Search

Mammaplasty is a widely performed surgical procedure worldwide, utilized for breast reconstruction, in the context of breast cancer treatment, and aesthetic purposes. To enhance post-operative outcomes and reduce risks (hematoma with required evacuation, capsular contracture, implant-associated infection and others), the controlled release of medicaments can be achieved using drug delivery systems based on cyclodextrins (CDs). In this study, our objective was to functionalize commercially available silicone breast implants with smooth and textured surfaces through in-situ polymerization of two CDs: β-CD/citric acid and 2-hydroxypropyl-β-CD/citric acid. This functionalization serves as a local drug delivery system for the controlled release of therapeutic molecules that potentially can be a preventive treatment for post-operative complications in mammaplasty interventions. Initially, we evaluated the pre-treatment of sample surfaces with O 2 plasma, followed by chitosan grafting. Subsequently, in-situ polymerization using both types of CDs was performed on implants. The results demonstrated that the proposed pre-treatment significantly increased the polymerization yield. The functionalized samples were characterized using microscopic and physicochemical techniques. To evaluate the efficacy of the proposed system for controlled drug delivery in augmentation mammaplasty, three different molecules were utilized: pirfenidone (PFD) for capsular contracture prevention, Rose Bengal (RB) as anticancer agent, and KR-12 peptide (KR-12) to prevent bacterial infection. The release kinetics of PFD, RB, and KR-12 were analyzed using the Korsmeyer-Peppas and monolithic solution mathematical models to identify the respective delivery mechanisms. The antibacterial effect of KR-12 was assessed against Staphylococcus epidermidis and Pseudomonas aeruginosa , revealing that the antibacterial rate of functionalized samples loaded with KR-12 was dependent on the diffusion coefficients. Finally, due to the immunomodulatory properties of KR-12 peptide on epithelial cells, this type of cells was employed to investigate the cytotoxicity of the functionalized samples. These assays confirmed the superior properties of functionalized samples compared to unprotected implants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Escobar, Carrera, Naveas, Pulido, Manso, Guarnieri, Lancellotti, Cotta, Corrales-Ureña, Rischka and Hernandez-Montelongo.)

Neurodegeneration, characterized by the progressive deterioration of neurons and glial cells, is a feature of Alzheimer's disease (AD). The present study aims to demonstrate that the onset and early progression of neurodegenerative processes in transgenic mice models of AD can be delayed by a cocktail of neurotrophic factors and derived peptides named Nosustrophine, a nootropic supplement made by a peptide complex extracted from the young porcine brain, ensuring neuroprotection and improving neuro-functional recovery. Experimental 3xTg-APP/Bin1/COPS5 transgenic mice models of AD were treated with Nosustrophine at two different early ages, and their neuropathological hallmark and behavior response were analyzed. Results showed that Nosustrophine increased the activity of the immune system and reduced pathological changes in the hippocampus and cortex by halting the development of amyloid plaques, mainly seen in mice of 3-4 months of age, indicating that its effect is more preventive than therapeutic. Taken together, the results indicate the potent neuroprotective activity of Nosustrophine and its stimulating effects on neuronal plasticity. This study shows for the first time an effective therapy using nootropic supplements against degenerative diseases, although further investigation is needed to understand their molecular pathways.

Background: Bone overgrowth after decompressive surgery for lumbar stenosis resulting in recurrence of neurological signs has not been reported in veterinary literature. However, there are few cases described in human medicine., Case Presentation: A 13-month-old entire female dog, a crossbreed between a Springer Spaniel and a Border Collie, weighing 24 kg, was referred with a 5-day history of progressive spastic paraplegia, indicative of a T3-L3 myelopathy. Magnetic resonance (MR) imaging revealed a right-sided L2-L3 compressive extradural lesion, compatible with epidural haemorrhage, which was confirmed by histopathology. The lesion was approached via right-sided L2-L3 hemilaminectomy and was successfully removed. One-year postoperatively the dog re-presented with pelvic limb ataxia. MR and computed tomography (CT) images demonstrated excessive vertebral bone formation affecting the right articular processes, ventral aspect of the spinous process of L2-L3, and contiguous vertebral laminae, causing spinal cord compression. Revision surgery was performed, and histopathology revealed normal or reactive osseous tissue with a possible chondroid metaplasia and endochondral ossification, failing to identify a definitive reason for the bone overgrowth. Nine-month postoperatively, imaging studies showed a similar vertebral overgrowth, resulting in minimal spinal cord compression. The patient remained stable with mild proprioceptive ataxia up until the last follow-up 18 months post-revision surgery., Conclusion: This is the first report in the veterinary literature of bone overgrowth after lumbar hemilaminectomy which resulted in neurological deficits and required a revision decompressive surgery., (© 2023. The Danish Veterinary Association.)

Pharmacogenetics and DNA methylation influence therapeutic outcomes and provide insights into potential therapeutic targets for brain-related disorders. To understand the effect of genetic polymorphisms on drug response and disease risk, we analyzed the relationship between global DNA methylation, drug-metabolizing enzymes, transport genes, and pathogenic gene phenotypes in serum samples from two groups of patients: Group A, which showed increased 5-methylcytosine (5mC) levels during clinical follow-up, and Group B, which exhibited no discernible change in 5mC levels. We identified specific SNPs in several metabolizing genes, including CYP1A2 , CYP2C9 , CYP4F2 , GSTP1 , and NAT2 , that were associated with differential drug responses. Specific SNPs in CYP had a significant impact on enzyme activity, leading to changes in phenotypic distribution between the two patient groups. Group B, which contained a lower frequency of normal metabolizers and a higher frequency of ultra-rapid metabolizers compared to patients in Group A, did not show an improvement in 5mC levels during follow-up. Furthermore, there were significant differences in phenotype distribution between patient Groups A and B for several SNPs associated with transporter genes ( ABCB1 , ABCC2 , SLC2A9 , SLC39A8 , and SLCO1B1 ) and pathogenic genes ( APOE , NBEA , and PTGS2 ). These findings appear to suggest that the interplay between pharmacogenomics and DNA methylation has important implications for improving treatment outcomes in patients with brain-related disorders.

The iboga alkaloids scaffold shows great potential as a pharmacophore in drug candidates for the treatment of neuropsychiatric disorders. Thus, the study of the reactivity of this type of motif is particularly useful for the generation of new analogs suitable for medicinal chemistry goals. In this article, we analyzed the oxidation pattern of ibogaine and voacangine using dioxygen, peroxo compounds, and iodine as oxidizing agents. Special focus was placed on the study of the regio- and stereochemistry of the oxidation processes according to the oxidative agent and starting material. We found that the C 16 -carboxymethyl ester present in voacangine stabilizes the whole molecule toward oxidation in comparison to ibogaine, especially in the indole ring, where 7-hydroxy- or 7-peroxy-indolenines can be obtained as oxidation products. Nevertheless, the ester moiety enhances the reactivity of the isoquinuclidinic nitrogen to afford C 3 -oxidized products through a regioselective iminium formation. This differential reactivity between ibogaine and voacangine was rationalized using computational DFT calculations. In addition, using qualitative and quantitative NMR experiments combined with theoretical calculations, the absolute stereochemistry at C 7 in the 7-hydroxyindolenine of voacangine was revised to be S , which corrects previous reports proposing an R configuration.

Dyslipidemia is a significant risk factor for cardiovascular disease and stroke. Our recent findings showed that RCI-1502, a bioproduct derived from the muscle of the European S. pilchardus, has lipid-lowering effects in the liver and heart in high-fat diet (HFD) fed mice. In the present follow-up study, we investigated the therapeutic potential of RCI-1502 on gene expression and DNA methylation in HFD-fed mice and in patients with dyslipidemia. Using LC-MS/MS, we identified 75 proteins in RCI-1502 that are primarily involved in binding and catalytic activity and which regulate pathways implicated in cardiovascular diseases. In HFD-fed mice, RCI-1502 treatment significantly reduced the expression of cardiovascular disease-related genes, including vascular cell adhesion molecule and angiotensin. RCI-1502 also decreased DNA methylation levels, which were elevated in HFD-fed mice, to levels similar to those in control animals. Furthermore, peripheral blood leukocyte DNA from dyslipidemic patients exhibited higher DNA methylation levels than healthy individuals, suggesting a potential association with cardiovascular risk. Serum analysis also revealed that RCI-1502 treatment regulated cholesterol and triglyceride levels in patients with dyslipidemia. Our findings appear to suggest that RCI-1502 is an epigenetic modulator for the treatment of cardiovascular diseases, specifically in individuals with dyslipidemia.

A 1-year-old Bernese Mountain dog presented with an acute onset of left thoracic limb lameness. Magnetic resonance imaging (MRI) of the left shoulder was performed, showing a subchondral bone defect in the caudomedial aspect of the humeral head. In addition, several round hypointense structures were visible in the biceps tendon sheath. A left shoulder arthroscopy was performed, which confirmed an osteochondritic lesion. Exploration of the biceps tendon sheath via a small open approach allowed retrieval of the fragments, which likely migrated from the joint. Histopathology confirmed the structures to be multiple osteochondritic fragments., (© 2023 American College of Veterinary Radiology.)

The current article presents a mixed qualitative-quantitative observational study of the effect of ayahuasca ritual on subjective experiences and personality traits on participants of a center specialized in the treatment of substance use disorder in Uruguay. When comparing the psychological traits of ayahuasca participants to a control group, quantitative results using the Zuckerman-Kuhlman-Aluja Personality Questionnaire showed statistically significant higher scores in Impulsive Sensation Seeking, Boredom Susceptibility, and Social Warmth scales. Qualitative analysis of ayahuasca experiences resulted in five main categories: emotional experiences (including social emotions such as love and empathy), corporal experiences, spiritual/transcendental experiences, personal experiences, and visions. Last, qualitative descriptions provide support for the importance of social interactions in the phenomenological manifestations of the psychedelic experience. Both quantitative and qualitative results suggest that the combination of social interactions and the pharmacological action of ayahuasca could facilitate the manifestation of social emotions during the ritual, and may contribute to the long-term increase of empathic and social aspects of personality.

While Cannabis sativa L. varieties have been traditionally characterized by their major cannabinoid profile, it is now well established that other plant metabolites can also have physiological effects, including minor cannabinoids, terpenes, and flavonoids. Given the multiple applications of cannabis in the medical field, it is therefore critical to characterize it according to its chemical composition (i.e., its metabolome) and not only its botanical traits. With this in mind, the cannabinoid and metabolomic profiles from inflorescences of two C. sativa varieties with either high Δ 9 -tetrahydrocannabinolic acid (THCA) or high cannabidiolic acid (CBDA) contents harvested at different times were studied. According to results from HPLC and NMR-based untargeted metabolomic analyses of organic and aqueous plant material extracts, we show that in addition to expected variations according to cannabinoid profiles, it is possible to distinguish between harvests of the same variety. In particular, it was possible to correlate variations in the metabolome with presence of powdery mildew, leading to the identification of molecular markers associated with this fungal infection in C. sativa ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Khiron Life Sciences Uruguay S.A. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication., (Copyright © 2023 Fernández, Castro, López-Radcenco, Rodriguez, Carrera, García-Carnelli and Moyna.)

Background & Aims: Model for End-Stage Liver Disease (MELD) score better predicts mortality in alcohol-associated hepatitis (AH) but could underestimate severity in women and malnourished patients. Using a global cohort, we assessed the ability of the MELD 3.0 score to predict short-term mortality in AH., Methods: This was a retrospective cohort study of patients admitted to hospital with AH from 2009 to 2019. The main outcome was all-cause 30-day mortality. We compared the AUC using DeLong's method and also performed a time-dependent AUC with competing risks analysis., Results: A total of 2,124 patients were included from 28 centres from 10 countries on three continents (median age 47.2 ± 11.2 years, 29.9% women, 71.3% with underlying cirrhosis). The median MELD 3.0 score at admission was 25 (20-33), with an estimated survival of 73.7% at 30 days. The MELD 3.0 score had a better performance in predicting 30-day mortality (AUC:0.761, 95%CI:0.732-0.791) compared with MELD sodium (MELD-Na; AUC: 0.744, 95% CI: 0.713-0.775; p  = 0.042) and Maddrey's discriminant function (mDF) (AUC: 0.724, 95% CI: 0.691-0.757; p  = 0.013). However, MELD 3.0 did not perform better than traditional MELD (AUC: 0.753, 95% CI: 0.723-0.783; p  = 0.300) and Age-Bilirubin-International Normalised Ratio-Creatinine (ABIC) (AUC:0.757, 95% CI: 0.727-0.788; p  = 0.765). These results were consistent in competing-risk analysis, where MELD 3.0 (AUC: 0.757, 95% CI: 0.724-0.790) predicted better 30-day mortality compared with MELD-Na (AUC: 0.739, 95% CI: 0.708-0.770; p  = 0.028) and mDF (AUC:0.717, 95% CI: 0.687-0.748; p  = 0.042). The MELD 3.0 score was significantly better in predicting renal replacement therapy requirements during admission compared with the other scores (AUC: 0.844, 95% CI: 0.805-0.883)., Conclusions: MELD 3.0 demonstrated better performance compared with MELD-Na and mDF in predicting 30-day and 90-day mortality, and was the best predictor of renal replacement therapy requirements during admission for AH. However, further prospective studies are needed to validate its extensive use in AH., Impact and Implications: Severe AH has high short-term mortality. The establishment of treatments and liver transplantation depends on mortality prediction. We evaluated the performance of the new MELD 3.0 score to predict short-term mortality in AH in a large global cohort. MELD 3.0 performed better in predicting 30- and 90-day mortality compared with MELD-Na and mDF, but was similar to MELD and ABIC scores. MELD 3.0 was the best predictor of renal replacement therapy requirements. Thus, further prospective studies are needed to support the wide use of MELD 3.0 in AH., (© 2023 The Author(s).)

Introduction: Opsoclonus-myoclonus-ataxia syndrome is a rare neuroinflammatory disorder with onset during childhood; aetiology may be paraneoplastic, para-infectious, or idiopathic. No biomarkers have yet been identified, and diagnosis is clinical. Better cognitive prognosis appears to be related to early onset of immunomodulatory therapy., Methods: We describe the epidemiological, clinical, therapeutic, and long-term prognostic characteristics of a cohort of 20 Spanish patients., Results: The mean age of onset was 21 months (range, 2-59). Ataxia and opsoclonus were the most frequent symptoms both at disease onset and throughout disease progression. The mean time from onset to diagnosis was 1.1 months. Neuroblast lineage tumours were detected in 45% of patients; these were treated with surgical resection in 7 cases and chemotherapy in 2. Cerebrospinal fluid analysis revealed pleocytosis in 4 cases (25%) and neither antineuronal antibodies nor oligoclonal bands were detected in any patient. Immunomodulatory drugs were used in all cases. Nine patients started combined immunomodulatory treatment at the time of diagnosis, and 5 patients after a mean of 2.2 months. In the long term, 6 of the 10 patients followed up for more than 5 years presented mild or moderate cognitive sequelae. Four patients presented relapses, generally coinciding with the decrease of corticosteroid doses., Conclusions: Early initiation of immunotherapy, as well as triple combination therapy, where needed, was associated with a lower frequency of cognitive impairment 2 years after onset., (Copyright © 2020 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

The presence of female athletes has only increased in recent years, as has the incidence of injuries in female sports activities. These injuries are conditioned by multiple factors, including hormonal agents. It is estimated that the menstrual cycle may be related to the predisposition to suffer an injury. However, a causal relationship has not yet been established. The aim of this study was to analyse the relationship between the menstrual cycle and injuries in female sports practice. A systematic search of the scientific literature available in PubMed, Medline, Scopus, Web of Science, and Sport Discus was carried out in January 2022. With 138 articles, only eight studies were found that met the selection criteria for this study. Peak estradiol is associated with increased laxity, strength, and poor use of neuromuscular control. Thus, the ovulatory phase is associated with an increased risk of injury. In conclusion, it seems that hormonal fluctuations throughout the menstrual cycle alter values such as laxity, strength, body temperature, and neuromuscular control, among others. This fact causes women to constantly adapt to hormonal variations, which exposes them to a higher risk of injury.

Neurodegenerative disorders (NDDs) are major health issues in Western countries. Despite significant efforts, no effective therapeutics for NDDs exist. Several drugs that target epigenetic mechanisms (epidrugs) have been recently developed for the treatment of NDDs, and several of these are currently being tested in clinical trials. Furthermore, various bioproducts have shown important biological effects for the potential prevention and treatment of these disorders. Here, we review the use of natural products as epidrugs to treat NDDs in order to explore the epigenetic effects and benefits of functional foods and natural bioproducts on neurodegeneration.

Obesity is a major health challenge worldwide, with implications for diabetes, hypertension and cardiovascular disease (CVD). Regular consumption of dark-meat fish is linked to a lower incidence of CVD and associated metabolic disorders due to the presence of long-chain omega-3 fatty acid ethyl esters in fish oils. The aim of the present study was to determine whether a marine compound like a sardine lipoprotein extract (RCI-1502), regulates fat accumulation in the heart of a high-fat diet-induced (HFD) mouse model of obesity. To investigate its effects in the heart and liver, we conducted a randomized, 12-week placebo-controlled study in which we analyzed the expression of vascular inflammation markers, obesity biochemical patterns and related CVD pathologies. Male HFD-fed mice treated with a RCI-1502-supplemented diet showed reduced body weight, abdominal fat tissue and pericardial fat pad mass density without systemic toxicity. RCI-1502 significantly reduced triacylglyceride, low-density lipoprotein and total-cholesterol concentrations in serum, but increased HDL-cholesterol levels. Our data show that RCI-1502 is beneficial for reducing obesity associated with a long-term HFD, possibly by exerting a protective effect on lipidic homeostasis, indicated also by histopathological analysis. These results collectively indicate that RCI-1502 acts as a cardiovascular therapeutic nutraceutical agent, which modulates fat-induced inflammation and improves metabolic health., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: Caesarean section is a surgical intervention that consists of the extraction of the fetus by abdominal route through the incision in the uterus. Like any surgical intervention, caesarean section is not exempt from complications and these can be classified as short-term (acute pain) and long-term (adhesions in the scar, lumbar and pelvic pain, intestinal obstruction and ectopic pregnancies). Physiotherapy has different tools to address these complications. The aim of this study was to review the scientific bibliography to know the effects of physiotherapy on patients who have given birth by cesarean section., Methods: A search for articles was carried out during the month of December 2021 in the databases: PubMed, Medline, Cinahl, Scopus, PEDro and WOS using the search terms Cesarean Section, Physical Therapy Modalities and Physical therapy. As an inclusion criterion, it was established that the type of study was a Randomized Clinical Trial (RCT)., Results: A total of 280 articles were obtained, of which 9 were selected after applying the eligibility criteria. In them, the most used physiotherapy intervention was electrotherapy, followed by massage therapy and therapeutic exercise. Studies show effects of these forms of physiotherapy, with a determined duration and frequency, with improvements in pain, activities of daily living, comfort level, joint ranges and reduction in the consumption of analgesics., Conclusions: Physiotherapy has various modalities with which to attend complications after cesarean section, both in an immediate and a late phase, especially highlighting the reduction of pain.

In this article, we identified a novel epileptogenic variant (G307R) of the gene SLC6A1 , which encodes the GABA transporter GAT-1. Our main goal was to investigate the pathogenic mechanisms of this variant, located near the neurotransmitter permeation pathway, and compare it with other variants located either in the permeation pathway or close to the lipid bilayer. The mutants G307R and A334P, close to the gates of the transporter, could be glycosylated with variable efficiency and reached the membrane, albeit inactive. Mutants located in the center of the permeation pathway (G297R) or close to the lipid bilayer (A128V, G550R) were retained in the endoplasmic reticulum. Applying an Elastic Network Model, to these and to other previously characterized variants, we found that G307R and A334P significantly perturb the structure and dynamics of the intracellular gate, which can explain their reduced activity, while for A228V and G362R, the reduced translocation to the membrane quantitatively accounts for the reduced activity. The addition of a chemical chaperone (4-phenylbutyric acid, PBA), which improves protein folding, increased the activity of GAT-1WT, as well as most of the assayed variants, including G307R, suggesting that PBA might also assist the conformational changes occurring during the alternative access transport cycle.

Information and Communication Technologies have led to a new way of life and, in particular, of socialization. The objective of this study is to analyse the image social media disseminate of news taken from digital newspapers, based on the opportunities and drawbacks attributed to smartphone use by teenagers. An essentially qualitative methodology was used, on a sample of 1704 news items published in digital newspapers. The results and conclusions show that smartphone use by teenagers improves development of their digital competence, presents new academic opportunities (through gamification or mobile learning) and provides them with digital tools for school and leisure. The widespread drawbacks reflect the effects of the device on the deterioration of health (dependence, stress, psychosocial problems) and emotions, thereby succinctly affecting academic performance. A noticeable increase of positive news about smartphones was published in the major newspapers in December, while that on its negative effects, in September.

Alzheimer's disease (AD), the most common cause of dementia, causes irreversible memory loss and cognitive deficits. Current AD drugs do not significantly improve cognitive function or cure the disease. Novel bioproducts are promising options for treating a variety of diseases, including neurodegenerative disorders. Targeting the epigenetic apparatus with bioactive compounds (epidrugs) may aid AD prevention treatment. The aims of this study were to determine the composition of a porcine brain-derived extract Nosustrophine, and whether treating young and older trigenic AD mice produced targeted epigenetic and neuroprotective effects against neurodegeneration. Nosustrophine regulated AD-related APOE and PSEN2 gene expression in young and older APP/BIN1/COPS5 mice, inflammation-related ( NOS3 and COX-2 ) gene expression in 3-4-month-old mice only, global (5mC)- and de novo DNA methylation ( DNMT3a ), HDAC3 expression and HDAC activity in 3-4-month-old mice; and SIRT1 expression and acetylated histone H3 protein levels in 8-9-month-old mice. Mass spectrometric analysis of Nosustrophine extracts revealed the presence of adenosylhomocysteinase, an enzyme implicated in DNA methylation, and nicotinamide phosphoribosyltransferase, which produces the NAD+ precursor, enhancing SIRT1 activity. Our findings show that Nosustrophine exerts substantial epigenetic effects against AD-related neurodegeneration and establishes Nosustrophine as a novel nutraceutical bioproduct with epigenetic properties (epinutraceutical) that may be therapeutically effective for prevention and early treatment for AD-related neurodegeneration.

Our clinical series comprises 124 patients with movement disorders (MDs) and/or ataxia with cerebellar atrophy (CA), many of them showing signs of neurodegeneration with brain iron accumulation (NBIA). Ten NBIA genes are accepted, although isolated cases compatible with abnormal brain iron deposits are known. The patients were evaluated using standardised clinical assessments of ataxia and MDs. First, NBIA genes were analysed by Sanger sequencing and 59 patients achieved a diagnosis, including the detection of the founder mutation PANK2 p.T528M in Romani people. Then, we used a custom panel MovDisord and/or exome sequencing; 29 cases were solved with a great genetic heterogeneity (34 different mutations in 23 genes). Three patients presented brain iron deposits with Fe-sensitive MRI sequences and mutations in FBXO7 , GLB1 , and KIF1A , suggesting an NBIA-like phenotype. Eleven patients showed very early-onset ataxia and CA with cortical hyperintensities caused by mutations in ITPR1 , KIF1A , SPTBN2 , PLA2G6 , PMPCA, and PRDX3 . The novel variants were investigated by structural modelling, luciferase analysis, transcript/minigenes studies, or immunofluorescence assays. Our findings expand the phenotypes and the genetics of MDs and ataxias with early-onset CA and cortical hyperintensities and highlight that the abnormal brain iron accumulation or early cerebellar gliosis may resembling an NBIA phenotype.

Magnetic resonance imaging (MRI) signal changes associated with ischemic stroke are typically described as T2w and FLAIR hyperintense, and T1w isointense lesions. Intralesional T1w hyperintensity is generally attributed to either a hemorrhagic stroke, or an ischemic stroke with hemorrhagic transition, and has an associated signal void on gradient echo (GE) sequences. Cases of ischemic stroke with T1w hyperintense signal in absence of associated signal void on GE sequences have been sporadically demonstrated in human stroke patients, as well as in dogs with experimentally induced ischemia of the middle cerebral artery. This multicenter retrospective descriptive study investigates the presence of T1w hyperintensity in canine stroke without associated signal void on GE sequences. High field (1.5 Tesla) MRI studies of 12 dogs with clinical presentation, MRI features, and cerebrospinal fluid results suggestive of non-hemorrhagic stroke were assessed. The time between the observed onset of clinical signs and MRI assessment was recorded. All 12 patients had an intralesional T1w hyperintense signal compared to gray and white matter, and absence of signal void on T2 * w GE or SWI sequences. Intralesional T1w hyperintensities were either homogenously distributed throughout the entire lesion (6/12) or had a rim-like peripheral distribution (6/12). The mean time between the recorded onset of clinical signs and MRI assessment was 3 days; however, the age range of lesions with T1w hyperintense signal observed was 1-21days, suggesting that such signal intensities can be observed in acute, subacute, or chronic stages of ischemic stroke. Follow-up was recorded for 7/12 cases, all of which showed evidence of neurological improvement while in hospital, and survived to discharge. Correlation of the age and MRI appearance of lesions in this study with similar lesions observed in human and experimental studies suggests that these T1w hyperintensities are likely caused by partial tissue infarction or selective neuronal necrosis, providing an alternative differential for these T1w hyperintensities observed., Competing Interests: Authors PW, SB, and IC were employed by Linnaeus Veterinary Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Weston, Behr, Garosi, Maeso and Carrera.)

Intervertebral disc disease, including intervertebral disc extrusions and protrusions, is the most common spinal cord disorder in dogs. Atypical and uncommon intervertebral disc herniations include intradural/intramedullary disc extrusion, intervertebral foraminal disc extrusion and intervertebral disc herniation (Schmorl's node). Intradural/extramedullary disc extrusion is the least common type of intervertebral disc herniation in veterinary medicine, characterized by extruded disc material within the intradural space. To date, only one study has been published in veterinary medicine reporting intradural/extramedullary disc extrusions. In this study, low field MRI was used, and the authors could not find any MRI features to diagnose with confidence an intradural/extramedullary disc location of the extruded disc material. The aim of this study was to describe the high field (1.5T) MRI characteristics of surgically confirmed intradural/extramedullary disc extrusions. This is a retrospective, multicentric and descriptive study. Inclusion criteria was surgical confirmation of intradural/extramedullary disc extrusion by durotomy and complete MRI study of the spine. Seven cases were included. Images were reviewed by a radiology resident and a certified radiologist, with emphasis on the following signs: "Golf-tee sign" (widening of the subarachnoid space cranial and caudal to the lesion), "Beak sign" (pointed and sharp compressive lesion) and "Y sign" (division of the dura and arachnoid layers). MRI showed a "Y sign" in all the cases (7/7) seen from the T2-weighted sagittal views, while "Golf-tee sign" was not recognized in any of the cases (0/7). Additionally, "beak sign" was present in half of the cases (4/7). "Y sign" maybe a reliable MRI feature for identifying intradural/medullary disc extrusions from the MRI study. As the arachnoid is peeled from the dura by the disc herniation there is a splitting of the arachnoid mater and the ventral dura. The intradural disc material will be surrounded by CSF signal intensity margin, giving the appearance of a Y, which can be identified from the T2-weighted sagittal images., Competing Interests: The authors declare that this study received funding from Linnaeus Veterinary Limited. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication., (Copyright © 2022 Casado, Fernandes, Lourinho, Gonçalves, Clark, Violini and Carrera.)

Introduction: Lung cancer is one of the most common malignancies worldwide and the leading cause of cancer-related death. Smoking is one of the main risk factors associated with this cancer. Treatment will depend on the form of cancer and its stage, existing many therapeutic possibilities. In this regard, therapeutic exercise plays an important role in lung cancer care, as well as the pulmonary rehabilitation and respiratory physical therapy., Purpose: To review the current scientific literature about the effects of therapeutic exercise in lung cancer., Method: A search was carried out in CINAHL, MEDLINE, PubMed, Scopus y Web of Science using de terms "Exercise Therapy" and "Lung Neoplasms". 141 studies were obtained, but only 19 were selected by adjusting to the inclusion and exclusion criteria. 10 of them were randomized controlled trials with a Jadad score between 2 and 3., Results: These works performed a large variety of interventions based on therapeutic exercise, classified in preoperative, postoperative, during treatment, post treatment and combination. Most focused on aerobic exercise, muscle strength and respiratory exercises., Conclusion: therapeutic exercise seems to be positive and obtain significant improvements in patients with lung cancer, regardless the moment of intervention and the type of exercise performed., Competing Interests: Declaration of competing interest None declared., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives:  (1) To compare the ability of standard computed tomography (CT) scale (SCTS) and extended CT scale (ECTS) images, produced using conventional CT technology, to provide detailed assessment of metal screws in vitro. (2) To assess how screw size, type, and orientation relative to the Z -axis of the gantry affect implant assessment. (3) To test the ability of SCTS, ECTS, and radiography to diagnose screw failure when there is negligible screw fragment displacement., Study Design:  Part 1: 12 screws of different size, type, and composition were scanned in three orientations (parallel or 0°; oblique or 45°; and perpendicular or 90°) relative to the Z -axis of the gantry. SCTS and ECTS reconstructions were made for each screw, in each plane, to assess implant shape, structure, and diameter. Part 2: fatigue-failure was induced in four screws commonly used to stabilize canine humeral intracondylar fissures. Screws were then reassembled achieving grossly perfect apposition and alignment of the fragments. Ability to detect implant failure was tested using SCTS, ECTS, and radiography., Results:  ECTS provided better screw assessment compared with SCTS resulting in clear visualization of the structure in 8/12 versus 0/12 screws and shape in 12/12 versus 11/12 screws; however, results were affected by screw size, type, and orientation. ECTS identified all in vitro screw fractures with negligible screw fragment displacement; however, success was affected by screw orientation: 4/4 fractures identified with a 90° angle, 1/4 for 45°, and 0/4 for 0°. SCTS and radiography did not identify any of them., Conclusion:  The results indicate that ECTS reconstructions are useful for assessment of metal screws and for detection of nondisplaced screw fractures., Competing Interests: None declared., (Thieme. All rights reserved.)

Ayahuasca is a psychedelic beverage originally from the Amazon rainforest used in different shamanic settings for medicinal, spiritual, and cultural purposes. It is prepared by boiling in water an admixture of the Amazonian vine Banisteriopsis caapi , which is a source of β-carboline alkaloids, with plants containing N,N -dimethyltryptamine, usually Psychotria viridis . While previous studies have focused on the detection and quantification of the alkaloids present in the drink, less attention has been given to other nonalkaloid components or the composition of the solids suspended in the beverage, which may also affect its psychoactive properties. In this study, we used nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) to study the composition of ayahuasca samples, to determine their alkaloid qualitative and quantitative profiles, as well as other major soluble and nonsoluble components. For the first time, fructose was detected as a major component of the samples, while harmine (a β-carboline previously described as an abundant alkaloid in ayahuasca) was found to be present in the solids suspended in the beverage. In addition, N,N -dimethyltryptamine (DMT), harmine, tetrahydroharmine, harmaline, and harmol were identified as the major alkaloids present in extracts of all samples. Finally, a novel, easy, and fast method using quantitative NMR was developed and validated to simultaneously quantify the content of these alkaloids found in each ayahuasca sample., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Alzheimer's Disease (AD) is a major health problem worldwide. The lack of efficacy of existing therapies for AD is because of diagnosis at late stages of the disease, limited knowledge of biomarkers, and molecular mechanisms of AD pathology, as well as conventional drugs that are focused on symptomatic rather than mechanistic features of the disease. The connection between epigenetics and AD, however, may be useful for the development of novel therapeutics or diagnostic biomarkers for AD. The aim of this study was to investigate a pathogenic role for epigenetics and other biomarkers in the male APP/BIN1/COPS5 triple-transgenic (3xTg) mouse model of AD. In the APP/BIN1/COPS5 3xTg-AD mouse hippocampus, sirtuin expression and activity decreased, HDAC3 expression and activity increased, PSEN1 mRNA levels were unchanged, PSEN2 and APOE expression was reduced, and levels of the pro-inflammatory marker IL-6 increased; levels of pro-inflammatory COX-2 and TNFα and apoptotic (NOS3) markers increased slightly, but these were non-significant. In fixed mouse-brain slices, immunoreactivity for CD11b and β-amyloid immunostaining increased. APP/BIN1/COPS5 3xTg-AD mice are a suitable model for evaluating epigenetic changes in AD, the discovery of new epigenetic-related biomarkers for AD diagnosis, and new epidrugs for the treatment of this neurodegenerative disease.

The first stage of the drug discovery process involves the identification of small compounds with biological activity. Iboga alkaloids are monoterpene indole alkaloids (MIAs) containing a fused isoquinuclidine-tetrahydroazepine ring. Both the natural products and the iboga-inspired synthetic analogs have shown a wide variety of biological activities. Herein, we describe the chemoenzymatic preparation of a small library of novel N -indolylethyl-substituted isoquinuclidines as iboga-inspired compounds, using toluene as a starting material and an imine Diels-Alder reaction as the key step in the synthesis. The new iboga series was investigated for its potential to promote the release of glial cell line-derived neurotrophic factor (GDNF) by C6 glioma cells, and to inhibit the growth of infective trypanosomes. GDNF is a neurotrophic factor widely recognized by its crucial role in development, survival, maintenance, and protection of dopaminergic neuronal circuitries affected in several neurological and psychiatric pathologies. Four compounds of the series showed promising activity as GDNF releasers, and a leading structure (compound 11 ) was identified for further studies. The same four compounds impaired the growth of bloodstream Trypanosoma brucei brucei (EC 50 1-8 μM) and two of them (compounds 6 and 14 ) showed a good selectivity index.

Background: Schizophrenia is a chronic mental illness that, in addition to its own psychopathology, causes cognitive, physical, metabolic, affective and social deterioration. The aim of this systematic review was to set up the effects on the bio-psycho-social state of exercise therapy in patients with schizophrenia., Methods: A systematic review was carried out in January 2021, based on a search strategy in the databases PubMed, Scopus, Medline, Cinhal and SportsDiscus. Moreover, bibliographies of articles and reviews related to the topic under study were consulted. Studies published in the last 5 years were identified, randomized clinical trials, with full access in English, which included interventions with therapeutic exercise and the evaluation of the effects they produce in patients with schizophrenia., Results: From 125 articles identified, 13 that fitted the criteria and the topic under study were finally included. In these cases, the most commonly used exercise therapy intervention is aerobic exercise, as well as yoga and tai chi. As aerobic exercise alternatives, pilates, stretching, toning and balance exercises have also been used. Studies showed effects of this type of exercise therapy, on a specific duration and frequency, with improvements in psychopathology, physical status, cognitive status, social functioning and functional capacity., Conclusions: Exercise therapy, mainly aerobic exercise, benefits patients with schizophrenia as a complement to pharmacological treatment by producing beneficial effects at the physical, cognitive, psychopathological and social levels.

Novel and effective chemotherapeutic agents are needed to improve cancer treatment. Epidrugs are currently used for cancer therapy but also exhibit toxicity. Targeting the epigenetic apparatus with bioproducts may aid cancer prevention and treatment. To determine whether the lipoprotein marine extract AntiGan shows epigenetic and antitumor effects, cultured HepG2 (hepatocellular carcinoma) and HCT116 (colorectal carcinoma) cell lines were treated with AntiGan (10, 50, 100, and to 500 µg/mL) for 24 h, 48 h, and 72 h. AntiGan (10 µg/mL) reduced cell viability after 48 h and increased Bax expression; AntiGan (10 and 50 µg/mL) increased caspase-3 immunoreactivity in HepG2 and HCT116 cells. AntiGan (10 and 50 µg/mL) attenuated COX-2 and IL-17 expression in both cell lines. AntiGan (10 µg/mL) increased 5mC levels in both cell types and reduced DNMT1 and DNMT3a expression in these cells. AntiGan (10 and 50 µg/mL) promoted DNMT3a immunoreactivity and reduced SIRT1 mRNA expression in both cell types. In HCT116 cells treated with AntiGan (10 µg/mL), SIRT1 immunoreactivity localized to nuclei and the cytoplasm; AntiGan (50 µg/mL) increased cytoplasmic SIRT1 localization in HCT116 cells. AntiGan is a novel antitumoral bioproduct with epigenetic properties (epinutraceutical) for treating liver and colorectal cancer.

Chronic low back pain (CLBP) is a prevalent disfunction in the spine, affecting both women and men. The implication of the abdominal muscles in this disfunction has been studied, including wrong breathing patterns or inactivity of this area. However, there is a lack of studies examining changes in thickness of abdominal with ultrasonography. Thus, the aim of this study is to analyze the differences in the thickness of abdominal muscles at rest and during breathing between subjects with and without CLBP. A total of 72 subjects were divided in two groups: participants with CLBP ( n = 36) and participants without CLBP ( n = 36). In both groups, the thickness of the four abdominal muscles was measured and compared at rest and during breathing with ultrasonography. In TrA and IO there were no significant differences between groups, but those subjects with CLBP increased the muscle thickness more than participants without pain during breathing. In EO there were no differences in muscle thickness between groups and between rest and breathing. In RA, subjects with CLBP showed less muscle thickness than subjects without pain during breathing, but no changes were found at rest. In conclusion, the deepest abdominal muscles, TrA and IO, appear to increase their thickness and RA appear to decrease more in subjects with CLBP, in comparison with healthy participants.

The differentiation of solitary intra-axial hematomas from hemorrhagic neoplasms based on their magnetic resonance imaging (MRI) features is challenging. The treatment and prognosis for these two disease entities are vastly different and distinction between them is often based on MRI findings alone. The aim of this study was to describe the 1.5 tesla MRI features of canine intra-axial hematomas and correlate these findings with the evolution of hemorrhages described in human brains. Retrospective evaluation of patient details, clinical signs, and MRI findings of dogs with intra-axial hematomas that were histopathologically confirmed or determined via repeat MRI study and/or resolution of neurological signs. Ten dogs met the inclusion criteria. All 10 hematoma lesions were determined to be 2-7 days in age. On MRI, all 10 hemorrhagic lesions were comprised of two distinct regions; a relatively thin T1-weighted (T1W), T2-weighted (T2W) and gradient echo (GRE) hypointense (9/10) peripheral border region and a large central region that was heterogenous but predominantly T1W, T2W and GRE hyperintense (8/10). The peripheral border region was complete in its integrity in all 10 cases on T2W and GRE sequences. Contrast enhancement was present in (6/10) hematoma lesions and was always peripheral in nature with no evidence of central enhancement associated with any of the lesions. An intra-axial hematoma should be suspected in solitary hemorrhagic space occupying lesions that have a complete hypointense peripheral rim, elicit a peripheral contrast enhancement pattern, and display the expected temporal pattern of hematoma evolution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Whitlock, Holdsworth, Morales, Garosi and Carrera.)

Epilepsy is one of the most common chronic, neurological diseases in humans and dogs and considered to be a network disease. In human epilepsy altered functional connectivity in different large-scale networks have been identified with functional resting state magnetic resonance imaging. Since large-scale resting state networks have been consistently identified in anesthetised dogs' application of this technique became promising in canine epilepsy research. The aim of the present study was to investigate differences in large-scale resting state networks in epileptic dogs compared to healthy controls. Our hypothesis was, that large-scale networks differ between epileptic dogs and healthy control dogs. A group of 17 dogs (Border Collies and Greater Swiss Mountain Dogs) with idiopathic epilepsy was compared to 20 healthy control dogs under a standardized sevoflurane anaesthesia protocol. Group level independent component analysis with dimensionality of 20 components, dual regression and two-sample t test were performed and revealed significantly increased functional connectivity in the anterior default mode network of idiopathic epileptic dogs compared to healthy control dogs (p = 0.00060). This group level differences between epileptic dogs and healthy control dogs identified using a rather simple data driven approach could serve as a starting point for more advanced resting state network analysis in epileptic dogs., (© 2021. The Author(s).)

Introduction: Alzheimer's disease models (ADMs) are currently used for drug development (DD). More than 20,000 molecules were screened for AD treatment over decades, with only one drug (Aducanumab)FDA-approved over the past 18 years. A revision of pathogenic concepts and ADMs are needed. Areas covered: The authors discuss herein preclinical models including: (i) in vitro models (cell lines, primary neuron cell cultures, iPSC-derived brain cells), (ii) ex vivo models, and (iii) in vivo models (artificial, transgenic, non-transgenic and induced). Expert opinion: The following types of ADMs have been reported: Mouse models (45.08%), Rat models (15.04%), Non-human Primate models (0.76%), Rabbit models (0.46%), Cat models (0.53%), Pig models (0.30%), Guinea pig models (0.15%), Octodon degu models (0.02%), Dog models (0.54%), Drosophila melanogaster models (1.79%), Zebrafish models (0.50%), Caenorhabditis elegans (1.21%), Cell culture models (3.31%), Cholinergic models (8.26%), Neurotoxic models (6.79%), Neuroinflammation models (6.92%), Neurovascular models (7.88%), and Microbiome models (0.45%).No single ADM faithfully reproduces all the pathogenic events in the human AD phenotype spectrum. ADMs should be different for (i) pathogenic studies vs basic DD, and (ii) preventive interventions vs symptomatic treatments. There cannot be an ideal ADM for DD, because AD is a spectrum of syndromes. DD can integrate pathogenic, mechanistic, metabolic, transporter and pleiotropic genes in a multisystem model.

Introduction: Spinal pain is one of the main reasons for seeking care; it usually appears during school age, increases with age, and is related to certain risk factors. The objective of this study is to analyze the prevalence of spinal pain among schoolchildren and examine associated factors., Population and Methods: Cross-sectional study with a questionnaire administered to schoolchildren aged 9-11 years. The prevalence of pain, physical activity, spine self-care, backpack use, and electronic device use were analyzed., Results: A total of 329 subjects were analyzed. The prevalence of spinal pain is 34.3%, with no differences observed between sexes. Pain severity is considered mild, with a mean severity of 1.99 ± 2.54 over 10 according to the Wong-Baker FACES® scale; in more than 50% of cases, pain had a short duration (less than 12 hours). Cervical pain was referred by 22.2% of schoolchildren, whereas dorsal and lumbar pain were reported by 14% and 11.9%, respectively. In addition, 47.9% referred pain in more than one region of the spine. Also, 73.3% of schoolchildren did physical activity outside school hours and 90.6% used electronic devices. An association was observed between the presence of pain and adequate postural hygiene habits., Conclusions: Schoolchildren referred spinal pain that was mild and short in duration, often in the cervical region. The association with risk factors indicates that children who referred pain have better postural habits., Competing Interests: None, (Sociedad Argentina de Pediatría.)

Background & Aims: Corticosteroids are the only effective therapy for severe alcohol-associated hepatitis (AH), defined by a model for end-stage liver disease (MELD) score >20. However, there are patients who may be too sick to benefit from therapy. Herein, we aimed to identify the range of MELD scores within which steroids are effective for AH., Methods: We performed a retrospective, international multicenter cohort study across 4 continents, including 3,380 adults with a clinical and/or histological diagnosis of AH. The main outcome was mortality at 30 days. We used a discrete-time survival analysis model, and MELD cut-offs were established using the transform-the-endpoints method., Results: In our cohort, median age was 49 (40-56) years, 76.5% were male, and 79% had underlying cirrhosis. Median MELD at admission was 24 (19-29). Survival was 88% (87-89) at 30 days, 77% (76-78) at 90 days, and 72% (72-74) at 180 days. A total of 1,225 patients received corticosteroids. In an adjusted-survival-model, corticosteroid use decreased 30-day mortality by 41% (hazard ratio [HR] 0.59; 0.47-0.74; p <0.001). Steroids only improved survival in patients with MELD scores between 21 (HR 0.61; 0.39-0.95; p = 0.027) and 51 (HR 0.72; 0.52-0.99; p = 0.041). The maximum effect of corticosteroid treatment (21-30% survival benefit) was observed with MELD scores between 25 (HR 0.58; 0.42-0.77; p <0.001) and 39 (HR 0.57; 0.41-0.79; p <0.001). No corticosteroid benefit was seen in patients with MELD >51. The type of corticosteroids used (prednisone, prednisolone, or methylprednisolone) was not associated with survival benefit (p = 0.247)., Conclusion: Corticosteroids improve 30-day survival only among patients with severe AH, especially with MELD scores between 25 and 39., Lay Summary: Alcohol-associated hepatitis is a condition where the liver is severely inflamed as a result of excess alcohol use. It is associated with high mortality and it is not clear whether the most commonly used treatments (corticosteroids) are effective, particularly in patients with very severe liver disease. In this worldwide study, the use of corticosteroids was associated with increased 30-day, but not 90- or 180-day, survival. The maximal benefit was observed in patients with an MELD score (a marker of severity of liver disease; higher scores signify worse disease) between 25-39. However, this benefit was lost in patients with the most severe liver disease (MELD score higher than 51)., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Atremorine is a novel bioproduct obtained by nondenaturing biotechnological processes from a genetic species of Vicia faba. Atremorine is a potent dopamine (DA) enhancer with powerful effects on the neuronal dopaminergic system, acting as a neuroprotective agent in Parkinson's disease (PD). Over 97% of PD patients respond to a single dose of Atremorine (5 g, p.o.) 1 h after administration. This response is gender-, time-, dose-, and genotype-dependent, with optimal doses ranging from 5 to 20 g/day, depending upon disease severity and concomitant medication. Drug-free patients show an increase in DA levels from 12.14 ± 0.34 pg/ml to 6463.21 ± 1306.90 pg/ml; and patients chronically treated with anti-PD drugs show an increase in DA levels from 1321.53 ± 389.94 pg/ml to 16,028.54 ± 4783.98 pg/ml, indicating that Atremorine potentiates the dopaminergic effects of conventional anti-PD drugs. Atremorine also influences the levels of other neurotransmitters (adrenaline, noradrenaline) and hormones which are regulated by DA (e.g., prolactin, PRL), with no effect on serotonin or histamine. The variability in Atremorine-induced DA response is highly attributable to pharmacogenetic factors. Polymorphic variants in pathogenic (SNCA, NUCKS1, ITGA8, GPNMB, GCH1, BCKDK, APOE, LRRK2, ACMSD), mechanistic (DRD2), metabolic (CYP2D6, CYP2C9, CYP2C19, CYP3A4/5, NAT2), transporter (ABCB1, SLC6A2, SLC6A3, SLC6A4) and pleiotropic genes (APOE) influence the DA response to Atremorine and its psychomotor and brain effects. Atremorine enhances DNA methylation and displays epigenetic activity via modulation of the pharmacoepigenetic network. Atremorine is a novel neuroprotective agent for dopaminergic neurons with potential prophylactic and therapeutic activity in PD., (© 2021 Wiley Periodicals LLC.)

Atremorine is a potent dopamine (DA) enhancer obtained by nondenaturing biotechnological processes from a genetic species of Vicia faba. Atremorine affects the neuronal dopaminergic system by acting as a neuroprotective agent against Parkinson's disease (PD). PD patients (N = 127) responded to a single dose of Atremorine (5 g, p.o.) 1 h after administration in a sex-, time-, dose-, and genotype-dependent fashion. Drug-free patients (N = 81) showed an increase in DA levels from 12.14 ± 0.34 pg/ml to 6463.21 ± 1306.90 pg/ml; and patients chronically treated with anti-PD drugs (N = 46) showed an increase in DA levels from 1321.53 ± 389.94 pg/ml to 16,028.54 ± 4783.98 pg/ml, indicating that Atremorine potentiates the dopaminergic effect of conventional anti-PD drugs. The variability in Atremorine-induced DA response is strongly attributable to pharmacogenetic factors. Polymorphic variants in pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes influence the DA response to Atremorine. Genetic variation in the DA (SLC6A3; rs460000), noradrenaline (NA) (SLC6A2; rs12708954, rs3785143, rs5569), and serotonin (5-HT) transporter (SLC6A4; rs2020934, rs2020936, rs4251417, rs6354) genes exert a genotype-dependent Atremorine-induced DA response in PD, with potential impact on the DA-related pharmacogenetic outcome and minimum effects on NA and 5-HT levels., (© 2021 Wiley Periodicals, LLC.)

Background and objective : Prior studies have reported an activation of abdominal muscles during hypopressive exercises in women with pelvic floor disfunction. However, no previous research analyzed the effects of hypopressive exercise on abdominal muscles in healthy populations to understand the normal biomechanics of this area. The aim of this study was to examine the thickness of abdominal muscles at rest and during hypopressive exercise in supine and standing positions with ultrasound imaging in healthy adults. Methods : A cross-sectional study was carried out in 99 healthy university students. The thickness of the abdominal muscles at rest and during hypopressive exercise was assessed with ultrasound imaging in supine and standing positions. Results : During hypopressive exercise, there was a significant increase in the muscle thickness of transversus abdominis ( p < 0.001) and internal oblique ( p < 0.001) in supine and standing positions. External oblique only increased its thickness significantly in the standing position ( p < 0.001) and rectus abdominis did not change during the hypopressive exercise in any position ( p > 0.05). In conclusion, hypopressive exercises seem to increase the thickness of the deepest and most stabilized muscles such as transversus abdominis and internal oblique. Conclusions : These findings should be considered for future interventions with hypopressive exercises in healthy subjects.

Background: The aim of this study is to evaluate risk factors for infection as well as infection rates after open reduction and internal fixation for distal tibia fractures with a distal tibia locking plate and/or isolated screws., Methods: This is a retrospective and descriptive study based on 55 patients treated in our Major Trauma Centre from January 2009 to December 2016. All patients were classified by age, sex, open or closed fracture, injury mechanism, comorbidities, fixation and time from injury to surgery. 22 extraarticular fractures AO/OTA 43-A and 33 intraarticular (14 cases 43-B and 19 43-C) were recorded. High energy trauma was related in 27 patients, while open fractures were observed in 10 patients. Splint until surgery was applied routinely while temporary external fixation (EF) was performed in 21 patients (7 extraarticular and 14 intraarticular). Patients were treated by 5 different consultant surgeons performing isolated screws (SC) in 20% of the surgeries, antero-medial locking distal tibia plate (AM) and anterolateral (AL) were used in 47% and 33% of the patients respectively. After assessing normality and homogeneity of the subgroups, statistical contrast tests were performed., Results: Infection rate was 31.5%, mainly caused by S. aureus. We obtained a statistically significant correlation between greater age and infection rate. In the same way, a positive statistical trend between infection and AL plating was found. The use of EF followed by ORIF was not observed as a risk factor for infection compared with splint followed by internal fixation, however, the group of patients in which a splint was used, a positive relationship was found between the infection rate and shorter time until the definitive fixation. No statistically significant associations were found between extra/intraarticular fracture pattern, use of corticosteroids or open fractures and infection rate., Conclusion: Greater age was a predisposing factor for infection. The use of external fixation before definitive ORIF seems to be a safe procedure regarding risk infection, and if an external fixation is not used, we recommend longer waiting time until definitive ORIF. Screw fixation or antero-medial plates, if allowed by fracture pattern, can be an option to avoid infection., Competing Interests: Declaration of Competing Interest None of the authors has any affiliations or financial links to any of the companies which implants were referred in the study. No specific funding was received to perform this study., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: The correct choice of surgical approaches in complex tibial plateau fractures is essential to achieve adequate reduction and fixation. Detailed fracture morphology and direction of columns displacement, that we have named the Main Deformity Direction (MDD), may aid in selecting the optimal surgical strategy. In this article we present a new algorithm based on MDD and column concepts. The aim of this study was to evaluate the outcomes of a group of tibial plateau fractures treated according to this algorithm. The secondary aim was to evaluate the incidence of the different MDD in our multicolumnar subgroup., Patients and Methods: Excluding isolated lateral one-column fractures, open fractures and patients not treated following this algorithm, 72 patients with tibial plateau fractures surgically treated with open reduction and internal fixation were collected retrospectively, from three trauma centers, from January 2015 to April 2019. Radiological assessment was performed to establish the columns involved and the MDD. Quality and maintenance of reduction and alignment, complications and functional outcomes were assessed., Results: Initial fracture analysis was performed in 72 patients (8 one-column, 35 two-column and 29 multicolumnar fractures). In the multicolumnar group, the posteromedial MDD was the most frequent pattern (17 of 29 patients). Four patients were excluded due to loss of follow-up, resulting 68 patients for final outcome analysis (7 one-column, 34 two-column and 27 multicolumnar). The average follow-up was 18 months (range: 6-52). Excellent/good outcomes were obtained in all one-column, 31 of 34 two-column and 25 of 27 multicolumnar fractures. Incomplete reduction was present in three patients. As complications, we had two loss of reduction, one conversion to knee arthroplasty, one nonunion and one deep infection. No patient presented neurological or vascular problems, knee instability or extension deficit., Conclusion: Satisfactory results have been obtained following the principles of our algorithm. In addition to the anatomical involvement of columns and segments, we believe that identifying the Main Deformity Direction (MDD) provides useful information for decision-making, especially in multicolumnar fractures. The most frequent MDD in our multicolumnar subgroup was the posteromedial MDD, but more than one-third presented a different MDD, requiring different surgical strategies., Competing Interests: Declaration of competing interest We have no conflicts of interest to disclose., (Copyright © 2021. Published by Elsevier Ltd.)

This study analyzes the effects of hypopressive exercises on the abdominal thickness of healthy subjects and compares the performance between women and men. We conducted a transversal observational study in 98 subjects (63% women). The muscle thickness is analyzed in transversus abdominis, internal oblique, external oblique, and rectus abdominis with ultrasound imaging at rest and during the hypopressive exercise (HE) in supine and standing position. Comparisons between rest and hypopressive exercise are carried out in the two different positions and between women and men. In the supine position, there is a significant activation of the transversus abdominis and internal oblique during hypopressive exercise ( p < 0.001), and it is similar in both sexes, the external oblique is only activated significantly by men ( p < 0.001) and rectus abdominis had no significant activation ( p > 0.05). Our results show that standing transversus abdominis and external oblique significantly increased their thickness during HE with higher effects in men. Internal oblique also increased significantly, but with higher effects in women, and rectus abdominis had no significant increase. Men had similar effects to women during HE, with an activation of the deepest abdominal muscles. The unequal anatomy and the position could explain the different results obtained between the sexes.

Iboga alkaloids are a group of monoterpenoid indole alkaloids with promising and intriguing biological activities. Ibogaine is the representative member of the series and has become widely known as a potent atypical psychedelic with promising effects to treat substance use disorder. Nowadays, an efficient and scalable enantioselective total synthesis of ibogaine and related iboga alkaloids is still lacking, so direct extraction from natural sources or semi-synthetic schemes are the methods of choice to obtain them in a preparative scale. In particular, ibogaine can be obtained either by a low yielding direct isolation from Tabernanthe iboga or using a semi-synthetic procedure from voacangine, an iboga alkaloid occurring in a higher yield in the root bark of Voacanga africana . In this work, we describe an optimized process to obtain voacangine from V. africana root bark as a precursor of the iboga scaffold. Using a direct acetone-based extraction procedure (0.5 kg of root bark), voacangine was isolated in ∼0.8% of root bark dried weight, while the major alkaloids isolated from the bark were identified as iboga-vobasinyl dimers (∼3.7%) such as voacamine and voacamidine. Since these alkaloids contain the voacangine moiety in their structure, the cleavage of the dimers was further optimized, affording an extra amount of voacangine in ∼50% isolated molar yield. In this manner, the total amount of voacangine obtained by application of the whole procedure to the plant material (extraction and dimer cleavage) could almost duplicate the content originally found in the root bark., Competing Interests: The authors declare the following competing financial interest(s): Diver Sellanes is the CEO of SIQUIMIA S.R.L. The rest of the authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Missense and frameshift pathogenic variants and microdeletions involving TBL1XR1 gene have been described in patients with intellectual disability, autism, Rett-like features and schizophrenia, some of them with the clinical diagnosis of Pierpont syndrome, a rare pattern of multiple congenital anomalies, but others without dysmorphic findings or with non-specific ones, and also patients with only some of the features associated with Pierpont syndrome. We here present a case with a de novo novel missense variant in TBL1XR1 gene with overlapping features with Pierpont syndrome and autism, a neurobehavioral manifestation not previously reported in Pierpont syndrome. This patient expands the phenotypic spectrum of TBL1XR1 gene pathogenic variants., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A 9-year-old, male neutered old English Sheepdog was presented for further investigation of altered mentation, impaired vision, and hemineglect syndrome of 10 days duration. An MRI study of the brain revealed multifocal, contrast-enhancing intra-axial lesions that had a stippled hypointense appearance in all sequences but lacked evidence of a strong signal void on T2* images. Histological examination of the brain postmortem confirmed the lesions were metastases arising from an osteosarcoma, which was later identified in the right humerus. To the authors' knowledge, these MRI characteristics of osteosarcoma metastases in the canine brain have not been previously reported., (© 2019 American College of Veterinary Radiology.)