Communicative Coping Behavior Checklist: Observation of Persons With Dementia in the Home Environment

Purpose of the Study: Communication contributes to increased stress, mortality, and decreased quality of life (QOL) for persons with dementia (PWD) and caregivers. PWD use communicative coping behaviors (CCBs) to manage the demands of the disease. However, most assessments neither look for nor give credit to communication behaviors. This is the first study to examine CCBs in the home environment as measured by the Communicative Coping Behavior Checklist (CCBC). Design and Methods: This cross-sectional quantitative study included 26 dementia and 18 cognitively normal control dyads. Raters observed their partners\u27 CCBs at home, over several weeks and completed the CCBC. We analyzed the endorsement rates (how often behaviors were observed by a rater) of emotion and activity-focused CCBs in dementia and control dyads. Results: The primary outcome was rate of CCB endorsement. Secondary outcomes included dementia diagnosis, cognitive status, depressive mood, life satisfaction (SWL) and QOL. Dementia dyads endorsed 11 of 23 CCBs significantly more than control dyads. Action-focused CCBs (p \u3c .001) were more frequent than emotion-focused CCBs (p = .004) in dementia dyads. Specific CCBs such as humor correlated with higher caregiver QOL (p = .019) and PWD\u27s SWL (p = .003). Another CCB, general humor, correlated with lower PWD\u27s SWL (p = .024). Implications: This was the first study to examine CCBs in the home environment comparing dementia and control dyads. Higher endorsement rates of action-focused than emotion-focused CCBs were seen in dementia dyads. We conclude that attention to CCBs during treatment and care will improve QOL and SWL of PWD and caregivers

Why sexual health clinics are important in the 2020s

To make services more accessible, acceptable and affordable, sexual health service delivery models have embraced innovation, technology, outreach and decentralisation. In particular, some routine high-volume services, like asymptomatic testing for sexually transmitted infections (STIs), can be delivered in general practice, online or in non-clinical settings. On the surface, sexual health clinics, like hospitals or other primary care clinics, might appear to be operating on a model that has not changed significantly in recent times. However, globally sexual healthcare needs are rising both in volume and complexity, not all of which can be adequately met through decentralised care. Sexual health clinics themselves are the site of considerable innovation. The importance of sexual health clinics in the diagnosis and treatment of symptomatic STIs is likely to increase with the increasing burden of disease, the complexity of treatment guidelines and the emergence of new infections. Services essential to patient health such as immediate or complex clinical care, partner notification and safeguarding, and activities essential to the health system like research, training and supervision require expertise to be located where it can be accessed and maintained at reasonable cost. We do not know whether increasing some services outside existing models can safely compensate for reducing other services inside them

Longitudinal Pooled Deep Sequencing of the Plasmodium vivax K12 Kelch Gene in Cambodia Reveals a Lack of Selection by Artemisinin

The emergence of artemisinin resistance among Plasmodium falciparum in the Greater Mekong subregion threatens malaria control interventions and is associated with multiple unique mutations in K13 (PF3D7_1343700). The aim of this study was to survey Cambodian Plasmodium vivax for mutations in the K13 ortholog (K12, PVX_083080) that might similarly confer artemisinin resistance. Extracted DNA from Cambodian isolates collected between 2009 and 2012 was pooled by province and year and submitted for next-generation sequencing. Single-nucleotide polymorphisms (SNPs) were identified using a pile-up approach that detected minority SNPs. Among the 14 pools, we found six unique SNPs, including three nonsynonymous SNPs, across six codons in K12. However, none of the SNPs were orthologous to artemisinin resistance–conferring mutations in PF3D7_1343700, and nonsynonymous changes did not persist through time within populations. These results suggest a lack of selection in the P. vivax population in Cambodia due to artemisinin drug pressure

Web-based alcohol screening and brief intervention for university students: a randomized trial.

IMPORTANCE: Unhealthy alcohol use is a leading contributor to the global burden of disease, particularly among young people. Systematic reviews suggest efficacy of web-based alcohol screening and brief intervention and call for effectiveness trials in settings where it could be sustainably delivered. OBJECTIVE: To evaluate a national web-based alcohol screening and brief intervention program. DESIGN, SETTING, AND PARTICIPANTS: A multisite, double-blind, parallel-group, individually randomized trial was conducted at 7 New Zealand universities. In April and May of 2010, invitations containing hyperlinks to the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) screening test were e-mailed to 14,991 students aged 17 to 24 years. INTERVENTIONS: Participants who screened positive (AUDIT-C score ≥4) were randomized to undergo screening alone or to 10 minutes of assessment and feedback (including comparisons with medical guidelines and peer norms) on alcohol expenditure, peak blood alcohol concentration, alcohol dependence, and access to help and information. MAIN OUTCOMES AND MEASURES: A fully automated 5-month follow-up assessment was conducted that measured 6 primary outcomes: consumption per typical occasion, drinking frequency, volume of alcohol consumed, an academic problems score, and whether participants exceeded medical guidelines for acute harm (binge drinking) and chronic harm (heavy drinking). A Bonferroni-corrected significance threshold of .0083 was used to account for the 6 comparisons and a sensitivity analysis was used to assess possible attrition bias. RESULTS: Of 5135 students screened, 3422 scored 4 or greater and were randomized, and 83% were followed up. There was a significant effect on 1 of the 6 prespecified outcomes. Relative to control participants, those who received intervention consumed less alcohol per typical drinking occasion (median 4 drinks [interquartile range {IQR}, 2-8] vs 5 drinks [IQR 2-8]; rate ratio [RR], 0.93 [99.17% CI, 0.86-1.00]; P = .005) but not less often (RR, 0.95 [99.17% CI, 0.88-1.03]; P = .08) or less overall (RR, 0.95 [99.17% CI, 0.81-1.10]; P = .33). Academic problem scores were not lower (RR, 0.91 [99.17% CI, 0.76-1.08]; P = .14) and effects on the risks of binge drinking (odds ratio [OR], 0.84 [99.17% CI, 0.67-1.05]; P = .04) and heavy drinking (OR, 0.77 [99.17% CI, 0.56-1.05]; P = .03) were not significantly significant. In a sensitivity analysis accounting for attrition, the effect on alcohol per typical drinking occasion was no longer statistically significant. CONCLUSIONS AND RELEVANCE: A national web-based alcohol screening and brief intervention program produced no significant reductions in the frequency or overall volume of drinking or academic problems. There remains a possibility of a small reduction in the amount of alcohol consumed per typical drinking occasion. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12610000279022

Short interfering RNA induced generation and translation of stable 5' mRNA cleavage intermediates

Sequence-specific degradation of homologous mRNA is the main mechanism by which short-interfering RNAs (siRNAs) suppress gene expression. Generally, it is assumed that the mRNA fragments resulting from Ago2 cleavage are rapidly degraded, thus making the transcript translation-incompetent. However, the molecular mechanisms involved in the post-cleavage mRNA decay are not completely understood and the fate of cleavage intermediates has been poorly studied. Using specific siRNAs and short-hairpin RNAs (shRNAs) we show that the 5′ and 3′ mRNA cleavage fragments of human papilloma virus type 16 (HPV-16) E6/7 mRNA, over-expressed in cervical malignancies, are unevenly degraded. Intriguingly, the 5′ mRNA fragment was more abundant and displayed a greater stability than the corresponding 3′ mRNA fragment in RNAi-treated cells. Further analysis revealed that the 5′ mRNA fragment was polysome-associated, indicating its active translation, and this was further confirmed by using tagged E7 protein to show that C-terminally truncated proteins were produced in treated cells. Overall, our findings provide new insight into the degradation of siRNA-targeted transcripts and show that RNAi can alter protein expression in cells as a result of preferential stabilization and translation of the 5′ cleavage fragment. These results challenge the current model of siRNA-mediated RNAi and provide a significant step forward towards understanding non-canonical pathways of siRNA gene silencing

Generalized substitution of isoencoding codons shortens the duration of papillomavirus L1 protein expression in transiently gene-transfected keratinocytes due to cell differentiation

Recently we reported that gene codon composition determines differentiation-dependent expression of the PV L1 genes in mouse primary keratinocytes (KCs) in vitro and in vivo (Zhao et al. 2005, Mol. Cell Biol. 25:8643–8655). Here, we investigated whether generalized substitution of isoencoding codons affects the duration of expression of PV L1 genes in mouse and human KCs in day 1 culture transiently transfected with native (Nat) and codon modified (Mod) L1 genes. Following transient transfection, KC continuously transcribed both Nat and Mod PV L1 genes for at least 12 days, with the levels of L1 mRNAs from the Mod L1 genes significantly higher than those from the Nat L1 genes. However, continuous L1 protein expression at day 9 post-transfection was observed for both mouse and human KCs transfected with the Nat L1 genes only. Further, aa-tRNAs prepared from D8 KC cultures enhanced translation of two PV Nat L1 DNAs in RRL lysate and PV Nat L1 mRNAs in D0 cell-free lysate, whereas aa-tRNAs from D0 KCs enhanced translation of PV Mod L1 mRNAs in D8 cell-free lysate. It appears that aa-tRNAs in less-differentiated and differentiated KCs differentially match the PV Nat and Mod L1 mRNAs to regulate their translations in vitro

High-resolution mapping of losses and gains of Earth’s tidal wetlands

Tidal wetlands are expected to respond dynamically to global environmental change, but the extent to which wetland losses have been offset by gains remains poorly understood. We developed a global analysis of satellite data to simultaneously monitor change in three highly interconnected intertidal ecosystem types—tidal flats, tidal marshes, and mangroves—from 1999 to 2019. Globally, 13,700 square kilometers of tidal wetlands have been lost, but these have been substantially offset by gains of 9700 km2, leading to a net change of −4000 km2 over two decades. We found that 27% of these losses and gains were associated with direct human activities such as conversion to agriculture and restoration of lost wetlands. All other changes were attributed to indirect drivers, including the effects of coastal processes and climate change

Approaches for Studying Fish Production: Do River and Lake Researchers Have Different Perspectives? – Extended Abstract

Biased perspectives of fisheries researchers may hinder scientific progress and effective management if limiting factors controlling productivity go unrecognized. We investigated whether river and lake researchers used different approaches when studying salmonid production and whether any differences were ecologically supported. We assessed 564 peer‐reviewed papers published between 1966 and 2012 that studied salmonid production or surrogate variables (e.g., abundance, growth, biomass, population) and classified them into five major predictor variable categories: physical habitat, fertility (i.e., nutrients, bottom‐up), biotic, temperature, and pollution. The review demonstrated that river researchers primarily analyzed physical habitat (65% of studies) and lake researchers primarily analyzed fertility (45%) and biotic (51%) variables. Nevertheless, understudied variables were often statistically significant predictors of production for lake and river systems and, combined with other evidence, suggests that unjustified a priori assumptions may dictate the choice of independent variables studied. Broader consideration of potential limiting factors on fish production, greater research effort on understudied genera, and increased publication in broadly scoped journals would likely promote integration between lentic and lotic perspectives and improve fisheries management

Gene expression profiling of postnatal lung development in the marsupial gray short-tailed opossum (Monodelphis domestica) highlights conserved developmental pathways and specific characteristics during lung organogenesis

BACKGROUND: After a short gestation, marsupials give birth to immature neonates with lungs that are not fully developed and in early life the neonate partially relies on gas exchange through the skin. Therefore, significant lung development occurs after birth in marsupials in contrast to eutherian mammals such as humans and mice where lung development occurs predominantly in the embryo. To explore the mechanisms of marsupial lung development in comparison to eutherians, morphological and gene expression analysis were conducted in the gray short-tailed opossum (Monodelphis domestica). RESULTS: Postnatal lung development of Monodelphis involves three key stages of development: (i) transition from late canalicular to early saccular stages, (ii) saccular and (iii) alveolar stages, similar to developmental stages overlapping the embryonic and perinatal period in eutherians. Differentially expressed genes were identified and correlated with developmental stages. Functional categories included growth factors, extracellular matrix protein (ECMs), transcriptional factors and signalling pathways related to branching morphogenesis, alveologenesis and vascularisation. Comparison with published data on mice highlighted the conserved importance of extracellular matrix remodelling and signalling pathways such as Wnt, Notch, IGF, TGFβ, retinoic acid and angiopoietin. The comparison also revealed changes in the mammalian gene expression program associated with the initiation of alveologenesis and birth, pointing to subtle differences between the non-functional embryonic lung of the eutherian mouse and the partially functional developing lung of the marsupial Monodelphis neonates. The data also highlighted a subset of contractile proteins specifically expressed in Monodelphis during and after alveologenesis. CONCLUSION: The results provide insights into marsupial lung development and support the potential of the marsupial model of postnatal development towards better understanding of the evolution of the mammalian bronchioalveolar lung

Cavin-1/PTRF alters prostate cancer cell-derived extracellular vesicle content and internalization to attenuate extracellular vesicle-mediated osteoclastogenesis and osteoblast proliferation

Background: Tumour-derived extracellular vesicles (EVs) play a role in tumour progression; however, the spectrum of molecular mechanisms regulating EV secretion and cargo selection remain to be fully elucidated. We have reported that cavin-1 expression in prostate cancer PC3 cells reduced the abundance of a subset of EV proteins, concomitant with reduced xenograft tumour growth and metastasis. Methods: We examined the functional outcomes and mechanisms of cavin-1 expression on PC3-derived EVs (PC3-EVs). Results: PC3-EVs were internalized by osteoclast precursor RAW264.7 cells and primary human osteoblasts (hOBs) in vitro, stimulating osteoclastogenesis 37-fold and hOB proliferation 1.5-fold, respectively. Strikingly, EVs derived from cavin-1-expressing PC3 cells (cavin-1-PC3-EVs) failed to induce multinucleate osteoblasts or hOB proliferation. Cavin-1 was not detected in EVs, indicating an indirect mechanism of action. EV morphology, size and quantity were also not affected by cavin-1 expression, suggesting that cavin-1 modulated EV cargo recruitment rather than release. While cavin-1-EVs had no osteoclastogenic function, they were internalized by RAW264.7 cells but at a reduced efficiency compared to control EVs. EV surface proteins are required for internalization of PC3-EVs by RAW264.7 cells, as proteinase K treatment abolished uptake of both control and cavin-1-PC3-EVs. Removal of sialic acid modifications by neuraminidase treatment increased the amount of control PC3-EVs internalized by RAW264.7 cells, without affecting cavin-1-PC3-EVs. This suggests that cavin-1 expression altered the glycosylation modifications on PC3-EV surface. Finally, cavin-1 expression did not affect EV in vivo tissue targeting as both control and cavin-1-PC3-EVs were predominantly retained in the lung and bone 24 hours after injection into mice. Discussion: Taken together, our results reveal a novel pathway for EV cargo sorting, and highlight the potential of utilizing cavin-1-mediated pathways to attenuate metastatic prostate cancer