Review of phase 2/3 trials in polymyalgia rheumatica and giant cell arteritis.

INTRODUCTION: GCA (giant cell arteritis) and PMR (polymyalgia rheumatica) are two overlapping inflammatory rheumatic conditions that are seen exclusively in older adults, sharing some common features. GCA is a clinical syndrome characterized by inflammation of the medium and large arteries, with both cranial and extracranial symptoms. PMR is a clinical syndrome characterized by stiffness in the neck, shoulder, and pelvic girdle muscles. Both are associated with constitutional symptoms. AREAS COVERED: In this review, we assess the established and upcoming treatments for GCA and PMR. We review the current treatment landscape, completed trials, and upcoming trials in these conditions, to identify new and promising therapies. EXPERT OPINION: Early use of glucocorticoids (GC) remains integral to the immediate management of PMR and GCA but being aware of patient co-morbidities that may influence treatment toxicity is paramount. As such GC sparing agents are required in the treatment of PMR. Currently there are limited treatment options available for PMR and GCA, and significant unmet needs remain. Newer mechanisms of action, and hence therapeutic options being studied include CD4 T cell co-stimulation blockade, IL-17 inhibition, IL-12/23 inhibition, GM-CSF inhibition, IL-1ß inhibition, TNF-α antagonist and Jak inhibition, among others, which will be discussed in this review.

Efficacy and Safety of Ketamine-Dexmedetomidine Versus Ketamine-Propofol Combination for Periprocedural Sedation: A Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: The combination of ketamine with propofol and dexmedetomidine has gained popularity for sedation and general anesthesia in different populations. In our meta-nalysis, we helped the anesthesiologists to know the efficiency and the efficacy of both combinations in adult and pediatric patients. METHODS: We searched PubMed, CENTRAL, Web of Science, and Scopus from inception to August 1, 2023. Our outcome parameters for efficacy were recovery time, pain score, and physician satisfaction while for safety were the related cardiorespiratory, neurological, and gastrointestinal adverse events. RECENT FINDINGS: Twenty-two trials were included with a total of 1429 patients. We found a significantly longer recovery time in the ketadex group of 7.59 min (95% CI, 4.92, 10.26; I2 = 94%) and a significantly less pain score of - 0.72 (95% CI, - 1.10, - 0.34; I2 = 0%). Adults had a significantly better physician satisfaction score with the ketofol group, odds ratio of 0.29 (95% CI, 0.12, 0.71; I2 = 0%). Recovery agitations were higher in the ketofol group with an odds ratio of 0.48 (95% CI, 0.24, 0.98; I2 = 36%). Furthermore, we found a significant difference between the combinations with a higher incidence in the ketadex group with pooled odds ratio of 1.75 (95% CI, 1.06, 2.88; I2 = 15%). Ketadex was associated with lower pain scores, hypoxic events and airway obstruction, and emergence agitation. At the same time, ketofol had much more clinician satisfaction which might be attributed to the shorter recovery time and lower incidence of nausea and vomiting. Therefore, we suppose that ketadex is the better combination in periprocedural sedation for both adult and pediatric patients who are not at greater risk for postoperative nausea and vomiting.

Similarity analysis of bioconvection of unsteady nonhomogeneous hybrid nanofluids influenced by motile microorganisms.

Motile bacteria in hybrid nanofluids cause bioconvection. Bacillus cereus, Pseudomonas viscosa, Bacillus brevis, Salmonella typhimurium, and Pseudomonas fluorescens were used to evaluate their effect and dispersion in the hybrid nanofluid. Using similarity analysis, a two-phase model for mixed bioconvection magnetohydrodynamic flow was developed using hybrid nanoparticles of Al2O3 and Cu (Cu-Al2O3/water). The parametric investigation, covering the magnetic parameter, permeability coefficient, nanoparticle shape factor, temperature ratio, radiation parameter, nanoparticle fraction ratio, Brownian parameter, thermophoresis parameter, motile bacteria diffusivity, chemotaxis parameter, and Nusselt, Reynold, Prandtl, Sherwood numbers, as well as the number of motile microorganisms', showed significant outcomes. Velocity and shear stresses are sensitive to M, Pr, and [Formula: see text]. Magnetic, radiation, and chemotaxis factors impact bacterial density. The hybrid nanofluid velocity decreases when the magnetic parameter, M, Prandtl number Pr increases, while it increases with the increasing of porosity coefficient, [Formula: see text], and the hybrid nanoparticle ratio Nf. The temperature distribution decreases with the increasing of Prandtl number and Nf. Increasing temperature differential and bacterium diffusivity increases bacterial aggregation.

Multimorbidity in rheumatoid arthritis: common mechanistic links and impact and challenges in routine clinical practice.

Early identification and management of multimorbidity in patients with rheumatic and musculoskeletal diseases (RMDs), such as RA, is an integral, but often neglected, aspect of care. The prevalence and incidence of conditions such as osteoporosis, cardiovascular disease, pulmonary disease and malignancies, often co-existing with RA, continues to have significant implications for the management of this patient group. Multimorbidity in RMDs can be associated with inflammatory disease activity and target organ damage. Lifestyle factors, such as smoking and inactivity, further contribute to the burden of disease. Inflammation is the underlying factor, not just in RA but also many comorbidities. The current framework of a treat-to-target approach focuses on achieving early remission and inflammatory activity suppression. We describe how the comorbidity burden in people with RMDs impacts on disease outcome and treatment response. The importance of addressing comorbidity at an early stage and adopting a patient centred approach is critical in modern practice.

Can the current monkeypox affect the heart? A systematic review of case series and case report.

BACKGROUND: Monkeypox is a zoonotic viral infection first reported in May 2022. Monkeypox cases present with prodromal symptoms, rash, and/or systemic complications. This study systematically reviews the monkeypox cases presented with any cardiac complications. METHODS: A systematic literature search was done to locate papers that discuss any cardiac complications associated with monkeypox; then, data were analyzed qualitatively. RESULTS: Nine articles, including the 13 cases that reported cardiac complications of the disease, were included in the review. Five cases previously had sex with men, and two cases had unprotected intercourse, which reveals the importance of the sexual route in disease transmission. All cases have a wide spectrum of cardiac complications, such as acute myocarditis, pericarditis, pericardial effusion, and myopericarditis. CONCLUSION: This study clarifies the potential for cardiac complications in monkeypox cases and provides avenues for future research to determine the underlying mechanism. Also, we found that the cases with pericarditis were treated with colchicine, and those with myocarditis were treated with supportive care or cardioprotective treatment (Bisoprolol and Ramipril). Furthermore, Tecovirimat is used as an antiviral drug for 14 days.

Natural remedies for Alzheimer's disease: A systematic review of randomized controlled trials.

Alzheimer's disease (AD) is the common type of dementia and is currently incurable. Existing FDA-approved AD drugs may not be effective for everyone, they cannot cure the disease nor stop its progression and their effects diminish over time. Therefore, the present review aimed to explore the role of natural alternatives in the treatment of AD. A systematic search was conducted using Ovid MEDLINE, CINAHL, Cochrane and PubMed databases and reference lists up to November 30, 2021. Only randomized control trials were included and appraised using the National Institute of Health framework. Data analysis showed that herbs like Gingko Biloba, Melissa Officinalis, Salvia officinalis, Ginseng and saffron alone or in combination with curcumin, low-fat diet, NuAD-Trail, and soy lecithin showed significant positive effects on AD. Moreover, combination of natural and pharmaceuticals has far better effects than only allopathic treatment. Thus, different herbal remedies in combination with FDA approved drugs are effective and more promising in treatment of AD.

Sildenafil for congenital heart diseases induced pulmonary hypertension, a meta-analysis of randomized controlled trials.

BACKGROUND: Sildenafil was first prescribed for angina pectoris and then for erectile dysfunction from its effects on vascular smooth muscle relaxation and vasodilatation. Recently, sildenafil has been proposed for congenital heart diseases induced pulmonary hypertension, which constitutes a huge burden on children's health and can attribute to fatal complications due to presence of unoxygenated blood in the systemic circulation. Therefore, our meta-analysis aims to further investigate the safety and efficacy of sildenafil on children population. METHODS: We searched the following electronic databases: PubMed, Cochrane CENTRAL, WOS, Embase, and Scopus from inception to April 20th, 2022. Randomized controlled trials that assess the efficacy of using sildenafil in comparison to a placebo or any other vasodilator drug were eligible for inclusion. The inverse variance method was used to pool study effect estimates using the random effect model. Effect sizes are provided in the form of mean difference (MD) with 95% confidence intervals (CI). RESULTS: Our study included 14 studies with (n = 849 children) with a mean age of 7.9 months old. Sildenafil showed a statistically significant decrease over placebo in mean and systolic pulmonary artery pressure (PAP) with MD -7.42 (95%CI [-13.13, -1.71], P = 0.01) and -8.02 (95%CI [-11.16, -4.88], P < 0.0001), respectively. Sildenafil revealed a decrease in mean aortic pressure and pulmonary artery/aortic pressure ratio over placebo with MD -0.34 (95%CI [-2.42, 1.73], P = 0.75) and MD -0.10 (95%CI [-0.11, -0.09], P < 0.00001), respectively. Regarding post corrective operations parameters, sildenafil had a statistically significant lower mechanical ventilation time, intensive care unit stay, and hospital stay over placebo with MD -19.43 (95%CI [-31.04, -7.81], s = 0.001), MD -34.85 (95%CI [-50.84, -18.87], P < 0.00001), and MD -41.87 (95%CI [-79.41, -4.33], P = 0.03), respectively. Nevertheless, no difference in mortality rates between sildenafil and placebo with OR 0.25 (95%CI 0.05, 1.30], P = 0.10) or tadalafil with OR 1 (95%CI 0.06, 17.12], P = 1). CONCLUSION: Sildenafil is a well-tolerated treatment in congenital heart diseases induced pulmonary hypertension, as it has proven its efficacy not only in lowering both PAP mean and systolic but also in reducing the ventilation time, intensive care unit and hospital stay with no difference observed regarding mortality rates.

Analysis of Hyperspectral Data to Develop an Approach for Document Images.

Hyperspectral data analysis is being utilized as an effective and compelling tool for image processing, providing unprecedented levels of information and insights for various applications. In this manuscript, we have compiled and presented a comprehensive overview of recent advances in hyperspectral data analysis that can provide assistance for the development of customized techniques for hyperspectral document images. We review the fundamental concepts of hyperspectral imaging, discuss various techniques for data acquisition, and examine state-of-the-art approaches to the preprocessing, feature extraction, and classification of hyperspectral data by taking into consideration the complexities of document images. We also explore the possibility of utilizing hyperspectral imaging for addressing critical challenges in document analysis, including document forgery, ink age estimation, and text extraction from degraded or damaged documents. Finally, we discuss the current limitations of hyperspectral imaging and identify future research directions in this rapidly evolving field. Our review provides a valuable resource for researchers and practitioners working on document image processing and highlights the potential of hyperspectral imaging for addressing complex challenges in this domain.

Perceptions of Post-Stroke Fatigue among Health Care Practitioners: A Qualitative Interview Study.

Background and Objectives: Post-Stroke Fatigue (PSF) is a complex, multidimensional, debilitating condition that affects almost half of all stroke survivors. This study explored the perceptions of physiatrists, physiotherapists, and occupational therapists about PSF and their experiences in managing patients with PSF in Saudi Arabia. Materials and Methods: Qualitative semi-structured interviews were conducted with participants from three different groups: eight physiotherapists (PTs), eight occupational therapists (OTs), and eight physiatrists (DRs). Using purposive sampling, participants with at least one year of experience in the field of PSF management were invited to take part. The data were analysed using inductive thematic analysis. Results: Twenty-four health care participants (eight PTs, eight OTs, eight DRs) were recruited. Five overarching themes encompassing various subthemes and sub-subthemes were generated: 'knowledge about post-stroke fatigue', 'diagnosing post-stroke fatigue', 'treatment approach', 'lack of awareness about post-stroke fatigue', and 'domains to improve'. The data indicated that participants used various strategies to manage PSF, including dietary changes, sleep hygiene, exercise, and energy conservation. Conclusions: Participants acknowledged that they lacked PSF-related management skills, despite possessing adequate knowledge about the management of stroke. Their openness to participating in activities that would improve their ability to diagnose and manage PSF was particularly striking.

Trade-offs in muscle physiology in selectively bred high runner mice.

A trade-off between locomotor speed and endurance occurs in various taxa, and is thought to be underpinned by a muscle-level trade-off. Among four replicate high runner (HR) lines of mice, selectively bred for voluntary wheel-running behavior, a negative correlation between average running speed and time spent running has evolved. We hypothesize that this trade-off is due to changes in muscle physiology. We studied the HR lines at generation 90, at which time one line (L3) is fixed for the mini-muscle phenotype, another is polymorphic (L6) and the others (L7, L8) lack mini-muscle individuals. We used in situ preparations to quantify the contractile properties of the triceps surae muscle complex. Maximal shortening velocity varied significantly, being lowest in mini-muscle mice (L3 mini=25.2 mm s-1, L6 mini=25.5 mm s-1), highest in normal-muscle mice L6 and L8 (40.4 and 50.3 mm s-1, respectively) and intermediate in normal-muscle L7 mice (37.2 mm s-1). Endurance, measured both as the slope of the decline in force and the proportion of initial force that could be sustained, also varied significantly. The slope was shallowest in mini-muscle mice (L3 mini=-0.00348, L6 mini=-0.00238), steepest in lines L6 and L8 (-0.01676 and -0.01853), and intermediate in L7 (-0.01145). Normalized sustained force was highest in mini-muscle mice (L3 mini=0.98, L6 mini=0.92) and lowest in L8 (0.36). There were significant, negative correlations between velocity and endurance metrics, indicating a muscle-level trade-off. However, this muscle-level trade-off does not seem to underpin the organismal-level speed and endurance trade-off previously reported as the ordering of the lines is reversed: the lines that run the fastest for the least time have the lowest muscle complex velocity and highest endurance.

CHANDELIER-ASSISTED VERSUS STANDARD SCLERAL BUCKLING FOR PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT: A Randomized Clinical Study.

PURPOSE: To compare anatomical outcomes, functional outcomes, and rate of complications of standard scleral buckling (SSB) versus chandelier-assisted scleral buckling (CSB) in phakic eyes with rhegmatogenous retinal detachment. METHODS: Patients were randomly assigned to either SSB or CSB. Surgical success/failure rate, corrected distance visual acuity, surgical operating time, and rate of intraoperative and postoperative complications including epiretinal membranes by spectral domain optical coherence tomography were compared between groups. RESULTS: A total of 50 eyes of 49 patients were included. At 6 months, there was no statistically significant difference between groups in primary success, or final anatomical success ( P > 0.9); mean corrected distance visual acuity at any visit ( P values >0.05); or mean surgical time: 120.3 ± 39.05 and 102.48 ± 43.76 minutes for the SSB and CSB, respectively ( P = 0.1). The CSB had a higher rate of postoperative complications (34.8%) compared with the SSB (3.8%) ( P < 0.05). On spectral domain optical coherence tomography, CSB had a statistically significant higher rate of epiretinal membranes compared with SSB (44% vs. 19% [ P < 0.05]) and showed vitreous entrapment in the chandelier sclerotomy site on the ultrasonic biomicroscopy. CONCLUSION: Chandelier-assisted scleral buckling surgery does not offer encouraging advantages over SSB. On the contrary, we detected a higher rate of complications with CSB especially epiretinal membranes development.

Implementation of a Miniaturized Planar Tri-Band Microstrip Patch Antenna for Wireless Sensors in Mobile Applications.

Antennas in wireless sensor networks (WSNs) are characterized by the enhanced capacity of the network, longer range of transmission, better spatial reuse, and lower interference. In this paper, we propose a planar patch antenna for mobile communication applications operating at 1.8, 3.5, and 5.4 GHz. A planar microstrip patch antenna (MPA) consists of two F-shaped resonators that enable operations at 1.8 and 3.5 GHz while operation at 5.4 GHz is achieved when the patch is truncated from the middle. The proposed planar patch is printed on a low-cost FR-4 substrate that is 1.6 mm in thickness. The equivalent circuit model is also designed to validate the reflection coefficient of the proposed antenna with the S11 obtained from the circuit model. It contains three RLC (resistor-inductor-capacitor) circuits for generating three frequency bands for the proposed antenna. Thereby, we obtained a good agreement between simulation and measurement results. The proposed antenna has an elliptically shaped radiation pattern at 1.8 and 3.5 GHz, while the broadside directional pattern is obtained at the 5.4 GHz frequency band. At 1.8, 3.5, and 5.4 GHz, the simulated peak realized gains of 2.34, 5.2, and 1.42 dB are obtained and compared to the experimental peak realized gains of 2.22, 5.18, and 1.38 dB at same frequencies. The results indicate that the proposed planar patch antenna can be utilized for mobile applications such as digital communication systems (DCS), worldwide interoperability for microwave access (WiMAX), and wireless local area networks (WLAN).

A Unique Appliance for Median Facial Cleft Management With Sleep Apnea due to Undeveloped Nasal Septum: A Rare Case Report.

The role of a prosthodontist in the management of facial cleft patients is the restoration of feeding, respiration, facial harmony, dental harmony and phonation. This case report presents the fabrication of an appliance for a pediatric patient with congenital median facial cleft who had sleep apnea due to the absence of nasal septum, which is a rare condition, with a unique method that fulfilled the patient's needs and improved quality of life. The patient also had median cleft lip and premaxilla along with hypertelorism.

Estimation of some heavy metals contamination in waste newspapers.

Heavy metals in waste newspapers produce varying degrees of contamination concerns during food consumption, and when heavy metals levels exceed the permissible level, they become harmful to human. Different types of waste newspapers were analyzed for As, Cd, Cr, Ni, Pb, Al, and Zn by ICP-OES. The digestion solution included 10 ml of 69% nitric acid and 2 ml of 30% hydrogen peroxide. Based on the results for light fonts, the average content of As, Cd, Cr, Ni, and Pb was 2.8, 1.5, 6.9, 5.6, and 5.0 µg/l, while was 3.4 and 0.18 mg/l for Al, and Zn, respectively. In bold fonts, the content of As, Cd, Cr, Ni, and Pb was 4.9, 2.4, 9.1, 7.9, and 7.0 µg/l, respectively, while Al and Zn were 5.7 mg/l and 0.32 mg/l, respectively. In the pictures, the levels of As, Cd, Cr, Ni, and Pb were 6.1, 2.99, 11.2, 9.4, and 8.99 µg/l, while Al and Zn were 8.2 and 0.39 mg/l, respectively. The results showed that all levels of heavy metals under study were within the specialized global councils' permitted limits.

Clinicopathological characteristics of ocular surface squamous neoplasia: a 10-year review form a referral tertiary centre in Nigeria.

BACKGROUND: Ocular surface squamous neoplasia (OSSN) is a heterogeneous group of proliferative squamous lesions on the ocular surface with varying biologic behaviours. This study aims to report the clinical profile and pathological characteristics of cases of OSSN seen at a tertiary referral centre in North West Nigeria. METHODS: A retrospective review of all cases of OSSN diagnosed over a 10-year period was done. RESULTS: OSSN accounted for 68 out of 91 ocular surface lesions affecting twice as many males as females and a peak incidence in the 30-39 years age group. They frequently presented as higher-grade and higher-stage lesions with invasive squamous cell carcinoma being the most frequently diagnosed OSSN. They also frequently showed an association with HIV infection and a relatively long duration of symptoms before presentation. CONCLUSION: OSSN occurs in a relatively young age group in our environment. Certain clinical and epidemiological features appear to predict the occurrence of higher-grade lesions, and this may help in the clinical prediction of likely pathologic grade and/or biologic behaviour of these lesions.

Long-term changes in ocular rigidity following scleral buckling for rhegmatogenous retinal detachment.

PURPOSE: To investigate the long-term effect of scleral buckling on corneal biomechanics and the effect of change of scleral properties on intraocular pressure (IOP) measurements. METHODS: This is a prospective case series, patients with rhegmatogenous retinal detachment prepared for scleral buckling were included. Goldmann applanation tonometry was used to measure IOP (GAT IOP). Ocular Response Analyzer (ORA) was used to measure corneal hysteresis (CH), corneal resistance factor (CRF), goldmann-corrected IOP (IOPg), and corneal-compensated IOP (IOPcc) preoperatively, and 1, 3, and 6 months postoperatively. RESULTS: Thirty-three eyes included in the final analysis, with an average age 38.4 ± 16.2 years. CH and CRF decreased significantly at first, third, sixth months post-scleral buckling; however, this effect decreased with time as follows; preoperative: 8.9 ± 1.5 and 8.5 ± 2.1, first month: 6.8 ± 1.6 and 7.1 ± 1.8 (P value = 0.00, 0.002), third month: 7.8 ± 1.5 and 7.6 ± 1.6 (P value = 0.001, 0.008), and sixth month: 7.7 ± 1.3 and 7.6 ± 1.7 (P value = 0.002, 0.055). IOP cc was 19.3 ± 3.6, 17.1 ± 4, and 17.6 ± 2.9 at 1, 3, and 6 months, and these readings were significantly higher than GAT (13.6 ± 7.6, 12.4 ± 5.1, and 12.1 ± 2.9, P values = 0.00) and IOPg (14.9 ± 3.6, 13.5 ± 4.1, and 13.9 ± 3.5, P values = 0.00). The change in CH at each visit is correlated with the difference between the IOPcc and GAT measurements. CONCLUSION: The conventional Goldmann applanation tonometry underestimates post buckle IOP measurements due corneal biomechanics changes. ORA might be an alternative and accurate method of measurement; however, further investigation is warranted.

Dietary and herbal supplements for weight loss: assessing the quality of patient information online.

BACKGROUND: Given the high prevalence of dietary and herbal supplement (DHS) use in tandem with the growing ease of internet access, patients commonly search online for consumer health information about these products. One common reason for DHSs use includes weight loss. Healthcare providers need to be aware of the quality of online information about DHSs for weight loss so they can adequately counsel their patients and provide them with guidance surrounding the identification of high-quality information resources. This study aimed to assess the quality of online DHSs consumer health information for weight loss that a "typical" patient might access online. METHODS: Six search terms were used to generate the first 20 websites on the Google search engine in four countries: Australia, Canada, the United Kingdom, and the United States (n = 480 websites). After applying exclusion criteria, eligible websites were quality assessed using the DISCERN instrument. This tool is comprised of 16 questions, each evaluated on a 5-point scale. The averages and standard deviations for each DISCERN instrument item, in addition to overall summed scores between 15 and 75 were calculated. RESULTS: Across 87 eligible websites, the mean summed score was 44.80 (SD = 11.53), while the mean overall DISCERN score of each website was 2.72 (SD = 0.99). In general, websites detailed and achieved their specified aims and described treatment benefits. However, most websites failed to describe the impact of treatment on overall quality of life and the impact of a no treatment option. The highest-scoring websites were largely government or health portal websites, while the lowest-scoring websites were largely commercial in nature. CONCLUSION: High variability in DISCERN instrument scores was found across all websites assessed. Healthcare providers should be aware of the fact that their patients may be accessing misinformation online surrounding the use of DHSs for weight loss. Therefore, it is important for healthcare providers to ensure that they are providing their patients with guidance on how to identify high-quality resources online, in order that safe, effective, and evidence-based decisions are made surrounding the use of DHSs for weight loss.

Histological, Histochemical, and Ultrastructural Approach to the Ductus Deferens in Male Nile Monitor Lizard (Varanus niloticus).

The ductus deferens is a fundamental part of the male genital tract and the continuation of the epididymal duct. As a male secondary sex organ, the ductus deferens plays a crucial role in the nourishment, storage, and maturation of spermatozoa. Some studies have provided information about the ductus deferens structure in reptiles; however, the full description of the ductus deferens remains to be clarified. The current study aimed to describe the Nile monitor lizard (Varanus niloticus) ductus deferens from histological, histochemical, and ultrastructural perspectives. The results revealed that the ductus deferens is formed histologically from two main cell types: principal and basal. The principal cells were tall and filled with periodic acid Schiff (+)/alcian blue (−) cytoplasmic granules. The basal cells were found just above the basement membrane. By transmission electron microscopy, the principal cells exhibited typical protein-secreting cell features. Additionally, some intraepithelial cells, such as halo cells, undifferentiated mesenchymal cells, and agranular leukocytes, were identified. This study presents the first detailed description of the Varanus niloticus ductus deferens. Further immunohistochemical studies are required to explore the function(s) of the cellular components.

Loss of RAR-α and RXR-α and enhanced caspase-3-dependent apoptosis in N-acetyl-p-aminophenol-induced liver injury in mice is tissue factor dependent.

Tissue factor (TF) activates the coagulation system and has an important role in the pathogenesis of various diseases. Our previous study stated that retinoid receptors (RAR-α and RXR-α) are released as a lipid droplet in monocrotaline/ lipopolysaccharide-induced idiosyncratic liver toxicity in mice. Herein, the interdependence between the release of retinoid receptors RAR-α and RXR-α and TF in Nacetyl-p-aminophenol (APAP)-induced mice liver toxicity, is investigated. Serum alanine transaminase (ALT) level, platelet and white blood cells (WBCs) counts, protein expression of fibrin, TF, cyclin D1 and cleaved caspase-3 in liver tissues are analyzed. In addition, histopathological evaluation and survival study are also performed. The results indicate that using of TF-antisense (TF-AS) deoxyoligonucleotide (ODN) injection (6 mg/kg), to block TF protein synthesis, significantly restores the elevated level of ALT and WBCs and corrects thrombocytopenia in mice injected with APAP. TF-AS prevents the peri-central overexpression of liver TF, fibrin, cyclin D1 and cleaved caspase- 3. The release of RXR-α and RAR-α droplets, in APAP treated sections, is inhibited upon treatment with TF-AS. In conclusion, the above findings designate that the released RXR-α and RAR-α in APAP liver toxicity is TF dependent. Additionally, the enhancement of cyclin D1 to caspase-3-dependent apoptosis can be prevented by blocking of TF protein synthesis.

Telehealth for delivery of haemophilia comprehensive care during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic caused an unprecedented impact to haemophilia healthcare delivery. In particular, rapid implementation of telehealth solutions was required to ensure continued access to comprehensive care. AIMS: To explore patient and healthcare provider (HCP) experience of telehealth in a European Haemophilia Comprehensive Care Centre. METHOD: A systematic evaluation was performed to survey patient and HCP experience and compare clinical activity levels with telehealth to in-person attendances. RESULTS: Public health measures implemented in March 2020 to reduce COVID-19 spread resulted in a 63% decrease in medical/nursing clinic consultation activity compared to the same period in 2019. Implementation of digital care pathways resulted in marked increase in activity (52% greater than 2019). Importantly, enhanced patient engagement was noted, with a 60% reduction in non-attendance rates. Survey of patients who had participated in medical/nursing teleconsultations demonstrated that teleconsultations improved access (79%), reduced inconvenience (82%), was easy to use (94%) and facilitated good communication with the HCP (97%). A survey exploring the telemedicine experience of HCPs, illustrated that HCPs were satisfied with teleconsultation and the majority (79%) would like to continue to offer teleconsultation as part of routine patient care. In addition to medical/nursing reviews, continued access to physiotherapy with virtual exercise classes for people with haemophilia and teleconsultation for acute dental issues was equally successful. CONCLUSION: During an unprecedented public health emergency, telehealth has enabled continued access to specialized haemophilia comprehensive care. Our novel findings show that this alternative is acceptable to both patients and HCPs and offers future novel opportunities.