Detecting the Major Degradation Products of Phosphorothioate Oligonucleotides by Chemical Derivatization and Weak Anion Exchange Chromatography.

Novel polar cysteine analogues have been synthesized for the derivatization of oligonucleotide depurination impurities that may be formed under acidic conditions. Depurination impurities belong to a group that includes deamination and phosphate diester impurities, which are similar in chemical structure to each other and the parent oligonucleotide, and thus coelute by most chromatographic separation methods. The polar cysteine analogues react with depurination impurities and enable their complete separation from the parent oligonucleotide by weak anion exchange (WAX) chromatography.

Transformations in prefrontal ensemble activity underlying rapid threat avoidance learning.

The capacity to learn cues that predict aversive outcomes, and understand how to avoid those outcomes, is critical for adaptive behavior. Naturalistic avoidance often means accessing a safe location, but whether a location is safe depends on the nature of the impending threat. These relationships must be rapidly learned if animals are to survive.

Developmentally distinct architectures in top-down circuits.

The medial prefrontal cortex (mPFC) plays a key role in learning, mood and decision making, including in how individuals respond to threats . mPFC undergoes a uniquely protracted development, with changes in synapse density, cortical thickness, long-range connectivity, and neuronal encoding properties continuing into early adulthood . Models suggest that before adulthood, the slow-developing mPFC cannot adequately regulate activity in faster-developing subcortical centers .

mouse model to induce mosaic gene expression in rod photoreceptors.

Photoreceptors are sensory neurons that capture light within their outer segment, a narrow cylindrical organelle stacked with disc-shaped membranes housing the visual pigment. Photoreceptors are the most abundant neurons in the retina and are tightly packed to maximize the capture of incoming light. As a result, it is challenging to visualize an individual cell within a crowded photoreceptor population.

BehaviorDEPOT is a simple, flexible tool for automated behavioral detection based on markerless pose tracking.

Quantitative descriptions of animal behavior are essential to study the neural substrates of cognitive and emotional processes. Analyses of naturalistic behaviors are often performed by hand or with expensive, inflexible commercial software. Recently, machine learning methods for markerless pose estimation enabled automated tracking of freely moving animals, including in labs with limited coding expertise.

Severe manifestations and treatment of COVID-19 in a transplanted patient with Fabry disease.

Fabry disease is an X linked disease caused by pathogenic variants in the gene. The cardiovascular and renal systems are most affected in Fabry patients and may require heart or kidney transplants in the late stages of the disease depending on severity of manifestations. Enzyme replacement therapy (ERT) has proven to delay progression of Fabry disease considerably, especially when started early in life.

One-Pot Synthesis of Indoles and Pyrazoles via Pd-Catalyzed Couplings/Cyclizations Enabled by Aqueous Micellar Catalysis.

An effective one-pot synthesis of either indoles or pyrazoles can be achieved via Pd-catalyzed aminations followed by subsequent cyclizations facilitated by aqueous micellar catalysis. This new technology includes efficient couplings with low loadings of palladium, a more stable source of the required hydrazine moiety, greater atom economy for the initial coupling, and reduced reaction temperatures, all leading to environmentally responsible processes.

Point-of-care Ultrasound Diagnosis of Pulmonary Embolism with Thrombus in Transit.

A 95-year-old female with a history of dementia and atrial fibrillation (not on anticoagulation) presented to the emergency department (ED) by ambulance from her skilled nursing facility due to hypoxia. Point-of-care ultrasound was performed, and showed evidence of a large mobile thrombus in the right ventricle on apical four-chamber view. Further evidence of associated right heart strain was seen on the corresponding parasternal short-axis view.

Stigma and negative self-perceptions of young people living with human immunodeficiency virus in Bandung, Indonesia: a case series.

Background: Young people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) (PLWA) are at risk for HIV stigma.

Methods: The HIV/AIDS Stigma Instrument for PLWA was administered to 36 young PLWA across six clinics in Bandung, Indonesia, to assess the fear of contagion (FC), verbal abuse (VA), social isolation (SI), workplace stigma (WS), health care neglect (HCN) and negative self-perception (NSP).

Results: The median scores for FC, VA, SI, WS and HCN were all 0 while the median score for NSP was 4.

Evaluation of a point of care ultrasound curriculum for Indonesian physicians taught by first-year medical students.

Background: The purpose of this study was to assess the short-term efficacy of a 4-week ultrasound curriculum taught by American first-year medical students to general practitioners working in public health care clinics, or puskesmas, in Bandung, Indonesia.

Methods: We performed a prospective, observational study of Indonesian health care practitioners from public clinics in Bandung, Indonesia. These practitioners were enrolled in a 4-week ultrasound training course taught by first-year American medical students.

Comparison of ultrasound-measured properties of the common carotid artery to tobacco smoke exposure in a cohort of Indonesian patients.

Background: The purpose of this study was to use point-of-care ultrasound (POCUS) to investigate the relationship between tobacco smoke exposure and the characteristics of the common carotid artery (CCA). The effect of both primary and secondary smoking on CCA properties was evaluated.

Methods: We performed a prospective cross-sectional study across 20 primary care clinics in Bandung, West Java, Indonesia in July 2016.

Loss of Arf4 causes severe degeneration of the exocrine pancreas but not cystic kidney disease or retinal degeneration.

Arf4 is proposed to be a critical regulator of membrane protein trafficking in early secretory pathway. More recently, Arf4 was also implicated in regulating ciliary trafficking, however, this has not been comprehensively tested in vivo. To directly address Arf4's role in ciliary transport, we deleted Arf4 specifically in either rod photoreceptor cells, kidney, or globally during the early postnatal period.

Effects of Co-solvents on Reactions Run under Micellar Catalysis Conditions.

The impact of varying percentages of an organic solvent added to reactions run in aqueous nanomicelles as the reaction medium has been investigated. Issues such as rates of reaction, percent conversion, and yield, as well as various practical aspects (e.g.

Hyperfamiliarity in Dementia and Mild Cognitive Impairment.

Introduction: Hyperfamiliarity, a phenomenon in which feelings of familiarity are evoked by novel stimuli, is well described in epilepsy and the lesioned brain. Abnormality of familiarity in Alzheimer's disease (AD) and mild cognitive impairment (MCI) have also been described in the literature, but more from a neuropsychological approach perspective. Currently, there is a lack of study on the real-life experience of familiarity abnormality in dementia and MCI.

Amide and Peptide Bond Formation in Water at Room Temperature.

A general and environmentally responsible method for the formation of amide/peptide bonds in an aqueous micellar medium is described. Use of uronium salt (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (COMU) as a coupling reagent, 2,6-lutidine, and TPGS-750-M represents mild conditions associated with these valuable types of couplings. The aqueous reaction medium is recyclable leading to low E Factors.

A palladium nanoparticle-nanomicelle combination for the stereoselective semihydrogenation of alkynes in water at room temperature.

The addition of NaBH4 to Pd(OAc)2 in water containing nanomicelles leads to the generation of H2 and Pd nanoparticles. Subsequent reduction of disubstituted alkynes affords Z-alkenes in high yields. These reactions are general, take place in water at ambient temperatures, and offer recycling of the aqueous reaction mixture along with low overall E Factors.

2-Aminobenzoxazole ligands of the hepatitis C virus internal ribosome entry site.

2-Aminobenzoxazoles have been synthesized as ligands for the hepatitis C virus (HCV) internal ribosome entry site (IRES) RNA. The compounds were designed to explore the less basic benzoxazole system as a replacement for the core scaffold in previously discovered benzimidazole viral translation inhibitors. Structure-activity relationships in the target binding of substituted benzoxazole ligands were investigated.

A new class of intramolecularly hydrogen-bonded dendrons based on a 2-methoxyisophthalamide repeat unit.

The synthesis and conformational properties of folded dendrons based on a 2-methoxyisophthalamide (2-OMe-IPA) repeat unit are described. The hydrodynamic properties of dendrons preorganized via the syn-syn conformational preference of 2-methoxyisophthalamide are compared with 2,6-pyridinedicarboxamide (2,6-pydic) analogues. The effect of subtle differences in the nature of the conformational equilibria that exist within the 2-OMe-IPA and 2,6-pydic repeat units on the global structural properties of the corresponding dendrons was explored computationally, by (1)H-DOSY NMR spectroscopy and time-resolved fluorescence anisotropy (TRFA) measurements.

Expanding dendrons. The photoisomerism of folded azobenzene dendrons.

Irradiation of a folded azobenzene dendron system triggers a large, reversible structural expansion. The dendrons adopt a compact helical conformation in the stable E form owing to the E geometry of azo linkage and the syn-syn preference of the dendritic branch points. E --> Z photoisomerization disrupts this folded conformation in a manner that decreases the packing efficiency and results in an expansion in hydrodynamic volume.

Behind the facial twitch: depressive symptoms in hemifacial spasm.

Background: Depression impairs psychosocial and occupational functioning and contributes to significant morbidity and mortality. Hemifacial spasm (HFS) causes social embarrassment and visual and verbal disability.

Objective: We examined; (1) the prevalence and predictive factors of depressive symptoms (Becks Depression Inventory (BDI) and clinical assessment) in HFS and (2) the sensitivity and specificity of BDI as a screening and diagnostic tool in HFS.