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Abstract: The utilization of biomaterials in the human body was first practiced several years ago to restore normal functional activities by replacing the impaired organs with bio-inspired materials without devastating the cells and tissues. Today, many advanced technologies are reported to be worthwhile to effectively prepare different categories of biomaterials with amplified properties and characteristics for therapeutic applications. When considering the prosperous aspects of biomaterials, keratin has proved to be a fascinating material and has allured many researchers in various novel scientific studies, especially in drug delivery systems. Keratin is a naturally derived fibrous protein with cysteine, proline, serine, and glycine as the main amino acid constituents and has been found to have remarkable properties. Although keratin exhibits excellence and loss of distinction, it is utilized effectively in drug delivery for treating various diseases. Certainly, keratin nanoparticles (KNPs) showed remarkable features, such as optimistic surface area, good encapsulation efficiency, and controlled release of drugs. However, there is a need for more research to know about the cell interaction with keratin nanoparticles in novel drug delivery management. Indeed, certain biological and mechanical factors in alpha and beta keratins are still ambiguous, and higher attentiveness is required. The major purpose of this review is to assess the prospective utility and outstanding features of keratin nanoparticles in drug delivery systems. Keratin types, source of extraction, and properties are reviewed in this article. The characteristics and development of KNP are highlighted. Furthermore, the importance of nanoparticles in drug delivery, drug release mechanisms, challenges, and the need for future research are discussed.

Osteoarthritis (OA) is an inflammatory disease that affects the cartilage and tissues around the joints, which results in excessive pain and stiffness. One of the most critical challenges for improving the therapeutic effect in osteoarthritis treatments is the current drug design utilizing functional polymers. Indeed, there is a need to design and develop novel therapeutic drugs for positive outcomes. In this view, glucosamine sulfate is a drug used to manage osteoarthritis (OA) because of its potential therapeutic effects on cartilage and ability to inhibit disease progression. This research aims to develop a Keratin/Chitosan/Glucosamine sulfate composite loaded functionalized multi-walled carbon nanotubes (MWCNT) as a potential carrier for the treatment of osteoarthritis. The nanocomposite was developed using various ratios of Keratin, Chitosan, Glucosamine sulfate, and MWCNT. Molecular docking analysis has been performed with (D-Glucosamine) and targeted proteins (PDB ID: 1HJV, 1ALU) to determine the binding affinity and interactions. Field Emission Scanning Electron Microscope (FESEM) study showed that the composite (KRT/CS/GLS) incorporated on the surface of functionalized multi-walled carbon nanotubes effectively. Fourier Transform Infrared spectroscopy (FTIR) analysis showed the presence of keratin, chitosan, and glucosamine sulfate in the nanocomposite and remained intact. X-ray diffraction (XRD) analysis indicated that the nature of the composite in MWCNT transformed from a crystalline to an amorphous state. Thermogravimetric (TGA) analysis revealed that the nanocomposite has a high thermal decomposition temperature of 420° C. The MTT assay results showed that 83% of cell viability has remained in RAW 264.7 cells at the maximum concentration (500μg/ml) of MWCNT-GLS/KRT/CS nanocomposite. Also, molecular docking results revealed the excellent binding affinity of D-Glucosamine to each protein structure (PDB ID: 1HJV and 1ALU).

The aerospace and defense industry's intense desire is to revamp the performance characteristics of space shuttle vehicles, military tanker vehicles by continuously driving the production of advanced materials with remarkable properties. Thus, the need for high strength and lower weight metals are increasing rapidly in these industries. In this view, many research works on composites have been proved, especially metal matrix composites (MMCs). Carbon nanotubes (CNTs) are rolled-up graphene sheets with superior mechanical, thermal, and electrical properties attracted by many researchers in fabrication with MMCs. Metal matrix composites are developed in making space shuttle components and jet engine parts due to their higher specific strength and wear resistance. Numerous experimental investigations were performed on CNT reinforced MMCs in the making of structural components in aerospace and military vehicles, but the challenge still exists in many factors such as the production of complex structural components with optimistic performance, poor scattering of CNT in MMCs due to the formation of agglomeration and to retain nanoscale properties in large fraction. The aim of this review is to discuss about the development of MMCs in aerospace and military applications, the importance of CNTs in the field of the aviation industry, challenges in aerospace and defense sectors, and highlighting the importance of various processing techniques adopted in the development of CNT reinforced MMCs.

BackgroundAmong immune mediated myopathies, anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) immune mediated necrotizing myopathy (IMNM) has been increasingly rec- ognised over the last two decades.Majority are associated with statin exposure and typically present with hovering high creatinine kinase (CK) and/or progressive proximal myopathy despite discontinuation of statin.MethodWe analysed the data of 18 cases of anti-HMGCR IMNM from West Midlands region from 2016 to 2022.Results16 had statin exposure. Only 1 was asymptomatic but the rest experienced progressive proximal myopathy. Strikingly, two-thirds reported dysphagia and 3 required Intensive Unit admissions.Anti-HMGCR antibody was positive in all cases. CK levels remained high (mean=9053IU/l) despite dis- continuation of statin. A trend of persistently high ALT, lowering creatinine and weight loss reflected smouldering muscle loss.The asymptomatic patient did not need treatment. Significant improvement/remission was achieved spontaneously in 1, with steroids or IVIG alone in 10 and with combined immunotherapies in the rest. 1 patient died despite improvement in CK level.ConclusionAnti-HMGCR IMNM, especially when associated with statin, responds well to immunotherapy. We suggest having a low threshold for checking anti-HMGCR antibody in patients with persistently high CK levels and/or proximal limb/pharyngeal muscle weakness, especially in the presence of statin exposure.

Amyotrophic lateral sclerosis is a progressive and devastating neurodegenerative disease. Despite decades of clinical trials, effective disease-modifying drugs remain scarce. To understand the challenges of trial design and delivery, we performed a systematic review of Phase II, Phase II/III and Phase III amyotrophic lateral sclerosis clinical drug trials on trial registries and PubMed between 2008 and 2019. We identified 125 trials, investigating 76 drugs and recruiting more than 15 000 people with amyotrophic lateral sclerosis. About 90% of trials used traditional fixed designs. The limitations in understanding of disease biology, outcome measures, resources and barriers to trial participation in a rapidly progressive, disabling and heterogenous disease hindered timely and definitive evaluation of drugs in two-arm trials. Innovative trial designs, especially adaptive platform trials may offer significant efficiency gains to this end. We propose a flexible and scalable multi-arm, multi-stage trial platform where opportunities to participate in a clinical trial can become the default for people with amyotrophic lateral sclerosis., Wong et al. reviewed historical approaches to clinical trials in amyotrophic lateral sclerosis. Lack of sensitive outcome measures, limitations in resources and barriers to trial participation were challenges for timely and definitive evaluation of drugs in two-arm trials. They concluded that future trials should be more flexible, scalable and efficient., Graphical Abstract Graphical Abstract

Background The major clinical feature of ataxia telangiectasia (A-T) is severe progressive neurodegeneration with onset in infancy. This classical A-T phenotype is caused by biallelic null mutations in the ATM gene, leading to the absence of ATM protein and increased cellular radiosensitivity. We report an unusual case of A-T in a 41-year-old mother, A-T210, who had very mild neurological symptoms despite complete loss of ATM protein. Methods A neurological examination was performed, cellular radiosensitivity was assessed, and the ATM gene was sequenced. Skin fibroblasts and a lymphoblastoid cell line (LCL) were assayed for ATM protein expression and kinase activity. Results Patient A-T210 showed mild chorea, dystonia, and gait ataxia, walked independently, and drove a car. LCL and skin fibroblasts were radiosensitive and did not express ATM protein. Two ATM-null mutations were identified. Conclusions The severe neurodegeneration resulting from loss of ATM can be mitigated in some circumstances. © 2012 Movement Disorder Society

Ataxia-telangiectasia mutated (ATM) is the gene mutated in the cancer-predisposing disorder ataxia-telangiectasia (A-T). We modeled ATM sequence variants identified in UK A-T patients to determine the stability and kinase activity of the resulting proteins as well as the distribution of these mutations across the coding region. Of 20 missense changes modeled, 10 proteins showed ATM kinase activity and 10 showed none. In the majority of cases the mutant ATM protein was unstable, although this was variable. Reduction in ATM kinase activity can result either from the presence of low levels of unstable mutant protein with relatively normal specific kinase activity or from stable mutant protein with deficient ATM kinase activation. Indeed, ATM mutant proteins without kinase activity toward downstream targets were still able to autophosphorylate on serine 1981, although in a much less efficient manner, suggesting that this was not sufficient for ATM activation. In terms of function, green fluorescent protein (GFP)-tagged kinase inactive ATM proteins could form ionizing radiation (IR)-induced foci (IRIF), at least temporarily, which colocalized with the DNA double-strand break (DSB) marker γH2AX. Consistent with this, both kinase active and inactive mutant ATM proteins were able to interfere with phosphorylation of targets by endogenous ATM. Since the majority of missense mutations occurred C-terminal to aa1966, including all 10 mutations with absence of kinase activity, the implication was that mutations N-terminal to this, with exceptions, are less likely to result in loss of kinase activity and therefore, are less likely to be identified in A-T patients. Hum Mutat 30:1–9, 2009. © 2009 Wiley-Liss, Inc.

Ataxia telangiectasia (A-T) typically presents with early-onset progressive cerebellar ataxia, oculomotor apraxia and later, oculo-cutaneous telangiectasia. Extrapyramidal symptoms, apart from chorea, are rare. In this paper, we report a case of A-T with an atypically mild and slowly progressive disease course. Although by history there was mild gait clumsiness in early childhood, the leading problem was that of dystonia with onset at age 15, in the absence of gross gait imbalance or ocular motor apraxia. Dystonia was generalized and with prominent oromandibular involvement. Unusually, a leash of telangiectasia was present on the posterior pharyngeal wall, while other features frequently associated with A-T were absent.

Adult tethered cord syndrome without spinal dysraphism is rare, and can present with subtle symptoms that could mimic other pathologies. As a result, timely diagnosis of this condition has proved to be a significant challenge. It is crucial for clinicians to be aware of adult tethered cord syndrome and its presenting symptoms in order to achieve early diagnosis and subsequent management. We present such a case with particular attention to the presenting history and examination. Following diagnosis, the patient underwent a laminectomy and cord untethering, resulting in significant improvement to his symptoms.

The non-contrast CT scan (Fig. 1 of Images in Neuroscience: Question) shows subarachnoid haemorrhage (SAH) within a right frontal lobe sulcus. While the arterial phase image (Fig. 2 of Images in Neuroscience: Question) of the digital subtraction angiography is normal, the early and late venous phase images (Fig. 3a and b of Images in Neuroscience: Question) demonstrate a persistent linear filling defect within the Vein of Trolard confirming thrombus. MRI to assess cerebral parenchyma shows a tubular structure showing high signal on T1-weighted imaging (Fig. 4a of Images in Neuroscience: Question) confined within the pre-central sulcus, indicating thrombus within a vessel or SAH. There is high signal on fluid attenuated inversion recovery MRI and blooming artefact on gradient echo imaging around the previously described tubular structure extending further along the sulcus (Fig. 4b and c of Images in Neuroscience: Question). Together with the CT scan findings and the venogram images, the MRI findings confirm Vein of Trolard thrombosis with adjacent SAH. Thunderclap headache is classically described as severe headache, which takes less than a minute or a few minutes from its onset to peak. The differential diagnosis for thunderclap headache includes SAH, cerebral venous sinus thrombosis, idiopathic benign recurrent headache disorder, arterial dissection, pituitary apoplexy, spontaneous intracranial hypotension, and hypertensive encephalopathy. Cerebral venous thrombosis confined to a cortical vein without involvement of the venous sinuses is rare. In our patient, this was associated with SAH. This phenomenon of SAH secondary to isolated cortical venous thrombosis has been described in a few