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Frontiers in Aging Neuroscience 2024is a widely used medicinal and edible herb with a rich chemical composition. Moreover, prescriptions containing are commonly used for the prevention and treatment of...
INTRODUCTION
is a widely used medicinal and edible herb with a rich chemical composition. Moreover, prescriptions containing are commonly used for the prevention and treatment of cardiovascular, cerebrovascular, and aging-related diseases. Recent pharmacological studies have confirmed the antioxidant and neuroprotective effects of , and, in recent years, this herb has also been used in the treatment of Alzheimer's disease (AD) and other neurodegenerative disorders. We have previously shown that 4,4'-methylenediphenol, a key active ingredient of , can mitigate amyloid-β (Aβ)-induced paralysis in AD model worms as well as prolong the lifespan of the animals, thus displaying potential as a treatment of AD.
METHODS
We investigated the effects of 4,4'-methylenediphenol on AD and aging through paralysis, lifespan, and behavioral assays. In addition, we determined the anti-AD effects of 4,4'-methylenediphenol by reactive oxygen species (ROS) assay, lipofuscin analysis, thioflavin S staining, metabolomics analysis, GFP reporter gene worm assay, and RNA interference assay and conducted in-depth studies on its mechanism of action.
RESULTS
4,4'-Methylenediphenol not only delayed paralysis onset and senescence in the AD model worms but also enhanced their motility and stress tolerance. Meanwhile, 4,4'-methylenediphenol treatment also reduced the contents of reactive oxygen species (ROS) and lipofuscin, and decreased Aβ protein deposition in the worms. Broad-spectrum targeted metabolomic analysis showed that 4,4'-methylenediphenol administration had a positive effect on the metabolite profile of the worms. In addition, 4,4'-methylenediphenol promoted the nuclear translocation of DAF-16 and upregulated the expression of SKN-1, SOD-3, and GST-4 in the respective GFP reporter lines, accompanied by an enhancement of antioxidant activity and a reduction in Aβ toxicity; importantly, our results suggested that these effects of 4,4'-methylenediphenol were mediated, at least partly, via the activation of DAF-16.
CONCLUSION
We have demonstrated that 4,4'-methylenediphenol can reduce Aβ-induced toxicity in AD model worms, suggesting that it has potential for development as an anti-AD drug. Our findings provide ideas and references for further research into the anti-AD effects of and its active ingredients.
PubMed: 38872629
DOI: 10.3389/fnagi.2024.1393721 -
CNS Neuroscience & Therapeutics Jun 2024Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease characterized by progressive death of upper and lower motor neurons, leading to generalized...
Arctigenin derivative A-1 ameliorates motor dysfunction and pathological manifestations in SOD1 transgenic mice via the AMPK/SIRT1/PGC-1α and AMPK/SIRT1/IL-1β/NF-κB pathways.
AIM
Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease characterized by progressive death of upper and lower motor neurons, leading to generalized muscle atrophy, paralysis, and even death. Mitochondrial damage and neuroinflammation play key roles in the pathogenesis of ALS. In the present study, the efficacy of A-1, a derivative of arctigenin with AMP-activated protein kinase (AMPK) and silent information regulator 1 (SIRT1) activation for ALS, was investigated.
METHODS
A-1 at 33.3 mg/kg was administrated in SOD1 transgenic mice orally from the 13th week for a 6-week treatment period. Motor ability was assessed before terminal anesthesia. Muscle atrophy and fibrosis, motor neurons, astrocytes, and microglia in the spinal cord were evaluated by H&E, Masson, Sirius Red, Nissl, and immunohistochemistry staining. Protein expression was detected with proteomics analysis, Western blotting, and ELISA. Mitochondrial adenosine triphosphate (ATP) and malondialdehyde (MDA) levels were measured using an assay kit.
RESULTS
A-1 administration in SOD1 mice enhanced mobility, decreased skeletal muscle atrophy and fibrosis, mitigated loss of spinal motor neurons, and reduced glial activation. Additionally, A-1 treatment improved mitochondrial function, evidenced by elevated ATP levels and increased expression of key mitochondrial-related proteins. The A-1 treatment group showed decreased levels of IL-1β, pIκBα/IκBα, and pNF-κB/NF-κB.
CONCLUSIONS
A-1 treatment reduced motor neuron loss, improved gastrocnemius atrophy, and delayed ALS progression through the AMPK/SIRT1/PGC-1α pathway, which promotes mitochondrial biogenesis. Furthermore, the AMPK/SIRT1/IL-1β/NF-κB pathway exerted neuroprotective effects by reducing neuroinflammation. These findings suggest A-1 as a promising therapeutic approach for ALS.
Topics: Animals; Mice, Transgenic; Sirtuin 1; Mice; NF-kappa B; AMP-Activated Protein Kinases; Furans; Amyotrophic Lateral Sclerosis; Interleukin-1beta; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Lignans; Signal Transduction; Superoxide Dismutase-1; Male; Motor Neurons; Spinal Cord
PubMed: 38872258
DOI: 10.1111/cns.14692 -
Neuromuscular Disorders : NMD May 2024Primary hypokalemic periodic paralysis (HypoPP) is a skeletal muscle channelopathy most commonly caused by pathogenic variants in the calcium channel gene, CACNA1S....
Primary hypokalemic periodic paralysis (HypoPP) is a skeletal muscle channelopathy most commonly caused by pathogenic variants in the calcium channel gene, CACNA1S. HypoPP can present with attacks of paralysis and/or permanent muscle weakness. Previous studies have shown that patients with HypoPP can have impaired quality of life (QoL). In this cross-sectional study, we aimed to describe the QoL in patients with HypoPP caused by pathogenic variants in CACNA1S using The Individualized Neuromuscular Quality of Life (INQoL) questionnaire, a validated tool to measure the QoL of patients with neuromuscular diseases (higher score, worse QoL). We showed that muscle weakness and fatigue were the symptoms with the greatest impact on participants' lives and that "activities", in the life domain of the INQoL, was most affected by HypoPP. Furthermore, we showed that the total INQoL score increased with age. Low QoL was primarily driven by progressive permanent muscle weakness and not attacks of paralysis, although half of the participants reported that attacks of paralysis challenged their daily life. The results suggest that special attention should be given to muscle weakness and fatigue in patients with HypoPP.
PubMed: 38870649
DOI: 10.1016/j.nmd.2024.05.012 -
Brain & Spine 2024Despite the relatively low prevalence of metastatic cervical spinal tumor, these entities give rise to more profound complications than thoracic and lumbar spinal tumor....
INTRODUCTION
Despite the relatively low prevalence of metastatic cervical spinal tumor, these entities give rise to more profound complications than thoracic and lumbar spinal tumor. However, it is regrettable that experimental investigation has thus far shown a dearth of attention to metastatic cervical spinal tumor.
RESEARCH QUESTION
What is the conceptualization and realization of quadriparesis resulting from metastatic cervical spinal tumor?
MATERIAL AND METHODS
Using Fischer 344 rats as the experimental cohort, this study orchestrated the engraftment of tumor cells procured from the 13762 MAT B III cell line (RRID: CVCL_3475), which represents mammary adenocarcinoma. These cells were engrafted into the vertebrae of the cervical spine. A comprehensive inquiry encompassing behavioral assessments, histological evaluations, and microangiographic analyses conducted after the aforementioned cellular transplantation was subsequently pursued.
RESULTS
The incidence of cervical paralysis was 61.1%. Notably, the evolution of paralysis was unfurled by two distinctive temporal phases within its natural history. A meticulous histological examination facilitated delineation of the tumor's posterior expansion within the spinal canal. Simultaneously, the tumor exhibited anterior and lateral encroachment on the spinal cord, inducing compression from all sides. Augmented by microangiographic investigations, conspicuous attenuation of stained blood vessels within the affected anterior horn and funiculus of the spinal cord was observed.
DISCUSSION AND CONCLUSION
The pathological advancement of paralysis stemming from metastatic cervical spinal tumor is now apprehended to unfurl through a biphasic phase. The initial phase is characterized by gradual unfurling spanning several days, juxtaposed against the second phase marked by swift and accelerated progression.
PubMed: 38868600
DOI: 10.1016/j.bas.2024.102842 -
Actas Espanolas de Psiquiatria Jun 2024A case of Kloos syndrome is presented, a rare psychopathological manifestation in psychiatry characterized by the experience of "time paralysis" related to an epileptic...
A case of Kloos syndrome is presented, a rare psychopathological manifestation in psychiatry characterized by the experience of "time paralysis" related to an epileptic focus in the left temporoparietal areas. This syndrome was identified through a detailed psychopathological analysis and detected by an electroencephalographic record. The patient's symptoms disappeared after receiving antiepileptic treatment with Carbamazepine. In this case report we highlight the detailed phenomenological and clinical analysis, as well as the importance of carrying out complementary tests when we are faced with unusual or sudden-onset symptoms without any trigger, as took place in the case exposed.
Topics: Humans; Syndrome; Male; Electroencephalography; Carbamazepine; Adult; Anticonvulsants
PubMed: 38863053
DOI: 10.62641/aep.v52i3.1599 -
Radiology and Oncology Jun 2024The aim of the study was to provide insight into the influence of the COVID-19 on the frequency and characteristics of urgent and emergent tracheostomies (TS), comparing...
BACKGROUND
The aim of the study was to provide insight into the influence of the COVID-19 on the frequency and characteristics of urgent and emergent tracheostomies (TS), comparing data collected both before and during the pandemic. Our two hypotheses were that and that .
PATIENTS AND METHODS
The research was retrospective. The study period included the two years before and after the COVID-19 outbreak in Slovenia. Forty-one patients in each period met the inclusion criteria. Their medical charts were reviewed. The anamnestic, clinical, surgical and anaesthesiological data were collected. The two groups of patients from corresponding time periods were statistically compared.
RESULTS
Predominantly men required the surgical resolution of acute upper airway obstruction (76% of patients). The causes for acute respiratory distress included head and neck cancer (62%), infections (20%), vocal cord paralysis (16%), and stenosis (2%). There were no statistically significant differences either in the (emergent/urgent) setting of TS or in the type of anaesthesia used. Both hypotheses were rejected. A statistically significant rise in use of the C-MAC laryngoscope during COVID-19 (from 3% to 15%) was reported.
CONCLUSIONS
The outbreak of COVID-19 did not have a statistically significant effect on the frequency of performing emergent and urgent tracheostomies nor on the use of general or local anaesthesia. It did, however, require a change of intubation technique. Consequently, a significant rise in the use of the C-MAC laryngoscope was noted.
PubMed: 38861690
DOI: 10.2478/raon-2024-0034 -
Langenbeck's Archives of Surgery Jun 2024Assessing vocal cord mobility is crucial for patients undergoing thyroid surgery. We aimed to evaluate the feasibility and efficacy of surgeon-performed transcutaneous... (Observational Study)
Observational Study
PURPOSE
Assessing vocal cord mobility is crucial for patients undergoing thyroid surgery. We aimed to evaluate the feasibility and efficacy of surgeon-performed transcutaneous laryngeal ultrasound (TLUS) compared to flexible nasolaryngoscopy.
METHOD
From February 2022 to December 2022, we conducted a prospective observational study on patients scheduled for total thyroidectomy at our Institution. All patients underwent TLUS followed by flexible nasolaryngoscopy by a blinded otolaryngologist. Findings were classified as normal or vocal cord movement impairment and then compared. Patients evaluable on TLUS were included in Group A, while those not evaluable were included in Group B, and their features were compared.
RESULTS
Group A included 180 patients, while Group B included 21 patients. Male sex (p < 0.001), age (p = 0.034), BMI (p < 0.001), thyroid volume (p = 0.038), and neck circumference (p < 0.001) were associated with Group B. TLUS showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%, 99.4%, 94.4%, 100%, and 99.4%, respectively. Cohen's K value was 0.984.
CONCLUSION
TLUS is a valid, easy-to-perform, non-invasive, and painless alternative for evaluating vocal cords in selected patients. It can be used either as a first level exam and as screening tool for selecting cases for flexible nasolaryngoscopy. TLUS should be integrated into routine thyroid ultrasound examination.
Topics: Humans; Thyroidectomy; Male; Female; Prospective Studies; Middle Aged; Ultrasonography; Adult; Laryngoscopy; Vocal Cords; Aged; Feasibility Studies; Sensitivity and Specificity; Postoperative Complications; Vocal Cord Paralysis
PubMed: 38861184
DOI: 10.1007/s00423-024-03362-4 -
The American Journal of Case Reports Jun 2024BACKGROUND Penetrating traumatic brain injury (TBI) caused by gunshots is a rare type of TBI that leads to poor outcomes and high mortality rates. Conducting a formal...
BACKGROUND Penetrating traumatic brain injury (TBI) caused by gunshots is a rare type of TBI that leads to poor outcomes and high mortality rates. Conducting a formal neuropsychological evaluation concerning a patient's neurologic status during the chronic recovery phase can be challenging. Furthermore, the clinical assessment of survivors of penetrating TBI has not been adequately documented in the available literature. Severe TBI in patients can provide valuable information about the functional significance of the damaged brain regions. This information can help inform our understanding of the brain's intricate neural network. CASE REPORT We present a case of a 29-year-old right-handed man who sustained a left-hemisphere TBI after a gunshot, causing extensive diffuse damage to the left cerebral and cerebellar hemispheres, mainly sparing the right hemisphere. The patient survived. The patient experienced spastic right-sided hemiplegia, facial hemiparesis, left hemiparesis, and right hemianopsia. Additionally, he had severe global aphasia, which caused difficulty comprehending verbal commands and recognizing printed letters or words within his visual field. However, his spontaneous facial expressions indicating emotions were preserved. The patient received a thorough neuropsychological assessment to evaluate his functional progress following a severe TBI and is deemed to have had a favorable outcome. CONCLUSIONS Research on cognitive function recovery following loss of the right cerebral hemisphere typically focuses on pediatric populations undergoing elective surgery to treat severe neurological disorders. In this rare instance of a favorable outcome, we assessed the capacity of the fully developed right hemisphere to sustain cognitive and emotional abilities, such as language.
Topics: Humans; Male; Adult; Wounds, Gunshot; Recovery of Function; Brain Injuries, Traumatic; Neuropsychological Tests; Head Injuries, Penetrating; Hemiplegia; Aphasia
PubMed: 38859569
DOI: 10.12659/AJCR.941601 -
Effect of nutritional status on occurrence of pneumonia after traumatic cervical spinal cord injury.Scientific Reports Jun 2024Pneumonia after cervical spinal cord injury (CSCI) is a common and serious complication; however, its nutrition-related etiology has not yet been elucidated. This study...
Pneumonia after cervical spinal cord injury (CSCI) is a common and serious complication; however, its nutrition-related etiology has not yet been elucidated. This study aimed to elucidate the effects of nutritional factors on pneumonia after CSCI. Patients with acute traumatic CSCI who were admitted within 3 days after injury and followed up for at least 3 months were retrospectively examined. Occurrence of pneumonia, nutritional status, severity of dysphagia, vital capacity, use of respirators, and motor scores for paralysis were evaluated. Of 182 patients included in this study, 33 (18%) developed pneumonia. Multiple logistic regression analysis revealed that low nutritional status, severe paralysis, and low vital capacity were significant risk factors for pneumonia. The severity of paralysis, respiratory dysfunction, and poor nutritional status can affect the occurrence of pneumonia after CSCI. In addition to respiratory management, nutritional assessment and intervention may play key roles in preventing pneumonia associated with spinal cord injury-induced immune depression. Nutritional care should be provided as soon as possible when the nutritional status of a patient worsens after an injury.
Topics: Humans; Spinal Cord Injuries; Nutritional Status; Male; Female; Middle Aged; Pneumonia; Adult; Retrospective Studies; Risk Factors; Aged; Cervical Cord
PubMed: 38858459
DOI: 10.1038/s41598-024-64121-5 -
Health Expectations : An International... Jun 2024The WHO advocates patient and public involvement as an ethical imperative, due to the value of the lived experience of patients. A deeper understanding of the shared...
BACKGROUND
The WHO advocates patient and public involvement as an ethical imperative, due to the value of the lived experience of patients. A deeper understanding of the shared meanings and underlying beliefs of healthcare professionals and managers for and against including patients in care pathway development.
OBJECTIVE
To explore the considerations of healthcare professionals and managers on the involvement of patients and public in care pathway development.
METHODS
In a medical rehabilitation centre we conducted a single case study that was part of a 2-year action research programme on blended care pathway development. Following 14 semistructured interviews with healthcare professionals and managers, we analysed their discourses on the value of patient involvement as well as the potential threats and opportunities.
RESULTS
We identified four discourses. Patient as expert frames involvement as relevant, as adding new perspectives and as required to fully understand the patient's needs. Skills and representation is based on the construct that obtaining valuable insights from patients requires certain skills and competences. Self-protection focusses on personal, interprofessional objections to patient involvement. Professional knows best reveals expertise-related reasons for avoiding or postponing involvement.
CONCLUSION
These discourses explain why patient and public involvement in care pathway development is sometimes postponed, limited in scope and level of participation, and/or avoided. The following strategies might minimise the paralysing effect of these discourses: strengthen the capabilities of all stakeholders involved; use a mix of complementary techniques to gain involvement in distinct phases of care pathway development; and create/facilitate a safe environment. Put together, these strategies would foster ongoing, reciprocal learning that could enhance patient involvement.
PATIENT OR PUBLIC CONTRIBUTION
This study belonged to an action research programme on blended care pathway development (developing an integrated, coordinated patient care plan that combines remote, digital telehealth applications, self-management tools and face-to-face care). Multidisciplinary teams took a quality collaborative approach to quality improvement (considering patients as stakeholders) to develop 11 blended care pathways. Although professionals and managers were instructed to invite patients onto their teams and to attend care pathway design workshops, few teams (3/11) actually did. Unravelling why this happened will help improve patient and public involvement in care pathway development.
Topics: Humans; Patient Participation; Critical Pathways; Health Personnel; Interviews as Topic; Attitude of Health Personnel; Qualitative Research
PubMed: 38855873
DOI: 10.1111/hex.14101