Retrospective analysis of 261 autopsies of penetrating cardiac injuries with emphasis on sociodemographic factors.

Penetrating cardiac injuries (PCIs) are highly lethal and several factors are related to its incidence and mortality. While most studies focus on characterizing patients who arrived at a medical facility alive and exploring the relationship between the degree of heart compromise and mortality, our study delved deeper into the topic. This study analyzed 261 autopsy reports from 2017 in Bogotá, Colombia, and characterized the factors surrounding PCI incidence and mortality while emphasizing the role of sociodemographic variables. Of these cases, 247 (94.6%) were males with a mean age of 29.19 ± 9.7 years. Weekends, holidays, and late hours had the highest incidence of PCIs. The victims' deaths occurred at the scene in 66 (25.3%) cases, and 65.1% of the victims died before receiving medical care. Upon admission, patients with vital signs were more likely to have been transported by taxi or a private vehicle. Two or more compromised cardiac chambers, increased time of transportation, trauma occurred in the city outskirts, and gunshot wounds were related to increased mortality. Our data is valuable for surgeons, health system managers, and policy analysts as we conducted a holistic assessment of the anatomical and sociodemographic factors that are closely associated with mortality following a PCI. Surgeons must recognize that PCIs can occur even when the entrance wound is outside the cardiac box. Reinforcing hospital infrastructure in the outskirts and improving the availability, accuracy, and response time of first responders may lead to improved patient mortality rates.

Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disease and the most frequent cause of progressive dementia in senior adults. It is characterized by memory loss and cognitive impairment secondary to cholinergic dysfunction and N-methyl-D-aspartate (NMDA)-mediated neurotoxicity. Intracellular neurofibrillary tangles, extracellular plaques composed of amyloid-ß (Aß), and selective neurodegeneration are the anatomopathological hallmarks of this disease. The dysregulation of calcium may be present in all the stages of AD, and it is associated with other pathophysiological mechanisms, such as mitochondrial failure, oxidative stress, and chronic neuroinflammation. Although the cytosolic calcium alterations in AD are not completely elucidated, some calcium-permeable channels, transporters, pumps, and receptors have been shown to be involved at the neuronal and glial levels. In particular, the relationship between glutamatergic NMDA receptor (NMDAR) activity and amyloidosis has been widely documented. Other pathophysiological mechanisms involved in calcium dyshomeostasis include the activation of L-type voltage-dependent calcium channels, transient receptor potential channels, and ryanodine receptors, among many others. This review aims to update the calcium-dysregulation mechanisms in AD and discuss targets and molecules with therapeutic potential based on their modulation.

Molecular and cellular mechanisms leading to catatonia: an integrative approach from clinical and preclinical evidence.

This review aims to describe the clinical spectrum of catatonia, in order to carefully assess the involvement of astrocytes, neurons, oligodendrocytes, and microglia, and articulate the available preclinical and clinical evidence to achieve a translational understanding of the cellular and molecular mechanisms behind this disorder. Catatonia is highly common in psychiatric and acutely ill patients, with prevalence ranging from 7.6% to 38%. It is usually present in different psychiatric conditions such as mood and psychotic disorders; it is also a consequence of folate deficiency, autoimmunity, paraneoplastic disorders, and even autistic spectrum disorders. Few therapeutic options are available due to its complexity and poorly understood physiopathology. We briefly revisit the traditional treatments used in catatonia, such as antipsychotics, electroconvulsive therapy, and benzodiazepines, before assessing novel therapeutics which aim to modulate molecular pathways through different mechanisms, including NMDA antagonism and its allosteric modulation, and anti-inflammatory drugs to modulate microglia reaction and mitigate oxidative stress, such as lithium, vitamin B12, and NMDAr positive allosteric modulators.

Revisiting Excitotoxicity in Traumatic Brain Injury: From Bench to Bedside.

Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality. Consequences vary from mild cognitive impairment to death and, no matter the severity of subsequent sequelae, it represents a high burden for affected patients and for the health care system. Brain trauma can cause neuronal death through mechanical forces that disrupt cell architecture, and other secondary consequences through mechanisms such as inflammation, oxidative stress, programmed cell death, and, most importantly, excitotoxicity. This review aims to provide a comprehensive understanding of the many classical and novel pathways implicated in tissue damage following TBI. We summarize the preclinical evidence of potential therapeutic interventions and describe the available clinical evaluation of novel drug targets such as vitamin B12 and ifenprodil, among others.