Design, synthesis and evaluation of a tripodal receptor for phosphatidylinositol phosphates

Phosphatidylinositol phosphates (PIPs) are membrane phospholipids that play crucial roles in a wide range of cellular processes. Their function is dictated by the number and positions of the phosphate groups in the inositol ring (with seven different PIPs being active in the cell). Therefore, there is significant interest in developing small-molecule receptors that can bind selectively to these species and in doing so affect their cellular function or be the basis for molecular probes. However, to date there are very few examples of such molecular receptors. Towards this aim, herein we report a novel tripodal molecule that acts as receptor for mono- and bis-phosphorylated PIPs in a cell free environment. To assess their affinity to PIPs we have developed a new cell free assay based on the ability of the receptor to prevent alkaline phosphatase from hydrolysing these substrates. The new receptor displays selectivity towards two out of the seven PIPs, namely PI(3)P and PI(3,4)P2. To rationalise these results, a DFT computational study was performed which corroborated the experimental results and provided insight into the host–guest binding mode

Breastfeeding media coverage and beliefs during the COVID-19 pandemic in Mexico: implications for breastfeeding equity

Background: Because breastfeeding offers short- and long- term health benefits to mothers and children, breastfeeding promotion and support is a public health priority. Evidence shows that SARS-CoV-2 is not likely to be transmitted via breastmilk. Moreover, antibodies against SARS-CoV-2 are thought to be contained in breastmilk of mothers with history of COVID-19 infection or vaccination. WHO recommends direct breastfeeding as the preferred infant feeding option during the COVID-19 pandemic, even among women with COVID-19; but conflicting practices have been adopted, which could widen existing inequities in breastfeeding. This study aims to describe how information about breastfeeding was communicated in Mexican media during the pandemic and assess Mexican adults’ beliefs regarding breastfeeding among mothers infected with COVID-19. Methods: We conducted a retrospective content analysis of media coverage on breastfeeding in Mexico between March 1 and September 24, 2020, excluding advertisements. For the content analysis, we performed both a sentiment analysis and an analysis based on strengths, weaknesses, opportunities, and threats (SWOT) for breastfeeding promotion. Additionally, we conducted a descriptive analysis of nationally representative data on adults’ beliefs about breastfeeding from the July 2020 round of the ENCOVID-19 survey in Mexico and stratified the results by gender, age, and socioeconomic status. Results: A total of 1014 publications on breastfeeding were identified on the internet and television and in newspapers and magazines. Most information was published during World Breastfeeding Week, celebrated in August. The sentiment analysis showed that 57.2% of all information was classified as positive. The SWOT analysis indicated that most information focused on current actions, messages, policies, or programs that enable breastfeeding (i.e., strengths) or those not currently in place but that may enable breastfeeding (i.e., opportunities) for breastfeeding promotion. However, ENCOVID-19 survey results showed that 67.3% of adults living in households with children under 3 years of age believe that mothers with COVID-19 should not breastfeed, and 19.8% do not know whether these mothers should breastfeed. These beliefs showed differences both by gender and by socioeconomic status. Conclusions: While the Mexican government endorsed the recommendation on breastfeeding during the COVID-19 pandemic, communication was sporadic, inconstant and unequal across types of media. There was a widespread notion that mothers with COVID-19 should not breastfeed and due to differences on beliefs by socioeconomic status, health inequities could be exacerbated by increasing the risk of poorer breastfeeding practices and preventing vulnerable groups from reaping the short and long-term benefits of breastfeeding

Identification and characterisation of G-quadruplex DNA-forming sequences in the Pseudomonas aeruginosa genome

A number of Gram-negative bacteria such as Pseudomonas aeruginosa are becoming resistant to front-line antibiotics. Consequently, there is a pressing need to find alternative bio-molecular targets for the development of new drugs. Since non-canonical DNA structures such as guanine-quadruplexes (G4s) have been implicated in regulating transcription, we were interested in determining whether there are putative quadruplex-forming sequences (PQS) in the genome of Pseudomonas aeruginosa. Using bioinformatic tools, we screened 36 genes potentially relevant to drug resistance for the presence of PQS and 10 of these were selected for biophysical characterisation (i.e. circular dichroism and thermal difference UV/Vis spectroscopy). These studies showed that three of these G-rich sequences (linked to murE, ftsB and mexC genes) form stable guanine-quadruplexes which were studied by NMR spectroscopy; detailed analysis of one of the sequences (mexC) confirmed that it adopts a two-quartet antiparallel quadruplex structure in the presence of K+ ions. We also show by FRET melting assays that small molecules can stabilise these three new G4 DNA structures under physiological conditions. These initial results could be of future interest in the development of new antibiotics with alternative bio-molecular targets which in turn would help tackle antimicrobial resistance

OA06.06 Impact of Systemic Anti-cancer Treatments on Outcomes of COVID-19 in Patients with Thoracic Cancers: CCC19 Registry Analysis

Introduction: Patients with thoracic cancers (TC) have one of the highest rates of mortality among patients with cancer and COVID-19. Data evaluating the impact of recent anti-cancer therapies on COVID-19 outcomes in patients with TC are confined to small heterogenous retrospective studies, with limited follow-up data. We analyzed data from the COVID-19 and Cancer Consortium (CCC19) (NCT04354701) to examine the impact of recent systemic therapies on the clinical outcomes of COVID-19 in patients with TC. Methods: The CCC19 registry was queried for adult patients with TC and lab-confirmed SARS-CoV-2 infection. Only patients with data quality scores of 0-4 were included in the analysis. The primary outcome was 30-day all-cause mortality. Secondary outcomes were need for oxygen supplementation, hospitalization, ICU admission, and mechanical ventilation. The outcomes were further stratified by demographics, smoking history, ECOG PS (0, 1, \u3e2), cancer status (remission, responding/stable, progressing) and type of systemic treatment \u3c3 months prior to COVID-19 (chemotherapy with or without immunotherapy, chemotherapy plus radiation, immunotherapy alone or targeted therapy). Results: From January 2020 to December 2021, 900 patients with thoracic cancer met the inclusion criteria. The median age was 70 years (IQR 62-77), 53% were female, 79% were former or current tobacco users, 56% of patients had ECOG PS of 0 or 1, and 34% of patients had active but stable or responding cancer. Fifty-three percent (N=477) of patients received at least one anti-cancer systemic therapy \u3c3 months prior to COVID-19 diagnosis. Chemotherapy with or without immunotherapy was the most prevalent treatment exposure (51%; N=242). After a median follow-up of 70 days (IQR 28-180), 30-day all-cause mortality was similar in patients who received any systemic cancer treatment versus no cancer treatment (23% and 22% respectively). Patients treated with immunotherapy and targeted therapy had the lowest mortality (15% and 18% respectively), the majority of whom were treated with palliative intent. Similar trends were also noted with secondary outcomes (Table 1). Conclusions: We report one of the largest studies evaluating the clinical outcomes of COVID-19 in the context of recent systemic anti-cancer treatments for TC. While continued caution is required when utilizing systemic treatments, delays in treatment may not be justified. The study provides reassuring data that patients receiving immunotherapy or targeted therapy even in the context of palliative treatment appear to have a lower risk for all-cause COVID-19 mortality. Further analysis exploring the prognostic factors associated with poor outcomes in patients with chemoradiation is planned

Impact of the COVID-19 Pandemic on Loneliness and Social Isolation: A Multi-Country Study

Copyright: © 2021 by the authors. The COVID-19 global pandemic and subsequent public health social measures have challenged our social and economic life, with increasing concerns around potentially rising levels of social isolation and loneliness. This paper is based on cross-sectional online survey data (available in 10 languages, from 2 June to 16 November 2020) with 20,398 respondents from 101 different countries. It aims to help increase our understanding of the global risk factors that are associated with social isolation and loneliness, irrespective of culture or country, to support evidence-based policy, services and public health interventions. We found the prevalence of severe loneliness was 21% during COVID-19 with 6% retrospectively reporting severe loneliness prior to the pandemic. A fifth were defined as isolated based on their usual connections, with 13% reporting a substantial increase in isolation during COVID-19. Personal finances and mental health were overarching and consistently cross-cutting predictors of loneliness and social isolation, both before and during the pandemic. With the likelihood of future waves of COVID-19 and related restrictions, it must be a public health priority to address the root causes of loneliness and social isolation and, in particular, address the needs of specific groups such as carers or those living alone

Determining the use of prophylactic antibiotics in breast cancer surgeries : a survey of practice

Q3Q2Background: Prophylactic antibiotics (PAs) are beneficial to breast cancer patients undergoing surgery because they prevent surgical site infection (SSI), but limited information regarding their use has been published. This study aims to determine the use of PAs prior to breast cancer surgery amongst breast surgeons in Colombia. Methods: An online survey was distributed amongst the breast surgeon members of the Colombian Association of Mastology, the only breast surgery society of Colombia. The scope of the questions included demographics, clinical practice characteristics, PA prescription characteristics, and the use of PAs in common breast surgical procedures. Results: The survey was distributed amongst eighty-eight breast surgeons of whom forty-seven responded (response rate: 53.4%). Forty surgeons (85.1%) reported using PAs prior to surgery of which >60% used PAs during mastectomy, axillary lymph node dissection, and/or breast reconstruction. Surgeons reported they targeted the use of PAs in cases in which patients had any of the following SSI risk factors: diabetes mellitus, drains in situ, obesity, and neoadjuvant therapy. The distribution of the self-reported PA dosing regimens was as follows: single pre-operative fixed-dose (27.7%), single preoperative dose followed by a second dose if the surgery was prolonged (44.7%), single preoperative dose followed by one or more postoperative doses for >24 hours (10.6%), and single preoperative weight-adjusted dose (2.1%). Conclusion: Although this group of breast surgeons is aware of the importance of PAs in breast cancer surgery there is a discrepancy in how they use it, specifically with regards to prescription and timeliness of drug administration. Our findings call for targeted quality-improvement initiatives, such as standardized national guidelines, which can provide sufficient evidence for all stakeholders and therefore facilitate best practice medicine for breast cancer surgery