The Helsinki approach to face transplantation

Aim

We herein describe the establishment of the Helsinki Vascularized Composite Allotransplantation (VCA) program and its execution in the first two face transplant cases.

Copy number variation and neuropsychiatric problems in females and males in the general population

Neurodevelopmental problems (NPs) are more common in males, whereas anxiety and depression are more common in females. Rare copy number variants (CNVs) have been implicated in neurodevelopmental disorders. The aim of this study was to characterize the relationship between rare CNVs with NPs, anxiety, and depression in a childhood population sample, as well as to examine sex‐specific effects. We analyzed a sample of N = 12,982 children, of whom 5.3% had narrowly defined NPs (clinically diagnosed), 20.9% had broadly defined NPs (based on validated screening measures, but no diagnosis), and 3.0% had clinically diagnosed anxiety or depression. Rare (<1% frequency) CNVs were categorized by size (100–500 kb or > 500 kb), type, and putative relevance to NPs. We tested for association of CNV categories with outcomes and examined sex‐specific effects. Medium deletions (OR[CI] = 1.18[1.05–1.33], p = .0053) and large duplications (OR[CI] = 1.45[1.19–1.75], p = .00017) were associated with broadly defined NPs. Large deletions (OR[CI] = 1.85[1.14–3.01], p = .013) were associated with narrowly defined NPs. There were no significant sex differences in CNV burden in individuals with NPs. Although CNVs were not associated with anxiety/depression in the whole sample, in individuals diagnosed with these disorders, females were more likely to have large CNVs (OR[CI] = 3.75[1.45–9.68], p = .0064). Rare CNVs are associated with both narrowly and broadly defined NPs in a general population sample of children. Our results also suggest that large, rare CNVs may show sex‐specific phenotypic effects.     

Gut feelings about smoking and coffee in Parkinson's disease

Strong epidemiologic evidence suggests that smokers and coffee drinkers have a lower risk of Parkinson's disease (PD). The explanation for this finding is still unknown, and the discussion has focused on two main hypotheses. The first suggests that PD patients have premorbid personality traits associated with dislike for coffee‐drinking and smoking. The second posits that caffeine and nicotine are neuroprotective. We propose an alternative third hypothesis, in which both cigarette and coffee consumption change the composition of the microbiota in the gut in a way that mitigates intestinal inflammation. This, in turn, would lead to less misfolding of the protein alpha‐synuclein in enteric nerves, reducing the risk of PD by minimizing propagation of the protein aggregates to the central nervous system, where they otherwise can induce neurodegeneration. © 2014 International Parkinson and Movement Disorder Society     

Cortical control of adaptation and sensory relay mode in the thalamus

A major synaptic input to the thalamus originates from neurons in cortical layer 6 (L6); however, the function of this cortico–thalamic pathway during sensory processing is not well understood. In the mouse whisker system, we found that optogenetic stimulation of L6 in vivo results in a mixture of hyperpolarization and depolarization in the thalamic target neurons. The hyperpolarization was transient, and for longer L6 activation (>200 ms), thalamic neurons reached a depolarized resting membrane potential which affected key features of thalamic sensory processing. Most importantly, L6 stimulation reduced the adaptation of thalamic responses to repetitive whisker stimulation, thereby allowing thalamic neurons to relay higher frequencies of sensory input. Furthermore, L6 controlled the thalamic response mode by shifting thalamo–cortical transmission from bursting to single spiking. Analysis of intracellular sensory responses suggests that L6 impacts these thalamic properties by controlling the resting membrane potential and the availability of the transient calcium current I_T, a hallmark of thalamic excitability. In summary, L6 input to the thalamus can shape both the overall gain and the temporal dynamics of sensory responses that reach the cortex.Sensory signals en route to the cortex undergo profound signal transformations in the thalamus. One important thalamic transformation is sensory adaptation. Adaptation is a common characteristic of sensory systems in which neural output adjusts to the statistics and dynamics of past stimuli, thereby better encoding small stimulus changes across a wide range of scales despite the limited range of possible neural outputs (1–3). Thalamic sensory adaptation is characterized by a steep decrease in action potential (AP) activity during sustained sensory stimulation (4–7), decreasing the efficacy at which subsequent sensory stimuli are transmitted to the cortex.The widely reported duality of thalamic response mode is another key property of thalamic information processing which further affects how sensory input reaches the cortex. In burst mode, sensory inputs are relayed as short, rapid clusters of APs; in contrast, in tonic mode the same inputs are translated into single APs. Both tonic and burst modes have been described during anesthesia/sleep and wakefulness/behavior, with a pronounced shift toward the tonic mode during alertness (8–12).Although the exact information content of thalamic bursts is not yet clear, it has been suggested that bursting may signal novel stimuli to the cortex, whereas the tonic mode enables linear encoding of fine stimulus details, e.g., when an object is examined (13, 14). One issue hampering the interpretation of burst/tonic responses is that currently it is unknown if the cortex itself is involved in the rapid changes in firing modes seen in the awake and anesthetized animal (15, 16) and which mechanisms initiate these shifts in vivo.On the biophysical level, the response mode depends on the resting membrane potential (RMP), which controls the availability of the transient low-threshold calcium current (I_T) (17). Depolarization decreases the size of the I_T-mediated low-threshold calcium spike (LTS), and fewer burst spikes are fired (18). Similarly, RMP influences adaptation in that depolarization reduces the voltage distance to the AP threshold, thereby increasing the probability that smaller, depressed inputs will trigger APs (6). Thus, the dynamics of the RMP may govern several key properties of signal transformation in the thalamus, thereby providing a common mechanism for controlling thalamic adaptation and response mode.Although subcortical inputs have been shown to influence thalamic firing modes (7, 9), we investigated the impact of cortical activity on thalamic sensory processing. Cortico–thalamic projections from cortical layer 6 (L6) are a likely candidate for regulating thalamic sensory processing with high spatial and temporal precision, because these projections provide a major input to the thalamus and, as shown by McCormick et al. (19), depolarize and modulate firing of thalamic cells in vitro.However, because of the inability to study sensory signals in brain slices, the role of L6 on thalamic input/output properties during sensory processing is not clear. Here, in the ventro posteromedial nucleus (VPM) of the mouse whisker thalamus, we investigate how L6 impacts the transmission of whisker inputs to the cortex. Recent advances in cell-type–specific approaches to dissect specific circuits in vivo (20–22) allowed us to activate the L6–thalamic pathway specifically and determine its impact on thalamic sensory processing.We found that cortical L6 can change key properties of thalamic sensory processing by controlling the interaction of intrinsic membrane properties and sensory inputs. This mechanism enables the cortex to control the frequency-dependent adaptation and the gain of its own input.     

Health‐related quality of life after kidney transplantation: who benefits the most?

The influence of dialysis modalities on HRQoL before and after kidney transplantation (KT) and the role of adherence to medication on HRQoL have not been fully studied. Sixty four dialysis patients who answered the 15D HRQoL survey during dialysis were surveyed again after KT. Adherence and employment were also investigated. The mean 15D score was highest among home hemodialysis patients (HHD) and lowest among in‐center hemodialysis patients (icHD). After KT, the mean 15D score improved significantly in 78.6% of peritoneal dialysis patients (PD), 47.6% of HHD, and 53.8% of icHD. Then, mean 15D score remained unchanged in 28.6% of HHD and in 23.1% of icHD patients. A deterioration in the 15D score occurred in 14.3% of PD, 23.1% of icHD, and 23.8% of HHD patients, and this was influenced by the number of pills (P = 0.04). Adherence to medication was the lowest in PD, timing being the most challenging task showing a connection to higher creatinine concentration (never forgot 1.41 mg/dl vs. forgot 2.08 mg/dl P = 0.05). Employed patients had a higher mean 15D score. The icHD and PD patients benefited the most from KT and HHD the least. Low pill burden and employment were linked to a better HRQoL.     

Temporal variation in out-of-hospital cardiac arrest with validated cardiac cause

Objective. Temporal variations in the occurrence of out-of-hospital cardiac arrest (OHCA) have been shown. Most previous studies have in common that they include individuals whom have received cardiopulmonary resuscitation (CPR) and thus excluding a great number of all the actual cases of OHCA when conducting a study. Therefore the aim of this study was to describe temporal variations of OHCA, regardless of whether CPR was performed or not. Design. All individuals aged 25–74 years in northern Sweden, 1989–2009, who suffered an out-of-hospital cardiac arrest with validated myocardial infarction aetiology (OHCA-V), regardless of whether CPR was performed or not, were included in this study, which resulted in 3357 individuals. Results. Regarding the diurnal variation, a daytime excess of OHCA-V was seen, with most occurring between 12:00–17:59 (29%) closely followed by the 06:00–11:59 time block (27%). In terms of the weekly variation, most OHCA-V was seen on Saturdays (17%), while January (11%), followed by December (9%), saw the highest incidence of the months. Conclusion. A temporal variation in OHCA-V is seen even when including cases where no CPR is attempted. However, this variation differs in some aspects to what some previous studies have shown, in that no clear morning or Monday peaks were seen. In order to explore potential triggers and underlying factors that influence OHCA, more studies like these are needed, preferably following standardized inclusion criteria and definitions of OHCA to better be able to compare results, all in order to develop the best possible preventive strategies.