Corrigendum: Spindle cell lipoma: a rare case report on the hallux.

The original article was published on February 15, 2024 and corrected on April 15, 2024.The revised version of the article corrects Figure 2. The changes appear in the revised online PDF copy of this article.

Comparative efficacy of low-volume retrobulbar anesthesia using three commercial local anesthetics in adult horses.

OBJECTIVE: To compare the efficacy of low-volume (5-mL) locoregional retrobulbar anesthesia ("retrobulbar block") by use of 3 commercial local anesthetic formulations. ANIMALS: 8 healthy adult mares. METHODS: A block-randomized, masked, controlled design was used. A single ultrasound-guided retrobulbar block was performed with 2% lidocaine, 2% mepivacaine, or 0.5% bupivacaine (n = 5 eyes/group). Contralateral eyes served as untreated controls. End points performed at baseline and time intervals up to 24 hours postblock included the following: assessment of neurophthalmic reflexes/responses, intraocular pressure, and vertical pupil diameter measurement, corneal and periocular esthesiometry, and observation for adverse effects. RESULTS: Low-volume block did not result in increased intraocular pressure or other adverse effects at any time point in any treatment group. Statistically significant corneal anesthesia (P < .001) was observed 1 minute after block in all groups, persisting through 4 hours after lidocaine or mepivacaine block and through 24 hours after bupivacaine block. Clinically significant periocular anesthesia was not observed in any group. Significant vertical pupil diameter increase (P < .05) was observed for up to 4 hours after lidocaine or mepivacaine block and 6 hours after bupivacaine block. CLINICAL RELEVANCE: Low-volume retrobulbar block with any of the 3 local anesthetic drugs evaluated was not associated with adverse effects. In terms of efficacy, mepivacaine block showed no clinical advantage over lidocaine block. However, bupivacaine block induced comparatively rapid and sustained corneal anesthesia. In comparison to published findings using a larger injection volume, low-volume retrobulbar block with lidocaine produced clinically comparable corneal anesthesia. However, periocular soft tissue anesthesia was not achieved with any local anesthetic drug at low volume.

Identification of Anaplasma marginale adhesins for entry into Dermacentor andersoni tick cells using phage display.

Anaplasma marginale is an obligate, intracellular, tick-borne bacterial pathogen that causes bovine anaplasmosis, an often severe, production-limiting disease of cattle found worldwide. Methods to control this disease are lacking, in large part due to major knowledge gaps in our understanding of the molecular underpinnings of basic host-pathogen interactions. For example, the surface proteins that serve as adhesins and, thus, likely play a role in pathogen entry into tick cells are largely unknown. To address this knowledge gap, we developed a phage display library and screened 66 A. marginale proteins for their ability to adhere to Dermacentor andersoni tick cells. From this screen, 17 candidate adhesins were identified, including OmpA and multiple members of the Msp1 family, including Msp1b, Mlp3, and Mlp4. We then measured the transcript of ompA and all members of the msp1 gene family through time, and determined that msp1b, mlp2, and mlp4 have increased transcript during tick cell infection, suggesting a possible role in host cell binding or entry. Finally, Msp1a, Msp1b, Mlp3, and OmpA were expressed as recombinant protein. When added to cultured tick cells prior to A. marginale infection, all proteins except the C-terminus of Msp1a reduced A. marginale entry by 2.2- to 4.7-fold. Except OmpA, these adhesins lack orthologs in related pathogens of humans and animals, including Anaplasma phagocytophilum and the Ehrlichia spp., thus limiting their utility in a universal tick transmission-blocking vaccine. However, this work greatly advances efforts toward developing methods to control bovine anaplasmosis and, thus, may help improve global food security.

Spindle cell lipoma: a rare case report on the hallux.

Spindle cell lipomas are a rare type of lipoma usually presenting in middle-aged to older men, often located on the posterior neck or shoulder; presentation on the foot is exceptionally uncommon. We report a 24-year-old man with spindle cell lipomas on the hallux of his left foot. He experienced an uneventful recovery after excision of the mass. We discuss clinical, radiologic, and histopathologic features of spindle cell lipomas and we review the differential diagnosis at this anatomic site.

Transient Seizure Clusters and Epileptiform Activity Following Widespread Bilateral Hippocampal Interneuron Ablation.

Interneuron loss is a prominent feature of temporal lobe epilepsy in both animals and humans and is hypothesized to be critical for epileptogenesis. As loss occurs concurrently with numerous other potentially proepileptogenic changes, however, the impact of interneuron loss in isolation remains unclear. For the present study, we developed an intersectional genetic approach to induce bilateral diphtheria toxin-mediated deletion of Vgat-expressing interneurons from dorsal and ventral hippocampus. In a separate group of mice, the same population was targeted for transient neuronal silencing with DREADDs. Interneuron ablation produced dramatic seizure clusters and persistent epileptiform activity. Surprisingly, after 1 week seizure activity declined precipitously and persistent epileptiform activity disappeared. Occasional seizures (≈1/day) persisted to the end of the experiment at 4 weeks. In contrast to the dramatic impact of interneuron ablation, transient silencing produced large numbers of interictal spikes, a significant but modest increase in seizure occurrence and changes in EEG frequency band power. Taken together, findings suggest that the hippocampus regains relative homeostasis-with occasional breakthrough seizures-in the face of an extensive and abrupt loss of interneurons.

Pathologic classification of a late-onset peripheral neuropathy in a spontaneous Labrador retriever dog model.

Late-onset peripheral neuropathy (LPN) is a heritable canine neuropathy commonly found in Labrador retrievers and is characterized by laryngeal paralysis and pelvic limb paresis. Our objective was to establish canine LPN as a model for human hereditary peripheral neuropathy by classifying it as either an axonopathy or myelinopathy and evaluating length-dependent degeneration. We conducted a motor nerve conduction study of the sciatic and ulnar nerves, electromyography (EMG) of appendicular and epaxial musculature, and histologic analysis of sciatic and recurrent laryngeal nerves in LPN-affected and control dogs. LPN-affected dogs exhibited significant decreases in compound muscle action potential (CMAP) amplitude, CMAP area, and pelvic limb latencies. However, no differences were found in motor nerve conduction velocity, residual latencies, or CMAP duration. Distal limb musculature showed greater EMG changes in LPN-affected dogs. Histologically, LPN-affected dogs exhibited a reduction in the number of large-diameter axons, especially in distal nerve regions. In conclusion, LPN in Labrador retrievers is a common, spontaneous, length-dependent peripheral axonopathy that is a novel animal model of age-related peripheral neuropathy that could be used for fundamental research and clinical trials.

The relationship between maladaptive health beliefs, pandemic-related stress, and health anxiety during the COVID-19 pandemic.

BACKGROUND: Research has demonstrated that people experience specific distress and anxiety regarding COVID-19. This distress may consist of interconnected symptom categories corresponding to a COVID stress syndrome. Susceptibility to COVID stress syndrome may be related to one's maladaptive health beliefs; however, no research has investigated the association between maladaptive health beliefs and COVID stress. The present study explored the impact of health beliefs on COVID stress, health anxiety, and associated psychological constructs. PARTICIPANTS AND PROCEDURE: This cross-sectional survey study included 221 adults (M age = 20.59, SD = 2.28). Participants completed an online survey including demographic questionnaires and self-report measures of health beliefs, COVID stress, health anxiety, and related psychological constructs. RESULTS: Health anxiety, anxiety sensitivity, state/trait anxiety, intolerance of uncertainty, and depression accounted for significant variance in COVID stress (F(6, 214) = 11.18, R2 = .24, p < .001). Health beliefs (i.e., perceived likelihood of illness, medical service inadequacy, and difficulty coping) were associated with greater COVID stress, although health beliefs were not found to mediate the relationship between health anxiety and COVID stress. CONCLUSIONS: Health beliefs were associated with greater COVID stress, although health beliefs did not mediate the relationship between health anxiety and COVID stress. The relationship between health anxiety and COVID stress may be better explained by other COVID-related cognitions (e.g., vaccine efficacy, dangerousness of COVID-19). The findings highlight the importance of peoples' health beliefs during the pandemic. Given anxiety's influence on peoples' behavioural responses to the pandemic, further research should identify COVID-specific cognitions for prevention of COVID stress and health anxiety.

Gemcitabine Modulates HLA-I Regulation to Improve Tumor Antigen Presentation by Pancreatic Cancer Cells.

Pancreatic cancer is a lethal disease, harboring a five-year overall survival rate of only 13%. Current treatment approaches thus require modulation, with attention shifting towards liberating the stalled efficacy of immunotherapies. Select chemotherapy drugs which possess inherent immune-modifying behaviors could revitalize immune activity against pancreatic tumors and potentiate immunotherapeutic success. In this study, we characterized the influence of gemcitabine, a chemotherapy drug approved for the treatment of pancreatic cancer, on tumor antigen presentation by human leukocyte antigen class I (HLA-I). Gemcitabine increased pancreatic cancer cells' HLA-I mRNA transcripts, total protein, surface expression, and surface stability. Temperature-dependent assay results indicated that the increased HLA-I stability may be due to reduced binding of low affinity peptides. Mass spectrometry analysis confirmed changes in the HLA-I-presented peptide pool post-treatment, and computational predictions suggested improved affinity and immunogenicity of peptides displayed solely by gemcitabine-treated cells. Most of the gemcitabine-exclusive peptides were derived from unique source proteins, with a notable overrepresentation of translation-related proteins. Gemcitabine also increased expression of select immunoproteasome subunits, providing a plausible mechanism for its modulation of the HLA-I-bound peptidome. Our work supports continued investigation of immunotherapies, including peptide-based vaccines, to be used with gemcitabine as new combination treatment modalities for pancreatic cancer.

Engineering the ChlorON Series: Turn-On Fluorescent Protein Sensors for Imaging Labile Chloride in Living Cells.

Beyond its role as the "queen of electrolytes", chloride can also serve as an allosteric regulator or even a signaling ion. To illuminate this essential anion across such a spectrum of biological processes, researchers have relied on fluorescence imaging with genetically encoded sensors. In large part, these have been derived from the green fluorescent protein found in the jellyfish Aequorea victoria. However, a standalone sensor with a turn-on intensiometric response at physiological pH has yet to be reported. Here, we address this technology gap by building on our discovery of the anion-sensitive fluorescent protein mNeonGreen (mNG). The targeted engineering of two non-coordinating residues, namely K143 and R195, in the chloride binding pocket of mNG coupled with an anion walking screening and selection strategy resulted in the ChlorON sensors: ChlorON-1 (K143W/R195L), ChlorON-2 (K143R/R195I), and ChlorON-3 (K143R/R195L). In vitro spectroscopy revealed that all three sensors display a robust turn-on fluorescence response to chloride (20- to 45-fold) across a wide range of affinities (Kd ≈ 30-285 mM). We further showcase how this unique sensing mechanism can be exploited to directly image labile chloride transport with spatial and temporal resolution in a cell model overexpressing the cystic fibrosis transmembrane conductance regulator. Building from this initial demonstration, we anticipate that the ChlorON technology will have broad utility, accelerating the path forward for fundamental and translational aspects of chloride biology.

Development of 2nd generation aminomethyl spectinomycins that overcome native efflux in Mycobacterium abscessus.

Mycobacterium abscessus (Mab), a nontuberculous mycobacterial (NTM) species, is an emerging pathogen with high intrinsic drug resistance. Current standard-of-care therapy results in poor outcomes, demonstrating the urgent need to develop effective antimycobacterial regimens. Through synthetic modification of spectinomycin (SPC), we have identified a distinct structural subclass of N-ethylene linked aminomethyl SPCs (eAmSPCs) that are up to 64-fold more potent against Mab over the parent SPC. Mechanism of action and crystallography studies demonstrate that the eAmSPCs display a mode of ribosomal inhibition consistent with SPC. However, they exert their increased antimicrobial activity through enhanced accumulation, largely by circumventing efflux mechanisms. The N-ethylene linkage within this series plays a critical role in avoiding TetV-mediated efflux, as lead eAmSPC 2593 displays a mere fourfold susceptibility improvement against Mab ΔtetV, in contrast to the 64-fold increase for SPC. Even a minor shortening of the linkage by a single carbon, akin to 1st generation AmSPC 1950, results in a substantial increase in MICs and a 16-fold rise in susceptibility against Mab ΔtetV. These shifts suggest that longer linkages might modify the kinetics of drug expulsion by TetV, ultimately shifting the equilibrium towards heightened intracellular concentrations and enhanced antimicrobial efficacy. Furthermore, lead eAmSPCs were also shown to synergize with various classes of anti-Mab antibiotics and retain activity against clinical isolates and other mycobacterial strains. Encouraging pharmacokinetic profiles coupled with robust efficacy in Mab murine infection models suggest that eAmSPCs hold the potential to be developed into treatments for Mab and other NTM infections.

A systematic review of attention-deficit/hyperactivity disorder in people living with cystic fibrosis.

There is a lack of research that has focused on attention-deficit hyperactivity disorder (ADHD) in people with cystic fibrosis (pwCF). Given ADHD is associated with executive functioning impairments, exploring ADHD in the context of living with cystic fibrosis (CF) is of great importance. The purpose of the current systematic review was to examine ADHD in pwCF across the lifespan in terms of its prevalence, its impact on various health outcomes, and treatments for managing ADHD. This systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Articles reporting studies of any design that focused on ADHD in pwCF were included. Studies were excluded if they did not meet this criterion and if they were written in languages other than English. PsycINFO, MEDLINE, EMBASE, and CINAHL databases were searched. Search items were based on three concepts: (1) terms related to CF, (2) terms related to ADHD, and (3) terms related to age. Ten studies were included in this systematic review. Reported prevalence rates of ADHD in pwCF ranged from 5.26% to 21.9%. The reported relationships between ADHD and CF and other health outcomes is inconsistent. In terms of treatment considerations, pharmacological interventions and behavioural strategies for managing ADHD in the context of living with CF have been reported as being successful. Additional research is needed to further explore ADHD in the CF population and health variables that may be associated with CF prognosis.

Attachment Orientation and Preferences for Partners' Emotional Responses in Stressful and Positive Situations.

Attachment theory proposes that close relationships help us to regulate our emotions in stressful and positive situations. However, no previous studies have examined preferences for a partner's emotional response to one's own stressful and positive situations or tested whether these preferences differ based on attachment orientation. This study examines the association of attachment orientation and preferences for partners' emotional responses relative to one's own emotional responses in stressful and positive contexts among 425 United States adults who were currently in a committed relationship of ≥6 months. Data were collected in 2020. Overall, participants preferred their partners to feel and express less distress, less worry, more calm, and more hope than themselves during stressful situations and for their partners to feel and express more excitement, pride, and hope than themselves during positive situations. Higher attachment anxiety predicted preferences for partners to feel and express more distress/worry in stressful situations, whereas higher attachment avoidance predicted preferences for partners to feel and express less hope in stressful situations. Statistical interactions of attachment anxiety × attachment avoidance indicated that the combination of low attachment anxiety and high attachment avoidance (dismissing avoidance) was associated with preferences for partners to feel and express less positive emotions in positive situations, whereas the combination of high attachment anxiety and high attachment avoidance (fearful avoidance) was associated with preferences for partners to feel and express more negative emotions in stressful situations and less positive emotions in positive situations. This investigation provides novel evidence for links between attachment orientation and preferences for partners' emotional responses in two theoretically important contexts, which has implications for the nature and function of emotion regulation in close relationships. Future research is needed to determine the generalizability of these findings to more collectivist cultural contexts.

Development and adaptation of the Emotion Regulation Skills Questionnaire for adolescents.

INTRODUCTION: The ability to effectively regulate one's emotions is important for adolescent mental health. However, extant assessments of how adolescents regulate their emotions can be expanded upon in several ways, including incorporating more strategies (e.g., cultural and spiritual) and positive emotions, and being informed by adolescents and expert consultation during the development process. Thus, our study aimed to improve the construct validity of an emotion regulation measure by adapting and refining the Emotion Regulation Skills Questionnaire (ERSQ) into an adolescent self-report. METHODS: We recruited 24 13-17-year-olds (12 males; 11 females; 1 gender fluid) via social media advertisement in the United States in 2020. We used an iterative qualitative approach in which we combined expert consultation, cognitive interviewing with adolescents, and top-down and bottom-up coding to review and provide feedback on the ERSQ. RESULTS: Findings of thematic analysis showed that a need for clarity in wording and inclusion of strategy examples across all sections of the ERSQ was needed. Adolescents also identified the need to replace the Silly/Excited section with a more age-appropriate positive emotion section. CONCLUSION: Findings indicate cognitive interviewing can be successfully completed in a virtual format when necessary, youth utilize a wider range of strategies to maintain or upregulate positive emotions than what is represented in current measures, and use of qualitative methods may have reduced construct underrepresentation and construct-irrelevant variance in the adapted ERSQ.

Pet ownership and mental health in United States adults during COVID-19.

The COVID-19 pandemic was associated with declines in mental health and increased interest in pet ownership. We aimed to extend past theories and research linking pet ownership and mental health by investigating whether pet ownership was associated with mental health during the initial phases of the COVID-19 pandemic in a sample of American adults. We also tested whether the association of pet ownership and mental health was moderated by relationship status. Participants were 2,906 American adults who were recruited for an online survey study between May 2020 and May 2021. Pet ownership was assessed via dichotomous self-report (yes/no) and mental health was assessed using a 13-item questionnaire. The sample was 69.2% female with an average age of 46.0 years. 36.1% of the sample owned a pet and 68.5% of the sample was currently partnered. There was no overall association of pet ownership and mental health during the COVID-19 pandemic (estimated mean difference (EMD) = 0.35, 95CI = -0.10, 0.80, p = 0.12). However, we found evidence for an association that was moderated by relationship status. Pet ownership was associated with better mental health among partnered individuals (EMD = 0.76, 95CI = 0.21, 1.30, p = 0.006). There was no association of pet ownership and mental health among unpartnered individuals (EMD = -0.41, 95CI = -1.20, 0.37, p = 0.30). Our findings suggest that relationship status may represent a critical moderator of the link between pet ownership and mental health. Future studies are needed to identify specific mechanisms of pet ownership that could explain its varied impact on the mental health of partnered and unpartnered individuals.

Istradefylline effects on tremor dominance (TD) and postural instability and gait difficulty (PIGD).

Background: In patients with Parkinson's Disease (PD), two distinct motor subtypes, tremor dominant (TD) and postural instability and gait difficulty (PIGD), can be differentiated using Unified Parkinson's Disease Rating Scale (UPDRS) sub-scores. This post hoc analysis of pooled data from eight pivotal studies examined the effect of treatment with istradefylline, a selective adenosine A2A receptor antagonist, on these subtypes. Methods: In eight randomized, placebo-controlled phase 2b/3 trials, patients on levodopa with carbidopa/benserazide experiencing motor complications received istradefylline (20 or 40 mg/day) or placebo for 12 or 16 weeks. TD subtype was defined by the UPDRS II/III items kinetic and postural tremor in right/left hand and (resting) tremor in the face, lips, chin, hands, or feet; PIGD items were freezing, walking, posture, gait, and postural instability. The ratio of mean scores from TD:PIGD items determined subtype (TD [TD:PIGD ratio ≥ 1.5], PIGD [TD:PIGD ratio ≤ 1.0], mixed-type [ratio 1-1.5]). Results: In total, 2719 patients were included (PIGD, n = 2165; TD, n = 118; mixed-type, n = 188; not evaluable, n = 248). Among TD subtype patients, the least-squares mean change from baseline versus placebo in UPDRS II/III TD-related total score was significant at 20 mg/day istradefylline (-2.21; 95 % CI, -4.05 to -0.36; p = 0.02). For PIGD subtype patients, there was a significant difference from placebo in UPDRS II/III PIGD-related total score at 40 mg/day istradefylline (-0.25; -0.43 to -0.06; p = 0.01). Conclusions: The data from this analysis of UPDRS-based motor subtypes suggest that istradefylline can improve motor disability in PD patients with motor fluctuations regardless of PD subtype. Future research should characterize the effects of istradefylline on tremor.

Chemical characterization of microplastic particles formed in airborne waste discharged from sewer pipe repairs.

Microplastic particles are of increasing environmental concern due to the widespread uncontrolled degradation of various commercial products made of plastic and their associated waste disposal. Recently, common technology used to repair sewer pipes was reported as one of the emission sources of airborne microplastics in urban areas. This research presents results of the multi-modal comprehensive chemical characterization of the microplastic particles related to waste discharged in the pipe repair process and compares particle composition with the components of uncured resin and cured plastic composite used in the process. Analysis of these materials employs complementary use of surface-enhanced Raman spectroscopy, scanning transmission X-ray spectro-microscopy, single particle mass spectrometry, and direct analysis in real-time high-resolution mass spectrometry. It is shown that the composition of the relatively large (100 µm) microplastic particles resembles components of plastic material used in the process. In contrast, the composition of the smaller (micrometer and sub-micrometer) particles is significantly different, suggesting their formation from unintended polymerization of water-soluble components occurring in drying droplets of the air-discharged waste. In addition, resin material type influences the composition of released microplastic particles. Results are further discussed to guide the detection and advanced characterization of airborne microplastics in future field and laboratory studies pertaining to sewer pipe repair technology.

High-throughput functional trait testing for bacterial pathogens.

Functional traits are characteristics that affect the fitness and metabolic function of a microorganism. There is growing interest in using high-throughput methods to characterize bacterial pathogens based on functional virulence traits. Traditional methods that phenotype a single organism for a single virulence trait can be time consuming and labor intensive. Alternatively, machine learning of whole-genome sequences (WGS) has shown some success in predicting virulence. However, relying solely on WGS can miss functional traits, particularly for organisms lacking classical virulence factors. We propose that high-throughput assays for functional virulence trait identification should become a prominent method of characterizing bacterial pathogens on a population scale. This work is critical as we move from compiling lists of bacterial species associated with disease to pathogen-agnostic approaches capable of detecting novel microbes. We discuss six key areas of functional trait testing and how advancing high-throughput methods could provide a greater understanding of pathogens.

Whole-genome sequence of Paenibacillus sp., isolated from soil, Fort Collins, Colorado, USA.

A whole genome sequence of a Paenibacillus sp. bacterium isolated from soil in Fort Collins, Colorado was obtained. This bacterium was of particular interest due to its antibiotic potential against Gram-positive pathogen surrogates.

Early Measures of TBI Severity Poorly Predict Later Individual Impairment in a Rat Fluid Percussion Model.

BACKGROUND: Multiple measures of injury severity are suggested as common data elements in preclinical traumatic brain injury (TBI) research. The robustness of these measures in characterizing injury severity is unclear. In particular, it is not known how reliably they predict individual outcomes after experimental TBI. METHODS: We assessed several commonly used measures of initial injury severity for their ability to predict chronic cognitive outcomes in a rat lateral fluid percussion (LFPI) model of TBI. At the time of injury, we assessed reflex righting time, neurologic severity scores, and 24 h weight loss. Sixty days after LFPI, we evaluated working memory using a spontaneous alternation T-maze task. RESULTS: We found that righting time and weight loss had no correlation to chronic T-maze performance, while neurologic severity score correlated weakly. DISCUSSION: Taken together, our results indicate that commonly used early measures of injury severity do not robustly predict longer-term outcomes. This finding parallels the uncertainty in predicting individual outcomes in TBI clinical populations.