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Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane, isoflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stressors such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:10,000 to 1: 250,000 anesthetics. However, the prevalence of the genetic abnormalities may be as great as one in 400 individuals. MH affects humans, certain pig breeds, dogs and horses. The classic signs of MH include hyperthermia, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, hyperkalaemia, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. An increase in end-tidal carbon dioxide despite increased minute ventilation provides an early diagnostic clue. In humans the syndrome is inherited in an autosomal dominant pattern, while in pigs it is autosomal recessive. Uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation leads to the pathophysiologic changes. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 400 variants have been identified in the RYR1 gene located on chromosome 19q13.1, and at least 34 are causal for MH. Less than 1 % of variants have been found in CACNA1S but not all of these are causal. Diagnostic testing involves the in vitro contracture response of biopsied muscle to halothane, caffeine, and in some centres ryanodine and 4-chloro-m-cresol. Elucidation of the genetic changes has led to the introduction of DNA testing for susceptibility to MH. Dantrolene sodium is a specific antagonist and should be available wherever general anesthesia is administered. Increased understanding of the clinical manifestation and pathophysiology of the syndrome, has lead to the mortality decreasing from 80 % thirty years ago to <5 % in 2006.

Magnetic fluid hyperthermia (MFH) treatment makes use of a suspension of superparamagnetic iron oxide nanoparticles, administered systemically or locally, in combination with an externally applied alternating magnetic field, to ablate target tissue by generating heat through a process called induction. The heat generated above the mammalian euthermic temperature of 37°C induces apoptotic cell death and/or enhances the susceptibility of the target tissue to other therapies such as radiation and chemotherapy. While most hyperthermia techniques currently in development are targeted towards cancer treatment, hyperthermia is also used to treat restenosis, to remove plaques, to ablate nerves and to alleviate pain by increasing regional blood flow. While RF hyperthermia can be directed invasively towards the site of treatment, non-invasive localization of heat through induction is challenging. In this review, we discuss recent progress in the field of RF magnetic fluid hyperthermia and introduce a new diagnostic imaging modality called magnetic particle imaging that allows for a focused theranostic approach encompassing treatment planning, treatment monitoring and spatially localized inductive heating.

Core body temperature is normally tightly regulated to within a few tenths of a degree. The major thermoregulatory defences in humans are sweating, arteriovenous shunt vasoconstriction, and shivering. The core temperature triggering each response defines its activation threshold. General anaesthetics greatly impair thermoregulation, synchronously reducing the thresholds for vasoconstriction and shivering. Neuraxial anaesthesia also impairs central thermoregulatory control, and prevents vasoconstriction and shivering in blocked areas. Consequently, unwarmed anaesthetised patients become hypothermic, typically by 1–2°C. Hypothermia results initially from an internal redistribution of body heat from the core to the periphery, followed by heat loss exceeding metabolic heat production. Complications of perioperative hypothermia include coagulopathy and increased transfusion requirement, surgical site infection, delayed drug metabolism, prolonged recovery, shivering, and thermal discomfort. Body temperature can be reliably measured in the oesophagus, nasopharynx, mouth, and bladder. The standard-of-care is to monitor core temperature and to maintain normothermia during general and neuraxial anaesthesia.

Ryanodine Receptors (RyRs) are massive channels that release Ca 2+ from the endoplasmic and sarcoplasmic reticulum. Hundreds of mutations are linked to malignant hyperthermia (MH), myopathies, and arrhythmias. Here, we explore the first MH mutation identified in humans by providing cryo-EM snapshots of the pig homolog, R615C, showing that it affects an interface between three solenoid regions. We also show the impact of apo-calmodulin (apoCaM) and how it can induce opening by bending of the bridging solenoid, mediated by its N-terminal lobe. For R615C RyR1, apoCaM binding abolishes a pathological ‘intermediate’ conformation, distributing the population to a mixture of open and closed channels, both different from the structure without apoCaM. Comparisons show that the mutation primarily affects the closed state, inducing partial movements linked to channel activation. This shows that disease mutations can cause distinct pathological conformations of the RyR and facilitate channel opening by disrupting interactions between different solenoid regions. Ryanodine Receptors (RyRs) release Ca2+ from the endoplasmic and sarcoplasmic reticulum. Mutations in RyR are linked to malignant hyperthermia (MH), myopathies, and arrhythmias. Here, a collection of cryoEM structures provides insights into the molecular consequences of MHrelated RyR mutation R615C, and how apoCaM opens RyR1.

Abstract BACKGROUND Despite the multitude of available treatments, glioblastoma (GBM) remains an aggressive and uniformly fatal tumor. Laser interstitial thermal therapy (LITT) is a novel, minimally invasive treatment that holds promise for treating patients with GBM who are not candidates for traditional open craniotomy. However, due to the recent introduction of LITT into clinical practice, large series that evaluate safety and long-term outcomes after LITT are lacking. OBJECTIVE To present our institution's series of over 50 GBM patients treated with LITT, with regard to safety, efficacy, and outcomes. METHODS We performed a retrospective descriptive study of patients with histologically proven GBM who underwent LITT. Data collected included demographics, tumor location and volume, tumor genetic markers, treatment volume, perioperative complications, and long-term follow-up data. RESULTS We performed 58 LITT treatments for GBM in 54 patients over 5.5 yr. Forty-one were recurrent tumors while 17 were frontline treatments. Forty GBMs were lobar in location, while 18 were in deep structures (thalamus, insula, corpus callosum). Average tumor volume was 12.5 ± 13.4 cm3. Average percentage of tumor treated with the yellow thermal damage threshold (TDT) line (dose equivalent of 43°C for 2 min) was 93.3% ± 10.6%, and with the blue TDT line (dose equivalent of 43°C for 10 min) was 88.0% ± 14.2%. There were 7 perioperative complications (12%) and 2 mortalities (3.4%). Median overall survival after LITT for the total cohort was 11.5 mo, and median progression-free survival 6.6 mo. CONCLUSION LITT appears to be a safe and effective treatment for GBM in properly selected patients. Graphical Abstract Graphical Abstract Video Abstract 10.1093/neuros/nyy375 Video Abstract 10.1093.neuros.nyy375 5821902691001

Magnetic hyperthermia (MH) has been introduced clinically as an alternative approach for the focal treatment of tumors. MH utilizes the heat generated by the magnetic nanoparticles (MNPs) when subjected to an alternating magnetic field (AMF). It has become an important topic in the nanomedical field due to their multitudes of advantages towards effective antitumor therapy such as high biosafety, deep tissue penetration, and targeted selective tumor killing. However, in order for MH to progress and to realize its paramount potential as an alternative choice for cancer treatment, tremendous challenges have to be overcome. Thus, the efficiency of MH therapy needs enhancement. In its recent 60-year of history, the field of MH has focused primarily on heating using MNPs for therapeutic applications. Increasing the thermal conversion efficiency of MNPs is the fundamental strategy for improving therapeutic efficacy. Recently, emerging experimental evidence indicates that MNPs-MH produces nano-scale heat effects without macroscopic temperature rise. A deep understanding of the effect of this localized induction heat for the destruction of subcellular/cellular structures further supports the efficacy of MH in improving therapeutic therapy. In this review, the currently available strategies for improving the antitumor therapeutic efficacy of MNPs-MH will be discussed. Firstly, the recent advancements in engineering MNP size, composition, shape, and surface to significantly improve their energy dissipation rates will be explored. Secondly, the latest studies depicting the effect of local induction heat for selectively disrupting cells/intracellular structures will be examined. Thirdly, strategies to enhance the therapeutics by combining MH therapy with chemotherapy, radiotherapy, immunotherapy, photothermal/photodynamic therapy (PDT), and gene therapy will be reviewed. Lastly, the prospect and significant challenges in MH-based antitumor therapy will be discussed. This review is to provide a comprehensive understanding of MH for improving antitumor therapeutic efficacy, which would be of utmost benefit towards guiding the users and for the future development of MNPs-MH towards successful application in medicine.

In Ghana, temperature check at various points of entry was adopted as a means of screening people for coronavirus disease 2019 without taking into consideration data on the local prevalence of fever associated with the disease. Our objective was to assess fever prevalence and its associated risk factors among patients hospitalised with coronavirus disease 2019 at the Eastern Regional Hospital, Koforidua in Ghana. We reviewed medical records of 301 coronavirus disease 2019 patients who were admitted at the Eastern Regional Hospital, Koforidua between May 5, 2020, and August 31, 2021. Data collected on a pre-designed extraction sheet was processed, entered and analysed using Microsoft excel 2019 and Stata/IC version 16.1 software. Prevalence of fever was estimated and a multivariable logistic regression model was fitted to establish risk factors associated with fever among hospitalised coronavirus disease 2019 patients. A relationship was accepted to be significant at 5% level of significance. The prevalence of fever among hospitalised coronavirus disease 2019 patients was 21.6% (95% CI, 17.1%-26.7%). Risk factors associated with fever were age group [0-19 years (AOR, 5.75; 95% CI, 1.46-22.68; p = 0.013); 20-39 years (AOR, 3.22; 95% CI, 1.42-7.29; p = 0.005)], comorbidity (AOR, 2.18; 95% CI, 1.04-4.59; p = 0.040), and disease severity [moderate (AOR, 3.89; 95% CI, 1.44-10.49; p = 0.007); severe (AOR, 4.08; 95% CI, 1.36-12.21; p = 0.012); critical (AOR, 4.85; 95% CI, 1.03-22.85; p = 0.046)]. The prevalence of fever was low among hospitalised coronavirus disease 2019 patients at the Eastern Regional Hospital, Koforidua. However, there was an increasing risk of fever as the disease severity progresses. Fever screening may be utilised better in disease of higher severity; it should not be used alone especially in mild disease.

In Ghana, temperature check at various points of entry was adopted as a means of screening people for coronavirus disease 2019 without taking into consideration data on the local prevalence of fever associated with the disease. Our objective was to assess fever prevalence and its associated risk factors among patients hospitalised with coronavirus disease 2019 at the Eastern Regional Hospital, Koforidua in Ghana. We reviewed medical records of 301 coronavirus disease 2019 patients who were admitted at the Eastern Regional Hospital, Koforidua between May 5, 2020, and August 31, 2021. Data collected on a pre-designed extraction sheet was processed, entered and analysed using Microsoft excel 2019 and Stata/IC version 16.1 software. Prevalence of fever was estimated and a multivariable logistic regression model was fitted to establish risk factors associated with fever among hospitalised coronavirus disease 2019 patients. A relationship was accepted to be significant at 5% level of significance. The prevalence of fever among hospitalised coronavirus disease 2019 patients was 21.6% (95% CI, 17.1%-26.7%). Risk factors associated with fever were age group [0-19 years (AOR, 5.75; 95% CI, 1.46-22.68; p = 0.013); 20-39 years (AOR, 3.22; 95% CI, 1.42-7.29; p = 0.005)], comorbidity (AOR, 2.18; 95% CI, 1.04-4.59; p = 0.040), and disease severity [moderate (AOR, 3.89; 95% CI, 1.44-10.49; p = 0.007); severe (AOR, 4.08; 95% CI, 1.36-12.21; p = 0.012); critical (AOR, 4.85; 95% CI, 1.03-22.85; p = 0.046)]. The prevalence of fever was low among hospitalised coronavirus disease 2019 patients at the Eastern Regional Hospital, Koforidua. However, there was an increasing risk of fever as the disease severity progresses. Fever screening may be utilised better in disease of higher severity; it should not be used alone especially in mild disease.

In Ghana, temperature check at various points of entry was adopted as a means of screening people for coronavirus disease 2019 without taking into consideration data on the local prevalence of fever associated with the disease. Our objective was to assess fever prevalence and its associated risk factors among patients hospitalised with coronavirus disease 2019 at the Eastern Regional Hospital, Koforidua in Ghana. We reviewed medical records of 301 coronavirus disease 2019 patients who were admitted at the Eastern Regional Hospital, Koforidua between May 5, 2020, and August 31, 2021. Data collected on a pre-designed extraction sheet was processed, entered and analysed using Microsoft excel 2019 and Stata/IC version 16.1 software. Prevalence of fever was estimated and a multivariable logistic regression model was fitted to establish risk factors associated with fever among hospitalised coronavirus disease 2019 patients. A relationship was accepted to be significant at 5% level of significance. The prevalence of fever among hospitalised coronavirus disease 2019 patients was 21.6% (95% CI, 17.1%-26.7%). Risk factors associated with fever were age group [0-19 years (AOR, 5.75; 95% CI, 1.46-22.68; p = 0.013); 20-39 years (AOR, 3.22; 95% CI, 1.42-7.29; p = 0.005)], comorbidity (AOR, 2.18; 95% CI, 1.04-4.59; p = 0.040), and disease severity [moderate (AOR, 3.89; 95% CI, 1.44-10.49; p = 0.007); severe (AOR, 4.08; 95% CI, 1.36-12.21; p = 0.012); critical (AOR, 4.85; 95% CI, 1.03-22.85; p = 0.046)]. The prevalence of fever was low among hospitalised coronavirus disease 2019 patients at the Eastern Regional Hospital, Koforidua. However, there was an increasing risk of fever as the disease severity progresses. Fever screening may be utilised better in disease of higher severity; it should not be used alone especially in mild disease.