ICC were Ano1-negative but maintained c-Kit expression, ii) NK1 and NK2 receptor immunoreactivity was increased and, in the SMC, mainly intracytoplasmatic, iii) SP-immunoreactivity was significantly reduced. Under TEM: i) ICC and SMC lacked typical caveolae but had few and large flask-shaped vesicles we called large-sized caveolae; ii) SMC and ICC contained an extraordinary high number of mitochondria; iii) neurons were unchanged. In conclusion, the present study shows important changes in SMC, ICC and neurons of the Cav-1-/- mice. Loss of Ano1 expression in the ICC and rearrangement of NK receptors in the SMC are interpretable as consequence of Cav-1/caveolae loss and possibly responsible for the impaired contractile activity. However, the impressive richness in mitochondria and the decrease in SP content might represent the ways to compensate the reduced calcium availability and the increased expression of NKr, allowing the maintenance of a certain cell function

Relaxin increases contractile activity and neuronal Nitric Oxide Synthase (nNOS) expression in the muscle coat of mouse colon

Since the first observations, many actions have been attributed to Relaxin (RLX), so that it has been defined a pleiotropic hormone. This peptide of 6000 Da is synthesized by reproductive organs both in females and males. In particular, in females RLX is produced by corpus luteum (30-150 pg/ml) and its highest plasma levels (900 pg/ml) are reached during pregnancy, when RLX is also released by the decidua and placenta. In pregnancy, RLX plays its traditional role as inhibitor of spontaneous myometrial contractions and maintains uterine quiescence. Recently, RLX has shown to affect the smooth muscle of mouse gastric fundus and small intestine, depressing its motility through a nitric oxide (NO)-mediated mechanism. In this study, we investigate the functional role of RLX in the muscle coat of female mouse colon. In the presence of 50 nmol/l RLX, continuous recordings of isometric tension showed a fast reduction of circular muscle tone, followed by a stable increase of contraction amplitude. This double effect was mimicked by the application of 40 μmol/l NaNO2, a NO donor, and completely blocked by 1 μmol/l ODQ, an inhibitor of cyclic GMP which represents the main intracellular mediator of NO actions. The treatment of the tissue with 1 μmol/l TTX prevented the decrease of muscle tone caused by RLX, indicating that this specific effect was neuronally triggered. To clarify the underling cellular mechanism, the neuronal Nitric Oxide Synthase (nNOS) expression was evaluated in colonic segments treated with (50 nmol/l) RLX for 10 min or 40 min. In particular, two different antibodies able to recognize respectively the neurogenic and the myogenic nNOS were used. Interestingly, at both times of treatment, we observed an increase of neurogenic nNOS immunoreactivity (IR) and a decrease in myogenic nNOS-IR. These two opposite effects result statistically significant. Present functional and morphological findings demonstrate that RLX produces a paradoxical effect in the colonic muscle coat which likely represents the final result of an interaction between the two splice variants of the nNOS enzyme

A new method for spatial mode shifting of stabilized optical cavities for the generation of dual-color X-rays

We propose an innovative method to shift the transversal position of the focal point of an optical cavity keeping it actively frequency stabilized. Our cavity is a 4 mirrors bow-tie cavity and the spatial shift of the resonant mode is obtained by properly rotating the two curved mirrors by piezo actuators. This method allows us to move the transversal position of the cavity focal point of 135 µm in a time of 50 ms, keeping the resonance condition of the cavity by means of the Pound–Drever–Hall technique. We propose to use this technique for the generation of 2-color X-rays via Inverse Compton Scattering (ICS). This technique exploits the large average power stored in the high finesse cavity by shifting the laser beam with respect to the electron beam trajectory, hence controlling the spatial superposition of the electron and photon beams in the interaction region. Arranging two cavities assembled one on top of the other, with different collision angle with the electron beam, allows the generation of X-ray bursts of different energies just by swiftly moving the two cavities, switching the two focal points onto the electron beam trajectory, thus activating in sequence two different ICS spectral lines

Arthrospira platensis F&M-C265 reduces cardiometabolic risk factors in rats fed a high fat diet

Clinical studies indicate that Arthrospira platensis (A. platensis) mitigates cardiometabolic risk factors, but the underlying mechanisms are very elusive. To fill this gap, Sprague-Dowley rats were fed either AIN-76 normal diet (5 % corn oil) or high-fat (HF; 30 % lard + 3 % corn oil) or HF + 5 % A. platensis F&M-C256 diet for 3 months. A. platensis F&M-C256 decreased blood triglycerides and total cholesterol, systolic and diastolic pressure and enhanced the expression of thermogenesis-related genes Prdm16, Dio2, PPARγ, Ucp1 and Lpl in visceral adipose tissue, compared to HF-diet. A. platensis reduced ANGPTL3 plasma levels and hepatic steatosis, prevented periaortic adipose tissue hypertrophy and increased aortic eNOS expression. These data provide some mechanistic evidence about the beneficial effects of A. platensis observed in human studies. Further controlled trials are needed to verify the clinical usefulness of A. platensis supplementation against metabolic disorders, to select the dosing regimens and the subgroup of patients with likelihood of benefit

Diabetic Csf1op/op Mice Lacking Macrophages Are Protected Against the Development of Delayed Gastric Emptying

Background & AimsDiabetic gastroparesis is associated with changes in interstitial cells of Cajal (ICC), neurons, and smooth muscle cells in both animal models and humans. Macrophages appear to be critical to the development of cellular damage that leads to delayed gastric emptying (GE), but the mechanisms involved are not well understood. Csf1op/op (Op/Op) mice lack biologically active Csf1 (macrophage colony stimulating factor), resulting in the absence of Csf1-dependent tissue macrophages. We used Csf1op/op mice to determine the role of macrophages in the development of delayed GE.MethodsAnimals were injected with streptozotocin to make them diabetic. GE was determined weekly. Immunohistochemistry was used to identify macrophages and ICC networks in the gastric muscular layers. Oxidative stress was measured by serum malondialdehyde (MDA) levels. Quantitative reverse-transcription polymerase chain reaction was used to measure levels of mRNA.ResultsCsf1op/op mice had normal ICC. With onset of diabetes both Csf1op/op and wild-type Csf1+/+ mice developed increased levels of oxidative stress (75.8 ± 9.1 and 41.2 ± 13.6 nmol/mL MDA, respectively). Wild-type Csf1+/+ mice developed delayed GE after the onset of diabetes (4 of 13) whereas no diabetic Csf1op/op mouse developed delayed GE (0 of 15, P = .035). The ICC were disrupted in diabetic wild-type Csf1+/+ mice with delayed GE but remained normal in diabetic Csf1op/op mice.ConclusionsCellular injury and development of delayed GE in diabetes requires the presence of muscle layer macrophages. Targeting macrophages may be an effective therapeutic option to prevent cellular damage and development of delayed GE in diabetes