Evidence of heat sensitivity in people with Parkinson's disease.

Examining how heat affects people with Parkinson's disease is essential for informing clinical decision-making, safety, well-being, and healthcare planning. While there is evidence that the neuropathology associated with Parkinson's disease affects thermoregulatory mechanisms, little attention has been given to the association of heat sensitivity to worsening symptoms and restricted daily activities in people with this progressive disease. Using a cross-sectional study design, we examined the experiences of people diagnosed with Parkinson's disease in the heat. Two-hundred and forty-seven people completed an online survey (age: 66.0 ± 9.2 years; sex: male = 102 (41.3%), female = 145 (58.7%)), of which 195 (78.9%) reported becoming more sensitive to heat with Parkinson's disease. Motor and nonmotor symptoms worsened with heat in 182 (73.7%) and 203 (82.2%) respondents, respectively. The most commonly reported symptoms to worsen included walking difficulties, balance impairment, stiffness, tremor, fatigue, sleep disturbances, excess sweating, difficulty concentrating, and light-headedness when standing. Concerningly, over half indicated an inability to work effectively in the heat, and nearly half reported that heat impacted their ability to perform household tasks and social activities. Overall, heat sensitivity was common in people with Parkinson's disease and had a significant impact on symptomology, day-to-day activities and quality of life.

Identification of global transcriptional variations in human peripheral blood mononuclear cells two months postheat injury helps categorization heat-tolerant or heat-intolerant phenotypes.

Thermal intolerance may limit activity in hostile environments. After heat illness, two physiologically distinct phenotypes evolve: heat tolerant (HT) and heat intolerant (HI). The recognition that heat illness alters gene expression justified revisiting the established physiological concept of HI. We used a DNA microarray to examine the global transcriptional response in peripheral blood mononuclear cells (PMBCs) from HI and HT phenotypes, categorized 2-mo postheat injury using a functional physiological heat-tolerance test (HTT, 40°C)-Recovery (R, 24°C) protocol. The impact of recurrent heat stress was studied in vitro using peripheral blood mononuclear cells (PBMCs) from controls (participants with no history of heat injury), HI, and HT (categorized by functional HTT) with a customized NanoString array. There were significant differences under basal conditions between the HI and HT. HI were more immunological alerted. Almost no shared genes were found between end-HTT and recovery phases, suggesting vast cellular plasticity. In HI, mitochondrial function was dysregulated, canonical pathways associated with exercise endurance-NRF2 and insulin were downregulated, whereas AMPK and peroxisome proliferator-activated receptor (PPAR) were upregulated. HT exhibited reciprocal responses, suggesting that energy dysregulation found in HI interfered with performance in the heat. The endoplasmic-reticulum stress response was also suppressed in HI. In vitro HTT (43°C) abolished differences between HI and HT PBMCs including the HSPs genes, whereas controls showed profound HSPs upregulation.

Exercise-induced heat sensitivity in patients with multiple sclerosis: Definition, prevalence, etiology, and management-A scoping review.

BACKGROUND: For persons with multiple sclerosis (pwMS), exercise is known to be safe and effective at treating several symptoms and it may even be disease-modifying. However, exercise can trigger heat intolerance, exercise-induced heat sensitivity (EIHS), which may cause some pwMS to refrain from exercise. No review has yet summarized the existing knowledge on EIHS in pwMS. Therefore, the purpose of the present review was to clarify the terminology, summarize both the prevalence of EIHS and the current knowledge of underlying mechanisms, and provide an overview of existing treatment options and clinical management of EIHS in pwMS. METHODS: A scoping review was performed. RESULTS: As no clear definition could be identified in the literature, we propose a definition of EIHS. Aspects related to EIHS are reported in 29-80 % of all pwMS. The mechanisms underlying EIHS are not well understood but seem to include axon demyelination, CNS lesions, abnormal sudomotor function and sweating, abnormal afferent thermosensory function, disease stability, and abnormal neuropsychological responses. The severity of EIHS depends on the applied exercise modality, intensity, and format, and can be further reduced when applying different cooling interventions or garments before and/or during exercise. CONCLUSION: EIHS appears frequently in pwMS, but the underlying mechanisms are still only sparsely understood. EIHS severity depends on exercise-related factors and can be reduced by cooling interventions.

Sensitivity and specificity of using exercise heart rate in a thermoneutral environment to predict heat tolerance status.

OBJECTIVES: Following heat illness, a return to activity may require passing a heat tolerance test (HTT). However, there are several logistical limitations to the widespread use of the HTT. Thus, it would be advantageous to develop a test that could be conducted in a thermoneutral (~22°C) environment to predict heat tolerance status. The purpose of the current study was to determine the sensitivity and specificity of using the criteria of a heart rate (HR) ≥130 bpm following 30 min of thermoneutral exercise in detecting heat-intolerant and heat-tolerant individuals. MATERIAL AND METHODS: Sixty-five subjects visited the lab on 3 separate days. The first visit consisted of completing a maximal oxygen uptake (VO2 max) test to assess cardiovascular fitness. For lab visits 2 and 3, subjects randomly completed a 2-hour walking treadmill test in either a hot (40°C, 40% relative humidity [RH]) or thermoneutral (22°C, 40% RH) environment. RESULTS: Forty-eight subjects were classified as heat-intolerant and 17 subjects as heat-tolerant. Using the criterion of a HR ≥130 bpm at 30 min of exercise in the thermoneutral environment, specificity (54%) and sensitivity (100%) of passing the HTT was calculated. Secondary analysis using multiple regression revealed 3 significant variables for predicting ending HR during the HTT. They were: 1) absolute VO2 max (l/min), 2) age, and 3) HR at 30 min of exercise during thermoneutral exercise. CONCLUSIONS: Exercise in a thermoneutral environment had a positive predictive value of 100%, thus, if a subject has a HR ≥130 bpm at 30 min of exercise in a thermoneutral environment, they are very likely to fail a subsequent 2-hour HTT in the heat and be classified as heat-intolerant. Therefore, prior screening has the potential to save time and money, along with providing safety to a heat-intolerant subject. Int J Occup Med Environ Health. 2023;36(2):192-200.

Current Clinical Concepts: Heat Tolerance Testing.

Heat tolerance testing (HTT) has been developed to assess readiness for work or exercise in the heat based on thermoregulation during exertion. Although the Israeli Defense Forces protocol has been the most widely used and referenced, other protocols and variables considered in the interpretation of the testing are emerging. Our purpose was to summarize the role of HTT after exertional heat stroke; assess the validity of HTT; and provide a review of best-practice recommendations to guide clinicians, coaches, and researchers in the performance, interpretation, and future direction of HTT. We also offer the strength of evidence for these recommendations using the Strength of Recommendation Taxonomy system.

[Life expectancy of mesocephalic, dolichocephalic and brachycephalic dog breeds in Switzerland]. / Lebenserwartung meso-, dolichound brachyzephaler Hunderassen in der Schweiz.

INTRODUCTION: Lifespan and time of death of dogs died in Switzerland between 2016 and 2020 were evaluated in order to increase the awareness of the public to animal welfare-related consequences of extreme brachycephalic breeding and to clarify the torture breeding problem of dogs suffering from brachycephalic obstructive airway syndrome (BOAS). Skull shape, body size, country of origin and altitude of the registered place of residence at the time of death were analysed in a set of anonymized data from the national animal database Amicus as potential factors influencing the life expectancy. Death rate during summer months and the altitude of the reported place of residence at death were analysed in relation to the skull shape to demonstrate the heat intolerance of brachycephalic dog breeds. The final dataset included 137 469 dogs. The average age of death of the study population was 11,8 years, mixed breeds reaching a higher average age of 12,4 years than purebred dogs with 11,5 years. Bodyweight classification, skull shape and the origin of the dogs had a significant effect on the average lifespan. Giant breeds reached with 9,0 years the lowest mean age compared to the other bodyweight categories. The mean life expectancy of brachycephalic dogs was 9,8 years, i.e., 2,1 and 1,7 years less than mesocephalic and dolichocephalic dogs, respectively. Brachycephalic dogs and dogs imported from abroad showed increased mortality at a young age.

INTRODUCTION: La durée de vie et le moment du décès des chiens morts en Suisse entre 2016 et 2020 ont été évalués afin de sensibiliser le public aux conséquences sur le bien-être animal de l'élevage brachycéphale extrême et de clarifier le problème des pratiques d'élevage cruelles des chiens souffrant du syndrome obstructif respiratoire brachycéphale (SORB). Outre la forme du crâne, la taille du corps, le pays d'origine et l'altitude du lieu de résidence enregistré au moment de la mort ont été analysés dans un ensemble de données anonymisées provenant de la base de données nationale sur les animaux Amicus, en tant que facteurs potentiels influençant la taille et le vieillissement. Le taux de mortalité pendant les mois d'été et l'altitude du lieu de résidence déclaré au moment du décès ont été analysés pour démontrer l'intolérance à la chaleur des races de chiens brachycéphales. L'ensemble de données final comprenait 137 469 chiens. L'âge moyen du décès de la population étudiée était de 11,8 ans, les chiens croisés atteignant un âge moyen plus élevé de 12,4 ans que les chiens de race pure avec 11,5 ans. La catégorie de poids, la forme du crâne et l'origine des chiens ont eu un effet significatif sur la durée de vie moyenne. Les races géantes ont atteint avec 9,0 ans l'âge moyen le plus bas par rapport aux autres catégories de poids. L'espérance de vie moyenne des chiens brachycéphales était de 9,8 ans, soit 2,1 et 1,7 ans de moins que celle des chiens mésocéphales et dolichocéphales. Les chiens brachycéphales et les chiens importés de l'étranger présentaient une mortalité accrue dans leur jeune âge.

A Rare Case of Hypohidrotic Ectodermal Dysplasia in a Seven-Year-Old Child.

Ectodermal dysplasias (EDs) encompass a large group of inherited disorders that affects two or more ectodermally derived structures. Hair, sweat glands, teeth, and nails are the most common ectodermal derivates affected. Other ectodermal structures that may be affected are ears, eyes, lips, and mucous membranes of the mouth or nose. During embryonic development, the ectoderm forms the outermost layer of the primary germ layers that give rise to the several structures that are commonly affected in ED. Therefore, ED manifests differently among patients, depending on the abnormality's combination and severity. Out of 150 distinctive syndromes, the most common syndromes within this group are hypohidrotic (defective sweat glands) and hidrotic (normal sweat glands). In addition, different types of inheritance patterns are found in ED; X-linked inheritance is by far the most common mode of inheritance. We present here the clinical case of hypohidrotic (anhidrotic) ED in a seven-year-old boy.

Clinical and histopathological studies on neurodegeneration and dysautonomia in buffalo calves during foot-and-mouth disease outbreaks in Egypt.

BACKGROUND AND AIM: Signs of dysautonomia were frequently observed in calves that died during foot-and-mouth disease (FMD) virus (FMDV) outbreaks in Egypt from 2015 to 2018. This study aimed to describe the clinical and histopathological features of the central nervous system in malignant cases of FMD and excluding possible concurrent bacterial, and bovine herpes virus 4 (BHV4) infections or both. MATERIALS AND METHODS: In this study, 335 FMDV-infected buffalo calves aged 1-22 months were clinically examined and followed until recovery or death. Of the 335 calves, 134 died (malignant group) and 201 recovered after exhibiting classic symptoms of FMD (recover group). The calves were subjected to clinical examination. For the malignant group, several laboratory trials were conducted to assess the possible cause/s of dysautonomia-related viral, bacterial, or concurrent infections. Koch's postulates and polymerase chain reaction were employed. Postmortem and histopathological examinations of nervous tissue were performed. RESULTS: In the malignant group, signs of dysautonomia were observed before death, including partial or complete gut dysfunction, loss of anal sphincter tone, rapid breathing sounds, fluctuating body temperature, and cardiac arrhythmias. In the malignant group, histopathological examination of the spinal cord, pons, medulla oblongata, hypothalamus, cerebellum, and cerebrum revealed demyelination, neuronal degeneration, and focal areas of malacia and gliosis. The nervous tissue and heart samples from malignant cases were positive for serotype O FMDV. CONCLUSION: Findings revealed in this study support the existence of neurodegeneration induced by FMDV infection in buffalo calves.

A basal heat stress test to detect military operational readiness after a 14-day operational heat acclimatization period.

A basal heat stress test (HST) to predict the magnitude of adaptive responses during heat acclimatization (HA) would be highly useful for the armed forces. The aim was to identify physiological markers assessed during a HST (three 8-min running sets at 50% of the speed at VO2max) performed just before a 14-day HA period that would identify participants still at "risk" at the end of HA. Individuals that responded poorly (large increases in rectal temperature [Trec] and heart rate [HR]) during the initial HST were more likely to respond favorably to HA (large reductions in Trec and HR). However, they were also more likely to exhibit lower tolerance to HST at D15. Basal Trec was found to efficiently discriminate participants showing a Trec > 38.5°C after HA, who are considered to be "at risk". Finally, participants were classified by quartiles based on basal Trec and HR at the end of the HST and physiological strain index (PSI). Most of the participants "at risk" were among the upper quartile (i.e. the least tolerant) of Trec and PSI (p = 0.011 for both). Overall, these results show that the individuals who are less tolerant to a basal HST are very likely to benefit the most from HA but they also remain less tolerant to heat at the end of HA than those who better tolerated the basal HST. A basal HST could therefore theoretically help the command to select the most-ready personnel in hot conditions while retaining those who are less tolerant 6.

When Should a Heat-Tolerance Test Be Scheduled After Clinical Recovery From an Exertional Heat Illness?

OBJECTIVE: Researchers have produced a hypothesis of transient heat intolerance (HI) after exertional heat stroke (EHS). Based on this hypothesis, heat-tolerance testing (HTT) has been postponed until weeks 6 to 8 after EHS and other types of exertional heat illness (EHI). We compared the HTT results of participants after either EHS or other EHI who were tested earlier (≤6-week group) versus those who were tested later (>6-week group) to verify the hypothesis. DESIGN: Cohort study. SETTING: Data obtained from records of military athletes who experienced EHS or EHI. PATIENTS OR OTHER PARTICIPANTS: All participants who underwent HTT after EHI or EHS experienced between 2014 and 2018 and for whom complete data regarding the severity of the event (rectal temperature, neurologic symptoms, and laboratory results) and HTT results were available were included. Participants with suspected EHS and those with other EHIs were evaluated separately. MAIN OUTCOME MEASURE(S): The percentages of participants with HI and mean probability of heat tolerance were compared between those tested within 6 weeks of the event and those tested later. RESULTS: A total of 186 participants were included in this study (EHS: 12 in the <6-week group, 9 in the >6-week group; EHI: 94 in the <6-week group, 71 in the >6-week group). In the EHS group, the percentages with HI (33% versus 44%, P = .67) and mean probability of heat tolerance (0.82 versus 0.82, P = .98) did not differ. In the EHI group, participants who were tested after 6 weeks had a greater chance of being diagnosed with HI (38% versus 21.3%, P < .02). CONCLUSIONS: The HTT results were similar between participants with EHS who were tested early (<6 weeks) and those tested late (>6 weeks). Further investigation of heat-tolerance changes in larger cohorts of patients after EHS is required to verify the theory of transient HI.

Natural history of X-linked hypohidrotic ectodermal dysplasia: a 5-year follow-up study.

BACKGROUND: X-linked hypohidrotic ectodermal dysplasia (XLHED) is caused by pathogenic variants of the gene EDA disrupting the prenatal development of ectodermal derivatives. Cardinal symptoms are hypotrichosis, lack of teeth, and hypo- or anhidrosis, but the disease may also evoke other clinical problems. This study aimed at investigating the clinical course of XLHED in early childhood as the basis for an evaluation of the efficacy of potential treatments. METHODS: 25 children (19 boys and 6 girls between 11 and 35 months of age) with genetically confirmed XLHED were enrolled in a long-term natural history study. Clinical data were collected both retrospectively using parent questionnaires and medical records (pregnancy, birth, infancy) and prospectively until the age of 60 months. General development, dentition, sweating ability, ocular, respiratory, and skin involvement were assessed by standardized clinical examination and yearly quantitative surveys. RESULTS: All male subjects suffered from persistent anhidrosis and heat intolerance, although a few sweat ducts were detected in some patients. Sweating ability of girls with XLHED ranged from strongly reduced to almost normal. In the male subjects, 1-12 deciduous teeth erupted and 0-8 tooth germs of the permanent dentition became detectable. Tooth numbers were higher but variable in the female group. Most affected boys had no more than three if any Meibomian glands per eyelid, most girls had fewer than 10. Many male subjects developed additional, sometimes severe health issues, such as obstructive airway conditions, chronic eczema, or dry eye disease. Adverse events included various XLHED-related infections, unexplained fever, allergic reactions, and retardation of psychomotor development. CONCLUSIONS: This first comprehensive study of the course of XLHED confirmed the early involvement of multiple organs, pointing to the need of early therapeutic intervention.

Exophthalmos and multinodular goitre, an unusual combination.

Multinodular goitre is not associated with eye disease, unless in a rare case of Marine-Lenhart syndrome where it coexists with Grave's disease. Therefore, other causes of exophthalmos need to be ruled out when the eye disease is seen in a patient with multinodular goitre. Confusion can arise in patients with features suggestive of Graves' ophthalmopathy in the absence of thyroid-stimulating hormone receptor autoantibodies and no evidence of other causes of exophthalmos. We present a case of multinodular goitre in a patient with exophthalmos which flared up after iodine contrast-based study. A 61-year-old Australian presented with a pre-syncopal attack and was diagnosed with toxic multinodular goitre. At the same time of investigations, to diagnose the possible cause of the pre-syncopal attack, computerised tomographic (CT) coronary artery angiogram was requested by a cardiologist. A few days after the iodine contrast-based imaging test was performed, he developed severe eye symptoms, with signs suggestive of Graves' orbitopathy. MRI of the orbit revealed features of the disease. Although he had pre-existing eye symptoms, they were not classical of thyroid eye disease. He eventually had orbital decompressive surgery. This case poses a diagnostic dilemma of a possible Graves' orbitopathy in a patient with multinodular goitre. Learning points: Graves' orbitopathy can occur in a patient with normal autothyroid antibodies. The absence of the thyroid antibodies does not rule out the disease in all cases. Graves' orbitopathy can coexist with multinodular goitre. Iodine-based compounds, in any form, can trigger severe symptoms, on the background of Graves' eye disease.

Clinical challenges of a co-secreting TSH/GH pituitary adenoma.

SUMMARY: Co-secreting thyrotropin/growth hormone (GH) pituitary adenomas are rare; their clinical presentation and long-term management are challenging. There is also a paucity of long-term data. Due to the cell of origin, these can behave as aggressive tumours. We report a case of a pituitary plurihormonal pit-1-derived macroadenoma, with overt clinical hyperthyroidism and minimal GH excess symptoms. The diagnosis was confirmed by pathology showing elevated thyroid and GH axes with failure of physiological GH suppression, elevated pituitary glycoprotein hormone alpha subunit (αGSU) and macroadenoma on imaging. Pre-operatively the patient was rendered euthyroid with carbimazole and underwent successful transphenoidal adenomectomy (TSA) with surgical cure. Histopathology displayed an elevated Ki-67 of 5.2%, necessitating long-term follow-up. LEARNING POINTS: Thyrotropinomas are rare and likely under-diagnosed due to under-recognition of secondary hyperthyroidism. Thyrotropinomas and other plurihormonal pit-1-derived adenomas are more aggressive adenomas according to WHO guidelines. Co-secretion occurs in 30% of thyrotropinomas, requiring diligent investigation and long-term follow-up of complications.

Thermoregulatory dysfunction in multiple sclerosis.

Multiple sclerosis (MS) is a progressive neurologic disorder that disrupts axonal myelin in the central nervous system. Demyelination produces alterations in saltatory conduction, slowed conduction velocity, and a predisposition to conduction block. An estimated 60-80% of MS patients experience temporary worsening of clinical signs and neurologic symptoms with heat exposure (Uhthoff's phenomenon). This heat intolerance in MS is related to the detrimental effects of increased temperature on action potential propagation in demyelinated axons, resulting in conduction slowing and/or block. Additionally, MS may produce impaired neural control of autonomic and endocrine functions. Isolating and interpreting mechanisms responsible for autonomic dysfunction due to MS can be difficult as it may involve sensory impairments, altered neural integration within the central nervous system, impaired effector responses, or combinations of all of these factors. MS lesions occur in areas of the brain responsible for the control and regulation of body temperature and thermoregulatory effector responses, resulting in impaired neural control of sudomotor pathways or neural-induced changes in eccrine sweat glands, as evidenced by observations of reduced sweating responses in MS patients. Although not comprehensive, some evidence exists concerning treatments (cooling, precooling, and pharmacologic) for the MS patient to preserve function and decrease symptom worsening during heat stress. This review focuses on four main themes influencing current understanding of thermoregulatory dysfunction in MS: (1) heat intolerance; (2) central regulation of body temperature; (3) thermoregulatory effector responses; and (4) countermeasures to improve or maintain function during thermal stress.

Persistent hyperthyroidism and de novo Graves' ophthalmopathy after total thyroidectomy.

We report a patient with Graves' disease who remained persistently hyperthyroid after a total thyroidectomy and also developed de novo Graves' ophthalmopathy 5 months after surgery. She was subsequently found to have a mature cystic teratoma containing struma ovarii after undergoing a total hysterectomy and salpingo-oophorectomy for an incidental ovarian lesion. LEARNING POINTS: It is important to investigate for other causes of primary hyperthyroidism when thyrotoxicosis persists after total thyroidectomy.TSH receptor antibody may persist after total thyroidectomy and may potentially contribute to the development of de novo Graves' ophthalmopathy.

How does multilevel upper airway surgery influence the lives of dogs with severe brachycephaly? Results of a structured pre- and postoperative owner questionnaire.

Brachycephalic airway syndrome in dogs is typified by a variety of anatomical abnormalities causing a diverse spectrum of clinical signs of varying intensity. This variability makes the assessment of the surgical outcome after upper airway surgery difficult. Using a structured questionnaire, the present study investigated the dog owner-perceived severity and frequency of a broad spectrum of welfare-relevant impairments 2 weeks before and 6 months after brachycephalic dogs underwent a recently developed multi-level upper airway surgery. All dogs underwent surgical treatment of stenotic nares (ala-vestibuloplasty), the nasal cavity (laser-assisted turbinectomy, LATE), the pharynx (palatoplasty and tonsillotomy), and if indicated, laryngeal surgery (laser-assisted ablation of everted ventricles and partial cuneiformectomy). Owners of brachycephalic dogs (n = 102) referred for upper airway surgery were eligible to participate. Questionnaire data from owners of 37 Pugs and 25 French bulldogs were evaluated. In all dogs, the clinical signs associated with brachycephaly improved markedly after surgery. Most encouraging was the striking reduction in life-threatening events by 90% (choking fits decreased from 60% to 5% and collapse from 27% to 3%). The incidence of sleeping problems decreased from 55% to 3%, and the occurrence of breathing sounds declined by approximately 50%. There was a marked improvement in exercise tolerance and a modest improvement in heat tolerance. Dogs with severe brachycephaly benefitted substantially from multi-level surgery, and there were particular improvements in the incidences of severe impairment and life-threatening events. However, despite the marked improvement perceived by dog owners, these dogs remained clinically affected and continued to show welfare-relevant impairments caused by these hereditary disorders.

How does severe brachycephaly affect dog's lives? Results of a structured preoperative owner questionnaire.

Brachycephalic syndrome (BS) is a complex canine disease, which is characterized by diverse clinical signs primarily involving the respiratory and gastrointestinal systems. Through a structured owner questionnaire, the present study investigated how owners perceived the frequency and severity of a broad spectrum of welfare-relevant impairments caused by this hereditary disease. One hundred owners of brachycephalic dogs (Pugs and French bulldogs) referred for surgical treatment of BS completed the questionnaire. As a basis for comparison, 20 owners of mesocephalic dogs also completed part of the questionnaire. Questionnaire responses revealed that in addition to the well-known respiratory signs, brachycephalic dogs experienced severe exercise intolerance and prolonged recovery time after physical exercise (88%), significant heat sensitivity (more severe signs at temperatures above 19°C; 50%) and a variety of sleep problems (56%). To our knowledge, this is the first study using a structured owner questionnaire specifically to investigate a broad range of problems caused by selective breeding for brachycephaly. In particular, decreased exercise tolerance, increased recovery time due to heat intolerance and the extent of sleep problems have either been underestimated in the past, or have severely worsened over recent generations of dogs. The extent and severity of clinical signs and their impact on quality of life greatly exceeded our expectations. This study emphasizes the major impact that selective breeding for extreme brachycephalic features has on animal welfare.