Designing and Validating a Hereditary Spastic Paraplegia-Specific Quality of Life Rating Scale (HSPQoL).

Patients with Hereditary Spastic Paraplegia (HSP) report reduced quality of life (QoL) compared to the general population. Generic QoL measures do not address disease-specific aspects such as spasticity, access to specialty HSP clinics, and bladder symptoms. We designed and validated a HSP-specific QoL scale (HSPQoL), intended for use in standard clinical settings and clinical trials.

The effect of novel vitamin D3 compounds on saliva samples from COVID-19 patients: a lab study.

Vitamin D has shown antimicrobial effects. This study aimed to explore the antiviral effects of vitamin D3 on saliva samples collected from patients with coronavirus disease-19 (COVID-19) and compare saliva and swab results to aid in policy development. Saliva and swab samples were collected from adult patients with a positive test for COVID-19 at the King Faisal Specialist Hospital and Research Centre, Jeddah.

Variation in Exon 29 of the NOS1 Gene Does Not Contribute to Parkinson's Disease in the North Karnataka Population.

Introduction: Nitric oxide (NO) overproduction has been found to have neurotoxic effects on the brain. Moreover, in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced, the suppression of the NO-synthesizing enzymes, such as neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS), has neuroprotective benefits in Parkinson's disease (PD). These findings imply that NOS may have a role in regulating the nigral dopaminergic neurons' tolerance to environmental stressors in PD.

Pharmacological rescue of mitochondrial and neuronal defects in hereditary spastic paraplegia patient neurons using high throughput assays.

is the most common form of autosomal recessive hereditary spastic paraplegia (HSP). There is a lack of HSP- human neuronal models to understand the disease mechanism and identify new drug treatments. We generated a human neuronal model of HSP- using induced pluripotent stem (iPS) cell technology.

Outcome Measures and Biomarkers for Clinical Trials in Hereditary Spastic Paraplegia: A Scoping Review.

Hereditary spastic paraplegia (HSP) is characterized by progressive lower limb spasticity. There is no disease-modifying treatment currently available. Therefore, standardized, validated outcome measures to facilitate clinical trials are urgently needed.

Generation of human-induced pluripotent-stem-cell-derived cortical neurons for high-throughput imaging of neurite morphology and neuron maturation.

High-throughput imaging allows in vitro assessment of neuron morphology for screening populations under developmental, homeostatic, and/or disease conditions. Here, we present a protocol to differentiate cryopreserved human cortical neuronal progenitors into mature cortical neurons for high-throughput imaging analysis. We describe the use of a notch signaling inhibitor to generate homogeneous neuronal populations at densities amenable to individual neurite identification.

Reduced acetylated α-tubulin in hereditary spastic paraplegia patient PBMCs.

HSP is the most common form of hereditary spastic paraplegia (HSP), a neurodegenerative disease causing lower limb spasticity. Previous studies using HSP patient-derived induced pluripotent stem cell cortical neurons have shown that patient neurons have reduced levels of acetylated α-tubulin, a form of stabilized microtubules, leading to a chain of downstream effects eventuating in increased vulnerability to axonal degeneration. Noscapine treatment rescued these downstream effects by restoring the levels of acetylated α-tubulin in patient neurons.

De-isolation of vaccinated COVID-19 health care workers using rapid antigen detection test.

Background: COVID-19 de-isolation guidelines of health care workers (HCW) were formulated based on evidence describing the duration of infectious viral shedding of the wild SARS-CoV-2 virus. During the periods of COVID-19 vaccination and variants, a test-based approach was recommended to end isolation of HCW, based on emerging data describing the viral kinetics of COVID-19 variants. While Rapid antigen detection tests (RADT) are increasingly used in the diagnosis of COVID-19, their use is limited in de-isolation.

Revisiting Middle East Respiratory Coronavirus (MERS-CoV) Outbreak Chest Radiographic Initial Findings, Temporal Progression, and Correlation to Outcomes: A Multicenter Study.

Objectives Accounts of initial and follow-up chest X-rays (CXRs) of the Middle East respiratory coronavirus (MERS-CoV) patients, and correlation with outcomes, are sparse. We retrospectively evaluated MERS-CoV CXRs initial findings, temporal progression, and outcomes correlation. Materials and methods Fifty-three real-time reverse-transcriptase-polymerase chain reaction (rRT-PCR)-confirmed MERS-CoV patients with CXRs were retrospectively identified from November 2013 to October 2014.

SARS-COV-2 Triggers the Development of Class I and Class II HLA Antibodies in Recovered Convalescent Plasma Donors.

Various studies have shown that SARS-CoV-2 is a highly immunogenic virus. It is known that different types of immunogenic viral pathogens could trigger the formation of HLA antibodies. Therefore, there is a concern that the SARS-CoV-2 could also induce the development of HLA antibodies in volunteers, who donate convalescent plasma after their recovery from COVID-19.

Data-Driven Prediction for COVID-19 Severity in Hospitalized Patients.

Clinicians urgently need reliable and stable tools to predict the severity of COVID-19 infection for hospitalized patients to enhance the utilization of hospital resources and supplies. Published COVID-19 related guidelines are frequently being updated, which impacts its utilization as a stable go-to resource for informing clinical and operational decision-making processes. In addition, many COVID-19 patient-level severity prediction tools that were developed during the early stages of the pandemic failed to perform well in the hospital setting due to many challenges including data availability, model generalization, and clinical validation.

Characteristics and outcome of tertiary care critically ill COVID-19 patients with multiple comorbidities admitted to the intensive care unit.

Purpose: We conducted this study to evaluate the characteristics and outcomes exclusively in high-risk coronavirus disease 2019 (COVID-19) tertiary care patients with multiple comorbidities, as very few have reported outcomes in this specific cohort.

Methods: All patients, with two or more risk factors for COVID-19 and Charlson Comorbidity Index (CCI) of >2, who were admitted to intensive care unit (ICU) between March and December 2020 were included. Their characteristics, ICU course, and outcomes as well as differences between nonsurvivors and survivors were evaluated.

Early use of tocilizumab in solid organ transplant recipients with COVID-19: A retrospective cohort study in Saudi Arabia.

Background: Tocilizumab was studied to reduce cytokine syndrome in patients with severe COVID-19 pneumonia in solid organ transplant (SOT) recipients with conflicting results. We aim to study the early use of tocilizumab in SOT with COVID-19 pneumonia on low flow oxygen.

Methods: This is a retrospective cohort study that was conducted in two transplant centers in Saudi Arabia among 46 SOT with COVID-19 comparing 21 patients who received tocilizumab to 25 patients who received standard of care.

Single cell morphology distinguishes genotype and drug effect in Hereditary Spastic Paraplegia.

A central need for neurodegenerative diseases is to find curative drugs for the many clinical subtypes, the causative gene for most cases being unknown. This requires the classification of disease cases at the genetic and cellular level, an understanding of disease aetiology in the subtypes and the development of phenotypic assays for high throughput screening of large compound libraries. Herein we describe a method that facilitates these requirements based on cell morphology that is being increasingly used as a readout defining cell state.

Comparison of characteristics and ventilatory course between coronavirus disease 2019 and Middle East respiratory syndrome patients with acute respiratory distress syndrome.

Background: Both coronavirus disease 2019 (COVID-19) and Middle East respiratory syndrome (MERS) can cause acute respiratory distress syndrome (ARDS); however, their ARDS course and characteristics have not been compared, which we evaluate in our study.

Methods: MERS patients with ARDS seen during the 2014 outbreak and COVID-19 patients with ARDS admitted between March and December 2020 in our hospital were included, and their clinical characteristics, ventilatory course, and outcomes were compared.

Results: Forty-nine and 14 patients met the inclusion criteria for ARDS in the COVID-19 and MERS groups, respectively.

Outcomes of patients with chronic plaque psoriasis and hidradenitis suppurativa on biologic therapy during the Covid-19 pandemic: A UK dermatology tertiary centre experience.

Retrospective review data from 183 patients with psoriasis and/or hidradenitis suppurativa from a UK tertiary dermatology centre, suggests biologic therapy does not confer a significant increased risk of contracting severe Covid-19 in this cohort. This is in line with a growing body of evidence which indicates that it is safe to continue using biologic therapies during the pandemic.

The Spectrum of Cutaneous Reactive Angiomatoses in End Stage Renal Failure.

Cutaneous reactive angiomatoses encompass a spectrum of conditions driven by underlying occlusive vasculopathy. We present 2 cases of reactive angioproliferation in the context of end-stage renal failure (ESRF) manifesting as painful cutaneous ulceration. The first case demonstrates histologic features of diffuse dermal angiomatosis.

Mitochondrial Function in Hereditary Spastic Paraplegia: Deficits in but Not Patient-Derived Stem Cells.

Mutations in and are common causes of hereditary spastic paraplegia (HSP). While some mutations cause paraplegin deficiency, other mutations cause increased paraplegin expression. Mitochondrial function has been studied in models that are paraplegin-deficient (human, mouse, and models with large exonic deletions, null mutations, or knockout models) but not in models of mutations that express paraplegin.

Genetic Architecture of Parkinson's Disease in the Indian Population: Harnessing Genetic Diversity to Address Critical Gaps in Parkinson's Disease Research.

Over the past two decades, our understanding of Parkinson's disease (PD) has been gleaned from the discoveries made in familial and/or sporadic forms of PD in the Caucasian population. The transferability and the clinical utility of genetic discoveries to other ethnically diverse populations are unknown. The Indian population has been under-represented in PD research.

Antibody-Free Targeted Proteomics Assay for Absolute Measurement of α-Tubulin Acetylation.

Acetylation of α-tubulin at conserved lysine 40 (K40) amino acid residue regulates microtubule dynamics and controls a wide range of cellular activities. Dysregulated microtubule dynamics characterized by differential α-tubulin acetylation is a hallmark of cancer, neurodegeneration, and other complex disorders. Hence, accurate quantitation of α-tubulin acetylation is required in human disease and animal model studies.

Oxidative Stress-Induced Axon Fragmentation Is a Consequence of Reduced Axonal Transport in Hereditary Spastic Paraplegia Patient Neurons.

Hereditary spastic paraplegia (HSP) is a group of inherited disorders characterized by progressive spasticity and paralysis of the lower limbs. Autosomal dominant mutations in gene account for ∼40% of adult-onset patients. We have previously shown that patient cells have reduced organelle transport and are therefore more sensitive to oxidative stress.