The interplay of rheumatoid arthritis and osteoporosis: exploring the pathogenesis and pharmacological approaches.

Rheumatoid arthritis (RA) and osteoporosis are two chronic disorders that are often seen together. RA is an autoimmune disorder that causes pain and inflammation in the joints, while osteoporosis is a disorder in which the bones become weak and fragile. Risk factors for bone loss in RA include disease activity, longer disease duration, erosive disease, autoantibody positivity, and joint damage leading to impaired physical activity. Recent research has shown that there is a complex interplay between immune cells, cytokines, and bone remodeling processes in both RA and osteoporosis. The bone remodeling process is regulated by cytokines and immune system signaling pathways, with osteoclasts activated through the RANK/RANKL/OPG pathway and the Wnt/DKK1/sclerostin pathway. Understanding these mechanisms can aid in developing targeted therapies for treatment of osteoporosis in RA patients. Current pharmacological approaches include anti-osteoporotic drugs such as bisphosphonates, denosumab, teriparatide, abaloparatide, raloxifene, and romosozumab. Conventional disease-modifying antirheumatic drugs such as methotrexate and biologicals including TNF inhibitors, IL-6 inhibitors, rituximab, and abatacept lower disease activity in RA and can improve bone metabolism by reducing inflammation but have limited impact on bone mineral density. This review will shed light on the relationship between osteoporosis and rheumatoid arthritis as well as the various factors that influence the onset of osteoporosis in RA patients. We also explore several treatment approaches to effectively managing osteoporosis in RA patients.

Sequelae of carbide-related thermo-chemical injury: A retrospective analysis.

Purpose: To describe the outcomes of eyes with calcium carbide (CaC2)-related thermo-chemical injury. Methods: This study included 28 eyes of 23 patients who presented with calcium carbide-related ocular burns. Only patients with more than three months of follow-up were included. Group A included 16 eyes with Dua's Grade I-III burns, while Group B included 12 eyes with Grade IV-VI burns. Electronic medical records were reviewed to provide data on the etiology of burn, presenting clinical signs and visual acuity, sequelae, and surgical interventions performed, both in the acute and chronic phases. Results: The overall mean age was 28.48 ± 11.8 years. Fifteen patients were injured while using carbide to create an explosion to scare away animals on farms. The median presenting BCVA (best-corrected visual acuity) in Group A (20/160) was significantly better than in Group B [(20/2000) (P = 0.002)]. Five eyes in Group A and one eye in Group B underwent medical management. There was no difference in the duration of follow-up for both groups (P = 0.24). The median final BCVA in Group A (20/32) was significantly better than in Group B [(20/200) (P = 0.02)]. Two eyes in Group A and nine eyes in Group B developed LSCD. Two eyes in Group B were phthisical at the last visit. Conclusion: Calcium carbide-related ocular injuries can result in significant visual morbidity in young adults. Early presentation and management may improve outcomes. Prevention of these injuries by increasing awareness and increasing advocacy efforts is necessary.

An Overview of the Pathophysiological Mechanisms of 3-Nitropropionic Acid (3-NPA) as a Neurotoxin in a Huntington's Disease Model and Its Relevance to Drug Discovery and Development.

Animal models are used to better understand the various mechanisms involved in the pathogenesis of diseases and explore potential pathways that will aid in discovering therapeutic targets. 3-Nitropropionic Acid (3-NPA) is a neurotoxin used to induce Huntington's disease (HD)-like symptoms in experimental animals. The 3-NPA is a fungus toxin that impairs the complex II (succinate dehydrogenase) activity of the mitochondria and reduces ATP synthesis, leading to excessive production of free radicals resulting in the degeneration of GABAergic medium spiny neurons (MSNs) in the striatum. This is characterized by motor impairments a key clinical manifestation of HD. 3-NPA has the potential to alter several cellular processes, including mitochondrial functions, oxidative stress, apoptosis, and neuroinflammation mimicking HD-like pathogenic conditions in animals. This review strives to provide a new insight towards the 3-NPA induced molecular dysfunctioning in developing an animal model of HD. Moreover, we summarise several preclinical studies that support the use of the 3-NPA-induced models for drug discovery and development in HD. This review is a collection of various articles that were published from 1977 to 2022 on Pubmed (1639), Web of Science (2139), and Scopus (2681), which are related to the 3-NPA induced animal model.

Use of Ethylenediaminetetraacetic Acid in Chronic Calcium-Based Chemical Injury.

PURPOSE: This study presents the successful management of a patient with chronic chemical-based injury using ethylenediaminetetraacetic acid (EDTA) chelation. METHODS: This is a case report of a 59-year-old man who presented to us 2 months after a bilateral, accidental, ocular injury with lime particles at his workplace. RESULTS: The patient was initially managed with extensive debridement and amniotic membrane grafting for both eyes. At 4-month follow-up, the left eye appeared to have extensive calcium-based plaques. 0.02N EDTA chelation was performed for his left eye. Postchelation, the visual acuity improved to 20/800. At 1-week follow-up, a repeat EDTA chelation was performed. The corneal clarity improved further, and the patient recovered a visual acuity of 20/200. CONCLUSIONS: EDTA chelation in the setting of calcium deposition in the chronic phase of chemical injuries can be reasonably effective.

Carbide Gun-Related Ocular Injuries: A Case Series.

PURPOSE: The purpose of this study was to report a case series of sight-threatening ocular injuries caused by calcium carbide guns used as fire crackers. METHODS: Medical records of 15 eyes of 14 patients with ocular injuries caused while using carbide guns, visiting the Institute, from January 2021 to January 2022, were retrospectively reviewed. The collected data included patients' demography (age, sex), presenting ophthalmic features, management, and outcome. Grade I and II ocular injuries were managed medically. All grade III-V injuries were managed using Amniotic Membrane Transplantation. RESULTS: All patients were male. The mean age of the patients was 23.57 ± 11.76 years. According to the Dua classification, 5 eyes (33.3%) had Grade I-II ocular surface burns, 3 eyes (20%) had grade III burns, and 7 eyes (46.6%) had grade IV-VI burns. Presenting visual acuity ranged between hand movements to 20/50, and in 6 eyes (40%), the visual acuity was ≤20/200. Five eyes were managed medically alone, and 10 (66.6%) eyes needed surgical intervention (Amniotic Membrane Transplantation). After a mean follow-up of 14.23 ± 11.92 weeks, complete epithelization was seen in 10 eyes (66.6%). Partial limbal stem cell deficiency and its sequelae such as conjunctivalization of the cornea were noted in 7 eyes (46.6%). CONCLUSIONS: Calcium carbide-related ocular injuries can result in corneal blindness secondary to limbal stem cell deficiency in young individuals. Loss of vision in this age group can lead to loss of economic productivity and cosmetic disfigurement. More advocacy efforts are thus needed to prevent these injuries.

Do farmers value rice varieties tolerant to droughts and floods? Evidence from a discrete choice experiment in Odisha, India.

Abiotic stresses such as droughts and floods significantly constrain rice production in India. New stress tolerant technologies have the potential to reduce yield variability and help insulate farmers from the risks posed by these hazards. Using discrete choice experiments conducted in rural Odisha, we estimate farmers' valuation for drought-tolerant (DT) and submergence-tolerant (SubT) traits embodied in rice cultivars. Our results demonstrate that farmers in both drought-prone as well as submergence prone regions value reduction in yield variability offered by new, stress-tolerant cultivars, and would generally be willing to pay a significant premium for these traits. While virtually all farmers perceive the threat of drought and are willing to pay for protection against drought risk, only farmers in flood-prone areas would be willing to pay for rice that can withstand being submerged for prolonged periods, suggesting the potential for market segmentation along geographical or ecological lines.