Clinical reading-related oculomotor assessment in visual snow syndrome / Evaluación oculomotora clínica relacionada con la lectura en el síndrome de nieve visual

Purpose: Visual snow syndrome (VSS) is a complex neurological condition presenting with an array of sensory, motor, and perceptual dysfunctions and related visual and non-visual symptoms. Recent laboratory studies have found subtle, basic, saccadic-based abnormalities in this population. The objective of the present investigation was to determine if saccadic-related problems could be confirmed and extended using three common clinical reading-related eye movement tests having well-developed protocols and normative databases. Methods: This was a retrospective analysis of 32 patients (ages 16–56 years) diagnosed with VSS in the first author's optometric practice. There was a battery of three reading-related tests: the Visagraph Reading Eye Movement Test, the Developmental Eye Movement (DEM) Test, and the RightEye Dynamic Vision Assessment Test, all performed using their standard documented protocols and large normative databases. Results: A high frequency of oculomotor deficits was found with all three tests. The greatest percentage was revealed with the Visagraph (56%) and the least with the RightEye (23%). A total of 77% of patients failed at least one of the three tests. Conclusion: The present findings confirm and extend earlier investigations revealing a high frequency of saccadic-based oculomotor problems in the VSS population, now including reading-related tasks. This is consistent with the more general oculomotor/motor problems found in these individuals.(AU)

Erratum: 120 Impact of Undergraduate Clinical Research Experience: Highlighting the UCLA Clinical and Translational Science Institute Research Associates Program (CTSI-RAP) - CORRIGENDUM.

[This corrects the article DOI: 10.1017/cts.2024.117.].

Asymptomatic endometrial cancer with Lynch syndrome; in a woman with primary infertility-A case report and literature review.

Lynch syndrome, also called hereditary non-polyposis colorectal cancer, is an autosomal dominant disorder characterized by germline pathogenic mutations in DNA mismatch repair genes-resulting in increased susceptibility to colorectal, endometrial, and other tumors. This case report presents an incidental finding of endometrial cancer with Lynch syndrome during investigation for primary infertility. A 34-year-old woman presented to the fertility clinic with unexplained primary infertility. Investigations showed possible endometrial polyp, 13 × 11 mm in size. Hysteroscopic polypectomy and endometrial biopsy revealed complex endometrial hyperplasia amounting to endometroid adenocarcinoma. The case was discussed at the West of Scotland Gynecology-Oncology MDT meeting-management options including fertility-sparing treatment or radical surgery were presented to the patient and she opted for the latter. A total laparoscopic hysterectomy with bilateral salpingo-oophorectomy was performed with pathology results consistent with well-differentiated endometroid adenocarcinoma Stage 1A. Peritoneal washings showed no malignant cells. Genetic testing confirmed a diagnosis of Lynch syndrome. On further questioning, it was revealed that the patient had a strong family history of colon cancer but had not previously met the criteria for genetic testing. She was referred to colorectal surgeons and underwent colonoscopy. This showed no abnormality; she was therefore scheduled for 2-yearly colonoscopic surveillance.

Correction: Development of Therapeutic Alliance and Social Presence in a Digital Intervention for Pediatric Concussion: Qualitative Exploratory Study.

[This corrects the article DOI: 10.2196/49133.].

First Report of Xanthomonas perforans Causing Bacterial Spot of Pepper (Capsicum annuum) in North Carolina.

North Carolina (NC) is the fifth largest producer of bell pepper (Capsicum annuum) in the US with an estimated 2,400 acres in production (NASS-USDA, 2022). A survey of bacterial diseases of peppers was initiated in 2020 after numerous bacterial spot outbreaks were reported in NC. Bacterial spot is caused by a complex of four Xanthomonads: X. euvesicatoria, X. vesicatoria, X. perforans, and X. hortorum pv. gardneri (Larrahondo-Rodríguez et al., 2022). If not preemptively managed, bacterial spot can cause up to 40% yield loss (Kousik and Ritchie, 1998). During the 2020 and 2021 growing seasons, 103 yellow mucoid colonies were isolated from plants representing 51 pepper cultivars symptomatic of bacterial spot, i.e., water-soaked leaf lesions that become necrotic spots on leaves and fruits across 22 commercial fields in NC following published methods (Klein-Gordon et al., 2021). All colonies were characterized to species using the qPCR species-specific primers and probes described by Strayer et al. 2016. Of the 103 colonies, 12 isolates tested positive for X. perforans. To confirm qPCR results, a Multi-Locus Sequence Analysis (MLSA) was run using fusA, gapA, gltA, gyrB, and lacF following previously described methods (Almeida et al., 2010) on three representative isolates: AHX61, collected in September 2020 from a field with 20% disease severity in Wake County on cv. Canary Bell; AHX261, collected in July 2021 from a field with 50% disease severity in Sampson County on Jalapeño; and AHX426, collected in August 2021 from a field with 50% disease severity in Dublin County on Jalapeño. All gene sequences were deposited to NCBI (GenBank Accessions: OQ799538-OQ799552) and compared to those from X. euvesicatoria, X. hortorum pv. gardneri, X. perforans, and X. vesicatoria type strains (Almeida et al., 2010). The MLSA showed AHX61, AHX261, and AHX426 cluster with X. perforans ICMP16690T, sharing 99-100% nucleotide similarity. Koch's postulates were performed with the three strains, Xp1484T [ X. perforans type strain, (Wilson 1987)], and water as a negative control. Three 10-week-old bell pepper plants (cv. Early Cal Wonder) were dip-inoculated in 600 mL of a bacterial suspension at an OD600 of 0.3 (~5x108 CFU/mL) and 0.04% Silwet L-77 per strain or water. All 18 plants were individually incubated in a plastic bag for 48 h post-inoculation at 28°C, 80% relative humidity, and 14 h:10 h light-dark cycle in a growth chamber, after which plastic bags were removed. Water-soaking and necrotic spots characteristic of bacterial spot were first observed at six days post-inoculation (dpi). At 14 dpi, symptomatic leaves were removed from treated plants to attempt pathogen re-isolation. Yellow mucoid colonies similar in morphology to those originally inoculated were recovered from all plants and confirmed to be X. perforans through sequencing; no isolates were recovered from water-treated plants. To our knowledge, this is the first time X. perforans is isolated in commercial bell pepper and specialty pepper fields in the state. This is an indication that the Xanthomonas population on peppers in the state is more diverse than previously reported and that pathogen populations will require monitoring for possible species shifts for this crop in NC.

Structure and Properties of Na2S-SiS2-P2S5-NaPO3 Glassy Solid Electrolytes.

In the development of sodium all-solid-state batteries (ASSBs), research efforts have focused on synthesizing highly conducting and electrochemically stable solid-state electrolytes. Glassy solid electrolytes (GSEs) have been considered very promising due to their tunable chemistry and resistance to dendrite growth. For these reasons, we focus here on the atomic-level structures and properties of GSEs in the compositional series (0.6-0.08y)Na2S + (0.4 + 0.08y)[(1 - y)[(1 - x)SiS2 + xPS5/2] + yNaPO3] (NaPSiSO). The mechanical moduli, glass transition temperatures, and temperature-dependent conductivity were determined and related to their short-range order structures that were determined using Raman, Fourier transform infrared, and 31P and 29Si magic angle spinning nuclear magnetic resonance spectroscopies. In addition, the conductivity activation energies were modeled using the Christensen-Martin-Anderson-Stuart model. These GSEs appear to be highly crystallization-resistant in the supercooled liquid region where no measurable crystallization below 450 °C could be observed in differential scanning calorimetry studies. Additionally, these GSEs were found to be highly conducting, with conductivities on the order of 10-5 (Ω cm)-1 at room temperature, and processable in the supercooled state without crystallization. For all these reasons, these NaPSiSO GSEs are considered to be highly competitive and easily processable candidate GSEs for enabling sodium ASSBs.

Understanding Coenzyme Q.

Coenzyme Q (CoQ), also known as ubiquinone, comprises a benzoquinone head group and a long isoprenoid sidechain. It is thus extremely hydrophobic and resides in membranes. It is best known for its complex function as an electron transporter in the mitochondrial electron transport chain (ETC) and in several other cellular processes. In fact, CoQ appears to be central to the redox balance of the cell. Remarkably, its structure and properties have not changed from bacteria to vertebrates. In metazoans, it is synthesized in all cells and is found in most, and maybe all, biological membranes. CoQ is also known as a nutritional supplement, mostly because of its involvement with antioxidant defenses. However, whether there is any health benefit from oral consumption of CoQ is not well established. Here we review the function of CoQ as a redox active molecule in the ETC and other enzymatic systems, its role as a pro-oxidant in reactive oxygen species generation, and its separate involvement in antioxidant mechanisms. We also review CoQ biosynthesis, which is particularly complex because of its extreme hydrophobicity, as well as the biological consequences of primary and secondary CoQ deficiency, including in human patients. Primary CoQ deficiency is a rare inborn condition due to mutation in CoQ biosynthetic genes. Secondary CoQ deficiency is much more common as it accompanies a variety of pathological conditions, including mitochondrial disorders as well as aging. In this context, we discuss the importance, but also the great difficulty, of alleviating CoQ deficiency by CoQ supplementation.

Nusinersen Initiation After Onset of Weakness Does Not Prevent Progression of Hip Instability.

BACKGROUND: We report changes in the natural history of hip instability with nusinersen treatment among patients with spinal muscular atrophy (SMA) type II after onset of weakness, historically wheelchair-bound but now potentially ambulatory in the era of disease-modifying therapy. METHODS: Patients with genetically confirmed diagnoses of SMA type II who received intrathecal nusinersen from January 1, 2018, to June 30, 2022, were screened for inclusion. Patients with less than 6 months of follow-up, or prior hip surgeries were excluded. Primary clinical outcome measures included scores from Hammersmith motor functional scale expanded (HMFSE), revised upper limb module (RULM), 6-minute walk test (6MWT), and ambulatory status. Radiographic outcomes, including Reimer migration index, the presence of scoliosis, and pelvic obliquity, were also assessed. Secondary outcomes involved comparisons with a historical cohort of SMA type II patients treated at our institution who never received nusinersen. RESULTS: Twenty hips from 5 boys and 5 girls were included in the analysis, with a mean follow-up of 3 years and 8 months. The median age at time of nusinersen initiation was 6.8 years old, ranging between 2.5 and 10.3 years. All patients developed lower limb motor weakness before nusinersen initiation. After treatment with nusinersen, 1 previously stable hip (5%) developed subluxation, 15 hips (75%) remain subluxated, 3 hips (15%) remain dislocated, and 1 hip (5%) remained stable, with a statistically significant difference between the pretreatment and posttreatment groups (P<0.01). Six patients (60%) were ambulatory at latest follow-up. Six patients (60%) had improved ambulatory ability; 2 had static ambulatory ability (20%); and 2 had deterioration in their walking ability. The median HFMSE score improved from 18.5 (range 0 to 46) to 22 (range 0 to 49) (P=0.813), whereas the median RULM score improved from 17 (range 2 to 28) to 21.5 (range 5 to 37), which was statistically significant (P=0.007). CONCLUSIONS: Hip instability persists despite treatment with nusinersen among patients with SMA type II who received nusinersen after onset of lower limb weakness. LEVEL OF EVIDENCE: Therapeutic Level IV.

Hair follicles modulate skin barrier function.

Our skin provides a protective barrier that shields us from our environment. Barrier function is typically associated with interfollicular epidermis; however, whether hair follicles influence this process remains unclear. Here, we utilize a potent genetic tool to probe barrier function by conditionally ablating a quintessential epidermal barrier gene, Abca12 , which is mutated in the most severe skin barrier disease, harlequin ichthyosis. With this tool, we deduced 4 ways by which hair follicles modulate skin barrier function. First, the upper hair follicle (uHF) forms a functioning barrier. Second, barrier disruption in the uHF elicits non-cell autonomous responses in the epidermis. Third, deleting Abca12 in the uHF impairs desquamation and blocks sebum release. Finally, barrier perturbation causes uHF cells to move into the epidermis. Neutralizing Il17a, whose expression is enriched in the uHF, partially alleviated some disease phenotypes. Altogether, our findings implicate hair follicles as multi-faceted regulators of skin barrier function.

The influence of perioperative enoxaparin on bleeding after TORS oropharyngectomy.

Perioperative enoxaparin is often avoided in patients undergoing transoral robotic (TORS) oropharyngectomy. Our goal was to quantify the risk of postoperative hemorrhage (POH) in patients receiving enoxaparin after TORS oropharyngectomy. This was a retrospective database cohort study set up in 89 separate healthcare organizations. The TriNetX electronic database was queried for patients with OPSCC who underwent TORS oropharyngectomy. Propensity-score matching was used to create two cohorts, one receiving and one not receiving perioperative enoxaparin. Outcome measures were the POH rate within 1 day of surgery ("primary") and POH rate within 2-30 days of surgery ("secondary"). 1109 patients undergoing TORS for OPSCC were identified, 400 of which received perioperative enoxaparin. One-to-one propensity score matching resulted in 310 patients per cohort. After matching, the primary POH rates between patients receiving and not receiving enoxaparin were 3.23% for both cohorts (OR 1.000, 95% CI 0.410 to 2.438). The secondary POH rates between those receiving and not receiving enoxaparin were 5.47% vs. 3.54% (OR 1.577, 95% CI 0.726 to 3.424). The number needed to harm (NNH) with perioperative enoxaparin use for secondary POH after TORS was 53; no difference was found in primary POH rates. While not statistically significant, the use of perioperative enoxaparin after TORS is associated with increased odds of secondary POH with a NNH of 53; no difference was found in rates of primary POH. For patients undergoing TORS, enoxaparin use requires careful weighing of the risks and benefits.

Inverse association between arterial stiffness and perceived fatigue independent of disability status and BMI in multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is an immune-mediated, neurodegenerative disease of the central nervous system. Fatigue represents one of the most prevalent and limiting symptoms of MS, and is associated with vascular dysfunction, notably increased arterial stiffness. OBJECTIVE: This study examined the relationship between arterial stiffness and perceived fatigue in persons with MS. METHODS: The sample of 52 persons with MS (71.2% Female; Age: 46.7 ± 12.3 yrs.) completed arterial stiffness and fatigue assessments as baseline for an exercise training intervention. Applanation tonometry measured arterial stiffness, pulsatility and waveform characteristics, and yielded the following outcomes: carotid-femoral pulse wave velocity (cfPWV), carotid pulse-pressure (cPP), and aortic augmentation pressure (AP). Perceived fatigue was measured using the Fatigue Severity Scale (FSS). RESULTS: The mean (SD) scores for cfPWV, cPP, and AP were 7.0 ± 1.8 m/s, 35.7 ± 8.8 mmHg, 8.2 ± 6.2 mmHg, respectively. The mean (SD) FSS score was 4.6 ± 1.4 and indicated elevated fatigue. There were statistically significant (p < .05) inverse correlations between cfPWV (r = -.32), cPP (r = -.37) and AP (r = -.32) with FSS scores, and the correlations remained significant even after controlling for disability, body mass index, age, and sex. CONCLUSION: Our results indicate a consistent pattern of inverse relationships between arterial stiffness, pulsatility, and waveforms with fatigue independent of disability, body mass index, age, and sex in MS. This could be explained by lower sympathetic activation linking higher arterial stiffness, pulsatility and augmentation pressure with lower fatigue in persons with MS.

Adjuvant-dependent impact of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus.

Whole virus-based inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide have been critical to the COVID-19 pandemic response. Although these vaccines are protective against homologous coronavirus infection, the emergence of novel variants and the presence of large zoonotic reservoirs harboring novel heterologous coronaviruses provide significant opportunities for vaccine breakthrough, which raises the risk of adverse outcomes like vaccine-associated enhanced respiratory disease. Here, we use a female mouse model of coronavirus disease to evaluate inactivated vaccine performance against either homologous challenge with SARS-CoV-2 or heterologous challenge with a bat-derived coronavirus that represents a potential emerging disease threat. We show that inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide can cause enhanced respiratory disease during heterologous infection, while use of an alternative adjuvant does not drive disease and promotes heterologous viral clearance. In this work, we highlight the impact of adjuvant selection on inactivated vaccine safety and efficacy against heterologous coronavirus infection.

AnnoSpat annotates cell types and quantifies cellular arrangements from spatial proteomics.

Cellular composition and anatomical organization influence normal and aberrant organ functions. Emerging spatial single-cell proteomic assays such as Image Mass Cytometry (IMC) and Co-Detection by Indexing (CODEX) have facilitated the study of cellular composition and organization by enabling high-throughput measurement of cells and their localization directly in intact tissues. However, annotation of cell types and quantification of their relative localization in tissues remain challenging. To address these unmet needs for atlas-scale datasets like Human Pancreas Analysis Program (HPAP), we develop AnnoSpat (Annotator and Spatial Pattern Finder) that uses neural network and point process algorithms to automatically identify cell types and quantify cell-cell proximity relationships. Our study of data from IMC and CODEX shows the higher performance of AnnoSpat in rapid and accurate annotation of cell types compared to alternative approaches. Moreover, the application of AnnoSpat to type 1 diabetic, non-diabetic autoantibody-positive, and non-diabetic organ donor cohorts recapitulates known islet pathobiology and shows differential dynamics of pancreatic polypeptide (PP) cell abundance and CD8+ T cells infiltration in islets during type 1 diabetes progression.

Genetic and phenotypic characterization of Parkinson's disease at the clinic-wide level.

Observational studies in Parkinson's disease (PD) deeply characterize relatively small numbers of participants. The Molecular Integration in Neurological Diagnosis Initiative seeks to characterize molecular and clinical features of every PD patient at the University of Pennsylvania (UPenn). The objectives of this study are to determine the feasibility of genetic characterization in PD and assess clinical features by sex and GBA1/LRRK2 status on a clinic-wide scale. All PD patients with clinical visits at the UPenn PD Center between 9/2018 and 12/2022 were eligible. Blood or saliva were collected, and a clinical questionnaire administered. Genotyping at 14 GBA1 and 8 LRRK2 variants was performed. PD symptoms were compared by sex and gene groups. 2063 patients were approached and 1,689 (82%) were enrolled, with 374 (18%) declining to participate. 608 (36%) females were enrolled, 159 (9%) carried a GBA1 variant, and 44 (3%) carried a LRRK2 variant. Compared with males, females across gene groups more frequently reported dystonia (53% vs 46%, p = 0.01) and anxiety (64% vs 55%, p < 0.01), but less frequently reported cognitive impairment (10% vs 49%, p < 0.01) and vivid dreaming (53% vs 60%, p = 0.01). GBA1 variant carriers more frequently reported anxiety (67% vs 57%, p = 0.04) and depression (62% vs 46%, p < 0.01) than non-carriers; LRRK2 variant carriers did not differ from non-carriers. We report feasibility for near-clinic-wide enrollment and characterization of individuals with PD during clinical visits at a high-volume academic center. Clinical symptoms differ by sex and GBA1, but not LRRK2, status.

Restoration age affects microbial-herbaceous plant interactions in an oak woodland.

In degraded ecosystems, soil microbial communities (SMCs) may influence the outcomes of ecological restoration. Restoration practices can affect SMCs, though it is unclear how variation in the onset of restoration activities in woodlands affects SMCs, how those SMCs influence the performance of hard-to-establish woodland forbs, and how different woodland forbs shape SMCs. In this study, we quantified soil properties and species abundances in an oak woodland restoration chronosequence (young, intermediate, and old restorations). We measured the growth of three woodland forb species when inoculated with live whole-soil from young, intermediate, or old restorations. We used DNA metabarcoding to characterize SMCs of each inoculum treatment and the soil after conditioning by each plant species. Our goals were to (1) understand how time since the onset of restoration affected soil abiotic properties, plant communities, and SMCs in a restoration chronosequence, (2) test growth responses of three forb species to whole-soil inoculum from restoration sites, and (3) characterize changes in SMCs before and after conditioning by each forb species. Younger restored woodlands had greater fire-sensitive tree species and lower concentrations of soil phosphorous than intermediate or older restored woodlands. Bacterial and fungal soil communities varied significantly among sites. Forbs exhibited the greatest growth in soil from the young restoration. Each forb species developed a unique soil microbial community. Our results highlight how restoration practices affect SMCs, which can in turn affect the growth of hard-to-establish forb species. Our results also highlight that the choice of forb species can alter SMCs, which could have long-term potential consequences for restoration success.

Fast, Efficient, Catalyst-Free Epoxidation of Butyl Rubber Using Oxone/Acetone for Improved Filler Dispersion.

Incorporation of a polar filler such as silica into a nonpolar rubber matrix is challenging and energy consuming due to their large difference in polarity. Epoxidation of carbon-carbon double bonds in unsaturated rubber, especially for rubber with low unsaturation such as butyl rubber, is an effective method to introduce polar functional groups to the rubber macromolecules for better filler dispersion. Although different epoxidation reagents including hydrogen peroxide (H2O2), peracid, and meta-chloroperoxybenzoic acid (mCPBA) have been previously reported, these reagents have different drawbacks. In this article, a metal-free epoxidation reagent, dimethyl dioxirane (DMDO), generated from acetone and Oxone is explored for efficient epoxidation of rubber with low unsaturation. The effects of the addition manner of the reactant Oxone and buffer sodium bicarbonate (NaHCO3) and reaction temperature on the epoxide formation are studied. Compared to peracid, a faster and more efficient epoxidation without the generation of a ring-opened product is achieved when DMDO is used as the epoxidation reagent. Furthermore, it is found that the epoxidation using DMDO is not sensitive to the water concentration in the rubber solution up to 20 wt %. The addition of quaternary ammonium salt as a phase transfer catalyst not only improves the conversion but also further increases the water tolerance to 25 wt %. The reaction conditions for preparation of epoxidized butyl rubber with different percentages of epoxide group are optimized by Design of Experiments (DoE). At the end, improved dispersion of silica in the matrix of epoxidized butyl rubber is achieved, as revealed by the rubber process analyzer (RPA) and atomic force microscopy (AFM).

Maternal residential exposure to solvents from industrial sources during pregnancy and childhood cancer risk in California.

BACKGROUND: Maternal solvent exposure has been suspected to increase offspring cancer risk. The study aimed to evaluate the associations between maternal residential exposure to solvents from industrial pollution during pregnancy and childhood cancer. METHODS: The present study included 15,744 cancer cases (aged 0-19 years at diagnosis) identified from California Cancer Registry and 283,141 controls randomly selected from California Birth Registry (20:1 frequency-matched by birth year: 1998-2016). We examined industrial releases of tetrachloroethylene and 1,1,1-trichloroethane within 3 km of the birth address, while we used a 5 km buffer for carbon disulfide. We calculated the total exposure from all linked Toxic Release Inventory sites during each index pregnancy and assigned "ever/never" and "high/low exposed/unexposed" exposure, using median values. We performed quadratic decay models to estimate cancer risks associated with maternal solvent exposure in pregnancy. RESULTS: 1,1,1-Trichloroethane was associated with rhabdomyosarcoma (adjusted Odds Ratio (aOR): 1.96; 95% Confidence Interval (CI): 1.16, 3.32) in the "ever exposed" group. Ever exposure to carbon disulfide was associated with increased risks of medulloblastoma (OR = 1.85, 95% CI 1.01, 3.40) and ependymoma (OR = 1.63, 95% CI 0.97, 2.74). CONCLUSIONS: Overall, our findings suggested maternal residential exposure to solvents from industrial sources might be associated with elevated childhood cancer risks.

Alcohol exacerbates psychosocial stress-induced neuropsychiatric symptoms: Attenuation by geraniol.

Adaptation to psychosocial stress is psychologically distressing, initiating/promoting comorbidity with alcohol use disorders. Emerging evidence moreover showed that ethanol (EtOH) exacerbates social-defeat stress (SDS)-induced behavioral impairments, neurobiological sequelae, and poor therapeutic outcomes. Hence, this study investigated the effects of geraniol, an isoprenoid monoterpenoid alcohol with neuroprotective functions on EtOH escalated SDS-induced behavioral impairments, and neurobiological sequelae in mice. Male mice chronically exposed to SDS for 14 days were repeatedly fed with EtOH (2 g/kg, p. o.) from days 8-14. From days 1-14, SDS-EtOH co-exposed mice were concurrently treated with geraniol (25 and 50 mg/kg) or fluoxetine (10 mg/kg) orally. After SDS-EtOH translational interactions, arrays of behavioral tasks were examined, followed by investigations of oxido-inflammatory, neurochemicals levels, monoamine oxidase-B and acetylcholinesterase activities in the striatum, prefrontal-cortex, and hippocampus. The glial fibrillary acid protein (GFAP) expression was also quantified in the prefrontal-cortex immunohistochemically. Adrenal weights, serum glucose and corticosterone concentrations were measured. EtOH exacerbated SDS-induced low-stress resilience, social impairment characterized by anxiety, depression, and memory deficits were attenuated by geraniol (50 and 100 mg/kg) and fluoxetine. In line with this, geraniol increased the levels of dopamine, serotonin, and glutamic-acid decarboxylase enzyme, accompanied by reduced monoamine oxidase-B and acetylcholinesterase activities in the prefrontal-cortex, hippocampus, and striatum. Geraniol inhibited SDS-EtOH-induced adrenal hypertrophy, corticosterone, TNF-α, IL-6 release, malondialdehyde and nitrite levels, with increased antioxidant activities. Immunohistochemical analyses revealed that geraniol enhanced GFAP immunoreactivity in the prefrontal-cortex relative to SDS-EtOH group. We concluded that geraniol ameliorates SDS-EtOH interaction-induced behavioral changes via normalization of neuroimmune-endocrine and neurochemical dysregulations in mice brains.

Anesthetic Oxygen Use and Sex Are Critical Factors in the FLASH Sparing Effect.

Purpose: Ultra High Dose-Rate (UHDR) radiation has been reported to spare normal tissue, compared with Conventional Dose-Rate (CDR) radiation. However, important work remains to be done to improve the reproducibility of the FLASH effect. A better understanding of the biologic factors that modulate the FLASH effect may shed light on the mechanism of FLASH sparing. Here, we evaluated whether sex and/or the use of 100% oxygen as a carrier gas during irradiation contribute to the variability of the FLASH effect. Methods and Materials: C57BL/6 mice (24 male, 24 female) were anesthetized using isoflurane mixed with either room air or 100% oxygen. Subsequently, the mice received 27 Gy of either 9 MeV electron UHDR or CDR to a 1.6 cm2 diameter area of the right leg skin using the Mobetron linear accelerator. The primary postradiation endpoint was time to full thickness skin ulceration. In a separate cohort of mice (4 male, 4 female), skin oxygenation was measured using PdG4 Oxyphor under identical anesthesia conditions. Results: Neither supplemental oxygen nor sex affected time to ulceration in CDR irradiated mice. In the UHDR group, skin damage occured earlier in male and female mice that received 100% oxygen compared room air and female mice ulcerated sooner than male mice. However, there was no significant difference in time to ulceration between male and female UHDR mice that received room air. Oxygen measurements showed that tissue oxygenation was significantly higher when using 100% oxygen as the anesthesia carrier gas than when using room air, and female mice showed higher levels of tissue oxygenation than male mice under 100% oxygen. Conclusions: The skin FLASH sparing effect is significantly reduced when using oxygen during anesthesia rather than room air. FLASH sparing was also reduced in female mice compared to male mice. Both tissue oxygenation and sex are likely sources of variability in UHDR studies. These results suggest an oxygen-based mechanism for FLASH, as well as a key role for sex in the FLASH skin sparing effect.