Novel flexible heteroarotinoid, SL-1-39, inhibits HER2-positive breast cancer cell proliferation by promoting lysosomal degradation of HER2.

SL-1-39 [1-(4-chloro-3-methylphenyl)-3-(4-nitrophenyl)thiourea] is a new flexible heteroarotinoid (Flex-Het) analog derived from the parental compound, SHetA2, previously shown to inhibit cell growth across multiple cancer types. The current study aims to determine growth inhibitory effects of SL-1-39 across the different subtypes of breast cancer cells and delineate its molecular mechanism. Our results demonstrate that while SL-1-39 blocks cell proliferation of all breast cancer subtypes tested, it has the highest efficacy against HER2+ breast cancer cells.

Embryonic origin and genetic basis of cave associated phenotypes in the isopod crustacean Asellus aquaticus.

Characteristics common to animals living in subterranean environments include the reduction or absence of eyes, lessened pigmentation and enhanced sensory systems. How these characteristics have evolved is poorly understood for the majority of cave dwelling species. In order to understand the evolution of these changes, this study uses an invertebrate model system, the freshwater isopod crustacean, Asellus aquaticus, to examine whether adult differences between cave and surface dwelling individuals first appear during embryonic development.

Effectiveness of a Modified Lifestyle-Integrated Functional Exercise Program in Residential Retirement Communities-A Pilot Study.

Abstract Aims: This study explored the effectiveness of a modified Lifestyle-integrated Functional Exercise program for increasing community-dwelling older adults' lower body strength and balance to decrease fall risk.

Methods: Purposive sampling of men and women aged 65 years and older, with or without a history of falls, living at retirement communities yielded 19 older adult participants, and 16 of the participants completed the 26-week integrated exercise program. The program consisted of five-group training sessions focused on how to integrate individualized exercises into everyday activities, followed by 20 weeks of independent practice with a booster session at Week 10 and two phone calls at Week 15 and Week 20.

Speciation Theory of Carcinogenesis Explains Karyotypic Individuality and Long Latencies of Cancers.

It has been known for over 100 years that cancers have individual karyotypes and arise only years to decades after initiating carcinogens. However, there is still no coherent theory to explain these definitive characteristics of cancer. The prevailing mutation theory holds that cancers are late because the primary cell must accumulate 3⁻8 causative mutations to become carcinogenic and that mutations, which induce chromosomal instability (CIN), generate the individual karyotypes of cancers.

Antimalarial proteasome inhibitor reveals collateral sensitivity from intersubunit interactions and fitness cost of resistance.

We describe noncovalent, reversible asparagine ethylenediamine (AsnEDA) inhibitors of the proteasome (Pf20S) β5 subunit that spare all active subunits of human constitutive and immuno-proteasomes. The compounds are active against erythrocytic, sexual, and liver-stage parasites, against parasites resistant to current antimalarials, and against strains from patients in Africa. The β5 inhibitors synergize with a β2 inhibitor in vitro and in mice and with artemisinin.

Common Genetic Basis of Eye and Pigment Loss in Two Distinct Cave Populations of the Isopod Crustacean Asellus aquaticus.

Repeated evolution of similar phenotypes is a widespread phenomenon found throughout the living world and it can proceed through the same or different genetic mechanisms. Cave animals with their convergent traits such as eye and pigment loss, as well as elongated appendages, are a striking example of the evolution of similar phenotypes. Yet, few cave species are amenable to genetic crossing and mapping techniques making it challenging to determine the genetic mechanisms causing their similar phenotypes.

Naturally Occurring Mentorship in a National Sample of First-Generation College Goers: A Promising Portal for Academic and Developmental Success.

Attending college is increasingly important to compete in this global world; however, young people whose parents did not attend college are significantly less likely to enroll in and finish college. Formal programs to support first-generation college goers are common, but not scalable to provide support to all young people who need it. Instead, mentoring that naturally occurs on these students' journeys into and out of college may be a more practical avenue for supporting their success.

Is cancer progression caused by gradual or simultaneous acquisitions of new chromosomes?

Background: Foulds defined, "Tumor progression (as a) permanent, irreversible qualitative change in one or more of its characters" (Cancer Res. 1954). Accordingly progressions, such as metastases and acquired drug-resistance, were since found to be subspecies of cancers with conserved and numerous new chromosomes.

Foraging Distance of the Argentine Ant in California Vineyards.

Argentine ants, Linepithema humile (Mayr) (Hymenoptera: Formicidae), form mutualisms with hemipteran pests in crop systems. In vineyards, they feed on honeydew produced by mealybugs and soft scales, which they tend and protect from natural enemies. Few options for controlling Argentine ants are available; one of the more effective approaches is to use liquid baits containing a low dose of an insecticide.

Engagement and outcomes in a digital Diabetes Prevention Program: 3-year update.

Objective: Translations of the Diabetes Prevention Program (DPP) have proliferated in recent years, with increasing expansion to digital formats. Although these DPP translations have consistently shown favorable clinical outcomes, long-term data for digital formats are limited. This study's objective was to examine clinical outcomes up to 3 years post-baseline and the relationship between program engagement and clinical outcomes in a digital DPP.

Changing Antimalarial Drug Sensitivities in Uganda.

Dihydroartemisinin-piperaquine (DP) has demonstrated excellent efficacy for the treatment and prevention of malaria in Uganda. However, resistance to both components of this regimen has emerged in Southeast Asia. The efficacy of artemether-lumefantrine, the first-line regimen to treat malaria in Uganda, has also been excellent, but continued pressure may select for parasites with decreased sensitivity to lumefantrine.

Novel flexible heteroarotinoid, SL-1-18, promotes ERα degradation to inhibit breast cancer cell growth.

SL-1-18 (1-(chrysen-6-yl)-3-(4-nitrophenyl)thiourea) is new flexible heteroarotinoid (Flex-Het) analog derived from the parent compound, SHetA2, and our previous study showed comparable activity to SHetA2 in terms of inhibiting ER+ breast cancer cell growth. This current study aims to determine the molecular mechanism underlying SL-1-18's effect on breast cancer cell growth. Our results indicate that SL-1-18 inhibits cell proliferation of ER+ breast cancer cells (MCF-7 and T-47D) by preventing cell cycle progression.

Formation of environmentally persistent free radicals (EPFRs) on ZnO at room temperature: Implications for the fundamental model of EPFR generation.

Environmentally persistent free radicals (EPFRs) have significant environmental and public health impacts. In this study, we demonstrate that EPFRs formed on ZnO nanoparticles provide two significant surprises. First, EPR spectroscopy shows that phenoxy radicals form readily on ZnO nanoparticles at room temperature, yielding EPR signals similar to those previously measured after 250°C exposures.

Evaluation of the Feasibility of a Home-Based TeleYoga Intervention in Participants with Both Chronic Obstructive Pulmonary Disease and Heart Failure.

Objective: Test the feasibility and clinical outcomes of a home-based videoconferencing yoga intervention in participants diagnosed with both Chronic Obstructive Pulmonary Disease (COPD) and heart failure (HF).

Background: Yoga has potential benefit for symptom relief in participants with COPD and with HF; however, functional impairment and transportation issues can hinder access to typical yoga classes.

Methods: A controlled, nonrandomized trial was conducted of an 8-week TeleYoga intervention versus an educational control (information leaflets mailed to participants with one weekly phone call).

A Variant PfCRT Isoform Can Contribute to Resistance to the First-Line Partner Drug Piperaquine.

Current efforts to reduce the global burden of malaria are threatened by the rapid spread throughout Asia of resistance to artemisinin-based combination therapies, which includes increasing rates of clinical failure with dihydroartemisinin plus piperaquine (PPQ) in Cambodia. Using zinc finger nuclease-based gene editing, we report that addition of the C101F mutation to the chloroquine (CQ) resistance-conferring PfCRT Dd2 isoform common to Asia can confer PPQ resistance to cultured parasites. Resistance was demonstrated as significantly higher PPQ concentrations causing 90% inhibition of parasite growth (IC) or 50% parasite killing (50% lethal dose [LD]).

Patient characteristics associated with false arrhythmia alarms in intensive care.

Introduction: A high rate of false arrhythmia alarms in the intensive care unit (ICU) leads to alarm fatigue, the condition of desensitization and potentially inappropriate silencing of alarms due to frequent invalid and nonactionable alarms, often referred to as false alarms.

Objective: The aim of this study was to identify patient characteristics, such as gender, age, body mass index, and diagnosis associated with frequent false arrhythmia alarms in the ICU.

Methods: This descriptive, observational study prospectively enrolled patients who were consecutively admitted to one of five adult ICUs (77 beds) at an urban medical center over a period of 31 days in 2013.

Spatiotemporal dynamics of the Southern California Asian citrus psyllid (Diaphorina citri) invasion.

Biological invasions are governed by spatial processes that tend to be distributed in non-random ways across landscapes. Characterizing the spatial and temporal heterogeneities of the introduction, establishment, and spread of non-native insect species is a key aspect of effectively managing their geographic expansion. The Asian citrus psyllid (Diaphorina citri), a vector of the bacterium associated with huanglongbing (HLB), poses a serious threat to commercial and residential citrus trees.

A potent antimalarial benzoxaborole targets a Plasmodium falciparum cleavage and polyadenylation specificity factor homologue.

Benzoxaboroles are effective against bacterial, fungal and protozoan pathogens. We report potent activity of the benzoxaborole AN3661 against Plasmodium falciparum laboratory-adapted strains (mean IC 32 nM), Ugandan field isolates (mean ex vivo IC 64 nM), and murine P. berghei and P.

Sleep disruption and duration in late pregnancy is associated with excess gestational weight gain among overweight and obese women.

Background: Poor sleep during pregnancy has been associated with poorer birth outcomes. High body mass index (BMI) is often associated with poor sleep, but little is known about the relationship between gestational weight gain and sleep in late pregnancy. The purpose of this study was to evaluate the relationships of both gestational weight gain and pre-pregnancy BMI to objective and subjective measures of sleep during late pregnancy.

Inherent variability of cancer-specific aneuploidy generates metastases.

Background: The genetic basis of metastasis is still unclear because metastases carry individual karyotypes and phenotypes, rather than consistent mutations, and are rare compared to conventional mutation. There is however correlative evidence that metastasis depends on cancer-specific aneuploidy, and that metastases are karyotypically related to parental cancers. Accordingly we propose that metastasis is a speciation event.

Geographically-weighted regression of knowledge and behaviour determinants to anti-malarial recommending and dispensing practice among medicine retailers in western Kenya: capacitating targeted interventions.

Background: Most patients with malaria seek treatment first in retail drug shops. Myriad studies have examined retailer behaviours and characteristics to understand the determinants to these behaviours. Geospatial methods are helpful in discovering if geographic location plays a role in the relationship between determinants and outcomes.

Identification of the First Marine-Derived Opioid Receptor "Balanced" Agonist with a Signaling Profile That Resembles the Endorphins.

Opioid therapeutics are excellent analgesics, whose utility is compromised by dependence. Morphine (1) and its clinically relevant derivatives such as OxyContin (2), Vicodin (3), and Dilaudid (4) are "biased" agonists at the μ opioid receptor (OR), wherein they engage G protein signaling but poorly engage β-arrestin and the endocytic machinery. In contrast, endorphins, the endogenous peptide agonists for ORs, are potent analgesics, show reduced liability for tolerance and dependence, and engage both G protein and β-arrestin pathways as "balanced" agonists.

Cultural group selection follows Darwin's classic syllogism for the operation of selection.

The main objective of our target article was to sketch the empirical case for the importance of selection at the level of groups on cultural variation. Such variation is massive in humans, but modest or absent in other species. Group selection processes acting on this variation is a framework for developing explanations of the unusual level of cooperation between non-relatives found in our species.

A Randomized, Double-Blind, Placebo-Controlled Trial of Low-Dose Sertraline in Young Children With Fragile X Syndrome.

Objective: Observational studies and anecdotal reports suggest that sertraline, a selective serotonin reuptake inhibitor, may improve language development in young children with fragile X syndrome (FXS).

Methods: The authors evaluated the efficacy of 6 months of treatment with low-dose sertraline in a randomized, double-blind, placebo-controlled trial in 52 children with FXS aged 2 to 6 years.

Results: Eighty-one subjects were screened for eligibility, and 57 were randomized to sertraline (27) or placebo (30).

The Normal Electrocardiogram: Resting 12-Lead and Electrocardiogram Monitoring in the Hospital.

The electrocardiogram (ECG) is a well-established diagnostic tool extensively used in clinical settings. Knowledge of cardiac rhythm and mastery of cardiac waveform interpretation are fundamental for intensive care nurses. Recognition of the normal findings for the 12-lead ECG and understanding the significance of changes from baseline in continuous cardiac monitoring are essential steps toward ensuring safe patient care.