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Regional and local determinants of drought resilience in tropical forests
Renan Köpp Hollunder
Mário Garbin

Renan Köpp Hollunder

and 3 more

July 12, 2021
The increase in severity of droughts associated with greater mortality and reduced vegetation growth is one of the main threats to tropical forests. Drought resilience of tropical forests is affected by multiple biotic and abiotic factors varying at different scales. Identifying those factors can help understanding the resilience to ongoing and future climate change. Altitude leads to high climate variation and to different forest formations, principally moist or dry tropical forests with contrasted vegetation structure. Each tropical forest can show distinct responses to droughts. Locally, topography is also a key factor controlling biotic and abiotic factors related to drought resilience in each forest type. Both dry tropical forests and ridges (steeper and drier habitats) are more sensitive to droughts than moist tropical forest and valleys (flatter and wetter habitats). The most important biotic factors are leaf economic and hydraulic plant traits, and vegetation structure. The most important abiotic factors are soil nutrients, water availability and microclimate. Here we show that topography has key roles controlling biotic and abiotic factors in each forest type. Our synthesis highlights that gradients of altitude and topography are essential to understand tropical forest’s resilience to future drought events. We described important factors related to drought resilience, however many important knowledge gaps remain. Filling those gaps will help improve future practices and studies about mitigation capacity, conservation, and restoration of tropical ecosystems.
Cord-blood respiratory syncytial virus antibodies and respiratory health in first 5-y...
Mari Takashima
Keith Grimwood

Mari Takashima

and 10 more

July 12, 2021
Objective: To determine the potential longer-term effects of maternal antenatal respiratory syncytial virus (RSV) vaccination, we examined the association between cord-blood RSV-neutralizing antibodies (RSV-NA) and RSV infections in the first 2-years of life, RSV-NA at 3-years, and respiratory health to age 5-years. Methods: Two community-based Australian birth cohorts were combined. For children with at least one atopic parent, paired serum RSV-NA levels were compared in cord-blood and at age 3-years. Weekly nasal swabs were collected in one cohort and during acute respiratory infections (ARI) in the other. Wheeze history up to age 5-years and physician-diagnosed asthma at 5-years was collected by parent report. Results: In 264 children, each log10 increase of cord-blood RSV-NA level was associated with 37% decreased risk (adjusted incidence-rate-ratio (aIRR) 0.63; 95% confidence interval (CI): 0.40–1.01) of RSV-ARI and 49% decreased risk (aIRR 0.51; 95%CI: 0.25–1.02) of RSV acute lower respiratory infections (ALRI) at 12–24 months of age. However, higher cord-blood RSV-NA was associated with increased risk of all-cause ALRI (aIRR 1.29; 95%CI: 0.99–1.69), wheeze-associated ALRI (aIRR 1.75; 95%CI: 1.08–2.82) and severe ALRI (aIRR 2.76; 95%CI: 1.63–4.70) at age 6–<12 months. Cord-blood RSV-NA was not associated with RSV-ARI in the first 6-months, RSV-NA levels at 3-years, or wheeze or asthma at 5-years. Conclusions: Higher levels of cord-blood RSV-NA did not protect against RSV infections during the first 6-months-of-life, time-to-first RSV-ARI, or wheeze or asthma in the first 5-years of life. Additional strategies to control RSV-related illness in childhood are needed.
Not out of the woods yet: signatures of the prolonged negative genetic consequences o...
Shou-Hsien Li
Yang Liu

Shou-Hsien Li

and 11 more

July 12, 2021
The long-term persistence of a population which has suffered a bottleneck partly depends on how historical demographic dynamics impacted its genetic diversity and the accumulation of deleterious mutations. Here we provide genomic evidence for the detrimental genetic effect of a recent population bottleneck in the endangered black-faced spoonbill (Platalea minor) even after its rapid population recovery. Our population genomic data suggest that the bird’s effective population size, Ne, had been relatively stable (7,500-9,000) since the end of the last glacial maximum; however, a recent brief yet severe bottleneck (Ne= 20) around the 1940s wiped out more than 99% of its historical Ne in roughly three generations. By comparing it with its sister species, the royal spoonbill (P. regia) whose conservation status is of lesser concern, we found that despite a more than 15-fold population recovery since 1988, genetic drift has led to higher levels of inbreeding (7.4 times more runs of homozygosity longer than 100 Kb) in the black-faced spoonbill than in the royal spoonbill genome. Although the two spoonbills have similar levels of genome-wide nucleotide diversity and heterozygosity, because of relaxed purifying selection, individual black-faced spoonbills carry 3% more nonsynonymous substitutions than royal spoonbills each of which is 7% more deleterious. Our results imply that the persistence of a threatened species cannot be inferred from a recovery in its population. They also highlight the necessity of continually using genomic indices to monitor its genetic health and employing all possible measures to assure its long-term persistence in the ever-changing environment.
Migration of Hem-o-lok clip into the common hepatic duct after laparoscopic bile duct...
Zhenhua Tan
Renrui Wan

Zhenhua Tan

and 3 more

July 12, 2021
Hem-o-lok clips are widely used in laparoscopic surgery. Hem-o-lok clips migration into the bile duct can lead to stone formation and granulation tissue hyperplasia. This report discusses a case wherein four clips migrated into the bile duct after laparoscopic bile duct exploration. The patient successfully underwent laparoscopy and choledocholithotomy.
A USP53 p.Cys228Arg variant is associated with autosomal recessive psychosis

José V Pardo

and 5 more

July 14, 2021
A document by Jose V. Pardo. Click on the document to view its contents.
Preliminary studies on apparent Mendelian psychotic disorders in consanguineous famil...

Ambreen Kanwal

and 4 more

July 14, 2021
A document by Jose V. Pardo. Click on the document to view its contents.
Translational and Clinical Pharmacology Considerations in Drug Repurposing for X-link...
Julianne Tieu
Siddhee Sahasrabudhe

Julianne Tieu

and 4 more

July 12, 2021
X-linked adrenoleukodystrophy (X-ALD) is an inherited, neurodegenerative rare disease that can result in devastating symptoms of blindness, gait disturbances, and spastic quadriparesis due to progressive demyelination. Typically, the disease progresses rapidly, causing death within the first decade of life. With limited treatments available, efforts to determine an effective therapy that can alter disease progression or mitigate symptoms have been undertaken for many years, particularly through drug repurposing. Repurposing has generally been guided through clinical experience and small trials. At this time, none of the drug candidates have been approved for use, which may be due, in part, to the lack of pharmacokinetic/pharmacodynamic (PK/PD) information on the repurposed medications in the target patient population. Greater consideration for the disease pathophysiology, drug pharmacology, and potential drug-target interactions, specifically at the site of action, would improve drug repurposing and facilitate development. Although there is a good understanding of X-ALD pathophysiology, the absence of information on drug targets, pharmacokinetics, and pharmacodynamics hinders the repurposing of drugs for this condition. Incorporating advanced translational and clinical pharmacological approaches in preclinical studies and early stages clinical trials will improve the success of repurposed drugs for X-ALD as well as other rare diseases.
Climate exerts stronger control on topsoil carbon persistence than plant input in alp...
Donghai Wu
Xiangtao Xu

Donghai Wu

and 2 more

July 12, 2021
Chen et al. (2021) concluded that plant input governs topsoil carbon persistence in alpine grasslands. We demonstrated that the excluded direct effect of precipitation on topsoil Δ14C in their analysis was in fact significant and strong. Our results provide an alternative viewpoint on the drivers of soil carbon turnover.
Attachment on mortar surfaces by cyanobacterium Gloeocapsa PCC 73106 and sequestratio...
Tingting Zhu
Mohamed Merroun

Tingting Zhu

and 3 more

July 12, 2021
Cyanobacterial carbonate precipitation induced by cells and extracellular polymeric substances (EPS) enhances mortar durability. The percentage of cell/EPS attachment regulates the effectiveness of the mortar restoration. This study investigates the cell coverage on mortar and microbially induced carbonate precipitation. Statistical analysis of results from scanning electron and fluorescence microscopy shows that the cell coverage was higher in the presence of UV-killed cells than living cells. Cells preferably attached to cement paste than sand grains, with a difference of one order of magnitude. The energy-dispersive X-ray spectroscopy analyses and Raman mapping suggest cyanobacteria used atmospheric CO2 to precipitate carbonates.
Ground state solutions for a Schrödinger-Poisson-Slater type with critical growth
JUN LEI
Jiafeng Zhang

JUN LEI

and 2 more

July 12, 2021
We study the existence of ground state solutions of a Schrödinger-Poisson-Slater type equation with critical growth. By using the Nehari-Pohozaev manifold, we obtain the existence of ground state solutions of this system.
Does effective population size affect rates of molecular evolution: mitochondrial dat...
Nahid Shokri Bousjein
Simon Tierney

Nahid Shokri Bousjein

and 3 more

July 12, 2021
Adaptive evolutionary theory argues that organisms with larger effective population size (Ne) should have higher rates of adaptive evolution and therefore greater capacity to win evolutionary arm races. However, in some certain cases species with much smaller Ne may be able to survive beside their opponents for an extensive evolutionary time. Neutral theory predicts that accelerated rates of molecular evolution in organisms with exceedingly small Ne is due to the effects of genetic drift and fixation of slightly deleterious mutations. We test this prediction in two obligate social parasite species and their respective host species from the bee tribe Allodapini. The parasites (genus Inquilina) have been locked into a tight coevolutionary arm races with their exclusive hosts (genus Exoneura) for ~15 million years, even though Inquilina exhibit Ne that are an order of magnitude smaller than their host. In this study, we compared rates of molecular evolution between host and parasite using nonsynonymous to synonymous substitution rate ratios (dN/dS) of eleven mitochondrial protein coding genes sequenced from transcriptomes. Tests of selection on mitochondrial genes indicated no significant differences between host and parasite dN/dS, with evidence for purifying selection acting on all mitochondrial genes of host and parasite species. Several potential factors which could weaken the inverse relationship between Ne and rate of molecular evolution are discussed.
Plants as alternative platforms for monoclonal antibodies productions.
Natalia Glumińska
Magdalena Krzesłowska

Natalia Glumińska

and 1 more

July 12, 2021
Monoclonal antibodies (mAbs) are widely used in medical therapy and diagnostics, veterinary therapy, and research. The demand for mAbs reaches several dozen tons per year and is constantly growing, approaching the limits of current production possibilities. Mammalian expression systems, which currently dominate the bioproduction industry, have limited production capacity and require high capital investment and production costs. Plants are becoming promising expression platforms due to their scalability, speed, low cost of production, low risk of contamination from animal pathogens and eukaryotic mechanisms of post-translational protein modification. The transgenic plants used for the production of mAbs can be obtained by stable transformation of plant cells as well as transient expression of foreign proteins. In this review, we extract a broad overview of articles, many of them from recent years, concerning modern approaches to producing monoclonal antibodies in plants, methods for modifying the carbohydrate profile of mAbs, and purifying the resulting product. We also present current data on the practical use of mAbs in medical therapies and potential methods of producing antibodies on a very large scale, able to meet the future market demand.
Graham-Little Piccardi Lassueur Syndrome and review of the literature
fares alkhayal
Fahad Alsudairy

fares alkhayal

and 3 more

July 12, 2021
Graham-Little Piccardi Lassueur Syndrome (GLPLS) is a rare variant of Lichen planopilaris (LPP) which characterized by triad of fibrosing alopecia of the scalp, non-fibrosing alopecia of the axilla and groin, and a follicular spinous papule over the body.
Non-medical use of baclofen: A case series and review of the literature
Jean Marc Pelerin
Lisa Fristot

Jean Marc Pelerin

and 5 more

July 12, 2021
Aims: Baclofen is widely used for spastic disorders, and most recently for addictive disorders. The first signals of baclofen abuse occurred in the last decade. This study aims to assess the motives, diversion sources and routes of administration associated with the non-medical use of baclofen and examine health problems related to the non-medical use of baclofen. Methods: Spontaneous reports of baclofen abuse reported to the addictovigilance center of East France were analyzed. A literature search was simultaneously conducted using PubMed®, Web of Sciences®, and Google Scholar® databases. Both searches were performed in February 2021 without a time limit. Results: Forty-six cases were analysed (33-from the literature review and 13-from addictovigilance base). Baclofen’s non-medical use mainly affected male subjects with addictive history, but cases of primary abuse in subjects without any substance abuse history were also observed. Euphoria search was the most common reason for misuse. Route of administration included oral, snorting and sublingual use. Physicians were a common source for misused baclofen, but cases involving illegal sources were also observed. Most of the patients misusing baclofen presented serious complications, mainly represented by neurological and respiratory disturbances. Physical and psychological dependence to baclofen was observed in three persons. Conclusion: Although baclofen abuse remains relatively infrequent or (most likely) underestimated, this study helped to confirm the intrinsic abuse potential of baclofen and make visible the baclofen-abuse-related health harms. Careful consideration and benefit-risk analysis should be employed when prescribing baclofen, and emergency departments should be aware of baclofen dangers in abuse situations.
Spacetime estimates and scattering theory for quasilinear Schrodinger equations in ar...
xianfa song

xianfa song

July 12, 2021
In this paper, we consider Cauchy problem of a quasilinear Schrodinger equation which has general form containing potential term, power type nonlinearity and Hartree type nonlinearity. The space dimension is arbitrary, that is, it is larger than or equals to one. First, we establish the local wellposedness of the solution and discuss the condition on the global existence of the solution. Next, we establish some conservation laws such as mass conservation law, energy conservation law, pseudoconformal conservation law of the solution. Based on these conservation laws, we give Morawetz type estimates, spacetime bounds for the global solution. Last, we take two ideas to establish scattering theory for the global solution in different functional spaces. The first idea is that we take different admissible pairs in Strichartz estimates for different terms on the right side of Duhamel's formula in order to keep each term independent, another one is that we factitiously let a continuous function be the sum of two piecewise functions and choose different admissible pairs in Strichartz estimates for the terms containing these functions.
Evaluation of the Effects of Different Rapid Maxillary Expansion Appliances on Obstru...
Gokcenur Gokce
Ozen K Basoglu

Gokcenur Gokce

and 2 more

July 12, 2021
Purpose The aim of this randomized clinical trial was to evaluate the effects of tooth tissue-borne (TTB), tooth-borne (TB), and bone-borne (BB) rapid maxillary expansion appliances on obstructive sleep apnea (OSA) severity. Trial design Three-arm parallel randomized controlled trial. Methods This study was designed in parallel with an allocation ratio of 1:1:1. Forty six patients with narrow maxilla and diagnosis of OSA recruited from the Department of Orthodontics, ### University were randomly assigned to three groups according to appliance used: tooth tissue-borne, tooth-borne and bone-borne expanders. The primary outcome of this study included polygraphic change in sleep parameters. Secondary outcome was the correction of posterior crossbite. Each subject underwent overnight sleep test with polygraphy at baseline and 3 month-follow-up of treatment. Randomization was performed using a computer-generated randomization program The outcome assessor was blinded to group assignment. For the statistical analysis, Kruskal-Wallis analysis and Dunn-Bonferroni tests were used for inter-group comparisons and Wilcoxon analysis was used for intra-group evalaution. p<0.05 was accepted statistically significant. Results The amount of expansion in maxillary width and upper intermolar width were similar in all goups (95% confidence interval [CI], p>0.05). The groups were similar in terms of apnea-hypopnea index (AHI) and oxygen saturation parameters at baseline (95% [CI], p>0.05). After 3 months of treatment, there was no significant decrease in AHI and oxygen desaturation index, and no increase in minimum and mean oxygen saturations (95% [CI], p>0.05). Supine AHI values were decreased by the tooth tissue-borne and tooth-borne appliances, but these changes were not significant (95% [CI], p>0.05). Harms No serious harm ocurred except mild gingivitis. Conclusions Similar skeletal and dental expansion of maxilla were observed after RME with all expanders. Although the decrease in AHI was not significant, RME can be used as an adjunct to the primary treatment in OSA patients.
A multi-method approach to analyze changes in gully characteristics between 2009 and...
Ikenna Osumgborogwu
John Wainwright

Ikenna Osumgborogwu

and 3 more

July 12, 2021
Gully erosion is the dominant environmental problem in southeast Nigeria and has led to loss of human and material resources. In this study, we evaluated changes in gully characteristics in southeast Nigeria between 2009 and 2018 using a multi-method approach including geotechnical investigations, analysis of high-resolution satellite imagery (2 – 5 m) and focus group discussions. Gully numbers increased from 26 to 39 and mean gully length increased from 0.39 to 0.43 km. We found that the soils in the study area have low cohesion and high sand content which make them susceptible to dispersal by erosive forces. Land adjacent to rivers had the highest concentration of gullies, and there was a sharp rise in slope from 10 – 58.2% within a distance less than 500 m from the river. Regarding potential gully-drivers, land-use changes were observed. Non-vegetated lands increased from 58.6 km2 to 144.7 km2 between 2009 and 2018, while reductions in fallowed lands from 281.2 km2 to 57.8 km2 were observed. Results from focus group meetings indicate there was no gullying in the area before the Nigerian civil war. Although war-time activities which led to initiation of oldest gullies have ceased, land-use changes likely increase volume of surface runoff. We infer that interactions between soil conditions which potentially enhance seepage erosion and higher surface runoff resulting from land-use changes have propagated gullying in the study area post-civil war.
IFNγR1 Deficiency Presenting with Visceral Leishmaniasis and Mycobacterium Avium infe...
Muhammad Khalid
Sonia Lemos

Muhammad Khalid

and 9 more

July 12, 2021
A document by Muhammad Khalid. Click on the document to view its contents.
Adventitious rooting in response to long-term cold: a possible mechanism of clonal gr...
Priyanka Mishra
Alice Vayssieres

Priyanka Mishra

and 4 more

July 12, 2021
Arctic alpine species experience extended periods of cold and unpredictable conditions during flowering. Thus, often, alpine plants use both sexual and asexual means of reproduction to maximise fitness and ensure reproductive success. We used the arctic alpine perennial Arabis alpina to explore the role of prolonged cold exposure on adventitious rooting. We exposed plants to 4°C for different durations and scored the presence of adventitious roots on the main stem and axillary branches. Our physiological studies demonstrated that the presence of adventitious roots positively correlates with increased duration of exposure to cold treatment, with 21 weeks at 4 °C saturating the effect of cold on adventitious rooting. On the main stem adventitious roots developed in specific internodes. Transcriptomic and histological studies indicated that adventitious roots in A. alpina stems are initiated during cold exposure and emerge after plants experience growth promoting conditions. The emergence of the adventitious root primordia correlates with an increase in auxin response and free endogenous auxin in the stems. Our results highlight the role of low temperature during clonal growth in alpine plants and provide insights on the molecular mechanisms involved at different stages of adventitious rooting.
Pleistocene expansion, anthropogenic pressure and ocean currents: Disentangling the p...
Ricardo Sousa
Joana Vasconcelos

Ricardo Sousa

and 8 more

July 12, 2021
Rising sea-level following the Last Glacial Maximum lead to fragmentation of coastal limpet populations between islands of the Archipelago of Madeira. This fragmentation is reinforced by recent heavy exploitation reducing effective population size on Madeira Island. We use the limpet P. aspera to understand how the role of processes at different time scales (i.e. changes in the sea level and overexploitation) can influence the genetic composition of an extant species, relating these processes to reproductive phenology and seasonal shifts in ocean currents. Twelve microsatellite genetic markers were used. A power analysis was used to evaluate the power of the microsatellite markers to detect a signal of population differentiation. Long-term past migrations were assessed using a Bayesian Markov Montecarlo approach in the software MIGRATE-n to estimate mutation-scaled migration rates (M = m/μ; m, probability of a lineage immigrating per generation; μ, mutation rate). Two scenarios were evaluated using an Approximate Bayesian Computation (ABC) in the software DIYABC 2.1 (i) Scenario 1: considered a population scenario from a reduced Ne at time t3 to a higher Ne at time t2; and (ii) Scenario 2 considering a reduction of Ne from a time t3 to a time t2. Colonization of the archipelago by Portuguese settlers six centuries ago probably led to an important decrease in the genetic diversity of the species (Ne). Contemporary gene flow strongly support a pattern of high asymmetric connectivity explained by the reproductive phenology of the species and spatio-temporal seasonal changes in the ocean currents. Spatio-temporal reconstructions using Bayesian methods, including coalescent and Approximate Bayesian Computation (ABC) approaches, suggest changes in the migration patterns from highly symmetric to highly asymmetric connectivity with subtle population differentiation as consequence of post-glacial maximum sea level rise during the Holocene.
Automating Complex Data Analysis: A Disruptive Business Opportunity
John F. McGowan, Ph.D.

John F. McGowan, Ph.D.

July 14, 2021
Complex data analysis is a multi-billion dollar business. Major data analysis tool makers alone report revenues totaling over $4 billion per year: SAS Institute ($3.2 Billion), IBM SPSS ($0.3-1.0 Billion), MathWorks ($850 Million), Wolfram Research (at least $40 million), and a number of less well known smaller firms. Medical businesses, financial firms, and science and engineering organizations spend billions of dollars per year on these tools and the salaries of the analysts, scientists, and engineers performing the analyses. Complex data analysis increasingly determines the approval of new drugs and medical treatments, medical treatment decisions for individual patients, investment decisions for banks, pensions, and individuals, important public policy decisions, and the design and development of products from airplanes and cars to smart watches and children's toys.
Shrimp-Allergic Patients in a Multi-Food Oral Immunotherapy Trial
Carla McGuire Davis
Diem-Tran Nguyen

Carla McGuire Davis

and 4 more

July 12, 2021
Title :Shrimp-Allergic Patients in a Multi-Food Oral Immunotherapy TrialAuthors :Diem-Tran I. Nguyen MD1, Sayantani B. Sindher MD2,3, R. Sharon Chinthrajah MD2,3, Kari Nadeau MD PhD2,3, Carla M. Davis MD1,41Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States2Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, CA, USA3Division of Pulmonary, Allergy and Critical Care Medicine, Dept of Medicine, Stanford, CA, USA.4Section of Immunology, Allergy and Retrovirology, Baylor College of Medicine and Texas Children’s Hospital, Houston, TX, United StatesCorresponding Author:Carla M. Daviscarlad@bcm.eduWord Count: 978To the Editor:Shellfish allergy is one of the most common food allergies in the United States accounting for approximately 25% of adulthood and 20% of childhood food allergies (FA).1,2Of the different types of shellfish, shrimp are considered the most allergenic. The prevalence of shellfish allergy in children is substantial at 1.3% and may result in a greater prevalence in the adult population (3%) given that shellfish allergies have a low rate of spontaneous resolution.2,3Shrimp allergy (SA) is a leading cause of severe food reactions and results in high rates of healthcare usage.4Nearly 50% of patients with SA experience at least one lifetime food allergy related Emergency Department visit, yet only 42% of adults and 61% of children with SA reported having a physician confirmed diagnosis.1,2The lack of physician confirmation of SA is concerning given the potentially life threatening consequences of accidental exposure.5Currently, there is no cure and the only management strategies are avoidance and treatment for severe reactions with epinephrine.6 However, avoidance can be difficult due to the high incidence of cross-contamination, requiring strict dietary limitations.Oral immunotherapy (OIT) has emerged as a promising treatment for FA. In OIT, patients ingest increasing doses of the allergenic food with the goal of achieving desensitization so that reactions are less severe. Once a maintenance dose is achieved, the allergen needs to be regularly ingested to preserve the desensitized state. Although OIT has been recently approved by the FDA for peanut allergies, there has been little data in shrimp allergic patients. In this case-series, we discuss a subset of three patients who received shrimp OIT as part of a phase II, multi-food, omalizumab-facilitated OIT clinical trial.Multi-food allergic patients were recruited to a multi-site clinical trial between January 1 and November 30, 2016. Full details of trial design, inclusion criteria, and exclusion criteria have been previously reported.7Patients initially underwent testing with skin prick testing (SPT), specific IgE testing, and double-blind placebo-controlled food challenge (DBPCFC) to confirm their allergy to their culprit foods. To be included, patients were required to have a positive SPT of> 6 mm wheal diameter, specific IgE> 0.35 kU/L, a total IgE <2,000 kU/L, and a clinical reaction with DBPCFCs at < 125 mg dose.Patients enrolled in this clinical trial received 0.016 mg/kg (IU/mL) omalizumab per month or 0.008 mg/kg (IU/mL) every two weeks (based on asthma dosing guidelines)7 from week 1-16. At week 8, multi-food OIT was started and escalated under an investigator-supervised multi-OIT up-dosing regimen to reach a maintenance dose of > 1g of each allergen. Participants who reached maintenance by week 28-29 were randomized and received week 30 DBPCFC to assess desensitization to the allergenic foods. Patients were then randomized to one of three arms: high dose maintenance (1000 mg), low dose maintenance (300 mg), or placebo (0 mg). This randomized dose was dispensed at the last week 30 DBPCFC and consumed until week 36. At week 36, DBPCFC was repeated to assess sustained unresponsiveness with differing daily doses of protein.A total of 70 patients were enrolled, with three found to have SA. Their demographic data and baseline characteristics are detailed in Table 1. All three patients also had asthma, allergic rhinitis, and atopic dermatitis. Each had a convincing clinical history, elevated total IgE, and positive SPT to a mixture of white, brown, and pink shrimp extract from Greer. The diagnosis was confirmed by a reaction during DBPCFC withLitopenaeus setiferus shrimp flour that was manufactured at a Good Manufacturing Practice facility at Stanford University.Clinical outcomes and adverse events are detailed in Table 2. All 3 patients tolerated dose escalation without serious adverse events or epinephrine requirement, were able to achieve maintenance dose, and did not have an allergic reaction at the Week 30 DBPCFC. Patient A was randomized to the placebo treatment arm while the other two patients were randomized to the 300 mg maintenance OIT arm. At Week 36, Patient A and Patient B had sustained unresponsiveness to 12,000 mg of shrimp extract. Patient C did not follow-up for assessment.It is encouraging that all 3 shrimp allergic patients in this multi-food OIT clinical trial were able to reach maintenance dose OIT (> 1g), and 2 out of 3 had no reaction with the 12g DBPCFC dose at Week 30. These results suggest that OIT is a potentially efficacious treatment for SA and warrants further study. There is little data on the optimal shrimp allergen product, dose escalation regimen, and adjunct therapies such as omalizumab to achieve desensitization.There are several known target allergens that contribute to SA. The first major allergen is tropomyosin, a heat-stable, actin-binding protein found in both muscle and non-muscle cells. Tropomyosin has been implicated as the source of significant cross-reactivity between species of mollusks, crustaceans, and non-shellfish such as cockroaches and mites.8,9Other shrimp allergens that have been identified include arginine kinase, myosin light chain, sarcoplasmic calcium-binding protein, hemocyanin, and troponin C.8,9 It is possible that patients with allergies to different shrimp components may have varied responses to OIT, and thus additional research is necessary to determine which patient subgroups are most likely to benefit from shrimp OIT.Our case series is limited by small sample size, with only three patients receiving shrimp OIT and two following up at week 36. Although all patients appeared to develop short-term tolerance by week 30, it is unclear how durable this response would be with long-term follow up. Furthermore, there are risks associated with OIT.SA is a common and serious food allergy that is underdiagnosed and often lifelong. There are currently no effective treatments other than strict avoidance, which can be difficult to achieve and lead to poor quality of life. Our case series presents initial evidence suggesting that shrimp OIT may be an effective strategy of addressing grave reactions faced by SA patients. Larger studies need to be performed to validate these findings.References :1. Gupta, R. S. et al.Prevalence and Severity of Food Allergies Among US Adults. JAMA Netw Open 2, e185630 (2019).2. Wang, H. T., Warren, C. M., Gupta, R. S. & Davis, C. M. Prevalence and Characteristics of Shellfish Allergy in the Pediatric Population of the United States. J. Allergy Clin. Immunol. Pract. 8, 1359–1370.e2 (2020).3. Zotova, V. et al.Low resolution rates of seafood allergy. J. Allergy Clin. Immunol. Pract. 7, 690–692 (2019).4. Ross, M. P. et al.Analysis of food-allergic and anaphylactic events in the National Electronic Injury Surveillance System. J. Allergy Clin. Immunol.121, 166–171 (2008).5. Tuano, K. T. S. et al. Improved diagnostic clarity in shrimp allergic non-dust-mite sensitized patients. Allergy Asthma Proc. 39, 377–383 (2018).6. Davis CM, Gupta RS, Aktas ON, Diaz V, Kamath SD, Lopata AL. Clinical Management of Seafood Allergy. J Allergy Clin Immunol Pract. 2020 Jan;8(1):37-44.7. Andorf, S. et al. A Phase 2 Randomized Controlled Multisite Study Using Omalizumab-facilitated Rapid Desensitization to Test Continued Discontinued Dosing in Multifood Allergic Individuals.EClinicalMedicine 7, 27–38 (2019).8. Faber, M. A. et al.Shellfish allergens: tropomyosin and beyond. Allergy 72, 842–848 (2017).9. Ruethers T, Taki AC, Johnston EB, Nugraha R, Le TTK, Kalic T, McLean TR, Kamath SD, Lopata AL. Seafood allergy: A comprehensive review of fish and shellfish allergens. Mol Immunol. 2018 Aug;100:28-57.
Catheter Ablation of Ventricular Tachycardia in LMNA Cardiomyopathy: Out of Sight but...
Ahmad Halawa
Paul Zei

Ahmad Halawa

and 5 more

July 12, 2021
Lamin Cardiomyopathy (LC) is associated with refractory ventricular arrhythmias. Catheter ablation success rate is low due to presence of multiple circuits and intramural substrate. We present a LC case presented with electrical storm. During catheter ablation, arrhythmia was easily inducible but activation mapping, including full epicardial and endocardial mapping, failed to demonstrate the full tachycardia cycle length (70% only) suggesting intramural activation. Critical isthmus was not identified even with successful concealed entrainment on both Endo/epicardial surfaces. This case shows that even combined endocardial and epicardial catheter approach can be ineffective in identifying the full arrhythmogenic substrate in LC.
COVID-19 and vertical transmission: assessing the expression of ACE2 / TMPRSS2 in the...
Max Beesley
Joseph Davidson

Max Beesley

and 12 more

July 12, 2021
Background: While pregnant women have been identified as a potentially at-risk group concerning COVID-19 infection, little is known regarding the susceptibility of the fetus to infection. Co-expression of ACE2 and TMPRSS2 has been identified as a pre-requisite for infection, and expression across different tissues is known to vary between children and adults. However, the expression of these proteins in the fetus is unknown. Methods: We performed a retrospective analysis of single cell data repositories. This data was then validated at both gene and protein level by performing qRT-PCR and two-colour immunohistochemistry on a library of second-trimester human fetal tissues. Findings: TMPRSS2 is present at both gene and protein level in the predominantly epithelial fetal tissues analysed. ACE2 is present at significant levels, only in the fetal intestine and kidney and is not expressed in the fetal lung. The placenta is also negative for the two proteins both during development and at term. Interpretation: This dataset indicates that the lungs are unlikely to be a viable route of SARS-CoV2 fetal infection. The fetal kidney, despite presenting both the proteins required for the infection, is anatomically protected from the exposure to the virus. However, the GI tract is likely to be susceptible to infection due to its high co-expression of both proteins, as well as its exposure to potentially infected amniotic fluid. Funding: This work was made possible by an MRC / UKRI COVID-19 Rapid response initiative grant (MR/V028480/1).
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