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How vector-borne disease shaped the course of human history
Tejas S. Athni
Marta Shocket

Tejas Athni

and 28 more

June 05, 2020
The extent to which vector-borne diseases (VBDs) have shaped human history remains under-recognized, even in the disease ecology community, despite several well-known examples. Although they represent a significant threat to global human health, accounting for more than one billion cases and one million deaths annually, VBDs have coexisted with humans since the advent of civilization and have migrated with humans around the world. Here, we synthesize historical, anthropological, and archaeological evidence and examine it through an ecological lens to illustrate how four major VBDs—plague, malaria, yellow fever, and trypanosomiasis—have shaped the course of human history through three main pathways: (1) outcomes of colonialism, imperialism, war, and conflict; (2) human interactions with the environment; and (3) intrasocietal human interactions. For example, malaria tipped the American Revolution toward the Continental Army; plague promoted reforestation in Europe; yellow fever entrenched African slavery in colonies in the Americas; trypanosomiasis impeded large settlements and central governments in pre-colonial sub-Saharan Africa. By drawing comparisons across diseases, time periods, and geographic locations, we show how VBDs have historically affected human populations, from the age of early Homo sapiens to the modern context, and how they continue to impact the world.
Semaphorin 4D induces an imbalance of Th17/Treg cells by activating the aryl hydrocar...
Jianmin Xie
Zitao Wang

Jianmin Xie

and 2 more

June 05, 2020
Objectives: to investigate the mechanism by which Sema4D affects the pathogenic progress of ankylosing spondylitis (AS). Methods: Soluble Sema4D (sSema4D) levels in serum were analyzed by enzyme-linked immunosorbent assay. The cell surface levels and transcripts of Sema4D were evaluated in CD4+ and CD19+ cells from the AS patients and healthy individuals. The mRNA expression levels were assessed by quantitative polymerase chain reaction (qPCR). The proportions of Treg cells and IL-17-producing T-cells (Th17 cells) differentiated from CD4+ T cells were analyzed by flow cytometric analysis. The aryl hydrocarbon receptor (AhR) agonistic effect of Sema4D was detected by analyzing the activation of downstream signaling pathways and target genes using Luciferase and EROD assay. Results: Levels of sSema4D were elevated in both serum from AS patients, and clinical features markers were correlated with serum sSema4D levels. Sema4D facilitated CD4+ T cells proliferation and Th17 cells differentiation and inhibited Treg cells differentiation by enhancing RORγt expression and reducing Foxp3 expression, with increasing expression and secretion of IL-17 and IL-22. It induced the expression and activity of AhR target gene CYP1A1 and XRE reporter activity via interaction with CD72. Conclusions: These findings indicate that Sema4D as a potent activator of T cells in the immune response contributes to the inflammation of AS by inducing imbalance in Th17 and Treg cell populations in an AhR-dependent manner, suggesting it is a crucial participant in AS pathogenesis.
No linkages between distributional and functional diversities of NK cells in differen...
Liyan Zhu
Tuohutaerbieke Marmar

Liyan Zhu

and 7 more

June 05, 2020
Natural killer (NK) cells play an important role in the control and even eradication of viral infections. Accumulated studies have shown that NK cells may clear HIV-1-infected cells through natural cytotoxicity or antibody-dependent cellular cytotoxicity (ADCC) ex vivo or in vitro. However, NK cell-directed HIV therapeutic strategies still remain elusive. In the present study, we verified that intracellular HIV DNA load in reactivated HLADR-CD4+ T cells could be significantly inhibited by soluble factors produced by activated NK cells in vitro. Furthermore, bulk NK cells and the cytotoxic CD16+CD56- subset in peripheral blood exhibited higher frequency, cytotoxic potentials, and IFN-γ-producing capacity than that in spleen and LNs. No discrepancies of intracellular SIV DNA or RNA level in resting CD4+ T cells were found among blood, spleen and LNs. Specially, no associations were found between distributional, functional and phenotypic diversities of NK cells and the sizes of intracellular SIV DNA or RNA in regional resting CD4+ T cells in peripheral blood, spleen and LNs. The only difference is that the ratios of SIV DNA/RNA among different organs were positively correlated with NK frequencies in lymphocytes. These results indicated that NK cells may play an inhibitory role on re-activation of latent SIV DNA, while fail to influence the long-term cumulative size of SIV latent DNA or RNA in regional lymphocytes in vivo. Our study suggests NK cell-directed treatment options aiming at HIV clearance still face big challenges.
Identification of peripheral CD154+ T-cells and HLA-DRB1 as biomarkers of acute cellu...
Francisco Boix
Isabel Legaz

Francisco Boix

and 16 more

June 05, 2020
Decreasing graft rejection and increasing graft and patient survival are great challenges facing liver transplantation (LT). Different T-cell subsets participates in the acute cellular rejection (ACR) of the allograft. Cell-mediated immunity markers of the recipient could help to understand the mechanisms underlying acute rejection. This study aimed to analyse CD4+CD154+ and CD8+CD154+ T-cells in a cohort of adult liver patients undergoing LT to determine the influence on ACR using multiparametric flow cytometry functional assay. Thiry patients were immunologically monitored at baseline and during 1 year post-transplant. Two groups were established, with (ACR) and without (NACR) acute cellular rejection. Leukocyte, total lymphocyte, percentages of CD4+CD154+ and CD8+CD154+ T-cells, HLA mismatch between recipient-donor and their relation with ACR as well as the acute rejection frequencies were analysed. T-cells were stimulated with concanavalin A (Con-A) and surface antigens were analysed by FACS analysis. A high percentage of CD4+CD154+ T-cells (p=0.001) and a low percentage of CD8+CD154+ T-cells (p=0.002) at baseline were statistically significant in ACR. A receiver operating characteristic analysis determined the cut-off values capable to stratify patients at high risk of ACR with high sensitivity and specificity for CD4+CD154+ (p=0.001) and CD8+CD154+ T-cells (p=0.002). In logistic regression analysis, CD4+CD154+, CD8+CD154+ and HLA mismatch were confirmed as independent risk factors to ACR. Post-transplant percentages of both T-cell subsets were significantly higher in ACR, despite variations compare to pre-transplant. These findings support the selection of candidates for LT based on the pre-transplant percentages of CD4+CD154+ and CD8+CD154+ T-cells in parallel with other transplant factors
The ENT Run Through Pilot: a questionnaire survey of 23 trainees
Elliot Heward
B. Nirmal Kumar

Elliot Heward

and 1 more

June 05, 2020
• ENT run through posts are extremely competitive requiring a median core surgical interview rank of 27 • Holding additional degrees and transitioning directly from foundation training may improve applicant success • Prior exposure to ENT is variable in successful ST1 applicants • The pilot has been successful in attracting candidates by providing geographical stability and encouraging early engagement with ENT UK • These results will enable development of the pilot programme and provide valuable information for those applying to an ENT run through post
New transoral approach to remove a hilar stone of the submandibular gland
Tsutomu Nomura
Masafumi Ohki

Tsutomu Nomura

and 4 more

June 05, 2020
Background: Surgical treatment for submandibular gland stones varies depending upon the site and size of the submandibular gland. With the transoral method, nerve damage and intraoperative bleeding in the direct incision over the hilar stones are possible. We used the lateral oral floor approach and report our procedure and the associated complications. Methods: Surgery was performed under general anesthesia. A 2–3 cm longitudinal mucosal incision was approximately parallel and outside of the Wharton’s duct. The surrounding tissues were peeled away and the incision was made just above the stone and the stone was extracted. Results: 2 males and 5 females enrolled in this study, all stones were removed without leaving residual stone fragments. One patient had slight hypoesthesia on one side of the tongue, which resolved in 1 month Conclusions: Hilar stone excision from the submandibular gland was performed using the lateral oral floor approach. There were few complications and the technique seemed to be effective for relatively large hilar stones.
FishCARD: Fish 12S California Current Specific Reference Database for Enhanced Metaba...
Zachary Gold
Emma Choi

Zachary Gold

and 7 more

June 05, 2020
DNA metabarcoding is an important tool for molecular ecology. However, metabarcoding effectiveness hinges on the quality of reference databases for taxa and loci of interest. This limitation is true for metabarcoding of marine fishes in the California Current Large Marine Ecosystem where there is a paucity of reference 12S barcodes. Here we present FishCARD, a California Current-specific fish 12S-specific reference barcode database. We barcoded 612 species using the MiFish metabarcoding primers; an addition of 258 species to the 459 California Current fish species with existing 12S barcodes from GenBank. The resulting FishCARD database covers 82.7% of California Current fishes, and it includes virtually all fishes sampled by large marine monitoring programs such as the Partnership for Interdisciplinary Studies of Coastal Oceans and California Cooperative Oceanic Fisheries Investigation. To demonstrate the importance of complete reference databases for eDNA metabarcoding, we compared species and reads identified from three 1L seawater samples collected off Santa Cruz Island, CA using GenBank sequences with and without our generated barcodes, as well as the FishCARD database curated here. The inclusion of our generated barcodes allowed the additional identification of 15 native taxa and 21.8% of total reads from eDNA samples. However, we found that half of all amplicon sequence variants (ASVs) generated by MiFish 12S primers were of non-vertebrate 16S origin, demonstrating a clear limitation of a widely employed fish metabarcoding primers. Despite these limitations, FishCARD provides an important genetic resource to enhance the effectiveness of marine metabarcoding efforts in the California Current Large Marine Ecosystem.
Ketamine Mouthwash versus Placebo in the Treatment of Severe Oral Mucositis Pain in C...
Satya Prakash
Dr J. P. Meena

Satya Prakash

and 6 more

June 05, 2020
Background and aims: Oral mucositis (OM) is common and distressing toxicity in children on chemotherapy. There is limited number of safe and effective therapeutic options available for OM. Ketamine oral rinse has shown promising results in few studies in adults. This randomized, double-blind placebo-controlled trial aimed to test the efficacy of ketamine mouthwash in reducing chemotherapy-induced severe OM pain in children. Methods: Children aged 8-18 years with severe OM were randomized to a single dose of ketamine mouthwash (4 mg/ml solution; dose 1 mg/kg) or a placebo. A sample size of 44 patients was determined. Pain score (6-point faces scale) was noted at baseline and 15, 30, 45, 60, 120, 180, and 240 min. The outcome variables were a reduction in pain score, need for rescue medications, and adverse events. Results: The baseline characteristics were comparable in the two groups. The mean OM pain at 60 min decreased by 1.64 points (CI 1.13-2.14) in the ketamine group and 1.32 points (CI 0.76-1.87) in the placebo group (p=0.425), with a group difference of 0.32 points. Rescue pain medication (at 60 min) was required in 13.6% in the ketamine group and 18.2% in the placebo group (p=1.000). There were no significant adverse events observed. Conclusions: Among children on cancer chemotherapy with severe OM, ketamine mouthwash at a dose of 1 mg/kg did not significantly reduce OM pain. It did not decrease the need for rescue pain medications. Further research is warranted to test higher doses of ketamine for a clinically significant effect.
The COVID-19 Ibuprofen controversy; a systematic review and meta-analysis of NSAIDs i...
Ricky Vaja
Jeffrey Chan

Ricky Vaja

and 7 more

June 05, 2020
In light of the recent safety concerns relating to NSAID use in COVID-19, we sought to evaluate cardiovascular and respiratory complications in patients taking NSAIDs during acute lower respiratory tract infections. We carried out a systematic review and meta-analysis of randomised controlled trials and observational studies. Studies of adult patients with short-term NSAID use during acute lower respiratory tract infections, including bacterial and viral infections, were included. Primary outcome was all-cause mortality. Secondary outcomes were cardiovascular, renal and respiratory complications. In total, eight studies including two randomised controlled trials, three retrospective and three prospective observational studies enrolling 44140 patients were included. Five of the studies were in patients with pneumonia, two in patients with Influenza, and one in patients with acute bronchitis. There was uncertainty as to the effects on mortality (RR 0.87 [0.63, 1.18]), but pleuro-pulmonary complications were more common with NSAID use (RR 2.62 [1.96, 3.50]). However, all studies exhibited high risks of bias, primarily due to confounding variables. Cardiovascular outcomes were not reported by any of the included studies. Short-term NSAID use during acute lower respiratory tract infections was associated with more pleuro-pulmonary complications although this may be due to confounding by indication. There remains significant uncertainty on the effects on mortality. Such results should be interpreted cautiously given the very low quality of evidence. Mechanistic and clinical studies addressing the captioned subject are urgently needed, especially in relation to COVID-19.
In vitro antioxidant properties and inhibitory effect of Plectranthus glandulosus lea...
Djamila Zouheira
Gabriel  Agbor Agbor

Djamila Zouheira

and 6 more

June 05, 2020
Background and Purpose : Oxidation of LDL has been suggested to be an initial step in the development of atherosclerosis. This research work deals with the evaluation of antioxidant potential of Plectranthus glandulosus leaves extracts and fractions as well as its protective effects against human LDL oxidation. Experimental Approach : A preliminary quantitative phytochemical screening was carried out. Antioxidant potential was evaluated employing in vitro hydrogen peroxide, nitric oxide scavenging assays and TAOC test. The human LDL oxidation induced by CuSO4 inhibition test was also performed. Key Results : Plectranthus glandulosus leaves exhibited the presence of 18.3% of saponines, 25.6% of terpenoids and 36.2% of flavonoids. EAF exhibited highest hydrogen peroxide and nitric oxide scavenger activity (IC50 13.63µg/ml and 24.59 µg/ml respectively). Ascorbic acid exhibited an IC50 value of 15.39µg/ml in hydrogen peroxide assay and 22.96 µg/ml in nitric oxide scavenging activity. EAF exhibited a higher TAOC (optical density 0.186±0.00) than that of ascorbic acid (0.162±0.001) at the concentration of 25µg/ml while at 200µg/ml N-BUTF exhibited a higher optical density (1.261±0.001) than that of ascorbic acid (1.065±0.001). EAF lengthened the lag time of the CD formation up to 150mins at the concentration 1mg/ml. TBARS formation inhibition at the concentration 0.5mg/ml, were no significant different between n-butanol (68.55%) ethyl acetate fraction (68.21%) and quercetin 67.69%). Conclusion and Implications : Plectranthus glandulosus is a promising prospect as an anti-atherosclerotic agent and needs a detailed study to establish the same.
Hydroxyurea in children with sickle cell disease in a resource-poor setting: Monitori...
Uche Nnebe-Agumadu
Innocent Adebayo

Uche Nnebe-Agumadu

and 6 more

June 05, 2020
Abstract Background: Effectiveness of hydroxyurea (HU) in SCD is well established. Unanswered questions persist about use in African children in terms of acceptability and monitoring. We determined real-life user-barriers, safety and effects of therapy among children using HU in Nigeria. Methods: We retrieved and reviewed case notes of children on hydroxyurea (10-15mg/kg/day followed by dose escalation) from January 2017 to June 2019, checked for adherence to drugs, clinics and laboratory tests; starting dose, toxicity and benefits (hematologic, clinical, parental satisfaction). A questionnaire complemented case note findings. Results 116 patients received hydroxyurea (mean dose of 18 mg/kg/ day). Improvement in general well-being was 91.25%, reduction in bone pain 83.3%, hospital admissions 71.9%, abdominal pain 62.3%, blood transfusion 56.1%. Sixteen percent voluntarily stopped HU because of cost and side effects. Sixty-seven percent of parents complained about daily drug use, frequency and cost of monitoring. Adherence to daily HU was 88.8%, doctor’s appointments 22.8%, hematology tests 17.5%, organ function 32.5%. Five patients had mild neutropenia. No significant hepatic or renal toxicity occurred. Common side effects were abdominal pain (18.4%) and headache (13.2%). Significant increase in hemoglobin, fetal hemoglobin, MCV and reduction in absolute neutrophil counts occurred. Conclusion: Hydroxyurea at 10-15mg/kg/day is safe, effective and acceptable to parents. Monitoring is challenging. Care-giver education, support services, staff training, HU clinics may improve utilization. HU protocols that reduce monitoring and yet provide good clinical and laboratory benefits are necessary. This study adds to the implementation science strategies that is needed to increase HU use in Nigeria.
Integrated DNA and RNA sequencing reveals targetable alterations in metastatic pediat...
Samara Potter
Jacquelyn Reuther

Samara Potter

and 18 more

June 05, 2020
Background: Pediatric papillary thyroid carcinoma (PTC) is clinically and biologically distinct from adult PTC. We sequenced a cohort of clinically-annotated pediatric PTC cases enriched for high-risk tumors to identify genetic alterations of relevance for diagnosis and therapy. Methods: Tumor DNA and RNA were extracted from FFPE tissue and subjected to next generation sequencing (NGS) library preparation using a custom 124 gene hybridization capture panel and the 75 gene Archer Oncology Research Panel, respectively. NGS libraries were sequenced on an Illumina MiSeq. Results: Thirty-six pediatric PTC cases were analyzed. Metastases were frequently observed to cervical lymph nodes (29/36, 81%), with pulmonary metastases less commonly found (10/36, 28%). Relapsed or refractory disease occurred in 18 patients (18/36, 50%). DNA sequencing revealed targetable mutations in 8 of 31 tumors tested (26%), most commonly BRAF p.V600E (n=6). RNA sequencing identified targetable fusions in 13 of 25 tumors tested (52%): RET (n=8), NTRK3 (n=4), and BRAF. Mutually-exclusive targetable alterations were discovered in 15 of the 20 tumors (75%) with both DNA and RNA analyzed. Fusion positive PTC was associated with multifocal disease, higher tumor staging, and higher American Thyroid Association (ATA) risk levels. Both BRAF V600E mutations and gene fusions were correlated with the presence of cervical metastases. Conclusions: Targetable alterations were identified in 75% of pediatric PTC cases with both DNA and RNA evaluated. Inclusion of RNA sequencing for detection of fusion genes is critical for evaluation of these tumors. Patients with fusion positive tumors were more likely to have features of high-risk disease.
Repurposing of thalidomide and its derivatives for the treatment of SARS-coV-2 infect...
Lakshmikirupa Sundaresan
Suvendu Giri

Lakshmikirupa Sundaresan

and 3 more

June 05, 2020
Background and Purpose: SARS-coV-2 pandemic continues to cause an unprecedented global destabilization. There is an urgent need to develop vaccines or identify molecules to treat severe cases and repurposing of drugs is the best approach at this hour. Thalidomide, despite having an infamous history has been successfully repurposed and tested for various disease conditions including inflammatory diseases and tumor. Few reports emphasize the use of thalidomide with a SARS-coV-2 pneumonia patient being successfully treated with thalidomide. Experimental Approach: A meta-analysis comparing the transcriptomes of SARS-coV-2 infected tissues with thalidomide and lenalidomide-induced transcriptomic changes in transformed lung, endothelial and hematopoietic models was performed. Key Results: Thalidomide and lenalidomide exhibited pleiotropic effects affecting a range of biological processes including inflammation, immune response, angiogenesis, MAPK signaling, NOD-like receptor signaling, TLR signaling, leukocyte differentiation and innate immunity, the processes which are aberrantly regulated in severe COVID-19 patients. In addition, we show the similarities between the expression profiles of SARS-coV-2 infected lung and systemic lupus erythematous. Conclusion and Implications: The present study recommends thalidomide analogs as a “better fit” to treat severe cases of novel viral infections, healing the damaged network by compensating the impairment caused by the Coronavirus disease-2019 (COVID-19).
Mechanistic insights into ventricular arrhythmogenesis of hydroxychloroquine and azit...
Gongxin Wang
Chieh-Ju Lu

Gongxin Wang

and 19 more

June 05, 2020
Background and Purpose: We investigate mechanisms for potential pro-arrhythmic effects of hydroxychloroquine (HCQ) alone, or combined with azithromycin (AZM), in Covid-19 management supplementing the limited available experimental cardiac safety data. Experimental Approach: We integrated patch-clamp studies utilizing In Vitro ProArrhythmia Assay Schema IC50 paradigms, molecular modelling, cardiac multi-electrode array and voltage (RH237) mapping, ECG studies, and Ca2+ (Rhod-2 AM) mapping in isolated Langendorff-perfused guinea-pig hearts with human in-silico ion current modelling. Key Results: HCQ blocked IKr and IK1 with IC50s (10±0.6 and 34±5.0 µM) within clinical therapeutic ranges, INa and ICaL at higher IC50s, leaving Ito and IKs unaffected. AZM produced minor inhibition of INa, ICaL, IKs, and IKr,, sparing IK1 and Ito. HCQ+AZM combined inhibited IKr and IK1 with IC50s of 7.7±0.8 µM and 30.4±3.0 µM, sparing INa, ICaL and Ito. Molecular modelling confirmed potential HCQ binding to hERG. HCQ slowed heart rate and ventricular conduction. It prolonged PR, QRS and QT intervals, and caused prolonged, more heterogeneous, action potential durations and intracellular Ca2+ transients. These effects were accentuated with combined HCQ+AZM treatment, which then elicited electrical alternans, re-entrant circuits and wave break. Modelling studies attributed these to integrated HCQ and AZM actions reducing IKr and IK1, thence altering cell Ca2+ homeostasis. Conclusion and implications: Combined HCQ+AZM treatment exerts pro-arrhythmic ventricular events by synergetically inhibiting IKr, IKs with resulting effects on cellular Ca2+ signalling, and action potential propagation and duration. These findings provide an electrophysiological basis for recent FDA cardiac safety guidelines cautioning against combining HCQ/AZM when treating Covid-19.
Coronavirus disease 2019 three months after hematopoietic stem cell transplant: a ped...
Charlotte Nazon
Aurelie Velay

Charlotte Nazon

and 4 more

June 05, 2020
Pediatric cases represent a small part of COVID-19 cases reported worldwide and children seem to be mostly asymptomatic. The specific risks for patients in pediatric oncology wards are not well known yet. We describe here a pediatric hematopoietic stem cell transplant recipient infected by SARS-CoV-2. Despite being at high potential risk of a severe form of COVID-19 the patient we report only presented a rhinitis. She developed anti-SARS-CoV-2 IgM at D14 and IgG at D56 only and had a positive RT-PCR after 42 days. So far, it seems that in this fragile population COVID-19 is largely pauci-symptomatic.
Covid-19: breaking bad news with social distancing in pediatric oncology
Nicolas André

Nicolas André

June 05, 2020
The covid-19 pandemic has forced citizens worldwide to rely on social distancing measures as the main tools to prevent the rapid spreading of the virus (1). In pediatric oncology, there were important initial concerns for immunocompromised patients who were considered to be at higher risk of developing severe form of the disease (2,3). Consequently, potential challenges (2) have been identified and advice given by the principal child cancer organizations (3). Although more experience from countries that have been facing the pandemic are being published, results are inconsistent so far ranging from reassuring in Milano (4), Madrid (5) or New York (6) to worrying in France where 4 out of 33 Covid-19 positive patients required intensive care and 1 death at last follow up (7).Over the last weeks, despite the pandemic we were able to maintain “normal“ care for pediatric cancer patients in our institution, including high-dose chemotherapy followed by peripheral stem cells transplantations, or recruitment in early phase clinical trials. Only follow-up visits have been re-scheduled or switched to remote consultations. After almost 2 months of lock-down and still ongoing social distancing measures, an unexpected challenge has emerged. Inddeed, during that period, as usual we had to break bad news: for diagnosis, for relapse or palliative care. Initially, when breaking bad news, I had the feeling something was going wrong, or at least was not going as usual. Was I doing something wrong? Was stress induced by a high level of anxiety due to the lack of specific information on the real risk for adolescents/children with cancer both among the medical team and or parents affecting the “breaking bad news” process?Why didn’t I take that teenagers in my arms after disclosing her a metastatic relapse and she looked in such a distress?Social distancing!Masks to start with. They are of course a barrier to saliva droplets potentially containing covid-19, but most importantly they are also a barrier to adequately transmit and discriminate emotions just relying on eyes expression, looks…beyond tears. Silent communication with long looks without words can sometimes be enough and better that long talks but do parents and children feel the same when half of the face is covered. I asked about it to one of my patients and he answered“I think can read your eyes” . By increasing the physical space between people to avoid virus spreading, but here again, for physicians and some parents/patients, holding hands, holding shoulders, hugging are important non-verbal elements of communications and help showing compassion.We might break social distancing to break bad news, but if not pre-agreed by the patient or its parents, is it acceptable? Couldn’t it be perceived as an additional threat, contribute to alter intuitive communication which is characterized by broad, shared goals and mutual respect?Breaking bad news while trying to maintain social distancing is an unexpected new challenge associated with Covid-19. We will very likely learn to better communicate, read & share our respective emotions even with masks and physical distancing and sometimes allow ourselves exceptions to social distancing. Meanwhile, this impact shall be further evaluated among all stakeholders: patients, their parents, and physicians and adapted strategies to better cope with it developed.
Climate and habitat configuration limit range expansion and patterns of dispersal in...
Robert Williams
Alison Dunn

Robert Williams

and 3 more

June 05, 2020
ABSTRACT Aim Invasive species are one of the main causes of biodiversity loss world-wide. As introduced populations increase in abundance and geographical range, so does the potential for negative impacts on native communities. As such, there is a need to better understand the processes driving range expansion as species become established in recipient landscapes. We investigated the potential for population growth and range expansion of introduced populations of a non-native lizard (Podarcis muralis), considering multi-scale factors influencing growth and spatial spread. Location England, UK Methods We collated records of P. muralis presence through field surveys and a citizen science campaign. We used presence-only models to predict climate suitability at a national scale (5km resolution), and fine-scale habitat suitability at the local scale (2m resolution). We then integrated local models into an individual-based modelling platform to simulate population dynamics and forecast range expansion for 10 populations in heterogeneous landscapes. Results National-scale models indicated climate suitability restricted to the southern parts of the UK, limited by a latitudinal cline in overwintering conditions. Patterns of population growth and range expansion were related to differences in local landscape configuration and heterogeneity. Growth curves suggest populations could be in the early stages of exponential growth. However, annual rates of range expansion are predicted to be low (5-16 m). Conclusions We conclude that extensive nationwide range expansion through secondary introduction is likely to be restricted by currently unsuitable climate beyond southern regions of the UK. However, exponential growth of local populations in habitats providing transport pathways is likely to increase opportunities for regional expansion. The broad habitat niche of P. muralis, coupled with configuration of habitat patches in the landscape, allows populations to increase locally with minimal dispersal.
Genotype‐phenotype correlation in patients with TSC2-PKD1 contiguous gene deletion sy...
Shunlai Shang
Yan Mei

Shunlai Shang

and 16 more

June 05, 2020
PKDTS is a progressive hereditary disease that leads to serious clinical symptoms and death. PKDTS cases are reported less frequently. Therefore, there are few studies on the correlation between genotype and phenotype. Similar studies on whether the missing fragments are concentrated in the thermogene are rare. Given the important value of diagnosing PKDTS, it is necessary to develop a diagnostic process. We firstly reported the clinical date of PKDTS patients in China ,also retrieved the case reports of PKDTS published in the past 22 years and summarized the clinical manifestations and genetic characteristics of these patients. Many PKDTS patients have the following symptoms: under 20 years of age, hemangiofibroma, multiple renal cysts, and mental retardation. We did not have find a relationship between clinical phenotype and genotype. The gene deletion of TSC2 and PKD1 is not a hotspot mutation. More reports with detailed clinical descriptions of PKDTS patients and Chinese patients show phenotypic heterogeneity. The gene deletion of TSC2 and PKD1 expanded the mutation database. Moreover, mTOR inhibitors are recommended for treatment. In addition, combining the advantages of exon sequencing and MLPA, we firstly developed a diagnostic process for the disease, which were helpful in detecting new PKDTS.
Pregnancy complications and birth outcomes in pregnant women with viral infections: a...
Dorina Supak
Boglárka Pethő

Dorina Supak

and 4 more

June 05, 2020
Objective: The aim of the present study was to estimate the effect of viral infections on the development of pregnancy complications and on birth outcome. Design: A population-based retrospective study. Setting and Population: 57,231 control pregnancies (without any birth-defects) were analysed in The Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA). Methods: Associations between viral infection exposures in the 1st trimester of pregnancy and pregnancy complications and birth outcomes were analysed using the non-exposure group as reference, adjusting for maternal age, highest education, and maternal tobacco use. Main Outcome Measures: Quantitative variables such as mean maternal age, birth weight and gestational age and categorical variables like pregnancy complications were evaluated in the group of viral infections and control mothers. Results: In total, 2,238 cases with maternal viral infections during pregnancy were identified in the HCCSCA (influenza: 2,016, enterovirus: 48, herpes simplex: 28, hepatitis B: 22, varicella-zoster: 14, respiratory syncytial virus: 11 and unspecified virus infections: 104). The incidences of threatened abortion (OR: 1.3, 95% CI: 1.2-1.5), threatened preterm birth (OR: 1.4, 95% CI: 1.1-1.7) and anaemia (OR: 1.4, 95% CI: 1.3-1.6) were higher in the mothers of cases. The risk of gestational diabetes was lower in the group of viral infections (OR: 0.4, 95% CI: 0.23-0.9). No significant differences have been detected in preterm birth, birth weight or IUGR between the infected and the control groups. Conclusions: The findings of this study suggest that viral infections during pregnancy do not exert a deleterious effect on birth outcomes.
Breastfeeding in neonates during the Coronavirus Disease 2019 pandemic in China: a cr...
Zhuxiao Ren
Dongchi Zhao

Zhuxiao Ren

and 5 more

June 05, 2020
Abstract Objective: To elucidate the current situation of breastfeeding in neonates in China and to investigate whether SARS-CoV-2 is transmitted through the mother’s milk. Design: A nationwide cross-sectional survey Setting: Three hundred and forty-four member hospitals of the Chinese Neonatologist Association network from 31 provinces in China. Sample: Nine hundred and fourteen neonatologists Main outcome measures: These included (1) breastfeeding practices in the obstetrics ward; (2) breastfeeding implementation for neonates admitted to neonatal intensive care unit (NICU); (3) presence of SARS-CoV-2 in the breast milk of COVID-19 positive mothers based on the real-time reverse transcriptase-polymerase chain reaction (RT-PCT) test results. Results: Breastfeeding was undermined during the COVID-19 pandemic. Of the 344 hospitals, 153 (44.48%) centers received breast milk from milk banks to feed babies in NICU. Eight (2.33%) Level III centers performed SARS-CoV-2 PCR tests on breast milk from 15 mothers with COVID-19 and found no SARS-CoV-2 RNA presence in breast milk. Moreover, none of the mothers engaged in breastfeeding. Further, only 52 (5.69%) neonatologists supported breastfeeding in mothers with COVID-19. Conclusions: Based on the available evidence, the benefits of breastfeeding for both infants and mothers outweigh the potential risk of SARS-CoV-2 transmission through breast milk. Amidst the COVID-19 pandemic, medical staff should encourage breastfeeding, in keeping with normal infant feeding guidelines, and provide skilled support to all mothers who choose to breastfeed.
Blockchain and Internet of Things in Higher Education    
Tanweer Alam

Tanweer Alam

and 1 more

June 05, 2020
Blockchain and Internet of Things in Higher EducationTanweer Alam1, Mohamed Benaida21,2Faculty of Computer and Information Systems, Islamic University of Madinah, Saudi Arabia*Corresponding Author: tanweer03@iu.edu.sa
Endovascular repair using an AFX cuff for stent graft induced new entry involved visc...
Takayuki Kadohama
kentaro kiryu

Takayuki Kadohama

and 9 more

June 05, 2020
We encountered a challenging case of endovascular repair for distal stent graft-induced new entry (SINE) using the AFX aortic cuff. Distal SINE was detected on follow-up computed tomography in a 68-year-old man who previously underwent primary thoracic endovascular aortic repair for Stanford type B chronic aortic dissection. The AFX aortic cuff was deployed via a previous endograft to just above the super mesenteric artery with blockage of the celiac artery origin. Postoperative computed tomography revealed no endoleak with a preferable conformation change of the externally mounted graft material of the AFX cuff against the tear (active-seal fixation).
A Mini-Thoracotomy Approach for Walking Veno-Arterial Extracorporeal Membranous Oxyge...
Eric Jeng
Alex Parker

Eric Jeng

and 2 more

June 05, 2020
Fulminant myocarditis is a rapidly progressive myocardial inflammation that commonly requires advanced therapies circulatory support. We report our management for a case of fulminant myocarditis and cardiogenic shock. The patient is a 36 year old gentleman who was admitted after a one week history of malaise. Upon admission he was lethargic with jugular venous distension to 10 cm. He was taken immediately for a heart catheterization and intra-aortic balloon pump placement. There was no obstructive coronary disease, and hemodynamics were consistent with biventricular failure. After multidisciplinary evaluation, we elected to proceed with emergent extracorporeal membranous oxygenation (ECMO). We utilize a Protek Duo Rapid Deployment (LivaNova, Mirandola, Italy) which is inserted via modified Seldinger technique through the left ventricular apex, terminating in the ascending aorta. Percutaneous right IJ bicaval via a y-ed Avalon Elite (Getinge, Goteborg, Sweden) approach is employed for venous drainage (Figure 1). We believe that with this alternative ECMO cannulation platform, we address the multitude of drawbacks that plague peripherally cannulated extracorporeal circulatory support, minimizing patient deconditioning and upper/lower extremity over/under perfusion complications, while providing sternal sparring antegrade arterial flow with ventricular unloading/venting. For two weeks the patient was ambulatory, but because we were unable to obtain an adequate offer during this interval, we transitioned to a bridge to bridge therapy. This case highlights an alternate strategy for central walking VA ECMO in the rare presentation of one patient’s progression from IABP to VA ECMO to durable BiVAD to heart transplantation during a single admission.
The road to clinical PET tracers must be  paved with good intentions            
SRSTT Radiopharmaconnect

SRSTT Radiopharmaconnect

February 23, 2022
Written by Fabien Caillé and Sylvain AuvityTranslational development of PET tracers from bench to clinical applications involves different expertise and requires the determination of numerous parameters to minimize pitfalls
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