Self-Organized Nanorod Arrays for Large-Area Surface-Enhanced Infrared Absorption.

Capabilities of highly sensitive surface-enhanced infrared absorption (SEIRA) spectroscopy are demonstrated by exploiting large-area templates (cm2) based on self-organized (SO) nanorod antennas. We engineered highly dense arrays of gold nanorod antennas featuring polarization-sensitive localized plasmon resonances, tunable over a broadband near- and mid-infrared (IR) spectrum, in overlap with the so-called "functional group" window. We demonstrate polarization-sensitive SEIRA activity, homogeneous over macroscopic areas and stable in time, by exploiting prototype self-assembled monolayers of IR-active octadecanthiol (ODT) molecules. The strong coupling between the plasmonic excitation and molecular stretching modes gives rise to characteristic Fano resonances in SEIRA. The SO engineering of the active hotspots in the arrays allows us to achieve signal amplitude improved up to 5.7%. This figure is competitive to the response of lithographic nanoantennas and is stable when the optical excitation spot varies from the micro- to macroscale, thus enabling highly sensitive SEIRA spectroscopy with cost-effective nanosensor devices.

Prognostic impact of Ki-67 proliferative index in resectable pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by complex biological features and poor prognosis. A prognostic stratification of PDAC would help to improve patient management. The aim of this study was to analyse the expression of Ki-67 in relation to prognosis in a cohort of patients with PDAC who had surgical treatment. Methods: Patients who had pancreatic resection between August 2010 and October 2014 for PDAC at two Italian centres were reviewed retrospectively. Patients with metastatic or locally advanced disease, those who received neoadjuvant chemotherapy, patients with PDAC arising from intraductal papillary mucinous neoplasm and those with missing data were excluded. Clinical and pathological data were retrieved and analysed. Ki-67 expression was evaluated using immunohistochemistry and patients were stratified into three subgroups. Survival analyses were performed for disease-free (DFS) and disease-specific (DSS) survival outcomes according to Ki-67 expression and tumour grading. Results: A total of 170 patients met the selection criteria. Ki-67 expression of 10 per cent or less, 11-50 per cent and more than 50 per cent significantly correlated with DFS and DSS outcomes (P = 0·016 and P = 0·002 respectively). Ki-67 index was an independent predictor of poor DFS (hazard ratio (HR) 0·52, 95 per cent c.i. 0·29 to 0·91; P = 0·022) and DSS (HR 0·53, 0·31 to 0·91; P = 0·022). Moreover, Ki-67 index correlated strongly with tumour grade (P < 0·001). Patients with PDAC classified as a G3 tumour with a Ki-67 index above 50 per cent had poor survival outcomes compared with other patients (P < 0·001 for both DFS and DSS). Conclusion: Ki-67 index could be of use in predicting the survival of patients with PDAC. Further investigation in larger cohorts is needed to validate these results.

Antecedentes: El adenocarcinoma ductal de páncreas (pancreatic ductal adenocarcinoma, PDAC) es una enfermedad agresiva con características biológicas complejas y pronóstico pobre. La estratificación pronóstica del PDAC ayudaría a mejorar el tratamiento del paciente. El objetivo de este estudio era analizar la expresión de Ki­67 como marcador pronóstico en una cohorte de pacientes con PDAC tratados quirúrgicamente. Métodos: Se efectuó un análisis retrospectivo de pacientes sometidos a resección pancreática por PDAC en dos centros italianos entre agosto de 2010 y octubre de 2014. Se excluyeron los pacientes con enfermedad metastásica o localmente avanzada, los tratados con quimioterapia neoadyuvante, los pacientes con PDAC originado en una neoplasia papilar mucinosa intraductal y aquellos pacientes con datos incompletos. Se analizaron los datos clínicos y anatomopatológicos. La expresión de Ki­67 se evaluó por inmunohistoquímica y los pacientes se estratificaron en tres grupos. Se calculó la supervivencia libre de enfermedad (disease­free survival, DFS) y la supervivencia específica de la enfermedad (disease­specific survival, DSS) según la expresión de Ki­67 y el grado tumoral. Resultados: Un total de 170 pacientes cumplió los criterios de selección. La expresión de Ki­67 del ≤ 10%, 11­50% y > 50% mostró una correlación significativa con los resultados de DFS y DSS (P = 0,016 y P = 0,002, respectivamente). El índice Ki­67 fue un predictor independiente de pobre DFS (cociente de riesgos instantáneos, hazard ratio, HR 0,52, i.c. del 95% 0,29­0,91; P = 0,022) y DSS (HR 0,53, i.c. del 95% 0,31­0,91; P = 0,022). Asimismo, el índice Ki­67 se correlacionaba fuertemente con el grado tumoral (P < 0,001). Los pacientes con un PDAC clasificado como tumor grado G3 y con un índice Ki­67 > 50% tenían peores resultados de supervivencia en comparación con otros pacientes (P < 0,001 para ambos DFS y DSS). Conclusión: El índice Ki­67 se puede utilizar como predictor de supervivencia en pacientes con PDAC. Hace falta seguir investigando para validar estos resultados en cohortes más grandes.

Mechanisms underlying the weight loss effects of RYGB and SG: similar, yet different.

The worldwide obesity epidemic continues unabated, adversely impacting upon global health and economies. People with severe obesity suffer the greatest adverse health consequences with reduced life expectancy. Currently, bariatric surgery is the most effective treatment for people with severe obesity, resulting in marked sustained weight loss, improved obesity-associated comorbidities and reduced mortality. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), the most common bariatric procedures undertaken globally, engender weight loss and metabolic improvements by mechanisms other than restriction and malabsorption. It is now clear that a plethora of gastrointestinal (GI) tract-derived signals plays a critical role in energy and glucose regulation. SG and RYGB, which alter GI anatomy and nutrient flow, impact upon these GI signals ultimately leading to weight loss and metabolic improvements. However, whilst highly effective overall, at individual level, post-operative outcomes are highly variable, with a proportion of patients experiencing poor long-term weight loss outcome and gaining little health benefit. RYGB and SG are markedly different anatomically and thus differentially impact upon GI signalling and bodyweight regulation. Here, we review the mechanisms proposed to cause weight loss following RYGB and SG. We highlight similarities and differences between these two procedures with a focus on gut hormones, bile acids and gut microbiota. A greater understanding of these procedure-related mechanisms will allow surgical procedure choice to be tailored to the individual to maximise post-surgery health outcomes and will facilitate the discovery of non-surgical treatments for people with obesity.

Public Health Efforts Can Impact Adoption of Current Susceptibility Breakpoints, but Closer Attention from Regulatory Bodies Is Needed.

Microbiological testing, including interpretation of antimicrobial susceptibility testing results using current breakpoints, is crucial for clinical care and infection control. Continued use of obsolete Enterobacteriaceae carbapenem breakpoints is common in clinical laboratories. The purposes of this study were (i) to determine why laboratories failed to update breakpoints and (ii) to provide support for breakpoint updates. The Los Angeles County Department of Public Health conducted a 1-year outreach program for 41 hospitals in Los Angeles County that had reported, in a prior survey of California laboratories, using obsolete Enterobacteriaceae carbapenem breakpoints. In-person interviews with hospital stakeholders and customized expert guidance and resources were provided to aid laboratories in updating breakpoints, including support from technical representatives from antimicrobial susceptibility testing device manufacturers. Forty-one hospitals were targeted, 7 of which had updated breakpoints since the prior survey. Of the 34 remaining hospitals, 27 (79%) assumed that their instruments applied current breakpoints, 17 (50%) were uncertain how to change breakpoints, and 10 (29%) lacked resources to perform a validation study for off-label use of the breakpoints on their systems. Only 7 hospitals (21%) were familiar with the FDA/CDC Antibiotic Resistance Isolate Bank. All hospitals launched a breakpoint update process; 16 (47%) successfully updated breakpoints, 12 (35%) received isolates from the CDC in order to validate breakpoints on their systems, and 6 (18%) were planning to update within 1 year. The public health intervention was moderately successful in identifying and overcoming barriers to updating Enterobacteriaceae carbapenem breakpoints in Los Angeles hospitals. However, the majority of targeted hospitals continued to use obsolete breakpoints despite 1 year of effort. These findings have important implications for the quality of patient care and patient safety. Other public health jurisdictions may want to utilize similar resources to bridge the patient safety gap, while manufacturers, the FDA, and others determine how best to address this growing public health issue.

Type 2 diabetes remission 2 years post Roux-en-Y gastric bypass and sleeve gastrectomy: the role of the weight loss and comparison of DiaRem and DiaBetter scores.

AIMS: The comparative efficacy of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy on Type 2 diabetes remission and the role of weight loss are unclear. The DiaRem diabetes remission prediction score uses HbA1c , age and diabetes medications but not diabetes duration. The aim of this study was to compare the DiaRem with the DiaBetter score that includes diabetes duration, upon combined (complete plus partial) 2-year post-surgery diabetes remission in people following RYGB and sleeve gastrectomy, and to investigate the relationship between weight loss and diabetes remission. METHODS: A retrospective single-centre cohort study of obese people with diabetes who underwent RYGB (107) or sleeve gastrectomy (103) and a validation cohort study (173) were undertaken. Diabetes remission, % weight loss, DiaRem, DiaBetter scores and areas under receiving operator characteristic (ROC) curves were calculated. The relationship between % weight loss and diabetes remission was investigated using logistic regression. RESULTS: The proportion of people achieving diabetes remission was highest for those with the lowest DiaBetter and DiaRem scores. Areas under the ROC curves were comparable [DiaBetter: 0.867 (95%CI: 0.817-0.916); DiaRem: 0.865 (95%CI: 0.814-0.915), P=0.856]. Two-year % weight loss was higher post RYGB [26.6 (95%CI: 24.8-28.4)] vs post-sleeve gastrectomy [20.6 (95%CI: 18.3-22.8), P<0.001]. RYGB had 151% higher odds of diabetes remission [OR 2.51 (95%CI: 1.12-5.60), P=0.025]. This association became non-significant when adjusted for % weight loss. CONCLUSION: DiaBetter and DiaRem scores predict diabetes remission following both procedures. Two-year % weight loss plays a key role in determining diabetes remission.

Correlation between gamma glutamyltransferase fractions and bone quality.

Gamma-glutamyltransferase (GGT) has been recently identified as a bone-resorbing factor. The aim of this study was to investigate the association between plasma GGT fractions levels and bone quality. Plasma GGT fractions were analysed by gel-filtration chromatography. Bone quality was established quantitatively by two micro-CT derived microarchitectural parameters: the BV/TV (mineralised bone volume/total volume), and the SMI (structure model index) that describes the rod-like (low resistant) or plate-like (high-resistant) shape of bone trabeculae. We enrolled 93 patients hospitalised for elective total hip replacement (group Arthrosis, n=46) or for proximal femoral fracture (group Fracture, n=47). Patients within the first quartile of BV/TV (Q1, osteoporotic patients, n=6) showed higher levels of b-GGT fraction [median (min-max): 3.37 (1.42­6.81)] compared to patients with normal bone density (fourth quartile Q4, n=10; 1.40 (0.83­4.36); p=0.0393]. Also, according to SMI, b-GGT value was higher in the subgroup with bone fragility [Q1, n=8: 1.36 (0.43­4.36); Q4, n=8: 5.10 (1.4 ­7.60); p=0.0117]. In conclusion, patients characterised by fragile bone structure showed specifically higher levels of plasma b-GGT activity thus suggesting fractional GGT analysis as a possible biomarker in the diagnosis of osteoporosis.

Autopsy after transcatheter aortic valve implantation.

Autopsy after transcatheter aortic valve implantation (TAVI) is a new field of interest in cardiovascular pathology. To identify the cause of death, it is important to be familiar with specific findings related to the time interval between the procedure and death. We aimed to provide an overview of the autopsy findings in patients with TAVI in their medical history divided by the timing of death with specific interest in the added value of autopsy over a solely clinically determined cause of death. In 8 European centres, 72 cases with autopsy reports were available. Autopsies were divided according to the time interval of death and reports were analysed. In 32 patients who died ≤72 h postprocedure, mortality resulted from cardiogenic or haemorrhagic shock in 62.5 and 34.4%, respectively. In 31 patients with mortality >72 h to ≤30 days, cardiogenic shock was the cause of death in 51.6% followed by sepsis (22.6%) and respiratory failure (9.7%). Of the nine patients with death >30 days, 88.9% died of sepsis, caused by infective endocarditis in half of them. At total of 12 patients revealed cerebrovascular complications. Autopsy revealed unexpected findings in 61.1% and resulted in a partly or completely different cause of death as was clinically determined. Autopsy on patients who underwent TAVI reveals specific patterns of cardiovascular pathology that clearly relate to the time interval between TAVI and death and significantly adds to the clinical diagnosis. Our data support the role of autopsy including investigation of the cerebrum in the quickly evolving era of cardiac device technology.

Hue-based quantification of mechanochromism towards a cost-effective detection of mechanical strain in polymer systems.

HSV is a digital colour space easily accessible by the transformation of RGB images. In this work, the hue parameter H was used to assess mechanically induced colour changes of the aggregation-sensitive fluorescent dye 4,4'-bis-(2-benzoxazolyl)stilbene (BBS), thus implementing a cheap and reliable method for the detection of mechanical deformation in a polymer matrix.

Calorie restriction and not glucagon-like peptide-1 explains the acute improvement in glucose control after gastric bypass in Type 2 diabetes.

AIMS: To compare directly the impact of glucagon-like peptide-1 secretion on glucose metabolism in individuals with Type 2 diabetes listed for Roux-en-Y gastric bypass surgery, randomized to be studied before and 7 days after undergoing Roux-en-Y gastric bypass or after following a very-low-calorie diet. METHODS: A semi-solid meal test was used to investigate glucose, insulin and glucagon-like peptide-1 response. Insulin secretion in response to intravenous glucose and arginine stimulus was measured. Hepatic and pancreatic fat content was quantified using magnetic resonance imaging. RESULTS: The decrease in fat mass was almost identical in the Roux-en-Y gastric bypass and the very-low-calorie diet groups (3.0±0.3 and 3.0±0.7kg). The early rise in plasma glucose level and in acute insulin secretion were greater after Roux-en-Y gastric bypass than after a very-low-calorie diet; however, the early rise in glucagon-like peptide-1 was disproportionately greater (sevenfold) after Roux-en-Y gastric bypass than after a very-low-calorie diet. This did not translate into a greater improvement in fasting glucose level or area under the curve for glucose. The reduction in liver fat was greater after Roux-en-Y gastric bypass (29.8±3.7 vs 18.6±4.0%) and the relationships between weight loss and reduction in liver fat differed between the Roux-en-Y gastric bypass group and the very-low-calorie diet group. CONCLUSIONS: This study shows that gastroenterostomy increases the rate of nutrient absorption, bringing about a commensurately rapid rise in insulin level; however, there was no association with the large post-meal rise in glucagon-like peptide-1, and post-meal glucose homeostasis was similar in the Roux-en-Y gastric bypass and very-low-calorie diet groups. (Clinical trials registry number: ISRCTN11969319.).

Advancements in quantum cascade laser-based infrared microscopy of aqueous media.

The large mid-infrared absorption coefficient of water frequently hampers the rapid, label-free infrared microscopy of biological objects in their natural aqueous environment. However, the high spectral power density of quantum cascade lasers is shifting this limitation such that mid-infrared absorbance images can be acquired in situ within signal-to-noise ratios of up to 100. Even at sample thicknesses well above 50 µm, signal-to-noise ratios above 10 are readily achieved. The quantum cascade laser-based microspectroscopy of aqueous media is exemplified by imaging an aqueous yeast solution and quantifying glucose consumption, ethanol generation as well as the production of carbon dioxide gas during fermentation.

Rapid identification of goblet cells in unstained colon thin sections by means of quantum cascade laser-based infrared microspectroscopy.

Changes in the volume covered by mucin-secreting goblet cell regions within colon thin sections may serve as a means to differentiate between ulcerative colitis and infectious colitis. Here we show that rapid, quantum cascade laser-based mid-infrared microspectroscopy might be able to contribute to the differential diagnosis of colitis ulcerosa, an inflammatory bowel disease. Infrared hyperspectral images of mouse colon thin sections were obtained within 7.5 minutes per section with a pixel size of 3.65 × 3.65 µm(2) and a field of view of 2.8 × 3.1 mm(2). The spectra were processed by training a random decision forest classifier on the basis of k-means clustering on one thin section. The trained algorithm was then applied to 5 further thin sections for a blinded validation and it was able to identify goblet cells in all sections. The rapid identification of goblet cells within these unstained, paraffinized thin sections of colon tissue was enabled by the high content of glycopeptides within the goblet cells as revealed by the pronounced spectral signatures in the 7.6 µm-8.6 µm and the 9.2 µm-9.7 µm wavelength ranges of the electromagnetic spectrum. More so, the simple calculation of the ratio between the absorbance values at 9.29 µm and 8.47 µm provides the potential to further shorten the time for measurement and analysis of a thin section down to well below 1 minute.

Surface chemistry and entrapment of magnesium nanoparticles into polymeric micelles: a highly biocompatible tool for photothermal therapy.

A novel highly biocompatible nanosystem containing Mg nanoparticles is reported, characterized and tested as a suitable and non-toxic tool for photothermal therapy.

Controlling the dynamics of a bidimensional gel above and below its percolation transition.

The morphology and the microscopic internal dynamics of a bidimensional gel formed by spontaneous aggregation of gold nanoparticles confined at the water surface are investigated by a suite of techniques, including grazing-incidence x-ray photon correlation spectroscopy (GI-XPCS). The range of concentrations studied spans across the percolation transition for the formation of the gel. The dynamical features observed by GI-XPCS are interpreted in view of the results of microscopic imaging; an intrinsic link between the mechanical modulus and internal dynamics is demonstrated for all the concentrations. Our work presents an example of a transition from a stretched to a compressed correlation function actively controlled by quasistatically varying the relevant thermodynamic variable. Moreover, by applying a model proposed some time ago by Duri and Cipelletti [Europhys. Lett. 76, 972 (2006)] we are able to build a master curve for the shape parameter, whose scaling factor allows us to quantify a "long-time displacement length." This characteristic length is shown to converge, as the concentration is increased, to the "short-time localization length" determined by pseudo-Debye-Waller analysis of the initial contrast. Finally, the intrinsic dynamics of the system is then compared with that induced by means of a delicate mechanical perturbation applied to the interface.

Liver transplantation in defects of cholesterol biosynthesis: the case of lathosterolosis.

We report the outcome of liver transplantation (LT) in the only surviving patient with lathosterolosis, a defect of cholesterol biosynthesis characterized by high lathosterol levels associated with progressive cholestasis, multiple congenital anomalies and mental retardation. From her diagnosis at age 2 she had shown autistic behavior, was unable to walk unaided and her sight was impaired by cataracts. By age 7 she developed end-stage liver disease. After a soul-searching discussion within the transplantation team, she was treated with LT as this represented her only lifesaving option. At 1-year follow-up, her lathosterol levels had returned to normal (0.61 mg/dL from 13.04 ± 2.65) and her nutrition improved. She began exploring her environment and walking by holding onto an adult's hand and then independently. Her brain magnetic resonance imaging (MRI) had shown a normal picture at age 1, whereas a volume reduction of white matter with ex vacuo ventricular dilatation and defective myelinization were observed before transplant. At 5-year follow-up, a complete biochemical recovery, an arrest of mental deterioration and a stable MRI picture were achieved, with a return to her every day life albeit with limitations. Timely liver transplant in defects of cholesterol biosynthesis might arrest the progression of neurological damage.

Experimental verification of the spectral shift between near- and far-field peak intensities of plasmonic infrared nanoantennas.

Theory predicts a distinct spectral shift between the near- and far-field optical response of plasmonic antennas. Here we combine near-field optical microscopy and far-field spectroscopy of individual infrared-resonant nanoantennas to verify experimentally this spectral shift. Numerical calculations corroborate our experimental results. We furthermore discuss the implications of this effect in surface-enhanced infrared spectroscopy.

Thyroglobulin autoantibodies of patients with subacute thyroiditis are restricted to a major B cell epitope.

BACKGROUND: Thyroglobulin autoantibodies (TgAb) can develop in patients with subacute thyroiditis (SAT). AIM: Comparison of the epitope pattern of TgAb of patients with SAT, Hashimoto's thyroiditis (HT) [autoimmune thyroid disease (AITD)] and non-toxic multinodular goiter (NTMG) (non-AITD). SUBJECTS AND METHODS: Serum TgAb from 10 patients with SAT, 45 with HT, and 19 with NTMG were evaluated. Serum TgAb binding to Tg was inhibited by 4 recombinant human TgAb-Fab, recognizing Tg epitope regions A, B, C, and D. The ability of single TgAb-Fab to inhibit the binding of serum TgAb to Tg was evaluated in enzymelinked immunosorbent assay. RESULTS: Levels of inhibition were different for all TgAb-Fab in the 3 groups of patients. Inhibition by region A TgAb-Fab in SAT [50.5 (30.3-62.5)%] (median and 25th to 75th percentiles) was similar to HT [49.0 (38.0-69.5)%] and significantly higher than in NTMG [25.0 (14.0-37.0)%]; by region B TgAb-Fab in SAT [0.0 (0.0-12.5)%] was significantly lower than in HT [28.0 (9.5-48.0)%] and similar to NTMG [9.0 (4.8-20.5)%]; by region C TgAb-Fab in SAT [9.5 (0.0-25.8)%] were similar to HT [23.0 (9.5-41)%] and NTMG [6.5 (1.7-21.5)%]; and by region D TgAb-Fab in SAT [0.0 (0.0-8.0)%] were lower than in HT [12.0 (1.0-28.5)%] and similar to NTMG [1.0 (0.0-5.0)%]. CONCLUSIONS: The epitope pattern of TgAb of SAT is restricted to the A region that is immunodominant in AITD and non-AITD. In the majority of patients with SAT, the autoimmune phenomena represent a non-specific and transient response to the release of thyroid antigens, rather than the expression of thyroid autoimmunity.

Criteria for histopathologic diagnosis of aortic disease consensus statement from the SIAPEC-IAP study group of "cardiovascular pathology" in collaboration with the association for Italian cardiovascular pathology.

Nowadays, the histopathological study of surgical specimens is an essential part of the diagnostic work-up in aortic disease, and not only in characterizing the neoplastic forms. Despite increasing clinico-therapeutic complexity of aortic pathology, the criteria for histopathological diagnosis have not been properly updated over the years, with the result that we find inconsistent terminology and little standardization of diagnostic criteria. In light of this consideration, the SIAPeC-IAP Study Group of "Cardiovascular Pathology", in collaboration with the Association for Italian Cardiovascular Pathology, has created this consensus document, with the aim of defining the features of histopathological substrates in the main non-neoplastic aortopathies (atherosclerotic, "degenerative"/non inflammatory, and inflammatory) and of systematizing diagnostic criteria even for the rare tumours of the aorta and pulmonary artery. The principal aims of the project are defining histopathological diagnostic criteria, standard nomenclature and classification, methodology and reporting of histopathological study and handling of aortic specimens. In addiction, some current issues and new knowledge emerging from basic aortic research are debated, with the aim of promoting a "modern" and up-to-date view of aortic pathology.

Infrared spectroscopic and electron microscopic characterization of gold nanogap structure fabricated by focused ion beam.

Using infrared spectroscopy of plasmonic resonances and mapping of elemental composition and structure, we investigated the correlation between optical and structural properties of nanometre-scale gaps in gold nanorod dimers fabricated by electron beam lithography (EBL) and focused ion beam (FIB) milling. In spite of their very similar scanning electron microscopy (SEM) images, a fully cut nanogap and a shallower cut with slight imperfection near the gap region were clearly distinguished by their strongly different infrared plasmonic resonance behaviour. The differences in the infrared spectra are related to different structural and chemical results from elaborated cross-sectional transmission electron micrographs and energy dispersive x-ray spectrometry (EDX) mapping of the gap region.

Evaporation and condensation of SiO and SiO2 studied by infrared spectroscopy.

Physical evaporation of SiO and SiO(2) under ultra-high vacuum conditions was monitored in situ with infrared spectroscopy at frequencies between 450 cm(-1) and 5000 cm(-1). The measured vibrational spectra of the condensed films are identical in both cases, for SiO and SiO(2) evaporation, and can be described with four Brendel oscillators located at 380 cm(-1), 713 cm(-1), 982 cm(-1), and 1101 cm(-1), corresponding to typical vibration modes in SiO.