Structure of tetrameric forms of the serotonin-gated 5-HT3A receptor ion channel.

Multimeric membrane proteins are produced in the endoplasmic reticulum and transported to their target membranes which, for ion channels, is typically the plasma membrane. Despite the availability of many fully assembled channel structures, our understanding of assembly intermediates, multimer assembly mechanisms, and potential functions of non-standard assemblies is limited. We demonstrate that the pentameric ligand-gated serotonin 5-HT3A receptor (5-HT3AR) can assemble to tetrameric forms and report the structures of the tetramers in plasma membranes of cell-derived microvesicles and in membrane memetics using cryo-electron microscopy and tomography. The tetrameric structures have near-symmetric transmembrane domains, and asymmetric extracellular domains, and can bind serotonin molecules. Computer simulations, based on our cryo-EM structures, were used to decipher the assembly pathway of pentameric 5-HT3R and suggest a potential functional role for the tetrameric receptors.

Unraveling the genetic background of individuals with a clinical familial hypercholesterolemia phenotype.

Familial hypercholesterolemia (FH) is a common genetic disorder of lipid metabolism caused by pathogenic/likely pathogenic variants in LDLR, APOB, and PCSK9 genes. Variants in FH-phenocopy genes (LDLRAP1, APOE, LIPA, ABCG5, and ABCG8), polygenic hypercholesterolemia, and hyperlipoprotein (a) [Lp(a)] can also mimic a clinical FH phenotype. We aim to present a new diagnostic tool to unravel the genetic background of clinical FH phenotype. Biochemical and genetic study was performed in 1,005 individuals with clinical diagnosis of FH, referred to the Portuguese FH Study. A next-generation sequencing panel, covering eight genes and eight SNPs to determine LDL-C polygenic risk score and LPA genetic score, was validated, and used in this study. FH was genetically confirmed in 417 index cases: 408 heterozygotes and 9 homozygotes. Cascade screening increased the identification to 1,000 FH individuals, including 11 homozygotes. FH-negative individuals (phenotype positive and genotype negative) have Lp(a) >50 mg/dl (30%), high polygenic risk score (16%), other monogenic lipid metabolism disorders (1%), and heterozygous pathogenic variants in FH-phenocopy genes (2%). Heterozygous variants of uncertain significance were identified in primary genes (12%) and phenocopy genes (7%). Overall, 42% of our cohort was genetically confirmed with FH. In the remaining individuals, other causes for high LDL-C were identified in 68%. Hyper-Lp(a) or polygenic hypercholesterolemia may be the cause of the clinical FH phenotype in almost half of FH-negative individuals. A small part has pathogenic variants in ABCG5/ABCG8 in heterozygosity that can cause hypercholesterolemia and should be further investigated. This extended next-generation sequencing panel identifies individuals with FH and FH-phenocopies, allowing to personalize each person's treatment according to the affected pathway.

Anti-inflammatory and healing effect of the polysaccharidic extract of Opuntia ficus-indica cladodes in cutaneous excisional wounds in rats.

This study aimed to investigate the anti-inflammatory and wound healing effects of the polysaccharide extract from Opuntia ficus-indica cladodes (TPL-Ofi) using a rat cutaneous wound model. After anaesthesia, four 7-mm-diameter dorsal wounds per animal (n = 6/group for each experimental day of evaluation) were created in female Wistar rats using a surgical punch. The animals were treated topically twice daily with TPL-Ofi (0.01-1%; treated group) or sterile saline (control group) for a period of 21 days. Ulcerated tissue was collected for analysis of histological parameters (inflammation score, number of polymorphonuclear, mononuclear, fibroblast/myofibroblasts and blood vessels), immunohistochemical (fibroblast growth factor 2 [FGF-2]) and oxidative stress markers (myeloperoxidase [MPO] and glutathione [GSH]). After 21 days of treatment, body weight, net organ weight and plasma biochemical levels were measured. TPL-Ofi, containing a total carbohydrate content of 65.5% and uronic acid at 2.8%, reduced oedema on the second day and increased the nociceptive threshold on the second and third days. TPL-Ofi reduced mononuclear infiltrate on the second and MPO activity on the fifth day. TPL-Ofi increased GSH levels on the second day, as well as fibroblast/myofibroblasts counts, neoangiogenesis and FGF-2 levels on the fifth and seventh days. No changes were observed in body weight, net organ weight or toxicology assessment. Topical application of TPL-Ofi exhibited anti-inflammatory and antinociceptive effects, ultimately improving wound healing in cutaneous wounds.

Caffeine plus haloperidol reduces fatigue in an experimental model of Parkinson's disease - a prospective to A2AR-D2R heterodimer antagonism.

Fatigue is a non-motor symptom of Parkinson's disease (PD). Adenosine 2A receptor (A2AR) and compromised dopamine neurotransmission are linked to fatigue. Studies demonstrate that A2AR antagonism potentiates dopamine transmission via dopamine receptor D2 (D2R). However, the heterodimer form of A2AR-D2R in the striatum prompted questions about the therapeutic targets for PD patients. This study investigates the effects of caffeine (A2AR non-selective antagonist) plus haloperidol (D2R selective antagonist) treatment in the fatigue induced by the reserpine model of PD. Reserpinized mice showed impaired motor control in the open field test (p < 0.05) and fatigue in the grip strength meter test (p < 0.05). L-DOPA and caffeine plus haloperidol similarly increased motor control (p < 0.05) and mitigated fatigue (p < 0.05). Our results support the A2AR-D2R heterodimer participation in the central fatigue of PD, and highlight the potential of A2AR-D2R antagonism in the management of PD.

Hepatitis E virus prevalence among HIV-2 infected individuals in central Portugal.

To date, no studies comparing the prevalence of hepatitis E virus (HEV) infection between the general and human immunodeficiency virus 2 (HIV-2) populations are available. With the purpose of filling this gap, this prevalence was assessed in the HIV-2 population from central Portugal. HEV seropositivity was 19.4%, which did not differ significantly from that found in the matched control population, and was not associated with CD4 cell count, HIV-2 viral load, and geographic origin or travel history to regions considered highly endemic for HEV. The results suggest that HIV-2 is not a risk factor for HEV infection, neither for an increased occurrence of chronic HEV infection.

Assessment of the association of myofibroblasts and structural components of the extracellular matrix with histopathological parameters of actinic cheilitis and lower lip squamous cell carcinoma.

BACKGROUND: To evaluate the presence of myofibroblasts (MFs) in the development of lip carcinogenesis, through the correlation of clinical, histomorphometric and immunohistochemical parameters, in actinic cheilitis (ACs) and lower lip squamous cell carcinomas (LLSCCs). METHODS: Samples of ACs, LLSCCs, and control group (CG) were prepared by tissue microarray (TMA) for immunohistochemical TGF-ß, α-SMA, and Ki-67 and histochemical hematoxylin and eosin, picrosirius red, and verhoeff van gieson reactions. Clinical and microscopic data were associated using the Mann-Whitney, Kruskal-Wallis/Dunn, and Spearman correlation tests (SPSS, p < 0.05). RESULTS: ACs showed higher number of α-SMA+ MFs when compared to CG (p = 0.034), and these cells were associated with the vertical expansion of solar elastosis (SE) itself (p = 0.027). Areas of SE had lower deposits of collagen (p < 0.001), immunostaining for TGF-ß (p < 0.001), and higher density of elastic fibers (p < 0.05) when compared to areas without SE. A positive correlation was observed between high-risk epithelial dysplasia (ED) and the proximity of SE to the dysplastic epithelium (p = 0.027). LLSCCs showed a higher number of α-SMA+ MFs about CG (p = 0.034), as well as a reduction in the deposition of total collagen (p = 0.009) in relation to ACs and CG. There was also a negative correlation between the amount of α-SMA+ cells and the accumulation of total collagen (p = 0.041). Collagen and elastic density loss was higher in larger tumors (p = 0.045) with nodal invasion (p = 0.047). CONCLUSIONS: Our findings show the possible role of MFs, collagen fibers, and elastosis areas in the lip carcinogenesis process.

Amniotic membrane modulates MMP9 and MMP12 gene and protein expression in experimental model of the hepatic fibrosis.

Hepatic fibrosis is characterized by excessive deposition of collagen in the hepatic parenchyma, which disturbs the normal architecture and function. We have shown that human amniotic membrane (AM) can be used as a patch on the whole liver surface, resulting in an extremely significant reduction in collagen deposition. The aim of this study was to investigate the effects of AM on the matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 12 (MMP12) genes and proteins expression by real time quantitative PCR and immunohistochemistry, respectively, as well as image analysis on biliary fibrosis induced in rats by the bile duct ligation (BDL).Two weeks after the BDL, an AM fragment was applied onto the liver, and four weeks later, the liver samples were collected. MMP9 and MMP12 genes were significantly over expressed in group treated with AM. The immunoexpression of MMP9 and MMP12 was observed in all groups. However, the quantitative image analysis demonstrated an increase of the area occupied only by MMP12 in the livers of AM-treated rats with respect to BDL rats. These findings suggest that the AM exerts its beneficial effects on biliary fibrosis by increasing the MMP12, which in turn reduces the excessive collagen deposition on liver tissue.

Influence of Fermentation Time and Inoculation of Starter Culture on the Chemical Composition of Fermented Natural Coffee Followed by Depulping.

Fermentation using starter cultures has been considered an alternative and economically viable technology for the production of specialty coffees. This type of technology promotes several benefits, such as increased sensory quality, control over the fermentation process, predictability of the final product and added value. Coffee (Coffea arabica L.) samples for this study were collected in Presidente Olegário - MG (2018/19 crop year) in the Cerrado region of Minas Gerais. The effects of natural fermentation and inoculation of the yeast Torulaspora delbrueckii and duration of fermentation (0, 24, 48, 72 and 96 hours) on the sensory and chemical quality (analysis of bioactive, volatile, and organic compounds and fatty acids) of coffee were evaluated. The objective of this study was to determine the effect of fermentation time and starter culture inoculation on the chemical composition of fermented coffees. Fermentation time significantly influenced the sensory description of the coffee beverage, with notes of honey, brown sugar and almond predominating up to 48 hours, for coffees fermented for 72 and 96 hours the notes described were and fruity, winey notes. The chemical composition was primarily influenced by fermentation time.

A Quantitative Evaluation of the Influence of Chemical Variables of Biomasses of Poplar SRC Commercial Clones in Torrefaction.

This study aimed to evaluate the influence in torrefaction of the chemical structure of biomasses from nine poplar commercial SRC clones, evaluated through analytical pyrolysis. The chemical data were integrated into a dataset including LHV gain, representative of torrefaction aptitude and six chemical variables obtained through analytical pyrolysis, which were: (i) CH2Cl2 extractives; (ii) total extractives; (iii) Py-lignin; (iv) holocellulose; (v) (syringil/guaiacyl) ratio; and (vi) (pentosan/hexosan) ratio. Significant univariate and bivariate linear relations were obtained with LHV gain from torrefaction as dependent variable vs. Py-lignin, CH2Cl2 extractives and (cP/cH) ratio. Representative results were: (i) a negative correlation of -0.82 and -0.76 between LHV gain and the (pentosan/hexosan) ratio and Py-lignin, respectively, and (ii) a positive correlation of 0.79 between LHV gain and CH2Cl2 extractive amounts. Factorial and discriminant analysis allowed for clustering the tested clones in three groups, evidencing relevant influences of (S/G) ratio, Py-lignin, and, to a lesser extent, (cP/cH) ratio in the classification of these groups, clearly showing the impact of chemical variables of feedstock in torrefaction. The results contribute: (i) to the validation of use of the expedite analytical pyrolysis technique for classification of biomasses in accordance with their torrefaction aptitude and, thereby, (ii) to optimizing strategies in technological issues as diverse as poplar clone genetic breeding and modeling biomass torrefaction and pyrolysis.

The lucky polyp: an unusual manifestation of chronic schistosomiasis.

A 23-year-old male from Brazil presented with bright red hematochezia. Proctological examination revealed grade II internal hemorrhoids, but flexible sigmoidoscopy uncovered a 6 mm-pedunculated polyp in the sigmoid colon, which was found to result from inflammatory reaction to Schistosoma mansoni egg deposition. The patient had no signs of portal hypertension and was successfully treated with praziquantel. This case underscores a rare presentation of chronic intestinal schistosomiasis and emphasizes the role of early diagnosis in preventing severe hepatic sequelae of chronic Schistosoma infection.

Biological and therapeutic implications of RKIP in Gastrointestinal Stromal Tumor (GIST): an integrated transcriptomic and proteomic analysis.

BACKGROUND: Gastrointestinal stromal tumors (GIST) represent a significant clinical challenge due to their metastatic potential and limited treatment options. Raf kinase inhibitor protein (RKIP), a suppressor of the MAPK signaling pathway, is downregulated in various cancers and acts as a metastasis suppressor. Our previous studies demonstrated low RKIP expression in GIST and its association with poor outcomes. This study aimed to expand on the previous findings and investigate the biological and therapeutic implications of RKIP loss on GIST. METHODS: To validate the RKIP prognostic significance, its expression was evaluated by immunohistochemistry in 142 bona fide GIST cases. The functional role of RKIP was evaluated in vitro, using the GIST-T1 cell line, which was knocked out for RKIP. The biological and therapeutic implications of RKIP were evaluated by invasion, migration, apoptosis, and 2D / 3D viability assays. Additionally, the transcriptome and proteome of RKIP knockout cells were determined by NanoString and mass spectrometry, respectively. RESULTS: Immunohistochemical analysis revealed the absence of RKIP in 25.3% of GIST cases, correlating with a tendency toward poor prognosis. Functional assays demonstrated that RKIP knockout increased GIST cells' invasion and migration potential by nearly 60%. Moreover, we found that RKIP knockout cells exhibited reduced responsiveness to Imatinib treatment and higher cellular viability in 2D and 3D in vitro models, as assessed by apoptosis-related protein expression. Through comprehensive genetic and proteomic profiling of RKIP knockout cells, we identified several putative RKIP-regulated proteins in GIST, such as COL3A1. CONCLUSIONS: Using a multidimensional integrative analysis, we identified, for the first time in GIST, molecules and pathways modulated by RKIP that may potentially drive metastasis and, consequently, poor prognosis in this disease.

The striatum drives the ergogenic effects of caffeine.

Caffeine is one of the main ergogenic resources used in exercise and sports. Previously, we reported the ergogenic mechanism of caffeine through neuronal A2AR antagonism in the central nervous system [1]. We now demonstrate that the striatum rules the ergogenic effects of caffeine through neuroplasticity changes. Thirty-four Swiss (8-10 weeks, 47 ± 1.5 g) and twenty-four C57BL/6J (8-10 weeks, 23.9 ± 0.4 g) adult male mice were studied behaviorly and electrophysiologically using caffeine and energy metabolism was studied in SH-SY5Y cells. Systemic (15 mg/kg, i.p.) or striatal (bilateral, 15 µg) caffeine was psychostimulant in the open field (p < 0.05) and increased grip efficiency (p < 0.05). Caffeine also shifted long-term depression (LTD) to potentiation (LTP) in striatal slices and increased the mitochondrial mass (p < 0.05) and membrane potential (p < 0.05) in SH-SY5Y dopaminergic cells. Our results demonstrate the role of the striatum in the ergogenic effects of caffeine, with changes in neuroplasticity and mitochondrial metabolism.

Zoledronate treatment exerts sex-independent effects on bone and dental physicochemical properties in mice jaw necrosis.

INTRODUCTION: Bisphosphonate (BF) therapy is strongly related to the occurrence of medication-related osteonecrosis of the jaw (ONJ). However, no previous study has evaluated if there are sex-related differences on the ONJ establishment together with bone biomechanical alterations, and if they could have a synergy with the ZA treatment. MATERIALS AND METHODS: This study aimed to analyze the physicochemical properties of mineralized tissues in a zoledronate (ZA)-related osteonecrosis mouse model, by a 2 × 2-factorial design, considering sex (female/male) and treatment (ZA/Saline) factors (n = 8/group). After three ZA (1.0 mg/kg) or saline administrations (days 0, 7, 14), the lower left second molar was extracted (day 42). Further ZA administration (day 49) and euthanasia (day 70) were conducted. After confirmation of ZA-induced jaw necrosis (histologic and microtomographic analysis), spectroscopic and mechanical parameters were assessed. RESULTS: ZA-treated groups presented lower bone density due to impaired healing of tooth extraction socket. Sex-related alterations were also observed, with lower bone density in females. Regarding biomechanical parameters, sex and treatment exerted independent influences. ZA, although decreasing flexural modulus and yield stress, increases stiffness mainly due to a higher bone volume. Females show less resistance to higher loads compared to males (considering dimension-independent parameters). Additionally, ZA increases crystallinity in bone and dental structure (p < 0.05). In summary, although strongly related to osteonecrosis occurrence, ZA modifies bone and dental mineral matrix, improving bone mechanical properties. CONCLUSION: Despite sex-dependent differences in bone biomechanics and density, osteonecrosis was established with no sex influence. No synergistic association between sex and treatment factors was observed in this study.

Lymphocyte Subsets in Cervicovaginal Lavage Specimens of HIV-Infected Women: A Surrogate Risk Marker of HPV-Associated Cervical Lesions.

INTRODUCTION: To better understand the role of mucosa immunity in the development of cervical carcinoma in HIV infection, cervical lymphocyte subsets were characterized in HIV+ and HIV- women, as well as their relation to HPV-associated cervical lesions. METHODS: Eighty-three (52 HIV+, 31 HIV-) cell suspensions of cervicovaginal lavage (CVL) and 52 HIV+ peripheral blood (PB) samples were assessed by flow cytometry to evaluate lymphoid populations. High-risk (HR) HPV was assessed in liquid-based cytology and HIV mRNA in PB in the same patients. RESULTS: Cervical CD4+ T cells and CD4+/CD8+ ratio were decreased (p < 0.0001) and cervical CD8+ T cells were increased (p = 0.0080) in HIV+ women. These patients had lower CD4+ T-cell percentages in CVL compared to PB (p = 0.0257), and the opposite was true for CD8+ T cells (p = 0.0104). They also had a higher prevalence of high-grade squamous intraepithelial lesions (SILs) with an increased prevalence of HR HPV. Cervical CD8+ T cells were increased in HR HPV+ patients (p = 0.0300) and related to higher prevalence of SILs (p = 0.0001). DISCUSSION/CONCLUSION: Cervical lymphoid populations can be characterized by flow cytometry, showing a distinct cervical T-cell compartment in HIV+ women. This may represent a surrogate risk marker of HPV-associated cervical lesions in this population and prompt further research on this subject, contributing to improving patients' management.

Can SARS-CoV-2 screening in oral biopsies aid epidemiological surveillance?

BACKGROUND: Three years after the first confirmed COVID-19 case in Brazil, the outcomes of Federal government omissions in managing the crisis and anti-science stance heading into the pandemic have become even more evident. With over 36 million confirmed cases and nearly 700 000 deaths up to January 2023, the country is one of the hardest-hit places in the world. The lack of mass-testing programs was a critical broken pillar responsible for the quick and uncontrolled SARS-CoV-2 spread throughout the Brazilian population. Faced with this situation, we aimed to perform the routine SARS-CoV-2 screening through RT-qPCR of oral biopsies samples to aid in the asymptomatic epidemiological surveillance during the principal outbreak periods. METHODS: We analyzed 649 formalin-fixed paraffin-embedded oral tissue samples from five important oral and maxillofacial pathology laboratories from the north, northeast, and southeast geographic regions of Brazil. We also sequenced the whole viral genome of positive cases to investigate SARS-CoV-2 variants. RESULTS: The virus was detected in 9/649 analyzed samples, of which three harbored the Variant of Concern Alpha (B.1.1.7). CONCLUSION: Although our approach did not value aiding asymptomatic epidemiological surveillance, we could successfully identify a using FFPE tissue samples. Therefore, we suggest using FFPE tissue samples from patients who have confirmed diagnosis of SARS-CoV-2 infection for phylogenetic reconstruction and contraindicate the routine laboratory screening of these samples as a tool for asymptomatic epidemiological surveillance.

Incidence and risk factors for polypharmacy among elderly people assisted by primary health care in Brazil.

BACKGROUND: Polypharmacy is recognized as a global public health problem and one of the greatest challenges related to the aging population. Few studies have investigated the incidence and risk factors for polypharmacy among elderly individuals. These studies provided important information on the issue but were developed in high-income countries. This study investigates the incidence and risk factors for polypharmacy among elderly people assisted by primary health care over a period of 11 years. METHODS: This was a census-based prospective longitudinal study that included people aged 60 years or older living in a small municipality in the state of Rio Grande do Sul, Brazil. The baseline occurred in 2010 and the second wave of the study occurred in 2021. The study population consisted of elderly individuals who did not use polypharmacy at baseline and were reinterviewed in 2021 (N = 128). Data collection in the first and second waves was performed through a household survey using a structured questionnaire. The dependent variable was polypharmacy, defined as the simultaneous use of 5 or more drugs. The independent variables included sociodemographic, health and functionality factors. For multivariate analyses, Poisson regression with robust variance was used, estimating the relative risk and 95% confidence intervals. RESULTS: The incidence of polypharmacy was 46.1% in the 11-year period. The highest number of health problems was a risk factor for polypharmacy (RR = 1.177; 95% CI 1.093-1.267). CONCLUSIONS: The incidence of polypharmacy among elderly people assisted in primary health care in Brazil is high. The number of diseases is a risk factor for polypharmacy. These results have implications for future primary health care practices and may support the development of policies, actions and services aimed at reducing polypharmacy and promoting the rational use of drugs in the population at higher risk.

Is photobiomodulation effective during maxillary expansion? A systematic review and meta-analysis.

We performed a systematic review on literature associated with meta-analyses to elucidate whether (I) low-level laser therapy (C) compared to placebo accelerates (O) bone neoformation in the region of the midpalatal suture in (P) patients undergoing transverse maxillary expansion. Two reviewers blindly performed targeted searches using the selection criteria (PICOS) in seven major databases and three grey literature databases, employing specific terms and their entrenchments. The RevMan® software (Review Manager, version 5.3, Cochrane Collaboration) was used to adapt the RoB summary illustration to the Cochrane 2.0 tool questions. Meta-analysis was performed using standardized mean difference (SMD) and Cohen's d calculation on random effects, tests for heterogeneity (I2 ) and publication bias (Egger and Begg), and one-of-out sensitivity analysis. GRADE (Grading of Recommendations Assessment, Development and Evaluation) was used for evidence quality analysis. Among the five studies included in the qualitative synthesis, three were included in the meta-analysis. All analysed studies were prospective randomized clinical trials. The risk of bias was such that the Egger (P = .1991) and Begg (P = .024) tests showed no significant risk of publication bias. The meta-analysis showed high heterogeneity (I2  = 81%, P < .00001), and 3 months after the operation, there was no significant difference between the photobiomodulation (PBMT) group and control group (P = .850) or between the subgroups of the periods evaluated after 3 months (P = 0.490). GRADE showed an SMD of 0.62. Photobiomodulation as an adjuvant therapy in patients undergoing transverse maxillary expansion has few benefits and is limited in shape, as it contributes to bone healing in the midpalatal suture region after a period of 3 months.

N-Methyl-(2S,4R)-trans-4-hydroxy-L-proline isolated Sideroxylon obtusifolium attenuates TPA-induced irritant contact dermatitis in mice.

Dermatitis is defined as a set of inflammatory diseases that affect the skin, with varied causes. Among the different types of dermatitis, contact dermatitis is the most prevalent. Although the current therapy is often effective, it is associated with adverse effects and the possibility of drug tolerance. N-Methyl-(2S, 4R)-trans-4-hydroxy-L-proline is a L-proline amino acid derivative found in the leaves of Sideroxylon obtusifolium, a species traditionally used to treat inflammatory diseases. The aim of this study was to investigate the topical anti-inflammatory effect of N-methyl-(2S, 4R)-trans-4-hydroxy-L-proline (NMP) in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced irritant contact dermatitis in mice. Topically administered NMP, at doses of 0.03 - 0.50 mg/ear, reduced TPA-induced ear edema and neutrophil migration, as evidenced by low tissue myeloperoxidase activity and verified by histological examination. In addition, NMP (0.06 mg/ear) reduced tissue levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß, INF-γ and MCP-1) and of the anti-inflammatory cytokine IL-10, and reduced gene expression of TNF-α, IL-6 and IL-1ß increased by TPA. The data suggest that N-methyl-(2S, 4R)-trans-4-hydroxy-L-proline acts as a topical anti-inflammatory agent that decreases the expression of inflammatory cytokines, making it useful for the treatment of skin inflammation. Further investigations are necessary for its development as a therapeutic agent.

Visual Thinking Strategies in medical education: a systematic review.

BACKGROUND: Arts-based pedagogical tools have been increasingly incorporated into medical education. Visual Thinking Strategies (VTS) is a research-based, constructivist teaching methodology that aims to improve visual literacy, critical thinking, and communication skills through the process of investigating works of art. Harvard Medical School pioneered the application of VTS within medical education in 2004. While there are several studies investigating the use of VTS, there is a need to systematically assess the different programs that exist for medical education and their efficacy in improving relevant clinical skills. This systematic review aims to critically analyse the available evidence of the effectiveness of VTS in medical education to guide future research and provide a framework to adapt medical curricula. METHODS: A systematic search of PubMed, PsycINFO, and Cochrane CENTRAL databases (through November 2022) was conducted to identify studies of VTS-based interventions in undergraduate and postgraduate medical education. Two reviewers independently screened citations for inclusion criteria, extracted data, and assessed risk of bias. The extracted data was then narratively synthesized. RESULTS: Of 5759 unique citations, 10 studies met the inclusion criteria. After reference review, one additional study was included. Therefore, 11 studies were included in our review. Of these, eight reported VTS-based interventions for undergraduate medical students and three reported interventions in residency training, specifically in dermatology and ophthalmology. The main goal of most studies was to increase observational or visual diagnostic skills. Three of the studies in undergraduate medical education and two in postgraduate achieved a statistically significant improvement in observational skills in post-course evaluations. Some studies reported increased tolerance for ambiguity and empathy. CONCLUSIONS: Although the studies varied considerably in study design, learning objectives, and outcomes, findings consistently indicate that the VTS approach can serve as a vehicle to develop crucial clinical competencies, encouraging more in-depth visual analysis that could be applied when observing a patient. Despite some limitations of the included studies (lack of control groups, self-selection bias, or non-standard outcome measures), the results of this review provide support for greater inclusion of VTS training in the medical curriculum.

Prevalence of postoperative pain after endodontic treatment using low and high concentrations of sodium hypochlorite: a systematic review and meta-analysis.

OBJECTIVES: To determine the prevalence of postoperative pain after endodontic treatment using low (LC) and high (HC) concentrations of sodium hypochlorite (NaOCl). MATERIALS AND METHODS: Six databases and the grey literature were searched to identify randomized clinical trials that evaluated postoperative pain after endodontic treatment using NaOCl. NaOCl concentrations were dichotomized into 'LC' (0.5% to 3%) and 'HC' (≥ 5%) and a proportion meta-analysis was applied to determine the postoperative pain prevalence: overall and according to pain intensity and postoperative time. The prevalence of patients using pain control medication was also determined. A significance level of 5% and a random effect model were applied for data analysis. Between-study heterogeneity was assessed by I2 index. Risk of bias (RoB) was assessed using the Cochrane Risk-of-Bias 2.0 tool. The certainty of evidence was assessed using the GRADE approach. RESULTS: Ten studies were included in the review and eight in the meta-analysis. The overall prevalence of postoperative pain was 45% in LC and 39% in HC. The prevalence of pain in LC and HC after 24 h was 25% and 40%, respectively. After 48 h, the prevalence decreased to 10% in LC and 25% in HC. 'Absent pain' was the most prevalent score. The prevalence of patients who used medication was 9% in LC and 15% in HC. Three studies were classified as 'high RoB', five as 'low RoB', and two as 'some concerns'. The certainty of evidence was very low. CONCLUSIONS: The overall prevalence of postoperative pain after endodontic treatment using LC and HC of NaOCl was 45% and 39%, respectively. CLINICAL RELEVANCE: Postoperative pain is common after endodontic treatment using NaOCl, but tends to decrease over time.