Magnetic Nanostructures and Stem Cells for Regenerative Medicine, Application in Liver Diseases.

The term "liver disease" refers to any hepatic condition that leads to tissue damage or altered hepatic function and can be induced by virus infections, autoimmunity, inherited genetic mutations, high consumption of alcohol or drugs, fat accumulation, and cancer. Some types of liver diseases are becoming more frequent worldwide. This can be related to increasing rates of obesity in developed countries, diet changes, higher alcohol intake, and even the coronavirus disease 2019 (COVID-19) pandemic was associated with increased liver disease-related deaths. Although the liver can regenerate, in cases of chronic damage or extensive fibrosis, the recovery of tissue mass is impossible, and a liver transplant is indicated. Because of reduced organ availability, it is necessary to search for alternative bioengineered solutions aiming for a cure or increased life expectancy while a transplant is not possible. Therefore, several groups were studying the possibility of stem cells transplantation as a therapeutic alternative since it is a promising strategy in regenerative medicine for treating various diseases. At the same time, nanotechnological advances can contribute to specifically targeting transplanted cells to injured sites using magnetic nanoparticles. In this review, we summarize multiple magnetic nanostructure-based strategies that are promising for treating liver diseases.

Contamination characteristics in runoff fractions from a nuclear facility in São Paulo, Brazil.

The stormwater runoff may act as a nonpoint pollutant source and contributes to aquatic ecosystem quality decay in urban environments. The aim of this work was to evaluate the runoff characteristics on the transport of total solids and total metals, as well as pH and conductivity responses during the rainfall evolution. During 2017 and 2018, 12 rain events were monitored in 4 sampling stations at a car parking lot located at Nuclear and Energy Research Institute (IPEN/CNEN) in São Paulo/Brazil. A 4-chamber integrated collector allowed the sequential/temporal runoff evolution assessment. The runoff composition, in decreasing order of quantities, was Ca > K > Mg > Si > Al > Fe > Na > Zn > Mn > Sr > Ti > Mo > V > Cu > B > Pb > Ni > Ce > Sb > Cr > La > U > Th > Cd. The amount of total solids, Al, and Fe exceeded the Brazilian water quality standards. Principal component analysis (PCA) identified the elemental clusters linked to the facility activity, soil, and traffic/atmospheric-related deposition. The results show that the runoff characteristics could be differentiated by pollutant source. Factors such as seasonal variation, rain event intensity, air mass from oceanic or continental origin, spatial distribution inside the monitoring area, and the intensity of the first flush must be considered in order to disentangle the elemental clusters and pollution source contributions. In winter, continental air masses were associated with higher concentrations of heavy metals in the surface runoff. Spatial changes with no seasonal variation were observed for U, Th, La, and Ce.

The impact of probiotics, prebiotics, and synbiotics on the biochemical, clinical, and immunological markers, as well as on the gut microbiota of obese hosts.

Obesity is currently considered a global epidemic and it leads to several alterations on the human body and its metabolism. There are evidences showing that the intestinal microbiota can influence on the pathogenesis of obesity. Microbiota plays a vital role not only in the digestion and absorption of nutrients, but also in the homeostatic maintenance of host immunity, metabolism, and gut barrier. Its dietary alteration is an important target in the treatment of obesity. Emerging evidence suggests that modifying the composition of the gut microbiota through probiotic, prebiotic, and synbiotic supplementation may be a viable adjuvant treatment option for obese individuals. In this review, the impact of probiotics, prebiotics, and synbiotics on the anthropometric profile, biochemical regulation, clinical, and immunological markers, as well as on the gut microbiota of obese hosts is described. It also emphasizes how changes in the composition and/or metabolic activity of the gut microbiota through the administration of nutrients with probiotic, prebiotic, or synbiotic properties can modulate the host's gene expression and metabolism, and thereby positively influence on the host's adipose tissue development and related metabolic disorders. The beneficial effects on the host's metabolism promoted by prebiotics, probiotics, and synbiotics have been successfully demonstrated by several studies. However, further investigation is needed to fully explain the cellular mechanisms of action of probiotics and prebiotics on human health, and also to elucidate the relationship between microbiota and obesity etiology, using well-designed, long-term, and large-scale clinical interventions.

Branchial bioenergetics dysfunction as a relevant pathophysiological mechanism in freshwater silver catfish (Rhamdia quelen) experimentally infected with Flavobacterium columnare.

Flavobacterium columnare, the causative agent of columnaris disease, is a serious bacterial disease responsible for causing devastating mortality rates in several species of freshwater fish, leading to severe economic losses in the aquaculture industry. Notwithstanding the enormous impacts this disease can have, very little is known regarding the interaction between the host and bacterium in terms of the mortality rate of silver catfish (Rhamdia quelen), as well its linkage to gill energetic homeostasis. Therefore, we conducted independent experiments to evaluate the mortality rates caused by F. columnare in silver catfish, as well as whether columnaris disease impairs the enzymes of the phosphoryl transfer network in gills of silver catfish and the pathways involved in this inhibition. Experiment I revealed that clinical signs started to appear 72 h post-infection (hpi), manifesting as lethargy, skin necrosis, fin erosion and gill discoloration. Silver catfish began to die at 96 hpi, and 100% mortality was observed at 120 hpi. Experiment II revealed that creatine kinase (CK, cytosolic and mitochondrial) and pyruvate kinase (PK) activities were inhibited in silver catfish experimentally infected with F. columnare, while no significant difference was observed between experimental and control groups with respect to adenylate kinase activity. Activity of the branchial sodium-potassium pump (Na+, K+-ATPase) was inhibited while reactive oxygen species (ROS) and lipid peroxidation levels were higher in silver catfish experimentally infected with F. columnare than in the control group at 72 hpi. Based on these data, the impairment of CK activity elicited by F. columnare caused a disruption in branchial energetic balance, possibly reducing ATP availability in the gills and provoking impairment of Na+, K +ATPase activity. The inhibition of CK and PK activities appears to be mediated by ROS overproduction and lipid peroxidation, both of which contribute to disease pathogenesis associated with branchial tissue.

Influence of curcumin on glycemic profile, inflammatory markers, and oxidative stress in HIV-infected individuals: A randomized controlled trial.

To evaluate the influence of curcumin supplementation on the glycemic profile, inflammatory markers, and oxidative stress in HIV-infected individuals under antiretroviral therapy. This double-blind, crossover, randomized clinical trial was composed of 20 subjects arranged initially into experimental group (n = 10) and placebo group (n = 10) groups, receiving 1,000 mg curcumin/day or microcrystalline cellulose/day, respectively, during a 30-day period and 12-day washout. Subsequently, the groups were switched to follow the crossover design. Fasting glucose and insulin, IL-10, tumor necrosis factor alpha, malonialdehyde, and reduced glutathione were measured. Food consumption was evaluated as a control variable. Descriptive statistics are presented as mean and standard deviation, and inferential analyses were performed from two-way analysis of variance and the magnitude of the effect. No significant improvements were observed in the glycemic, inflammatory, or oxidative stress profiles. Although the mean serum fasting glucose levels and the homeostatic model assessment index presented qualitative improvement in the CG, this result should be interpreted with caution since the observed variation may represent acceptable fluctuation, in addition to the small difference between the means, added to the large variation observed in the standard deviation. Supplementation with curcumin in HIV-infected individuals undergoing antiretroviral therapy and training did not improve the glycemic, inflammatory, or oxidative stress profiles.

Impact of curcumin on energy metabolism in HIV infection: A case study.

Prolonged use of antiretroviral therapy (ART) has been associated with dyslipidemia and impaired energy substrate oxidation (SOxi). Curcumin is a natural bioactive compound, which interacts with molecular targets and holds important metabolic properties. The aim of this study was to evaluate the effect of curcumin supplementation on energetic metabolism of an adult female with HIV/AIDS and under ART. The intervention was performed with 500 mg/day of curcumin for 27 days. Glycemic and lipid profile and SOxi at rest were evaluated before and after intervention. After intervention, improvement of lipid profile and insulin sensibility was observed. Moreover, there was a positive modulation of SOxi at rest. Oral curcumin supplementation can positively modulate the energy metabolism of people living with HIV/AIDS using the ART. However, clinical studies are required in order to confirm our findings in a representative sample.

Methionine and methionine sulfoxide treatment induces M1/classical macrophage polarization and modulates oxidative stress and purinergic signaling parameters.

Methionine is an essential amino acid involved in critical metabolic process, and regulation of methionine flux through metabolism is important to supply this amino acid for cell needs. Elevation in plasma methionine commonly occurs due to mutations in methionine-metabolizing enzymes, such as methionine adenosyltransferase. Hypermethioninemic patients exhibit clinical manifestations, including neuronal and liver disorders involving inflammation and tissue injury, which pathophysiology is not completely established. Here, we hypothesize that alterations in macrophage inflammatory response may contribute to deleterious effects of hypermethioninemia. To this end, macrophage primary cultures were exposed to methionine (1 mM) and/or its metabolite methionine sulfoxide (0.5 mM), and M1/proinflammatory or M2/anti-inflammatory macrophage polarization was evaluated. In addition, inflammation-related pathways including oxidative stress parameters, as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities; reactive oxygen species (ROS) production, and purinergic signaling, as ATP/ADP/AMPase activities, were investigated. Methionine and/or methionine sulfoxide induced M1/classical macrophage activation, which is related to proinflammatory responses characterized by increased iNOS activity and TNF-α release. Further experiments showed that treatments promoted alterations on redox state of macrophages by differentially modulated SOD and CAT activities and ROS levels. Finally, methionine and/or methionine sulfoxide treatment also altered the extracellular nucleotide metabolism, promoting an increase of ATPase/ADPase activities in macrophages. In conclusion, these findings contribute to better understand the participation of proinflammatory responses in cell injury observed in hypermethioninemic patients.

Direct UV-Triggered Thiol-ene Cross-Linking of Electrospun Polyester Fibers from Unsaturated Poly(macrolactone)s and Their Drug Loading by Solvent Swelling.

Electrospinning is considered a relatively simple and versatile technique to form high porosity porous scaffolds with micron to nanoscale fibers for biomedical applications. Here, electrospinning of unsaturated aliphatic polyglobalide (PGl) into well-defined fibers with an average diameter of 9 µm is demonstrated. Addition of a dithiol cross-linker and a photoinitiator to the polymer solution enabled the UV-triggered intracross-linking of the fibers during the spinning process. The in situ cross-linking of the fibers resulted in amorphous material able to swell up to 14% in tetrahydrofurane (THF) without losing the fiber morphology. Seeding mesenchymal stem cells (MSCs) onto both cross-linked and non-cross-linked PGl fibers proved their compatibility with MSCs and suitability as scaffolds for cell growth and proliferation of MSCs. Moreover, the ability to directly load cross-linked PGl with hydrophobic molecules by soaking the fiber mesh in solution is shown with Rhodamine B and Indomethacin, a hydrophobic anti-inflammatory drug. This marks an advantage over conventional aliphatic polyesters and opens opportunities for the design of drug loaded polyester scaffolds for biomedical applications or tissue engineering.

Acute administration of methionine and/or methionine sulfoxide impairs redox status and induces apoptosis in rat cerebral cortex.

High plasma levels of methionine (Met) and its metabolites such as methionine sulfoxide (MetO) may occur in several genetic abnormalities. Patients with hypermethioninemia can present neurological dysfunction; however, the neurotoxicity mechanisms induced by these amino acids remain unknown. The aim of the present work was to study the effects of Met and/or MetO on oxidative stress, genotoxicity, cytotoxicity and to evaluate whether the cell death mechanism is mediated by apoptosis in the cerebral cortex of young rats. Forty-eight Wistar rats were divided into groups: saline, Met 0.4 g/Kg, MetO 0.1 g/Kg and Met 0.4 g/Kg + MetO 0.1 g/Kg, and were euthanized 1 and 3 h after subcutaneous injection. Results showed that TBARS levels were enhanced by MetO and Met+MetO 1 h and 3 h after treatment. ROS was increased at 3 h by Met, MetO and Met+MetO. SOD activity was increased in the Met group, while CAT was reduced in all experimental groups 1 h and 3 h after treatment. GPx activity was enhanced 1 h after treatment by Met, MetO and Met+MetO, however it was reduced in the same experimental groups 3 h after administration of amino acids. Caspase-3, caspase-9 and DNA damage was increased and cell viability was reduced by Met, MetO and Met+MetO at 3 h. Also, Met, MetO and Met+MetO, after 3 h, enhanced early and late apoptosis cells. Mitochondrial electrochemical potential was decreased by MetO and Met+MetO 1 h and 3 h after treatment. These findings help understand the mechanisms involved in neurotoxicity induced by hypermethioninemia.

Upstream Pathways Controlling Mitochondrial Function in Major Psychosis: A Focus on Bipolar Disorder.

Mitochondrial dysfunction is commonly observed in bipolar disorder (BD) and schizophrenia (SCZ) and may be a central feature of psychosis. These illnesses are complex and heterogeneous, which is reflected by the complexity of the processes regulating mitochondrial function. Mitochondria are typically associated with energy production; however, dysfunction of mitochondria affects not only energy production but also vital cellular processes, including the formation of reactive oxygen species, cell cycle and survival, intracellular Ca(2+) homeostasis, and neurotransmission. In this review, we characterize the upstream components controlling mitochondrial function, including 1) mutations in nuclear and mitochondrial DNA, 2) mitochondrial dynamics, and 3) intracellular Ca(2+) homeostasis. Characterizing and understanding the upstream factors that regulate mitochondrial function is essential to understand progression of these illnesses and develop biomarkers and therapeutics.

Influence of Cysteine and Tryptophan Substitution on DNA-Binding Activity on Maize α-Hairpinin Antimicrobial Peptide.

For almost four decades, antimicrobial peptides have been studied, and new classes are being discovered. However, for therapeutic use of these molecules, issues related to the mechanism of action must be answered. In this work, the antimicrobial activity of the hairpinin MBP-1 was studied by the synthesis of two variants, one replacing cysteines and one tryptophan with alanine. Antibacterial activity was abolished in both variants. No membrane disturbance, even in concentrations higher than those required to inhibit the bacteria, was observed in SEM microscopy. The gel retardation assay showed that MBP-1 possesses a higher DNA-binding ability than variants. Finally, molecular modelling showed that the lack of cysteines resulted in structure destabilization and lack of tryptophan resulted in a less flexible peptide, with less solvent assessable surface area, both characteristics that could contribute to absence of activity. In summary, the data here reported add more information about the multiple mechanisms of action of α-hairpinins.

Enhancing regenerative medicine with self-healing hydrogels: A solution for tissue repair and advanced cyborganic healthcare devices.

Considering the global burden related to tissue and organ injuries or failures, self-healing hydrogels may be an attractive therapeutic alternative for the future. Self-healing hydrogels are highly hydrated 3D structures with the ability to self-heal after breaking, this property is attributable to a variety of dynamic non-covalent and covalent bonds that are able to re-linking within the matrix. Self-healing ability specially benefits minimal invasive medical treatments with cell-delivery support. Moreover, those tissue-engineered self-healing hydrogels network have demonstrated effectiveness for myriad purposes; for instance, they could act as delivery-platforms for different cargos (drugs, growth factors, cells, among others) in tissues such as bone, cartilage, nerve or skin. Besides, self-healing hydrogels have currently found their way into new and novel applications; for example, with the development of the self-healing adhesive hydrogels, by merely aiding surgical closing processes and by providing biomaterial-tissue adhesion. Furthermore, conductive hydrogels permit the stimuli and monitoring of natural electrical signals, which facilitated a better fitting of hydrogels in native tissue or the diagnosis of various health diseases. Lastly, self-healing hydrogels could be part of cyborganics - a merge between biology and machinery - which can pave the way to a finer healthcare devices for diagnostics and precision therapies.

Who is who within the universe of TREM-like transcripts (TREML)?

The Triggering Receptor Expressed on Myeloid Cells (TREM) family of receptors plays a crucial role in the immune response across various species. Particularly, TREM-1 and TREM-2 have been extensively studied, both in terms of their applications and their expression sites and signaling pathways. However, the same is not observed for the other family members collectively known as TREM-like-transcripts (TREML). The TREML family consists of eight receptors, with TREML1-5 identified in humans and mice, TREML-6 exclusive found in mice, TREML-7 in dogs and horses, and TREML-8 in rabbits and opossums. Despite the limited data available on the TREML members, they have been implicated in different immune and non-immune activities, which have been proposed to display both pro and anti-inflammatory activities, and to influence fundamental biological processes such as coagulation, bone and neurological development. In this review, we have compiled available information regarding the already discovered members of the family and provided foundational framework for understanding the function, localization, and therapeutic potential of all TREML members. Additionally, we hope that this review may shed light on this family of receptors, whose underlying mechanisms are still awaiting elucidation, while emphasizing the need for future studies to explore their functions and potential therapeutic application.

Methionine and methionine sulfoxide alter parameters of oxidative stress in the liver of young rats: in vitro and in vivo studies.

It has been shown that elevation of plasma methionine (Met) and its metabolites may occur in several genetic abnormalities. In this study we investigated the in vitro and in vivo effects of the Met and methionine sulfoxide (MetO) on oxidative stress parameters in the liver of rats. For in vitro studies, liver homogenates were incubated with Met, MetO, and Mix (Met + MetO). For in vivo studies, the animals were divided into groups: saline, Met 0.4 g/kg, MetO 0.1 g/kg, and Met 0.4 g/kg + MetO 0.1 g/kg. The animals were euthanized 1 and 3 h after injection. In vitro results showed that Met 1 and 2 mM and Mix increased catalase (CAT) activity. Superoxide dismutase (SOD) was enhanced by Met 1 and 2 mM, MetO 0.5 mM, and Mix. Dichlorofluorescein oxidation was increased by Met 1 mM and Mix. In vivo results showed that Met, MetO, and Mix decreased TBARS levels at 1 h. Total thiol content decreased 1 h after and increased 3 h after MetO and Met plus MetO administrations. Carbonyl content was enhanced by Met and was reduced by MetO 1 h after administration. Met, MetO and Met plus MetO decreased CAT activity 1 and 3 h after administration. Furthermore, only MetO increased SOD activity. In addition, Met, MetO, and Mix decreased dichlorofluorescein oxidation at 1 and 3 h. Our data indicate that Met/MetO in vivo and in vitro modify liver homeostasis by altering the redox cellular state. However, the hepatic changes caused by these compounds suggest a short-time adaptation of this tissue.

Emerging immunomodulatory strategies for cell therapeutics.

Cellular therapies are poised to transform the field of medicine by restoring dysfunctional tissues and treating various diseases in a dynamic manner not achievable by conventional pharmaceutics. Spanning various therapeutic areas inclusive of cancer, regenerative medicine, and immune disorders, cellular therapies comprise stem or non-stem cells derived from various sources. Despite numerous clinical approvals or trials underway, the host immune response presents a critical impediment to the widespread adoption and success of cellular therapies. Here, we review current research and clinical advances in immunomodulatory strategies to mitigate immune rejection or promote immune tolerance to cellular therapies. We discuss the potential of these immunomodulatory interventions to accelerate translation or maximize the prospects of improving therapeutic outcomes of cellular therapies for clinical success.

Prognosis of a new episode of low-back pain in a community inception cohort.

BACKGROUND: Most studies investigating the prognosis of low back pain (LBP) enrol people presenting for care, rather than all people who have an episode of LBP. We aimed to describe the prognosis of an acute episode of LBP in a community inception cohort. METHODS: We used data from two previous studies investigating recurrence of LBP. Participants without current LBP were contacted monthly to assess if they had experienced a new episode of LBP. 366 participants reporting a new episode of LBP were included in the current study. The primary outcome was duration of the new episode of LBP. Secondary outcomes were average and worst pain during the episode and the proportion of participants seeking care. RESULTS: The median duration of the episode was 5 days (95% CI 3.99 to 6.02). The cumulative probability of recovery was 70.0% (95% CI 65.3 to 74.7) before 1 week, 86.1% (95% CI 82.6 to 89.6) before 3 weeks, 90.9% (95% CI 88.0 to 93.8) before 6 weeks, and 93.5% (95% CI 90.8 to 96.0) before 12 weeks. The mean average pain intensity was 3.7 (SD ± 1.5), and the mean worst pain intensity was 5.6 (SD ± 1.9). The proportion of patients who sought care was 39.5% (95% CI 33.9 to 46.4). CONCLUSIONS: This study found most episodes of LBP recover rapidly and more quickly than typically reported for clinical populations. The worst pain during the episode was typically moderate despite the rapid recovery for most people. Approximately 40% of the participants who experienced an episode of LBP sought care. SIGNIFICANCE: This study describes the prognosis of an acute episode of LBP in a community inception cohort. This study found the majority of episodes of LBP, in community-dwelling adults, recover rapidly (median of 5 days) and more quickly than typically reported for clinical populations. The community should be reassured about the favourable prognosis of acute LBP.

Refrigerated modified Knott concentrate enables long-term morphological viability of canine blood microfilariae.

There are several methods of laboratory diagnosis of filarids, the most used are the thick smear and the Knott method. Both are quick to perform, have a low cost and allow observing the presence, quantifying and analyzing the morphological characteristics of microfilariae. Knowing the morphological viability of fixed microfilariae is of practical importance, as it allows the transport of samples to a laboratory, facilitates epidemiological studies , and allows the storage of samples for didactic. Thus, the aim of this study was to evaluate the morphological viability of microfilariae fixed in the refrigerated modified knott test using 2% formalin. To perform the modified Knott technique, 10 samples of microfilaremic dogs aged over 6 months were used. To evaluate the morphological viability time of the microfilariae in the modified Knott concentrate, the evaluations were repeated after intervals of 0, 1, 7, 30, 60, 120, 180, 240, and 304 days. In the present study, we did not verify any difference in the morphology of the microfilariae in any of the analyzed intervals from day 0 to 304 days, and it is possible to conclude that the use of 2% formalin in the modified Knott technique allows the microfilariae to be identified in a period of 304 days. days after processing the sample without changes in its morphology.

Existem diversos métodos de diagnóstico laboratorial de filarídeos, os mais utilizados são a gota espessa e o método do Knott. Ambos são de rápida execução, possui baixo custo e permitem observar a presença, quantificar e analisar as características morfológicas das microfilárias. Conhecer a viabilidade morfológica das microfilárias fixadas tem importância prática, pois permite o transporte de amostras para um laboratório, facilita estudos epidemiológicos, e permite o armazenamento de amostras para fins didáticos. Desta maneira, o objetivo do trabalho foi avaliar a viabilidade morfológica das microfilárias fixadas em teste do knott modificado refrigerado utilizando formalina a 2%. Para realização da técnica de knott modificado foram utilizadas 10 amostras de cães microfilarêmicos, com idade superior a 6 meses. Para avaliar o tempo de viabilidade morfológica das microfilárias no concentrado de Knott modificado, foram repedidas as avaliações após intervalos de 0,1,7, 30, 60, 120, 180, 240 e 304 dias. No presente estudo não verificamos diferença na morfologia das microfilárias em nenhum dos intervalos analisados deste do dia 0 até 304 dias, sendo possível concluir que a utilização da formalina a 2% na técnica de Knott modificada permite que as microfilárias possam ser identificadas em período de 304 dias após o processamento da amostra sem que ocorram alterações na sua morfologia.

Recurrence of an Episode of Low Back Pain: An Inception Cohort Study in Emergency Departments.

OBJECTIVES: To (1) determine the 1-year estimate of recurrence of low back pain (LBP) in a cohort of people presenting to emergency departments who have recently recovered from an episode of acute LBP in a middle-income country, (2) estimate a recurrence of LBP stratified by the STarT Back Screening Tool (SBST), and (3) determine prognostic factors for the recurrence of LBP. DESIGN: Prospective inception cohort study. METHODS: We included 238 patients who presented to emergency departments with recent-onset nonspecific LBP in São Paulo, Brazil. The outcome was the recurrence of an episode of LBP, assessed using 2 definitions: (1) 12-month recall alone and (2) pain measurements at follow-up. Prognostic factors were determined by logistic regression. RESULTS: Within 1 year, the estimated recurrence of an episode of LBP ranged from 35% (79/225 events) (first definition) to 44% (100/226 events) (second definition). When patients were stratified by the SBST, the estimate of recurrence ranged from 29% to 37% (21-27/73 events) for low-risk patients, from 33% to 39% (24-28/72 events) for medium-risk patients, and from 43% to 56% (34-45/80 events) for high-risk patients. Age, perceived risk of persistent LBP, and disability were independent prognostic factors associated with LBP recurrence within 1 year. CONCLUSION: After recovering from a previous episode of acute LBP, 4 in every 10 patients experienced a recurrence within 1 year. This estimate varied depending on the classification used in the SBST. Within 1 year, age, perceived risk of persistent LBP, and baseline disability were predictors of recurrence. J Orthop Sports Phys Ther 2022;52(7):484-492. Epub: 18 May 2022. doi:10.2519/jospt.2022.10775.

No prognostic model for people with recent-onset low back pain has yet been demonstrated to be suitable for use in clinical practice: a systematic review.

OBJECTIVE: What model development and external validation studies exist that focus on the prognosis of patients with recent-onset low back pain (LBP)? What is the performance (in terms of discrimination and calibration) of these clinical prediction models? METHODS: Systematic searches on MEDLINE, Embase and CINAHL were conducted. Model development and/or external validation studies of patients with recent-onset LBP were selected. Models predicting outcomes of pain, disability, sick leave, work absence and self-reported recovery, with at least 12 weeks of follow-up, were included. Risk of bias was assessed using the PROBAST instrument. RESULTS: We identified 17 prognostic models developed to predict outcomes in people with recent-onset LBP: six models were in the development phase and 11 were in the validation phase. The most assessed prediction model was the Original Örebro Musculoskeletal Pain Questionnaire. The Da Silva Clinical Prediction Model was the only model, from a study with low risk of bias, that presented acceptable discrimination, demonstrating 'good' performance in predicting recovery from pain (C-statistic 0.71, 95% CI 0.63 to 0.78) and overall acceptable agreement in calibration. CONCLUSION: Most prediction models for prognosis of patients with recent-onset LBP did not perform well at discrimination, few studies reported calibration and their performance varied across studies. It seems premature to advocate use of the available models, at their current state of development and validation, for low back pain in primary care, considering their generally poor methods and performance. REGISTRATION: CRD42020160988.

Immunotherapeutic nanoparticles: From autoimmune disease control to the development of vaccines.

The development of nanoparticles (NPs) with potential therapeutic uses represents an area of vast interest in the scientific community during the last years. Recently, the pandemic caused by COVID-19 motivated a race for vaccines creation to overcome the crisis generated. This is a good demonstration that nanotechnology will most likely be the basis of future immunotherapy. Moreover, the number of publications based on nanosystems has significantly increased in recent years and it is expected that most of these developments can go on to experimentation in clinical stages soon. The therapeutic use of NPs to combat different diseases such as cancer, allergies or autoimmune diseases will depend on their characteristics, their targets, and the transported molecules. This review presents an in-depth analysis of recent advances that have been developed in order to obtain novel nanoparticulate based tools for the treatment of allergies, autoimmune diseases and for their use in vaccines. Moreover, it is highlighted that by providing targeted delivery an increase in the potential of vaccines to induce an immune response is expected in the future. Definitively, the here gathered analysis is a good demonstration that nanotechnology will be the basis of future immunotherapy.