Previous studies reported that a mild, non-protein-denaturing, fever-like temperature increase induced the unfolded protein response (UPR) in mammalian cells. Our dSTORM super-resolution microscopy experiments revealed that the master regulator of the UPR, the IRE1 (inositol-requiring enzyme 1) protein, is clustered as a result of UPR activation in a human osteosarcoma cell line (U2OS) upon mild heat stress. Using ER thermo yellow, a temperature-sensitive fluorescent probe targeted to the endoplasmic reticulum (ER), we detected significant intracellular thermogenesis in mouse embryonic fibroblast (MEF) cells. Temperatures reached at least 8 °C higher than the external environment (40 °C), resulting in exceptionally high ER temperatures similar to those previously described for mitochondria. Mild heat-induced thermogenesis in the ER of MEF cells was likely due to the uncoupling of the Ca2+/ATPase (SERCA) pump. The high ER temperatures initiated a pronounced cytosolic heat-shock response in MEF cells, which was significantly lower in U2OS cells in which both the ER thermogenesis and SERCA pump uncoupling were absent. Our results suggest that depending on intrinsic cellular properties, mild hyperthermia-induced intracellular thermogenesis defines the cellular response mechanism and determines the outcome of hyperthermic stress.

Brugada syndrome (BrS) is characterized by ST segment elevations in the right precordial leads, V1 - V3, with additional findings of ventricular arrhythmias and family history (FH) of sudden cardiac death (SCD) at a young age. Here, we describe a case of hyperthermia, unveiling the Brugada electrocardiography (EKG) pattern and the resolution of EKG findings with appropriate hyperthermia management. It is important to distinguish the Brugada EKG pattern from other causes of ST elevations and treat appropriately to prevent patients from developing ventricular fibrillation and SCD. It is key to identify environmental triggers in patients presenting with Brugada EKG pattern and closely monitor for ventricular fibrillation. Educating patients on prompt fever treatment with antipyretics and avoiding medications like sodium channel blockers during the febrile event is paramount to counter patients going into ventricular fibrillation. It is also crucial for close follow-up of these patients, offering them genetic testing for BrS and screening families of patients with BrS.

BACKGROUND: Devices that increase the penetrance of intravesical chemotherapeutics are emerging as alternatives to classical Bacillus Calmette Guérin (BCG) treatment.
OBJECTIVE: To compare the efficacy of mitomycin C applied with the electromotive drug delivery device (MMC-EMDA) versus BCG in patients with intermediate and high-risk non-muscle-invasive bladder cancer (NMIBC) without carcinoma in situ (CIS).
METHODS: Prospective non-randomized study in which 47 patients received MMC-EMDA (40 mg of MMC diluted in 50 mg of distilled water at 20 mA for 30 min. Regimen of 6 weekly and then 6 monthly instillations) and 48 patients received BCG (50 mg of OncoCITE® diluted in 50 ml of normal saline for 60 min. Regimen of 6 weekly instillations and then 3 weekly instillations at months 3, 6 and 12). The primary endpoint was the recurrence-free rate (RFR) at 24 months. Secondary endpoints were time to recurrence and progression-free rate (PFR) at 24 months follow-up.
RESULTS: Baseline patient assessment and mean follow-up time were similar in both groups (MMC-EMDA group: 26.4 months; BCG group: 28.4 months (p = 0.44)). The RFR at 24 months was 80.9% for the MMC-EMDA group and 77.1% for the BCG group (p = 0.969). The mean time to recurrence was 12.5 months in the MMC-EMDA group and 14 months in the BCG group (p = 0.681). At 24 months, PFR was 97.9% in the MMC-EMDA group and 93.8% in the BCG group (p = 0.419).
CONCLUSIONS: No differences were found between MMC-EMDA and BCG treatments in patients with high-risk and intermediate-risk NMIBC without CIS.

UNASSIGNED: To investigate how passive hyperthermia affect the resting-state functional brain activity based on an acute mouse model after heat stress exposure.
UNASSIGNED: Twenty-eight rs-fMRI data of C57BL/6J male mice which weighing about 24 ∼ 29 g and aged 12 ∼ 16 weeks were collected. The mice in the hyperthermia group (HT, 40 °C ± 0.5 °C, 40 min) were subjected to passive hyperthermia before the anesthesia preparation for scanning. While the normal control group (NC) was subjected to normothermia condition (NC, 20 °C ± 2 °C, 40 min). After data preprocessing, we performed independent component analysis (ICA) and region of interested (ROI)-ROI functional connectivity (FC) analyses on the data of both HT (n = 13) and NC (n = 15).
UNASSIGNED: The group ICA analysis showed that the HT and the NC both included 11 intrinsic connectivity networks (ICNs), and can be divided into four types of networks: the cortical network (CN), the subcortical network (SN), the default mode network (DMN), and cerebellar networks. CN and SN belongs to sensorimotor network. Compared with NC, the functional network organization of ICNs in the HT was altered and the overall functional intensity was decreased. Furthermore, 13 ROIs were selected in CN, SN, and DMN for further ROI-ROI FC analysis. The ROI-ROI FC analysis showed that passive hyperthermia exposure significantly reduced the FC strength in the overall brain represented by CN, SN, DMN of mice.
UNASSIGNED: Prolonged exposure to high temperature has a greater impact on the overall perception and cognitive level of mice, which might help understand the relationship between neuronal activities and physiological thermal sensation and regulation as well as behavioral changes.

Magnetic resonance thermometry (MRT) can measure in-vivo 3D-temperature changes in real-time and noninvasively. However, for the oropharynx region and the entire head and neck, motion potentially introduces large artifacts. Considering long treatment times of 60-90 min, this study aims to evaluate whether MRT around the oropharynx is clinically feasible for hyperthermia treatments and quantify the effects of breathing and swallowing on MRT performance. A 3D-ME-FGRE sequence was used in a phantom cooling down and around the oropharynx of five volunteers over ∼75 min. The imaging protocol consisted of imaging with acceleration (ARC = 2), number of image averages (NEX = 1,2 and 3). For volunteers, the acquisitions included a breath-hold scan and scans with deliberate swallowing. MRT performance was quantified in neck muscle, spinal cord and masseter muscle, using mean average error (MAE), mean error (ME) and spatial standard deviation (SD). In phantom, an increase in NEX leads to a significant decrease in SD, but MAE and ME were unchanged. No significant difference was found in volunteers between the different scans. There was a significant difference between the regions evaluated: neck muscle had the best MAE (=1.96 °C) and SD (=0.82 °C), followed by spinal cord (MAE = 3.17 °C, SD = 0.92 °C) and masseter muscle (MAE = 4.53 °C, SD = 1.16 °C). Concerning the ME, spinal cord did best, then neck muscle and masseter muscle, with values of -0.64 °C, 1.15 °C and -3.05 °C respectively. Breathing, swallowing, and different ways of imaging (acceleration and NEX) do not significantly influence the MRT performance in the oropharynx region. The ROI selected however, leads to significant differences.

Liposome formulations of the cancer drug doxorubicin have been developed to address the severe side effects that result from administration of this drug in a conventional formulation. Among them, thermosensitive liposomal doxorubicin presents enhanced tumor targeting and efficient drug release when combined with mild hyperthermia localized to the tumor site. Exploiting the radiosensitizing benefits of localized thermal therapy, the integration of radiation therapy with the thermally activated liposomal system is posited to amplify the anti-tumor efficacy. This study explored a synergistic therapeutic strategy that combines thermosensitive liposomal doxorubicin, mild hyperthermia, and radiotherapy, using an orthotopic murine model of breast cancer. The protocol of sequential multi-modal treatment, incorporating low-dose chemotherapy and radiotherapy, substantially postponed the progression of primary tumor growth in comparison to the application of monotherapy at elevated dosages. Improvements in unheated distant lesions were also observed. Furthermore, the toxicity associated with the combination treatment was comparable to that of either thermosensitive liposome treatment or radiation alone at low doses. These outcomes underscore the potential of multi-modal therapeutic strategies to refine treatment efficacy while concurrently diminishing adverse effects in the management of breast cancer, providing valuable insight for the future refinement of thermosensitive liposomal doxorubicin applications.

The global incidence of cancer continues to rise, posing a significant public health concern. Although numerous cancer therapies exist, each has limitations and complications. The present study explores alternative cancer treatment approaches, combining hyperthermia and photodynamic therapy (PDT). Magnetic nanoparticles (MNPs) and amine-functionalized carbon quantum dots (A-CQDs) were synthesized separately and then covalently conjugated to form a single nanosystem for combinational therapy (M-CQDs). The successful conjugation was confirmed using zeta potential, Fourier transform infrared spectroscopy (FT-IR), and UV-visible spectroscopy. Morphological examination in transmission electron microscopy (TEM) further verified the conjugation of CQDs with MNPs. Energy dispersive X-ray spectroscopy (EDX) revealed that M-CQDs contain approximately 12 weight percentages of carbon. Hyperthermia studies showed that both MNP and M-CQDs maintain a constant therapeutic temperature at lower frequencies (260.84 kHz) with high specific absorption rates (SAR) of 118.11 and 95.04 W/g, respectively. In vitro studies demonstrated that MNPs, A-CQDs, and M-CQDs are non-toxic, and combinational therapy (PDT + hyperthermia) resulted in significantly lower cell viability (~4%) compared to individual therapies. Similar results were obtained with Hoechst and propidium iodide (PI) staining assays. Hence, the combination therapy of PDT and hyperthermia shows promise as a potential alternative to conventional therapies, and it could be further explored in combination with existing conventional treatments.

OBJECTIVE: Peritoneal carcinomatosis (PC) presents a major challenge in the treatment of late-stage, solid tumors, with traditional therapies limited by poor drug penetration. We evaluated a novel hyperthermic pressurized intraperitoneal aerosol chemotherapy (HPIPAC) system using a human abdominal cavity model for its efficacy against AGS gastric cancer cells.
METHODS: A model simulating the human abdominal cavity and AGS gastric cancer cell line cultured dishes were used to assess the efficacy of the HPIPAC system. Cell viability was measured to evaluate the impact of HPIPAC under 6 different conditions: heat alone, PIPAC with paclitaxel (PTX), PTX alone, normal saline (NS) alone, heat with NS, and HPIPAC with PTX.
RESULTS: Results showed a significant reduction in cell viability with HPIPAC combined with PTX, indicating enhanced cytotoxic effects. Immediately after treatment, the average cell viability was 66.6%, which decreased to 49.2% after 48 hours and to a further 19.6% after 120 hours of incubation, demonstrating the sustained efficacy of the treatment. In contrast, control groups exhibited a recovery in cell viability; heat alone showed cell viability increasing from 90.8% to 94.4%, PIPAC with PTX from 82.7% to 89.7%, PTX only from 73.3% to 74.8%, NS only from 90.9% to 98.3%, and heat with NS from 74.4% to 84.7%.
CONCLUSIONS: The HPIPAC system with PTX exhibits a promising approach in the treatment of PC in gastric cancer, significantly reducing cell viability. Despite certain limitations, this study highlights the system\'s potential to enhance treatment outcomes. Future efforts should focus on refining HPIPAC and validating its effectiveness in clinical settings.

This research sought to evaluate the thermal zones of the upper body and firefighter personal protective equipment (PPE) immediately following uncompensable heat stress (0.03 °C increase/min). We hypothesized that the frontal portion of the head and the inside of the firefighter helmet would be the hottest as measured by infrared thermography. This hypothesis was due to previous research demonstrating that the head accounts for ∼8-10% of the body surface area, but it accounts for ∼20% of the overall body heat dissipation during moderate exercise. Twenty participants performed a 21-min graded treadmill exercise protocol (Altered Modified Naughton) in an environmental chamber (35 °C, 50 % humidity) in firefighter PPE. The body areas analyzed were the frontal area of the head, chest, abdomen, arm, neck, upper back, and lower back. The areas of the PPE that were analyzed were the inside of the helmet and the jacket. The hottest areas of the body post-exercise were the frontal area of the head (mean: 37.3 ± 0.4 °C), chest (mean: 37.5 ± 0.3 °C), and upper back (mean: 37.3 ± 0.4 °C). The coldest area of the upper body was the abdomen (mean: 36.1 ± 0.4 °C). The peak temperature of the inside of the helmet increased (p < 0.001) by 9.8 °C from 27.7 ± 1.6 °C to 37.4 ± 0.7 °C, and the inside of the jacket increased (p < 0.001) by 7.3 °C from 29.2 ± 1.7 °C to 36.5 ± 0.4 °C. The results of this study are relevant for cooling strategies for firefighters.

Birds maintain some of the highest body temperatures among endothermic animals. Often deemed a selective advantage for heat tolerance, high body temperatures also limits birds\' thermal safety margin before reaching lethal levels. Recent modelling suggests that sustained effort in Arctic birds might be restricted at mild air temperatures, which may require reductions in activity to avoid overheating, with expected negative impacts on reproductive performance. We measured within-individual changes in body temperature in calm birds and then in response to an experimental increase in activity in an outdoor captive population of Arctic, cold-specialised snow buntings (Plectrophenax nivalis), exposed to naturally varying air temperatures (- 15 to 36 °C). Calm buntings exhibited a modal body temperature range from 39.9 to 42.6 °C. However, we detected a significant increase in body temperature within minutes of shifting calm birds to active flight, with strong evidence for a positive effect of air temperature on body temperature (slope = 0.04 °C/ °C). Importantly, by an ambient temperature of 9 °C, flying buntings were already generating body temperatures ≥ 45 °C, approaching the upper thermal limits of organismal performance (45-47 °C). With known limited evaporative heat dissipation capacities in these birds, our results support the recent prediction that free-living buntings operating at maximal sustainable rates will increasingly need to rely on behavioural thermoregulatory strategies to regulate body temperature, to the detriment of nestling growth and survival.