Effects of creatine supplementation on muscle metabolism in an Alzheimer mouse model

Alzheimer’s disease (AD), the most common form of dementia in the elderly, is a global issue affecting about 24 million individuals. Because AD is a systemic pathology, dementia is not the only leading factor contributing to loss of independence in AD patients. AD may also impair skeletal muscle metabolism and function. Creatine (CR) supplementation may enhance skeletal muscle hypertrophy/mass and function in sarcopenia and muscular dystrophies, but has yet to be studied in AD. This study examined the effect of oral CR on muscle metabolism in a triple-transgenic (3xTg) AD mouse model. Twenty-four, 3×Tg AD mice (~8 month-old) were randomly assigned to control (CON) or CR (3% w/w) diet. Bodyweights and feed intakes were measured throughout the 8-week study. Lower limb (quadriceps muscle; QM and gastrocnemius; GM) and upper limb muscles (triceps; TM) were collected to analyze levels of CR, total protein, DNA, RNA, amino acids (AA), adenosine triphosphate (ATP), adenosine diphosphate (ADP), total and phosphorylated p70 ribosomal S6 kinase (p70S6K). Data (mean ± SEM) were assessed by analysis of variance (ANOVA) and Fisher’s least significant difference (LSD) post hoc test. In comparison to the CON group, CR supplementation increased CR content in both GM (p=0.002) and QM (p=0.037), with higher (p=0.032) ATP/ADP ratio in CR in comparison with CON in QM. A higher protein concentration (p<0.0001) was notable in GM of CR supplemented group vs. CON. Total branched-chain AA levels in QM increased 2-fold (p< 0.0001) in CR groups. Additionally, CR resulted in a higher (p<0.05) protein/DNA ratio; an index of muscle cell size, in both QM and GM for CR groups. The index of cell capacity for protein synthesis (RNA/DNA ratio) in GM was also higher (p=0.001) in CR groups. However, phosphorylation (activation) level of p70S6K, an integral component in protein synthesis signalling pathway, did not show any significant differences in female (p=0.161) and male (p=0.292) CR supplemented groups compared with CON. To conclude, CR supplementation is capable of inducing muscle hypertrophy/growth parameters in the 3×Tg AD mouse model, thereby enhancing protein synthesis capacity in skeletal muscles, thus possibly promoting muscle function in AD.May 201

Ten years of injectable platelet-rich fibrin.

The use of platelet-rich fibrin (PRF) has seen widespread advantages over platelet-rich plasma (PRP) in many fields of medicine. However, until 2014, PRF remained clinically available only in its solid clotted form. Modifications to centrifugation protocols and tube technology have led to the development of a liquid injectable version of PRF (i-PRF). This narrative review takes a look back at the technological developments made throughout the past decade and further elaborates on their future clinical applications. Topics covered include improvements in isolation techniques and protocols, ways to further concentrate i-PRF, and the clinical impact and relevance of cooling i-PRF. Next, various uses of i-PRF are discussed, including its use in regenerative periodontology, implantology, endodontics, temporomandibular joint injections, and orthodontic tooth movement. Furthermore, various indications in medicine are also covered, including its use in sports injuries and osteoarthritis of various joints, treatment of diabetic ulcers/wound care, and facial esthetics and hair regrowth. Finally, future applications are discussed, mainly its use as a drug delivery vehicle for small biomolecules, such as growth factors, antibiotics, exosomes, and other medications that may benefit from the controlled and gradual release of biomolecules over time

Evaluation of Response Inhibition in the Face of Cognitive and Emotional Stimuli in Patients with Frontal Lobe Tumors before and after Surgery

Introduction: The functions of specialized brain parts undoubtedly influence emotional inhibition. Numerous studies have considered the prefrontal cortex of the brain’s two hemispheres to be responsible for this behavior. However, few studies have addressed the question of to what degree a change in this brain unit can affect response inhibition and reaction time in the face of emotional stimuli. Therefore, the current study aimed to investigate emotional behavior in patients with frontal lobe gliomas. Materials and Methods: In this quasi-experimental research, the Integrated Visual and Auditory (IVA) test and affective Go/No-Go task in the areas of happiness and anger, focusing on response accuracy and reaction time were performed for 16 patients with frontal lobe lesions and 20 healthy individuals. These tests were repeated three months after surgery. The t-test, Wilcoxon signed rank test, Mann-Whitney, and their related equivalence test were applied for statistical analysis. Results: The results revealed that following surgery, there was an improvement in the patients’ reaction times and response accuracy to both emotional stimuli especially against the stimulus of anger exist. The IVA results showed the significant improvement in neurocognitive condition of all patients following surgery. Conclusion: Toward improving the emotional conditions, lesion resection surgery could significantly help these patients regain their normal cognitive function. However, a difference was seen between patients and healthy individuals

Diffusion tensor tractograghy can affect treatment strategy to remove brain occupying mass lesions

Radical resection of a pathological lesion along with the preservation of eloquent cerebral tissue is the principle goal of neurosurgery. Brain lesions are usually diagnosed by conventional magnetic resonance imaging (MRI), but this method is unable to describe the relationship between lesions and neighboring specific white matter (WM) tracts. Diffusion tensor tractograghy (DTT) is a new sophisticated imaging modality to reveal the neural fibers and their relationships with lesions. In the current study we assess that how diffusion tensor tractograghy can affect on treatment planning in patients afflicted by different types of brain lesions. In this prospective observational study, eight patients with brain mass lesion underwent conventional brain MRI pulse sequences and DTT imaging with 1.5 Tesla system using 64 independent diffusion encoding directions between December 2011 to January 2013.Acquired images were assessed by the neuroradiologist and neurosurgeon. Finally, the treatment strategies were compared using data before and after the tractograghy. The treatment strategy in six patients changed from radiotherapy into the craniotomy by using tractograghy data, in one patient changed from radio surgery to craniotomy and in one patient, neurosurgeon preferred to avoid operation. As we can infer from this study, based on the tractograghy results, the treatment technique may be changed, and the treatment plan could be devised with more accuracy and in case of surgery, may lead to less post-operative neurological deficits and better outcome results

Eruption of the Permanent First Premolar Associated with a Mandibular Keratocystic Odontogenic Tumor after Marsupialization in a 9-year-old Boy: A Case Report with 2 years of follow-up

Amongst odontogenic cysts, keratocystic odontogenic tumor (KOT) is a benign intra-osseous lesion, characterized by corrugated parakeratinized uniform stratified squamous epithelium, with potential for aggressive behavior and high tendency to recur. There are multiple treatment modalities for this cyst. Some surgeons prefer the conservative treatments such as marsupialization while the others prefer invasive treatments such as radical resection. The aim of this study was to present a case of KOT involving the right mandibular premolar area with an impacted tooth in a 9-year-old boy treated by marsupialization. The treatment resulted in eruption of the mandibular first premolar, and no signs of recurrence were observed after two years. Marsupialization was found to be an effective treatment in inducing the eruption of mandibular premolar associated with KOT in preadolescents and can be a reliable procedure to reduce recurrence tendency of KOT

Untargeted LC-HRMS-based metabolomics to identify novel biomarkers of metastatic colorectal cancer

Colorectal cancer is one of the main causes of cancer death worldwide, and novel biomarkers are urgently needed for its early diagnosis and treatment. The utilization of metabolomics to identify and quantify metabolites in body fluids may allow the detection of changes in their concentrations that could serve as diagnostic markers for colorectal cancer and may also represent new therapeutic targets. Metabolomics generates a pathophysiological ‘fingerprint’ that is unique to each individual. The purpose of our study was to identify a differential metabolomic signature for metastatic colorectal cancer. Serum samples from 60 healthy controls and 65 patients with metastatic colorectal cancer were studied by liquid chromatography coupled to high-resolution mass spectrometry in an untargeted metabolomic approach. Multivariate analysis revealed a separation between patients with metastatic colorectal cancer and healthy controls, who significantly differed in serum concentrations of one endocannabinoid, two glycerophospholipids, and two sphingolipids. These findings demonstrate that metabolomics using liquid-chromatography coupled to high-resolution mass spectrometry offers a potent diagnostic tool for metastatic colorectal cancer.This study was supported by a grant (n° 15CC056/DTS17/00081- ISCIII-FEDER) from the Fundación para la Investigación Biosanitaria de Andalucía Oriental (FIBAO) and Roche Pharma S.L. Authors from the Fundación MEDINA acknowledge the receipt of financial support from this public-private partnership of Merck Sharp & Dohme de España S.A. with the University of Granada and Andalusian Regional Government (PIN-0474-2016)

The Immune Landscape of Cancer

We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes—wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant—characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis. Specific driver mutations correlated with lower (CTNNB1, NRAS, or IDH1) or higher (BRAF, TP53, or CASP8) leukocyte levels across all cancers. Multiple control modalities of the intracellular and extracellular networks (transcription, microRNAs, copy number, and epigenetic processes) were involved in tumor-immune cell interactions, both across and within immune subtypes. Our immunogenomics pipeline to characterize these heterogeneous tumors and the resulting data are intended to serve as a resource for future targeted studies to further advance the field. Thorsson et al. present immunogenomics analyses of more than 10,000 tumors, identifying six immune subtypes that encompass multiple cancer types and are hypothesized to define immune response patterns impacting prognosis. This work provides a resource for understanding tumor-immune interactions, with implications for identifying ways to advance research on immunotherapy