The potential role of miRNA therapies in spinal muscle atrophy.

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by low levels of full-length survival motor neuron (SMN) protein due to the loss of the survival motor neuron 1 (SMN1) gene and inefficient splicing of the survival motor neuron 2 (SMN2) gene, which mostly affects alpha motor neurons of the lower spinal cord. Despite the U.S. Food and Drug Administration (FDA) approved SMN-dependent therapies including Nusinersen, Zolgensma® and Evrysdi™, SMA is still a devastating disease as these existing expensive drugs may not be sufficient and thus, remains a need for additional therapies. The involvement of microRNAs (miRNAs) in SMA is expanding because miRNAs are important mediators of gene expression as each miRNA could target a number of genes. Hence, miRNA-based therapy could be utilized in treating this genetic disorder. However, the delivery of miRNAs into the target cells remains an obstacle in SMA, as there is no effective delivery system to date. This review highlights the potential strategies for intracellular miRNA delivery into target cells and current challenges in miRNA delivery. Furthermore, we provide the future prospects of miRNA-based therapeutic strategies in SMA.

Occurrence of Acanthamoeba genotypes in Central West Malaysian environments.

Acanthamoeba species are ubiquitous free-living protozoa that can be found worldwide. Occasionally, it can become parasitic and the causative agent of acanthamoebic keratitis (AK) and Granulomatous Amoebic Encephalitis (GAE) in man. A total of 160 environmental samples and 225 naturally-infected animal corneal swabs were collected for Acanthamoeba cultivation. Acanthamoeba was found to be high in samples collected from environments (85%, 136/160) compared to infected animal corneas (24.89%, 56/225) by microscopic examination. Analysis of nucleotide sequence of 18S rRNA gene of all the 192 cultivable Acanthamoeba isolates revealed 4 genotypes (T3, T4. T5 and T15) with T4 as the most prevalent (69.27%, 133/192) followed by T5 (20.31%), T15 (9.90%) and T3 (0.52%). Genotype T4 was from the strain of A. castellanii U07401 (44.27%), A. castellanii U07409 (20.83%) and A. polyphagaAY026243 (4.17%), but interestingly, only A. castellanii U07401 was detected in naturally infected corneal samples. In environmental samples, T4 was commonly detected in all samples including dry soil, dust, wet debris, wet soil and water. Among the T4, A. castellanii (U07409) strains were detected high occurrence in dry (45%) followed by aquatic (32.50%) and moist (22.50%) samples but however A. castellanii (U07401) strains were dominant in dry samples of soil and dust (93.10%). Subsequently, genotype T5 of A. lenticulata (U94741) strains were dominant in samples collected from aquatic environments (58.97%). In summary, A. castellanii (U07401) strains were found dominant in both environmental and corneal swab samples. Therefore, these strains are possibly the most virulent and dry soil or dusts are the most possible source of Acanthamoeba infection in cats and dogs corneas.

Management of Symmetrical Peripheral Gangrene.

Symmetrical peripheral gangrene (SPG) is a rare, debilitating disease that deserves more widespread concern among the medical fraternities. The objective of this review is to outline the etiology, pathology findings, and management practices of SPG. About 18%-40% mortality rate was reported, and survivors have high frequency of multiple limb amputations. SPG is the hallmark of disseminated intravascular coagulation (DIC). The main pathogenesis theory, to date, is microthrombosis associated with disturbed procoagulant-anticoagulant balance. The treatment of SPG is largely anecdotal and theoretically involves heparin-based anticoagulation and substitution of natural anticoagulants. Early recognition, prompt management of DIC, and underlying conditions may halt the progression of the disease. The multicenter randomized controlled trial should be set up to formulate the proper treatment guidelines.

Salvage of elbow function in chronic complex elbow fracture dislocation with total elbow arthroplasty: a case report.

In patients with an elbow fracture dislocation the incidence of radial head fracture is 36%, where as coronoid process fractures occur in 13%, and olecranon fractures in 4% of patients. Combination of all these fractures with a 'terrible triad' is rarely reported in the literature. We describe a 40 year old lady involved in a polytrauma who had head injury, pnuemothorax and an open fracture dislocation of the left elbow. The Injury Severity Score initially on admission was 44. She presented with chronic elbow instability with pain 1 year later. A semi constrained total elbow arthroplasty (TEA) with a Coonrad-Morrey prosthesis was performed in this complex injury involving fractures of the coronoid, olecranon, proximal third of the ulna and radial head malunion with heterotrophic ossification around the elbow joint. Although the survivorship of total elbow replacements has improved, it is still a procedure reserved to older patients with low functional demand. At 1-year follow-up, the patient had full range in flexion and extension. The Mayo Elbow Performance Score (MEPS) was 100. TEA is a procedure which gains function and stability in a terrible triad elbow.

Salvage of elbow function in chronic complex elbow fracture dislocation with total elbow arthroplasty: a case report

In patients with an elbow fracture dislocation the incidence of radial head fracture is 36%, where as coronoid process fractures occur in 13%, and olecranon fractures in 4% of patients. Combination of all these fractures with a 'terrible triad' is rarely reported in the literature. We describe a 40 year old lady involved in a polytrauma who had head injury, pnuemothorax and an open fracture dislocation of the left elbow. The Injury Severity Score initially on admission was 44. She presented with chronic elbow instability with pain 1 year later. A semi constrained total elbow arthroplasty (TEA) with a Coonrad-Morrey prosthesis was performed in this complex injury involving fractures of the coronoid, olecranon, proximal third of the ulna and radial head malunion with heterotrophic ossification around the elbow joint. Although the survivorship of total elbow replacements has improved, it is still a procedure reserved to older patients with low functional demand. At 1-year follow-up, the patient had full range in flexion and extension. The Mayo Elbow Performance Score (MEPS) was 100. TEA is a procedure which gains function and stability in a terrible triad elbow.