Enhanced bacterial cancer therapy delivering therapeutic RNA interference of c-Myc.

Background: Bacterial cancer therapy was first trialled in patients at the end of the nineteenth century. More recently, tumour-targeting bacteria have been harnessed to deliver plasmid-expressed therapeutic interfering RNA to a range of solid tumours. A major limitation to clinical translation of this is the short-term nature of RNA interference in vivo due to plasmid instability.

Program-Based Lung Cancer Care: A Prospective Observational Tumor Registry Linkage Study.

Introduction: Low-dose computed tomography screening (LDCT) and lung nodule programs (LNP) promote early lung cancer detection, improve survival; Multidisciplinary Care Programs (MDC) promote guideline-concordant care. The impact of such program-based care on "real-world" lung cancer survival is unquantified. We evaluated outcomes of lung cancer care delivered through structured programs in a community health care system.

Seroprevalence and predisposing factors of rabies antibodies in unvaccinated dogs in Sierra Leone.

Objective: This study determines the seroprevalence and associated factors of rabies in unvaccinated dogs in Sierra Leone.

Background: Rabies control is poorly coordinated in Sierra Leone which was ranked as the third hungriest country in the world. Due to limited access to rabies vaccines, the need for comprehensive serological data on dogs for control of the disease is expedient.

Modification of Diet to Reduce the Stemness and Tumorigenicity of Murine and Human Intestinal Cells.

Scope: Black raspberries (BRBs) have colorectal cancer (CRC) chemo-preventative effects. As CRC originates from an intestinal stem cell (ISC) this study has investigated the impact of BRBs on normal and mutant ISCs.

Methods And Results: Mice with an inducible Apc mutation in either the ISC (Lgr5CreER ) or intestinal crypt (AhCre/VillinCreER ) are fed a control or 10% BRB-supplemented diet.

Survival Impact of an Enhanced Multidisciplinary Thoracic Oncology Conference in a Regional Community Health Care System.

Introduction: We compared NSCLC treatment and survival within and outside a multidisciplinary model of care from a large community health care system.

Methods: We implemented a rigorously benchmarked "enhanced" Multidisciplinary Thoracic Oncology Conference (eMTOC) and used Tumor Registry data (2011-2017) to evaluate guideline-concordant care. Because eMTOC was located in metropolitan Memphis, we separated non-MTOC patient by metropolitan and regional location.

Missense variants in the N-terminal domain of the A isoform of FHF2/FGF13 cause an X-linked developmental and epileptic encephalopathy.

Fibroblast growth factor homologous factors (FHFs) are intracellular proteins which regulate voltage-gated sodium (Na) channels in the brain and other tissues. FHF dysfunction has been linked to neurological disorders including epilepsy. Here, we describe two sibling pairs and three unrelated males who presented in infancy with intractable focal seizures and severe developmental delay.

Rurality, Stage-Stratified Use of Treatment Modalities, and Survival of Non-small Cell Lung Cancer.

Background: To eliminate them, non-small cell lung cancer (NSCLC) care and outcome disparities need to be better understood.

Research Question: How does rurality interact with NSCLC care and outcome disparities?

Study Design And Methods: We examined guideline-concordant use of active treatment for NSCLC across five institutions in one community-based health care system spanning 44% of the Delta Regional Authority catchment area from 2011 to 2017. Institution- and patient-level rurality were based on Rural-Urban Commuting Area codes.

The performance evaluation of a urine malaria test (UMT) kit for the diagnosis of malaria in individuals with fever in south-east Nigeria: cross-sectional analytical study.

Background: Accurate rapid diagnosis is one of the important steps in the effort to reduce morbidity and mortality of malaria. Blood-specific malaria rapid diagnostic tests (RDTs) are currently in use but other body fluid specific diagnostic test kits are being developed. The aim of the present study was to evaluate the performance characteristics of a one-step Urine Malaria Test™ (UMT) dipstick in detecting Plasmodium falciparum HRP2, a poly-histidine antigen in urine of febrile patients for malaria diagnosis.

Fourier transform infrared for noninvasive optical diagnosis of oral, oropharyngeal, and laryngeal cancer.

The 5-year survival rate for advanced head and neck cancers is 50%. There is currently no noninvasive method or effective screening procedure available to diagnose head and neck cancer at the earliest stages when it is still highly curable. This study aims to show how Fourier transform infrared (FTIR) spectroscopy could be used as a sensitive, noninvasive, low cost technique to diagnose head and neck cancer at an earlier stage and, thus, increase the likelihood of survival.

Metabolic analyses elucidate non-trivial gene targets for amplifying dihydroartemisinic acid production in yeast.

Synthetic biology enables metabolic engineering of industrial microbes to synthesize value-added molecules. In this, a major challenge is the efficient redirection of carbon to the desired metabolic pathways. Pinpointing strategies toward this goal requires an in-depth investigation of the metabolic landscape of the organism, particularly primary metabolism, to identify precursor and cofactor availability for the target compound.

Engaging adolescent mothers in a longitudinal mental health intervention study: challenges and lessons learned.

Little is known about recruiting and retaining adolescent mothers in research studies. Investigators who study adolescent mothers have been guided by trial and error, clinical experience, qualitative inquiry, literature of special populations, or the advice of stakeholders. This paper describes the challenges and lessons learned in engaging adolescent mothers in a longitudinal community-based mental health intervention study.

Motorcycle helmets and rider safety: a legislative crisis.

Over the past four decades, motorcycle helmet laws within the United States have been in a state of flux and have been shaped by the conflicting influences of the federal government's initiatives to shape state policies and motorcycle advocates' persistent lobbying efforts. Examination of individual state experiences with motorcycle helmet legislation demonstrates that universal motorcycle helmet laws effectively promote helmet use compliance, reduce morbidity and mortality in motorcycle crashes, and lower the health care costs and associated societal burdens of these crash victims. Motorcycle advocates have challenged the implementation of these laws and directly influenced the weakening or frank repeal of these laws to negative consequence.

Two unusual anatomic variations create a diagnostic dilemma in distal ulnar nerve compression.

Diagnosis of peripheral neuropathies is based upon patterns of functional deficits and electrodiagnostic testing. However, anatomic variations can lead to confounding patterns of physical and electrodiagnostic findings. Authors present a case of ulnar nerve compression due to a rare combination of anatomic variations, aberrant branching pattern, and FCU insertion at the wrist, which posed a diagnostic and therapeutic dilemma.

[Cp*IrCl2]2-catalyzed indirect functionalization of alcohols: novel strategies for the synthesis of substituted indoles.

We report novel iridium(III)-catalyzed reactions that afford substituted indoles via the indirect functionalization of alcohols via C-3 selective alkylation of indoles with alcohols and a one-pot cascade strategy from amino- or nitro-phenyl ethyl alcohols, which incorporates oxidative cyclization and C-3 alkylation.

Sequential one-pot bimetallic Ir(III)/Pd(0) catalysed mono-/bis-alkylation and spirocyclisation processes of 1,3-dimethylbarbituric acid and allenes.

Microwave assisted indirect functionalization of alcohols with 1,3-dimethylbarbituric acid followed by spirocyclisation employing a sequential one-pot Ir(III)/Pd(0) catalysed process, involving the formation of three new C-C bonds, one spirocyclic ring and one di- or tri-substituted exocyclic alkene, is described.

Efficient solvent-free selective monoalkylation of arylacetonitriles with mono-, bis-, and tris-primary alcohols catalyzed by a Cp*Ir complex.

Our objectives were to develop catalytic atom-economic processes accessing and/or incorporating versatile functionality using aryl/heteroaryl acetonitriles as substrates. We report essentially solvent-free [Cp*IrCl2]2 catalyzed redox neutral processes whereby substituted acetonitriles react with primary alcohols to deliver monosubstituted aryl/heteroaryl acetonitriles in excellent yield. We further demonstrate that such processes can be achieved by conventional or microwave heating and that bis- and tris-primary alcohols are also processed efficiently.

Amination of ethers using chloramine-T hydrate and a copper(I) catalyst.

Amination of C-H bonds activated by ether oxygen atoms is facile with chloramine-T as nitrene source and copper(I) chloride in acetonitrile as catalyst. For cyclic ethers the hemiaminal products are generally stable and can be isolated pure. For acyclic ethers, the hemiaminal products, as expected, fragment with elimination of alcohol to yield imines.

Me-DuPHOS-Rh-Catalyzed Asymmetric Synthesis of the Pivotal Glutarate Intermediate for Candoxatril.

A greatly improved process has been developed for synthesis of the glutarate derivative 2, a key intermediate required for Pfizer's drug candoxatril. The cationic (R,R)-Me-DuPHOS-Rh catalyst was found to allow highly efficient and enantioselective hydrogenation of a unique carboxylate substrate (5) to afford the desired product in >99% ee and high yield (95%). The robust nature of the process was validated on a 12 kg reaction scale.

A dimensional classification of autism spectrum disorder by social communication domains.

Objective: To investigate whether "social communication" could be used to assess severity of symptoms in autism spectrum disorder. Social communication refers to the communication of cognitive and emotional information through facial expression, gesture, and prosody and through implicit understanding of pragmatics and of theory of mind.

Method: Subjects were evaluated by raters using the Autism Diagnostic interview-Revised and either the Autism Diagnostic Observation Schedule or the Pre-Linguistic Autism Diagnostic Observation Schedule.

Nocturnal serum melatonin profile in major depression in children and adolescents.

Background: In major depression, biological rhythm disturbances in sleep, appetite, and mood suggest dysregulation in neuroendocrine functions, possibly in the pineal gland. In this study, pineal gland function was examined by measuring nocturnal serum melatonin levels during both wakefulness and sleep in depressed children and adolescents.

Methods: Twenty-two youths aged 8 to 17 years primarily with major depression were compared with 19 controls.

The agonist selectivity of a mouse B1 bradykinin receptor differs from human and rabbit B1 receptors.

A genomic clone encoding the mouse B1 receptor was isolated by homology to the human B1 receptor cDNA. The deduced amino acid sequence of the mouse B1 receptor is 72% identical to the human B1 receptor and 73% identical to the rabbit B1 receptor. Ligand binding studies of the mouse B1 receptor expressed in COS cells indicate that it has the pharmacological properties associated with the B1 receptor subtype.

Expression cloning of a human B1 bradykinin receptor.

A cDNA clone encoding a human B1 bradykinin receptor was isolated from a human embryonic lung fibroblast cDNA library by expression cloning. The photoprotein aequorin was utilized as an indicator of the ability of the B1 receptor agonist [des-Arg10]kallidin to mediate Ca2+ mobilization in Xenopus laevis oocytes injected with RNA. A clone was isolated with a 1307-nucleotide insert which contains an open reading frame encoding a 353-amino acid protein with the characteristics of a G-protein-coupled receptor.