Krabbe disease: A personal perspective and hypothesis.

Krabbe disease (KD) or globoid cell leukodystrophy (GLD) is one of the lysosomal disorders affecting central and peripheral nervous systems (CNS and PNS). It is caused by mutations on the galactocerebrosidase (GALC) gene. Affected individuals accumulate undegraded substrates and suffer from neuroinflammation.

Key considerations in formulation development for gene therapy products.

Gene therapy emerged as an important area of research and led to the success of multiple product approvals in the clinic. The number of clinical trials for this class of therapeutics is expected to grow over the next decade. Gene therapy products are complex and heterogeneous, employ different types of vectors and are susceptible to degradation.

Advances in the Diagnosis and Treatment of Krabbe Disease.

Krabbe disease is an autosomal recessive leukodystrophy caused by pathogenic variants in the galactocerebrosidase (GALC) gene. GALC activity is needed for the lysosomal hydrolysis of galactosylceramide, an important component of myelin. While most patients are infants, older patients are also diagnosed.

Can early treatment of twitcher mice with high dose AAVrh10-GALC eliminate the need for BMT?

Krabbe disease (KD) is an autosomal recessive disorder caused by mutations in the galactocerebrosidase (GALC) gene resulting in neuro-inflammation and defective myelination in the central and peripheral nervous systems. Most infantile patients present with clinical features before six months of age and die before two years of age. The only treatment available for pre-symptomatic or mildly affected individuals is hematopoietic stem cell transplantation (HSCT).

Persistent Shoulder Pain After Anterior Cervical Discectomy and Fusion (ACDF): Another Dual Pathology.

Purpose It is often difficult for the clinician to isolate the etiology of pain occurring either in the neck or shoulder because of the reason that neck pain can refer to the shoulder and vice versa. Concordance research has found that around one in 10 patients who were referred for cervical radiculopathy had comorbid shoulder pathology. The goal of this research is to analyze and correlate risk factors for persistent shoulder pain (non-dermatomal) following cervical spine surgery.

Enzyme replacement combinational therapy: effective treatments for mucopolysaccharidoses.

Introduction: Mucopolysaccharidoses (MPS), as a group of inherited lysosomal storage disorders (LSDs), are clinically heterogeneous and characterized by multi-systemic manifestations, such as skeletal abnormalities and neurological dysfunctions. The currently used enzyme replacement therapy (ERT) might be associated with several limitations including the low biodistribution of the enzymes into the main targets, immunological responses against foreign enzymes, and the high cost of the treatment procedure. Therefore, a suitable combination approach can be considered for the successful treatment of each type of MPS.

Role of Pregabalin to Decrease Postoperative Pain in Microdiscectomy: A Randomized Clinical Trial.

Purpose The purpose of this study is to compare the effect of pregabalin in reducing the neuropathic pain in postoperative patients who have undergone single-level microdiscectomy for prolapsed intervertebral lumbar disc. Methods A randomized control clinical trial was conducted from June 2018 to April 2020 in three campuses Dr. Ziauddin University Hospital, Karachi, by two spinal surgeons.

GO/PAMAM as a High Capacity Adsorbent for Removal of Alizarin Red S: Selective Separation of Dyes.

Adsorption of Alizarin Red S (ARS) on graphene oxide/poly(amidoamine) (GO/PAMAM) was studied at different ARS initial concentrations, temperatures, pHs, shaking rates and contact times. Adsorption sites of GO/PAMAM were phenolic -OHgroup of GO and amine groups (-NH2, -NH3+ and -NHR2+) of PAMAM dendrimer moieties of GO/PAMAM. At pH = 2 and 318 K, maximum adsorption capacity of the adsorbent was 1275.

Ilizarov Fixation Method of Tibia Plateau Fractures: A Prospective Observational Study.

Background:  Tibia plateau fractures are most commonly managed with open reduction and internal fixation (ORIF) technique, external fixation via minimally invasive technique are an excellent alternative. The aim of this study was to assess the results of tibia plateau fractures by using the Ilizarov external fixator. The analysis was done both clinically and radiologically.

BioImpacts: An emerging global journal.

The toddling has now grown into a young adult with strong opinions and perspectives, to a high-quality journal, and it has not been raised but by a family of professional editors, reviewers, authors, and even readers who had fantasized about a bright future and that fantasies are now coming true one-by-one.

Conditions for combining gene therapy with bone marrow transplantation in murine Krabbe disease.

Krabbe disease (KD) is an autosomal recessive lysosomal disorder caused by mutations in the galactocerebrosidase (GALC) gene. This results in defective myelination in the peripheral and central nervous systems due to low GALC activity. Treatment at this time is limited to hematopoietic stem cell transplantation (HSCT) in pre-symptomatic individuals.

Epitope-based vaccine design: a comprehensive overview of bioinformatics approaches.

Computational epitope-based vaccine design is the cornerstone of vaccine development. Owing to the selection of proper compositions [antigens (Ags), epitopes, peptide linkers, and intramolecular adjuvants], epitope-based vaccines are considered a cost- and time-effective approach resulting in the development of vaccines with maximal therapeutic efficacy and minimal adverse reactions. In this review, we provide insights into in silico epitope-based vaccine design and highlight vaccinology procedures used for the development of the next-generation vaccines with high effectiveness.

Bioengineered smart bacterial carriers for combinational targeted therapy of solid tumours.

Despite many endeavours for the development of new anticancer drugs, effective therapy of solid tumours remains a challenging issue. The current cancer chemotherapies may associate with two important limitations, including the lack/trivial specificity of treatment modalities towards diseased cells/tissues resulting in undesired side effects, and the emergence of drug-resistance mechanisms by tumour cells causing the failure of the treatment. Much attention, therefore, has currently been paid to develop smart and highly specific anticancer agents with maximal therapeutic impacts and minimal side effects.

Mathematical Models to Shed Light on Amyloid-Beta and Tau Protein Dependent Pathologies in Alzheimer's Disease.

The number of patients suffering from dementia due to Alzheimer's disease (AD) is constantly rising worldwide. This has accordingly resulted in huge burdens on the health systems and involved families. Lack of profound understanding of neural networking in normal brain and their interruption in AD makes the treatment of this neurodegenerative multifaceted disease a challenging issue.

Peptide-mediated drug delivery across the blood-brain barrier for targeting brain tumors.

Introduction: Transportation of the nutrients and other substances from the blood to the brain is selectively controlled by the brain capillary endothelial cells that form a restrictive barrier, so-called blood-brain barrier (BBB). Currently, there is no unimpeachable approach to overcome the BBB obstructiveness because the existing options are either invasive or ineffective.

Areas Covered: This review delineates the biological impacts of BBB on brain drug delivery and targeting.

Targeted enzyme delivery systems in lysosomal disorders: an innovative form of therapy for mucopolysaccharidosis.

Mucopolysaccharidoses (MPSs), which are inherited lysosomal storage disorders caused by the accumulation of undegraded glycosaminoglycans, can affect the central nervous system (CNS) and elicit cognitive and behavioral issues. Currently used enzyme replacement therapy methodologies often fail to adequately treat the manifestations of the disease in the CNS and other organs such as bone, cartilage, cornea, and heart. Targeted enzyme delivery systems (EDSs) can efficiently cross biological barriers such as blood-brain barrier and provide maximal therapeutic effects with minimal side effects, and hence, offer great clinical benefits over the currently used conventional enzyme replacement therapies.

Enzyme replacement therapies: what is the best option?

Despite many beneficial outcomes of the conventional enzyme replacement therapy (ERT), several limitations such as the high-cost of the treatment and various inadvertent side effects including the occurrence of an immunological response against the infused enzyme and development of resistance to enzymes persist. These issues may limit the desired therapeutic outcomes of a majority of the lysosomal storage diseases (LSDs). Furthermore, the biodistribution of the recombinant enzymes into the target cells within the central nervous system (CNS), bone, cartilage, cornea, and heart still remain unresolved.

Lurasidone Induced Thrombocytopenia: Is it a Signal of Drug Induced Myelosuppression?

The U.S. Food and Drug Administration (FDA) has approved a supplemental new drug application Lurasidone (Latuda, Sunovion Pharmaceuticals), an atypical antipsychotic, for the treatment of schizophrenia in adolescents 13-17 years of age.

Spectrophotometric analysis of thrombolytic activity: SATA assay.

Measurement of thrombolytic activity is crucial for research and development of novel thrombolytics. It is a key factor in the assessment of the effectiveness of conventionally used thrombolytic therapies in the clinic. Previous methods used for the assessment of thrombolytic activity are often associated with some drawbacks such as being costly, time-consuming, complex with low accuracy.

Novel PET and Near Infrared Imaging Probes for the Specific Detection of Bacterial Infections Associated With Cardiac Devices.

Objectives: The aim of this study was to develop imaging agents to detect early stage infections in implantable cardiac devices.

Background: Bacteria ingest maltodextrins through the specific maltodextrin transporter. We developed probes conjugated with either a fluorescent dye (maltohexaose fluorescent dye probe [MDP]) or a F-18 (F18 fluoromaltohexaose) and determined their usefulness in a model of infections associated with implanted cardiac devices.

A Trimethoprim Conjugate of Thiomaltose Has Enhanced Antibacterial Efficacy In Vivo.

Trimethoprim is one of the most widely used antibiotics in the world. However, its efficacy is frequently limited by its poor water solubility and dose limiting toxicity. Prodrug strategies based on conjugation of oligosaccharides to trimethoprim have great potential for increasing the solubility of trimethoprim and lowering its toxicity, but they have been challenging to develop due to the sensitivity of trimethoprim to chemical modifications, and the rapid degradation of oligosaccharides in serum.

Study of Adsorption Mechanism of Congo Red on Graphene Oxide/PAMAM Nanocomposite.

Graphene oxide/poly(amidoamine) (GO/PAMAM) nanocomposite adsorbed high quantities of congo red (CR) anionic dye in 0.1 M NaCl solution, with the maximum adsorption capacity of 198 mg·g. The kinetics and thermodynamics of adsorption were investigated to elucidate the effects of pH, temperature, shaking rate, ionic strength, and contact time.

Debate on human aging and lifespan.

The issue of human lifespan has long been a matter of controversy among scientists. In spite of the recent claim by Dong et al that human lifespan is limited to 115 years, with the mounting improvements in biotechnology and scientific understanding of aging, we may be confident that aging will slow down over the course of the current century extending human longevity much longer than 115 years.

Recent advances in targeted delivery of tissue plasminogen activator for enhanced thrombolysis in ischaemic stroke.

Tissue plasminogen activator (tPA) is the only FDA approved medical treatment for the ischaemic stroke. However, it associates with some inevitable limitations, including: short therapeutic window, extremely short half-life and low penetration in large clots. Systemic administration may lead to complications such as haemorrhagic conversion in the brain and relapse in the form of re-occlusion.