Dual disorder: does expert clinical experience support the rationale for cariprazine use?

Comorbid substance use disorder (SUD) in patients with schizophrenia (dual disorder, DD) is a frequent occurrence in the psychiatric clinical practice and is positively associated with poorer outcomes. Despite a very high co-prevalence, clinical guidelines for SUD and severe mental illnesses tend to give limited consideration to co-existing disorders regarding diagnosis and management. This article is the result of a meeting held in February 2023 to discuss common challenges and best clinical practice initiatives for patients with schizophrenia and DD in different treatment settings. The authors identified issues in the clinical approach to DD in schizophrenia spectrum disorders and suggested the most suitable management based on their experience as a group of experts, identifying possible improvement areas. In conclusion, the panel recommends that individuals with DD should be cared for in a single center. Pharmacologic treatment in individuals with DD needing both control of symptoms related to schizophrenia spectrum disorders and substance withdrawal should ideally be based on using a non-sedative antipsychotic with anti-craving activity.

Fluorimetric determination of aqueous formaldehyde employing heating and ultrasound-assisted approach through its derivatization with a ß-diketone-nickel(2+) complex immobilized in a PMMA flow cell.

Formaldehyde (FA) is a highly toxic substance present in many matrices, including freshwater as well as found in natural mechanisms such as rainfall and combustion of organic matter. Consumption of water contaminated with high levels of FA can cause severe short-term or long-term health problems. Due to these health risks, procedures are necessary to determine and quantify FA in aqua sources This paper reports on a study of fluorimetric determination of FA using a nickel(2 + )-diketonate coordination compound immobilized as a solid precursor. The compound was characterized by electronic absorption, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetry (TG), optical microscopy (OM), and scanner electron microscopy (SEM). The methodology was based on the reaction of the synthesized compound with an ammoniacal buffer generating a selective reagent for formaldehyde: fluoral-P. The product of the reaction generates 3,5-diacetyl-1,4-dihydrolutidine (DDL), which is responsible for the fluorescence of the system. Several parameters such as temperature, duration of heating time, and dilution effect with the best effects were studied to carry out FA determination. Under the optimum experimental conditions, a linear response ranging from 1.0 to 10.0 mg/L FA (R = 0.997 and n = 10), and a detection (3σ criterion) and quantification (10 σ criterion) limit estimated at 0.129 and 0.389 mg/L, respectively were achieved. The FA analysis was able to be conducted in 05 min with a relative standard deviation estimated at 1.10 %.

In Vitro, Oral Acute, and Repeated 28-Day Oral Dose Toxicity of a Mixed-Valence Polyoxovanadate Cluster.

Polyoxovanadates (POV) are a subgroup of polyoxometalates (POM), which are nanosized clusters with reported biological activities. This manuscript describes the first toxicity evaluation of a mixed-valence polyoxovanadate, pentadecavanadate, (Me4N)6[V15O36Cl], abbreviated as V15. Cytotoxicity experiments using peripheral blood mononuclear cells (PBMC), larvae of Artemia salina Leach, and in vivo oral acute and repeated 28-day doses in mice was carried out. The LC50 values in PBMC cells and A. salina were 17.5 ± 5.8 µmol L-1, and 17.9 µg L-1, respectively, which indicates high cytotoxic activity. The toxicity in mice was not observed upon acute exposure in a single dose, however, the V15 repeated 28-day oral administration demonstrated high toxicity using 25 mg/kg, 50 mg/kg and, 300 mg/kg doses. The biochemical and hematological analyses during the 28-day administration of V15 showed significant alteration of the metabolic parameters related to the kidney and liver, suggesting moderate toxicity. The V15 toxicity was attributed to the oxidative stress and lipid peroxidation, once thiobarbituric acid (TBAR) levels significantly increased in both males and females treated with high doses of the POV and also in males treated with a lower dose of the POV. This is the first study reporting a treatment-related mortality in animals acutely administrated with a mixed-valence POV, contrasting with the well-known, less toxic decavanadate. These results document the toxicity of this mixed-valence POV, which may not be suitable for biomedical applications.

Reconstrução da ponta nasal: relatos de casos e revisão histórica / Nasal tip reconstruction: case reports and historical review

As amputações traumáticas da ponta nasal são lesões desfigurantes, que determinam importante rejeição social, impondo ao paciente um sofrimento adicional, além daqueles já causados pela ferida e suas limitações funcionais decorrentes do traumatismo. Tais defeitos representam um desafio para os cirurgiões plásticos, e existem diversas técnicas que poderão ser adotadas para tratar este mesmo tipo de defeito. Neste trabalho são mostrados inicialmente três casos de amputação traumática exclusivamente da ponta nasal com seus respectivos tratamentos, para em seguida apresentar uma revisão histórica e discussão das diversas técnicas utilizadas para reconstrução da ponta nasal, avaliando comparativamente e enfatizando a evolução técnica no armamentário da cirurgia plástica.

Traumatic amputations of the nasal tip are disfiguring injuries, which determine important social rejection, imposing additional suffering on the patient and those already caused by the wound and its functional limitations resulting from the trauma. Such defects represent a challenge for plastic surgeons, and several techniques can be adopted to treat this type of defect. This work shows three cases of traumatic amputation exclusively of the nasal tip with their respective treatments. They present a historical review and discussion of the different techniques used for nasal tip reconstruction, comparatively evaluating and emphasizing the technical evolution in plastic surgery armament.

Substituent effects on intramolecular Schmidt reactions: a theoretical study on the formation of bridged lactams.

The competitive formation of isomeric bridged lactams via acid-catalyzed intramolecular Schmidt reactions from 3-azidoethylcyclopentanones is explored using density functional theory (DFT) calculations, primarily performed at the M06-2X/6-311++G(d,p) level of theory. The results indicate that specific substituents installed at α-carbons can efficiently control the regioselectivity of the reaction by lone pair-cation interactions or steric hindrance reversing the main product preference, whereas cation-π interactions are not so effective.

Characteristic Substituent Effect Model for the Infrared Intensities of the X2CY (X = H, F, Cl, Br; Y = O, S) Molecules.

Many years ago, the gas-phase infrared fundamental intensities of Cl2CS were determined within experimental error from the experimental intensities and frequencies of F2CO, Cl2CO, and F2CS. An additive characteristic substituent shift relationship between atomic polar tensors of these molecules formed the basis for these calculations. Here, QCISD/cc-pVTZ-level Quantum Theory of Atoms In Molecules (QTAIM) individual charge, charge transfer, and polarization contributions to these atomic polar tensor elements are shown to obey the same basic relationship for the extended X2CY (Y = O, S; X = H, F, Cl, Br) family of molecules. QTAIM charge and polarization contributions, as well as the total equilibrium dipole moments of the X2CY molecules, also follow this characteristic substituent shift model. The root-mean-sqaure error for the 231 estimates of these parameters is 0.14 e or only about 1% of the total 10 e range of the Atomic Polar Tensor (APT) contributions determined from the wave functions. The substituent effect APT contribution estimates were used to calculate the infrared intensities of the X2CY molecules. Although one serious discrepancy was observed for one of the CH stretching vibrations of H2CS, accurate values were within 45 km·mol-1 or about 7% of the 656 km·mol-1 intensity range predicted by the QCISD/cc-pVTZ wave functions. Hirshfeld charge, charge transfer, and polarization contributions are also found to follow this model, although their charge parameters do not follow electronegativity expectations.

Optimising plasma clozapine levels to improve treatment response: an individual patient data meta-analysis and receiver operating characteristic curve analysis.

BACKGROUND: Although clozapine is the most efficacious medication for treatment-refractory schizophrenia, not all patients will have an adequate response. Optimising clozapine dose using therapeutic drug monitoring could therefore maximise response. AIMS: Using individual patient data, we undertook a receiver operating characteristic (ROC) curve analysis to determine an optimal therapeutic range for clozapine levels to guide clinical practice. METHOD: We conducted a systematic review of PubMed, PsycINFO and Embase for studies that provided individual participant level data on clozapine levels and response. These data were analysed using ROC curves to determine the prediction performance of plasma clozapine levels for treatment response. RESULTS: We included data on 294 individual participants from nine studies. ROC analysis yielded an area under the curve of 0.612. The clozapine level at the point of optimal diagnostic benefit was 372 ng/mL; at this level, the response sensitivity was 57.3%, and specificity 65.7%. The interquartile range for treatment response was 223-558 ng/mL. There was no improvement in ROC performance with mixed models including patient gender, age or length of trial. Clozapine dose and clozapine concentration to dose ratio did not provide significantly meaningful prediction of response to clozapine. CONCLUSIONS: Clozapine dose should be optimised based on clozapine therapeutic levels. We found that a range between 250 and 550 ng/mL could be recommended, while noting that a level of >350 ng/mL is the most optimal for response. Although some patients may not respond without clozapine levels >550 ng/mL, the benefits should be weighed against the increased risk of adverse drug reactions.

The antihyperglycemic and hypolipidemic activities of a sulfur-oxidovanadium(IV) complex.

This study describes the synthesis, characterization, and biological activity of a new class of antidiabetic oxidovanadium(IV)-complexes with S2O2 coordination mode. The target complex 3,6-dithio-1,8-octanediolatooxidovanadium(IV), abbreviated as ([VIVO(octd)]), where octd = 3,6-dithio-1,8-octanediol, is formed from the reaction between the 3,6-dithio-1,8-octanediol and vanadyl sulfate (VIVOSO4). The effects of treatment with ([VIVO(octd)] on blood glucose, lipidic profile, body weight, food intake, water intake, urinary volume, glycogen levels, and biomarkers for liver toxicity were investigated using a streptozotocin (STZ)-induced diabetic Wistar rats model. The results have shown that the [VIVO(octd)] complex caused a significant decrease in blood glucose (247.6 ± 19.3 mg/dL vs 430.1 ± 37.6 mg/dL diabetic group, p < 0.05), triglycerides (TG, 50%) and very low-density cholesterol (VLDL-C, 50%) levels in STZ-diabetic rats after 3 weeks of treatment. The [VIVO(octd)] has shown antihyperglycemic activity in diabetic rats as well as a reduction in elevated lipid levels. Time-dependent studies using EPR and 51V NMR spectroscopy of [VIVO(octd)] were done in aqueous solutions to determine the complex stability and species present in the oral gavage solution used for complex administration. The spectroscopic studies have shown that the antidiabetic/hypolipidemic activity could be attributed to [VIVO(octd)], vanadium species resulting from redox processes, the hydrolysis of [VIVO(octd)] and its decomposition products, or some combination of these factors. In summary, the oxidovanadium(IV) complex containing the S2O2 donor ligand has desirable antidiabetic properties eliminating the symptoms of Diabetes mellitus and its comorbidities.

The RNA-Binding Protein ProQ Promotes Antibiotic Persistence in Salmonella.

Bacterial populations can survive exposure to antibiotics through transient phenotypic and gene expression changes. These changes can be attributed to a small subpopulation of bacteria, giving rise to antibiotic persistence. Although this phenomenon has been known for decades, much remains to be learned about the mechanisms that drive persister formation. The RNA-binding protein ProQ has recently emerged as a global regulator of gene expression. Here, we show that ProQ impacts persister formation in Salmonella. In vitro, ProQ contributes to growth arrest in a subset of cells that are able to survive treatment at high concentrations of different antibiotics. The underlying mechanism for ProQ-dependent persister formation involves the activation of metabolically costly processes, including the flagellar pathway and the type III protein secretion system encoded on Salmonella pathogenicity island 2. Importantly, we show that the ProQ-dependent phenotype is relevant during macrophage infection and allows Salmonella to survive the combined action of host immune defenses and antibiotics. Together, our data highlight the importance of ProQ in Salmonella persistence and pathogenesis. IMPORTANCE Bacteria can avoid eradication by antibiotics through a phenomenon known as persistence. Persister cells arise through phenotypic heterogeneity and constitute a small fraction of dormant cells within a population of actively growing bacteria, which is susceptible to antibiotic killing. In this study, we show that ProQ, an RNA-binding protein and global regulator of gene expression, promotes persisters in the human pathogen Salmonella enterica serovar Typhimurium. Bacteria lacking the proQ gene outcompete wild-type bacteria under laboratory conditions, are less prone to enter growth dormancy, and form fewer persister cells. The basis for these phenotypes lies in ProQ's ability to activate energy-consuming cellular processes, including flagellar motility and protein secretion. Importantly, we show that ProQ contributes to the persister phenotype during Salmonella infection of macrophages, indicating an important role of this global regulator in Salmonella pathogenesis.

Infrared intensities of [Formula: see text]: a true challenge for DFT methods.

Absolute infrared intensities of [Formula: see text] were evaluated with a great variety of DFT and ab initio methods and basis sets. It is shown that the intensities calculated by different levels of theory may not agree with each other even in the qualitative (weak/strong) sense. Geometrical parameters, as well as net atomic charges evaluated from multiple partition schemes, did not vary as much as the intensities and thus cannot explain the tremendous differences found for the latter. As there are no experimental estimates for the intensities to guide the theoretical evaluation, deciding on the best level of theory is reduced to comparisons between the different DFT methods and QCISD or CCSD, believed to be the best theoretical estimates in the set. The differences found among the various DFT methods suggest the development of new methods, instead of converging to a focal point, is rather diverging.

Incidence of tick-borne spotted fever group Rickettsia species in rodents in two regions in Kazakhstan.

Records on the distribution of Rickettsia spp. in their natural hosts in Central Asia are incomplete. Rodents and small mammals are potential natural reservoirs for Rickettsiae in their natural lifecycle. Studies about the maintenance of Rickettsia in wild animals are available for Western nations, but-to our knowledge-no studies and data are available in the Republic of Kazakhstan so far. The first case description of Rickettsioses in Kazakhstan was made in the 1950ies in the Almaty region and now Kyzylorda, East Kazakhstan, Pavlodar and North Kazakhstan are endemic areas. The existence of murine and endemic typhus was proven in arthropod vectors in the regions Kyzylorda and Almaty. Here we show for the first time investigations on tick-borne Rickettsia species detected by a pan-rickettsial citrate synthase gene (gltA) real-time PCR in ear lobes of small mammals (n = 624) in Kazakhstan. From all analysed small mammals 2.72% were positive for Rickettsia raoultii, R. slovaca or R. conorii. Sequencing of the rickettsial gene OmpAIV and the 23S-5S interspacer region revealed a similar heritage of identified Rickettsia species that was observed in ticks in previous studies from the region. In summary, this study proves that rodents in Kazakhstan serve as a natural reservoir of Rickettsia spp.

Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders.

Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10-3; R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p = 0.01; R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p = 6.84×10-4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p = 8.44×10-3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p = 3.78×10-7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia.

Unavoidable failure of point charge descriptions of electronic density changes for out-of-plane distortions.

Population analyses based on point charge approximations accurately estimating the equilibrium dipole moment will systematically fail when predicting infrared intensities of out-of-plane vibrations of planar molecules, whereas models based on both charges and dipoles will always succeed. It is not a matter of how the model is devised but rather how many degrees of freedom are available for the calculation. Population analyses based on point charges are very limited in terms of the amount of meaningful chemical information they provide, whereas models employing both atomic charges and atomic dipoles should be preferred for molecular distortions. A good model should be able to correctly describe not only static, equilibrium structures but also distorted geometries in order to correctly assess information from vibrating molecules. The limitations of point charge models also hold for distortions much larger than those encountered vibrationally.

Acute Exposure to Biogenic Nanosilver Produced from Fusarium oxysporum in a Neotropical Fish.

Biogenic nanosilver (bNAg) has emerged as a potentially less toxic alternative to synthetic nanosilver. However, no studies have evaluated its effects on a fish species from the Neotropical region. Thus, our aim was to evaluate the effects of a bNAg on the Neotropical fish Prochilodus lineatus. For this purpose, after 24 h of exposure to 100 µg L-1 of bNAg, blood samples were collected to evaluate hematological, genotoxic, and plasma parameters. Gills and liver were sampled to evaluate biomarkers of oxidative stress and brain samples were used to assess neurotoxicity. The fish presented hyperglycemia, an increased number of erythrocytes, a reduction in antioxidant enzyme activity in both tissues evaluated, and a decrease in lipid peroxidation in the gills. We concluded that P. lineatus is a sensitive species to this nanoparticle, since it presented alterations in several biomarkers after an acute exposure.

Characterization of the shoulder net joint moment during manual wheelchair propulsion using four functional axes.

Understanding how individuals distribute mechanical demand imposed on their upper extremity during physically demanding activities provides meaningful insights to preserve function and mitigate detrimental mechanical loading of the shoulder. In this study, we hypothesized that parameterization of the shoulder net joint moment using four functional axes could characterize distribution tendencies about the shoulder during manual wheelchair propulsion and that regardless of demographics, a shoulder flexor dominant NJM distribution would be predominantly used by individuals with paraplegia (n = 130). Forces and kinematics of the upper extremity and trunk were quantified using motion capture and an instrumented wheel during steady state manual wheelchair propulsion at self-selected fast speeds on a stationary ergometer. The results indicate that parsing out the internal/external rotation component of the shoulder net joint moment about the upper arm and distributing the remainder across the three orthogonal axes of the torso was successful in identifying common shoulder net joint moment distribution techniques used across individuals with paraplegia during manual wheelchair propulsion. Distribution tendencies were predominantly flexor dominant across injury level, gender, time since injury, body mass index, and height demographics. The 4-axis parameterization of the shoulder NJM effectively differentiated moment distribution tendencies used by individuals during manual wheelchair propulsion using a functionally relevant representation of shoulder kinetics. Use of the four-axis parameterization of joint kinetics in future studies is expected to provide important insights that can advance knowledge, preserve function, and inform clinical decisions.

A nascent polypeptide sequence modulates DnaA translation elongation in response to nutrient availability.

The ability to regulate DNA replication initiation in response to changing nutrient conditions is an important feature of most cell types. In bacteria, DNA replication is triggered by the initiator protein DnaA, which has long been suggested to respond to nutritional changes; nevertheless, the underlying mechanisms remain poorly understood. Here, we report a novel mechanism that adjusts DnaA synthesis in response to nutrient availability in Caulobacter crescentus. By performing a detailed biochemical and genetic analysis of the dnaA mRNA, we identified a sequence downstream of the dnaA start codon that inhibits DnaA translation elongation upon carbon exhaustion. Our data show that the corresponding peptide sequence, but not the mRNA secondary structure or the codon choice, is critical for this response, suggesting that specific amino acids in the growing DnaA nascent chain tune translational efficiency. Our study provides new insights into DnaA regulation and highlights the importance of translation elongation as a regulatory target. We propose that translation regulation by nascent chain sequences, like the one described, might constitute a general strategy for modulating the synthesis rate of specific proteins under changing conditions.

Electrostatics Explains the Reverse Lewis Acidity of BH3 and Boron Trihalides: Infrared Intensities and a Relative Energy Gradient (REG) Analysis of IQA Energies.

The reaction path for the formation of BX3-NH3 (X = H, F, Cl, Br) complexes was divided into two processes: (i) rehybridization of the acid while adopting a pyramidal geometry, and (ii) the complex formation from the pyramidal geometries of the acid and base. The interacting quantum atom (IQA) method was used to investigate the Lewis acidity trend of these compounds. This topological analysis suggests that the boron-halogen bond exhibits a considerable degree of ionicity. A relative energy gradient (REG) analysis on IQA energies indicates that the acid-base complex formation is highly dependent on electrostatic energy. With increasing halogen electronegativity, a higher degree of ionicity of the B-X is observed, causing an increase in the absolute value of X and B charges. This increases not only the attractive electrostatic energy between the acid and base but also enhances the repulsive energy. The latter is the main factor behind the acidity trend exhibited by trihalides. Changes in geometry are relevant only for complexes where BH3 acts as an acid, where lower steric hindrance facilitates the adoption of the pyramidal geometry observed in the complex. The CCTDP analysis shows that infrared intensities of BX3-NH3 are determined mostly by the atomic charges and not by the charge transfer or polarization. The opposite is observed in covalent analogues.

Resultados radiológicos y funcionales en fracturas de platillo tibial de alta energía / Radiological and functional results in high-energy tibial plate fractures

Resumen: Introducción: Las fracturas de platillo tibial por mecanismos de alta energía son lesiones graves que ocurren sobre una articulación de carga. Son difíciles de abordar, ya que además de afectar la estructura ósea de la pierna suelen tener lesiones de partes blandas asociadas. Objetivo: Evaluar los resultados radiológicos y funcionales de las fracturas de platillo tibial de alta energía con un mínimo seguimiento de un año. Material y métodos: Estudio retrospectivo, observacional y multicéntrico. Análisis de los resultados radiológicos y funcionales en el tratamiento de fracturas de platillo tibial de alta energía tratadas mediante reducción abierta y fijación interna (RAFI) entre 2014 y 2019. Resultados: 54 fracturas tratadas mediante RAFI. Seguimiento un año, 98.1% de consolidación en 13 semanas de promedio, 83.4% sin alteraciones del eje en plano coronal, 74% sin ensanchamiento articular postoperatorio. Escalas funcionales: Lysholm 82.1 puntos promedio y Oxford Knee Score (OKS) 39.5 puntos promedio. Conclusión: El rango de movilidad articular se redujo luego de una fractura de platillos tibiales de alta energía, pero con buenos resultados funcionales. Cuanto menor deseje y menor ensanchamiento radiográfico postoperatorio, se obtienen mejores resultados.

Abstract: Introduction: The tibial plateau fractures due to high-energy mechanisms are serious injuries that occur on a load bearing joint. These are difficult to approach because, also affect the bone structure of the leg, they usually have associated soft tissue injuries. Objective: To evaluate the radiological and functional results of high-energy tibial plateau fractures with a minimum follow-up of one year. Material and methods: Retrospective, observational and multicenter study. Analysis of radiological and functional outcomes in the treatment of high-energy tibial plateau fractures, treated by open reduction and internal fixation (ORIF) between 2014 and 2019. Results: 54 fractures treated by ORIF. Follow-up one year. 98.1% consolidation in 13 weeks on average. 83.4% without alterations of the axis in the coronal plane. 74% without postoperative joint widening. Functional scores: Lysholm 82.1 average points and Oxford Knee Score (OKS) 39.5 average points. Conclusion: The joint range of motion was reduced after a high-energy tibial plateau fracture, but with good functional results. The less off axis and less post-operative radiographic widening, the better results are obtained.

Are "GAPT Charges" Really Just Charges?

Generalized atomic polar tensor (GAPT) has turned into a very popular charge model since it was proposed three decades ago. During this period, several works aiming to compare different partition schemes have included it among their tested models. Nonetheless, GAPT exhibits a set of unique features that prevent it from being directly comparable to "standard" partition schemes. We take this opportunity to explore some of these features, mainly related to the need of evaluating multiple geometries and the dynamic character of GAPT, and show how to obtain the static and dynamic parts of GAPT from any static charge model in the literature. We also present a conceptual evaluation of charge models that aims to explain, at least partially, why GAPT and quantum theory of atoms in molecules (QTAIM) charges are strongly correlated with one another, even though they seem to be constructed under very different frameworks. Similar to GAPT, infrared charges (also derived from atomic polar tensors of planar molecules) are also shown to provide an improved interpretation if they are described as a combination of static charges and changing atomic dipoles rather than just experimental static atomic charges.

The sodium iodide symporter (NIS): novel applications for radionuclide imaging and treatment.

Cloning of the sodium iodide symporter (NIS) 25 years ago has opened an exciting chapter in molecular thyroidology with the characterization of NIS as one of the most powerful theranostic genes and the development of a promising gene therapy strategy based on image-guided selective NIS gene transfer in non-thyroidal tumors followed by application of 131I or alternative radionuclides, such as 188Re and 211At. Over the past two decades, significant progress has been made in the development of the NIS gene therapy concept, from local NIS gene delivery towards promising new applications in disseminated disease, in particular through the use of oncolytic viruses, non-viral polyplexes, and genetically engineered MSCs as highly effective, highly selective and flexible gene delivery vehicles. In addition to allowing the robust therapeutic application of radioiodine in non-thyroid cancer settings, these studies have also been able to take advantage of NIS as a sensitive reporter gene that allows temporal and spatial monitoring of vector biodistribution, replication, and elimination - critically important issues for preclinical development and clinical translation.