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.

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.

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.

Outcomes of Apert Syndrome Hand Reconstruction With Tilapia Skin: A Prospective Study.

BACKGROUND: Tilapia skin has already been used in various medical scenarios, but there are no studies showing the use of tilapia skin for hand reconstruction in Apert syndrome. The objective of this study is to determine whether the use of tilapia skin during graft bed preparation for children with Apert syndrome can shorten wound reepithelialization intervals, reduce the number of dressing changes, and decrease patient discomfort. METHODS: This is a prospective study on consecutive patients with Apert syndrome who underwent hand reconstruction at our Hospital. Patients were divided into 2 groups: (1) a control group consisting of patients who underwent conventional digit separation hand reconstruction surgery (2) an experimental group consisting of patients who underwent similar digit separation hand reconstruction surgery that commenced with the placement of a thin layer of tilapia skin at the raw commissures during a first operation, which was subsequently replaced by an autologous skin graft during a second operation staged 10 days postoperatively. Pain assessment was performed using the Visual Analog Scale. The number of dressing changes was also assessed. A T test compared the total number of dressings changes and pain data. RESULTS: Experimental group patients (n = 8) required an average of 9.4 days of daily dressing changes, and control group patients (n = 5) required an average of 20.8 days of daily dressing changes ( P < 0.05) and tended to experience significantly less pain when compared with patients in the control group ( P = 0.079). CONCLUSION: Tilapia skin can shorten wound reepithelialization intervals by reducing the total number of dressing changes.

Are Metabolic Power Distribution and Accelerometer-Based Global Positioning System Variables Associated With Odds Ratios of Noncontact Injuries in Professional Soccer Players?

ABSTRACT: Nobari, H, Alves, AR, Abbasi, H, Khezri, D, Zamorano, AD, and Bowman, TG. Are metabolic power distribution and accelerometer-based GPS variables associated with odds ratios of noncontact injuries in professional soccer players? J Strength Cond Res 37(9): 1809-1814, 2023-The present study was intended to i) investigate the relationship between metabolic power average (MPA), acceleration (AcZ) and deceleration (DcZ) zones, and their differences (Δ) on 3 load levels with noncontact injuries in professional players throughout a full soccer season and ii) to analyze the injury risk associated between high-load versus low-load levels for each of the aforementioned parameters with odds ratios (OR) and relative risk (RR), respectively. Twenty-one professional soccer players (age = 28.3 ± 3.9 years) were monitored during a full season (48 weeks) through global positioning system (GPS). A relationship between MPA and accelerometer-based GPS, mainly in explosive actions (i.e., AcZs and DcZs), was found. A higher incidence of injuries in the high-load weeks compared with the low-load weeks were reported (mainly in MPA, AcZ1, AcZ2, and DcZ3 variables). Moreover, significant means of OR (mean = 4.3) and RR (mean = 2.6) of noncontact injuries were established in intense periods with higher metabolic load (i.e., power accelerations, AcZ1, x2 = 0.022). Our results may be useful for coaches, sports scientists, and researchers regarding the optimization of the athletes' performance, as well as providing insights about the impact of intense exercise.

Potential of Atlantic Codfish (Gadus morhua) Skin Collagen for Skincare Biomaterials.

Collagen is the major structural protein in extracellular matrix present in connective tissues, including skin, being considered a promising material for skin regeneration. Marine organisms have been attracting interest amongst the industry as an alternative collagen source. In the present work, Atlantic codfish skin collagen was analyzed, to evaluate its potential for skincare. The collagen was extracted from two different skin batches (food industry by-product) using acetic acid (ASColl), confirming the method reproducibility since no significant yield differences were observed. The extracts characterization confirmed a profile compatible with type I collagen, without significant differences between batches or with bovine skin collagen (a reference material in biomedicine). Thermal analyses suggested ASColl's native structure loss at 25 °C, and an inferior thermal stability to bovine skin collagen. No cytotoxicity was found for ASColl up to 10 mg/mL in keratinocytes (HaCaT cells). ASColl was used to develop membranes, which revealed smooth surfaces without significative morphological or biodegradability differences between batches. Their water absorption capacity and water contact angle indicated a hydrophilic feature. The metabolic activity and proliferation of HaCaT were improved by the membranes. Hence, ASColl membranes exhibited attractive characteristics to be applied in the biomedical and cosmeceutical field envisaging skincare.

Bio-Prospecting of Crude Leaf Extracts from Thirteen Plants of Brazilian Cerrado Biome on Human Glioma Cell Lines.

(1) Background: Malignant gliomas are aggressive tumors characterized by fast cellular growth and highly invasive properties. Despite all biological and clinical advances in therapy, the standard treatment remains essentially palliative. Therefore, searching for alternative therapies that minimize adverse symptoms and improve glioblastoma patients' outcomes is imperative. Natural products represent an essential source in the discovery of such new drugs. Plants from the cerrado biome have been receiving increased attention due to the presence of secondary metabolites with significant therapeutic potential. (2) Aim: This study provides data on the cytotoxic potential of 13 leaf extracts obtained from plants of 5 families (Anacardiaceae, Annonaceae, Fabaceae, Melastomataceae e Siparunaceae) found in the Brazilian cerrado biome on a panel of 5 glioma cell lines and one normal astrocyte. (3) Methods: The effect of crude extracts on cell viability was evaluated by MTS assay. Mass spectrometry (ESI FT-ICR MS) was performed to identify the secondary metabolites classes presented in the crude extracts and partitions. (4) Results: Our results revealed the cytotoxic potential of Melastomataceae species Miconia cuspidata, Miconia albicans, and Miconia chamissois. Additionally, comparing the four partitions obtained from M. chamissois crude extract indicates that the chloroform partition had the greatest cytotoxic activity against the glioma cell lines. The partitions also showed a mean IC50 close to chemotherapy, temozolomide; nevertheless, lower toxicity against normal astrocytes. Analysis of secondary metabolites classes presented in these crude extracts and partitions indicates the presence of phenolic compounds. (5) Conclusions: These findings highlight M. chamissois chloroform partition as a promising component and may guide the search for the development of additional new anticancer therapies.

Isolated Jejunal Crohn's Disease: a challenging diagnosis.

A 27-year-old Nepalese male presented with recurrent abdominal pain accompanied by a lower stool consistency over the past 2 years. These episodes occurred several times a year, lasting 1 to 2 weeks, and resolved spontaneously, after adjustment of diet and/or medication for symptomatic control (e.g., antispasmodics, probiotics). Over the last year, the patient had undergone an extensive diagnostic investigation, which revealed no alterations in the laboratory workup, abdominal scan, esophagogastroduodenoscopy, and colonoscopy, including biopsies of the duodenum, and colon, so the symptoms have been attributed to irritable bowel syndrome. However, the symptoms had become more frequent, so the patient was referred to our gastroenterology department. We repeated and extended the work-up. Laboratory investigations showed an elevated erythrocyte sedimentation rate and faecal calprotectin. The remaining laboratory as well an extensive stool workup for infection were unremarkable. Esophagogastroduodenoscopy and ileocolonoscopy were normal. Small bowel capsule endoscopy revealed jejunal mucosa with lymphangiectasias, pseudopolypoids formations and superficial longitudinal ulcers, these findings were corroborated by the double-balloon enteroscopy, and biopsies showed marked architectural distortion, chronic inflammatory infiltrate, and an epithelioid granuloma. The clinical, endoscopic, biochemical, and histological findings were consistent with isolated jejunal Crohn's disease. The patient started adalimumab with complete remission after one year. We present this case given its exuberant endoscopic findings and due to the difficulty in making the diagnosis due to its rarity, location, and unspecific presentation.