PI3Kγ inhibition circumvents inflammation and vascular leak in SARS-CoV-2 and other infections.

Virulent infectious agents such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and methicillin-resistant Staphylococcus aureus (MRSA) induce tissue damage that recruits neutrophils, monocyte, and macrophages, leading to T cell exhaustion, fibrosis, vascular leak, epithelial cell depletion, and fatal organ damage. Neutrophils, monocytes, and macrophages recruited to pathogen-infected lungs, including SARS-CoV-2-infected lungs, express phosphatidylinositol 3-kinase gamma (PI3Kγ), a signaling protein that coordinates both granulocyte and monocyte trafficking to diseased tissues and immune-suppressive, profibrotic transcription in myeloid cells. PI3Kγ deletion and inhibition with the clinical PI3Kγ inhibitor eganelisib promoted survival in models of infectious diseases, including SARS-CoV-2 and MRSA, by suppressing inflammation, vascular leak, organ damage, and cytokine storm. These results demonstrate essential roles for PI3Kγ in inflammatory lung disease and support the potential use of PI3Kγ inhibitors to suppress inflammation in severe infectious diseases.

Evaluation of Bioactive Compounds and Antioxidant Activity in 51 Minor Tropical Fruits of Ecuador.

Less common tropical fruits have been the subject of little research, leaving a vast field to be explored. In this context, a comprehensive study was carried out on the bioactive compounds and antioxidant capacity of 51 non-traditional fruits consumed in Ecuador. Vitamin C, organic acids, carotenoids, and phenolic compounds were evaluated using microextraction and rapid resolution liquid chromatography (RRLC) techniques, while antioxidant activity was measured using microplate readings. The results showed high levels of vitamin C (768.2 mg/100 g DW) in Dovyalis hebecarpa, total organic acids (37.2 g/100 g DW) in Passiflora tripartita, carotenoids (487.0 mg/100 g DW) in Momordica charantia, phenolic compounds (535.4 mg/g DW) in Nephelium lappaceum, Pourouma cecropiifolia (161.4 µmol TE/g DW) and Morus alba (80.5 µmol AAE/g DW) in antioxidant activity. Effective extraction of carotenoids was also observed using a mixture of methanol: acetone: dichloromethane (1:1:2) with an extraction time of 2 min, while an 80% solution of 0.1% acidified methanol with hydrochloric acid with an extraction time of 3 min was highly effective for phenolics in fruit. These results provide a valuable basis for optimising future extraction processes of bioactive compounds from non-traditional fruits, with significant implications for their potential use in various nutritional and pharmaceutical contexts.

Effects of six pyrimidine analogs on the growth of Tetrahymena thermophila and their implications in pyrimidine metabolism.

Tetrahymena are ciliated protists that have been used to study the effects of toxic chemicals, including anticancer drugs. In this study, we tested the inhibitory effects of six pyrimidine analogs (5-fluorouracil, floxuridine, 5'-deoxy-5-fluorouridine, 5-fluorouridine, gemcitabine, and cytarabine) on wild-type CU428 and conditional mutant NP1 Tetrahymena thermophila at room temperature and the restrictive temperature (37°C) where NP1 does not form the oral apparatus. We found that phagocytosis was not required for pyrimidine analog entry and that all tested pyrimidine analogs inhibited growth except for cytarabine. IC50 values did not significantly differ between CU428 and NP1 for the same analog at either room temperature or 37°C. To investigate the mechanism of inhibition, we used two pyrimidine bases (uracil and thymine) and three nucleosides (uridine, thymidine, and 5-methyluridine) to determine whether the inhibitory effects from the pyrimidine analogs were reversible. We found that the inhibitory effects from 5-fluorouracil could be reversed by uracil and thymine, from floxuridine could be reversed by thymidine, and from 5'-deoxy-5-fluorouridine could be reversed by uracil. None of the tested nucleobases or nucleosides could reverse the inhibitory effects of gemcitabine or 5-fluorouridine. Our results suggest that the five pyrimidine analogs act on different sites to inhibit T. thermophila growth and that nucleobases and nucleosides are metabolized differently in Tetrahymena.

Is low-dose naltrexone effective in chronic pain management?

YES. Low-dose naltrexone is as effective as amitriptyline in the treatment of painful diabetic neuropathy and has a superior safety profile (strength of recommendation [SOR], B; single randomized controlled trial [RCT]). Low-dose naltrexone significantly reduced pain by 32% in inflammatory conditions and 44% in neuropathic conditions (SOR, B; single retrospective cohort study). Doses as low as 5.4 mg were found to reduce pain in 95% of patients with fibromyalgia (SOR, B; single prospective dose-response study).

Trust in government actors and COVID-19 vaccination uptake among Hispanics and Latinos in the U.S.

Although the federal government has made official recommendations to the public advocating vaccinations against COVID-19 various communities have decided against doing so. In this regard, various studies have indicated that trust in government to provide accurate information about vaccines during a pandemic are related to whether people get vaccinated. Various studies have investigated factors contributing to vaccine decision-making, but none specifically focus on Hispanic and Latinos in the United States. This study identifies factors associated with COVID-19 vaccination among Hispanics and Latinos using a nation-wide, phone-based survey. Using data generated by the Kaiser Family Foundation's COVID-19 Vaccine Monitor, collected in June 2021, a logistic regression on the decision to get vaccinated, trust in various governmental actors, in addition to demographic variables such as age, race, employment status, parental status, employment status, and income are observed to be significant in Hispanics' and Latinos' decision to be vaccinated against COVID-19. As a byproduct of these findings, recommendations for future research are provided that relate to expanding our understanding of these factors among different ethnicities of Latinos.

Impact of Isolation During the COVID-19 Pandemic on the Patient Burden of Parkinson's Disease: A PMD Alliance Survey.

Purpose: As the COVID-19 pandemic resulted in social restrictions around the globe, this cross-sectional survey aimed to assess the impact of social isolation on self- or proxy-reported symptoms of Parkinson's disease (PD) during the pandemic. Patients and Methods: The survey was distributed among 7109 subscribers of the Parkinson and Movement Disorders Alliance (PMD Alliance) News and Information list and was open only to people with PD (PwP) and care partners (CP, defined as main caregivers of PwP and serving as proxy respondents). No attempt was made to identify PwP and CP pairs. The survey was distributed online using Survey Monkey between 01/06/2021 and 02/27/2021. Respondents were grouped by level of social support from outside of their household during the pandemic (decreased or maintained [ie, the same as pre-pandemic or increased]). Results: Of 7109 invited participants, 718 responded to the survey (response rate 10.1%). PwP (self-reports) accounted for 70.6% of respondents and CP (proxy reports) for 29.4%. Decreased social support from outside of the household during the COVID-19 pandemic (58.5% of all responses) was significantly associated with increases in sadness/depression and anxiety, compared with maintained levels of social support (p < 0.0001 for both comparisons). It was also associated with increased burden of several non-motor (decline in memory, problem solving, or communication, p = 0.0009; new or worsening confusion, p < 0.0001; new or worsening delusions, p = 0.018) and motor PD symptoms. Conclusion: Decline in social support from outside of the household during the COVID-19 pandemic showed a statistically significant and negative association with the burden of mood and non-motor symptoms of PD. These results call for increased vigilance towards non-motor symptoms in PwP experiencing social isolation and highlight the need for stronger provider focus on encouraging PwP and their CPs to build and maintain social connections and engagements.

The likelihood of having a household emergency plan: understanding factors in the US context.

Individual household emergency planning is the most fundamental and can be the least expensive way to prepare for natural disasters. However, despite government and nonprofit educational campaigns, many Americans still do not have a household plan. Using a national sample of Americans, this research observes factors that influence people's likelihood of developing a household emergency plan. Based on the analysis, people's efficacy in preparedness activities, previous exposure to disasters and preparedness information positively influence the likelihood that someone will have developed a household emergency plan. Alternatively, demographic variables such as being Hispanic/Latino, identifying as Asian, and being a renter decrease the likelihood that someone will have developed a plan in the American context.  But, the reason for these negative relationships are unclear. Subsequent to the analysis, recommendations for future research are provided to better understand observed relationships.

Returning to normalcy in the short term: a preliminary examination of recovery from Hurricane Harvey among individuals with home damage.

This study focuses on coastal counties in Texas, United States, affected by Hurricane Harvey in 2017 to gauge the influence of individual and contextual characteristics on people's ability to return to normalcy in the short term. Data from a survey conducted by the Kaiser Family Foundation and the Episcopal Health Foundation between October and November 2017 were utilised in the analysis. The paper observes, based on the results of an ordered logistic regression, and contrary to previous work, that age, gender, levels of poverty, and social capital are not significant predictors of a return to normalcy. However, indicators such as whether a person evacuated, if he/she identified as Hispanic/Latino, the extent of damage sustained to one's home, and if one's automobile was damaged or destroyed are shown to affect recovery. A discussion of the potential reasons for these findings is provided as a means of informing future research on disaster recovery.

Somatic Mutations and Ancestry Markers in Hispanic Lung Cancer Patients.

INTRODUCTION: To address the lack of genomic data from Hispanic/Latino (H/L) patients with lung cancer, the Latino Lung Cancer Registry was established to collect patient data and biospecimens from H/L patients. METHODS: This retrospective observational study examined lung cancer tumor samples from 163 H/L patients, and tumor-derived DNA was subjected to targeted-exome sequencing (>1000 genes, including EGFR, KRAS, serine/threonine kinase 11 gene [STK11], and tumor protein p53 gene [TP53]) and ancestry analysis. Mutation frequencies in this H/L cohort were compared with those in a similar cohort of non-Hispanic white (NHW) patients and correlated with ancestry, sex, smoking status, and tumor histologic type. RESULTS: Of the adenocarcinomas in the H/L cohort (n = 120), 31% had EGFR mutations, versus 17% in the NHW control group (p < 0.001). KRAS (20% versus 38% [p = 0.002]) and STK11 (8% versus 16% [p = 0.065]) mutations occurred at lower frequency, and mutations in TP53 occurred at similar frequency (46% versus 40% [p = 0.355]) in H/L and NHW patients, respectively. Within the Hispanic cohort, ancestry influenced the rate of TP53 mutations (p = 0.009) and may have influenced the rate of EGFR, KRAS, and STK11 mutations. CONCLUSIONS: Driver mutations in H/L patients with lung adenocarcinoma differ in frequency from those in NHW patients associated with their indigenous American ancestry. The spectrum of driver mutations needs to be further assessed in the H/L population.

Effects of repetition on age differences in associative recognition.

The study reported here examined the effect of repetition on age differences in associative recognition using a paradigm designed to encourage recollection at test. Young and older adults studied lists of unrelated word pairs presented one, two, four, or eight times. Test lists contained old (intact) pairs, pairs consisting of old words that had been studied with other partners (rearranged lures), and pairs consisting of two unstudied words (new lures). Participants gave old/new responses and then indicated whether their responses were based on details that they could recollect or on familiarity. Older adults exhibited an ironic effect of repetition-an increase in false alarms on rearranged lures with more study opportunities-whereas young adults did not. Older adults also claimed to recall details of the study episode for rearranged lures whose constituent words were presented more frequently, but this was not true for young adults. Although both young and older adults said that they based correct rejections of rearranged lures on memory for details of the study episode, this effect was stronger for young adults. The observed age differences are consistent with older adults having reduced use of recollection in associative recognition tasks.

Early2 factor (E2F) deregulation is a prognostic and predictive biomarker in lung adenocarcinoma.

Clinicians routinely prescribe adjuvant chemotherapy (ACT) for resected non-small cell lung cancer patients. However, ACT only improves five-year disease-free survival in stage I-III non-small cell lung cancer by 5-15%, with most patients deriving no benefit. Herein, deregulation of the E2F pathway was explored as a biomarker in lung adenocarcinoma patients. An E2F pathway scoring system, based on 74 E2F-regulated genes, was trained for RNA from two platforms: fresh-frozen (FF) or formalin-fixed paraffin-embedded (FFPE) tissues. The E2F score was tested as a prognostic biomarker in five FF-based cohorts and two FFPE-based cohorts. The E2F score was tested as a predictive biomarker in two randomized clinical trials; JBR10 and the NATCH (Neo-Adjuvant Taxol-Carboplatin Hope) trial. The E2F score was prognostic in untreated patients in all seven datasets examined (p < 0.05). Stage-specific analysis of combined cohorts demonstrated that the E2F score was prognostic in stage I patients (p = 0.0495 to <0.001; hazard ratio, HR, =2.04- 2.22) with a similar trend in other stages. The E2F score was strongly predictive in stage II patients from the two combined randomized clinical trials with a significant differential treatment effect (p = 0.015). Specifically, ACT improved survival in stage II patients with high E2F (p = 0.01; HR= 0.21). The 5-year survival increased from 18% to 81%. In contrast, in patients with low E2F, 5-year survival was 57% in untreated patients and 41% in ACT-treated patients with a HR of 1.55 (p = 0.47). In summary, the E2F score provides valuable prognostic information for Stage I and predictive information for Stage II lung adenocarcinoma patients and should be further explored as a decision support tool for their treatment.

Disaster relief volunteerism: Evaluating cities' planning for the usage and management of spontaneous volunteers.

This exploratory study sought to observe the perceptions, usage, and planned management of spontaneous volunteers in disaster planning and response within various urban environments. The authors discuss the perceptions of spontaneous volunteerism in America, specifically the challenges of using spontaneous volunteers in disaster response activities. A content analysis of the 50 largest cities in the US Office of Emergency Management Web sites and a survey instrument administered to emergency managers in these 50 cities were used to explore various questions raised throughout the discussion of the literature. The authors found significant discrepancies between what is stated in the disaster plans of cities and what emergency managers claim is covered in their plans. Of the managers surveyed, only a handful mention spontaneous volunteers in their plans at all, and even fewer cities discuss them extensively. In addition, stated perceptions of the value of spontaneous volunteers may impact both how we plan for them and the value they provide.