5 research outputs found

    Fc<i>ő≥</i>RIIa - dependent platelet activation identified in COVID-19 vaccine-induced immune thrombotic thrombocytopenia-, heparin-induced thrombocytopenia, streptokinase- and anisoylated plasminogen-streptokinase activator complex-induced platelet activation

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    Coronavirus disease 2019 (COVID-19), which was caused by the coronavirus - severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was globally responsible for remarkable morbidity and mortality. Several highly effective vaccines for COVID-19 were developed and disseminated worldwide within an unprecedented timescale. Rare but dangerous clotting and thrombocytopenia events, and subsequent coagulation abnormalities, have been reported after massive vaccination against SARS-CoV-2. Soon after their global rollout, reports of a morbid clinical syndrome following vaccination with adenovirus-DNA-based vaccines appeared. In the spring of 2021, reports of a novel, rare and morbid clinical syndrome, with clinically devastating and fatal complication after vaccination with adenovirus-based coronavirus vaccines (Janssen/Johnson & Johnson and Astra-Zeneca vaccines) led to a brief suspension of their use by several countries. Those complications were associated with unusual cerebral and splanchnic venous thrombosis, and circulating autoantibodies directed against anti-platelet factor 4 (PF4), a protein secreted from platelets, leading to the designation: Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT). The reported VITT incidence remains very low and does not affect the overall benefit of immunization, however, if left untreated, VITT can be debilitating or even fatal. VITT resembled specific adverse drugs' reactions that also involved the production of autoantibodies and subsequent abnormal platelet activation through platelet Fcő≥RIIa. These unusual but well-documented drug reactions were heparin-induced thrombocytopenia (HIT), streptokinase- (SK), and anisoylated plasminogen-streptokinase activator complex- (APSAC) associated with platelet-activating antibodies. There was considerable overlapping of clinical features between VITT, COVID-19 and these adverse drugs' reactions. We review the phenomenon of VITT against the backdrop of shared and common mechanisms that underlie HIT-, SK-, and APSAC-platelet Fcő≥RIIa-dependent platelet activation. An understanding of VITT's pathogenesis may be achieved by comparing and contrasting VITT-, HIT-, SK- and APSAC-induced platelet activation mechanisms, their respective physiopathology and similarities. Discussing these conditions in parallel provides insight into complex immunological disorders and diseases associated with abnormal hemostasis and thrombosis in particular.¬†</p

    Exploring non-pharmacological methods for pre-operative pain management

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    The management of pain is an essential aspect of surgical care, and pain levels in post-operative patients vary case by case. Treating postoperative pain is crucial as it leads to better outcomes and reduces risk of long term pain. While post-operative analgesics has been the mainstay of treatment, this mini-review explores an emerging concept which is preoperative pain management, with promising potential. Such interventions include educating patients on the expected pain outcomes and available pain medications. Non-pharmacological methods such as relaxation exercises have also proven to be effective after abdominal surgery, and educating patients on the existence of such methods pre-operatively encourages them to make use of available therapies. A major area of importance is the pre-operative psychological and emotional wellbeing of patients, as it is a strong predictor of pain and pain prognosis. Cognitive Behavioral Therapy can be effectively used to tackle preoperative anxiety and reduce pain levels. Hypnosis is another developing modality for decreasing stress. Lastly, long term pre-operative opioid use has been linked with higher pain scores and longer pain duration. This provides the basis on which pre-operative opioid weaning can lead to favorable post-operative pain outcomes. While many of these methods have not been experimented on recipients of abdominal surgery in specific, it still paves the path for newer pain control strategies that can eventually be adopted for visceral surgery patients. This review points the reader and researchers to new and developing areas that hold the potential to revolutionize current established pain management guidelines. </p

    The association between stress, emotional states, and tinnitus: a mini-review

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    Extensive literature supporting the view of tinnitus induced stress in patients is available. However, limited evidence has been produced studying the opposite, that is, does stress cause tinnitus? The hypothalamus pituitary adrenal axis, one of the main neuroendocrine systems involved in stress response, is commonly disturbed in tinnitus patients. Patients with chronic tinnitus have been shown to develop abnormal responses to psycho-social stress, where the hypothalamus pituitary adrenal axis response is weaker and delayed, suggesting chronic stress contributes to the development of chronic tinnitus. The sympathetic branch of the autonomic nervous system also plays a major role in stress response and its chronic hyperactivity seems to be involved in developing tinnitus. Psycho-social stress has been shown to share the same probability of developing tinnitus as occupational noise and contributes to worsening tinnitus. Additionally, exposure to high stress levels and occupational noise doubles the likelihood of developing tinnitus. Interestingly, short-term stress has been shown to protect the cochlea in animals, but chronic stress exposure has negative consequences. Emotional stress also worsens pre-existing tinnitus and is identified as an important indicator of tinnitus severity. Although there is limited body of literature, stress does seem to play a vital role in the development of tinnitus. This review aims to highlight the association between stress, emotional states, and the development of tinnitus while also addressing the neural and hormonal pathways involved. </p

    Inhibition of aquaporins as a potential adjunct to breast cancer cryotherapy

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    Cryoablation is an emerging type of treatment for cancer. The sensitization of tumors using cryosensitizing agents prior to treatment enhances ablation efficiency and may improve clinical outcomes. Water efflux, which is regulated by aquaporin channels, contributes to cancer cell damage achieved through cryoablation. An increase in aquaporin (AQP) 3 is cryoprotective, whereas its inhibition augments cryodamage. The present study aimed to investigate aquaporin (AQP1, AQP3 and AQP5) gene expression and cellular localization in response to cryoinjury. Cultured breast cancer cells (MDA-MB-231 and MCF-7) were exposed to freezing to induce cryoinjury. RNA and protein extracts were then analyzed using reverse transcription-quantitative PCR and western blotting, respectively. Localization of aquaporins was studied using immunocytochemistry. Additionally, cells were transfected with small interfering RNA to silence aquaporin gene expression and cell viability was assessed using the Sulforhodamine B assay. Cryoinjury did not influence gene expression of AQPs, except for a 4-fold increase of AQP1 expression in MDA-MD-231 cells. There were no clear differences in AQP protein expression for either cell lines upon exposure to frozen and non-frozen temperatures, with the exception of fainter AQP5 bands for non-frozen MCF-7 cells. The exposure of cancer cells to freezing temperatures altered the localization of AQP1 and AQP3 proteins in both MCF-7 and MDA-MD-231 cells. The silencing of AQP1, AQP3 and AQP5 exacerbated MDA-MD-231 cell damage associated with freezing compared with control siRNA. This was also observed with AQP3 and AQP5 silencing in MCF-7 cells. Inhibition of aquaporins may potentially enhance cryoinjury. This cryosensitizing process may be used as an adjunct to breast cancer cryotherapy, especially in the border area targeted by cryoablation where freezing temperatures are not cold enough to induce cellular damage

    Beneficial use and potential effectiveness of physical activity in managing autism spectrum disorder

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    Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by poor social and communication skills. Therapeutic interventions are behavioral and educational-normally delivered as structured programs. Several well-established programs exist and most of them do not incorporate physical activity and exercise as core elements. Deficiencies in motor skills are associated with ASD and physical activity has been shown to reduce maladaptive behaviors with autistics. However, the notion of exercise being employed to manage autism is controversial. Meta-analysis and systematic reviews have concluded that physical activity has positive effects on social skills and behavior in young children and adolescents with autism. Activities such as martial arts have been singled out as being particularly beneficial. Established programs such as TEACCH have been successfully modified, as research trials, to be more physical activity-based and have shown positive results. Studies have also reinforced the importance of the role of parental involvement in delivering programs based on physical activity. There is a paucity of research evidence about the long-term effects of physical activity-based interventions. There is also disparity over the detailed nature of the activities and exercises that compose an effective program. Each person with autism has a highly individualized set of symptoms and characteristics for which highly individualized programs are warranted. This is especially true for physical activity programs
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