Cardiovascular disease in the Peruvian Andes: local perceptions, barriers, and paths to preventing chronic diseases in the Cajamarca region

Objectives: Public health interventions can be improved by understanding peoples' explanatory models of disease. We explore awareness and perceptions of cardiovascular diseases (CVD) and options for preventative actions in young adults living in rural Andean communities. Methods: We used convenience sampling to select 46 men and women from communities in Cajamarca (Peru). Subjects participated in eight focus groups where they discussed their understanding and perceived causes of CVD as well as barriers and pathways to healthy lifestyles. Results: Fresh foods, physical activity, unpleasant emotions, and healthcare access were cited as important determinants of healthy lifestyles. Barriers to healthy diets included lacking nutritional knowledge, fluctuating food prices, and limited access to foodstuffs. Women felt particularly vulnerable to CVD and identified gendered barriers to manage stress and engage in sports. Low health literacy, poor doctor-patient relationships, and long distances prevented participants from fully accessing healthcare. Conclusion: CVD prevention interventions should consider local knowledge of these diseases and of healthy lifestyles, and harness ongoing programmes that have successfully promoted good nutrition in children and pregnant women. In concert with public-private parterships, governments should include disease prevention interventions for the entire family

Water Insecurity, Self-reported Physical Health, and Objective Measures of Biological Health in the Peruvian Amazon

ObjectivesThis study examines the associations between water insecurity, self-reported physical health, and objective measures of biological health among 225 Awajún adults (107 women; 118 men) living in the Peruvian Amazon, a “water-abundant” region.MethodsA survey, which included multiple measures of self-reported physical health, and objective measures of biological health such as blood pressure and nutritional and immune biomarkers.ResultsGreater water insecurity was associated with multiple measures of self-reported physical health, including higher incidence of reported diarrhea, nausea, back pain, headaches, chest pain, fatigue, dizziness, overall poor perceived health, and “being sick.” These symptoms align with the physical strain associated with water acquisition and with drinking contaminated water. A significant association between higher water insecurity and lower systolic blood pressure emerged, which may be linked to dehydration. None of the other biomarkers, including those for nutrition, infection, and stress were significantly associated with water insecurity scores.ConclusionsThese analyses add to the growing body of research examining the associations between water insecurity and health. Biocultural anthropologists are well-positioned to continue probing these connections. Future research will investigate relationships between measures of water insecurity and biomarkers for gastrointestinal infection and inflammation in water-scarce and water-abundant contexts

Tapinarof in the treatment of psoriasis: A review of the unique mechanism of action of a novel therapeutic AhR modulating agent (TAMA)

Tapinarof, a novel, first-in-class small-molecule topical therapeutic aryl hydrocarbon receptor (AhR) modulating agent (TAMA), is in clinical development for the treatment of psoriasis and atopic dermatitis. The efficacy of tapinarof in psoriasis is attributed to its specific binding and activation of AhR, a ligand-dependent transcription factor, leading to the downregulation of pro-inflammatory cytokines, including interleukin-17, and regulation of skin barrier protein expression to promote skin barrier normalization. AhR signaling regulates gene expression in immune cells and skin cells, and has critical roles in the regulation of skin homeostasis. Tapinarof-mediated AhR signaling underlies the mechanistic basis for the significant efficacy and acceptable tolerability observed in early phase clinical trials of tapinarof cream in the treatment of psoriasis

Early anthropoid femora reveal divergent adaptive trajectories in catarrhine hind-limb evolution

The divergence of crown catarrhines—i.e., the split of cercopithecoids (Old World monkeys) from hominoids (apes and humans)—is a poorly understood phase in our shared evolutionary history with other primates. The two groups differ in the anatomy of the hip joint, a pattern that has been linked to their locomotor strategies: relatively restricted motion in cercopithecoids vs. more eclectic movements in hominoids. Here we take advantage of the first well-preserved proximal femur of the early Oligocene stem catarrhine Aegyptopithecus to investigate the evolution of this anatomical region using 3D morphometric and phylogenetically-informed evolutionary analyses. Our analyses reveal that cercopithecoids and hominoids have undergone divergent evolutionary transformations of the proximal femur from a similar ancestral morphology that is not seen in any living anthropoid, but is preserved in Aegyptopithecus, stem platyrrhines, and stem cercopithecoids. These results highlight the relevance of fossil evidence for illuminating key adaptive shifts in primate evolution

The long noncoding RNA, treRNA, decreases DNA damage and is associated with poor response to chemotherapy in chronic lymphocytic leukemia.

The study of long noncoding RNAs (lncRNAs) is an emerging area of cancer research, in part due to their ability to serve as disease biomarkers. However, few studies have investigated lncRNAs in chronic lymphocytic leukemia (CLL). We have identified one particular lncRNA, treRNA, which is overexpressed in CLL B-cells. We measured transcript expression in 144 CLL patient samples and separated samples into high or low expression of treRNA relative to the overall median. We found that high expression of treRNA is significantly associated with shorter time to treatment. High treRNA also correlates with poor prognostic indicators such as unmutated IGHV and high ZAP70 protein expression. We validated these initial findings in samples collected in a clinical trial comparing the nucleoside analog fludarabine alone or in combination with the alkylating agent cyclophosphamide in untreated CLL samples collected prior to starting therapy (E2997). High expression of treRNA was independently prognostic for shorter progression free survival in patients receiving fludarabine plus cyclophosphamide. Given these results, in order to study the role of treRNA in DNA damage response we generated a model cell line system where treRNA was over-expressed in the human B-CLL cell line OSU-CLL. Relative to the vector control line, there was less cell death in OSU-CLL over-expressing treRNA after exposure to fludarabine and mafosfamide, due in part to a reduction in DNA damage. Therefore, we suggest that treRNA is a novel biomarker in CLL associated with aggressive disease and poor response to chemotherapy through enhanced protection against cytotoxic mediated DNA damage

Permeability changes and effect of chemotherapy in brain adjacent to tumor in an experimental model of metastatic brain tumor from breast cancer

Abstract Background: Brain tumor vasculature can be significantly compromised and leakier than that of normal brain blood vessels. Little is known if there are vascular permeability alterations in the brain adjacent to tumor (BAT). Changes in BAT permeability may also lead to increased drug permeation in the BAT, which may exert toxicity on cells of the central nervous system. Herein, we studied permeation changes in BAT using quantitative fluorescent microscopy and autoradiography, while the effect of chemotherapy within the BAT region was determined by staining for activated astrocytes. Methods: Human metastatic breast cancer cells (MDA-MB-231Br) were injected into left ventricle of female NuNu mice. Metastases were allowed to grow for 28 days, after which animals were injected fluorescent tracers Texas Red (625 Da) or Texas Red dextran (3 kDa) or a chemotherapeutic agent 14C-paclitaxel. The accumulation of tracers and 14C-paclitaxel in BAT were determined by using quantitative fluorescent microscopy and autoradiography respectively. The effect of chemotherapy in BAT was determined by staining for activated astrocytes. Results: The mean permeability of texas Red (625 Da) within BAT region increased 1.0 to 2.5-fold when compared to normal brain, whereas, Texas Red dextran (3 kDa) demonstrated mean permeability increase ranging from 1.0 to 1.8-fold compared to normal brain. The Kin values in the BAT for both Texas Red (625 Da) and Texas Red dextran (3 kDa) were found to be 4.32 ± 0.2 × 105 mL/s/g and 1.6 ± 1.4 × 105 mL/s/g respectively and found to be significantly higher than the normal brain. We also found that there is significant increase in accumulation of 14C-Paclitaxel in BAT compared to the normal brain. We also observed animals treated with chemotherapy (paclitaxel (10 mg/kg), erubilin (1.5 mg/kg) and docetaxel (10 mg/kg)) showed activated astrocytes in BAT. Conclusions: Our data showed increased permeation of fluorescent tracers and 14C-paclitaxel in the BAT. This increased permeation lead to elevated levels of activated astrocytes in BAT region in the animals treated with chemotherapy

Towards the development of an EIT-based stretchable sensor for multi-touch industrial human-computer interaction systems

In human-computer interaction studies, an interaction is often considered as a kind of information or discrete internal states of an individual that can be transmitted in a loss-free manner from people to computing interfaces (or robotic interfaces) and vice-versa. This project aims to investigate processes capable of communicating and cooperating by adjusting their schedules to match the evolving execution circumstances, in a way that maximise the quality of their joint activities. By enabling human-computer interactions, the process will emerge as a framework based on the concept of expectancy, demand, and need of the human and computer together, for understanding the interplay between people and computers. The idea of this work is to utilise touch feedback from humans as a channel for communication thanks to an artificial sensitive skin made of a thin, flexible, and stretchable material acting as transducer. As a proof of concept, we demonstrate that the first prototype of our artificial sensitive skin can detect surface contacts and show their locations with an image reconstructing the internal electrical conductivity of the sensor

Tapinarof Cream 1% Once Daily for the Treatment of Plaque Psoriasis: Case Photography of Clinical Outcomes from Three Phase 3 Trials

Tapinarof cream 1% (VTAMA(®); Dermavant Sciences, Inc.) is a non-steroidal, topical, aryl hydrocarbon receptor agonist approved by the US Food and Drug Administration (FDA) to treat plaque psoriasis in adults and under investigation for the treatment of psoriasis in children down to 2 years of age, and for atopic dermatitis in adults and children down to 2 years of age. The PSOARING phase 3 clinical trial program evaluated tapinarof cream 1% once daily (QD) in adults with mild to severe plaque psoriasis for up to 52 weeks (NCT03956355, NCT03983980, NCT04053387). Here we present case photography documenting outcomes in the PSOARING trials. Cases illustrate various outcomes across different body areas, including responses meeting the formal FDA-mandated regulatory endpoint of a Physician Global Assessment (PGA) score of 0 (clear) or 1 (almost clear) and a decrease of at least 2 points from baseline at week 12, meaningful clinical improvement not meeting this formal endpoint, patient-reported outcomes, and pre-specified adverse events of special interest (AESIs). Tapinarof cream 1% QD demonstrated rapid and highly statistically significant efficacy, with improvements in disease activity and quality of life. In addition, a high rate (40.9%; n = 312/763) of complete disease clearance (PGA = 0) was achieved, and improvements exceeding National Psoriasis Foundation treatment goals were demonstrated. After first achieving complete disease clearance (PGA = 0), patients treated with tapinarof experienced an approximately 4-month remittive effect off therapy. Incidence and severity of folliculitis and contact dermatitis AESIs were generally mild or moderate, localized to the site of application, and associated with low discontinuation rates. Medical images are of importance in trials of dermatologic therapies to inform clinical decision-making and enhance patient assessment. Tapinarof cream 1% QD is efficacious and well tolerated in patients with mild to severe plaque psoriasis, with clinically relevant improvements seen early in the course of treatment. Clinicaltrials.gov numbers: NCT03956355, NCT03983980, NCT04053387