DNA Condensation by Peptide-Conjugated PAMAM Dendrimers. Influence of Peptide Charge.

Nucleic acid delivery to cells is an important therapeutic strategy that requires the transport of nucleic acids to intracellular compartments and their protection from enzymatic degradation. This can be achieved through the complexation of the nucleic acids with polycations. Poly(amidoamine) (PAMAM) dendrimers and peptide-conjugated dendrimers have been investigated as delivery vectors. Inspired by these studies and the role of flexible peptide domains in protein-DNA interactions, we studied the impact of conjugating two peptides (tails) to generation 2 (G2) PAMAM dendrimers on DNA condensation and polyplex formation. Using gel electrophoresis, dye exclusion assays, atomic force microscopy, and Monte Carlo simulations, it is shown that the steric impact of neutral peptide tails is to hinder the formation of DNA-G2 polyplexes composed of multiple DNA chains. If the tails are negatively charged, which results in overall neutral G2 conjugates, then the interaction of G2 with DNA is hindered. Increasing the net positive charge of the tails resulted in the complexation capacity of G2 with the DNA being restored. While DNA complexation is obtained for a similar net charge balance for G2 and G2 conjugates with positive tails, fewer of the latter are required to achieve a comparable condensation degree. Furthermore, it is shown that about 40% of the DNA remains accessible to binding by small molecules. Overall, this shows that tuning the net charge of peptide tails conjugated to PAMAM dendrimers offers a handle to control the complexation capacity of DNA, which can be explored as a novel route for optimization as gene delivery vehicles.

A Rare Case of Mediastinal Mass: Thymoma and Thymic Tumor.

Thymomas and thymic carcinomas are rare mediastinal neoplasms arising from thymic epithelial cells, and the presence of synchronous or metachronous primary thymic neoplasms in a single patient is an extremely rare event. Thymoma patients appear to have an inherent predisposition toward developing additional neoplasms. This additionally presents a diagnostic challenge, revealing the importance of multidisciplinary expertise to the management of these patients. This is a case report of a patient with a thymoma and thymic carcinoma, submitted to surgical resection and postoperative radiotherapy.

Peracetic acid as a disinfectant for wastewater reuse - Regulation (EU) 2020/741 application on a pilot-scale.

Water scarcity affects already a large part of the world's population. To overcome this situation, water management is needed, and wastewater reuse must be implemented and included as a new approach. To achieve that objective water quality must comply with the parameters established in the Regulation (EU) 2020/741 of the European Parliament and the Council of the European Union and new treatment solutions have to be developed. The main goal of this pilot study was to evaluate the peracetic acid (PAA) disinfection efficiency in a real wastewater treatment plant (WWTP) in order to accomplish the wastewater reuse objective. To this end, six disinfection conditions were studied, three PAA doses (5, 10, and 15) and three contact times (5, 10, and 15) based on the commonly used disinfection operational conditions in real WWTP. Comparing the Total Suspended Solids (TSS), turbidity, Biological Oxygen Demand (BOD5) and Escherichia coli content, after and before the disinfection step, was possible to conclude that PAA ensures the Regulation (EU) 2020/741 requirements and that the disinfected effluent can be reused for several uses. All the conditions in which the PAA dose was 15 mg/L and the condition with 10 mg/L of PAA with a contact time of 15 min were the most promising, presenting the second highest water quality class achieved. The results of this study illustrate the potential of PAA as an alternative disinfectant for wastewater treatment and, bring it closer to the water reuse objective by presenting several possibilities for water uses.

Adult Native Joint Septic Arthritis: A Nine-Year Retrospective Analysis in a Portuguese University Hospital.

INTRODUCTION: Septic arthritis of a native joint represents a medical emergency. Drainage and effective antibiotic treatment are critical to avoid joint destruction and long-term impairment. The aim of this study was to evaluate epidemiological and clinical characteristics of patients with the diagnosis of septic arthritis to help establish local guidelines for empirical antibiotic treatment. MATERIAL AND METHODS: Retrospective analysis of adult patients admitted at Centro Hospitalar Universitário do Porto from 2009 to 2017 with suspected native joint septic arthritis. Relevant demographics, microbiology findings and respective antibiotic susceptibilities were analysed. RESULTS: Ninety-seven patients, predominantly males (59.8%) with a median age of 61 years old were included. The most commonly reported comorbidity associated with septic arthritis was diabetes mellitus (20.6%). The knee was the most commonly affected joint (71.1%). Arthrocentesis was performed in all patients, but only 50.5% had positive microbial growth in the synovial fluid. Staphylococcus aureus was the most frequently identified microorganism, 86% of which were methicillin susceptible. Gram-negative bacteria were the causative agent in 15% of cases. A wide range of empirical antibiotic regimens were prescribed with a combination of vancomycin/carbapenem being the most common (30.9%). Analysis of antibiotic susceptibility profiles revealed that amoxicillin/clavulanate would have been appropriate as the initial regimen in 89% of cases. DISCUSSION: The main causative pathogen was Staphylococcus aureus, with methicillin resistant Staphylococcus aureus remaining rare. The proportion of Gram-negative bacteria implies that these agents should be covered by empirical treatment, although no case of Pseudomonas infection has been identified. Therefore, antipseudomonal coverage is not necessary in empirical regimens. CONCLUSION: Routine coverage of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa is not warranted but must be considered when specific risk factors are found. Amoxicillin/clavulanate can provide adequate antibiotic coverage as an empirical treatment for adult native joint septic arthritis. Its use may allow a reduction in use of broader spectrum antibiotics.

Introdução: A artrite séptica representa uma patologia grave que pode levar à destruição articular e diminuição funcional a longo prazo. Adicionalmente à drenagem articular, uma antibioterapia efetiva é crucial. O objetivo deste estudo consistiu em avaliar as características epidemiológicas e clínicas dos doentes admitidos com diagnóstico de artrite séptica e analisar a terapêutica antimicrobiana, estabelecendo orientações locais de tratamento antibiótico empírico. Material e Métodos: Análise retrospetiva de doentes adultos admitidos no Centro Hospitalar Universitário do Porto com artrite séptica de articulação nativa de 2009 a 2017. Foram revistos os resultados microbiológicos, os perfis de suscetibilidade aos antimicrobianos e os registos médicos. Resultados: Dos 97 doentes incluídos, 59,8% eram do género masculino, com uma idade média de 61 anos. A comorbilidade mais comum foi a diabetes mellitus (20,6%). O joelho foi a articulação mais afetada (71,1%). Realizou-se artrocentese em todos os doentes, com isolamento microbiano em 50,5% dos produtos. O Staphylococcus aureus foi o microrganismo mais frequente, sendo sensível à meticilina, em 86% dos casos. As bactérias Gram-negativo foram o agente causal em 15% das infeções. A associação do carbapenemo e vancomicina foi a antibioterapia empírica mais comummente iniciada (30,9%), embora em 89% dos casos a amoxicilina/clavulanato teria sido apropriada como regime inicial. Discussão: O principal agente etiológico foi o Staphylococcus aureus, continuando o Staphylococcus aureus resistente à meticilina a ser um agente raro. A percentagem de bactérias Gram-negativo implica a sua cobertura como terapêutica empírica, embora não tenha havido casos de infeção por Pseudomonas. Por isso, a utilização empírica de um antibiótico com atividade antipseudomónica não é necessária. Conclusão: A cobertura antibiótica de Staphylococcus aureus resistente à meticilina e Pseudomonas não é obrigatória, mas pode ser considerada na presença de alguns fatores de risco específicos. A amoxicilina/ clavulanato é uma antibioterapia empírica adequada para a artrite séptica de articulação nativa, permitindo reduzir a utilização inadequada de antibióticos de espectro mais alargado.

Study of the Potential of Water Treatment Sludges in the Removal of Emerging Pollutants.

Presently, water quantity and quality problems persist both in developed and developing countries, and concerns have been raised about the presence of emerging pollutants (EPs) in water. The circular economy provides ways of achieving sustainable resource management that can be implemented in the water sector, such as the reuse of drinking water treatment sludges (WTSs). This study evaluated the potential of WTS containing a high concentration of activated carbon for the removal of two EPs: the steroid hormones 17ß-estradiol (E2) and 17α-ethinylestradiol (EE2). To this end, WTSs from two Portuguese water treatment plants (WTPs) were characterised and tested for their hormone adsorbance potential. Both WTSs showed a promising adsorption potential for the two hormones studied due to their textural and chemical properties. For WTS1, the final concentration for both hormones was lower than the limit of quantification (LOQ). As for WTS2, the results for E2 removal were similar to WTS1, although for EE2, the removal efficiency was lower (around 50%). The overall results indicate that this method may lead to new ways of using this erstwhile residue as a possible adsorbent material for the removal of several EPs present in wastewaters or other matrixes, and as such contributing to the achievement of Sustainable Development Goals (SDG) targets.

Efficient DNA Condensation Induced by Chiral ß-Amino Acid-Based Cationic Surfactants.

Four cationic chiral amino acid-based surfactants, cis- and trans-1 and cis- and trans-2, have been studied as DNA-condensing agents with enhanced properties and the absence of cell toxicity. The polar head of the surfactant is made of a cyclobutane ß-amino acid in which the amino group is a hydrochloride salt and the carboxyl group is involved in an amide bond, allowing the link with hydrophobic C12 (surfactant 1) or C16 (surfactant 2) chains. The ability of these surfactants to condense DNA was investigated using a dye exclusion assay, gel electrophoresis, and circular dichroism and compared with the well-studied dodecyltrimethylammonium bromide (DTAB) and cetyltrimethylammonium bromide (CTAB). The surfactant with the longest chain length and the trans stereochemistry (trans-2) was found to be the most efficient in condensing the DNA, including CTAB. Surfactant cis-2 was found to be less efficient, probably due to its poorer solubility. The ß-amino acid surfactants with the shorter chain length behaved similarly, such that the cis/trans stereochemistry does not seem to play a role in this case. Interestingly, these were also found to induce DNA condensation for the same concentration as trans-2 and CTAB but showed a lower binding cooperativity. Therefore, a longer alkyl chain only slightly improved the effectiveness of these surfactants. Further, atomic force microscopy revealed that they compact DNA into small complexes of about 55-110 nm in diameter.

Influence of macromolecular crowding on the charge regulation of intrinsically disordered proteins.

In this work we study the coupling between ionization and conformational properties of two IDPs, histatin-5 and ß-amyloid 42, in the presence of neutral and charged crowders. The latter is modeled to resemble bovine serum albumin (BSA). With this aim, semi-grand canonical Monte Carlo simulations are performed, so that the IDP charge is a dynamic property, undergoing protonation/deprotonation processes. Both ionization properties (global and specific amino acid charge and binding capacitance) and radius of gyration are analyzed in a large range of pH values and salt concentrations. Without crowder agents, the titration curve of histatin-5, a polycation, is salt-dependent while that of ß-amyloid 42, a polyampholyte, is almost unaffected. The salt concentration is found to be particularly relevant at pH values where the protein binding capacitance (directly linked with charge fluctuation) is larger. Upon addition of neutral crowders, charge regulation is observed in histatin-5, while for ß-amyloid 42 this effect is very small. The main mechanism for charge regulation is found to be the effective increase in the ionic strength due to the excluded volume. In the presence of charged crowders, a significant increase in the charge of both IDPs is observed in almost all the pH range. In this case, the IDP charge is altered not only by the increase in the effective ionic strength but also by its direct electrostatic interaction with the charged crowders.

Macrophagic myofasciitis: an atypical presentation for a rare disease with a challenging approach.

Macrophagic myofasciitis (MMF) is a rare immune-mediated myopathy that seems to be triggered by aluminium hydroxide adjuvant used in vaccines. Its presentation is relatively heterogeneous and treatment with steroids leads to improvement, although there is little evidence regarding the role of other immunosuppressants. The histological findings in MMF seem to be the result of an abnormal presence in the inoculation site of aluminium, which can induce an immune-mediated muscular disease in susceptible persons. The authors describe the case of a patient with an atypical presentation of macrophagic myofasciitis, with histological confirmation in a muscle biopsy distant from the inoculation site, and a good therapeutic response to tacrolimus and mycophenolate mofetil, as well as a discussion on the pathologic basis, controversies and emerging treatments for this condition.

Viscous Leptomeningeal Pseudotumoural Masses and Multiple Cranial Neuropathy - Severe Presentation of Neurosarcoidosis.

We present a case of a 56-year-old man with a history of episcleritis (left) and cluster headache (left) who had a penetrating trauma of the left eye leading to amaurosis 1 month previously. Since then, he developed multiple cranial neuropathy of the right side (V, VII, VIII, IX, X, XI and XII cranial pairs). Magnetic resonance imaging (MRI) revealed an infiltrative lesion of the base of the skull which extended to the retropharyngeal and jugular space, which progressed to multiple leptomeningeal masses extending to the clivus, despite aggressive immunosuppression. Rebiopsy of 1 meningeal mass supported the diagnosis of neurosarcoidosis. The patient finally responded to high-dose prolonged infliximab therapy, with complete remission. LEARNING POINTS: Neurosarcoidosis can present as multiple cranial neuropathy, with extensive nerve involvement depending on the brain and meningeal lesions.Large leptomeningeal pseudotumoural granulomatous masses should be promptly biopsied and lead to aggressive immunosuppressive treatment.Immunosuppressant weaning should be carried out cautiously to avoid rebound worsening.

Donor-derived fatal hyperinfection strongyloidiasis in renal transplant recipient.

Strongyloides stercoralis is a nematode, endemic in tropical and subtropical areas. Strongyloidiasis has been reported in recipients of hematopoietic stem cells, kidney, liver, heart, intestine, and pancreas, eventually presenting as disseminated strongyloidiasis and hyperinfection syndrome (SHS) which is associated with high mortality. We report one case of a recent renal transplant recipient, who presented with gastrointestinal and respiratory symptoms, evolving into shock. The identification of Strongyloides stercoralis in the bronchoalveolar lavage (BAL) lead us to the diagnosis of SHS. Treatment with subcutaneous ivermectin was started, however the patient did not survive. Retrospective serum donor analysis allowed us to identify the donor as the source of infection.

The use of peracetic acid for estrogen removal from urban wastewaters: E2 as a case study.

17ß-Estradiol (E2) is a natural estrogen produced by the feminine endocrine system. It is excreted mainly through urine and feces. Exposure to E2 may affect the reproductive system of both animals and humans, especially since the removal of E2 in conventional processes and technologies present in the wastewater treatment plants is not sufficient. Chlorine is one of the most studied and used oxidant worldwide. Although there are studies that demonstrate the endocrine disrupting compounds removal like E2, its reaction with organic matter can originate by-products, namely, trihalomethanes, which are known to have high toxic potential. The main aim of the present study was to evaluate the removal of E2 (50 µg E2 L-1-maximum concentration) using peracetic acid (PAA), a seeming cleaner and innocuous alternative to chlorine. To this end, a series of jar tests were performed, using different peracetic acid concentrations (1, 5, 10, and 15 mg L-1) and contact times (10, 15, and 20 min). The results obtained showed that a peracetic acid concentration of 15 mg L-1 with a contact time of 20 min had a removal efficacy of approximately 100%. The second main goal of this study was to evaluate the ecotoxicological potential of the tested treatments on the zebrafish Danio rerio. Several oxidative stress biomarkers were evaluated, namely glutathione S-transferase, lipid peroxidation, and catalase, besides vitellogenin. Both peracetic acid and E2 caused significant increases in the oxidative stress biomarkers, although this did not lead to increased lipid peroxidation levels. In addition, peracetic acid significantly decreased the estrogenic activity of E2, as indicated by decreased vitellogenin levels. Peracetic acid demonstrated to have great potential as an alternative disinfectant for chlorine treatments, and indications for future research are discussed.

Efficacy assessment of peracetic acid in the removal of synthetic 17α-ethinyl estradiol contraceptive hormone in wastewater.

Increasing concerns have been raised on endocrine disrupting chemicals like the sex hormone 17α-ethinylestradiol (EE2), the more since traditional wastewater (WW) treatments appear to be ineffective for their removal. The efficacy of the relatively novel disinfectant peracetic acid (PAA) in EE2 removal was evaluated, as well as its potential effects on WW quality parameters. The treatments tested for EE2 removal were also evaluated in terms of toxicity, through the determination of biochemical responses (antioxidant enzymes, lipid peroxidation and vitellogenin induction) using zebrafish (Danio rerio) as a biological model. PAA contact times less than 20 min appeared insufficient regardless of the PAA dose tested, but a 100% EE2 removal was attained at a PAA concentration of 15 mg/L with a contact time of 20 min. Total suspended solids, chemical oxygen demand and pH in PAA treatments remained well within levels set in European legislation for WW discharge. EE2 induced significant increased vitellogenin (VTG) levels in both female and male fish, indicating increased estrogenic activity, especially in males suggesting an endocrine disruption effect. With the addition of PAA (15 mg/L), however, VTG levels in both sexes returned to control values. Although this PAA treatment showed increased levels of the antioxidant enzyme catalase, the lipid peroxidation levels were similar or even lower than in controls. Overall the results suggest that the use of PAA appears a promising way forward as a less toxic alternative to chlorine disinfection with high efficiency in the removal of EDC like EE2.

Hyponatremic Coma after Bowel Preparation.

INTRODUCTION: Colonoscopy is a useful tool in modern medicine and is increasingly employed for both diagnostic and treatment purposes. However, bowel preparations can cause electrolyte imbalance, with the risk apparently related to the type of bowel cleansing solution used, the age of the patient and their comorbidities. Symptomatic hyponatremia, especially coma, is a rare complication of oral bowel preparation for colonoscopy and is thought to result from excessive antidiuretic hormone secretion. CASE DESCRIPTION: The authors report the case of a 48-year-old man who developed symptomatic hyponatremia (coma) after bowel preparation with sodium picosulfate/magnesium oxide/citric acid prior to a colonoscopy. The patient was admitted to an intensive care unit where other causes of coma were excluded. The symptoms of hyponatremia rapidly resolved after sodium level correction with intravenous administration of hypertonic saline. DISCUSSION: Hyponatremic coma is an uncommon but serious complication of colonoscopy bowel preparation. Patients at risk (>65 years old, chronic kidney disease, heart failure, history of electrolyte problems, or taking thiazide diuretics, angiotensin-converting-enzyme inhibitors or antidepressants) should be closely monitored during bowel cleansing and macrogol-based solutions should preferably be used. LEARNING POINTS: The association between coma and hyponatremia should be kept in mind when patients undergo bowel preparation, especially if they have chronic kidney disease, heart failure, a history of electrolyte problems or are taking diuretics or antidepressants.Patients should be closely monitored (and their metabolic profile checked before bowel cleansing) and a low threshold maintained for investigation and treatment initiation in case of symptom development.Medications with the potential to cause fluid and electrolytes disturbances such as diuretics and antidepressants should be stopped or reduced in dose while the patient is undergoing bowel preparation.

Role of Protein Self-Association on DNA Condensation and Nucleoid Stability in a Bacterial Cell Model.

Bacterial cells do not have a nuclear membrane that encompasses and isolates the genetic material. In addition, they do not possess histone proteins, which are responsible for the first levels of genome condensation in eukaryotes. Instead, there is a number of more or less specific nucleoid-associated proteins that induce DNA bridging, wrapping and bending. Many of these proteins self-assemble into oligomers. The crowded environment of cells is also believed to contribute to DNA condensation due to excluded volume effects. Ribosomes are protein-RNA complexes found in large concentrations in the cytosol of cells. They are overall negatively charged and some DNA-binding proteins have been reported to also bind to ribosomes. Here the effect of protein self-association on DNA condensation and stability of DNA-protein complexes is explored using Monte Carlo simulations and a simple coarse-grained model. The DNA-binding proteins are described as positively charged dimers with the same linear charge density as the DNA, described using a bead and spring model. The crowding molecules are simply described as hard-spheres with varying charge density. It was found that applying a weak attractive potential between protein dimers leads to their association in the vicinity of the DNA (but not in its absence), which greatly enhances the condensation of the model DNA. The presence of neutral crowding agents does not affect the DNA conformation in the presence or absence of protein dimers. For weakly self-associating proteins, the presence of negatively charged crowding particles induces the dissociation of the DNA-protein complex due to the partition of the proteins between the DNA and the crowders. Protein dimers with stronger association potentials, on the other hand, stabilize the nucleoid, even in the presence of highly charged crowders. The interactions between protein dimers and crowding agents are not completely prevented and a few crowding molecules typically bind to the nucleoid.

Nanoparticle-Hydrogel Composites: From Molecular Interactions to Macroscopic Behavior.

Hydrogels are materials used in a variety of applications, ranging from tissue engineering to drug delivery. The incorporation of nanoparticles to yield composite hydrogels has gained substantial momentum over the years since these afford tailor-making and extend material mechanical properties far beyond those achievable through molecular design of the network component. Here, we review different procedures that have been used to integrate nanoparticles into hydrogels; the types of interactions acting between polymers and nanoparticles; and how these underpin the improved mechanical and optical properties of the gels, including the self-healing ability of these composite gels, as well as serving as the basis for future development. In a less explored approach, hydrogels have been used as dispersants of nanomaterials, allowing a larger exposure of the surface of the nanomaterial and thus a better performance in catalytic and sensor applications. Furthermore, the reporting capacity of integrated nanoparticles in hydrogels to assess hydrogel properties, such as equilibrium swelling and elasticity, is highlighted.

pH-Dependent Polyelectrolyte Bridging of Charged Nanoparticles.

Systems comprised of polyelectrolytes and charged nanoparticles are of great technological interest, being common components in formulations among other uses. The colloidal stability of formulations is an important issue, and thus a lot of effort has been made to study the interactions of individual components in these systems. Here, the complexation and adsorption of an annealed (pH-dependent) polyelectrolyte to two spherical nanoparticles has been studied using coarse-grained Monte Carlo simulations. This has been done mainly by varying the solution pH and separation distance (concentration) between the nanoparticles. The polyelectrolyte charge distribution is seen to vary with nanoparticle separation distance, and its ability to bridge both nanoparticles changes with pH. The flexible polyelectrolyte creates compact, multilink bridges at short nanoparticle separation distances and evolves to a stretched single-link bridge at longer distances, where a larger fraction of the polyelectrolyte wraps around the nanoparticles. The annealed polyelectrolyte is also compared with a quenched polyelectrolyte of similar fixed fractional charge. Here, a difference is found in the adsorption ability at low pH/ionization due to the ability of the annealed polyelectrolytes to concentrate charges in the vicinity of the nanoparticle. At intermediate polyelectrolyte charge fractions and with increasing nanoparticle separation distances, the annealed system is able to link nanoparticles at larger distances as compared to the quenched, in good agreement with experimental observations. The results in this work contribute to the understanding of the effect of annealed polyelectrolytes and pH variations in the phase behavior of polyelectrolyte-nanoparticle systems, potentially aiding in the design and optimization of pH-responsive systems.

Adsorption of charged macromolecules upon multicomponent responsive surfaces.

Adsorption of polyions onto charged surfaces has long been recognized as a crucial phenomenon in biological and technological applications. An intuitive model relating polyelectrolyte adsorption with the imposed features of polarizable surfaces of different compositions and charges is proposed based on Monte Carlo simulations using a coarse-grained approach. The excellent performance of the equation allows simultaneously describing a wide range of adsorption regimes and accounting for specific non-monotonic trends. For a constant surface charge density, the surface composition governs adsorption, promoting variations exceeding 100%. Adsorption increases with the number of attractive charges in the surface until reaching a maximum, decreasing thereafter due to the presence of polyanion-like charged particles. The presence of crowders hampers adsorption. These results can be used to efficiently predict and modulate the interaction between charged macromolecules and different substrates with direct implications in de novo designs of vehicles and biomedical devices.

In vitro studies of DNA condensation by bridging protein in a crowding environment.

The macromolecules of the bacterial cell occupy 20-40% of the total cytosol volume, and crowded environments have long been known to compact and stabilize DNA. Nevertheless, investigations on DNA-protein binding are generally performed in the absence of crowding, which may yield an incomplete understanding of how nucleoid-assembling proteins work. A family of such proteins, abundant in Gram-negative bacteria, is the histone-like nucleoid structuring proteins (H-NS). Herein, the synergistic role of macromolecular crowding (mimicked using polyethylene glycol, PEG) and H-NS was investigated using fluorescence correlation spectroscopy (FCS) and enzyme protection assays. We show that crowding enhances the binding of H-NS to the AT-rich tracks of the DNA, where it preferentially binds to, protecting these tracks towards enzyme digestion, inducing some DNA condensation, and inhibiting the biological function of DNA. We further suggest that the looping of DNA chains, induced by H-NS, contributes to the synergistic effect of DNA-binding protein and crowding agents, on DNA condensation.

Neuropsychiatric Systemic Lupus Erythematosus Involvement: Towards a Tailored Approach to Our Patients?

Neuropsychiatric involvement in systemic lupus erythematosus (NPSLE) is a complex condition that remains poorly understood, and includes heterogeneous manifestations involving both the central and peripheral nervous system, with disabling effects. There are several models to improve NPSLE diagnosis when a neurological syndrome is present. In the last couple of years, the growing knowledge of the role of cytokines and antibodies in NPSLE, as well as the development of new functional imaging techniques, has brought some insights into the physiopathology of the disease, but their validation for clinical use remains undetermined. Furthermore, besides the classic clinical approach, a new tool for screening the 19 NPSLE syndromes has also been developed. Regarding NPSLE therapeutics, there is still no evidence-based treatment approach, but some data support the safety of biological medication when classic treatment fails. Despite the tendency to reclassify SLE patients in clinical and immunological subsets, we hope that these data will inspire medical professionals to approach NPSLE in a manner more tailored to the individual patient.