Objective Prenatal screening for aneuploidies is best achieved in the first trimester when there is no reliable screening test for spina bifida. Early ultrasound features may be too complex for ...routine screening. We assessed screening potential of simple and reproducible fetal biometric measurements at 11-14 weeks of gestation. Study Design A total of 34,951 unselected consecutive pregnancies included 18 with spina bifida. Another 28 cases were referred for assessment. Biometric measurements were expressed in multiples of the median for crown-rump length. Results Biparietal diameter (BPD) was smaller in spina bifida ( P < .0001). In all, 22 of 44 (50%) cases with spina bifida aperta had a BPD <5th centile. BPD was independent of maternal adiposity and smoking status. Conclusion Simple and reproducible BPD at 11-14 weeks of gestation could detect half the cases of open fetal spina bifida by identifying 5% of pregnancies for expert scanning in first- and second-trimester examinations of the fetal spine and cranium.
Residents of prisons have experienced disproportionate COVID-19-related health harms. To control outbreaks, many prisons in the USA restricted in-person activities, which are now resuming even as ...viral variants proliferate. This study aims to use mathematical modelling to assess the risks and harms of COVID-19 outbreaks in prisons under a range of policies, including resumption of activities.
We obtained daily resident-level data for all California state prisons from Jan 1, 2020, to May 15, 2021, describing prison layouts, housing status, sociodemographic and health characteristics, participation in activities, and COVID-19 testing, infection, and vaccination status. We developed a transmission-dynamic stochastic microsimulation parameterised by the California data and published literature. After an initial infection is introduced to a prison, the model evaluates the effect of various policy scenarios on infections and hospitalisations over 200 days. Scenarios vary by vaccine coverage, baseline immunity (0%, 25%, or 50%), resumption of activities, and use of non-pharmaceutical interventions (NPIs) that reduce transmission by 75%. We simulated five prison types that differ by residential layout and demographics, and estimated outcomes with and without repeated infection introductions over the 200 days.
If a viral variant is introduced into a prison that has resumed pre-2020 contact levels, has moderate vaccine coverage (ranging from 36% to 76% among residents, dependent on age, with 40% coverage for staff), and has no baseline immunity, 23–74% of residents are expected to be infected over 200 days. High vaccination coverage (90%) coupled with NPIs reduces cumulative infections to 2–54%. Even in prisons with low room occupancies (ie, no more than two occupants) and low levels of cumulative infections (ie, <10%), hospitalisation risks are substantial when these prisons house medically vulnerable populations. Risks of large outbreaks (>20% of residents infected) are substantially higher if infections are repeatedly introduced.
Balancing benefits of resuming activities against risks of outbreaks presents challenging trade-offs. After achieving high vaccine coverage, prisons with mostly one-to-two-person cells that have higher baseline immunity from previous outbreaks can resume in-person activities with low risk of a widespread new outbreak, provided they maintain widespread NPIs, continue testing, and take measures to protect the medically vulnerable.
Horowitz Family Foundation, National Institute on Drug Abuse, Centers for Disease Control and Prevention, National Science Foundation, Open Society Foundation, Advanced Micro Devices.
Acute hepatopancreatic necrosis disease (AHPND) is a newly emerging shrimp disease that has severely damaged the global shrimp industry. AHPND is caused by toxic strains of
that have acquired a ..."selfish plasmid" encoding the deadly binary toxins PirA
/PirB
To better understand the repertoire of virulence factors in AHPND-causing
, we conducted a comparative analysis using the genome sequences of the clinical strain RIMD2210633 and of environmental non-AHPND and toxic AHPND isolates of
Interestingly, we found that all of the AHPND strains, but none of the non-AHPND strains, harbor the antibacterial type VI secretion system 1 (T6SS1), which we previously identified and characterized in the clinical isolate RIMD2210633. This finding suggests that the acquisition of this T6SS might confer to AHPND-causing
a fitness advantage over competing bacteria and facilitate shrimp infection. Additionally, we found highly dynamic effector loci in the T6SS1 of AHPND-causing strains, leading to diverse effector repertoires. Our discovery provides novel insights into AHPND-causing pathogens and reveals a potential target for disease control.
Acute hepatopancreatic necrosis disease (AHPND) is a serious disease that has caused severe damage and significant financial losses to the global shrimp industry. To better understand and prevent this shrimp disease, it is essential to thoroughly characterize its causative agent,
Although the plasmid-encoded binary toxins PirA
/PirB
have been shown to be the primary cause of AHPND, it remains unknown whether other virulent factors are commonly present in
and might play important roles during shrimp infection. Here, we analyzed the genome sequences of clinical, non-AHPND, and AHPND strains to characterize their repertoires of key virulence determinants. Our studies reveal that an antibacterial type VI secretion system is associated with the AHPND strains and differentiates them from non-AHPND strains, similar to what was seen with the PirA/PirB toxins. We propose that T6SS1 provides a selective advantage during shrimp infections.
Positron emission tomography (PET) image quality in both clinical and preclinical environments highly depends on an accurate knowledge of the detector hardware to correct for image quality degrading ...effects like gain, temperature, and photon detection efficiency variations of the individual crystals. In conventional PET systems some of these variations are typically corrected using a dedicated calibration scan in which the scanner performance for a well-known activity source is measured. We propose an alternative method for estimating the relative sensitivity of each detector pixel using the coincidences as well as the singles emission data of each PET scan. The overall idea is to compare the total sum of all measured single photons before coincidence processing in each crystal with a steadily low-frequent distribution that can normally be expected. Both the estimated activity and the estimated detector sensitivity are simultaneously improved by using an extended iterative reconstruction scheme. This way we ensure the use of an optimal calibration correction (with the exception of a global factor) for each data set, even if the scanner performance has changed between two scans. Data measured with a preclinical PET scanner (HYPERIon-I) which uses analog silicon photomultipliers in combination with a custom-made ASIC shows a significant increase of image quality and homogeneity using the proposed method.
Background: Microtubules (MTs) buckle and bear load during myocyte contraction, a behavior enhanced by post-translational detyrosination. This buckling suggests a spring-like resistance against ...myocyte shortening, which could store energy and aid myocyte relaxation. Despite this visual suggestion of elastic behavior, the precise mechanical contribution of the cardiac MT network remains to be defined.
Methods: Here we experimentally and computationally probe the mechanical contribution of stable MTs and their influence on myocyte function. We use multiple approaches to interrogate viscoelasticity and cell shortening in primary murine myocytes in which either MTs are depolymerized or detyrosination is suppressed and use the results to inform a mathematical model of myocyte viscoelasticity.
Results: MT ablation by colchicine concurrently enhances both the degree of shortening and speed of relaxation, a finding inconsistent with simple spring-like MT behavior and suggestive of a viscoelastic mechanism. Axial stretch and transverse indentation confirm that MTs increase myocyte viscoelasticity. Specifically, increasing the rate of strain amplifies the MT contribution to myocyte stiffness. Suppressing MT detyrosination with parthenolide or via overexpression of tubulin tyrosine ligase has mechanical consequences that closely resemble colchicine, suggesting that the mechanical impact of MTs relies on a detyrosination-dependent linkage with the myocyte cytoskeleton. Mathematical modeling affirms that alterations in cell shortening conferred by either MT destabilization or tyrosination can be attributed to internal changes in myocyte viscoelasticity.
Conclusions: The results suggest that the cardiac MT network regulates contractile amplitudes and kinetics by acting as a cytoskeletal shock-absorber, whereby MTs provide breakable cross-links between the sarcomeric and nonsarcomeric cytoskeleton that resist rapid length changes during both shortening and stretch.
Estimate the prevalence of neuropathic pain (NeP) among chronic pain patients attending Brazilian hospitals and pain clinics in São Paulo, Ceara, and Bahia and explore clinical characteristics by ...subtypes: painful diabetic peripheral neuropathy (pDPN), central neuropathic pain (CNP), chronic low back pain with a neuropathic component (CLBP-NeP), postherpetic neuralgia (PHN), post-traumatic neuropathic pain (PTN), and post-surgical neuropathic pain (PSN).
Physicians screened patients reporting chronic pain for ≥3 months (n=2,118) for probable NeP, using the Douleur Neuropathique 4 questionnaire and physician assessment, and reported their NeP subtype(s), symptoms, and medications. Identified NeP patients completed a questionnaire including treatment experiences, quality of life EuroQol 5 Dimensions EQ-5D), pain severity and interference (Brief Pain Inventory BPI), and Work Productivity and Activity Impairment scales. Descriptive analyses were performed by NeP subtype.
The prevalence of probable NeP was 14.5% (n=307). NeP patients were mostly female (80.5%), middle-aged (mean M=52.5, SD=13.9), and Pardo (44.3%). Of those diagnosed with an NeP subtype (n=209), the largest proportions were CLBP-NeP (36.8%), followed by pDPN (18.7%), CNP (17.7%), PTN (17.2%), PSN (13.4%), and PHN (3.3%). Across subtypes, the most widely reported symptoms were numbness (range: 62.2%-89.7%) and hyperalgesia (range: 32.1%-76.9%) and the most commonly prescribed pain analgesics were NSAID (range: 18.2%-57.1%), opioids (range: 0.0%-39.3%), and antiepileptics (range: 18.2%-57.1%). PTN and PSN patients reported the least favorable EQ-5D index scores (M=0.42, SD=0.19) and BPI-Pain Severity scores (M=7.0, SD=1.9), respectively. Those diagnosed with CNP had the least favorable BPI-Pain Interference scores (M=6.0, SD=2.7). Patients with PHN reported the least impairment based on EQ-5D index scores (M=0.60, SD=0.04). Those with pDPN had the most favorable BPI scores (BPI-Pain Severity: M=4.6, SD=2.3; BPI-Pain Interference: M=4.7, SD=2.7).
Evaluation of chronic pain patients in Brazil yielded a 14.5% probable NeP prevalence. NSAIDs and opioids were commonly used, and there was a high incidence of NeP-related symptoms with varying levels of dysfunction across subtypes.
Summary
Shifts from coral to algae dominance of corals reefs have been correlated to fish biomass loss and increased microbial metabolism. Here we investigated reef benthic and planktonic primary ...production, benthic dissolved organic carbon (DOC) release and bacterial growth efficiency in the Abrolhos Bank, South Atlantic. Benthic DOC release rates are higher while water column bacterial growth efficiency is lower at impacted reefs. A trophic model based on the benthic and planktonic primary production was able to predict the observed relative fish biomass in healthy reefs. In contrast, in impacted reefs, the observed omnivorous fish biomass is higher, while that of the herbivorous/coralivorous fish is lower than predicted by the primary production‐based model. Incorporating recycling of benthic‐derived carbon in the model through microbial and sponge loops explains the difference and predicts the relative fish biomass in both reef types. Increased benthic carbon release rates and bacterial carbon metabolism, but decreased bacterial growth efficiency could lead to carbon losses through respiration and account for the uncoupling of benthic and fish production in phase‐shifting reefs. Carbon recycling by microbial and sponge loops seems to promote an increase of small‐bodied fish productivity in phase‐shifting coral reefs.
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