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Patient-reported outcomes from a randomized, double-blind, placebo controlled, phase III study of baricitinib placebo in patients with moderately to severely active rheumatoid arthritis and an inadequate response to methotrexate therapy: results from the RA-BALANCE study.

Ther Adv Musculoskelet Dis 2021 20;13:1759720X211006964. Epub 2021 Apr 20.

Department of Rheumatology and Immunity, Center of Clinical Immunology, Peking University People's Hospital, Xicheng District, Beijing, P.R. China.

Introduction: To assess the effect of baricitinib on patient-reported outcomes (PROs) in patients with moderately to severely active rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX).

Methods: This was a 52-week, randomized, double-blind, placebo controlled, phase III study in patients with RA who had an inadequate response to MTX. Patients ( = 290) receiving stable background MTX were randomly assigned (1:1) to receive placebo or baricitinib 4 mg once daily with a primary endpoint at week 12. Read More

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Combined real-time fMRI and real time fNIRS brain computer interface (BCI): Training of volitional wrist extension after stroke, a case series pilot study.

PLoS One 2021 6;16(5):e0250431. Epub 2021 May 6.

Brain Rehabilitation Research Center, Malcom Randall VA Medical Center, Gainesville, Florida, United States of America.

Objective: Pilot testing of real time functional magnetic resonance imaging (rt-fMRI) and real time functional near infrared spectroscopy (rt-fNIRS) as brain computer interface (BCI) neural feedback systems combined with motor learning for motor recovery in chronic severely impaired stroke survivors.

Approach: We enrolled a four-case series and administered three sequential rt-fMRI and ten rt-fNIRS neural feedback sessions interleaved with motor learning sessions. Measures were: Arm Motor Assessment Tool, functional domain (AMAT-F; 13 complex functional tasks), Fugl-Meyer arm coordination scale (FM); active wrist extension range of motion (ROM); volume of activation (fMRI); and fNIRS HbO concentration. Read More

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Ethylene vinyl alcohol copolymer to treat an intracranial arteriovenous malformation in a dog.

J Vet Intern Med 2021 May 6. Epub 2021 May 6.

Veterinary Medical Teaching Hospital, University of California-Davis, School of Veterinary Medicine, Davis, California, USA.

A 6-year-old neutered male German shepherd dog was evaluated for obtundation, blindness, and bilateral exophthalmos. A magnetic resonance imaging scan of the brain was performed and identified an arteriovenous malformation (AVM) with several feeding arterial branches, and venous drainage through the cavernous sinus. Venous vessels rostral to the AVM were severely distended and extended into the retrobulbar spaces. Read More

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Clinically-Relevant ABC Transporter for Anti-Cancer Drug Resistance.

Front Pharmacol 2021 19;12:648407. Epub 2021 Apr 19.

State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China.

Multiple drug resistance (MDR), referring to the resistance of cancer cells to a broad spectrum of structurally and mechanistically unrelated drugs across membranes, severely impairs the response to chemotherapy and leads to chemotherapy failure. Overexpression of ATP binding cassette (ABC) transporters is a major contributing factor resulting in MDR, which can recognize and mediate the efflux of diverse drugs from cancer cells, thereby decreasing intracellular drug concentration. Therefore, modulators of ABC transporter could be used in combination with standard chemotherapeutic anticancer drugs to augment the therapeutic efficacy. Read More

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Phenotypic Recapitulation and Correction of Desmoglein-2-deficient Cardiomyopathy using Human Induced Pluripotent Stem Cell-derived Cardiomyocytes.

Hum Mol Genet 2021 May 5. Epub 2021 May 5.

Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.

Desmoglein-2, encoded by DSG2, is one of the desmosome proteins that maintains the structural integrity of tissues, including heart. Genetic mutations in DSG2 cause arrhythmogenic cardiomyopathy, mainly in an autosomal dominant manner. Here, we identified a homozygous stop-gain mutations in DSG2 (c. Read More

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The role of biomechanical forces and MALAT1/miR-329-5p/PRIP signalling on glucocorticoid-induced osteonecrosis of the femoral head.

J Cell Mol Med 2021 May 3. Epub 2021 May 3.

Department of Orthopedics, Guizhou Provincial People's Hospital, Guiyang, China.

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a common orthopaedic disease. GIONFH primarily manifests clinically as hip pain in the early stages, followed by the collapse of the femoral head, narrowing of the hip joint space and damage to the acetabulum, resulting in severely impaired mobility. However, the pathogenesis of GIONFH is not clearly understood. Read More

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F3RNet: full-resolution residual registration network for deformable image registration.

Int J Comput Assist Radiol Surg 2021 May 3. Epub 2021 May 3.

Brigham and Women's Hospital, Harvard Medical School, Boston, 02115, USA.

Purpose: Deformable image registration (DIR) is essential for many image-guided therapies. Recently, deep learning approaches have gained substantial popularity and success in DIR. Most deep learning approaches use the so-called mono-stream high-to-low, low-to-high network structure and can achieve satisfactory overall registration results. Read More

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The acyl chains of phosphoinositide PIP3 alter the structure and function of nuclear receptor Steroidogenic Factor-1 (NR5A1).

J Lipid Res 2021 Apr 29:100081. Epub 2021 Apr 29.

Vanderbilt University School of Medicine, Dept. of Pharmacology, Nashville, TN 37232; Vanderbilt University Medical Center, Dept. of Medicine, Division of Diabetes, Endocrinology and Metabolism; and the Vanderbilt Diabetes Research and Training Center, Nashville, TN 37232; Vanderbilt University Genomic Medicine Training Program, Nashville, TN 37232; Vanderbilt University School of Medicine, Dept. of Biochemistry, Nashville, TN 37232; Vanderbilt University Center for Structural Biology, Nashville, TN 37232. Electronic address:

Nuclear receptors are transcription factors that bind lipids, an event that induces a structural conformation of the receptor that favors interaction with transcriptional coactivators. The nuclear receptor Steroidogenic Factor-1 (SF-1, NR5A1) binds the signaling phosphoinositides PI(4,5)P2 (PIP2) and PI(3,4,5)P3 (PIP3), and our previous crystal structures showed how the phosphoinositide headgroups regulate SF-1 function. However, what role the acyl chains play in regulating SF-1 structure remains unaddressed. Read More

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Comorbidity patterns in people with multiple sclerosis: A latent class.

Eur J Neurol 2021 Apr 30. Epub 2021 Apr 30.

Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, 7000, Australia.

Objective: To identify clinically meaningful comorbidity patterns and their associations with the demographics/clinical characteristics of people with Multiple Sclerosis (MS).

Study Design And Setting: We conducted latent class analysis to identify clinically distinct comorbidity patterns in MS using the 15 most common comorbidities among 1,518 Australian MS Longitudinal Study participants. The associations between demographics/clinical characteristics and comorbidity patterns were examined using log-binomial and multinomial logistic regression. Read More

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Vertical Bite Rehabilitation of Severely Worn Dentitions with Direct Composite Restorations: Clinical Performance up to 11 Years.

J Clin Med 2021 Apr 16;10(8). Epub 2021 Apr 16.

Department of Conservative and Preventive Dentistry, Center for Dental Medicine, University of Zurich, 8032 Zurich, Switzerland.

Our aim was to evaluate the clinical performance of direct composite restorations placed in patients with severely worn dentitions at an increased vertical dimension of occlusion, after up to 11 years. One hundred and sixty-four teeth in 13 patients with severely worn dentitions had been reconstructed with either microhybrid (first cohort; = 59) or nanofilled (second cohort; = 105) composite restorations at increased vertical dimension of occlusion using a wax-up-based template-aided placement technique. From the dental records, information about repair and replacement of restorations was obtained. Read More

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Clinically Relevant Concentrations of Polymyxin B and Meropenem Synergistically Kill Multidrug-Resistant and Minimize Biofilm Formation.

Antibiotics (Basel) 2021 Apr 8;10(4). Epub 2021 Apr 8.

Infection and Immunity Program, Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.

The emergence of antibiotic resistance has severely impaired the treatment of chronic respiratory infections caused by multidrug-resistant (MDR) . Since the reintroduction of polymyxins as a last-line therapy against MDR Gram-negative bacteria, resistance to its monotherapy and recurrent infections continue to be reported and synergistic antibiotic combinations have been investigated. In this study, comprehensive in vitro microbiological evaluations including synergy panel screening, population analysis profiling, time-kill kinetics, anti-biofilm formation and membrane damage analysis studies were conducted to evaluate the combination of polymyxin B and meropenem against biofilm-producing, polymyxin-resistant MDR . Read More

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Trans-bronchial lung cryobiopsy in patients at high-risk of complications.

BMC Pulm Med 2021 Apr 26;21(1):135. Epub 2021 Apr 26.

Department of Pneumology, Hôpital Erasme, Université libre de Bruxelles, 808 route de Lennik, 1070, Brussels, Belgium.

Background: The surgical lung biopsy (SLB) is the recommended sampling technique when the pathological analysis of the lung is required in the work-up of an interstitial lung disease (ILD) but trans-bronchial lung cryobiopsy (TBLC) is increasingly recognized as an alternative approach. As TBLCs have lower mortality and morbidity risks than SLB, this study aimed to investigate the safety of TBLCs in patients at higher risk of complications and for whom SLB was not considered as an alternative.

Method: This prospective study was conducted in two hospitals in which TBLCs were performed in patients with body mass index (BMI) > 35, and/or older than 75 years, and/or with severely impaired lung function (FVC < 50% or DLCO < 30%), and/or systolic pulmonary artery pressure > 45 mmHg, and/or a clinically significant cardiac disease. Read More

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Relationship between sodium removal, hydration and outcomes in peritoneal dialysis patients.

Nephrology (Carlton) 2021 Apr 23. Epub 2021 Apr 23.

Departments of Renal Medicine and Transplantation, Barts Health NHS Trust, London, United Kingdom.

Background: Fluid overload (FO) in peritoneal dialysis (PD) patients is associated with mortality. We explore if low daily sodium removal is an independent risk factor for mortality. We examined severely FO PD patients established for >1 year in expectation that PD prescription would have been optimized for solute clearance and ultrafiltration. Read More

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Hysterectomy via vaginal Natural Orifice Transluminal Endoscopic Surgery in virgin patients: a first feasibility study.

J Obstet Gynaecol 2021 Apr 23:1-6. Epub 2021 Apr 23.

Department of Gynaecology and Obstetrics, Imelda Hospital, Bonheiden, Belgium.

Vaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) is a minimally invasive, scar-free technique that uses a vaginal colpotomy to access the peritoneal cavity. Hysterectomy via vNOTES has shown to be technically feasible and safe, with shorter hospital stay and lower postoperative pain scores. Moreover, vNOTES adds the advantages of endoscopy to those of vaginal surgery and thereby broadens the indications of a conventional vaginal hysterectomy. Read More

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Effect of Cytokine Adsorption on Survival and Circulatory Stabilization in Patients Receiving Extracorporeal Cardiopulmonary Resuscitation.

ASAIO J 2021 Apr 19. Epub 2021 Apr 19.

From the Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Germany Heidelberg Institute of Global Health, University of Heidelberg, Heidelberg, Germany Department of Cardiovascular Surgery, Heart Center Freiburg University, University of Freiburg, Freiburg, Germany Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, USA.

Even after the introduction of extracorporeal cardiopulmonary resuscitation (ECPR), survival after cardiac arrest remains poor. Excess release of vasoactive cytokines may be a reason for cardiovascular instability and death after ECPR. Recently, an extracorporeal cytokine adsorption device (CytoSorb) to reduce elevated levels of circulating cytokines has been introduced. Read More

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Successful Management of Refractory Torsades De Pointes Due to Drug-Induced Long QT Syndrome Guided by Point-of-Care Monitoring of Ionized Magnesium.

Cureus 2021 Mar 17;13(3):e13939. Epub 2021 Mar 17.

Department of Anesthesiology, Saitama Medical Center, Saitama Medical University, Kawagoe, JPN.

Ionized magnesium (iMg) is the physiologically active fraction, although total magnesium (tMg) is often used clinically because a dedicated electrode is required to measure the iMg concentration. The tMg concentration is not correlated with the iMg concentration, especially in severely ill patients. In this report, a case of refractory torsades de pointes (TdP) due to drug-induced long QT syndrome was successfully treated with high-dose magnesium sulfate guided by point-of-care monitoring of the iMg concentration. Read More

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Fat Embolism Syndrome - A Qualitative Review of its Incidence, Presentation, Pathogenesis and Management.

Malays Orthop J 2021 Mar;15(1):1-11

Department of Trauma and Orthopaedics, Galway University Hospitals, Galway, Ireland.

Fat Embolism Syndrome (FES) is a poorly defined clinical phenomenon which has been attributed to fat emboli entering the circulation. It is common, and its clinical presentation may be either subtle or dramatic and life threatening. This is a review of the history, causes, pathophysiology, presentation, diagnosis and management of FES. Read More

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Homozygous Familial Hypercholesterolemia.

J Atheroscler Thromb 2021 Apr 18. Epub 2021 Apr 18.

Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center Research Institute.

Familial hypercholesterolemia (FH) is an inherited disorder with retarded clearance of plasma LDL caused by mutations of the genes involved in the LDL receptor-mediated pathway and most of them exhibit autosomal dominant inheritance. Homozygotes of FH (HoFH) may have plasma LDL-C levels, which are at least twice as high as those of heterozygous FH (HeFH) and therefore four times higher than normal levels. Prevalence of HoFH had been estimated as 1 in 1,000,000 before but more recent genetic analysis surveys predict 1 in 170,000 to 300,000. Read More

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Fractionated radiation severely reduces the number of CD8 T cells and mature antigen presenting cells within lung tumors.

Int J Radiat Oncol Biol Phys 2021 Apr 15. Epub 2021 Apr 15.

Laboratory of Molecular and Cellular Therapy (LMCT), Department of Biomedical Sciences, Vrije Universiteit Brussel, Brussels, Belgium. Electronic address:

Purpose: The combination of standard-of-care radiotherapy (RT) with immunotherapy is moving to the mainstream of non-small cell lung cancer (NSCLC) treatment. Multiple preclinical studies reported on the CD8 T cell stimulating properties of RT, resulting in abscopal therapeutic effects. A literature search demonstrates that most preclinical lung cancer studies applied subcutaneous lung tumor models. Read More

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Screening of PCSK9 and LDLR genetic variants in Familial Hypercholesterolemia (FH) patients in India.

J Hum Genet 2021 Apr 16. Epub 2021 Apr 16.

Department of Laboratory Medicine, P. D Hinduja Hospital & Medical Research Centre, Mumbai, India.

Familial Hypercholesterolemia (FH) is an autosomal, dominant, inherited disorder characterized by severely elevated LDL-cholesterol (LDL-C) levels with high risk for Coronary Artery Disease (CAD). There are limited genetic studies especially on genes other than Low Density Lipoprotein receptor (LDLR) conducted in Indian population. Thus, our aim was to screen the entire Proprotein Convertase Subtilisin/Kexin type 9 gene (PCSK9) gene & hotspot exons 3, 4 and 9 of LDLR gene in FH cases and controls. Read More

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Assessing Personality Pathology Response Sets in Perpetrators of Intimate Partner Violence.

J Interpers Violence 2021 Apr 16:8862605211001482. Epub 2021 Apr 16.

University of Southern Denmark, Campusvej 55, Odense M, Denmark.

Self-report personality inventories may be useful in directing perpetrators of intimate partner violence (IPV) to appropriate intervention programs. They may also have predictive capabilities in assessing the likelihood of desistance or persistence of IPV. However, validity problems are inherent in self-report clinical tools, particularly in forensic settings. Read More

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A novel dentin bonding scheme based on extrafibrillar demineralization combined with covalent adhesion using a dry-bonding technique.

Bioact Mater 2021 Oct 23;6(10):3557-3567. Epub 2021 Mar 23.

National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, China.

Dentin bonding is a dynamic process that involves the penetration of adhesive resin monomers into the extrafibrillar and intrafibrillar demineralized collagen matrix using a wet-bonding technique. However, adhesive resin monomers lack the capacity to infiltrate the intrafibrillar space, and the excess water that is introduced by the wet-bonding technique remains at the bonding interface. This imperfectly bonded interface is inclined to hydrolytic degradation, severely jeopardizing the longevity of bonded clinical restorations. Read More

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October 2021

Relationship of physical function with quality of life in older patients with acute heart failure.

J Am Geriatr Soc 2021 Apr 10. Epub 2021 Apr 10.

Section of Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States.

Background: Older patients with acute decompensated heart failure (ADHF) have severely impaired physical function (PF) and quality of life (QOL). However, relationships between impairments in PF and QOL are unknown but are relevant to clinical practice and trial design.

Methods: We assessed 202 consecutive patients hospitalized with ADHF in the multicenter Rehabilitation Therapy in Older Acute HF Patients (REHAB-HF) Trial. Read More

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Over three decades of natural history of limb girdle muscular dystrophy type R1/2A and R2/2B: Mathematical modelling of a multifactorial study.

Neuromuscul Disord 2021 Feb 27. Epub 2021 Feb 27.

Scientific Institute IRCCS E. Medea, NeuroMuscular Unit, Bosisio Parini, LC, Italy.

We aimed to describe the natural history of Limb Girdle Muscular Dystrophy type 2A and 2B over more than three decades by considering muscular strength, motor, cardiac and respiratory function. 428 visits of nineteen 2A and twenty 2B patients were retrospectively analysed through a regression model to create the curves of evolution with disease duration of muscle strength (through Medical Research Council grading), motor function measure scale (D1, D2 and D3 domains) and cardio-pulmonary function tests. Clinically relevant muscular and motor function alterations occurred after the first decade of disease, while mild respiratory function alterations started after the second, with preserved cardiac function. Read More

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February 2021

High prevalence and mortality due to Histoplasma capsulatum in the Brazilian Amazon: An autopsy study.

PLoS Negl Trop Dis 2021 Apr 5;15(4):e0009286. Epub 2021 Apr 5.

ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.

Background: Histoplasmosis is acquired by inhalation of spores of the dimorphic fungus Histoplasma spp. Although this pathogen is distributed worldwide, it is more prevalent in the Americas. However, the real burden of histoplasmosis remains undefined in many endemic regions. Read More

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Bioengineering Clinically Relevant Cardiomyocytes and Cardiac Tissues from Pluripotent Stem Cells.

Int J Mol Sci 2021 Mar 16;22(6). Epub 2021 Mar 16.

ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, University of Wollongong, Wollongong 2500, Australia.

The regenerative capacity of cardiomyocytes is insufficient to functionally recover damaged tissue, and as such, ischaemic heart disease forms the largest proportion of cardiovascular associated deaths. Human-induced pluripotent stem cells (hiPSCs) have enormous potential for developing patient specific cardiomyocytes for modelling heart disease, patient-based cardiac toxicity testing and potentially replacement therapy. However, traditional protocols for hiPSC-derived cardiomyocytes yield mixed populations of atrial, ventricular and nodal-like cells with immature cardiac properties. Read More

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First Case of Autochthonous Equine Theileriosis in Austria.

Pathogens 2021 Mar 4;10(3). Epub 2021 Mar 4.

Department of Pathobiology, Institute of Parasitology, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.

A 23-year-old pregnant warmblood mare from Güssing, Eastern Austria, presented with apathy, anemia, fever, tachycardia and tachypnoea, and a severely elevated serum amyloid A concentration. The horse had a poor body condition and showed thoracic and pericardial effusions, and later dependent edema and icteric mucous membranes. Blood smear and molecular analyses revealed an infection with . Read More

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Serial Ultrasonographic and Real-Time Elastosonographic Assessment of the Ovine Common Calcaneal Tendon, after an Experimentally Induced Tendinopathy.

Vet Sci 2021 Mar 25;8(4). Epub 2021 Mar 25.

Scuola di Bioscienze e Medicina Veterinaria, Università degli studi di Camerino, UO di Chirurgia, 62024 Matelica, Italy.

Real-time elastosonography (RTE) is a recently described, non-invasive, ultrasonographic technique developed to assess tissue elasticity. The main aim of this study was to investigate the ultrasonographic and elastosonographic appearance of the common calcaneal tendon (CCT) in an ovine model, and to monitor the progression of tendon healing after an experimentally-induced tendinopathy. Sound tendons were initially evaluated (T) with a caliper and by a single operator with ultrasound. Read More

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Spectral analysis of severely overlapping spectra based on newly developed mathematical filtration techniques and ratio spectra manipulations: An application to the concurrent determination of dapoxetine and sildenafil in combined dosage form.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jul 19;255:119715. Epub 2021 Mar 19.

Pharmaceutical Chemistry Department, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt. Electronic address:

Background: Dapoxetine hydrochloride (DAP) and sildenafil citrate (SIL) have proven clinically effective in the treatment of comorbid conditions like erectile dysfunction and premature ejaculation. The analysis of DAP and SIL combinations represents a challenge because of the severe overlap of these compounds' spectra. Six newly developed methods were proven effective for resolving such a challenging overlap. Read More

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Insomnia in adults with cystic fibrosis: strong association with anxiety/depression and impaired quality of life.

BMC Pulm Med 2021 Apr 1;21(1):108. Epub 2021 Apr 1.

Service Des Maladies Respiratoires, CHU Reims, 45, Rue Cognacq Jay Reims Cedex, 51092, Reims, France.

Background: While sleep disruption is a common complaint among children with cystic fibrosis (CF), only a few studies have investigated insomnia in adults. The aim of this study was to identify factors associated with insomnia in clinically stable adult CF patients.

Methods: Twenty-eight CF patients (18M/10F), with a median age of 27 (22-34) (median (interquartile range) years and a median of forced expiratory volume in one second of 72 (39-93) % predicted completed questionnaires on insomnia (Insomnia Severity Index, ISI), sleep quality (PSQI), daytime sleepiness (Epworth), restless legs syndrome (IRLS), pain (NRS), anxiety/depression (HAD) and quality of life (CFQ-R 14+). Read More

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