Discoveries (Craiova, Romania)最新文献

Parkinson's disease affects millions worldwide and is characterized by alpha-synuclein accumulation and loss of dopaminergic neurons in the brain. Until now, there is no cure for Parkinson's disease, and the existing treatments aim to alleviate symptoms. Parkinson's disease diagnosis is primarily based on clinical observation of bradykinesia, mood, and cognition symptoms. Nonetheless, clinical diagnosis has its drawbacks since symptoms of parkinson's disease only manifest in later stages and can be similar to those of other conditions, such as essential tremors or atypical Parkinsonian syndromes. Molecular imaging techniques, including magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), and positron emission tomography (PET), can objectively detect changes in the brain's neurochemical processes and help diagnose and study neurodegenerative diseases. The paper discusses functional imaging objectives, the tracers employed for imaging, and the condition of each target in Parkinson's disease. Functional imaging can bestow invaluable revelations concerning the intricate mechanisms underlying both motor and nonmotor impairments in Parkinson's disease while concurrently illuminating the involvement of striatal dopamine in behavioral phenomena extending beyond mere motor regulation. Furthermore, this cutting-edge technology exhibits great potential in investigating the preclinical stage of the ailment, thereby enhancing our comprehension of the merits and limitations associated with surgical interventions and the efficacy of neuroprotective approaches.

C-reactive protein (CRP) is a ring-shaped pentameric protein synthesized in the liver via CRP gene transcription. It is an inflammatory marker, whose serum levels can be measured using traditional and high-sensitivity tests. In healthy adults, the normal CRP serum concentrations vary between 0.8 mg/L and 3.0 mg/L. These can be grouped into low-, moderate-, and high-risk categories according to CRP levels of less than 1, 1-3, and greater than 3 mg/L, respectively. Elevated levels have been observed in infections, autoimmune diseases, neurodegenerative disorders, and malignancies. However, it is not specific to any disease. Serum CRP levels have also been shown to indicate the risk of cardiovascular disease, owing to their role as inflammatory markers in atherosclerosis, coronary artery disease, and peripheral arterial disease. Furthermore, its role in autoimmune diseases, such as Systemic Lupus Erythematosus and rheumatoid arthritis, and its involvement in the development of cancers, including breast, colorectal, ovarian, prostate, and lung cancers, have also been studied. The involvement of CRP in determining the course of infection and differentiating between bacterial and viral infections has also been investigated. This review summarizes the published literature on C-reactive protein and its role in disease management and progression.

Brain aneurysms, also known as cerebral aneurysms, are the growths of the parent artery. Based on their shape, aneurysms can be categorized as saccular or non-saccular. Several factors have been linked to multiple brain aneurysms but the most prevalent is arterial hypertension. In the treatment of cerebral aneurysms, endovascular techniques like coil embolization have essentially taken the place of surgical clipping. Brain aneurysm treatment has undergone a revolutionary change owing to flow diverters. They are now used for complex aneurysms that are unresponsive to standard therapies, in addition to unruptured lesions that were previously treated with standard surgical or coil-based endovascular procedures. Flow diversion has shown to be a more successful treatment for aneurysms than other approaches due to its reduced complication and high recovery rate. We discuss the case of a patient who arrived with headache and was subsequently diagnosed with numerous aneurysms of the left internal carotid artery. Flow diverter stenting was employed to thrombose our patient's existing aneurysms, followed by dual antiplatelet therapy (Ticagrelor and Thrombo ASS) as a post-procedural need. Despite the fact that our patient had both large and minor aneurysms impacting challenging locations, there were no complications after treatment.

Mammary myofibroblastoma (MM) is an uncommon, benign mesenchymal neoplasm with a favourable prognosis. Its resemblance to various other benign and malignant lesions of the breast makes precise diagnosis challenging when examining biopsy samples. The rarity of mammary myofibroblastoma in India and worldwide underscores the importance of our case report, as we aim to contribute to the existing literature and expand the knowledge base of this neoplasm. Furthermore, we have delved into the diagnostic complexities associated with this lesion and highlighted the ancillary techniques employed to achieve an accurate and reliable diagnosis.

Implant placement for dental rehabilitation has gained more popularity among patients in the recent past. Dental Implants are the workhorse of dentistry. Previously, the implants were placed with the help of the traditional freehand approach. Even though the conventional technique was successful, it has his own shortcomings. Various methods have been introduced, like stent -guided implant placement and navigation guided implant placement, that enhance the precision of implant position. The three different methods for placing the implants are freehand approach, static navigation and dynamic navigation. Among these approaches, the dynamic navigation system is a promising technology in implant dentistry. The dynamic navigation system is being used successfully in various other fields and is well known for its accuracy. It gives an advantage to clinician by providing real-time three-dimensional position of implant and better clinical and patient related treatment outcomes. This review summarizes- the literature and evidence available on dynamic navigation, its potential application, advantages, disadvantages with future directions.

A large number of products are synthesized and packaged in membrane vesicles to be secreted from cells to carry out essential physiological functions such as nerve transmission, digestion and immune response. How do cells secrete with great precision a portion of the vesicle contents?These questions have been answered through the work of Dr. Bhanu P. Jena, a cell physiologist and chemist at Wayne State University School of Medicine in Detroit Already in the mid 1990s he discovered that pancreatic acinar cells possess secretory portals (porosomes) at the cell plasma membrane that govern the transport and secretion of digestive enzymes. During the next twenty-five years, Jena characterized in great detail the molecular mechanisms underlying this secretory process. He also showed that similar "secretory portals", or "porosomes", are present in all cell types including endocrine cells secreting hormones and brain neurons secreting neurotransmitters.The principles discovered and described by Bhanu P. Jena turned out to be universal, operating similarly in all animal cells. A number of human hereditary diseases are caused by mutations in some of the nearly 30 proteins composing the porosome complex. Jena's discovery of the porosome, in addition to providing a deep understanding of cell secretion, has also contributed to the establishment of a drug development platform (https://www.porosome.com) for the treatment of a wide range of diseases. Among the therapeutic application is porosome reconstitution in stem cell derived beta cells, for the treatment of Type 1 diabetes and holds great promise for the cure of cystic fibrosis.

Glioblastoma is the most aggressive and commonest primary malignant brain tumour. Current standard of care includes surgery, radiation, and alkylating agent chemotherapy. Despite multimodal treatment, the survival of glioblastoma patients is dismal. Loss of O6-methylguanine-DNA-methyltransferase(MGMT) protein expression due to promoter methylation reduces glioma cell DNA repair activity and resistance to alkylating agents. Thus, in world health organization (WHO) grade 4 diffuse glioma patients treated with an alkylating agent, methylated MGMT promoter is currently being considered a clinically relevant prognostic as well as predictive biomarker. Our aim was to assess the frequency of MGMT promoter methylation in WHO grade 4 diffuse glioma patients and study their prognostic role and clinicopathological correlations. A two-year prospective cohort research was conducted on 89 WHO grade 4 diffuse glioma patients. The clinical and demographic data were retrieved from our hospital information system. MGMT methylation was assessed using methylation specific polymerase chain reaction. Data was analysed using SPSS-24 software. We studied 89 cases of WHO grade 4 diffuse glioma, of which 38.2% showed methylation of MGMT promoter. There was no significant difference in age, sex, location of tumor and clinical presentation between the methylated and unmethylated groups. A statistically significant association of methylated MGMT promoter was observed with isocitrate dehydrogenase-1 (IDH1) protein expression (p = 0.050) and alpha-thalassemia/mental retardation syndrome X-linked (ATRX) loss (p = 0.003). No significant association was noted with p53 overexpression (p = 0.492) and Ki-67 index (p = 0.698). The median overall survival in these patients receiving standard radiotherapy and concomitant temozolomide chemotherapy showed a trend towards better survival in group with methylated MGMT promoter (p < 0.001). Our study suggests that methylation of MGMT promoter is more frequent in the subset of grade 4 diffuse gliomas that significantly exhibit IDH1 immunopositivity and loss of ATRX expression. Also, patients who receive radiation therapy and simultaneous temozolomide chemotherapy have a considerably better prognosis and treatment outcome, if the promoter region of MGMT is methylated.

Alzheimer's disease (AD) has witnessed a gradual rise in its prevalence in recent decades, particularly impacting a substantial segment of individuals aged 85 and above. The core pathological features of AD involve the presence of amyloid-β (Aβ) plaques and neurofibrillary tangles formed due to the hyperphosphorylation of tau protein. Current AD treatments primarily provide symptomatic relief without addressing the fundamental disease progression. Given the sluggish pace of finding a definitive AD cure, research has shifted its focus towards pioneering approaches. There is an increasing emphasis on targeting the early stages of AD, with the aim of intervening before irreversible pathological changes take hold, thus preserving cognitive function and neuronal health. In recent years, significant strides have been made in the development and subsequent clinical testing of disease-modifying therapies (DMTs) designed to potentially alter the underlying pathophysiology of AD. These therapeutic strategies involve the utilization of monoclonal antibodies (mAbs) specifically directed at Aβ. Some of the drugs falling into this category include aducanumab, bapineuzumab, gantenerumab, solanezumab, and lecanemab. These treatment approaches are grounded in the hypothesis that a systemic failure in clearing Aβ contributes to the initiation and progression of AD. Recently, aducanumab and lecanemab have received FDA approval for the treatment of AD with mild cognitive impairment. This review offers a comprehensive summation of recent research endeavors that delve into the therapeutic effects and clinical trial outcomes of aducanumab and lecanemab in individuals afflicted by AD.

Background: Platelet Inhibition and Clinical Outcomes (PLATO) was a multicenter, randomized double-blind trial assessing efficacy and safety of ticagrelor versus clopidogrel in patients with acute coronary syndrome. The reported mortality benefit of ticagrelor in the PLATO trial has been challenged for over decade, and never confirmed in later trials.

Objective: To compare if there were any differences when deaths were reported to the FDAby the sponsors or by independent Contract Research Organizations (CRO).

Methods: We obtained the complete PLATO deaths dataset reported to the FDA and revealed that some events were inaccurately reported favoring ticagrelor. The entire FDA list contains precisely detailed 938 PLATO deaths. The CRO reported outcomes from the USA, Russia, Georgia, and most of Ukraine, while sites in 39 other countries were controlled by the trial sponsors. We compared vascular- (code "11"), non-vascular- (code "12"), and unknown (code "97") deaths triaged by the reporting source.

Results: Overall, most PLATO deaths were vascular (n=677), less non-vascular (n=159) andunexpectedly many of "other" (n=7) or "unknown" (n=95) origin reported either by sponsors (n=807) or CRO (n=131). The trial sponsors reported more clopidogrel deaths from vascular (313 vs.239), non-vascular (86 vs.58) and unknown (53 vs. 26) causes.In contrast, CRO-monitored sites reported significantly (72 vs. 53; p<0.01) more ticagrelordeaths than after clopidogrel from vascular (51 vs.39), non-vascular (8 vs.7) and unknown (10 vs. 4) causes.

Conclusion: Deaths were reported differently by sponsors and CRO within the same trial. Since some deaths were misreported by PLATO sponsors, only the CRO data seems mostly reliable. Among all countries, the CRO - reported PLATO-USA outcomes represent the largest and most realistic dataset of realistic evidence suggesting ticagrelor inferiority to clopidogrel for all primary endpoint components including vascular death.

Objective: The long-term extrapulmonary sequelae of COVID-19 after recovery from the critical stage at the intensive care unit (ICU) are still unclear. Some post-COVID symptoms are prevalent even after a one-year follow-up. To explore the relationship between high sensitivity C-reactive protein (hs-CRP) and hyperglycemia with cardiovascular diseases in non-diabetic COVID-19 patients. To determine whether increased fasting blood sugar (FBS) levels are associated with elevated hs-CRP and to explore whether hs-CRP can serve as a prognostic indicator to predict cardiovascular outcome.

Methods: FBS and hs-CRP values of 26 non-diabetic COVID-19 patients were collected from their medical records at JIPMER hospital. In one-year follow-up of these 26 patients, 2mL of blood sample was collected for the analysis of FBS, HbA1c, and hs-CRP.

Results: hs-CRP increased in 23% of follow-up patients who were at high risk, and 42.3% of participants were at average risk for cardiovascular disease. High and average-risk groups of survivors showed a positive correlation of hs-CRP with FBS and HbA1c levels, and these patients should be carefully monitored.

Conclusion: ICU survivors with elevated hs-CRP need periodic check-ups for cardiovascular diseases. We suggest that hs-CRP could be used as an early prognostic indicator of cardiovascular diseases and can reduce the risk.