Haplotype editing with CRISPR/Cas9 as a therapeutic approach for dominant-negative missense mutations in .

Inactivation of disease alleles by allele-specific editing is a promising approach to treat dominant-negative genetic disorders, provided the causative gene is haplo-sufficient. We previously edited a dominant missense mutation with inactivating frameshifts and rescued disease-relevant phenotypes in induced pluripotent stem cell (iPSC)-derived motor neurons. However, a multitude of different missense mutations cause disease.

Environmental dependence of geometrical efficiency for the scintillation cell in radon and thoron measurement.

222Rn is recognized as a matter of international concern for human health risk. Because 220Rn as well as 222Rn coexist in the natural environment, thoron sometimes influences the experiment for radon measurement. It is important to measure radon and thoron separately to evaluate the risk of the exposure to 222Rn.

Graft Versus Host Disease Prophylaxis in Matched Donor Stem Cell Transplantation: Post-transplantation Cyclophosphamide Combinations Versus Methotrexate/Tacrolimus.

Background: The use of post-transplant cyclophosphamide (PTCy) is highly effective in preventing graft versus host disease (GVHD) for haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT). There is limited data on the role of PTCy as GVHD prophylaxis in matched-sibling and fully matched-unrelated donor (MSD/MUD) allo-HSCT.

Methods: Our single-center retrospective study aims to compare outcomes of PTCy alone or in combination with mycophenolate mofetil and tacrolimus (PTCy/MMF/TAC) relative to methotrexate and tacrolimus (MTX/TAC).

Stereotactic Radiosurgery With Versus Without Neoadjuvant Endovascular Embolization for Brain Arteriovenous Malformations With Associated Intracranial Aneurysms.

Background And Objectives: Stereotactic radiosurgery (SRS) with neoadjuvant embolization is a treatment strategy for brain arteriovenous malformations (AVMs), especially for those with large nidal volume or concomitant aneurysms. The aim of this study was to assess the effects of pre-SRS embolization in AVMs with an associated intracranial aneurysm (IA).

Methods: The International Radiosurgery Research Foundation AVM database from 1987 to 2018 was retrospectively reviewed.

Progress test as an assessment for learning approach in an Infectious Diseases Residency Program: a case study.

Assessment is an essential component for all educational programs and must check competence acquirement while foster and promote learning. Progress Test (PT) is well recognized to assess cognitive knowledge, clinical reasoning and decision making in the clinical context, offering important information about the individual performance and program quality. It is widely used in Brazilian and international medical schools; however, it still has little role in assessing medical residents in Brazil.

Topical Diclofenac Versus Oral Ibuprofen Versus Diclofenac + Ibuprofen for Emergency Department Patients With Acute Low Back Pain: A Randomized Study.

Study Objective: Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are useful for a variety of musculoskeletal injuries. It is not known whether topical NSAIDs should be used for patients presenting with acute nonradicular musculoskeletal low back pain.

Methods: We conducted a randomized, placebo-controlled double-blind study in which patients 18 to 69 years of age visiting the emergency department (ED) with acute, nontraumatic, nonradicular, musculoskeletal low back pain were randomized at the time of discharge to treatment with 400 mg oral ibuprofen + placebo topical gel, 1% diclofenac topical gel + oral placebo, or 400 mg ibuprofen + 1% diclofenac topical gel.

Development of calculation tool for iodine 131 biodistribution depending on the aerosol particle distribution.

Radiation damage to tissues depends on radiation exposure levels. Therefore, we have studied accurate estimations of radiation exposure levels so far. Recently, we developed a tool that can calculate the respiratory tract deposition of radionuclides based on polydisperse particle size distribution.

Randomized Trial Comparing Low- vs High-Dose IV Dexamethasone for Patients With Moderate to Severe Migraine.

Background And Objectives: Dexamethasone decreases the frequency of migraine recurrence after emergency department (ED) discharge. However, the optimal dose of dexamethasone is unknown. We hypothesized that dexamethasone 16 mg IV would allow greater rates of sustained headache relief than 4 mg when coadministered with metoclopramide 10 mg IV.

Clinical and Imaging Outcomes After Trigeminal Schwannoma Radiosurgery: Results From a Multicenter, International Cohort Study.

Background And Objectives: An international, multicenter, retrospective study was conducted to evaluate the long-term clinical outcomes and tumor control rates after stereotactic radiosurgery (SRS) for trigeminal schwannoma.

Methods: Patient data (N = 309) were collected from 14 international radiosurgery centers. The median patient age was 50 years (range 11-87 years).

A Randomized Study of Intravenous Hydromorphone Versus Intravenous Acetaminophen for Older Adult Patients with Acute Severe Pain.

Study Objective: We conducted a randomized study to compare the efficacy and adverse event profile of 1,000 mg of intravenous acetaminophen to that of 0.5 mg of intravenous hydromorphone among patients aged 65 years or more with acute pain of severity that was sufficient enough to warrant intravenous opioids.

Methods: This randomized comparative effectiveness study with 162 participants was conducted in 2 urban emergency departments (EDs).

Tension pneumoventricle in a patient with a ventriculoperitoneal shunt and an ethmoidal meningoencephalocele.

Background: Tension pneumoventricle is a rare, life-threatening complication. It has been rarely described in patients with ventriculoperitoneal (VP) shunts.

Case Description: A 28-year-old male patient with a VP shunt became progressively lethargic after falling from his wheelchair.

Assessment of COVID-19 Vaccination Practices for 16 Vaccination Providers in Puerto Rico, 2021.

Objective: To assess COVID-19 vaccine providers' adherence to best practices and identify knowledge and practice gaps to guide corrective actions and retraining activities in Puerto Rico.

Methods: A CDC supportive evaluation tool was modified to collect information on vaccine storage, handling, preparation, administration, and post-vaccination care. Assessment visits to COVID-19 vaccine providers in Puerto Rico were conducted a month after the availability of COVID-19 vaccines in the island.

A Randomized, Placebo-Controlled Study of Intranasal Fentanyl as an Analgesic Adjunct For Incision and Drainage of Abscess.

Background: Incision and drainage (I&D) of abscesses is one of the most painful procedures performed in emergency departments (EDs).

Objective: We tested the following hypothesis: The addition of intranasal fentanyl to the standard practice of local infiltration with lidocaine would provide better pain control than lidocaine alone for adult ED patients undergoing I&D.

Methods: This was a randomized, double-blind study.

New bicyclic [3.2.1] octane neolignan derivative from .

bicyclic [3.2.1] octane neolignans have garnered increasing interest, because of their unique structural features and biological activities.

Allele-Specific Gene Editing Rescues Pathology in a Human Model of Charcot-Marie-Tooth Disease Type 2E.

Many neuromuscular disorders are caused by dominant missense mutations that lead to dominant-negative or gain-of-function pathology. This category of disease is challenging to address via drug treatment or gene augmentation therapy because these strategies may not eliminate the effects of the mutant protein or RNA. Thus, effective treatments are severely lacking for these dominant diseases, which often cause severe disability or death.

Adverse radiation effects in volume-staged radiosurgery for large arteriovenous malformations: a multiinstitutional study.

Objective: The optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. One approach is volume-staged stereotactic radiosurgery (VS-SRS). The authors previously reported efficacy of VS-SRS for large AVMs in a multiinstitutional cohort; here they focus on risk of symptomatic adverse radiation effects (AREs).

Bioengineered optogenetic model of human neuromuscular junction.

Functional human tissues engineered from patient-specific induced pluripotent stem cells (hiPSCs) hold great promise for investigating the progression, mechanisms, and treatment of musculoskeletal diseases in a controlled and systematic manner. For example, bioengineered models of innervated human skeletal muscle could be used to identify novel therapeutic targets and treatments for patients with complex central and peripheral nervous system disorders. There is a need to develop standardized and objective quantitative methods for engineering and using these complex tissues, in order increase their robustness, reproducibility, and predictiveness across users.

Effect of Prior Embolization on Outcomes After Stereotactic Radiosurgery for Pediatric Brain Arteriovenous Malformations: An International Multicenter Study.

Background: Pediatric brain arteriovenous malformations (AVMs) are a significant cause of morbidity but the role of multimodal therapy in the treatment of these lesions is not well understood.

Objective: To compare the outcomes of stereotactic radiosurgery (SRS) with and without prior embolization for pediatric AVMs.

Methods: We retrospectively evaluated the International Radiosurgery Research Foundation pediatric AVM database.

Pre- and post-COVID-19 evaluation of antimicrobial susceptibility for healthcare-associated infections in the intensive care unit of a tertiary hospital.

Introduction: Antimicrobial resistance has worsened since the onset of COVID-19.

Methods: This study involved patients admitted to the adult intensive care unit (ICU) of a tertiary hospital. Pre- and post-COVID-19 data were analyzed.

A randomized controlled trial of ibuprofen versus ketorolac versus diclofenac for acute, nonradicular low back pain.

Objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line medication for acute low back pain (LBP). It is unclear if the choice of NSAID impacts outcomes. We compared ibuprofen, ketorolac, and diclofenac for the treatment of acute, nonradicular LBP.

Antioxidant Nanomedicine Significantly Enhances the Survival Benefit of Radiation Cancer Therapy by Mitigating Oxidative Stress-Induced Side Effects.

Oxidative stress-induced off-target effects limit the therapeutic window of radiation therapy. Although many antioxidants have been evaluated as radioprotective agents, none of them are in widespread clinical use, owing to the side effects of the antioxidants themselves and the lack of apparent benefit. Aiming for a truly effective radioprotective agent in radiation cancer therapy, the performance of a self-assembling antioxidant nanoparticle (herein denoted as redox nanoparticle; RNP) is evaluated in the local irradiation of a subcutaneous tumor-bearing mouse model.