Proven Marker Research Articles

Early neutrophil gelatinase-associated lipocalin (NGAL) measurement could rule out future acute kidney injury in patients with acute coronary syndrome-Prospective observational study.

The diagnosis of acute kidney injury (AKI) is of importance among patients with ST segment elevation (STEMI) undergoing primary coronary intervention (PCI). It is often delayed given the need in serial measurements of creatinine or other serum markers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proven marker for AKI, although its role as an early predictor in this setting was scarcely addressed before and was the aim of our study. Prospective observational study including 133 patients with STEMI treated with PCI. Plasma NGAL was drawn immediately before PCI (NGAL-0) and 24 h after (NGAL-24). Similar analysis of C-reactive protein (CRP) was performed for additional comparison. Mean age was 62 ± 13 years, 78% were men, and 20 (15%) developed AKI after admission. Patients with AKI after admission demonstrated higher levels of NGAL-0 (164 vs. 95 ng/mL; p < 0.001) and NGAL-24 (142 vs. 93 ng/mL; p < 0.001). Levels of NGAL-0 and NGAL-24 were similar within the AKI and non-AKI groups. Using ROC curve analysis, NGAL-0 had best predictive ability for AKI development (AUC 0.841, 95% CI 0.80-0.96), compared with NGAL-24 (0.783, 95% CI 0.74-0.85), CRP-0 (0.701, 95% CI 0.58-0.83), and CRP-24 (0.781, 95% CI 0.66-0.90). The optimal NGAL-0 cutoff for AKI prediction was 125 ng/mL, with 70% sensitivity, 84% specificity, and 94% negative predictive value. Among STEMI patients, NGAL measurement upon admission are associated with AKI and may serve as a reliable marker for early AKI detection. Future studies may direct risk stratification using this single test can direct personalized evaluations during the admission, and focused interventions to prevent AKI.

Dark pottery from the early Iron Age in southern Veneto, Italy: The provenance issue under the adoption of specific technological procedures

One of the earliest known settlements of Pre-Roman Padua, Veneto Region (north-eastern Italy) was located in the very centre of the present-day city. The archaeological excavations revealed structures related to craft activities (metallurgical and pottery workshops) and residential areas datable from the late 9th to the 1st century BCE. A large pyrotechnic structure formed by an earthen block densely filled and covered by broken ceramic vessels was found, bringing to light the earliest foundry of the Pre-Roman Padua known to date. Many potsherds found in the site correspond to a regional ceramic class that included coarse and fine wares mainly composed of very dark ceramic bodies. A multi-analytical study based on macroscopic and petrographic descriptions as well as mineralogical, geochemical and microstructural analyses, was carried out in order to state the technological choices adopted for producing these dark vessels and the provenance of the raw materials. A poorly manufacturing was adopted to produce the common pottery, resulting coarse wares uneven textured, while the fine wares were produced by adopting the purification of the base clays and/or the tempering of the clay pastes. Common geo-resources were used, consisting in illitic-chloritic clays rich in quartz and feldspars, the firing regime conditions covered a range of maximum temperatures (normally under 850 °C) and the temper was constituted by silicate (chiefly quartzite, rhyolite and trachyte rock fragments) and/or carbonate (calcite and/or dolomite) inclusions, that were added after having been grounded and/or sieved. The specific mineral and lithic markers of provenance identified in the sherds confirmed the correspondence of this pottery with a local production. However, the specific technological choices that were carried out must be taking into consideration, since the purification removed the larger grains originally present in the base clays and the tempering influenced the chemical composition of the sherds. The different degree of purification of the base clays and the differential tempering procedures that were accomplished point out the adoption of very specific recipes to produce the fine wares, suggesting the correspondence of this local ceramic class with diverse sub-productions and the high level of specialization achieved by the potters in southern Veneto during the Early Iron Age.

Markers for meat provenance and authenticity with an account of its defining factors and quality characteristics - a review.

Provenance is becoming increasingly important in meat supply chains as it lends products higher perceived quality. However, its precise definition and interpretation along with its associated characteristics factors have remained somewhat elusive. This review meticulously defines meat provenance while dissecting the essential factors and associated quality attributes that constitute its essence and are subsequently employed to establish pertinent markers for provenance. Meat provenance emerges as a multi-dimensional construct stemming from the adept management of a constellation of factors relating to geographical origin, farm production system, traceability, and authenticity. Through intricate interactions, these factors unveil innate originality that not only forges a distinct reputation but also imparts a unique typicity to the meat product. Gaining insights into a meat product's provenance becomes attainable by scrutinizing its pertinent composition and organoleptic quality traits. Trace elements and stable isotopes stand out as provenance markers, forging a direct connection to both geographical origin and dietary sources. While somewhat less direct in linkage, other markers such as plant biomarkers, fatty acid composition, pH levels, flavour and aromatic compounds along with organoleptic characteristics contribute to the overall understanding of provenance. Additionally, the identification of animal species and breeds serves as key markers, particularly in the context of protected geographical indications. The study findings are useful for the various stakeholders of how the information for meat provenance can be linked with intrinsic and extrinsic factors for meat quality and protecting the integrity of the supply chain with special reference to traceability and authenticity. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Provenance of the Bronze Age lapis lazuli pieces from the Early Urban Center of Konar Sandal, Jiroft, Southern Iran

The sources of lapis lazuli objects found in the Bronze Age of the Iranian Plateau and its trade routes have been a subject of interest and a research question. Four archaeological pieces of lapis lazuli recovered from a stone-working workshop in the Bronze Age site of Konar Sandal South (Jiroft Plain), southern Iran, were analyzed using X-ray diffraction (XRD) and scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS) techniques to characterize the mineralogical composition and the possible provenance of raw materials. Results showed that these objects are identical based on their composition, presenting diopside and specific trace element proportions as provenance markers. Comparison with available data from Iranian archaeological sites and ancient resources from Central Asia revealed that these finds may have been imported from lapis lazuli mines located at Badakhshan in Afghanistan, as they were supplied raw materials for ancient lapis lazuli objects of Iran.

Right Atrial Remodeling and Outcome in Patients with Secondary Tricuspid Regurgitation

In patients with secondary tricuspid regurgitation (STR), right atrial remodeling (RAR) is a proven marker of disease progression. However, the prognostic value of RAR, assessed by indexed right atrial volume (RAVi) and reservoir strain (RAS), remains to be clarified. Accordingly, the aim of our study is to investigate the association with outcome of RAR in patients with STR. We enrolled 397 patients (44% men, 72.7±13years old) with mild to severe STR. Complete two-dimensional and speckle-tracking echocardiography analysis of right atrial and right ventricular (RV) size and function were obtained in all patients. The primary end point was the composite of death from any cause and heart failure hospitalization. After a median follow-up of 15months (interquartile range, 6-23), the end point was reached by 158 patients (39%). Patients with RAS <13% and RAVi >48mL/m2 had significantly lower survival rates compared to patients with RAS ≥13% and RAVi ≤48mL/m2 (log-rank P<.001). On multivariable analysis, RAS <13% (hazard ratio, 2.11; 95% CI, 1.43-3.11; P<.001) and RAVi > 48mL/m2 (hazard ratio, 1.49; 95% CI, 1.01-2.18; P=.04) remained associated with the combined end point, even after adjusting for RV free-wall longitudinal strain, significant chronic kidney disease, and New York Heart Association class. Secondary tricuspid regurgitation excess mortality increased exponentially with values of 18.2% and 51.3mL/m2 for RAS and RAVi, respectively. In nested models, the addition of RAS and RAVi provided incremental prognostic value over clinical, conventional echocardiographic parameters of RV size and function and RV free-wall longitudinal strain. In patients with STR, RAR was independently associated with mortality and heart failure hospitalization. Assessment of RAR could improve risk stratification of patients with STR, potentially identifying those who may benefit from optimization of medical therapy and a closer follow-up.

Свинцовые пломбы поствизантийского Мангупа

The aim of this research is to introduce into the scholarship a new group of sigillographic materials, or the lead cloth seals. The collection of 23 artefacts was divided into two types according to their morphological characteristics. The cloth seals of type 1 consist of two lead discs, and the cloth seals of type 2 of four discs. Type 1 comprises of three variants. All the artefacts have been interpreted as cloth seals used as markers of provenance and quality standards in the European textile industry from the Middle Ages and the Modern Period. The cloth seals of type 1 seals originate from the territory of 1425–1475 palace and date to the period when the palace existed. There is no parallel to the said cloth seal found so far. The cloth seals of type 2 were uncovered at the area of the Mangup basilica; they date from the seventeenth century and originate from England, with one artefact from the Suffolk. The textiles sealed with the artefacts of types 1 and 2 possibly came to Mangup by trade or as “diplomatic gifts.”

Narcotic Use under Probation and Parole Supervision - A longitudinal Study of Risk-group-specific Recidivism under Abstinence Conditions

The aim of this long-term study was to record substance-specific prevalences of illegal use of narcotics despite court-imposed abstinence requirements. Urine assays were obtained by a public health department on the basis of administrative assistance for the probation department of a district court. The individual and valid allocation of these urine samples was ensured using a proven marker system. After postal dispatch, laboratory chemical analyses for narcotics residues were carried out in an external laboratory via enzyme immunoassay and validation by mass spectrography in the case of positive narcotics results. On the basis of all available routine data, a pooled data set covering a total of fourteen consecutive calendar years (2006-2019) was generated digitally and evaluated anonymously. From a total of 380 subjects (female: 13% versus male: 87%; average age: 30.4 years), 13,500 individual narcotic substance analyses from 2,941 urine samples were available. In 2.7% of all individual analyses, at least one of eight potential narcotic substances was detected, whereby the highest overall prevalences in the sense of a relapse were found for cannabis with 3.7% and for opiates with 2.4%. In contrast, there were almost no residues for barbiturates and LSD and no positive evidence for buprenorphine and PCP. As expected, most relapses in all narcotics groups were found in the age groups from 18 to 35 years. Strikingly, more women than men violated the court abstinence order with amphetamines, while relapses with the other seven narcotics groups occurred predominantly among men. In the course of the entire observation period, the most marked fluctuations in relapse rates were found for cannabis, opiates and cocaine. The use of narcotic substances during probation and parole supervision does not appear to be a rare occurrence and has received little professional attention. Increased attention to this group-specific recidivism and more studies on this topic should help reduce this deficit.

Right atrial remodeling and outcome in patients with secondary tricuspid regurgitation

Abstract Funding Acknowledgements Type of funding sources: None. Background Secondary tricuspid regurgitation (STR) is independently associated with patients’ morbidity and mortality and right atrial remodeling (RAR) is a proven marker of disease progression. Purpose The aim of our study is to investigate the prognostic value of RAR in terms of RA volume (RAVi) and strain (RAS) in patients with STR. Methods We retrospectively enrolled 400 adult patients (46% men, 72.5±14.0 years) with both atrial and ventricular STR (mild 26%, moderate 40%, severe 34%). Exclusion criteria were primary TR, cardiac implantable electronic device, previous TV intervention, poor apical acoustic window, and lack of follow-up. Complete two-dimensional echocardiography, including right atrial volume (RAVi), speckle-tracking analyses of RA reservoir strain (RARS) and right ventricular strain (RVLS) on focused apical 4-chamber views, were obtained. The primary outcome was the composite endpoint of death from any cause and heart failure hospitalization. Results After a median follow-up of 13 months (IQR: 6–23), the combined endpoint was reached by 158 patients (39%). Patients who experienced events had larger RV and RA size, more impaired RVLS and RARS, and higher pulmonary artery pressure. By receiving operating curve (ROC) analysis, the ideal cut-offs for RARS and RAVi were 14% and 48 mL/m2 (p&amp;lt;0.0001). RAS &amp;lt; 14% [HR 2.40, p&amp;lt;0.0001] and RAVi &amp;gt; 48 mL/m2 [HR 2.10, p&amp;lt;0.0001] were strongly associated with outcome. Patients with both RAS &amp;lt; 14% and RAVi &amp;gt; 48 mL/m2 had significantly lower survival rates compared to patients with RAS ≥ 14% and RAVi ≤ 48 mL/m2 (log-rank χ²= 31 and χ²= 22 respectively, p&amp;lt;0.001) (Figure 1). RAS &amp;lt;14% was associated with higher cumulative event rates, regardless of baseline patients’ rhythm (log-rank χ²= 35, p&amp;lt;0.001). Moreover, patients having both RAS &amp;lt;14% and RAVi &amp;gt;48 mL/m2 had a higher rate of adverse events (log-rank χ²= 53, p&amp;lt;0.001) compared to those with a single RA parameter abnormal, or those who had both parameters normal. On multivariable analysis, RAS &amp;gt;14% (HR1.53; 95% CI, 1.00–2.33; p = 0.02) and RAVi &amp;gt;48 mL/m2 (HR 1.42; 95% CI, 0.96–2.11; p = 0.04) remained independently associated with the combined endpoint. RAR provided incremental prognostic value over RV size and function, including RVLS. Conclusions In patients with STR, RARS is associated with an increased risk for HF hospitalization and all-cause mortality. Assessment of RARS could improve risk stratification of patients with STR, potentially identifying those who may benefit from optimization of medical therapy and earlier surgical/percutaneous treatment. Figure 1. Kaplan-Meier plots for the analysis of the cumulative event-free survival according to RAS (Panel A) and RAVi (Panel B) values.

Application of principal component analysis to µ-PIXE data in lapis lazuli provenance studies

The application of multivariate analysis is extremely useful when dealing with large datasets and can be applied also in provenance studies. In this work, Principal Component Analysis (PCA) was applied for the first time to the study of the provenance of lapis lazuli rocks used for glyptic art in ancient times, on a database including four different sources in Afghanistan, Tajikistan, Siberia and Myanmar. Results of the application of PCA on µ-PIXE data collected in mineralogical phases contained in lapis lazuli rocks, in particular diopside and pyrite, confirmed the role of some trace element contents as characteristics for different provenances, i.e. as provenance markers. As an additional important result, PCA seems to strengthen the role of previously found weaker markers (i.e. trace elements not sufficient alone to distinguish univocally among provenances) such as, for example, the coexistence of high Ti, V, Cr and Mn concentrations in diopside in Afghan lapis lazuli. This can be relevant when other discriminant phases like pyrite cannot be found in the sample or are not suitable for analysis.Moreover, for geological purposes and to try to distinguish among different quarries inside an extraction area, a study on intra-provenance variability was carried out on diopside data for Myanmar and Siberian samples. The separation into three groups for Myanmar samples, previously identified by means of minero-petrographic and elemental analysis, is confirmed and a partial differentiation was identified also for samples coming from the two Siberian areas of Sludyanka River and Malaya Bistraya River.

Micro-PIXE and micro-IBIL characterization of lapis lazuli samples from Myanmar mines and implications for provenance study

The provenance of raw lapis lazuli used since the Neolithic Age for the realization of carved artefacts can be pivoting for the reconstruction of ancient trade routes. The role of main provider of this material in ancient times is generally attributed to the Badakhshan quarries (Afghanistan), although other deposits could have been exploited as well since antiquity. The systematic multi-technique analysis of lapis lazuli rocks coming from four known source areas (located in present-day Afghanistan, Tajikistan, Siberia and Chile) has led in the last years to the compilation of a protocol for provenance determination. The protocol is based on differences in the physical–chemical properties measured with non-invasive techniques (Ion Beam Analysis (IBA)), making it suitable also for precious ancient artefacts. In this work, 10 new reference samples from the Mogok quarry (Myanmar), previously subjected to a complete petrographic and mineralogical characterization, have been analysed employing mu-PIXE (Proton Induced X-ray Emission) and mu-IBIL (Ion Beam Induced Luminescence) techniques. The subdivision of Myanmar samples into three groups, previously suggested, is corroborated by diopside trace elements concentrations. The results also allow to include Myanmar as a new provenance in the analytical protocol, indicating that provenance markers such as presence/absence of wollastonite, altered pyrites and Sr content are still valid to discriminate also the Myanmar lapis lazuli from Chilean or Siberian ones. New weaker markers (Zn content in diopside, Se and Cu contents in pyrite) are proposed for the discrimination of Myanmar from Afghan or Tajik provenances; however, from the analysis it arose the need of investigating new mineral phases with IBA to find strong markers for a definitive discrimination with samples from Southwest Asia.

Association between the novel biomarker oxidised LDL/beta 2 glycoprotein I complexes and coronary artery calcification with cardiovascular outcomes – a long term prospective study. Prospective study

Coronary artery calcium (CAC) score is a proven marker associated with major cardiovascular (CV) events. Oxidised LDL/beta 2 glycoprotein I (oxLDL/ß2GPI) complexes are proatherogenic markers that separately have been shown to be elevated in patients with coronary artery disease (CAD). It is unknown how this complex relate to CAC in predicting long term CV outcomes.

Efficacy of blood parameters in predicting the severity of gestational hypertension and preeclampsia

The aim of this retrospective study was to demonstrate the effectiveness of APRI, DNI, NLR, PLR, and PDW in predicting the severity of gestational hypertension (GHT) and PE and to determine whether these factors can be used as screening tools. Normotensive pregnant women (n = 792) served as the control group. 1,213 single pregnant women who met the following criteria for a GHT diagnosis were included in the study group. We found a significantly higher mean PLR and NLR value. The mean PDW value was significantly lower in the control group than in the other groups. The SPE group had a significantly higher mean APRI score. The groups did not differ by their DNI. We determined PDW and APRI as independent parameters that predicted SPE by multiple logistic regression analysis. In retrospective analysis of blood samples taken from these participants below week 20, we found that the APRI value differed significantly between the control and SPE groups. NLR, PLR, DNI, and PDW had no clinical significance. We further suggested that APRI may provide a clinical indication of progression from hypertensive pregnancy disorders to SPE, which seems to be a promising implication that should be verified by further studies. IMPACT STATEMENT What is already known on this subject? Hypertensive disorders in pregnancy are a major cause of maternal and perinatal morbidity and mortality. Screening pregnant women for risk factors for developing hypertensive disorders and identifying women at high risk in early pregnancy and initiating prophylactic treatment are important for pregnancy monitoring and planning in experienced centres. Because only 30% of women who will develop preeclampsia can be predicted by risk factors, the combined use of laboratory tests and imaging with risk factors to calculate a woman’s risk of developing preeclampsia is currently being investigated. However, no proven marker has yet been found. What do the results of this study add? In our study, we found that NLR, PLR, DNI, and PDW have no clinical significance in assessing the risk of developing gestational hypertension and preeclampsia and in predicting the severity of preeclampsia. However, in our study, we found that APRI can provide a clinical indication of the progression of hypertensive pregnancy to SPE. What are the implications of these findings for clinical practice and/or further research? This study represents an important contribution to the literature because it is the first study to examine the association between APRI and HT in pregnancy.

Predictive Accuracy of Neutrophil-to-Lymphocyte Ratio on Severity and Outcomes in COVID-19 Patients

Background/Aims: Neutrophil-to-lymphocyte ratio (NLR) is a proven marker in coronavirus disease 2019 (COVID-19) severity and mortality. However, the utility of a sequential NLR 2 (on day 5) in comparison to baseline NLR in predicting clinical outcomes and severity remains largely unexplored. Methods: This was a hospital-based retrospective observational study. Results: Higher mortality (19.9% vs. 48%) and a more severe disease (14.8% vs. 21%) were observed with elevated NLR 1 and NLR 2, respectively. NLR 2 at a cutoff of 9.88 was a better predictor of mortality, when compared to NLR 1 at 5.67, and NLR 2 has a strong correlation with mortality rates in COVID-19. Conclusion: Our study demonstrated that NLR 1 and NLR 2 were more reliable predictors of mortality than disease severity; in comparison, NLR 2 is a more accurate predictor of mortality than NLR 1. The study unravels the potential role of a sequential NLR 2, to have a better correlation in predicting the clinical severity and outcomes. The potential role of NLR 2 in assessing the interim progression of the disease and thereby initiating specific interventions at critical junctures to influence the outcome is unveiled and merits exploration in detail by larger studies.

A bioavailable strontium (87Sr/86Sr) isoscape for Aotearoa New Zealand: Implications for food forensics and biosecurity.

As people, animals and materials are transported across increasingly large distances in a globalized world, threats to our biosecurity and food security are rising. Aotearoa New Zealand is an island nation with many endemic species, a strong local agricultural industry, and a need to protect these from pest threats, as well as the economy from fraudulent commodities. Mitigation of such threats is much more effective if their origins and pathways for entry are understood. We propose that this may be addressed in Aotearoa using strontium isotope analysis of both pests and products. Bioavailable radiogenic isotopes of strontium are ubiquitous markers of provenance that are increasingly used to trace the origin of animals and plants as well as products, but currently a baseline map across Aotearoa is lacking, preventing use of this technique. Here, we have improved an existing methodology to develop a regional bioavailable strontium isoscape using the best available geospatial datasets for Aotearoa. The isoscape explains 53% of the variation (R2 = 0.53 and RMSE = 0.00098) across the region, for which the primary drivers are the underlying geology, soil pH, and aerosol deposition (dust and sea salt). We tested the potential of this model to determine the origin of cow milk produced across Aotearoa. Predictions for cow milk (n = 33) highlighted all potential origin locations that share similar 87Sr/86Sr values, with the closest predictions averaging 7.05 km away from their true place of origin. These results demonstrate that this bioavailable strontium isoscape is effective for tracing locally produced agricultural products in Aotearoa. Accordingly, it could be used to certify the origin of Aotearoa's products, while also helping to determine if new pest detections were of locally breeding populations or not, or to raise awareness of imported illegal agricultural products.

An Overview on Actual Knowledge About Immunohistochemical and Molecular Features of Vitality, Focusing on the Growing Evidence and Analysis to Distinguish Between Suicidal and Simulated Hanging.

In forensic practice, the pathologist is often asked to determine whether a hanging was committed as suicide or as a simulated hanging (when a dead body is suspended after death). When exterior evidence of violence is absent and the crime scene investigation fails to identify useful proof, it is nearly impossible to tell whether the dead body was suspended or not. As a result, determining whether the ligature mark was created during life or not should rely on the research and demonstration of vital reactions on the ligature mark. The main purpose of this review article is to provide a summary of current knowledge about the histological and immunohistochemical characteristics of vitality in hanging. The authors also aim to identify the most significant vitality markers on ligature marks for further scientific validation and to propose a standardized diagnostic protocol for hanging. The study was conducted according to the Preferred Reporting Items for Systematic Review (PRISMA) Protocol. Relevant scientific papers were found from PubMed up to April 2021, using the following keywords: hanging AND skin AND vitality. Three main points were studied: ligature mark dehydration, immunological response to mechanical injury, and apoptosis induction as a result of the previous points. An increase in apoptosis is evident in the ligature mark (due to physical and chemical processes involved), as demonstrated by FLICE-inhibitory protein (FLIP) depletion. Immunohistochemical detection of Aquaporin 3 (AQP3) and increase in the concentration of different electrolytes rely solely on ligature mark dehydration. Also, microRNAs (MiRNAs) could become reliable forensic biomarkers for ligature mark vitality diagnosis in the near future. To ensure high reliability in court cases, forensic investigation in hanging should rely on modern and proven markers, even a mix of several markers.

Petrographic Characterization of Late Roman African Pottery from J.W. Salomonson’s Surveys: 3. The Workshops of Henchir el Biar and Bordj el Djerbi

This paper focuses on the petrographic characterization of African Red Slip Ware from the North Tunisian workshops of Henchir el Biar and Bordj el Djerbi surveyed by J.W. Salomonson in 1968. Binocular observation and thin section analysis have been combined to identify the micro-and macroscopic provenance markers of both workshops that lie within a short distance in the Mejerda Valley. The results of this research, in agreement with previous chemical studies, demonstrated that not only is it possible to petrographically distinguish the workshops of Bordj el Djerbi and Henchir el Biar from each other, but in most cases also from the neighboring workshop of El Mahrine, which generally shows finer fabrics. These data are particularly interesting as the three workshops form a homogeneous group in terms of typology and macroscopic characteristics. Moreover, the apparent petrographic and technological similarities between a few samples and some other not yet located ARS productions open the discussion of the possible presence of other workshops in the same area of the Mejerda Valley.

Evaluation of plasma protein C and antithrombin levels in patients with tuberculosis

Background Tuberculosis (TB) is a global health problem and thromboembolic complications, when occurring, are often fatal, with no proven markers to predict. The most common type is latent tuberculosis infection (LTBI); however, patients can develop active TB disease and become infectious. Managing LTBI properly can prevent active disease evolution, and exclusion of active TB is the main primary question in LTBI management. Protein C (PC) and antithrombin (AT) are natural anticoagulants with anti-inflammatory properties, so they are suggested to have a role in hypercoagulability due to inflammatory processes. Aim To correlate PC and AT levels in TB patients with patients’ coagulable and clinical state. Patients and methods Sixty patients (20 pretreatment, 20 posttreatment active TB, and 20 LTBI) and 20 normal-controls were included. Activity levels of PC and AT were measured and correlated to patients’ coagulable and clinical states, and routine laboratory results. Results Activity levels of PC and AT are significantly low in active TB, increasing with treatment, and normal in LTBI. No thromboembolic events were detected in all patients included, so correlation with PC and AT could not be verified. Conclusion Active TB is associated with hypercoagulable state, with low activity levels of PC and AT. Both proteins are suggested to be used as adjuvant markers of activation of LTBI and during their pretreatment assessment, together with monitoring therapeutic response in patients with active TB.

Urine N-acetyl-Ser-Asp-Lys-Pro measurement as a versatile biomarker to assess adherence to angiotensin-converting enzyme inhibitors.

Poor adherence to treatment is a major health issue in hypertension. The large number of drugs to be detected limits the implementation of chemical adherence testing by liquid chromatography/mass spectrometry (LC-MS/MS). AcSDKP, a peptide accumulating in the presence of angiotensin-converting-enzyme inhibitor (ACEI) treatment, has been validated as a proven marker of adherence by enzyme-linked immunosorbent assay. Our aim was to validate urine measurements of AcSDKP compared with active metabolites of various ACEI, measured simultaneously by LC-MS/MS. We first studied the time-dependent relationships between urinary perindoprilat and AcSDKP in a pharmacokinetic/pharmacodynamic study in healthy volunteers. We then compared the sensitivity and specificity of urinary AcSDKP vs. three ACEI active metabolites (enalaprilat, perindoprilat, ramiprilat) taken as reference to detect nonadherence in spot urine samples from a prospective cohort of hypertensive outpatients. The urinary excretion profiles of AcSDKP and perindoprilat were similar, exhibited a significant correlation, and showed excellent agreement in healthy volunteers. In patients, we found a similar agreement between AcSDKP and the three ACEI metabolites urinary concentrations. The sensitivity and specificity for adherence assessment of urine AcSDKP was 92.2 and 100%, respectively. We observed a difference in the evaluation of good adherence between ACEI metabolites (85.7%) and AcSDKP (79.0%) because of discrepancies in samples where AcSDKP reached undetectability quicker than ACEI metabolites. This characteristic of AcSDKP is of particular interest and could better reflect the true adherence status of patients. Overall, spot urine AcSDKP measurement by LC-MS/MS is a reliable marker of the intake of ACEI treatment and could substitute ACEI metabolites detection.

Geochemical and isotopic provenance determination of gypsum used for stucco artworks: application to Florentine stucco reliefs

Gypsiferous rocks of Tuscany and derived materials (i.e. alabaster, stucco and gesso) have been frequently used as sculptural materials. Remarkable examples are attested from the Renaissance Florence. At the junction of two ongoing programs, dealing respectively with the study of 15th century stucco reliefs (called Madonne di gesso) and the provenance of European alabasters used in artworks, an investigation on raw gypsum supply was conducted via a geological survey in the surroundings of Florence. Looking for geochemical provenance markers, a multi-analytical approach was carried out on 30 geo-referenced rock samples. In particular, trace elements, related both to gypsum and synsedimentary minerals, and gypsum multi isotopic fingerprints (S, O, Sr) were tested. The results obtained are discussed, disclosing insights in the geo-sourcing of raw materials used for stucco reliefs in Florentine workshops.

Generation, analysis, and transformation of macro-chloroplast Potato (Solanum tuberosum) lines for chloroplast biotechnology

Chloroplast biotechnology is a route for novel crop metabolic engineering. The potential bio-confinement of transgenes, the high protein expression and the possibility to organize genes into operons represent considerable advantages that make chloroplasts valuable targets in agricultural biotechnology. In the last 3 decades, chloroplast genomes from a few economically important crops have been successfully transformed. The main bottlenecks that prevent efficient transformation in a greater number of crops include the dearth of proven selectable marker gene-selection combinations and tissue culture methods for efficient regeneration of transplastomic plants. The prospects of increasing organelle size are attractive from several perspectives, including an increase in the surface area of potential targets. As a proof-of-concept, we generated Solanum tuberosum (potato) macro-chloroplast lines overexpressing the tubulin-like GTPase protein gene FtsZ1 from Arabidopsis thaliana. Macro-chloroplast lines exhibited delayed growth at anthesis; however, at the time of harvest there was no significant difference in height between macro-chloroplast and wild-type lines. Macro-chloroplasts were successfully transformed by biolistic DNA-delivery and efficiently regenerated into homoplasmic transplastomic lines. We also demonstrated that macro-chloroplasts accumulate the same amount of heterologous protein than wild-type organelles, confirming efficient usage in plastid engineering. Advantages and limitations of using enlarge compartments in chloroplast biotechnology are discussed.