Discovery of Clinical Candidate NT-0796, a Brain-Penetrant and Highly Potent NLRP3 Inflammasome Inhibitor for Neuroinflammatory Disorders.

The NLRP3 inflammasome is a component of the innate immune system involved in the production of proinflammatory cytokines. Neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, have been shown to have a component driven by NLRP3 inflammasome activation. Diseases such as these with large unmet medical needs have resulted in an interest in inhibiting the NLRP3 inflammasome as a potential pharmacological treatment, but to date, no marketed drugs specifically targeting NLRP3 have been approved.

Prevalence of genital Mycoplasma in pregnancies with shortened cervix.

Objective: To determine whether colonisation with genital Mycoplasma species (spp.) in patients presenting with a shortened cervix before 34th week of pregnancy is associated with preterm birth.

Methods: The collection of this retrospective study consisted of 100 pregnant women who presented to a German Tertiary Perinatal Center between 2017 and 2020 due to a shortened cervix defined as a cervical length of 25 mm or shorter measured by transvaginal ultrasound before 34 weeks of gestation.

Thermoresponsive Coiled-Coil Peptide-Polymer Grafts.

Alkyl halide side groups are selectively incorporated into monodispersed, computationally designed coiled-coil-forming peptide nanoparticles. Poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) is polymerized from the coiled-coil periphery using photoinitiated atom transfer radical polymerization (photoATRP) to synthesize well-defined, thermoresponsive star copolymer architectures. This facile synthetic route is readily extended to other monomers for a range of new complex star-polymer macromolecules.

Long-distance tmFRET using bipyridyl- and phenanthroline-based ligands.

With the great progress on determining protein structures over the last decade comes a renewed appreciation that structures must be combined with dynamics and energetics to understand function. Fluorescence spectroscopy, specifically Förster resonance energy transfer (FRET), provides a great window into dynamics and energetics due to its application at physiological temperatures and ability to measure dynamics on the ångström scale. We have recently advanced transition metal FRET (tmFRET) to study allosteric regulation of maltose binding protein and have reported measurements of maltose-dependent distance changes with an accuracy of ~1.

Measuring conformational equilibria in allosteric proteins with time-resolved tmFRET.

Proteins are the workhorses of biology, orchestrating a myriad of cellular functions through intricate conformational changes. Protein allostery, the phenomenon where binding of ligands or environmental changes induce conformational rearrangements in the protein, is fundamental to these processes. We have previously shown that transition metal Förster resonance energy transfer (tmFRET) can be used to interrogate the conformational rearrangements associated with protein allostery and have recently introduced novel FRET acceptors utilizing metal-bipyridyl derivatives to measure long (>20 Å) intramolecular distances in proteins.

Near-Infrared Spectroscopy to Guide and Understand Effects of Red Blood Cell Transfusion.

This review is a summary of available evidence regarding the use of near-infrared spectroscopy (NIRS) to help better guide and understand the effects of red blood cell (RBC) transfusion in neonatal patients. We review recent literature demonstrating the changes that take place in regional tissue oxygen saturation (rSO) resulting from RBC transfusion. We also discuss in detail if any correlation exists between rSO and hemoglobin values in neonates.

Epicardial Devices in Pediatrics and Congenital Heart Disease.

Epicardial cardiac implantable electronic device implant remains a common option in pediatric patients and certain patients with congenital heart disease due to patient size, complex anatomy, residual intracardiac shunts, and prior surgery precluding transvenous implant. Advantages include the lack of thromboembolic and vascular risks and ability to implant during concomitant surgery. Significant disadvantages include the occurrence of lead dysfunction that can result in bradycardia events in pacemaker patients, inappropriate shocks in implantable cardiac defibrillator patients, and overall a more invasive procedure.

Eradication of cervical canal colonization associated with prophylactic cervical cerclage: the look further study.

Objectives: The perioperative management of the cervical cerclage procedure is not unified. In general population controlling microbiome cervical status does not affect obstetric outcomes, but it might be beneficial in patients with cervical insufficiency. The aim of our study was to present the obstetric, neonatal and pediatric outcomes of patients undergoing the cervical cerclage placement procedure in our obstetric department using a regimen of care that includes control of the microbiological status of the cervix and elimination of the pathogens detected.

Nickel-Mediated Alkyl-, Acyl-, and Sulfonylcyanation of [1.1.1]Propellane.

The replacement of traditional functional groups with polycyclic scaffolds has been increasingly rewarding in medicinal chemistry programs. Over the decades, 1,-disubstituted bicyclo[1.1.

Transient susceptibility imaging as a measure of hemodynamic compromise: A pilot study.

Background And Purpose: The purpose of this study was to test the hypothesis that hemodynamically compromised brains exhibit transient changes in magnetic susceptibility throughout the cardiac cycle, and to model these changes using Linear System Theory to extract an index that reflects cerebrovascular reserve.

Materials And Methods: Eleven patients with angiographically-confirmed intracranial atherosclerotic disease with >50% stenosis were imaged with susceptibility weighted, cardiac-gated single shot images of cerebral Oxygen Extraction Fraction (OEF) at different timepoints of the cardiac cycle. Cardiac gating of the OEF acquisition allowed interrogation of oxygenated blood and the detection of changes throughout the cardiac cycle.

Iron-Catalyzed Intermolecular C-H Amination Assisted by an Isolated Iron-Imido Radical Intermediate.

Here we report the use of a base metal complex [( pyrpyrr )Fe(OEt )] (1-OEt ) ( pyrpyrr =3,5-tBu -bis(pyrrolyl)pyridine) as a catalyst for intermolecular amination of C -H bonds of 9,10-dihydroanthracene (2 a) using 2,4,6-trimethyl phenyl azide (3 a) as the nitrene source. The reaction is complete within one hour at 80 °C using as low as 2 mol % 1-OEt with control in selectivity for single C-H amination versus double C-H amination. Catalytic C-H amination reactions can be extended to other substrates such as cyclohexadiene and xanthene derivatives and can tolerate a variety of aryl azides having methyl groups in both ortho positions.

Recent Discovery, Development, and Synthetic Applications of Formic Acid Salts in Photochemistry.

The advancement of sustainable photoredox catalysis in synthetic organic chemistry has evolved immensely because of the development of versatile and cost-effective reagents. In recent years, a substantial effort has been dedicated to exploring the utility of formic acid salts in various photochemical reactions. In this context, formates have demonstrated diverse capabilities, functioning as reductants, sources of carbonyl groups, and reagents for hydrogen atom transfer.

Barriers and Facilitators to Behavioral Healthcare for Women Veterans: a Mixed-Methods Analysis of the Current Landscape.

Women veterans have historically faced barriers to behavioral health treatment, particularly through the VA. In conjunction, there have been changes in behavioral healthcare delivery resulting from efforts to improve care for women veterans and the COVID-19 pandemic (e.g.

Cerclage in complete placenta previa preventing preterm labor: A rare case report.

Placenta previa often leads to antepartum hemorrhage, which warrants the patient for emergency room admission. The bleeding occurs mainly due to cervical dilation, which could be caused by cervical incompetence. Cervical cerclage has been considered as the primary treatment for cervical incompetence.

A Comparison of Ketamine and Midazolam as First-Line Anesthetic Infusions for Pediatric Status Epilepticus.

Background: Pediatric refractory status epilepticus (RSE) often requires management with anesthetic infusions, but few data compare first-line anesthetics. This study aimed to compare the efficacy and adverse effects of midazolam and ketamine infusions as first-line anesthetics for pediatric RSE.

Methods: Retrospective single-center study of consecutive study participants treated with ketamine or midazolam as the first-line anesthetic infusions for RSE at a quaternary care children's hospital from December 1, 2017, until September 15, 2021.

Difluoromethyl-1,3,4-oxadiazoles Are Selective, Mechanism-Based, and Essentially Irreversible Inhibitors of Histone Deacetylase .

Histone deacetylase (HDAC6) is an important drug target in oncological and non-oncological diseases. Most available HDAC6 inhibitors (HDAC6i) utilize hydroxamic acids as a zinc-binding group, which limits therapeutic opportunities due to its genotoxic potential. Recently, difluoromethyl-1,3,4-oxadiazoles (DFMOs) were reported as potent and selective HDAC6i but their mode of inhibition remained enigmatic.

Case report: Combination of veno-arterial extracorporeal membrane oxygenation and intra-aortic balloon pump in a young male patient with refractory cardiogenic shock due to aluminum phosphide poisoning.

Background: Acute toxic myocardial damage may be accompanied by the development of cardiogenic shock (CS), the mortality from which is still unacceptably high. Since there is no specific antidote for many types of toxins, treatment of such patients includes various measures of hemodynamic and respiratory support. The paper presents a case of refractory CS due to possible aluminum phosphide (AP) poisoning.

Chronic Hepatitis B: Treat all Who Are Viremic?

The main aim of antiviral therapy in patients with chronic hepatitis B (CHB) is to prevent disease progression and reduce the risk of hepatocellular carcinoma (HCC). In general, treatment is recommended for select patient groups viewed as being at higher risk of developing adverse outcomes from CHB. However, patients who do not meet treatment criteria under current international guidelines may still benefit from antiviral therapy to reduce CHB-related complications.

Outpatient management of established bronchopulmonary dysplasia: An update.

As the incidence of infants with bronchopulmonary dyspasia (BPD) has continued to rise, so has their rate of survival. Their medical management is often complex and requires the use of numerous therapies such as steroids, bronchodilators, diuretics and modalities to deliver supplemental oxygen and positive pressure. It also requires multi-disciplinary care to ensure adequate growth and to optimize neurodevelopmental outcomes.

The first USA continental record of coffee leaf rust () on coffee () in southwest Florida, USA.

Coffee leaf rust (CLR), caused by Hemileia vastatrix Berk. & Broome (Zaghouaniaceae) is considered the most significant fungal disease of Coffea arabica L. (Rubiaceae), from which berries are harvested and processed to obtain coffee beverage (Talhinhas et al.

Susceptibility of centipede tongavine () commercially grown in nurseries in Florida to aroid leaf rust ().

Epipremnum pinnatum (L.) Engl., (Araceae, Monocots) known as dragon-tail plant or centipede tongavine, is the most cultivated aroid species worldwide (Boyce 2004).

34th Annual Meeting of the Society for Light Treatment and Biological Rhythms (SLTBR), 30 May-1 June, Lausanne, Switzerland.

The Society for Light Treatment and Biological Rhythms (SLTBR) held this year's annual meeting at the Ecole Polytechnique Fédérale (EPFL) in Lausanne, Switzerland from 30 May to 1 June in conjunction with the Day Light Academy (DLA) [...

The development, content and response process validation of a caregiver-reported severity measure for CDKL5 deficiency disorder.

Background: CDKL5 Deficiency Disorder (CDD) is a severe X-linked developmental and epileptic encephalopathy. Existing developmental outcome measures have floor effects and cannot capture incremental changes in symptoms. We modified the caregiver portion of a CDD clinical severity assessment (CCSA) and assessed content and response-process validity.

Behavior change versus stability during the college-to-work transition: Life course and the "stickiness" of alcohol misuse at career entry.

To what extent and under what conditions do college graduates disengage from employment-incompatible behaviors during the college-to-work transition? Drawing from the life course perspective, we proposed a model highlighting considerable stability of employment-incompatible behaviors during initial months of organizational socialization. Our model predicted that maturing out of such behaviors, which is expected by employers and beneficial to career adjustment, would be more likely to occur given a conducive transition context. Using a large dataset tracking graduates from their last semester in college to up to approximately 1.