The costs of the immune memory within generations.

Immune response is evolutionary costly, but it is not clear whether these costs affect energetic expenditure (short-term cost), growth (medium-term cost), or reproduction (long-term cost). We tested the costs of immune memory in Tenebrio molitor against Metarhizium brunneum. To do this, we used two groups of T. molitor larvae: (a) the control group, which was injected first with Tween solution and 10 days later with M. brunneum and (b) the memory group, which was first injected with M. brunneum and 10 days later with M. brunneum. Compared to controls, larvae of the memory group were more likely to survive, but they also had an increased metabolic rate (CO2 production), spent a long time before becoming pupae, and had a shorter time from pupae to adulthood. In the adult stage, control females preferred control males, but there was no significant difference in the preference of memory females. Finally, control and memory males preferred control females. These results confirm that immune memory has costs in terms of energetic expenditure, growth, and reproduction. To the best of our knowledge, this is the first experimental demonstration that immune memory in larvae is traded-off with adult sexual selection involving mate choice.

A proof of principle study of atomoxetine for the prevention of vasovagal syncope: the Prevention of Syncope Trial VI.

AIMS: There are few effective therapies for vasovagal syncope (VVS). Pharmacological norepinephrine transporter (NET) inhibition increases sympathetic tone and decreases tilt-induced syncope in healthy subjects. Atomoxetine is a potent and highly selective NET inhibitor. We tested the hypothesis that atomoxetine prevents tilt-induced syncope. METHODS AND RESULTS: Vasovagal syncope patients were given two doses of study drug [randomized to atomoxetine 40 mg (n = 27) or matched placebo (n = 29)] 12 h apart, followed by a 60-min drug-free head-up tilt table test. Beat-to-beat heart rate (HR), blood pressure (BP), and cardiac haemodynamics were recorded using non-invasive techniques and stroke volume modelling. Patients were 35 ± 14 years (73% female) with medians of 12 lifetime and 3 prior year faints. Fewer subjects fainted with atomoxetine than with placebo [10/29 vs. 19/27; P = 0.003; risk ratio 0.49 (confidence interval 0.28-0.86)], but equal numbers of patients developed presyncope or syncope (23/29 vs. 21/27). Of patients who developed only presyncope, 87% (13/15) had received atomoxetine. Patients with syncope had lower nadir mean arterial pressure than subjects with only presyncope (39 ± 18 vs. 69 ± 18 mmHg, P < 0.0001), and this was due to lower trough HRs in subjects with syncope (67 ± 30 vs. 103 ± 32 b.p.m., P = 0.006) and insignificantly lower cardiac index (2.20 ± 1.36 vs. 2.84 ± 1.05 L/min/m2, P = 0.075). There were no significant differences in stroke volume index (32 ± 6 vs. 35 ± 5 mL/m2, P = 0.29) or systemic vascular resistance index (2156 ± 602 vs. 1790 ± 793 dynes*s/cm5*m2, P = 0.72). CONCLUSION: Norepinephrine transporter inhibition significantly decreased the risk of tilt-induced syncope in VVS subjects, mainly by blunting reflex bradycardia, thereby preventing final falls in cardiac index and BP.

Cardiovascular profile in postural orthostatic tachycardia syndrome and Ehlers-Danlos syndrome type III.

The cardiovascular profile of postural orthostatic tachycardia syndrome + Ehlers-Danlos syndrome hypermobility type (POTS + EDSIII) has not been described, despite suggestions that it plays a role in orthostatic intolerance. We studied nine individuals diagnosed with POTS + EDSIII and found that the arterial stiffness and cardiac profiles of patients with POTS + EDSIII were comparable to those of age- and sex-matched controls, suggesting an alternate explanation for orthostatic intolerance.

Fungal infections in patients after recovering from COVID-19: a systematic review.

Background and aims: The presence of fungal infections has been described in patients after recovering from COVID-19. This study aims to conduct a systematic review of studies that reported fungal infections (Mucor spp., Pneumocystis jirovecii, or Aspergillus spp.) in adults after recovering from COVID-19. Methods: We performed a systematic review through PubMed, Web of Science, OVID-Medline, Embase, and Scopus. The study selection process was performed independently and by at least two authors. We performed a risk of bias assessment using the Newcastle-Ottawa Scale for cohort and case-control studies, and the Joanna Briggs Institute's Checklists for Case Series and Case Reports. Results: The systematic search found 33 studies meeting all inclusion criteria. There was a total population of 774 participants, ranging from 21 to 87 years. From them, 746 developed a fungal infection. In 19 studies, Mucor spp. was reported as the main mycosis. In 10 studies, P. jirovecii was reported as the main mycosis. In seven studies, Aspergillus spp. was reported as the main mycosis. Regarding the quality assessment, 12 studies were classified as low risk of bias and the remaining studies as high risk of bias. Conclusion: Patients' clinical presentation and prognosis after recovering from COVID-19 with fungal infection differ from those reported patients with acute COVID-19 infection and those without COVID-19 infection.

Association of vitamin B12, folate, and homocysteine with COVID-19 severity and mortality: A systematic review and meta-analysis.

Objective: We aimed to review the available evidence on the association between vitamin B12, folate, and homocysteine levels with worse outcomes among COVID-19 patients. Methods: The search was carried out in ten databases simultaneously run on 10 May 2023, without language restrictions. We included cross-sectional, case-control, and cohort studies. The random-effects meta-analysis was performed using the Sidik-Jonkman method and corrected 95% confidence intervals using the truncated Knapp-Hartung standard errors. Standardized mean difference and 95% CI was used as the measure effect size. Results: Thirteen articles were included in this review (n = 2134). Patients with COVID-19 who did not survive had the highest serum vitamin B12 values (SMD: 1.05; 95% CI: 0.31-1.78; p = 0.01, I2 = 91.22%). In contrast, low serum folate values were associated with patients with severe COVID-19 (SMD: -0.77; 95% CI: -1.35 to -0.19; p = 0.02, I2 = 59.09%). The remaining tested differences did not yield significant results. Conclusion: Elevated serum levels of vitamin B12 were associated with higher mortality in patients with COVID-19. Severe cases of COVID-19 were associated with low serum folate levels. Future studies should incorporate a larger sample size.

Serological and molecular detection of dengue virus in animals: A systematic review and meta-analysis.

Introduction: Dengue is a vector-borne disease, especially important in tropical and subtropical areas. The first presentation of many arboviral diseases occurred mainly in animals, including multiple Alphaviruses and Flaviviruses, such as dengue. Objective: To determine the serological and molecular frequency of the dengue virus in animals. Methods: A systematic literature review was carried out in five databases for the proportion of animals infected with dengue, defined by molecular and serological tests. A meta-analysis was performed using a random-effects model to calculate the pooled prevalence and 95% confidence intervals (CI). Cochran?s Q test and the I2 statistic were used to assess the heterogeneity between the two studies. Results: The presence of dengue in bats, primates, birds, sheep, horses, cattle, pigs, rodents and buffaloes, according to serological methods, had a prevalence of 10%, 29%, 8%, 1%, 11%, 0%, 49%, 2%, 7%, respectively. According to molecular methods, the presence of dengue in bats had a seroprevalence of 6.0%. Conclusion: The present study confirms the presence of the Dengue virus in a large group of animal species, with potential implications as possible reservoirs of this virus, raising the possibility of zoonotic transmission.

Highly pathogenic avian influenza A(H5N1) in animals: A systematic review and meta-analysis.

Introduction: Avian influenza A H5N1 is a significant global public health threat. Although relevant, systematic reviews about its prevalence in animals are lacking. Methods: We performed a systematic literature review in bibliographic databases to assess the prevalence of H5N1 in animals. A meta-analysis with a random-effects model was performed to calculate the pooled prevalence and 95 % confidence intervals (95%CI). In addition, measures of heterogeneity (Cochran's Q statistic and I2 test) were reported. Results: The literature search yielded 1359 articles, of which 33 studies were fully valid for analysis, including 96,909 animals. The pooled prevalence for H5N1 in birds (n = 90,045, 24 studies) was 5.0 % (95%CI: 4.0-6.0 %; I2 = 99.21); in pigs (n = 3,178, 4 studies) was 1.0 % (95%CI: 0.0-1.0 %); in cats (n = 2,911, 4 studies) was 0.0 % (95%CI: 0.0-1.0 %); and in dogs (n = 479, 3 studies) was 0.0 % (95%CI: 0.0-2.0 %). Conclusions: While the occurrence of H5N1 in animals might be comparatively limited compared to other influenza viruses, its impact on public health can be substantial when it transmits to humans. This virus can potentially induce severe illness and has been linked to previous outbreaks. Therefore, it is essential to closely monitor and comprehend the factors influencing the prevalence of H5N1 in both avian and human populations to develop effective disease control and prevention strategies.

Vitamin B12, folate, and homocysteine in metabolic syndrome: a systematic review and meta-analysis.

Background & aims: Metabolic syndrome (MetS) is associated with life-threatening conditions. Several studies have reported an association of vitamin B12, folic acid, or homocysteine (Hcy) levels with MetS. This systematic review and meta-analysis assessed the association of vitamin B12, folic acid, and Hcy levels with MetS. Methods: PubMed, Scopus, Embase, Ovid/Medline, and Web of Science were searched up to February 13, 2023. Cross-sectional, case-control, or cohort studies were included. A random-effects model was performed using the DerSimonian and Laird method to estimate the between-study variance. Effect measures were expressed as odds ratios (OR) with their corresponding 95% confidence intervals (95% CI). Between-study heterogeneity was evaluated using Cochran's Q test and the I2 statistic. Results: Sixty-six articles (n = 87,988 patients) were included. Higher vitamin B12 levels were inversely associated with MetS (OR = 0.87; 95% CI: 0.81-0.93; p < 0.01; I2 = 90%). Higher Hcy levels were associated with MetS (OR = 1.19; 95% CI: 1.14-1.24; p < 0.01; I2 = 90%). Folate levels were not associated with MetS (OR = 0.83; 95% CI: 0.66-1.03; p = 0.09; I2 = 90%). Conclusion: Higher vitamin B12 levels were inversely associated with MetS, whereas higher Hcy levels were associated with MetS. Studies assessing the pathways underlying this association are required.

2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure.

Cardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing-induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre-procedure evaluation and preparation, implant procedure management, follow-up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure.

Cardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing-induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre-procedure evaluation and preparation, implant procedure management, follow-up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

Canadian Cardiovascular Society Position Statement on Postural Orthostatic Tachycardia Syndrome (POTS) and Related Disorders of Chronic Orthostatic Intolerance.

The current definition of postural orthostatic tachycardia syndrome (POTS) dates back to a small case series of patients with a subacute illness who presented with excessive orthostatic tachycardia and orthostatic intolerance, in the absence of another recognized disease. Conventional POTS criteria require an excessive orthostatic tachycardia in the absence of substantial orthostatic hypotension, and predominant symptoms of orthostatic intolerance, worse with upright posture and better with recumbence. POTS is a heterogeneous syndrome with likely several underlying pathophysiological processes, and not a specific disease. The primary panel for this Canadian Cardiovascular Society position statement sought to provide a contemporary update of the best evidence for the evaluation and treatment of POTS. We performed a systemic review of evidence for the evaluation of treatment of POTS using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, and developed recommendations on the basis of the Canadian Cardiovascular Society approach to position statements. One identified problem was that numerous patients who did not meet criteria for POTS would still be given that diagnoses by providers to validate the illness even though this diagnosis is incorrect. This includes patients with postural symptoms without tachycardia, orthostatic tachycardia without symptoms, and those with orthostatic tachycardia but another overt cause for excessive tachycardia. We developed a novel nomenclature ecosystem for orthostatic intolerance syndromes to increase clarity. We also provide more clarity on how to interpret the orthostatic vital signs. These concepts will need to be prospectively assessed.

Canadian Cardiovascular Society Clinical Practice Update on the Assessment and Management of Syncope.

Syncope is a symptom that occurs in multiple settings and has a variety of underlying causes, ranging from benign to life threatening. Determining the underlying diagnosis and prognosis can be challenging and often results in an unstructured approach to evaluation, which is ineffective and costly. In this first ever document, the Canadian Cardiovascular Society (CCS) provides a clinical practice update on the assessment and management of syncope. It highlights similarities and differences between the 2017 American College of Cardiology/American Heart Association/Heart Rhythm Society and the 2018 European Society of Cardiology guidelines, draws on new data following a thorough review of medical literature, and takes the best available evidence and clinical experience to provide clinical practice tips. Where appropriate, a focus on a Canadian perspective is emphasized in order to illuminate larger international issues. This document represents the consensus of a Canadian panel comprised of multidisciplinary experts on this topic with a mandate to formulate disease-specific advice. The primary writing panel wrote the document, followed by peer review from the secondary writing panel. The CCS Guidelines Committee reviewed and approved the statement. The practice tips represent the consensus opinion of the primary writing panel authors, endorsed by the CCS. The CCS clinical practice update on the assessment and management of syncope focuses on epidemiology, the initial evaluation including risk stratification and disposition from the emergency department, initial diagnostic work-up, management of vasovagal syncope and orthostatic hypotension, and syncope and driving.

Virulence Factors of the Entomopathogenic Genus Metarhizium.

The fungal genus Metarhizium has been used as an entomopathogen worldwide for approximately 140 years, and its mechanism of infection and its virulence factors have been studied. The present review is a compilation of virulence factors described in the literature to date and their participation in specific stages of the infection process.

YHR150w and YDR479c encode peroxisomal integral membrane proteins involved in the regulation of peroxisome number, size, and distribution in Saccharomyces cerevisiae.

The peroxin Pex24p of the yeast Yarrowia lipolytica exhibits high sequence similarity to two hypothetical proteins, Yhr150p and Ydr479p, encoded by the Saccharomyces cerevisiae genome. Like YlPex24p, both Yhr150p and Ydr479p have been shown to be integral to the peroxisomal membrane, but unlike YlPex24p, their levels of synthesis are not increased upon a shift of cells from glucose- to oleic acid-containing medium. Peroxisomes of cells deleted for either or both of the YHR150w and YDR479c genes are increased in number, exhibit extensive clustering, are smaller in area than peroxisomes of wild-type cells, and often exhibit membrane thickening between adjacent peroxisomes in a cluster. Peroxisomes isolated from cells deleted for both genes have a decreased buoyant density compared with peroxisomes isolated from wild-type cells and still exhibit clustering and peroxisomal membrane thickening. Overexpression of the genes PEX25 or VPS1, but not the gene PEX11, restored the wild-type phenotype to cells deleted for one or both of the YHR150w and YDR479c genes. Together, our data suggest a role for Yhr150p and Ydr479p, together with Pex25p and Vps1p, in regulating peroxisome number, size, and distribution in S. cerevisiae. Because of their role in peroxisome dynamics, YHR150w and YDR479c have been designated as PEX28 and PEX29, respectively, and their encoded peroxins as Pex28p and Pex29p.

Integration of the Pokeweed miRNA and mRNA Transcriptomes Reveals Targeting of Jasmonic Acid-Responsive Genes.

The American pokeweed plant, Phytolacca americana, displays broad-spectrum resistance to plant viruses and is a heavy metal hyperaccumulator. However, little is known about the regulation of biotic and abiotic stress responses in this non-model plant. To investigate the control of miRNAs in gene expression, we sequenced the small RNA transcriptome of pokeweed treated with jasmonic acid (JA), a hormone that mediates pathogen defense and stress tolerance. We predicted 145 miRNAs responsive to JA, most of which were unique to pokeweed. These miRNAs were low in abundance and condition-specific, with discrete expression change. Integration of paired mRNA-Seq expression data enabled us to identify correlated, novel JA-responsive targets that mediate hormone biosynthesis, signal transduction, and pathogen defense. The expression of approximately half the pairs was positively correlated, an uncommon finding that we functionally validated by mRNA cleavage. Importantly, we report that a pokeweed-specific miRNA targets the transcript of OPR3, novel evidence that a miRNA regulates a JA biosynthesis enzyme. This first large-scale small RNA study of a Phytolaccaceae family member shows that miRNA-mediated control is a significant component of the JA response, associated with widespread changes in expression of genes required for stress adaptation.

Application of Syncope Guidelines in the Emergency Department Do Not Reduce Admission Rates: A Retrospective Cohort Study.

BACKGROUND: Low-risk syncope accounts for a large proportion of hospital admissions; however, inpatient investigations are often not necessary and are rarely diagnostic. Reducing the number of low-risk syncope admissions can likely lower health care resource consumption and overall expenditure. Application of syncope guidelines by physicians in the emergency department provides a standardized approach that may potentially reduce admissions and lead to health care resource utilization savings. METHODS: A retrospective chart review of 1229 syncope presentations was conducted at 2 major academic centres spanning 1 year. Three major society guidelines and position statements were applied to determine the effect on admission rates. RESULTS: A total of 1031 true syncope charts were included in the analysis; 407 (39%) were admitted and 624 (61%) were discharged by the treating physician (MD). There was a significant difference in the mean [standard deviation] age (75 [14] vs 55 [22]) and baseline cardiovascular disease, including congestive heart failure 51/407 (13%) vs 28/624 (5%), coronary artery disease 125/407 (31%) vs 91/624 (15%), and structural heart disease 36/407 (9%) vs 26/624 (4%), between admitted and not admitted patients, respectively (P < 0.01). All guidelines warranted more low-risk admissions when compared with 19% by the MD: Canadian Cardiovascular Society 34% (P < 0.01), American College of Emergency Physicians 22% (P = 0.03), and European Society of Cardiology 26% (P < 0.01). CONCLUSION: In conclusion, application of the current syncope guidelines to an emergency department population is unlikely to reduce low-risk hospital admissions.

Pex30p, Pex31p, and Pex32p form a family of peroxisomal integral membrane proteins regulating peroxisome size and number in Saccharomyces cerevisiae.

The peroxin Pex23p of the yeast Yarrowia lipolytica exhibits high sequence similarity to the hypothetical proteins Ylr324p, Ygr004p, and Ybr168p encoded by the Saccharomyces cerevisiae genome. Ylr324p, Ygr004p, and Ybr168p are integral to the peroxisomal membrane and act to control peroxisome number and size. Synthesis of Ylr324p and Ybr168p, but not of Ygr004p, is induced during incubation of cells in oleic acid-containing medium, the metabolism of which requires intact peroxisomes. Cells deleted for YLR324w exhibit increased numbers of peroxisomes, whereas cells deleted for YGR004w or YBR168w exhibit enlarged peroxisomes. Ylr324p and Ybr168p cannot functionally substitute for one another or for Ygr004p, whereas Ygr004p shows partial functional redundancy with Ylr324p and Ybr168p. Ylr324p, Ygr004p, and Ybr168p interact within themselves and with Pex28p and Pex29p, which have been shown also to regulate peroxisome size and number. Systematic deletion of genes demonstrated that PEX28 and PEX29 function upstream of YLR324w, YGR004w, and YBR168w in the regulation of peroxisome proliferation. Our data suggest a role for Ylr324p, Ygr004p, and Ybr168p--now designated Pex30p, Pex31p, and Pex32p, respectively--together with Pex28p and Pex29p in controlling peroxisome size and proliferation in Saccharomyces cerevisiae.

Pex11-related proteins in peroxisome dynamics: a role for the novel peroxin Pex27p in controlling peroxisome size and number in Saccharomyces cerevisiae.

Transcriptome profiling identified the gene PEX25 encoding Pex25p, a peroxisomal membrane peroxin required for the regulation of peroxisome size and maintenance in Saccharomyces cerevisiae. Pex25p is related to a protein of unknown function encoded by the open reading frame, YOR193w, of the S. cerevisiae genome. Yor193p is a peripheral peroxisomal membrane protein that exhibits high sequence similarity not only to Pex25p but also to the peroxisomal membrane peroxin Pex11p. Unlike Pex25p and Pex11p, Yor193p is constitutively expressed in wild-type cells grown in oleic acid-containing medium, the metabolism of which requires intact peroxisomes. Cells deleted for the YOR193w gene show a few enlarged peroxisomes. Peroxisomes are greatly enlarged in cells harboring double deletions of the YOR193w and PEX25 genes, the YOR193w and PEX11 genes, and the PEX25 and PEX11 genes. Yeast two-hybrid analyses showed that Yor193p interacts with Pex25p and itself, Pex25p interacts with Yor193p and itself, and Pex11p interacts only with itself. Overexpression of YOR193w, PEX25, or PEX11 led to peroxisome proliferation and the formation of small peroxisomes. Our data suggest a role for Yor193p, renamed Pex27p, in controlling peroxisome size and number in S. cerevisiae.

Methylation on RNA: A Potential Mechanism Related to Immune Priming within But Not across Generations.

Invertebrate immune priming is a growing field in immunology. This phenomenon refers to the ability of invertebrates to generate a more vigorous immune response to a second encounter with a specific pathogen and can occur within and across generations. Although the precise mechanism has not been elucidated, it has been suggested that methylation of DNA is a cornerstone for this phenomenon. Here, using a novel method of analytical chemistry (a reversed-phase liquid chromatography procedure) and the beetle Tenebrio molitor as a model system, we did not find evidence to support this hypothesis taking into account the percentage of methylated cytosine entities in DNA (5mdC) within or across generations. However, we found a lower percentage of methylated cytosine entities in RNA (5mC) within but not across generations in immune priming experiments with adults against the bacteria Micrococcus lysodeikticus and larvae against the fungus Metarhizium anisopliae. To our knowledge, this is the first report suggesting a role of differential methylation on RNA during immune priming within generations.