Exploring the role of circ-0091579/miR-1225-5p and circ-HIPK3/miR-338-3p axes in the pathogenesis of postmenopausal osteoporosis.

CircRNAs have been increasingly appreciated as modulators of osteoporosis. This study investigated the expression of circ-0091579 and circ-HIPK3 in PBMCs of postmenopausal women with osteopenia and osteoporosis, aiming to underline their molecular mechanisms involved in pathogenesis of the disease. Seventy patients were stratified into two groups: 35 with osteopenia and 35 with osteoporosis, along with 30 healthy controls. Expressions of circ-0091579 and circ-HIPK3, miR-1225-5p and miR-338-3p, together with NF-κB, were assessed using RT-PCR. Keap1, Nrf2, and MAFB were determined using Western blot, while RANKL, OPG, IL-1ß, and IL-6 were measured by ELISA. GSH and MDA were estimated colorimetrically. Data revealed that circ-0091579 was markedly upregulated, whereas miR-1225-5p was downregulated in patients relative to controls. Additionally, circ-HIPK3 was significantly decreased, while miR-338-3p was increased in the diseased groups. Circ-0091579 was directly correlated with RANKL/OPG, NF-κB, IL-1ß, IL-6 and MDA, while inversely correlated with miR-1225-5p, T-score, BMD and GSH. Meanwhile, circ-HIPK3 and miR-338-3p were interrelated in an opposite manner. Eventually, the interplay among these downstream players induced an imbalance in bone homeostasis, triggering osteoporosis. Notably, these circRNAs differentiated patients from controls and those with osteopenia from osteoporotic ones. Thus, they could serve as biomarkers for early detection and tracking of osteoporosis.

Strategies used to reduce harms associated with fentanyl exposure among rural people who use drugs: multi-site qualitative findings from the rural opioid initiative.

AIM: Illicitly manufactured fentanyl and its analogs are the primary drivers of opioid overdose deaths in the United States (U.S.). People who use drugs may be exposed to fentanyl or its analogs intentionally or unintentionally. This study sought to identify strategies used by rural people who use drugs to reduce harms associated with unintentional fentanyl exposure. METHODS: This analysis focused on 349 semi-structured qualitative interviews across 10 states and 58 rural counties in the U.S conducted between 2018 and 2020. Interview guides were collaboratively standardized across sites and included questions about drug use history (including drugs currently used, frequency of use, mode of administration) and questions specific to fentanyl. Deductive coding was used to code all data, then inductive coding of overdose and fentanyl codes was conducted by an interdisciplinary writing team. RESULTS: Participants described being concerned that fentanyl had saturated the drug market, in both stimulant and opioid supplies. Participants utilized strategies including: (1) avoiding drugs that were perceived to contain fentanyl, (2) buying drugs from trusted sources, (3) using fentanyl test strips, 4) using small doses and non-injection routes, (5) using with other people, (6) tasting, smelling, and looking at drugs before use, and (7) carrying and using naloxone. Most people who used drugs used a combination of these strategies as there was an overwhelming fear of fatal overdose. CONCLUSION: People who use drugs living in rural areas of the U.S. are aware that fentanyl is in their drug supply and use several strategies to prevent associated harms, including fatal overdose. Increasing access to harm reduction tools (e.g., fentanyl test strips, naloxone) and services (e.g., community drug checking, syringe services programs, overdose prevention centers) should be prioritized to address the polysubstance-involved overdose crisis. These efforts should target persons who use opioids and other drugs that may contain fentanyl.

Management of a dentigerous cyst; a ten-year clinicopathological study.

BACKGROUND: Dentigerous cysts, deemed of developmental origin, are benign odontogenic cysts characterized by a gradual growth rate. Their occurrence is twice as prevalent in men compared to women. These cysts are recognized as the most frequent developmental cysts affecting the jaws, with a typical manifestation in individuals aged 20 to 40, while infrequently identified in young children. Notably, dentigerous cysts have the potential to attain significant dimensions, resulting in painless enlargement of the jaw and subsequent deformation. OBJECTIVES: To assess the clinicopathological features and management of ten years of experience with dentigerous cysts. METHODS: A challenging cases were reported from reviewed records of the patients who were treated by the surgical intervention of various dentigerous cysts throughout the period of ten years, 2012-2022 and only histologically confirmed cases were selected, at Ramadi Teaching Hospital in addition to Rashid, Razi, Zuhur Private Hospitals and private clinics in Iraq. RESULTS: 76 patients were included in this clinicopathological research. The highest age group affected was ≤ 18 years (68.4%), 54% were male, the mandible was more affected (63.1%) than the maxilla (36.9%). Marsupialization was applied to 30.3% of the cases, while enucleation was carried out in 69.7%. CONCLUSIONS: The significance of meticulous examination of radiographs and the consequences associated with undetected and untreated ailments is affirmed by this case study. A comprehensive understanding of oral pathology serves as a valuable resource for dentists, facilitating accurate diagnosis, appropriate referrals, and the provision of anticipatory guidance to patients striving to achieve optimal oral health across various age groups.

Overdose responses among rural people who use drugs: A multi-regional qualitative study.

BACKGROUND: Efforts to distribute naloxone have equipped more people with the ability to reverse opioid overdoses but people who use drugs are often reluctant to call 911 due to concerns for legal repercussions. Rural communities face unique challenges in reducing overdose deaths compared to urban communities, including limited access to harm reduction services as well as greater concerns about stigma and privacy. METHODS: The Rural Opioid Initiative was funded in 2017 to better understand the health-related harms associated with the opioid crisis in rural US communities and consists of eight studies spanning ten states and 65 counties. Each study conducted semi-structured qualitative interviews with people who use drugs to understand contextual factors influencing drug use and health behaviors. We analyzed qualitative data from seven studies with data available at the time of analysis to understand peer response to overdose. RESULTS: Of the 304 participants interviewed, 55% were men, 70% were white, 80% reported current injection drug use, and 60% reported methamphetamine use. Similar to what has been found in studies focused on urban settings, people who use drugs in rural communities use a range of strategies to reverse overdoses, including non-evidence-based approaches. Several reported that multiple doses of naloxone are needed to reverse overdose. Three themes emerged around the willingness to call 911, including (1) hesitancy to call 911 for fear of legal consequences, (2) negative perceptions or experiences with law enforcement officers, and (3) efforts to obtain medical intervention while avoiding identification/law enforcement involvement. CONCLUSION: People who use drugs employ multiple strategies to attempt overdose reversal, including non-evidence-based approaches. Greater education about the most effective and least harmful strategies is needed. Reluctance to call 911 is rooted in concerns about potential legal consequences as well as perceptions about law enforcement officers, which may be heightened in rural communities where people who use drugs are more easily identified by law enforcement. People who use drugs will go to great strides to connect their peers to needed medical services, suggesting that comprehensive interventions to reduce interactions with law enforcement officers and eliminate legal consequences for reporting overdoses are critical.

Alirocumab boosts antioxidant status and halts inflammation in rat model of sepsis-induced nephrotoxicity via modulation of Nrf2/HO-1, PCSK9/HMGB1/NF-ᴋB/NLRP3 and Fractalkine/CX3CR1 hubs.

Acute kidney injury (AKI) is a devastating consequence of sepsis, accompanied by high mortality rates. It was suggested that inflammatory pathways are closely linked to the pathogenesis of lipopolysaccharide (LPS)-induced AKI. Inflammatory signaling, including PCSK9, HMGB1/RAGE/TLR4/MYD88/NF-κB, NLRP3/caspase-1 and Fractalkine/CX3CR1 are considered major forerunners in this link. Alirocumab, PCSK9 inhibitor, with remarkable anti-inflammatory features. Accordingly, this study aimed to elucidate the antibacterial effect of alirocumab against E. coli in vitro. Additionally, evaluation of the potential nephroprotective effects of alirocumab against LPS-induced AKI in rats, highlighting the potential underlying mechanisms involved in these beneficial actions. Thirty-six adult male Wistar rats were assorted into three groups (n=12). Group I; was a normal control group, whereas sepsis-mediated AKI was induced in groups II and III through single-dose intraperitoneal injection of LPS on day 16. In group III, animals were given alirocumab. The results revealed that LPS-induced AKI was mitigated by alirocumab, evidenced by amelioration in renal function tests (creatinine, cystatin C, KIM-1, and NGAL); oxidative stress biomarkers (Nrf2, HO-1, TAC, and MDA); apoptotic markers and renal histopathological findings. Besides, alirocumab pronouncedly hindered LPS-mediated inflammatory response, confirmed by diminishing HMGB1, TNF-α, IL-1ß, and caspase-1 contents; the gene expression of PCSK9, RAGE, NF-ᴋB and Fractalkine/CX3CR1, along with mRNA expression of TLR4, MYD88, and NLRP3. Regarding the antibacterial actions, results showed that alirocumab displayed potential anti-bacterial activity against pathogenic gram-negative E. coli. In conclusion, alirocumab elicited nephroprotective activities against LPS-induced AKI via modulation of Nrf2/HO-1, PCSK9, HMGB1/RAGE/TLR4/MYD88/NF-ᴋB/NLRP3/Caspase-1, Fractalkine/CX3R1 and apoptotic axes.

HIV Activist Identity, Commitment, and Orientation Scale (HAICOS): Psychometric Evaluation to Assess Clinician's Propensity Towards HIV Activism in Malaysia.

HIV activism has a long history of advancing HIV treatment and is critical in dismantling HIV-related stigma. This study evaluated the psychometric quality of the HIV Activist Identity, Commitment, and Orientation Scale (HAICOS) to assess clinicians' propensity towards HIV activism in Malaysia. From November 2022 to March 2023, 74 general practitioners and primary care physicians in Malaysia participated in the study. The exploratory factor analysis (EFA) extracted an internally consistent three-factor solution with 13 items: (1) HIV activist identity and commitment, orientation towards (2) day-to-day, and (3) structural activism. The Cronbach's alpha value was 0.91, and intra-class correlation coefficient for test-retest reliability was 0.86. Stigma-related (prejudice and discrimination intent) and clinical practice (comfort in performing clinical tasks with key populations and knowledge about HIV pre-exposure prophylaxis) measures supported the construct validity of the scale. The study provided concise, structurally valid, and reliable measures to evaluate HIV activism among clinicians.

RESUMEN: El activismo del VIH tiene una larga historia de avanzar el tratamiento del VIH y es crítico para desmantelar el estigma relacionado al VIH. Este estudio evaluó la calidad psicométrica de la Escala de Identidad, Compromiso y Orientación de Activistas del VIH (HAICOS) para evaluar la propensión de los médicos hacia el activismo del VIH en Malasia. Desde noviembre del 2022 hasta marzo del 2023, 74 médicos generales y de atención primaria en Malasia participaron en este estudio. El análisis factorial exploratorio (AFE) extrajo una solución de tres factores internamente consistente con 13 ítems: (1) identidad y compromiso del activismo del VIH; orientación hacia (2) el activismo cotidiano y (3) el activismo estructural. El valor alfa de Cronbach fue de 0.91 y el coeficiente de correlación intraclase para la confiabilidad prueba-reprueba fue de 0.86. Las medidas relacionadas con el estigma (prejuicio e intención de discriminación) y la práctica clínica (comodidad realizando tareas clínicas con poblaciones claves y conocimiento sobre la profilaxis pre-exposición del VIH) respaldaron la validez de constructo de la escala. El estudio proporcionó medidas concisas, estructuralmente válidas y confiables para evaluar el activismo de VIH entre los médicos.

Novel insights into gut health: Cilostazol strengthens gut integrity by adjusting TLR-2/NF-κB/IL-23 and CD44/AKT/GSK-3ß/cyclin-D1 trajectories in methotrexate-induced mucositis model.

Methotrexate (MTX)-induced gastrointestinal mucositis is a common adverse effect characterized by redox imbalance and overproduction of inflammatory mediators that perturb intestinal integrity. Currently, there is no definitive treatment for this condition and its prevention is still far beyond comprehension. Because of its pleiotropic pharmacological actions, we aimed to explore the potential mechanisms through which cilostazol (CILO) can protect against MTX-induced intestinal mucositis. Wistar rats were allocated into 4 groups, control, CILO (100 mg/kg, p.o for 14 days), MTX (7.5 mg/kg for 4 successive days), and CILO + MTX. The improving effect of CILO on the morphological structure was confirmed by an upturn in the histopathological and transition electron microscope examinations evidenced by the increased jejunal villus height/width and the crypt depth besides the maintenance of tight junctions. These findings were verified biochemically; on the molecular level, CILO reduced the MTX-induced lipid peroxidation, cleaved caspase-3, p53, and the inflammatory parameters (TLR-2, NF-κB, IL-23, TNF-α, IL-1ß), while increasing the anti-inflammatory marker IL-10 and the antioxidant enzyme SOD. Moreover, CILO decreased the injurious axis AKT/GSK-3ß/cyclin-D1, and CD44+, but increased the immunoexpression of the cell proliferating marker PCNA. CILO also upheld the intestinal barrier by enhancing the tight junction molecules (ZO-1, claudin-4) and the E-cadherin/ß-catenin complex while abating the mesenchymal marker vimentin. In conclusion, CILO protected gut integrity by reducing the epithelial-mesenchymal transition process, the MTX-induced oxidative, apoptotic, and inflammatory mediators, and turning off the CD44/AKT/GSK-3ß/cyclin D1 trajectory and intensifying the expression of PCNA.

The relationship between felt stigma and non-fatal overdose among rural people who use drugs.

BACKGROUND: Drug overdose deaths in the United States exceeded 100,000 in 2021 and 2022. Substance use stigma is a major barrier to treatment and harm reduction utilization and is a priority target in ending the overdose epidemic. However, little is known about the relationship between stigma and overdose, especially in rural areas. We aimed to characterize the association between felt stigma and non-fatal overdose in a multi-state sample of rural-dwelling people who use drugs. METHODS: Between January 2018 and March 2020, 2,608 people reporting past 30-day opioid use were recruited via modified chain-referral sampling in rural areas across 10 states. Participants completed a computer-assisted survey of substance use and substance-related attitudes, behaviors, and experiences. We used multivariable logistic regression with generalized estimating equations to test the association between felt stigma and recent non-fatal overdose. RESULTS: 6.6% of participants (n = 173) reported an overdose in the past 30 days. Recent non-fatal overdose was significantly associated with felt stigma after adjusting for demographic and substance use-related covariates (aOR: 1.47, 95% CI: 1.20-1.81). The association remained significant in sensitivity analyses on component fear of enacted stigma items (aOR: 1.48, 95% CI: 1.20-1.83) and an internalized stigma item (aOR: 1.51, 95% CI: 1.07-2.14). CONCLUSIONS: Felt stigma related to substance use is associated with higher risk of non-fatal overdose in rural-dwelling people who use drugs. Stigma reduction interventions and tailored services for those experiencing high stigma are underutilized approaches that may mitigate overdose risk.

How do people who use opioids express their qualities and capacities? An assessment of attitudes, behaviors, and opportunities.

People who nonmedically use drugs (PWUD) face intricate social issues that suppress self-actualization, communal integration, and overall health and wellness. "Strengths-based" approaches, an under-used pedagogy and practice in addiction medicine, underscore the significance of identifying and recognizing the inherent and acquired skills, attributes, and capacities of PWUD. A strengths-based approach engenders client affirmation and improves their capacity to reduce drug use-related harms by leveraging existing capabilities. Exploring this paradigm, we conducted and analyzed interviews with 46 PWUD who were clients at syringe services programs in New York City and rural southern Illinois, two areas with elevated rates of opioid-related morbidity and mortality, to assess respondents' perceived strengths. We located two primary thematic modalities in which strengths-based ethos is expressed: individuals (1) being and advocate and resource for harm reduction knowledge and practices and (2) engaging in acts of continuous self-actualization. These dynamics demonstrate PWUD strengths populating and manifesting in complex ways that both affirm and challenge humanist and biomedical notions of individual agency, as PWUD refract enacted, anticipated, and perceived stigmas. In conclusion, programs that blend evidence-based, systems-level interventions on drug use stigma and disenfranchisement with meso and micro-level strengths-based interventions that affirm and leverage personal identity, decision-making capacity, and endemic knowledge may help disrupt health promotion cleavages among PWUD.

Normative High-Resolution Pharyngeal Manometry: Impact of Age, Size of System, and Sex on Primary Metrics and Pressure Stability.

There have been many reports of normative pharyngeal swallowing pressures using high-resolution pharyngeal manometry, but there is a fair amount of between-subject variance in reported pressure parameters. The purpose of this study was to put forward normative pharyngeal high-resolution manometry measures across the lifespan and investigate the effects of age, size of system, and sex. High-resolution pharyngeal manometry was performed on 98 healthy adults (43 males) between the ages 21 and 89. Pressure duration, maxima, integral, and within-individual variability metrics were averaged over 10 swallows of 10-ml thin liquid. Multiple linear and logistic regressions with model fitting were used to examine how pharyngeal pressures relate to age, pharyngeal size, and sex. Age was associated with tongue base maximum pressure, tongue base maximum variability, and upper esophageal sphincter-integrated relaxation pressure (F3,92 = 6.69; p < 0.001; adjusted R2 = 0.15). Pharyngeal area during bolus hold was associated with velopharynx integral (F1,89 = 5.362; p = 0.02; adjusted R2 = 0.05), and there was no significant model relating pharyngeal pressures to C2-C4 length (p < 0.05). Sex differences were best described by tongue base integral and hypopharynx maximum variability (χ2 = 10.27; p = 0.006; pseudo R2 = 0.14). Normative data reveal the distribution of swallow pressure metrics which need to be accounted for when addressing dysphagia patients, the importance of pressure interactions in normal swallow, and address the relative stability of swallow metrics with normal aging.

Melatonin enhances captopril mediated cardioprotective effects and improves mitochondrial dynamics in male Wistar rats with chronic heart failure.

Mitochondrial dysfunction is a recent emerging research scope that proved to be involved in many cardiovascular diseases culminating in chronic heart failure (CHF), which remains one of the primary causes of morbidity and mortality. This study investigated the added cardio-protective effects of exogenous melatonin administration to conventional captopril therapy in isoproterenol (ISO) exposed rats with CHF. Five groups of Wistar rats were recruited; (I): Control group, (II): (ISO group), (III): (ISO + captopril group), (IV): (ISO + melatonin group) and (V): (ISO + melatonin/captopril group). Cardiac function parameters and some oxidant, inflammatory and fibrotic markers were investigated. Moreover; mRNA expression of mitochondrial mitophagy [parkin & PTEN induced kinase 1 (PINK1)], biogenesis [Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)], fusion [mitofusin 2 (Mfn2)] and fission [dynamin-related protein 1 (DRP-1)] parameters in rat's myocardium were evaluated. Rats' myocardium was histo-pathologically and immunohistochemically evaluated for Beclin1 and Sirt3 expression. The present study revealed that captopril and melatonin ameliorated cardiac injury, oxidative stress biomarkers, and pro-inflammatory cytokines in ISO-exposed rats. These protective effects could be attributed to mitochondrial dynamic proteins control (i.e. enhanced the mRNA expression of parkin, PINK1, PGC-1α and Mfn2, while reduced DRP-1 mRNA expression). Also, Beclin1 and Sirt3 cardiac immunoreactivity were improved. Combined captopril and melatonin therapy showed a better response than either agent alone. Melatonin enhanced myocardial mitochondrial dynamics and Sirt3 expression in CHF rats and may represent a promising upcoming therapy added to conventional heart failure treatment.

Cost-effectiveness analysis of upadacitinib as a treatment option for patients with rheumatoid arthritis in the Kingdom of Saudi Arabia.

AIM: To evaluate cost-effectiveness of upadacitinib (targeted synthetic-disease modifying anti-rheumatic drug [ts-DMARD]) as first-line (1 L) treatment versus current treatment among patients with rheumatoid arthritis (RA) in the Kingdom of Saudi Arabia (KSA), who had an inadequate response to prior conventional-synthetic (csDMARDs) and/or biologic-DMARDs (bDMARDs). METHODS: This Excel-based model included patients with moderate (Disease Activity Score [DAS28]: >3.2 to ≤5.1) or severe RA (DAS28 > 5.1). Cost-effectiveness of current treatment (1 L: adalimumab-originator/biosimilar; second-line (2 L): other bDMARDs/tofacitinib) was compared against a new treatment involving two scenarios (1 L: upadacitinib, 2 L: adalimumab-biosimilar [scenario-1]/adalimumab-originator [scenario-2]) for a 10-year time-horizon from societal perspective. Model outcomes included direct and indirect costs, quality-adjusted life-years (QALYs), hospitalization days, number of orthopedic surgeries, and incremental cost-utility ratio (ICUR) per QALY. RESULTS: With the current pathway, estimated total societal costs for 100 RA patients over 10-year period were Saudi Riyal (SAR) 50,450,354 (United States dollars [USD] 13,453,428) (moderate RA) and SAR50,013,945 (USD13,337,052) (severe RA). New pathway (scenario-1) showed that in patients with moderate-to-severe RA, upadacitinib led to higher QALY gain (+8.99 and +15.63) at lower societal cost (cost difference: -SAR2,023,522 [-USD539,606] and -SAR3,373,029 [-USD899,474], respectively). Thus, as 1 L, upadacitinib projects "dominant" ICUR per QALY over current pathway. Moreover, in alternate pathway (scenario-2), upadacitinib also projects "dominant" ICUR per QALY for patient with severe RA (QALY gain: +15.63; cost difference: -SAR 164,536 [-USD43,876]). However, moderate RA was associated with additional cost of SAR1,255,696 (USD334,852) for improved QALY (+8.99) over current pathway (ICUR per QALY: SAR139,742 [USD37,264]). Both scenarios resulted in reduced hospitalization days (scenario-1: -14.83 days; scenario-2: -11.41 days) and number of orthopedic surgeries (scenario-1: -8.36; scenario-2: -6.54) for moderate-to-severe RA over the current treatment pathway. CONCLUSION: Upadacitinib as 1 L treatment in moderate-to-severe RA can considerably reduce healthcare resource burden in KSA, majorly due to reduced drug administration/monitoring/hospitalization/surgical and indirect costs.

Experiences of Dermatologists and Patients Regarding Psoriasis and Its Connection to Psoriatic Arthritis in Saudi Arabia.

Purpose: Psoriasis is a chronic, inflammatory, immune-mediated skin disease that has significant impact on a patient's quality of life, yet it remains challenging for dermatologists to successfully identify and manage. Without effective screening, diagnosis and treatments, psoriasis can potentially progress to psoriatic arthritis. A descriptive, observational cross-sectional study of Saudi Arabian dermatologists and patients with psoriasis was conducted to explore dermatologist and patient perspectives of psoriasis, including diagnosis, management, disease course and unmet needs. Patients and Methods: This study involved a quantitative questionnaire administered to 31 dermatologists and 90 patients with psoriasis at eight medical centers and was analyzed using descriptive statistics. Results: Dermatologists and patients perceived that psoriasis treatment was initiated promptly and that follow-up visits were sufficient. Their perspectives differed in the time to diagnosis and patient reaction, symptom severity, input into treatment goals and educational needs. The dermatologists' concerns about underdiagnosed psoriasis (13%) were primarily related to patient awareness (87%), physician awareness (58%), and the absence of a regular screening program (52%). Only 31% of patients with psoriasis were highly satisfied with their psoriasis treatment, with 78% experiencing unpleasant symptoms of pain or swelling in joints indicative of psoriatic arthritis. However, only 56% of these patients reported these symptoms to their physicians. When dermatologists were made aware of this difference, referrals to a rheumatologist increased. Conclusion: The study highlights the importance of strengthening psoriasis management by enhancing dermatologist referral and screening practices, adopting a multidisciplinary approach to care, and improving education and resources for physicians and patients. These results can help to inform the improvement of psoriasis screening, diagnosis and treatment strategies and ensure that expectations meet treatment outcomes. Further research exploring the dermatologist and patient perspectives of the disease pathway from psoriasis to psoriatic arthritis and tailor-made treatment approaches is recommended.

Citrus clementine Peel Essential Oil Ameliorates Potassium Dichromate-Induced Lung Injury: Insights into the PI3K/AKT Pathway.

Acute Lung Injury (ALI) is a life-threatening syndrome that has been identified as a potential complication of COVID-19. There is a critical need to shed light on the underlying mechanistic pathways and explore novel therapeutic strategies. This study aimed to examine the potential therapeutic effects of Citrus clementine essential oil (CCEO) in treating potassium dichromate (PDC)-induced ALI. The chemical profile of CCEO was created through GC-MS analysis. An in vivo study in rats was conducted to evaluate the effect of CCEO administrated via two different delivery systems (oral/inhalation) in mitigating acute lung injury (ALI) induced by intranasal instillation of PDC. Eight volatile compounds were identified, with monoterpene hydrocarbons accounting for 97.03% of the identified constituents, including 88.84% of D-limonene. CCEO at doses of 100 and 200 mg/kg bw exhibited antioxidant and anti-inflammatory properties. These significant antioxidant properties were revealed through the reduction of malondialdehyde (MDA) and the restoration of reduced glutathione (GSH). In addition, inflammation reduction was observed by decreasing levels of cytokines tumor necrosis factor-α and tumor growth factor-ß (TNF-α and TGF-ß), along with an increase in phosphatidylinositide-3-kinase (PI3K) and Akt overexpression in lung tissue homogenate, in both oral and inhalation routes, compared to the PDC-induced group. These results were supported by histopathological studies and immunohistochemical assessment of TGF-ß levels in lung tissues. These findings revealed that CCEO plays an integral role in relieving ALI induced by intranasal PDC and suggests it as a promising remedy.

Protective Effect of Topiramate against Diabetic Retinopathy and Computational Approach Recognizing the Role of NLRP3/IL-1ß/TNF-α Signaling.

The possible impact of topiramate against diabetic retinopathy (DREN) and its molecular mechanisms in relation to the nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome has not been studied before. Thus, in the present study, we aimed to utilize a computational approach to investigate the possible protective effect of topiramate on experimental DREN and explore its impact on NLRP3/interlukin-1ß signaling and brain-derived neurotrophic factor (BDNF) expression. Male albino mice were distributed to four experimental groups and assigned the following categorizations: (i) saline, (ii) diabetic, (iii) diabetic + topiramate 10 mg/kg and (iv) diabetic + topiramate 30 mg/kg. We observed shrinkage of total retinal thickness and elevation in retinal glutamate, malondialdehyde, NLRP3 and interlukin-1ß but decreased glutathione (GSH) levels in the diabetic mice. Additionally, retinal ultra-structures in the diabetic group showed abnormalities and vacuolations in the pigmented epithelium, the photoreceptor segment, the outer nuclear layer, the inner nuclear layer and the ganglion cell layer (GCL). Mice treated with topiramate 10 or 30 mg/kg showed downregulation in retinal malondialdehyde, NLRP3 and interlukin-1ß levels; improvements in the retinal pathologies; enhanced immunostaining for BDNF and improved ultra-structures in different retinal layers. Overall, the current results suggest topiramate as a neuroprotective agent for DREN, and future studies are warranted to further elucidate the mechanism of its protective action.

Exploring Impact of Multidisciplinary Care on Patient Activation in Saudi Rheumatoid Arthritis Patients: A Cross-Sectional Survey-Extended Results from the COPARA National Project.

Introduction: Multidisciplinary setting in healthcare provide positive patient outcomes. Objective: To evaluate the impact of specialized rheumatology clinics (multidisciplinary settings) on the activation and engagement of rheumatoid arthritis (RA) patients. Material and Methods: This cross-sectional survey assessed patient activation using the patient activation measure-13. Participants attending Specialized Rheumatology Clinics (SRC multidisciplinary clinics) were compared with age- and sex-matched patients attending Standard of Care (SOC). The study was observational in nature, assessing several demographic and therapeutic options and their relation to the clinical setting and patient activation. Results: This study included 117 SRC matched RA patients with 117 SOC. The majority of the included patients were female (n=211, 90.2%), >40 years of age (n=177, 75.6%), and had intermediate-to-high education (n=147, 62.8%). Patients in the SRC were also more likely to have activation levels 3 and 4 with an odds ratio of 3.194 (95% confidence interval [CI] 1.835-5.562, p<0.001). In addition, SRC participants were more likely to be in levels 3 and 4 activation, even after adjustment for confounding variables, with an adjusted odds ratio of 2.401 (95% CI 1.121-4.758, p=0.012) and 2.175 (95% CI 1.127-4.196, p=0.020), respectively. Conclusion: Establishing SRC for RA patients seems to have a positive impact on patient activation and engagement and adds to the previously explored benefits of multidisciplinary care in chronic disease management.

Exploring factors influencing patient activation in Saudi rheumatoid arthritis patients: A Nationwide Cross-Sectional Survey-Results from the COPARA study.

OBJECTIVES: To evaluate patient activation in rheumatoid arthritis (RA) patients using patient activation measure 13 (PAM-13) on a national level in Saudi Arabia. METHOD: A national survey was administered across multiple centers in Saudi Arabia. Patient activation was assessed using the PAM-13. The Compliance Questionnaire for Rheumatology (CQR) and the RA Impact of Disease (RAID) tool were also administered. The data from the survey were analyzed, and the results were stratified based on activation level. All factors affecting patient activation were explored and reported. RESULTS: A total of 1241 participants were included. Most of the patients were females (85%), the mean age was 47 (±14), and most patients lived in the central region (47%). The mean (±standard deviation) patient activation score was 578.7 (±13.0). Patient activation was affected by multiple factors: demographic characteristics, such as education, with a beta value of 1.11 (95% confidence interval [CI] 0.64 ̶1.58, p < .001). Higher CQR scores were associated with higher activation levels, with a beta value of 2.61 (95% CI 0.80 ̶4.44, p = .005), and higher RAID scores were associated with lower activation levels, with a beta value of 3.13 (95% CI 1.36 ̶4.91, p = .001). CONCLUSIONS: Patient activation was affected by several demographic characteristics and the impact of RA. A higher activation may improve compliance. Future longitudinal studies are required to confirm these findings and should explore the underlying mechanism of these effects.

"I would do anything but that": Attitudes towards sex work among rural people who use drugs.

BACKGROUND: Stigma towards people who use drugs and those who engage in sex work is well-documented, leading to consequences such as reduced access to health services and support, especially in rural milieus. Stigma reduction has been recognized as a priority in the opioid overdose crisis, but little attention has been paid to within-group attitudes and beliefs. This study aimed to explore how people who use drugs in rural counties across the United States appraise sex work by themselves or other community members. METHODS: Qualitative interview data came from the Rural Opioid Initiative (ROI), a project coordinated by research teams across 65 rural counties in 10 states. Interviews were individual and conducted from 2018 to 2020. All participants reported past 30-day opioid use and/or any injection drug use. A working group coded the data, then used an iterative inductive-deductive approach to organize data into themes of stigma among people who use drugs, focusing on stigma towards sex work. RESULTS: Across sites, 355 interviews were conducted. Mean participant age was 36, 55 % of participants were male, and 93 % were white. Participants expressed negative attitudes towards sex work as a function of its criminal-legal repercussions or framed sex work as morally transgressive. Many appraisals were gendered, with the behavior conveyed as being "easier" for women who were often described as "whores," with more neutral terms used to describe men. Some viewed sex work as an implicit "exchange" for drugs. Several participants noted a lack of agency as a feature leading to involvement in sex work, with partner power dynamics influencing an individual's behavior. Finally, a few participants acknowledged the circumstances under which they would newly engage in sex work. CONCLUSION: We identified several patterns by which people who use drugs evaluate community members who sell sex. These included gendered and morally-charged forms of stigma, which may represent barriers to community acceptance and support among this subgroup.

Healthy eating perceptions of mothers and caregivers of children in South Africa.

Background: The perceptions of mothers and caregivers of children attending early childhood development (ECD) centres play a very critical role in promoting healthy eating habits in children and impact long-term health consequences. Food preferences that are developed during childhood continue into adolescence and adulthood and are difficult to change. Aim: The aim of the study was to assess the perception of mothers and caregivers of children attending ECD centres regarding healthy eating practices. Setting: The study was conducted in ECD centres in Gauteng, North West and Limpopo. Methods: A quantitative descriptive design was used to collect data among 290 respondents using a structured, researcher-administered questionnaire. Results: The findings indicated that the majority (77%) of respondents did not believe that choosing a healthy diet is a matter of knowing foods that are good and bad for health. The majority (59%) of respondents believed that the food they eat and drinks are healthy and see no need to make changes. Conclusion: The study findings showed that the majority of respondents lack awareness about choosing healthy diets. Furthermore, the current dietary patterns of respondents and their children will remain the same as long as the mothers and caregivers feel that the food they eat is healthy. Contribution: The findings of the study contribute to the appropriate measures of educating mothers and caregivers in offering healthy diets to children at home and in early childhood centres.

"As safe as possible": a qualitative study of opioid withdrawal and risk behavior among people who use illegal opioids.

BACKGROUND: Opioid withdrawal is a regular occurrence among many people who use illicit opioids (PWUIO) that has also been shown to increase their willingness to engage in risk-involved behavior. The proliferation of fentanyl in the illicit opioid market may have amplified this relationship, potentially putting PWUIO at greater risk of negative health outcomes. Understanding the relationship between withdrawal and risk-involved behavior may also have important implications for the ways that problematic drug use is conceptualized, particularly in disease models of addiction, which position risk behavior as evidence of pathology that helps to justify ontological distinctions between addicts and non-addicts. Examining withdrawal, and its role in PWUIO's willingness to engage in risk, may aid in the development of alternative theories of risk involvement and create discursive spaces for de-medicalizing and de-othering people who use illegal drugs. METHODS: This article is based on 32 semi-structured interviews with PWUIO in the New York City area who also reported recent withdrawal experience. Interviews were conducted remotely between April and August 2022 and recorded for later transcription. Data were then coded and analyzed based on a combination of inductive and deductive coding strategies and informed by the literature. RESULTS: Participants described a strong relationship between withdrawal and their willingness to engage in risk-involved behavior that was exacerbated by the proliferation of fentanyl. Yet, their descriptions did not align with narratives of risk as a product of bad decisions made by individuals. Rather, data demonstrated the substantial role of social and structural context, particularly drug policies like prohibition and criminalization, in the kinds of risks that PWUIO faced and their ability to respond to them. CONCLUSIONS: Withdrawal should be taken more seriously both from an ethical perspective and as an important catalyst of risk behavior. However, theories that position activities taken to avoid withdrawal as irrational and as evidence of pathology are poorly aligned with the complexity of PWUIO's actual lives. We recommend the use of less deterministic and less medicalized theories of risk that better account for differences between how people view the world, and for the role of socio-structural forces in the production of risk.