Theoretical modelling predicts that both direct and delayed density-dependence are key factors to generate population cycles. Deciphering density-dependent processes that lead to variable population growth characterizing different phases of the cycles remain challenging. This is particularly the case for the period of prolonged low densities, which is inherently data deficient. However, demographic analyses based on long-term capture-mark-recapture datasets can help resolve this question. We relied on a 16-yr (2004-2019) live-trapping program to analyse the summer demography and movements of a cyclic brown lemming population in the Canadian Arctic. More specifically, we examined if inversely density-dependent processes could explain why population growth can remain low during the prolonged low phase. We found that the proportion of females in the population was inversely density-dependent with a strong male-biased sex ratio at low densities but not at high densities. However, survival of adult females was higher than adult males, but both had lower survival at low densities than at high ones. Distances moved by both adult males and females were density-dependent, and proportion of females in reproductive condition was weakly density-dependent as it tended to increase at low density. Individual body condition, measured as monthly change in body mass, was not density-dependent. Overall, the strong male-biased sex ratio at very low densities suggests a loss of reproductive potential due to the rarity of females and appears to be the most susceptible demographic factor that could contribute to the prolonged low phase in cyclic brown lemmings. What leads to this sex-bias in the first place is still unclear, potentially owing to our trapping period limited to the summer, but we suggest that it could be due to high predations rate on breeding females in winter.

Sodium glucose co-transporter 2 inhibitors (SGLT-2i’s) significantly improve cardiovascular outcome in both diabetic and non-diabetic patients. Preclinical studies suggest that SGLT-2i’s directly affect endothelial function in a glucose-independent manner. The effects of SGLT-2i’s include reduction of oxidative stress and inflammatory reaction in endothelial cells. Furthermore, SGLT2i’s have been shown to restore endothelial-related vasodilation and to regulate angiogenesis. The favorable cardiovascular effects of SGLT-2i’s might be mediated via multiple pathways: 1) by inhibition of the overactive sodium-hydrogen exchanger; 2) by reduction of nicotinamide adenine dinucleotide phosphate oxidases expression; 3) by alleviation of mitochondrial injury; 4) by the suppression of inflammatory-related signaling pathways (e.g. by affecting nuclear factor kappa beta); 5) by modulation of glycolysis, as well as 6) by restoring impaired nitric oxide bioavailability. This review focuses on the most recent progress and existing gaps in preclinical investigations concerning the direct effects of SGLT-2i’s on endothelial dysfunction and their underlying mechanisms.

Letter to the Editor: Interesting clinical observationTitle: Acute Exacerbation of Graft-versus-Host Disease following SARS-CoV2 infection after Hematopoietic Stem Cell Transplant in Two Pediatric PatientsRunning Title: Graft-versus-Host Disease and SARS-CoV2 infectionAuthors: Michelle Choe1,2* Caridad Martinez1,2, Robert Krance1,2, Erin Doherty1,2ORCID:Michelle Choe: 0000-0001-9850-9435Institutional Affiliation:1 Hematology and Cancer Center, Texas Children’s Hospital, Houston, Texas2 Department of Pediatrics, Baylor College of Medicine, Houston, Texas*Corresponding Author:Michelle Choe, MD6701 Fannin St. Ste. 1510Houston, TX 77030P: 832-822-4242F: 832-825-1453Abbreviations key:

We present the case of a middle-aged man who developed an infective endocarditis of the tricuspid valve caused by methicillin-sensitive Staphylococcus aureus and associated with a very large vegetation (nearly 5 cm). Besides the quite unusual size of the vegetation, this report highlights that severe right-sided endocarditis can occur in the absence of classical risk factors (intravenous drug abuse, presence of a cardiac implantable electronic device or other intravascular device, and underlying right-sided cardiac anomaly) and that some cases of severe tricuspid endocarditis can be successfully treated by partial excision and patch repair.

AIM: To improve the tolerability and therapeutic application of histone deacetylase inhibitors (HDACi), by application of an esterase-sensitive motif (ESM), to target pharmacological activity directly to mononuclear myeloid cells expressing the processing enzyme carboxylesterase-1 (CES1). METHODS. This first-in-human study comprised of single and multiple ascending dose cohorts to determine safety and tolerability. Pharmacodynamic parameters included acetylation, cytokine inhibition and intracellular concentrations of processed acid metabolite in isolated monocytes. Mechanistic work was conducted in vitro and in a CES1/Es1elo mouse strain. RESULTS. ESM-HDAC391 was well tolerated whilst showing robust targeted mechanistic engagement, as demonstrated by selective retention of compound and increased acetylation in monocytes plus inhibition of ex vivo stimulated cytokine production. Importantly, common clinical HDACi toxicities were not observed. ESM-HDAC391 treatment was accompanied by the novel finding of a dose-dependent monocyte depletion that was transient and reversible. In-depth characterisation of monocyte depletion in a transgenic mouse model (CES1/Es1elo) suggested that CSF1R loss on circulating cells contributes to ESM-HDAC-mediated depletion. Further mechanistic investigations using human monocytes in vitro demonstrated HDACi-mediated change in myeloid fate through modulation of CSF1R and downstream effects on cell differentiation. CONCLUSION. These findings demonstrate selective targeting of monocytes in humans using the ESM approach and identify monocytopaenia as a novel outcome of ESM-HDACi treatment, with implications for the potential benefit of these molecules in myeloid-driven diseases.

Background: Left ventricular outflow tract pseudoaneurysm is a rare but potentially fatal complication of aortic valve replacement, infective endocarditis, and suture dehiscence. Left ventricular-aortic discontinuity is a severe and uncommon manifestation of IE. For patients who have a long-standing history of endocarditis, peri-annular lesions in the aortic valve may rupture, leading to the rare occurrence of complete, or total, left ventricular-aortic discontinuity. Methods: We present a case of complete postoperative left ventricular-aortic discontinuity and massive circumferential left ventricular outflow tract pseudoaneurysm discovered during a 3-month follow-up visit. Results: Post-operative cardiac CT of a patient demonstrated dehiscence of a recently placed surgical aortic valve from the left ventricular outflow tract, with massive circumferential pseudoaneurysm formation. Only a small remnant of the membranous interventricular septum connected the aortic root to the heart, informing the diagnosis of complete left ventricular-aortic discontinuity. Conclusion: The clinical presentation of a left ventricular outflow tract pseudoaneurysm with concomitant left ventricular-aortic discontinuity is commonly nonspecific or clinically silent; thus, it requires a high index of suspicion and use of multimodality imaging for diagnosis and management.

Objective: To explore the duration of the active phase of the second stage of labour in relation to maternal prepregnant body mass index (BMI). Design: Retrospective cohort study. Setting: Labour wards of three Norwegian university hospitals, 2012-2019. Population: Nulliparous and parous women without previous caesarean section with a live singleton foetus in cephalic presentation and spontaneous onset of labour, corresponding to the Ten Group Classification System (TGCS) group 1 and 3. Methods: Women were stratified to BMI groups according to WHO classification, and estimated median duration of the active phase of the second stage of labour was calculated using Kaplan-Meier analyses. We performed stratified analyses in women with and without epidural analgesia and oxytocin augmentation. Finally, we calculated the Hazard Ratio (HR) of delivery using Cox regression analyses. Caesarean sections and operative vaginal deliveries during the active phase were censored. Main Outcome Measures: Estimated median duration of the active phase of second stage of labour. Results: The final study population comprised 23516 women in TGCS group 1 and 27255 in group 3. Increasing BMI was associated with shorter estimated median duration of the active phase in both TGCS groups. The pattern remained when performing stratified analyses for epidural and oxytocin analgesia. The HR for delivery increased significantly with increasing BMI analysed as a continuous variable; HR 1,019 (95%CI 1.016-1.023) in TGCS group 1 and HR 1,017 (95%CI 1.014-1.020) in TGCS group 3. Conclusion: Increasing BMI was associated with shorter estimated median duration of the active second stage Funding: None.

Nutritional support is essential in the critical care of the very preterm infant, however, study of the potential role of nutrition in the multifactorial pathogenesis of bronchopulmonary dysplasia (BPD) is limited. Achievement of full enteral feeding faster has not been shown to be harmful and may be of benefit in extremely preterm infants. This commentary discusses the studied risk and potential benefits of more rapid enteral feeding advancement in extremely preterm infants.

We report a 36-year-old male with an atypical variant of lipoma occurring on an atypical site.

The aim of our clinical image is to emphasize the value of a careful skin examination in the diagnosis of early-onset sarcoidosis in children.

1. Cattle grazing profoundly affects abiotic and biotic characteristics of ecosystems. While most research has been performed on grasslands, the effect of large managed ungulates on forest ecosystems has largely been neglected. 2. Compared to a baseline semi-natural state, we investigated how long-term cattle grazing of birch forest patches affected the abiotic state and the ecological community (microbes and invertebrates) of the soil subsystem. 3. Grazing strongly modified the soil abiotic environment by increasing phosphorus content, pH and bulk density, while reducing the C:N ratio. The reduced C:N-ratio was strongly associated with a lower microbial biomass, mainly caused by a reduction of fungal biomass. This was linked to a decrease in fungivorous nematode abundance and the nematode channel index, indicating a relative uplift in the importance of the bacterial energy-channel in the nematode assemblages. 4. Cattle grazing highly modified invertebrate community composition producing distinct assemblages from the semi-natural situation. Richness and abundance of microarthropods was consistently reduced by grazing (excepting collembolan richness) and grazing-associated changes in soil pH, Olsen P and reduced soil pore volume (bulk density) limiting niche space and refuge from physical disturbance. Anecic earthworm species predominated in grazed patches, but were absent from ungrazed forest, and may benefit from manure inputs, while their deep vertical burrowing behaviour protects them from physical disturbance. 5. Perturbation of birch forest habitat by long-term ungulate grazing profoundly modified soil biodiversity, either directly through increased physical disturbance and manure input or indirectly by modifying soil abiotic conditions. Comparative analyses revealed the ecosystem engineering potential of large ungulate grazers in forest systems through major shifts in the composition and structure of microbial and invertebrate assemblages, including the potential for reduced energy flow through the fungal decomposition pathway. The precise consequences for trophic interactions and biodiversity-ecosystem function relationships remains to be established, however.

Livestock trading through live animal markets are potential pathways for the introduction and spread of economically important pathogens like the African swine fever virus (ASFV) to new areas in several countries. Due to the high demand for live pigs in Nigeria both for restocking and slaughter, live pigs are sold at designated live pig markets (LPM) in the country. This involves movement of pigs over long distances. Despite, reports of ASF outbreaks following restocking of pigs bought from LPMs, there is paucity of information on the role of LPMs in the epidemiology of ASF. In this study, data and pig samples (whole blood, sera, tissue) were collected from 4 selected LPMs in Nigeria (Dawaki, Katsit, Numan & Pandam) between 2019 and 2020. Samples were analysed by polymerase chain reaction (PCR) and Enzyme-linked Immunosorbent Assay (ELISA). Four genes of ASFV positive samples were characterized to identify the circulating genotypes. Results revealed trade activities involving transportation of pigs from these selected markets to 42 major cities and towns in thirteen (13) States of Nigeria. PCR results revealed an overall ASF prevalence of 10.77% (66/613). ASFV was confirmed by PCR in all the selected LPMs with a prevalence rate of 3.13%-23.81%. The phylogeny revealed genotype I and serogroup 4 based on the p72 protein that encodes the B646L gene and the EP402R gene encoding the CD2V. While sequence analysis of CVR of B602L gene revealed 8 tetrameric repeats variants, six of which have never been reported in Nigeria. Analysis of sera samples recorded a seroprevalence of 6.9% (16/217) within the study period. Findings from this study show that LPM are hotspots and channels for transmission and continuous spread of ASFV in Nigeria. Therefore, for ASF to be controlled in Nigeria, disease surveillance and regulation at LPMs are critical.

To the Editor,Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E (IgE) mediated food allergy that predominantly affects infants and is characterized by repetitive vomiting that occurs 1–4 h after the ingestion of causative food. The etiology and underlying mechanisms of FPIES are not well understood. Recently, egg yolk (EY) has been recognized as a major causative food of FPIES.1,2 Most FPIES patients achieve tolerance with age;3 however, the practice management of EY-associated FPIES (EY-FPIES) has yet to be established. In a preliminary analysis of EY-FPIES, we found that the patients who acquired tolerance to EY had been diagnosed at a significantly younger age than non-tolerated patients despite no difference in the age of onset between both patients. This suggested that the early diagnosis and intervention is beneficial for tolerance acquisition in EY-FPIES. To investigate this further, we compared clinical outcomes between the early and late diagnosis of EY-FPIES.The present study enrolled 21 patients with EY-FPIES (1) diagnosed by positive oral food challenge (OFC) tests at our hospital between April 2018 and April 2021 who (2) subsequently underwent OFC to evaluate tolerance acquisition (re-OFC) at least once. The open OFC was performed by ingestion of a single dose once or three divided doses every 30 minutes. OFC was considered positive for FPIES based on delayed abdominal reactions without immediate skin or respiratory reactions. After confirmation by OFC, we instructed all patients to continue complete elimination of EY, regardless of threshold doses of OFC. We retrospectively collected data from electronic medical records on sex, age of first ingestion of EY, disease onset, first visit to our hospital, diagnosis, specific IgE (sIgE) to EY measured by ImmunoCAP test at diagnosis, asymptomatic histories of EY consumption before onset, the number of symptomatic episodes before diagnosis, the period between the first ingestion of EY and diagnosis of EY-FPIES, and age of tolerance acquisition. Tolerance acquisition was defined by (1) negative OFC and (2) the ability of daily EY consumption without FPIES reactions for three months at home. We divided the patients into the following two groups according to their age at the time of diagnosis: the early diagnosis (ED) group (<12 months) and the late diagnosis (LD) group (≥12 months), and compared the clinical features between both groups. A sIgE value higher than 0.35 UA/ml was defined as positive. Statistical analyses were performed using GraphPad Prism 9. The Mann-Whitney U test was used to compare nonparametric independent samples between the groups. Tolerance acquisition during follow-up was analyzed using a Kaplan–Meier survival curve and the log-rank test. P-value <0.05 was considered statistically significant. This study was approved by the Institutional Review Board of the KKR Sapporo Medical Center (2021-06).Patients’ characteristics are shown in Table 1. The ED group consisted of 12 patients (57.1%), 10 (83.3%) of whom acquired tolerance to EY, and the LD group consisted of nine patients (42.9%), three (33.3%) of whom acquired tolerance to EY. Among 21 patients with EY-associated FPIES, a total of 35 re-OFCs were performed, with a median interval of seven months (interquartile range [IQR], 6–11 months) (Figure 1). The median ages that re-OFC proved negative in ED and LD groups were 16 and 26 months, respectively (p = 0.014) (Table 1). The time to tolerance acquisition was significantly longer in the LD group than that in the ED group, as shown in the Kaplan–Meier analysis (log-rank, p = 0.0015) (Figure 2). The median ages of onset and first visit to our hospital were significantly younger in the ED group than those in the LD group (Table 1). All patients had a history of three episodes (IQR 2–6) of asymptomatic consumption before onset. Although the median age of the first introduction of EY in the ED group was younger than that in the LD group (six months vs. eight months, p = 0.004), there was no significant difference in the median number of asymptomatic consumptions before onset and the period between the first introduction and onset between the groups. The period between the first introduction of EY and FPIES diagnosis was shorter in the ED group than that in the LD group (2.5 months vs. 7 months, p = 0.0002).We demonstrated that the ED group achieved tolerance at a higher rate than the LD group, suggesting that early diagnosis and intervention predict favorable prognosis in EY-FPIES. Consistent with a previous report,4 all patients with EY-FPIES had histories of asymptomatic consumption before disease onset. Involvement of both innate and adaptive immunities with resultant proinflammatory cytokine production has been suggested in the pathology of acute FPIES.5 Our results suggest that the development of EY-FPIES requires sensitization of the adaptive immune system. T helper (Th)2 and Th17 cells are considered as key players of the immune response in FPIES,6 which is reflected by local infiltration of eosinophils and neutrophils, respectively. Adaptive immunity of infants shows dynamic changes with a rapid decline of regulatory T cells and maturation of Th17, while Th2 dominance is preserved.7 Additionally, the intestinal barrier function immaturity was also observed, resulting in a higher permeability of antigens across the intestines.8 Thus, early infants may be predisposed to FPIES because of immunological as well as anatomical immaturity. Although both ED and LD groups shared a similar interval between the first introduction of EY and onset, the period between the onset and diagnosis in the ED group was significantly shorter than that in the LD group. Our results suggest that an earlier elimination of EY after onset prevents the complete development of EY-FPIES.The median age at onset in the 21 patients with EY-FPIES was 8 months (IQR, 7–9 months), which is comparable to previous reports.9 Similar to another report,9 13 patients (65.0%) achieved tolerance at the median age of 16 months. This is earlier than the median age reported in a European series that demonstrates a 50% cumulative probability of resolution at the age of 41 months.10Notably, the median age of diagnosis is older (12 months) in that study compared with that in our series. Thus, the different clinical courses may attribute to differences in age of diagnosis. Otherwise, the clinical course may depend on ethnicity. In 2017, the Japanese Society of Pediatric Allergy and Clinical Immunology recommended the early introduction of EY to infants with a high risk for IgE-mediated egg allergy. This might have increased the number of early-onset EY-FPIES in Japan. Our results suggest that a first re-OFC seven months after the diagnosis is reasonable for preventing unnecessary food avoidance in EY-FPIES.Our study is limited by a retrospective review of a small number of patients from a single institute. Additionally, accidental exposures after diagnosis occurred in one patient in the LD group, influencing the scheduling of re-OFC. Moreover, we evaluated solely patients with a confirmational diagnosis by OFC, which might be insufficient to reflect the whole heterogeneity of EY-FPIES.Conclusively, the ED group achieved tolerance in EY-FPIES earlier compared with the LD group. Early diagnosis and complete elimination of EY may be beneficial for EY-FPIES.

Background: Valve-sparing aortic root replacement such as the re-implantation (David) procedure is becoming increasingly popular. Despite the fact that the procedure is technically more complex, long-term studies demonstrated that excellent clinical outcomes in selected patients with durable repair are achievable. Benefits of minimal access cardiac surgery have stimulated enthusiasm in the use of this approach for valve-sparing aortic root replacement. Methods: We have reviewed available literature on the topic of valve-sparing aortic root replacement (David procedure) via minimally invasive approach through upper hemisternotomy in an attempt to assess current trends and to recognize potential advantages of this technique. Patient selection and preoperative work-up play important role in performing minimally invasive David procedure safely. Surgical technique is similar to the standard David procedure, with several exceptions, and is performed via upper hemisternotomy. Results and Conclusion: Evidence from non-randomized observational and comparative studies demonstrated excellent clinical outcomes of minimally invasive David procedure in selected patients with comparable perioperative mortality to the conventional technique. To date, elective David procedure with a minimal access technique has been performed in low- and intermediate-risk patients. We believe that minimally invasive David procedure could be particularly useful in young patients (Marfan syndrome, bicuspid AV) as it allows faster recovery with improved cosmesis. A decision to perform minimally invasive David procedure should be individualized to each patient and based on the experience of the team. Further large prospective randomized studies with long-term follow-up are still needed to confirm durability of minimal access technique.

Aims The treatment with the wearable cardioverter defibrillator (WCD) may protect against sudden cardiac death (SCD) as a bridging therapy until a cardioverter-defibrillator may be implanted. We analyzed in a multicenter setting a consecutive patient cohort wearing WCD to explore gender differences. Methods and results We analyzed 708 consecutive patients, 579 from whom were males and 129 females (age, 60.5±14 vs. 61.6±17 years old; p=0.44). All patients were divided into age quartiles for analysis. While the rate of ischemic cardiomyopathy (ICM) as a cause of prescription of WCD was significantly higher in males as compared to females (42.7% vs. 26.4%; p=0.001), females received it more frequently due to non-ischemic cardiomyopathy (NICM) (55.8% vs. 42.7%); p=0.009). The wear time of WCD was equivalent in both groups (21.1±4.3 hours/days in males vs. 21.5±4.4 hours/days in females; p=0.27; and 62.6±44.3 days in males vs. 56.5±39 days in females; p=0.15). Mortality was comparable in both groups at 2-year-follow-up (6.8% in males vs. 9.7% in females; p=0.55). Appropriate WCD shocks and the incidence of device implantations were similar in both groups (2.4% in males vs. 3.9% in females; p=0.07) (35.1% in males vs. 31.8% in females; p=0.37), respectively. In age quartile analysis, compliance was observed more in older patients as compared to adult patients (87.8% vs. 68.3%; p<0.001). Conclusion Compliance for wearing WCD was excellent regardless of gender. Furthermore, mortality and the incidence of device implantations were comparable in both groups. Appropriate WCD shocks tended to be higher in females as compared to males.

The aim of this article is to investigate the well-posedness and stability problems of the so-called Kawahara equation under the presence of an interior delayed damping. The system is shown to be well-posed. Furthermore, we prove that the trivial solution is exponentially stable in spite of the delay effect. Specifically, local and semi-global stability results are established according to the properties of the spatial distribution of the delay term.

The Ocean covers two-third of our planet and has great biological heterogeneity. Marine organisms like algae, vertebrates, invertebrates, and microbes are known to provide many natural products with biological activities as well potent sources of biomaterials for therapeutic, biomedical, biosensors, and climate stabilization. Over the years, the field of biosensors have gained huge attention due to their extraordinary ability in providing early diseases diagnosis and treatment as well as environmental pollutants. This review focuses on various biomaterials (Carbohydrtae polymers, proteins, polyacids etc) of marine origin such as Alginate, Chitin, Chitosan, Fucoidan, Carrageenan, Chondroitin Sulfate (CS), Hyaluronic acid (HA), Collagen, marine pigments, marine nanoparticles, Hydroxyapatite (HAp), Biosilica, lectins, and marine whole cell. Further, it mentions the source of such marine biomaterials and their promising evolution for the development of biosensors that are potent to be employed in the biomedical, environmental science and agricultural sciences domains.

The biodiversity in mountainous ecosystems is high but is threatened by rapid environmental change. Urbanization and other anthropogenic factors in the mountains surrounding cities can affect land use and spatial fragmentation. Moreover, patterns of habitat are closely related to elevation and have a major effect on montane biodiversity. The aim of this study was to analyze the effects of spatial fragmentation on the vertical distribution pattern of bird diversity by characterizing the structure of the bird community, species diversity, and landscape factors at different altitudes. From 2016 to 2019, this study made a four-years continuous monitoring of the breeding biric belts. The result indicated Mount Tai harbored a high bird diversity. Bird richness, abundance and Shannon-Wiener index decreased with latitude in Mount Tai. Moreover, the composition of bird communities varied along altitudinal gradients and supported some special species in different elevational bands. Road density, number of habitat patches, patch density, and the percentage of forest significantly affected bird diversity. The effect of patch density was higher compared with other landscape factors. Sufficient habitat and more patches in the low-mountain belt supported higher bird diversity. The middle-mountain belt and high-mountain belt showed contrasting patterns. Our results highlight the effects of ongoing urbanization and human activities on montane biodiversity and emphasize the need for artificial habitats in the mountains surrounding cities to be managed.