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Modification threat in a cohort of US patients young compared to Fifty five undergoing principal optional complete hip arthroplasty.
The advantages and limitations of such models are highlighted. We also discussed the great potential of proteomic technologies in unraveling the molecular mechanism of schizophrenia through animal models.Modeling schizophrenia is challenging due to the uniquely human component of psychiatric disorders. Despite several advances in cellular and animal modeling, postmortem brain tissue derived from patients is still one of the extremely few sources of information that comprises brain complexity, human genetics, and patient experiences. Additionally, postmortem tissue from patients with schizophrenia can be used to drive hypotheses that can then be validated in other models, involving either other animals or an in vitro approach. While evaluating high-throughput and sensitive techniques, shotgun proteomics allows for the identification and quantitation of thousands of proteins present in biological systems. In the context of schizophrenia, proteomics can map differentially regulated proteins throughout brain regions of patients with schizophrenia, generating a large amount of information regarding the disorder's pathophysiology. In this chapter, our aim is to bring the literature up to date regarding proteomics tools applied to postmortem brains from patients with schizophrenia, additionally discussing new findings, roads, and perspectives for the comprehension of this severe disorder.Acute myeloid leukemia (AML) is a heterogeneous malignancy affecting myeloid cells in the bone marrow (BM) but can spread giving rise to impaired hematopoiesis. AML incidence increases with age and is associated with poor prognostic outcomes. read more There has been a disconnect between the success of novel drug compounds observed in preclinical studies of hematological malignancy and less than exceptional therapeutic responses in clinical trials. This review aims to provide a state-of-the-art overview on the different preclinical models of AML available to expand insights into disease pathology and as preclinical screening tools. Deciphering the complex physiological and pathological processes and developing predictive preclinical models are key to understanding disease progression and fundamental in the development and testing of new effective drug treatments. Standard scaffold-free suspension models fail to recapitulate the complex environment where AML occurs. To this end, we review advances in scaffold/matrix-based 3D models and outline the most recent advances in on-chip technology. We also provide an overview of clinically relevant animal models and review the expanding use of patient-derived samples, which offer the prospect to create more "patient specific" screening tools either in the guise of 3D matrix models, microphysiological "organ-on-chip" tools or xenograft models and discuss representative examples.Stigma is defined by the World Health Organization (WHO) as "a mark of shame, disgrace or disapproval that results in an individual being rejected, discriminated against and excluded from participating in a number of different areas of society". Extensive literature searches have documented stigma in the context of health. Among the physical health conditions that are associated with stigma, chronic pain deserves particular attention. Stigma experienced by individuals with chronic pain affects their entire life. Literature identifies multiple dimensions or types of stigma, including public stigma, structural stigma and internalized stigma. Recent literature supports the biopsychosocial model of pain, according to which biological, psychological and sociocultural variables interact in a dynamic manner to shape an individual's response to chronic pain. Chronic pain affects a higher proportion of women than men around the world. There is an inadequate education of health care professionals regarding pain assessment and their insecurity to manage patients with chronic pain. A first-line intervention strategy could be to promote pain education and to expand knowledge and assessment of chronic pain, as recently highlighted for headache disorders, paradigmatically for resistant or refractory migraine, whose diagnosis, without an adequate education to understand the possible fluctuations of the disease, may have profound psychological implications with the idea of insolvability and contribute to stigmatizing the patient.As a widely used anti-tumor anthracycline, the accumulation of Doxorubicin (DOX) in body causes irreparable cardiomyocyte damage and therefore is limited in clinical application. Strategies to prevent from DOX-associated cardiotoxicity are urgent for patients who undergo DOX-based chemotherapy. Since oxidative stress injury being the major reason for myocardial toxicity of DOX, here we demonstrated that, Alpha-lipoic acid (ALA), which is a reductive agent, plays a cardioprotective role in attenuating DOX-induced cardiotoxicity by inhibiting pyruvate dehydrogenase kinase 4 (PDK4) expression. In vivo, the beneficial effect of ALA was evidenced by increased survival rate, mechanical contraction, and oxidative phosphorylation, while decreased reactive oxidative species (ROS) and apoptosis. In vitro, PDK4 overexpression remarkably increased DOX-induced apoptosis and ROS production in H9C2 cells. Notably, the protective effect of ALA was abrogated by PDK4 overexpression. We further used PDK4 knockout mice to identify the role of PDK4 in DOX-induced cardiotoxicity. Results elicited that PDK4 deficiency showed a consistent effect in protecting DOX cardiotoxicity as ALA treatment, which was evidenced by restored redox homeostasis and mitochondrial metabolism, finally inhibited myocardial injury. In conclusion, the cardioprotective role of ALA against DOX cardiotoxicity was dependent on PDK4-mediated regulation of oxidative stress and mitochondria metabolism.Many drugs carry some risk of QT interval prolongation, which can lead to life-threatening dysrhythmias including Torsades de Pointes (TdP). CredibleMeds.org identifies medications categorized as "Known Risk of TdP" but does not stratify risk in acute supratherapeutic ingestions. We sought to determine the proportion of cases exhibiting QTc prolongation and life-threatening dysrhythmias including ventricular tachycardia (VT)/ventricular fibrillation (VF), TdP, and asystole in patients exposed to these substances. Retrospective chart review of cases reported to our Regional Poison Center from 2014 to 2019 of exposures to one or more of the "Known Risk" substances was performed. Demographics, therapies, clinical effects, and medical outcome for each case were analyzed. There were 1125 exposures, of which 760 had a documented QTc interval. QTc ≥ 500 ms was reported in 138 (18.2%) of the 760 cases. The most common "Known Risk" substances were citalopram, escitalopram and cocaine. Although not in the "Known Risk" category, mirtazapine, amitriptyline, diphenhydramine, and trazodone had a statistically significant association with QTc > 500 ms. Life-threatening dysrhythmias occurred in 13 cases, with VT/VF in 6 of the 760 (0.8%) cases, and one case of TdP. Flecainide (OR 11.1, 95% CI 2.2-55.8) and methadone (OR 7.1, 95% CI 2.1-23.4) were associated with increased risk of all life-threatening dysrhythmias. Exposures to medications on the Credible Meds list of "Known Risk of TdP" QTc prolongation is common, but life-threatening dysrhythmias are rare. Mirtazapine, amitriptyline, diphenhydramine, and trazodone were associated with prolonged QTc. Flecainide and methadone had the highest associated risk of life-threatening dysrhythmias.
Pregnancy is associated with the activation of the hypothalamus-pituitary-adrenal axis, which can cause a misdiagnosis of Cushing's syndrome. The aim of this study is to evaluate the impact of pregnancy after pituitary surgery on the recurrence rate in Cushing's disease (CD) patients.

This was a retrospective study in a tertiary center. Between 1990 and 2020, 355 CD patients underwent pituitary surgery. Of those, we included 113 female patients who were ≤ 45 years old (median age of 32 years, 14-45), PS remission, a follow-up of ≥6 months (median of 122 months, 6-402) and an available obstetric history. Recurrence was defined as the diagnosis of Cushing's syndrome via at least two altered first-line methods. The patients were divided into two subgroups according to pregnancy no pregnancy or pregnancy prior to CD diagnosis (NP/PP) and pregnancy after CD pituitary surgery (PA).

Overall, recurrence occurred in 43 out of 113 patients (38%). A higher recurrence rate was seen in the PA subgroup (11/22, 50%), but there was no significant difference between the NP/PP subgroup (32/91, 35%). No difference in survival-free recurrence (SFR) was found between NP/PP and PA subgroups. The lower SFR was related to a higher PS plasma ACTH and normal pituitary at pathological analyses.

There was no difference in the recurrence rate in patients according to pregnancy history. Other studies with higher numbers of patients are needed to confirm these data.
There was no difference in the recurrence rate in patients according to pregnancy history. Other studies with higher numbers of patients are needed to confirm these data.In this study, deaths from lightning strikes in Eastern Turkey revealed distinct patterns in lifestyle and physical injury. Farmers, sailors, and those engaged in outdoor sports are all at risk of being struck by lightning. Death from a lightning strike is associated with cardiovascular and central nervous system damage. This study examines cases of autopsies that were performed on bodies that had suffered a lightning strike, including sociodemographic data, burns on the body, injured regions, histopathological findings, and causes of death. This retrospective evaluation included 17 cases. The cases comprised 88.2% males and 11.8% females, with a mean age of 41.5 years. The person's occupation was farmer in 29.4% of the cases and shepherd in 70.6%. Their deaths occurred most frequently in the summer months. Deaths associated with lightning strikes are more frequent in east of Turkey than in other regions, as agriculture and livestock are common sources of income. The majority of the victims among the cases were males working outside because of their occupations. Histopathologically, subarachnoid fresh bleeding was seen in five cases, subpleural fresh bleeding in the lungs in five cases, and interlobular rupture in the lungs in three cases. Deaths associated with lightning strikes have been correlated with a low level of education in this subject. This study is the largest case study of deaths associated with lightning strikes in Turkey.During a helicopter exercise, due to the scarce visibility caused by the presence of snow, a collision between a landing helicopter and one already on the ground occurred. The 40-year-old pilot of the already landed aircraft was killed as a result of a direct propeller impact in the right side of the pilot's cockpit, while the co-pilot remained uninjured. At autopsy, the macroscopic characteristic findings in the form of cut injuries and amputations along the axis of the rotor blade impact as well as a 3D reconstruction through CT-Scan were analyzed and discussed for a thorough reconstruction of the injuries and the dynamics.
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