Acetylene Tunes Microbial Growth During Aerobic Cometabolism of Trichloroethene.

Microbial aerobic cometabolism is a possible treatment approach for large, dilute trichloroethene (TCE) plumes at groundwater contaminated sites. Rapid microbial growth and bioclogging pose a persistent problem in bioremediation schemes. Bioclogging reduces soil porosity and permeability, which negatively affects substrate distribution and contaminant treatment efficacy while also increasing the operation and maintenance costs of bioremediation. In this study, we evaluated the ability of acetylene, an oxygenase enzyme-specific inhibitor, to decrease biomass production while maintaining aerobic TCE cometabolism capacity upon removal of acetylene. We first exposed propane-metabolizing cultures (pure and mixed) to 5% acetylene (v v-1) for 1, 2, 4, and 8 d and we then verified TCE aerobic cometabolic activity. Exposure to acetylene overall decreased biomass production and TCE degradation rates while retaining the TCE degradation capacity. In the mixed culture, exposure to acetylene for 1-8 d showed minimal effects on the composition and relative abundance of TCE cometabolizing bacterial taxa. TCE aerobic cometabolism and incubation conditions exerted more notable effects on microbial ecology than did acetylene. Acetylene appears to be a viable approach to control biomass production that may lessen the likelihood of bioclogging during TCE cometabolism. The findings from this study may lead to advancements in aerobic cometabolism remediation technologies for dilute plumes.

Acute Trem2 reduction triggers increased microglial phagocytosis, slowing amyloid deposition in mice.

Heterozygous genetic variants within the TREM2 gene show a strong association with increased Alzheimer's disease (AD) risk. Amyloid beta-depositing mouse models haploinsufficient or null for Trem2 have identified important relationships among TREM2, microglia, and AD pathology; however, results are challenging to interpret in the context of varying microglial phenotypes and disease progression. We hypothesized that acute Trem2 reduction may alter amyloid pathology and microglial responses independent of genetic Trem2 deletion in mouse models. We developed antisense oligonucleotides (ASOs) that potently but transiently lower Trem2 messenger RNA throughout the brain and administered them to APP/PS1 mice at varying stages of plaque pathology. Late-stage ASO-mediated Trem2 knockdown significantly reduced plaque deposition and attenuated microglial association around plaque deposits when evaluated 1 mo after ASO injection. Changes in microglial gene signatures 1 wk after ASO administration and phagocytosis measured in ASO-treated cells together indicate that microglia may be activated with short-term Trem2 reduction. These results suggest a time- and/or dose-dependent role for TREM2 in mediating plaque deposition and microglial responses in which loss of TREM2 function may be beneficial for microglial activation and plaque removal in an acute context.

What came first, the virus or the egg: Innate immunity during viral coinfections.

Infections with any pathogen can be severe and present with numerous complications caused by the pathogen or the host immune response to the invading microbe. However, coinfections, also called polymicrobial infections or secondary infections, can further exacerbate disease. Coinfections are more common than is often appreciated. In this review, we focus specifically on coinfections between viruses and other viruses, bacteria, parasites, or fungi. Importantly, innate immune signaling and innate immune cells that facilitate clearance of the initial viral infection can affect host susceptibility to coinfections. Understanding these immune imbalances may facilitate better diagnosis, prevention, and treatment of such coinfections.

Hybrid 23/25-Gauge Direct Perfluorocarbon Liquid-Silicone Oil Exchange.

PURPOSE: To describe a novel technique for direct perfluorocarbon liquid (PFCL)-silicone oil exchange that aims to reduce the inherent risk of intraoperative intraocular pressure spike. METHODS: We use the conventional setup for passive PFCL-silicone exchange, but intentionally create a mismatch between the passive PFCL aspiration and the active silicone injection that favors the PFCL extrusion. This is achieved by converting one port to a large gauge one-23 or 20-gauge. RESULTS: We did not note the occurrence of high intraocular pressure spikes with this technique as noted by disk pallor or attenuated vessels. CONCLUSION: A hybrid 23/25-gauge technique for direct PFCL-silicone oil exchange is safe and reduces the risk of intraoperative intraocular pressure spike.

Transgenerational plasticity alters parasite fitness in changing environments.

Transgenerational plasticity can help organisms respond rapidly to changing environments. Most prior studies of transgenerational plasticity in host­parasite interactions have focused on the host, leaving us with a limited understanding of transgenerational plasticity of parasites. We tested whether exposure to elevated temperatures while spores are developing can modify the ability of those spores to infect new hosts, as well as the growth and virulence of the next generation of parasites in the new host. We exposed Daphnia dentifera to its naturally co-occurring fungal parasite Metschnikowia bicuspidata, rearing the parasite at cooler (20°C) or warmer (24°C) temperatures and then, factorially, using those spores to infect at 20 and 24°C. Infections by parasites reared at warmer past temperatures produced more mature spores, but only when the current infections were at cooler temperatures. Moreover, the percentage of mature spores was impacted by both rearing and current temperatures, and was highest for infections with spores reared in a warmer environment that infected hosts in a cooler environment. In contrast, virulence was influenced only by current temperatures. These results demonstrate transgenerational plasticity of parasites in response to temperature changes, with fitness impacts that are dependent on both past and current environments.

Testing the effectiveness of the Developing Inclusive Youth program: A multisite randomized control trial.

The Developing Inclusive Youth program is a classroom-based, individually administered video tool that depicts peer-based social and racial exclusion, combined with teacher-led discussions. A multisite randomized control trial was implemented with 983 participants (502 females; 58.5% White, 41.5% Ethnic/racial minority; Mage  = 9.64 years) in 48 third-, fourth-, and fifth-grade classrooms across six schools. Children in the program were more likely to view interracial and same-race peer exclusion as wrong, associate positive traits with peers of different racial, ethnic, and gender backgrounds, and report play with peers from diverse backgrounds than were children in the control group. Many approaches are necessary to achieve antiracism in schools. This intervention is one component of this goal for developmental science.

Tempering Expectations for Outpatient Total Knee Arthroplasty for Patients Over 70.

BACKGROUND: Total knee arthroplasty (TKA) is now considered an outpatient procedure, yet advanced age impacts patients' ability to achieve outpatient discharge. Therefore, the purpose of this study is to determine the rate of successful outpatient discharge for TKA patients above 70 years of age and identify potential barriers to success. METHODS: This retrospective review included 352 unilateral TKA patients. The rapid discharge protocol was followed for all patients with the intention of discharge within a 24-hour period. Successful outpatient discharge was classified as ≤24-hour stay and failure was any stay exceeding a 24-hour period in the hospital. Univariate logistic regressions were performed to determine the influence of independent variables on discharge status for all patients and only patients >70 years old. RESULTS: Overall, 46 patients (13%) failed to achieve outpatient discharge, with 35 (76%) patients being ≥70 years old. For patients ≥70, age was not a predictive variable for failure to achieve outpatient discharge (P = .484). However, being female (odds ratio 3.273, 95% confidence interval 1.286-8.325, P = .013) and the use of an assistive walking device (odds ratio 3.031, 95% confidence interval 1.387-6.625, P = .005) remained independent contributors to prolonged hospital stay. CONCLUSION: With patients ≥70 years old more likely to require >24-hour stays, age should be an evaluated metric for justifying higher levels of reimbursement. Although TKA is now considered an outpatient procedure, greater consideration should be given to patients ≥70 years old for higher levels of reimbursement as outpatient discharge is less likely to be successful.

Water-Soluble NIR Absorbing and Emitting Indolizine Cyanine and Indolizine Squaraine Dyes for Biological Imaging.

Organic dyes that absorb and emit in the near-infrared (NIR) region are potentially noninvasive, high-resolution, and rapid biological imaging materials. Indolizine donor-based cyanine and squaraine dyes with water-solubilizing sulfonate groups were targeted in this study due to strong absorptions and emissions in the NIR region. As previously observed for nonwater-soluble derivatives, the indolizine group with water-solubilizing groups retains a substantial shift toward longer wavelengths for both absorption and emission with squaraines and cyanines relative to classically researched indoline donor analogues. Very high quantum yields (as much as 58%) have been observed with absorption and emission >700 nm in fetal bovine serum. Photostability studies, cell culture cytotoxicity, and cell uptake specificity profiles were all studied for these dyes, demonstrating exceptional biological imaging suitability.

Tibial Intraosseous Insertion in Pediatric Emergency Care: A Review Based upon Postmortem Computed Tomography.

Objective: The proximal tibia is a recommended and commonly used site for pediatric emergency intraosseous vascular access (IO). During forensic whole body postmortem computed tomography (PMCT), we evaluated accuracy of emergency placement of tibial IO access.Methods: We conducted a retrospective review of 92 state medical examiner cases to assess presence and placement of tibial IO needles. Insertions were classified as successful (needle tip in the medullary portion of the bone) or unsuccessful (all other non-medullary placements) based upon position of the needle tip. Medical records were reviewed for patient age, equipment, and where an insertion was attempted, as well as if IO placement occurred in a prehospital or hospital environment.Results: Thirty-one cases with 42 tibial devices (aged 3 weeks to 16 years, median 4 months) were identified. In 25 insertions (60%), the needle tip was in satisfactory position. In 17 placements (40%), needle tip was unsatisfactory and included tibia perforation (6), tip embedded in the cortex (6), and needle missed the bone (5). In patients older than 6 months, all six placements of a 15-mm needle were successful. In infants age 6 months or younger, 14 placements (56%) were successful and 11 (44%) unsuccessful. The 25-mm IO needle was successfully placed in five of six children older than 6 months. In infants age 6 months or younger, the 25-mm needle was unsuccessfully placed in five of five attempts.Conclusion: In infants 6 months of age or younger, tibial IO needle insertion had a 53% failure rate (non-medullary placement). Failures occur during both prehospital and emergency department care. In infants age 6 months or younger, use of a 25-mm needle should be avoided. Procedures for IO insertion in infants age 6 months or younger should be reviewed and modification considered.

Tau reduction in the presence of amyloid-ß prevents tau pathology and neuronal death in vivo.

Several studies have now supported the use of a tau lowering agent as a possible therapy in the treatment of tauopathy disorders, including Alzheimer's disease. In human Alzheimer's disease, however, concurrent amyloid-ß deposition appears to synergize and accelerate tau pathological changes. Thus far, tau reduction strategies that have been tested in vivo have been examined in the setting of tau pathology without confounding amyloid-ß deposition. To determine whether reducing total human tau expression in a transgenic model where there is concurrent amyloid-ß plaque formation can still reduce tau pathology and protect against neuronal loss, we have taken advantage of the regulatable tau transgene in APP/PS1 × rTg4510 mice. These mice develop both neurofibrillary tangles as well as amyloid-ß plaques throughout the cortex and hippocampus. By suppressing human tau expression for 6 months in the APP/PS1 × rTg4510 mice using doxycycline, AT8 tau pathology, bioactivity, and astrogliosis were reduced, though importantly to a lesser extent than lowering tau in the rTg4510 alone mice. Based on non-denaturing gels and proteinase K digestions, the remaining tau aggregates in the presence of amyloid-ß exhibit a longer-lived aggregate conformation. Nonetheless, lowering the expression of the human tau transgene was sufficient to equally ameliorate thioflavin-S positive tangles and prevent neuronal loss equally well in both the APP/PS1 × rTg4510 mice and the rTg4510 cohort. Together, these results suggest that, although amyloid-ß stabilizes tau aggregates, lowering total tau levels is still an effective strategy for the treatment of tau pathology and neuronal loss even in the presence of amyloid-ß deposition.

Wrist pain: a systematic review of prevalence and risk factors- what is the role of occupation and activity?

OBJECTIVE: To evaluate the prevalence and risk factors of wrist pain. METHODS: Systematic review. DATA SOURCES: The MEDLINE and EMBASE via OVID, CINAHL and SPORTDiscus via EBSCO databases were searched from database inception to 9th March 2018. Specific criteria were used to define inclusion and exclusion. Data was extracted independently by a pair of reviewers. RESULTS: In total 32 cross sectional studies were identified for inclusion (1 with a longitudinal component). The median prevalence of wrist pain in the general population and non-manual workers within the short term (within last week) was 6 and 4.2% within the medium term (> 1 week and within a year). The median prevalence of wrist pain in physically demanding occupations and sports people was 10% within the short term and 24% within the medium term. Non-modifiable factors associated with wrist pain included increased age (1 study in adults and 3 studies in children/adolescents) and female sex (2 studies). Modifiable risk factors included high job physical strain (2 studies), high job psychological strain (1 study), abnormal physeal morphology in children/adolescents (2 studies), high frequency impact tool use (1 study) and effort reward imbalance (1 study). CONCLUSIONS: Wrist pain is highly prevalent in groups who partake in physically demanding activities from day to day such as manual labourers and sportspeople. It is less prevalent in the general population and non-manual workers, although there is a relative lack of research in the general population. TRIAL REGISTRATION: The review protocol was registered with PROSPERO under the registration number CRD42018090834. LEVEL OF EVIDENCE: 1 (Prognostic study).

Pediatric postmortem computed tomography: initial experience at a children's hospital in the United States.

Postmortem CT might provide valuable information in determining the cause of death and understanding disease processes, particularly when combined with traditional autopsy. Pediatric applications of postmortem imaging represent a new and rapidly growing field. We describe our experience in establishing a pediatric postmortem CT program and present a discussion of the distinct challenges in developing this type of program in the United States of America, where forensic practice varies from other countries. We give a brief overview of recent literature along with the common imaging findings on postmortem CT that can simulate antemortem pathology.

Orthogonal Comparison of Molecular Signatures of Kidney Transplants With Subclinical and Clinical Acute Rejection: Equivalent Performance Is Agnostic to Both Technology and Platform.

We performed orthogonal technology comparisons of concurrent peripheral blood and biopsy tissue samples from 69 kidney transplant recipients who underwent comprehensive algorithm-driven clinical phenotyping. The sample cohort included patients with normal protocol biopsies and stable transplant (sTx) function (n = 25), subclinical acute rejection (subAR, n = 23), and clinical acute rejection (cAR, n = 21). Comparisons between microarray and RNA sequencing (RNA-seq) signatures were performed and demonstrated a strong correlation between the blood and tissue compartments for both technology platforms. A number of shared differentially expressed genes and pathways between subAR and cAR in both platforms strongly suggest that these two clinical phenotypes form a continuum of alloimmune activation. SubAR is associated with fewer or less expressed genes than cAR in blood, whereas in biopsy tissues, this clinical phenotype demonstrates a more robust molecular signature for both platforms. The discovery work done in this study confirms a clear ability to detect gene expression profiles for sTx, subAR, and cAR in both blood and biopsy tissue, yielding equivalent predictive performance that is agnostic to both technology and platform. Our data also provide strong biological insights into the molecular mechanisms underlying these signatures, underscoring their logistical potential as molecular diagnostics to improve clinical outcomes following kidney transplantation.

Belzutifan-induced regression of retinal capillary hemangioblastoma: A case-series.

Purpose: To report a series of three patients with von Hippel-Lindau (VHL) disease who demonstrated regression of their retinal hemangioblastomas (RH) using belzutifan in conjunction with photocoagulation therapy. Observations: Patient 1, a 23-year-old female, presented with multiple RHs in her right eye (OD) that were lasered. Her left eye (OS) revealed a large inferotemporal RH that measured approximately 2.1 mm2. Systemic belzutifan was administered. Four months after initiation of treatment, the lesion regressed to 1.4 mm2, but belzutifan was not well-tolerated and was discontinued due to side effects. At the date of belzutifan discontinuation, the lesion measured about 1.1 mm2. Focal laser photocoagulation was applied. The lesion regressed to around 0.6 mm2. Two additional laser treatments were applied one month later. On the most recent follow-up, the lesion was completely fibrosed.Patient 2, a 32-year-old male, presented with one RH OD and two RHs OS. Belzutifan was administered for one month before the patient began experiencing side effects of the medication. Consequently, the dose of belzutifan was decreased. After one month with the lowered dose, laser coagulation was applied to OS. In the most recent follow-up, five months after the initial presentation, the lesions remain less vascularized and reduced in size.Patient 3, is a 44-year-old male with a large RH OD. Following seven months of belzutifan daily, there was a significant reduction in the RH size. Conclusions: Belzutifan, a hypoxia-inducible factor inhibitor, is an FDA-approved medication for VHL disease associated with renal cell carcinoma, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors that do not require immediate surgical resection. Because of the high incidence of VHL-associated RHs, adjuvant laser photocoagulation therapy when belzutifan is suspended or withheld can allow for the regression of large lesions. In this case series, we also propose a reproducible and technically simple method to measure RH lesions size, using Optos fundus imaging.

Computational and AI-driven 3D structural analysis of human papillomavirus (HPV) oncoproteins E5, E6, and E7 reveal significant divergence of HPV E5 between low-risk and high-risk genotypes.

There are over 220 identified genotypes of Human papillomavirus (HPV), and the HPV genome encodes 3 major oncogenes, E5, E6, and E7. Conservation and divergence in protein sequence and function between low-risk versus high-risk oncogenic HPV genotypes has not been fully characterized. Here, we used modern computational and structural folding algorithms to perform a comparative analysis of HPV E5, E6, and E7 between multiple low risk and high risk genotypes. We first identified significantly greater sequence divergence in E5 between low- and high-risk genotypes compared to E6 and E7. Next, we used AlphaFold to model the structure of papillomavirus proteins and complexes with high confidence, including some with no established consensus structure. We observed that HPV E5, but not E6 or E7, had a dramatically different 3D structure between low-risk and high-risk genotypes. To our knowledge, this is the first comparative analysis of HPV proteins using Alphafold artificial intelligence (AI) system. The marked differences in E5 sequence and structure in high-risk HPVs may contribute in important and underappreciated ways to the development of HPV-associated cancers.

Science resource inequalities viewed as less wrong when girls are disadvantaged.

In response to some resource inequalities, children give priority to moral concerns. Yet, in others, children show ingroup preferences in their evaluations and resource allocations. The present study built upon this knowledge by investigating children's and young adults' (N = 144; 5-6-year-olds, M age = 5.83, SD age = .97; 9-11-year-olds, M age = 10.74, SD age = .68; and young adults, M age = 19.92, SD age = 1.10) evaluations and allocation decisions in a science inequality context. Participants viewed vignettes in which male and female groups received unequal amounts of science supplies, then evaluated the acceptability of the resource inequalities, allocated new boxes of science supplies between the groups, and provided justifications for their choices. Results revealed both children and young adults evaluated inequalities of science resources less negatively when girls were disadvantaged than when boys were disadvantaged. Further, 5- to 6-year-old participants and male participants rectified science resource inequalities to a greater extent when the inequality disadvantaged boys compared to when it disadvantaged girls. Generally, participants who used moral reasoning to justify their responses negatively evaluated and rectified the resource inequalities, whereas participants who used group-focused reasoning positively evaluated and perpetuated the inequalities, though some age and participant gender findings emerged. Together, these findings reveal subtle gender biases that may contribute to perpetuating gender-based science inequalities both in childhood and adulthood.

HEMOGLOBIN C TRAIT PRESENTING WITH BILATERAL CENTRAL RETINAL VEIN OCCLUSION.

PURPOSE: To report a case of bilateral sequential, central retinal vein occlusion (CRVO) in a man with newly diagnosed hemoglobin C trait. METHODS: A 67-year-old man presented with a one-month history of declining visual acuity. He was diagnosed with left CRVO. Bilateral temporal retinal ischemia and arteriovenous anastomoses on fluorescein angiography suggestive of sickle cell retinopathy prompted a systemic work-up. Hemoglobin electrophoresis revealed an underlying hemoglobin C trait. Six-months after his initial presentation, the patient developed symptomatic right CRVO. RESULTS: The initial left CRVO was complicated by optic disc swelling and macular edema. Intravitreal antiangiogenic therapy was initiated and the macular edema resolved. The left eye subsequently developed an epiretinal membrane which was surgically removed. Macular edema in the right eye also resolved after intravitreal antiangiogenic therapy. CONCLUSION: This is the first reported case of bilateral CRVO in a case of hemoglobin C trait. It is possible that erythrocyte inflexibility, caused by hemoglobin C-induced dehydration and crystallization, acted concomitantly with hypertension to produce occlusive microangiopathy. This case highlights the need for further investigation in patients presenting with central retinal vein occlusion, especially when bilateral, or when retinal angiography reveals bilateral pathology.

Transgenerational plasticity in a zooplankton in response to elevated temperature and parasitism.

Organisms are increasingly facing multiple stressors, which can simultaneously interact to cause unpredictable impacts compared with a single stressor alone. Recent evidence suggests that phenotypic plasticity can allow for rapid responses to altered environments, including biotic and abiotic stressors, both within a generation and across generations (transgenerational plasticity). Parents can potentially "prime" their offspring to better cope with similar stressors or, alternatively, might produce offspring that are less fit because of energetic constraints. At present, it remains unclear exactly how biotic and abiotic stressors jointly mediate the responses of transgenerational plasticity and whether this plasticity is adaptive. Here, we test the effects of biotic and abiotic environmental changes on within- and transgenerational plasticity using a Daphnia-Metschnikowia zooplankton-fungal parasite system. By exposing parents and their offspring consecutively to the single and combined effects of elevated temperature and parasite infection, we showed that transgenerational plasticity induced by temperature and parasite stress influenced host fecundity and lifespan; offsprings of mothers who were exposed to one of the stressors were better able to tolerate elevated temperature, compared with the offspring of mothers who were exposed to neither or both stressors. Yet, the negative effects caused by parasite infection were much stronger, and this greater reduction in host fitness was not mitigated by transgenerational plasticity. We also showed that elevated temperature led to a lower average immune response, and that the relationship between immune response and lifetime fecundity reversed under elevated temperature: the daughters of exposed mothers showed decreased fecundity with increased hemocyte production at ambient temperature but the opposite relationship at elevated temperature. Together, our results highlight the need to address questions at the interface of multiple stressors and transgenerational plasticity and the importance of considering multiple fitness-associated traits when evaluating the adaptive value of transgenerational plasticity under changing environments.

Temperature modifies trait-mediated infection outcomes in a Daphnia-fungal parasite system.

One major concern related to climate change is that elevated temperatures will drive increases in parasite outbreaks. Increasing temperature is known to alter host traits and host-parasite interactions, but we know relatively little about how these are connected mechanistically-that is, about how warmer temperatures impact the relationship between epidemiologically relevant host traits and infection outcomes. Here, we used a zooplankton-fungus (Daphnia dentifera-Metschnikowia bicuspidata) disease system to experimentally investigate how temperature impacted physical barriers to infection and cellular immune responses. We found that Daphnia reared at warmer temperatures had more robust physical barriers to infection but decreased cellular immune responses during the initial infection process. Infected hosts at warmer temperatures also suffered greater reductions in fecundity and lifespan. Furthermore, the relationship between a key trait-gut epithelium thickness, a physical barrier-and the likelihood of terminal infection reversed at warmer temperatures. Together, our results highlight the complex ways that temperatures can modulate host-parasite interactions and show that different defense components can have qualitatively different responses to warmer temperatures, highlighting the importance of considering key host traits when predicting disease dynamics in a warmer world. This article is part of the theme issue 'Infectious disease ecology and evolution in a changing world'.