Compromised heat loss leads to a delayed ice slurry induced reduction in heat storage.

Compromised heat loss due to limited convection and evaporation can increase thermal strain. We aimed to determine the effectiveness of ice slurry ingestion to reduce thermal strain following hyperthermia in a state of compromised heat loss. Twelve healthy males (age: 25 ± 4y) underwent hot water immersion to elevate rectal temperature (Trec) by 1.82 ± 0.08°C on four occasions. In the subsequent 60-min of seated recovery, participants ingested either 6.8 g·kg-1 of ice slurry (-0.6°C) or control drink (37°C) in ambient conditions (21 ± 1°C, 39 ± 10% relative humidity), wearing either t-shirt and shorts (2 trials: ICE and CON) or a whole-body sweat suit (2 trials: ICE-SS and CON-SS). Trec and mean skin temperature (Tsk) were recorded and a two-compartment thermometry model of heat storage was calculated. Heat storage was lower in ICE compared with CON at 20-40min (p ≤ 0.044, d ≥ 0.88) and for ICE-SS compared with CON-SS at 40-60 min (p ≤ 0.012, d ≥ 0.93). Trec was lower in ICE compared with CON from 30-60min (p ≤ 0.034, d ≥ 0.65), with a trend for a reduced Trec in ICE-SS compared with CON-SS at 40min (p = 0.079, d = 0.60). A greater Tsk was found in ICE-SS and CON-SS compared with ICE and CON (p < 0.001, d ≥ 3.37). A trend for a lower Tsk for ICE compared with CON was found at 20-40min (p ≤ 0.099, d ≥ 0.53), no differences were found for ICE-SS vs CON-SS (p ≥ 0.554, d ≤ 0.43). Ice slurry ingestion can effectively reduce heat storage when heat loss through convection and evaporation is compromised, relevant to those wearing personal protective equipment or those with compromised sweat loss. Compromised heat loss delays the reduction in heat storage, possibly related to ice slurry ingestion not lowering Tsk.

RTN2 deficiency results in an autosomal recessive distal motor neuropathy with lower limb spasticity.

Heterozygous RTN2 variants have been previously identified in a limited cohort of families affected by autosomal dominant spastic paraplegia (SPG12-OMIM:604805) with a variable age of onset. Nevertheless, the definitive validity of SPG12 remains to be confidently confirmed due to the scarcity of supporting evidence. In this study, we identified and validated seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven consanguineous families with distal hereditary motor neuropathy (dHMN) using exome, genome and Sanger sequencing coupled with deep-phenotyping. All affected individuals (seven males and seven females, aged 9-50 years) exhibited weakness in the distal upper and lower limbs, lower limb spasticity and hyperreflexia, with onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography. Despite a slowly progressive disease course, all patients remained ambulatory over a mean disease duration of 19.71 ± 13.70 years. Characterization of Caenorhabditis elegans RTN2 homologous loss-of-function variants demonstrated morphological and behavioural differences compared with the parental strain. Treatment of the mutant with an endoplasmic/sarcoplasmic reticulum Ca2+ reuptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences, suggesting a potential therapeutic benefit for RTN2-disorder. Despite RTN2 being an endoplasmic reticulum (ER)-resident membrane shaping protein, our analysis of patient fibroblast cells did not find significant alterations in ER structure or the response to ER stress. Our findings delineate a distinct form of autosomal recessive dHMN with pyramidal features associated with RTN2 deficiency. This phenotype shares similarities with SIGMAR1-related dHMN and Silver-like syndromes, providing valuable insights into the clinical spectrum and potential therapeutic strategies for RTN2-related dHMN.

Rectal and gastrointestinal temperature differ during passive heating and subsequent recovery.

We aimed to compare rectal temperature (Trec) and gastro-intestinal temperature (TGI) during passive heating and subsequent recovery with and without ice slurry ingestion. Twelve males (age: 25 ± 4 years, body mass index: 25.7 ± 2.5 kg m-2) were immersed in hot water on two occasions (Trec elevation: 1.82 ± 0.08°C). In the subsequent 60-min recovery in ambient conditions, participants ingested either 6.8 g kg-1 of ice slurry (-0.6°C, ICE) or control drink (37°C, CON). During passive heating, Trec was lower than TGI (P < 0.001), in the recovery, Trec was higher than TGI (P < 0.001). During passive heating, mean bias and 95%LoA (Limits of Agreement) were -0.10(±0.25)°C and -0.12(±0.36)°C for CON and ICE, respectively. In the recovery, mean bias and 95%LoA were 0.30(±0.60)°C and 0.42(±0.63)°C for CON and ICE, respectively. Trec and TGI differed during both heating and recovery, and less favourable agreement between Trec and TGI was found in the recovery from passive heating with or without ice slurry ingestion.