A challenge to the expected: Lack of longitudinal associations between the early caregiving environment, executive functions in toddlerhood, and self-regulation at 6 years.

Previous research and theory indicate an importance of the quality of the early caregiving environment in the development of self-regulation. However, it is unclear how attachment security and maternal sensitivity, two related but distinct aspects of the early caregiving environment, may differentially predict self-regulation at school start and whether a distinction between hot and cool executive function is informative in characterizing such predictions through mediation. In a 5-year longitudinal study (n = 108), we examined these associations using measures of maternal sensitivity and attachment security at 10-12 months, executive function at 4 years, and self-regulation at 6 years. Surprisingly, and despite methodological rigor, we found few significant bivariate associations between the study variables. We found no credible evidence of a longitudinal association between maternal sensitivity or attachment security in infancy and self-regulation at 6 years, or between executive function at 4 years and self-regulation at 6 years. The lack of bivariate longitudinal associations precluded us from building mediation models as intended. We discuss our null findings in terms of their potential theoretical implications, as well as how measurement type, reliability, and validity, may play a key role in determining longitudinal associations between early caregiving factors and later self-regulation and related abilities. RESEARCH HIGHLIGHTS: The early caregiving environment has been implicated in the development of later self-regulation, which includes more basic skills, such as hot and cool executive functions (EF). In a 5-year longitudinal study, with a sample of 108 children, we rigorously measured aspects of early caregiving, EF, and self-regulation. We found no significant longitudinal associations between early caregiving and self-regulation at 6 years, nor between EF at 4 years and self-regulation at 6 years. These null results highlight the complexity of modeling self-regulation development and raise critical questions about general methodological conventions within self-regulation development research.

The influence of anterior cingulate GABA+ and glutamate on emotion regulation and reactivity in adolescents and adults.

During adolescence, emotion regulation and reactivity are still developing and are in many ways qualitatively different from adulthood. However, the neurobiological processes underpinning these differences remain poorly understood, including the role of maturing neurotransmitter systems. We combined magnetic resonance spectroscopy in the dorsal anterior cingulate cortex (dACC) and self-reported emotion regulation and reactivity in a sample of typically developed adolescents (n = 37; 13-16 years) and adults (n = 39; 30-40 years), and found that adolescents had higher levels of glutamate to total creatine (tCr) ratio in the dACC than adults. A glutamate Í age group interaction indicated a differential relation between dACC glutamate levels and emotion regulation in adolescents and adults, and within-group follow-up analyses showed that higher levels of glutamate/tCr were related to worse emotion regulation skills in adolescents. We found no age-group differences in gamma-aminobutyric acid+macromolecules (GABA+) levels; however, emotion reactivity was positively related to GABA+/tCr in the adult group, but not in the adolescent group. The results demonstrate that there are developmental changes in the concentration of glutamate, but not GABA+, within the dACC from adolescence to adulthood, in accordance with previous findings indicating earlier maturation of the GABA-ergic than the glutamatergic system. Functionally, glutamate and GABA+ are positively related to emotion regulation and reactivity, respectively, in the mature brain. In the adolescent brain, however, glutamate is negatively related to emotion regulation, and GABA+ is not related to emotion reactivity. The findings are consistent with synaptic pruning of glutamatergic synapses from adolescence to adulthood and highlight the importance of brain maturational processes underlying age-related differences in emotion processing.

Dopamine and fear memory formation in the human amygdala.

Learning which environmental cues that predict danger is crucial for survival and accomplished through Pavlovian fear conditioning. In humans and rodents alike, fear conditioning is amygdala-dependent and rests on similar neurocircuitry. Rodent studies have implicated a causative role for dopamine in the amygdala during fear memory formation, but the role of dopamine in aversive learning in humans is unclear. Here, we show dopamine release in the amygdala and striatum during fear learning in humans. Using simultaneous positron emission tomography and functional magnetic resonance imaging, we demonstrate that the amount of dopamine release is linked to strength of conditioned fear responses and linearly coupled to learning-induced activity in the amygdala. Thus, like in rodents, formation of amygdala-dependent fear memories in humans seems to be facilitated by endogenous dopamine release, supporting an evolutionary conserved neurochemical mechanism for aversive memory formation.

Progressive Voxel-Wise Homotopic Connectivity from childhood to adulthood: Age-related functional asymmetry in resting-state functional magnetic resonance imaging.

Homotopic connectivity during resting state has been proposed as a risk marker for neurologic and psychiatric conditions, but a precise characterization of its trajectory through development is currently lacking. Voxel-Mirrored Homotopic Connectivity (VMHC) was evaluated in a sample of 85 neurotypical individuals aged 7-18 years. VMHC associations with age, handedness, sex, and motion were explored at the voxel-wise level. VMHC correlates were also explored within 14 functional networks. Primary and secondary outcomes were repeated in a sample of 107 adults aged 21-50 years. In adults, VMHC was negatively correlated with age only in the posterior insula (false discovery rate p < .05, >30-voxel clusters), while a distributed effect among the medial axis was observed in minors. Four out of 14 considered networks showed significant negative correlations between VMHC and age in minors (basal ganglia r = -.280, p = .010; anterior salience r = -.245, p = .024; language r = -.222, p = .041; primary visual r = -.257, p = .017), but not adults. In minors, a positive effect of motion on VMHC was observed only in the putamen. Sex did not significantly influence age effects on VMHC. The current study showed a specific decrease in VMHC for minors as a function of age, but not adults, supporting the notion that interhemispheric interactions can shape late neurodevelopment.

Expression and co-expression of serotonin and dopamine transporters in social anxiety disorder: a multitracer positron emission tomography study.

Serotonin and dopamine are putatively involved in the etiology and treatment of anxiety disorders, but positron emission tomography (PET) studies probing the two neurotransmitters in the same individuals are lacking. The aim of this multitracer PET study was to evaluate the regional expression and co-expression of the transporter proteins for serotonin (SERT) and dopamine (DAT) in patients with social anxiety disorder (SAD). Voxel-wise binding potentials (BPND) for SERT and DAT were determined in 27 patients with SAD and 43 age- and sex-matched healthy controls, using the radioligands [11C]DASB (3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile) and [11C]PE2I (N-(3-iodopro-2E-enyl)-2beta-carbomethoxy-3beta-(4'-methylphenyl)nortropane). Results showed that, within transmitter systems, SAD patients exhibited higher SERT binding in the nucleus accumbens while DAT availability in the amygdala, hippocampus, and putamen correlated positively with symptom severity. At a more lenient statistical threshold, SERT and DAT BPND were also higher in other striatal and limbic regions in patients, and correlated with symptom severity, whereas no brain region showed higher binding in healthy controls. Moreover, SERT/DAT co-expression was significantly higher in SAD patients in the amygdala, nucleus accumbens, caudate, putamen, and posterior ventral thalamus, while lower co-expression was noted in the dorsomedial thalamus. Follow-up logistic regression analysis confirmed that SAD diagnosis was significantly predicted by the statistical interaction between SERT and DAT availability, in the amygdala, putamen, and dorsomedial thalamus. Thus, SAD was associated with mainly increased expression and co-expression of the transporters for serotonin and dopamine in fear and reward-related brain regions. Resultant monoamine dysregulation may underlie SAD symptomatology and constitute a target for treatment.

COUP-TFI/Nr2f1 Orchestrates Intrinsic Neuronal Activity during Development of the Somatosensory Cortex.

The formation of functional cortical maps in the cerebral cortex results from a timely regulated interaction between intrinsic genetic mechanisms and electrical activity. To understand how transcriptional regulation influences network activity and neuronal excitability within the neocortex, we used mice deficient for Nr2f1 (also known as COUP-TFI), a key determinant of primary somatosensory (S1) area specification during development. We found that the cortical loss of Nr2f1 impacts on spontaneous network activity and synchronization of S1 cortex at perinatal stages. In addition, we observed alterations in the intrinsic excitability and morphological features of layer V pyramidal neurons. Accordingly, we identified distinct voltage-gated ion channels regulated by Nr2f1 that might directly influence intrinsic bioelectrical properties during critical time windows of S1 cortex specification. Altogether, our data suggest a tight link between Nr2f1 and neuronal excitability in the developmental sequence that ultimately sculpts the emergence of cortical network activity within the immature neocortex.

Hippocampal Mossy Fibers Synapses in CA3 Pyramidal Cells Are Altered at an Early Stage in a Mouse Model of Alzheimer's Disease.

Early Alzheimer's disease (AD) affects the brain non-uniformly, causing hippocampal memory deficits long before wide-spread brain degeneration becomes evident. Here we addressed whether mossy fiber inputs from the dentate gyrus onto CA3 principal cells are affected in an AD mouse model before amyloid ß plaque deposition. We recorded from CA3 pyramidal cells in a slice preparation from 6-month-old male APP/PS1 mice, and studied synaptic properties and intrinsic excitability. In parallel we performed a morphometric analysis of mossy fiber synapses following viral based labeling and 3D-reconstruction. We found that the basal structural and functional properties as well as presynaptic short-term plasticity at mossy fiber synapses are unaltered at 6 months in APP/PS1 mice. However, transient potentiation of synaptic transmission mediated by activity-dependent release of lipids was abolished. Whereas the presynaptic form of mossy fiber long-term potentiation (LTP) was not affected, the postsynaptic LTP of NMDAR-EPSCs was reduced. In addition, we also report an impairment in feedforward inhibition in CA3 pyramidal cells. This study, together with our previous work describing deficits at CA3-CA3 synapses, provides evidence that early AD affects synapses in a projection-dependent manner at the level of a single neuronal population.SIGNIFICANCE STATEMENT Because loss of episodic memory is considered the cognitive hallmark of Alzheimer's disease (AD), it is important to study whether synaptic circuits involved in the encoding of episodic memory are compromised in AD mouse models. Here we probe alterations in the synaptic connections between the dentate gyrus and CA3, which are thought to be critical for enabling episodic memories to be formed and stored in CA3. We found that forms of synaptic plasticity specific to these synaptic connections are markedly impaired at an early stage in a mouse model of AD, before deposition of ß amyloid plaques. Together with previous work describing deficits at CA3-CA3 synapses, we provide evidence that early AD affects synapses in an input-dependent manner within a single neuronal population.

Dysfunctional Autism Risk Genes Cause Circuit-Specific Connectivity Deficits With Distinct Developmental Trajectories.

Autism spectrum disorders (ASD) are a set of complex neurodevelopmental disorders for which there is currently no targeted therapeutic approach. It is thought that alterations of genes regulating migration and synapse formation during development affect neural circuit formation and result in aberrant connectivity within distinct circuits that underlie abnormal behaviors. However, it is unknown whether deviant developmental trajectories are circuit-specific for a given autism risk-gene. We used MRI to probe changes in functional and structural connectivity from childhood to adulthood in Fragile-X (Fmr1-/y) and contactin-associated (CNTNAP2-/-) knockout mice. Young Fmr1-/y mice (30 days postnatal) presented with a robust hypoconnectivity phenotype in corticocortico and corticostriatal circuits in areas associated with sensory information processing, which was maintained until adulthood. Conversely, only small differences in hippocampal and striatal areas were present during early postnatal development in CNTNAP2-/- mice, while major connectivity deficits in prefrontal and limbic pathways developed between adolescence and adulthood. These findings are supported by viral tracing and electron micrograph approaches and define 2 clearly distinct connectivity endophenotypes within the autism spectrum. We conclude that the genetic background of ASD strongly influences which circuits are most affected, the nature of the phenotype, and the developmental time course of the associated changes.

Combining escitalopram and cognitive-behavioural therapy for social anxiety disorder: randomised controlled fMRI trial.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioural therapy (CBT) are often used concomitantly to treat social anxiety disorder (SAD), but few studies have examined the effect of this combination. AIMS: To evaluate whether adding escitalopram to internet-delivered CBT (ICBT) improves clinical outcome and alters brain reactivity and connectivity in SAD. METHOD: Double-blind, randomised, placebo-controlled neuroimaging trial of ICBT combined either with escitalopram (n = 24) or placebo (n = 24), including a 15-month clinical follow-up (trial registration: ISRCTN24929928). RESULTS: Escitalopram+ICBT, relative to placebo+ICBT, resulted in significantly more clinical responders, larger reductions in anticipatory speech state anxiety at post-treatment and larger reductions in social anxiety symptom severity at 15-month follow-up and at a trend-level (P = 0.09) at post-treatment. Right amygdala reactivity to emotional faces also decreased more in the escitalopram+ICBT combination relative to placebo+ICBT, and in treatment responders relative to non-responders. CONCLUSIONS: Adding escitalopram improves the outcome of ICBT for SAD and decreased amygdala reactivity is important for anxiolytic treatment response.

The effect of combined hormonal contraceptives use on brain reactivity during response inhibition.

OBJECTIVES: Cognitive control, which can be described as the ability to moderate impulses, has not previously been investigated in users of combined hormonal contraception (CHC). Given the suggested modulatory role of ovarian steroids in prefrontal dopaminergic function, which in turn taps into cognitive control, this randomised, double-blinded, placebo-controlled oral contraceptive trial set out to investigate the brain activity pattern during response inhibition in CHC users. METHODS: Thirty-four women were randomised to one treatment cycle with a levonorgestrel-containing CHC or placebo. The women performed a Go/NoGo task to measure brain activity during response inhibition by use of event-related functional magnetic resonance imaging (fMRI) prior to and during the CHC/placebo treatment cycle. RESULTS: No differences between CHC and placebo users in number of correct inhibitions were found during treatment, but only women on CHC significantly improved their performance between the baseline and treatment assessments. During the treatment cycle CHC users displayed decreased activity in the right middle frontal gyrus in comparison with placebo users. No other significant activations were evident between treatment groups or within groups. CONCLUSION: Overall, CHC use had marginal effects on brain activity during response inhibition. If anything, the findings of the study may suggest reduced effort or increased efficiency in maintaining orbitofrontal cortex inhibitory cognitive control when using a combined oral contraceptive.

Microsurgical Lymphatic Vessel Transplantation.

BACKGROUND: Lymphedema often arises after a regional interruption during cancer treatment, for example after lymph node resection the axilla or the groin. Lymphatic vessels as vascular grafts may overcome these lymphatic gaps. METHOD: Experiments in rats and dogs were performed for developing this method. Volume measurements, lymphoscintigraphies, proof of patency by MRI and radiology as well as quality of life studies were performed in patients. RESULTS: Long-term follow-up studies revealed significantly reduced volumes, significant improvement of lymphatic outflow shown by lymphoscintigraphy, long-term patency of the grafts for more than 10 years, and improved quality of life after surgery compared with the situation with conservative treatment before surgery. CONCLUSION: Vascular grafts using the patients own lymphatic vessels are able to successfully reconstruct a locally interrupted lymphatic pathway.

Stimulated emission depletion (STED) microscopy reveals nanoscale defects in the developmental trajectory of dendritic spine morphogenesis in a mouse model of fragile X syndrome.

Dendritic spines are basic units of neuronal information processing and their structure is closely reflected in their function. Defects in synaptic development are common in neurodevelopmental disorders, making detailed knowledge of age-dependent changes in spine morphology essential for understanding disease mechanisms. However, little is known about the functionally important fine-morphological structures, such as spine necks, due to the limited spatial resolution of conventional light microscopy. Using stimulated emission depletion microscopy (STED), we examined spine morphology at the nanoscale during normal development in mice, and tested the hypothesis that it is impaired in a mouse model of fragile X syndrome (FXS). In contrast to common belief, we find that, in normal development, spine heads become smaller, while their necks become wider and shorter, indicating that synapse compartmentalization decreases substantially with age. In the mouse model of FXS, this developmental trajectory is largely intact, with only subtle differences that are dependent on age and brain region. Together, our findings challenge current dogmas of both normal spine development as well as spine dysgenesis in FXS, highlighting the importance of super-resolution imaging approaches for elucidating structure-function relationships of dendritic spines.

Correction of asymmetric pectus excavatum using a virtually designed silicone implant.

BACKGROUND: An extended asymmetric funnel chest deformity with the breast gland located in the thoracic mold can lead to a fictitious aplasia of the breast. The authors termed this condition "pseudo-Amazon syndrome" because the breast tissue and the pectoralis muscle are fully developed. METHODS: This report presents a detailed technical approach to the fabrication of a precise-fitting custom-made silicone implant. The design of the implant was achieved using a computed tomography (CT) data set and rapid prototyping. The volumes of the "hidden" and the normal breasts measured preoperatively by processing the CT data were similar. These volumes were compared with the breast volumes measured by three-dimensional photography 4 years postoperatively to assess the predictability of the volume congruency. The silicone implant was surgically placed in the epicostal plane and extended almost over the right hemithorax. RESULTS: The implantation was performed without the necessity of further trimming. Both the surgeon and the patient rated the aesthetic and functional long-term result as good in terms of symmetry and the possibility of exercise without restrictions. The final breast volume of the surgically treated side was 95 % of the volume of the normal contralateral breast. CONCLUSION: The described method reduces the operation time and the operative trauma by primary implant fit. However, the method is rather elaborate and the production process is expensive. This in turn reduces the generation of proceeds to a minimum. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A Psychometric Evaluation of the Expanded Version of the Inventory of Depression and Anxiety Symptoms (IDAS-II) in Children and Adolescents.

The expanded version of the Inventory of Depression and Anxiety Symptoms (IDAS-II) is a self-report measure of 18 empirically derived internalizing symptom dimensions. The measure has shown good psychometric properties in adults but has never been evaluated in children and adolescents. A Swedish version of the IDAS-II was administered to 633 children and adolescents (Mage =16.6 [SD = 2.0]) and 203 adults (Mage = 35.4 [SD = 12.1]). The model/data fit of the 18-factor structure was excellent in both samples and measurement invariance across age groups was supported. All scales showed good to excellent internal consistency and psychometric properties replicated in the younger youth sample (< 16 years). Among youth, good convergent validity was established for all scales and divergent validity for most scales. The IDAS-II was better at identifying youth with current mental health problems than an internationally recommended scale of internalizing symptoms. In conclusion, the IDAS-II shows promise as a measure of internalizing symptoms in youth.

Neural correlates of individual differences in multimodal emotion recognition ability.

Studies have reported substantial variability in emotion recognition ability (ERA) - an important social skill - but possible neural underpinnings for such individual differences are not well understood. This functional magnetic resonance imaging (fMRI) study investigated neural responses during emotion recognition in young adults (N = 49) who were selected for inclusion based on their performance (high or low) during previous testing of ERA. Participants were asked to judge brief video recordings in a forced-choice emotion recognition task, wherein stimuli were presented in visual, auditory and multimodal (audiovisual) blocks. Emotion recognition rates during brain scanning confirmed that individuals with high (vs low) ERA received higher accuracy for all presentation blocks. fMRI-analyses focused on key regions of interest (ROIs) involved in the processing of multimodal emotion expressions, based on previous meta-analyses. In neural response to emotional stimuli contrasted with neutral stimuli, individuals with high (vs low) ERA showed higher activation in the following ROIs during the multimodal condition: right middle superior temporal gyrus (mSTG), right posterior superior temporal sulcus (PSTS), and right inferior frontal cortex (IFC). Overall, results suggest that individual variability in ERA may be reflected across several stages of decisional processing, including extraction (mSTG), integration (PSTS) and evaluation (IFC) of emotional information.

Investigating heart rate variability measures during pregnancy as predictors of postpartum depression and anxiety: an exploratory study.

Perinatal affective disorders are common, but standard screening measures reliant on subjective self-reports might not be sufficient to identify pregnant women at-risk for developing postpartum depression and anxiety. Lower heart rate variability (HRV) has been shown to be associated with affective disorders. The current exploratory study aimed to evaluate the predictive utility of late pregnancy HRV measurements of postpartum affective symptoms. A subset of participants from the BASIC study (Uppsala, Sweden) took part in a sub-study at pregnancy week 38 where HRV was measured before and after a mild stressor (n = 122). Outcome measures were 6-week postpartum depression and anxiety symptoms as quantified by the Edinburgh Postnatal Depression Scale (EPDS) and the Beck Anxiety Inventory (BAI). In total, 112 women were included in a depression outcome analysis and 106 women were included in an anxiety outcome analysis. Group comparisons indicated that lower pregnancy HRV was associated with depressive or anxious symptomatology at 6 weeks postpartum. Elastic net logistic regression analyses indicated that HRV indices alone were not predictive of postpartum depression or anxiety outcomes, but HRV indices were selected as predictors in a combined model with background and pregnancy variables. ROC curves for the combined models gave an area under the curve (AUC) of 0.93 for the depression outcome and an AUC of 0.83 for the anxiety outcome. HRV indices predictive of postpartum depression generally differed from those predictive of postpartum anxiety. HRV indices did not significantly improve prediction models comprised of psychological measures only in women with pregnancy depression or anxiety.

Validation of parametric methods for [¹¹C]PE2I positron emission tomography.

OBJECTIVES: The radioligand [(11)C]PE2I is highly selective for dopamine transporter (DAT) and can be used in vivo for investigation of changes in DAT concentration, progression of disease and validation of treatment using positron emission tomography (PET). DAT is an important protein for regulation of central dopamine concentration and DAT deficiency has been associated with several neurodegenerative and neuropsychiatric disorders. Accurate parametric images are a prerequisite for clinical application of [(11)C]PE2I. The purpose of this study was to evaluate different methods for producing [(11)C]PE2I parametric images, showing binding potential (BPND) and relative delivery (R1) at the voxel level, using clinical data as well as simulations. METHODS: Investigations were made in twelve subjects either with social anxiety disorder (n=6) or parkinsonian syndrome (n=6), each receiving an 80 min dynamic PET scan. All subjects underwent a T1-weighted MRI scan which was co-registered to the PET images and used for definition of regions of interest using a probabilistic template (PVElab). Two basis function implementations (receptor parametric mapping: RPM, RPM2) of the simplified reference tissue model (SRTM) and three multilinear reference tissue models (MRTMo, MRTM and MRTM2) were used for computation of parametric BPND and R1 images. In addition, reference Logan and standard uptake value ratio (SUVr) were investigated. Evaluations of BPND and R1 images were performed using linear regression to compare the parametric methods to region-based analyses with SRTM and cerebellar gray matter as reference region. Accuracy and precision of each method were assessed by simulations. RESULTS: Correlation and slope of linear regression between parametric and region-based BPND and R1 values in both striatum and extra-striatal regions were optimal for RPM (R(2)=0.99 for both BPND and R1; slopes 0.99 and 0.98 for BPND and R1, respectively, in striatum). In addition, accuracy and precision were best for RPM and RPM2. CONCLUSION: The basis function methods provided more robust estimations of the parameters compared to the other models and performed best in simulations. RPM, a basis function implementation of SRTM, is the preferred method for voxel level analysis of [(11)C]PE2I PET studies.

Blinding integrity of dorsomedial prefrontal intermittent theta burst stimulation in depression.

Background: The antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) is partly placebo, making blinding integrity important. Blinding of high-frequency rTMS and intermittent theta burst stimulation (iTBS) has been reported as successful at study end. However, blinding integrity at study start is rarely reported. The aim of this study was to investigate blinding integrity during a treatment course of iTBS over the dorsomedial prefrontal cortex (DMPFC) in depression. Methods: Forty-nine patients with depression from a double-blind-designed randomized controlled trial (NCT02905604) were included. Patients received either active or sham iTBS over the DMPFC with a placebo coil. The sham group received iTBS-synchronized transcutaneous electrical nerve stimulation. Results: After one session, 74% of participants were able to correctly guess their treatment allocation. This was above chance level (p = 0.001). The percentage dropped to 64% and 56% after the fifth and last sessions. Belonging to the active group influenced the choice to guess "active" (odds ratio: 11.7, 95% CI 2.5-53.7). A higher treatment intensity of the sham treatment increased the probability to guess "active", but pain did not influence the choice. Conclusions: Blinding integrity in iTBS trials must be investigated at study start to avoid uncontrolled confounding. Better sham methods are needed.

Investigations on the donor limb after harvest of lymphatic vessels for lymphedema surgery.

OBJECTIVE: Microsurgical lymphatic vessel transplantation is one of the well-established therapies for lymphedema. Lymphatic vessels are harvested from a healthy thigh and transplanted into lymphedematous limbs to create a lymphatic bypass. Its benefit on lymphatic drainage has already been proven. However, to the best of our knowledge, the effect on the lymphatic function of the donor site has not yet been studied. Our aim was to evaluate the long-term postoperative lymphatic function in the donor site by clinical and scintigraphic examinations and a patient questionnaire. METHODS: A consecutive series of 25 women (mean age, 57.2 years) who had undergone follow-up after lymph vessel transplantation to treat secondary lymphedema of the arm comprised the study group. Lymphatic vessel function of the donor site was evaluated by circumferential measurements of the limb and, in nine cases, by lymphatic scintigraphy. Additionally, a questionnaire was used to assess the patients' pre- and postoperative complaints for the donor limb and quality of life. Separately, the medical records of 100 patients who had undergone lymphatic harvest and been followed up were reviewed for documented signs of lymphatic function of the donor limb. RESULTS: The lymphatic grafts were harvested from the thigh (left, n = 9; right, n = 16) and transplanted to bridge the region of lymphatic obstruction in the axilla. The mean follow-up period was 4.5 years after surgery. None of the patients had shown significant changes in the circumference of the donor limb or pathologic findings via lymphatic scintigraphy. None of the patients had reported any impairment in the donor leg or showed symptoms of postoperative lymphedema or erysipelas. CONCLUSIONS: Our results have shown that harvesting lymphatic vessels from the thigh for lymphatic vessel transplantation is possible without significant donor site morbidity.

Acute low dose caffeine affects behavior profile and activity, an examination of male rats with high or low anxiety-like behavior.

Anxiety disorders affect up to one third of the population. Caffeine, an adenosine receptor antagonist, is thought to have a dose-dependent effect on anxiety. We recently showed that a high dose of caffeine (50 mg/kg) differentially affected anxiety-like behavior in rats with high or low baseline anxiety-like behavior, replicating findings using relatively high doses in human patient samples. It is not known if low doses of caffeine have similar effects. The elevated plus maze (EPM) was used to categorize male Wistar rats (13 weeks of age) into groups of high or low anxiety-like behavior. Behavior was evaluated using the multivariate concentric square field (MCSF) test and the EPM after a low 10 mg/kg dose of caffeine. Multivariate data analysis demonstrated that caffeine decreased the differences between the high and low anxiety group, whereas the separation remained for the high and low control groups. For the caffeine treated rats, univariate statistics showed an increase in parameters regarding activity in the EPM and duration in the slope of the MCSF. Regarding risk-taking, shelter-seeking, and exploratory behavior, caffeine did not affect the groups differently. In conclusion, these results demonstrate increased activity in the caffeine-treated rats, together with a potentially anxiolytic effect and increased impulsivity that did not differ between the baseline anxiety groups. In contrast to high caffeine doses, a low dose does not generally affect rats with high anxiety at baseline differently than rats with low anxiety-like behavior. Further studies are warranted to fully elucidate the effects of caffeine in anxiety.