Biological sex does not independently influence time-dependent changes in core temperature and sweating of children exercising in uncompensable heat stress.

PURPOSE: To investigate the influence of biological sex, independent of differences in aerobic fitness and body fatness, on the change in gastro-intestinal temperature (∆Tgi) and whole-body sweat rate (WBSR) of children exercising under uncompensable heat stress. METHODS: Seventeen boys (mean±SD; 13.7±1.3 years) and 18 girls (13.7±1.4) years) walked for 45 min at a fixed rate of metabolic heat production per kg body mass (8 W·kg-1) in 40°C and 30% relative humidity. Sex and V̇O2peak were entered into a Bayesian hierarchical general additive model (HGAM) for Tgi. Sex, V̇O2peak and the evaporative requirement for heat balance (Ereq) were entered into a Bayesian hierarchical linear regression for WBSR. For 26 (12 M, 14 F) of the 35 children with measured body composition, body fat percentage was entered in a separate HGAM and hierarchical linear regression for Tgi and WBSR respectively. RESULTS: Conditional on sex-specific mean V̇O2peak, ∆Tgi was 1.00°C [90% credible intervals: 0.84, 1.16] for boys and 1.17°C [1.01, 1.33] for girls, with a difference of 0.17°C [-0.39, 0.06]. When sex differences in V̇O2peak were accounted for, the difference in ∆Tgi between boys and girls was 0.01°C [-0.25, 0.22]. The difference in WBSR between boys and girls was 0.03 L·h-1 [-0.02, 0.07], when isolated from differences in Ereq. The difference in ∆Tgi between boys and girls was -0.10°C [-0.38, 0.17] when sex differences in body fat (%) were accounted for. CONCLUSION: Biological sex did not independently influence the ∆Tgi and WBSR of children exercising under uncompensable heat stress.

Reliability and validity of the MX3 portable sweat sodium analyser during exercise in warm conditions.

PURPOSE: Accurately measuring sweat sodium concentration ([Na+]) in the field is advantageous for coaches, scientists, and dieticians looking to tailor hydration strategies. The MX3 hydration testing system is a new portable analyser that uses pre-calibrated biosensors to measure sweat [Na+]. This study aimed to assess the validity and reliability of the MX3 hydration testing system. METHODS: Thirty-one (11 females) recreationally active participants completed one experimental trial. During this trial, participants exercised at a self-selected pace for 45 min in a warm environment (31.5 ± 0.8 °C, 63.2 ± 1.3% relative humidity). Sweat samples were collected from three measurement sites using absorbent patches. The samples were then analysed for sweat [Na+] using both the MX3 hydration testing system and the Horiba LAQUAtwin-NA-11. The reliability of the MX3 hydration testing system was determined following two measurements of the same sweat sample. RESULTS: The mean difference between measurements was 0.1 mmoL·L-1 (95% limits of agreement (LoA): - 9.2, 9.4). The analyser demonstrated a coefficient of variation (CV) of 5.6% and the standard error of measurement was 3.3 mmoL·L-1. When compared to the Horiba LAQUAtwin-NA-11, there was a mean difference of - 1.7 mmoL·L-1 (95% LoA: - 0.25 X ¯ , 0.25 X ¯ ) and the CV was 9.8%. CONCLUSION: The MX3 hydration testing system demonstrated very good single-trial reliability, moderate agreement and a very good CV relative to the Horiba LAQUAtwin-Na-11. To further validate its performance, the MX3 hydration testing system should be compared with analytical techniques known for superior reliability and validity.

A partial Drp1 knockout improves autophagy flux independent of mitochondrial function.

BACKGROUND: Dynamin-related protein 1 (Drp1) plays a critical role in mitochondrial dynamics. Partial inhibition of this protein is protective in experimental models of neurological disorders such as Parkinson's disease and Alzheimer's disease. The protective mechanism has been attributed primarily to improved mitochondrial function. However, the observations that Drp1 inhibition reduces protein aggregation in such neurological disorders suggest the involvement of autophagy. To investigate this potential novel protective mechanism of Drp1 inhibition, a model with impaired autophagy without mitochondrial involvement is needed. METHODS: We characterized the effects of manganese (Mn), which causes parkinsonian-like symptoms in humans, on autophagy and mitochondria by performing dose-response studies in two cell culture models (stable autophagy HeLa reporter cells and N27 rat immortalized dopamine neuronal cells). Mitochondrial function was assessed using the Seahorse Flux Analyzer. Autophagy flux was monitored by quantifying the number of autophagosomes and autolysosomes, as well as the levels of other autophagy proteins. To strengthen the in vitro data, multiple mouse models (autophagy reporter mice and mutant Drp1+/- mice and their wild-type littermates) were orally treated with a low chronic Mn regimen that was previously reported to increase α-synuclein aggregation and transmission via exosomes. RNAseq, laser captured microdissection, immunofluorescence, immunoblotting, stereological cell counting, and behavioural studies were used. RESULTS IN VITRO: data demonstrate that at low non-toxic concentrations, Mn impaired autophagy flux but not mitochondrial function and morphology. In the mouse midbrain, RNAseq data further confirmed autophagy pathways were dysregulated but not mitochondrial related genes. Additionally, Mn selectively impaired autophagy in the nigral dopamine neurons but not the nearby nigral GABA neurons. In cells with a partial Drp1-knockdown and Drp1+/- mice, Mn induced autophagic impairment was significantly prevented. Consistent with these observations, Mn increased the levels of proteinase-K resistant α-synuclein and Drp1-knockdown protected against this pathology. CONCLUSIONS: This study demonstrates that improved autophagy flux is a separate mechanism conferred by Drp1 inhibition independent of its role in mitochondrial fission. Given that impaired autophagy and mitochondrial dysfunction are two prominent features of neurodegenerative diseases, the combined protective mechanisms targeting these two pathways conferred by Drp1 inhibition make this protein an attractive therapeutic target.

Auditing the Representation of Females Versus Males in Heat Adaptation Research.

The aim of this audit was to quantify female representation in research on heat adaptation. Using a standardized audit tool, the PubMed database was searched for heat adaptation literature from inception to February 2023. Studies were included if they investigated heat adaptation among female and male adults (≥18-50 years) who were free from noncommunicable diseases, with heat adaptation the primary or secondary outcome of interest. The number and sex of participants, athletic caliber, menstrual status, research theme, journal impact factor, Altmetric score, Field-Weighted Citation Impact, and type of heat exposure were extracted. A total of 477 studies were identified in this audit, including 7,707 participants with ∼13% of these being female. Most studies investigated male-only cohorts (∼74%, n = 5,672 males), with ∼5% (n = 360 females) including female-only cohorts. Of the 126 studies that included females, only 10% provided some evidence of appropriate methodological control to account for ovarian hormone status, with no study meeting best-practice recommendations. Of the included female participants, 40% were able to be classified to an athletic caliber, with 67% of these being allocated to Tier 2 (i.e., trained/developmental) or below. Exercise heat acclimation was the dominant method of heat exposure (437 interventions), with 21 studies investigating sex differences in exercise heat acclimation interventions. We recommend that future research on heat adaptation in female participants use methodological approaches that consider the potential impact of sexual dimorphism on study outcomes to provide evidence-based guidelines for female athletes preparing for exercise or competition in hot conditions.

Effect of sportswear on performance and physiological heat strain during prolonged running in moderately hot conditions.

INTRODUCTION: This study examined the impact of different upper-torso sportswear technologies on the performance and physiological heat strain of well-trained and national-level athletes during prolonged running in moderately hot conditions. METHODS: A randomized crossover design was employed in which 20 well-trained (n = 16) and national-level (n = 4) athletes completed four experimental trials in moderately hot conditions (35°C, 30% relative humidity). In each trial, participants ran at 70% of their peak oxygen uptake (70% V̇O2peak ) for 60 min, while wearing a different upper-body garment: cotton t-shirt, t-shirt with sweat-wicking fabric, compression t-shirt, and t-shirt with aluminum dots lining the inside of the upper back of the garment. Running speed was adjusted to elicit the predetermined oxygen consumption associated with 70% V̇O2peak . Physiological (core and skin temperatures, total body water loss, and urine specific gravity) and perceptual (thermal comfort and sensation, ratings of perceived exertion, and garment cooling functionality) parameters along with running speed at 70% V̇O2peak were continuously recorded. RESULTS: No significant differences were observed between the four garments for running speed at 70% V̇O2peak , physiological heat strain, and perceptual responses (all p > 0.05). The tested athletes reported larger areas of perceived suboptimal cooling functionality in the cotton t-shirt and the t-shirt with aluminum dots relative to the sweat-wicking and compression t-shirts (d: 0.43-0.52). CONCLUSION: There were not differences among the tested garments regarding running speed at 70% V̇O2peak , physiological heat strain, and perceptual responses in well-trained and national-level endurance athletes exercising in moderate heat.

Influence of Biological Sex and Fitness on Core Temperature Change and Sweating in Children Exercising in Warm Conditions.

PURPOSE: This study aimed to investigate the associations of biological sex and aerobic fitness (i.e., V̇O 2peak ) on the change in gastrointestinal temperature (∆ Tgi ) and whole-body sweat rate (WBSR) of children exercising in warm conditions. METHODS: Thirty-eight children (17 boys, mean ± SD = 13.7 ± 1.2 yr; 21 girls, 13.6 ± 1.8 yr) walked for 45 min at a fixed rate of metabolic heat production (8 W·kg -1 ) in 30°C and 40% relative humidity. Biological sex and relative V̇O 2peak were entered as predictors into a Bayesian hierarchical generalized additive model for Tgi . For a subsample of 13 girls with measured body composition, body fat percent was entered into a separate hierarchical generalized additive model for Tgi . Sex, V̇O 2peak , and the evaporative requirement for heat balance ( Ereq ) were entered into a Bayesian hierarchical linear regression for WBSR. RESULTS: The mean ∆ Tgi for boys was 0.71°C (90% credible interval = 0.60-0.82) and for girls 0.78°C (0.68-0.88). A predicted 20 mL·kg -1 ·min -1 higher V̇O 2peak resulted in a 0.19°C (-0.03 to 0.43) and 0.24°C (0.07-0.40) lower ∆ Tgi in boys and girls, respectively. A predicted ~13% lower body fat in the subsample of girls resulted in a 0.15°C (-0.12 to 0.45) lower ∆ Tgi . When Ereq was standardized to the grand mean, the difference in WBSR between boys and girls was -0.00 L·h -1 (-0.06 to 0.06), and a 20-mL·kg -1 ·min -1 higher predicted V̇O 2peak resulted in a mean difference in WBSR of -0.07 L·h -1 (-0.15 to 0.00). CONCLUSIONS: Biological sex did not independently influence ∆ Tgi and WBSR in children. However, a higher predicted V̇O 2peak resulted in a lower ∆ Tgi of children, which was not associated with a greater WBSR, but may be related to differences in body fat percent between high and low fitness individuals.

Quantifying Exercise Heat Acclimatisation in Athletes and Military Personnel: A Systematic Review and Meta-analysis.

BACKGROUND: Athletes and military personnel are often expected to compete and work in hot and/or humid environments, where decrements in performance and an increased risk of exertional heat illness are prevalent. A physiological strategy for reducing the adverse effects of heat stress is to acclimatise to the heat. OBJECTIVE: The aim of this systematic review was to quantify the effects of relocating to a hotter climate to undergo heat acclimatisation in athletes and military personnel. ELIGIBILITY CRITERIA: Studies investigating the effects of heat acclimatisation in non-acclimatised athletes and military personnel via relocation to a hot climate for < 6 weeks were included. DATA SOURCES: MEDLINE, SPORTDiscus, CINAHL Plus with Full Text and Scopus were searched from inception to June 2022. RISK OF BIAS: A modified version of the McMaster critical review form was utilised independently by two authors to assess the risk of bias. DATA SYNTHESIS: A Bayesian multi-level meta-analysis was conducted on five outcome measures, including resting core temperature and heart rate, the change in core temperature and heart rate during a heat response test and sweat rate. Wet-bulb globe temperature (WBGT), daily training duration and protocol length were used as predictor variables. Along with posterior means and 90% credible intervals (CrI), the probability of direction (Pd) was calculated. RESULTS: Eighteen articles from twelve independent studies were included. Fourteen articles (nine studies) provided data for the meta-analyses. Whilst accounting for WBGT, daily training duration and protocol length, population estimates indicated a reduction in resting core temperature and heart rate of - 0.19 °C [90% CrI: - 0.41 to 0.05, Pd = 91%] and - 6 beats·min-1 [90% CrI: - 16 to 5, Pd = 83%], respectively. Furthermore, the rise in core temperature and heart rate during a heat response test were attenuated by - 0.24 °C [90% CrI: - 0.67 to 0.20, Pd = 85%] and - 7 beats·min-1 [90% CrI: - 18 to 4, Pd = 87%]. Changes in sweat rate were conflicting (0.01 L·h-1 [90% CrI: - 0.38 to 0.40, Pd = 53%]), primarily due to two studies demonstrating a reduction in sweat rate following heat acclimatisation. CONCLUSIONS: Data from athletes and military personnel relocating to a hotter climate were consistent with a reduction in resting core temperature and heart rate, in addition to an attenuated rise in core temperature and heart rate during an exercise-based heat response test. An increase in sweat rate is also attainable, with the extent of these adaptations dependent on WBGT, daily training duration and protocol length. PROSPERO REGISTRATION: CRD42022337761.

From Alpha to Omicron: How Different Variants of Concern of the SARS-Coronavirus-2 Impacted the World.

SARS-CoV-2, the virus that causes COVID-19, is prone to mutations and the generation of genetic variants. Since its first outbreak in 2019, SARS-CoV-2 has continually evolved, resulting in the emergence of several lineages and variants of concern (VOC) that have gained more efficient transmission, severity, and immune evasion properties. The World Health Organization has given these variants names according to the letters of the Greek Alphabet, starting with the Alpha (B.1.1.7) variant, which emerged in 2020, followed by the Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) variants. This review explores the genetic variation among different VOCs of SARS-CoV-2 and how the emergence of variants made a global impact on the pandemic.

The Association of Age and Sex With Joint Angles and Coordination During Unanticipated Cutting in Soccer Players.

Deficits in movement patterns during cutting while running might place soccer players at risk of injury. The objective was to compare joint angles and intersegment coordination between sexes and ages during an unanticipated side-step cutting task in soccer players. This cross-sectional study recruited 11 male (four adolescents and seven adults) and 10 female (six adolescents and four adults) soccer players. Three-dimensional motion capture was used to measure lower-extremity joint and segment angles as participants performed an unanticipated cutting task. Hierarchical linear models examined relationships between joint angle characteristics with age and sex. Continuous relative phase was used to quantify intersegment coordination amplitude and variability. These values were compared between age and sex groups using analysis of covariance. Adult males had greater hip flexion angle excursions than adolescent males, while adult females had smaller excursions than adolescent females (p = .011). Females had smaller changes in hip flexion angles (p = .045), greater hip adduction angles (p = .043), and greater ankle eversion angles (p = .009) than males. Adolescents had greater hip internal rotation (p = .044) and knee flexion (p = .033) angles than adults, but smaller changes in knee flexion angles at precontact compared with stance/foot off (p < .001). For intersegment coordination, females were more out-of-phase than males in the foot/shank segment in the sagittal plane. There were no differences in intersegment coordination variability between groups. Differences in joint motion during an unanticipated cutting task were present between age groups and sexes. Injury prevention programs or training programs may be able target specific deficits to lower injury risk and improve performance.

Adapting a Telehealth Network for Emergency COVID-19 Pandemic Response, 2020-2021.

In March 2020, a Tribal telehealth program-the Indian Country Extension for Community Health Outcomes (ECHO)-added emergency COVID-19 to its programming to support the pandemic response. A long-standing relationship with a network of Indian Health Service, Tribal, and urban Indian clinicians supported a rapid launch of the COVID-19 telehealth program. This nationwide service offered primary care clinicians and staff serving American Indian/Alaska Native people access to virtual learning opportunities, expert clinical recommendations, technical assistance, and capacity building. From March 12, 2020, through April 30, 2021, the program provided 85 clinical sessions in 12 months, with an average participation of 120 attendees per clinic (N = 11 710). Attendees could complete a voluntary evaluation form for each session via an online link. A total of 2595 forms were completed. Attendees came from 33 states and 206 unique locations, primarily from the Pacific Northwest (n = 931, 35.9%). Most pharmacists (78.1%), providers (ie, medical doctor, doctor of osteopathy, advanced practice nurse, physician assistant, or clinical nurse midwife; 70.8%), and nurses (59.6%) gave the sessions the highest rating of "very satisfied." The highest proportion of attendees indicating that they planned a change in practice were pharmacists (68.0%), nurses, (64.1%), and providers (61.3%). Most attendees (93.1%) said that the COVID-19 sessions gave them a sense of social support. Lessons learned were that (1) a telehealth platform can be quickly retasked for emergency response with no further delays, (2) a telehealth network can be scaled up quickly with participation from preexisting relationships, and (3) the platform is flexible and adaptable to the needs of participants. An existing telehealth program can be a key part of timely, relevant, large-scale emergency readiness and response efforts.

Influence of sex and biological maturation on the sudomotor response to exercise-heat stress: are girls disadvantaged?

Both adult females and children have been reported to have a lower sweating capacity and thus reduced evaporative heat loss potential that may increase their susceptibility to exertional hyperthermia in the heat. Compared with males, females have a lower maximal sweat rate and thus a theoretically lower maximum skin wettedness due to a lower sweat output per gland. Similarly, children have been suggested to be disadvantaged in high ambient temperatures due to a lower sweat production and therefore reduced evaporative capacity, despite modifications of heat transfer due to physical attributes and possible evaporative efficiency. The reported reductions in the sudomotor activity of females and children suggest a lower sweating capacity in girls. However, because of the complexities of isolating sex and maturation from the confounding effects of morphological differences (e.g., body surface area-to-mass ratio) and metabolic heat production, limited evidence exists supporting whether children, and, more specifically, girls are at a thermoregulatory disadvantage. Furthermore, a limited number of child-adult comparison studies involve females and very few studies have directly compared regional and whole body sudomotor activity between boys and girls. This minireview highlights the exercise-induced sudomotor response of females and children, summarizes previous research investigating the sudomotor response to exercise in girls, and suggests important areas for further research.

Seasonal Heat Acclimatisation in Healthy Adults: A Systematic Review.

BACKGROUND: Physiological heat adaptations can be induced following various protocols that use either artificially controlled (i.e. acclimation) or naturally occurring (i.e. acclimatisation) environments. During the summer months in seasonal climates, adequate exposure to outdoor environmental heat stress should lead to transient seasonal heat acclimatisation. OBJECTIVES: The aim of the systematic review was to assess the available literature and characterise seasonal heat acclimatisation during the summer months and identify key factors that influence the magnitude of adaptation. ELIGIBILITY CRITERIA: English language, full-text articles that assessed seasonal heat acclimatisation on the same sample of healthy adults a minimum of 3 months apart were included. DATA SOURCES: Studies were identified using first- and second-order search terms in the databases MEDLINE, SPORTDiscus, CINAHL Plus with Full Text, Scopus and Cochrane, with the last search taking place on 15 July 2021. RISK OF BIAS: Studies were independently assessed by two authors for the risk of bias using a modified version of the McMaster critical review form. DATA EXTRACTION: Data for the following outcome variables were extracted: participant age, sex, body mass, height, body fat percentage, maximal oxygen uptake, time spent exercising outdoors (i.e. intensity, duration, environmental conditions), heat response test (i.e. protocol, time between tests), core temperature, skin temperature, heart rate, whole-body sweat loss, whole-body and local sweat rate, sweat sodium concentration, skin blood flow and plasma volume changes. RESULTS: Twenty-nine studies were included in this systematic review, including 561 participants across eight countries with a mean summer daytime wet-bulb globe temperature (WBGT) of 24.9 °C (range: 19.5-29.8 °C). Two studies reported a reduction in resting core temperature (0.16 °C; p < 0.05), 11 reported an increased sweat rate (range: 0.03-0.53 L·h-1; p < 0.05), two observed a reduced heart rate during a heat response test (range: 3-8 beats·min-1; p < 0.05), and six noted a reduced sweat sodium concentration (range: - 22 to - 59%; p < 0.05) following summer. The adaptations were associated with a mean summer WBGT of 25.2 °C (range: 19.6-28.7 °C). LIMITATIONS: The available studies primarily focussed on healthy male adults and demonstrated large differences in the reporting of factors that influence the development of seasonal heat acclimatisation, namely, exposure time and duration, exercise task and environmental conditions. CONCLUSIONS: Seasonal heat acclimatisation is induced across various climates in healthy adults. The magnitude of adaptation is dependent on a combination of environmental and physical activity characteristics. Providing environmental conditions are conducive to adaptation, the duration and intensity of outdoor physical activity, along with the timing of exposures, can influence seasonal heat acclimatisation. Future research should ensure the documentation of these factors to allow for a better characterisation of seasonal heat acclimatisation. PROSPERO REGISTRATION: CRD42020201883.

Prevalence and mechanisms of injuries in water polo: a systematic review.

OBJECTIVE: To summarise the information available in the literature on the prevalence of injuries in water polo and injury risk factors. METHODS: Protocol was registered on Open Science Framework. MEDLINE, CINAHL, Embase and SPORTDiscus databases were searched for keywords relating to water polo and injuries on 3 February 2021. References were searched for additional studies. Only original research papers in English or French were included, and studies without an injured group were excluded. A data extraction file was made based on the Cochrane Collaboration recommendations. Study quality was evaluated with the Newcastle-Ottawa scales for cohorts and a modified version for cross-sectional studies. RESULTS: The initial search yielded 581 articles, with 5 more added from reference lists, but only 41 remained after removing duplicates and applying inclusion/exclusion criteria. Thirty-one articles identified the head, fingers and shoulders as the most common sites of injury. Ten articles on mechanism of injury focused mainly on the shoulder, with degenerative changes, posture, scapular alignment, strength, flexibility and overhead shooting kinematics as the main injury risk factors. Publication types included cohort studies, cross-sectional studies, and one case series. CONCLUSIONS: Most traumatic injuries affect the hands and the head from unexpected contact with the ball or opponents. Conversely, training injuries seem to affect mainly the shoulder area. Low level evidence suggests a correlation between shoulder injuries and lack of strength or flexibility as well as large volumes of overhead throwing. Further prospective research is needed to investigate risk factors for other body areas.

Polarizable Material from a Conjunctival Biopsy in a Patient with Sarcoidosis.

PURPOSE: Conjunctival biopsies may contain polarizable material in patients with sarcoidosis despite no history of prior trauma or eye surgeries. PROCEDURES: A 39-year-old male with uveitic glaucoma presented with decreased vision and throbbing pain in his right eye. His intraocular pressure was elevated, and his vision was reduced to hand motion. Due to persistently elevated intraocular pressure refractory to medical treatment, the patient underwent a glaucoma drainage device procedure. During the procedure, a yellow, nodular conjunctival growth was noted and biopsied. RESULTS: Histopathological examination revealed multiple nonnecrotizing granulomata, some of which contained polarizable material. CONCLUSIONS: Biopsies of patients with sarcoidosis may contain polarizable material without evidence of foreign body inoculation.

Choroidal Ganglioneuroma and Orbital Plexiform Neurofibroma Presenting as Buphthalmos in an Infant With Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF-1) is an autosomal dominant familial tumor predisposition syndrome characterized by the growth of benign and malignant tumors involving the peripheral and central nervous system. In the following report, the authors describe a case of a 1-year-old child with NF-1, who underwent enucleation for a blind, proptotic, painful eye with subsequent histopathological examination revealing choroidal ganglioneuroma, a very rare entity.

Unilateral conjunctival AL kappa amyloidosis with trace evidence of systemic amyloidosis.

BACKGROUND: Amyloidosis is a systemic disorder that results from the tissue deposition of various proteins with distinctive morphological characteristics. Conjunctival amyloidosis is a rare variant which is generally localized and not associated with systemic involvement. CASE REPORT: We present here a case of 47-year-old female patient with right eyelid swelling that progressed over a 12 year period and eventually underwent surgery with pathology showing AL conjunctival amyloidosis. Unlike in most other reported cases of localized amyloidosis, she was noted to have amyloid deposition in the bone marrow and gastrointestinal tract upon extensive evaluation without any evidence of underlying plasma cell dyscrasia. She has been on observation without evidence of systemic progression or recurrence of conjunctival amyloid. CONCLUSIONS: Although it initially appeared that our case represented an isolated form of AL (kappa)-type conjunctival amyloidosis, systemic evaluation revealed trace amount of amyloid in the bone marrow and GI tract. It is feasible that upon very close scrutiny patients with seemingly localized AL amyloidosis may have trace amounts of amyloid involving other organs and based on experience from this single patient we believe that it is safe to observe such patients closely rather than pursue systemic therapy.