Cytotoxic evaluation of pure and doped iron oxide nanoparticles on cancer cells: a magnetic fluid hyperthermia perspective.

The need of the hour with respect to cancer treatment is a targeted approach with minimal or nil ramifications. Apropos, magnetic fluid hyperthermia (MFH) is emerging as a potential therapeutic strategy with anticipated reduced side effects for solid tumors. MFH causes cytotoxicity due to the heat generated owing to Hysteresis, Neel, and Brownian relaxation losses once magnetic nanoparticles (MNPs) carrying cancer cells are placed under an alternating magnetic field. With respect to MFH, iron oxide-based MNPs have been most extensively studied to date compared to other metal oxides with magnetic properties. The effectiveness of MFH relies on the composition, coating, size, physical and biocompatible properties of the MNPs. Pure iron oxide and doped iron oxide MNPs have been utilized to study their effects on cancer cell killing through MFH. This review evaluates the biocompatibility of pure and doped iron oxide MNPs and their subsequent hyperthermic effect for effectively killing cancer cells in vitro and in vivo.

Generating and monitoring mild hyperthermia using a ring array ultrasound transducer.

OBJECTIVE: To demonstrate the feasibility of using a ring array ultrasound (US) transducer, guided by ultrasound tomography (UST), for generating and monitoring mild hyperthermia (MHTh). METHODS: In silico and in vitro experiments were designed to evaluate the efficacy of a ring array US transducer for generating MHTh and monitoring changes in temperature. In a series of in silico studies, we compared the acoustic focal profiles produced by a ring array US transducer transmitting at different frequencies and further investigated the effectiveness of UST-guidance in implementing aberration correction to enhance the focal profile. In vitro experiments evaluated the capability of using a ring array US transducer to generate and maintain MHTh and the accuracy of using UST to monitor temperature changes. RESULTS: The simulations demonstrated that a ring array US transducer achieves symmetrical and localized acoustic focusing. In a heterogenous tissue model, a ring array US transducer achieved a superior acoustic focus by implementing aberration correction with guidance from UST. In vitro experiments demonstrated the capability of a ring array US transducer to generate MHTh in a tissue-mimicking phantom in an average of 117 ± 18 s and subsequently maintain MHTh. Lastly, a ring array US transducer utilized UST to track temperature changes in a preheated water-filled inclusion while it passively cooled from 45 °C to 25 °C, with a maximum error of 0.58 °C. CONCLUSION: A ring array US transducer can noninvasively generate and monitor MHTh, overcoming many limitations of current clinical systems. The closed geometry of the transducer is optimal for acoustic focusing and UST-guidance allows for improved aberration correction in a heterogenous medium. Utilizing UST thermometry with the same ring array US transducer will allow for implementing an image-guided, temperature-controlled, all-acoustic MHTh system.

Myopathic manifestations across the adult lifespan of patients with malignant hyperthermia susceptibility: a narrative review.

Malignant hyperthermia susceptibility (MHS) designates individuals at risk of developing a hypermetabolic reaction triggered by halogenated anaesthetics or the depolarising neuromuscular blocking agent suxamethonium. Over the past few decades, beyond the operating theatre, myopathic manifestations impacting daily life are increasingly recognised as a prevalent phenomenon in MHS patients. At the request of the European Malignant Hyperthermia Group, we reviewed the literature and gathered the opinion of experts to define MHS-related myopathy as a distinct phenotype expressed across the adult lifespan of MHS patients unrelated to anaesthetic exposure; this serves to raise awareness about non-anaesthetic manifestations, potential therapies, and management of MHS-related myopathy. We focused on the clinical presentation, biochemical and histopathological findings, and the impact on patient well-being. The spectrum of symptoms of MHS-related myopathy encompasses muscle cramps, stiffness, myalgias, rhabdomyolysis, and weakness, with a wide age range of onset mainly during adulthood. Histopathological analysis can reveal nonspecific abnormalities suggestive of RYR1 involvement, while metabolic profiling reflects altered energy metabolism in MHS muscle. Myopathic manifestations can significantly impact patient quality of life and lead to functional limitations and socio-economic burden. While currently available therapies can provide symptomatic relief, there is a need for further research into targeted treatments addressing the underlying pathophysiology. Counselling early after establishing the MHS diagnosis, followed by multidisciplinary management involving various medical specialties, is crucial to optimise patient care.

Radiofrequency-responsive black phosphorus nanogel crosslinked with cisplatin for precise synergy in multi-modal tumor therapies.

Radiofrequency-responsive nanoparticles (RFNPs) have drawn increasingly attentions as RF energy absorbing antenna to enhance antitumor efficacy of radiofrequency ablation (RFA). However, it remains a huge challenge for inorganic RFNPs to precisely synergize RFA with other antitumor modes in a clinically acceptable way on bio-safety and bio-compatibility. In this work, RF-responsive black phosphorus (BP) nanogel (BP-Pt@PNA) was successfully fabricated by crosslinking coordination of cisplatin with BP and temperature sensitive polymer PNA. BP-Pt@PNA exhibited strong RF-heating effect and RF-induced pulsatile release of cisplatin. Under RF irradiation, BP-Pt@PNA exhibited cytotoxic enhancement on 4T1 cells. By the synergistic effect of BP and cisplatin, BP-Pt@PNA achieved RF-stimulated systemic immune effect, thus induced enhance suppression on tumor growth and metastasis. Moreover, BP-Pt@PNA realized long-term drug retention in tumor and favorable embolization to tumor-feeding arteries. With high drug loading capacity and favorable bio-safety and bio-degradability, BP-Pt@PNA is expected as an ideal RFNP for precisely synergizing RFA with other antitumor modes in clinical application.

Plasmonic nanophotothermal therapy: Destruction of 500 mm3 subcutaneous human basal cell carcinoma with gold nanoparticles and near infrared laser.

SIGNIFICANCE: Multilesional basal cell carcinoma (BCC) are spread on sun exposed skin areas, including arms, face and back. The first-line treatment remains the surgical resection or Mohs surgery. Despite its high complexity, Mohs surgery is well practiced in USA and Germany and presents very good results both in esthetic and in carcinology point of view. Large lesions more than 2 cm remain challenging to remove by topical cream used in photodynamic therapy (PDT). If these larger lesions are not treated in less than 1 month, they could grow deeply in the skin, thus enhancing the risk of reoccurrence and the severity of the disease. Despite this model herein studied, that is non melanoma skin cancer is a good prognostic cancer, the therapy aims to be applied to more aggressive melanoma skin cancers. AIM: Total regression of large cutaneous lesions less than 1 month with no reoccurrence. APPROACH: Tumor induction on murine model bearing a 500 mm3 subcutaneous lesion. Increasing dose of gold nanoparticles at fixed initial concentration C0 = 0.3 mg/mL, infused into the tumor then exposition of the region of interest to NIR medical laser to assess the therapy. One or two intratumoral administration(s) were compared to surgery and control, that is no treatment, laser alone or nanoparticles alone. RESULTS: Gold nanoparticles alone or the NIR laser alone did not induce the tumor regression. The combination of laser and nanoparticles called plasmonic nanophotothermal therapy induced apoptosis. Derma and hypoderm do not show any visible gold nanoparticles and demonstrated a good cicatrization process. CONCLUSION: Plasmonic nanophotothermal therapy using two doses of gold nanoparticles was the only protocol that proved its efficacy on large lesions in 14 days, that is 500 mm3 on a murine model bearing human basal cell carcinoma.

The Atypical Face of Neuroleptic Malignant Syndrome: A Case Report of Ileus and Absent Rigidity.

Neuroleptic malignant syndrome (NMS) is a rare life-threatening condition associated with the use of antipsychotic medications. This case report describes a male patient in his early 30s who presented with fever, breathlessness, and lower limb weakness, ultimately diagnosed with NMS despite the absence of muscular rigidity. On examination, he was febrile, tachycardic, and tachypneic with an oxygen saturation of 88% and elevated blood pressure. On auscultation diffuse crepitations in both lungs were revealed. Neurological assessment indicated motor strength of 3/5 in both lower limbs, without rigidity, sensory loss, or cerebellar signs. It was noted that he was on irregular atypical antipsychotic medication for the past one year. Laboratory investigations revealed leukocytosis, elevated transaminases, dyselectrolytemia, elevated creatine phosphokinase (CPK), and serum creatinine. NMS was not initially considered due to the lack of muscular rigidity. However, the patient later developed autonomic dysregulation manifestations, such as paralytic ileus. Once organic causes were excluded, NMS was diagnosed. Supportive therapy included 23 cycles of hemodialysis and colonic decompression for pseudo-obstruction. He was treated with intravenous fluids and dopamine receptor agonist medications. NMS usually presents with fever, muscular rigidity, altered mental status, and autonomic instability; yet, the absence of muscular rigidity in this patient is a distinctive and unusual feature.

Spermatozoon-propelled microcellular submarines combining innate magnetic hyperthermia with derived nanotherapies for thrombolysis and ischemia mitigation.

Thrombotic cardiovascular diseases are a prevalent factor contributing to both physical impairment and mortality. Thrombolysis and ischemic mitigation have emerged as leading contemporary therapeutic approaches for addressing the consequences of ischemic injury and reperfusion damage. Herein, an innovative cellular-cloaked spermatozoon-driven microcellular submarine (SPCS), comprised of multimodal motifs, was designed to integrate nano-assembly thrombolytics with an immunomodulatory ability derived from innate magnetic hyperthermia. Rheotaxis-based navigation was utilized to home to and cross the clot barrier, and finally accumulate in ischemic vascular organs, where the thrombolytic motif was "switched-on" by the action of thrombus magnetic red blood cell-driven magnetic hyperthermia. In a murine model, the SPCS system combining innate magnetic hyperthermia demonstrated the capacity to augment delivery efficacy, produce nanotherapeutic outcomes, exhibit potent thrombolytic activity, and ameliorate ischemic tissue damage. These findings underscore the multifaceted potential of our designed approach, offering both thrombolytic and ischemia-mitigating effects. Given its extended therapeutic effects and thrombus-targeting capability, this biocompatible SPCS system holds promise as an innovative therapeutic agent for enhancing efficacy and preventing risks after managing thrombosis.

Electrical Stimulation Promotes Endocytosis of Magnetic Nanoparticles by Cancer Cells.

Nanomaterials are increasingly used in biomedical imaging and cancer therapy, and how to improve the endocytosis of nanomaterials by cells is a key issue. The application of alternating current (AC) electrical stimulation to osteosarcoma cells (MG-63) here can increase the cellular endocytosis of Fe3O4 nanoparticles (diameter: 50 nm) by 52.46% via macropinocytosis. This can be ascribed to the decrease in F-actin content and the increase in intracellular Ca2+ concentration. Transmission electron microscope, immunofluorescence staining, western blot, flow cytometry, and inductively coupled plasma emission spectrometer analyses support this interpretation. The application of electrical stimulation decreases the cell viability in magnetic hyperthermia by 47.6% and increases the signal intensity of magnetic resonance imaging by 29%. Similar enhanced endocytosis is observed for breast cancer cells (MCF-7), glioblastoma cells (U-87 MG), melanoma cells (A-375), and bladder cancer cells (TCCSUP), and also for Fe3O4 nanoparticles with the diameters of 20 and 100 nm, and Zn0.54Co0.46Cr0.65Fe1.35O4 nanoparticles with the diameter of 70 nm. It seems the electrical stimulation has the potential to improve the diagnostic and therapeutic effects of magnetic nanoparticles by promoting endocytosis.

Thiopentone-based total intravenous anaesthesia for a patient with carnitine palmitoyltransferase II deficiency and malignant hyperthermia susceptibility.

In this case report, we discuss the use of a thiopentone infusion for the maintenance of anaesthesia in a patient with confirmed malignant hyperthermia susceptibility and carnitine palmitoyltransferase 2 deficiency. The concurrence of both diagnoses precluded the use of both propofol-based total intravenous anaesthesia and volatile inhalational anaesthesia. This patient had been anaesthetised previously with a triple infusion regimen of thiopentone, midazolam and remifentanil and this was a unique opportunity to compare the two instances. Electroencephalogram-based depth of anaesthesia monitoring was in routine use by the time of the second anaesthetic, and thus, the thiopentone infusion could be adjusted accordingly, resulting in a more rapid emergence time. We hope that this case may serve as an example of suitable anaesthetic alternative should both propofol infusion and inhalational anaesthesia not be an option.

Physical activities aid in tumor prevention: A finite element study of bio-heat transfer in healthy and malignant breast tissues.

The objective of the present research is to explore the temperature diffusion in healthy and cancerous tissues, with a specific focus on how physical activity impacts on the weakening of breast tumors. Previous research lacked numerical analysis regarding the effectiveness of physical activity in tumor prevention or attenuation, prompting an investigation into the mechanism behind physical activity and tumor prevention from a bio-heat transfer perspective. The study employs a realistic model of human breasts and tumors in COMSOL Multiphysics® to analyze temperature distribution by utilizing Penne's bio-heat equation. The research examines their influence on tissue temperature by varying tumor diameter (10-20 mm) and exercise intensities (such as walking speeds and other activities like carpentry, swimming, and marathon running). Results demonstrate that cancerous tissues generate notably more heat than normal tissues at rest and during physical activity. Smaller tumors exhibit higher temperatures during exercise, emphasizing the significance of tumor size in treatment effectiveness. Tumor temperatures range between 40 and 43.2 °C, while healthy tissue temperatures remain below 41 °C during physical activity. High-intensity exercises, particularly swimming, walking at 1.8 m/s, and marathon running, display a therapeutic effect on tumors, increasing effectiveness with intensity. The temperatures of healthy and malignant tissues rise noticeably due to constant metabolic heat and decreased blood flow. The study also identifies the optimal duration of high-intensity exercise, recommending at least 20 min for optimal therapeutic outcomes. The outcomes of this research would help individuals, doctors, and cancer researchers understand and weaken malignant tissues.

Effect of precipitating agent, N2 gas, extract volume and pH on the magnetic properties of magnetite nanoparticles by green synthesis from aqueous pomegranate peel extract.

Superparamagnetic nanoparticles (SPMNPs) have attracted considerable attention in biomedicine, particularly magnetic hyperthermia for cancer treatment. However, the development of efficient and eco-friendly methods for synthesizing SPMNPs remains a challenge. This study reports on a green synthesis approach for SPMNPs using pomegranate peel extract as a stabilizing agent. The effects of various synthesis parameters, including the type of precipitating agent (NH3 and NaOH), N2 gas, extract volume, and pH, were systematically investigated with regard to the size, morphology, and magnetic properties of the nanoparticles. The results showed that reducing the volume of the extract increased the saturation magnetization of the nanoparticles. N2 gas was found to be essential in preventing the oxidation of the nanoparticles. The type of precipitating agent also affected the size and magnetization of the nanoparticles, with NaOH leading to the synthesis of SPMNPs with higher magnetization (∼4 times) compared to NH3. Additionally, nanoparticles synthesized at pH 10 exhibited higher magnetization than those synthesized at pH 8 and 12. In conclusion, the optimized synthesis conditions significantly affected the magnetization and stability of SPMNPs. These nanoparticles are suitable for use in magnetic nanofluid hyperthermia applications.

Compensatory reserve index during central hypovolemia and volume loading in healthy young and older hyperthermic adults: A pilot study.

The compensatory reserve index (CRI), derived from machine learning algorithms from peripherally obtained photoplethysmography signals, provides a non-invasive assessment of cardiovascular stability, that may be useful clinically. Briefly, the CRI device provides a value between 0 and 1, with 1 reflecting full compensable capabilities and 0 reflecting little to no compensable capabilities. However, the CRI algorithm was developed in younger to middle aged adults, such that it is unknown if older age modulates CRI responses to cardiovascular challenges. In young and older subjects, we compared CRI responses to normothermic and hyperthermic progressive lower body negative pressure (LBNP), and volume loading with saline infusion. Eleven younger (20-36 years) and 10 older (61-75 years) healthy participants underwent (1) graded normothermic LBNP up to 30 mmHg, (2) graded hyperthermic (1.5°C increase in blood temperature) LBNP up to 30 mmHg, and (3) infusion of 15 mL/kg saline (volume loading) with hyperthermia maintained. CRI was obtained throughout each procedure. CRI at 30 mmHg LBNP was 0.18 and 0.24 units greater in the older group during normothermic and hyperthermic LBNP, respectively. However, CRI was not different between age groups at any other LBNP stage, nor did CRI change with volume loading regardless of age. In response to passive hyperthermia alone, regression analyses showed that heart rate was the strongest predictor of CRI. Blood temperature, rate pressure product, and stroke volume were also predictive of CRI but to a lesser extent. In conclusion, age attenuates the reduction in CRI during progressive normothermic and hyperthermic LBNP, but only at 30 mmHg. Second, the CRI was unchanged during volume loading in all subjects. Future studies should determine whether the age differences in CRI reflect age differences in LBNP tolerance.

Hyperthermia and radiotherapy: physiological basis for a synergistic effect.

In cancer treatment, mild hyperthermia (HT) represents an old, but recently revived opportunity to increase the efficacy of radiotherapy (RT) without increasing side effects, thereby widening the therapeutic window. HT disrupts cellular homeostasis by acting on multiple targets, and its combination with RT produces synergistic antitumoral effects on specific pathophysiological mechanisms, associated to DNA damage and repair, hypoxia, stemness and immunostimulation. HT is furthermore associated to direct tumor cell kill, particularly in higher temperature levels. A phenomenon of temporary resistance to heat, known as thermotolerance, follows each HT session. Cancer treatment requires innovative concepts and combinations to be tested but, for a meaningful development of clinical trials, the understanding of the underlying mechanisms of the tested modalities is essential. In this mini-review, we aimed to describe the synergistic effects of the combination of HT with RT as well as the phenomena of thermal shock and thermotolerance, in order to stimulate clinicians in new, clinically relevant concepts and combinations, which become particularly relevant in the era of technological advents in both modalities but also cancer immunotherapy.

Livestock-Forest integrated system attenuates deleterious heat stress effects in bovine oocytes.

Global warming poses significant challenges to the fertility of tropical dairy cattle. One promising approach to mitigate heat stress effects on reproductive function and reduce the carbon footprint is the use of integrated livestock-forest (ILF) systems. The aim of this study was to investigate the effects of two different systems, namely Full Sun (FS) and ILF, on maternal hyperthermia and oocyte quality of Holstein and Girolando heifers during the tropical summer season. The temperature-humidity index (THI) data revealed intense heat stress during the experiment. Both the system (P<0.01) and the breed (P<0.01) factors had a significant impact on vaginal temperature, being hyperthermia more pronounced in the FS system and in the Holstein breed. Over the five time points collected at a 33-day interval, we observed distinct patterns for ILF (P=0.65) and FS (P<0.001) systems, suggesting an adaptive response in animals kept in FS systems. Furthermore, oocyte quality assessment revealed an effect of the system for oocyte diameter (P<0.001) and levels of IGFBP2 (P<0.001), and caspase 3 levels showed a decrease in ILF compared to FS for both Holstein (P<0.001) and Girolando (P<0.001) breeds. Collectively, these parameters indicate that oocyte quality during the summer months was superior in animals maintained in the ILF system. In conclusion, the ILF system demonstrated promising results in attenuating maternal hyperthermia and mitigating its effects on oocyte quality. Additionally, our observations suggest that animals in the FS system may exhibit an adaptive response to heat stress.

The hybrid nanosystem for the identification and magnetic hyperthermia immunotherapy of metastatic sentinel lymph nodes as a multifunctional theranostic agent.

Lymphatic metastasis is the main cause of early-stage tumor spread, making the identification and therapy of metastatic sentinel lymph nodes (SLNs) are highly desirable in clinic. Currently, suspected malignant SLNs typically undergo a series of independent operations in clinical practice, including imaging, staining, sentinel lymph node biopsy (SLNB) and lymph node dissection (LND), which brings inconvenience to diagnosis and treatment, and may cause postoperative complications for patients. Moreover, the ordinary removal of tumor-draining lymph nodes (TDLNs) may do harm to systemic immunity required for tumor eradication. Hence, we utilized the hybrid nanosystem (SPIOs + RPPs) we constructed before for the integrated staining, ultrasound imaging, and therapy of metastatic SLNs. In this study, SPIOs + RPPs could migrate into SLNs successfully to stain them black for easy visual identification. Beyond staining, the hybrid nanosystem could realize contrast enhanced ultrasound (CEUS) imaging in SLNs. Meanwhile, it could inhibit cancer cells to lower the tumor burden and reverse immune-suppressive microenvironment of metastatic SLNs effectively via magnetic hyperthermia immunotherapy in VX2 tumor-bearing rabbits with popliteal fossa lymph node metastasis. These findings indicate that SPIOs + RPPs is a potential multifunctional theranostic agent for detection and therapy of lymphatic metastasis.

Advances in magnetic induction hyperthermia.

Magnetic induction hyperthermia (MIH), is a technique that has developed rapidly in recent years in the field of tumor thermotherapy. It implants a magnetic heating medium (millimeter-sized heat seeds, micron-sized magnetic particles and nanometer-sized magnetic fluids, etc.) inside the tumor. The material heats up under the induction of an external alternating magnetic field (100-500 kHz), which causes a high temperature zone to rapidly form in the local biological tissues and induces apoptosis in tumor cells. Magnetic induction hyperthermia has the advantages of high safety, strong targeting, repeatable treatment, and the size of the incision during treatment is negligible compared to surgical resection, and is currently used in clinical treatment. However, the millimeter-scale heat seed heating that is typically used in treatments can result in uneven temperatures within the tissue. Common MIH heating devices are bulky and complex in design, and are not easy for medical staff to get their hands on, which are issues that limit the diffusion of MIH. In this view, this paper will discuss the basic theoretical research on MIH and the progress of MIH-related technologies, with a focus on the latest research and development results and research hotspots of nanoscale ferromagnetic media and magnetic heat therapy devices, as well as the validation results and therapeutic efficacy of the new MIH technology on animal experiments and clinical trials. In this paper, it is found that induction heating using magnetic nanoparticles improves the uniformity of the temperature field, and the magneto-thermal properties of nanoscale ferromagnetic materials are significantly improved. The heating device was miniaturized to simplify the operation steps, while the focusing of the magnetic field was locally enhanced. However, there are fewer studies on the biotoxicity aspects of nanomedicines, and the localized alternating magnetic field uniformity used for heating and the safety of the alternating magnetic field after irradiation of the human body have not been sufficiently discussed. Ultimately, the purpose of this paper is to advance research related to magnetic induction thermotherapy that can be applied in clinical treatment.

On-demand Opto-Laser activatable nanoSilver ThermoGel for treatment of full-thickness diabetic wound in a mouse model.

Patients suffering from diabetes mellitus are prone to develop diabetic wounds that are non-treatable with conventional therapies. Hence, there is an urgent need of hour to develop the therapy that will overcome the lacunas of conventional therapies. This investigation reports the Quality by Design-guided one-pot green synthesis of unique Opto-Laser activatable nanoSilver ThermoGel (OL→nSil-ThermoGel) for hyperthermia-assisted treatment of full-thickness diabetic wounds in mice models. The characterization findings confirmed the formation of spherical-shaped nanometric Opto-Laser activatable nanoSilver (30.75 ± 2.7 nm; ∆T: 37 ± 0.2 °C â†’ 66.2 ± 0.1 °C; at 1.8 W/cm2 NIR laser density). The findings indicated acceptable in vitro cytocompatibility and significant keratinocyte migration (95.04 ± 0.07 %) activity of OL→nSil towards HaCaT cells. The rheological data of OL→nSil hybridized in situ thermoresponsive gel (OL→nSil-ThermoGel) showed the gelling temperature at 32 ± 2 °C. In vivo studies on full-thickness diabetic wounds in a Mouse model showed OL→nSil-ThermoGel accelerated wound closure (94.42 ± 1.03 %) and increased collagen synthesis, angiogenesis, and decreased inflammatory markers. Similarly, immunohistochemistry study showed significant angiogenesis and faster phenotypic switching of fibroblasts to myofibroblasts in OL→nSil-ThermoGel treated diabetic wounds. Histological evaluation revealed a marked rise in keratinocyte migration, organized collagen deposition, and early regeneration of the epithelial layer compared to the diabetic wound control. In conclusion, the OL→nSil-ThermoGel modulates the cytokines, re-epithelialization, protein expression, and growth factors, thereby improving the repair and regeneration of diabetic wounds in mice.

Thermotolerance in Angus cattle is related to hair coat characteristics but not to coat color.

This study evaluated the impact of coat color (CC) and hair coat characteristics (HC) on productive and physiological traits related to thermotolerance in Angus heifers. The goal was to determine if HC and/or CC were reliable indicators of thermotolerance on a large scale for future breeding programs. Ninety-three 15-month-old Angus heifers (52 black, 41 red) were evaluated in three periods on a beef cattle farm in Brazil. Heifers were classified by CC and HC, and body weight, body condition score (BCS), and reproductive tract score (RTS) were compared between groups. In the summer evaluation, surface temperature (infrared thermography), internal temperature (intravaginal sensors), sweating rate, and behavior were assessed in a subset of heifers. Temperature-humidity index (THI) was calculated using meteorological data. The proportion of heifers with short, fine, and smooth hair (HC1) increased (P < 0.05) over the evaluations. Heifers with thick, long, and woolly hair (HC3) had lower (P < 0.05) body weights than those with finer coats, regardless of CC. Black heifers had greater (P < 0.05) puberty rates than red heifers in the first two evaluations. At a THI of 66, black heifers with HC1 exhibited a lower (P < 0.05) internal temperature compared to black heifers with HC3. At a THI of 75, all heifers with HC1 had lower (P < 0.05) internal temperatures, regardless of CC. Red heifers and those with HC3 experienced hyperthermia for longer (P < 0.05) periods. Neither HC nor CC affected (P > 0.05) surface temperatures or sweating rates. At a THI of 72, more black heifers remained standing, suggesting behavioral adaptation. In conclusion, coat color and characteristics influence thermal stress and performance in Angus heifers, though color impact is limited. Internal temperature monitoring effectively determines thermotolerance. In tropical regions, selecting for short, fine, smooth hair may improve heat tolerance.

Combining stress inoculation with virtual reality simulation training of malignant hyperthermia.

BACKGROUND: Limited research has been conducted on how healthcare simulation can mitigate clinician stress. Stress exposure training (SET) has been shown to decrease stress's impact on performance. Combining SET with virtual reality (VR) simulation training has not yet been explored in the context of stress inoculation. The primary purpose of this pilot study was to determine if a VR module could induce stress. The secondary purpose was to determine if repeated exposure to stressors could decrease stress response in a simulated environment. METHODS: Medical students were recruited to partake in VR simulation modules aimed at treatment of malignant hyperthermia (MH). Those in the SET group were exposed to stressful stimuli during training modules, while those in the Control group were not. Both groups then completed a Test Module with the presence of stressful stimuli. Objective and subjective indicators of stress were measured after each module. RESULTS: Both groups indicated increases in perceived stress and module stressfulness after Training Module 1 and decreases after Training Module 2. After the Test Module, the Control group experienced significant elevation in perceived stress (p = .05), and the SET group had a significant decrease in perceived module stressfulness (p < .05). Both groups had a decrease in perceived competence after Training Module 1 (p < .001) and an increase after Training Module 2 (p < .001), with the SET group having significant elevation after the Test Module (p < .01). Both groups found the VR module to be feasible as a teaching tool. Objectively, the SET group showed an upward trend in electrodermal activity (EDA) from the Tutorial to Test Modules (p < .05), with the Control group showing a decrease after Training Module 2 (p = .05) and an increase after the Test Module (p < .01). CONCLUSIONS: A VR module targeting treatment of MH successfully induced stress and was regarded favorably by participants. Those in the SET group perceived less stress and more competence after the Test Module than those in the Control. Findings suggest that repeated exposure to stressors through VR may desensitize participants from future stress in a simulated environment.

Individuals and Families Affected by RYR1-Related Diseases - The Patient/Caregiver Perspective.

Background and objective: Pathogenic variants of RYR1, the gene encoding the principal sarcoplasmic reticulum calcium release channel (RyR1) with a crucial role in excitation-contraction coupling, are among the most common genetic causes of non-dystrophic neuromuscular disorders. We recently conducted a questionnaire study focusing on functional impairments, fatigue, and quality of life (QoL) in patients with RYR1-related diseases (RYR1-RD) throughout the recognized disease spectrum. In this previous questionnaire study the medical perspective was taken, reflective of a study protocol designed by neurologists and psychologists. With this present study we wanted to specifically address the patient perspective. Methods: Together with affected individuals, family members, and advocates concerned with RYR1-RD, we developed an online patient survey that was completed by 227 patients or their parents/other caretakers (143 females and 84 males, 0-85 years). We invited 12 individuals, representing most of the patient group based on age, sex, race, and type and severity of diagnosis, to share their personal experiences on living with a RYR1-RD during an international workshop in July 2022. Data were analyzed through a mixed-methods approach, employing both a quantitative analysis of the survey results and a qualitative analysis of the testimonials. Results: Data obtained from the combined quantitative and qualitative analyses provide important insights on six topics: 1) Diagnosis; 2) Symptoms and impact of the condition; 3) Physical activity; 4) Treatment; 5) Clinical research and studies; and 6) Expectations. Conclusions: Together, this study provides a unique patient perspective on the RYR1-RD spectrum, associated disease impact, suitable physical activities and expectations of future treatments and trials, and thus, offers an essential contribution to future research.