DNA nanotechnology: new adventures for an old warhorse

As the blueprint of life, the natural exploits of DNA are admirable. However, DNA should not only be viewed within a biological context. It is an elegantly simple yet functionally complex chemical polymer with properties that make it an ideal platform for engineering new nanotechnologies. Rapidly advancing synthesis and sequencing technologies are enabling novel unnatural applications for DNA beyond the realm of genetics. Here we explore the chemical biology of DNA nanotechnology for emerging applications in communication and digital data storage. Early studies of DNA as an alternative to magnetic and optical storage mediums have not only been promising, but have demonstrated the potential of DNA to revolutionize the way we interact with digital data in the future.United States. Defense Advanced Research Projects Agency (Contract FA8721-05-C-0002)National Institutes of Health (U.S.) (Grant 1R01EB017755)National Institutes of Health (U.S.) (Grant 1DP2OD008435)National Institutes of Health (U.S.) (Grant 1P50GM098792

Development of algorithms for determining heart failure with reduced and preserved ejection fraction using nationwide electronic healthcare records in the UK

Background: Determining heart failure (HF) phenotypes in routine electronic health records (EHR) is challenging. We aimed to develop and validate EHR algorithms for identification of specific HF phenotypes, using Read codes in combination with selected patient characteristics. Methods: We used The Healthcare Improvement Network (THIN). The study population included a random sample of individuals with HF diagnostic codes (HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF) and non-specific HF) selected from all participants registered in the THIN database between 1 January 2015 and 30 September 2017. Confirmed diagnoses were determined in a randomly selected subgroup of 500 patients via GP questionnaires including a review of all available cardiovascular investigations. Confirmed diagnoses of HFrEF and HFpEF were based on four criteria. Based on these data, we calculated a positive predictive value (PPV) of predefined algorithms which consisted of a combination of Read codes and additional information such as echocardiogram results and HF medication records. Results: The final cohort from which we drew the 500 patient random sample consisted of 10 275 patients. Response rate to the questionnaire was 77.2%. A small proportion (18%) of the overall HF patient population were coded with specific HF phenotype Read codes. For HFrEF, algorithms achieving over 80% PPV included definite, possible or non-specific HF HFrEF codes when combined with at least two of the drugs used to treat HFrEF. Only in non-specific HF coding did the use of three drugs (rather than two) contribute to an improvement of the PPV for HFrEF. HFpEF was only accurately defined with specific codes. In the absence of specific coding for HFpEF, the PPV was consistently below 50%. Conclusions: Prescription for HF medication can reliably be used to find HFrEF patients in the UK, even in the absence of a specific Read code for HFrEF. Algorithms using non-specific coding could not reliably find HFpEF patients

Gastric Fistula in the Chest After Sleeve Gastrectomy: a Systematic Review of Diagnostic and Treatment Options

This study aimed to establish the optimal diagnostic and treatment algorithm for the management of gastric fistula in the chest (GFIC) after sleeve gastrectomy (SG) through a systematic review of published cases. A multi-database search was performed, which produced 1182 results, of which 26 studies were included in this systematic review. The initial presentation included subphrenic collections, leaks, or (recurrent) pneumonia with associated symptoms such as persistent cough, fever, and/or dyspnea. Computed tomography (CT) scan in combination with either upper gastrointestinal (UGI) series or an esophagogastroduodenoscopy (EGD) was used to adequately diagnose the fistulas. Initial treatment was either with clips and/or clips and stents that were placed endoscopically. When unsuccessful in the majority of the cases, the surgical treatment consisted of total gastrectomy and Roux-en-Y esophagojejunostomy in a laparoscopic or open fashion

Reporting of sex as a variable in cardiovascular studies using cultured cells

<p>Abstract</p> <p>Background</p> <p>Chromosomal complement, including that provided by the sex chromosomes, influences expression of proteins and molecular signaling in every cell. However, less than 50% of the scientific studies published in 2009 using experimental animals reported sex as a biological variable. Because every cell has a sex, we conducted a literature review to determine the extent to which sex is reported as a variable in cardiovascular studies on cultured cells.</p> <p>Methods</p> <p>Articles from 10 cardiovascular journals with high impact factors (<it>Circulation</it>, <it>J Am Coll Cardiol</it>, <it>Eur Heart J</it>, <it>Circ Res</it>, <it>Arterioscler Thromb Vasc Biol</it>, <it>Cardiovasc Res</it>, <it>J Mol Cell Cardiol</it>, <it>Am J Physiol Heart Circ Physiol</it>, <it>J Heart Lung Transplant and J Cardiovasc Pharmacol</it>) and published in 2010 were searched using terms 'cultured' and 'cells' in any order to determine if the sex of those cells was reported. Studies using established cell lines were excluded.</p> <p>Results</p> <p>Using two separate search strategies, we found that only 25 of 90 articles (28%) and 20 of 101 articles (19.8%) reported the sex of cells. Of those reporting the sex of cells, most (68.9%; n = 31) used only male cells and none used exclusively female cells. In studies reporting the sex of cells of cardiovascular origin, 40% used vascular smooth-muscle cells, and 30% used stem/progenitor cells. In studies using cells of human origin, 35% did not report the sex of those cells. None of the studies using neonatal cardiac myocytes reported the sex of those cells.</p> <p>Conclusions</p> <p>The complement of sex chromosomes in cells studied in culture has the potential to affect expression of proteins and 'mechanistic' signaling pathways. Therefore, consistent with scientific excellence, editorial policies should require reporting sex of cells used in <it>in vitro </it>experiments.</p

Splenic Abscess Following Sleeve Gastrectomy: A Systematic Review of Clinical Presentation and Management Methods

BACKGROUND: Splenic abscess is a rare complication following sleeve gastrectomy. METHODS: We performed a systematic review to clarify its clinical significance, presentation, and management. PubMed, Embase, MEDLINE, Google Scholar, and the Cochrane Library were searched up to the 19th of July 2020. A total of 18 patients were included, of which 11 were female and 7 were male. The mean age was 34.1 ± 12.3 years, and the mean body mass index was 45.8 ± 7.6 kg/m2. Type 2 diabetes mellitus was reported in 11.1% of patients and hypertension in 22.2%. Fever was the most common presenting symptom seen in 17 (94.4%) patients, followed by abdominal pain in 10 (55.6%). The mean duration from surgery to presentation was 98.6 ± 132.7 days (range 10–547 days). Computed tomography was used for investigations in 17/18 (94.4%) patients. Seven patients had reported leak, three reported bleeding, and 2 reported pleural effusion. Thirteen patients had unilocular abscess. All patients were treated with antibiotics. Four patients needed total parenteral nutrition, and three were given proton pump inhibitor. In total, 11 patients needed percutaneous drainage as a part of treatment and 11 patients needed total splenectomy and 1 needed partial splenectomy. CONCLUSION: Splenic abscess following sleeve gastrectomy is a rare identity. The etiology of formation of splenic abscess needs further studies. A computed tomography of the abdomen with contrast is the preferred diagnostic tool. There is no gold standard treatment for splenic abscess

Stabilization and Anticancer Enhancing Activity of the Peptide Nisin by Cyclodextrin-Based Nanosponges against Colon and Breast Cancer Cells

The great variability of cancer types demands novel drugs with broad spectrum, this is the case of Nisin, a polycyclic antibacterial peptide that recently has been considered for prevention of cancer cells growth. As an accepted food additive, this drug would be very useful for intestinal cancers, but the peptide nature would make easier its degradation by digestion procedures. For that reason, the aim of present study to investigate the protective effect of two different β-cyclodextrin-based nanosponges (carbonyl diimidazole and pyromellitic dianhydride) and their anti-cancer enhancement effect of Nisin-Z encapsulated with against colon cancer cells (HT-29). To extend its possible use, a comparison with breast (MCF-7) cancer cell was carried out. The physicochemical properties, loading efficiency, and release kinetics of Nisin complex with nanosponges were studied. Then, tricin-SDS-PAGE electrophoresis was used to understand the effect of NSs on stability of Nisin-Z in the presence of gastric peptidase pepsin. In addition, the cytotoxicity and cell membrane damage of Nisin Z were evaluated by using the MTT and LDH assay, which was complemented via Annexin-V/ Propidium Iodide (PI) by using flowcytometry. CD-NS are able to complex Nisin-Z with an encapsulation efficiency around 90%. A protective effect of Nisin-Z complexed with CD-NSs was observed in presence of pepsin. An increase in the percentage of apoptotic cells was observed when the cancer cells were exposed to Nisin Z complexed with nanosponges. Interestingly, Nisin Z free and loaded on PMDA/CDI-NSs is more selectively toxic towards HT-29 cells than MCF-7 cancer cells. These results indicated that nanosponges might be good candidates to protect peptides and deliver drugs against intestinal cancers

Defining the relationship between COPD and CVD: what are the implications for clinical practice?

Cardiovascular diseases (CVDs) are arguably the most important comorbidities in chronic obstructive pulmonary disease (COPD). CVDs are common in people with COPD, and their presence is associated with increased risk for hospitalization, longer length of stay and all-cause and CVD-related mortality. The economic burden associated with CVD in this population is considerable and the cumulative cost of treating comorbidities may even exceed that of treating COPD itself. Our understanding of the biological mechanisms that link COPD and various forms of CVD has improved significantly over the past decade. But despite broad acceptance of the prognostic significance of CVDs in COPD, there remains widespread under-recognition and undertreatment of comorbid CVD in this population. The reasons for this are unclear; however institutional barriers and a lack of evidence-based guidelines for the management of CVD in people with COPD may be contributory factors. In this review, we summarize current knowledge relating to the prevalence and incidence of CVD in people with COPD and the mechanisms that underlie their coexistence. We discuss the implications for clinical practice and highlight opportunities for improved prevention and treatment of CVD in people with COPD. While we advocate more active assessment for signs of cardiovascular conditions across all age groups and all stages of COPD severity, we suggest targeting those aged under 65 years. Evidence indicates that the increased risks for CVD are particularly pronounced in COPD patients in mid-to-late-middle-age and thus it is in this age group that the benefits of early intervention may prove to be the most effective