Photobiomodulation therapy reverses spermatogenesis arrest in hyperthermia-induced azoospermia mouse model.

Testicular heat stress leads to impairment of spermatogenesis in mammals. Involved mechanism in this vulnerability to heat-induced injury remains unclear, and research is being conducted to find an approach to reverse spermatogenesis arrest caused by hyperthermia. Recently, different studies have utilized photobiomodulation therapy (PBMT) therapy for the improvement of sperm criteria and fertility. This study aimed at evaluating the effect of PBMT on the improvement of spermatogenesis in mouse models of hyperthermia-induced azoospermia. A total of 32 male NMRI mice were equally divided into four groups consisting of control, hyperthermia, hyperthermia + Laser 0.03 J/cm2, and hyperthermia + Laser 0.2 J/cm2. To induce scrotal hyperthermia, mice were anesthetized and placed in a hot water bath at 43 °C for 20 min for 5 weeks. Then, PBMT was operated for 21 days using 0.03 J/cm2 and 0.2 J/cm2 laser energy densities in the Laser 0.03 and Laser 0.2 groups, respectively. Results revealed that PBMT with lower intensity (0.03 J/cm2) increased succinate dehydrogenase (SDH) activity and glutathione (GSH)/oxidized glutathione (GSSG) ratio in hyperthermia-induced azoospermia mice. At the same time, low-level PBMT reduced reactive oxygen species (ROS), mitochondrial membrane potential, and lipid peroxidation levels in the azoospermia model. These alterations accompanied the restoration of spermatogenesis manifested by the elevated number of testicular cells, increased volume and length of seminiferous tubules, and production of mature spermatozoa. After conducting experiments and analyzing the results, it has been revealed that the use of PBMT at a dosage of 0.03 J/cm2 has shown remarkable healing effects in the heat-induced azoospermia mouse model.

Circadian rhythm of preferred temperature in fish: Behavioural thermoregulation linked to daily photocycles in zebrafish and Nile tilapia.

Ectothermic vertebrates, e.g. fish, maintain their body temperature within a specific physiological range mainly through behavioural thermoregulation. Here, we characterise the presence of daily rhythms of thermal preference in two phylogenetically distant and well-studied fish species: the zebrafish (Danio rerio), an experimental model, and the Nile tilapia (Oreochromis niloticus), an aquaculture species. We created a non-continuous temperature gradient using multichambered tanks according to the natural environmental range for each species. Each species was allowed to freely choose their preferred temperature during the 24h cycle over a long-term period. Both species displayed strikingly consistent temporal daily rhythms of thermal preference with higher temperatures being selected during the second half of the light phase and lower temperatures at the end of the dark phase, with mean acrophases at Zeitgeber Time (ZT) 5.37 h (zebrafish) and ZT 12.5 h (tilapia). Interestingly, when moved to the experimental tank, only tilapia displayed consistent preference for higher temperatures and took longer time to establish the thermal rhythms. Our findings highlight the importance of integrating both light-driven daily rhythm and thermal choice to refine our understanding of fish biology and improve the management and welfare of the diversity of fish species used in research and food production.

Altered skeletal muscle sarco-endoplasmic reticulum Ca2+-ATPase calcium transport efficiency after a thermogenic stimulus.

Exposure to predator threat induces a rapid and robust increase in skeletal muscle thermogenesis in rats. The central nervous system relays threat information to skeletal muscle through activation of the sympathetic nervous system, but muscle mechanisms mediating this thermogenesis remain unidentified. Given the relevance of sarcolipin-mediated futile calcium cycling through the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) pump to mammalian muscle nonshivering thermogenesis, we hypothesized that this plays a role in contextually induced muscle thermogenesis as well. This was assessed by measuring enzymatic activity of SERCA and sarcoplasmic reticulum Ca2+ transport, where the apparent coupling ratio (Ca2+ uptake rate divided by ATPase activity rate at a standard Ca2+ concentration) was predicted to decrease in association with muscle thermogenesis. Sprague-Dawley rats exposed to predator (ferret) odor (PO) showed a rapid decrease in the apparent coupling ratio in the soleus muscle, indicating SERCA uncoupling compared with control-odor-exposed rats. A rat model of high aerobic fitness and elevated muscle thermogenesis also demonstrated soleus muscle SERCA uncoupling relative to their obesity-prone, low-fitness counterparts. Both the high- and low-aerobic fitness rats showed soleus SERCA uncoupling with exposure to PO. Finally, no increase in sarcolipin expression in soleus muscle was detected with PO exposure. This dataset implicates muscle uncoupling of SERCA Ca2+ transport and ATP hydrolysis, likely through altered SERCA or sarcolipin function outside of translational regulation, as one contributor to the muscle thermogenesis provoked by exposure to predator threat. These data support the involvement of SERCA uncoupling in both muscle thermogenic induction and enhanced aerobic capacity.

Immobilization, cardiopulmonary and blood gas effects of ketamine-butorphanol-medetomidine versus butorphanol-midazolam-medetomidine in free-ranging serval (Leptailurus serval).

OBJECTIVE: To compare ketamine-butorphanol-medetomidine (KBM) with butorphanol-midazolam-medetomidine (BMM) immobilization of serval. STUDY DESIGN: Blinded, randomized trial. ANIMALS: A total of 23 captures [KBM: five females, six males; 10.7 kg (mean); BMM: 10 females, two males; 9.6 kg]. METHODS: Serval were cage trapped and immobilized using the assigned drug combination delivered via a blow dart into gluteal muscles. Prior to darting, a stress score was assigned (0: calm; to 3: markedly stressed). Drug combinations were dosed based on estimated body weights: 8.0, 0.4 and 0.08 mg kg-1 for KBM and 0.4, 0.3 and 0.08 mg kg-1 for BMM, respectively. Time to first handling, duration of anaesthesia and recovery times were recorded. Physiological variables including blood glucose and body temperature were recorded at 5 minute intervals. Atipamezole (5 mg mg-1 medetomidine) and naltrexone (2 mg mg-1 butorphanol) were administered intramuscularly prior to recovery. Data, presented as mean values, were analysed using general linear mixed model and Spearman's correlation (stress score, glucose, temperature); significance was p < 0.05. RESULTS: Doses based on actual body weights were 8.7, 0.4 and 0.09 mg kg-1 for KBM and 0.5, 0.4 and 0.09 mg kg-1 for BMM, respectively. Time to first handling was 10.2 and 13.3 minutes for KBM and BMM, respectively (p = 0.033). Both combinations provided cardiovascular stability during anaesthesia that lasted a minimum of 35 minutes. Recovery was rapid and calm overall, but ataxia was noted in KBM. Stress score was strongly correlated to blood glucose (r2 = 0.788; p = 0.001) and temperature (r2 = 0.634; p = 0.015). CONCLUSIONS AND CLINICAL RELEVANCE: Both combinations produced similar effective immobilization that was cardiovascularly stable in serval. Overall, BMM is recommended because it is fully antagonizable. A calm, quiet environment before drug administration is essential to avoid capture-induced hyperglycaemia and hyperthermia.

Sexual Dimorphism in Stress-induced Hyperthermia in SNAP25Δ3 mice, a mouse model with disabled Gßγ regulation of the exocytotic fusion apparatus.

Behavioral assays in the mouse can show marked differences between male and female animals of a given genotype. These differences identified in such preclinical studies may have important clinical implications. We recently made a mouse model with impaired presynaptic inhibition through Gßγ-SNARE signaling. Here, we examine the role of sexual dimorphism in the severity of the phenotypes of this model, the SNAP25Δ3 mouse. In males, we already reported that SNAP25Δ3 homozygotes demonstrated phenotypes in motor coordination, nociception, spatial memory and stress processing. We now report that while minimal sexually dimorphic effects were observed for the nociceptive, motor or memory phenotypes, large differences were observed in the stress-induced hyperthermia paradigm, with male SNAP25Δ3 homozygotes exhibiting an increase in body temperature subsequent to handling relative to wild-type littermates, while no such genotype-dependent effect was observed in females. This suggests sexually dimorphic mechanisms of Gßγ-SNARE signaling for stress processing or thermoregulation within the mouse. Second, we examined the effects of heterozygosity with respect to the SNAP25Δ3 mutation. Heterozygote SNAP25Δ3 animals were tested alongside homozygote and wild-type littermates in all of the aforementioned paradigms and displayed phenotypes similar to wild-type animals or an intermediate state. From this, we conclude that the SNAP25Δ3 mutation does not behave in an autosomal dominant manner, but rather displays incomplete dominance for many phenotypes.

Do Alternative Cooling Methods Have Effective Cooling Rates for Hyperthermia Compared With Previously Established CWI Cooling Rates?

Clinical Scenario: In the last few years, there have been several studies examining alternative cooling strategies in the treatment of exertional heat stroke (EHS). Morbidity and mortality with EHS are associated with how long the patient's core body temperature remains above the critical threshold of 40.5°C. Although cold-water immersion (CWI) is the gold standard of treatment when cooling a patient with EHS, more recent alternative cooling techniques have been examined for use in settings where CWI may not be feasible (ie, remote locations). Clinical Question: Do alternative cooling methods have effective core body temperature cooling rates for hyperthermia compared with previously established CWI cooling rates? Summary of Key Findings: The authors searched for studies using alternative cooling methods to cool hyperthermic individuals. To be included, the studies needed a PEDro score ≥6 and a level of evidence ≥2. They found 9 studies related to our focused clinical question; of these, 5 studies met the inclusion criteria. The cooling rates for hand cooling, cold-water shower, and ice-sheet cooling were 0.03°C/min, 0.08°C/min, and 0.06°C/min, respectively, whereas the tarp-assisted cooling with oscillation (TACO) method was the only method that had an acceptable cooling rate (range 0.14-0.17°C/min). Clinical Bottom Line: When treating EHS, if CWI is not available, the tarp-assisted cooling method may be a reasonable alternative. Clinicians should not use cold shower, hand cooling, or ice-sheet cooling if better cooling methods are available. Clinicians should always use CWI when available. Strength of Recommendation: Five level 2 studies with PEDro scores ≥6 suggest the TACO method is the only alternative cooling method that decreases core body temperature at a similar, though slower, rate of CWI. Hand cooling, cold showering, and ice-sheet cooling do not decrease core body temperature at an appropriate rate and should not be used in EHS situations if a modality with a better cooling rate is available.

Significance of hyperechoic marks observed during high-intensity focused ultrasound (HIFU) ablation of benign thyroid nodules.

OBJECTIVE: To examine the association between the appearance of hyperechoic marks (HEMs) during high-intensity focused ultrasound (HIFU) ablation of benign thyroid nodules and nodule shrinkage at 6 months. METHODS: One hundred and thirty-six patients who underwent HIFU for benign thyroid nodule were analysed. An independent person carefully examined the B-mode ultrasonography screen for the appearance of HEMs after each pulse. The proportion of HEMs (%) was calculated by: [(Number of pulses that resulted in HEMs) / (Total number of pulses given per treatment) × 100] while the nodule shrinkage was measured by volume reduction ratio (VRR) = [Baseline volume-volume at 6 months]/[Baseline volume] * 100. Treatment success was defined as VRR ≥ 50 %. RESULTS: Patients with HEMs (n=91) had significantly greater 6-month VRR than those without HEMs (n=45) (65.76 % vs. 36.76 %, p<0.001). By regression analysis, after adjusting for age and energy per pulse, smaller nodule volume at baseline (OR 1.143, 95 % CI 1.038-1.256, p=0.006) and appearance of HEMs (OR 275.44, 95 % CI 26.63-2848.98, p<0.001) were independent predictors for treatment success. CONCLUSIONS: The appearance of HEMs during treatment was an independent determinant of treatment success following single-session HIFU ablation of benign thyroid nodule. KEY POINTS: • HIFU is a safe and effective treatment for benign thyroid nodules. • Lower BMI and greater applied power increase likelihood of hyperechoic marks. • The appearance of hyperechoic marks during HIFU affects subsequent treatment outcome.

Investigating factors affecting the body temperature of dogs competing in cross country (canicross) races in the UK.

Increasing numbers of people are running with their dogs, particularly in harness through the sport canicross. Whilst canicross races are typically held in the winter months, some human centred events are encouraging running with dogs in summer months, potentially putting dogs at risk of heat related injuries, including heatstroke. The aim of this project was to investigate the effects of ambient conditions and running speed on post-race temperature of canicross dogs in the UK, and investigate the potential risk of heatstroke to canicross racing dogs. The effects of canine characteristics (e.g. gender, coat colour) were explored in order to identify factors that could increase the risk of exercise-induced hyperthermia (defined as body temperature exceeding the upper normal limit of 38.8°C).108 dogs were recruited from 10 race days, where ambient conditions ranged from - 5 to 11°C measured as universal thermal comfort index (UTCI). 281 post race tympanic membrane temperatures were recorded, ranging from 37.0-42.5°C. There was a weak correlation between speed and post-race temperature (r = 0.269, P < 0.001). Whilst no correlation between any single environmental factor or UTCI and post-race temperature was found, the proportion of dogs developing exercise-induced hyperthermia during the race increased with UTCI (r = 0.688, P = 0.028). Male dogs (χ(1) = 18.286, P < 0.001), and dark coated dogs (χ(2) = 8.234, P = 0.014), were significantly more likely to finish the race with a temperature exceeding 40.6°C. Prolonged elevati°n of body temperature above this temperature is likely to cause heatstroke. At every race dogs exceeded this critical temperature, with 10.7% (n = 30) of the overall study population exceeding this temperature throughout the study period. The results suggest male dogs, dark coloured dogs, and increased speed of running all increase the risk of heatstroke in racing canicross dogs. Further research is required to investigate the impact of environmental conditions on post-race cooling, to better understand safe running conditions for dogs.

The basolateral amygdala can mediate the effects of fear memory on sleep independently of fear behavior and the peripheral stress response.

Fear conditioning associated with inescapable shock training (ST) and fearful context re-exposure (CR) alone can produce significant behavioral fear, a stress response and alterations in subsequent REM sleep. These alterations may vary among animals and are mediated by the basolateral nucleus of the amygdala (BLA). Here, we used the GABAA agonist, muscimol (Mus), to inactivate BLA prior to CR and examined the effects on sleep, freezing and stress-induced hyperthermia (SIH). Wistar rats (n=28) were implanted with electrodes for recording sleep, data loggers for recording core body temperature, and with cannulae aimed bilaterally into BLA. After recovery, the animals were habituated to the injection procedure and baseline sleep was recorded. On experimental day 1, rats received ST (20 footshocks, 0.8mA, 0.5s duration, 60s interstimulus interval). On experimental day 7, the rats received microinjections (0.5µl) into BLA of either Mus (1.0µM; n=13) or vehicle (Veh; n=15) prior to CR (CR1). On experimental day 21, the animals experienced a second CR (CR2) without Mus. For analysis, the rats were separated into 4 groups: (Veh-vulnerable (Veh-Vul; n=8), Veh-resilient (Veh-Res; n=7), Mus-vulnerable (Mus-Vul; n=7), and Mus-resilient (Mus-Res; n=6)) based on whether or not REM was decreased, compared to baseline, during the first 4h following ST. Pre-CR1 inactivation of BLA did not alter freezing or SIH, but did block the reduction in REM in the Mus-Vul group compared to the Veh-Vul group. These data indicate that BLA is an important region for mediating the effects of fearful memories on sleep.

It's cool to be dominant: social status alters short-term risks of heat stress.

Climate change has the potential to trigger social change. As a first step towards understanding mechanisms determining the vulnerability of animal societies to rising temperatures, we investigated interactions between social rank and thermoregulation in three arid-zone bird species: fawn-coloured lark (Mirafra africanoides, territorial); African red-eyed bulbul (Pycnonotus nigricans, loosely social) and sociable weaver (Philetairus socius, complex cooperative societies). We assessed relationships between body temperature (Tb), air temperature (Ta) and social rank in captive groups in the Kalahari Desert. Socially dominant weavers and bulbuls had lower mean Tb than subordinate conspecifics, and dominant individuals of all species maintained more stable Tb as Ta increased. Dominant bulbuls and larks tended to monopolise available shade, but dominant weavers did not. Nevertheless, dominant weavers thermoregulated more precisely, despite expending no more behavioural effort on thermoregulation than subordinates. Increasingly unequal risks associated with heat stress may have implications for the stability of animal societies in warmer climates.

The Effect of Manual Restraint on Physiological Parameters in Barred Owls ( Strix varia ).

Manual restraint is commonly necessary when working with avian species in medical, laboratory, and field settings. Despite their prevalence, little is known about the stress response in raptorial bird species. To further understand the effect of restraint on the stress response in birds of prey, 12 barred owls ( Strix varia ) were manually restrained for 15 minutes. Physiological parameters (cloacal temperature, respiratory rate, heart rate) were followed over time and recorded at defined points during the restraint period. Heart rate decreased significantly over the restraint period by a mean ± SD of -73 ± 46 beats/min. Respiratory rate also decreased significantly (median: -11 breaths/min, interquartile range: -8 to -18). Cloacal temperature increased significantly over time in manually restrained owls (median: +1.5°C [+2.7°F], interquartile range: 1.3°C-2.1°C [2.3°F-3.8°F]). This study is the first to document stress hyperthermia in an owl species. Similar to another raptorial bird, the red-tailed hawk ( Buteo jamaicensis ), both heart rate and respiratory rate decreased and cloacal temperature increased over time in restrained barred owls. Barred owls appear to cope differently to restraint stress when compared to psittacine species.

Changes in Physiologic Parameters and Effects of Hooding in Red-tailed Hawks ( Buteo jamaicensis ) During Manual Restraint.

Manual restraint in birds of prey is required for many veterinary and research procedures. To investigate the effects of handling stress on physiologic parameters in raptorial birds, 8 red-tailed hawks ( Buteo jamaicensis ) were manually restrained over a 15-minute period. Respiratory rate (RR), heart rate (HR), and cloacal temperature were monitored over time and recorded at defined intervals during the experiment. The effect of hooding on physiologic variables was also evaluated in a complete crossover design. Both RR and HR decreased significantly during the 15-minute restraint period (HR, -80 ± 101.4 beats/min [bpm], [P < .01]; RR, -17.5 ± 22.6 breaths/min, [P < .05]). Hooded birds had significantly lower HRs and RRs at 15 minutes of restraint (HR: 232.5 ± 26 bpm, [P < .037]; RR: 33.1 ± 6.7 breaths/min, [P < .05]) compared to birds restrained without a hood (HR: 280 ± 74.1 bpm; RR: 51.5 ± 28.8 breaths/min). Cloacal temperature increased significantly in all manually restrained birds (+2.2 ± 0.7°C, [P < .01]), with a comparable increase in hooded and nonhooded birds. In this study of the effects of manual restraint on red-tailed hawks, hooding versus nonhooding amplified the decrease in HR and RR but had no effect on stress-induced hyperthermia.

Fish can show emotional fever: stress-induced hyperthermia in zebrafish.

Whether fishes are sentient beings remains an unresolved and controversial question. Among characteristics thought to reflect a low level of sentience in fishes is an inability to show stress-induced hyperthermia (SIH), a transient rise in body temperature shown in response to a variety of stressors. This is a real fever response, so is often referred to as 'emotional fever'. It has been suggested that the capacity for emotional fever evolved only in amniotes (mammals, birds and reptiles), in association with the evolution of consciousness in these groups. According to this view, lack of emotional fever in fishes reflects a lack of consciousness. We report here on a study in which six zebrafish groups with access to a temperature gradient were either left as undisturbed controls or subjected to a short period of confinement. The results were striking: compared to controls, stressed zebrafish spent significantly more time at higher temperatures, achieving an estimated rise in body temperature of about 2-4°C. Thus, zebrafish clearly have the capacity to show emotional fever. While the link between emotion and consciousness is still debated, this finding removes a key argument for lack of consciousness in fishes.

Urinary cytokines in patients treated with intravesical mitomycin-C with and without hyperthermia.

OBJECTIVES: To explore whether urinary cytokine and chemokine (CK) levels differed between cold mitomycin-C (cold-MMC)-treated patients and chemohyperthermia (C-HT)-treated patients, to shed light on the possible molecular mechanisms that might explain the superior outcome of C-HT. Furthermore, CK-differences were explored between C-HT responders and C-HT non-responders. METHODS: Twelve NMIBC patients were included. Nine received six-weekly C-HT, and three received four-weekly cold-MMC instillations. Urine was collected on 8-12 time points before and after every treatment. MDC, IL-2, IL-6, IL-8, IP-10, MCP-1 and RANTES were determined by Luminex(®)-analysis. RESULTS: Elevated urinary CK levels were observed in both groups after treatment. In general, CK-peaks were lower in the cold-MMC group in comparison with levels in the C-HT group. Significant higher MCP-1 and IL-6 levels were observed in C-HT-treated patients. Additionally, significant cumulative effects were observed for IP-10 and IL-2. However, IP-10 and IL-2 levels did not significantly differ between treatments. MDC levels after the first week of treatment were significantly higher in the C-HT responders compared with the non-responders. CONCLUSION: MMC treatment leads to elevated urinary CK levels with significantly higher MCP-1 and IL-6 levels in C-HT-treated patients. Increased MDC levels after the first C-HT instillation appear to be related to good clinical outcome and might be of additional value to personalize treatment. Studies involving more patients and longer follow-up are needed to substantiate this observation.

Brown adipose tissue thermogenesis contributes to emotional hyperthermia in a resident rat suddenly confronted with an intruder rat.

Body temperature increases when individuals experience salient, emotionally significant events. There is controversy concerning the contribution of nonshivering thermogenesis in brown adipose tissue (BAT) to emotional hyperthermia. In the present study we compared BAT, core body, and brain temperature, and tail blood flow, simultaneously measured, to determine whether BAT thermogenesis contributes to emotional hyperthermia in a resident Sprague-Dawley rat when an intruder rat, either freely-moving or confined to a small cage, is suddenly introduced into the cage of the resident rat for 30 min. Introduction of the intruder rat promptly increased BAT, body, and brain temperatures in the resident rat. For the caged intruder these temperature increases were 1.4 ± 0.2, 0.8 ± 0.1, 1.0 ± 0.1°C, respectively, with the increase in BAT temperature being significantly greater (P < 0.01) than the increases in body and brain. The initial 5-min slope of the BAT temperature record (0.18 ± 0.02°C/min) was significantly greater (P < 0.01) than the corresponding value for body (0.10 ± 0.01°C/min) and brain (0.09 ± 0.02°C/min). Tail artery pulse amplitude fell acutely when the intruder rat was introduced, possibly contributing to the increases in body and brain temperature. Prior blockade of ß3 adrenoceptors (SR59230A 10 mg/kg ip) significantly reduced the amplitude of each temperature increase. Intruder-evoked increases in BAT temperature were similar in resident rats maintained at 11°C for 3 days. In the caged intruder situation there is no bodily contact between the rats, so the stimulus is psychological rather than physical. Our study thus demonstrates that BAT thermogenesis contributes to increases in body and brain temperature occurring during emotional hyperthermia.

Use of infrared thermography to detect reactions to stressful events: does animal personality matter?

The study of the relationship between animal stress and personality for free-ranging animals is limited and provides contrasting results. The perception of stressors by an individual may vary due to its personality, and certain personality traits may help individuals to better cope with them. Using non-invasive infrared thermography (IRT), we investigated the link between physiological and behavioral components expressed during an acute stress event by free-ranging Fremont's squirrels (Tamiasciurus fremonti). We expected that, during the acute stress event of being approached by the researcher, individuals that showed a fast pace-of-life syndrome (bolder, more active, and less social/more aggressive) based on an arena test would exhibit stronger sympathetic-adrenal-medullary system reactivity showing a more intense stress-induced hyperthermia (high core body temperature and low peripheral temperature) than individuals with a slow pace of life (shy, less active, and more social). We successfully employed IRT technology to images of Fremont's squirrels with identification of the individuals' body parts (eye, nose, ear, hind foot). However, we found no support for our hypothesis. Squirrels' body surface temperatures told us more about a squirrel's external environment and less about the thermal state of the body in that environment following a stressful event. Further studies need to assess how to make IRT effective and efficient in the field and improve its performance in studying the relationships between physiology and personality in wildlife.

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.

Use of Infrared Thermography and Heart Rate Variability to Evaluate Autonomic Activity in Domestic Animals.

Most of the responses present in animals when exposed to stressors are mediated by the autonomic nervous system. The sympathetic nervous system, known as the one responsible for the "fight or flight" reaction, triggers cardiovascular changes such as tachycardia or vasomotor alterations to restore homeostasis. Increase in body temperature in stressed animals also activates peripheral compensatory mechanisms such as cutaneous vasodilation to increase heat exchange. Since changes in skin blood flow influence the amount of heat dissipation, infrared thermography is suggested as a tool that can detect said changes. The present review aims to analyze the application of infrared thermography as a method to assess stress-related autonomic activity, and their association with the cardiovascular and heart rate variability in domestic animals.

Cannabidiol exhibits anxiolytic-like effects and antipsychotic-like effects in mice models.

Cannabidiol (CBD), a non-psychoactive compound derived from the cannabis plant, has been confirmed to induce anxiolytic-like and antipsychotic-like effects. However, the exact mechanisms remain unclear. This study substantiated CBD's interaction with the 5-HT1A receptor (5-HT1AR) in vitro (CHO cells expressing human 5-HT1AR) and in vivo (rat lower lip retraction test, LLR test). We then assessed the impact of CBD in mice using the stress-induced hyperthermia (SIH) model and the phencyclidine (PCP)-induced negative symptoms of schizophrenia model, respectively. Concurrently, we investigated whether WAY-100635, a typical 5-HT1AR antagonist, could attenuate these effects. Furthermore, the neurotransmitter changes through high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) were studied. Results revealed that CBD exhibits selective 5-HT1AR agonists-mediated effects in the rat lower lip retraction test, aligning with the robust agonistic (EC50 = 1.75 µM) profile observed in CHO cells. CBD at 3 mg/kg significantly reduced SIH (ΔT), a response that WAY-100635 abolished. Chronic administration of CBD at 100 mg/kg mitigated the increase in PCP-induced immobility time in the forced swim test (FST) and tail suspension test (TST). Moreover, it induced significant alterations in gamma-aminobutyric acid (GABA) and norepinephrine (NE) levels within the hippocampus (HPC). Thus, we concluded that the 5-HT1AR mediates CBD's anxiolytic-like effects. Additionally, CBD's effects on the negative symptoms of schizophrenia may be linked to changes in GABA and NE levels in the hippocampus. These findings offer novel insights for advancing the exploration of CBD's anxiolytic-like and antipsychotic-like effects.

The effect of SSRIs on unconditioned anxiety: a systematic review and meta-analysis of animal studies.

RATIONALE: Selective serotonin reuptake inhibitors (SSRIs) are the first choice of treatment for anxiety-like disorders. However, which aspects of anxiety are affected by SSRIs is not yet fully understood. OBJECTIVE: We aimed to systematically review the effect of six clinically effective SSRIs on four aspects of unconditioned anxiety: approach-avoidance behaviour (elevated plus maze), repetitive behaviour (marble burying), distress behaviour (ultrasonic vocalization), and activation of the autonomous nervous system (stress-induced hyperthermia). METHODS: We identified publications by searching Medline and Embase databases and assessed the risk of bias. A random effects meta-analysis was performed and moderator effects were analysed with Bayesian penalized meta-regression. RESULTS: Our search yielded 105 elevated plus maze, 63 marble burying, 11 ultrasonic vocalization, and 7 stress-induced hyperthermia articles. Meta-analysis suggested that SSRIs reduce anxiety-like behaviour in the elevated plus maze, marble burying and ultrasonic vocalization test and that effects are moderated by pre-existing stress conditions (elevated plus maze) and dose dependency (marble burying) but not by duration of treatment or type of SSRI. The reporting quality was low, publication bias was likely, and heterogeneity was high. CONCLUSION: SSRIs seem to reduce a broad range of unconditioned anxiety-associated behaviours. These results should be interpreted with caution due to a high risk of bias, likely occurrence of publication bias, substantial heterogeneity and limited moderator data availability. Our review demonstrates the importance of including bias assessments when interpreting meta-analysis results. We further recommend improving the reporting quality, the conduct of animal research, and the publication of all results regardless of significance.