Degenerative Neurological Diseases Research Articles

Cuproptosis and physical training: A review.

Copper is an essential element in the human body, involved in many physiological and metabolic functions, including coagulation, oxidative metabolism, and hormone production. The maintenance of copper homeostasis within cells is a complex procedure that is intrinsically controlled by a multitude of intricate mechanisms. Disorders of copper homeostasis encompass a wide range of pathological conditions, including degenerative neurological diseases, metabolic disorders, cardio-cerebrovascular diseases, and tumors. Cuproptosis, a recently identified non-apoptotic mode of cell death mode, is characterized by copper dependence and the regulation of mitochondrial respiration. Cuproptosis represents a novel form of cell death distinct from the previously described modes, including apoptosis, necrosis, pyroptosis, and ferroptosis. Excess copper has been shown to induce cuproptosis by stimulating protein toxic stress responses via copper-dependent abnormal oligomerization of lipoylation proteins within the tricarboxylic acid cycle and the subsequent reduction of iron-sulfur cluster protein levels. Ferredoxin1 facilitates the lipoacylation of dihydrolipoyl transacetylase, which in turn degrades iron-sulfur cluster proteins by reducing Cu2+ to Cu+, thereby inducing cell death. Furthermore, copper homeostasis is regulated by the copper transporter, and disturbances in this homeostasis result in cuproptosis. Current evidence suggests that cuproptosis plays an important role in the onset and development of several cardiovascular diseases. Copper-chelating agents, including ammonium tetrathiomolybdate (VI) and DL-penicillamine, have been shown to facilitate the alleviation of cardiovascular disease by inhibiting cuproptosis. It is hypothesized that oxidative phosphorylation inhibitors such as physical training may inhibit cuproptosis by inhibiting the protein stress response. In conclusion, the implementation of physical training may be a viable strategy to reducte the incidence of cuproptosis.

Ecklonia cava Polyphenols Have a Preventive Effect on Parkinson's Disease through the Activation of the Nrf2-ARE Pathway.

Parkinson's disease (PD) is a degenerative neurological disorder defined by the deterioration and loss of dopamine-producing neurons in the substantia nigra, leading to a range of motor impairments and non-motor symptoms. The underlying mechanism of this neurodegeneration remains unclear. This research examined the neuroprotective properties of Ecklonia cava polyphenols (ECPs) in mitigating neuronal damage induced by rotenone via the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway. Using human neuroblastoma SH-SY5Y cells and PD model mice, we found that ECP, rich in the antioxidant polyphenol phlorotannin, boosted the gene expression and functionality of the antioxidant enzyme NAD(P)H quinone oxidoreductase-1. ECP also promoted Nrf2 nuclear translocation and increased p62 expression, suggesting that p62 helps sustain Nrf2 activation via a positive feedback loop. The neuroprotective effect of ECP was significantly reduced by Compound C (CC), an AMP-activated protein kinase (AMPK) inhibitor, which also suppressed Nrf2 nuclear translocation. In PD model mice, ECPs improved motor functions impaired by rotenone, as assessed by the pole test and wire-hanging test, and restored intestinal motor function and colon tissue morphology. Additionally, ECPs increased tyrosine hydroxylase expression in the substantia nigra, indicating a protective effect on dopaminergic neurons. These findings suggest that ECP has a preventative effect on PD.

Comparative transcriptomics revealed neurodevelopmental impairments and ferroptosis induced by extremely small iron oxide nanoparticles.

Iron oxide nanoparticles are a type of nanomaterial composed of iron oxide (Fe3O4 or Fe2O3) and have a wide range of applications in magnetic resonance imaging. Compared to iron oxide nanoparticles, extremely small iron oxide nanoparticles (ESIONPs) (∼3nm in diameter) can improve the imaging performance due to a smaller size. However, there are currently no reports on the potential toxic effects of ESIONPs on the human body. In this study, we applied ESIONPs to a zebrafish model and performed weighted gene co-expression network analysis (WGCNA) on differentially expressed genes (DEGs) in zebrafish embryos of 48 hpf, 72 hpf, 96 hpf, and 120 hpf using RNA-seq technology. The key hub genes related to neurotoxicity and ferroptosis were identified, and further experiments also demonstrated that ESIONPs impaired the neuronal and muscle development of zebrafish, and induced ferroptosis, leading to oxidative stress, cell apoptosis, and inflammatory response. Here, for the first time, we analyzed the potential toxic effects of ESIONPs through WGCNA. Our studies indicate that ESIONPs might have neurotoxicity and could induce ferroptosis, while abnormal accumulation of iron ions might increase the risk of early degenerative neurological diseases.

Detecting the symptoms of Parkinson’s disease with non-standard video

BackgroundNeurodegenerative diseases, such as Parkinson’s disease (PD), necessitate frequent clinical visits and monitoring to identify changes in motor symptoms and provide appropriate care. By applying machine learning techniques to video data, automated video analysis has emerged as a promising approach to track and analyze motor symptoms, which could facilitate more timely intervention. However, existing solutions often rely on specialized equipment and recording procedures, which limits their usability in unstructured settings like the home. In this study, we developed a method to detect PD symptoms from unstructured videos of clinical assessments, without the need for specialized equipment or recording procedures.MethodsTwenty-eight individuals with Parkinson’s disease completed a video-recorded motor examination that included the finger-to-nose and hand pronation-supination tasks. Clinical staff provided ground truth scores for the level of Parkinsonian symptoms present. For each video, we used a pre-existing model called PIXIE to measure the location of several joints on the person’s body and quantify how they were moving. Features derived from the joint angles and trajectories, designed to be robust to recording angle, were then used to train two types of machine-learning classifiers (random forests and support vector machines) to detect the presence of PD symptoms.ResultsThe support vector machine trained on the finger-to-nose task had an F1 score of 0.93 while the random forest trained on the same task yielded an F1 score of 0.85. The support vector machine and random forest trained on the hand pronation-supination task had F1 scores of 0.20 and 0.33, respectively.ConclusionThese results demonstrate the feasibility of developing video analysis tools to track motor symptoms across variable perspectives. These tools do not work equally well for all tasks, however. This technology has the potential to overcome barriers to access for many individuals with degenerative neurological diseases like PD, providing them with a more convenient and timely method to monitor symptom progression, without requiring a structured video recording procedure. Ultimately, more frequent and objective home assessments of motor function could enable more precise telehealth optimization of interventions to improve clinical outcomes inside and outside of the clinic.

Unraveling the Connection: Pain and Endoplasmic Reticulum Stress.

Pain is a complex and multifaceted experience. Recent research has increasingly focused on the role of endoplasmic reticulum (ER) stress in the induction and modulation of pain. The ER is an essential organelle for cells and plays a key role in protein folding and calcium dynamics. Various pathological conditions, such as ischemia, hypoxia, toxic substances, and increased protein production, may disturb protein folding, causing an increase in misfolding proteins in the ER. Such an overload of the folding process leads to ER stress and causes the unfolded protein response (UPR), which increases folding capacity in the ER. Uncompensated ER stress impairs intracellular signaling and cell function, resulting in various diseases, such as diabetes and degenerative neurological diseases. ER stress may be a critical universal mechanism underlying human diseases. Pain sensations involve the central as well as peripheral nervous systems. Several preclinical studies indicate that ER stress in the nervous system is enhanced in various painful states, especially in neuropathic pain conditions. The purpose of this narrative review is to uncover the intricate relationship between ER stress and pain, exploring molecular pathways, implications for various pain conditions, and potential therapeutic strategies.

Rehabilitation management of postmenopausal osteoporosis associated with degenerative neurological conditions

Abstract: Background: The evolving association of neurological disorders such as Parkinson's disease (PD) and stroke may aggravate postmenopausal osteoporosis. In this situation, inactivity and lack of movement are the main factors that contribute contribute to exacerbate osteoporosis and the occurrence of osteoporotic fractures. Material and Methods: We present the case of a 62-year-old female patient diagnosed with diffuse postmenopausal osteoporosis, Parkinson's dis-ease, and left frontal ischemic lacuna. 6 months before admission to our rehabilitation clinic, she suffered a trauma by falling that resulted in an L3 vertebral fracture and a right forearm fracture. L2-L4 posterior segmental spinal fusion and right forearm osteosynthesis were performed. Post-operatively, a motor deficit was found in the lower limbs. She was diagnosed clinically and fol-lowing neurophysiological investigations with bilateral external popliteal sciatic nerve paresis. In these circumstances, the patient suffered a new trauma, resulting in an open fracture at the same level of the right forearm which also required surgical treatment. Results and discussion: Following the rehabilitation program, the evolution was favorable with improved functioning and partial restoration of walking. Conclusion: The association of degenerative neurological and bone meta-bolic diseases in this case led to significant disability, making the rehabilitation process more challenging.

Retrospective study of lumbar disc herniation in a hospital in North-Eastern Romania

Abstract: Lumbar disc herniation is a degenerative neurological disorder characterized by a notable rise in incidence and prevalence among the population in modern times. It is primarily caused by factors such as microtrauma, sedentary lifestyle, prolonged static postures, excessive time spent at the computer, and overexertion. Materials and methods: A study was conducted retrospectively from 2022 to 2023 on patients who were admitted with lumbar disc herniation, at the Neurosurgery Hospital "Prof. N. Oblu”, in Iași.The research focused on showcasing the aspects of disc issues/pathology in the North Eastern re-gion.Findings; The research included 1969 individuals with a majority noted among par-ticipants, from rural areas and females.The majority of patients fell into the adult age range of 41 60 years. Surgical procedures were performed on 71% of the patients while conservative treatment was administered to the remaining 29%.The distribution of ages shows that most individuals undergoing surgery or receiving conservative treatment fall, within the adult age range of 41 to 60 years. Surgery is performed on 71% of patients while conservative treatment is given in 29% of cases.All patients were advised to undergo follow up remedial therapy upon discharge. We faced challenges in evaluating the level of adherence which posed a limitation in our study.Conclusions: The study brings to the forefront the need for reparative therapy for patient’s socio-professional and family reinte-gration and improvement of quality of life.

Enlightening the mechanism of ferroptosis in epileptic heart.

Epilepsy is a chronic neurological degenerative disease with a high incidence, affecting all age groups. Refractory Epilepsy (RE) occurs in approximately 30-40% of cases with a higher risk of sudden unexpected death in epilepsy (SUDEP). Recent studies have shown that spontaneous seizures developed in epilepsy can be related to an increase in oxidative stress and reactive oxygen derivatives (ROS) production. Increasing ROS concentration causes lipid peroxidation, protein oxidation, destruction of nuclear genetic material, enzyme inhibition, and cell death by a mechanism known as "ferroptosis" (Fts). Inactivation of glutathione peroxidase 4 (GPX4) induces Fts, while oxidative stress is linked with increased intracellular free iron (Fe+2) concentration. Fts is also a non-apoptotic programmed cell death mechanism, where a hypoxia-inducible factor 1 alpha (HIF-141) dependent hypoxic stress-like condition appears to occur with accumulation of iron and cytotoxic ROS in affected cells. Assuming convulsive crises as hypoxic stress, repetitive convulsive/hypoxic stress can be an effective inducer of the "epileptic heart" (EH), which is characterized by altered autonomic function and a high risk of malignant or fatal bradycardia. We previously reported that experimental recurrent seizures induce cardiomyocyte Fts associated with SUDEP. Furthermore, several genes related to Fts and hypoxia have recently been identified in acute myocardial infarction. An emerging theme from recent studies indicates that inhibition of GPX4 through modulating expression or activities of the xCT antiporter system (SLC7A11) governs cell sensitivity to oxidative stress from ferroptosis. Furthermore, during hypoxia, an increased expression of stress transcriptional factor ATF3 can promote Fts induced by erastin in a HIF-141-dependent manner. We propose that inhibition of Fts with ROS scavengers, iron chelators, antioxidants, and transaminase inhibitors could provide a therapeutic effect in epilepsy and improve the prognosis of SUDEP risk by protecting the heart from ferroptosis.

Protective effects of myricetin and morin on neurological damage in Aβ1–42/Al3+ -induced Alzheimer’s disease model of rats

Alzheimer's disease (AD) is a degenerative neurological disorder with unclear pathogenesis. Single-target drugs have very limited efficacy in treating AD, but synthetic multi-target drugs have poor efficacy and safety. Therefore, finding suitable natural multi-target drugs against AD is of great interest for research studies. We chose two flavonols, myricetin and morin, for the relevant study. In this study, we used microinjection of Aβ1–42 oligomers into the CA1 region of rat hippocampus, combined with gavage of Aluminum chloride hexahydrate (AlCl3·6H2O) solution to establish AD rat models, and myricetin and morin were selected as intervening drugs to explore the protective effects against neurological impairment. Experimental results showed that myricetin or morin could reduce the production of Aβ, Tubulin-associated unit (Tau), and Phosphorylated tubulin-associated unit (p-Tau), down-regulate the expression of relevant inflammatory factors, reduce hippocampal cell apoptosis in rats. There was a significant increase in the activity of adenosine triphosphatase, catalase, total superoxide dismutase, and the content of glutathione in the brain tissue. However, the content of malondialdehyde, inducible nitric oxide synthase, and the activity of acetylcholinesterase were decreased in the brain tissue. These two flavonols can regulate the imbalance of monoamine and amino acid neurotransmitter levels. In conclusion, Myricetin or morin can effectively improve learning and memory dysfunction in AD rats induced by Aβ1–42/Al3+ through anti-oxidative stress and anti-apoptotic features.

Machine learning based on functional and structural connectivity in mild cognitive impairment

ObjectiveAlzheimer's disease (AD) is a chronic, degenerative neurological disorder characterized by progressive cognitive decline and mental behavioral abnormalities. Mild cognitive impairment (MCI) is regarded as a transitional stage in the progression from normal elderly individuals to patients with AD. While studies have identified abnormalities in brain connectivity in patients with MCI, including functional and structural connectivity, accurately identifying patients with MCI in clinical screening remains challenging. We hypothesized that utilizing machine learning (ML) based on both functional and structural connectivity could yield meaningful results in distinguishing between patients with MCI and normal elderly individuals, so as to provide valuable information for early diagnosis and precise evaluation of patients with MCI. MethodsFollowing clinical criteria, we recruited 32 patients with MCI for the patient group, and 32 normal elderly individuals for the control group. All subjects underwent examinations for resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI). Subsequently, significant functional and structural connectivity features were selected and combined with a support vector machine for classification of the patient and control groups. ResultsWe observed significantly different functional connectivity in the frontal lobe and putamen between the MCI group and normal controls. The results based on functional connectivity features demonstrated a classification accuracy of 71.88% and an area under the curve (AUC) value of 0.78. In terms of structural connectivity, we found that decreased fractional anisotropy in patients with MCI was significantly associated with Montreal Cognitive Assessment scores, specifically in regions such as the precuneus and cingulate gyrus. The classification results using the structural connectivity feature yielded an accuracy of 92.19% and an AUC value of 0.99. Lastly, combining functional and structural connectivity features resulted in a classification accuracy and AUC value of 93.75% and 0.99, respectively. ConclusionsIn this study, we demonstrated a high classification performance, underscoring the potential of both brain functional and structural connectivity in distinguishing patients with MCI from normal elderly individuals. Furthermore, the integration of functional connectivity and structural connectivity features indicated that utilizing rs-fMRI and DTI could enhance the accuracy and specificity of identifying patients with MCI compared with relying on a single neuroimaging technique.

De Novo Screening and Mirror Image Isomerization of Linear Peptides Targeting α7 Nicotinic Acetylcholine Receptor.

As ligand-gated ion channels, nicotinic acetylcholine receptors (nAChRs) are widely distributed in the central and peripheral nervous systems and are associated with the pathogenesis of various degenerative neurological diseases. Here, we report the results of phage display-based de novo screening of an 11-residue linear peptide (named LKP1794) that targets the α7 nAChR, which is among the most abundant nAChR subtypes in the brain. Moreover, two d-peptides were generated through mirror image and/or primary sequence inverso isomerization (termed DRKP1794 and DKP1794) and displayed improved inhibitory effects (IC50 = 0.86 and 0.35 μM, respectively) on α7 nAChR compared with the parent l-peptide LKP1794 (IC50 = 2.48 μM), which markedly enhanced serum stability. A peptide-based fluorescence probe was developed using proteolytically resistant DKP1794 to specifically image the α7 nAChR in living cells. This work provides a new peptide tool to achieve inhibitory modulation and specifically image the α7 nAChR.

Histone deacetylase inhibitors VPA and WT161 ameliorate the pathological features and cognitive impairments of the APP/PS1 Alzheimer’s disease mouse model by regulating the expression of APP secretases

BackgroundAlzheimer’s disease (AD) is a degenerative neurological disorder. Recent studies have indicated that histone deacetylases (HDACs) are among the most prominent epigenetic therapy targets and that HDAC inhibitors have therapeutic effects on AD. Here, we identified sodium valproate (VPA), a pan-HDAC inhibitor, and WT161, a novel HDAC6 selective inhibitor, as potential therapeutic agents for AD. Underlying molecular mechanisms were investigated.MethodsA cellular model, N2a-APPswe, was established via lentiviral infection, and the APPswe/PSEN1dE9 transgenic mouse model was employed in the study. LC–MS/MS was applied to quantify the concentration of WT161 in the mouse brain. Western blotting, immunohistochemical staining, thioflavin-S staining and ELISA were applied to detect protein expression in cells, tissues, or serum. RNA interference was utilized to knockdown the expression of specific genes in cells. The cognitive function of mice was assessed via the nest-building test, novel object recognition test and Morris water maze test.ResultsPrevious studies have focused mainly on the impact of HDAC inhibitors on histone deacetylase activity. Our study discovered that VPA and WT161 can downregulate the expression of multiple HDACs, such as HDAC1 and HDAC6, in both AD cell and mouse models. Moreover, they also affect the expression of APP and APP secretases (BACE1, PSEN1, ADAM10). RNA interference and subsequent vitamin C induction further confirmed that the expression of APP and APP secretases is indeed regulated by HDAC1 and HDAC6, with the JNK pathway being the intermediate link in this regulatory process. Through the above pathways, VPA and WT161 effectively reduced Aβ deposition in both AD cell and mouse models and significantly improved cognitive function in AD mice.ConclusionsIn general, we have discovered that the HDAC6-JNK-APP secretases cascade is an important pathway for VPA and WT161 to exert their therapeutic effects on AD. Investigations into the safety and efficacy of VPA and WT161 were also conducted, providing essential preclinical evidence for assessing these two epigenetic drugs for the treatment of AD.

Effects of sleep deprivation on typical neurotransmitters

Several evidence suggests that sleep deprivation (SD) leads to significant changes in the function of neurotransmitter receptors in different nerve cell types. So far, research in this area has focused on brain regions that promote wakefulness and sleep and the hippocampus, which is involved in learning and memory. When wakefulness is longer than the natural duration, there are some selective disruptions in the brain’s sensory processing and cognitive performance.The author of this article discusses sleep deprivation and brain self-clearance patterns, and then explores the relationship between three typical neurotransmitters and sleep deprivation, as well as the detection and change trends of neurotransmitters and their metabolites.It can then be used to assist in the early diagnosis of certain diseases.Of the three neurotransmitters, two can be defined as pleasure neurotransmitters and one is associated with the degenerative neurological disease AD(Alzheimer’s disease). The author also found that there are different response patterns between these neurotransmitters and SD.

AYURVEDA MANAGEMENT OF KAMPAVAT WITH SPECIAL REFERENCE TO PARKINSON’SDISEASE – A CASE STUDY

Parkinson’s disease is a progressive degenerative neurological disorder which mainly affects the motor system of body and it is characterized by resting tremors, slowness of movements, rigidity, gait disturbances/postural instability. It is correlated with Kampavata [Disease associated with tremors in body] in Ayurveda, as it is characterized by Sarvanga Kampa/ShiroKampa [tremors all over body or tremors in head]. It is a Vata vyadhi which occurs due to pathological increase of Chala Guna [Moving property] of Vata. Treatment consists of both internal and external administration of different forms aimed to reverse pathology of Vata imbalance. Here, a case of 65 years female patient presented with tremors in both hands and neck, unable to walk since 2 years. Patient was treated with Panchakarma therapies; like nasya (administration of medicated oil through nasal route) Basti and Shaman Aushadhis. The patient got remarkable relief in symptoms with above Panchakarma and Ayurveda medicines.

Retinal ganglion cells in a mouse model of Alzheimer's disease: A temporal study

Aims/Purpose: Alzheimer's disease (AD) is a degenerative neurological disorder characterized by the progressive loss of neurons and their synapses in the brain. Similar alterations have been observed in the retina even before they manifest in the brain. The retina has been proposed as a readily accessible biomarker for AD. In a previous work utilizing a murine model of AD (APPNL‐F/NL‐F), changes in retinal thickness, as measured by optical coherence tomography (OCT), were observed at 15 and 17 months. The objective of this study was to quantitatively assess the population of retinal ganglion cells (RGCs) in this same AD murine model over a specified time period and compare it with wild‐type (WT) mice.Methods: To quantitatively assess the population of retinal ganglion cells we used two study groups: the APPNL‐F/NL‐F model throughout the time period of (6, 9, 12, 17, and 20 months) and compared with wild‐type (WT) mice age matched (n = 30 in both groups). The quantification of retinal ganglion cells (RGCs) was conducted using immunohistochemical analysis with the Brn3a marker. This analysis was performed using a semi‐automatic algorithm implemented in the MatLab environment, which was developed by the Ramón Castroviejo Institute for Ophthalmic Research. For the analysis, the entire retina was considered and segmented into the peripapillary, intermediate, and peripheral zones.Results: A statistically significant decresase (p < 0.05) in the population of Brn3a + cells was observed in the APPNL‐F/NL‐F group compared to the WT group. This decreased was found in the total retina at 12 months, in the peripapillary zone at 9, 12, and 20 months, and in the intermediate zone at 12 months of the study.Conclusions: The APPNL‐F/NL‐F mouse model exhibits RGCs loss at 9, 12, and 20 months, mirroring the patterns observed in human cases. These findings suggest that the model holds promise for investigating and studying mechanisms related to RGC degeneration in Alzheimer's disease.

Prosopagnosia: face blindness and its association with neurological disorders.

Loss of facial recognition or prosopagnosia has been well-recognized for over a century. It has been categorized as developmental or acquired depending on whether the onset is in early childhood or beyond, and acquired cases can have degenerative or non-degenerative aetiologies. Prosopagnosia has been linked to involvement of the fusiform gyri, mainly in the right hemisphere. The literature on prosopagnosia comprises case reports and small case series. We aim to assess demographic, clinical and imaging characteristics and neurological and neuropathological disorders associated with a diagnosis of prosopagnosia in a large cohort. Patients were categorized as developmental versus acquired; those with acquired prosopagnosia were further subdivided into degenerative versus non-degenerative, based on neurological aetiology. We assessed regional involvement on [18F] fluorodeoxyglucose-PET and MRI of the right and left frontal, temporal, parietal and occipital lobes. The Intake and Referral Center at the Mayo Clinic identified 487 patients with possible prosopagnosia, of which 336 met study criteria for probable or definite prosopagnosia. Ten patients, 80.0% male, had developmental prosopagnosia including one with Niemann-Pick type C and another with a forkhead box G1 gene mutation. Of the 326 with acquired prosopagnosia, 235 (72.1%) were categorized as degenerative, 91 (27.9%) as non-degenerative. The most common degenerative diagnoses were posterior cortical atrophy, primary prosopagnosia syndrome, Alzheimer's disease dementia and semantic dementia, with each diagnosis accounting for >10% of this group. The most common non-degenerative diagnoses were infarcts (ischaemic and haemorrhagic), epilepsy-related and primary brain tumours, each accounting for >10%. We identified a group of patients with non-degenerative transient prosopagnosia in which facial recognition loss improved or resolved over time. These patients had migraine-related prosopagnosia, posterior reversible encephalopathy syndrome, delirium, hypoxic encephalopathy and ischaemic infarcts. On [18F] fluorodeoxyglucose-PET, the temporal lobes proved to be the most frequently affected regions in 117 patients with degenerative prosopagnosia, while in 82 patients with non-degenerative prosopagnosia, MRI revealed the right temporal and right occipital lobes as most affected by a focal lesion. The most common pathological findings in those with degenerative prosopagnosia were frontotemporal lobar degeneration with hippocampal sclerosis and mixed Alzheimer's and Lewy body disease pathology. In this large case series of patients diagnosed with prosopagnosia, we observed that facial recognition loss occurs across a wide range of acquired degenerative and non-degenerative neurological disorders, most commonly in males with developmental prosopagnosia. The right temporal and occipital lobes, and connecting fusiform gyrus, are key areas. Multiple different pathologies cause degenerative prosopagnosia.

Clinical outcomes of intensive care unit patients infected with multidrug-resistant gram-negative bacteria treated with ceftazidime/avibactam and ceftolozane/tazobactam.

In intensive care units (ICUs), infection rates range from 18 to 54%, which is five to ten times higher than those observed in other hospital units, with a mortality rate of 9% to 60%. In recent decades, the susceptibility pattern has changed and Gram-Negative Bacteria (GNB) have become a threat due to their high frequency of multidrug resistance associated with a scarcity of therapeutic options. However, the drugs Ceftolozane/Tazobactam (C/T) and Ceftazidime/Avibactam (C/A) are demonstrating good clinical and microbiological response in the treatment of severe nosocomial infections. Therefore, this study aims to evaluate the clinical outcome of patients with severe infections caused by Multidrug-Resistant (MDR) GNB treated with C/T and C/A. Our study evaluates a total of 131 patients who received treatment with C/T and C/A due to infections caused by MDR GNB within the period from 2018 to 2021. The main infections were urinary tract (46,6%) and respiratory (26,7%) infections. Pseudomonas aeruginosa was the prevailing agent in the sample evaluation (34.3%), followed by Klebsiella pneumoniae (30,1%). About 54,9% of patients showed a favorable response, with culture negativation in 66,4% of the samples, with no discrepancy in negativations when comparing ages: 67,7% in young and 66% in elderly patients. Among the patients, 62,6% received monotherapy with C/T and C/A with a better response observed with monotherapy compared to combination therapy (58,6% vs 41,4%). The overall mortality rate was 45%, with MDR GNB infections responsible for 33,9% of these deaths, and the others (66,1%) due to factors such as oncological, hematological, and degenerative neurological diseases. In regards to hematological aspect, 35,1% of patients showed changes, with 28,2% of them presenting anemia, 4,5% thrombocytopenia, and 2,5% thrombocytosis. Concerning the use of invasive devices, higher mortality was observed in patients on mechanical ventilation (52%). In this manner, it was possible to observe that therapy with C/T and C/A yielded a favorable clinical outcome in patients with severe infections caused by MDR GNB in the study. These drugs also demonstrated good tolerability regardless of age or the presence of preexisting comorbidities and were deemed safe when assessing adverse effects. Our data also demonstrate the importance of determining the mechanism of resistance to carbapenems so that these drugs can be used more effectively and rationally.

Efficacy of exercise rehabilitation for managing patients with Alzheimer's disease.

Alzheimer's disease (AD) is a progressive and degenerative neurological disease characterized by the deterioration of cognitive functions. While a definitive cure and optimal medication to impede disease progression are currently unavailable, a plethora of studies have highlighted the potential advantages of exercise rehabilitation for managing this condition. Those studies show that exercise rehabilitation can enhance cognitive function and improve the quality of life for individuals affected by AD. Therefore, exercise rehabilitation has been regarded as one of the most important strategies for managing patients with AD. Herein, we provide a comprehensive analysis of the currently available findings on exercise rehabilitation in patients with AD, with a focus on the exercise types which have shown efficacy when implemented alone or combined with other treatment methods, as well as the potential mechanisms underlying these positive effects. Specifically, we explain how exercise may improve the brain microenvironment and neuronal plasticity. In conclusion, exercise is a cost-effective intervention to enhance cognitive performance and improve quality of life in patients with mild to moderate cognitive dysfunction. Therefore, it can potentially become both a physical activity and a tailored intervention. This review may aid the development of more effective and individualized treatment strategies to address the challenges imposed by this debilitating disease, especially in low- and middle-income countries.

Comparative Efficacy of Anti-Amyloid and Non-Antiamyloid Drugs for Treatment of Alzheimer’s Disease: A Network Meta-Analysis

BACKGROUND: Alzheimer’s disease is a degenerative neurological disorder that contributes 60-80% of all dementia cases, typically occurring at the age of 65 years. Currently available therapeutics for treatment are only capable of limiting the progression of cognitive decline. The focus of many Alzheimer’s disease drug therapies involves the hypothesized cause of pathogenesis in the disease, beta protein in the brain. Based on the Preferred Reporting Items for Meta-Analysis (PRISMA) for Network Meta-Analyses (NMA) framework, the present study was conducted to compare the efficacy of such drugs that target beta-amyloid directly or indirectly, with that of other treatments studied in randomized controlled trials. METHODS: Utilizing a network meta-analysis, direct and indirect comparisons between interventions could be done, providing a ranking of intervention in terms of efficacy in treating cognitive symptoms of Alzheimer’s disease. RESULTS: A total of 33 studies were included in four analyses of intervention trials that reported cognitive outcomes measured by Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) or Mini-Mental State Examination (MMSE) score. Based on the findings, anti-amyloid agents did not show a marked advantage over other therapies in improving cognitive scores. Results showed that parasympathomimetic agents were consistently ranked higher in terms of Surface Under the Cumulative Ranking (SUCRA) score, with anti-tau agents providing a possible superiority over all other interventions at improving MMSE scores for treatments lasting longer than 24 weeks. High-dose anti-amyloid therapies were effective at improving MMSE score in short term treatments lasting not more than 24 weeks but fall behind other drugs in longer durations. CONCLUSION: For better understanding on the choice of anti-amyloid and non-antiamyloid therapies, future well-designed large studies including safety outcome and cost- benefit analyses on the different interventions are recommended. Additionally, anti-tau therapies show a clearer potential over anti-amyloid therapies and should thus be given more focus in future drug research.

Neuroprotective potential of Afzelin: A novel approach for alleviating catalepsy and modulating Bcl-2 expression in Parkinson's disease therapy

The lost dopaminergic neurons in the brain prevent mobility in Parkinson's disease (PD). It is impossible to stop the disease's progress by means of symptoms management. Research focuses on oxidative stress, mitochondrial dysfunction, and neuronal degeneration. Exploration of potential neuroprotective drugs against prosurvival B-cell lymphoma 2 (Bcl-2) protein is ongoing. An investigable cause behind PD, as well as preventive measures, could be discovered considering the association between such behavioural manifestations (cataleptic behaviours) and PD. The compound Afzelin, known to guard the nervous system, was chosen for this study. The study was done on rats divided into six different groups. First, there was a control group. The other group was treated with Reserpine (RES) (1 mg/kg). The third group received RES (1 mg/kg) and levodopa (30 mg/kg). The remaining three groups were given RES (1 mg/kg) in conjunction with Afzelin at the following doses: 5 mg/kg, 10 mg/kg, and 20 mg/kg. Cataleptic behavior and mobility in rats was assessed using the rotarod, open field, and modified forced-swim tests. thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), biogenic amines, and Bcl-2 level in rat tissue homogenates were considered. According to the study's findings, the rats treated through co-administration of RES and Afzelin improved significantly in their cataleptic behaviours and locomotor activity. In addition, administering Afzelin itself caused Bcl-2 expression, which could have some neuroprotection properties. This study provides meaningful information on the effectiveness of Afzelin in handling catalepsy and other degenerative neurologic disorders. As a result, other studies need to be conducted to establish the reasons behind the reactions and determine the long-term effects of Afzelin on these conditions.