Engineering Tumor Stroma Morphogenesis Using Dynamic Cell-Matrix Spheroid Assembly.

The tumor microenvironment consists of resident tumor cells organized within a compositionally diverse, three-dimensional (3D) extracellular matrix (ECM) network that cannot be replicated in vitro using bottom-up synthesis. We report a new self-assembly system to engineer ECM-rich 3D MatriSpheres wherein tumor cells actively organize and concentrate microgram quantities of decellularized ECM dispersions which modulate cell phenotype. 3D colorectal cancer (CRC) MatriSpheres were created using decellularized small intestine submucosa (SIS) as an orthotopic ECM source that had greater proteomic homology to CRC tumor ECM than traditional ECM formulations such as Matrigel.

Pediatric Population Management Classification for Children with Medical Complexity.

Improving the overall care of children with medical complexity (CMC) is often beset by challenges in proactively identifying the population most in need of clinical management and quality improvement. The objective of the current study was to create a system to better capture longitudinal risk for sustained and elevated utilization across time using real-time electronic health record (EHR) data. A new Pediatric Population Management Classification (PPMC), drawn from visit diagnoses and continuity problem lists within the EHR of a tristate health system, was compared with an existing complex chronic conditions (CCC) system for agreement (with weighted κ) on identifying CCMC, as well as persistence of elevated charges and utilization from 2016 to 2019.

Accounting for unobserved population dynamics and aging error in close-kin mark-recapture assessments.

Obtaining robust estimates of population abundance is a central challenge hindering the conservation and management of many threatened and exploited species. Close-kin mark-recapture (CKMR) is a genetics-based approach that has strong potential to improve the monitoring of data-limited species by enabling estimates of abundance, survival, and other parameters for populations that are challenging to assess. However, CKMR models have received limited sensitivity testing under realistic population dynamics and sampling scenarios, impeding the application of the method in population monitoring programs and stock assessments.

Long-term efficacy of high-frequency (10 kHz) spinal cord stimulation for the treatment of painful diabetic neuropathy: 24-Month results of a randomized controlled trial.

Aims: To evaluate the long-term efficacy of high-frequency (10 kHz) spinal cord stimulation (SCS) for treating refractory painful diabetic neuropathy (PDN).

Methods: The SENZA-PDN study was a prospective, multicenter, randomized controlled trial that compared conventional medical management (CMM) alone with 10 kHz SCS plus CMM (10 kHz SCS+CMM) in 216 patients with refractory PDN. After 6 months, participants with insufficient pain relief could cross over to the other treatment.

Gene therapy for glycogen storage diseases.

Glycogen storage disorders (GSDs) are inherited disorders of metabolism resulting from the deficiency of individual enzymes involved in the synthesis, transport, and degradation of glycogen. This literature review summarizes the development of gene therapy for the GSDs. The abnormal accumulation of glycogen and deficiency of glucose production in GSDs lead to unique symptoms based upon the enzyme step and tissues involved, such as liver and kidney involvement associated with severe hypoglycemia during fasting and the risk of long-term complications including hepatic adenoma/carcinoma and end stage kidney disease in GSD Ia from glucose-6-phosphatase deficiency, and cardiac/skeletal/smooth muscle involvement associated with myopathy +/- cardiomyopathy and the risk for cardiorespiratory failure in Pompe disease.

Phenotypically driven subgroups of ASD display distinct metabolomic profiles.

Autism Spectrum Disorder (ASD) is a heterogeneous condition that includes a broad range of characteristics and associated comorbidities; however, the biology underlying the variability in phenotypes is not well understood. As ASD impacts approximately 1 in 100 children globally, there is an urgent need to better understand the biological mechanisms that contribute to features of ASD. In this study, we leveraged rich phenotypic and diagnostic information related to ASD in 2001 individuals aged 4 to 17 years from the Simons Simplex Collection to derive phenotypically driven subgroups and investigate their respective metabolomes.

Characterization of phenotypic range in DYRK1A haploinsufficiency syndrome using standardized behavioral measures.

DYRK1A haploinsufficiency syndrome is a well-established neurodevelopmental disorder, but detailed information on the range of cognitive and behavioral issues associated with the condition is limited. We studied 24 participants with likely pathogenic or pathogenic variants in DYRK1A through the Simons Searchlight study and systematically assessed their medical history and development using standardized instruments: Vineland Adaptive Behavior Scale II (VABS-II) and Child Behavior Checklists/1.5-5 and 6-18 (CBCL/1.

Efficacious Androgen Hormone Administration in Combination with Adeno-Associated Virus Vector-Mediated Gene Therapy in Female Mice with Pompe Disease.

Pompe disease is an autosomal recessive lysosomal storage disorder caused by deficiency of acid α-glucosidase (GAA), resulting in skeletal muscle weakness and cardiomyopathy that progresses despite currently available therapy in some patients. The development of gene therapy with adeno-associated virus (AAV) vectors revealed a sex-dependent decrease in efficacy in female mice with Pompe disease. This study evaluated the effect of testosterone on gene therapy with an AAV2/8 vector containing a liver-specific promoter to drive expression of GAA (AAV2/8-LSPhGAA) in female GAA-knockout (KO) mice that were implanted with pellets containing testosterone propionate before vector administration.

A Real-World Analysis of High-Frequency 10 kHz Spinal Cord Stimulation for the Treatment of Painful Diabetic Peripheral Neuropathy.

Background: Diabetes is one of the most prevalent chronic health conditions and diabetic neuropathy one of its most prevalent and debilitating complications. While there are treatments available for painful diabetic peripheral neuropathy (pDPN), their effectiveness is limited.

Method: This retrospective, multi-center, real-world review assessed pain relief and functional improvements for consecutive patients with diabetic neuropathy aged ≥18 years of age who were permanently implanted with a high-frequency (10 kHz) spinal cord stimulation (SCS) device.

Remote Diabetic Foot Temperature Monitoring for Early Detection of Diabetic Foot Ulcers: A Cost-Effectiveness Analysis.

Background: Foot temperature monitoring for the prevention and early detection of diabetic foot ulcers (DFU) is evidence-based and recommended in clinical practice. However, easy-to-use remote monitoring tools have been lacking, thereby preventing widespread adoption.

Objective: To evaluate the cost-effectiveness of remote foot temperature monitoring (RFTM) (Siren's Neurofabric™ Diabetic socks) in addition to standard of care (SoC) versus SoC alone for early detection of DFU with diabetic neuropathy and a moderate to high risk of DFU.

Increased insulin signaling in the Anopheles stephensi fat body regulates metabolism and enhances the host response to both bacterial challenge and Plasmodium falciparum infection.

In vertebrates and invertebrates, the insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) cascade is highly conserved and plays a vital role in many different physiological processes. Among the many tissues that respond to IIS in mosquitoes, the fat body has a central role in metabolism, lifespan, reproduction, and innate immunity. We previously demonstrated that fat body specific expression of active Akt, a key IIS signaling molecule, in adult Anopheles stephensi and Aedes aegypti activated the IIS cascade and extended lifespan.

Using Quality Improvement and Technology to Improve Social Supports for Hospitalized Children.

Objectives: To develop and test the feasibility of a caregiver self-administered social needs screener, a Web-based searchable community resource map, and a process map for implementation of these tools as part of social needs screening and referral on a pediatric inpatient unit.

Methods: A multidisciplinary team used quality improvement methodology to develop an electronic social needs screener, resource map Web site, and electronic health record enhancements. A process map for implementation of these tools was refined through plan-do-study-act cycles before full implementation.

Forensic hair analysis - Worldwide survey results.

Forensic hair analysis remains under the microscope. Although hair evidence can yield information pertinent to an investigation, past issues with associated expert testimony endure. The aim of this survey was to gain a better understanding of hair analysts by expanding on past findings by assessing methodology, terminology and bias, analysing demographic and workplace data and allowing participants to comment on current and future issues in hair analysis.

Availability of Services and Caregiver Burden: Supporting Individuals With Neurogenetic Conditions During the COVID-19 Pandemic.

Because of the COVID-19 pandemic, in-person services for individuals with neurodevelopmental disabilities were disrupted globally, resulting in a transition to remote delivery of services and therapies. For individuals with neurogenetic conditions, reliance on nonclinical caregivers to facilitate all therapies and care was unprecedented. The study aimed to (1) describe caregivers' reported impact on their dependent's services, therapies, medical needs, and impact on themselves as a result of the COVID-19 pandemic and (2) assess the relationship between the extent of disruption of services and the degree of self-reported caregiver burden.

Effect of High-frequency (10-kHz) Spinal Cord Stimulation in Patients With Painful Diabetic Neuropathy: A Randomized Clinical Trial.

Importance: Many patients with diabetic peripheral neuropathy experience chronic pain and inadequate relief despite best available medical treatments.

Objective: To determine whether 10-kHz spinal cord stimulation (SCS) improves outcomes for patients with refractory painful diabetic neuropathy (PDN).

Design, Setting, And Participants: The prospective, multicenter, open-label SENZA-PDN randomized clinical trial compared conventional medical management (CMM) with 10-kHz SCS plus CMM.

Contemporary issues in forensic science-Worldwide survey results.

Forensic science continues to be openly challenged and criticized. The aim of this study was to gain an understanding of forensic workplaces and the perceived current and potential future issues from forensic scientists via a detailed survey. An online survey was designed and disseminated to forensic practitioners and researchers worldwide.

The CHOICES Study: Facility Level Comparative Cost, Resource Utilization, and Outcomes Analysis of Myomectomy Compared to Transcervical Fibroid Ablation.

Purpose: The CHOICES study compared short-term resource utilization, facility costs, and perioperative patient outcomes between transcervical fibroid ablation (TFA) with the Sonata® system and myomectomy through a case-matched comparative trial design. This is the first facility-level comparative study conducted for TFA.

Patients And Methods: The study enrolled 88 patients from 4 centers equally divided among the two cohorts.

New spectrum of COVID-19 manifestations in children: Kawasaki-like syndrome and hyperinflammatory response.

In April 2020, data began emerging on Kawasaki-like syndrome and hyperinflammatory response in children with COVID-19. Since then, much has been published on the presentation of COVID-19 in pediatric patients, including its association with Kawasaki disease and the multisystem inflammatory syndrome in children (MIS-C). However, questions still remain regarding the risk factors, pathogenesis, prognosis, and specific therapy for these manifestations of COVID-19.

Synthesis, Structure-Activity Relationship, and Mechanistic Studies of Aminoquinazolinones Displaying Antimycobacterial Activity.

Phenotypic whole-cell screening against () in glycerol-alanine-salts supplemented with Tween 80 and iron (GASTE-Fe) media led to the identification of a 2-aminoquinazolinone hit compound, sulfone which was optimized for solubility by replacing the sulfone moiety with a sulfoxide . The synthesis and structure-activity relationship (SAR) studies identified several compounds with potent antimycobacterial activity, which were metabolically stable and noncytotoxic. Compound displayed favorable properties and was therefore selected for pharmacokinetic (PK) studies where it was found to be extensively metabolized to the sulfone .