The effects of neuron morphology and spatial distribution on the selectivity of dorsal root ganglion stimulation.

OBJECTIVE: For prosthesis users, sensory feedback that appears to come from the missing limb can improve function, confidence, and phantom limb pain. Numerous pre-clinical studies have considered stimulation via penetrating microelectrodes at the dorsal root ganglion (DRG) as a potential approach for somatosensory neuroprostheses. However, to develop clinically translatable neuroprosthetic devices, a less invasive approach, such as stimulation via epineural macroelectrodes, would be preferable. This work explores the feasibility of using such electrodes to deliver focal sensory feedback by examining the mechanisms of selective activation in response to stimulation via epineural electrodes compared with penetrating electrodes. Approach: We developed computational models of the DRG, representing the biophysical properties of the DRG and surrounding tissue to evaluate neural responses to stimulation via penetrating microelectrodes and epineural macroelectrodes. To assess the role of properties such as neuron morphology and spatial arrangement we designed three models, including one that contained only axons (axon only), one with pseudounipolar neurons arranged randomly (random), and one with pseudounipolar neurons placed according to a realistic spatial distribution (realistic). Main results: Our models demonstrate that activation in response to stimulation via epineural electrodes in a realistic model is commonly initiated in the axon initial segment adjacent to the cell body, whereas penetrating electrodes commonly elicit responses in t-junctions and axons. Moreover, we see a wider dynamic range for epineural electrodes compared with penetrating electrodes. This difference appears to be driven by the spatial organization and neuron morphology of the realistic DRG. Significance: We demonstrate that the anatomical features of the DRG make it a potentially effective target for epineural stimulation to deliver focal sensations from the limbs. Specifically, we show that epineural stimulation at the DRG can be highly selective thanks to the neuroanatomical arrangement of the DRG, making this a promising approach for future neuroprosthetic development. .

Risk Factors for Perioperative Nerve Injury Related to Total Hip Arthroplasty.

Background: Nerve injury following total hip arthroplasty (THA) is a rare but serious adverse event. While prior studies have reported risk factors for nerve injury related to THA, they are limited to institutional data or small sample sizes. The current study aimed to leverage a large, national database to assess independent risk factors for sustaining nerve injury with THA. Methods: The 2010-2021 PearlDiver M157 database was queried for adult THA cases. Those with nerve injury within 90 days of THA were identified. Patient age, sex, body mass index (BMI), Elixhauser comorbidity index (ECI), fracture indication, and surgery type (index vs revision) were assessed for correlation with nerve injury by multivariate analyses. Results: Out of 750,695 THAs, 2659 (0.35%) had nerve injuries. Multivariate analysis revealed independent predictors of nerve injury in decreasing odds ratio (OR) order to include: revision procedure (OR: 2.13), female sex (OR 1.35), ECI (ECI 1-2 [OR 1.27], ECI 3-4 [OR 1.43], and ECI ≥5 [OR 1.59]) and age (OR 1.02 per decade decrease) (P < .05 for each). Pertinent negatives by multivariate analysis included underweight BMI (<20), and fracture indication. Individuals with morbidly obese BMI status (≥35) had a decreased risk of nerve injury (OR 0.84, P = .019). Conclusions: THA-related nerve injury was found to be low at 0.35%. Factors independently associated with this adverse outcome were defined, of which the greatest risk was seen in revision procedures. These risk factors, derived from the largest cohort to date, may be helpful for risk stratification and patient counseling.

Effectiveness of low to moderate potency topical corticosteroids for phimosis resolution in children: results of a network meta-analysis.

PURPOSE: The use of topical corticosteroids (TCSs) has become an efficient, less-invasive treatment for phimosis. Whether any significant difference in efficacy exists between TCSs based on their potency is unclear. METHODS: Electronic databases were searched up to March 2024 for randomised controlled trials (RCTs) comparing the use of any type or concentration of TCSs with placebo or no treatment in boys with any degree of physician diagnosed phimosis. A random-effects network meta-analysis (NMA) using a consistency model within a frequentist approach was employed. The primary outcome was partial or complete resolution of phimosis reported as a pooled risk ratio (RR) with 95% CI. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities. RESULTS: Seventeen RCTs, containing 2057 participants were identified. NMA suggested that, compared with control, the high (RR 3.19 (95% CI 1.42 to 7.16), moderate (RR 2.68 (95% CI 1.87 to 3.83) and low (RR 3.05 (95% CI 1.63 to 5.71) potency TCSs statistically significantly increased complete or partial clinical resolution of phimosis. The SUCRA plot revealed that high potency (SUCRA = 0.76) was ranked first followed by low and moderate TCSs. When we assessed comparative efficacy among TCSs based on potency, none of the classes were superior to others. The certainty of the evidence for an effect of moderate potent TCSs was that of moderate GRADE quality. CONCLUSION: Moderate to low potency TCSs are of comparable therapeutic effect in the treatment of phimosis to that of highly potent formulations. More high-quality RCTs are warranted.

A preliminary study exploring the effects of transcutaneous spinal cord stimulation on spinal excitability and phantom limb pain in people with a transtibial amputation.

Objective. Phantom limb pain (PLP) is debilitating and affects over 70% of people with lower-limb amputation. Other neuropathic pain conditions correspond with increased spinal excitability, which can be measured using reflexes andF-waves. Spinal cord neuromodulation can be used to reduce neuropathic pain in a variety of conditions and may affect spinal excitability, but has not been extensively used for treating PLP. Here, we propose using a non-invasive neuromodulation method, transcutaneous spinal cord stimulation (tSCS), to reduce PLP and modulate spinal excitability after transtibial amputation.Approach. We recruited three participants, two males (5- and 9-years post-amputation, traumatic and alcohol-induced neuropathy) and one female (3 months post-amputation, diabetic neuropathy) for this 5 d study. We measured pain using the McGill Pain Questionnaire (MPQ), visual analog scale (VAS), and pain pressure threshold (PPT) test. We measured spinal reflex and motoneuron excitability using posterior root-muscle (PRM) reflexes andF-waves, respectively. We delivered tSCS for 30 min d-1for 5 d.Main Results. After 5 d of tSCS, MPQ scores decreased by clinically-meaningful amounts for all participants from 34.0 ± 7.0-18.3 ± 6.8; however, there were no clinically-significant decreases in VAS scores. Two participants had increased PPTs across the residual limb (Day 1: 5.4 ± 1.6 lbf; Day 5: 11.4 ± 1.0 lbf).F-waves had normal latencies but small amplitudes. PRM reflexes had high thresholds (59.5 ± 6.1µC) and low amplitudes, suggesting that in PLP, the spinal cord is hypoexcitable. After 5 d of tSCS, reflex thresholds decreased significantly (38.6 ± 12.2µC;p< 0.001).Significance. These preliminary results in this non-placebo-controlled study suggest that, overall, limb amputation and PLP may be associated with reduced spinal excitability and tSCS can increase spinal excitability and reduce PLP.

X-ray Irradiation Reduces Live Aspergillus flavus Viability but Not Aflatoxin B1 in Naturally Contaminated Maize.

Food crops around the world are commonly contaminated with Aspergillus flavus, which can produce the carcinogenic mycotoxin aflatoxin B1 (AFB1). The objective of this study is to test an X-ray irradiation sterilization method for studying AFB1 in contaminated maize samples in the laboratory. Maize that had been naturally contaminated with 300 ppb AFB1 by the growth of aflatoxigenic A. flavus was ground and then irradiated at 0.0, 1.0, 1.5, 2.0, 2.5, and 3.0 kGy. A. flavus was quantified by dilution plating on potato dextrose agar (PDA) and modified Rose Bengal media (MDRB) for viability and qPCR for gene presence. AFB1 was quantified by HPLC and ELISA. A. flavus viability, but not gene copies, significantly decreased with increasing doses of radiation (PDA: p < 0.001; MDRB: p < 0.001; qPCR: p = 0.026). AFB1 concentration did not significantly change with increasing doses of radiation (HPLC: p = 0.153; ELISA: p = 0.567). Our results imply that X-ray irradiation is an effective means of reducing viable A. flavus without affecting AFB1 concentrations. Reducing the hazard of fungal spores and halting AFB1 production at the targeted dose are important steps to safely and reproducibly move forward research on the global mycotoxin challenge.

A comprehensive chemotyping and gonadal regulation of seven kisspeptinergic neuronal populations in the mouse brain.

Herein, we present a systematic analysis, using dual and multiplex RNAscope methods, of seven kisspeptinergic neuronal populations, based on their chemotyping and distribution throughout the mouse brain. The co-expression of mRNAs coding for neuropeptides, for excitatory and inhibitory transmitter vesicular transporters, and for sex steroid receptors are described in four hypothalamic and three extra-hypothalamic nuclei. These include a newly characterized kisspeptin-expressing ventral premammillary nucleus cell group co-expressing vesicular glutamate transporter 2, pituitary adenylate cyclase-activating polypeptide and neurotensin mRNAs. Kisspeptin mRNA ( Kiss1) was observed within both somatic and dendritic compartments at a single-cell level in two hypothalamic sites, a prominent and previously undescribed feature of kisspeptin neurons in these two cell groups. Patterns of altered Kiss1 expression following gonadectomy among these seven KP populations suggest that androgen receptor signaling may also play a previously unremarked role in gonadal feedback regulation of kisspeptinergic neuronal function. Data from this study provide a chemoanatomical basis for hypothesis generation regarding the functional diversity of kisspeptinergic signaling in hypothalamic and extrahypothalamic brain.

Viscolin-mediated antiapoptotic and neuroprotective effects in cortical neurons exposed to oxygen-glucose deprivation and rats subjected to transient focal cerebral ischemia.

OBJECTIVE: Previously, we have successfully purified and synthesized viscolin, an agent derived from Viscum coloratum extract, which has shown significant potential in the treatment of stroke. Our study aimed to evaluate the neuroprotective effects of viscolin. METHODS: We first assessed the cytotoxicity of viscolin on primary neuronal cultures and determined its antioxidant and radical scavenging properties. Subsequently, we identified the optimal dose-response of viscolin in protecting against glutamate-induced neurotoxicity. RESULTS: Our results demonstrated that viscolin at a concentration of 10 µM effectively reduced neuronal cell death up to 6 hours after glutamate-induced neurotoxicity. Additionally, we investigated the therapeutic window of opportunity and the potential of viscolin in preventing necrotic and apoptotic damage in cultured neurons exposed to oxygen glucose deprivation-induced neurotoxicity. Our findings showed that viscolin treatment significantly reduced DNA breakage, prevented the release of cytochrome c from mitochondria to cytosol, increased the expression of anti-apoptotic protein Bcl-2, decreased the expression of pro-apoptotic protein Bax, and reduced the number of TUNEL-positive cells. Additionally, our in vivo investigation demonstrated a reduction in brain infarction following middle cerebral artery occlusion. CONCLUSION: Viscolin has potential utility as a therapeutic agent in the treatment of stroke.

Bacterial single-cell RNA sequencing captures biofilm transcriptional heterogeneity and differential responses to immune pressure.

Biofilm formation is an important mechanism of survival and persistence for many bacterial pathogens. These multicellular communities contain subpopulations of cells that display vast metabolic and transcriptional diversity along with high recalcitrance to antibiotics and host immune defenses. Investigating the complex heterogeneity within biofilm has been hindered by the lack of a sensitive and high-throughput method to assess stochastic transcriptional activity and regulation between bacterial subpopulations, which requires single-cell resolution. We have developed an optimized bacterial single-cell RNA sequencing method, BaSSSh-seq, to study Staphylococcus aureus diversity during biofilm growth and transcriptional adaptations following immune cell exposure. We validated the ability of BaSSSh-seq to capture extensive transcriptional heterogeneity during biofilm compared to planktonic growth. Application of new computational tools revealed transcriptional regulatory networks across the heterogeneous biofilm subpopulations and identification of gene sets that were associated with a trajectory from planktonic to biofilm growth. BaSSSh-seq also detected alterations in biofilm metabolism, stress response, and virulence that were tailored to distinct immune cell populations. This work provides an innovative platform to explore biofilm dynamics at single-cell resolution, unlocking the potential for identifying biofilm adaptations to environmental signals and immune pressure.

Declining glacier cover drives changes in aquatic macroinvertebrate biodiversity in the Cordillera Blanca, Perú.

Ongoing climate change threatens the biodiversity of glacier-fed river ecosystems worldwide through shifts in water availability and timing, temperature, chemistry, and channel stability. However, tropical glacier-fed rivers have received little attention compared to those in temperate and Arctic biomes, despite their unique biodiversity potentially responding differently due to additional stress from higher altitude locations thus lower oxygen availability, diurnal freeze-thaw cycles, and annual monsoon rainfall disturbances. However, tropical glacier-fed rivers have received little attention compared to those in temperate and Arctic biomes, despite their unique biodiversity potentially responding differently due to additional stress from higher altitude locations thus lower oxygen availability, diurnal freeze-thaw cycles, and annual monsoon rainfall disturbances. This study quantified aquatic biodiversity responses to decreasing glacier cover in the Cordillera Blanca range of the Peruvian Andes. Ten rivers were studied along a gradient of decreasing glacier cover in the Parón, Huaytapallana, and Llanganuco basins, with a specific focus on macroinvertebrates and physicochemical parameters in both the dry and wet seasons. We found higher temperatures, more stable and lower turbidity rivers as glacier cover decreased, which were related significantly to higher local diversity and lower ß-diversity. Analysis of similarity revealed significant differences in the macroinvertebrate community among rivers with high, medium, or low glacier cover, illustrating turnover from specialists to generalists as glacial influence decreased. Redundancy analysis demonstrated that there were more species found to prefer stable beds and water temperatures in medium and low glacier cover in a catchment rivers. However, certain taxa in groups such as Paraheptagyia, Orthocladiinae, Anomalocosmoecus, and Limonia may be adapted to high glacial influence habitats and at risk of glacier retreat. Although species composition was different to other biomes, the Cordillera Blanca rivers showed similar benthic macroinvertebrate biodiversity responses to glacier retreat, supporting the hypothesis that climate change will have predictable effects on aquatic biodiversity in mountain ranges worldwide.

Substantia Nigra Pathology, Contact Sports Play, and Parkinsonism in Chronic Traumatic Encephalopathy.

Importance: Parkinsonism is associated with traumatic brain injury and chronic traumatic encephalopathy (CTE), a neurodegenerative disease associated with repetitive head impact (RHI) exposure, but the neuropathologic substrates that underlie parkinsonism in individuals with CTE are yet to be defined. Objective: To evaluate the frequency of parkinsonism in individuals with CTE and the association of RHI and neuropathologic substrates with parkinsonism in these individuals. Design, Setting, and Participants: This cross-sectional study included brain donors with neuropathologically diagnosed CTE without other significant neurodegenerative disease and with information on parkinsonism from the Understanding Neurologic Injury and Traumatic Encephalopathy brain bank between July 2015 and May 2022. Exposure: Years of contact sports participation as a proxy for RHI. Main Outcomes and Measures: The main outcomes were frequency of parkinsonism in individuals with CTE and associations between (1) RHI with substantia nigra (SN) Lewy bodies (LBs) and neurofibrillary tangles (NFTs); (2) LBs, NFTs, and arteriolosclerosis with SN neuronal loss; and (3) SN neuronal loss, LBs, NFTs, and arteriolosclerosis with parkinsonism, tested by age-adjusted logistic regressions. Results: Of 481 male brain donors with neuropathologically diagnosed CTE, parkinsonism occurred frequently in individuals with CTE (119 [24.7%]; 362 [75.3%] did not have parkinsonism). Participants with parkinsonism had a higher mean (SD) age at death (71.5 [13.0] years) than participants without parkinsonism (54.1 [19.3] years) (P < .001) and higher rates of dementia (104 [87.4%] vs 105 [29.0%]), visual hallucinations (45 [37.8%] vs 51 [14.1%]), and probable rapid eye movement sleep behavior disorder (52 [43.7%] vs 58 [16.0%]) (P < .001 for all). Participants with parkinsonism had a more severe CTE stage (eg, stage IV: 35 [29.4%] vs 39 [10.8%]) and nigral pathology than those without parkinsonism (NFTs: 50 of 117 [42.7%] vs 103 of 344 [29.9%]; P = .01; neuronal loss: 61 of 117 [52.1%] vs 59 of 344 [17.1%]; P < .001; and LBs: 28 of 116 [24.1%] vs 20 of 342 [5.8%]; P < .001). Years of contact sports participation were associated with SN NFTs (adjusted odds ratio [AOR], 1.04; 95% CI, 1.00-1.07; P = .03) and neuronal loss (AOR, 1.05; 95% CI, 1.01-1.08; P = .02). Nigral neuronal loss (AOR, 2.61; 95% CI, 1.52-4.47; P < .001) and LBs (AOR, 2.29; 95% CI, 1.15-4.57; P = .02) were associated with parkinsonism. However, SN neuronal loss was associated with SN LBs (AOR, 4.48; 95% CI, 2.25-8.92; P < .001), SN NFTs (AOR, 2.51; 95% CI, 1.52-4.15; P < .001), and arteriolosclerosis (AOR, 2.27; 95% CI, 1.33-3.85; P = .002). In American football players, regression analysis demonstrated that SN NFTs and neuronal loss mediated the association between years of play and parkinsonism in the context of CTE (ß, 0.012; 95% CI, 0.001-0.038). Conclusions and Relevance: In this cross-sectional study of contact sports athletes with CTE, years of contact sports participation were associated with SN tau pathology and neuronal loss, and these pathologies were associated with parkinsonism. Repetitive head impacts may incite neuropathologic processes that lead to symptoms of parkinsonism in individuals with CTE.

Factor analysis of the Chinese version of the Autism Spectrum Quotient 10 and its association with schizotypal traits in adolescents and young adults in Hong Kong.

BACKGROUND: There is evidence suggesting that autistic traits are associated with schizotypal traits. This study examined the factor structure of the Autism Spectrum Quotient 10 (AQ-10) and its associations with schizotypal traits (measured by the Schizotypal Personality Questionnaire-Brief [SPQ-B]) in a cohort of Chinese adolescents and young adults. METHODS: Invitation letters, stratified by locations and housing types, were randomly sent to individuals aged 15 to 24 years for participation. Assessments were made using face-to-face or online interviews. Autistic traits were assessed using the Chinese version of the AQ-10. Schizotypal personality traits were assessed using the Chinese version of the 22-item SPQ-B. RESULTS: In total, 395 male and 536 female participants (mean age, 19.93 years) were recruited between July 2020 and May 2021. Exploratory factor analysis of the AQ-10 yielded three factors (theory of mind, task switching, and attention deficits) explaining 55.11% of the total variance. Autistic traits were positively correlated with schizotypal traits of disorganised features (r = 0.21, p < 0.001), interpersonal relationship deficits (r = 0.19, p < 0.001), and cognitive-perceptual deficits (r = 0.11, p = 0.001). CONCLUSION: In Chinese adolescents and young adults, autistic traits, especially task switching and attention deficits (compared with theory of mind) are more closely correlated with schizotypal personality traits. Disentangling the overlapping and diametrical structure of autistic traits and schizotypal traits may help understand their aetiologies, assessment, and interventions.

Untangling biliary reconstruction in liver transplants for primary sclerosing cholangitis.

BACKGROUND: Biliary reconstruction technique during liver transplant (LT) for primary sclerosing cholangitis (PSC) remains controversial. This study aimed to evaluate the incidence of biliary complications in patients with PSC having a duct-to-duct (DD) anastomosis or Roux-en-Y hepaticojejunostomy (HJ). METHODS: A retrospective medical record review of patients with PSC undergoing LT at a single center between June 1st, 2000 and December 31st, 2022 was performed. Primary and secondary endpoints were the incidence of biliary strictures (anastomotic [BAS] and non-anastomotic strictures [NAS]) and non-stricture complications, respectively. Univariable and multivariable regression analyses were performed to identify associations with BAS formation. Patient survival was assessed using a Kaplan-Meier curve. RESULTS: From 105 transplants performed for 101 patients, 54 (51.4%) and 51 (48.5%) received DD and HJ anastomoses. Mean recipient age and follow-up was 47 ± 13 years and 98 ± 69 months. BAS was more common (48.1% vs. 27.5%, OR 2.45, 95% CI 1.09-5.54, p = 0.03) and occurred earlier (4.8 months, IQR 2.3-13.1 vs. 41.8 months, IQR 7.2-88.7, p = 0.001) in the DD than the HJ group. NAS (seen in 36.2% of transplants) had a comparable incidence (p = 0.53) in HJ (38.9%) and DD (33.3%) groups. No difference was seen between cohorts regarding time to NAS, requirement for extended biliary dilatation programs (clinically significant biliary stricture), bile leak, and graft failure. On multivariable analysis, only the anastomotic technique was associated with BAS (DD adjusted OR 3.00, 95% CI 1.19-7.56, p = 0.02). CONCLUSION: In carefully selected patients with PSC, DD anastomosis yielded similar outcomes to HJ anastomosis after liver transplantation.

Characterization of mycobacteriophage Adephagia cytotoxic proteins.

Mycobacterium phage Adephagia is a cluster K phage that infects Mycobacterium smegmatis and some strains of Mycobacterium pathogens. Adephagia has a siphoviral virion morphology and is temperate. Its genome is 59,646 bp long and codes for one tRNA gene and 94 predicted protein-coding genes; most genes not associated with virion structure and assembly are functionally ill-defined. Here, we determined the Adephagia gene expression patterns in lytic and lysogenic growth and used structural predictions to assign additional gene functions. We characterized 66 nonstructural genes for their toxic phenotypes when expressed in M. smegmatis, and we show that 25 of these (38%) are either toxic or strongly inhibit growth, resulting in either reduced viability or small colony sizes. Some of these genes are predicted to be involved in DNA metabolism or regulation, but others are of unknown function. We also characterize the HicAB-like toxin-antitoxin (TA) system encoded by Adephagia (gp91 and gp90, respectively) and show that the gp90 antitoxin is lysogenically expressed, abrogates gp91 toxicity, and is required for normal lytic and lysogenic growth.

Motor Cortex Latent Dynamics Encode Spatial and Temporal Arm Movement Parameters Independently.

The fluid movement of an arm requires multiple spatiotemporal parameters to be set independently. Recent studies have argued that arm movements are generated by the collective dynamics of neurons in motor cortex. An untested prediction of this hypothesis is that independent parameters of movement must map to independent components of the neural dynamics. Using a task where three male monkeys made a sequence of reaching movements to randomly placed targets, we show that the spatial and temporal parameters of arm movements are independently encoded in the low-dimensional trajectories of population activity in motor cortex: each movement's direction corresponds to a fixed neural trajectory through neural state space and its speed to how quickly that trajectory is traversed. Recurrent neural network models show that this coding allows independent control over the spatial and temporal parameters of movement by separate network parameters. Our results support a key prediction of the dynamical systems view of motor cortex, and also argue that not all parameters of movement are defined by different trajectories of population activity.

Less is more: selection from a small set of options improves BCI velocity control.

We designed the discrete direction selection (DDS) decoder for intracortical brain computer interface (iBCI) cursor control and showed that it outperformed currently used decoders in a human-operated real-time iBCI simulator and in monkey iBCI use. Unlike virtually all existing decoders that map between neural activity and continuous velocity commands, DDS uses neural activity to select among a small menu of preset cursor velocities. We compared closed-loop cursor control across four visits by each of 48 naïve, able-bodied human subjects using either DDS or one of three common continuous velocity decoders: direct regression with assist (an affine map from neural activity to cursor velocity), ReFIT, and the velocity Kalman Filter. DDS outperformed all three by a substantial margin. Subsequently, a monkey using an iBCI also had substantially better performance with DDS than with the Wiener filter decoder (direct regression decoder that includes time history). Discretizing the decoded velocity with DDS effectively traded high resolution velocity commands for less tortuous and lower noise trajectories, highlighting the potential benefits of simplifying online iBCI control.

The emerging role of human papillomavirus in lung cancer.

Lung cancer stands as one of the most lethal diseases and is the foremost cause of cancer-related mortalities worldwide. The pathophysiology of lung cancer is multifaceted, and it includes multiple cell signaling pathways and other complex factors such as oxidative stress and genetics. The association of HPV with lung carcinogenesis was first proposed in 1979, and since then, scientists worldwide have been putting forward several hypotheses to establish a relationship between this virus and lung cancer. Although studies have reported the presence of HPV in lung cancer, the exact mechanism of entry and the route of transmission have not been elucidated clearly till date. Numerous studies across the globe have detected differentially expressed HPV oncoproteins in lung cancer patients and found their association with the critical cell signaling pathways that leads to the development and progression of lung cancer. Many reports have also provided evidence stating the involvement of HPV in determining the survival status of lung cancer patients. The present review recapitulates the studies evincing the association of HPV and lung cancer, its route of transmission and mechanism of action; the detection of the virus and treatment opportunities for HPV-positive lung cancer; and the severity associated with this disease. Therefore, this will provide an explicit idea and would help to develop preventive measures and specific as well as effective treatment for HPV-associated lung carcinogenesis.

A multi-method exploration of a cardiac rehabilitation service delivered by registered Clinical Exercise Physiologists in the UK: key learnings for current and new services.

BACKGROUND: Cardiac rehabilitation has been identified as having the most homogenous clinical exercise service structure in the United Kingdom (UK), but inconsistencies are evident in staff roles and qualifications within and across services. The recognition of Clinical Exercise Physiologists (CEPs) as a registered health professional in 2021 in the UK, provides a potential solution to standardise the cardiac rehabilitation workforce. This case study examined, in a purposefully selected cardiac exercise service that employed registered CEPs, (i) how staff knowledge, skills and competencies contribute to the provision of the service, (ii) how these components assist in creating effective service teams, and (iii) the existing challenges from staff and patient perspectives. METHODS: A multi-method qualitative approach (inc., semi-structured interviews, observations, field notes and researcher reflections) was employed with the researcher immersed for 12-weeks within the service. The Consolidated Framework for Implementation Research was used as an overarching guide for data collection. Data derived from registered CEPs (n = 5), clinical nurse specialists (n = 2), dietitians (n = 1), service managers/leads (n = 2) and patients (n = 7) were thematically analysed. RESULTS: Registered CEPs delivered innovative exercise prescription based on their training, continued professional development (CPD), academic qualifications and involvement in research studies as part of the service. Exposure to a wide multidisciplinary team (MDT) allowed skill and competency transfer in areas such as clinical assessments. Developing an effective behaviour change strategy was challenging with delivery of lifestyle information more effective during less formal conversations compared to timetabled education sessions. CONCLUSIONS: Registered CEPs have the specialist knowledge and skills to undertake and implement the latest evidence-based exercise prescription in a cardiac rehabilitation setting. An MDT service structure enables a more effective team upskilling through shared peer experiences, observations and collaborative working between healthcare professionals.

Total Hip Arthroplasty in Patients Who Have Factor V Leiden: Elevated Risks Isolated to Venous Thromboembolism Events.

BACKGROUND: Total hip arthroplasty (THA) is a common procedure that requires consideration of preexisting comorbidities. Factor V Leiden (FVL), an inherited thrombophilia, is one such condition that predisposes patients to venous thromboembolism (VTE, deep vein thrombosis, and pulmonary embolism). The present study aimed to characterize the risks associated with FVL patients undergoing THA and evaluate the effect of VTE chemoprophylactic agents on these risks. METHODS: A total of 544,022 adult patients who underwent primary THA for osteoarthritis indications between 2010 and October 2021 were identified in an administrative claims database. Of these, FVL was identified in 1,138 (0.21%). Patients who had and did not have FVL were matched at a 1:4 ratio (1,131 with FVL and 4,519 without FVL) based on age, sex, and Elixhauser comorbidity index. Univariable and multivariable analyses were assessed for 90-day complications. Implant survival at 5 years was assessed and compared with log-rank tests. The relative use of different chemoprophylactic agents, including aspirin, warfarin, heparin, or direct oral anticoagulant (DOAC), was assessed. Bleeding events and VTE were compared for those prescribed either aspirin or warfarin, heparin, or DOAC. A Bonferroni correction was applied. RESULTS: On multivariable analysis, FVL patients were found to have increased odds of 90-day deep vein thrombosis (odds ratio (OR) = 9.20), pulmonary embolism (OR = 6.89), and aggregated severe and all adverse events (OR = 4.74 and 1.98, respectively), but not elevated risk of other perioperative adverse events or 5-year reoperations. More potent chemoprophylactic agents (warfarin, heparin, DOAC) reduced, but did not completely eliminate, the increased VTE risks (without increasing bleeding events). CONCLUSIONS: This study quantified the significantly elevated VTE risk associated with FVL patients undergoing THA. The lack of difference in other specific adverse events and 5-year reoperations is reassuring. Clearly, chemoprophylactic agents are important in this population and may need further attention.

Anti-oxidative and anti-inflammatory effects of Ginkgo biloba extract (EGb761) on hindlimb skeletal muscle ischemia-reperfusion injury in rats.

In posterior spine surgery, retractors exert pressure on paraspinal muscles, elevating intramuscular pressure and compromising blood flow, potentially causing muscle injury during ischemia-reperfusion. Ginkgo biloba extract (EGb 761), known for its antioxidant and free radical scavenging properties and its role in treating cerebrovascular diseases, is investigated for its protective effects against muscle ischemia-reperfusion injury in vitro and in vivo. Animals were randomly divided into the control group, receiving normal saline, and experimental groups, receiving varying doses of EGb761 (25/50/100/200 mg/kg). A 2-h hind limb tourniquet-induced ischemia was followed by reperfusion. Blood samples collected pre-ischemia and 24 h post-reperfusion, along with muscle tissue samples after 24 h, demonstrated that EGb761 at 1000 µg/mL effectively inhibited IL-6 and TNF-α secretion in RAW 264.7 cells without cytotoxicity. EGb761 significantly reduced nitric oxide (NO) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity, and increased glutathione (GSH) levels compared to the control after 24 h. Muscle tissue sections revealed more severe damage in the control group, indicating EGb761's potential in mitigating inflammatory responses and oxidative stress during ischemia-reperfusion injury, effectively protecting against muscle damage.

The potential role of chronic pain and the polytrauma clinical triad in predicting prodromal PD: A cross-sectional study of U.S. Veterans.

Introduction: The research criteria for prodromal Parkinson disease (pPD) depends on prospectively validated clinical inputs with large effect sizes and/or high prevalence. Neither traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), nor chronic pain are currently included in the calculator, despite recent evidence of association with pPD. These conditions are widely prevalent, co-occurring, and already known to confer risk of REM behavior disorder (RBD) and PD. Few studies have examined PD risk in the context of TBI and PTSD; none have examined chronic pain. This study aimed to measure the risk of pPD caused by TBI, PTSD, and chronic pain. Methods: 216 US Veterans were enrolled who had self-reported recurrent or persistent pain for at least three months. Of these, 44 met criteria for PTSD, 39 for TBI, and 41 for all three conditions. Several pain, sleep, affective, and trauma questionnaires were administered. Participants' history of RBD was determined via self-report, with a subset undergoing confirmatory video polysomnography. Results: A greater proportion of Veterans with chronic pain met criteria for RBD (36 % vs. 10 %) and pPD (18.0 % vs. 8.3 %) compared to controls. Proportions were increased in RBD (70 %) and pPD (27 %) when chronic pain co-occurred with TBI and PTSD. Partial effects were seen with just TBI or PTSD alone. When analyzed as continuous variables, polytrauma symptom severity correlated with pPD probability (r = 0.28, P = 0.03). Conclusion: These data demonstrate the potential utility of chronic pain, TBI, and PTSD in the prediction of pPD, and the importance of trauma-related factors in the pathogenesis of PD.