Phylogenetic trees in insects are frequently dated by applying a "standard" mitochondrial DNA (mtDNA) clock estimated at 2.3% My(-1), but despite its wide use reliable calibration points have been ...lacking. Here, we used a well-established biogeographic barrier, the mid-Aegean trench separating the western and eastern Aegean archipelago, to estimate substitution rates in tenebrionid beetles. Cytochrome oxidase I (cox1) for six codistributed genera across 28 islands (444 individuals) on both sides of the mid-Aegean trench revealed 60 independently coalescing entities delimited with a mixed Yule-coalescent model. One representative per entity was used for phylogenetic analysis of mitochondrial (cox1, 16S rRNA) and nuclear (Mp20, 28S rRNA) genes. Six nodes marked geographically congruent east-west splits whose separation was largely contemporaneous and likely to reflect the formation of the mid-Aegean trench at 9-12 Mya. Based on these "known" dates, a divergence rate of 3.54% My(-1) for the cox1 gene (2.69% when combined with the 16S rRNA gene) was obtained under the preferred partitioning scheme and substitution model selected using Bayes factors. An extensive survey suggests that discrepancies in mtDNA substitution rates in the entomological literature can be attributed to the use of different substitution models, the use of different mitochondrial gene regions, mixing of intraspecific with interspecific data, and not accounting for variance in coalescent times or postseparation gene flow. Different treatments of these factors in the literature confound estimates of mtDNA substitution rates in opposing directions and obscure lineage-specific differences in rates when comparing data from various sources.
Eosinophilic esophagitis (EoE) represents a chronic, immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by ...eosinophil-predominant inflammation. With few exceptions, 15 eosinophils per high-power field (peak value) in ≥1 biopsy specimens are considered a minimum threshold for a diagnosis of EoE. The disease is restricted to the esophagus, and other causes of esophageal eosinophilia should be excluded, specifically proton pump inhibitor-responsive esophageal eosinophilia. This position paper aims at providing practical guidelines for the management of children and adolescents with EoE.
Relevant literature from searches of PubMed, CINAHL, and recent guidelines was reviewed. In the absence of an evidence base, recommendations reflect the expert opinion of the authors. Final consensus was obtained during 3 face-to-face meetings of the Gastroenterology Committee and 1 teleconference.
The cornerstone of treatment is an elimination diet (targeted or empiric elimination diet, amino acid-based formula) and/or swallowed, topical corticosteroids. Systemic corticosteroids are reserved for severe symptoms requiring rapid relief or where other treatments have failed. Esophageal dilatation is an option in children with EoE who have esophageal stenosis unresponsive to drug therapy. Maintenance treatment may be required in case of frequent relapse, although an optimal regimen still needs to be determined.
EoE is a chronic, relapsing inflammatory disease with largely unquantified long-term consequences. Investigations and treatment are tailored to the individual and must not create more morbidity for the patient and family than the disease itself. Better maintenance treatment as well as biomarkers for assessing treatment response and predicting long-term complications is urgently needed.
Suicide and seasonality Christodoulou, C.; Douzenis, A.; Papadopoulos, F. C. ...
Acta psychiatrica Scandinavica,
February 2012, Letnik:
125, Številka:
2
Journal Article
Recenzirano
Christodoulou C, Douzenis A, Papadopoulos FC, Papadopoulou A, Bouras G, Gournellis R, Lykouras L. Suicide and seasonality.
Objective: Seasonal variation of deaths by suicide offers an important ...pathway in the study of possible suicide determinants of suicide and consequently suicide prevention.
Method: We conducted a review of the literature on suicide seasonality, assessing articles published between 1979 and 2009.
Results: The majority of the studies confirm a peak in spring, mainly for men, older individuals, and violent methods of suicide. A secondary peak during autumn is observed. There is no common seasonality pattern for suicide methods. However, there are also certain studies that did not confirm seasonal variation. Inconsistent results with reduced, unchanged, and even increased suicide seasonality have been reported. Aspects on the association between seasonality and suicides are discussed. Except sex, age, and method of suicide, other parameters were taken into account to find more specific characteristics of seasonality in suicides as well. The influence of clinical, bioclimatic, sociodemographic as well as biological factors seems to affect the seasonal variation.
Conclusion: Studies from both the Northern and the Southern hemisphere report a seasonal pattern for suicides. These studies are not only an important source of epidemiological data for suicides but also represent a global effort to uncover hidden parameters of this self‐destructive behaviour.
Summary Background Hot flushes affect 70% of menopausal women and often severely impact physical, psychosocial, sexual, and overall wellbeing. Hormone replacement therapy is effective but is not ...without risk. Neurokinin B signalling is increased in menopausal women, and has been implicated as an important mediator of hot flushes. Methods This phase 2, randomised, double-blind, placebo-controlled, single-centre, crossover trial assessed the effectiveness of an oral neurokinin 3 receptor antagonist (MLE4901) on menopausal hot flushes. Eligible participants were healthy women aged 40–62 years, having seven or more hot flushes in every 24 h of which some were reported as being severe or bothersome, who had not had a menstrual period for at least 12 months, and who had not been taking any medication shown to improve menopausal flushes in the preceding 8 weeks. Participants received 4 weeks of MLE4901 (40 mg, orally, twice daily) and placebo (orally, twice daily) in random order separated by a 2 week washout period. Randomisation was completed by a central computer, and participants were allocated to treatment number in numerical order. The primary outcome was the total number of hot flushes during the final week of both treatment periods. Analyses were by intention to treat and per protocol using generalised linear mixed models and standard crossover analysis. All analyses were prespecified in the study protocol. The trial is registered at ClinicalTrials.gov , number NCT02668185. Findings 68 women were screened between Feb 3 and Oct 10, 2016, of which 37 were randomly assigned and included in an intention-to-treat analysis. 28 participants completed the trial and were included in a per-protocol analysis. MLE4901 significantly reduced the total weekly number of hot flushes by 45 percentage points (95% CI 22–67) compared with the placebo (intention-to-treat adjusted means: placebo 49·01 95% CI 40·81–58·56 vs MLE4901 19·35 15·99–23·42; adjusted estimate of difference 29·66 17·39–42·87, p<0·0001). Treatment was well tolerated. Three participants developed a transaminase rise (alanine aminotransferase 4·5–5·9 times the upper limit of normal) with a normal bilirubin 28 days after starting MLE4901, which normalised within 90 days. Interpretation Treatment with a neurokinin 3 receptor antagonist (MLE4901) could be practice changing as it safely and effectively relieves hot flush symptoms without the need for oestrogen exposure. Larger scale studies of longer duration are now indicated. Funding UK Medical Research Council and National Institute for Health Research.
IntroductionDiabetes mellitus is a chronic progressive disease, which has been associated with various mental and physical health problems, including sexual disorders. However, especially among ...female patients the potential effects of diabetes on sexual functioning have been understudied.ObjectivesThe aim of this study was to investigate the perceived sexual functioning in patients with diabetes mellitus compared to a group of healthy controls, as well as to explore its possible association with depression, anxiety, self-esteem, well-being and adult romantic attachement.MethodsThe study included 125 patients with diabetes and an equal number of healthy controls. All participants completed the following psychometric scales: Experiences in Close Relationships- Revised (ECR-R), Hospital Anxiety and Depression Scale (HADS), Rosenberg Self-Esteem Scale (RSE), Mental Health Continuum Short Form (MHC-SF), as well as Female Sexual Function Index (FSFI) and International Index of Erectile Function (IIEF) for female and male participants, respectively.ResultsThe results did not reveal a significant relationship between diabetes and sexual functioning, as no statistically significant differences emerged between patients and healthy controls neither among men nor women. However, in patients with diabetes, a positive correlation was found between perceived sexual dysfunction and depression, anxiety, and avoidant and anxious attachment, as well as a negative correlation with self-esteem and well-being.ConclusionsThe findings highlight the importance of investigating sexual functioning among individuals with diabetes mellitus, especially women, as well as its relationship with crucial psychological factors.Disclosure of InterestNone Declared
Cathepsin S is a cysteine protease and regulator of autophagy with possible involvement in periodontitis. The objective of this study was to investigate whether cathepsin S is involved in the ...pathogenesis of periodontal diseases. Human periodontal fibroblasts were cultured under inflammatory and infectious conditions elicited by interleukin-1β and Fusobacterium nucleatum, respectively. An array-based approach was used to analyze differential expression of autophagy-associated genes. Cathepsin S was upregulated most strongly and thus further studied in vitro at gene and protein levels. In vivo, gingival tissue biopsies from rats with ligature-induced periodontitis and from periodontitis patients were also analyzed at transcriptional and protein levels. Multiple gene expression changes due to interleukin-1β and F. nucleatum were observed in vitro. Both stimulants caused a significant cathepsin S upregulation. A significantly elevated cathepsin S expression in gingival biopsies from rats with experimental periodontitis was found in vivo, as compared to that from control. Gingival biopsies from periodontitis patients showed a significantly higher cathepsin S expression than those from healthy gingiva. Our findings provide original evidence that cathepsin S is increased in periodontal cells and tissues under inflammatory and infectious conditions, suggesting a critical role of this autophagy-associated molecule in the pathogenesis of periodontitis.
Severe acute respiratory coronavirus 2 (SARS-CoV-2) infection in the young and healthy usually results in an asymptomatic or mild viral syndrome, possibly through an erythropoietin (EPO)-dependent, ...protective evolutionary landscape. In the old and in the presence of co-morbidities, however, a potentially lethal coronavirus disease 2019 (COVID-19) cytokine storm, through unrestrained renin-angiotensin aldosterone system (RAAS) hyperactivity, has been described. Multifunctional microRNA-155 (miR-155) elevation in malaria, dengue virus (DENV), the thalassemias, and SARS-CoV-1/2, plays critical antiviral and cardiovascular roles through its targeted translational repression of over 140 genes. In the present review, we propose a plausible miR-155-dependent mechanism whereby the translational repression of
AGRT1
,
Arginase-2
and
Ets-1
, reshapes RAAS towards Angiotensin II (Ang II) type 2 (AT2R)-mediated balanced, tolerable, and SARS-CoV-2-protective cardiovascular phenotypes. In addition, it enhances EPO secretion and endothelial nitric oxide synthase activation and substrate availability, and negates proinflammatory Ang II effects. Disrupted miR-155 repression of AT1R + 1166C-allele, significantly associated with adverse cardiovascular and COVID-19 outcomes, manifests its decisive role in RAAS modulation.
BACH1
and
SOCS1
repression creates an anti-inflammatory and cytoprotective milieu, robustly inducing antiviral interferons. MiR-155 dysregulation in the elderly, and in comorbidities, allows unimpeded RAAS hyperactivity to progress towards a particularly aggressive COVID-19 course. Elevated miR-155 in thalassemia plausibly engenders a favorable cardiovascular profile and protection against malaria, DENV, and SARS-CoV-2. MiR-155 modulating pharmaceutical approaches could offer novel therapeutic options in COVID-19.
AXL
is the gene that encodes the Anexelekto (AXL) receptor tyrosine kinase that demonstrates significant roles in various cellular processes, including cell growth, survival, and migration. ...Anexelekto is a Greek word meaning excessive and uncontrolled, semantically implying the crucial involvement of AXL in cancer and immune biology, and in promoting cancer metastasis. AXL overexpression appears to drive epithelial to mesenchymal transition, tumor angiogenesis, decreased antitumor immune response, and resistance to therapeutic agents. Recently, AXL has been reported to play important roles in several viral infections, including SARS-CoV-2. We have previously outlined the importance of microRNAs (miRNAs, miRs) and especially miR-155 in SARS-CoV-2 pathophysiology through regulation of the Renin–Angiotensin Aldosterone System (RAAS) and influence on several aspects of host innate immunity. MiRNAs are negative regulators of gene expression, decreasing the stability of target RNAs or limiting their translation and, enthrallingly, miR-155 is also involved in AXL homeostasis—both endogenously and pharmaceutically using repurposed drugs (e.g., metformin)—highlighting thrifty evolutionary host innate immunity mechanisms that successfully can thwart viral entry and replication. Cancer, infections, and immune system disturbances will increasingly involve miRNA diagnostics and therapeutics in the future.
The severe acute respiratory coronavirus 2 (SARS-CoV-2) infection demonstrates a highly variable and unpredictable course. Several reports have claimed a smoker’s paradox in coronavirus disease 2019 ...(COVID-19), in line with previous suggestions that smoking is associated with better survival after acute myocardial infarction and appears protective in preeclampsia. Several plausible physiological explanations exist accounting for the paradoxical observation of smoking engendering protection against SARS-CoV-2 infection. In this review, we delineate novel mechanisms whereby smoking habits and smokers’ genetic polymorphism status affecting various nitric oxide (NO) pathways (endothelial NO synthase, cytochrome P450 (CYP450), erythropoietin receptor (EPOR); β-common receptor (βcR)), along with tobacco smoke modulation of microRNA-155 and aryl-hydrocarbon receptor (AHR) effects, may be important determinators of SARS-CoV-2 infection and COVID-19 course. While transient NO bioavailability increase and beneficial immunoregulatory modulations through the above-mentioned pathways using exogenous, endogenous, genetic and/or therapeutic modalities may have direct and specific, viricidal SARS-CoV-2 effects, employing tobacco smoke inhalation to achieve protection equals self-harm. Tobacco smoking remains the leading cause of death, illness, and impoverishment.
This guideline provides recommendations for the diagnosis and management of suspected cow's-milk protein allergy (CMPA) in Europe. It presents a practical approach with a diagnostic algorithm and is ...based on recently published evidence-based guidelines on CMPA.
If CMPA is suspected by history and examination, then strict allergen avoidance is initiated. In certain circumstances (eg, a clear history of immediate symptoms, a life-threatening reaction with a positive test for CMP-specific IgE), the diagnosis can be made without a milk challenge. In all other circumstances, a controlled oral food challenge (open or blind) under medical supervision is required to confirm or exclude the diagnosis of CMPA.
In breast-fed infants, the mother should start a strict CMP-free diet. Non-breast-fed infants with confirmed CMPA should receive an extensively hydrolyzed protein-based formula with proven efficacy in appropriate clinical trials; amino acids-based formulae are reserved for certain situations. Soy protein formula, if tolerated, is an option beyond 6 months of age. Nutritional counseling and regular monitoring of growth are mandatory in all age groups requiring CMP exclusion. REEVALUATION: Patients should be reevaluated every 6 to 12 months to assess whether they have developed tolerance to CMP. This is achieved in >75% by 3 years of age and >90% by 6 years of age. Inappropriate or overly long dietary eliminations should be avoided. Such restrictions may impair the quality of life of both child and family, induce improper growth, and incur unnecessary health care costs.
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