mHealth learning strategies to support behaviour change in individuals using wheelchairs and/or scooters: a systematic review.

Purpose: The purpose of this systematic review of the literature is to build understanding of the key elements and recommendations for the design of mHealth technology for individuals using wheelchairs and/or scooters and identify key features associated with the use of mHealth to support healthy behaviour changes for this population.

Materials And Methods: Eight major electronic databases were systematically searched to identify mobile health (mHealth) interventions, which targeted adult WC/S users. Independent reviewers used Endnote and Covidence to manage articles meeting review criteria and to exclude duplicates.

Searching for the social determinants of health: observations from evidence synthesis publications.

Background: The social determinants of health (SDOH) are the focus of an exponentially increasing number of publications, including evidence syntheses. However, there is not an established standard for searching for SDOH literature. This study seeks to identify published evidence syntheses pertaining to the SDOH, analyzing the search strategies used and the studies included within these reviews.

Using Dry Dispersion Laser Diffraction to Assess Dispersibility in Spheronized Agglomerate Formulations.

In this study, dry dispersion laser diffraction was used to study the dispersibility of spheronized agglomerate formulations and identify geometric particle size metrics that correlated well with aerodynamic particle size distribution (APSD). Eleven unique batches of agglomerates were prepared for both laser diffraction and cascade impaction testing. Correlations between the particle size distribution (PSD) and aerodynamic particle size distribution (APSD) metrics for the eleven agglomerate batches were determined in a semi-empirical manner.

Islatravir Dimer: Crystal Form Dependence of a Radiation-Induced Degradation Product.

A rare example of crystal form-dependent, gamma radiation-induced degradation is presented. Islatravir is known to exist in several polymorphic forms, but only one of these forms shows the generation of a specific dimer degradation product under gamma irradiation. Extended gamma irradiation studies demonstrated that only one of the known crystalline forms shows an appreciable rate of dimer formation.

Impact of Processing Methods on the Physico-chemical Properties of Posaconazole Amorphous Solid Dispersions.

Background & Purpose: Different methods have been exploited to generate amorphous solid dispersions (ASDs) of poorly water-soluble drugs. However, the impact of processing methods on drug stability and dissolution hasn't been studied extensively. The purpose of the current study is to investigate the impact of the two common ASD processing methods, hot-melt extrusion (HME) and spray drying, on the chemical/physical stability and supersaturation of Posaconazole (Posa) based ASDs.

The case of the disappearing librarians: analyzing documentation of librarians' contributions to systematic reviews.

Objective: The study aimed to analyze the documented role of a librarian in published systematic reviews and meta-analyses whose registered protocols mentioned librarian involvement. The intention was to identify how, or if, librarians' involvement was formally documented, how their contributions were described, and if there were any potential connections between this documentation and basic metrics of search reproducibility and quality.

Methods: Reviews whose PROSPERO protocols were registered in 2017 and 2018 and that also specifically mentioned a librarian were analyzed for documentation of the librarian's involvement.

Discovery of Arylsulfonamide Na1.7 Inhibitors: IVIVC, MPO Methods, and Optimization of Selectivity Profile.

The voltage-gated sodium channel Na1.7 continues to be a high-profile target for the treatment of various pain afflictions due to its strong human genetic validation. While isoform selective molecules have been discovered and advanced into the clinic, to date, this target has yet to bear fruit in the form of marketed therapeutics for the treatment of pain.

A comparison of HIV outpatient care in primary and secondary healthcare-level settings in Zimbabwe.

Setting: Decentralisation of HIV care to nurse-led primary care services is being implemented across low- and middle-income countries in sub-Saharan Africa.

Objective: To compare services offered to clients attending for HIV care at a physician-led and a nurse-led service in Harare, Zimbabwe.

Design: A cross-sectional study was performed at Harare Central Hospital (HCH) and Budiriro Primary Care Clinic (PCC) from June to August 2018.

Synthesis of Islatravir Enabled by a Catalytic, Enantioselective Alkynylation of a Ketone.

The synthesis of the potent anti-HIV investigational treatment islatravir is described. The key step in this synthesis is a highly enantioselective catalytic asymmetric alkynylation of a ketone. This reaction is a rare example of the asymmetric addition of an alkyne nucleophile to a ketone through ligand-accelerated catalysis that was performed on a greater than 100 g scale.

Interpreting Release Performance from Long-Acting Parenteral Nanosuspensions Using USP-4 Dissolution and Spectroscopic Techniques.

Injectable sustained release dosage forms have emerged as desirable therapeutic routes for patients that require life-long treatments. The prevalence of drug molecules with low aqueous solubility and bioavailability has added momentum toward the development of suspension-based long-acting parenteral (LAP) formulations; the previously undesirable physicochemical properties of Biopharmaceutics Classification System (BCS) Class II/IV compounds are best suited for extended release applications. Effective release (IVR) testing of crystalline suspensions affirms product quality during early-stage development and provides connections with performance.

A Microsoft Excel Approach to Reduce Errors and Increase Efficiency in Systematic Searching.

Developing a search strategy for a systematic review is a time-consuming process in which small errors around the formatting and compilation of terms can have large consequences. Microsoft Excel was identified as a potentially useful software to streamline the process and reduce manual errors. Ultimately a spreadsheet was created that largely automates the process of creating a single-line search string with correctly formatted terms, Boolean operators and parentheses.

Expression of genes in the skeletal muscle of individuals with cachexia/sarcopenia: A systematic review.

Background: Cachexia occurs in individuals affected by chronic diseases in which systemic inflammation leads to fatigue, debilitation, decreased physical activity and sarcopenia. The pathogenesis of cachexia-associated sarcopenia is not fully understood.

Objectives: The aim of this systematic review is to summarize the current evidence on genes expressed in the skeletal muscles of humans with chronic disease-associated cachexia and/or sarcopenia (cases) compared to controls and to assess the strength of such evidence.

C NMR-Based Approaches for Solving Challenging Stereochemical Problems.

Determining the configuration of proton-deficient molecules is challenging using conventional NMR methods including nuclear Overhauser effect (NOE) and the proton-dependent J-based configuration analysis (JBCA). The problem is exacerbated when only one stereoisomer is available. Alternative methods based on the utilization of C NMR chemical shifts, C-C homonuclear couplings measured at natural abundance, and residual chemical shift anisotropy measurements in conjunction with density functional theory calculations are illustrated with a proton-deficient model compound.

Discovery of a Photoinduced Dark Catalytic Cycle Using in Situ LED-NMR Spectroscopy.

We report the use of LED-NMR spectroscopy to study the reaction mechanism of a newly discovered photoinduced iron-catalyzed cycloisomerization of alkynols to cyclic enol ethers. By understanding on/off ligand binding to the catalyst, we were able to appropriately design reaction conditions to balance catalyst activity and stability. LED-NMR was demonstrated to be a powerful tool in elucidating reaction mechanisms of photochemical reactions.

Beyond optical rotation: what's left is not always right in total synthesis.

This work describes the application of vibrational (VCD) and electronic (ECD) circular dichroism spectroscopy to solve the longstanding debate around the absolute configuration of (+)-frondosin B (). The absolute configuration of (+)- could confidently be assigned as () using these spectroscopic techniques. The discrepancy in the optical rotation (OR) values obtained in previous studies can be attributed to an undetected minor impurity ( 7%) that arose unexpectedly in a key step late in the synthesis.

Model for the Enantioselectivity of Asymmetric Intramolecular Alkylations by Bis-Quaternized Cinchona Alkaloid-Derived Catalysts.

A model for the stereoselectivity of intramolecular alkylations by N,N'-disubstituted cinchona alkaloids reported by Xiang et al. was established using density functional theory (DFT) calculations. The stereocontrol is based on the minimal distortion of the transition state (TS) and catalyst required to achieve favorable electrostatic interactions in the favored TS.

A rational pre-catalyst design for bis-phosphine mono-oxide palladium catalyzed reactions.

Significant catalyst loading reduction and increased reaction robustness have been achieved for a Pd-catalyzed asymmetric intramolecular C-N coupling through comprehensive mechanistic studies. Detailed kinetic, spectroscopic, and crystallographic analyses revealed that the mono-oxidation of the bis-phosphine ligand is critical for a successful transformation. P NMR studies provided an understanding of the inefficient activation of the Pd(OAc)/(,)-QuinoxP* pre-catalyst to form the active bis-phosphine mono-oxide-Pd(0) catalyst with competitive formation of a less active (,)-QuinoxP*·PdBr complex.

A multifunctional catalyst that stereoselectively assembles prodrugs.

The catalytic stereoselective synthesis of compounds with chiral phosphorus centers remains an unsolved problem. State-of-the-art methods rely on resolution or stoichiometric chiral auxiliaries. Phosphoramidate prodrugs are a critical component of pronucleotide (ProTide) therapies used in the treatment of viral disease and cancer.

Discovery of the 3-Imino-1,2,4-thiadiazinane 1,1-Dioxide Derivative Verubecestat (MK-8931)-A β-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor for the Treatment of Alzheimer's Disease.

Verubecestat 3 (MK-8931), a diaryl amide-substituted 3-imino-1,2,4-thiadiazinane 1,1-dioxide derivative, is a high-affinity β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor currently undergoing Phase 3 clinical evaluation for the treatment of mild to moderate and prodromal Alzheimer's disease. Although not selective over the closely related aspartyl protease BACE2, verubecestat has high selectivity for BACE1 over other key aspartyl proteases, notably cathepsin D, and profoundly lowers CSF and brain Aβ levels in rats and nonhuman primates and CSF Aβ levels in humans. In this annotation, we describe the discovery of 3, including design, validation, and selected SAR around the novel iminothiadiazinane dioxide core as well as aspects of its preclinical and Phase 1 clinical characterization.

The Discovery of Quinoxaline-Based Metathesis Catalysts from Synthesis of Grazoprevir (MK-5172).

Olefin metathesis (OM) is a reliable and practical synthetic methodology for challenging carbon-carbon bond formations. While existing catalysts can effect many of these transformations, the synthesis and development of new catalysts is essential to increase the application breadth of OM and to achieve improved catalyst activity. The unexpected initial discovery of a novel olefin metathesis catalyst derived from synthetic efforts toward the HCV therapeutic agent grazoprevir (MK-5172) is described.

Promotion of a Ti-Mediated Mannich Reaction by a Proton Source.

Low temperature NMR studies revealed that a diastereoselective Mannich reaction between a phenyl oxazolidone-derived titanium enolate and an aromatic aldimine was found to occur only after introduction of a proton source. While various protic additives could be used to promote the transformation, the best results were obtained using AcOH to afford the corresponding Mannich products in high diastereoselectivities and yields.

Assessment of the Stoichiometry of Multicomponent Crystals Using Only X-ray Powder Diffraction Data.

Knowledge of the unit cell volume of a crystalline form and the expected space filling requirements of an API molecule can be used to determine if a crystalline material is likely to be multicomponent, such as a solvate, hydrate, salt, or a co-crystal. The unit cell information can be readily accessed from powder diffraction data alone utilizing powder indexing methodology. If the unit cell has additional space not likely attributable to the API entity, then there is either a void or another component within the crystal lattice.

Discovery of SCH 900229, a Potent Presenilin 1 Selective γ-Secretase Inhibitor for the Treatment of Alzheimer's Disease.

An exploration of the SAR of the side chain of a novel tricyclic series of γ-secretase inhibitors led to the identification of compound (-)-16 (SCH 900229), which is a potent and PS1 selective inhibitor of γ-secretase (Aβ40 IC50 = 1.3 nM). Compound (-)-16 demonstrated excellent lowering of Aβ after oral administration in preclinical animal models and was advanced to human clinical trials for further development as a therapeutic agent for the treatment of Alzheimer's disease.