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Neonatal infections remain an important cause of neonatal morbidity and mortality worldwide. Neonatal sepsis is a systemic infection that can be classified as early-onset or late-onset pending the timing of presentation. The pathophysiology and causative pathogens of neonatal sepsis vary, with early-onset sepsis being associated with a vertically transmitted infection from mother to neonate versus late onset sepsis being commonly associated with nosocomial infections. The signs and symptoms of neonatal sepsis mimic those associated with prematurity, making timely diagnosis difficult for treating clinicians. The management of neonatal sepsis is centered around obtaining adequate culture data and initiation of broad-spectrum parenteral antibiotics. Controversies surrounding the management of neonatal sepsis include the administration of empiric antibiotics, given recent clinical studies associating early antibiotic use with clinical sequelae such as late-onset sepsis, necrotizing enterocolitis, and death in the preterm, low-birthweight infant population.Neonates experience significant moderate and severe postoperative pain. Effective postoperative pain management in neonates is required to minimize acute and long-term effects of neonatal pain. Protecting the developing nervous system from persistent sensitization of pain pathways and developing primary hyperalgesia is essential. Opioids and acetaminophen are commonly analgesics used for pain control. Regional anesthesia provides adequate intraoperative and postoperative analgesia in neonates. It decreases exposure to opioids, reduces adverse drug effects, and facilitates early extubation. It suppresses the stress response and can prevent long-term behavioral responses to pain. The most common blocks performed in neonates are neuraxial blocks. Using ultrasound increased the number of peripheral nerve blocks performed in neonates. Recently, various peripheral nerve blocks (paravertebral, transverse abdominis plane, rectus sheath, quadratus lumborum, erector spinae plane blocks) were safely used. Many studies support analgesic efficacy but highlight neonates' unpredictability and variability of fascial blocks.Neurovascular disorders is a heterogenous group of diseases, including one of the most time critical disorders in emergency medicine; stroke. Sex differences are extensively described in neurovascular disorders, ranging from differences in symptom presentation, risk factors, treatment and outcomes. For example, women with stroke, more often present with generalized weakness, reduced consciousness and headache than men. Furthermore, there are differences in risk factors, outcomes and in the effect of secondary prevention. Women have a higher risk of cerebral venous thrombosis and developing cerebral aneurysms. In general, women have been underrepresented in trials on neurovascular disorders. This chapter provides an extensive overview of sex differences in stroke in general and in the differences specially seen in ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage and in cerebral venous thrombosis.The high incidence of concussions/mild traumatic brain injury and the significant number of people with persisting concussion symptoms as well as the concern for delayed, neurodegenerative effects of concussions makes them a major public health concern. There is much to learn on concussions with respect to pathophysiology as well as vulnerability and resiliency factors. The heterogeneity in outcome after a concussion warrants a more personalized approach to better understand the biological and psychosocial factors that may affect outcome. In this chapter we address biological sex and gender as they impact different aspects of concussion including incidence, risk factors and outcome. As well, this chapter will provide a more fulsome overview of intimate partner violence, an often-overlooked cause of concussion in women. Applying the sex and gender lens to concussion/mild traumatic brain injury is imperative for discovery of its pathophysiology and moving closer to treatments.Migraine is one of the leading causes of disability worldwide, especially in women younger than 50 years old. Migraine has three times higher prevalence in women than in men and tends to decrease after the menopausal transition. check details Migraine has different clinical features in people of different ages. Clinical symptoms and factors associated with migraine can be various in women and men. Women have special types of migraine, such as pure menstrual migraine and menstrually related migraine. Besides, clinical symptoms of migraine can change during pregnancy, postpartum and lactation. Women are significantly more often than men consulting a doctor because of migraine. These features of migraine lead to different treatment and management strategies in females and males of different ages. Migraine therefore is a disorder that demonstrates the necessity of a personalization of healthcare-ensuring the proper treatment for the right patient, at the right time. Considering all the available literature and guidelines, in this chapter several strategies for management of acute and prophylactic treatments of migraine, according to sex and age differences, are discussed. The purpose of this chapter is to provide a useful piece of information improving the treatment and management of migraine.Chronic pain affects 20% of adults and is one of the leading causes of disability worldwide. Women and girls are disproportionally affected by chronic pain. About half of chronic pain conditions are more common in women, with only 20% having a higher prevalence in men. There are also sex and gender differences in acute pain sensitivity. Pain is a subjective experience made up of sensory, cognitive, and emotional components. Consequently, there are multiple dimensions through which sex and gender can influence the pain experience. Historically, most preclinical pain research was conducted exclusively in male animals. However, recent studies that included females have revealed significant sex differences in the physiological mechanisms underlying pain, including sex specific involvement of different genes and proteins as well as distinct interactions between hormones and the immune system that influence the transmission of pain signals. Human neuroimaging has revealed sex and gender differences in the neural circuitry associated with pain, including sex specific brain alterations in chronic pain conditions. Clinical pain research suggests that gender can affect how an individual contextualizes and copes with pain. Gender may also influence the susceptibility to develop chronic pain. Sex and gender biases can impact how pain is perceived and treated clinically. Furthermore, the efficacy and side effects associated with different pain treatments can vary according to sex and gender. Therefore, preclinical and clinical research must include sex and gender analyses to understand basic mechanisms of pain and its relief, and to develop personalized pain treatment.The importance of sex differences in neurological disorders has been increasingly acknowledged in recent clinical and basic research studies, but the complex biology and genetics underlying sex-linked biological heterogeneity and its brain-to-body impact remained incompletely understood. Men and women differ substantially in their susceptibility to certain neurological diseases, in the severity of symptoms, prognosis as well as the nature and efficacy of their response to treatments. The detailed mechanisms underlying these differences, especially at the molecular level, are being addressed in many studies but leave a lot to be further revealed. Here, we provide an overview of recent advances in our understanding of how sex differences in the brain and brain-body signaling contribute to neurological disorders and further present some future prospects entailed in terms of diagnostics and therapeutics.Sex and gender differences in epilepsy are important influencing factors in epilepsy care. In epilepsy, the hormonal differences between the sexes are important as they impact specific treatment considerations for patients at various life stages particularly during early adulthood with establishment of the menstrual cycle, pregnancy, perimenopause and menopause. Choice of antiseizure medication may have direct consequences on hormonal cycles, hormonal contraception, pregnancy and fetal risk of major congenital malformation. Conversely hormones whether intrinsic or extrinsically administered may have direct impact on antiseizure medications and seizure control. This chapter explores these important influences on the management of persons with epilepsy.The dementia landscape has undergone a striking paradigm shift. The advances in understanding of neurodegeneration and proteinopathies has changed our approach to patients with cognitive impairment. Firstly, it has recently been shown that the various proteinopathies that are the cause of the dementia begin to build up long before the appearance of any obvious symptoms. This has cemented the idea that there is an urgency in diagnosis as it occurs very late in the pathophysiology of these diseases. Secondly, that accurate diagnosis is required to deliver targeted therapies, that is precision medicine. With this latter point, the realization that various factors of a person need to be considered as they may impact the presentation and progression of disease has risen to the forefront. Two of these factors aside from race and age are biological sex and gender (social construct), as both can have tremendous impact on manifestation of disease. This chapter will cover what is known and remains to be known on the interaction of sex and gender with some of the major causes of dementia.Multiple sclerosis (MS), Neuromyelitis optica spectrum disorder (NMOSD) and Myelin-Oligodendrocyte-Glycoprotein antibody associated disorder (MOGAD) are demyelinating disorders of the central nervous system (CNS) of autoimmune origin. Here, we summarize general considerations on sex-specific differences in the immunopathogenesis and hormonal influences as well as key clinical and epidemiological elements. Gender-specific issues are widely neglected starting with the lacking separation of sex as a biological variable and gender comprising the sociocultural components. As for other autoimmune diseases, female preponderance is common in MS and NMOSD. However, sex distribution in MOGAD seems equal. As in MS, immunotherapy in NMOSD and MOGAD is crucial to prevent further disease activity. Therefore, we assessed data on sex differences of the currently licensed disease-modifying treatments for efficacy and safety. This topic seems widely neglected with only fragmented information resulting from post-hoc analyses of clinical trials or real-world post-marketing studies afflicted with lacking power and/or inherent sources of bias. In summary, biological hypotheses of sex differences including genetic factors, the constitution of the immune system and hormonal influences are based upon human and preclinical data, especially for the paradigmatic disease of MS whereas specific data for NMOSD and MOGAD are widely lacking. Epidemiological and clinical differences between men and women are well described for MS and to some extent for NMOSD, yet, with remaining contradictory findings. MOGAD needs further detailed investigation. Sex-specific analyses of safety and efficacy of long-term immunotherapies need to be addressed in future studies designed and powered to answer the pressing questions and to optimize and individualize treatment.

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