Rejected

Emergence agitation (EA), which is also referred to as emergence delirium, can lead to clinically significant consequences. The mechanism of EA remains unclear. Proposed contributors to EA include age, male sex, type of surgery, emergency operation, use of inhalational anesthetics with low blood-gas partition coefficients, long duration of surgery, anticholinergics, premedication with benzodiazepines, voiding urgency, postoperative pain, and the presence of invasive devices. If pre- or intraoperative objective monitoring could predict the occurrence of agitation during emergence, this would help to reduce the adverse consequences of EA. Several tools are available for assessing EA; however, its incidence varies considerably according to the assessment tool and definition of EA used, due to the absence of standardized clinical research practice guidelines. Total intravenous anesthesia, propofol, μ-opioid agonists, N-methyl-D-aspartate receptor antagonists, nefopam, α2-adrenoreceptor agonists, regional analgesia, multimodal analgesia, parent-present induction, and preoperative education for surgery may contribute to prevention of EA. However, it is difficult to identify patients at high risk for EA and to properly apply EA prevention methods in various clinical situations, because both risk factors and preventive strategies often show inconsistent results depending on the methodology of the study and the patients assessed. This review discusses the most important research topics related to EA and directions for future research.

: The spacious active site cavity of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) shows a great versatility for a variety of binding modes for modulators of activity, inhibitors, and activators, some of which are clinically used drugs.: There are at least four well-documented CA inhibition mechanisms and the same number of binding modes for CA inhibitors (CAIs), one of which superposes with the binding of activators (CAAs). They include (i) coordination to the catalytic metal ion; (ii) anchoring to the water molecule coordinated to the metal ion; (iii) occlusion of the active site entrance; and (iv) binding outside the active site. A large number of chemical classes of CAIs show these binding modes explored in detail by kinetic, crystallographic, and other techniques. The tail approach was applied to all of them and allowed many classes of highly isoform-selective inhibitors. This is the subject of our review.: All active site regions of CAs accommodate inhibitors to bind, which is reflected in very different inhibition profiles for such compounds and the possibility to design drugs with effective action and new applications, such as for the management of hypoxic tumors, neuropathic pain, cerebral ischemia, arthritis, and degenerative disorders.

Optimal pain management in the palliative care setting often requires multiple pharmacological interventions including novel and off-label therapies. Ketamine is an anesthetic agent with increasing evidence supporting its use for pain. Through -methyl-d-aspartate antagonism and activity at opioid receptors, it is an adjuvant to traditional analgesics with the benefit of being opioid sparing. Ketamine has a wide safety profile with limited reports of overdose. Little is published on supratherpeutic dosing in the pain setting. We report a case of a 41-year-old male with refractory nociceptive and neuropathic cancer-related pain. Conventional therapies were ineffective. Ketamine was initiated to reduce opioid burden and attenuate pain with good response. The patient received an iatrogenic overdose (10 times ordered dose) of the drug. Several self-limited physiologic and psychologic reactions were observed during subsequent monitoring. This is a study and analysis of a patient with refractory nociceptive and neuropathic pain syndrome treated with ketamine who sustained an iatrogenic overdose of ketamine. Ketamine's use to treat pain is increasing along with its evidence of efficacy. Despite ketamine's wide safety profile, the medication is not without risk, especially in palliative care wherein patients are on multiple drugs with potentially severe interactions. Careful examination of the risks of overdose, especially of the various formulations of the drug, is needed.

Metastasis in the pineal region is a rare condition. To best of our knowledge, there is no case report of isolated pineal metastasis secondary to acute lymphocytic leukemia (ALL). The aim of this study is to show the pineal gland involvement of ALL in a case for the first time in the literature. A 25-year-old male patient diagnosed with ALL 2 years ago presented with headache and visual impairment. Brain magnetic resonance imaging (MRI) revealed a well-defined solid lesion which was revealed intensive enhancement after contrast. On diffusion-weighted images, the lesion showed significant diffusion restriction. Three months after therapy, control MRI demonstrated a completely resorbed pineal lesion. The pineal region may be a possible site of metastasis and involvement due to the absence of a blood-brain barrier, and should not be overlooked in patients with not only solid cancers but also ALL.

Ocimum basilicum L. is a perennial herb that has been used in traditional Asian Indian medicine for thousands of years as a natural anti-inflammatory, antibiotic, diuretic, and analgesic.

The morphology of scabies, a mite infestation of worldwide proportion, is characterized by a variety of cutaneous lesions. Patients with classic scabies present with characteristic burrows often located on the web spaces of the fingers and toes. Scabies surrepticius refers to the non-classic atypical presentation of scabies; establishing the diagnosis of scabies in these individuals can be difficult. To facilitate the diagnosis of scabies, criteria have been proposed by the International Alliance for the Control of Scabies (IACS). These criteria are intended for scabies research; however, they can be utilized by clinicians to establish either a confirmed diagnosis, a clinical diagnosis or a suspected diagnosis of scabies. Visualization of mites, eggs or feces is necessary for a confirmed diagnosis of scabies. A clinical diagnosis can be established by observation of either genital lesions in men or burrows or classically distributed classical lesions in individuals with two historic features: pruritus and close contact with an individual who itches and has classically distributed classical scabetic lesions. The clinical features and management of a woman residing in an assisted living environment with a confirmed diagnosis of scabies and a man with a clinical diagnosis of scabies are described. The criteria for the suspected diagnosis of scabies require either one historic feature and typical lesions in a typical distribution or both historic features and the presence of atypical lesions or an atypical distribution of the skin lesions. Once the diagnosis of scabies is established, not only the patient but also close contacts should receive treatment with either a topical medication (such as permethrin 5% cream) or a systemic drug (ivermectin) or both. The number and frequency of treatments are variable; classic scabies typically is managed with a total of two treatments performed weekly to biweekly. Patients with crusted scabies usually require multiple topical and oral antiscabetic treatments in addition to topical keratolytic therapy. Bacterial impetiginization or infection (most commonly by Staphylococcus aureus or Streptococcus pyogenes) can complicate scabies infestation and potentially result in cellulitis, abscess, sepsis, rheumatic fever, rheumatic heart disease and post-streptococcal glomerulonephritis; therefore, in some patients, systemic antimicrobial therapy may be necessary in addition to scabies-directed treatment. In addition to systemic antihistamines, oral and/or topical corticosteroids may be used to provide symptomatic pruritus relief once the diagnosis of scabies has been established and mite-directed treatment has been initiated. The clinician should consider several potential causes (such as inadequate treatment, reinfection, mite resistance, delusions of parasitosis and the development of a new non-scabetic dermatosis) in scabies patients who fail to respond to treatment with a topical or oral scabicide therapy.

Acute nasal symptoms are troublesome for patients. In addition, these symptoms are encountered frequently by individuals because of common infectious diseases, especially rhinovirus, giving rise to a 'common cold'. Acute nasal symptoms include rhinorrhoea, sneezing, nasal itch and congestion. Of these, nasal congestion is the most irritating. Because topical nasal decongestants provide rapid and dramatic relief from these symptoms, especially nasal congestion, they are frequently used and abused by patients. Guidance for indications, choice of most efficacious decongestant and recommendations for limiting side effects are thus essential to be imparted to patients by doctors.

Addison disease, corticosteroid withdrawal, and taking synthetic growth hormone have been linked with development of intracranial hypertension, but there is still debate on whether administration of other exogenous hormones plays a role in precipitating elevated pressure. The growing use of hormonal therapy for gender affirmation provides an opportunity to explore this possibility.

Serious infection elicits inflammatory processes that act through a range of molecular pathways, including cytokine signaling. It is not established however that noradrenaline (NA), a widely distributed neurotransmitter in the brain that is also a principal output molecule of the sympathetic nervous system, can produce psychological effects associated with infection. This paper puts forth the hypothesis that through neural-immune crosstalk, serious infection increases noradrenergic signaling, both in the central nervous system and in peripheral organs. In this manner, elevated noradrenergic transmission may help produce basic symptoms of infection such as fever, fatigue, aches and pains (including headache), nausea, and loss of appetite. NA may also promote cognitive impairment, major depression, unipolar mania, and even epileptic seizures in some cases. The paper focuses on three major types of infection: influenza (viral), tuberculosis (bacterial), malaria (parasitic), while also summarizing the potential relationship between NA and human immunodeficiency virus (HIV) infection. Four lines of evidence are used to test association between NA and influenza, tuberculosis, and malaria: direct measures of NA and its metabolites; and incidence of hypertension, bipolar mania, and epileptic seizures, since the latter three conditions may be associated with elevated NA. In addition, heart rate variability data are examined with respect to a number of infectious diseases, since those data provide information on sympathetic nervous system activity. While the data do not unequivocally support elevated noradrenergic signaling promoting psychological symptomatology with infection, many studies are consistent with this view.

To observe the role of cerebrospinal fluid (CSF) TP53 gene mutation in lung cancer associated meningitis. A retrospective analysis was performed on 35 patients diagnosed with lung cancer associated meningitis at the Second Hospital of Hebei Medical University from December 2015 to December 2018.All patients underwent the next-generation sequencing of CSF, and TP53 gene was found to be mutant or wild type, including 23 patients with TP53 mutant type and 12 patients with TP53 wild type. The clinical characteristics, CSF leukocyte, protein, glucose, chloride, Karnofsky performance (KPS) and overall survival were observed. Headache, nausea and vomiting were the main clinical manifestations in both groups.There were no significant differences in CSF pressure, leukocyte, biochemical indicators and KPS between the two groups. The average time from diagnosis of lung cancer to diagnosis of lung cancer associated meningitis in the TP53 mutant group was significantly shorter than that in the TP53 wild type group (5.79 months vs 25.5 months).The median survival time of patients in the TP53 mutant group from lung cancer diagnosis to the observation endpoint was 19.77 months, while it was 88.73 months in the TP53 wild type group, and the difference was statistically significant (0.043). Mutation in the tumor suppressor gene TP53 can be detected in the CSF of patients with lung cancer associated meningitis. Patients with such mutation have earlier meningeal metastasis and shorter median survival time.