Rumen-protected methionine supplementation during the transition period under artificially induced heat stress: Effects on cow-calf performance.

Dairy cows experiencing heat stress (HS) during the precalving portion of the transition period give birth to smaller calves and produce less milk and milk protein. Supplementation of rumen-protected methionine (RPM) has been shown to modulate protein, energy, and placenta metabolism, making it a potential candidate to ameliorate HS effects. We investigated the effects of supplementing RPM to transition cows under HS induced by electric heat blanket (EHB) on cow-calf performance. Six weeks before expected calving, 53 Holstein cows were housed in a tiestall barn and fed a control diet (CON, 2.2% Met of MP) or a CON diet supplemented with SmartamineM (MET, 2.6% Met of MP, Adisseo Inc., France). Four weeks precalving, all MET and half CON cows were fitted with an EHB. The other half of the CON cows were considered thermoneutral (TN), resulting in 3 treatments: CONTN (n = 19), CONHS (n = 17), and METHS (n = 17). Respiratory rate (RR), skin temperature (ST), and rectal temperature (RT) were measured thrice weekly and core body temperatures recorded biweekly. Postcalving BW and BCS were recorded weekly, and DMI was calculated and averaged weekly. Milk yield was recorded daily and milk components were analyzed every third DIM. Biweekly AA and weekly nonesterified fatty acids (NEFA), BHB, insulin, and glucose were measured from plasma. Calf birth weight and 24 h growth, thermoregulation, and hematology profile were measured and apparent efficiency of absorption (AEA) of immunoglobulins was calculated. Data were analyzed using the MIXED procedure of SAS with 2 preplanned orthogonal contrasts: CONTN versus the average of CONHS and METHS (C1) and CONHS versus METHS (C2). Relative to TN, EHB cows had increased RT during the postcalving weeks and increased RR and ST during the entire transition period. Body weight, BCS, DMI, and milk yield were not affected by the EHB or RPM. However, protein percentage and SNF were lower in CONHS, relative to METHS cows. At calving, METHS dams had higher glucose concentrations, relative to CONHS, and during the postcalving weeks, the EHB cows had lower NEFA concentrations than TN cows. Calf birthweight and AEA were reduced by HS, whereas RR was increased by HS. Calf withers height tended to be shorter and RT were lower in CONHS, compared with METHS heifers. Overall, RPM supplementation to transition cows reverts the negative effect of HS on blood glucose concentration at calving and milk protein percentage in the dams and increases wither height while decreasing RT in the calf.

Effect of spinal cord injury on the skin temperature of different regions of interest during a graded exercise test in a moderate temperature environment.

The gradient between core and skin temperature is a relevant factor in heat exchange between the human body and the environment, but people with spinal cord injury (SCI), due to their autonomic dysfunction, have impaired mechanisms that condition skin temperature response. This study aimed to determine how SCI affects skin temperature response in different ROIs during a graded exercise test in a moderate temperature environment. 32 participants were included in the study [SCI (N = 16); Non-SCI (N = 16)]. A graded exercise test was conducted on an arm crank ergometer, with a staged duration of 3 min separated by 1 min of rest. Skin temperature was measured using infrared thermography at rest, after each interval and during recovery. Individuals with SCI exhibited lower skin temperature in the anterior leg during exercise than Non-SCI (p < 0.001). During recovery, SCI athletes experienced a lower skin temperature restoration in the anterior arm, posterior arm and anterior leg (p < 0.05). The anterior leg is an interesting region to measure during exercise in people with SCI for assessing the physiological effect of the injury, probably for the autonomic dysfunction in skin temperature regulation, but the effect observed during recovery in the arms suggests the presence of different mechanisms involved in skin temperature regulation.

Novel Perspective on Molecular and Cellular Adaptations of the Mammary Gland-Regulating Milk Constituents and Immunity of Heat-Stressed Dairy Cows.

Climate change with increasing ambient temperatures negatively influences the biology of dairy cows and their milk production in the mammary gland (MG). This study aimed to elucidate the MG proteome, differences in milk composition, and ruminal short-chain fatty acid concentrations of dairy cows experiencing 7 days of heat stress [HS, 28 °C, temperature humidity index (THI) = 76], pair-feeding (PF), or ad libitum feeding (CON) at thermoneutrality (16 °C, THI = 60). Ruminal acetate, acetate/propionate ratio, and milk urea concentrations were greater, whereas milk protein and lactose were lower in HS than in control cows. Proteome analysis revealed an induced bacterial invasion of epithelial cells, leukocyte transendothelial migration, reduction of the pyruvate and carbon metabolism, and platelet activation in the MG of HS compared to CON or PF cows. These results highlight adaptive metabolic and immune responses to mitigate the negative effects of ambient heat in the MG.

Voluntary head dunking after exercise-induced hyperthermia rapidly reduces core body temperature in dogs.

OBJECTIVE: To evaluate field-applicable cooling methods for treatment of exercise-induced hyperthermia in dogs. METHODS: In this randomized, crossover study from June 27, 2023, to July 24, 2023, 12 working dogs exercised for 10 minutes until core body temperature reached 40.6 °C or above or ≥ 2 signs of heat stress were observed. Four different cooling protocols were evaluated: (1) neck chemical ice packs (2), (2) a wet (22 °C) neck towel, (3) wet (22 °C) axillae towels, or (4) voluntary head immersion ("dunking") into (22 °C) water. After intervention, dogs rested and were monitored for 40 minutes. RESULTS: The dunking protocol, which included limited water ingestion, produced the lowest mean core temperature in the initial 5 minutes after exercise, in the subsequent 35 minutes during which dogs cooled to baseline temperature and was the only protocol to prevent the initial postexercise temperature rise. All methods resulted in return to baseline temperature. CONCLUSIONS: Trained voluntary head dunk with limited water ingestion results in rapid cooling in field situations of exercise-induced hyperthermia in dogs with normal mental status and ability to pause panting. CLINICAL RELEVANCE: "Cool first, transport second" reduces morbidity and mortality of acute heat injury. When whole-body water immersion is not an option, the trained voluntary head dunk in mentally appropriate dogs prevents postexercise rise and rapidly reduces core body temperature within the first 5 minutes. Alternatively, allowing the dog to drink controlled amounts of cool water and pouring water on the dog's head may provide some benefit but warrants further study.

Propofol binds and inhibits skeletal muscle ryanodine receptor 1.

BACKGROUND: As the primary Ca2+ release channel in skeletal muscle sarcoplasmic reticulum (SR), mutations in type 1 ryanodine receptor (RyR1) or its binding partners underlie a constellation of muscle disorders, including malignant hyperthermia (MH). In patients with MH mutations, triggering agents including halogenated volatile anaesthetics bias RyR1 to an open state resulting in uncontrolled Ca2+ release, increased sarcomere tension, and heat production. Propofol does not trigger MH and is commonly used for patients at risk of MH. The atomic-level interactions of any anaesthetic with RyR1 are unknown. METHODS: RyR1 opening was measured by [3H]ryanodine binding in heavy SR vesicles (wild type) and single-channel recordings of MH mutant R615C RyR1 in planar lipid bilayers, each exposed to propofol or the photoaffinity ligand analogue m-azipropofol (AziPm). Activator-mediated wild-type RyR1 opening as a function of propofol concentration was measured by Fura-2 Ca2+ imaging of human skeletal myotubes. AziPm binding sites, reflecting propofol binding, were identified on RyR1 using photoaffinity labelling. Propofol binding affinity to a photoadducted site was predicted using molecular dynamics (MD) simulation. RESULTS: Both propofol and AziPm decreased RyR1 opening in planar lipid bilayers (P<0.01) and heavy SR vesicles, and inhibited activator-induced Ca2+ release from human skeletal myotube SR. Several putative propofol binding sites on RyR1 were photoadducted by AziPm. MD simulation predicted propofol KD values of 55.8 µM and 1.4 µM in the V4828 pocket in open and closed RyR1, respectively. CONCLUSIONS: Propofol demonstrated direct binding and inhibition of RyR1 at clinically plausible concentrations, consistent with the hypothesis that propofol partially mitigates MH by inhibition of induced Ca2+ flux through RyR1.

Nanoengineered Injectable Hydrogel: An Advanced Radioprotective Barrier with Magnetic Hyperthermia Synergy.

Despite its effectiveness in eradicating cancer cells, current tumor radiotherapy often causes irreversible damage to the surrounding healthy tissues. To address this issue and enhance therapeutic outcomes, we developed a multifunctional injectable hydrogel that integrates electromagnetic shielding and magnetothermal effects. This innovation aims to improve the efficacy of brachytherapy while protecting adjacent normal tissues. Recognizing the limitations of existing hydrogel materials in terms of stretchability, durability, and single functionality, we engineered a composite hydrogel by self-assembling nickel nanoparticles on the surface of liquid metal particles and embedding them into an injectable hydrogel matrix. The resulting composite material demonstrates superior electromagnetic interference shielding performance (74.89 dB) and a rapid magnetothermal heating rate (10.9 °C/min), significantly enhancing its in vivo applicability. The experimental results confirm that this innovative nanocomposite hydrogel effectively attenuates electromagnetic waves during brachytherapy, thereby protecting normal tissues surrounding the tumor and enhancing radiotherapy efficacy through magnetothermal therapy. This study advances the safety and effectiveness of cancer treatments and provides new insights into the development of multifunctional biomedical materials, promoting the innovative application of nanotechnology in the medical field.

Dual-Modal Near-Infrared Organic Nanoparticles: Integrating Mild Hyperthermia Phototherapy with Fluorescence Imaging.

Purpose: Our study seeks to develop dual-modal organic-nanoagents for cancer therapy and real-time fluorescence imaging, followed by their pre-clinical evaluation on a murine model. Integrating NIR molecular imaging with nanotechnology, our aim is to improve outcomes for early-stage cutaneous melanoma by offering more effective and less invasive methods. This approach has the potential to enhance both photothermal therapy (PTT) and Sentinel Lymph Node Biopsy (SLNB) procedures for melanoma patients. Methods: NIR-797-isothiocyanate was encapsulated in poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles (NPs) using a two-step protocol, followed by thorough characterization, including assessing loading efficiency, fluorescence stability, and photothermal conversion. Biocompatibility and cellular uptake were tested in vitro on melanoma cells, while PTT assay, with real-time thermal monitoring, was performed in vivo on tumor-bearing mice under irradiation with an 808 nm laser. Finally, ex vivo fluorescence microscopy, histopathological assay, and TEM imaging were performed. Results: Our PLGA NPs, with a diameter of 270 nm, negative charge, and 60% NIR-797 loading efficiency, demonstrated excellent stability and fluorescence properties, as well as efficient light-to-heat conversion. In vitro studies confirmed their biocompatibility and cellular internalization. In vivo experiments demonstrated their efficacy as photothermal agents, inducing mild hyperthermia with temperatures reaching up to 43.8 °C. Ex vivo microscopy of tumor tissue confirmed persistent NIR fluorescence and uniform distribution of the NPs. Histopathological and TEM assays revealed early apoptosis, immune cell response, ultrastructural damage, and intracellular material debris resulting from combined NP treatment and irradiation. Additionally, TEM analyses of irradiated zone margins showed attenuated cellular damage, highlighting the precision and effectiveness of our targeted treatment approach. Conclusion: Specifically tailored for dual-modal NIR functionality, our NPs offer a novel approach in cancer PTT and real-time fluorescence monitoring, signaling a promising avenue toward clinical translation.

Risperidone suppresses caffeine-induced hyperthermia and hyperactivity in rats.

Caffeine, a methylxanthine alkaloid, works as a nonselective adenosine receptor antagonist. It is the most widely used psychostimulant drug worldwide. However, caffeine overdose can lead to acute intoxication, posing a clinical problem. Hyperthermia and hyperactivity are associated issues with acute caffeine intoxication; however, no definitive treatment exists. This study aimed to assess the ability of risperidone to attenuate caffeine-induced hyperthermia and hyperactivity while elucidating the unknown mechanisms of caffeine intoxication. The rats received intraperitoneal injections of saline, risperidone (0.25 mg/kg, 0.5 mg/kg), WAY-100635, ketanserin, haloperidol, sulpiride, or SCH 23390, 5 min after the administration of caffeine (25 mg/kg). Subcutaneous temperature and activity counts were measured using nano tag ® for up to 90 min. In vivo microdialysis was used to determine the effect of risperidone on caffeine-induced elevation of dopamine (DA), serotonin (5-HT), and noradrenaline (NA) concentrations in the anterior hypothalamus. Rats were injected with caffeine (25 mg/kg), followed by saline or risperidone (0.5 mg/kg) 5 min later. The levels of DA, 5-HT, and noradrenaline were measured every 15 min for up to 90 min after caffeine administration. Risperidone and 5-HT2A receptor antagonist ketanserin attenuated caffeine-induced hyperthermia and hyperactivity. Haloperidol and dopamine D1 antagonist SCH-23390 exacerbated hyperthermia without any effect on the hyperactivity. In the microdialysis study, risperidone treatment further attenuated caffeine-induced 5-HT elevation, but not DA and NA. Our results indicate that risperidone attenuates caffeine-induced hyperthermia and hyperactivity by blocking 5-HT2A receptor activity and may be potentially useful for treating caffeine intoxication.

The Effect of Water Dousing on Heat Strain and Performance During Endurance Running in the Heat.

OBJECTIVES: Assess the effect of water dousing on heat strain and performance during self- and fixed-paced exercise in the heat. DESIGN: Crossover, block-randomized controlled trial. METHODS: Thirteen trained runners completed a 10-km time trial (TT) and 60-minute fixed-pace run (60% velocity of V˙O2max) in a 30.4 °C, 47.4% relative humidity environment using either water dousing (DOUSE) or no dousing (CON). RESULTS: Ten-kilometer TT performance was faster in DOUSE compared to CON (44:11 [40:48, 47:34] vs 44:38 [41:21, 47:56] min:s; P = .033). Change in core temperature (Tc) was not different between groups during the TT (+0.02 [-0.04, 0.07] °C in DOUSE; P = .853) or fixed-pace run (+0.02 [-0.15, 0.18] °C; P = .848). Change in mean skin temperature was lower in DOUSE during the TT (-1.80 [-2.15, -1.46] °C; P < .001) and fixed-pace run (-1.38 [-1.81, -0.96] °C; P < .001). Heart rate was lower for DOUSE during the fixed-pace run (-3.5 [-6.8, -0.2] beats/min; P = .041) but not during the TT (-0.2 [-2.5, 2.1] beats/min; P = .853). Thermal sensation was lower for DOUSE during the TT (-49.3 [-72.1, -26.1] mm; P < .001) and fixed-pace run (-44.7 [-59.7, -29.6] mm; P < .001). Rating of perceived exertion was not different between groups for the TT (-0.2 [-0.7, 0.3]; P = .390) or fixed-pace run (-0.2 [-0.8, 0.4]; P = .480). Sweat rate was lower for DOUSE for the TT (-0.37 [-0.53, -0.22] L/h; P < .001) and fixed-pace run (-0.37 [-0.48, -0.26] L/h; P < .001). CONCLUSION: Water dousing improves 10-km TT performance in the heat but does not affect Tc. The positive change in thermal perception (via lower skin temperature) during the TT likely drives this benefit.

Gold nanorod-assisted theranostic solution for nonvisible residual disease in bladder cancer.

Residual nonvisible bladder cancer after proper treatment caused by technological and therapeutic limitations is responsible for tumor relapse and progression. This study aimed to demonstrate the feasibility of a solution for simultaneous detection and treatment of bladder cancer lesions smaller than one millimeter. The α5ß1 integrin was identified as a specific marker in 81% of human high-grade nonmuscle invasive bladder cancers and used as a target for the delivery of targeted gold nanorods (GNRs). In a preclinical model of orthotopic bladder cancer expressing the α5ß1 integrin, the photoacoustic imaging of targeted GNRs visualized lesions smaller than one millimeter, and their irradiation with continuous laser was used to induce GNR-assisted hyperthermia. Necrosis of the tumor mass, improved survival, and computational modeling were applied to demonstrate the efficacy and safety of this solution. Our study highlights the potential of the GNR-assisted theranostic strategy as a complementary solution in clinical practice to reduce the risk of nonvisible residual bladder cancer after current treatment. Further validation through clinical studies will support the findings of the present study.

Multifrequency operation of an intracavitary monopole with sliding broadband choke for delivering hyperthermia treatment with variable coverage.

Microwave applicators reported for intracavitary hyperthermia (HT) operate at single frequency and deliver fixed treatment coverage at the tumor target. In this work, we report multifrequency operation of a water-cooled monopole antenna with a sliding broadband ferrite choke for delivering intracavitary HT to the cervix with variable spatial coverage. Spatially varying treatment coverage is achieved by varying the choke position with respect to the monopole using a mechanical sliding arrangement and exciting the antenna at the modified resonant frequency. Multifrequency operation of the antenna prototype is demonstrated over 700-1000 MHz using a straight intrauterine cervix applicator. Numerical simulations confirm the ability to deliver targeted HT with axial extent varying between 35.4 and 62.0 mm by controlling the sliding choke and coupling water temperature. Applicator prototype measurements in tissue mimicking phantoms confirm multifrequency operation of the antenna and its ability to induce axially varying intracavitary HT coverage to match the tumor size using a single applicator.

Microwave devices used for targeted internal hyperthermia treatment typically operate at fixed frequency and provide fixed treatment coverage to the tumor. In this study, we introduce a new approach using a water-cooled monopole antenna with a sliding broadband ferrite choke to treat cervical cancer with varying tumor volumes. The proposed antenna can be operated at multiple frequencies to adjust the treatment volume. By sliding the choke along the antenna, the antenna can be tuned to different frequencies and deliver spatially varying treatment coverage to suit the clinical target volume. Laboratory assessment shows that this antenna can be operated over 700 to 1000 MHz to deliver treatment coverage with axial extent varying over 35.4 to 62.0 mm, depending on the choke position and water temperature. Experiments on tissue mimicking phantoms confirm that this method enables precise control of hyperthermia treatment coverage to match the tumor size using a single device.

Surviving a classic heat stroke/hyperthermia > 42 °C - a case report.

INTRODUCTION: Classic heat stroke is a severe trauma which can lead to multi-organ dysfunctions and is associated with a high mortality. CASE PRESENTATION: In this case report we present a 73-year-old patient with a classic heat stroke. His initial core body temperature was over 42 °C and he had a GCS of 3. Due to severe burn injuries the patient was transferred to a specialized burn center. The patient developed different organ failures and showed a prolonged course on the intensive care unit. Although the patient demonstrated different impaired organ systems, he recovered completely after receiving painstaking supportive therapy. CONCLUSIONS: This is a rare case of a patient who fully recovered after a heat stroke with a temperature over 42 °C and severe sequelae.

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.

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.

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.

Alternating magnetic field guiding system for MNP hyperthermia treatment of deep-seated cancers.

OBJECTIVES: Demonstrate the potential application of a novel, endoscope-like device to guide and focus an alternating magnetic field (AMF) for treating deep-seated cancers via magnetic nanoparticle hyperthermia (MNPH). METHODS: AMF delivery, MNP activation, and eddy current distribution characteristics are investigated through experimental studies in phantoms and computational simulations using a full 3-dimensional human model. The 3D simulations compare the novel device to traditional AMF designs, including a MagForce-like, two-coil system (used clinically) and a single surface-coil system. RESULTS: The results demonstrate that this approach can deliver the same magnetic field strength at the prostate's centroid as traditional AMF designs, while reducing eddy current heating by 2 to 6 times. At the same level of normal tissue heating, this method provides 5.0 times, 1.5 times, and 0.92 times the magnetic field strength to the nearest, centroid, and farthest regions of the prostate, respectively. CONCLUSIONS: These results demonstrate proof-of-concept for an endoscopic magnetic field guiding and focusing system capable of delivering clinically relevant AMF from a distance. This innovative approach offers a promising alternative to conventional field delivery methods by directing AMF through the body, concentrating it in the tumor region, reducing eddy currents in surrounding healthy tissue, and avoiding exposure of nearby metallic implants.

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.

Investigation of antibacterial and anticancer activities of copper, aluminum and nickel doped zinc sulfide nanoparticles.

First time compared the different metals doped ZnS nanoparticles for antibacterial and liver cancer cell line. In this study, copper, aluminum and nickel doped ZnS NPs were synthesized via co-precipitation method. The XRD analysis was confirmed the presence of cubic crystal structure and crystallite size decreased from 6 to 3 nm with doping elements. While as SEM micro-grains were revealed slightly irregular and agglomerated morphology with the presence of dopant elements. The presence of different dopant elements such as Cu, Al and Ni in ZnS NPs was identified via EDX analysis. The FTIR results demonstrate various vibrational stretching and bending modes attached to the surface of ZnS nanomaterials. After that the well diffusion method was used to conduct in-vitro bioassays for evaluation of antibacterial and anticancer activities against E.coli and B.cereus, as well as HepG2 liver cancer cell line. Our findings unveil exceptional results with maximum inhibition zone of approximately 9 to 23 mm observed against E.coli and 12 to 27 mm against B.cereus, respectively. In addition, the significant reduction in cell viability was achieved against the HepG2 liver cancer cell line. These favorable results highlight the potential of Ni doped ZnS NPs for various biomedical applications. In future, the doped ZnS nanomaterials will be suitable for hyperthermia therapy and wound healing process.

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.

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.