Depression, loneliness, and lower social activity as partial mediators of the association between visual impairment and cognitive decline.

OBJECTIVES: Sensory impairment is a hypothesized risk factor for cognitive decline; however, the psychosocial pathways are not well understood. We evaluated whether the association between visual impairment (VI) and cognitive decline was partially mediated via depressive symptoms, loneliness, or social activity. METHODS: We used data from 2601 older adults enrolled in the Memory and Aging Project in 1997 and the Minority Aging Research Study in 2004 with neuropsychological tests across five domains measured annually for up to 16 years. VI was assessed with the Rosenbaum Pocket Vision Screener. Depressive symptoms, loneliness, and social activity were self-reported using validated scales. We used structural equation models to estimate the associations of VI with baseline and change in cognitive function, directly and indirectly through each mediator (depressive symptoms, loneliness, and social activity). We evaluated mediation via "psychological distress" using a latent variable combining depressive symptoms and loneliness. RESULTS: The association between VI and global cognitive decline was mediated via lower social activity (indirect effect) [95% confidence interval (CI)] of linear slope: -0.025 (-0.048, -0.011), via loneliness (-0.011 [95% CI: -0.028, -0.002]), and via psychological distress (-0.017 [95% CI: -0.042, -0.003]). We did not find sufficient evidence for mediation via depressive symptoms alone. CONCLUSIONS: The harmful effect of VI on cognitive decline may be partially mediated through loneliness and lower social activity.

IL-13Rα2/TGF-ß bispecific CAR-T cells counter TGF-ß-mediated immune suppression and potentiate anti-tumor responses in glioblastoma.

BACKGROUND: Chimeric antigen receptor (CAR)-T cell therapies targeting glioblastoma (GBM)-associated antigens such as interleukin-13 receptor subunit alpha-2 (IL-13Rα2) have achieved limited clinical efficacy to date, in part due to an immunosuppressive tumor microenvironment (TME) characterized by inhibitory molecules such as transforming growth factor-beta (TGF-ß). The aim of this study was to engineer more potent GBM-targeting CAR-T cells by countering TGF-ß-mediated immune suppression in the TME. METHODS: We engineered a single-chain, bispecific CAR targeting IL-13Rα2 and TGF-ß, which programs tumor-specific T cells to convert TGF-ß from an immunosuppressant to an immunostimulant. Bispecific IL-13Rα2/TGF-ß CAR-T cells were evaluated for efficacy and safety against both patient-derived GBM xenografts and syngeneic models of murine glioma. RESULTS: Treatment with IL-13Rα2/TGF-ß CAR-T cells leads to greater T-cell infiltration and reduced suppressive myeloid cell presence in the tumor-bearing brain compared to treatment with conventional IL-13Rα2 CAR-T cells, resulting in improved survival in both patient-derived GBM xenografts and syngeneic models of murine glioma. CONCLUSION: Our findings demonstrate that by reprogramming tumor-specific T-cell responses to TGF-ß, bispecific IL-13Rα2/TGF-ß CAR-T cells resist and remodel the immunosuppressive TME to drive potent anti-tumor responses in GBM.

Suffering more in imagination than in reality? Mental imagery and fear generalization.

Mental imagery may represent a weaker form of perception and, thus, mental images may be more ambiguous than visual percepts. If correct, the acquisition of fear would be less specific for imagined fears in comparison to perceptual fears, perhaps facilitating broader fear generalization. To test this idea, a two-day differential fear conditioning experiment (N = 98) was conducted. On day one, two groups of participants underwent differential fear conditioning such that a specific Gabor patch orientation (CS+) was paired with mild shocks (US) while a second Gabor patch of orthogonal orientation (CS-) was never paired with shock. Critically, one group imagined the Gabor patches and the other group was visually presented the Gabor patches. Next, both groups were presented visual Gabor patches of similar orientations (GCS) to the CS+. On day two, to assess the persistence of imagined fear, participants returned to the lab and were tested on the GCS devoid of shock. For day one, in contrast to our primary hypothesis, both self-report and skin conductance response measures did not show a significant interaction between the GCS and groups. On day two, both measures demonstrated a persistence of imagined fear, without US delivery. Taken together, rather than demonstrating an overgeneralization effect, the results from this study suggest that imagery-based fear conditioning generalizes to a similar extent as perceptually acquired fear conditioning. Further, the persistence of imagery-based fear may have unique extinction qualities in comparison to perceptual-based fear.

Elucidating and Optimizing the Photochemical Mechanism of Coumarin-Caged Tertiary Amines.

Photoactivatable or "caged" pharmacological agents combine the high spatiotemporal specificity of light application with the molecular specificity of drugs. A key factor in all optopharmacology experiments is the mechanism of uncaging, which dictates the photochemical quantum yield and determines the byproducts produced by the light-driven chemical reaction. In previous work, we demonstrated that coumarin-based photolabile groups could be used to cage tertiary amine drugs as quaternary ammonium salts. Although stable, water-soluble, and useful for experiments in brain tissue, these first-generation compounds exhibit relatively low uncaging quantum yield (Φu < 1%) and release the toxic byproduct formaldehyde upon photolysis. Here, we elucidate the photochemical mechanisms of coumarin-caged tertiary amines and then optimize the major pathway using chemical modification. We discovered that the combination of 3,3-dicarboxyazetidine and bromine substituents shift the mechanism of release to heterolysis, eliminating the formaldehyde byproduct and giving photolabile tertiary amine drugs with Φu > 20%─a 35-fold increase in uncaging efficiency. This new "ABC" cage allows synthesis of improved photoactivatable derivatives of escitalopram and nicotine along with a novel caged agonist of the oxytocin receptor.

Migrating Mobile Applications to the Web: Adult Crash Cart Training.

Nurses and clinicians require knowledge and training of their facilities' code blue response cart to manage emergency scenarios. However, the nurses who access the carts change frequently through turnover and role changes. An augmented reality training solution was built for mobile devices, but encountered distribution and access challenges. This study evaluated the conversion of the mobile application to a desktop-based version deployed via a learning management system. Eight hundred fifty clinicians were assigned the interactive learning product, which collected anonymous usage data and an optional feedback survey within the module. Of 850 assigned users, 468 completed the module, and 338 completed the feedback survey. Respondents indicated a positive difference of 25.3% in retrospective pre/post confidence and an appreciation for the features of the product. Performance measured by decreasing total item search time appeared to level off after three plays. The format transition was successful, allowing the same widespread distribution as the mobile versions of [X]. Feedback gathered will drive improvements in the module.

The Interprofessional Standardized Patient Experience: An Effective Interprofessional Education Activity for Prelicensure Health Professional Students.

Introduction: For future success in the modern health care environment, health professions students require effective interprofessional education experiences to develop their perceptions of other professionals on the health care team. The Interprofessional Standardized Patient Experience (ISPE) is an interprofessional education activity for prelicensure health professional students in nursing, pharmacy, physical therapy, medicine, social work, and occupational therapy. Methods: The ISPE involved collaboration among students to conduct a subjective interview. Students from six health care professions individually interviewed a simulated patient while being observed by students from other professions. A structured faculty-guided debriefing session followed the comprehensive interview process. Students completed a voluntary pre- and post-ISPE survey with interprofessional questions and feedback on the activity. Descriptive statistics were used to analyze individual responses. Differences in student opinions by student profession and by the number of professions present were examined using chi-square tests. Results: Over 4 consecutive academic years, 1,265 students completed the ISPE, and 1,028 completed the pre- and post-ISPE surveys. Analysis of the survey responses indicated that the ISPE enhanced student awareness of the functions of an interprofessional team and increased student knowledge of the roles of different health care professions. Students rated the ISPE as a valuable experience. Differences were noted in some of the measures by profession and group size. Discussion: A single ISPE had a significant impact on prelicensure students' perceptions. The ISPE is a novel and effective approach to interprofessional education that students appreciate.

PI3Kγ inhibition circumvents inflammation and vascular leak in SARS-CoV-2 and other infections.

Virulent infectious agents such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and methicillin-resistant Staphylococcus aureus (MRSA) induce tissue damage that recruits neutrophils, monocyte, and macrophages, leading to T cell exhaustion, fibrosis, vascular leak, epithelial cell depletion, and fatal organ damage. Neutrophils, monocytes, and macrophages recruited to pathogen-infected lungs, including SARS-CoV-2-infected lungs, express phosphatidylinositol 3-kinase gamma (PI3Kγ), a signaling protein that coordinates both granulocyte and monocyte trafficking to diseased tissues and immune-suppressive, profibrotic transcription in myeloid cells. PI3Kγ deletion and inhibition with the clinical PI3Kγ inhibitor eganelisib promoted survival in models of infectious diseases, including SARS-CoV-2 and MRSA, by suppressing inflammation, vascular leak, organ damage, and cytokine storm. These results demonstrate essential roles for PI3Kγ in inflammatory lung disease and support the potential use of PI3Kγ inhibitors to suppress inflammation in severe infectious diseases.

Her village: experiences of drug-involved women in a female-only aftercare program in the Philippines.

PURPOSE: Women are exposed to vulnerabilities that can lead to drug use or hinder recovery. However, there is a dearth of studies on recovery programs for women. This study aims to add to the literature by examining the feasibility of a women-only aftercare program for recovering users in the Philippines. DESIGN/METHODOLOGY/APPROACH: The study used a mixed-method design with pre and post-program surveys used to measure changes in participants' recovery capital. Focused group discussions elicited participants' context, their reactions, perceived outcomes and suggestions on the program. FINDINGS: Women in the program shared narratives of pain, trauma and abuse before treatment. Participants reported significant improvements in personal, community and family recovery capital dimensions. The program enabled personal growth in the form of new knowledge, skills and self-confidence. The women-only program also provided a safe space for women, to receive support from other women, community members and family. However, the women continue to face continuing challenges related to stigma and discrimination and a lack of livelihood opportunities. RESEARCH LIMITATIONS/IMPLICATIONS: A limitation of the study was its small sample size and the lack of a control group. Another limitation was the variability in treatment received by the women, which could have affected overall outcomes. Future studies using a randomized control trial and longitudinal designs may provide more robust conclusions on the effectiveness of the program. PRACTICAL IMPLICATIONS: Given punitive contexts, gender-sensitive and trauma-informed programs and services for women involved in drug use could potentially mitigate the abuse, stigma and vulnerabilities they experience. ORIGINALITY/VALUE: This study contributes to the sparse literature on women-only aftercare, particularly in countries that criminalize drug use.

Use of allopurinol to manage skewed 6-mercaptopurine metabolism in pediatric maintenance acute lymphoblastic leukemia treatment.

BACKGROUND: 6-mercaptopurine is a cornerstone of maintenance therapy for pediatric ALL. Response to 6MP is typically determined by the ANC. Therapeutic ANC range while receiving 6MP is between 500 and 1500/µL. In addition to desired myelosuppression, 6MP is associated with multiple adverse drug effects. Increased doses of 6MP can lead to therapeutic ANC values; however, patients may experience adverse effects before obtaining therapeutic myelosuppression, often deemed "skewed metabolism." Allopurinol may potentially correct skewed 6MP metabolism. PROCEDURE: Pediatric patients with ALL with 6MMP and 6TGN metabolites drawn during maintenance therapy were analyzed for allopurinol use. The primary outcome evaluated the percentage of time spent in therapeutic ANC range before and after allopurinol initiation. In addition, the difference in 6MMP:6TGN ratios before and after allopurinol initiation, incidence of hepatotoxicity, and rates of relapse, were analyzed. RESULTS: Ninety-five patients were included for analysis. Thirty-two (34%) patients received allopurinol. There were no significant differences in baseline demographics between the patients who received allopurinol and those who did not. When comparing ANC values pre- and post-allopurinol initiation, a statistically significant increase in the percentage of time spent in therapeutic range was observed (27% vs. 43%; p = .03). In addition, when comparing metabolite ratios pre- and post-allopurinol initiation, a statistically significant decrease in 6MMP:6TGN metabolite ratio values was observed (86.7 vs. 3.6; p < .0001). CONCLUSIONS: Allopurinol significantly increased the percent time in therapeutic ANC range and can be safely utilized to significantly lower the ratio of 6MMP:6TGN metabolites, alleviating the undesirable side effects of 6MMP, and optimizing the anti-leukemic effects associated with 6TGN.

Custom silicone Y-stents for the management of anastomotic stenosis in lung transplant recipients.

BACKGROUND: Airway stenting may be needed to manage anastomotic complications in lung transplant recipients. Conventional stenting strategies may be inadequate due to anatomic variations between the recipient and donor or involvement of both the anastomosis and lobar bronchi. METHODS: We investigated the efficacy of 3D-designed patient-specific silicone Y-stents in managing this scenario. 9 patients with complex airway stenosis underwent custom stent insertion after either failing traditional management strategies or having anatomy not suitable for conventional stents. CT images were uploaded to stent design software to make a virtual stent model. 3D printing technology was then used to make a mold for the final silicone stent which was implanted via rigid bronchoscopy. Forced expiratory volume in 1 s (FEV1) was measured pre- and post-stent placement. RESULTS: 78 % of patients experienced an increase in their FEV1 after stent insertion, (p = 0.001, 0.02 at 30 and 90 days respectively). Unplanned bronchoscopies primarily occurred due to mucous plugging. 2 patients had sufficient airway remodeling allowing for stent removal. CONCLUSIONS: Personalized 3D-designed Y-stents demonstrate promising results for managing complicated airway stenosis, offering improved lung function and potential long-term benefits for lung transplant recipients.

Identifying Sources of Entanglement Loss in Photodriven Molecular Electron Spin Teleportation.

We report on an electron donor-electron acceptor-stable radical (D-A-R•) molecule in which an electron spin state first prepared on R• is followed by photogeneration of an entangled singlet 1[D•+-A•-] spin pair to produce D•+-A•--R•. Since the A•- and R• spins within D•+-A•--R• are uncorrelated, spin teleportation from R• to D•+ occurs with a maximal 25% efficiency only for the singlet pair 1(A•--R•) by spin-allowed electron transfer from A•- to R•. However, since 1[D•+-A•-] is sufficiently long-lived, coherent spin mixing involving the unreactive 3(A•--R•) population affects entanglement and teleportation within D•+-A•--R•. Pulse electron paramagnetic resonance experiments show a direct correlation between electron spin flip-flops and entanglement loss, providing information for designing molecular materials to serve as nanoscale quantum device interconnects.

Mind the Decimal Point: A Case of Diazoxide Overdose-Induced Ileus.

Diazoxide is the only medication approved by the United States Food and Drug Administration for the treatment of hyperinsulinism-induced hypoglycemia. Overdose is infrequently reported. This case describes a preterm four-week-old male who was prescribed diazoxide and chlorothiazide for perinatal stress-induced hyperinsulinism. The patient presented to the emergency department with feeding intolerance and abdominal distension following an accidental 10-fold diazoxide overdose. On presentation, vital signs were remarkable for tachycardia and intermittent tachypnea. Physical exam revealed a grossly distended abdomen. Laboratory abnormalities included a glucose of 216 mg/dL, sodium of 132 mmol/L, and chloride of 98 mmol/L. Abdominal X-ray interpretation found moderate gaseous distension suggestive of generalized ileus. The patient was admitted to the neonatal intensive care unit (NICU), and a nasogastric tube was placed. He received intravenous dextrose fluids, and enteral feeds were resumed as serial X-rays showed interval improvement. The patient remained in the NICU for several days to monitor bowel movements and resolution of ileus and he was discharged after improvement. While diazoxide overdose is rarely reported, and ileus due to such is documented even less frequently, 10-fold medication dose errors are common among infants. The source of the 10-fold mistake is often decimal points, leading zeros, or trailing zeros. Utilizing the smallest possible syringe for the prescribed dose may reduce the incidence of medication errors.

Triple Aspiration Versus Conventional Aspiration Techniques: A Randomized In-Vitro Evaluation.

BACKGROUND AND PURPOSE: A single aspiration maneuver using a large volume syringe is a common and effective technique for aspiration thrombectomy. Multiple aspiration cycles using large aspiration syringes has been proposed as a means to improve efficacy over single aspiration. In this study, we sought to investigate the efficacy of a "triple aspiration technique" where a large volume syringe is cycled three times prior to catheter retraction during aspiration thrombectomy. MATERIALS AND METHODS: A 3D-printed adult vasculature was used as a benchtop thrombectomy platform. Fibrin-rich and red blood cell-rich clots were prepared in centrifuge tubes using human plasma, red blood cells, and calcium chloride. Next, clots were placed in the carotid terminus of the model, and the performances of three different aspiration techniques-triple syringe, single syringe, and continuous pump aspiration-were compared in a randomized manner (1:1:1). Outcomes of interest included first-pass efficacy (FPE), complete clot removal (final mTICI 2c/3), the number of thrombectomy attempts to achieve mTICI 2c/3, vacuum pressure, and distal embolization. The distal emboli were detected using a 70-micron cell strainer placed at the outflow of the model and quantified using an image processing algorithm. The vacuum pressures were measured using a pressure transducer (Honeywell, NC, USA). RESULTS: A total of 102 replicates were performed, 34 for each technique. The triple aspiration technique provided a significantly higher rate of FPE than the syringe and pump aspiration techniques (67.6% vs. 41.1%, p= 0.02). Additionally, the triple aspiration technique achieved complete clot removal with a significantly lower number of thrombectomy attempts compared to single syringe aspiration (1.2 ± 0.5 vs. 1.8 ± 0.8, p=0.005). The triple aspiration technique generated significantly higher vacuum pressure than both the single syringe and vacuum pump aspiration (28.3 ± 0.2 vs. 27.2 ± 0.3 (p= 0.002) and 26.2 ± 0.4 (p=0.001), respectively). The differences in complete clot removal and distal embolization parameters were not statistically significantly different across the groups. CONCLUSIONS: Our findings suggest that the triple aspiration technique can improve FPE rates and vacuum pressure in aspiration thrombectomy. Further studies are needed to examine the safety and efficacy of triple aspiration in the clinical setting. ABBREVIATIONS: AcommA = anterior communicating artery; FPE = first pass efficacy; ICA = internal carotid artery; MCA = middle cerebral artery; MT = mechanical thrombectomy; mTICI = modified thrombolysis in cerebral infarction scale; PcommA = posterior communicating artery.

An International, Multicenter Feasibility Study on Active and Continuous Irrigation With Cerebrospinal Fluid Exchange for Improving Outcomes in Cerebral Ventriculitis.

BACKGROUND AND OBJECTIVES: Cerebral ventriculitis remains a challenging neurosurgical condition because of poor outcomes including mortality rates of nearly 80% and a prolonged course of treatment in survivors. Despite current conventional management, outcomes in some cases remain unsatisfactory, with no definitive therapeutic guidelines. This feasibility study aims to explore the use of a novel active, continuous irrigation and drainage system (IRRAflow [IRRAS AB]) combined with intraventricular drug delivery for patients with cerebral ventriculitis. METHODS: We conducted a multicenter, international, retrospective study of patients with ventriculitis who were treated with use of the IRRAflow system. Data collected included patient demographics, comorbidities, admission Glasgow Coma Scale score, baseline modified Rankin Scale (mRS) score, and imaging findings. Catheter occlusions, infections, and shunt placement were recorded for outcome assessment, along with discharge mRS scores and in-hospital deaths. RESULTS: Four centers contributed data for a total of 21 patients who had IRRAflow placement for treatment of ventriculitis. Thirteen (61.9%) were men (mean age = 49.8 ± 14.87 years). The median baseline mRS score was 1. The median Glasgow Coma Scale score at admission was 13. The etiology of ventriculitis was iatrogenic in 12 (57.1%) patients and secondary to an abscess in 9 (42.9%). No cases reported hemorrhage or failure of IRRAflow placement. Antibiotics were administered through the IRRAflow system in 13 (61.9%) cases in addition to systemic dosing. Sixteen (76.2%) patients had significant clinical improvement and resolution of ventriculitis. Seven (33.3%) patients required shunt placement after resolution because of persistent hydrocephalus. There were 6 (28.6%) in-hospital deaths. CONCLUSION: The use of active irrigation with drainage for continuous delivery of intraventricular irrigation fluid with antibiotics led to dramatically low mortality. In our case series, it led to a marked improvement in neurological status, imaging findings, and cerebrospinal fluid profiles, making it a technically feasible and safe treatment for ventriculitis.

Chronic Rhinosinusitis Risk after Maxillectomy with Microvascular Reconstruction.

INTRODUCTION: Chronic rhinosinusitis (CRS) can be associated with tumors involving the maxillary sinus, but outcomes after undergoing maxillectomy with free flap reconstruction remain unclear. METHODS: A retrospective analysis of medical records was performed to evaluate evidence of CRS in patients who underwent maxillectomy with free flap reconstruction at a single tertiary care academic institution from 2013 through 2020. RESULTS: Eighty-four patients were assessed. Nineteen (22.6%) patients were diagnosed with CRS after surgery, 23 (27.4%) patients were treated for sinus symptoms, and 49 (58.3%) had radiographic evidence of sinus inflammation for more than 6 months. Risk factors for requiring sinus treatment included adjuvant or neoadjuvant chemotherapy (p = 0.002) and pre-operative use of sinus medication (p < 0.001). Radiographic evidence of sinusitis 6 months after surgery is also closely associated with sinusitis treatment (p = 0.051). CONCLUSIONS: CRS may be underdiagnosed in patients undergoing maxillectomy with microvascular reconstruction. Further evaluation into patient sinus disease and symptoms following neoplastic surgery may lead to a higher quality of life in some long-term survivors.

Amygdala Volume and Depression Symptoms in Young Adolescents Who Use Cannabis.

INTRODUCTION: Both cannabis use and depressive symptomology increase in prevalence throughout adolescence. Concurrently, the brain is undergoing neurodevelopment in important limbic regions, such as the amygdala. Prior research indicates the amygdala may also be related to cannabis use and depressive symptoms. We aimed to investigate the effects of adolescent cannabis use on amygdala volumes as well as the interaction of cannabis use and amygdala morphometry on depressive symptoms in youth. METHOD: Two-hundred-twenty-four participants (ages 12-15), balanced by sex assigned at birth, were selected from a sub-sample of the Adolescent Brain Cognitive Development (ABCD) Study based on hair toxicology and self-report measures of cannabis use. Participants positive for cannabinoids in hair and/or self-reported cannabis use were demographically matched to youth with no self-reported or confirmed cannabis use. The guardians of these youth reported depression symptoms on the Child Behavioral Checklist. Linear mixed effect models were run investigating cannabis use group on amygdala volumes bilaterally, controlling for whole brain volume and random effects of scanner type. Additional analyses examined cannabis group status and bilateral amygdala volume on depression symptoms. RESULTS: Cannabis use was not significantly associated with amygdala volume but was associated with increased depressive symptoms (p<0.01). Cannabis group interacted with amygdala volume, such that individuals with smaller volumes had increased depressive symptoms within the cannabis group (p's<0.01-0.02). CONCLUSION: Aberrations in amygdala volume based on cannabis use were not found in early adolescence; however, more depressive symptoms were related to cannabis group. Youth who use cannabis and have smaller amygdala volumes were at increased risk for depressive symptomology, suggesting potential neurovulnerabilities to cannabis use.

Association of circulating tumor DNA with patient prognosis in surgically resected renal cell carcinoma.

BACKGROUND: Despite complete resection, 20%-50% of patients with localized renal cell carcinoma (RCC) experience recurrence within 5 years. Accurate assessment of prognosis in high-risk patients would aid in improving outcomes. Here we evaluate the use of circulating tumor DNA (ctDNA) in RCC using banked samples and clinical data from a single institution. METHODS: The cohort consisted of 45 RCC patients (≥pT1b) who underwent complete resection. The presence of ctDNA in plasma was determined using a personalized, tumor-informed ctDNA assay (Signatera RUO, Natera, Inc.). Relationships with outcomes and other relevant clinical variables were assessed. The median follow-up was 62 months. RESULTS: Plasma ctDNA was detected in 18 out of 36 patients (50%) pre-operatively and was associated with increased tumor size (mean 9.3 cm vs. 7.0 cm, P < .05) and high Fuhrman grade (60% grades III-IV vs 27% grade II, P = .07). The presence of ctDNA, either pre-operatively or at any time post-operatively, was associated with inferior relapse-free survival (HR = 2.70, P = .046; HR = 3.23, P = .003, respectively). Among patients who were ctDNA positive at any time point, the sensitivity of relapse prediction was 84% with a PPV of 90%. Of note, ctDNA positivity at a post-surgical time point revealed a PPV of 100% and NPV of 64%. The lack of ctDNA detection at both time points yielded an NPV of 80%. CONCLUSIONS: Detection of plasma ctDNA using a personalized assay is prognostic of recurrence in patients with resected RCC. Herein, we describe a successful approach for its application and identify potential limitations to be addressed in future studies.

Vaccine strains of Rift Valley fever virus exhibit attenuation at the maternal-fetal placental interface.

Rift Valley fever virus (RVFV) infection causes abortions in ruminant livestock and is associated with an increased likelihood of miscarriages in women. Using sheep and human placenta explant cultures, we sought to identify tissues at the maternal-fetal interface targeted by RVFV. Sheep villi and fetal membranes were highly permissive to RVFV infection resulting in markedly higher virus titers than human cultures. Sheep cultures were most permissive to wild-type RVFV and ΔNSm infection, while live-attenuated RVFV vaccines (LAVs; MP-12, ΔNSs, and ΔNSs/ΔNSm) exhibited reduced replication. The human fetal membrane restricted wild-type and LAV replication, and when infection occurred, it was prominent on the maternal-facing side. Type I and type III interferons were induced in human villi exposed to LAVs lacking the NSs protein. This study supports the use of sheep and human placenta explants to understand vertical transmission of RVFV in mammals and whether LAVs are attenuated at the maternal-fetal interface.IMPORTANCEA direct comparison of replication of Rift Valley fever virus (RVFV) in sheep and human placental explants reveals comparative efficiencies and permissivity to infection and replication. Vaccine strains of RVFV demonstrated reduced infection and replication capacity in the mammalian placenta. This study represents the first direct cross-host comparison of the vertical transmission capacity of this high-priority emerging mosquito-transmitted virus.

Defining cage subsidence in anterior, oblique, and lateral lumbar spine fusion approaches: a systematic review of the literature.

One of the most common complications of lumbar fusions is cage subsidence, which leads to collapse of disc height and reappearance of the presenting symptomology. However, definitions of cage subsidence are inconsistent, leading to a variety of subsidence calculation methodologies and thresholds. To review previously published literature on cage subsidence in order to present the most common methods for calculating and defining subsidence in the anterior lumbar interbody fusion (ALIF), oblique lateral interbody fusion (OLIF), and lateral lumbar interbody fusion (LLIF) approaches. A search was completed in PubMed and Embase with inclusion criteria focused on identifying any study that provided descriptions of the method, imaging modality, or subsidence threshold used to calculate the presence of cage subsidence. A total of 69 articles were included in the final analysis, of which 18 (26.1%) reported on the ALIF approach, 22 (31.9%) on the OLIF approach, and 31 (44.9%) on the LLIF approach, 2 of which reported on more than one approach. ALIF articles most commonly calculated the loss of disc height over time with a subsidence threshold of > 2 mm. Most OLIF articles calculated the total amount of cage migration into the vertebral bodies, with a threshold of > 2 mm. LLIF was the only approach in which most articles applied the same method for calculation, namely, a grading scale for classifying the loss of disc height over time. We recommend future articles adhere to the most common methodologies presented here to ensure accuracy and generalizability in reporting cage subsidence.