Development,optimization and characterization of glycyrrhetinic acid–chitosan nanoparticles of atorvastatin for liver targeting

Glycyrrhetinic acid-modified chitosan (mGA-suc-CTS) is used as liver-targeted carrier for drug delivery. In this study, nanoparticles were prepared by ionic gelation process, and glycyrrhetinic acid act as the targeting ligand. The structure of the product was confirmed by IR and NMR techniques. The main aim of this study was to deliver atorvastatin directly to the liver by using same conjugate and reduce the associated side-effects, i.e. hepatotoxicity at high dose. Characterization of the developed formulation was performed by differential scanning calorimetry, particle size measurements and cellular uptake studies. Release profile, pharmacokinetics studies and organ distribution studies showed that developed formulation shows a relative higher liver uptake. The optimized formulation showed increased plasma concentration than the CTS nanoparticles as well as plain drug and the accumulation in the liver was nearly 2.59 times more than that of obtained with the CTS nanoparticles. Pharmaceutical and pharmacological indicators suggested that the proposed strategy can be successfully utilized for liver targeting of therapeutics.     

Targeting inflammation in lower-risk MDS

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Role of amniotic membrane transplantation in treating acute ocular manifestations in Steven–Johnson syndrome and its long-term impact

Background:Steven–Johnson syndrome (SJS) is a serious disorder affecting the skin and mucous membrane, causing multiple flaccid bullae and purpuric rashes with sheet-like epithelial detachment including the ocular surface. The long-term outcomes following SJS are dismal and manifest as corneal vascularization, lid-wiper keratopathy, and severe dry eyes. The disease course can be modified if amniotic membrane graft is performed at the first week of disease, and the above-said complications can be avoided. This procedure thus not only decreases the morbidity but also improves the quality of life.Purpose:This video discusses the long-term sequelae of SJS which can be modified with timely intervention during the acute stage and thus significantly decreases morbidity.Synopsis:The video demonstrates the simple technique of amniotic membrane transplantation in the acute stage in SJS and its impact in long run.Highlights:There should be a low threshold for doing early amniotic membrane transplantation in patients with SJS with ocular surface involvement. Early intervention can change the disease course and decrease disease morbidity significantly.Video link: https://youtu.be/qgIiVcW56Oo     

The Effect of Customized and Silicon Insoles on Mid- and Hindfoot in Adult Flexible Pes Planovalgus

BackgroundFlexible flat foot or pes planovalgus is a common foot deformity, and silicone and customized insole are commonly used as a non-operative treatment modality of flexible planovalgus. However, there are inadequate data and limited evidence available regarding the immediate effects of their use in midfoot and hindfoot of adults. The aim of this study is to quantify and compare the radiological parameters immediately on weightbearing with silicon and customized insoles and without them to assess the effect on midfoot and hindfoot of the flexible planovalgus in adults.MethodsA total number of 11 (8 females and 3 males) subjects with flexible pes planovalgus deformity without any other foot deformity were included in the study. Each patient was assessed three times in a random sequence without and with use of either silicon insoles or customized insole. The radiographic parameters without insole, with silicon insole, and with customized insole conditions were calculated using online available computer software Kinovea.ResultsOne-way ANOVA analysis was performed between groups (without insole, with silicone insole and with customized insole). The hindfoot parameters depicted that calcaneal inclination angle (CIA) was significant increased (P = 0.000) and talar declination angle (TDA) was significantly decreased (P = 0.003) only with the use of customized insole compared to without insole. The midfoot parameters depicted that the first metatarsal angle (FMA) and talonavicular coverage angle (TCA) were significantly lower with customized insole (P = 0.00) as compared to other two groups and significantly lower with silicone insole (P = 0.00) as compared to without insole group.ConclusionThe results imply that the compressibility of the insole material affects the forefoot and hindfoot biomechanics differently. This study concludes that silicone insole affects only the midfoot which bears 45% of bodyweight and customized insole affects both midfoot and more importantly the hindfoot which bears 55% of bodyweight.     

A Pan-Canadian Consensus Statement on First-Line PARP Inhibitor Maintenance for Advanced,High-Grade Serous and Endometrioid Tubal,Ovarian, and Primary Peritoneal Cancers

The majority of patients with advanced, high-grade epithelial-tubo ovarian cancer (EOC) respond well to initial treatment with platinum-based chemotherapy; however, up to 80% of patients will experience a recurrence. Poly(ADP-ribose) Polymerase (PARP) inhibitors have been established as a standard of care maintenance therapy to prolong remission and prevent relapse following a response to first-line platinum-chemotherapy. Olaparib and niraparib are the PARP inhibitors currently approved for use in the first-line maintenance setting in Canada. Selection of maintenance therapy requires consideration of patient and tumour factors, presence of germline and somatic mutations, expected drug toxicity profile, and treatment access. This paper discusses the current clinical evidence for first-line PARP inhibitor maintenance therapy in patients with advanced, high-grade EOC and presents consensus statements and a treatment algorithm to aid Canadian oncologists on the selection and use of PARP inhibitors within the Canadian EOC treatment landscape.     

Exploring the Barriers and Motivators to Dietary Adherence among Caregivers of Children with Disorders of Amino Acid Metabolism (AAMDs): A Qualitative Study

Dietary intervention is generally accepted as the mainstay of treatment for patients with disorders of amino acid metabolism (AAMDs). However, dietary adherence to a low-protein diet is always reported as a common challenge among these patients. This study explored the perception of barriers and motivators to dietary adherence among caregivers of AAMD patients in Malaysia. Twenty caregivers of children with AAMDs receiving ongoing treatment at the genetic clinic participated in an online focus group discussion from November to December 2021. Findings showed a total of five interrelated main themes identified from focus group discussion (FGD) exploring parents’ experiences related to the management of their child’s daily diet. The barriers to dietary adherence were burden of dietary treatment, diet and dietary behavior, parenting challenges, limited knowledge related to dietary treatment, and challenges in healthcare system delivery. Key factors facilitating good dietary adherence include good knowledge of dietary treatment, parental coping strategies, social coping, and dietary behavior. In conclusion, despite the existence of several barriers to the implementation of dietary treatment, caregivers managed to use a wide range of coping strategies to overcome some, if not all, of the challenges. The important next step is to develop, in conjunction with multidisciplinary healthcare professionals, feasible implementation strategies that could address these barriers and at the same time improve the quality of life of caregivers.