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Xiang-Rong Bai,1,* Jing-Rong Cao,2,* Zhi-Zhou Wang,1 Wen-Chao Li,1 Dian-Dian Chen,2 Ran Lou,3 Xin Qu,4 Su-Ying Yan1 1Department of Pharmacy, Xuan Wu Hospital Capital Medical University, National Gerontic Disease Clinical Research Center, Beijing, 100053, People’s Republic of China; 2Department of Clinical Laboratory, Xuan Wu Hospital Capital Medical University, National Gerontic Disease Clinical Research Center, Beijing, 100053, People’s Republic of China; 3Department of Intensive Medicine, Xuan Wu Hospital Capital Medical University, National Gerontic Disease Clinical Research Center, Beijing, 100053, People’s Republic of China; 4Intensive Care Unit, Department of Neurosurgery, Xuan Wu Hospital Capital Medical University, National Gerontic Disease Clinical Research Center, Beijing, 100053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Su-Ying Yan, Department of Pharmacy, Xuan Wu Hospital Capital Medical University, National Gerontic Disease Clinical Research Center, No. 45 Changchun Street, Xi Cheng District, Beijing, 100053, People’s Republic of China, Tel/Fax +86 10-63012837, Email yansuying10@sina.cnPurpose: Tigecycline is an agent for carbapenemase-producing Klebsiella pneumonia (KPC-KP), given its penetration into lung tissues. Our study focused on the molecular and clinical efficacy of tigecycline for hospital-acquired pneumonia (HAP) in the ICU.Patients and Methods: A retrospective cohort study of 52 adult KPC-KP HAP patients by searching hospital medical records from January 2018 to December 2020 was established to investigate the epidemiology of KPC-KP infections for tigecycline treatment and the associated clinical efficacy of tigecycline. The KPC-KP isolates underwent multilocus sequence typing. Molecular typing, antimicrobial resistance, and virulence profiling were also analyzed by whole-genome sequencing of KPC-KP.Results: Among 52 patients with KPC-KP, the ICU mortality rate was 14/52 (27%), and there was no significant statistical difference in mortality between the effective group and failure group (p = 0.754). However, the duration of tigecycline was statistically different between the two groups of patients (14.4 vs 10 days, p=0.046). The total bacterial clearance rate was 6/52 (11.5%). There was no significant statistical difference in both groups (p=0.416). Antibiotic resistance genes (aac3iia) and virulence gene (AREO-iutA, Capsule-wzc) were negatively correlated with clinical efficacy (p = 0.011, OR = 1.237).Conclusions: Blakpc was the main carbapenemase in all K. pneumoniae strains. ST11-KL64 KPC-KP was the most common virulence factors in KPC-KP isolates. This study suggested that antibiotic resistance genes (aac3iia) and virulence gene (AREO-iutA, Capsule-wzc) were independent mortality risk factors for patients with Klebsiella pneumoniae carbapenemase-2 producing K. pneumoniae infections, when during the tigecycline treatment. Molecular analysis of K. pneumoniae may provide an option when choosing the antimicrobial treatment.Keywords: Klebsiella pneumoniae, carbapenemase, virulence factors, resistance genes, hospital-acquired pneumonia

Shu-Chen Dong,1,* Huan-Huan Sha,1,* Xiao-Yue Xu,1 Tian-Mu Hu,2 Rui Lou,1 Huizi Li,1 Jian-Zhong Wu,1 Chen Dan,1 Jifeng Feng1 1Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, China; 2Department of Biological Science, Purdue University, West Lafayette, IN, USA *These authors contributed equally to this work Abstract: Glutathione S-transferase π (GSTπ) is a Phase II metabolic enzyme that is an important facilitator of cellular detoxification. Traditional dogma asserts that GSTπ functions to catalyze glutathione (GSH)-substrate conjunction to preserve the macromolecule upon exposure to oxidative stress, thus defending cells against various toxic compounds. Over the past 20 years, abnormal GSTπ expression has been linked to the occurrence of tumor resistance to chemotherapy drugs, demonstrating that this enzyme possesses functions beyond metabolism. This revelation reveals exciting possibilities in the realm of drug discovery, as GSTπ inhibitors and its prodrugs offer a feasible strategy in designing anticancer drugs with the primary purpose of reversing tumor resistance. In connection with the authors’ current research, we provide a review on the biological function of GSTπ and current developments in GSTπ-targeting drugs, as well as the prospects of future strategies. Keywords: tumor resistance, glutathione S-transferase pi, drug treatment

The study investigated the difficulties encountered by Grade 11 teachers in teaching Senior High School General Mathematics, the reasons for the problems, and the strategies employed by teachers in overcoming the challenges with an end view of developing training design. The sequential explanatory mixed methods design was used in the study with the aid of a questionnaire checklist and an interview to validate the answers generated by the questionnaires. The study revealed that the challenges in teaching emerged due to time constraints and mastery issues of contents. Though teachers were pedagogically and technologically equipped to teach the course, however, some have poor time management and link to peers to share the best strategies to cope with the problems. Hence, training, as well as seminars and workshops for the unmastered competencies/contents and the competencies with no strategies applied to deal with the difficulties in teaching, are to be provided to Grade 11 General Mathematics teachers by implementing the training design developed by the researchers.

Microplastic, resulting from the breakdown of larger plastic objects, poses substantial threats to ecosystems and human health. This research addresses the escalating environmental concern of airborne microplastics by developing a low-cost detection machine employing infrared sensors. The near-infrared light is attached to the machine for detection using the sensors. Different types of microplastic, specifically less than 5mm, are used. There are 3 types of plastics used for detection, 30 pieces each of polyethylene, polystyrene, and polyester microplastics. Each type of microplastic is tested for detection in different time frames, 1, 2, 3, 4, and 5 minutes each, and the three types of plastics are combined randomly for the last detection with the same number of minutes. Because of the final results, it can determine the effectiveness of the sensor in detecting airborne microplastics in terms of the number of correctly detected microplastics. In conclusion, this research advances our capacity to detect airborne microplastics, contributing to environmental conservation and public health protection. The detection machine's development and the insights gained from the study have broader implications for standardizing methodologies, advancing technology, and fostering collaborative efforts in addressing the challenges posed by airborne microplastics. [ABSTRACT FROM AUTHOR]

BackgroundThere is an urgent need to better understand the factors that predict mental wellbeing in vocationally active adults during globally turbulent times.AimTo explore the relationship between psychological detachment from work (postulated as a key recovery activity from work) in the first national COVID-19 lockdown with health, wellbeing, and life satisfaction of working age-adults one year later, within the context of a global pandemic.MethodsWellbeing of the Workforce (WoW) was a prospective longitudinal cohort study, with two waves of data collection (Time 1, April-June 2020: T1 n = 337; Time 2, March-April 2021: T2 = 169) corresponding with the first and third national COVID-19 lockdowns in the UK. Participants were >18 years, who were employed or self-employed and working in the UK. Descriptive and parametric (t-tests and linear regression) and nonparametric (chi square tests) inferential statistics were employed.ResultsRisk for major depression (T1: 20.0% to T2: 29.0%, p = .002), poor general health (T1: 4.7% to T2: 0%, p = .002) and poor life satisfaction (T1: 15.4% to T2: 25.4%, p = .002) worsened over time, moderate-to-severe anxiety remained stable (T1: 26.1% to T2: 30.2%, p = .15). Low psychological detachment from work was more prevalent in the first wave (T1: 21.4% and T2: 16.0%), with a moderate improvement observed from T1 to T2 (t (129) = -7.09, p < .001). No differences were observed with work status (employed/self-employed), except for self-employed workers being more likely to report poor general health at T1 (16.1%, p = .002). Better psychological wellbeing, lower anxiety and higher life satisfaction at T2 were observed in those who reported better psychological detachment from work at T1 (β = .21, p = .01; β = -.43, p < .001; β = .32, p = .003, respectively), and in those who improved in this recovery activity from T1 to T2 (β = .36, p < .001; β = -.27, p < .001; β = .27, p = .008, respectively), controlling for age, gender and ethnicity.ConclusionThe ability to psychologically detach from work during the first pandemic lockdown, and improvement in this recovery activity over time, predicted better mental wellbeing and quality of life in vocationally active adults after one year of a global crisis, irrespective of work status. Interventions to encourage workers to psychologically detach from work may help to support employee wellbeing at all times, not only in the extreme circumstances of pandemics and economic uncertainty.

Abstract Background People who use illicit drugs cumulate medical and psychosocial vulnerabilities, justifying a rounded health approach. Both caregivers and patients can form barriers to accessing care, leading to inadequate care. This study aimed to identify the needs and expectations of such patients in general practice. Methods Qualitative research was conducted using semi-structured interviews with 23 people with illicit substance use disorder in Brussels in 2020. Multicentric recruitment was conducted to obtain a heterogeneous mix of sociodemographic profiles and care trajectories. Thematic analysis was performed using RQDA package software. Results Participants highlighted several vulnerabilities. These include the presence of significant self-stigmatization and guilt, sometimes to the extent of self-dehumanization, even after years of care, and overdoses masking suicide attempts and early memory disorders. Multiple substance use, smoking in almost all participants, and misuse of benzodiazepines were also noted. The majority of participants expressed the need for an open-minded, non-stigmatizing and empathic GP with a holistic approach that could guide them throughout their life course. The competencies of the GPs in the field of addiction seemed secondary to the participants. Knowledge and good collaboration with the mental health network were assets. Conclusion Participants expressed the need for GPs with good interpersonal skills, including a non-stigmatizing attitude. The care coordinator role of the GP was highlighted as a key element, as it was a holistic approach focusing on global health (including the social determinants of health) and not only on substance use disorders.

Northern sand lance (Ammodytes dubius) are essential forage fish in most offshore, temperate-to-polar waters on the Northwest Atlantic shelf (NWA), but their population structure and genetic separation from the American sand lance (A. americanus) remain unresolved. We assembled a reference genome for A. dubius (first in the Ammodytidae) and then used low-coverage whole genome sequencing on 262 specimens collected across the species distribution (Mid-Atlantic Bight to Greenland) to quantify genetic differentiation between geographic regions based on single nucleotide polymorphisms. We found strong separation between A. dubius from locations north and south of the Scotian Shelf, largely due to massive genetic differentiation spanning most of chromosomes 21 and 24. Genetic distance increased with geographic distance in the smaller southern cluster but not in the larger northern cluster, where genetic homogeneity appeared across large geographic distances (>103 km). The two genetic clusters coincide with a clear break in winter sea surface temperature, suggesting that differential offspring survival, rather than limited transport, causes a break in realized connectivity. Nuclear and mitochondrial DNA both clearly delineated A. dubius from A. americanus , thereby confirming a species boundary through spatial niche partitioning into inshore (A. americanus) and offshore (A. dubius) sand lance species on the NWA. [ABSTRACT FROM AUTHOR]

Abstract Introduction People with substance use disorder (SUD) deal with stigmatization in various areas of life, including healthcare system. In this study, we investigated the attitudes of final-year medical students towards SUD people and attempted to understand their influence. Methods We conducted a two-stage cluster analysis (hierarchical ascending classification followed by K-means clustering) based on the “beSAAS”. We administrated this 23-item questionnaire to 923 final-year medical students in Belgium (response rate = 71,1%). Sociodemographic characteristics were compared between the clusters. Results Four clusters of students with specific characteristics were identified in this study. The first, “The Inclusives” (including 27,9% of respondents) had the least negative attitudes; they wanted to specialize mainly in psychiatry and gynecology. The second, “The Centrists" (23,6%) consisted mainly of male students. They had many private and professional experiences with substance use and considered themselves less healthy than others did. Most wanted to specialize in pediatrics and general practice. Their attitudes were slightly negative towards people with SUD. The third, “The Moralists” (27,6%), were mainly older, from non-European countries, had the least experience with substance use (or contact mainly in hospitals), had the less high mother’s level of education and reported excellent health. They were heading toward other specialties. They had the most stereotypes and moralism, and less treatment optimism. The fourth, “The Specialist care-oriented” (20,8%), were the most in favor of specialized treatment. This group had a higher proportion of Belgian, females, and students who had specific contact with this population. They especially intended to specialize in internal medicine. Conclusion This study revealed 4 profiles of medical students with different attitudes towards SUD people. “The Moralists”, including more than a quarter of the respondents, were characterized by strong stereotypes and moralism and little treatment optimism. These clusters could contribute to the design of a learner-centered program aimed at addressing stigma within the main curriculum.