CNTF Mediates Neurotrophic Factor Secretion and Fluid Absorption in Human Retinal Pigment Epithelium

Ciliary neurotrophic factor (CNTF) protects photoreceptors and regulates their phototransduction machinery, but little is known about CNTF's effects on retinal pigment epithelial (RPE) physiology. Therefore, we determined the expression and localization of CNTF receptors and the physiological consequence of their activation in primary cultures of human fetal RPE (hfRPE). Cultured hfRPE express CNTF, CT1, and OsM and their receptors, including CNTFRα, LIFRβ, gp130, and OsMRβ, all localized mainly at the apical membrane. Exogenous CNTF, CT1, or OsM induces STAT3 phosphorylation, and OsM also induces the phosphorylation of ERK1/2 (p44/42 MAP kinase). CNTF increases RPE survivability, but not rates of phagocytosis. CNTF increases secretion of NT3 to the apical bath and decreases that of VEGF, IL8, and TGFβ2. It also significantly increases fluid absorption (JV) across intact monolayers of hfRPE by activating CFTR chloride channels at the basolateral membrane. CNTF induces profound changes in RPE cell biology, biochemistry, and physiology, including the increase in cell survival, polarized secretion of cytokines/neurotrophic factors, and the increase in steady-state fluid absorption mediated by JAK/STAT3 signaling. In vivo, these changes, taken together, could serve to regulate the microenvironment around the distal retinal/RPE/Bruch's membrane complex and provide protection against neurodegenerative disease

Efficacy and Safety of Naproxen Gel in Musculoskeletal Pain Management: A Prospective Cohort Study

Introduction: Naproxen is effective for various musculoskeletal conditions and has a longer half-life, making it a favourable choice for sustained relief. Additionally, there is a potential unmet need for guidelines on the usage of topical Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in the Asia-Pacific region. A study on naproxen 10% gel aims to address this need and increase awareness of its therapeutic potential in the region. Aim: To assess the efficacy and safety of naproxen 10% gel in relieving pain associated with lower back, knee, cervical, synovitis, bursitis, muscle sprain, and tendinitis. Materials and Methods: This prospective, cohort, observational, open-label, single-arm, multicentric study was conducted at 458 centres in India, including Ahmedabad, Bengaluru, Chandigarh, Chennai, Delhi, Guwahati, Hyderabad, Indore, Jaipur, Kolkata, Lucknow, Meerut, Mumbai, Patna, and Pune, between February 2023 and May 2023. The data was collected from outpatient settings/clinics of orthopaedicians and clinicians who have been prescribing topical naproxen 10% gel to their patients. The study included patients aged 18 to 60 years of either sex who were suffering from back pain, muscle pain, sprains, frozen shoulder, arthritis, acute low back ache (non-specific), or pain. The data was captured during the scheduled follow-up visits planned by the treating clinician, with data recorded at 3, 5, 10, and 15 days. At the baseline visit, demographic details (age, sex, weight, height, body mass index, and symptoms), Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale score, pain intensity on movement score, Visual Analogue Scale (VAS), and overall pain score were obtained. Results: Out of 10,587 patients, 10,265 completed the present study. The majority of patients had lower back pain (n=3386, 32.99%) and knee pain (n=3184, 31.02%). The average pain intensity on movement score of patients with bursitis significantly decreased from the baseline to 15 days {mean change {95% Confidence Interval (CI)}: 6.04 (5.89, 6.20); p<0.001}. Post-naproxen treatment, the average pain intensity, WOMAC pain score, VAS, and overall pain score significantly decreased from baseline to day 15 in patients with knee pain and lower back pain. A significant improvement in WOMAC, WOMAC pain (5.42 vs 17.98), WOMAC stiffness (1.49 vs 5.75), and WOMAC physical function score (18.93 vs 56.21) at day 15 was observed in patients with a muscle sprain. Adverse Events (AE) were reported in 173 (1.69%) patients overall, with dryness (n=125) being the most common, followed by erythema (n=20) and pruritus (n=17). Conclusion: Naproxen 10% gel is an effective topical treatment for lower back pain, knee pain, cervical pain, synovitis, bursitis, muscle sprain, and tendinitis. It could prove helpful in patients where the side-effects of oral NSAIDs are to be avoided

Cosmos: An SDL Based Hardware/Software Codesign Environment

International audienceThe goal of this chapter is to introduce COSMOS, a methodology and an environment for the specification and synthesis of mixed systems composed of hardware (HW) and software (SW) starting from system level specifications. The application domain aimed at is communicating heterogeneous systems. The description model used permits an efficient manipulation of complex communication protocol. The resulting target is a mixed architecture that can be either a circuit, a card or a network of distributed processors. The current version of the COSMOS project provides a model for the representation of systems as well as basic primitives for synthesis at the system level. It allows a semi-automatic synthesis starting from system level specifications on an heterogeneous architecture. The ongoing work consists of a study and realisation of systematic partitioning strategies and efficient methods for the estimation and synthesis of communication. The principal choices of languages, representation models and architectures very much favour the design of telecommunication systems. COSMOS uses the SDL (ITU standard) language for the system specification. The result of partitioning and communication synthesis is an executable model of an heterogeneous architecture described in C (ANSI standard) and VHDL (IEEE standard) languages. The COSMOS environment is built around an intermediate format, called SOLAR, designed to facilitate the migration between systems specifications and hardware descriptions. SOLAR permits representation of high level concepts using the hardware semantics. The model is general containing an extended finite state machine and a powerful communication model

Pesticide Residues

METHODOLOGY for residue analysis has advanced rapidly during the current review period, from November 1962 through October 1964. Notable progress has been made in the development and refinement of methods of analysis by which any or all of a large number of pesticide residue chemicals can be detected and measured in one general operation. This is of particular significance because great interest has developed-outside the scientific community as well as within - in the possible presence of pesticide chemicals in all parts of our environment, including man himself. Only by the use of improved methodology will it be possible to accomplish the task of detecting, identifying, and measuring the many possible residual pesticide chemicals. It is only after the presence or absence of these chemicals in any part of our environment has been proved unequivocally that the medical man, the lawyer, the lawmaker, the administrators in government and in industry, and other interested groups can assess the significance of such residues. There are 300 to 400 chemicals registered for use on food products alone, and a few hundred more are registered for other uses whereby they may become part of our environment. The chemist cannot know which of the hundreds of possible pesticide chemical residues to look for in samples of air, water, soil, plants, human and animal tissues, prepared foods, etc. There is an urgent need for general procedures that can identify and measure a large number of chemicals at one time. They must be highly sensitive and accurate, since it is essential that all monitoring of our environment be at a level considerably below any tolerance or otherwise critical level, so that trends can be more readily recognized and assessed for significance. Upward or downward trends in any portion of our environment will be recognizable only when the methodology becomes sufficiently sensitive and accurate so that analyses in the fraction-of-a-part-per-million or even part-per-billion range become routinely dependable (Fischbach, H. Pub. 1082, National Research Council, p. 55, Nov. 29,1962)