Isolation and expansion of thymus-derived regulatory T cells for use in pediatric heart transplant patients

Regulatory T-cells (Tregs) are a subset of T cells generated in the thymus with intrinsic immunosuppressive properties. Phase I clinical trials have shown safety and feasibility of Treg infusion to promote immune tolerance and new studies are ongoing to evaluate their efficacy. During heart transplantation, thymic tissue is routinely discarded providing an attractive source of Tregs. In this study, we developed a GMP-compatible protocol for expanding sorted thymus-derived CD3⁺CD4⁺CD25⁺CD127^– (Tregs) as well as CD3⁺CD4⁺CD25⁺CD127^–CD45RA⁺ (RA⁺Tregs) cells. We aimed to understand whether thymic RA⁺Tregs can be isolated and expanded offering an advantage in terms of stability as it has been previously shown for circulating adult CD45RA⁺ Tregs. We show that both Tregs and RA⁺Tregs could be expanded in large numbers and the presence of rapamycin is essential to inhibit the growth of IFN-γ producing cells. High levels of FOXP3, CTLA4, and CD25 expression, demethylation of the FOXP3 promoter, and high suppressive ability were found with no differences between Tregs and RA⁺Tregs. After freezing and thawing, all Treg preparations maintained their suppressive ability, stability, as well as CD25 and FOXP3 expression. The number of thymic Tregs that could be isolated with our protocol, their fold expansion, and functional characteristics allow the clinical application of this cell population to promote tolerance in pediatric heart transplant patients.     

Osteoporosis treatment with zoledronic acid in pediatric population at a university hospital in Western Saudi Arabia: A 13-year experience

Objectives:

To highlight the clinical benefit, efficacy, and safety of zoledronic acid (ZA) therapy in children and adolescents with primary and secondary osteoporosis.

Methods:

This is a retrospective observational study of 131 children and adolescents visiting the Pediatric Endocrine Clinic at King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia, between January 2002 and January 2015. Clinical and laboratory data were collected for each patient and adverse events were evaluated.

Results:

The mean patient age was 11.43 years. There was a significant decrease in the number of fractures after ZA treatment for primary osteoporosis (p=0.000) and in secondary osteoporosis (p=0.005). There was a significant decrease in both osteocalcin (p=0.001) and C-terminal telopeptide (p=0.003) in patients with primary osteoporosis, as well as osteocalcin (p=0.003) and C-terminal telopeptide (p=0.008) in patients with secondary osteoporosis after treatment.

Conclusion:

The use of ZA in children and adolescent appears to have favorable effects on fracture rate and quality of life, including pain and mobility in symptomatic individuals. Intravenous ZA is comparable to other bisphosphonate agents in its efficacy and safety and features a more convenient infusion protocol with no documented long-term complications, thus, we advise its use in pediatric population.Once a concern exclusively in the elderly, osteoporosis is becoming a major concern among the global pediatric population.1 Despite being the most common human metabolic disorder in adults, its prevalence in the pediatric population is not well identified. Osteoporosis is generally characterized by a decrease in bone mass and density that can lead to an increased fracture susceptibility. As childhood and adolescence are critical periods for skeletal maturity, as well as bone growth and strength, osteoporosis can hamper those parameters in various ways. Therefore, teenagers should be targeted as an at-risk population, and preventive measures should be implemented to maximize bone mass, and theoretically decrease lifelong fracture risk. Causes of childhood osteoporosis are classified into primary; those that are due to an intrinsic bone abnormality (usually genetic in origin), and secondary; those that are due to underlying medical conditions, or their treatment. Both primary and secondary osteoporosis have been observed and considered in this study population. Bisphosphonates are pyrophosphate analogs that increase bone mineral density (BMD) by inhibiting bone resorption, which favors bone formation during remodeling.2,3 They are currently the main pharmacological agents for the management of childhood osteoporosis.4 Zoledronic acid (ZA; Zometa Inc., Novartis Pharma AG, Lichtstrasse, Switzerland) is a new-generation heterocyclic nitrogen-containing bisphosphonate that has demonstrated markedly higher potency, and a greater therapeutic ratio in clinical trials than earlier generation bisphosphonates, including pamidronate.5,6 Up to date, many studies have investigated bisphosphonate treatment primarily with the use of pamidronate in many bone related diseases.7 As to the ZA treatment of pediatric osteoporosis, there are no published data on long-term use, safety and efficacy. Moreover, there are no Saudi local, Arabian, or even internationally published data on a large study number of children receiving ZA. In this study, we aim to review a 13-year experience with primary and secondary causes of osteoporosis, as well as the efficacy, and safety of intravenous ZA as the treatment of choice in our pediatric population at the King Abdulaziz University Hospital (KAUH), Jeddah, Kingdom of Saudi Arabia (KSA).     

Efficiency of diode laser and ultrasonic-activated irrigation in retreatment of gutta percha and bioceramic sealer: An in vitro study

This study was to determine the effectiveness of diode laser (LI) and ultrasonic (UI)-activated irrigation with or without a surfactant as adjunct techniques during the retreatment of gutta-percha and tricalcium silicate-based sealer (BC) sealer. Forty-two single-rooted premolars were instrumented and filled with gutta-percha and BC sealer, then retreated using NiTi retreatment rotary files. Teeth were randomly divided into three equal groups: Control (manual irrigation), UI and LI groups. Each group was subdivided into 2.5% NaOCl irrigant and ChlorCid™️ Surf subgroups. The amount of material removed following UI and LI was significantly greater than that of manual irrigation (p < 0.0001). However, there was no significant difference between the surfactant subgroups, irrespective of irrigation technique (p = 1.00, p = 0.535, p = 0.805). The use of UI and LI adjuncts to NiTi rotary retreatment techniques showed significant improvement in gutta-percha with BC sealer removal. However, surfactants had no effect on the efficacy.     

Seroprevalence of SARS-CoV-2 Binding and Neutralizing Antibodies in Healthcare Workers during the Epidemic Peak in Referral Hospitals and Quarantine Sites: Saudi Arabia

Healthcare workers (HCWs) are at high risk for SARS-CoV-2 infection compared to the general population. Here, we aimed to evaluate and characterize the SARS-CoV-2 seropositivity rate in randomly collected samples among HCWs from the largest referral hospitals and quarantine sites during the peak of the COVID-19 epidemic in the city of Jeddah, the second largest city in Saudi Arabia, using a cross-sectional analytic study design. Out of 693 participants recruited from 29 June to 10 August 2020, 223 (32.2%, 95% CI: 28.8–35.8) were found to be confirmed seropositive for SARS-CoV-2 antibodies, and among those 197 (88.3%) had never been diagnosed with COVID-19. Seropositivity was not significantly associated with participants reporting COVID-19 compatible symptoms as most seropositive HCW participants 140 (62.8%) were asymptomatic. The large proportion of asymptomatic SARS-CoV-2 cases detected in our study demands periodic testing as a general hospital policy.     

Oral gel loaded with penciclovir–lavender oil nanoemulsion to enhance bioavailability and alleviate pain associated with herpes labialis

Herpes labialis, caused by herpes simplex virus type 1, is usually characterized by painful skin or mucosal lesions. Penciclovir (PV) tablets are found to be effective against herpes labialis but suffer from poor oral bioavailability. This study aimed to combine the benefits of PV and lavender oil (LO), which exhibits anesthetic activity, in the form of a self-nanoemulsifying drug delivery system (SNEDDS) for the treatment of herpes labialis. Toward this purpose, LO (oil), Labrasol:Labrafil M1944 CS in the ratio of 6:4 (surfactant mixture), and Lauroglycol-FCC (co-surfactant, selected based on the solubility of PV) were evaluated as the independent factors using a distance quadratic mixture design. The formulation was optimized for the minimum globule size and maximum stability index and was determined to contain 14% LO, 40.5% Labrasol:Labrafil 1944 (6:4), and 45.5% Lauroglycol-FCC. The optimized PV-LO-SNEDDS was embedded in chitosan hydrogel and the resulting formulations coded by (O3) were prepared and evaluated. The rheological studies demonstrated a combined pseudoplastic and thixotropic behavior with the highest flux of PV permeation across sheep buccal mucosa. Compared to a marketed 1% PV cream, the O3 formulation exhibited a significantly higher and sustained PV release, nearly twice the PV permeability, and a relative bioavailability of 180%. Overall, results confirm that the O3 formulation can provide an efficient delivery system for PV to reach oral mucosa and subsequent prolonged PV release. Thus, the PV-LO-SNEDDS embedded oral gel is promising and can be further evaluated in clinical settings to establish its therapeutic use in herpes labialis.     

Patient-guided modifications of oral anticoagulant drug intake during Ramadan fasting: a multicenter cross-sectional study

Journal of Thrombosis and Thrombolysis - Fasting Ramadan is known to influence patients’ medication adherence. Data on patients’ behavior to oral anticoagulant (OAC) drug intake during...