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Late Quaternary crustal uplift is well recognized in northeast Sicily, southern Italy, a region also prone to damaging earthquakes such as the 1908 "Messina" earthquake (Mw 7.1), the deadliest seismic event reported within the Italian Earthquake Catalogue. Yet it is still understudied if, within the Milazzo Peninsula, crustal uplift rates are varying spatially and temporally and whether they may be either influenced by (i) local upper‐plate faulting activity or (ii) deep geodynamic processes. To investigate the long‐term crustal vertical movements in northeast Sicily, we have mapped a flight of Middle‐Late Pleistocene marine terraces within the Milazzo Peninsula and in its southern area and refined their chronology, using a synchronous correlation approach driven by published age controls. This has allowed a new calculation of the associated crustal uplift rates, along a north–south oriented coastal‐parallel transect within the investigated area. Our results show a decreasing uplift rate from south to north across the Milazzo Peninsula and beyond, and that the associated rates of uplift have been constant through the Late Quaternary. This spatially varying yet temporally constant vertical deformation helps to constrain the amount of uplift, allowing us to explore which is the driving mechanism(s), proposing a few related scenarios. We discuss our results in terms of tectonic implications and emphasize the importance of using appropriate approaches, as such applying a synchronous correlation method, to refine chronologies of undated palaeoshorelines when used for tectonic investigations. [ABSTRACT FROM AUTHOR]

The article discusses the prevalence of protective antibodies against measles among healthcare workers (HCWs) at a university hospital in Milan, Italy, from 2019 to 2023. It highlights the importance of vaccination for HCWs to prevent outbreaks of vaccine-preventable infections. The study found that 83% of HCWs had protective antibodies, with higher rates in older age groups. Seroconversion was observed in 88% of HCWs who received a booster dose of the MMR vaccine. The study emphasizes the significance of antibody testing and vaccination promotion among HCWs to prevent measles infections. [Extracted from the article]

Background: A survey of laboratories in North American and Europe that routinely conduct fetal skeletal examinations was performed with the purpose of (1) understanding current terminology used for classifying skeletal findings in developmental toxicity (DT) studies and (2) understanding the criteria used to identify relatively common findings that sufficiently deviate from normal. The goal was to promote terminology harmonization and improve interlaboratory consistency in the criteria used to identify developmental anomalies. Methods: The survey, designed based on terminology for developmental anomalies recommended by an international collaboration (Makris et al., Congenital Anomalies, 2009;49(3):123–246), was conducted by a subgroup (authors of this publication) of the Royal Society of Biology's International Register of Fetal Morphologists (IRFM). Results: Individual and summarized anonymized responses are provided here. The authors, who are expert fetal morphologists with experience performing fetal examinations, reviewed the responses and generated recommendations on preferred terminology and criteria for determining when morphological variations deviate from normal and warrant recording of the findings for skeletal observations in Sprague Dawley (SD) fetal rats. The objective of these recommendations is to complement Makris et al. (Congenital Anomalies, 2009;49(3):123–246). Conclusion: The broad application will improve interlaboratory harmonization of recording fetal skeleton findings in developmental toxicity studies intended for regulatory submissions, including SEND (Standard for Exchange of Nonclinical Data). [ABSTRACT FROM AUTHOR]

Recent progress in satellite observations has provided unprecedented opportunities to monitor vegetation activity at global scale. However, a major challenge in fully utilizing remotely sensed data to constrain land surface models (LSMs) lies in inconsistencies between simulated and observed quantities. For example, gross primary productivity (GPP) and transpiration (T) that traditional LSMs simulate are not directly measurable from space, although they can be inferred from spaceborne observations using assumptions that are inconsistent with those LSMs. In comparison, canopy reflectance and fluorescence spectra that satellites can detect are not modeled by traditional LSMs. To bridge these quantities, we presented an overview of the next generation land model developed within the Climate Modeling Alliance (CliMA), and simulated global GPP, T, and hyperspectral canopy radiative transfer (RT; 400–2,500 nm for reflectance, 640–850 nm for fluorescence) at hourly time step and 1° spatial resolution using CliMA Land. CliMA Land predicts vegetation indices and outgoing radiances, including solar‐induced chlorophyll fluorescence (SIF), normalized difference vegetation index (NDVI), enhanced vegetation index (EVI), and near infrared reflectance of vegetation (NIRv) for any given sun‐sensor geometry. The spatial patterns of modeled GPP, T, SIF, NDVI, EVI, and NIRv correlate significantly with existing data‐driven products (mean R2 = 0.777 for 9 products). CliMA Land would be also useful in high temporal resolution simulations, for example, providing insights into when GPP, SIF, and NIRv diverge. Plain Language Summary: Terrestrial plants exchange water for CO2, but there is not a direct way to measure the carbon gain and water loss at the global scale. Researchers often use eddy covariance flux tower measurements and satellite observations to infer vegetation gross primary productivity (GPP) and transpiration (T). However, flux towers with high temporal resolution are too sparsely distributed, and satellites with high spatial coverage can only detect vegetation properties indirectly, such as solar induced chlorophyll fluorescence, rather than GPP and T themselves. We bridge these two aspects in a new generation land surface model that simultaneously simulates GPP and T, as well as spectrally resolved canopy radiative transfer. We compare our model outputs directly to not only GPP and T estimations but also satellite retrievals of fluorescence and vegetation indices. We show that our new model can represent how GPP and T, as well as canopy radiative properties vary across the globe. Key Points: Overview of Climate Modeling Alliance Land model at the global scale and comparison to existing productsVegetation gross primary productivity, transpiration, and hyperspectral canopy radiative transfer are simulated simultaneouslyModeled fluxes and canopy reflectance and fluorescence well capture the spatial patterns across the globe compared to existing observations [ABSTRACT FROM AUTHOR]

Background and Purpose: High‐resolution three‐dimensional (3D) post‐contrast imaging of the brain is essential for comprehensive evaluation of inflammatory, neoplastic, and neurovascular diseases of the brain. 3D T1‐weighted spin‐echo‐based sequences offer increased sensitivity for the detection of enhancing lesions but are relatively prolonged examinations. We evaluated whether a highly accelerated Wave‐controlled aliasing in parallel imaging (Wave‐CAIPI) post‐contrast 3D T1‐sampling perfection with application‐optimized contrasts using different flip angle evolutions (T1‐SPACE) sequence (Wave‐T1‐SPACE) was noninferior to the standard high‐resolution 3D T1‐SPACE sequence for visualizing enhancing lesions with comparable diagnostic quality. Methods: One hundred and three consecutive patients were prospectively evaluated with a standard post‐contrast 3D T1‐SPACE sequence (acquisition time [TA] = 4 min 19 s) and an optimized Wave‐CAIPI 3D T1‐SPACE sequence (TA = 1 min 40 s) that was nearly three times faster than the standard sequence. Two blinded neuroradiologists performed a head‐to‐head comparison to evaluate the visualization of enhancing pathology, perception of artifacts, and overall diagnostic quality. A 15% margin was used to test whether post‐contrast Wave‐T1‐SPACE was noninferior to standard T1‐SPACE. Results: Wave‐T1‐SPACE was noninferior to standard T1‐SPACE for delineating parenchymal and meningeal enhancing pathology (p < 0.01). Wave‐T1‐SPACE showed marginally higher background noise compared to the standard sequence and was noninferior in the overall diagnostic quality (p = 0.03). Conclusions: Our findings show that Wave‐T1‐SPACE was noninferior to standard T1‐SPACE for visualization of enhancing pathology and overall diagnostic quality with a three‐fold reduction in acquisition time compared to the standard sequence. Wave‐T1‐SPACE may be used to accelerate 3D post‐contrast T1‐weighted spin‐echo imaging without loss of clinically important information. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study is to evaluate the effect of orthodontic forces in healthy or diseased periodontium of rats submitted/not submitted to cigarette smoke inhalation. Material and methods: Fifty‐six male Wistar rats were allocated into two groups of conditions: smoking and non‐smoking. Each group was divided into the following subgroups: control (C), orthodontic tooth movement (OTM), ligature‐induced periodontitis (P) and P+OTM (POTM), with n = 14 each. Periodontitis was induced in the lower first molar by cotton ligature, and a 4 mm closed stainless steel spring was used for orthodontic movement. Animals were exposed to the smoke of 10 cigarettes for 8 minutes, 3 times a day for 60 days before P induction and OTM. Evaluation parameters were macroscopic analysis of dental movement, bone loss and bone density. In addition, the receptor activator of nuclear factor‐kappaB (RANK) immunostaining and RANK ligand/osteoprotegerin ratio in the furcation region were assessed. Results: There was no statistically significant difference between groups, ie, smoking and non‐smoking conditions (P = .338). Bone loss intragroup analysis between the P and POTM groups was not significant in smoking (P = 1) and non‐smoking (P = .5) conditions; both were different from OTM and C in each condition. Regarding bone density, POTM and P were significant to C (P < .05). The POTM group was significant to the P and C (P = .001) regarding dental movement. The RANK ligand/osteoprotegerin ratio in the non‐smoking condition was higher in P and POTM compared to C and OTM and to P and POTM in the smoking condition. RANK immunostaining was significant in the smoking condition for the P and POTM groups (P < .05). Conclusion: Within the limitations of the present study, it was concluded that cigarette smoke inhalation had no influence on the evaluated groups, even with the presence of low levels of nicotine, carbon monoxide and tar. The POTM groups did not present greater bone loss compared to P groups, thus periodontal disease is essential for bone loss. [ABSTRACT FROM AUTHOR]

In injection site sarcoma ( ISS) in cats lateral as well as deep margins should be correctly planned for a successful surgical outcome. The discrepancy between clinical and computed tomography ( CT) measurements of dimension in resectable tumour has led to possible bias that affects the subsequent surgical dose. The aim of this study was to prospectively investigate the agreement between clinical and CT measurements of dimension in newly diagnosed ISS in cats. Fifty-three client-owned cats that underwent both clinical and CT measurements of the length and width of ISS were included. CT measurements showed a tendency towards being larger than clinical dimensions, and this difference increased with increasing tumour size. Based on our results, in further studies focusing on ISS in cats, the kind of assessment used to define tumour dimensions ( CT versus clinic) should be declared and specified to properly consider surgical results and prognostic impact of this variable. [ABSTRACT FROM AUTHOR]

The thermal resistance along the thickness of In3SbTe2 crystalline nanowires was measured using the scanning thermal microscopy in 3 ω mode. The nanowires were grown by metal organic vapor deposition, exploiting the VLS mechanism induced by Au metal-catalyst nanoparticles and harvested on a SiO2/Si substrate. Two nanowires with different thickness (13 and 23 nm) were investigated. The thermal resistance of the nanowires was determined using two different approaches; the first one exploits the experimental data, whereas the second one is more sophisticated, since it involves a minimization procedure. Both methods led to comparable values of the thermal resistance along the transverse direction (thickness) of the nanowire. The obtained results were explained starting from the mean free path of phonons calculated in the In3SbTe2 bulk. [ABSTRACT FROM AUTHOR]

The variability in water quality and zooplankton community structure during downstream transport was investigated in the Po river (Italy) using for the first time a Lagrangian sampling approach. Two surveys were conducted, one in spring under relatively high discharge levels, and one at low flows in summer. Twelve stations along a 332-km stretch of the river's lowland reach and four major tributaries were sampled. A hydrodynamic modelling system was used to determine water transport time along the river, with a satisfying fit between simulated and observed discharge values. No clear downstream trend in phosphorus and nitrogen concentrations was found. Conversely, a marked longitudinal decrease in dissolved silica supports the hypothesis of increasing downstream silica limitation during the phytoplankton growing season. In spring, at low residence time, no apparent plankton growth was observed during downstream transport. In summer, higher temperatures and lower turbulence and turbidity associated with longer residence time stimulated algal growth and in-stream reproduction of fast-growing rotifer taxa, with the gradual downstream development of a truly potamal assemblage and the increase of the ratio of euplanktonic to littoral/epibenthic rotifer taxa. Crustacean zooplankton density was generally low. The importance of biotic interactions within the zooplankton in driving community abundance and composition appeared to increase in the downstream direction, paralleled by a decrease in the influence of physical forcing. Tributary influence was especially evident where severe anthropogenic alterations of river hydrology and trophic status resulted in enhanced plankton growth, ultimately affecting zooplankton structure in the main river. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background and Objective This study aimed to assess the effect of multiple sessions of a low-level laser therapy (LLLT) adjuvant to scaling and root planing (SRP) on the treatment of experimental periodontitis (EP) in rats treated with 5-fluorouracil (5- FU). Material and Methods A total of 120 rats were divided into five groups: no treatment (NT); treatment with 5- FU (60 and 40 mg/kg) and no local periodontal treatment (5FU); treatment with 5- FU and SRP (5FU-SRP); treatment with 5- FU, SRP and one LLLT session (660 nm; 0.035 W; 4.2 J; 120 s) (5 FU- SRP-1LLLT); and treatment with 5- FU, SRP and four LLLT sessions (0, 24, 48 and 72 h) (5 FU- SRP-4LLLT). EP was induced in the mandibular molars through ligature placement. The alveolar bone loss (ABL) area in the furcation region was analysed histometrically. TRAP, proliferating cell nuclear antigen, RANKL, osteoprotegerin and activated caspase-3 patterns were analysed by immunolabeling. Prostaglandin E2 was quantified using an ELISA, and tumour necrosis factor α and interleukin-6 were assessed using the multiplex method. The prevalence rates of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella nigrescens, Prevotella intermedia and Fusobacterium nucleatum were assessed using the PCR method. The data were subjected to statistical analysis (α = 5%). Results 5 FU, 5 FU- SRP and 5 FU- SRP-1 LLLT treatment groups showed higher ABL compared with the NT group (p < 0.05), whereas the 5 FU- SRP-4 LLLT group showed lower ABL compared with the 5 FU group on day 7 and decreased RANKL immunolabeling (p < 0.05). Conclusion Treatment with 5- FU worsened EP, and multiple LLLT sessions adjuvant to SRP seemed to improve periodontitis in rats subjected to 5- FU chemotherapy. [ABSTRACT FROM AUTHOR]

The temperature dependent thermal conductivity of In-Sb-Te thin films has been measured by modulated photothermal radiometry in the 20-550 °C range for samples with different Te content. Significant changes with temperature are observed and ascribed to a sequence of structural transformations on the basis of in-situ Raman spectra. The data suggest that the as-deposited material consisting of a mixture of polycrystalline InSb0.8Te0.2and amorphous Te first undergoes a progressive crystallization of the amorphous part, mostly above 300 °C. Further increase in temperature above 460 °C leads, for higher Te content in the alloy, to the formation of crystalline In3SbTe2, intertwined with a less conductive compound, possibly InTe and/or InSb. Upon cooling to room temperature, the initial polycrystalline InSb0.8Te0.2phase is mostly recovered along with other compounds, with a slightly higher thermal conductivity than that of the as deposited material. (© 2016 WILEY-VCH Verlag GmbH &Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Background and Objective This study assessed the effects of the local use of Saccharomyces cerevisiae as monotherapy and as an adjuvant to the mechanical treatment of ligature-induced periodontitis in rats. Material and Methods Periodontitis was induced in 72 rats via the installation of a ligature around the mandibular first molar. After 7 d, the ligature was removed and the rats were placed in one of the following groups: no treatment (C; n = 18); scaling and root planing ( SRP; n = 18); local irrigation with probiotics ( PRO; n = 18); and SRP followed by local irrigation with probiotics ( SRP/ PRO; n = 18). Six rats from each group were killed at 7, 15 and 30 d. The histological characteristics, alveolar bone loss ( ABL) and immunolabeling of tumor necrosis factor alpha ( TNF-α), interleukin-1beta ( IL-1β), interleukin-10 ( IL-10) and TRAP on the furcation area of the first molar were assessed. Results The PRO group showed features of acceleration of the tissue-repair process during the entire experiment. On day 15, there was less ABL in the SRP/ PRO group compared with the C group. There were fewer TRAP-positive cells in the SRP and SRP/ PRO groups at 30 d. There was less immunostaining for TNF-α in the PRO and SRP/ PRO groups and less immunostaining for IL-1β in the PRO group. However, there was more immunostaining for IL-10 in the PRO group on day 15. Conclusion Local use of the probiotic did not result in any adverse effects on periodontal tissues. When used as monotherapy or as an adjuvant, the probiotic was effective at controlling periodontitis in rats. [ABSTRACT FROM AUTHOR]

In this work, the self-assembly of In3Sb1Te2 and In-doped Sb4Te1 nanowires (NWs) for phase change memories application was achieved by metal organic chemical vapor deposition, coupled with vapor-liquid-solid (VLS) mechanism, catalyzed by Au nanoparticles. Single crystal In3Sb1Te2 and In-doped Sb4Te1 NWs were obtained for different reactor pressures at 325 °C. The parameters influencing the NW self-assembly were studied and the compositional, morphological, and structural analysis of the grown structures was performed, also comparing the effect of the used substrate (crystalline Si and SiO2). In both cases, NWs of several micrometer in length and with diameters as small as 15 nm were obtained. [ABSTRACT FROM AUTHOR]

Background and Objective Antimicrobial therapy can suppress periodontal pathogens and increase the effectiveness of conventional mechanical treatment. The aim of this study was to assess bone loss and the immune inflammatory response of rats under the influence of two photosensitizing agents ( MB and TBO) at two different concentrations in antimicrobial photodynamic therapy ( aPDT), used as an adjuvant therapy in the treatment of periodontitis. Material and Methods Periodontitis was induced in the mandibular first molars of 162 rats. The animals were divided into nine groups: G1 - scaling and root planing ( SRP); G2 - SRP plus 100 μg/mL of methylene blue ( MB); G3 - SRP plus 10 mg/mL of MB; G4 - SRP plus 100 μg/mL of toluidine blue ( TBO); G5 - SRP plus 10 mg/mL of TBO; G6 - SRP plus 100 μg/mL of MB and laser; G7 - SRP plus 10 mg/mL of MB and laser; G8 - SRP plus 100 μg/mL of TBO and laser; and G9 - SRP plus 10 mg/mL of TBO and laser. Six animals from each group were euthanized 7, 15, or 30 d after treatment. Bone loss ( BL) in the furcation region was evaluated using histomorphometric and immunohistochemical analyses to detect the receptor activator of nuclear factor-Κappa B ligand ( RANKL), osteoprotegerin ( OPG) and tartrate-resistant acid phosphatase ( TRAP). Results There was significantly less BL in animals treated with aPDT using low concentrations of MB and TBO at 7, 15 and 30 d. Immunohistochemical analysis revealed decreased RANKL and increased OPG in the aPDT groups and decreased TRAP-positive cells in G6 and G8. Conclusions aPDT, using low concentrations of MB and TBO, was the most effective adjuvant therapy to SRP, acting indirectly as a downregulator of the molecular mechanisms that control bone resorption in periodontitis. [ABSTRACT FROM AUTHOR]

Histochemical and morphometric analyses were performed to characterize the fibre-type composition of two forelimb muscles of the South American subterranean rodent Ctenomys talarum. The studied muscles were the triceps lateralis, an extensor of the elbow, and the teres major, a flexor of the shoulder. It was found that these muscles had an elevated proportion of fast oxidative-glycolytic ( FOG) fibres, and lower proportions of slow oxidative ( SO) and fast glycolytic ( FG) fibres. This composition probably qualifies the teres major and triceps muscles to perform the sustained effort required in tunnelling excavation. The results were discussed considering published data on fibre-type composition of mammals having different modes of life and digging behaviour. We here suggest that C. talarum has the potential of generating forces linked to rapid, powerful movements during sustained periods by means of an elevated proportion of FOG fibres, together with osteological changes that result in a great mechanical advantage of the forelimb muscles. [ABSTRACT FROM AUTHOR]

Recent alternatives to technological applications most commonly employed when the production of extremocompounds is approached at bioreactor scale, in batch, fed-batch, and continuous mode, are summarized. Each operational mode is analyzed in the light of the more decisive variables affecting the performance of this kind of biological processes, namely, bioreactor configurations, culture medium design, operating conditions, or downstream processing. Bringing together genetic and bioreaction engineering with separation techniques is already the recommended strategy to solve the typical problems faced in bioprocesses with extremophiles and will serve to open up new opportunities for the development of unexplored fields such as renewable energies. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To identify the mediator responsible for the impact of chronic inflammation on skeletal development in children (bone loss, defective peak bone mass accrual, stunted growth), we evaluated the effects of chronic interleukin-6 (IL-6) overexpression on the skeletons of growing prepubertal mice. METHODS: We studied IL-6-transgenic mice that had high circulating IL-6 levels since birth. Trabecular and cortical bone structure were analyzed by microcomputed tomography. Epiphyseal ossification, growth plates, and calvariae were studied by histology/histomorphometry. Osteoclastogenesis, osteoblast function/differentiation, and the effects of IL-6 on bone cells were studied in vitro. Osteoblast gene expression was evaluated by reverse transcriptase-polymerase chain reaction. The mineral apposition rate was evaluated dynamically in cortical bone by in vivo double fluorescence labeling. RESULTS: In prepubertal IL-6-transgenic mice, we observed osteopenia, with severe alterations in cortical and trabecular bone microarchitecture, as well as uncoupling of bone formation from resorption, with decreased osteoblast and increased osteoclast number and activity. Increased osteoclastogenesis and reduced osteoblast activity, secondary to decreased precursor proliferation and osteoblast function, were present. IL-6-transgenic mice also showed impaired development of growth plates and epiphyseal ossification centers. Intramembranous and endochondral ossification and the mineral apposition rate were markedly affected, showing the presence of defective ossification. CONCLUSION: Chronic overexpression of IL-6 alone induces a skeletal phenotype closely resembling growth and skeletal abnormalities observed in children with chronic inflammatory diseases, pointing to IL-6 as a pivotal mediator of the impact of chronic inflammation on postnatal skeletal development. We hypothesize that IL-6-modifying drugs may reduce skeletal defects and prevent the growth retardation associated with these diseases. [ABSTRACT FROM AUTHOR]

Background: Although administration of gastroprotective drugs may reduce the risk of peptic ulcers associated with the chronic use of non-steroidal anti-inflammatory drugs or aspirin, no consensus exists as to whether this co-therapy is effective for short-term prevention, particularly in old age. Aim: To evaluate the risk of peptic ulcer associated with acute and chronic non-steroidal anti-inflammatory drugs or aspirin therapy in elderly subjects, and the influence of antisecretory treatment on this risk. Methods: The study included 676 elderly non-steroidal anti-inflammatory drugs or aspirin users and 2435 non-users who consecutively underwent upper gastro- intestinal endoscopy. The use of non-steroidal anti-inflammatory drugs and/or aspirin as well as antisecretory drugs (H2-blockers and proton-pump inhibitors) was evaluated by a structured interview. Diagnosis of gastric and duodenal ulcer as well as Helicobacter pylon infection were carried out by endoscopy and histological examination of the gastric mucosa. Results: About 47.3% of patients were acute and 52.7% chronic users of non-steroidal anti-inflammatory drugs or aspirin. The risk of peptic ulcer, adjusted for age, gender, H. pylon infection and antisecretory drug use was higher in acute (gastric ulcer: odds ratio, OR = 4.47, 95% CI: 3.19-6.26 and duodenal ulcer: OR = 2.39, 95% CI: 1.73-3.31) than chronic users (gastric ulcer: OR = 2.80, 95% CI: 1.97-3.99 and duodenal ulcer: OR = 1.68, 95% CI: 1.22-2.33). Proton-pump inhibitor treatment was associated with a reduced risk of peptic ulcer in both acute (OR = 0.70, 95% CI: 0.24- 2.04) and chronic (OR = 0.32, 95% CI: 0.15-0.67) non-steroidal anti-inflammatory drugs/aspirin users. Conversely, concomitant treatment with H2-blockers was associated with a significantly higher risk of peptic ulcer both in acute (OR = 10.9, 95% CI: 3.87-30.9) and chronic (OR = 6.26, 95% CI: 2.56-15.3) non-steroidal anti-inflammatory drugs/aspirin users than non-users. Proton-pump inhibitor treatment resulted in an absolute risk reduction of peptic ulcer by 3 6.6% in acute and 34.6% in chronic non-steroidal anti-inflammatory drugs/aspirin users; indeed, the number needed to treat to avoid one peptic ulcer in elderly non-steroidal anti-inflammatory drugs/aspirin users was three both in acute and chronic users. Conclusions: These findings suggest that proton-pump inhibitor co-treatment is advisable in symptomatic elderly patients who need to be treated with non-steroidal anti-inflammatory drugs and/or aspirin for a short period of time. [ABSTRACT FROM AUTHOR]

Involving patients more in decisions about their own care requires doctors to be trained in effective ways of communicating information and in developing competences to negotiate levels of patient involvement which are most appropriate for each case. The aim of this study was to determine the cost of such training and identify which service resource variables are subsequently affected. An explanatory cluster randomized crossover trial was carried out which involved training general practitioners (GPs) in the use of risk communication (RC) tools, shared decision making (SDM) competences or both. Continuing care by GPs of patients with one of four chronic conditions (menopausal symptoms, menorrhagia, atrial fibrillation, prostatism) was reviewed before and after training. Cost of training was assessed by prospective monitoring of resources used. Data on prescribing, referrals and investigations were collected via questionnaires to participating practitioners. Data on follow-up GP consultations were extracted from medical records. Three two-level logistic models were performed to investigate the probability of training having an effect on prescribing, referrals and investigations ordered at the review consultation. Training cost £1218 per practitioner which increased the cost of a consultation by £2.89. Training in SDM or combined with RC significantly affected the probability of a prescription being issued to women with menopausal symptoms and menorrhagia (although RC on its own had no effect) but did not significantly affect prescribing for patients with prostatism or atrial fibrillation. It did not significantly affect the probability of investigations, referrals or follow-up GP visits for any of the conditions. Unless training has a major influence on consultation length, it is unlikely to have any major impacts on cost. [ABSTRACT FROM AUTHOR]

A previously healthy 71-year-old Caucasian woman presented with an ulcer on her left leg. She had a 5-month history of bilateral, indurated erythematous, and had purplish nodules and plaques on both lower extremities. One of the plaques on the right leg had ulcerated and healed spontaneously. The present ulceration began as a small opening at an incisional biopsy site. Later, she developed two adjacent ulcers that coalesced into a larger ulcer. She was not taking any medication, and there was no history of exposure to tuberculosis. Examination of the right leg demonstrated two hyperpigmented, indurated plaques, one on the calf and one over the medial malleolus. On the left posterior calf there was another hyperpigmented, indurated plaque with a central area of ulceration measuring 9 × 2 cm. The ulcer bed had a mixture of fibrinous adherent tissue and granulation tissue. (Fig. 1) There was no peripheral edema, varicose veins, nor signs of peripheral neuropathy. Peripheral pulses and capillary refilling were within normal limits. The ankle brachial index was greater than 1.0 bilaterally. Biopsy of a subcutaneous nodule revealed a superficial and deep perivascular lymphocytic infiltrate with an admixture of neutrophils and numerous extravasated red blood cells. Mixed septal and lobular panniculitis consisting of an inflammatory infiltrate of histiocytes, giant cells, and neutrophils was observed. Focal neutrophilic microabscesses in the deep dermis and fibrinoid necrosis of small blood vessels were present in the deep dermis and subcutaneous tissue (Figs 2 and 3). A smear was negative for acid fast bacilli. A diagnosis of nodular vasculitis was made. A complete blood count with differential and platelets was within normal limits, tuberculin testing was negative twice, and antineutrophil cytoplasmic antibodies (p-ANCA, c-ANCA) were also negative. Fungal, mycobacterial and bacterial cultures were negative. Chest X-rays were normal. The patient received... [ABSTRACT FROM AUTHOR]

Cavernous lymphangiomas are characterized by penetration through the subcutaneous areas between the muscular septa and represent rare variants of the more common superficial lymphangioma. Although frequently described in the fetus when involving the posterior aspect of the neck (i.e. cystic hygroma), involvement of the craniofacial region is rare. We describe the prenatal findings in a case of cavernous lymphangioma of the fetal face and neck, which extended caudally to envelop the larynx and the trachea. The anomaly was assessed by two- and three-dimensional (3D) ultrasound. The latter approach was used thoroughly both during counseling with the couple and during consultation with the pediatric surgeon. This case report confirms the usefulness of the 3D approach in the management of rare fetal anomalies. In particular, the possibility of navigating the volume facilitated consultation with the pediatric surgeon and counseling of the parents. [ABSTRACT FROM AUTHOR]

Background and purpose: Late‐onset Pompe disease (LOPD) is a rare, multisystem disorder that is well established to mainly impair skeletal muscle function. Systematic studies exploring brain functions in LOPD are lacking. The aim of this study was to detect morphological and functional brain alterations as well as neuropsychological impairment in LOPD. Methods: We studied 21 patients (10 male, mean age 49 ± 18.4 years) with defined diagnosis of LOPD, divided into two groups: one with pre‐symptomatic hyperCKemia with no muscle weakness and the second with limb‐girdle muscle weakness. All patients underwent 3T magnetic resonance imaging (MRI) to obtain morphological/angiographic evaluation as well as normalized cortical brain volume and resting‐state functional MRI. Fazekas score was applied to quantify white matter lesions, whereas Smoker's criteria were used to examine dolichoectasia. A complete neuropsychological assessment was performed. Results: The MRI data showed that 12/21 patients (57%) demonstrated signs of cerebral vasculopathy, with a Fazekas score >2 in 67%. According to Smoker's criteria, 11/21 patients (52%) had a dolichoectasia of the vertebrobasilar system; an intracranial aneurysm was detected in 3/21 patients (14%). Resting‐state functional MRI demonstrated significantly decreased brain connectivity in the salience network with a more relevant reduction in the bilateral middle and superior frontal gyrus. Gray matter atrophy correlated with age and disease duration. A mild impairment in executive functions was also identified. Conclusions: In this LOPD cohort the results showed morphological and functional brain alterations with mild neuropsychological dysfunction, mainly in the limb‐girdle muscle weakness group. Cerebrovascular alterations seemed to be not related to common risk factors, suggesting a major role of enzymatic deficiency in the pathogenesis of brain abnormalities. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article on Lipodystrophia centrifugalis abdominalis infantilis (LCAI) that was published in the previous issue.

Background: Recent data in nonpregnant individuals suggest a protective effect of influenza vaccination against SARS-CoV-2 infection and its severity., Objectives: Our primary objective was to evaluate whether influenza vaccination was associated with COVID-19 severity and pregnancy and neonatal outcomes among those infected with SARS-CoV-2. The secondary objective was to examine the association between influenza vaccination and SARS-CoV-2 infection., Study Design: Secondary analysis of a multicenter retrospective cohort of pregnant people who tested positive for SARS-CoV-2 between March and August 2020, and a cohort of random deliveries during the same time period. The associations between 2019 influenza vaccination and the primary outcome of moderate-to-critical COVID-19 as well as maternal and perinatal outcomes were examined among all people who tested positive for SARS-CoV-2 between March and August 2020. The association between 2019 influenza vaccination and having a positive SARS-CoV-2 test was examined among a cohort of individuals who delivered on randomly selected dates between March and August 2020. Univariable and multivariable analyses were performed., Results: Of 2325 people who tested positive for SARS-CoV-2, 1068 (45.9%) were vaccinated against influenza in 2019. Those who received the influenza vaccine were older, leaner, more likely to have private insurance, and identify as White or Hispanic. They were less likely to smoke tobacco and identify as Black. Overall, 419 (18.0%) had moderate, 193 (8.3%) severe, and 52 (2.2%) critical COVID-19. There was no association between influenza vaccination and moderate-to-critical COVID-19 (29.2% vs. 28.0%, adjusted OR 1.10, 95% CI 0.90-1.34) or adverse maternal and perinatal outcomes among those who tested positive. Of 8152 people who delivered in 2020, 4658 (57.1%) received the influenza vaccine. Prior vaccination was not associated with a difference in the odds of SARS-CoV-2 infection (3.8% vs. 4.2%, adjusted OR 0.94, 95% CI 0.74-1.19)., Conclusion: Prior influenza vaccination was not associated with decreased severity of COVID-19 or lower odds of SARS-CoV-2 infection in pregnancy., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: To assess and compare the metabolic and vascular effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) in the clinical practice of patients with type 2 diabetes in Italy., Materials and Methods: GIOIA is a 2-year prospective, multicentre, quasi-experimental study that enrolled patients with type 2 diabetes initiating SGLT-2i or DPP-4i for inadequate glycaemic control [glycated haemoglobin (HbA1c) >7%] between March 2018 and March 2021. The primary endpoints were changes in markers of organ damage [carotid intima-media thickness (CIMT), albuminuria, myocardial function] and HbA1c from baseline to year 2., Results: In total, 1150 patients were enrolled in the study (SGLT-2i n = 580, DPP-4i n = 570). Patients initiated on SGLT-2i were younger (about 6 years) and heavier (about 11 kg), had higher HbA1c level (1% more), more albuminuria and cardiovascular events (16% more) than patients initiated on DPP-4i. CIMT and echocardiographic parameters were not significantly different. Propensity score matching yielded two groups, each consisting of 155 patients with diabetes with similar baseline characteristics. Despite a significant similar reduction in HbA1c levels in both groups (-0.8%), more patients on SGLT-2i had regression of CIMT and albuminuria (22% and 10%, respectively, p < .001 vs. DPP-4i); more patients on DPP-4i had progression of CIMT and albuminuria (23% and 28%, respectively, p < .001 vs. SGLT-2i). Left ventricular ejection fraction improved slightly (3%, p = .043) on SGLT-2i only., Conclusions: In a real-world setting, both SGLT-2i and DPP-4i improve glycaemic control persisting after 2 years of treatment, with a robust effect on both CIMT and albuminuria regression for SGLT-2i as compared with DPP-4i in the propensity score matching., (© 2024 John Wiley & Sons Ltd.)

Senescence of adipose precursor cells (APC) impairs adipogenesis, contributes to the age-related subcutaneous adipose tissue (SAT) dysfunction, and increases risk of type 2 diabetes (T2D). First-degree relatives of T2D individuals (FDR) feature restricted adipogenesis, reflecting the detrimental effects of APC senescence earlier in life and rendering FDR more vulnerable to T2D. Epigenetics may contribute to these abnormalities but the underlying mechanisms remain unclear. In previous methylome comparison in APC from FDR and individuals with no diabetes familiarity (CTRL), ZMAT3 emerged as one of the top-ranked senescence-related genes featuring hypomethylation in FDR and associated with T2D risk. Here, we investigated whether and how DNA methylation changes at ZMAT3 promote early APC senescence. APC from FDR individuals revealed increases in multiple senescence markers compared to CTRL. Senescence in these cells was accompanied by ZMAT3 hypomethylation, which caused ZMAT3 upregulation. Demethylation at this gene in CTRL APC led to increased ZMAT3 expression and premature senescence, which were reverted by ZMAT3 siRNA. Furthermore, ZMAT3 overexpression in APC determined senescence and activation of the p53/p21 pathway, as observed in FDR APC. Adipogenesis was also inhibited in ZMAT3-overexpressing APC. In FDR APC, rescue of ZMAT3 methylation through senolytic exposure simultaneously downregulated ZMAT3 expression and improved adipogenesis. Interestingly, in human SAT, aging and T2D were associated with significantly increased expression of both ZMAT3 and the P53 senescence marker. Thus, DNA hypomethylation causes ZMAT3 upregulation in FDR APC accompanied by acquisition of the senescence phenotype and impaired adipogenesis, which may contribute to FDR predisposition for T2D., (© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background and Aims: Farnesoid X receptor (FXR) plays a key role in bile acid and lipid homeostasis. Experimental evidence suggests that it can modulate liver damage related to nonalcoholic fatty liver disease (NAFLD). We examined the impact of the NR1H4 rs35724 G>C, encoding for FXR, on liver damage in a large cohort of patients at risk of steatohepatitis., Methods: We considered 2,660 consecutive individuals at risk of steatohepatitis with liver histology. The rs35724 G>C polymorphisms were genotyped by TaqMan assays. Gene expression was evaluated by RNASeq in a subset of patients (n = 124)., Results: The NR1H4 rs35724 CC genotype, after adjusting for clinic-metabolic and genetic confounders and for enrolling centre, was protective against severity of steatosis (GG vs CC OR 0.77, 95% CI 0.62-0.95; P = .01), steatohepatitis (GG vs CC OR 0.62, 95% CI 0.47-0.83; P = .001) and severity of fibrosis (GG vs CC OR 0.83, 95% CI 0.67-0.98; P = .04). The C allele was associated with higher total circulating cholesterol (P = .01). Patients carrying the NR1H4 rs35724 C allele had significantly higher hepatic mRNA levels of FXR and were associated with higher hepatic FGFR4 and Cyp39A1 that are in turn involved in bile acid synthesis., Conclusions: Increased hepatic FXR expression due to the NR1H4 rs35724 C allele is linked to higher serum cholesterol but protects against steatosis, steatohepatitis and liver fibrosis. The translational relevance of these results for patient risk stratification and FXR-targeted therapy warrants further investigation., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A meta-analysis of cardiorenal outcomes of sodium-glucose co-transporter-2 inhibitors (SGLT-2is) available in Europe or the United States in patients with type 2 diabetes (T2D) is presented. An electronic search up to 6 January 2021 was conducted to determine eligible trials. A total of eight cardiorenal outcomes trials of SGLT-2is (empagliflozin, canagliflozin, dapagliflozin, ertugliflozin and sotagliflozin) were identified, with 65,587 patients. Data were analysed using a random effects model. Overall, SGLT-2is were associated with a 12% reduced risk of major adverse cardiovascular events (MACE; HR = 0.88; 95% CI, 0.83-0.93; Q statistic, p = .19), with no significant heterogeneity (p for interaction = .465) between subgroups of patients with or without cardiovascular disease (CVD). The risk of the composite renal outcome was significantly reduced by treatment with SGLT-2is (HR = 0.61, 95% CI, 0.54-0.70), with no significant heterogeneity of associations with outcome (I 2 = 37%, p = .11), and no difference in the risk between patients with or without CVD (p for interaction = .665). SGLT-2is have moderate benefits on MACE and major benefits on the progression of diabetic kidney disease., (© 2021 John Wiley & Sons Ltd.)

Aim: In order to disclose relations between reduction of haemoglobin A1c (HbA1c) levels and risk of major cardiovascular events (MACE), we performed a meta-analysis with metaregression of all cardiovascular outcome trials (CVOTs) so far published in patients with type 2 diabetes (T2D)., Materials and Methods: An electronic search up to February 10, 2020 was conducted to determine eligible trials. Pooled summary estimates and 95% confidence intervals (CI) were calculated according to the random effects model using the Paule-Mandel method; restricted maximum likelihood estimators were used to estimate model parameters in the metaregression., Results: The 15 CVOTs included evaluated 138,250 patients. In the pooled analysis, the risk of MACE was significantly reduced by 9% (hazard ratio, HR = 0.91, 0.87-0.95, P <0.001) as compared with placebo, with significant heterogeneity between trials (I 2 = 44%, P = 0.060) There was a robust relation between the reduction in achieved HbA1c at the end of the trial and the HR reduction for MACE (beta = -0.3169, P = 0.029), explaining most (78%) of the between-study variance; this relation was totally driven by the risk reduction of non-fatal stroke only, which explained 100% of between-study variance, and apparently restricted to the class of glucagon-like peptide 1 receptor agonists (GLP-1RAs). There was no relation between the reduction in achieved HbA1c and the HR for heart failure (variance explained = 0%) or all-cause mortality (variance explained = 6%)., Conclusion: The blood glucose reduction observed in CVOTs may play some role in reducing the risk of non-fatal stroke, at least during treatment with GLP-1RAs, without affecting the other two components of MACE., (© 2020 John Wiley & Sons Ltd.)

A meta-analysis of cardiovascular outcome trials (CVOTs) comparing glucagon-like peptide-1 receptor agonists (GLP-1RAs) and placebo concerning cardiorenal outcomes in patients with type 2 diabetes (T2D) is presented. An electronic search without language restrictions up to June 15, 2019 was conducted to determine eligible trials. A meta-analysis of available trial data was undertaken, using a random-effects model to calculate overall hazard ratios (HRs) and 95% confidence intervals (CIs). Data from seven CVOTs, comprising 56 004 patients (68.9% with established cardiovascular disease) were included. GLP-1RA reduced major cardiovascular events (MACE) by 13% (HR, 0.87; 95% CI, 0.80-0.96; P = 0.011) with a non-significant heterogeneity between subgroups of patients with and without cardiovascular disease (CVD) (P = 0.220). GLP-1RA also reduced the risk of cardiovascular death by 12%, of non-fatal stroke by 16%, of hospitalization for heart failure by 9%, of all-cause mortality by 11%, and the broad composite kidney outcome by 17%; the latter appeared to be driven only by a reduction in macroalbuminuria (HR, 0.76 [0.68-0.86]; P = 0.003). GLP-1RAs have moderate benefits concerning MACE, and also reduce hospitalization for heart failure and all-cause mortality; they also robustly reduce the incidence of macroalbuminuria, without affecting the progression of diabetic renal disease., (© 2019 John Wiley & Sons Ltd.)

Solid organ and stem cell transplant recipients have an increased risk of developing cutaneous infections, which often are refractory to conventional treatment (Euvrard et al., Journal of the American Academy of Dermatology, 2001, 44, 932-939). Molluscum contagiosum, a common self-limited disease primarily affecting children, can be more severe and unresponsive to therapy in transplant patients (Gardner & Ormond, Clinical and Experimental Dermatology, 2006, 31, 452-453). Candida immunotherapy has been widely used for the treatment of warts, and recently its application has been expanded to include treatment of symptomatic molluscum in pediatric patients (Enns & Evans, Pediatric Dermatology, 2011, 28, 254-258; Maronn et al., Pediatric Dermatology, 2008, 25, 189-192). However, to our knowledge there have been no reports in the literature of its utility in the setting of adult transplant or immunocompromised patients. Herein, we report a case of successful treatment of refractory molluscum contagiosum in a stem cell transplant patient with Candida immunotherapy., (© 2019 Wiley Periodicals, Inc.)

Background: Although considered as a first-group carcinogen, indoor tanning is a common practice in Europe. Euromelanoma is a pan-European skin cancer prevention campaign., Objectives: To compare several European countries in terms of the prevalence and determinants of sunbed use., Methods: Participants in the Euromelanoma campaigns filled in questionnaires containing demographics and risk factors, including type/duration of sunbed use. Multivariate analyses adjusted for age, gender, education, skin type and year of survey were employed to assess factors independently associated with sunbed use in each country., Results: In total, 227 888 individuals (67.4% females, median age 44, 63.4% highly educated, 71.9% skin types III-VI) from 30 countries participated. Overall, the prevalence of sunbed ever use was 10.6% (≤19-year-olds: 5.9%; 20 to 35-year-olds: 17.0%; >35-year-olds: 8.3%). Females displayed a higher prevalence than males in all countries. Balkan countries displayed the highest female/male ratios (≥4). Sunbed use was significantly more prevalent among skin type III-VI (14/30 countries) and highly educated participants (11/30 countries). Significant correlations were found between sunbed use prevalence and countries' latitude (P < 0.001) and sunshine (P = 0.002); Italy and Spain represented exceptions towards excessive exposure. Very different prevalence rates were found for Spain (19.3%) and Portugal (2.0%). Scandinavian countries ranked highest in sunbed use among ≤19-year-olds, Baltic countries among 20 to 35-year-olds., Conclusions: Sunbed use prevalence was higher in northern, sun-deprived countries, with the exception of Italy and Spain. The main determinants of sunbed use were age (young adults) and gender (females), whereas education and skin type had a less relevant effect. Geographic particularities were found in four regions: Iberian (prevalence ten times higher in Spain than Portugal), Balkan (prevalence disproportionately higher among women), Baltic (highest prevalence among young adults) and Scandinavian (highest prevalence among adolescents). These data have public health relevance for future interventions aimed at reducing sunbed use in Europe., (© 2019 European Academy of Dermatology and Venereology.)

Although exposure to indoor tanning has been established as a clear risk factor for skin cancer, sunbeds are still commonly used in Europe. Understanding the determinants of sunbed use in Europe is key to plan educational interventions, behavioural strategies and legislative measures, which should be tailored to subgroups with different risk profiles. Evidences show that the typical sunbed users in Europe are young-adult women, with intermediate skin type, a current employment and a medium/high socio-economic status. Typical users display sun-seeking behaviours and other risky behaviours such as smoking. Indoor tanning seems more common in northern than southern Europe. However, sunbed use remains common in fair-skinned individuals and among adolescents/pre-adolescents. Commonly reported reasons for sunbed use in Europe include aesthetic motives (i.e. looking attractive), the pursue of a prevacation tan, the influence of peers/parents engaging in the same habit, and the treatment of health conditions. The most commonly reported places to get an artificial tan in Europe are tanning studios and beauty salons. However, sunbeds are also available in sport venues, such as swimming pools and gyms, hotels and private houses. All these factors should be taken into account when planning educational, behavioural and legislative interventions to reduce the popularity of artificial tanning in Europe., (© 2019 European Academy of Dermatology and Venereology.)

Introduction: Sunbed use has been significantly associated with increased risk of melanoma and non-melanoma skin cancer (NMSC), but its relationship with melanoma's risk factors such as high nevus count, atypical nevi and lentigines is poorly studied. Euromelanoma is a skin cancer prevention campaign conducted all over Europe. It offers a once-a-year screening during which participants' data, including sunbed use and phenotype, are collected via questionnaires., Objectives: To investigate the association of sunbed use with nevus count, atypical nevi, lentigines and suspicion of skin cancer., Methods: To ensure reliability of the data, we defined inclusion and exclusion criteria for countries' eligibility for the risk analysis. Multivariate logistic regression models (including age, gender, education, skin type, family history of melanoma, personal history of skin cancer, any sun exposure and any sunscreen use) were used to calculate summary odds ratios (SORs) of each clinical endpoint for ever sunbed use., Results: Overall, 227 888 individuals from 30 countries completed the Euromelanoma questionnaire. After the data quality check, 16 countries were eligible for the multivariate analysis, for a total of 145 980 participants (64.8% females; median age 43 years; 62.3% highly educated; 28.5% skin type I-II; 11.0% ever sunbed use). Ever sunbed use was independently associated with nevus count >50 [SOR = 1.05 (1.01-1.10)], atypical nevi [SOR = 1.04 (1.00-1.09)], lentigines [SOR = 1.16 (1.04-1.29)] and suspicion of melanoma [SOR = 1.13 (1.00-1.27)]. Conversely, no significant association was found between ever sunbed use and suspicion of NMSC [SOR = 1.00 (0.91-1.10)]., Conclusions: Indoor tanning is significantly associated with well-recognized risk factors for melanoma (including high nevus count, presence of atypical nevi and lentigines) as well as suspicion of melanoma within the Euromelanoma screenees. In order to reduce the prevalence of melanoma risk factors, avoidance/discontinuation of sunbed use should always be encouraged, especially but not exclusively for individuals with high-risk phenotypes., (© 2019 European Academy of Dermatology and Venereology.)

Background: The use of UV-emitting tanning devices for cosmetic purposes is associated with an increased risk of melanoma and non-melanoma skin cancer. Young women are the most frequent users, therefore, there is an increasing concern about the regulation of sunbed use., Objective: The primary objective is to assess the current legislation on sunbed use among European countries., Methods: We developed a 30-item questionnaire to gather the most relevant information about sunbed use legislation. The questionnaire was sent to Euromelanoma coordinators and to designated coordinators out of the Euromelanoma network., Results: We obtained a response rate of 64%. More than 25% of the countries did not report any specific legislation. Roughly one-third of the countries does not have a restriction for minors. Even in countries with a specific legislation, a lack or insufficient enforcement of age limit was observed in up to 100% of the inspections based on the PROSAFE report from 2012. Self-tanning devices were reported in 50%, and almost 40% of countries do not require supervision of use. Although a warning display is required in 77% of cases, a signed informed consent is not required in 80%. In the vast majority of cases, the number of licensed or closed tanning centres is unknown., Conclusions: Despite the evidence of its harmful effects, and its frequent use by young people, many of whom are at high risk of skin cancer because of fair skin, a significant number of European countries lack a specific legislation on tanning devices. In order to limit the access of young people to sunbeds, a more strictly enforced regulation is needed, as well as regulation regarding advertisement, and location of tanning centres, in addition to health promotion campaigns that target the vulnerable population of young women seeking its use for improved cosmesis., (© 2019 European Academy of Dermatology and Venereology.)

A meta-analysis is presented of randomized controlled trials (RCTs) comparing free or fixed combinations of a glucagon-like peptide-1 receptor agonist plus basal insulin versus insulin intensification on metabolic control in patients with type 2 diabetes. Electronic databases were searched for RCTs assessing changes in HbA1c, proportion of patients at HbA1c target of <7% (53 mmol/mol), hypoglycaemia and body weight. A random-effect model was used to calculate the weighted mean difference (WMD) or relative risk (RR) with 95% CI. Eleven RCTs were identified, lasting 24-30 weeks and involving 6176 patients. In the overall analysis, the combination therapy led to a mean HbA1c decrease significantly greater than insulin up-titration (WMD -0.53%, 95% CI, -0.66, -0.40%, P < 0.001), more patients at HbA1c target (RR 1.69, 95% CI, 1.42, 2.00, P < 0.001), similar hypoglycaemic events (RR 0.97, 95% CI, 0.84, 1.12, P = 0.114), and reduction in body weight (WMD -1.9, 95% CI -2.3, -1.4, P < 0.001), with heterogeneity (I 2 > 71%, P < 0.001). Results did not differ in either the free or fixed combination subgroups. Combination strategies, either free or fixed, represent a good option for intensifying basal insulin therapy in patients with type 2 diabetes who need amelioration of glycaemic control., (© 2018 John Wiley & Sons Ltd.)

Rationale, Aims and Objectives: Numerous scientific publications have confirmed that percutaneous laser thermal ablation (LTA) represents a possible therapeutic option in selected patients with benign thyroid nodules. A study was carried out to evaluate the feasibility of adopting the LTA technique to treat benign thyroid nodules in a teaching and research hospital in northern Italy., Methods: A cost analysis from a company's perspective determined the impact of adoption of the new technique on the overall Hospital budget, considering currently available equipment, infrastructure and personnel, equipment costs and treatment tariffs., Results: The cost analysis shows that, strictly from an economic point of view, any provision of the LTA technique will result as a loss on the Hospital's balance sheet. However, it does not estimate the extent of the impact on the overall budget because it did not evaluate the savings that such a technique would make with respect to alternative therapeutic treatments. Therefore, the Hospital policy management decided to extend the current agreement with a private authorized health care structure that already carries out LTA. Also, although difficult to express in economic terms, this new technique would undoubtedly raise the profile and enhance the reputation of the Hospital., Conclusions: Using the new technique in these patients could cut costs for the entire regional health care system, widen the experience of the Hospital's endocrinology team and offer the potential for the procedure also to be provided by operators on a freelance basis within the Hospital., (© 2014 John Wiley & Sons, Ltd.)