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INFβ treatment affects global DNA methylation in monocytes of patients with multiple sclerosis.

J Neuroimmunol 2021 Apr 7;355:577563. Epub 2021 Apr 7.

Universidade Federal de São Paulo, UNIFESP, Disciplina de Neurologia, Rua Pedro de Toledo, 650, Vila Cldementino, Zip Code: 04039-002 São Paulo, SP, Brazil. Electronic address:

The combination of genetic and epigenetic influences alters the development of complex diseases. Aberrant patterns of DNA methylation are associated with inflammation and clinical activity in MS. We evaluated the differences between global DNA methylation in lymphocytes and monocytes of patients with MS compared to healthy controls. Read More

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A selective p53 activator and anticancer agent to improve colorectal cancer therapy.

Cell Rep 2021 Apr;35(2):108982

LAQV/REQUIMTE, Laboratório de Microbiologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal. Electronic address:

Impairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). Read More

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Dual targeting of the epigenome via FACT complex and histone deacetylase is a potent treatment strategy for DIPG.

Cell Rep 2021 Apr;35(2):108994

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia; School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia; Kid's Cancer Centre, Sydney Children's Hospital, Randwick, NSW, Australia. Electronic address:

Diffuse intrinsic pontine glioma (DIPG) is an aggressive and incurable childhood brain tumor for which new treatments are needed. CBL0137 is an anti-cancer compound developed from quinacrine that targets facilitates chromatin transcription (FACT), a chromatin remodeling complex involved in transcription, replication, and DNA repair. We show that CBL0137 displays profound cytotoxic activity against a panel of patient-derived DIPG cultures by restoring tumor suppressor TP53 and Rb activity. Read More

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Splice it up: Atypical transcripts to boost leukemia immunotherapy.

Immunity 2021 Apr;54(4):608-610

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address:

Neoantigens are prime targets for cancer immunotherapy, but their identification in low mutational burden malignancies remains challenging. In this issue of Immunity, Ehx et al. show that atypical transcripts, and particularly retained introns, expand the spectrum of leukemia immunotherapy targets. Read More

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Antimicrobial treatment of Erysipelatoclostridium ramosum invasive infections: a systematic review.

Rev Inst Med Trop Sao Paulo 2021 12;63:e30. Epub 2021 Apr 12.

University of Kragujevac, Faculty of Medical Sciences, Department of Pharmacy, Kragujevac, Serbia.

The aim of this systematic review was to determine the causal role of Erysipelatoclostridium ramosum in specific invasive infections in humans, and to assess the clinical outcome of antibiotic therapy used to treat them. Several electronic databases were systematically searched for clinical trials, observational studies or individual cases on patients of any age and gender with a systemic inflammatory response syndrome (SIRS) due to E. ramosum isolated from body fluids or tissues in which it is not normally present. Read More

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The role of nursing care in the type 2 diabetes treatment associated with chronic liver diseases.

Eur J Gastroenterol Hepatol 2021 Apr 9. Epub 2021 Apr 9.

Gastroenterology Department Nursing Department, The First Affiliated Hospital of Hainan Medical University, Haikou City, Hainan Province, China.

Objective: Diabetes is the fifth leading cause of death in the People's Republic of China. The aim of the article is to compare the effects of nursing care on the laboratory findings and ultrasound results of diabetic patients with chronic liver diseases (CLD) who were treated with antiglycemic drugs.

Methods: Diabetic were patients treated with metformin hydrochloride in combination with gliclazide, pioglitazone hydrochloride, sitagliptin, exenatide or liraglutide. Read More

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Diabetic Foot Amputation Prevention During COVID-19.

Adv Skin Wound Care 2021 May;34(5):1-4

Kshitij Shankhdhar, MBBS, MD, PhD, is Diabetologist, L.K. Diabetes Centre, Indira Nagar, Lucknow, India. The author has disclosed no financial relationships related to this article. Submitted October 15, 2020; accepted in revised form December 4, 2020.

Abstract: In this case report, the treatment of a patient with a diabetic foot ulcer on his left foot was interrupted by the novel coronavirus 2019 pandemic lockdown in India. The author guided the patient via telephone and online services. Based on the history given by the patient, the lesion started as blistering from improperly fitted footwear that then evolved into multiple infected ulcerations on the dorsal surface of the great toe (osteomyelitis with septic arthritis of the joint). Read More

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Multimodal Treatments and Outcomes for Anaplastic Thyroid Cancer Before and After Tyrosine Kinase Inhibitor Therapy: A Real-World Experience.

Eur J Endocrinol 2021 Apr 1. Epub 2021 Apr 1.

J Chung, Medicine, Samsung Medical Center, Seoul, Korea (the Republic of).

Background: Anaplastic thyroid cancer (ATC) has dismal prognosis, and there is no effective treatment. We aimed to evaluate the efficacy of tyrosine kinase inhibitor (TKI) therapy in real world clinic, and to suggest the most effective treatment modality according to the combination of treatments.

Methods: This retrospective study evaluated clinical outcomes and cause of death with multimodal treatments in patients with ATC at Samsung Medical Center. Read More

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Four-Week Daily Calcipotriene/Betamethasone Dipropionate Foam Is Highly Efficacious in Patients With Psoriasis (PSO-LONG Lead-in Phase).

J Drugs Dermatol 2021 Apr;20(4):436-441

Background: Psoriasis is a chronic disease requiring long-term treatment strategies. Optimal strategies should include initial rapid relief of symptoms followed by long-term management to maintain remission. This 4-week open-label phase of a long-term proactive management phase 3 trial aimed to select responders to once daily, fixed-dose combination calcipotriene 0. Read More

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A Phase 3, Randomized Trial Demonstrating the Improved Efficacy and Patient Acceptability of Fixed Dose Calcipotriene and Betamethasone Dipropionate Cream.

J Drugs Dermatol 2021 Apr;20(4):420-425

Background: The fixed dose combination of calcipotriene and betamethasone dipropionate (CAL/BDP) is a well-established, efficacious, and safe topical treatment of psoriasis.

Method: A Phase 3, multicenter, randomized, investigator-blind, active, and vehicle-controlled trial enrolling 796 patients with moderate to severe psoriasis according to the Physician Global Assessment (PGA) scale. Products were applied once daily for 8 weeks. Read More

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Efficacy and Safety of Flexible Hyaluronic Acid Fillers in Lip and Perioral Enhancement.

J Drugs Dermatol 2021 Apr;20(4):402-408

Background: Since lips have a significant role in facial aesthetic perception, lip augmentation is an increasingly popular aesthetic procedure.

Objective: To evaluate aesthetic improvement and facial dynamics with hyaluronic acid (HA) fillers in the lips and perioral region at 8 weeks after the last treatment compared to pre-treatment.

Methods And Materials: In this open-label study, all subjects received HARK in the lips, and an additional group also received HARR and/or HARD in nasolabial folds (NLFs) and marionette lines (MLs). Read More

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Associations between second-line glucose-lowering combination therapies with metformin and HbA , body weight, quality of life, hypoglycaemic events, and glucose-lowering treatment intensification: the DISCOVER study.

Diabetes Obes Metab 2021 Apr 14. Epub 2021 Apr 14.

AstraZeneca, Gaithersburg, Maryland, USA.

Aims: Using data from DISCOVER, a 3-year, prospective, global observational study of patients with type 2 diabetes initiating second-line glucose-lowering therapy, we sought to explore the effects of second-line dual combinations therapies plus metformin on body weight, glycated haemoglobin (HbA ), health-related quality of life, and risks of hypoglycaemia and further treatment intensification.

Materials And Methods: Adjusted changes from baseline in weight, HbA , and 36-item Short Form Health Survey version 2 (SF-36v2) summary scores at 6, 12, 24, and 36 months were assessed using linear mixed models. Risk of hypoglycaemia and further intensification were assessed using interval censored analyses. Read More

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Regular treatment with formoterol and an inhaled corticosteroid versus regular treatment with salmeterol and an inhaled corticosteroid for chronic asthma: serious adverse events.

Cochrane Database Syst Rev 2021 Apr 14;4:CD007694. Epub 2021 Apr 14.

Cochrane Airways, Population Health Research Institute, St George's, University of London, London, UK.

Background: Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness, and cough. Treatment with inhaled steroids and bronchodilators can result in good control of symptoms, prevention of further morbidity, and improved quality of life. However, an increase in serious adverse events with the use of both regular formoterol and regular salmeterol (long-acting beta₂-agonists) compared with placebo for chronic asthma has been demonstrated in previous Cochrane Reviews. Read More

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Perioperative hemodynamic optimization: from guidelines to implementation-an experts' opinion paper.

Ann Intensive Care 2021 Apr 14;11(1):58. Epub 2021 Apr 14.

Département d'Anesthésie-Réanimation, Hôpital Bichat Claude Bernard, AP-HP Nord, Paris, France.

Despite a large body of evidence, the implementation of guidelines on hemodynamic optimization and goal-directed therapy remains limited in daily routine practice. To facilitate/accelerate this implementation, a panel of experts in the field proposes an approach based on six relevant questions/answers that are frequently mentioned by clinicians, using a critical appraisal of the literature and a modified Delphi process. The mean arterial pressure is a major determinant of organ perfusion, so that the authors unanimously recommend not to tolerate absolute values below 65 mmHg during surgery to reduce the risk of postoperative organ dysfunction. Read More

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Randomized Phase II Trial of Capecitabine and Lapatinib with or without IMC-A12 (Cituxumumab) in Patients with HER2-Positive Advanced Breast Cancer Previously Treated with Trastuzumab and Chemotherapy: NCCTG N0733 (Alliance).

Breast Cancer Res Treat 2021 Apr 14. Epub 2021 Apr 14.

Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA.

Purpose: To compare efficacy and safety of capecitabine and lapatinib with or without IMC-A12 (cituxumumab) in patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab.

Patients And Methods: Following an initial safety run-in cohort, patients were randomized 1:2 to Arm A (capecitabine and lapatinib) or to Arm B (capecitabine, lapatinib, and cituxumumab). Given the frequency of non-hematologic grade ≥ 3 adverse events in those receiving the three-drug combination in the safety cohort, lapatinib and capecitabine doses were reduced in Arm B only. Read More

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A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors.

Invest New Drugs 2021 Apr 14. Epub 2021 Apr 14.

Eli Lilly and Company, Indianapolis, IN, USA.

Background LY3022855 is a recombinant, immunoglobulin, human monoclonal antibody targeting the colony-stimulating factor-1 receptor. This phase 1 trial determined the safety, pharmacokinetics, and antitumor activity of LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid cancers who had received standard anti-cancer treatments. Methods In Part A (dose-escalation), patients received intravenous (IV) LY3022855 25/50/75/100 mg once weekly (QW) combined with durvalumab 750 mg once every two weeks (Q2W) IV or LY3022855 50 or 100 mg QW IV with tremelimumab 75/225/750 mg once every four weeks. Read More

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Immunotherapy in Cervical Cancer.

Curr Oncol Rep 2021 Apr 14;23(6):61. Epub 2021 Apr 14.

Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, LSOG Bld. Room 305, 333 Cedar Street, PO Box 208063, New Haven, CT, 06520-8063, USA.

Purpose Of Review: This review aims to summarize the current immunotherapy studies and the potential targeted therapies showing promise in the treatment of cervical cancer.

Recent Findings: There are promising ongoing monotherapy and combination therapy trials using different immune checkpoint inhibitors, poly adenosine diphosphate ribose polymerase inhibitors, tumor angiogenesis inhibitors (i.e. Read More

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Early microvascular complications in type 1 and type 2 diabetes: recent developments and updates.

Pediatr Nephrol 2021 Apr 14. Epub 2021 Apr 14.

Department of Pediatrics, Section of Pediatric Endocrinology, Children's Hospital Colorado and University of Colorado Anschutz Medical Campus, 13123 E. 16th Avenue, Box B265, Aurora, CO, 80045, USA.

The prevalence of youth-onset diabetes is progressing rapidly worldwide, and poor glycemic control, in combination with prolonged diabetes duration and comorbidities including hypertension, has led to the early development of microvascular complications including diabetic kidney disease, retinopathy, and neuropathy. Pediatric populations with type 1 (T1D) and type 2 (T2D) diabetes are classically underdiagnosed with microvascular complications, and this leads to both undertreatment and insufficient attention to the mitigation of risk factors that could help attenuate further progression of complications and decrease the likelihood for long-term morbidity and mortality. This narrative review aims to present a comprehensive summary of the epidemiology, risk factors, symptoms, screening practices, and treatment options, including future opportunities for treatment advancement, for microvascular complications in youth with T1D and T2D. Read More

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Assessment of long-term functional maintenance of primary human hepatocytes to predict drug-induced hepatoxicity in vitro.

Arch Toxicol 2021 Apr 14. Epub 2021 Apr 14.

Department of Anesthesiology, Renji Hospital, Jiaotong University School of Medicine, Shanghai, China.

Hepatocytes are the main cell components of the liver and perform metabolic, detoxification, and endocrine functions. Functional hepatocytes are of great value in drug development, toxicity evaluation, and cell therapy for liver diseases. In recent years, an increasing number of in vitro models have been developed to screen drugs and test their toxicity. Read More

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Fabrication of Large-Scale High-Mobility Flexible Transparent Zinc Oxide Single Crystal Wafers.

ACS Appl Mater Interfaces 2021 Apr 14. Epub 2021 Apr 14.

Department of Materials Science and Engineering, National Chiao Tung University, Hsinchu 30010, Taiwan.

Single crystal wafers, such as silicon, are the fundamental carriers of advanced electronic devices. However, these wafers exhibit rigidity without mechanical flexibility, limiting their applications in flexible electronics. Here, we propose a new approach to fabricate 1. Read More

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Nicotine induces morphological and functional changes in astrocytes via nicotinic receptor activity.

Glia 2021 Apr 14. Epub 2021 Apr 14.

Department of Chemistry, University of Kentucky, Lexington, Kentucky, USA.

Nicotine is a highly addictive compound present in tobacco, which causes the release of dopamine in different regions of the brain. Recent studies have shown that astrocytes express nicotinic acetylcholine receptors (nAChRs) and mediate calcium signaling. In this study, we examine the morphological and functional adaptations of astrocytes due to nicotine exposure. Read More

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Superior antihypertensive and cardioprotective effects of chlorthalidone compared with hydrochlorothiazide.

Drugs Today (Barc) 2021 Apr;57(4):291-301

INTEGRIS Baptist Medical Center, Oklahoma City, Oklahoma, USA.

Diuretics are the most commonly used drugs for the treatment of hypertension, either alone or in combination with other antihypertensive drugs. Of all diuretics, hydrochlorothiazide (HCTZ) and chlorthalidone (CTD) are the most commonly used, with HCTZ being the most widely prescribed diuretic. Recent studies have shown that CTD is a better diuretic with superior antihypertensive effectiveness and cardiovascular protection. Read More

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Prospective evaluation of a change in dietary therapy in dogs with steroid-resistant protein-losing enteropathy.

J Small Anim Pract 2021 Apr 13. Epub 2021 Apr 13.

Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, 80523, USA.

Objective: To describe the clinical effect of dietary alteration as a sole change to therapy in dogs with steroid-resistant protein-losing enteropathy.

Materials And Methods: Prospective study. Eligible enrolled dogs received dietary alteration as sole change to their therapeutic plan. Read More

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Management of primary immune thrombocytopenia in a real-world setting in Japan: eltrombopag versus corticosteroids.

Int J Hematol 2021 Apr 13. Epub 2021 Apr 13.

Department of Blood Transfusion, Osaka University Hospital, Suita, Osaka, Japan.

This real-world study in Japan assessed the long-term safety of persistent use of eltrombopag compared to corticosteroids. Overall, 1887 patients with primary immune thrombocytopenia were included in the study cohort, based on hospital claims data. Eltrombopag was frequently used as a second- or third-line therapy (monotherapy: 13. Read More

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"Present and future of immunotherapy in Neuroendocrine Tumors".

Rev Endocr Metab Disord 2021 Apr 14. Epub 2021 Apr 14.

Endocrinology Unit, IRCCS AOU San Martino, Genoa, Italy.

Immunotherapy, so promising in many neoplasms, still does not have a precise role in the treatment of neuroendocrine neoplasms (NENs). In this article, we provide an overview on the current knowledge about immunotherapy with immune checkpoint inhibitors (ICIs) applied to NENs, evaluating future perspectives in this setting of tumors.Evidence so far available for ICIs in gastroenteropancreatic (GEP)-NENs is definitively not as robust as for other tumors such as Small Cell Lung Cancer or Merkel Cell Carcinoma. Read More

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Comparison of outpatient and inpatient spa therapy in knee osteoarthritis.

Int J Biometeorol 2021 Apr 14. Epub 2021 Apr 14.

Medical Faculty, Department of Physical Medicine and Rehabilitation, Bolu Abant Izzet Baysal University, 14020, Bolu, Turkey.

Osteoarthritis (OA) is a common condition that impacts many people worldwide and involves weight-bearing joints, resulting in chronic pain. In this study, we aimed to compare the effectiveness of inpatient and outpatient physical therapy modalities and spa combination treatments on pain and functional status in patients with knee osteoarthritis. Seventy-four patients diagnosed with primary knee osteoarthritis were included in this study. Read More

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Glucose-Lowering Medication Use in CKD: Analysis of US Medicare Beneficiaries Between 2007 and 2016.

Kidney Med 2021 Mar-Apr;3(2):173-182.e1. Epub 2020 Dec 30.

Department of Pharmaceutical Care & Health Systems, University of Minnesota, College of Pharmacy, Minneapolis, MN.

Background: Information regarding the use of glucose-lowering medications in patients with chronic kidney disease (CKD) is limited.

Study Design: Retrospective cohort study.

Setting & Participants: Medicare 5% random sample of patients with CKD with type 2 diabetes, 2007 to 2016. Read More

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December 2020

Effects of the combination of second-generation antipsychotics on serum concentrations of aripiprazole and dehydroaripiprazole in Chinese patients with schizophrenia.

Gen Psychiatr 2021 29;34(2):e100423. Epub 2021 Mar 29.

Department of Biochemistry and Psychopharmacology, Shanghai Mental Health Center, Shanghai, China.

Background: Aripiprazole (ARI) is often prescribed alone or in combination with other second-generation antipsychotics (SGAs) to treat patients with schizophrenia. However, this may increase the potential clinical significance of drug-drug interactions. Therapeutic drug monitoring (TDM) is an important and fundamental tool both when administering ARI alone and in combination with other SGAs to monitor ARI pharmacokinetics, adjust the dosage and thereby achieve more effective and safer treatment. Read More

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The effect of low-dose radiation spillage during stereotactic radiosurgery for brain metastases on the development of de novo metastases.

Clin Transl Radiat Oncol 2021 May 29;28:79-84. Epub 2021 Mar 29.

Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.

Purpose/objectives: Stereotactic radiosurgery (SRS) for metastatic disease to the brain is associated with higher in-brain failures compared to whole brain radiation therapy (WBRT). Here we investigated the relationship between low-dose fall off during SRS and location of new brain lesions.

Materials And Methods: One hundred sixty-seven patients treated with single fraction or fractionated SRS for intact or resected brain metastases at our institution from January 2016 to June 2018 were reviewed. Read More

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Optimal diuretic strategies in heart failure.

Ann Transl Med 2021 Mar;9(6):517

Division of Cardiovascular Diseases, University of Alabama at Birmingham, Birmingham, AL, USA.

Heart failure (HF) is one of the major causes of morbidity and mortality in the world. According to a 2019 American Heart Association report, about 6.2 million American adults had HF between 2013 and 2016, being responsible for almost 1 million admissions. Read More

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