The longitudinal behavioral effects of acute exposure to galactic cosmic radiation in female C57BL/6J mice: Implications for deep space missions, female crews, and potential antioxidant countermeasures.

Galactic cosmic radiation (GCR) is an unavoidable risk to astronauts that may affect mission success. Male rodents exposed to 33-beam-GCR (33-GCR) show short-term cognitive deficits but reports on female rodents and long-term assessment are lacking. We asked: What are the longitudinal behavioral effects of 33-GCR on female mice? Also, can an antioxidant/anti-inflammatory compound (CDDO-EA) mitigate the impact of 33-GCR? Mature (6-month-old) C57BL/6J female mice received CDDO-EA (400 µg/g of food) or a control diet (vehicle, Veh) for 5 days and Sham-irradiation (IRR) or whole-body 33-GCR (0.75Gy) on the 4th day. Three-months post-IRR, mice underwent two touchscreen-platform tests: (1) location discrimination reversal (tests behavior pattern separation and cognitive flexibility, abilities reliant on the dentate gyrus) and (2) stimulus-response learning/extinction. Mice then underwent arena-based behavior tests (e.g. open field, 3-chamber social interaction). At the experiment's end (14.25-month post-IRR), an index relevant to neurogenesis was quantified (doublecortin-immunoreactive [DCX+] dentate gyrus immature neurons). Female mice exposed to Veh/Sham vs. Veh/33-GCR had similar pattern separation (% correct to 1st reversal). There were two effects of diet: CDDO-EA/Sham and CDDO-EA/33-GCR mice had better pattern separation vs. their respective control groups (Veh/Sham, Veh/33-GCR), and CDDO-EA/33-GCR mice had better cognitive flexibility (reversal number) vs. Veh/33-GCR mice. One radiation effect/CDDO-EA countereffect also emerged: Veh/33-GCR mice had slower stimulus-response learning (days to completion) vs. all other groups, including CDDO-EA/33-GCR mice. In general, all mice showed normal anxiety-like behavior, exploration, and habituation to novel environments. There was also a change relevant to neurogenesis: Veh/33-GCR mice had fewer DCX+ dentate gyrus immature neurons vs. Veh/Sham mice. Our study implies space radiation is a risk to a female crew's longitudinal mission-relevant cognitive processes and CDDO-EA is a potential dietary countermeasure for space-radiation CNS risks.

Neurofibroma with glomus-like bodies: A novel association-Thoughts about origin.

A neurofibroma with focal glomus-like body differentiation is an unusual phenomenon recently encountered in an excision specimen from the right lateral distal forearm of a 26-year-old man. Glomus cells are modified smooth muscle cells normally present in glomus-like bodies but can also be found in glomus tumors (GT) or lesions considered in the spectrum of GT, including myopericytoma, myofibroma, and angiolipoma. Neurofibromas are peripheral nerve sheath tumors derived from the neural crest cells. While both GT and its variants and neurofibroma are thought to be derived from different cell types, there is growing evidence that glomus cells have a neural crest origin. This is based on multiple theories, with some overlapping pathways, including neural crest cell differentiation, Schwann cell reprogramming, VEGF expression, and NF1 gene biallelic inactivation. This report adds to the growing evidence of possible neural crest origin for glomus cells and would help explain finding glomus-like bodies scattered through a neurofibroma.

A survey regarding the role of UK dietitians in spiritual care.

BACKGROUND: Users of dietetic services have unmet spiritual needs, although no study has yet explored dietitians' opinion, perceptions or experience of assessing spiritual needs and delivering spiritual care in clinical practice. METHODS: A cross-sectional survey assessed the role of UK dietitians in spiritual care. RESULTS: Thirty-seven practicing dietitians, with experience ranging from newly qualified to over 21 years of practice, took part in the survey containing open and closed questions. Almost half (49%) of dietitians said they always conducted spiritual assessments and most (57%) said they sometimes made a referral for spiritual concerns. When spiritual issues arose, dietitians were highly likely to listen well (score 4.6 out of 5) and encourage service users in their own (the service user) spiritual or religious practices (score 4 out of 5). However, the likelihood of taking the initiative and enquiring about religious and spiritual issues was lower (score <3 out of 5) in all areas of practice including end of life care. This may have been because confidence around spiritual care was also low (score 4.7 out of 10), uncertainty was high (score >3.5 out of 5) and there was a strong desire to receive training (>4 out of 5). Qualitative responses expanded further on these results suggesting that there was positive "intention" to provide spiritual care, but lack of training was a significant barrier (qualitative theme: "inadequacies"). The recognition of necessity but uncertainty of how to meet spiritual needs was also shown through qualitative findings to be a source of "emotional labour", particularly where there were conflicting beliefs between a dietitian and service user. CONCLUSIONS: Although limited by a small sample size, these results provide new knowledge that spiritual care is considered an important part of the dietitians' role and that this is the case regardless of the dietitians own spiritual identity or religion. Dietitians would value training in spiritual care so that they can support service user needs more readily and confidently.

The influence of religiosity on food choice among British Muslims: A qualitative study.

Background: Religiosity is known to have a socio-cultural influence on food choice. However, to date, research exploring the influence of Islam on food selection has almost exclusively focused on fasting during Ramadan and has not explored the influences of Islam on everyday food choices among Muslim people. Aim: This qualitative study explored the influence of Islamic religiosity on everyday food choices among Muslim people. Methods: Thirty-two adult participants residing in the United Kingdom (n = 16 faith leaders and n = 16 lay Muslim people) were recruited from three Sunni mosques, and data was collected using semi-structured interviews. The data was analysed using reflexive thematic analysis and a constant comparison method was applied to draw out similarities and differences between faith leaders and lay Muslim people. Results: The results revealed that Islamic religiosity had an influence over food choice with two main overarching themes 1) Demonstrating religious obedience through food choices and, 2) Spheres of influence on food choice; and five sub-themes 1a) Trusting in familiar food providers, 1b) Verification of halal authenticity, 1c) Seeking purity within food, 2a) The Prophet Muhammed (Peace Be Upon Him) as a role model for food choice and, 2b) Islamic jurisprudence. Conclusion: These findings provide important insights into the influence of Islam on food choice and could be used support the design of faith-informed dietary interventions among Muslim people. Further research is required to examine the role of faith-informed dietary intervention in the Muslim community.

Simultaneous arterial spin labeling functional MRI and fluorodeoxyglucose PET in mild chronic traumatic brain injury.

BACKGROUND AND PURPOSE: To determine the effect of mild chronic traumatic brain injury (cTBI) on cerebral blood flow and metabolism. METHODS: 62 cTBI and 40 healthy controls (HCs) with no prior history of cTBI underwent both pulsed arterial spin labeling functional magnetic resonance imaging (PASL-fMRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) scanning via a Siemens mMR (simultaneous PET/MRI) scanner. 30 participants also took part in a series of neuropsychological clinical measures (NCMs). Images were processed using statistical parametric mapping software relevant to each modality to generate relative cerebral blood flow (rCBF) and glucose metabolic standardized uptake value ratio (gSUVR) grey matter maps. A voxel-wise two-sample T-test and two-tailed gaussian random field correction for multiple comparisons was performed. RESULTS: cTBI patients showed a significant increase in rCBF and gSUVR in the right thalamus as well as a decrease in bilateral occipital lobes and calcarine sulci. An inverse relationship between rCBF and gSUVR was found in the left frontal lobe, the left precuneus and regions in the right temporal lobe. Within those regions rCBF values correlated with 9 distinct NCMs and gSUVR with 3. CONCLUSION: Simultaneous PASL-fMRI and FDG-PET can identify functional changes in a mild cTBI population. Within this population FDG-PET identified more regions of functional disturbance than ASL fMRI and NCMs are shown to correlate with rCBF and glucose metabolism (gSUVR) in various brain regions. As a result, both imaging modalities contribute to understanding the underlying pathophysiology and clinical course of mild chronic traumatic brain injury.

Antipsoriatic Effect of Silymarin NLCs Based Gel: In Vitro and In Vivo Activity.

Psoriasis is a chronic inflammatory disorder affecting over 100 million people, requires long-term therapy. Current treatments offer only symptomatic relief. However, phytoconstituents-based therapies like Silymarin (SLM) have shown promising effects. The study aims to develop, optimize, and evaluate a novel stable SLM NLC gel to improve anti-psoriatic activity by enhancing its permeability and retention into the dermal layer. SLM NLC formulation was prepared and optimized using 32 full factorial designs. The formulation was evaluated for the particle size, PDI, zeta potential, and % entrapment efficiency, evaluated by Transmission electron microscopy and thermal analysis. The freeze dried and prepared NLC-loaded gel was evaluated for physicochemical parameters, ex-vivo, and in-vivo studies. SLM-loaded NLC shows 624 nm particle size, 0.41 PDI, 92.95% entrapment efficiency, and -31.6 mV zeta potential. The sphere form of NLCs was confirmed using TEM. Controlled drug release was observed in ex vivo studies, low PASI score compared to disease control. Further, the levels of IL-6, TNF-α, and NF-κB were also reduced. The results are supported by histopathology showing minimal parakeratosis indicated in the SLM NLC-treated group. Prepared NLC-based shows enhance topical penetration and decrease the thickness of psoriatic plaques in the in vivo study.

Ocular manifestations of liver disease: an important diagnostic aid.

PURPOSE: This review examined existing literature to determine various ocular manifestations of liver pathologies, with a focus on metabolic deficiencies as well as viral and immune liver conditions. METHODS: Recent data were compiled from PubMed from 2000 to 2020 using keywords that were relevant to the assessed pathologies. Ocular presentations of several liver pathologies were researched and then summarized in a comprehensive form. RESULTS: Several ocular manifestations of liver disease were related to vitamin A deficiency, as liver disease is associated with impaired vitamin A homeostasis. Alcoholic liver cirrhosis can result in vitamin A deficiency, presenting with Bitot spots, xerosis, and corneal necrosis. Congenital liver diseases such as mucopolysaccharidoses and peroxisomal disorders are also linked with ocular signs. Viral causes of liver disease have associations with conditions like retinal vasculitis, keratoconjunctivitis sicca, retinopathies, Mooren's ulcer, and Sjogren's syndrome. Autoimmune hepatitis has been linked to peripheral ulcerative keratitis and uveitis. CONCLUSIONS: Building strong associations between ocular and liver pathology will allow for early detection of such conditions, leading to the early implementation of management strategies. While this review outlines several of the existing connections between hepatic and ophthalmic disease, further research is needed in the area in order to strengthen these associations.

Pseudolymphoma to Lymphoma: A Case of Chronic Reactive Lymphoid Hyperplasia Transforming to Primary Cutaneous Marginal Zone Lymphoma.

ABSTRACT: Primary cutaneous marginal zone lymphoma (PCMZL) is a low-grade malignant B-cell lymphoma that originates from the skin. It often presents as erythematous solitary or multiple papules, nodules, and/or plaques. It is one of the 3 main subtypes of primary cutaneous B-cell lymphomas. PCMZLs are believed to develop from chronic antigenic stimulation such as from tick-borne bacteria, vaccines, tattoo pigment, or other foreign body. In addition, cutaneous lymphoid hyperplasia, a documented precursor to malignant PCMZL, often presents in response to areas of chronic inflammation. Cutaneous lymphoid hyperplasia and PCMZL share several clinical and histological similarities that require clinicopathologic suspicion, immunohistochemical ancillary studies, and histopathologic analysis to accurately differentiate the 2 entities. Although gene rearrangement studies have historically been of limited value in the diagnosis of PCMZL, recent studies investigating molecular markers have identified the presence of multiple genetic abnormalities that have helped to better characterize the disease and aid in diagnosis. In addition, newer studies have found associations between PCMZL and gastrointestinal disorders, including Helicobacter pylori and inflammatory bowel disorders. In this article, we describe a case of a 56-year-old patient with a history of ulcerative colitis presenting with chronic reactive lymphoid hyperplasia that transformed to primary cutaneous marginal zone lymphoma.

Novel teprotumumab treatment of severe thyroid dermopathy; ototoxicity as an adverse side effect.

Pretibial myxedema, more generally thyroid dermopathy, results from mucopolysaccharide accumulation in the dermis, typically between the knee and dorsal foot. Thyroid dermopathy presents in Graves disease, but can occur in Hashimoto thyroiditis, primary hypothyroidism, and euthyroid patients. Treatment of thyroid eye disease with teprotumumab is established in the literature, with few case reports also showing improvement in pretibial myxedema. Reported is a 76-year-old man with thyroid eye disease and pretibial myxedema treated with teprotumumab; improvement was demonstrated in both conditions. He developed "muffled" hearing as an adverse effect, a complication not widely published in the dermatology literature. At 18 months post-treatment, his symptoms are stable without recurrence, but hypoacusis persists. Given the long-term efficacy and side-effects, dermatologists should recognize the potential benefits and risks of using teprotumumab for thyroid dermopathy. A baseline audiogram may be considered prior to therapy. Additionally, longitudinal data is needed to document the benefits and risks of this novel therapy.

Non-psoriatic uses of calcipotriol: a concise updated review.

Calcipotriol (calcipotriene) is a synthetic vitamin D3 derivative that is a standard treatment option for psoriasis. It is generally well tolerated with minimal side effects. Due to its ability to reduce keratinocyte proliferation and induce keratinocyte differentiation as well as its immunomodulatory effects, calcipotriol has been used to treat a variety of skin disorders such as atopic dermatitis, actinic keratoses, lichen planus, seborrheic keratoses, and vitiligo [1]. We surveyed the literature examining the use of calcipotriol for non-psoriatic dermatologic disease.

Lenalidomide-induced symmetrical drug-related intertriginous and flexural exanthema.

Symmetric drug-related intertriginous and flexural exanthema (SDRIFE) is a cutaneous drug reaction that presents with symmetrical erythema in the flexures. The reaction typically appears hours-to-days after drug exposure but has been reported to occur months after drug initiation. Diagnostic criteria include cutaneous reaction after exposure to a systemic drug, erythema of the gluteal region and/or V-shaped erythema of the inguinal areas, involvement of an additional intertriginous site, symmetry, and absence of systemic involvement. The rash typically presents as macular erythema. However, variations in morphology have been reported including papules, pustules, vesicles, and bullae. The histopathology of SDRIFE is non-specific and the diagnosis is made clinically. Cessation of the causative drug leads to gradual rash resolution. Beta-lactam antibiotics are the most implicated medications but case reports describe SDRIFE following monoclonal antibodies, chemotherapeutic agents, and various other medications. We present a patient with SDRIFE secondary to lenalidomide, an immunomodulatory agent. This case highlights the importance of considering SDRIFE in the differential diagnosis of patients presenting with intertriginous erythema.

Spiritual Care within Dietetic Practice: A Systematic Literature Review.

Registered dietitians assess, diagnose and treat nutritional problems. Although integral to healthcare, their role in spiritual care is unknown. We conducted a systematic review of spiritual needs and spiritual care in nutrition and dietetic practice. Subject Headings and keywords were used to search Medline, CINAHL, PsycINFO and AMED for studies exploring spiritual care and nutrition or dietetic practice. From 1433 records, 13 studies were included. Medium quality evidence showed unmet spiritual needs among dietetic patients suffering from cancer, COPD, heart failure and diabetes. Unmet needs occurred in patients from a variety of ethnicities, religions and none. However, dietitians were only involved in spiritual care regarding nutrition and hydration at the end of life. Integrating spiritual screening and sign-posting within dietetic practice is prudent, but clinical trials are needed to evaluate its effectiveness.

Could COVID-19 mark a turning point for global action on climate change?

COVID-19 and climate change are both threats of immense proportions, however, the differing perception of climate change as far-off, projected and unpredictable, persists as a marked barrier to global action. COVID-19 is increasing awareness of the connection between human actions and environmental consequences. The current slowdown of fossil fuel use has given a glimpse of the quitter, cleaner and more caring world that effective climate change could also achieve. Decisions made in coming months can either "lock in" economic development patterns that will do permanent and escalating damage to the ecological systems, or, if wisely taken, can promote a healthier and greener world.

Modularity maximization as a flexible and generic framework for brain network exploratory analysis.

The modular structure of brain networks supports specialized information processing, complex dynamics, and cost-efficient spatial embedding. Inter-individual variation in modular structure has been linked to differences in performance, disease, and development. There exist many data-driven methods for detecting and comparing modular structure, the most popular of which is modularity maximization. Although modularity maximization is a general framework that can be modified and reparamaterized to address domain-specific research questions, its application to neuroscientific datasets has, thus far, been narrow. Here, we highlight several strategies in which the "out-of-the-box" version of modularity maximization can be extended to address questions specific to neuroscience. First, we present approaches for detecting "space-independent" modules and for applying modularity maximization to signed matrices. Next, we show that the modularity maximization frame is well-suited for detecting task- and condition-specific modules. Finally, we highlight the role of multi-layer models in detecting and tracking modules across time, tasks, subjects, and modalities. In summary, modularity maximization is a flexible and general framework that can be adapted to detect modular structure resulting from a wide range of hypotheses. This article highlights multiple frontiers for future research and applications.

Structure and function insights garnered from in silico modeling of the thrombospondin type-1 domain-containing 7A antigen.

The thrombospondin type-1 domain containing 7A (THSD7A) protein is known to be one of the antigens responsible for the autoimmune disorder idiopathic membranous nephropathy. The structure of this antigen is currently unsolved experimentally. Here we present a homology model of the extracellular portion of the THSD7A antigen. The structure was evaluated for folding patterns, epitope site prediction, and function was predicted. Results show that this protein contains 21 extracellular domains and with the exception of the first two domains, has a regular repeating pattern of TSP-1-like followed by F-spondin-like domains. Our results indicate the presence of a novel Trp-ladder sequence of WxxxxW in the TSP-1-like domains. Of the 21 domains, 18 were shown to have epitope binding sites as predicted by epitopia. Several of the F-spondin-like domains have insertions in the canonical TSP fold, most notably the coiled coil region in domain 4, which may be utilized in protein-protein binding interactions, suggesting that this protein functions as a heparan sulfate binding site.

Cutting-edge Advances in Nanocarrier-Facilitated Topical Drug Delivery Systems for Targeted Skin Cancer Therapy: A Comprehensive Review.

Skin cancer is one of the most common and complex types of the disease, resulting in a high mortality rate worldwide. Skin cancer can be treated with chemotherapy, surgery, radiotherapy, etc. In most cases, a patient's condition and the type of skin cancer determine the recommended treatment options. As a result of poor penetration of the drug into stratum corneum or lesions, low efficacy, and higher concentrations of active pharmaceutical ingredients required to achieve a therapeutic effect, the efficacy of skin cancer therapy has been limited. The high dose requirement, as well as poor bioavailability at the site of action, causes skin inflammation, which greatly hinders drug absorption. This review mainly focuses on research on nanocarriers for sitespecific and controlled delivery of therapeutics for skin cancer treatment. The information related to various nanocarriers systems for skin cancer will be illustrated. This also focused on patents, clinical trials, and research carried out in the field of liposomes, niosomes, ethosomes, nanoparticles, microemulsion, nanoemulsions, gels, nanogels, hydrogels, dendrimers, and nanofibers for treating skin cancer. Nanotechnology-based therapy has shown great promise in controlling skin cancer and can be used to deliver drugs more effectively.

Accidental Organophosphate Poisoning in a Toddler: A Case Report.

While accidental poisoning is fairly common in children, the data are sparse when organophosphate (OP) is considered the culprit toxin. Only case reports of such patients from the Southeast Asian Region have been documented, despite it contributing largely to the global burden of organophosphorus poisoning in the adult population. This can be attributed to difficulty in diagnosing children because of varied presentations in the pediatric population and unreliable or unavailable exposure history. We present a case of a 19-month-old toddler who presented to the ED with OP poisoning, which proved to be a diagnostic and management challenge because of more common differentials and the unavailability of a clear history.