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Michael Weekes

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Nick K. Jones1,2*, Lucy Rivett1,2*, Chris Workman3, Mark Ferris3, Ashley Shaw1, Cambridge COVID-19 Collaboration1,4, Paul J. Lehner1,4, Rob Howes5, Giles Wright3, Nicholas J. Matheson1,4,6¶, Michael P. Weekes1,7¶1 Cambridge University NHS Hospitals Foundation Trust, Cambridge, UK2 Clinical Microbiology & Public Health Laboratory, Public Health England, Cambridge, UK3 Occupational Health and Wellbeing, Cambridge Biomedical Campus, Cambridge, UK4 Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, UK5 Cambridge COVID-19 Testing Centre and AstraZeneca, Anne Mclaren Building, Cambridge, UK6 NHS Blood and Transplant, Cambridge, UK7 Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK*Joint first authorship¶Joint last authorshipCorrespondence: [email protected] UK has initiated mass COVID-19 immunisation, with healthcare workers (HCWs) given early priority because of the potential for workplace exposure and risk of onward transmission to patients. The UK’s Joint Committee on Vaccination and Immunisation has recommended maximising the number of people vaccinated with first doses at the expense of early booster vaccinations, based on single dose efficacy against symptomatic COVID-19 disease.1-3At the time of writing, three COVID-19 vaccines have been granted emergency use authorisation in the UK, including the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech). A vital outstanding question is whether this vaccine prevents or promotes asymptomatic SARS-CoV-2 infection, rather than symptomatic COVID-19 disease, because sub-clinical infection following vaccination could continue to drive transmission. This is especially important because many UK HCWs have received this vaccine, and nosocomial COVID-19 infection has been a persistent problem.Through the implementation of a 24 h-turnaround PCR-based comprehensive HCW screening programme at Cambridge University Hospitals NHS Foundation Trust (CUHNFT), we previously demonstrated the frequent presence of pauci- and asymptomatic infection amongst HCWs during the UK’s first wave of the COVID-19 pandemic.4 Here, we evaluate the effect of first-dose BNT162b2 vaccination on test positivity rates and cycle threshold (Ct) values in the asymptomatic arm of our programme, which now offers weekly screening to all staff.Vaccination of HCWs at CUHNFT began on 8th December 2020, with mass vaccination from 8th January 2021. Here, we analyse data from the two weeks spanning 18thto 31st January 2021, during which: (a) the prevalence of COVID-19 amongst HCWs remained approximately constant; and (b) we screened comparable numbers of vaccinated and unvaccinated HCWs. Over this period, 4,408 (week 1) and 4,411 (week 2) PCR tests were performed from individuals reporting well to work. We stratified HCWs <12 days or > 12 days post-vaccination because this was the point at which protection against symptomatic infection began to appear in phase III clinical trial.226/3,252 (0·80%) tests from unvaccinated HCWs were positive (Ct<36), compared to 13/3,535 (0·37%) from HCWs <12 days post-vaccination and 4/1,989 (0·20%) tests from HCWs ≥12 days post-vaccination (p=0·023 and p=0·004, respectively; Fisher’s exact test, Figure). This suggests a four-fold decrease in the risk of asymptomatic SARS-CoV-2 infection amongst HCWs ≥12 days post-vaccination, compared to unvaccinated HCWs, with an intermediate effect amongst HCWs <12 days post-vaccination.A marked reduction in infections was also seen when analyses were repeated with: (a) inclusion of HCWs testing positive through both the symptomatic and asymptomatic arms of the programme (56/3,282 (1·71%) unvaccinated vs 8/1,997 (0·40%) ≥12 days post-vaccination, 4·3-fold reduction, p=0·00001); (b) inclusion of PCR tests which were positive at the limit of detection (Ct>36, 42/3,268 (1·29%) vs 15/2,000 (0·75%), 1·7-fold reduction, p=0·075); and (c) extension of the period of analysis to include six weeks from December 28th to February 7th 2021 (113/14,083 (0·80%) vs 5/4,872 (0·10%), 7·8-fold reduction, p=1x10-9). In addition, the median Ct value of positive tests showed a non-significant trend towards increase between unvaccinated HCWs and HCWs > 12 days post-vaccination (23·3 to 30·3, Figure), suggesting that samples from vaccinated individuals had lower viral loads.We therefore provide real-world evidence for a high level of protection against asymptomatic SARS-CoV-2 infection after a single dose of BNT162b2 vaccine, at a time of predominant transmission of the UK COVID-19 variant of concern 202012/01 (lineage B.1.1.7), and amongst a population with a relatively low frequency of prior infection (7.2% antibody positive).5This work was funded by a Wellcome Senior Clinical Research Fellowship to MPW (108070/Z/15/Z), a Wellcome Principal Research Fellowship to PJL (210688/Z/18/Z), and an MRC Clinician Scientist Fellowship (MR/P008801/1) and NHSBT workpackage (WPA15-02) to NJM. Funding was also received from Addenbrooke’s Charitable Trust and the Cambridge Biomedical Research Centre. We also acknowledge contributions from all staff at CUHNFT Occupational Health and Wellbeing and the Cambridge COVID-19 Testing Centre.

Guangming Wang

and 4 more

Tam Hunt

and 1 more

Tam Hunt [1], Jonathan SchoolerUniversity of California Santa Barbara Synchronization, harmonization, vibrations, or simply resonance in its most general sense seems to have an integral relationship with consciousness itself. One of the possible “neural correlates of consciousness” in mammalian brains is a combination of gamma, beta and theta synchrony. More broadly, we see similar kinds of resonance patterns in living and non-living structures of many types. What clues can resonance provide about the nature of consciousness more generally? This paper provides an overview of resonating structures in the fields of neuroscience, biology and physics and attempts to coalesce these data into a solution to what we see as the “easy part” of the Hard Problem, which is generally known as the “combination problem” or the “binding problem.” The combination problem asks: how do micro-conscious entities combine into a higher-level macro-consciousness? The proposed solution in the context of mammalian consciousness suggests that a shared resonance is what allows different parts of the brain to achieve a phase transition in the speed and bandwidth of information flows between the constituent parts. This phase transition allows for richer varieties of consciousness to arise, with the character and content of that consciousness in each moment determined by the particular set of constituent neurons. We also offer more general insights into the ontology of consciousness and suggest that consciousness manifests as a relatively smooth continuum of increasing richness in all physical processes, distinguishing our view from emergentist materialism. We refer to this approach as a (general) resonance theory of consciousness and offer some responses to Chalmers’ questions about the different kinds of “combination problem.”  At the heart of the universe is a steady, insistent beat: the sound of cycles in sync…. [T]hese feats of synchrony occur spontaneously, almost as if nature has an eerie yearning for order. Steven Strogatz, Sync: How Order Emerges From Chaos in the Universe, Nature and Daily Life (2003) If you want to find the secrets of the universe, think in terms of energy, frequency and vibration.Nikola Tesla (1942) I.               Introduction Is there an “easy part” and a “hard part” to the Hard Problem of consciousness? In this paper, we suggest that there is. The harder part is arriving at a philosophical position with respect to the relationship of matter and mind. This paper is about the “easy part” of the Hard Problem but we address the “hard part” briefly in this introduction.  We have both arrived, after much deliberation, at the position of panpsychism or panexperientialism (all matter has at least some associated mind/experience and vice versa). This is the view that all things and processes have both mental and physical aspects. Matter and mind are two sides of the same coin.  Panpsychism is one of many possible approaches that addresses the “hard part” of the Hard Problem. We adopt this position for all the reasons various authors have listed (Chalmers 1996, Griffin 1997, Hunt 2011, Goff 2017). This first step is particularly powerful if we adopt the Whiteheadian version of panpsychism (Whitehead 1929).  Reaching a position on this fundamental question of how mind relates to matter must be based on a “weight of plausibility” approach, rather than on definitive evidence, because establishing definitive evidence with respect to the presence of mind/experience is difficult. We must generally rely on examining various “behavioral correlates of consciousness” in judging whether entities other than ourselves are conscious – even with respect to other humans—since the only consciousness we can know with certainty is our own. Positing that matter and mind are two sides of the same coin explains the problem of consciousness insofar as it avoids the problems of emergence because under this approach consciousness doesn’t emerge. Consciousness is, rather, always present, at some level, even in the simplest of processes, but it “complexifies” as matter complexifies, and vice versa. Consciousness starts very simple and becomes more complex and rich under the right conditions, which in our proposed framework rely on resonance mechanisms. Matter and mind are two sides of the coin. Neither is primary; they are coequal.  We acknowledge the challenges of adopting this perspective, but encourage readers to consider the many compelling reasons to consider it that are reviewed elsewhere (Chalmers 1996, Griffin 1998, Hunt 2011, Goff 2017, Schooler, Schooler, & Hunt, 2011; Schooler, 2015).  Taking a position on the overarching ontology is the first step in addressing the Hard Problem. But this leads to the related questions: at what level of organization does consciousness reside in any particular process? Is a rock conscious? A chair? An ant? A bacterium? Or are only the smaller constituents, such as atoms or molecules, of these entities conscious? And if there is some degree of consciousness even in atoms and molecules, as panpsychism suggests (albeit of a very rudimentary nature, an important point to remember), how do these micro-conscious entities combine into the higher-level and obvious consciousness we witness in entities like humans and other mammals?  This set of questions is known as the “combination problem,” another now-classic problem in the philosophy of mind, and is what we describe here as the “easy part” of the Hard Problem. Our characterization of this part of the problem as “easy”[2] is, of course, more than a little tongue in cheek. The authors have discussed frequently with each other what part of the Hard Problem should be labeled the easier part and which the harder part. Regardless of the labels we choose, however, this paper focuses on our suggested solution to the combination problem.  Various solutions to the combination problem have been proposed but none have gained widespread acceptance. This paper further elaborates a proposed solution to the combination problem that we first described in Hunt 2011 and Schooler, Hunt, and Schooler 2011. The proposed solution rests on the idea of resonance, a shared vibratory frequency, which can also be called synchrony or field coherence. We will generally use resonance and “sync,” short for synchrony, interchangeably in this paper. We describe the approach as a general resonance theory of consciousness or just “general resonance theory” (GRT). GRT is a field theory of consciousness wherein the various specific fields associated with matter and energy are the seat of conscious awareness.  A summary of our approach appears in Appendix 1.  All things in our universe are constantly in motion, in process. Even objects that appear to be stationary are in fact vibrating, oscillating, resonating, at specific frequencies. So all things are actually processes. Resonance is a specific type of motion, characterized by synchronized oscillation between two states.  An interesting phenomenon occurs when different vibrating processes come into proximity: they will often start vibrating together at the same frequency. They “sync up,” sometimes in ways that can seem mysterious, and allow for richer and faster information and energy flows (Figure 1 offers a schematic). Examining this phenomenon leads to potentially deep insights about the nature of consciousness in both the human/mammalian context but also at a deeper ontological level.

Susanne Schilling*^

and 9 more

Jessica mead

and 6 more

The construct of wellbeing has been criticised as a neoliberal construction of western individualism that ignores wider systemic issues including increasing burden of chronic disease, widening inequality, concerns over environmental degradation and anthropogenic climate change. While these criticisms overlook recent developments, there remains a need for biopsychosocial models that extend theoretical grounding beyond individual wellbeing, incorporating overlapping contextual issues relating to community and environment. Our first GENIAL model \cite{Kemp_2017} provided a more expansive view of pathways to longevity in the context of individual health and wellbeing, emphasising bidirectional links to positive social ties and the impact of sociocultural factors. In this paper, we build on these ideas and propose GENIAL 2.0, focusing on intersecting individual-community-environmental contributions to health and wellbeing, and laying an evidence-based, theoretical framework on which future research and innovative therapeutic innovations could be based. We suggest that our transdisciplinary model of wellbeing - focusing on individual, community and environmental contributions to personal wellbeing - will help to move the research field forward. In reconceptualising wellbeing, GENIAL 2.0 bridges the gap between psychological science and population health health systems, and presents opportunities for enhancing the health and wellbeing of people living with chronic conditions. Implications for future generations including the very survival of our species are discussed.  

Mark Ferris

and 14 more

IntroductionConsistent with World Health Organization (WHO) advice [1], UK Infection Protection Control guidance recommends that healthcare workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) should use fluid resistant surgical masks type IIR (FRSMs) as respiratory protective equipment (RPE), unless aerosol generating procedures (AGPs) are being undertaken or are likely, when a filtering face piece 3 (FFP3) respirator should be used [2]. In a recent update, an FFP3 respirator is recommended if “an unacceptable risk of transmission remains following rigorous application of the hierarchy of control” [3]. Conversely, guidance from the Centers for Disease Control and Prevention (CDC) recommends that HCWs caring for patients with COVID-19 should use an N95 or higher level respirator [4]. WHO guidance suggests that a respirator, such as FFP3, may be used for HCWs in the absence of AGPs if availability or cost is not an issue [1].A recent systematic review undertaken for PHE concluded that: “patients with SARS-CoV-2 infection who are breathing, talking or coughing generate both respiratory droplets and aerosols, but FRSM (and where required, eye protection) are considered to provide adequate staff protection” [5]. Nevertheless, FFP3 respirators are more effective in preventing aerosol transmission than FRSMs, and observational data suggests that they may improve protection for HCWs [6]. It has therefore been suggested that respirators should be considered as a means of affording the best available protection [7], and some organisations have decided to provide FFP3 (or equivalent) respirators to HCWs caring for COVID-19 patients, despite a lack of mandate from local or national guidelines [8].Data from the HCW testing programme at Cambridge University Hospitals NHS Foundation Trust (CUHNFT) during the first wave of the UK severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic indicated a higher incidence of infection amongst HCWs caring for patients with COVID-19, compared with those who did not [9]. Subsequent studies have confirmed this observation [10, 11]. This disparity persisted at CUHNFT in December 2020, despite control measures consistent with PHE guidance and audits indicating good compliance. The CUHNFT infection control committee therefore implemented a change of RPE for staff on “red” (COVID-19) wards from FRSMs to FFP3 respirators. In this study, we analyse the incidence of SARS-CoV-2 infection in HCWs before and after this transition.

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Claus Kohfahl

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The knowledge of soil moisture spatio-temporal variability is highly relevant for water resources management. This is especially significant in highly demanding areas of arid and semiarid regions where sensitive ecosystems, agriculture and recreational areas are competing for water resources. This study reports an analysis of the spatial-temporal variability of soil moisture data for a small to medium-scale network in a coastal wetland of southwestern Spain. Measurements were taken from 5 sites located in the Doñana National Park, with an extension of approx. 25 × 3 km over the time-period of one hydrological year from September 2017 to September 2018. Absolute soil moisture was separated in two components: the temporal mean (time-invariant term) and the deviations from the mean or anomalies (time-variant term). The time-invariant component was generally the main contributor to the total spatial variance of absolute soil moisture data and it was mostly controlled by the groundwater levels in the area. Nevertheless, the time variant terms have a huge effect on soil moisture variability in very dry states at all 5 sites. Time-dependent patterns were found between average soil moisture state and the variance and covariance of both the time-variant and time-invariant components of soil moisture, which could be used for the up and downscaling of soil moisture from satellite data. Those patterns were only affected by heavy rainfalls giving rise to hysteretic behavior. This study shows that even though groundwater level is a time-variant variable, it significantly affects soil moisture’s time-variant and time-invariant terms.

Andrea Casella

and 5 more

Stimulus-driven actions are preceded by preparatory brain activity that can be expressed by event-related potentials (ERP). Literature on this topic has mainly focused on simple actions, such as the finger keypress, finding activity in frontal, parietal, and occipital areas detectable up to two seconds before the stimulus onset. However, little is known about the preparatory brain activity when the action complexity increases, and specific brain areas designated to achieve movement integration intervene. The main aim of this paper is to identify the time course of preparatory brain activity associated with actions of increasing complexity using ERP analysis and a visuomotor discrimination task. Motor complexity was manipulated by asking nineteen volunteers to provide their response by simply pressing a key or by adding to the keypress arm extensions (reaching) alone, or in combination with a standing step (involving the whole body). Results showed that these actions of increasing levels of complexity appear to be associated with different patterns of preparatory brain activity. Specifically, the simple keypress was characterized by the largest motor excitatory preparation in premotor areas paralleled by the largest prefrontal inhibitory/attentional control. Reaching presented a dominant parietal preparation confirming the role of these integration areas in reaching actions toward a goal. Stepping was characterized by localized activity in the bilateral dorsomedial parieto-occipital areas attributable to sensory readiness, for the approaching stimulus. In conclusion, the brain is able to optimally anticipate any stimulus-driven action modulating the activity in the brain areas specialized in the preparation of that action type.

Ante Damjanović

and 5 more

Mucoepidermoid carcinoma: A case reportDaniela Kraljević MD, PhD 1 / Ante Damjanović MD1 / Tamara Nikše MD 1 / Ivan Pavić MD, PhD 2 / Iva Mihatov Štefanović MD, PhD3 / Josip Pejić MD41 UCH Mostar, Pediatric Clinic, Department of Pulmonology and Alergology2 Children’s Hospital Zagreb, Pediatric Clinic, Department of Pediatric Pulmonology, Allergology, Immunology and Rheumatology3 CHC „Sestre Milosrdnice“ Zagreb, Pediatric Clinic, Department of Endocrinology, Diabetes, Pulmonology and Allergology4 CH Dubrava, Surgery Clinic, Department for thoracic surgeryCorrenspondence: Ante Damjanović, MD, UCH Mostar, Pediatric Clinic, Department of pulmonology and alergology, Bijeli Brijeg, 88 000, Mostar, Bosnia and HerzegovinaEmail: [email protected] pulmonology, cancer, lungs1 INTRODUCTIONPrimary lung neoplasms in children are rare. A significantly larger number of lung neoplasms are secondary neoplasms, mostly metastases from some other primary tumor process.1 Primary lung tumors in children, although rare, are mostly malignant (75% of cases). Carcinoids account for 40% of these tumors, bronchogenic carcinomas for 17% of cases, and pleuropulmonary blastomas for about 15% of cases.2 Mucoepidermoid carcinoma is the most common type of salivary gland carcinoma in the adult population. It can also be found in the bronchi and in the thyroid gland. It is not frequently found in the lungs, especially in children, where it constitutes approximately 0.1-0.2% of all primary lung tumors.3It originates from glandular tissue identical to that of the salivary glands, which is located in the submucosa of the trachea and bronchi.4 We will present a rare case of mucoepidermoid carcinoma of the right bronchus in a six-year-old girl who was hospitalized due to right-sided pneumonia and pleural effusion.2 CASE PRESENTATIONA six-year-old patient was referred to our clinic due to an elevated body temperature, shivering, and vomiting. Laboratory diagnostics were performed at the local Health Center (CRP 338 mg/L, WBC 18.8 x 10^9/L (neutrophils 78%)), along with a chest X-ray, which revealed right-sided pneumonia with pleural effusion. The patient had previously experienced chickenpox seven months ago and had two episodes of pneumonia since, which were treated on an outpatient basis.The clinical examination of the patient revealed the following: Subfebrile temperature (37.8°C), tachycardia (118/min); reduced breath sounds on auscultation over the right lung, with no breath sounds heard at the base. Additional radiological assessment (ultrasound of the lung base) confirmed the presence of pleural effusion.Parenteral (ceftriaxone, clindamycin) and oral (azithromycin) antimicrobial therapy was prescribed, and a pediatric surgeon was consulted. There was no indication for pleural drainage.The patient responded positively to the prescribed therapy, becoming afebrile on the fifth day of hospitalization. Follow-up X-rays showed partial regression of the previously described inflammatory changes, and a follow-up ultrasound confirmed the regression of pleural effusion. The girl was discharged for home treatment with continued oral antimicrobial therapy (cefpodoxime), with a scheduled follow-up appointment at the clinic.

Gonca BURAN

and 1 more

Background: Infertility is an important problem that is increasing worldwide and affecting individuals physiologically, psychologically, and socially. Purpose: To determine the effect of the social-emotional capacities of infertile individuals on their stress levels and ability to cope with infertility stress. Methods: The cross-sectional study was conducted with a total of 428 men and women diagnosed with infertility at a University Hospital Fertility Center. Data were collected with the Infertility Stress Scale (COMPI-FPSS), the Infertility Stress Coping Strategies Scales (COMPI-CSS) and the Social Emotional Capacity Measurement Tool in Infertile Individuals (SCREENIVF), and surveys gathering demographic and infertility information. Results: The average age of the women was 32.92± 4.95 years and the average age of their husbands was 34.86± 4.77 years. The mean scores of individual (t = 2.536, p = 0.012), marital (t= 3.633, p = 0.026), and social stresses (t = 2.987, p = 0.034) due to infertility, which are COMPI-FPSS subgroups, were statistically significantly higher for women than for men. The correlation between active avoidance coping, passive avoidance coping, and helplessness shows that active avoidance coping methods and passive avoidant coping methods are associated with increased helplessness (r=447, p< .001; r=414, p< .001, respectively). The study model showed that while the independent variable of social-emotional capacity was associated with infertility stress (p <.001), age (p < .05), and years of marriage (p < .001), the relationship of methods of coping with infertility stress was insignificant. The factors included in the model explain 23.2% of social-emotional capacity (R 2=0.232, F (6;421) =21.196; p<.001). Conclusion: Women who undergo infertility treatment have more personal, marital, and social stress than men. While the social-emotional capacities of infertile individuals affect the infertility stress caused by personal, marital, and social stress, it is not related to the methods used by the individual to cope with infertility stress. Considering these risk factors can help determine counseling approaches.
Rationale: In the outpatient setting, inhaled corticosteroids (ICS) are frequently given to children with bronchopulmonary dysplasia (BPD) for treatment of respiratory and asthma associated symptoms. In this study we sought to determine if correlations existed between ICS use and ICS initiation and patient characteristics and outpatient respiratory outcomes. Methods: This study included children with the diagnosis of BPD (n=661) who were seen in outpatient pulmonary clinics at the Children’s Hospital of Philadelphia between 2016-2021. Chart review was used to determine patient demographics, use and timing of ICS initiation, asthma diagnosis and acute care usage following initial hospital discharge. Results: At the first pulmonary visit, 9.2% of children had been prescribed an ICS at NICU discharge, 13.9% had been prescribed an ICS after NICU discharge but before their first pulmonary appointment, and 6.9% were prescribed an ICS at completion of initial pulmonary visit. Children started on an ICS as outpatients, had a higher likelihood of ER visits (adjusted OR: 2.68 ±0.7), hospitalizations (4.81 ± 1.16) and a diagnosis of asthma (3.58 ± 0.84), compared to children never on an ICS. Of those diagnosed with asthma, children prescribed an ICS in the outpatient setting received the diagnosis at an earlier age. No associations between NICU BPD severity scores and ICS use were found. Conclusions: This study identifies an outpatient BPD phenotype associated with ICS use and ICS initiation independent of NICU severity score. Additionally, outpatient ICS initiation correlates with a subsequent diagnosis of asthma and acute care usage in children with BPD.

Maria Symeonaki

and 6 more

This study offers an insightful glimpse into the experiences of working men and women in Greece during the unprecedented first lockdown from March to May 2020. As the pandemic enforced restrictions that led to teleworking, parents found themselves overwhelmed with the simultaneous demands of work, home-schooling, and childcare, all without external support. This situation severely tested work-life balance and placed additional strain on relationships between partners due to the increased burden of unpaid work. This paper shares findings from the Greek segment of the "Covid19-Health emergency and work-life balance" research, conducted across six countries during the pandemic's initial surge using a standardized online questionnaire and quota sampling. The study included 840 Greek participants aged 18 to 70, analysing the pandemic's effects on work relations, workspace and time organization, job performance, the balance between paid and unpaid work, domestic roles and tasks division, and familial and partner relationships. Employing a work-life balance Likert scale (WLB) with 8 items based on Hayman (2005) and Fisher-McAuley et al. (2003), the study utilized multinomial logistic regression to delve into factors affecting work-life balance during COVID-19. This statistical method predicts outcomes based on a mix of continuous and categorical predictors, aiming to identify individuals with high or low WLB scores using sociodemographic variables such as gender, education level, age group, and marital status.

Anali Riahi

and 4 more

Pseudomonas aeruginosa is a commonly found Gram-negative bacterium in healthcare facilities and is renowned for its ability to form biofilms and its virulence factors that are controlled by quorum sensing (QS) systems. The increasing prevalence of multidrug-resistant strains of this bacterium poses a significant challenge in the field of medicine. Consequently, the exploration of novel antimicrobial agents has become a top priority. This research aims to optimize chitosan derived from white shrimp (Metapenaeus affinis) using the Response Surface Methodology computational approach. The objective is to investigate chitosan’s potential as a solution for inhibiting QS activity and biofilm formation in P. aeruginosa ATCC 10145. Under optimized conditions, chitin treated (NaOH: 1.41 M) for 15.75 hours, HCl (7.49% vol) for 2.01 hours, at a deacetylation temperature of 81.15 °C. Resulting chitosan exhibited a degree of deacetylation exceeding 93.98%, as confirmed by Fourier-transform infrared spectral analysis, indicating its high purity. The extracted chitosan demonstrated a significant synergistic antibiotic effect against P. aeruginosa when combined with ceftazidime, enhancing its bactericidal activity by up to 15-fold. In addition, sub-MIC concentrations of extracted chitosan (10 and 100 μg/mL) successfully reduced the production of pyocyanin and rhamnolipid, as well as the swimming motility, protease activity and biofilm formation in comparison to the control group. Moreover, chitosan treatment downregulated the RhlR and LasR genes in P. aeruginosa when compared to the control group (P<0.05). The optimized chitosan extract shows significant potential as a coating agent for surgical equipment, effectively preventing nosocomial infections caused by P. aeruginosa pathogens.

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Karma Norbu

and 3 more

Introduction: Scrub typhus is a neglected life threatening acute febrile illness caused by bacteria Orientia tsutsugamushi and it is a vector-borne zoonotic disease. In 2009, scrub typhus outbreak at Gedu has awakened Bhutan on the awareness and testing of the disease.Information and data of the study highlights the need for in depth surveillance, awareness among prescribers and initiate preventive measures in the country. Methods: We used retrospective descriptive study through review of laboratory registers across three health centres in Zhemgang district, south central Bhutan. The laboratories registers have been transcribed into CSV file using Microsoft excel. Variables of interest were collected from the registers and then analysed using open statistical software R, (R Core Team (2020). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria.) And use of mStats package, (MyoMinnOo (2020). mStats: Epidemiological DataAnalysis. R package version 3.4.0.) Results: Of the total 922 tests prescribed for suspected scrub typhus in the three health centers in Zhemgang, only 8.2 % (n=76) were tested positive. Of these, Panbang Hospital had highest reported positive for scrub typhus with 56.6 %( n=43) followed by Yebilaptsa Hospital 35.5 %( n=27) and Zhemgang Hospital with 7.9 %( n=6). The female gender is comparably more affected as opposed to male with 57.9% (n=44) of the positive cases being female. The prevalence of scrub typhus seems to be affected by the seasonal variation as the months of Spring, Summer and Autumn together accounts for 98.7%(n=75) of total positive cases. The year 2019 noted significant scrub typhus cases accounting to 89.5 %(n=68) of the total positive cases over the two years. Conclusions:The overall tests tested positive of the scrub typhus infection within two years was 8.2%.

Selahattin Semiz

and 2 more

Monoclonal antibodies (MAbs) are powerful therapeutic tools in modern medicine and represent a rapidly expanding multi-billion USD market. While bioprocesses are generally well understood and optimized for MAbs, online quality control remains challenging. Notably, N-glycosylation is a critical quality attribute of MAbs as it affects binding to Fcγ receptors (FcγR), impacting the efficacy and safety of MAbs. Traditional N-glycosylation characterization methods are ill-suited for online monitoring of a bioreactor; in contrast, surface plasmon resonance (SPR) represents a promising avenue, as SPR biosensors can record MAb-FcγR interactions in real-time and without labelling. In this study, we produced five lots of differentially glycosylated Trastuzumab (TZM) and finely characterized their glycosylation profile by HILIC-UPLC chromatography. We then compared the interaction kinetics of these MAb lots with four FcγRs including FcγRIIA and FcγRIIB at 5 oC and 25 oC. When interacting with FcγRIIA/B at low temperature, the differentially glycosylated MAb lots exhibited distinct kinetic behaviours, contrary to room-temperature experiments. Galactosylated TZM (1) and core fucosylated TZM (2) could be discriminated and even quantified using an analytical technique based on the area under the curve (AUC) of the signal recorded during the dissociation phase of a SPR sensorgram describing the interaction with FcγRIIA (1) or FcγRII2B (2). Because of the rapidity of the proposed method (less than 5 minutes per measurement) and the small sample concentration it requires (as low as 30 nM, exact concentration not required), it could be a valuable process analytical technology for MAb glycosylation monitoring.

Ivy Bourgeault

and 2 more

The global health workforce crisis, simmering for decades, was brought to a rolling boil by the COVID-19 Pandemic in 2020. With scarce literature, evidence, or best practices to draw from, countries around the world moved to flex their workforces to meet acute challenges of the pandemic, facing demands related to patient volume, patient acuity, and worker vulnerability and absenteeism. One early hypothesis suggested that the acute, short-term pandemic phase would be followed by several waves of resource demands extending over the longer term. However, as the acute phase of the pandemic abated, temporary workforce policies expired and others were repealed with a view of returning to “normal”. The workforce needs of subsequent phases of pandemic effects were largely ignored despite our new equilibrium resting nowhere near our pre-COVID baseline. In this paper, we describe Canada’s early pandemic workforce response. We report the results of an environmental scan of the early workforce strategies adopted in Canada during the first COVID wave of the COVID 19 pandemic. Within a three-part framework for supporting a sustainable health workforce, we describe 470 strategies and policies that aimed to increase the numbers and flexibility of health workers in Canada, and to maximise their continued availability to work. These strategies targeted all types of health workers and roles, enabling changes to the places health work is done, the way in which care is delivered, and the mechanisms by which it is regulated. Telehealth strategies and virtual care were the most prevalent, followed by role expansion, licensure flexibility, mental health supports for workers, and return to practice of retirees. We explore the degree to which these short-term, acute response strategies might be adapted or extended to support the evolving workforce’s long-term needs.

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