bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequestosome 1 (p62) mitigates hypoxia-induced cardiac dysfunction by stabilizing hypoxia-inducible factor 1α and nuclear factor erythroid 2-related factor 2
Authors: Ghosh Rajeshwary , Fatahian Amir Nima , Rouzbehani Omid M T , Hathaway Marissa A , Mosleh Tariq , Vinod Vishaka , Vowles Sidney , Stephens Sophie L , Chung Siu-Lai Desmond , Cao Isaac D , Jonnavithula Anila , Symons J David , Boudina Sihem
Published: February 2024

Aims

Heart failure due to ischaemic heart disease (IHD) is a leading cause of mortality worldwide. A major contributing factor to IHD-induced cardiac damage is hypoxia. Sequestosome 1 (p62) is a multi-functional adaptor protein with pleiotropic roles in autophagy, proteostasis, inflammation, and cancer. Despite abundant expression in cardiomyocytes, the role of p62 in cardiac physiology is not well understood. We hypothesized that cardiomyocyte-specific p62 deletion evokes hypoxia-induced cardiac pathology by impairing hypoxia-inducible factor 1α (Hif-1α) and nuclear factor erythroid 2-related factor 2 (Nrf2) signalling.

Methods and results

Adult mice with germline deletion of cardiomyocyte p62 exhibited mild cardiac dysfunction under normoxic conditions. Transcriptomic analyses revealed a selective impairment in Nrf2 target genes in the hearts from these mice. Demonstrating the functional importance of this adaptor protein, adult mice with inducible depletion of cardiomyocyte p62 displayed hypoxia-induced contractile dysfunction, oxidative stress, and cell death. Mechanistically, p62-depleted hearts exhibit impaired Hif-1α and Nrf2 transcriptional activity. Because findings from these two murine models suggested a cardioprotective role for p62, mechanisms were evaluated using H9c2 cardiomyoblasts. Loss of p62 in H9c2 cells exposed to hypoxia reduced Hif-1α and Nrf2 protein levels. Further, the lack of p62 decreased Nrf2 protein expression, nuclear translocation, and transcriptional activity. Repressed Nrf2 activity associated with heightened Nrf2-Keap1 co-localization in p62-deficient cells, which was concurrent with increased Nrf2 ubiquitination facilitated by the E3 ligase Cullin 3, followed by proteasomal-mediated degradation. Substantiating our results, a gain of p62 in H9c2 cells stabilized Nrf2 and increased the transcriptional activity of Nrf2 downstream targets.

Conclusion

Cardiac p62 mitigates hypoxia-induced cardiac dysfunction by stabilizing Hif-1α and Nrf2.
Nutritional support in the cardiac intensive care unit
Authors: Frederiks Pascal , Peetermans Marijke , Wilmer Alexander
Published: February 2024

Optimal care of critically ill patients in the cardiac intensive care unit includes adequate nutritional support. This review highlights the high prevalence of malnutrition in acute heart failure, acute coronary syndrome, cardiogenic shock, and post-cardiac arrest and its adverse impact on prognosis. There is a lack of robust evidence regarding appropriate nutritional support in this patient population. Initiation of nutritional support with a comprehensive assessment of the patient’s nutritional status is critical. High-risk cardiac patients who are not critically ill can receive oral nutrition adapted to individual risk factors or deficiencies, although overfeeding should be avoided in the acute phase. For critically ill patients at risk of or with malnutrition on admission, general principles include initiation of nutritional support within 48 h of admission, preference for enteral over parenteral nutrition, preference for hypocaloric nutrition in the first week of intensive care unit admission, and adequate micronutrient supplementation. Enteral nutrition in haemodynamically unstable patients carries a risk, albeit low, of intestinal ischaemia. In the case of malnutrition, the risk of refeeding syndrome should always be considered.
Early and mid-term outcomes after aortic valve replacement using a novel tissue bioprosthesis: a systematic review
Authors: Sef Davorin , Thet Myat Soe , Klokocovnik Tomislav , Luthra Suvitesh
Published: February 2024

OBJECTIVES

While current data show a clear trend towards the use of bioprosthetic valves during aortic valve replacement (AVR), durability of bioprosthetic valves remains the most important concern. We conducted a 1st systematic review of all available evidence that analysed early and mid-term outcomes after AVR using the Inspiris RESILIA™ bioprosthesis.

METHODS

A systematic literature search was performed to identify all relevant studies evaluating early and mid-term outcomes after AVR using the Inspiris RESILIA bioprosthesis and including at least 20 patients with no restriction on the publication date. Subgroup meta-analysis was performed to compare Inspiris RESILIA and PERIMOUNT Magna Ease bioprosthesis and to pool the early postoperative mortality and stroke rates.

RESULTS

A total of 416 studies were identified, of which 15 studies met the eligibility criteria. The studies included a total of 3202 patients with an average follow-up of up to 5.3 years. The average age of patients across the studies was 52.2–75.1 years. Isolated AVR was performed in 39.0–86.4% of patients. In-hospital or 30-day postoperative mortality was 0–2.8%. At the mid-term follow-up, freedom from all-cause mortality was up to 85.4%. Among studies with mid-term follow-up, trace/mild paravalvular leak was detected in 0–3.0%, while major paravalvular leak was found only in up to 2.0% of patients. No statistically significant differences in terms of mortality (P = 0.98, odds ratio 1.02, 95% confidence interval 0.36–2.83) and stroke (P = 0.98, odds ratio 1.01, 95% confidence interval 0.38–2.73) between the Inspiris RESILIA bioprosthesis and PERIMOUNT Magna Ease bioprosthesis were observed in the subgroup meta-analysis.

CONCLUSIONS

Mid-term data on the safety and haemodynamic performance of the novel aortic bioprosthesis are encouraging. Further comparative studies with other bioprostheses and longer follow-up are still required to endorse durability and safety of the novel bioprosthesis.
Association between cardiovascular risk profile and impaired microvascular function in a Swedish middle-aged cohort (the SCAPIS study)
Authors: Bergstrand Sara , Jonasson Hanna , Fredriksson Ingemar , Larsson Marcus , Östgren Carl Johan , Strömberg Tomas
Published: February 2024

Aims

The aim was to investigate the relationship between microvascular function, cardiovascular risk profile, and subclinical atherosclerotic burden.

Methods and results

The study enrolled 3809 individuals, 50–65 years old, participating in the population-based observational cross-sectional Swedish CArdioPulmonary bioImage Study. Microvascular function was assessed in forearm skin using an arterial occlusion and release protocol determining peak blood oxygen saturation (OxyP). Cardiovascular risk was calculated using the updated Systematic Coronary Risk Evaluation [SCORE2; 10-year risk of fatal and non-fatal cardiovascular disease (CVD) events]. The OxyP was compared with coronary artery calcification score (CACS) and to plaques in the carotid arteries. Individuals with OxyP values in the lowest quartile (Q1; impaired microvascular function) had a mean SCORE2 of 5.8% compared with 3.8% in those with the highest values of OxyP (Q4), a relative risk increase of 53%. The risk of having a SCORE2 > 10% was five times higher for those in Q1 (odds ratio: 4.96, 95% confidence interval: 2.76–8.93) vs. Q4 when adjusting for body mass index and high-sensitivity C-reactive protein. The OxyP was lower in individuals with CACS > 0 and in those with both carotid plaques and CACS > 0, compared with individuals without subclinical atherosclerotic burdens (87.5 ± 5.6% and 86.9 ± 6.0%, vs. 88.6 ± 5.8%, P < 0.01).

Conclusion

In a population without CVD or diabetes mellitus, impaired microvascular function is associated with cardiovascular risk profiles such as higher SCORE2 risk and CACS. We suggest that OxyP may serve as a microcirculatory functional marker of subclinical atherosclerosis and CVD risk that is not detected by structural assessments.
Recommended and observed statin use among US adults with and without cancer
Authors: Kobo Ofer , Michos Erin D , Roguin Ariel , Bagur Rodrigo , Gulati Martha , Mamas Mamas A
Published: February 2024

Aims

Patients with cancer are at increased cardiovascular (CV) risk. We aimed to compare the recommended and observed statin use among individuals with and without cancer.

Methods and results

Using three 2-year cycles from the National Health and Nutrition Examination Survey (2013–18), we analysed data from 17 050 US adults. We compared the prevalence of Class 1 statin recommendations and use between individuals with and without cancer, overall, and among different demographic groups. Individuals with a history of cancer were older and had a higher burden of comorbidities. Stratified by age groups, they were more likely to have a secondary prevention indication compared with individuals without cancer but not a primary prevention indication for statin. Among individuals with an indication for statin therapy, the prevalence of statin use was higher in the cancer group compared with those without cancer (60.8% vs. 47.8%, P < 0.001), regardless of sex, type of indication (primary vs. secondary prevention), and education level. However, the higher prevalence of statin use in the cancer group was noted among younger individuals, ethnic minorities, and those with lower family income.

Conclusion

Our finding highlights the importance of optimization of CV health in patients with cancer, as individuals with cancer were more likely to have a Class 1 indication for statin treatment when compared with individuals without cancer. Important differences in statin use among cohorts based on sex, age, ethnicity, and socioeconomic status were identified, which may provide a framework through which CV risk factor control can be targeted in this population.

Key findings

Higher statin use in cancer patients: Among those with Class 1 recommendation to take statins, 60.8% of cancer patients were using them, compared with 47.8% of non-cancer individuals, indicating a greater adherence to heart health recommendations in the cancer group. Demographic variations in statin use: The study found notable differences in statin use among younger individuals, ethnic minorities, and those with lower income within the cancer patient group, suggesting disparities in how these subgroups manage their cardiovascular health.
Temperature and sex shape reproductive barriers in a climate change hotspot
Authors: Gallegos Cristóbal , Hodgins Kathryn A , Monro Keyne
Published: February 2024

Climate change is altering species ranges and reproductive interactions in existing ranges, offering species new scope to mate and hybridize. The outcomes will depend on how environmental factors shape reproductive barriers across life stages, yet this is rarely assessed across the environments that species encounter in nature. We assess prezygotic and postzygotic barriers, and their dependence on temperature and parental sex, in species of a reef-building tubeworm (Galeolaria) from a fast-warming biodiversity hotspot in southern Australia. By replicating pure and reciprocal hybrid crosses across 5 temperatures spanning species’ thermal ranges, we estimate thermal tolerance curves (defining niches) for crosses and reproductive isolation at each temperature. By also replicating crosses at 3 life stages, we partition the contributions of prezygotic barriers at fertilization, postzygotic barriers at embryogenesis, and postzygotic barriers at larval development to reproductive isolation. We show that barriers are weaker at fertilization and embryogenesis, but stronger and more temperature sensitive at larval development, as species diverge in thermal niche. Asymmetry of barriers between parental sexes, moreover, suggests a complex interplay between niche differentiation and maternal inheritance. Our findings point to a key role for temperature in reproductive isolation, but also challenges for predicting the fate of isolation in future climates.
Increased production of isobutanol from xylose through metabolic engineering of Saccharomyces cerevisiae overexpressing transcription factor Znf1 and exogenous genes
Authors: Songdech Pattanan , Butkinaree Chutikarn , Yingchutrakul Yodying , Promdonkoy Peerada , Runguphan Weerawat , Soontorngun Nitnipa
Published: February 2024

Only trace amount of isobutanol is produced by the native Saccharomyces cerevisiae via degradation of amino acids. Despite several attempts using engineered yeast strains expressing exogenous genes, catabolite repression of glucose must be maintained together with high activity of downstream enzymes, involving iron–sulfur assimilation and isobutanol production. Here, we examined novel roles of nonfermentable carbon transcription factor Znf1 in isobutanol production during xylose utilization. RNA-seq analysis showed that Znf1 activates genes in valine biosynthesis, Ehrlich pathway and iron–sulfur assimilation while coupled deletion or downregulated expression of BUD21 further increased isobutanol biosynthesis from xylose. Overexpression of ZNF1 and xylose-reductase/dehydrogenase (XR-XDH) variants, a xylose-specific sugar transporter, xylulokinase, and enzymes of isobutanol pathway in the engineered S. cerevisiae pho13gre3Δ strain resulted in the superb ZNXISO strain, capable of producing high levels of isobutanol from xylose. The isobutanol titer of 14.809 ± 0.400 g/L was achieved, following addition of 0.05 g/L FeSO4.7H2O in 5 L bioreactor. It corresponded to 155.88 mg/g xylose consumed and + 264.75% improvement in isobutanol yield. This work highlights a new regulatory control of alternative carbon sources by Znf1 on various metabolic pathways. Importantly, we provide a foundational step toward more sustainable production of advanced biofuels from the second most abundant carbon source xylose.
Associations of Neurological Biomarkers in Serum With Gait Measures: The Cardiovascular Health Study
Authors: Nadkarni Abhijay N , Mukamal Kenneth J , Zhu Xiaonan , Siscovick David , Brach Jennifer S , Jacob Mini , Seshadri Sudha , Abe Temidayo , Rosano Caterina , Djousse Luc , Rosso Andrea L
Published: February 2024

Background

Gait impairment leads to increased mobility decline and may have neurological contributions. This study explores how neurological biomarkers are related to gait in older adults.

Methods

We studied participants in the Cardiovascular Health Study, a population-based cohort of older Americans, who underwent a serum biomarker assessment from samples collected in 1996–1997 for neurofilament light chain (NfL), glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1, and total tau (n = 1 959, mean age = 78.0 years, 60.8% female). In a subsample (n = 380), cross-sectional associations with quantitative gait measures were explored. This subsample was assessed on a mat for gait speed, step length, double support time, step time, step length variability, and step time variability. Gait speed was also measured over a 15-ft walkway annually from 1996–1997 to 1998–1999 for longitudinal analyses. Linear regression models assessed cross-sectional associations of biomarkers with gait measures, whereas mixed effects models assessed longitudinal gait speed change from baseline to 1998–1999.

Results

Neurofilament light chain was significantly associated with annual gait speed decline (standardized β = −0.64 m/s, 95% CI: [−1.23, −0.06]) after adjustment for demographic and health factors. Among gait mat-assessed phenotypes, NfL was also cross-sectionally associated with gait speed (β = 0.001 m/s [0.0003, 0.002]) but not with other gait measures. None of the remaining biomarkers were significantly related to gait in either longitudinal or cross-sectional analyses.

Conclusions

Higher NfL levels were related to greater annual gait speed decline. Gait speed decline may be related to axonal degeneration. The clinical utility of NfL should be explored.
Diagnostic Accuracy of the FRAIL Scale, Groningen Frailty Indicator, Tilburg Frailty Indicator, and PRISMA-7 for Frailty Screening Among Older Adults in Community Settings: A Systematic Review and Network Meta-Analysis
Authors: Vo Nhi Thi , Tu Yu-Kang , Lin Kuan-Chia , Chiu Hsiao-Yean , Huang Hui-Chuan
Published: February 2024

Background and Objectives

This study aimed to investigate the diagnostic accuracy of four questionnaire-based tools (i.e., the FRAIL scale, Groningen Frailty Indicator [GFI], Tilburg Frailty Indicator [TFI], and PRISMA-7) for screening frailty in older adults.

Research Design and Methods

The 4 databases comprising the Cumulative Index to Nursing and Allied Health Literature, Embase, PubMed, and ProQuest were searched from inception to June 20, 2023. Study quality comprising risks of bias and applicability was assessed via a QUADAS-2 questionnaire. A bivariate network meta-analysis model and Youden’s index were performed to identify the optimal tool and cutoff points.

Results

In total, 20 studies comprising 13 for FRAIL, 7 for GFI, 6 for TFI, and 5 for PRISMA-7 were included. Regarding study quality appraisal, all studies had high risks of bias for study quality assessment domains. Values of the pooled sensitivity of the FRAIL scale, GFI, TFI, and PRISMA-7 were 0.58, 0.74, 0.66, and 0.73, respectively. Values of the pooled specificity of the FRAIL scale, GFI, TFI, and PRISMA-7 were 0.92, 0.77, 0.84, and 0.86, respectively. The Youden’s index was obtained for the FRAIL scale with a cutoff of 2 points (Youden’s index = 0.65), indicating that the FRAIL scale with a cutoff of 2 points was the optimal tool for frailty screening in older adults.

Discussion and Implications

The FRAIL scale comprising 5 self-assessed items is a suitable tool for interview older adults for early frailty detection in community settings; it has the advantages of being short, simple, and easy to respond to.
Citizen engagement in national health insurance in rural western Kenya
Authors: Maritim Beryl , Koon Adam D , Kimaina Allan , Goudge Jane
Published: February 2024

Effective citizen engagement is crucial for the success of social health insurance, yet little is known about the mechanisms used to involve citizens in low- and middle-income countries. This paper explores citizen engagement efforts by the National Health Insurance Fund (NHIF) and their impact on health insurance coverage within rural informal worker households in western Kenya. Our study employed a mixed methods design, including a cross-sectional household survey (n = 1773), in-depth household interviews (n = 36), six focus group discussions with community stakeholders and key informant interviews (n = 11) with policymakers. The findings reveal that NHIF is widely recognized, but knowledge of its services, feedback mechanisms and accountability systems is limited. NHIF enrolment among respondents is low (11%). The majority (63%) are aware of NHIF, but only 32% know about the benefit package. There was higher awareness of the benefit package (60%) among those with NHIF compared to those without (28%). Satisfaction with the NHIF benefit package was expressed by only 48% of the insured. Nearly all respondents (93%) are unaware of mechanisms to provide feedback or raise complaints with NHIF. Of those who are aware, the majority (57%) mention visiting NHIF offices for assistance. Most respondents (97%) lack awareness of NHIF’s performance reporting mechanisms and express a desire to learn. Negative media reports about NHIF’s performance erode trust, contributing to low enrolment and member attrition. Our study underscores the urgency of prioritizing citizen engagement to address low enrolment and attrition rates. We recommend evaluating current citizen engagement procedures to enhance citizen accountability and incorporate their voices. Equally important is the need to build the capacity of health facility staff handling NHIF clients in providing information and addressing complaints. Transparency and information accessibility, including the sharing of performance reports, will foster trust in the insurer. Lastly, standardizing messaging and translations for diverse audiences, particularly rural informal workers, is crucial.
El proceso constituyente en Islandia: Un caso de éxito sin final felizThe Constitutional Process in Iceland: A case of success without a happy ending
Authors: Núñez Rafael Rubio
Published: February 2024

The drafting of the new constitution in Iceland has been the subject of numerous studies. Most of them highlight the success of the initiative, pointing to the set of innovative mechanisms incorporated into the process. However, we cannot ignore that the process did not achieve its goal of changing the Constitution. The reasons, which can serve as lessons for other processes of this nature, can be found in the initiation of the project during a deep crisis; the lack of clear objectives; the absence of a clear definition of tasks; the confusion between participation and deliberation, which generated some expectation confusion and progressive disillusionment, and the gap between the mobilized society and public representatives.
‘Taking Responsibility for the White Collective’: Implicated Subjects and Transformative Justice in the United States
Authors: McEvoy Bretton J
Published: February 2024

ABSTRACT∞

Transitional justice largely ignores that majority of actors who, though not directly responsible for violence, are structurally implicated in systems of injustice that (re)produce violence. Their absence is incompatible with the normative goals of the ‘transformative justice’ agenda, which include targeting the causes of (structural) violence, a project decidedly shaped by the presence of implicated subjects, especially in cases of historical injustice. This article engages a select group of implicated subjects – anti-racist white activists in the United States – to examine what their endeavours and struggles to reckon with their implication in the ongoing histories of racism and white supremacy can tell us about the boundaries of a transformative justice model. Drawing upon nine months of participant observation and 30 in-depth interviews within predominantly white activist spaces in the Greater Boston area, I contend that viewing transitional justice from the lens of implicated subjects serves to trouble the field’s transformative aspirations.
Do dietary interventions exert clinically important effects on the bioavailability of β-lactam antibiotics? A systematic review with meta-analyses
Authors: Wiesner Agnieszka , Zagrodzki Paweł , Paśko Paweł
Published: February 2024

Background

Managing drug–food interactions may help to achieve the optimal action and safety profile of β-lactam antibiotics.

Methods

We conducted a systematic review with meta-analyses in adherence to PRISMA guidelines for 32 β-lactams. We included 166 studies assessing the impact of food, beverages, antacids or mineral supplements on the pharmacokinetic (PK) parameters or PK/pharmacodynamic (PK/PD) indices.

Results

Eighteen of 25 β-lactams for which data on food impact were available had clinically important interactions. We observed the highest negative influence of food (AUC or Cmax decreased by >40%) for ampicillin, cefaclor (immediate-release formulations), cefroxadine, cefradine, cloxacillin, oxacillin, penicillin V (liquid formulations and tablets) and sultamicillin, whereas the highest positive influence (AUC or Cmax increased by >45%) for cefditoren pivoxil, cefuroxime and tebipenem pivoxil (extended-release tablets). Significantly lower bioavailability in the presence of antacids or mineral supplements occurred for 4 of 13 analysed β-lactams, with the highest negative impact for cefdinir (with iron salts) and moderate for cefpodoxime proxetil (with antacids). Data on beverage impact were limited to 11 antibiotics. With milk, the extent of absorption was decreased by >40% for cefalexin, cefradine, penicillin G and penicillin V, whereas it was moderately increased for cefuroxime. No significant interaction occurred with cranberry juice for two tested drugs (amoxicillin and cefaclor).

Conclusions

Factors such as physicochemical features of antibiotics, drug formulation, type of intervention, and patient’s health state may influence interactions. Due to the poor actuality and diverse methodology of included studies and unproportionate data availability for individual drugs, we judged the quality of evidence as low.
Evaluation of Busulfan as a Third-Party Immunoassay on a Clinical Chemistry Analyzer
Authors: Zhou Janet R , To Andrea , Fritz James , Jung Benjamin , Yazdanpanah Mehrdad , Kulasingam Vathany
Published: February 2024

Background

Busulfan is widely used in conditioning regimens to prepare patients for hematopoietic stem cell transplantation. Therapeutic drug monitoring (TDM) is critical due to large inter- and intra-individual variability in busulfan pharmacokinetics, and the risk of adverse consequences of toxicity including hepatic veno-occlusive disease. Busulfan is most commonly measured by liquid chromatography–mass spectrometry (LC-MS/MS), which is not as widely available in clinical laboratories as automated routine clinical chemistry analyzers. The objective was to perform analytical verification of a busulfan immunoassay on the Abbott Alinity c platform.

Methods

The MyCare Oncology busulfan immunoassay was configured as a third-party reagent on the Abbott Alinity c. Imprecision, linearity, sample carryover, and onboard stability of reagent studies were evaluated. The performance of the busulfan immunoassay using the Abbott Alinity c was compared to the Beckman Coulter AU480 using sodium heparinized plasma, as well as to LC-MS/MS using lithium heparinized plasma.

Results

The imprecision goal of 8% was met, and linearity within the analytical measurement range of 240 to 1700 ng/mL was verified. Sample carryover was negligible, and the reagents were stable onboard for at least 84 days. The busulfan immunoassay correlated well with LC-MS/MS (slope = 0.949, y-intercept = −7.8 ng/mL, r2 = 0.9935) and the Beckman Coulter AU480 (slope = 1.090, y-intercept = −34.5 ng/mL, r2 = 0.9988).

Conclusions

This study demonstrated successful analytical verification of a busulfan third-party immunoassay on the Abbott Alinity c platform. The ability to perform TDM of busulfan on a routine clinical chemistry analyzer will positively impact turnaround times to improve patient outcomes.
A validated dilute-and-shoot LC–MS-MS urine screening for the analysis of 95 illicit drugs and medicines: Insights from clinical and forensic Brazilian cases
Authors: Dos Santos Bruno Pereira , Birk Letícia , Schwarz Patrícia , Sebben Viviane Cristina , Sgaravatti Ângela Malysz , de Gouveia Giovanna Cristiano , Silva Petry Adriana Ubirajara , de Menezes Francisco Paz , Gonzaga Alexsandro Pinto , Schlickmann Paula Flores , Arbo Marcelo Dutra , de Oliveira Tiago Franco , Eller Sarah
Published: February 2024

Urine toxicological analysis is a relevant tool in both clinical and forensic scenarios, enabling the diagnosis of acute poisonings, elucidation of deaths, verification of substance use in the workplace and identification of drug-facilitated crimes. For these analyses, the dilute-and-shoot technique associated with liquid chromatography coupled with tandem mass spectrometry (LC–MS-MS) is a promising alternative since it has demonstrated satisfactory results and broad applicability. This study developed and validated a comprehensive LC–MS-MS screening method to analyze 95 illicit drugs and medicines in urine samples and application to clinical and forensic Brazilian cases. The dilute-and-shoot protocol was defined through multivariate optimization studies and was set using 100 µL of sample and 300 µL of solvent. The total chromatographic run time was 7.5 min. The method was validated following the recommendations of the ANSI/ASB Standard 036 Guideline. The lower limits of quantification varied from 20 to 100 ng/mL. Within-run and between-run precision coefficient of variations% were <20%, and bias was within ± 20%. Only 4 of the 95 analytes presented significant ionization suppression or enhancement (>25%). As proof of applicability, 839 urine samples from in vivo and postmortem cases were analyzed. In total, 90.9% of the analyzed samples were positive for at least one substance, and 78 of the 95 analytes were detected. The most prevalent substances were lidocaine (40.2%), acetaminophen (38.0%) and benzoylecgonine (31.5%). The developed method proved to be an efficient and simplified alternative for analyzing 95 therapeutic and illicit drugs in urine samples. Additionally, the results obtained from sample analysis are essential for understanding the profile of Brazilian substance use, serving as a valuable database for the promotion of health and safety public policies.
Potential exhaled breath biomarkers identified in chlorine-exposed mice
Authors: Jonasson Sofia , Magnusson Roger , Wingfors Håkan , Gustafsson Åsa , Rankin Gregory , Elfsmark Linda , Mörén Lina
Published: February 2024

Exhaled breath (EB) contains various volatile organic compounds (VOCs) that can indicate specific biological or pathological processes in the body. Analytical techniques like gas chromatography–mass spectrometry (GC–MS) can be used to detect and measure these exhaled biomarkers. In this study, the objective was to develop a non-invasive method of EB sampling in animals that were awake, as well as to analyze EB for volatile biomarkers specific for chlorine exposure and/or diagnostic biomarkers for chlorine-induced acute lung injury (ALI). To achieve this, a custom-made sampling device was used to collect EB samples from 19 female Balb/c mice. EB was sampled both pre-exposure (serving as internal control) and 30 min after exposure to chlorine. EB was collected on thermal desorption tubes and subsequently analyzed for VOCs by GC–MS. The following day, the extent of airway injury was assessed in the animals by examining neutrophils in the bronchoalveolar lavage fluid. VOC analysis revealed alterations in the EB biomarker pattern post-chlorine exposure, with eight biomarkers displaying increased levels and six exhibiting decreased levels following exposure. Four chlorinated compounds: trichloromethane, chloroacetone, 1,1-dichloroacetone and dichloroacetonitrile, were increased in chlorine-exposed mice, suggesting their specificity as chlorine EB biomarkers. Furthermore, chlorine-exposed mice displayed a neutrophilic inflammatory response and body weight loss 24 h following exposure. In conclusion, all animals developed an airway inflammation characterized by neutrophil infiltration and a specific EB pattern that could be extracted after chlorine exposure. Monitoring EB samples can readily and non-invasively provide valuable information on biomarkers for diagnosis of chlorine-induced ALI, confirming chlorine exposures.
Dubowski’s stages of alcohol influence and clinical signs and symptoms of drunkenness in relation to a person’s blood-alcohol concentration—Historical background
Authors: Jones Alan Wayne
Published: February 2024

This article traces the origin of various charts and tables delineating the stages of alcohol influence in relation to the clinical signs and symptoms of drunkenness and a person’s blood-alcohol concentration (BAC). In forensic science and legal medicine, the most widely used such table was created by Professor Kurt M. Dubowski (University of Oklahoma). The first version of the Dubowski alcohol table was published in 1957, and minor modifications appeared in various articles and book chapters until the final version was published in 2012. Seven stages of alcohol influence were identified including subclinical (sobriety), euphoria, excitement, confusion, stupor, alcoholic coma and death. The BAC causing death was initially reported as 0.45+ g%, although the latest version cited a mean and median BAC of 0.36 g% with a 90% range from 0.21 g% to 0.50 g%. An important feature of the Dubowski alcohol table was the overlapping ranges of BAC for each of the stages of alcohol influence. This was done to reflect variations in the physiological effects of ethanol on the nervous system between different individuals. Information gleaned from the Dubowski table is not intended to apply to any specific individual but more generally for a population of social drinkers, not regular heavy drinkers or alcoholics. Under real-world conditions, much will depend on a person’s age, race, gender, pattern of drinking, habituation to alcohol and the development of central nervous tolerance. The impairment effects of ethanol also depend to some extent on whether observations are made on the rising or declining phase of the blood-alcohol curve (Mellanby effect). There will always be some individuals who do not exhibit the expected behavioral impairment effects of ethanol, such as regular heavy drinkers and those suffering from an alcohol use disorder.
Two albums of drawings by Lombard masters of the sixteenth and early seventeenth centuries, from the estate of the Clary-Aldringen family
Authors: Zlatohlávková Eliška , Zlatohlávek Martin
Published: February 2024

Two albums of drawings by Lombard masters of the Renaissance period (sixteenth and early seventeenth centuries), the contents of which are now in museums in the Czech Republic and Slovakia, constitute one of the most valuable collections of drawings preserved in Bohemia from the seventeenth century. Apparently originally the property of Antonio Maria Viani (1555/60–1630), it remains impossible to identify with certainty who collected the drawings at some time before 1676 and pasted them into the two albums, or how they came to be in the possession of the Clary-Aldringen family, from whose hands they eventually passed into public ownership. The aim of this article is to trace the records of this extraordinary collection in the possession of the Clary-Aldringen family since 1676, and its fate after 1945. While one of the albums was later dismembered and the constituent drawings were variously treated, we have been able to trace almost the whole of this collection.
Emphasizing Writing Acts: The Exclamation Point in German as a Lexical Operator for Verum
Authors: Bücking Sebastian
Published: February 2024

This paper is concerned with the interpretation of the exclamation point in German; for example, Es hat geschneit! ‘It has been snowing!’. I argue that the exclamation point contributes a lexical operator for verum at the layer of writing acts. Specifically, it introduces the writer’s wish to ensure the recognition of the writing act in its scope. This lexicon-based proposal builds on a lexicon-based analysis of verum focus. However, while verum focus is related to the propositional layer, the exclamation point is argued to relate to the act layer. The following advantages are defended: (i) The proposal accounts for both the functional kinship between exclamation points and verum focus and their distributional differences. On the one hand, both means introduce affirmative emphasis by a bouletic attitude; on the other hand, the exclamation point has a much wider distribution than verum focus, as it is not bound to contexts that provide a controversy between a proposition and its negation. (ii) The difference in semantic scope can be traced back to a structural difference. While verum focus is integrated into its host clause, exclamation points occupy a peripheral structural position, which is typical of act modifiers. (iii) The lexicon-based approach to the interpretation of exclamation points has noteworthy broader implications. It provides an independent cross-modal piece of evidence in favor of a lexicon-based analysis of verum focus instead of a focus-based one. Furthermore, it is amenable to a formal compositional implementation. This implementation comprises first steps toward a formal model of writing acts in terms of Commitment Space Semantics and advances the general hypothesis that the graphematic form licenses a systematic mapping from form to meaning in its own right.
Macroeconomic and financial mixed frequency factors in a big data environment
Authors: Peng Weijia , Swanson Norman R , Yang Xiye , Yao Chun
Published: February 2024

In this paper, we evaluate the predictive content of 3 new business condition indexes and uncertainty measures that are estimated using high-frequency financial and low-frequency macroeconomic time series data. More specifically, our measures are defined as latent factors that are extracted from a state space model that includes multiple different frequencies of non-parametrically estimated components of quadratic variation, as well as mixed frequency macroeconomic variables. When forecasting growth rates of various monthly financial and macroeconomic variables, use of our new mixed frequency factors is shown to result in significant improvement in predictive performance, relative to a number of benchmark models. Additionally, when used to forecast corporate yields, predictive gains associated with the use of our measures are shown to be monotonically increasing, as one moves from predicting higher to lower rated bonds. This is consistent with the existence of a natural pricing channel wherein financial risk (as measured using our volatility factors) contains more predictive information for lower grade bonds. We also find that a variety of extant risk factors including the Aruoba et al. [(2009a). Real-time measurement of business conditions. Journal of Business & Economic Statistics, 27(4), 417427] business conditions index also contain marginal predictive content for the variables that we examine, although their inclusion does not reduce the usefulness of our measures.
Symptomatic syndrome of inappropriate anti-diuretic hormone as a rare early presentation of primary thymic carcinoma: a case report
Authors: Samsuddin Muhammad Juffri , Yaacob Siti Sara , Razi Adli Azam Bin Mohammad
Published: February 2024

Syndrome of inappropriate anti-diuretic hormone (SIADH) can be presented as a paraneoplastic syndrome in primary malignancies involving the lung and brain. However, the development of SIADH in primary thymic carcinoma is poorly documented. We report a case of an elderly, with an initial presentation of symptomatic persistent hyponatremia as a paraneoplastic syndrome of SIADH with an incidental finding of anterior mediastinal mass confirmed on imaging. Further investigations are consistent with the diagnosis of poorly differentiated locally advanced thymic carcinoma with lung infiltration (T3N1Mx). The patient underwent an En-bloc total thymectomy and subsequently completed adjuvant chemotherapy and further follow-up showed a complete resolution of hyponatraemic SIADH. In conclusion, SIADH may be presented as a paraneoplastic syndrome in primary thymic carcinoma and early detection of thymic malignancy is paramount to ensure early diagnosis and prognostication.
Delayed care-seeking in international migrant workers with imported malaria in China
Authors: Gu Jiyue , Cao Yuanyuan , Chai Liying , Xu Enyu , Liu Kaixuan , Chong Zeyin , Zhang Yuying , Zou Dandan , Xu Yuhui , Wang Jian , Müller Olaf , Cao Jun , Zhu Guoding , Lu Guangyu
Published: February 2024

Background

Imported malaria cases continue to pose major challenges in China as well as in other countries that have achieved elimination. Early diagnosis and treatment of each imported malaria case is the key to successfully maintaining malaria elimination success. This study aimed to build an easy-to-use predictive nomogram to predict and intervene against delayed care-seeking among international migrant workers with imported malaria.

Methods

A prediction model was built based on cases with imported malaria from 2012 to 2019, in Jiangsu Province, China. Routine surveillance information (e.g. sex, age, symptoms, origin country and length of stay abroad), data on the place of initial care-seeking and the gross domestic product (GDP) of the destination city were extracted. Multivariate logistic regression was performed to identify independent predictors and a nomogram was established to predict the risk of delayed care-seeking. The discrimination and calibration of the nomogram was performed using area under the curve and calibration plots. In addition, four machine learning models were used to make a comparison.

Results

Of 2255 patients with imported malaria, 636 (28.2%) sought care within 24 h after symptom onset, and 577 (25.6%) sought care 3 days after symptom onset. Development of symptoms before entry into China, initial care-seeking from superior healthcare facilities and a higher GDP level of the destination city were significantly associated with delayed care-seeking among migrant workers with imported malaria. Based on these independent risk factors, an easy-to-use and intuitive nomogram was established. The calibration curves of the nomogram showed good consistency.

Conclusions

The tool provides public health practitioners with a method for the early detection of delayed care-seeking risk among international migrant workers with imported malaria, which may be of significance in improving post-travel healthcare for labour migrants, reducing the risk of severe malaria, preventing malaria reintroduction and sustaining achievements in malaria elimination.
Seroprevalence of dengue, Japanese encephalitis and Zika among long-term expatriates in Thailand
Authors: Kitro Amornphat , Imad Hisham Ahmed , Pisutsan Phimphan , Matsee Wasin , Sirikul Wachiranun , Sapbamrer Ratana , Rapheal Erica , Fernandez Stefan , Cotrone Thomas S , Farmer Aaron R , Hunsawong Taweewun , Silachamroon Udomsak , Chatapat Lapakorn , Olanwijitwong Jutarmas , Salee Parichat , Anderson Kathryn B , Piyaphanee Watcharapong
Published: February 2024

Background

Travel to Southeast Asia increases the likelihood of acquiring mosquito-borne Flavivirus infections such as dengue (DENV), Japanese encephalitis (JEV) and Zika viruses (ZIKV). Expatriates are long-term travellers who have a higher risk of mosquito-borne illness at their destination country. The purpose of this study was to evaluate the seroprevalence of DENV, JEV and ZIKV infections and the determinants contributing to seropositivity among expatriates living in Thailand.

Methods

A cross-sectional study was performed from December 2017 to February 2020. Expatriates from non-Flavivirus endemic countries were recruited. 5 mL of blood was collected for DENV 1–4, JEV and ZIKV antibody testing by plaque reduction neutralization test (PRNT50). Individuals with vaccination histories or diagnoses for dengue, Japanese encephalitis, yellow fever and tick-borne encephalitis were excluded.

Results

Among 254 participants, most participants (83.1%) were male, the mean age was 65 years and the median duration of stay in Thailand was 6 years. Seroprevalence rate of any Flavivirus, non-specific DENV, DENV1–4, JEV and ZIKV were 34.3, 30.7, 20.5, 18.1, 18.9, 10.6, 4.7 and 2.8%, respectively. The presence of neutralizing antibodies against DENV1–4 positively correlates with the duration of stay in Thailand. DENV seropositivity was associated with living in urban areas (aOR 2.75, 95% CI 1.36–5.57). Expatriates were unlikely to have detectable anti-JEV antibodies regardless of time spent in a JEV-endemic area. No risk factors were identified that were significantly associated with JEV or ZIKV seropositivity. Only 48.4% received pre-travel counselling services, while only 18.9% visited a travel medicine specialist.

Conclusions

A high proportion (34.3%) of long-term expatriates living in Thailand were seropositive for flavivirus, mainly from dengue (30.7%). To minimize risk, travel medicine practitioners should provide adequate pre-travel health risk information on mosquito-borne flavivirus infection and offer advice on mosquito bite prevention strategies. Dengue vaccine might be considered in high-risk travellers such as long-term expatriate.
Integrating sexual and reproductive health into pre-travel consultations
Authors: Santaolaya Carlos , Malhotra Juhi , Fowler James A , Warzywoda Sarah , Debattista Joe , Mills Deborah J , Lau Colleen , Furuya-Kanamori Luis , Durham Jo , Mullens Amy B , Istiko Satrio N , Dean Judith A
Published: February 2024

Background

Casual sex during travel is a major preventable factor in the global transmission of sexually transmissible infections (STI). Pre-travel consults present an excellent opportunity for practitioners to educate travellers about sexual and reproductive health (SRH) and safety. This scoping review aims to explore and understand the extent to which SRH is included in pre-travel consultations.

Methods

PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Scopus, Medline and Web of Science were systematically searched for primary research articles exploring whether health care practitioners (HCP) included SRH in pre-travel consultations. Extracted findings were synthesized and presented in narrative form.

Results

Findings across 13 articles suggest HCPs infrequently broached SRH in pre-travel consultations with HCP discomfort, and lack of time and resources presented as key barriers. Urban practice settings, HCP experience, training in travel medicine and traveller characteristics such as sexual orientation were positively associated with discussions about SRH. SRH advice reported was general in nature, primarily focusing on safer sex, condoms or unspecified STI advice. Risk assessments based solely on age or stereotypes around sexual preferences led to key aspects of SRH care being missed for some (e.g. SRH was less likely to be discussed with older travellers).

Conclusions

HCPs frequently miss opportunities to integrate SRH into pre-travel consultations. Strategies to promote HCP confidence and awareness present a promising means to boost the frequency and quality of SRH advice disseminated. Integrating culturally safe and responsive SRH history-taking and advice into pre-travel consultations may contribute to global reductions in STI transmission and promote traveller SRH well-being.
A decalogue for personalized travel health assistance with AI-driven chatbots
Authors: Baglivo Francesco , De Angelis Luigi , Cruschelli Gianluca , Rizzo Caterina
Published: February 2024

This article delves into the innovative integration of AI-driven chatbots in travel medicine, proposing a decalogue for creating effective, personalized health assistance tools with a practical example (a custom GPT, with OpenAI GPT-4).
Oligogalacturonide application increases resistance to Fusarium head blight in durum wheat
Authors: Bigini Valentina , Sillo Fabiano , Giulietti Sarah , Pontiggia Daniela , Giovannini Luca , Balestrini Raffaella , Savatin Daniel V
Published: February 2024

Fusariosis causes substantial yield losses in the wheat crop worldwide and compromises food safety because of the presence of toxins associated with the fungal disease. Among the current approaches to crop protection, the use of elicitors able to activate natural defense mechanisms in plants is a strategy gaining increasing attention. Several studies indicate that applications of plant cell-wall-derived elicitors, such as oligogalacturonides (OGs) derived from partial degradation of pectin, induce local and systemic resistance against plant pathogens. The aim of this study was to establish the efficacy of OGs in protecting durum wheat (Triticum turgidum subsp. durum), which is characterized by an extreme susceptibility to Fusarium graminearum. To evaluate the functionality of OGs, spikes and seedlings of cv. Svevo were inoculated with OGs, F. graminearum spores, and a co-treatment of both. Results demonstrated that OGs are active elicitors of wheat defenses, triggering typical immune marker genes and determining regulation of fungal genes. Moreover, bioassays on spikes and transcriptomic analyses on seedlings showed that OGs can regulate relevant physiological processes in Svevo with dose-dependent specificity. Thus, the OG sensing system plays an important role in fine tuning immune signaling pathways in durum wheat.