Neurocutaneous Diseases: Diagnosis, Management, and Treatment.

Neurocutaneous disorders, also known as phakomatoses, are congenital and acquired syndromes resulting in simultaneous neurologic and cutaneous involvement. In several of these conditions, the genetic phenomenon is understood, providing a pivotal role in the development of therapeutic options. This review encompasses the discussion of the genetic and clinical involvement of neurocutaneous disorders, and examines clinical management and treatment options. With the current advances in genetics, the role of precision medicine and targeted therapy play a substantial role in addressing the management of these conditions. The interconnectedness between therapeutic options highlights the importance of precision medicine in treating each disorder's unique molecular pathway. This review provides an extensive synthesis of ongoing and current therapeutics in the management of such clinically unique and challenging conditions.

A genome-wide cytotoxicity screen of cluster F1 mycobacteriophage Girr reveals novel inhibitors of Mycobacterium smegmatis growth.

Over the past decade, thousands of bacteriophage genomes have been sequenced and annotated. A striking observation from this work is that known structural features and functions cannot be assigned for >65% of the encoded proteins. One approach to begin experimentally elucidating the function of these uncharacterized gene products is genome-wide screening to identify phage genes that confer phenotypes of interest like inhibition of host growth. This study describes the results of a screen evaluating the effects of overexpressing each gene encoded by the temperate Cluster F1 mycobacteriophage Girr on the growth of the host bacterium Mycobacterium smegmatis. Overexpression of 29 of the 102 Girr genes (~28% of the genome) resulted in mild to severe cytotoxicity. Of the 29 toxic genes described, 12 have no known function and are predominately small proteins of <125 amino acids. Overexpression of the majority of these 12 cytotoxic no known functions proteins resulted in moderate to severe growth reduction and represent novel antimicrobial products. The remaining 17 toxic genes have predicted functions, encoding products involved in phage structure, DNA replication/modification, DNA binding/gene regulation, or other enzymatic activity. Comparison of this dataset with prior genome-wide cytotoxicity screens of mycobacteriophages Waterfoul and Hammy reveals some common functional themes, though several of the predicted Girr functions associated with cytotoxicity in our report, including genes involved in lysogeny, have not been described previously. This study, completed as part of the HHMI-supported SEA-GENES project, highlights the power of parallel, genome-wide overexpression screens to identify novel interactions between phages and their hosts.

Leukodystrophy Imaging: Insights for Diagnostic Dilemmas.

Leukodystrophies, a group of rare demyelinating disorders, mainly affect the CNS. Clinical presentation of different types of leukodystrophies can be nonspecific, and thus, imaging techniques like MRI can be used for a more definitive diagnosis. These diseases are characterized as cerebral lesions with characteristic demyelinating patterns which can be used as differentiating tools. In this review, we talk about these MRI study findings for each leukodystrophy, associated genetics, blood work that can help in differentiation, emerging diagnostics, and a follow-up imaging strategy. The leukodystrophies discussed in this paper include X-linked adrenoleukodystrophy, metachromatic leukodystrophy, Krabbe's disease, Pelizaeus-Merzbacher disease, Alexander's disease, Canavan disease, and Aicardi-Goutières Syndrome.

An assessment of radiology resident competency in identifying suppurative retropharyngeal lymphadenitis: an examination using the WIDI SIM platform.

BACKGROUND AND PURPOSE: Suppurative retropharyngeal lymphadenitis is a retropharyngeal space infection almost exclusively seen in the young (4-8 years old) pediatric population. It can be misdiagnosed as a retropharyngeal abscess, leading to unnecessary invasive treatment procedures. This retrospective study aims to assess radiology residents' ability to independently identify CT imaging findings and make a definitive diagnosis of suppurative retropharyngeal lymphadenitis in a simulated call environment. MATERIALS AND METHODS: The Wisdom in Diagnostic Imaging Emergent/Critical Care Radiology Simulation (WIDI SIM) is a computer-aided emergency imaging simulation proven to be a reliable method for assessing resident preparedness for independent radiology call. The simulation included 65 cases across various imaging modalities of varying complexity, including normal studies, with one case specifically targeting suppurative retropharyngeal adenitis identification. Residents' free text responses were manually scored by faculty members using a standardized grading rubric, with errors subsequently classified by type. RESULTS: A total of 543 radiology residents were tested in three separate years on the imaging findings of suppurative retropharyngeal lymphadenitis using the Wisdom in Diagnostic Imaging simulation web-based testing platform. Suppurative retropharyngeal lymphadenitis was consistently underdiagnosed by radiology residents being tested for call readiness irrespective of the numbers of years in training. On average, only 3.5% of radiology residents were able to correctly identify suppurative retropharyngeal lymphadenitis on a contrast-enhanced computed tomography (CT). CONCLUSIONS: Our findings underscore a potential gap in radiology residency training related to the accurate identification of suppurative retropharyngeal lymphadenitis, highlighting the potential need for enhanced educational efforts in this area.

Amyotrophic Lateral Sclerosis: From Mechanisms to Current, Emerging, and Alternative Therapeutics.

Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disease affecting the motor neurons. Although the etiology remains unknown, mutations in superoxide dismutase 1 have been observed in patients with familial ALS, resulting in increased calcium in the cells and leading to cell death. Additionally, studies in patients with the C9orf72 repeat expansion have shown lower age of onset, cognitive and behavioral impairments, and reduced survival. Accumulation of TDP-43 in the cytoplasm of neurons and glial cells caused by the loss of UBQLN2 has been shown to lead to mitotoxicity and proteasomal overload. Early diagnosis of ALS is necessary for the optimization of care between a patient's neurologist and interdisciplinary team members to ensure the best outcomes possible. Proper management between physical therapy, occupation therapy, and pharmaceutical medications can improve ALS symptoms, achieving the highest quality of life possible for the patient. The current therapeutic medication recommended for ALS is Riluzole, but new therapies are emerging. This paper analyzes mechanisms of injury and progression of ALS along while analyzing current, emerging, and alternative therapeutics targeting ALS.

Neurologic orphan diseases: Emerging innovations and role for genetic treatments.

Orphan diseases are rare diseases that affect less than 200000 individuals within the United States. Most orphan diseases are of neurologic and genetic origin. With the current advances in technology, more funding has been devoted to developing therapeutic agents for patients with these conditions. In our review, we highlight emerging options for patients with neurologic orphan diseases, specifically including diseases resulting in muscular deterioration, epilepsy, seizures, neurodegenerative movement disorders, inhibited cognitive development, neuron deterioration, and tumors. After extensive literature review, gene therapy offers a promising route for the treatment of neurologic orphan diseases. The use of clustered regularly interspaced palindromic repeats/Cas9 has demonstrated positive results in experiments investigating its role in several diseases. Additionally, the use of adeno-associated viral vectors has shown improvement in survival, motor function, and developmental milestones, while also demonstrating reversal of sensory ataxia and cardiomyopathy in Friedreich ataxia patients. Antisense oligonucleotides have also been used in some neurologic orphan diseases with positive outcomes. Mammalian target of rapamycin inhibitors are currently being investigated and have reduced abnormal cell growth, proliferation, and angiogenesis. Emerging innovations and the role of genetic treatments open a new window of opportunity for the treatment of neurologic orphan diseases.

Mapping the Glymphatic Pathway Using Imaging Advances.

The glymphatic system is a newly discovered waste-clearing system that is analogous to the lymphatic system in our central nervous system. Furthermore, disruption in the glymphatic system has also been associated with many neurodegenerative disorders (e.g., Alzheimer's disease), traumatic brain injury, and subarachnoid hemorrhage. Thus, understanding the function and structure of this system can play a key role in researching the progression and prognoses of these diseases. In this review article, we discuss the current ways to map the glymphatic system and address the advances being made in preclinical mapping. As mentioned, the concept of the glymphatic system is relatively new, and thus, more research needs to be conducted in order to therapeutically intervene via this system.

Characterizing Consumer Smartphone Apps for Virtual Reality-Based Exposure Therapy: Content Analysis.

BACKGROUND: In vivo exposure therapy is the most effective treatment for phobias but is often impractical. Virtual reality exposure therapy (VRET) can help overcome critical barriers to in vivo exposure therapy. However, accessible mobile software related to VRET is not well understood. OBJECTIVE: The purpose of our study is to describe the landscape of accessible smartphone apps with potential utility for clinical VRET. METHODS: We conducted a content analysis of publicly available smartphone apps related to virtual reality on the Google Play Store and the Apple App Store as of March 2020. RESULTS: The initial search yielded 525 apps, with 84 apps (52 on the Google Play Store and 32 on the Apple App Store) included for analysis. The most common phobic stimulus depicted was bodies of water or weather events (25/84, 29.8%), followed by heights (24/84, 28.6%), and animals (23/84, 27.4%). More than half of the apps were visually abstract (39/84, 53.5%). Most apps were free to use (48/84, 57.1%), while the rest were free to try (22/84, 26.2%) or required payment for use (14/84, 16.7%), with the highest cost for use being US $6. The average overall app rating was 2.9 stars out of 5, but the number of ratings ranged from 0 to 49,233. None of the 84 apps advertised compliance with the Health Insurance Portability and Accountability Act, offered the ability to monitor data, provided clinician control over variables in the app experiences, or explicitly stated use by or development with clinicians. CONCLUSIONS: None of the smartphone apps reviewed were explicitly developed for phobia therapy. However, 16 of the 84 included apps were considered ideal candidates to investigate further as part of treatment due to their accessibility, depiction of phobia-relevant stimuli, low or no cost, and high user scores. Most of these apps were visually abstract and free to use, making them accessible and potentially flexible as part of clinical exposure hierarchies. However, none of the apps were designed for clinical use, nor did they provide tools for clinician workflows. Formal evaluation of these accessible smartphone apps is needed to understand the clinical potential of accessible VRET solutions.

Provision of Care by "Real World" Telemental Health Providers.

Despite its effectiveness, limited research has examined the provision of telemental health (TMH) and how practices may vary according to treatment paradigm. We surveyed 276 community mental health providers registered with a commercial telemedicine platform. Most providers reported primarily offering TMH services to adults with anxiety, depression, and trauma-and stressor-related disorders in individual therapy formats. Approximately 82% of TMH providers reported endorsing the use of Cognitive Behavioral Therapy (CBT) in their remote practice. The most commonly used in-session and between-session (i.e., homework) exercises included coping and emotion regulation, problem solving, mindfulness, interpersonal skills, relaxation, and modifying and addressing core beliefs. CBT TMH providers had a higher odds of using in-session and homework exercises and assigning them through postal mail, email or fax methods, as compared to non-CBT TMH providers. TMH providers, regardless of treatment paradigm, felt that assigning homework was neither easy nor difficult and they believed their patients were somewhat-to-moderately compliant to their assigned exercises. CBT TMH providers also collected clinical information from their patients more often than non-CBT TMH providers. They reported being less satisfied with their method, which was identified most often as paper-based surveys and forms. Overall, TMH providers employ evidence-based treatments to their patients remotely, with CBT TMH providers most likely to do so. Findings highlight the need for innovative solutions to improve how TMH providers that endorse following the CBT treatment paradigm remotely assign homework and collect clinical data to increase their satisfaction via telemedicine.