Open-boundary molecular dynamics of ultrasound using supramolecular water models.

Ultrasound can be used to manipulate protein function and activity, as well as for targeted drug delivery, making it a powerful diagnostic and therapeutic modality with wide applications in sonochemistry, nanotechnology, and engineering. However, a general particle-based approach to ultrasound modeling remains challenging due to the significant disparity between characteristic time scales governing ultrasound propagation. In this study, we use open-boundary molecular dynamics to simulate ultrasound waves in liquid water under ambient conditions by employing supramolecular water models, i.

Performance of Dysmorphology-Based Screening for Genetic Disorders in Pediatric Congenital Heart Disease Supports Wider Genetic Testing.

Background: Dysmorphology evaluation is important for congenital heart disease (CHD) assessment, but there are no prior investigations quantifying the screening performance compared to standardized genetics evaluations. We investigated this through systematic dysmorphology assessment in CHD patients with standardized genetic testing in primarily pediatric patients with CHD.

Methods: Dysmorphology evaluations preceding genetic testing results allowed us to test for associations between dysmorphic status and genetic diagnoses while adjusting for extracardiac anomalies (ECAs).

A multifunctional protein pre-coated metal-organic framework for targeted delivery with deep tissue penetration.

Targeted drug delivery using metal-organic frameworks (MOFs) has shown significant progress. However, the tumor microenvironment (TME) impedes efficient MOF particle transfer into tumor cells. To tackle this issue, we pre-coated nano-sized MOF-808 particles with multifunctional proteins: glutathione S-transferase (GST)-affibody (Afb) and collagenase, aiming to navigate the TME more effectively.

Unveiling the Power of Cloaking Metal-Organic Framework Platforms via Supramolecular Antibody Conjugation.

Targeted drug delivery systems based on metal-organic frameworks (MOFs) have progressed tremendously since inception and are now widely applicable in diverse scientific fields. However, translating MOF agents directly to targeted drug delivery systems remains a challenge due to the biomolecular corona phenomenon. Here, we observed that supramolecular conjugation of antibodies to the surface of MOF particles (MOF-808) via electrostatic interactions and coordination bonding can reduce protein adhesion in biological environments and show stealth shields.

Outcomes in 14 live births resulting from Pegvaliase-treated pregnancies in PKU-affected females.

Background: Adults with PKU have difficulty maintaining plasma phenylalanine (Phe) in the range that is safe for neurologic function. Elevated plasma Phe is a risk factor for congenital anomalies and developmental delay in offspring resulting from pregnancies with poor Phe control in women with PKU. Enzyme supplementation with pegvaliase allows adults with PKU to eat an unrestricted diet and have plasma Phe levels in a safe range for pregnancy but pegvaliase has not been approved for use in pregnant females with PKU.

Deciphering Reaction Products in Formamidine-Based Perovskites with Methylammonium Chloride Additive.

The fabrication of formamidinium lead iodide (FAPbI) perovskite solar cells (PSCs) involves the addition of methylammonium chloride (MACl) to promote low-temperature α-phase formation and grain growth. However, as the added MACl deprotonates and volatilizes into methylamine (MA) and HCl for removal, MA can chemically interact with formamidinium (FA), forming methyl formamidinium (MFA) as a byproduct. Despite its significance, the chemical interactions among FAPbI perovskites, MACl additives, and their byproducts remain poorly understood.

Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: results from long-term open-label study.

Objective: This study assessed the effect of 1-year administration of diazoxide choline extended-release tablet (DCCR) on hyperphagia and other complications of Prader-Willi syndrome (PWS).

Methods: The authors studied 125 participants with PWS, age ≥ 4 years, who were enrolled in the DESTINY PWS Phase 3 study and who received DCCR for up to 52 weeks in DESTINY PWS and/or its open-label extension. The primary efficacy endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score.

Metal-Organic Framework-Supported Catalase Delivery for Enhanced Photodynamic Therapy via Hypoxia Mitigation.

Tumor hypoxia poses a significant challenge in photodynamic therapy (PDT), which uses molecular oxygen to produce reactive oxygen species upon light excitation of a photosensitizer. For hypoxia mitigation, an enzyme catalase (CAT) can be beneficially used to convert intracellular hydrogen peroxide to molecular oxygen, but its utility is significantly limited due to the intrinsic membrane impermeability. Herein, we present direct integration of CAT into the outer surface of unmodified metal-organic framework (MOF) nanoparticles (NPs) via supramolecular interactions for effective cellular entry of CAT and consequent enhancement of PDT.

Symmetry-Mismatched SBU Transformation in MOFs: Postsynthetic Metal Exchange from Zn to Fe and Its Effects on Gas Adsorption and Dye Selectivity.

This research explores the alteration of metal-organic frameworks (MOFs) using a method called postsynthetic metal exchange. We focus on the shift from a Zn-based MOF containing a [ZnO(COO)] secondary building unit (SBU) of octahedral site symmetry (ANT-1(Zn)) to a Fe-based one with a [FeO(COO)] SBU of trigonal prismatic site symmetry (ANT-1(Fe)). The symmetry-mismatched SBU transformation cleverly maintains the MOF's overall structure by adjusting the conformation of the flexible 1,3,5-benzenetribenzoate linker to alleviate the framework strain.

Relationship satisfaction in adults with phenylketonuria is positively associated with following recommended treatment, having a partner involved in management, and maintaining good health.

Rationale: Phenylketonuria (PKU) is a metabolic condition that requires treatment for life. There is increasing evidence that chronic illnesses put strain on relationships and marriages. However, no studies have examined the unique factors that metabolic conditions have on affected individuals and their relationship satisfaction.

Diazoxide Choline Extended-Release Tablet in People With Prader-Willi Syndrome: A Double-Blind, Placebo-Controlled Trial.

Context: Prader-Willi syndrome (PWS) is a rare neurobehavioral-metabolic disease caused by the lack of paternally expressed genes in the chromosome 15q11-q13 region, characterized by hypotonia, neurocognitive problems, behavioral difficulties, endocrinopathies, and hyperphagia resulting in severe obesity if not controlled.

Objective: The primary end point was change from baseline in hyperphagia using the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). Other end points included Global Impression Scores, and changes in body composition, behaviors, and hormones.

Ligand functionalization of defect-engineered Ni-MOF-74.

Incorporating functionality into the framework of metal-organic frameworks (MOFs) has attracted substantial interest because the physical and chemical properties of MOFs can be tuned by functionalizing pores. The ligand functionalization of MOF-74 is challenging because of its pristine organic ligand and framework structure. Herein, we report a series of ligand-functionalized Ni-MOF-74 derivatives synthesized by defect engineering using a mixed-ligand approach.

Comparison of willingness and preference for genetic counseling via telemedicine: before vs. during the COVID-19 pandemic.

The COVID-19 pandemic required genetic counseling services, like most outpatient healthcare, to rapidly adopt a telemedicine model. Understanding the trends in patients' preferences for telemedicine relative to in-person service delivery both before and after the advent of the COVID-19 pandemic may aid in navigating how best to integrate telemedicine in a post-COVID-19 era. Our study explored how respondents' willingness to use, and preference for, telemedicine differed from before to after the onset of the COVID-19 pandemic.

Furan oxidation by Mn(iii)/Co(ii) catalysts - application to benzofuran synthesis.

Furans containing a β-ketoester group at 2-position undergo oxidative ring-opening by Mn(iii)/Co(ii) catalysts under an O atmosphere to produce 1,4-dicarbonyl moieties through an endoperoxide intermediate, which consecutively cyclized with the β-ketoester unit to afford 4-hydroxy-2-cyclohexen-1-ones. This oxidation/cyclization products were efficiently transformed into versatile benzofuran derivatives after consecutive aromatization and Paal-Knorr reaction.

Spatial distribution modulation of mixed building blocks in metal-organic frameworks.

The placement of mixed building blocks at precise locations in metal-organic frameworks is critical to creating pore environments suitable for advanced applications. Here we show that the spatial distribution of mixed building blocks in metal-organic frameworks can be modulated by exploiting the different temperature sensitivities of the diffusion coefficients and exchange rate constants of the building blocks. By tuning the reaction temperature of the forward linker exchange from one metal-organic framework to another isoreticular metal-organic framework, core-shell microstructural and uniform microstructural metal-organic frameworks are obtained.

Creating Tunable Mesoporosity by Temperature-Driven Localized Crystallite Agglomeration.

A new synthetic approach for tunable mesoporous metal-organic frameworks (MeMs) is developed. In this approach, mesopores are created in the process of heat conversion of highly mosaic metal-organic framework (MOF) crystals with non-interpenetrated low-density nanocrystallites into MOF crystals with two-fold interpenetrated high-density nanocrystallites. The two-fold interpenetration reduces the volume of the nanocrystallites in the mosaic crystal, and the accompanying localized agglomeration of the nanocrystallites results in the formation of mesopores among the localized crystallite agglomerates.

Use of pegvaliase in the management of phenylketonuria: Case series of early experience in US clinics.

Objective: To present a case series that illustrates real-world use of pegvaliase based on the initial experiences of US healthcare providers.

Methods: Sixteen healthcare providers from 14 centers across the US with substantial clinical experience in treating patients with phenylketonuria (PKU) with pegvaliase in the two-plus years since FDA approval (May 2018) provided cases that exemplified important lessons from their initial experiences treating patients with pegvaliase. Key lessons from each case and takeaway points were discussed in both live and virtual meetings.

Rapid Access Palliative Radiation Therapy Clinics: The Evidence Is There, but Where Are the Clinics? An Australian and New Zealand Perspective.

Purpose: First developed in Canada in the 1990s, Rapid Access Palliative Radiation Therapy (RAPRT) clinics have subsequently spread internationally to expedite treatment for near end-of-life patients, sparing them the need for multiple visits to the department. A "classical" RAPRT clinic is herein defined as "a dedicated clinic specifically established to enable (ideally) same day consultation, planning for, and delivery of palliative radiation treatment." The aim of this work was to determine the current status of these clinics in Australia and New Zealand (ANZ).

Palynziq clinic: One year and 43 patients later.

Pegvaliase-pqpz (Palynziq) is an enzyme substitution therapy FDA approved May 2018 to treat phenylketonuria in adults with blood phenylalanine levels greater than 600 μmol/L (10 mg/dL). Pegvaliase is administered via subcutaneous injection and carries a high risk of side effects including anaphylaxis. A consensus statement on its use recommends careful education and monitoring of patients.

Superprotonic Conductivity of MOF-808 Achieved by Controlling the Binding Mode of Grafted Sulfamate.

A metal-organic framework (MOF) having superprotonic conductivity, MOF-808, is prepared by modulating the binding mode of the sulfamate (SA) moieties grafted onto the metal clusters. The activation of the SA-grafted MOF-808 at 150 °C changes the binding mode of the grafted SA from monodentate to bridging bidentate, thus converting the neutral amido (-S-NH ) moiety of the grafted SA to the more acidic cationic sulfiliminium (-S=NH ) moiety. Further, the acidic sulfiliminium moiety of MOF-808-4SA-150 results in more efficient proton conduction than the amido moiety of MOF-808-4SA-60.

Association between FSHR and ESR1 gene variants and ovarian response to gonadotropin in Egyptian women undergoing ICSI treatment.

The unpredictable variability in patients' responses to gonadotropins represents one of the most intractable IVF treatment problems. Identifying the genetic variants associated with ovarian responses to gonadotropins is an important step towards developing individualised pharmacogenetics protocols for ovarian stimulation. The purpose of the current study was to evaluate correlations between FSHR rs6165, FSHR rs616, and ESR1 rs2234693 gene variants and the degree of ovarian response to gonadotropin in Egyptian women undergoing ICSI treatment.