Subjective ratings of fear are associated with frontal late positive potential asymmetry,but not with early brain activity over the occipital and centro-parietal cortices

The human frontal cortex is asymmetrically involved in motivational and affective processing. Several studies have shown that the left-frontal hemisphere is related to positive and approach-related affect, whereas the right-frontal hemisphere is related to negative and withdrawal-related affect. The present study aimed to investigate whether evolutionarily threatening stimuli modulate asymmetrical frontal activity. We examined hemispheric differences in frontal late positive potentials (f-LPP asymmetry) and frontal alpha power activation (frontal alpha asymmetry, FAA) in response to images depicting snakes, spiders, butterflies, and birds. Results showed that the late component of f-LPP asymmetry, but not FAA, was modulated by the category of stimuli. Specifically, threatening stimuli (snakes and spiders) evoked a relatively large late f-LPP over the right-frontal hemisphere than non-threatening stimuli (birds and butterflies). Moreover, this relatively great right-frontal activity was positively associated with the subjective ratings of fear. Importantly, the subjective ratings of fear were not associated with early brain activity over the occipital or centro-parietal cortices. These results suggest that late f-LPP asymmetry may reflect higher order affective processes, specifically the subjective appraisal of threatening stimuli and the subjective experience of fear, that are independent of the fast and automatic processing of evolutionarily significant and affectively arousing stimuli.     

Loss of cutaneous microbial diversity during first 3 weeks of life in very low birthweight infants

Neonatal sepsis (NS) is a frequent problem in neonatal intensive care, especially in preterm and very low birthweight (VLBW) infants. The objective of the study was to characterize the cutaneous bacterial microbiome in VLBW infants treated in the neonatal intensive care unit (NICU). Non‐invasive skin microbiome specimens were taken repeatedly from 12 VLBW infants during treatment in NICU starting on the first day of life. All infants received benzylpenicillin and netilmicin during the first 1‐5 postnatal days. Samples were also collected from incubators. High cutaneous microbial diversity was present at birth in 11 of 12 of the infants, but the diversity decreased substantially after the first weeks of life in all infants regardless of their infection status. After the loss of diversity, one Staphylococcus operational taxonomic unit dominated the skin microbiome. Recovery of microbial diversity was seen in six of 12 neonates. The microbiome of incubators showed typical environmental bacterial genera. Maternal antibiotic treatment, the aetiology of the preterm birth or being born by C‐section did not appear to affect the diversity of skin microbiota at birth, and no correlation was found between cutaneous microbiome and NS.     

Serum dehydroepiandrosterone sulfate concentration as an indicator of adrenocortical suppression during inhaled steroid therapy in adult asthmatic patients

OBJECTIVE: Supraphysiological doses of exogenous glucocorticosteroids cause adrenocortical suppression. Dehydroepiandrosterone sulfate (DHEA-S) is the most abundant adrenal androgen and estrogen precursor. We studied to what extent inhaled glucocorticosteroid therapy for asthma decreases serum DHEA-S concentrations. DESIGN AND METHODS: We measured serum DHEA-S and cortisol concentrations in 101 adult patients with newly detected mild asthma before and after 2 and 12 weeks of treatment with inhaled glucocorticosteroids. The patients were randomized to receive budesonide 200 microg/day (low dose group, n=50) or 800 microg/day (high dose group, n=51) in two parallel groups double-blindly. RESULTS: In the low dose group, serum DHEA-S concentrations decreased from the baseline by a mean of 8 % (95 % confidence interval (CI), 3-13 %, P<0.01) after 2 weeks of therapy, and by 2 % (95 % CI, 9 % decrease to 5 % increase, NS) after 12 weeks. In the high dose group, the respective decreases were 16 % (95 % CI, 10-21 %, P<0.001) and 18 % (95 % CI, 12-24 %, P<0.001). The difference between the treatment groups was significant at both 2 and 12 weeks. During the 12 week treatment period the baseline concentrations of serum cortisol did not decrease in the low dose group, while in the high dose group the decrease was significant at 12 weeks (P<0.01), but not at 2 weeks. The forced expiratory volume in 1 s improved equally well in both groups. CONCLUSIONS: Inhaled budesonide decreased serum DHEA-S concentrations, which may indicate adrenocortical suppression. Reduced adrenal production of androgen and estrogen precursors may increase the risk of osteoporosis especially in postmenopausal women.     

Spatial aspects of oncogenic signalling determine the response to combination therapy in slice explants from Kras‐driven lung tumours

A key question in precision medicine is how functional heterogeneity in solid tumours informs therapeutic sensitivity. We demonstrate that spatial characteristics of oncogenic signalling and therapy response can be modelled in precision‐cut slices from Kras‐driven non‐small‐cell lung cancer with varying histopathologies. Unexpectedly, profiling of in situ tumours demonstrated that signalling stratifies mostly according to histopathology, showing enhanced AKT and SRC activity in adenosquamous carcinoma, and mitogen‐activated protein kinase (MAPK) activity in adenocarcinoma. In addition, high intertumour and intratumour variability was detected, particularly of MAPK and mammalian target of rapamycin (mTOR) complex 1 activity. Using short‐term treatment of slice explants, we showed that cytotoxic responses to combination MAPK and phosphoinositide 3‐kinase–mTOR inhibition correlate with the spatially defined activities of both pathways. Thus, whereas genetic drivers determine histopathology spectra, histopathology‐associated and spatially variable signalling activities determine drug sensitivity. Our study is in support of spatial aspects of signalling heterogeneity being considered in clinical diagnostic settings, particularly to guide the selection of drug combinations. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Arthritis and arthralgia three years after Sindbis virus infection: clinical follow-up of a cohort of 49 patients

Sindbis virus (SINV) emerges as large human outbreaks in northern Europe every 7 years. Similar to many other alphaviruses, SINV is a mosquito-borne causative agent of a rash-arthritis. Previous reports suggest that in many alphavirus infections joint symptoms might persist for years. A prospective cohort of 49 patients was physically examined 3 y after verified acute SINV infection to reveal persistent joint symptoms. We carefully searched for a temporal association between the infection and current symptoms, and took into account other medical conditions. Sera were collected and analysed with enzyme immunoassays. Arthritis (swelling and tenderness on physical examination) was diagnosed in 4.1% (2/49) of the patients. Tenderness on palpation or in movement of a joint was found in 14.3% of the patients in the rheumatological examination, and an additional 10.2% complained of persisting arthralgia at the interview. Thus, 24.5% of the patients had joint manifestations attributable to the infection 3 y earlier. A positive IgM antibody response persisted in 3/49 of the patients; both patients with arthritis were in this group. As one-quarter of the patients were symptomatic 3 y after infection, it seems that persistent symptoms of SINV infection have considerable public health implications in areas with high seroprevalence.     

Incidence of schizophrenia in a nationwide cohort of patients with type 1 diabetes mellitus

CONTEXT: Patients with schizophrenia have an increased risk of type 2 diabetes mellitus. However, very few studies have dealt with the association of type 1 diabetes and schizophrenia. Preliminary evidence points to a possible inverse association. OBJECTIVE: To investigate the incidence of schizophrenia in a nationwide cohort of patients with type 1 diabetes born in 1950 through 1959 in Finland. DESIGN: A cohort study of individuals born in 1950 through 1959 with a follow-up of 1969 through 1991. SETTING: Finland. PATIENTS: All individuals born in 1950 through 1959 with type 1 diabetes were identified through nationwide registers. The incidence of schizophrenia until 1992 among the total 1950-1959 cohort and in individuals with type 1 diabetes was calculated using information from 3 health care registers. MAIN OUTCOME MEASURE: Incidence of schizophrenia. RESULTS: The incidence of schizophrenia was 0.21 per 10 000 person-years in the group with type 1 diabetes and 0.56 per 10 000 person-years in the group without type 1 diabetes (P < .001). CONCLUSION: The incidence of schizophrenia is decreased in patients with type 1 diabetes.     

Influence of the rate of temperature change on thermal thresholds in man

Thermal thresholds (cool, warm, heat, heat pain) were determined in four skin regions (cheek, glabrous skin of the hand, hairy forearm, leg) of eight healthy human subjects. The thermostimulator was composed of Peltier elements and three rates of continuous stimulation were used: 1.4, 2.4, and 3.9 degrees C/s. Warm, heat, and heat pain thresholds increased with increasing rate of temperature change, and the increase was of equal magnitude with these three thresholds. However, the effect of increasing stimulus rate on cool thresholds was nonsignificant. Similar results were obtained in all skin regions studied. It is suggested that liminal warm, heat, and heat pain sensations are mediated by afferent fibers with conduction velocities of the same range (C-fibers) whereas liminal cool sensations are signaled by faster conducting afferent fibers.     

The antinociceptive action of an α2-adrenoceptor agonist in the spinal dorsal horn is due to a direct spinal action and not to activation of Descending Inhibition

In this electrophysiological study we tried to find out whether the spinal antinociceptive effect of a supraspinaly administered α₂-adrenoceptor agonist is due to a direct spinal effect or to activation of descending inhibition. The responses to wide-dynamic range (WDR) neurons of the spinal dorsal horn were studied following application of medetomidine, a selective α₂-adrenergic agonist, into the rostroventromedial medulla (RVM) or directly onto the spinal cord of the Intact and in spinal rats. The noxious electrical stimuli were applied to the ipsilateral receptive field in the plantar region of the hind paw, and responses mediated by A- and C-fibers to WDR neurons were separately evaluated. The reversal of medetomidine-induced effects was attempted by a systemic administration of atipamezole, a selective α₂-adronoceptor antagonist. Medetomldine injection into the RVM produced a dose-dependent, atipamezole-reversible attenuation of the C-fiber-mediated responses to WDR neurons of the spinal dorsal horn in both intact and spinal rats. Paradoxically, the spinal aMFnociceptive effect of supraspinally administered medstomidine was stronger in spinal rats. The A-fiber-mediated responses were significantly less attenuated by medetomidine than the C-fiber-mediated responses to the WDR neurons. Also a direct application of medetomidine onto the spinal cord produced a dose-dependent, atipamezole-reversible attenuation of the C-fiber-mediated responses, and this effect was identical in intact and in spinal rats. The medetomidins doses producing spinal antinociception were considerably lower with a direct spinal application than with a supraspinal application. These results indicate that spinal antinocicsption following spinal or supraspinal application of an α₂-adrenergic agonist is due to a direct activation of spinal α₂-adrenoceptors and not to descending inhibition. Activation of supraspinal α₂-adrenoceptors counteracts the spinal antinociceptive effect.     

Age-Related Differences in the Frequency of Ketoacidosis at Diagnosis of Type 1 Diabetes in Children and Adolescents

OBJECTIVE

We studied the prevalence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in children in Finland.

RESEARCH DESIGN AND METHODS

From 2002 to 2005, data on virtually all children <15 years of age diagnosed with type 1 diabetes (n = 1,656) in Finland were collected.

RESULTS

DKA was present in 19.4% of the case subjects, and 4.3% had severe DKA. In children aged 0–4, 5–9, and 10–14 years, DKA was present in 16.5, 14.8, and 26.4%, respectively (P < 0.001). Severe DKA occurred in 3.7, 3.1, and 5.9%, respectively (P = 0.048). DKA was present in 30.1% and severe DKA in 7.8% of children aged <2 years.

CONCLUSION

The overall frequency of DKA in children is low in Finland at diagnosis of type 1 diabetes. However, both children <2 years of age and adolescents aged 10–14 years are at increased risk of DKA.The incidence of diabetic ketoacidosis (DKA) in children with newly diagnosed type 1 diabetes may be decreasing in developed countries (1,2).