Engineering active lysostaphin variants that incorporate noncanonical amino acids and characterizing the effects of site-specific PEGylation.

We describe a facile strategy to identify sites for the incorporation of noncanonical amino acids into lysostaphin-an enzyme that degrades the cell wall of Staphylococcus aureus-while retaining stapholytic activity. We used this strategy to generate active variants of lysostaphin incorporating para-azidophenylalanine. The incorporation of this "reactive handle" enabled the orthogonal site-specific modification of the enzyme variants with polyethylene glycol (PEG) using copper-free click cycloaddition. PEGylated lysostaphin variants could retain their stapholytic activity, with the extent of retention depending on the site of modification and the PEG molecular weight. The site-specific modification of lysostaphin could be useful not only for PEGylation to improve biocompatibility but also for the incorporation of the enzyme into hydrogels and other biomaterials and for studies of protein structure and dynamics. Moreover, the approach described herein could be readily applied to identify suitable sites for the incorporation of reactive handles into other proteins of interest.

Pivot to prevent bowel cancer: Reflections on adapting an Aboriginal bowel cancer screening awareness program to a digital call to action-A commentary.

ISSUE ADDRESSED: The Sydney Local Health District (SLHD) Health Promotion Unit was awarded a Cancer Institute NSW grant to raise awareness of bowel cancer and promote the National Bowel Cancer Screening Program (NBCSP) among Aboriginal communities in SLHD. The COVID-19 pandemic thwarted initial plans for face-to-face workshops and plans pivoted to digital products and dissemination of messages on a range of communication platforms. DISCUSSION: The coronavirus (COVID-19) pandemic provided staff with the freedom, flexibility, and ability to be creative in ways not possible prior to the pandemic and ultimately ended up with a superior product with a reach further than anticipated. A more comprehensive suite of digital resources addressing barriers to bowel cancer screening in the Aboriginal community was produced that is able to be used more broadly. These resources have reached a much larger population group through websites, social media, as well as TV and radio advertisements, and have the potential to be used and adapted in other local health districts and states across Australia. CONCLUSION: Adapting an Aboriginal bowel cancer screening awareness program to a digital platform is a promising approach. SO WHAT?: COVID-19 provided an opportunity to create new long-lasting partnerships and to be creative beyond the scope of the original grant. This in turn produced a product with a reach further than anticipated that can also be built on and sustained.

Prevalence of colistin heteroresistance in carbapenem-resistant Pseudomonas aeruginosa and association with clinical outcomes in patients: an observational study.

OBJECTIVES: To describe the prevalence of colistin heteroresistance in carbapenem-resistant Pseudomonas aeruginosa (CRPA) and evaluate the association with clinical outcomes. METHODS: Colistin heteroresistance was evaluated in CRPA isolates collected from patients without cystic fibrosis in Atlanta, Georgia, USA using two definitions: HR1, growth at 4 and 8 mg/L of colistin at a frequency ≥1 × 10-6 the main population; and HR2, growth at a colistin concentration ≥8× the MIC of the main population at a frequency ≥1 × 10-7. A modified population analysis profile (mPAP) technique was compared with reference PAP for detecting heteroresistance. For adults hospitalized at the time of or within 1 week of CRPA culture, multivariable logistic regression estimated the association between heteroresistance and 90 day mortality. RESULTS: Of 143 colistin-susceptible CRPA isolates, 8 (6%) met the HR1 definition and 37 (26%) met the HR2 definition. Compared with the reference PAP, mPAP had a sensitivity and specificity of 50% and 100% for HR1 and 32% and 99% for HR2. Of 82 hospitalized patients, 45 (56%) were male and the median age was 63 years (IQR 49-73). Heteroresistance was not associated with 90 day mortality using HR1 (0% in heteroresistant versus 22% in non-heteroresistant group; P = 0.6) or HR2 (12% in heteroresistant versus 24% in non-heteroresistant group; P = 0.4; adjusted OR 0.8; 95% CI 0.2-3.4). CONCLUSIONS: Colistin heteroresistance was identified in up to 26% of patients with CRPA in our sample, although the prevalence varied depending on the definition. We did not observe an apparent association between colistin heteroresistance and 90 day mortality.

Experiencing the SARS-CoV-2 Pandemic Whilst Living With Cancer.

The SARS-CoV-2 pandemic has resulted in considerable consequences for many cancer patients, exacerbating pre-existing systemic health system limitations as well as creating new challenges. From socially distanced clinics and the widespread introduction of telehealth, to the halting of clinical trials and the reassessment of what constitutes "essential" treatment, care in oncology has abruptly changed. There is currently limited analysis of cancer patients' experiences of the pandemic and its impacts on illness, wellness, and everyday life. Through semi-structured interviews with 54 people living with cancer during the 2020 phase of the SARS-CoV-2 pandemic in Australia, we explore how patients experience illness and care in reflecting upon a range of pandemic challenges, including delay, distance, and vulnerability. We find that in some cases, these pandemic conditions redefined the meaning of essential cancer care, reconfigured expectations around clinical trials, constructed new affective distances, and amplified dread and fear for people living with cancer.

A sociology of precision-in-practice: The affective and temporal complexities of everyday clinical care.

The idea of 'precision medicine', which has gained increasing traction since the early 2000s, is now ubiquitous in health and medicine. Though varied in its implementation across fields, precision medicine has raised hopes of revolutionary treatments and has spurred the proliferation of novel therapeutics, the alteration of professional trajectories and various reconfigurations of health/care. Nowhere is the promise of precision medicine more apparent, nor further institutionalised, than in the field of oncology. While the transformative potential of precision medicine is widely taken for granted, there remains scant attention to how it is being experienced at the coalface of care. Here, drawing on the perspectives of 54 cancer care professionals gleaned through eight focus group discussions in two hospitals in Australia, we explore clinicians' experiences of the day-to-day dynamics of precision-in-practice. We illustrate some of the affective and temporal complexities, analysed here under the rubrics of enchantment, acceleration and distraction that are emerging alongside the uptake of precision medicine in the field of oncology. We argue that these complexities, and their dis/continuities with earlier iterations of cancer care, demonstrate the need for sociological analyses of precision medicine as it is being implemented in practice and its varied effects on 'routine' care.

Insights on the Synthesis, Crystal and Electronic Structures, and Optical and Thermoelectric Properties of Sr1- xSb xHfSe3 Orthorhombic Perovskite.

Single-phase polycrystalline powders of Sr1- xSb xHfSe3 ( x = 0, 0.005, 0.01), a new member of the chalcogenide perovskites, were synthesized using a combination of high temperature solid-state reaction and mechanical alloying approaches. Structural analysis using single-crystal as well as powder X-ray diffraction revealed that the synthesized materials are isostructural with SrZrSe3, crystallizing in the orthorhombic space group Pnma (#62) with lattice parameters a = 8.901(2) Å; b = 3.943(1) Å; c = 14.480(3) Å; and Z = 4 for the x = 0 composition. Thermal conductivity data of SrHfSe3 revealed low values ranging from 0.9 to 1.3 W m-1 K-1 from 300 to 700 K, which is further lowered to 0.77 W m-1 K-1 by doping with 1 mol % Sb for Sr. Electronic property measurements indicate that the compound is quite insulating with an electrical conductivity of 2.9 S/cm at 873 K, which was improved to 6.7 S/cm by 0.5 mol % Sb doping. Thermopower data revealed that SrHfSe3 is a p-type semiconductor with thermopower values reaching a maximum of 287 µV/K at 873 K for the 1.0 mol % Sb sample. The optical band gap of Sr1- xSb xHfSe3 samples, as determined by density functional theory calculations and the diffuse reflectance method, is ∼1.00 eV and increases with Sb concentration to 1.15 eV. Careful analysis of the partial densities of states (PDOS) indicates that the band gap in SrHfSe3 is essentially determined by the Se-4p and Hf-5d orbitals with little to no contribution from Sr atoms. Typically, band edges of p- and d-character are a good indication of potentially strong absorption coefficient due to the high density of states of the localized p and d orbitals. This points to potential application of SrHfSe3 as absorbing layer in photovoltaic devices.

Crystal Structure and Thermoelectric Properties of the 7,7L Lillianite Homologue Pb6Bi2Se9.

Pb6Bi2Se9, the selenium analogue of heyrovsyite, crystallizes in the orthorhombic space group Cmcm (#63) with a = 4.257(1) Å, b = 14.105(3) Å, and c = 32.412(7) Å at 300 K. Its crystal structure consists of two NaCl-type layers, A and B, with equal thickness, N1 = N2 = 7, where N is the number of edge-sharing [Pb/Bi]Se6 octahedra along the central diagonal. In the crystal structure, adjacent layers are arranged along the c-axis such that bridging bicapped trigonal prisms, PbSe8, are located on a pseudomirror plane parallel to (001). Therefore, Pb6Bi2Se9 corresponds to a 7,7L member of the lillianite homologous series. Electronic transport measurements indicate that the compound is a heavily doped narrow band gap n-type semiconductor, with electrical conductivity and thermopower values of 350 S/cm and -53 µV/K at 300 K. Interestingly, the compound exhibits a moderately low thermal conductivity, ∼1.1 W/mK, in the whole temperature range, owing to its complex crystal structure, which enables strong phonon scattering at the twin boundaries between adjacent NaCl-type layers A and B. The dimensionless figure of merit, ZT, increases with temperature to 0.25 at 673 K.

Coexistence of high-T(c) ferromagnetism and n-type electrical conductivity in FeBi2Se4.

The discovery of n-type ferromagnetic semiconductors (n-FMSs) exhibiting high electrical conductivity and Curie temperature (Tc) above 300 K would dramatically improve semiconductor spintronics and pave the way for the fabrication of spin-based semiconducting devices. However, the realization of high-Tc n-FMSs and p-FMSs in conventional high-symmetry semiconductors has proven extremely difficult due to the strongly coupled and interacting magnetic and semiconducting sublattices. Here we show that decoupling the two functional sublattices in the low-symmetry semiconductor FeBi2Se4 enables unprecedented coexistence of high n-type electrical conduction and ferromagnetism with Tc ≈ 450 K. The structure of FeBi2Se4 consists of well-ordered magnetic sublattices built of [FenSe4n+2]∞ single-chain edge-sharing octahedra, coherently embedded within the three-dimensional Bi-rich semiconducting framework. Magnetotransport data reveal a negative magnetoresistance, indicating spin-polarization of itinerant conducting electrons. These findings demonstrate that decoupling magnetic and semiconducting sublattices allows access to high-Tc n- and p-FMSs as well as helps unveil the mechanism of carrier-mediated ferromagnetism in spintronic materials.

High-Tc Ferromagnetism and Electron Transport in p-Type Fe(1-x)Sn(x)Sb2Se4 Semiconductors.

Single-phase polycrystalline powders of Fe(1-x)Sn(x)Sb2Se4 (x = 0 and 0.13) were synthesized by a solid-state reaction of the elements at 773 K. X-ray diffraction on Fe0.87Sn0.13Sb2Se4 single-crystal and powder samples indicates that the compound is isostructural to FeSb2Se4 in the temperature range from 80 to 500 K, crystallizing in the monoclinic space group C2/m (No. 12). Electron-transport data reveal a marginal alteration in the resistivity, whereas the thermopower drops by ∼60%. This suggests a decrease in the activation energy upon isoelectronic substitution of 13% Fe by Sn. Magnetic susceptibility and magnetization measurements from 2 to 500 K reveal that the Fe(1-x)Sb2Sn(x)Se4 phases exhibit ferromagnetic behavior up to ∼450 K (x = 0) and 325 K (x = 0.13). Magnetotransport data for FeSb2Se4 reveal large negative magnetoresistance, suggesting spin polarization of free carriers in the sample. The high-Tc ferromagnetism in Fe(1-x)Sn(x)Sb2Se4 phases and the decrease in Tc of the Fe0.87Sn0.13Sb2Se4 sample are rationalized by taking into account (1) the separation between neighboring magnetic centers in the crystal structures and (2) the formation of bound magnetic polarons, which overlap to induce long-range ferromagnetic ordering.

Pb7Bi4Se13: a lillianite homologue with promising thermoelectric properties.

Pb(7)Bi(4)Se(13) crystallizes in the monoclinic space group C2/m (No. 12) with a = 13.991(3) Å, b = 4.262(2) Å, c = 23.432(5) Å, and ß = 98.3(3)° at 300 K. In its three-dimensional structure, two NaCl-type layers A and B with respective thicknesses N(1) = 5 and N(2) = 4 [N = number of edge-sharing (Pb/Bi)Se6 octahedra along the central diagonal] are arranged along the c axis in such a way that the bridging monocapped trigonal prisms, PbSe7, are located on a pseudomirror plane parallel to (001). This complex atomic-scale structure results in a remarkably low thermal conductivity (∼0.33 W m(-1) K(-1) at 300 K). Electronic structure calculations and diffuse-reflectance measurements indicate that Pb(7)Bi(4)Se(13) is a narrow-gap semiconductor with an indirect band gap of 0.23 eV. Multiple peaks and valleys were observed near the band edges, suggesting that Pb(7)Bi(4)Se(13) is a promising compound for both n- and p-type doping. Electronic-transport data on the as-grown material reveal an n-type degenerate semiconducting behavior with a large thermopower (∼-160 µV K(-1) at 300 K) and a relatively low electrical resistivity. The inherently low thermal conductivity of Pb(7)Bi(4)Se(13) and its tunable electronic properties point to a high thermoelectric figure of merit for properly optimized samples.

Purity or perversion? from taboo to fact: kindergarten teachers' reflections on age-normal sexuality.

Many educators and pedagogues around the world face challenging situations in their everyday work. Being caught off guard when children begin to explore their bodies and show curiosity about body parts and sexual issues is one of the most uncomfortable realities in the work of educating our children and can generate a series of worrying questions, such as, "Is this child* normal? Should I stop him/ her from masturbating? What should I tell him/her?. Although talking to children about body changes and sexual matters may seem strange or embarrassing, providing correct and age-appropriate information is one of the most important things kindergarten employees can do to ensure that children grow up protected, healthy and safe in their bodies. The current study is based on empirical evidence from focus group interviews with 18 kindergarten teachers from four different kindergartens. The aim is to provide a real overview regarding kindergarten employees' experiences when it comes to their work with sexual development in small children. The findings show that sexuality is still a taboo even in western societies, as it is usually linked to abuse or pathological behavior. Additionally, key information about lack of focus on these topics in pedagogical educational programs is provided. Furthermore, the informants highlight the importance of knowledge and resources for them to feel in control and in confidence to face these challenges. Future directions and tips are provided to improve the educational field and ensure a healthy and balanced development which is after all part of all children's rights.

Hope in the era of precision oncology: a qualitative study of informal caregivers' experiences.

OBJECTIVES: To explore informal caregivers' perspectives on precision medicine in cancer care. DESIGN: Semi-structured interviews with the informal caregivers of people living with cancer and receiving targeted/immunotherapies. Interview transcripts were analysed thematically using a framework approach. SETTING: Recruitment was facilitated by two hospitals and five Australian cancer community groups. PARTICIPANTS: Informal caregivers (n=28; 16 men, 12 women; aged 18-80) of people living with cancer and receiving targeted/immunotherapies. RESULTS: Thematic analysis identified three findings, centred largely on the pervasive theme of hope in relation to precision therapies including: (1) precision as a key component of caregivers' hope; (2) hope as a collective practice between patients, caregivers, clinicians and others, which entailed work and obligation for caregivers; and (3) hope as linked to expectations of further scientific progress, even if there may be no personal, immediate benefit. CONCLUSIONS: Innovation and change in precision oncology are rapidly reconfiguring the parameters of hope for patients and caregivers, creating new and difficult relational moments and experiences in everyday life and in clinical encounters. In the context of a shifting therapeutic landscape, caregivers' experiences illustrate the need to understand hope as collectively produced, as emotional and moral labour, and as entangled in broader cultural expectations of medical advances. Such understandings may help clinicians as they guide patients and caregivers through the complexities of diagnosis, treatment, emerging evidence and possible futures in the precision era. Developing a better understanding of informal caregivers' experiences of caring for patients receiving precision therapies is important for improving support to patients and their caregivers.

The Enduring Effects of COVID for Cancer Care: Learning from Real-Life Clinical Practice.

For three years, COVID-19 has circulated among our communities and around the world, fundamentally changing social interactions, health care systems, and service delivery. For people living with (and receiving treatment for) cancer, pandemic conditions presented significant additional hurdles in an already unstable and shifting environment, including disrupted personal contact with care providers, interrupted access to clinical trials, distanced therapeutic encounters, multiple immune vulnerabilities, and new forms of financial precarity. In a 2020 perspective in this journal, we examined how COVID-19 was reshaping cancer care in the early stages of the pandemic and how these changes might endure into the future. Three years later, and in light of a series of interviews with patients and their caregivers from the United States and Australia conducted during the pandemic, we return to consider the potential legacy effects of the pandemic on cancer care. While some challenges to care provision and survivorship were unforeseen, others accentuated and amplified existing problems experienced by patients, caregivers, and health care providers. Both are likely to have enduring effects in the "post-pandemic" world, raising the importance of focusing on lessons that can be learned for the future.

Development of a Broth Microdilution Method To Characterize Chlorhexidine MICs among Bacteria Collected from 2005 to 2019 at Three U.S. Sites.

Chlorhexidine bathing to prevent transmission of multidrug-resistant organisms has been adopted by many U.S. hospitals, but increasing chlorhexidine use has raised concerns about possible emergence of resistance. We sought to establish a broth microdilution method for determining chlorhexidine MICs and then used the method to evaluate chlorhexidine MICs for bacteria that can cause health care-associated infections. We adapted a broth microdilution method for determining chlorhexidine MICs, poured panels, established quality control ranges, and tested Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae complex isolates collected at three U.S. sites. Chlorhexidine MICs were determined for 535 isolates including 129 S. aureus, 156 E. coli, 142 K. pneumoniae, and 108 E. cloacae complex isolates. The respective MIC distributions for each species ranged from 1 to 8 mg/L (MIC50 = 2 mg/L and MIC90 = 4 mg/L), 1 to 64 mg/L (MIC50 = 2 mg/L and MIC90 = 4 mg/L), 4 to 64 mg/L (MIC50 = 16 mg/L and MIC90 = 32 mg/L), and 1 to >64 mg/L (MIC50 = 16 mg/L and MIC90 = 64 mg/L). We successfully adapted a broth microdilution procedure that several laboratories were able to use to determine the chlorhexidine MICs of bacterial isolates. This method could be used to investigate whether chlorhexidine MICs are increasing. IMPORTANCE Chlorhexidine bathing to prevent transmission of multidrug-resistant organisms and reduce health care-associated infections has been adopted by many hospitals. There is concern about the possible unintended consequences of using this agent widely. One possible unintended consequence is decreased susceptibility to chlorhexidine, but there are not readily available methods to perform this evaluation. We developed a method for chlorhexidine MIC testing that can be used to evaluate for possible unintended consequences.

The changing faces of autism: The fluctuating international diagnostic criteria and the resulting inclusion and exclusion-A Norwegian perspective.

The common understanding of autism spectrum disorders (ASD) has gone through a number of permutations since the first description in 1943. Throughout these shifting understandings, there have been a number of behaviors and diagnostic criteria associated with the condition, many of which are missing in the most recent classifications. The rates of diagnoses of autism have increased greatly. However, there is no reason to think there has been any change in occurrence over the last 70 years, suggesting rather an increase in our knowledge and awareness. Autism has been the subject of several misapprehensions and misrepresentations throughout history. This might be due to heterogeneity of the cases. In addition, the diagnosing of autism spectrum disorders is mainly based on observation and behavioral interpretation, and thus dependent on subjective perceptions of the clinicians themselves. This current scoping review article intends to provide a view on the evolution of the concept of autism and the current stance within Norwegian scholarship, and how it is shaped by international discourses and cultural diversities Such changing concepts especially impacts people with the diagnosis, as it can affect their access to social services, as well as their self-identification as people with ASD.

High Rates of New Delhi Metallo-ß-Lactamase Carbapenemase Genes in Multi-Drug Resistant Gram-Negative Bacteria in Nicaragua.

Antimicrobial resistance (AMR) is a global public health crisis. Much of the burden of AMR in resource-limited settings remains unknown. This pilot study characterized clinical isolates of multidrug-resistant Gram-negative rods (MDR-GNRs) from Nicaragua. New Delhi metallo-ß-lactamase (NDM) carbapenemase genes were detected in 60% of isolates. Enterobacteriaceae had the highest rates of NDM detection, with 92% (50/54 isolates) positive by polymerase chain reaction (PCR). Pulsed-field gel electrophoresis (PFGE) analysis revealed patterns of clustering among isolates by two factors: plasmid profiles and year of culture. These findings of very high rates of NDM-carbapenemase genes in MDR-GNRs from hospitals throughout Nicaragua are alarming. Further research is needed to determine clinical and epidemiologic factors associated with multidrug-resistant isolates and to guide interventions to limit further spread.

The Paradoxical Effects of COVID-19 on Cancer Care: Current Context and Potential Lasting Impacts.

Coronavirus disease 2019 (COVID-19) has fundamentally disrupted the practice of oncology, shifting care onto virtual platforms, rearranging the logistics and economics of running a successful clinical practice and research, and in some contexts, redefining what treatments patients with cancer should and can receive. Since the start of the pandemic in early 2020, there has been considerable emphasis placed on the implications for patients with cancer in terms of their vulnerability to the virus and potential exposure in healthcare settings. But little emphasis has been placed on the significant, and potentially enduring, consequences of COVID-19 for how cancer care is delivered. In this article, we outline the importance of a focus on the effects of COVID-19 for oncology practice during and potentially after the pandemic, focusing on key shifts that are already evident, including: the pivot to online consultations, shifts in access to clinical trial and definitions of "essential care," the changing economics of practice, and the potential legacy effects of rapidly implemented changes in cancer care. COVID-19 is reshaping oncology practice, clinical trials, and delivery of cancer care broadly, and these changes might endure well beyond the short- to mid-term of the active pandemic. Therefore, shifts in practice brought about by the pandemic must be accompanied by improved training and awareness, enhanced infrastructure, and evidence-based support if they are to harness the positives and offset the potential negative consequences of the impacts of COVID-19 on cancer care.

Is Beauty in the Hand of the Writer? Influences of Aesthetic Preferences through Script Directions, Cultural, and Neurological Factors: A Literature Review.

Human experience surrounding the appreciation of beauty is not static. Many factors such as script direction and cultural differences directly impact whether, how and why we consider images beautiful. In an earlier study, Pérez González showed that 19th-century Iranian and Spanish professional photographers manifest lateral biases linked to reading writing direction in their compositions. The present paper aims to provide a general review on this topic and intends to highlight the most relevant studies reporting preferences in the appreciation of beauty in individuals with different reading and writing directions and belonging to different cultural backgrounds.