Sex Differences in Biomarkers of End-Organ Damage following Exertional Heat Stroke in Humans.

Women are participating in military and athletic activities in the heat in increasing numbers, but potential sex differences in sequelae from exertional heat illness remain poorly understood. We tested the hypothesis that women suffering from exertional heat stroke (EHS) would have similar severity of organ damage biomarkers compared to men, as measured in a hospital setting. We studied women and men presenting with EHS to the emergency department at Fort Moore, GA. We measured creatinine (CR), creatine kinase (CK), alanine-transaminase (ALT), aspartate aminotransferase (AST), and estimated glomerular filtration rate (eGFR). Core temperature was also assessed by medical personnel. Biomarker data were obtained for 62 EHS cases (11 women). Men were significantly taller, and heavier, had larger BMI and body surface area (p<0.05 for all). Highest recorded body core temperature was not different between groups (women: 41.11°C (40.06,41.67); men: 41.11°C (40.28,41.72), p=0.57). Women had significantly lower peak CR (women: 1.39 (1.2,1.48) mgꞏdL-1; men: 1.75 (1.53,2.16) mgꞏdL-1, p<0.01) and peak CK (women: 584 (268,2412) UꞏL-1; men: 2183 (724,5856) U•L-1, p=0.02). Peak ALT and AST were not different between groups; during recovery time points, ALT and AST were either similar or lower in women. Women spent approximately half as much time in the hospital following admittance compared to men. Our findings suggest that women may be less susceptible to organ injury resulting from EHS. Further research is necessary to understand the pathophysiology underlying these differences and how biomarkers of end-organ damage severity can differ between women and men following EHS.

Age above all: The impact of storage duration in mice resuscitated with whole blood or packed red blood cells and plasma in a hemorrhagic shock model.

BACKGROUND: The use of whole blood compared with a balanced ratio of components in trauma resuscitation remains an area of ongoing investigation. One factor that may affect outcomes is the age of the blood product transfused. We used a murine model of blood banking and hemorrhagic shock resuscitation to compare the effect of storage duration in whole blood and packed red blood cells on the recipient inflammatory response. METHODS: Murine whole blood or packed red blood cells were evaluated for the red blood cells storage lesion up to 14 days. Mice underwent hemorrhagic shock followed by resuscitation with whole blood or packed red blood cells combined with equal volume of thawed plasma (1:1) stored for 1, 7, or 14 days. Serum and lung cytokine/chemokine levels were measured and leukocyte infiltration determined via immunohistochemistry. RESULTS: Both whole blood and packed red blood cells develop a blood storage lesion. Four hours after resuscitation, mice resuscitated with either day 14 whole blood or 1:1 demonstrated increased inflammatory cytokines and chemokines with similar findings within lung tissue compared with mice resuscitated with whole blood and 1:1 products stored for 1 or 7 days. CONCLUSIONS: Resuscitation with murine packed red blood cells or whole blood stored for 14 days produces a pronounced recipient inflammatory response compared with those units stored for lesser durations. Given the shorter storage duration of human whole blood to packed RBCs, resuscitation with whole blood within current storage limits may represent an advantageous resuscitation strategy compared with older packed red blood cells.

A review of visual analysis reporting procedures in the functional communication training literature.

Few guidelines exist for conducting and reporting visual analysis procedures and results in single-case research. Previous research examining how authors describe their analytic procedures and results has found that authors use key terms such as level, trend, and variability infrequently. Additionally, in a previous review, the authors rarely agreed with the original study authors on their conclusions. The purpose of this study was to document single-case researchers' analytic procedures, including use of key visual analysis terms; description of data features; within- and between-condition analysis; and inclusion of descriptive statistics, effect sizes, or inferential statistics in the literature on a common Tier 3 behavior intervention, functional communication training. We also compared our determinations about functional relations to the authors' conclusions. Our results suggest that most authors describe level, but almost a third did not describe trend or variability. Agreement with study authors was better than in previous studies but still below minimally acceptable thresholds. We discuss areas for future research and implications for reporting the analysis and results of single-case research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Osteopontin deletion attenuates cyst growth but exacerbates fibrosis in mice with cystic kidney disease.

Osteopontin (OPN) is a multi-functional glycoprotein that coordinates the innate immune response, prevents nanocrystal formation in renal tubule fluid, and is a biomarker for kidney injury. OPN expression is markedly increased in cystic epithelial cells of polycystic kidney disease (PKD) kidneys; however, its role in PKD progression remains unclear. We investigated the in vitro effects of recombinant OPN on the proliferation of tubular epithelial cells from PKD and normal human kidneys and in vivo effects of OPN deletion on kidney cyst formation, fibrosis, and mineral metabolism in pcy/pcy mice, a non-orthologous model of autosomal-dominant PKD. In vitro studies revealed that OPN enhanced the proliferation of PKD cells but had no effect on normal kidney cells. Deletion of OPN in pcy/pcy mice significantly reduced kidney cyst burden; however, this was accompanied by increased fibrosis and no change in kidney function. The loss of OPN had no effect on kidney macrophage numbers, cyst epithelial cell proliferation, or apoptosis. Furthermore, there was no difference in kidney mineral deposition or mineral metabolism parameters between pcy/pcy mice with and without OPN expression. Global deletion of OPN reduced kidney cyst burden, while paradoxically exacerbating kidney fibrosis in mice with cystic kidney disease.

The updated mouse universal genotyping array bioinformatic pipeline improves genetic QC in laboratory mice.

The MiniMUGA genotyping array is a popular tool for genetic quality control of laboratory mice and genotyping samples from most experimental crosses involving laboratory strains, particularly for reduced complexity crosses. The content of the production version of the MiniMUGA array is fixed; however, there is the opportunity to improve the array's performance and the associated report's usefulness by leveraging thousands of samples genotyped since the initial description of MiniMUGA. Here, we report our efforts to update and improve marker annotation, increase the number and the reliability of the consensus genotypes for classical inbred strains and substrains, and increase the number of constructs reliably detected with MiniMUGA. In addition, we have implemented key changes in the informatics pipeline to identify and quantify the contribution of specific genetic backgrounds to the makeup of a given sample, remove arbitrary thresholds, include the Y Chromosome and mitochondrial genome in the ideogram, and improve robust detection of the presence of commercially available substrains based on diagnostic alleles. Finally, we have updated the layout of the report to simplify the interpretation and completeness of the analysis and added a section summarizing the ideogram in table format. These changes will be of general interest to the mouse research community and will be instrumental in our goal of improving the rigor and reproducibility of mouse-based biomedical research.

Internal validation of modified Mirels' scoring system for pathologic femur fractures.

BACKGROUND: The proximal femur is a common site of bone metastasis. The Mirels' score is a frequently utilized system to identify patients at risk for pathologic fracture and while it has consistently demonstrated strong sensitivity, specificity has been relatively poor. Our group previously developed a Modified Mirels' scoring system which demonstrated improved ability to predict cases at risk of fracture in this patient population through modification of the Mirels' location score. The purpose of the present study is to internally validate this newly developed scoring system on an independent patient series. METHODS: Retrospective review was performed to identify patients who were evaluated for proximal femoral bone lesions. Patients were stratified into one of two groups: 1) those who went on to fracture within 4 months after initial evaluation (Fracture Group) and 2) those who did not fracture within 4 months of initial evaluation (No Fracture Group). Retrospective chart review was performed to assign an Original Mirels' (OM) Score and Modified Mirels' (MM) score to each patient at the time of initial evaluation. Descriptive statistics, logistic regression, receiver operating curve, and net benefit analyses were performed to determine the predictability of fractures when utilizing both scoring systems. RESULTS: The use of the MM scoring improved fracture prediction over OM scoring for patients observed over a 4 month follow up based on logistic regression. Decision curve analysis showed that there was a net benefit using the MM score over the OM scoring for a full range of fracture threshold probabilities. Fracture prevalence was similar for current internal validation dataset when compared to the dataset of our index study with a comparable reduction in misclassification of fracture prediction when utilizing the modified scoring system versus the original. CONCLUSIONS: Use of MM scoring was found to improve fracture prediction over OM scoring when tested on an internal validation set of patients with disseminated metastatic lesions to the proximal femur. The improvement in fracture prediction demonstrated in the present study mirrored the results of our index study during which the MM system was developed.

Spectroscopic Properties and Reactivity of a MnIII-hydroperoxo Complex that is Stable at Room Temperature.

Manganese catalysts that activate hydrogen peroxide have seen increased use in organic transformations, such as olefin epoxidation and alkane C-H bond oxidation. Proposed mechanisms for these catalysts involve the formation and activation of MnIII-hydroperoxo intermediates. Examples of well-defined MnIII-hydroperoxo complexes are rare, and the properties of these species are often inferred from MnIIIalkylperoxo analogues. In this study, we show that the reaction of the MnIII-hydroxo complex [MnIII(OH)(6Medpaq)]+ (1) with hydrogen peroxide and acid results in the formation of a dark-green MnIII-hydroperoxo species [MnIII(OOH)(6Medpaq)]+ (2). The formulation of 2 is based on electronic absorption, 1H NMR, IR, and ESI-MS data. The thermal decay of 2 follows a first order process, and variable-temperature kinetic studies of the decay of 2 yielded activation parameters that could be compared with those of a MnIII-alkylperoxo analogue. Complex 2 reacts with the hydrogen-atom donor TEMPOH two-fold faster than the MnIII-hydroxo complex 1. Complex 2 also oxidizes PPh3, and this MnIII-hydroperoxo species is 600-fold more reactive with this substrate than its MnIII-alkylperoxo analogue [MnIII(OOtBu)(6Medpaq)]+. DFT and time-dependent (TD) DFT computations are used to compare the electronic structure of 2 with similar MnIII-hydroperoxo and MnIII-alkylperoxo complexes.

Incorporating Transition Metal Ions into Uranium Oxide Hydrates: The Role of Zn(II) and the Effect of the Addition of Cs(I) Ions.

The synthesis of two zinc-bearing uranium oxide hydrate (UOH) materials has been achieved, and their crystal structures, obtained via single-crystal X-ray diffraction using synchrotron radiation, and additional structural and spectroscopic properties are reported herein. Although both structures incorporate Zn2+ cations, the two differ significantly. The compound Zn2(OH)2(H2O)5[(UO2)10UO14(H2O)3] (UOHF-Zn), forming a framework-type structure in the P1̅ space group, was composed of ß-U3O8 layers pillared by uranyl polyhedra, with the Zn2+ cations incorporated within the framework channels. In contrast, the compound Cs2Zn(H2O)4[(UO2)4O3(OH)4]2·3H2O (UOH-Zn) crystallized in the Cmc21 space group with a schoepite-like uranyl oxide hydroxide layered topology and both Zn2+ and Cs+ cations making up the interlayer species. The apparent driving force for the differences in the structures was the change from KOH to CsOH during synthesis, with the smaller K+ ions excluded in lieu of a higher proportion of Zn2+ (U/Zn ratio of 5.5:1) in UOHF-Zn, whereas in UOH-Zn, the larger Cs+ ions were preferentially incorporated at the expense of fewer Zn2+ cations (U/Cs/Zn ratio of 8:2:1). Highlighted in this work is the effect of the chemical species and, in particular, their ionic radius on UOH formation, further improving the understanding of UO2 alteration in the setting of deep geological repositories.

A structural and functional model for alkene dioxygenases.

In this article, we report sterically-controlled iron sites based on non-chelating bulky imidazole ligands. Adding 6 equiv. of 1,2-dimethylimidazole (1,2-Me2Im) to Fe(OTf)2⋅2CH3CN affords the first example of a 5-coordinate imidazole­iron complex ([Fe(1,2-Me2Im)5](OTf)2, 1). The structure is distorted square pyramidal (τ5 = 0.41). When an iPr group is substituted for the methyl group at the 2-position on the imidazole (2-iPr-1-MeIm), the 14-electron complex ([Fe(2-iPr-1-MeIm)4](OTf)2, 2) is obtained. This complex exhibits slightly distorted tetrahedral geometry (τ'4 = 0.93) with four N-donors and serves as a 4-His iron structural model complex for carotenoid cleavage dioxygenases (CCD). The electronic structure of 1 and 2 were characterized by Mössbauer spectroscopy. Reactions of 1 and 2 with model olefin substrates (1-R-4-(1-methoxyprop-1-en-2-yl)benzene; R = Me or Br) in the presence of oxygen result in olefin cleavage yielding ketone and aldehyde products, although 2 yields more products than 1. Support for a proposed reaction mechanism for 2 is offered from Density Functional Theory (DFT) calculations.

Cobalt-60, Barium-133, Cesium-137, and Europium-152 migration from cementitious sources through sediment under field conditions.

Safe and effective storage of radioactive waste is essential to protect human and environmental health. Due to the potential for accidental releases and the severity of the associated risks, it is imperative to further understand radionuclide transport should an accident occur. This study was the second set of measurements conducted in 2022 of an ongoing experiment that has analyzed the vadose zone migration of radionuclides from cementitious wasteforms at the Savannah River Site over the last ten years. The radionuclides introduced within the sources are prominent constituents of radioactive waste or analogs for other groups or series of radionuclides. Lysimeters were first analyzed in 2016 using a collimated high-purity germanium gamma-ray spectrometer to non-destructively measure the concentration of each radionuclide in the sediment column as a function of depth. Following these measurements, the lysimeters were redeployed for another 4 years. All radionuclides in all lysimeters were observed to transport further during the redeployment period; however, the extent of migration varied with the material used for introduction. Except for 137Cs, migration through the sediment control system increased with decreasing ionic potential (ionic charge/radius); migration order: 152Eu < 137Cs < 60Co < 133Ba. Overall, the cementitious wasteforms were observed to decrease radionuclide migration extent relative to natural vadose zone conditions. In both cementitious wasteforms, the migration extent increased in the order 152Eu < 133Ba<60Co < 137Cs. However, less migration was measured when the radionuclides were incorporated into a reducing grout wasteform. The novelty of this paper is the demonstration of a technique capable of creating non-destructive measurements over decade time scales. Ultimately, this work provides insight into the long-term migration of alkali, alkali earth, divalent transition metal, and trivalent (e.g., lanthanide and actinide element) isotopes.

Electrocochleography-Based Tonotopic Map: I. Place Coding of the Human Cochlea With Hearing Loss.

OBJECTIVES: Due to the challenges of direct in vivo measurements in humans, previous studies of cochlear tonotopy primarily utilized human cadavers and animal models. This study uses cochlear implant electrodes as a tool for intracochlear recordings of acoustically evoked responses to achieve two primary goals: (1) to map the in vivo tonotopy of the human cochlea, and (2) to assess the impact of sound intensity and the creation of an artificial "third window" on this tonotopic map. DESIGN: Fifty patients with hearing loss received cochlear implant electrode arrays. Postimplantation, pure-tone acoustic stimuli (0.25 to 4 kHz) were delivered, and electrophysiological responses were recorded from all 22 electrode contacts. The analysis included fast Fourier transformation to determine the amplitude of the first harmonic, indicative of predominantly outer hair cell activity, and tuning curves to identify the best frequency (BF) electrode. These measures, coupled with postoperative imaging for precise electrode localization, facilitated the construction of an in vivo frequency-position function. The study included a specific examination of 2 patients with auditory neuropathy spectrum disorder (ANSD), with preserved cochlear function as assessed by present distortion-product otoacoustic emissions, to determine the impact of sound intensity on the frequency-position map. In addition, the electrophysiological map was recorded in a patient undergoing a translabyrinthine craniotomy for vestibular schwannoma removal, before and after creating an artificial third window, to explore whether an experimental artifact conducted in cadaveric experiments, as was performed in von Békésy landmark experiments, would produce a shift in the frequency-position map. RESULTS: A significant deviation from the Greenwood model was observed in the electrophysiological frequency-position function, particularly at high-intensity stimulations. In subjects with hearing loss, frequency tuning, and BF location remained consistent across sound intensities. In contrast, ANSD patients exhibited Greenwood-like place coding at low intensities (~40 dB SPL) and a basal shift in BF location at higher intensities (~70 dB SPL or greater). Notably, creating an artificial "third-window" did not alter the frequency-position map. CONCLUSIONS: This study successfully maps in vivo tonotopy of human cochleae with hearing loss, demonstrating a near-octave shift from traditional frequency-position maps. In patients with ANSD, representing more typical cochlear function, intermediate intensity levels (~70 to 80 dB SPL) produced results similar to high-intensity stimulation. These findings highlight the influence of stimulus intensity on the cochlear operational point in subjects with hearing loss. This knowledge could enhance cochlear implant programming and improve auditory rehabilitation by more accurately aligning electrode stimulation with natural cochlear responses.

Centralized Quality Assurance of Stereotactic Body Radiation Therapy for the Veterans Affairs Cooperative Studies Program Study Number 2005: A Phase 3 Randomized Trial of Lung Cancer Surgery or Stereotactic Radiotherapy for Operable Early-Stage Non-Small Cell Lung Cancer (VALOR).

BACKGROUND: The phase III Veterans Affairs Lung cancer surgery Or stereotactic Radiotherapy (VALOR) study implemented centralized quality assurance (QA) to mitigate risks of protocol deviations. This report summarizes quality and compliance for the first 100 participants treated with SBRT in this study. METHODS: A centralized QA program was developed to credential and monitor study sites to ensure standard-of-care lung stereotactic body radiation therapy (SBRT) treatments are delivered to participants. Requirements were adapted from protocols established by the National Cancer Institute's Image and Radiation Oncology Core, which provides oversight for clinical trials sponsored by the NCI's National Clinical Trials Network. RESULTS: The first 100 lung SBRT treatment plans were reviewed from April 2017 to October 2022. Tumor contours were appropriate in all submissions. PTV expansions were less than the minimum 5 mm requirement in 2% of cases. Critical organ-at-risk (OAR) structures were contoured accurately for the proximal bronchial tree, trachea, esophagus, spinal cord, and brachial plexus in 75%, 92%, 100%, 100%, and 95% of cases. Prescriptions were appropriate in 98% of cases; two central tumors were treated using a peripheral tumor dose prescription while meeting OAR constraints. PTV V100% values were above the protocol-defined minimum of 94% in all but one submission. The median Dmax within the PTV was 125.4% (105.8% - 149.0%, standard deviation ±8.7%). High-dose conformality (<1.2) and intermediate-dose compactness (R50% and D2cm) indices were acceptable or deviation acceptable in 100% and 94% of cases, respectively. CONCLUSIONS: The first 100 participants randomized to SBRT in this study were appropriately treated without safety concerns. A response to the incorrect prescriptions led to preventative measures without further recurrences. The program was developed in a healthcare system without prior experience with a centralized RT QA program and may serve as a reference for other institutions.

Contemporary short-term peri-operative outcomes of open primary retroperitoneal lymph node dissection.

OBJECTIVES: To provide current peri-operative outcomes and short-term complication rates for open primary retroperitoneal lymph node dissection (RPLND), with analysis of risk factors for complications. PATIENTS AND METHODS: Using the Indiana University Testicular Cancer database, we performed a retrospective analysis of all patients who underwent open primary RPLND over the study period (2018-2021). The primary outcomes of interest were the preoperative profile of patients undergoing surgery, complication rates, and identification of risk factors associated with complications. We used chi-squared, Fisher's exact and unpaired t-tests in our analyses. RESULTS: A total of 165 patients were identified. The median body mass index (BMI) was 28.6 kg/m2. Patients most often had clinical stage IIA (39%) or IIB testicular cancer (36%). The median estimated blood loss was 150 mL, with no transfusions required. Higher BMI was noted in patients that sustained any complication vs those with normal recovery (34.95 vs 28 kg/m2; P = 0.0042). The median length of hospital stay was 3 days. The overall complication rate was low (8.48%), with two major postoperative complications, including one case of chylous ascites (0.6%), and no deaths in the 30-day period. The study was limited by its retrospective design and short-term follow-up. CONCLUSIONS: We found that open primary RPLND has an acceptable morbidity profile, even among a predominantly overweight cohort. Low blood loss, short hospital stay, minimal chylous ascites risk, and rare major postoperative complications should be the benchmark for retroperitoneal lymph node dissection.

Evaluating constraints associated with farmers' adaptation strategies to climate change impact on farming in the tropical environment.

The persistent threat of climate change poses challenges to food security, despite numerous adaptation strategies, necessitating attention to achieve sustainable livelihoods. This study conducted a survey among 220 farmers in fifteen selected rural communities from five political wards in Ondo West Local Government Area, Ondo State, Nigeria, using a multistage sampling technique. Both descriptive and inferential statistical methods were used to analyse data obtained. The results indicated that 90 % of the farmers had knowledge of consequences of climate change, while 75 % have adopted various strategies to cope with the menace. The data were factorable at p ≤ 0.05 using KMO and Bartlett's tests. Four variables were extracted out of nine analysed as significant to the explanation of constraints to CC adaptation strategies, namely: engagement in other jobs (16.499 %); farmers' experience with the varying nature of weather patterns (14.526 %); farm size variation (13.485 %); and the difficulty posed by coping with recurring erratic rainfall (11.925 %). All four variables identified and extracted explained 56.446 % of the constraints hindering farmers from coping with climate change. The study recommended further studies to identify other variables that could be accountable for the constraints in coping with the climate change scenario in the study area. The contributions of farmers' experiences to the failure of various strategies in coping with climate change form the nexus to other extracted variables and, therefore, need further investigation for sustainable agriculture globally.

Direct inference of the distribution of fitness effects of spontaneous mutations from recombinant inbred C. elegans mutation accumulation lines.

The distribution of fitness effects (DFE) of new mutations plays a central role in evolutionary biology. Estimates of the DFE from experimental Mutation Accumulation (MA) lines are compromised by the complete linkage disequilibrium (LD) between mutations in different lines. To reduce LD, we constructed two sets of recombinant inbred lines from a cross of two C. elegans MA lines. One set of lines ("RIAILs") was intercrossed for ten generations prior to ten generations of selfing; the second set of lines ("RILs") omitted the intercrossing. Residual LD in the RIAILs is much less than in the RILs, which affects the inferred DFE when the sets of lines are analyzed separately. The best-fit model estimated from all lines (RIAILs + RILs) infers a large fraction of mutations with positive effects (∼40%); models that constrain mutations to have negative effects fit much worse. The conclusion is the same using only the RILs. For the RIAILs, however, models that constrain mutations to have negative effects fit nearly as well as models that allow positive effects. When mutations in high LD are pooled into haplotypes, the inferred DFE becomes increasingly negative-skewed and leptokurtic. We conclude that the conventional wisdom - most mutations have effects near zero, a handful of mutations have effects that are substantially negative and mutations with positive effects are very rare - is likely correct, and that unless it can be shown otherwise, estimates of the DFE that infer a substantial fraction of mutations with positive effects are likely confounded by LD.

Modelling the female torso and breast during physical activity: Implications on spinal loading.

Methods of modelling the female torso during physical activity often neglect the position and movement of the breast. This novel investigation compares three female torso modelling approaches that differ in complexity (integrated breast, fixed breast, dynamic breast) to determine the effect on spinal joint moments during running and jumping. The commonly used integrated breast model distributed breast mass within the torso, the fixed breast model attached the mass of the breasts to fixed positions on the anterior of the torso, and a new dynamic breast model enabled relative motion between the breasts and anterior torso. Key findings demonstrated minimal differences in lumbar spine moments (<0.05 Nm/kg; 4%) between integrated breast and fixed breast models but greater differences, up to 0.86 Nm/kg (68%) during running and 0.89 Nm/kg (82%) during jumping, when breast motion was included. Thoracic spine moments revealed similar patterns with minimal differences (<0.05 Nm/kg; 11%) between integrated breast and fixed breast models and greater differences, up to 0.48 Nm/kg (92%) during running and 0.63 Nm/kg (66%) during jumping, with the dynamic breast model. Future female musculoskeletal models should consider including breast mass and motion to avoid mis-representing spinal loading in females during running and jumping.

A nanobody interaction with SARS-COV-2 Spike allows the versatile targeting of lentivirus vectors.

While investigating methods to target gene delivery vectors to specific cell types, we examined the potential of using a nanobody against the SARS-CoV-2 Spike protein receptor-binding domain to direct lentivirus infection of Spike-expressing cells. Using four different approaches, we found that lentiviruses with surface-exposed nanobody domains selectively infect Spike-expressing cells. Targeting is dependent on the fusion function of the Spike protein, and conforms to a model in which nanobody binding to the Spike protein triggers the Spike fusion machinery. The nanobody-Spike interaction also is capable of directing cell-cell fusion and the selective infection of nanobody-expressing cells by Spike-pseudotyped lentivirus vectors. Significantly, cells infected with SARS-CoV-2 are efficiently and selectively infected by lentivirus vectors pseudotyped with a chimeric nanobody protein. Our results suggest that cells infected by any virus that forms syncytia may be targeted for gene delivery by using an appropriate nanobody or virus receptor mimic. Vectors modified in this fashion may prove useful in the delivery of immunomodulators to infected foci to mitigate the effects of viral infections.IMPORTANCEWe have discovered that lentiviruses decorated on their surfaces with a nanobody against the SARS-CoV-2 Spike protein selectively infect Spike-expressing cells. Infection is dependent on the specificity of the nanobody and the fusion function of the Spike protein and conforms to a reverse fusion model, in which nanobody binding to Spike triggers the Spike fusion machinery. The nanobody-Spike interaction also can drive cell-cell fusion and infection of nanobody-expressing cells with viruses carrying the Spike protein. Importantly, cells infected with SARS-CoV-2 are selectively infected with nanobody-decorated lentiviruses. These results suggest that cells infected by any virus that expresses an active receptor-binding fusion protein may be targeted by vectors for delivery of cargoes to mitigate infections.

Longitudinal associations of effort and reward at work with changes in cognitive function: evidence from a national study of U.S. workers.

PURPOSE: This study aimed to examine longitudinal associations of workplace effort and reward with changes in cognitive function among United States workers. METHODS: Data from the national, population-based Midlife in the United States (MIDUS) study with a 9-year follow-up were used. Validated workplace effort and reward scales were measured at baseline, and cognitive outcomes (including composite cognition, episodic memory, and executive functioning) were measured with the Brief Test of Adult Cognition by Telephone (BTACT) at baseline and follow-up. Multivariable linear regression analyses based on generalized estimating equations (GEE) examined the longitudinal associations under study. RESULTS: Among this worker sample of 1,399, after accounting for demographics, socioeconomics, lifestyle behaviors, health conditions, and job control, high reward at baseline was associated with increased composite cognition (regression coefficient: 0.118 [95% CI: 0.049, 0.187]), episodic memory (0.106 [0.024, 0.188]), and executive functioning (0.123 [0.055, 0.191]) during follow-up. The joint exposure of 'high effort and high reward' was also associated with increased composite cognition (0.130 [0.030, 0.231]), episodic memory (0.131 [0.012, 0.250]), and executive functioning (0.117 [0.017, 0.216]), while the combination of 'low effort and high reward' was associated with increased composite cognition (0.106 [0.009, 0.204]) and executive functioning (0.139 [0.042, 0.235]). CONCLUSION: Findings suggest that workplace high reward is related to improved cognitive scores among United States workers. Future research should investigate larger cohorts over longer timespans and expand into disease outcomes such as dementia. If these findings emerge as causal, relevant workplace rewards to promote worker cognitive health should be considered.