Function and biochemistry of the dorsolateral prefrontal cortex during placebo analgesia: how the certainty of prior experiences shapes endogenous pain relief.

Prior experiences, conditioning cues, and expectations of improvement are essential for placebo analgesia expression. The dorsolateral prefrontal cortex is considered a key region for converting these factors into placebo responses. Since dorsolateral prefrontal cortex neuromodulation can attenuate or amplify placebo, we sought to investigate dorsolateral prefrontal cortex biochemistry and function in 38 healthy individuals during placebo analgesia. After conditioning participants to expect pain relief from a placebo "lidocaine" cream, we collected baseline magnetic resonance spectroscopy (1H-MRS) at 7 Tesla over the right dorsolateral prefrontal cortex. Following this, functional magnetic resonance imaging scans were collected during which identical noxious heat stimuli were delivered to the control and placebo-treated forearm sites. There was no significant difference in the concentration of gamma-aminobutyric acid, glutamate, Myo-inositol, or N-acetylaspartate at the level of the right dorsolateral prefrontal cortex between placebo responders and nonresponders. However, we identified a significant inverse relationship between the excitatory neurotransmitter glutamate and pain rating variability during conditioning. Moreover, we found placebo-related activation within the right dorsolateral prefrontal cortex and altered functional magnetic resonance imaging coupling between the dorsolateral prefrontal cortex and the midbrain periaqueductal gray, which also correlated with dorsolateral prefrontal cortex glutamate. These data suggest that the dorsolateral prefrontal cortex formulates stimulus-response relationships during conditioning, which are then translated to altered cortico-brainstem functional relationships and placebo analgesia expression.

A comprehensive guide to MEGA-PRESS for GABA measurement.

The aim of this guideline is to provide a series of evidence-based recommendations that allow those new to using MEGA-PRESS to produce high-quality data for the measurement of GABA levels using edited magnetic resonance spectroscopy with the MEGA-PRESS sequence at 3T. GABA is the main inhibitory neurotransmitter of the central nervous system and has been increasingly studied due to its relevance in many clinical disorders of the central nervous system. MEGA-PRESS is the most widely used method for quantification of GABA at 3T, but is technically challenging and operates at a low signal-to-noise ratio. Therefore, the acquisition of high-quality MRS data relies on avoiding numerous pitfalls and observing important caveats. The guideline was developed by a working party that consisted of experts in MRS and experts in guideline development and implementation, together with key stakeholders. Strictly following a translational framework, we first identified evidence using a systematically conducted scoping literature review, then synthesized and graded the quality of evidence that formed recommendations. These recommendations were then sent to a panel of 21 world leaders in MRS for feedback and approval using a modified-Delphi process across two rounds. The final guideline consists of 23 recommendations across six domains essential for GABA MRS acquisition (Parameters, Practicalities, Data acquisition, Confounders, Quality/reporting, Post-processing). Overall, 78% of recommendations were formed from high-quality evidence, and 91% received agreement from over 80% of the expert panel. These 23 expert-reviewed recommendations and accompanying extended documentation form a readily useable guideline to allow those new to using MEGA-PRESS to design appropriate MEGA-PRESS study protocols and generate high-quality data.

Optimizing VAP scars after childhood cancer treatment: a pilot study.

PURPOSE: Majority of pediatric cancer patients are treated with chemotherapy using Venous Access Ports (VAP). However, after surgical removal of the VAP prominent scars often remain and standard care is lacking. METHODS: Patients (N = 20) who were willing to participate were included prior to surgical removal of their VAP. All patients were off therapy at time of VAP removal. Patients had the option to either choose from Dermatix®, meridian color therapy (MCT), or no additional treatment (NAT). Assessment of scars was done prior to and 3, 6, and 12 months after surgical VAP removal using Patient and Observer Scar Assessment Scales (POSAS) questionnaires. To identify whether Dermatix® or MCT is associated with better scar healing than without additional treatment, Mann-Whitney U tests were used. RESULTS: After 12 months of follow-up, both patients and dermatologists noted VAP scars had healed better after MCT compared to those without treatment (P = 0.010 for both POSAS patient and POSAS observer). No significant differences were observed between VAP scars after Dermatix® use and those with no treatment. CONCLUSIONS: Scar healing after MCT significantly improved, whereas Dermatix® treatment showed no significant differences compared to NAT. To translate this to daily care, a larger prospective study is needed to validate these findings.

Neuroblastoma between 1990 and 2014 in the Netherlands: Increased incidence and improved survival of high-risk neuroblastoma.

PURPOSE: Long-term trends in neuroblastoma incidence and survival in unscreened populations are unknown. We explored trends in incidence, stage at diagnosis, treatment and survival of neuroblastoma in the Netherlands from 1990 to 2014. METHODS: The Netherlands Cancer Registry provided data on all patients aged <18 years diagnosed with a neuroblastoma. Trends in incidence and stage were evaluated by calculating the average annual percentage change (AAPC). Univariate and multivariable survival analyses were performed for stage 4 disease to test whether changes in treatment are associated with survival. RESULTS: Of the 593 newly diagnosed neuroblastoma cases, 45% was <18 months of age at diagnosis and 52% had stage 4 disease. The age-standardized incidence rate for stage 4 disease increased at all ages from 3.2 to 5.3 per million children per year (AAPC + 2.9%, p < .01). This increase was solely for patients ≥18 months old (3.0-5.4; AAPC +3.3%, p = .01). Five-year OS of all patients increased from 44 ± 5% to 61 ± 4% from 1990 to 2014 (p < .01) and from 19 ± 6% to 44 ± 6% (p < .01) for patients with stage 4 disease. Multivariable analysis revealed that high-dose chemotherapy followed by autologous stem cell rescue and anti-GD2-based immunotherapy were associated with this survival increase (HR 0.46, p < .01 and HR 0.37, p < .01, respectively). CONCLUSION: Incidence of stage 4 neuroblastoma increased exclusively in patients aged ≥18 months since 1990, whereas the incidence of other stages remained stable. The 5-year OS of stage 4 patients improved, mostly due to the introduction of high-dose chemotherapy followed by stem cell rescue and immunotherapy.

Thoracolumbar spinal fixation for camptocormia in Parkinson's disease.

A man with early non-fluctuating Parkinson's disease developed disabling camptocormia. The patient was treated with posterior thoracolumbar fixation, which subsequently had to be augmented with anterior interbody fusion. Although the patient ultimately achieved excellent sagittal correction, his postoperative course was complicated and prolonged. Therefore, although this case demonstrates that spinal fixation surgery can be successful, it should probably only be offered after subthalamic nucleus deep brain stimulation has been unsuccessful, or for well motivated patients who express a strong wish for this major reconstructive surgery.

[Experience with the s-GAP flap for autologous breast reconstruction]. / Der Stellenwert der s-GAP-Lappenplastik in der Brustrekonstruktion - Ein Erfahrungsbericht.

In breast reconstruction with autologous tissue the DIEP flap has become the gold standard in recent years. The superior gluteal artery perforator (s-GAP) flap is an alternative harvested from the buttock. We present our experience with the s-GAP flap and discuss its role in breast reconstruction. All s-GAP flaps performed for breast reconstruction in the Department of Plastic and Hand Surgery, Behandlungszentrum Vogtareuth from June 2002 until February 2007 were retrospectively analysed. Out of 59 flaps 4 flaps failed, the success rate was 94 %. Partial or fat necrosis occurred in 2 cases. The s-GAP flap served as a safe reconstructive alternative to the DIEP flap. Advantages of the s-GAP flap are reliable perforators, the safe vascular supply and the firm fat structure which facilitates the breast reconstruction. The donor site morbidity is minimal, the gluteal muscles stay intact and the scar is easy to hide in the underwear. Disadvantages are a demanding preparation with a prolonged operating time compared to the DIEP flap. The s-GAP flap is a reliable and safe option for autologeous breast reconstruction. It is the method of choice for staged bilateral breast reconstruction or if the DIEP flap is not available, particularly in the thin patient.

[Free axillary flaps: a versatile area for harvesting of plicable flaps with a nearly undetectable scar]. / Freie, mikrovaskuläre axilläre Lappenplastiken - vielseitig verwendbar, gut formbar und narbenarmer Hebedefekt.

BACKGROUND: This article is about 7 cases of free axillary flaps based on the lateral thoracic vessels. PATIENTS AND METHODS: Preoperative ultrasound markings were performed. Indications were defects which needed very smooth and plicable flaps for coverage with a short and well detectable scar. RESULTS: Flap loss was not noticed, dissection was demanding due to the very small venous drainage of the flaps and took all over 6.5 hours. A comparison with standard flaps of the subscapular vascular system is given. CONCLUSIONS: The authors recommend the free axillary flap based on the lateral thoracic vessels as a versatile flap for special indications.

Does long-term chloramphenicol cause anaemia in Malawi?

Common clinical practice in many tropical paediatric departments is that chloramphenicol courses are limited to 2 weeks due to concerns about anaemia. However, this approach is not supported by current research and animal models. We used chloramphenicol for 6 weeks in 146 children with septic arthritis. All the children improved clinically. Most children were anaemic on presentation (mean haemoglobin [Hb] 8.43 SD 1.9), but the anaemia improved rapidly with clinical resolution of the infection and was maintained at 6 months after presentation (mean Hb 10.57 SD 1.86).

Isolation and characterization of Thermococcus barossii, sp. nov., a hyperthermophilic archaeon isolated from a hydrothermal vent flange formation.

A new hyperthermophilic microorganism, Thermococcus barossii, was isolated from rock fragments of a hydrothermal vent flange formation, located along the East Pacific Rise of the Juan de Fuca Ridge. This organism is obligately anaerobic and grows over a temperature range of at least 60-92 degrees C in artificial seawater-based media, containing elemental sulfur, tryptone and yeast extract. The addition of a maltooligosaccharide mixture and tungsten to this medium improved growth to some extent. At the Topt for growth (82.5 degrees C), cell densities as high as 4 x 10(8) cells/ml could be obtained in 18-liter batch fermentations, with a doubling time of approximately 40 minutes, if culture access to elemental sulfur was sufficient. In continuous culture at the same temperature, comparable cell densities could be obtained but only at slower growth rates. Morphologically, T. barossii is coccoid-shaped, forming irregularly-shaped spheres; under optimal conditions, these coccoids become more regular and smaller, a characteristic of other hyperthermophilic archaea. Negatively-stained preparations showed no pili or flagella associated with the cell surface. 16S rRNA sequencing reveals that T. barossii is most similar to Thermococcus celer (99.7%). Yet, further comparisons with T. celer showed that T. barossii is a new Thermococcus species: different growth temperature optimum (82.5 degrees C vs. 88 degrees C), obligate requirement for sulfur, higher G + C content (60% vs. 56.7%) and 47.7% DNA-DNA hybridization. The nucleotide and translated amino acid sequence for the gene encoding a DNA polymerase from T. barossii was compared to sequences of related genes from other Thermacoccales. The polymerase phylogenies were congruent with those obtained from the 16S rRNA phylogenetic analyses. Based on the high degree of similarity among members of the genus Termococcus for the criteria used thus far, aspects of enzymology may be an important mechanism of differenting one species from another.

Inhibition of nitric oxide synthesis attenuates alcohol consumption in two strains of alcohol-preferring rats.

The effect of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on voluntary alcohol consumption was examined in two different strains of alcohol-preferring rats, in a continuous-access, two-bottle-choice paradigm. Compared with the vehicle, intraperitoneal injections of L-NAME significantly and dose-dependently (10, 30, and 60 mg/kg) suppressed alcohol intake and preference in both alcohol-preferring (P) and Fawn-Hooded (FH) rats. The effect of the highest dose of L-NAME was nonspecific; it caused general decreases in consumption of alcohol, water, and food. Repeated injection of L-NAME (30 mg/kg) for 4 consecutive days significantly attenuated alcohol intake, but tolerance developed after 3 days of treatment. A single administration of a high dose of L-NAME (60 mg/kg) did not influence the blood alcohol concentrations, which suggests a possible central effect. Furthermore, a moderate dose of 30 mg/kg L-NAME, which selectively inhibited alcohol intake, did not exert a significant effect on telemetrically measured heart rate, core body temperature, and gross motor activity of alcohol naive Fawn-Hooded rats. These results suggest an involvement of nitric oxide in alcohol drinking behavior. Although the true mechanism(s) of action is not yet clear, it can be speculated that L-NAME may exert its action indirectly by modulating neurotransmitters proposed to be involved in alcohol drinking and/or by influencing other neuronal factors, such as neuronal Ca2+ channels, which have been shown to be involved in alcohol drinking behavior.

[The free gracilis perforator flap for autologous breast reconstruction]. / Der freie Grazilis-Perforator-Lappen zur autologen Brustrekonstruktion.

The free gracilis perforator flap is an alternative possibility for autologous breast reconstruction, if previous abdominal operations preclude this donor site, or if there is atypical distribution of fat tissue. The perforator flap is based on the main pedicle of the gracilis muscle. The muscle itself and its innervation can be completely preserved, if the angiosome of this vascular pedicle offers sufficient tissue. In skinny patients however it may be necessary to include the neighbouring angiosome of the second gracilis pedicle by means of the intramuscular anastomosis between both pedicles. In such a case a thin muscle strip with the joining vessel must be included in the flap. The bulk of the gracilis muscle and its motor nerve can, however, still be preserved. Breast reconstruction with this technique was successfully performed on six patients (two bilateral). It is a good alternative to a reconstruction with gluteal, or anteromedial, or lateral thigh perforator flaps.

[Myosonographic evaluation of rectus abdominis muscle function after DIEP flap breast reconstruction]. / Myosonographische Funktionsprüfung des M. rectus abdominis nach DIEP-Lappenplastik zur autologen Brustrekonstruktion.

Donor-site morbidity following autologous breast reconstruction is a well-known disadvantage of free or pedicled TRAM flaps. Bulging and weakness of the abdominal wall and sometimes even hernias occur. Due to recent technical advances in microsurgery, there are different possibilities for breast reconstruction like the deep inferior epigastric perforator (DIEP) flap which is harvested without rectus muscle. First studies describe good aesthetic results without the complication of hernias and disadvantage of abdominal wall weakness. Myosonography is a new method to test the dynamic rectus muscle function and evaluate the donor-site morbidity after DIEP flap breast reconstruction. This study aims to analyze the value of myosonographic measurements to evaluate the donor-site morbidity following perforator flap elevation of the abdominal wall. Between November 2000 and August 2001, 34 patients at the Markus Hospital in Frankfurt/Main, Germany received breast reconstruction with a DIEP flap. Myosonographic examinations pre- and postoperatively were performed. Furthermore, clinical testing of rectus muscle function with the Janda score in combination with a questionnaire about impairment in daily activities and subjective opinion about discomfort took place. Two months postoperatively, myosonography showed almost identical rectus muscle function at the side of the vessel preparation compared to the contralateral side. Good aesthetic results were also achieved. The absolute muscle thickness at maximum contraction and the difference of muscle thickness between relaxation and contraction were almost identical on both sides. Myosonography is a non-invasive and inexpensive method to test rectus muscle function providing exact and reliable data. Results of this study confirm the hypothesis of lower donor-site morbidity caused by DIEP flaps compared to free or pedicled TRAM flaps. The DIEP flap method for autologous breast reconstruction is highly accepted by patients because of good aesthetic results combined with the lowest possible donor-site morbidity. After more than 180 DIEP flaps with good aesthetic results without abdominal wall hernias this method has become the "gold standard" for autologous breast reconstruction in our department.

[Anatomy of the dorsal mid-hand arteries--anatomic study and review of the literature]. / Anatomie der dorsalen Mittelhandarterien--Anatomische Untersuchung und Literaturübersicht.

By dissections of 20 cold-preserved hands, we investigated the dorsal metacarpal arteries (DMA) with regard to reliability, origin and anastomoses. The first dorsal metacarpal artery showed a trifurcation with three vessels: Ramus ulnaris (A. metacarpalis dorsalis I), Ramus medialis and Ramus radialis (A. ulnodorsalis pollicis). The DMA II to IV were observed medially in their respective intermetacarpal spaces. The A. metacarpalis dorsalis V was unreliable in reaching the skin of dorsal proximal phalanges as in the DMA IV. Most reliable for reaching the skin of dorsal proximal phalanges were the radial arteries--first, second and third dorsal metacarpal arteries. The dorsal digital arteries originate close to one another at the level of the metacarpophalangeal joints. There was an increase of epifascial position, from radial to ulnar. Irregular palmar intermetacarpal anastomoses were found proximal to the ligamentum metacarpale transversum profundum but nearly consistently in the web space.

Syndesmosis screws: how many, what diameter, where and should they be removed? A literature review.

Although screw fixation remains the most commonly used method of syndesmosis fixation, the ideal screw size, placement, and number remain controversial. In addition, there has been debate as to whether the screw should always be removed, and a number of studies have looked at radiological and functional outcomes. In addition a number of cadaveric models have been developed, but the correlation between cadaveric findings and functional outcomes remains unclear. This systematic review of the literature aims to summarise the available evidence on how many screws should be placed, of what diameter, through how many cortices, at what level, and whether they should be removed.

[A neonate with the 'blueberry muffin syndrome']. / Een neonaat met het 'blueberry muffin' syndroom.

A term born girl showed livid papules and macules disseminated over her body, directly postpartum. She was examined by the pediatrician, who recognized this as the 'blueberry muffin syndrome'. Blood examination showed a modest increase of erythroblasts. Skin biopsy indicated the presence of hematologic malignancy. Bone marrow puncture revealed the diagnosis 'acute myeloid leukemia'. Other causes of the blueberry muffin syndrome are congenital infections, neuroblastoma and rhabdomyosarcoma.

Patella fracture in a boy with bilateral inferior pole bipartite patellae.

We present the case of a 12 year old boy who had bilateral inferior pole fragment (Saupe type 1) bipartite patellae, and who sustained a traumatic separation through the right patella while playing basket ball, the left remaining asymptomatic. We have reviewed and discussed the previously published literature and case reports.

How useful is templating for total knee replacement component sizing?

This study aims to assess the accuracy of digital templating at our institution, by comparing the templated component sizes with those implanted, and to determine whether templating the preoperative films had any measurable difference on the radiographic outcome, and if, where there was a mismatch between the implanted and templated sizes, the templated size would have been preferable. While a number of studies have evaluated the accuracy of both acetate and digital templating, none has to our knowledge looked back at post-operative radiographs and reviewed these in light of the templated and implanted sizes. Data was collected from 90 PFC Sigma (DePuy, UK) total knee replacements done sequentially, 45 of whom were templated digitally using a calibrating ball and Agfa Orthopaedic Tools software. Postoperative radiographs were graded independently for correct sizing. All templates were within one size of the implanted prosthesis. The femoral component appeared to be more often oversized on the postoperative radiographs in the non-templated group. In addition, most tibial trays that were found be too small had been templated to a larger size. There was a trend towards tibial trays templated too large to have been templated to a smaller size. We conclude that digital templating with a calibrating device is a useful part of preoperative planning for total knee arthroplasty.

White-out from a Wii: traumatic haemothorax sustained playing Nintendo Wii.

A case is reported of a patient who sustained a significant haemothorax while playing with a Nintendo Wii console.

Increased potency and longevity of gene silencing using validated Dicer substrates.

Chemically synthesized small interfering RNAs (siRNAs) are tools used for silencing the expression of a single gene. They are mainly employed in basic research applications, but may also have great potential in therapeutic applications. Longer double-stranded RNAs, such as Dicer-substrate 27mers, trigger gene silencing through the intrinsic RNAi pathway. The design of these Dicer-substrate 27mers has been optimized so they can be oriented by Dicer to consistently select the antisense (guide) strand after cleavage to shorter siRNAs, leading to predictable mRNA cleavage. In this paper we describe evidence that these Dicer-substrate 27mers produce more potent and sustained gene silencing for four genes when compared with synthetic 21mers that have the same guide-strand sequence. Furthermore, improved silencing by these 27mers is often more pronounced at lower concentrations.