SUMMARY Median motor and sensory nerves were examined in 20 healthy subjects. Superficial stimulating and recording electrodes were used, and the nerves were examined at natural skin temperature, after cooling and after heating of the arm. The conduction velocity for the fastest and slow conducting sensory fibres (temperature range 1 7-37°C), and for the fastest conducting motor fibres (temperature range 19-38°C) increased non-linearly with increase in skin temperature. Similarly, distal motor latencies increased non-linearly with decrease in skin temperature. The effect of temperature was most pronounced in the low temperature range, and change in conduction velocity per degree centigrade was reduced toward higher skin temperature. Sensory nerve response duration increased linearly with decline in skin temperature. Sensory and motor amplitude did not show any significant relation to skin temperature.Nerve conduction studies have been performed in animals since 1850.' Techniques for the examination of motor nerve function in man have been established since 1948, and for sensory nerve function since 1956,23 and have later been improved. They are now widely used both in routine clinical investigation of nerve and muscle disorders, and for investigation of the possible physiological changes in nerves exposed to altered environmental influences.Temperature changes influence peripheral nerve function. To what extent and whether the effect is the same along the temperature scale, is still disputed.' 16 Nerve conduction studies are usually performed using surface electrodes, and as distal skin temperature varies, the effect of temperature is important both in routine neurophysiology and as an aspect of nerve physiology.The aim of this study was therefore to evaluate the influence of temperature changes on normal human sensory and motor nerve conduction, and to compare the results obtained to previous studies.

Epidemiological studies suggest that father’s smoking might influence their future children’s health, but few studies have addressed whether paternal line effects might be related to altered DNA methylation patterns in the offspring. To investigate a potential association between fathers’ smoking exposures and offspring DNA methylation using epigenome-wide association studies. We used data from 195 males and females (11–54 years) participating in two population-based cohorts. DNA methylation was quantified in whole blood using Illumina Infinium MethylationEPIC Beadchip. Comb-p was used to analyse differentially methylated regions (DMRs). Robust multivariate linear models, adjusted for personal/maternal smoking and cell-type proportion, were used to analyse offspring differentially associated probes (DMPs) related to paternal smoking. In sensitivity analyses, we adjusted for socio-economic position and clustering by family. Adjustment for inflation was based on estimation of the empirical null distribution in BACON. Enrichment and pathway analyses were performed on genes annotated to cytosine-phosphate-guanine (CpG) sites using the gometh function in missMethyl. We identified six significant DMRs (Sidak-corrected P values: 0.0006–0.0173), associated with paternal smoking, annotated to genes involved in innate and adaptive immunity, fatty acid synthesis, development and function of neuronal systems and cellular processes. DMP analysis identified 33 CpGs [false discovery rate (FDR)  < 0.05]. Following adjustment for genomic control (λ = 1.462), no DMPs remained epigenome-wide significant (FDR < 0.05). This hypothesis-generating study found that fathers’ smoking was associated with differential methylation in their adolescent and adult offspring. Future studies are needed to explore the intriguing hypothesis that fathers’ exposures might persistently modify their future offspring’s epigenome.

Rationale: Experimental studies suggest that exposures may impact respiratory health across generations via epigenetic changes transmitted specifically through male germ cells. Studies in humans are however limited. We aim to identify epigenetic marks in offspring associated with fathers preconception smoking. Methods: We conducted epigenome-wide association studies (EWAS) in the RHINESSA cohort on fathers any preconception smoking (N=875 offspring) and fathers pubertal onset smoking <15 years (N=304), using Infinium MethylationEPIC Beadchip arrays, adjusting for offspring age, maternal smoking and personal smoking. EWAS of maternal and offspring personal smoking were performed for replication. Results: Fathers smoking commencing preconception was associated with methylation of blood DNA in offspring at two Cytosine-phosphate-Guanine sites (CpGs) (False Discovery Rate (FDR) <0.05) in PRR5 and CENPP. Fathers pubertal onset smoking was associated with 19 CpGs (FDR <0.05) mapped to 14 genes (TLR9, DNTT, FAM53B, NCAPG2, PSTPIP2, MBIP, C2orf39, NTRK2, DNAJC14, CDO1, PRAP1, TPCN1, IRS1 and CSF1R). These differentially methylated sites were hypermethylated and associated with promoter regions capable of gene silencing. Some of these sites were associated with offspring outcomes in this cohort including ever-asthma (NTRK2), ever-wheezing (DNAJC14, TPCN1), weight (FAM53B, NTRK2) and BMI (FAM53B, NTRK2) (P< 0.05). Pathway analysis showed enrichment for gene ontology pathways including regulation of gene expression, inflammation and innate immune responses. Conclusion: Fathers preconception smoking, particularly in puberty, is associated with offspring DNA methylation, providing evidence that epigenetic mechanisms may underly epidemiological observations that pubertal paternal smoking increases risk of offspring asthma, low lung function and obesity. Key Words: Preconception, paternal effects, tobacco smoke, epigenetic, Epigenome-Wide Association Study, DNA methylation, RHINESSA