University of Puerto Rico at Carolina

The graphene family has captured the interest and the imagination of an increasing number of scientists working in different fields, ranging from composites to flexible electronics. In the area of biomedical applications, graphene is especially involved in drug delivery, biosensing and tissue engineering, with strong contributions to the whole nanomedicine area. Besides the interesting results obtained so far and the evident success, there are still many problems to solve, on the way to the manufacturing of biomedical devices, including the lack of standardization in the production of the graphene family members. Control of lateral size, aggregation state (single vs. few layers) and oxidation state (unmodified graphene vs. oxidized graphenes) is essential for the translation of this material into clinical assays. In this Tutorial Review we critically describe the latest developments of the graphene family materials into the biomedical field. We analyze graphene-based devices starting from graphene synthetic strategies, functionalization and processibility protocols up to the final in vitro and in vivo applications. We also address the toxicological impact and the limitations in translating graphene materials into advanced clinical tools. Finally, new trends and guidelines for future developments are presented.

OBJECTIVES: To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders. METHODS: 751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007-8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005-7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases. CONCLUSIONS: Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.

With the long term objective to build the next generation of devices from the molecular scale, scientists have explored extensively in the past two decades the Prussian blue derivatives and their remarkable physico-chemical properties. In particular, the exquisite Fe/Co system displays tuneable optical and magnetic behaviours associated with thermally and photo-induced metal-to-metal electron transfer processes. Recently, numerous research groups have been involved in the transfer of these electronic properties to new Fe/Co coordination networks of lower dimensionality as well as soluble molecular analogues in order to facilitate their manipulation and integration into devices. In this review, the most representative examples of tridimensional Fe/Co Prussian blue compounds are described, focusing on the techniques used to understand their photomagnetic properties. Subsequently, the different strategies employed toward the design of new low dimensional Prussian blue analogues based on a rational molecular building block approach are discussed emphasizing the advantages of these functional molecular systems.

Ultra-large graphene oxide sheets exhibit unique viscoelastic properties, making them a new class of soft material. We provide fundamental insights enabling development of various fabrication techniques utilizing this 2D material.

Ti_nC_n−1T_x2D-sheets are functionalized using a new etching environment allowing the modification of their surface chemistry and production of rationalized TiO₂@MXene nanocomposites.

Summary 1. Current emphasis on species conservation requires the development of specific distribution models. Several modelling methods are available, but their performance has seldom been compared. We therefore used discriminant analysis, logistic regression and artificial neural networks with environmental data to predict the presence or absence of six river birds along 180 Himalayan streams. We applied each method to calibration sites and independent test sites. With logistic regression, we compared performance in predicting presence–absence using map‐derived predictors (river slope and altitude) as opposed to detailed data from a standardized river habitat survey (RHS). 2. Using the entire calibration data, overall success at predicting presence or absence was only slightly greater using artificial neural networks (89–100%) than either logistic regression (75–92%) or discriminant analysis (81–95%), and on this criterion all methods gave good performance. 3. When applied to independent test data, overall prediction success averaged 71–80%, with logistic regression marginally but significantly out‐performing the other methods. Encouragingly for researchers with limited data, model performance in jack‐knife tests faithfully represented performance in more rigorous validations where calibration ( n = 119) and test sites ( n = 61) were in separate geographical regions. 4. All three methods predicted true absences (83–92% success) better than true presences (31–44%). Results from logistic regression were the most variable across species, but positive prediction declined with increasing species rarity in each method. 5. Applications with logistic regression illustrated that significant habitat predictors varied between data sets within species. Hypotheses about causal effects by habitat structure on distribution were thus difficult to erect or test. Logistic regression also showed that detailed data from the river habitat survey substantially improved positive prediction by comparison with prediction using slope or altitude alone. 6. We conclude that discriminant analysis, logistic regression and artificial neural networks differ only marginally in performance when predicting species distributions. Model choice should therefore depend on the nature of the data, on the needs of any particular analysis, and on whether assumptions for each method are satisfied. All three methods share drawbacks due to systematic effects by species rarity on performance measures. They also share limitations due to the correlative nature of survey data often used for model development at the spatial scales required in macro‐ecology and conservation biology. Tests with independent data, using a wider range of performance measures than those used traditionally, will be important in examining models and testing hypotheses for such applications.

Tailoring the specific magnetic properties of any material relies on the topological control of the constituent metal ion building blocks. Although this general approach does not seem to be easily applied to traditional inorganic bulk magnets, coordination chemistry offers a unique tool to delicately tune, for instance, the properties of molecules that behave as "magnets", the so-called single-molecule magnets (SMMs). Although many interesting SMMs have been prepared by a more or less serendipitous approach, the assembly of predesigned, isolatable molecular entities into higher nuclearity complexes constitutes an elegant and fascinating strategy. This Feature article focuses on the use of building blocks or modules (both terms being used indiscriminately) to direct the structure, and therefore also the magnetic properties, of metal ion complexes exhibiting SMM behaviour.

Major drivers of gains or losses in soil organic carbon (SOC) include land management, land-use change, and climate change. Thousands of original studies have focused on these drivers of SOC change and are now compiled in a growing number of meta-analyses. To critically assess the research efforts in this domain, we retrieved and characterized 192 meta-analyses of SOC stocks or concentrations. These meta-analyses comprise more than 13,200 original studies conducted from 1910 to 2020 in 150 countries. First, we show that, despite a growing number of studies over time, the geographical coverage of studies is limited. For example, the effect of land management, land-use change, and climate change on SOC has been only occasionally studied in North and Central Africa, and in the Middle East and Central Asia. Second, the meta-analyses investigated a limited number of land management practices, mostly mineral fertilization, organic amendments, and tillage. Third, the meta-analyses demonstrated relatively low quality and transparency. Lastly, we discuss the mismatch between the increasing number of studies and the need for more local, reusable, and diversified knowledge on how to preserve high SOC stocks or restore depleted SOC stocks.

The emission and absorption of Cs₂AgBiBr₆ are dominated by the strong carriers–phonon coupling.

Covering: 2013 to 2019 The exploration of the chemical diversity of extracts from various biological sources has led to major drug discoveries. Over the past two decades, despite the introduction of advanced methodologies for natural product (NP) research (e.g., dereplication and high content screening), successful accounts of the validation of NPs as lead therapeutic candidates have been limited. In this context, one of the main challenges faced is related to working with crude natural extracts because of their complex composition and the inadequacies of classical bioguided isolation studies given the pace of high-throughput screening campaigns. In line with the development of metabolomics, genomics and chemometrics, significant advances in metabolite profiling have been achieved and have generated high-quality massive genome and metabolome data on natural extracts. The unambiguous identification of each individual NP in an extract using generic methods remains challenging. However, the establishment of structural links among NPs via molecular network analysis and the determination of common features of extract composition have provided invaluable information to the scientific community. In this context, new multi-informational-based profiling approaches integrating taxonomic and/or bioactivity data can hold promise for the discovery and development of new bioactive compounds and return NPs back to an exciting era of development. In this article, we examine recent studies that have the potential to improve the efficiency of NP prioritisation and to accelerate the targeted isolation of key NPs. Perspectives on the field's evolution are discussed.

OBJECTIVES: To assess the efficacy and safety of steroid injections for patients with tendonitis of the shoulder or elbow. METHODS: A systematic review of the literature using PubMed, EMBASE, the Cochrane library and manual searches was performed until April 2008. All randomised controlled trials (RCTs) reporting the efficacy on pain or functional disability, and/or the safety of steroid injections, versus placebo, non-steroidal anti-inflammatory drugs (NSAIDs) or physiotherapy in patients with tendonitis were selected. Pooled effect size (ES) was calculated by meta-analysis using the Mantel-Haenszel method. RESULTS: In all, 20 RCTs were analysed (744 patients treated by injections and 987 patients treated by controls; 618 shoulders and 1113 elbows). The pooled analysis indicated only short-term effectiveness of steroids versus the pooled controls for pain and function (eg, pain at week 1-3 ES = 1.18 (95% CI 0.27 to 2.09), pain at week 4-8 ES = 1.30 (95% CI 0.55 to 2.04), pain at week 12-24 ES = -0.38 (95% CI -0.85 to 0.08) and pain at week 48 ES = 0.07 (95% CI -0.60 to 0.75)). Sensitivity analyses indicated similar results whatever the localisation, type of steroid and type of comparator except for NSAIDs: steroid injections were not significantly better than NSAIDs in the short-term. Steroid injections appeared more effective than pooled other treatments in acute or subacute tendonitis. The main side effects were transient pain after injection (10.7% of corticosteroid injections) and skin modification (4.0%). CONCLUSIONS: Steroid injections are well tolerated and more effective for tendonitis in the short-term than pooled other treatments, though similar to NSAIDs. No long-term benefit was shown.

This study examines how parent-child interaction therapy (PCIT) was adapted for Puerto Rican parents of children aged 4-6 with hyperactivity and other significant behavior problems. Four steps were followed: (1) translation and preliminary adaptation of the treatment manual, (2) application of the treatment to 9 families as part of an exploratory study using repeated measures, (3) treatment revision and refinement, and (4) in-depth interviews with parents (n=15) and clinical psychologists (n=5) from Puerto Rico who provided feedback on treatment process and components. Throughout this process, cultural elements and modifications were recommended to be incorporated into the treatment protocol. Both quantitative and qualitative results suggest that PCIT seems to be an acceptable intervention for this population, with some minor changes. Parents reported a high level of satisfaction, a significant reduction in children's externalizing behavior problems, and reduction of parenting stress and improvement in their parenting practices. Psychologists also evaluated positively the treatment protocol and recommended its use. Results from this study may inform clinicians and researchers who work with Latino families about relevant issues to be considered to promote their participation in behavioral family interventions and to enhance their acceptability and effectiveness.

The role of intracellular Ca2+ signaling in starvation-induced autophagy remains unclear. Here, we examined Ca2+ dynamics during starvation-induced autophagy and the underlying molecular mechanisms. Tightly correlating with autophagy stimulation, we observed a remodeling of the Ca2+ signalosome. First, short periods of starvation (1 to 3 h) caused a prominent increase of the ER Ca2+-store content and enhanced agonist-induced Ca2+ release. The mechanism involved the upregulation of intralumenal ER Ca2+-binding proteins, calreticulin and Grp78/BiP, which increased the ER Ca2+-buffering capacity and reduced the ER Ca2+ leak. Second, starvation led to Ins(1,4,5)P3R sensitization. Immunoprecipitation experiments showed that during starvation Beclin 1, released from Bcl-2, first bound with increasing efficiency to Ins(1,4,5)P3Rs; after reaching a maximal binding after 3 h, binding, however, decreased again. The interaction site of Beclin 1 was determined to be present in the N-terminal Ins(1,4,5)P3-binding domain of the Ins(1,4,5)P3R. The starvation-induced Ins(1,4,5)P3R sensitization was abolished in cells treated with BECN1 siRNA, but not with ATG5 siRNA, pointing toward an essential role of Beclin 1 in this process. Moreover, recombinant Beclin 1 sensitized Ins(1,4,5)P3Rs in 45Ca2+-flux assays, indicating a direct regulation of Ins(1,4,5)P3R activity by Beclin 1. Finally, we found that Ins(1,4,5)P3R-mediated Ca2+ signaling was critical for starvation-induced autophagy stimulation, since the Ca2+ chelator BAPTA-AM as well as the Ins(1,4,5)P3R inhibitor xestospongin B abolished the increase in LC3 lipidation and GFP-LC3-puncta formation. Hence, our results indicate a tight and essential interrelation between intracellular Ca2+ signaling and autophagy stimulation as a proximal event in response to starvation.

OBJECTIVE: To determine the pattern of demyelinating disorders (DDs) occurring during anti-TNF-α therapy. METHODS: Between June 2005 and April 2008, 1800 French rheumatologists and internists were contacted to report cases of DDs occurring in patients treated with anti-TNF-α. RESULTS: After a median of 10.2 (1.5-39.9) months of treatment, 33 patients developed DDs: 22 had CNS and 11 peripheral nervous system (PNS) involvement. Underlying diseases were RA (n = 16), AS (n = 11), PsA (n = 4), JIA (n = 1) and PM (n = 1). Anti-TNF-α was infliximab (n = 15), etanercept (n = 12) or adalimumab (n = 6). CNS involvement was encephalic lesions (n = 16), transverse myelitis (n = 8) or retrobulbar optic neuritis (n = 5). Cerebrospinal fluid (CSF) analysis in 16 patients and MRI in 20 patients were abnormal. All patients discontinued anti-TNF-α. Fifteen patients required steroids. Twenty patients initially improved. Five patients developed multiple sclerosis. PNS involvement was chronic (n = 9) or acute inflammatory demyelinating polyneuropathy (n = 2). CSF analysis revealed an increased protein level in nine patients. Nerve conduction studies confirmed DD in all these patients. Anti-TNF-α was discontinued in 10 patients and 8 received i.v. immunoglobulins. Two patients relapsed after introduction of another anti-TNF-α. Overall, a causal relationship between anti-TNF-α and DD was considered as probable in 31 patients and definite in 2 who had positive rechallenge. CONCLUSION: Causal relationship between anti-TNF-α and induction of DD remains unclear, but in some cases the chronology of clinical events is suggestive. Nevertheless, DD might persist despite treatment discontinuation, suggesting that anti-TNF-α could trigger the demyelinating process, which further evolves independently.

L'analyse technologique d'industries lithiques du Paleolithique inferieur et moyen montre que, contrairement a la vision restrictive qu'offrait l'analyse typologique, ces industries sont techniquement extremement diversifiees et ne peuvent pas etre arbitrairement regroupees. Cette diversite resulte de l'existence de sous-systemes techniques mis en evidence par l'analyse des chaines et schemas operatoires et dont la stabilite repose sur des constructions volumetriques, ou nucleus configures. A chaque construction correspond une tres grande variabilite qui est le corollaire de la stabilite de la structure technique. Il devient possible de determiner ce qui est susceptible de varier et ce qui est invariable au risque de destructurer le systeme de production. Cette grille de lecture ne peut interpreter les differences etablies

= 1/2) configuration. The slow relaxation of the magnetization in this complex, i.e. its single-molecule magnet (SMM) properties, is revealed under an applied dc field. Multireference quantum mechanical calculations indicate that this SMM behavior originates from an anisotropic ground doublet stabilized by spin-orbit coupling. Consistent theoretical and experiment data show that the resulting magnetization dynamics in this system is dominated by ground state quantum tunneling, while its temperature dependence is influenced by Raman relaxation.

Recent studies have pointed out the importance of polyelectrolyte assembly in the elaboration of innovative nanomaterials. Beyond their structures, many important questions on the thermodynamics of association remain unanswered. Here, we investigate the complexation between poly(diallyldimethylammonium chloride) (PDADMAC) and poly(sodium acrylate) (PANa) chains using a combination of three techniques: isothermal titration calorimetry (ITC), static and dynamic light scattering and electrophoresis. Upon addition of PDADMAC to PANa or vice-versa, the results obtained by the different techniques agree well with each other, and reveal a two-step process. The primary process is the formation of highly charged polyelectrolyte complexes of size 100 nm. The secondary process is the transition towards a coacervate phase made of rich and poor polymer droplets. The binding isotherms measured are accounted for using a phenomenological model that provides the thermodynamic parameters for each reaction. Small positive enthalpies and large positive entropies consistent with a counterion release scenario are found throughout this study. Furthermore, this work stresses the importance of the underestimated formulation pathway or mixing order in polyelectrolyte complexation.

A large number of graphene and other 2D materials are currently used for the development of new technologies, increasingly entering different industrial sectors. Interrogating the impact of such 2D materials on health and environment is crucial for both modulating their potential toxicity in living organisms and eliminating them from the environment. In this context, understanding if 2D materials are bio-persistent is mandatory. In this review we describe the importance of biodegradability and decomposition of 2D materials. We initially cover the biodegradation of graphene family materials, followed by other emerging classes of 2D materials including transition metal dichalcogenides and oxides, Xenes, Mxenes and other non-metallic 2D materials. We explain the role of defects and functional groups, introduced onto the surface of the materials during their preparation, and the consequences of chemical functionalization on biodegradability. In strong relation to the chemistry on 2D materials, we describe the concept of "degradation-by-design" that we contributed to develop, and which concerns the covalent modification with appropriate molecules to enhance the biodegradability of 2D materials. Finally, we cover the importance of designing new biodegradable 2D conjugates and devices for biomedical applications as drug delivery carriers, in bioelectronics, and tissue engineering. We would like to highlight that the biodegradation of 2D materials mainly depends on the type of material, the chemical functionalization, the aqueous dispersibility and the redox potentials of the different oxidative environments. Biodegradation is one of the necessary conditions for the safe application of 2D materials. Therefore, we hope that this review will help to better understand their biodegradation processes, and will stimulate the chemists to explore new chemical strategies to design safer products, composites and devices containing 2D materials.

were prepared leading to slightly stronger LecB binding and biofilm inhibition. Finally synergistic application of a LecB specific non-bactericidal antibiofilm dendrimer with the antibiotic tobramycin at sub-inhibitory concentrations of both compounds allowed effective biofilm inhibition and dispersal.

High massic catalytic currents and long-term stability are reached in a thermostable H₂/O₂enzymatic fuel cell.