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Seminars in Oncology Nursing Jun 2024Duloxetine, the only American Society of Clinical Oncology (ASCO) treatment recommended for chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors, is not...
OBJECTIVES
Duloxetine, the only American Society of Clinical Oncology (ASCO) treatment recommended for chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors, is not effective for 40% of survivors. This study examined the ability of a duloxetine-prazosin combination to prevent the development of allodynia and hyperalgesia in a rat model of oxaliplatin-induced peripheral neuropathy (OPIN).
METHODS
Female (n = 24) and male (n = 41) rats were started on duloxetine (15 mg), prazosin (2 mg), or a duloxetine-prazosin combination one week prior to administration of the chemotherapy drug, oxaliplatin, and continued the duloxetine-prazosin combination for 32 days. Behavioral testing for mechanical allodynia and mechanical hyperalgesia was done with selected von Frey filaments over the course of the study.
RESULTS
Overall percent paw withdrawal for rats that received the duloxetine-prazosin combination was significantly lower in female (p < .001 for both conditions) and male (p = .029 for allodynia; p < .001 for hyperalgesia) than those that received water. No significant posttreatment differences were found for allodynia or hyperalgesia between rats treated with duloxetine and rats that received the duloxetine-prazosin combination in either sex.
CONCLUSIONS
These finding provide preliminary evidence that a duloxetine-prazosin combination can prevent the posttreatment development of allodynia and hyperalgesia in both male and female rats; however, the results suggest that the duloxetine-prazosin combination is no more efficacious than duloxetine alone in preventing chronic OIPN.
IMPLICATIONS FOR NURSING PRACTICE
The profession of nursing is built on clinical practice supported by scientific research. The current study addressed the clinical practice problem of prevention and management of painful OIPN, which is a priority area in oncology nursing.
PubMed: 38897856
DOI: 10.1016/j.soncn.2024.151686 -
Health Expectations : An International... Jun 2024Surgery can help patients with leg pain caused by sciatica recover faster, but by 12 months outcomes are similar to nonsurgical management. For many the decision to have...
BACKGROUND
Surgery can help patients with leg pain caused by sciatica recover faster, but by 12 months outcomes are similar to nonsurgical management. For many the decision to have surgery may require reflection, and patient decision aids are an evidence-based clinical tool that can help guide patients through this decision.
OBJECTIVE
The aim of this study was to develop and refine a decision aid for patients with sciatica who are deciding whether to have surgery or 'wait and see' (i.e., try nonsurgical management first).
DESIGN
Semistructured interviews with think-aloud user-testing protocol.
PARTICIPANTS
Twenty clinicians and 20 patients with lived experience of low back pain or sciatica.
OUTCOME MEASURES
Items from Technology Acceptance Model, Preparation for Decision Making Scale and Decision Quality Instrument for Herniated Disc 2.0 (knowledge instrument).
METHODS
The prototype integrated relevant research with working group perspectives, decision aid standards and health literacy guidelines. The research team refined the prototype through seven rounds of user-testing, which involved discussing user-testing feedback and implementing changes before progressing to the next round.
RESULTS
As a result of working group feedback, the decision aid was divided into sections: before, during and after a visit to the surgeon. Across all rounds of user-testing, clinicians rated the resource 5.9/7 (SD = 1.0) for perceived usefulness, and 6.0/7 for perceived ease of use (SD = 0.8). Patients reported the decision aid was easy to understand, on average correctly answering 3.4/5 knowledge questions (SD = 1.2) about surgery for sciatica. The grade reading score for the website was 9.0. Patients scored highly on preparation for decision-making (4.4/5, SD = 0.7), suggesting strong potential to empower patients. Interview feedback showed that patients and clinicians felt the decision aid would encourage question-asking and help patients reflect on personal values.
CONCLUSIONS
Clinicians found the decision aid acceptable, patients found it was easy to understand and both groups felt it would empower patients to actively engage in their care and come to an informed decision that aligned with personal values. Input from the working group and user-testing was crucial for ensuring that the decision aid met patient and clinician needs.
PATIENT OR PUBLIC CONTRIBUTION
Patients and clinicians contributed to prototype development via the working group.
Topics: Humans; Sciatica; Decision Support Techniques; Female; Male; Adult; Middle Aged; Interviews as Topic; Decision Making; Patient Participation
PubMed: 38896009
DOI: 10.1111/hex.14111 -
Journal of Inflammation Research 2024Pyroptosis is a pro-inflammatory form of cell death resulting from the activation of gasdermins (GSDMs) pore-forming proteins and the release of several pro-inflammatory... (Review)
Review
Pyroptosis is a pro-inflammatory form of cell death resulting from the activation of gasdermins (GSDMs) pore-forming proteins and the release of several pro-inflammatory factors. However, inflammasomes are the intracellular protein complexes that cleave gasdermin D (GSDMD), leading to the formation of robust cell membrane pores and the initiation of pyroptosis. Inflammasome activation and gasdermin-mediated membrane pore formation are the important intrinsic processes in the classical pyroptotic signaling pathway. Overactivation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome triggers pyroptosis and amplifies inflammation. Current evidence suggests that the overactivation of inflammasomes and pyroptosis may further induce the progression of cancers, nerve injury, inflammatory disorders and metabolic dysfunctions. Current evidence also indicates that pyroptosis-dependent cell death accelerates the progression of diabetes and its frequent consequences including diabetic peripheral neuropathy (DPN). Pyroptosis-mediated inflammatory reaction further exacerbates DPN-mediated CNS injury. Accumulating evidence shows that several molecular signaling mechanisms trigger pyroptosis in insulin-producing cells, further leading to the development of DPN. Numerous studies have suggested that certain natural compounds or drugs may possess promising pharmacological properties by modulating inflammasomes and pyroptosis, thereby offering potential preventive and practical therapeutic approaches for the treatment and management of DPN. This review elaborates on the underlying molecular mechanisms of pyroptosis and explores possible therapeutic strategies for regulating pyroptosis-regulated cell death in the pharmacological treatment of DPN.
PubMed: 38895141
DOI: 10.2147/JIR.S465203 -
Sensors (Basel, Switzerland) May 2024This study investigated the reliability of measuring the median nerve cross-sectional area (CSA) at the carpal tunnel inlet using a handheld ultrasound device (HUD)...
This study investigated the reliability of measuring the median nerve cross-sectional area (CSA) at the carpal tunnel inlet using a handheld ultrasound device (HUD) compared to a standard ultrasound system, focusing on intra- and inter-operator reproducibility among novice and expert operators. Employing a prospective cross-sectional design, 37 asymptomatic adults were assessed using both devices, with measurements taken by an expert with over five years of experience and a novice with less than six months. The CSA was determined using manual tracing and ellipse methods, with reproducibility evaluated through intraclass correlation coefficients (ICCs) and agreement assessed via Bland-Altman plots. Results showed a high degree of agreement between the devices, with excellent intra-operator reproducibility (ICC > 0.80) for the expert, and moderate reproducibility for the novice (ICCs ranging from 0.539 to 0.841). Inter-operator reliability was generally moderate, indicating acceptable consistency across different experience levels. The study concludes that HUDs are comparable to standard ultrasound systems for assessing median nerve CSA in asymptomatic subjects, with both devices providing reliable measurements. This supports the use of HUDs in diverse clinical environments, particularly where access to traditional ultrasound is limited. Further research with a larger sample and symptomatic patients is recommended to validate these findings.
Topics: Humans; Median Nerve; Ultrasonography; Male; Female; Adult; Reproducibility of Results; Cross-Sectional Studies; Middle Aged; Prospective Studies; Carpal Tunnel Syndrome
PubMed: 38894235
DOI: 10.3390/s24113444 -
Molecules (Basel, Switzerland) May 2024Over the years, there has been notable progress in understanding the pathogenesis and treatment modalities of diabetes and its complications, including the application... (Review)
Review
Over the years, there has been notable progress in understanding the pathogenesis and treatment modalities of diabetes and its complications, including the application of metabolomics in the study of diabetes, capturing attention from researchers worldwide. Advanced mass spectrometry, including gas chromatography-tandem mass spectrometry (GC-MS/MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS), etc., has significantly broadened the spectrum of detectable metabolites, even at lower concentrations. Advanced mass spectrometry has emerged as a powerful tool in diabetes research, particularly in the context of metabolomics. By leveraging the precision and sensitivity of advanced mass spectrometry techniques, researchers have unlocked a wealth of information within the metabolome. This technology has enabled the identification and quantification of potential biomarkers associated with diabetes and its complications, providing new ideas and methods for clinical diagnostics and metabolic studies. Moreover, it offers a less invasive, or even non-invasive, means of tracking disease progression, evaluating treatment efficacy, and understanding the underlying metabolic alterations in diabetes. This paper summarizes advanced mass spectrometry for the application of metabolomics in diabetes mellitus, gestational diabetes mellitus, diabetic peripheral neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic encephalopathy, diabetic cardiomyopathy, and diabetic foot ulcers and organizes some of the potential biomarkers of the different complications with the aim of providing ideas and methods for subsequent in-depth metabolic research and searching for new ways of treating the disease.
Topics: Humans; Biomarkers; Metabolomics; Diabetes Mellitus; Diabetes Complications; Tandem Mass Spectrometry; Mass Spectrometry; Animals
PubMed: 38893405
DOI: 10.3390/molecules29112530 -
International Journal of Molecular... May 2024The cellular distribution and changes in CX3CL1/fractalkine and its receptor CX3CR1 protein levels in the trigeminal subnucleus caudalis (TSC) of rats with unilateral...
Dynamics of Cellular Regulation of Fractalkine/CX3CL1 and Its Receptor CX3CR1 in the Rat Trigeminal Subnucleus Caudalis after Unilateral Infraorbital Nerve Lesion-Extended Cellular Signaling of the CX3CL1/CX3CR1 Axis in the Development of Trigeminal Neuropathic Pain.
The cellular distribution and changes in CX3CL1/fractalkine and its receptor CX3CR1 protein levels in the trigeminal subnucleus caudalis (TSC) of rats with unilateral infraorbital nerve ligation (IONL) were investigated on postoperation days 1, 3, 7, and 14 (POD1, POD3, POD7, and POD14, respectively) and compared with those of sham-operated and naïve controls. Behavioral tests revealed a significant increase in tactile hypersensitivity bilaterally in the vibrissal pads of both sham- and IONL-operated animals from POD1 to POD7, with a trend towards normalization in sham controls at POD14. Image analysis revealed increased CX3CL1 immunofluorescence (IF) intensities bilaterally in the TSC neurons of both sham- and IONL-operated rats at all survival periods. Reactive astrocytes in the ipsilateral TSC also displayed CX3CL1-IF from POD3 to POD14. At POD1 and POD3, microglial cells showed high levels of CX3CR1-IF, which decreased by POD7 and POD14. Conversely, CX3CR1 was increased in TSC neurons and reactive astrocytes at POD7 and POD14, which coincided with high levels of CX3CL1-IF and ADAM17-IF. This indicates that CX3CL1/CX3CR1 may be involved in reciprocal signaling between TSC neurons and reactive astrocytes. The level of CatS-IF in microglial cells suggests that soluble CX3CL1 may be involved in neuron-microglial cell signaling at POD3 and POD7, while ADAM17 allows this release at all studied time points. These results indicate an extended CX3CL1/CX3CR1 signaling axis and its role in the crosstalk between TSC neurons and glial cells during the development of trigeminal neuropathic pain.
Topics: Animals; Chemokine CX3CL1; Rats; CX3C Chemokine Receptor 1; Male; Signal Transduction; Microglia; Trigeminal Neuralgia; Neurons; Astrocytes; Neuralgia; Rats, Sprague-Dawley
PubMed: 38892268
DOI: 10.3390/ijms25116069 -
International Journal of Molecular... May 2024Paclitaxel, a microtubule-stabilizing chemotherapy drug, can cause severe paclitaxel-induced peripheral neuropathic pain (PIPNP). The roles of transient receptor...
Paclitaxel, a microtubule-stabilizing chemotherapy drug, can cause severe paclitaxel-induced peripheral neuropathic pain (PIPNP). The roles of transient receptor potential (TRP) ion channel vanilloid 1 (TRPV1, a nociceptor and heat sensor) and melastatin 8 (TRPM8, a cold sensor) in PIPNP remain controversial. In this study, Western blotting, immunofluorescence staining, and calcium imaging revealed that the expression and functional activity of TRPV1 were upregulated in rat dorsal root ganglion (DRG) neurons in PIPNP. Behavioral assessments using the von Frey and brush tests demonstrated that mechanical hyperalgesia in PIPNP was significantly inhibited by intraperitoneal or intrathecal administration of the TRPV1 antagonist capsazepine, indicating that TRPV1 played a key role in PIPNP. Conversely, the expression of TRPM8 protein decreased and its channel activity was reduced in DRG neurons. Furthermore, activation of TRPM8 via topical application of menthol or intrathecal injection of WS-12 attenuated the mechanical pain. Mechanistically, the TRPV1 activity triggered by capsaicin (a TRPV1 agonist) was reduced after menthol application in cultured DRG neurons, especially in the paclitaxel-treated group. These findings showed that upregulation of TRPV1 and inhibition of TRPM8 are involved in the generation of PIPNP, and they suggested that inhibition of TRPV1 function in DRG neurons via activation of TRPM8 might underlie the analgesic effects of menthol.
Topics: Animals; Paclitaxel; TRPM Cation Channels; TRPV Cation Channels; Ganglia, Spinal; Rats; Neuralgia; Male; Rats, Sprague-Dawley; Hyperalgesia; Capsaicin; Neurons
PubMed: 38892000
DOI: 10.3390/ijms25115813 -
International Journal of Molecular... May 2024Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of photoreceptors and retinal pigment epithelial atrophy, leading to severe visual...
Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of photoreceptors and retinal pigment epithelial atrophy, leading to severe visual impairment or blindness. RP can be classified as nonsyndromic or syndromic with complex clinical phenotypes. Three unrelated Polish probands affected with retinitis pigmentosa coexisting with cerebellar ataxia were recruited for this study. Clinical heterogeneity and delayed appearance of typical disease symptoms significantly prolonged the patients' diagnostic process. Therefore, many clinical and genetic tests have been performed in the past. Here, we provide detailed clinical and genetic analysis results of the patients. Whole-exome sequencing (WES) and targeted NGS analysis allow the identification of four novel and two previously reported variants in the following genes: , , and The use of next-generation sequencing (NGS) methods finally allowed for confirmation of the clinical diagnosis. Ultra-rare diseases such as PHARC, PCARP, and Oliver-McFarlane syndromes were diagnosed in patients, respectively. Our findings confirmed the importance of the application of next-generation sequencing methods, especially in ultra-rare genetic disorders with overlapping features.
Topics: Humans; Retinitis Pigmentosa; Male; Female; Exome Sequencing; Pedigree; High-Throughput Nucleotide Sequencing; Adult; Cerebellar Ataxia; Membrane Transport Proteins; Monoacylglycerol Lipases; Mutation; Ataxia; Phenotype; Acyltransferases; Cataract; Phospholipases; Polyneuropathies
PubMed: 38891946
DOI: 10.3390/ijms25115759 -
BMJ Open Jun 2024The occurrence of hand and forearm disorders related to vibration exposure, adjusted for relevant background factors, is scarcely reported. We analysed the prevalence of...
OBJECTIVES
The occurrence of hand and forearm disorders related to vibration exposure, adjusted for relevant background factors, is scarcely reported. We analysed the prevalence of such conditions in a large population cohort, stratified by sex, and associations with exposure to vibrating hand-held tools.
DESIGN
This is a retrospective cohort study.
SETTING
Individuals in the Malmö Diet and Cancer Study cohort (MDCS; inclusion 1991-1996; followed until 2018) were asked, 'does your work involve working with vibrating hand-held tools?' (response: 'not at all', 'some' and 'much'). Data were cross-linked with national registers to identify treatment for carpal tunnel syndrome (CTS), ulnar nerve entrapment (UNE), Dupuytren's disease, trigger finger or first carpometacarpal joint (CMC-1) osteoarthritis (OA). Cox regression models, unadjusted and adjusted (age, sex, prevalent diabetes, smoking, hypertension and alcohol consumption), were performed to analyse the effects of reported vibration exposure.
PARTICIPANTS
Individuals in the MDCS who had answered the questionnaire on vibration exposure (14 342 out of the originally 30 446 individuals in MDCS) were included in the study.
RESULTS
In total, 12 220/14 342 individuals (76%) reported 'no' exposure, 1392/14 342 (9%) 'some' and 730/14 342 (5%) 'much' exposure to vibrating hand-held tools. In men, 'much' exposure was independently associated with CTS (HR 1.71 (95% CI 1.11 to 2.62)) and UNE (HR 2.42 (95% CI 1.15 to 5.07)). 'Some' exposure was independently associated with UNE in men (HR 2.10 (95% CI 1.12 to 3.95)). 'Much' exposure was independently associated with trigger finger in women (HR 2.73 (95% CI 1.49 to 4.99)). We found no effect of vibration exposure on Dupuytren's disease or CMC-1 OA. 'Much' vibration exposure predicted any hand and forearm diagnosis in men (HR 1.44 (95% CI 1.08 to 1.80)), but not in women.
CONCLUSIONS
Vibration exposure by hand-held tools increases the risk of developing CTS and UNE and any common hand and forearm conditions in men, whereas women only risk trigger finger and CMC-1 OA. Adjustment for relevant confounders in vibration exposure is crucial.
Topics: Humans; Male; Female; Retrospective Studies; Sweden; Middle Aged; Vibration; Carpal Tunnel Syndrome; Aged; Occupational Exposure; Occupational Diseases; Trigger Finger Disorder; Dupuytren Contracture; Hand; Prevalence; Risk Factors; Ulnar Nerve Compression Syndromes; Adult; Proportional Hazards Models
PubMed: 38890140
DOI: 10.1136/bmjopen-2023-080777 -
Journal of Otolaryngology - Head & Neck... 2024This study aims to provide an overview of dizziness post head injury in those with prominent features for central vestibular dysfunction (CVD) in comparison to those...
OBJECTIVES
This study aims to provide an overview of dizziness post head injury in those with prominent features for central vestibular dysfunction (CVD) in comparison to those with a post-traumatic peripheral vestibular etiology.
STUDY DESIGN
Retrospective.
SETTING
University Health Network (UHN) Workplace Safety and Insurance Board (WSIB) database from 1988 to 2018 were evaluated for post-traumatic dizziness.
METHODS
The UHN WSIB neurotology database (n = 4291) between 1998 and 2018 was retrospectively studied for head-injured workers presenting with features for CVD associated with trauma. All patients had a detailed neurotological history and examination, audiovestibular testing that included video nystagmography (VNG) and cervical vestibular-evoked myogenic potentials (cVEMPs). Imaging studies including routine brain and high-resolution temporal bone computed tomography (CT) scans and/or intracranial magnetic resonance imaging (MRI) were available for the majority of injured workers.
RESULTS
Among 4291 head-injured workers with dizziness, 23 were diagnosed with features/findings denoting CVD. Complaints of imbalance were significantly more common in those with CVD compared to vertigo and headache in those with peripheral vestibular dysfunction. Atypical positional nystagmus, oculomotor abnormalities and facial paralysis were more common in those with CVD.
CONCLUSION
Symptomatic post-traumatic central vestibular injury is uncommon. It occurred primarily following high-impact trauma and was reflective for a more severe head injury where shearing effects on the brain often resulted in diffuse axonal injury. Complaints of persistent imbalance and ataxia were more common than complaints of vertigo. Eye movement abnormalities were highly indicative for central nervous system injury even in those with minimal change on CT/MRI.
Topics: Humans; Retrospective Studies; Male; Craniocerebral Trauma; Female; Adult; Dizziness; Middle Aged; Vestibular Diseases; Vestibular Evoked Myogenic Potentials; Vestibular Function Tests; Magnetic Resonance Imaging; Tomography, X-Ray Computed
PubMed: 38888938
DOI: 10.1177/19160216241250354