Multitalented Synthetic Antimicrobial Peptides and Their Antibacterial, Antifungal and Antiviral Mechanisms

Despite the great strides in healthcare during the last century, some challenges still remained unanswered. The development of multi-drug resistant bacteria, the alarming growth of fungal infections, the emerging/re-emerging of viral diseases are yet a worldwide threat. Since the discovery of natural antimicrobial peptides able to broadly hit several pathogens, peptide-based therapeutics have been under the lenses of the researchers. This review aims to focus on synthetic peptides and elucidate their multifaceted mechanisms of action as antiviral, antibacterial and antifungal agents. Antimicrobial peptides generally affect highly preserved structures, e.g., the phospholipid membrane via pore formation or other constitutive targets like peptidoglycans in Gram-negative and Gram-positive bacteria, and glucan in the fungal cell wall. Additionally, some peptides are particularly active on biofilm destabilizing the microbial communities. They can also act intracellularly, e.g., on protein biosynthesis or DNA replication. Their intracellular properties are extended upon viral infection since peptides can influence several steps along the virus life cycle starting from viral receptor-cell interaction to the budding. Besides their mode of action, improvements in manufacturing to increase their half-life and performances are also taken into consideration together with advantages and impairments in the clinical usage. Thus far, the progress of new synthetic peptide-based approaches is making them a promising tool to counteract emerging infections.

Distinctive features of ertapenem mono-resistant carbapenem-resistant Enterobacterales in the United States: A cohort study

Background Carbapenem-resistant Enterobacterales (CRE) are highly antibiotic-resistant bacteria. Whether CRE resistant only to ertapenem among carbapenems (ertapenem “mono-resistant”) represent a unique CRE subset with regards to risk factors, carbapenemase genes, and outcomes is unknown. Methods We analyzed surveillance data from nine CDC Emerging Infections Program (EIP) sites. A case was the first isolation of a carbapenem-resistant Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, K. oxytoca, K. pneumoniae, or K. variicola from a normally sterile site or urine in an EIP catchment area resident in 2016-2017. We compared risk factors, carbapenemase genes, antibiotic susceptibility, and mortality of ertapenem “mono-resistant” cases to “other” CRE cases (resistant to ≥1 carbapenem other than ertapenem), and analyzed risk factors for mortality. Results Of 2009 cases, 1249 (62.2%) were ertapenem mono-resistant and 760 (37.8%) were other CRE. Ertapenem mono-resistant CRE cases were more frequently ≥80 years old (29.1% vs. 19.5%, p<0.0001) and female (67.9% vs 59.0%, p<0.0001). Ertapenem mono-resistant isolates were more likely to be Enterobacter cloacae complex (48.4% vs. 15.4%, p<0.0001) but less likely to be isolated from a normally sterile site (7.1% vs. 11.7%, p<0.01) or have a carbapenemase gene (2.4% vs. 47.4%, p<0.0001). Ertapenem mono-resistance was not associated with 90-day mortality in logistic regression models. Carbapenemase-positive isolates were associated with mortality (odds ratio 1.93, 95% confidence interval 1.30-2.86). Conclusions Ertapenem mono-resistant CRE rarely have carbapenemase genes and have distinct clinical and microbiologic characteristics from other CRE. These findings may inform antibiotic choice and infection prevention practices, particularly when carbapenemase testing is not available.

Genomic and Virological Characterization of SARS-CoV-2 Variants in a Subset of Unvaccinated and Vaccinated U.S. Military Personnel

The emergence of SARS-CoV-2 variants complicates efforts to control the COVID-19 pandemic. Increasing genomic surveillance of SARS-CoV-2 is imperative for early detection of emerging variants, to trace the movement of variants, and to monitor effectiveness of countermeasures. Additionally, determining the amount of viable virus present in clinical samples is helpful to better understand the impact these variants have on viral shedding. In this study, we analyzed nasal swab samples collected between March 2020 and early November 2021 from a cohort of United States (U.S.) military personnel and healthcare system beneficiaries stationed worldwide as a part of the Defense Health Agency (DHA) Global Emerging Infections Surveillance (GEIS) program. SARS-CoV-2 quantitative real time reverse-transcription PCR (qRT-PCR) positive samples were characterized by next-generation sequencing and a subset was analyzed for isolation and quantification of viable virus. Not surprisingly, we found that the Delta variant is the predominant strain circulating among U.S. military personnel beginning in July 2021 and primarily represents cases of vaccine breakthrough infections (VBIs). Among VBIs, we found a 50-fold increase in viable virus in nasal swab samples from Delta variant cases when compared to cases involving other variants. Notably, we found a 40-fold increase in viable virus in nasal swab samples from VBIs involving Delta as compared to unvaccinated personnel infected with other variants prior to the availability of approved vaccines. This study provides important insight about the genomic and virological characterization of SARS-CoV-2 isolates from a unique study population with a global presence.

Problems of bioethics in modern medicine

Modern scientific advances in medical science and practice require a new perspective on the life and rights of the individual, starting from its embryo in the womb, and therefore the discussions devoted to the study of various aspects of the human right to health and life are simply condemned to a particular relevance in current conditions. Modern bioethics is designed to address ethical issues of medicine and biology, as well as related technologies, considering social, legal and environmental aspects. The objective of the study is to identify current ethical issues in medicine and biology as well as related technologies, considering social, legal and environmental aspects. The article analyzes the directions for the development of bioethics in the health system, human rights as a source of bioethical principles and behavioral criteria in various fields of its application. The bioethics problems of the major achievements of modern biological and medical sciences – stem cell therapy, human cloning, euthanasia, organ and tissue transplantation, certain aspects of resuscitation, which often conflict with moral and ethical criteria. The problem of emerging infections that create local or international emergencies is discussed. A clear example is the pandemic of a new disease – the COVID-19, which confirms humanity’s unpreparability to resist the spread of respiratory viral infections. Conclusion. Modern biological and medical research requires a rethinking of existing bioethical and legal postulates. They must go through a certain path of transformation to meet the requirements of today. It is important to improve the legal regulation without which the boundary between the subject and the object of study will remain potentially uncertain.

Evaluating Rates and Determinants of COVID-19 Vaccine Hesitancy for Adults and Children in the Singapore Population: Strengthening Our Community’s Resilience against Threats from Emerging Infections (SOCRATEs) Cohort

COVID-19 vaccines are crucial for achieving sufficient immunisation coverage to manage the pandemic, but vaccine hesitancy persists. This study aimed to investigate the prevalence and determinants of vaccine hesitancy in adults and in parents for vaccinating their children using an integrated social cognition model. A community-based cohort in Singapore [N = 1623] completed a survey (wave 25) between June and July 2021 which measured their risk perceptions, distress, trust, vaccination beliefs, and vaccine intentions/behaviours. Results indicated low rates of hesitancy (9.9%) for own vaccination, with most concerns citing side effects, safety, and hasty development. Remaining respondents were vaccinated (69%) or intended to vaccinate (21%). The multivariable model (non-vaccinated respondents) indicated that, living with people in poor health, subjective norm, moral norm, benefits, and necessity of vaccination were associated with lower vaccine hesitancy (R2 Cox & Snell: 51.4% p < 0.001). Hesitancy rates were higher for children’s vaccination (15.9%), with male gender, lower perceived vaccine benefits, high COVID-19 risk perceptions, vaccination concerns, and necessity beliefs associated with higher odds of parental vaccine hesitancy (R2 Cox & Snell = 36.4%; p < 0.001). While levels of vaccine acceptance are high, more targeted messages are needed. For adults’ vaccination, more emphasis should be on benefits and social gains, while for parental hesitancy, messages related to safety should be prioritised.

How Did the COVID-19 Lockdown Affect Children and Adolescent's Well-Being: Spanish Parents, Children, and Adolescents Respond

Background: During the COVID-19 pandemic, lockdown strategies have been widely used to contain SARS-CoV-2 virus spread. Children and adolescents are especially vulnerable to suffering psychological effects as result of such measures. In Spain, children were enforced to a strict home lockdown for 42 days during the first wave. Here, we studied the effects of lockdown in children and adolescents through an online questionnaire.Methods: A cross-sectional study was conducted in Spain using an open online survey from July (after the lockdown resulting from the first pandemic wave) to November 2020 (second wave). We included families with children under 16 years-old living in Spain. Parents answered a survey regarding the lockdown effects on their children and were instructed to invite their children from 7 to 16 years-old (mandatory scholar age in Spain) to respond a specific set of questions. Answers were collected through an application programming interface system, and data analysis was performed using R.Results: We included 1,957 families who completed the questionnaires, covering a total of 3,347 children. The specific children's questionnaire was completed by 167 kids (7–11 years-old), and 100 adolescents (12–16 years-old). Children, in general, showed high resilience and capability to adapt to new situations. Sleeping problems were reported in more than half of the children (54%) and adolescents (59%), and these were strongly associated with less time doing sports and spending more than 5 h per day using electronic devices. Parents perceived their children to gain weight (41%), be more irritable and anxious (63%) and sadder (46%). Parents and children differed significantly when evaluating children's sleeping disturbances.Conclusions: Enforced lockdown measures and isolation can have a negative impact on children and adolescent's mental health and well-being. In future waves of the current pandemic, or in the light of potential epidemics of new emerging infections, lockdown measures targeting children, and adolescents should be reconsidered taking into account their infectiousness potential and their age-specific needs, especially to facilitate physical activity and to limit time spent on electronic devices.

COVID-19 management in social care in England: a systematic review of changing policies and newspaper reported staff perspectives.

Adult social care has been a major focus of public attention and infection control guidance during the COVID-19 pandemic, with a high mortality both for carers and those receiving care. To protect themselves and others from infection, staff in residential and domiciliary care settings had to quickly adapt to infection control measures that heavily impacted on their working and every-day life, whilst navigating new responsibilities, uncertainties and anxieties. We sought to explore the production and reception of guidance and look at ways these can be adapted to improve the working life of care staff in domiciliary and residential care whilst reducing the risk of SARS-CoV-2 transmission amid this pandemic and of future emerging infections. We conducted two complementary and integrated systematic reviews of published documents in the pre-vaccination era: (1) National guidance for social care (conducted between 29 July to 28 October 2020), and (2) Newspaper coverage of infection control issues in social care (conducted between 27th July to 10th September 2020). Three higher order common themes emerged in the integrated systematic review of guidance documents and newspaper articles: a) Testing, b) Personal Protective Equipment, c) Employment. The reviews revealed a sharp disjunction between the content of infection control guidance and its usability and applicability in social care settings. We suggest that infection control guidance needs to be better adapted to social care settings and informed by the sector. The practicalities of care work and care settings need to be at the core of the process for guidance to be relevant and effective. Modes and timings of communications also need to be optimised.

Identifying patient-level risk factors associated with non-β-lactam resistance outcomes in invasive methicillin-resistant Staphylococcus aureus infections in the United States using chain graphs

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common causes of hospital- and community-acquired infections. MRSA is resistant to many antibiotics, including β-lactam antibiotics, fluoroquinolones, lincosamides, macrolides, aminoglycosides, tetracyclines, and chloramphenicol. Graphical models such as chain graphs can be used to quantify and visualize the interactions among multiple resistant outcomes and their explanatory variables. In this study, we analyzed MRSA surveillance data collected by the Centers for Disease Control and Prevention (CDC) as part of the Emerging Infections Program (EIP) using chain graphs with the objective of identifying risk factors for individual phenotypic resistance outcomes (reported as minimum inhibitory concentration, MIC) while considering the correlations among themselves. Some phenotypic resistances have low connectivity to other outcomes or predictors (e.g. tetracycline, vancomycin, doxycycline, and rifampin). Levofloxacin was the only resistant associated with healthcare use. Blood culture was the most common predictor of MIC. Patients with positive blood culture had significantly increased MIC to chloramphenicol, erythromycin, gentamicin, lincomycin, and mupirocin, and decreased daptomycin and rifampin MICs. Chain graphs show the unique and common risk factors associated with resistance outcomes.