Rejected

P2 purinergic receptors are involved in the normal function of the kidney, bladder, and prostate via signaling that occurs in response to extracellular nucleotides. Dysregulation of these receptors is common in pathological states and often associated with disease initiation, progression, or aggressiveness. Indeed, P2 purinergic receptor expression is altered across multiple urologic disorders including chronic kidney disease, polycystic kidney disease, interstitial cystitis, urinary incontinence, overactive bladder syndrome, prostatitis, and benign prostatic hyperplasia. P2 purinergic receptors are likewise indirectly associated with these disorders via receptor-mediated inflammation and pain, a common characteristic across most urologic disorders. Furthermore, select P2 purinergic receptors are overexpressed in urologic cancer including renal cell carcinoma, urothelial carcinoma, and prostate adenocarcinoma, and pre-clinical studies depict P2 purinergic receptors as potential therapeutic targets. Herein, we highlight the compelling evidence for the exploration of P2 purinergic receptors as biomarkers and therapeutic targets in urologic cancers and other urologic disease. Likewise, there is currently optimism for P2 purinergic receptor-targeted therapeutics for the treatment of inflammation and pain associated with urologic diseases. Further exploration of the common pathways linking P2 purinergic receptor dysregulation to urologic disease might ultimately help in gaining new mechanistic insight into disease processes and therapeutic targeting.

Epidemiological studies have shown that a substantial proportion of acute coronary events occur in individuals who lack the traditional high-risk cardiovascular (CV) profile. Mental stress is an emerging risk and prognostic factor for coronary artery disease and stroke, independently of conventional risk factors. It is associated with an increased rate of CV events. Acute mental stress may develop as a result of anger, fear, or job strain, as well as consequence of earthquakes or hurricanes. Chronic stress may develop as a result of long-term or repetitive stress exposure, such as job-related stress, low socioeconomic status, financial problems, depression, and type A and type D personality. While the response to acute mental stress may result in acute coronary events, the relationship of chronic stress with increased risk of coronary artery disease (CAD) is mainly due to acceleration of atherosclerosis. Emotionally stressful stimuli are processed by a network of cortical and subcortical brain regions, including the prefrontal cortex, insula, amygdala, hypothalamus, and hippocampus. This system is involved in the interpretation of relevance of environmental stimuli, according to individual's memory, past experience, and current context. The brain transduces the cognitive process of emotional stimuli into hemodynamic, neuroendocrine, and immune changes, called fight or flight response, through the autonomic nervous system and the hypothalamic-pituitary-adrenal axis. These changes may induce transient myocardial ischemia, defined as mental stress-induced myocardial ischemia (MSIMI) in patients with and without significant coronary obstruction. The clinical consequences may be angina, myocardial infarction, arrhythmias, and left ventricular dysfunction. Although MSIMI is associated with a substantial increase in CV mortality, it is usually underestimated because it arises without pain in most cases. MSIMI occurs at lower levels of cardiac work than exercise-induced ischemia, suggesting that the impairment of myocardial blood flow is mainly due to paradoxical coronary vasoconstriction and microvascular dysfunction.

The investigators aimed to describe the clinical experience of a single center reporting on neuropsychiatric findings among patients experiencing persistent symptoms as part of post-acute sequelae of SARS-CoV-2 (PASC) infection.

The management of sedation in the setting of COVID-19 ("COVID") by Ego et al. […].

A man in his 70s presented with a 4-day history of bilateral frontal headache and heaviness of the face. He was unable to close either of his eyes, to wrinkle his forehead bilaterally and to raise either corner of his mouth. The patient was admitted with a diagnosis of bilateral facial palsy. From history, epidemiology, physical and laboratory findings, Bell's palsy was considered more probable than viral infection, Guillain-Barré syndrome and sarcoidosis. Oral administration of prednisolone, valacyclovir and mecobalamin were initiated promptly, which improved his symptoms. In areas in which Lyme disease is not endemic, we believe that Bell's palsy is the most probable cause of isolated bilateral facial palsy. Patients with bilateral facial paralysis under the suspicion of Bell's palsy should be immediately started on steroid therapy.

Interleukin 31 belongs to the IL-6 superfamily, and it is an itch mediator already studied in several diseases, comprising atopic dermatitis, allergic pathologies, and onco-hematological conditions. This research aims to assess the role of this cytokine in the pathogenesis of these conditions and its potential therapeutic role. The research has been conducted on articles, excluding reviews and meta-analysis, both on animals and humans. The results showed that IL-31 plays a crucial role in the pathogenesis of systemic skin manifestations, prognosis, and itch severity. Traditional therapies target this interleukin indirectly, but monoclonal antibodies (Mab) directed against it have shown efficacy and safety profiles comparable with biological drugs that are already available. Future perspectives could include the development of new antibodies against IL-31 both for humans and animals, thus adding a new approach to the therapy, which often has proven to be prolonged and specific for each patient.

Effective analgesia after total hip arthroplasty must minimize pain and optimize early ambulation. Lumbar plexus blocks (LPBs) provide analgesia but may cause motor weakness. Quadratus lumborum blocks (QLBs) may provide analgesia with preserved motor strength.

Transcranial magnetic stimulation (TMS) has emerged as a novel technique to stimulate the human brain through the scalp. Over the years, identifying the optimal brain region and stimulation parameters has been a subject of debate in the literature on therapeutic uses of repetitive TMS (rTMS). Nevertheless, the primary motor cortex (M1) has been a conventional target for rTMS to treat motor symptoms, such as hemiplegia and spasticity, as it controls the voluntary movement of the body. However, with an expanding knowledge base of the M1 cortical and subcortical connections, M1-rTMS has shown a therapeutic efficacy that goes beyond the conventional motor rehabilitation to involve pain, headache, fatigue, dysphagia, speech and voice impairments, sleep disorders, cognitive dysfunction, disorders of consciousness, anxiety, depression, and bladder dysfunction. In this review, we summarize the latest evidence on using M1-rTMS to treat non-motor symptoms of diverse etiologies and discuss the potential mechanistic rationale behind the management of each of these symptoms.

Poststroke thalamic pain (PS-TP), a type of central poststroke pain, has been challenged to improve the rehabilitation outcomes and quality of life after a stroke. It has been shown in 2.7-25% of stroke survivors; however, the treatment of PS-TP remains difficult, and in majority of them it often failed to manage the pain and hypersensitivity effectively, despite the different pharmacotherapies as well as invasive interventions. Central imbalance, central disinhibition, central sensitization, other thalamic adaptative changes, and local inflammatory responses have been considered as its possible pathogenesis. Allodynia and hyperalgesia, as well as the chronic sensitization of pain, are mainly targeted in the management of PS-TP. Commonly recommended first- and second-lines of pharmacological therapies, including traditional medications, e.g., antidepressants, anticonvulsants, opioid analgesics, and lamotrigine, were more effective than others. Nonpharmacological interventions, such as transcranial magnetic or direct current brain stimulations, vestibular caloric stimulation, epidural motor cortex stimulation, and deep brain stimulation, were effective in some cases/small-sized studies and can be recommended in the management of therapy-resistant PS-TP. Interestingly, the stimulation to other areas, e.g., the motor cortex, periventricular/periaqueductal gray matter, and thalamus/internal capsule, showed more effect than the stimulation to the thalamus alone. Further studies on brain or spinal stimulation are required for evidence.