Search

Abstract Background The continuous exposure of blood to a non-biological surface during extracorporeal membrane oxygenation (ECMO) may lead to progressive thrombus formation in the oxygenator, hemolysis and consequently impaired gas exchange. In most centers oxygenator performance is monitored only on a once daily basis. Carboxyhemoglobin (COHb) is generated upon red cell lysis and is routinely measured with any co-oximetry performed to surveille gas exchange and acid–base homeostasis every couple of hours. This retrospective cohort study aims to evaluate COHb in the arterial blood gas as a novel marker of oxygenator dysfunction and its predictive value for imminent oxygenator change. Results Out of the 484 screened patients on ECMO 89, cumulatively requiring 116 oxygenator changes within 1833 patient days, including 19,692 arterial COHb measurements were analyzed. Higher COHb levels were associated with lower post-oxygenator pO2 (estimate for log(COHb): − 2.176 [95% CI − 2.927, − 1.427], p

Abstract Background Clogging is characterized by a progressive impairment of transmembrane patency in renal replacement devices and occurs due to obstruction of pores by unknown molecules. If citrate-based anti-coagulation is used, clogging can manifest as a metabolic alkalosis accompanied by hypernatremia and hypercalcemia, primarily a consequence of Na3Citrate infusion. An increased incidence of clogging has been observed during the COVID-19 pandemic. However, precise factors contributing to the formation remain uncertain. This investigation aimed to analyze its incidence and assessed time-varying trajectories of associated factors in critically ill patients on continuous renal replacement therapy (CRRT). Methods In this retrospective, single-center data analysis, we evaluated COVID-19 patients undergoing CRRT and admitted to critical care between March 2020 and December 2021. We assessed the proportional incidence of clogging surrogates in the overall population and subgroups based on the specific CRRT devices employed at our institution, including multiFiltrate (Fresenius Medical Care) and Prismaflex System (Baxter). Moderate and severe clogging were defined as Na > 145 or ≥ 150 mmol/l and HCO3 − > 28.0 or ≥ 30 mmol/l, respectively, with a total albumin-corrected calcium > 2.54 mmol/l. A mixed effect model was introduced to investigate factors associated with development of clogging. Results Fifty-three patients with 240 CRRT runs were analyzed. Moderate and severe clogging occurred in 15% (8/53) and 19% (10/53) of patients, respectively. Twenty-seven percent (37/136) of CRRTs conducted with a multiFiltrate device met the criteria for clogging, whereas no clogging could be observed in patients dialyzed with the Prismaflex System. Occurrence of clogging was associated with elevated triglyceride plasma levels at filter start (p = 0.013), amount of enteral nutrition (p = 0.002) and an increasing white blood cell count over time (p = 0.002). Conclusions Clogging seems to be a frequently observed phenomenon in critically ill COVID-19 patients. The presence of hypertriglyceridemia, combined with systemic inflammation, may facilitate the development of an impermeable secondary membrane within filters, thereby contributing to compromised membrane patency.

Abstract Most rust resistance genes thus far isolated from wheat have a very limited number of functional alleles. Here, we report the isolation of most of the alleles at wheat stem rust resistance gene locus SR9. The seven previously reported resistance alleles (Sr9a, Sr9b, Sr9d, Sr9e, Sr9f, Sr9g, and Sr9h) are characterised using a synergistic strategy. Loss-of-function mutants and/or transgenic complementation are used to confirm Sr9b, two haplotypes of Sr9e (Sr9e_h1 and Sr9e_h2), Sr9g, and Sr9h. Each allele encodes a highly related nucleotide-binding site leucine-rich repeat (NB-LRR) type immune receptor, containing an unusual long LRR domain, that confers resistance to a unique spectrum of isolates of the wheat stem rust pathogen. The only SR9 protein effective against stem rust pathogen race TTKSK (Ug99), SR9H, differs from SR9B by a single amino acid. SR9B and SR9G resistance proteins are also distinguished by only a single amino acid. The SR9 allelic series found in the B subgenome are orthologs of wheat stem rust resistance gene Sr21 located in the A subgenome with around 85% identity in protein sequences. Together, our results show that functional diversification of allelic variants at the SR9 locus involves single and multiple amino acid changes that recognize isolates of wheat stem rust.

ABSTRACTBackground: On 4 August 2020, an explosion occurred in Beirut, Lebanon. Hundreds of people were killed, thousands injured and displaced. An initiative was rapidly initiated to provide remote support informed by psychological first aid for the mental health of Lebanese young adults affected by the blast. However, little is known about recipients’ experiences of such initiatives.Objective: This study aimed to qualitatively explore the experiences of supporters and recipients in the community-led initiative following the blast.Method: We recruited a diverse sample of four supporters and four Lebanese recipients who took part in the Beirut initiative. Semi-structured interviews were conducted with participants. Reflexive thematic analysis was used to analyse the qualitative data.Results: We developed five themes from the qualitative interviews, which highlighted ideas around accessibility, alienation, the relationship, elements of the safe space created by the initiative, and unmet needs and areas for improvement. Recipients described the detrimental impact of the blast on their mental health within the Lebanese context and beyond. Recipients and supporters elucidated complex experiences of the support and its impact.Conclusions: Our findings suggest remote support has the potential to be acceptable for young adults in Lebanon. Further research into support informed by psychological first aid after similar crisis events is warranted.

IntroductionPersons with behavioral variant frontotemporal dementia (bvFTD) can exhibit apparently antisocial behaviors. An example is their tendency to adopt utilitarian choices in sacrificial moral dilemmas, i.e. harmful actions to promote overall welfare. Moral cognition models interpret such tendencies as deriving from a lack of emotional engagement and selective impairment in prosocial sentiments.MethodsWe applied a qualitative approach to test those theoretical assumptions and to further explore the emotional experiences and values of people with bvFTD while they contemplate moral scenarios. We conducted semistructured interviews with 14 participants: 7 persons with bvFTD and 7 older healthy controls. Transcripts were coded using ATLAS.ti 5.0.ResultsDuring the moral reasoning task, persons with bvFTD reported more positive emotions than negative and showed significantly less cognitive precision in their moral reasoning compared to controls. Persons with bvFTD also organized their choices predominantly around kindness and altruism, and their responses reflected higher rule compliance. Our study showed that bvFTD persons’ utilitarian responses to moral dilemmas did not arise from an emotionally disengaged or antisocial perspective. Instead, they were underpinned by positive emotionality and prosocial values.DiscussionThese findings enrich current understandings of moral cognition and highlight the importance of incorporating mixed methods approaches in dementia research that take into consideration the viewpoint of cognitively impaired individuals

One influential framework for examining human moral cognition has been a dual process model, in which utilitarian judgment (e.g., infliction of harm for the greater good) is associated with cognitive control processes, while non-utilitarian judgment (e.g., avoiding such harms) is associated with emotional, automatic processes. Another framework of moral cognition, the two-dimensional model of utilitarian psychology, posits that utilitarian choices may reflect either instrumental harm, i.e., inflicting harm on an individual for the greater good; or impartial beneficence, i.e., impartially and altruistically acting for the benefit of the overall welfare. We evaluated preregistered hypotheses (https://osf.io/m425d) derived from these models of moral cognition in a sample of 275 neurologically healthy older adults. Our results suggest that both the dual process and two-dimensional models provided insights regarding utilitarian reasoning, including three cardinal domains of conflict between utilitarianism and common-sense morality: agent-centered permissions, special obligations, and personal rights. One prediction of the dual process-based model was supported by our findings, with higher emotionality associated with decreased endorsement of utilitarian judgments (b = - 0.12, p

Abstract Background A higher-than-usual resistance to standard sedation regimens in COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) has led to the frequent use of the second-line anaesthetic agent ketamine. Simultaneously, an increased incidence of cholangiopathies in mechanically ventilated patients receiving prolonged infusion of high-dose ketamine has been noted. Therefore, the objective of this study was to investigate a potential dose–response relationship between ketamine and bilirubin levels. Methods Post hoc analysis of a prospective observational cohort of patients suffering from COVID-19-associated ARDS between March 2020 and August 2021. A time-varying, multivariable adjusted, cumulative weighted exposure mixed-effects model was employed to analyse the exposure–effect relationship between ketamine infusion and total bilirubin levels. Results Two-hundred forty-three critically ill patients were included into the analysis. Ketamine was infused to 170 (70%) patients at a rate of 1.4 [0.9–2.0] mg/kg/h for 9 [4–18] days. The mixed-effects model revealed a positively correlated infusion duration–effect as well as dose–effect relationship between ketamine infusion and rising bilirubin levels (p

Dementia caregiving, besides encompassing various challenges in tandem to the diagnosis of the care recipient, is associated with decreased psychological well-being and mental health. Accordingly, caregivers’ wellbeing has an impact on the quality of care they provide and on the relationship quality with the person in their care. The aim of the present study is to examine the effectiveness of a mindfulness-based intervention on relational and psychological wellbeing, tailored to the needs of dementia caregivers. This clinical trial (NCT04977245) will apply a randomized controlled mixed method design. Caregivers will be randomly allocated to either the mindfulness intervention or the active control group. The intervention arm is based on experiential learning and is targeted to promote caregivers’ well-being and empowerment. Assessments will include, standardized self-report questionnaires, task performance measures, and qualitative measures. All assessments will be held at three time points (baseline; t0, 0 months, post-intervention; t1, 2 months, and after maintenance; t2, 3 months) focused on three core domains (1. relational well-being, 2. psychological well-being, and 3. dementia patient’s lifestyle/activities). The primary outcome will be relational well-being, and data will be analyzed using linear mixed modelling.

ObjectiveVeno-venous (V-V) extracorporeal membrane oxygenation (ECMO) is increasingly used to support patients with severe acute respiratory distress syndrome (ARDS). In case of additional cardio-circulatory failure, some experienced centers upgrade the V-V ECMO with an additional arterial return cannula (termed V-VA ECMO). Here we analyzed short- and long-term outcome together with potential predictors of mortality.DesignMulticenter, retrospective analysis between January 2008 and September 2021.SettingThree tertiary care ECMO centers in Germany (Hannover, Bonn) and Switzerland (Zurich).PatientsSeventy-three V-V ECMO patients with ARDS and additional acute cardio-circulatory deterioration required an upgrade to V-VA ECMO were included in this study.Measurements and main resultsFifty-three patients required an upgrade from V-V to V-VA and 20 patients were directly triple cannulated. Median (Interquartile Range) age was 49 (28–57) years and SOFA score was 14 (12–17) at V-VA ECMO upgrade. Vasoactive-inotropic score decreased from 53 (12–123) at V-VA ECMO upgrade to 9 (3–37) after 24 h of V-VA ECMO support. Weaning from V-VA and V-V ECMO was successful in 47 (64%) and 40 (55%) patients, respectively. Duration of ECMO support was 12 (6–22) days and ICU length of stay was 32 (16–46) days. Overall ICU mortality was 48% and hospital mortality 51%. Two additional patients died after hospital discharge while the remaining patients survived up to two years (with six patients being lost to follow-up). The vast majority of patients was free from higher degree persistent organ dysfunction at follow-up. A SOFA score > 14 and higher lactate concentrations at the day of V-VA upgrade were independent predictors of mortality in the multivariate regression analysis.ConclusionIn this analysis, the use of V-VA ECMO in patients with ARDS and concomitant cardiocirculatory failure was associated with a hospital survival of about 50%, and most of these patients survived up to 2 years. A SOFA score > 14 and elevated lactate levels at the day of V-VA upgrade predict unfavorable outcome.

OBJECTIVES:. Herpes simplex virus (HSV)-2 is a rare cause of hepatitis that can lead to acute liver failure (ALF) and often death. The earlier the initiation of acyclovir treatment the better the survival. With regard to ALF, controlled randomized data support the use of therapeutic plasma exchange (TPE) both as bridge to recovery or transplantation—possibly by modulating the systemic inflammatory response and by replacing coagulation factors. Seraph 100 Microbind Affinity Blood Filter (Seraph; Ex Thera Medical, Martinez, CA), a novel extracorporeal adsorption device, removes living pathogens by binding to a heparin-coated surface was shown to efficiently clear HSV-2 particles in vitro. Here, we tested the combination of Seraph with TPE to reduce a massive HSV-2 viral load to reach a situation in that liver transplantation would be feasible. DESIGN:. Explorative study. SETTING:. Academic tertiary care transplant center. PATIENT:. Single patient with HSV-2–induced ALF. INTERVENTIONS:. TPE + Seraph 100 Microbind Affinity Blood Filter. MEASUREMENTS AND MAIN RESULTS:. We report Seraph clearance data of HSV-2 and of Epstein-Barr virus (EBV) in vivo as well as total viral elimination by TPE. Genome copies/mL of HSV-2 and EBV in EDTA plasma were measured by polymerase chain reaction every 60 minutes over 6 hours after starting Seraph both systemically and post adsorber. Also, HSV-2 and EBV were quantified before and after TPE and in the removed apheresis plasma. We found a total elimination of 1.81 × e11 HSV-2 copies and 2.11 × e6 EBV copies with a single TPE (exchange volume of 5L; 1.5× calculated plasma volume). Whole blood clearance of HSV-2 in the first 6 hours of treatment was 6.64 mL/min (4.98–12.92 mL/min). Despite much lower baseline viremia, clearance of EBV was higher 36.62 mL/min (22.67–53.48 mL/min). CONCLUSIONS:. TPE was able to remove circulating HSV-2 copies by 25% and EBV copies by 40% from the blood. On the other hand, clearance of HSV-2 by Seraph was clinically irrelevant, but Seraph seemed to be far more effective of removing EBV, implicating a possible use in EBV-associated pathologies, but this requires further study.

Qualified professionals in science, technology, engineering, and mathematics (STEM) and STEM education are in increasingly short supply globally. Role models can help increase women's representation in STEM, both at entry and senior levels. The study objectives were to identify the characteristics of role models in STEM higher education and careers and to investigate the differences in role model characteristics between career stages and between genders. We used a mixed-methods methodology involving a questionnaire and interviews. The participants, 788 alumni and final-year undergraduate and graduate students from a STEM research university, responded to the questionnaire, and ten leading women in STEM professions were interviewed. The questionnaire results indicated that a higher proportion of women than men reported being influenced by a role model during their studies. Seven key characteristics of role models were identified from the open-ended responses and the interviews: "ambitious," "charismatic," "empathic and encouraging," "inspiring," "knowledgeable," "gifted," and "professional." The most frequent characteristics women mentioned were "empathic and encouraging." The research findings support and align with the social cognitive career theory (SCCT), demonstrating how role modeling, which is part of the environmental theme, boosts intrinsic motivation--part of the personal theme, for individuals in STEM, especially women. These processes impact women's determination and professional performance--part of the behavioral theme. Based on our findings, to advance toward a STEM workforce characterized by greater fairness, we recommend designing and deploying structured mentoring programs and forums in STEM departments that can provide young women with more role models for success and thus with more hope for success in these fields.

Objective: To evaluate the duration of combined orthodontic and orthognathic surgical cases treated either in the public or private health system in Western Australia.

Background & Aims: Gastric dysfunction in the elderly may cause reduced food intake, frailty, and increased mortality. The pacemaker and neuromodulator cells interstitial cells of Cajal (ICC) decline with age in humans, and their loss contributes to gastric dysfunction in progeric klotho mice hypomorphic for the anti-aging Klotho protein. The mechanisms of ICC depletion remain unclear. Klotho attenuates Wnt (wingless-type MMTV integration site) signaling. Here, we examined whether unopposed Wnt signaling could underlie aging-associated ICC loss by up-regulating transformation related protein TRP53 in ICC stem cells (ICC-SC). Methods: Mice aged 1–107 weeks, klotho mice, APCΔ468 mice with overactive Wnt signaling, mouse ICC-SC, and human gastric smooth muscles were studied by RNA sequencing, reverse transcription–polymerase chain reaction, immunoblots, immunofluorescence, histochemistry, flow cytometry, and methyltetrazolium, ethynyl/bromodeoxyuridine incorporation, and ex-vivo gastric compliance assays. Cells were manipulated pharmacologically and by gene overexpression and RNA interference. Results: The klotho and aged mice showed similar ICC loss and impaired gastric compliance. ICC-SC decline preceded ICC depletion. Canonical Wnt signaling and TRP53 increased in gastric muscles of klotho and aged mice and middle-aged humans. Overstimulated canonical Wnt signaling increased DNA damage response and TRP53 and reduced ICC-SC self-renewal and gastric ICC. TRP53 induction persistently inhibited G1/S and G2/M cell cycle phase transitions without activating apoptosis, autophagy, cellular quiescence, or canonical markers/mediators of senescence. G1/S block reflected increased cyclin-dependent kinase inhibitor 1B and reduced cyclin D1 from reduced extracellular signal-regulated kinase activity. Conclusions: Increased Wnt signaling causes age-related ICC loss by up-regulating TRP53, which induces persistent ICC-SC cell cycle arrest without up-regulating canonical senescence markers.

Large-scale, unbiased proteomics studies of biological samples like plasma are constrained by the complexity of the proteome. Herein, the authors develop a highly parallel protein quantitation platform leveraging multi nanoparticle protein coronas for deep proteome sampling and biomarker discovery.

Contemporary orthodontic and surgical treatment goals are primarily focussed on achieving optimal aesthetic soft tissue outcomes in three dimensions. It is important, therefore, to establish valid three-dimensional normative models to assist in clinical decision-making. Ideally, such models should be customised to a patient’s individual facial proportions. The aim of this study was to establish the most pleasing computer generated 3D facial form using a community-based sample population.

Background: Renal tubular acidosis (RTA) is an extremely rare cause of metabolic acidosis (10 in 100,000). RTA has been linked neither to pregnancy nor to severe coronavirus disease 2019 (COVID-19). The purpose of this study was to analyze the prevalence and clinical course of normal anion gap metabolic acidosis in critically ill pregnant COVID-19 patients and to compare them to an age-matched nonpregnant female patient cohort. Methods: Secondary analysis was conducted on a prospective observational cohort of critically ill patients suffering from COVID-19 consecutively admitted to a tertiary intensive care unit (ICU) between February 2020 and April 2021. Results: A total of 321 COVID-19 patients required admission to the ICU; 95 (30%) were female, and 18 (19%) were of childbearing age. Seven of eight (88%) pregnant women (all in the last trimester) required advanced respiratory support due to COVID-19. The estimated glomerular filtration rate was 135 (123–158) mL/min/m2 body surface area, and six pregnant women (86%) were diagnosed with a normal, respiratory compensated, anion gap metabolic acidosis (pHmin 7.3 (7.18–7.31), HCO3−min 14.8 (12.8–18.6) mmol/L, and paCO2 3.4 (3.3–4.5) kPa). Three (43%) acidotic pregnant women fulfilled diagnostic criteria for RTA. All women recovered spontaneously within less 7 days. Conclusions: Metabolic acidosis seems to be very common (85%) in pregnant critically ill COVID-19 patients, and the prevalence of RTA might be higher than normal. It remains to be demonstrated if this observation is an indirect epiphenomenon or due to a direct viral effect on the tubular epithelium.

The COVID-19 pandemic poses many real-world moral dilemmas, which can pit the needs and rights of the many against the needs and rights of the few. We investigated moral judgments in the context of the contemporary global crisis among older adults, who are at greatest personal risk from the pandemic. We hypothesized that during this pandemic, individuals would give fewer utilitarian responses to hypothetical dilemmas, accompanied by higher levels of confidence and emotion elicitation. Our pre-registered analysis (https://osf.io/g2wtp) involved two waves of data collection, before (2014) and during (2020) the COVID-19 pandemic, regarding three categories of moral dilemmas (personal rights, agent-centered permissions, and special obligations). While utilitarian responses considered across all categories of dilemma did not differ, participants during the 2020 wave gave fewer utilitarian responses to dilemmas involving personal rights; that is, they were less willing to violate the personal rights of others to produce the best overall outcomes.

ObjectivesSexual violence can have a destructive impact on the lives of people. It is more common in unstable conditions such as during displacement or migration of people. On the Greek island of Lesvos, Médecins Sans Frontières provided medical care to survivors of sexual violence among the population of asylum seekers. This study describes the patterns of sexual violence reported by migrants and asylum seekers and the clinical care provided to them.MethodsThis is a descriptive study, using routine program data. The study population consisted of migrants and asylum seekers treated for conditions related to sexual violence at the Médecins Sans Frontières clinic on Lesvos Island (September 2017-January 2018).ResultsThere were 215 survivors of sexual violence who presented for care, of whom 60 (28%) were male. The majority of incidents reported (94%) were cases of rape; 174 (81%) of survivors were from Africa and 185 (86%) of the incidents occurred over a month before presentation. Half the incidents (118) occurred in transit, mainly in Turkey, and 76 (35%) in the country of origin; 10 cases (5%) occurred on Lesvos. The perpetrator was known to the survivor in 23% of the cases. The need for mental health care exceeded the capacity of available mental care services.ConclusionEven though the majority of cases delayed seeking medical care after the incident, it is crucial that access to mental health services is guaranteed for those in need. Such access and security measures for people in transit need to be put in place along migration routes, including in countries nominally considered safe, and secure routes need to be developed.

This essay sheds light on how a film distribution apparatus, which aimed to cater to the entire population as one, in effect ushered in a process of collectivization of cultural life experience, as well as media aesthetics, in postwar Japan. While public discourses on nationhood were discouraged in postwar Japan, information and other textual contents about nationhood flowed freely. The national space as a unified location started to re-reform in the mid-1950s. This was after the country regained its sovereignty, and a new medium―television―emerged in the public sphere. However, more than these two factors, I argue that it was the film studio distribution apparatus labeled the “program picture,” which enabled an imaginary reunification of viewership throughout the country. Although not entirely unique to the postwar era, this distribution system was predicated on economic models of vertical integration, which in the midst of several medial transformations, established a dominant cinematic aesthetics that has been equally disseminated throughout the country.

Background. Coronary Heart Disease (CHD) is the main highlight of the major cardiovascular diseases. In Indonesia, CHD is the leading cause of death from all deaths, with rates reaching 26.4%, which is four times greater than cancer mortality rates. Objective. This study aims to determine whether dyslipidemia associated with hypertension increases the risks for the incidence of CHD in Harapan Kita Hospital, National Cardiovascular Center, Jakarta, or does not. Methods. The study design was case control. The sample was 163 respondents, 82 respondents in the case group and 81 respondents in the control group. The data were analyzed by using logistic regression. Results. In the CHD group, the percentage of respondents with dyslipidemia was 50%, while in the control group, the percentage of respondents with dyslipidemia was 17.3%. The relationship of dyslipidemia with the incidence of CHD differed according to hypertension status. After being controlled for age, in hypertensive respondents, those with dyslipidemia was 18.1 times more likely to develop CHD compared with those nondyslipidemic, whereas in nonhypertensive respondents, those with dyslipidemia was 2.5 times more likely to develop CHD compared with those nondyslipidemic. Recommendation. It is recommended that the community have medical checkup regularly and change lifestyles by taking healthy diet to control lipid profile and blood pressure.

It is an undisputed fact that women played an integral role in the development of modern Japanese literature. As early as the late nineteenth century, Ichiyo Higuchi broke through the [...]