Search

Lavinia Davidescu,1 Grigoriy Ursol,2 Oleksii Korzh,3 Vikranth Deshmukh,4 Lesia Kuryk,5 Monja-Marie Nortje,6 Olga Godlevska,3 Gilles Devouassoux,7 Eduard Khodosh,8 Elliot Israel,9,10 Alain Moussy,11 Colin D Mansfield,11 Olivier Hermine,11– 13 Pascal Chanez14 1Department of Pulmonology, University of Oradea, Oradea, Romania; 2Medical and Diagnostic Center of Private Enterprise of Private Production Company “Acinus”, Kropyvnytskyi, Ukraine; 3Department of General Practice - Family Medicine, Kharkiv Medical Academy of Postgraduate Education, Kharkiv, Ukraine; 4Department of Pulmonary Medicine, Respira Hospital, Nagpur, Maharashtra, India; 5National Institute of Phthisiology and Pulmonology Named After F.G. Yanovsky of National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine; 6Moriana Clinical Research, Brandfort, South Africa; 7Department of Pulmonology, Hôpital de la Croix Rousse, GHN, HCL and Université Claude Bernard Lyon 1, Lyon, France; 8Department of Pulmonology, Municipal Nonprofit Enterprise, City Clinical Hospital #13, Kharkiv, Ukraine; 9Harvard Medical School, Boston, MA, USA; 10Division of Pulmonary and Critical Care Medicine and Allergy and Immunology, Brigham and Women’s Hospital, Boston, MA, USA; 11AB Science, Paris, France; 12Imagine Institute, INSERM UMR 1163 and CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implication, Hôpital Necker, Paris, France; 13Université Paris Descartes, Sorbonne Paris Cité, Paris, France; 14Clinique des Bronches, Allergie et Sommeil, APHM Hôpital Nord, C2VN Center INSERM INRAE UMR1062, Aix-Marseille Université, Marseille, FranceCorrespondence: Pascal Chanez, Clinique des Bronches, Allergie et Sommeil, APHM Hôpital Nord, C2VN Center INSERM INRAE UMR1062, Aix-Marseille Université, Marseille, France, Tel +33 6 50 71 07 05, Email Pascal.CHANEZ@univ-amu.frBackground: Masitinib is an oral tyrosine kinase inhibitor that selectively targets mast cell activity and platelet-derived growth factor receptor (PDGFR) signaling, both of which are implicated in various mechanisms of asthma pathogenesis.Objective: Assessment of masitinib as an add-on to standard maintenance therapy as compared with placebo in the treatment of oral corticosteroid-dependent severe asthma.Methods: We conducted a randomized (2:1), placebo-controlled study of masitinib (6 mg/kg/d) in adults with severe asthma uncontrolled by high dose inhaled corticosteroids and long-acting beta-adrenoreceptor agonists plus oral corticosteroids (OCS) (≥ 7.5 mg/d). No minimum baseline blood eosinophil count was specified. Following a protocol amendment, the primary endpoint was reduction of annualized severe asthma exacerbation rate adjusted for the overall time on treatment (SAER). Subgroup analysis according to yearly cumulative OCS intake was also performed, a higher OCS dose indicating more severe asthma that is harder to control.Results: Following an average exposure of approximately 13 months, masitinib (n = 240) reduced the SAER by 35% relative to placebo (n = 115) (rate ratio (RR) 0.65 (95% CI [0.47– 0.90]; P = 0.010)). For patients with eosinophil ≥ 150 cell/μL, masitinib (n = 181) reduced SAER by 38% relative to placebo (n = 87); RR 0.62 (95% CI [0.42– 0.91]; P = 0.016). Benefit of masitinib was shown to increase in the most severely affected patients (OCS intake of > 1000 mg/year), with a significant (P < 0.01) reduction in SAER of 50%– 70%. Safety was consistent with the known masitinib profile.Conclusion: Orally administered masitinib reduces the risk of asthma exacerbations in severe asthma patients, with an acceptable safety profile. Masitinib may potentially provide a new treatment option for oral corticosteroid-dependent severe asthma.Keywords: asthma clinical trials, asthma medication, mast cells, tyrosine kinases, severe asthma

Pradeep Talwalkar,1 Vaishali Deshmukh,2 Milind Bhole3 1Endocrinology, Talwalkar Diabetes Clinic, Mumbai, India; 2Endocrinology, Shree Hospital, Pune, India; 3Medical Affairs, Abbott India Ltd, Mumbai, India Purpose: To determine the prevalence of hypothyroidism in patients with type 2 diabetes mellitus (T2DM), hypertension, and both T2DM and hypertension (T2DM + hypertension) in India. Patients and methods: In this cross-sectional observational study, adult patients with an established or newly diagnosed T2DM, hypertension, and T2DM + hypertension who were visiting their physicians for a routine clinical checkup were enrolled across 29 sites in India. All the patient-related data were extracted from their medical records. The prevalence of hypothyroidism was evaluated by thyroid function test (levels of serum free thyroxine, free triiodothyronine, and thyroid-stimulating hormone [TSH]). The proportion of obese and overweight hypothyroid patients and dose of thyroxine in overt and subclinical hypothyroidism (SCH) cases (as per TSH values) were assessed during the study. The results were summarized by descriptive statistics. Results: A total of 1,508 patients (T2DM: 504; hypertension: 501; T2DM + hypertension: 503) were enrolled in the study. The prevalence of hypothyroidism in patients with T2DM, hypertension, and T2DM + hypertension was 24.8%, 33.5%, and 28.9%, respectively. The overall prevalence of hypothyroidism in T2DM (n=1,002) and hypertension (n=1,001) was 26.9% and 31.2%, respectively. The proportion of obese against overweight hypothyroid patients was higher in all indications (T2DM: 16.5% vs 3.4%; hypertension: 23.8% vs 5.4%; T2DM + hypertension: 21.5% vs 3.8%). A considerable proportion of patients with SCH was prescribed thyroxine in T2DM (61.5%), hypertension (61%), and T2DM + hypertension (62.5%) cases. The most commonly prescribed dose (mean) of thyroxine was 50 and 25 µg for overt hypothyroidism and SCH cases, respectively, in all cohorts. Conclusion: There is a high (>20%) prevalence of hypothyroidism in patients with T2DM, hypertension, and T2DM + hypertension. Screening for hypothyroidism should be routinely considered for early diagnosis and effective management. Keywords: hypertension, hypothyroidism, prevalence, type 2 diabetes mellitus

ObjectivesOsteoarthritis (OA) is a degenerative disease characterized by loss of cartilage and increased subchondral bone within synovial joints. Wnt signaling affects the pathogenesis of OA as this pathway modulates both the differentiation of osteoblasts and chondrocytes, and production of catabolic proteases. A novel small-molecule Wnt pathway inhibitor, SM04690, was evaluated in a series of in vitro and in vivo animal studies to determine its effects on chondrogenesis, cartilage protection and synovial-lined joint pathology.DesignA high-throughput screen was performed using a cell-based reporter assay for Wnt pathway activity to develop a small molecule designated SM04690. Its properties were evaluated in bone-marrow-derived human mesenchymal stem cells (hMSCs) to assess chondrocyte differentiation and effects on cartilage catabolism by immunocytochemistry and gene expression, and glycosaminoglycan breakdown. In vivo effects of SM04690 on Wnt signaling, cartilage regeneration and protection were measured using biochemical and histopathological techniques in a rodent acute cruciate ligament tear and partial medial meniscectomy (ACLT + pMMx) OA model.ResultsSM04690 induced hMSC differentiation into mature, functional chondrocytes and decreased cartilage catabolic marker levels compared to vehicle. A single SM04690 intra-articular (IA) injection was efficacious in a rodent OA model, with increased cartilage thickness, evidence for cartilage regeneration, and protection from cartilage catabolism observed, resulting in significantly improved Osteoarthritis Research Society International (OARSI) histology scores and biomarkers, compared to vehicle.ConclusionsSM04690 induced chondrogenesis and appeared to inhibit joint destruction in a rat OA model, and is a candidate for a potential disease modifying therapy for OA.

This article is devoted to the study of Kaluza-Klein space-time filled with cosmic string and attractive massive scalar field in the presence of minimally interacting dark energy in general relativity. Some physically significant conditions have been utilized to obtain a deterministic solution of the field equations. The behavior of cosmological parameters such as volume, scalar field, deceleration parameter, equation of state (EoS) parameter, statefinder parameter, Om diagnostic are discussed. It is also worth noting that the conclusions of the cosmological parameter are consistent with modern observational data. [ABSTRACT FROM AUTHOR]

A five-dimensional Bianchi type-III string cosmological model is studied with a onedimensional cosmic string in the presence of zero mass scalar field in the context of the Lyra manifold. Exact solutions of Einstein's field equations are obtained by assuming quadratic equation of state (EoS) of the form, where is a constant and strictly. The physical and geometrical aspects of the investigated model are analyzed in detail. [ABSTRACT FROM AUTHOR]

Rasashastra is a pharmaceutics branch of Ayurveda describing scientific methods to convert metals and minerals into bio-compatible formulations used individually or plant admixed to enhance their bioavailability and efficacy. In the present study, red ochre (Gairik) powder was processed in cow's ghee by textual method of roasting. The steps of preparation and changes in the properties therein were documented and validated in triplicate batches to develop a monograph. Ayurvedic and basic tests were performed to determine the properties of Shuddha Gairik. The physical characterization included Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD), Fourier Transform Infra-red (FT-IR), Dynamic Light Scattering (DLS) and Thermo-gravimetric Analysis (TGA). Elemental composition was estimated by titration and gravimetric analysis while heavy metal limits were assessed using Inductively Coupled Plasma Optical Emission Spectrophotometry (ICPOES). This study depicted that crude red ochre, containing Kaolinite with high iron percentage, on roasting in cow's ghee led to the formation of fatty acids adsorbed red ochre particles. The developed monograph will be a guideline to the Ayurvedic industry for precise formulation of Shuddha Gairik. This will help researchers for better understanding the importance of Ayurvedic methods of pharmaceutical preparations and carry out their mechanistic studies in various diseases. [ABSTRACT FROM AUTHOR]

In the last few years, a cluster of anatomical discoveries has been reported which overturned the long existing dogmas about the structure and function of human body. First to come was the discovery that established the existence of a lymphatic system pertaining to the central nervous system (CNS). CNS was believed to be anatomically immune privileged owing to the absence of any lymphatics and presence of the blood-brain barrier around it, but latest research has established beyond any reasonable doubt that true lymphatic channels carry immune cells in meninges thus challenging the existing theory. Studies also supported the presence of a 'Glymphatic system' (created by the perivascular spaces lined with the leptomeninges and a sheath of glial cells) in the CNS draining interstitial metabolic waste from CNS. The second discovery unraveled the previously unknown parts of the human mesentery in adult and established that it is a continuous entity all along the intra-abdominal gut tube against the previous notion that it is fragmented in the adult humans. A very recently reported third discovery demonstrated a previously unknown tissue component—'interstitium'—a networked collagen bound fluid-filled space existent in a number of human organs. All these structures bear considerable applied importance towards the pathogenesis, prognostic and diagnostic investigations and management of human diseases. This article attempts to present a brief review of all three remarkable discoveries and emphasizes their applied importance within the realm of medical sciences. [ABSTRACT FROM AUTHOR]

Background: Diabetic foot ulcers and infections are a common complication of diabetes. Holistic patient care requires dissemination of knowledge about prevention to avoid amputation and associated morbidity, early diagnosis and apt treatment. Healthcare costs of diabetic ulcers are high as complete treatment requires long term monitoring and high cost of rehabilitation in amputees. Methods: The study design is retrospective observational study. All data was retrospectively procured from the Medical Record Department. From January 2019 to December 2019, two hundred and twenty patients with diabetic foot infections who had been treated with oral or parenteral antibiotics in the previous 5 to 15 days were chosen. Results: The gram negative bacteria (88%) were most commonly isolated. Gram positive organisms contributed to 11% and candida spp. to 1% of swab culture. All patients with Staphylococci in wound swab were 100% sensitivity to vancomycin & linezolid. Teicoplanin, vancomycin, and clindamycin had 100% sensitivity against MRSA in wound swab. Patients with E. coli in wound swab had maximum sensitivity to colistin. Ceftriaxone which has been used conventionally was found less sensitive for E. coli and Klebsiella. Conclusion: Piperacillin tazobactam combination for gram negative coverage in accordance to sensitivity pattern of community acquired infection is recommended because conventionally used ceftriaxone is less sensitive. For gram positive diabetic foot ulcers/ infections which were seen to be hospital acquired, linezolid is recommended for full course.

Background: Inhalation therapy with corticosteroids and long-acting β 2 -agonists has been the mainstay of asthma management. However, choosing the correct inhaler technique is essential to effectively deliver the medication to the lungs to attain good asthma control. Objective: This study aimed to evaluate asthma control and device usability with salmeterol/fluticasone fixed-dose combination (FDC) administered through Synchrobreathe ® , a breath-actuated inhaler (BAI), in Indian patients with persistent asthma (EVOLVE study). Design: The present study was a prospective, open-label, non-comparative, multi-center, observational study. Methods: The study enrolled 490 patients with documented diagnoses of asthma who were treatment-naive or uncontrolled due to poor inhaler technique associated with a previous device. The primary endpoint was a change from baseline in the Asthma Control Questionnaire-6 (ACQ-6) score at week 12. Results: Mean ACQ-6 score reduced from 2.2 ± 1.07 (baseline) to 0.4 ± 0.49 (mean change: –1.9 ± 1.12, p