Age-associated alterations of brain mitochondria energetics.

The study aimed to explore the role of age-associated elevated cytosolic Ca2+ in changes of brain mitochondria energetic processes. Two groups of rats, young adults (4 months) and advanced old (24 months), were evaluated for potential alterations of mitochondrial parameters, the oxidative phosphorylation (OxPhos), membrane potential, calcium retention capacity, activity of glutamate/aspartate carrier (aralar), and ROS formation. We demonstrated that the brain mitochondria of older animals have a lower resistance to Ca2+ stress with resulting consequences. The suppressed complex I OxPhos and decreased membrane potential were accompanied by reduction of the Ca2+ threshold required for induction of mPTP. The Ca2+ binding sites of mitochondrial aralar mediated a lower activity of old brain mitochondria. The altered interaction between aralar and mPTP may underlie mitochondrial dysregulation leading to energetic depression during aging. At the advanced stages of aging, the declined metabolism is accompanied by the diminished oxidative background.

Magnetic resonance imaging validation of medial transthyroid ultrasound-guided stellate ganglion block: A pilot study.

OBJECTIVE: Ultrasound-guided stellate ganglion block (usSGB) facilitates improved accuracy of needle position and application of lesser volumes of local anesthetic (LA). Approaches of usSGB, however, have not fully been optimized with respect to efficacy and technical convenience. This pilot study examined the anatomical position and spatial distribution of a small volume of LA injectate dispensed by medial transthyroid usSGB via magnetic resonance imaging (MRI) and assessment of its effect on cervical sympathetic nerves. METHODS: Twelve healthy males were tested in a double-blinded within-subject design. In a total of 37 usSGB, 3 ml of LA and saline 0.9% solution were injected intramuscularly into the longus colli muscle (LCM) preventing uncontrollable spread of LA within cervical structures. Immediately after injection, distribution of injectate was traced by MRI. Twenty-four out of the 37 usSGB-injections with 3 ml ropivacaine 1% (verum) and saline 0.9% (placebo) were compared. Efficacy of usSGB was assessed by the appearance of oculosympathetic paresis and increases in skin temperature. RESULTS: All usSGBs were positioned in the proximity of the LCM muscle belly. Most of the axial injectate was distributed within the transversal plane between the middle section of C5 and the upper section of T1 vertebra. Signs of oculosympathetic paresis and skin temperature increase were found exclusively under verum conditions. CONCLUSION: This pilot study demonstrated the feasibility of medial transthyroid usSGB using an out-of-plane technique and a volume of 3 ml of LA. Further studies are required to establish the relative value and safety of this technique compared to other published approaches.

Ethical Pain and Terminal Chaperonage.

Terminal chaperonage embedded in palliative care deeply resonates with human needs and has undergone significant advances in the past decades. At the same time, it is in jeopardy due to austerity measures in healthcare. Its comprehensive translation in philanthropic end-of-life practice necessitates reflection on underlying ethical issues. This chapter addresses ethical aspects arising in pain and terminal chaperonage and deduces important ethical imperatives in the wake of the palliative mandate. The imperatives affect the deployment of resources necessary for a humane pain and terminal chaperonage, one that is to be comprehensive and flexible in design and implementation at the same time. Furthermore, they are concerned with critical implications for dying clients emerging from the idiosyncratic properties of opioids with respect to their potential to induce mental status alterations. Given that living and dying are profoundly mental by nature, the human mind plays a fundamental role in the command of both. Based on this, this chapter also outlines the essentials of terminal thought plasticity and affect catharsis en route to a mindful, decent death. It identifies and advocates eight most fundamental affective, respectively cognitive fields of the human mind, the "Ensemble of the essential eight iridescent fields of relinquishment", whose adaptable, culturally sensitive facilitation in mental management prior to death may have to be considered the core ethical imperative in terminal chaperonage - in true congruence with philanthropic end-of-life care.

Effectiveness, Safety, and Predictive Potential in Ultrasound-Guided Stellate Ganglion Blockades for the Treatment of Sympathetically Maintained Pain.

BACKGROUND: Evaluating the effectiveness of stellate ganglion blockades (SGBs) proves challenging, since the criteria defining a successful blockade are controversial. This may be one reason for the scarcity of studies on this topic, thus forcing clinical guidelines to remain conservative in recommending SGBs. Moreover, factors to predict which patients will benefit from blockade series are not yet available. OBJECTIVES: The objectives of this study were to evaluate through a clinical approach SGBs' effectiveness performed under ultrasound guidance (us-SGB) and to identify factors to predict effectiveness. METHODS: We retrospectively analyzed 809 us-SGBs in 105 patients with complex regional pain syndrome (CRPS) and neuropathic pain syndromes (all potentially including sympathetically maintained pain) regarding pain reduction. Volume and type of local anesthetics, magnitude of pain, temperature of the dorsal hands, heart rate, blood pressure, and occurrence of Horner's syndrome or complications were assessed. RESULTS: Pain reduction after a blockade series was highly significant and showed no significant correlation with change of temperature, vital signs, or Horner's syndrome. For patients with neuropathic pain, the predictive potential for pain reduction following a blockade series lies within the range of pain reduction after the first blockade. In a literature comparison, incidences of complications (hoarseness 3.9%, dysphagia 3.4%, hematoma 0.6%) were lower than in non-ultrasound-guided techniques. CONCLUSIONS: Data indicate that us-SGBs are safe and effective in reducing sympathetically maintained pain in patients with CRPS and neuropathic pain syndromes. Pain reduction after the first blockade may predict total pain reduction after a blockade series. Other clinical measures seem unsuitable to predict effectiveness.

Patient survey on Invisalign® treatment comparing [corrected] the SmartTrack® material to the previously used [corrected] aligner material.

OBJECTIVES: In 2013, a novel material SmartTrack® was introduced to replace the previous material used for Invisalign® aligners. We conducted this study to test how this transition was accepted by patients during ongoing Invisalign® treatment. METHODS: We surveyed a total of 72 patients (68 % women, 32 % men, mean age: 29.3 ± 9.2 years) who had worn the new material for a mean of 6 months. They completed a questionnaire with 25 items that compared both materials in terms of pain, pressure upon insertion, comfort, mucosal irritation, phonetics, discoloration, and taste. RESULTS: On a numerical rating scale (NRS) ranging from 0 to 10, the new aligner material was rated by the respondents to cause significantly (p < 0.001) less maximum pain than the old material (2.8 vs. 3.8). Significant reductions were obtained for duration of pain (p < 0.001) and duration of pressure (2.5 vs. 1.9 days; p = 0.001) upon insertion of the aligners. Over 90 % of the respondents indicated less or equal pain during eating, felt that the new material offered a tighter fit, and provided more favorable ratings for impairment, durability, and discoloration. Improved comfort was reported by 50 % of the respondents. CONCLUSIONS: The new material was favorably rated by the patients and showed significant reductions in pain intensity, pain duration, and pressure upon insertion. Important clinical parameters like overall comfort and impairment also were improved. The clinical effectiveness of the new material remains to be investigated.

Body-Related Emotions in Posttraumatic Stress Disorder Following Childhood Sexual Abuse.

Traumatic experiences are associated with emotions such as anxiety, shame, guilt, disgust, and anger. For patients who have experienced child sexual abuse, these emotions might be triggered by perceptions of their own body. The aim of this study was to investigate the extent of the association of the body to traumatic experiences and to discern the emotions linked to trauma-associated body areas. Ninety-seven female participants were assigned to four groups: post-traumatic stress disorder following child sexual abuse with co-occurring borderline personality disorder, post-traumatic stress disorder following child sexual abuse without co-occurring borderline personality disorder, borderline personality disorder without post-traumatic stress disorder, and healthy controls. Participants rated 26 body areas regarding their association with trauma and 7 emotions. Emotions were assessed by questionnaires. Results suggest that specific areas of the body are associated with trauma and linked to highly aversive emotions. In post-traumatic stress disorder patients, the areas associated with highly negative emotions were the pubic region and inner thighs. Thus, the patient's body may act as a trigger for traumatic memories.

No evidence for differential dose effects of hydrocortisone on intrusive memories in female patients with complex post-traumatic stress disorder--a randomized, double-blind, placebo-controlled, crossover study.

BACKGROUND: Post-traumatic stress disorder is characterized by intrusive traumatic memories. Presently, a controversial debate is ongoing regarding whether reduced cortisol secretion in post-traumatic stress disorder promotes an automatic retrieval of trauma-associated memories. Hence, a pharmacological elevation of cortisol was proposed to decrease post-traumatic stress disorder symptoms, particularly intrusions. The present study investigated the impact of two different doses of hydrocortisone on automatic memory retrieval using a randomized, double-blind, placebo-controlled, crossover study in 30 inpatients with post-traumatic stress disorder. METHODS: All participants were female and received various psychotropic medications. They were randomly assigned to one of two groups within a crossover design: they received either 1 week placebo followed by 1 week hydrocortisone 10/d, followed by 1 week placebo, followed by hydrocortisone 30 mg/d (15 participants) or 1 week hydrocortisone 30 mg/d, followed by 1 week placebo, followed by 1 week hydrocortisone 10 mg/d, followed by 1 week placebo (15 participants). The outcome measures were the frequency and the intensity of intrusions, the overall symptomatology of post-traumatic stress disorder and the general psychopathology. RESULTS: We did not find any differences in the frequency and the intensity of post-traumatic stress disorder-related intrusions between the 10 mg hydrocortisone, the 30 mg hydrocortisone and the placebo condition. All effect sizes for the hydrocortisone condition vs. placebo were very small. Additionally, the overall symptomatology of post-traumatic stress disorder and the general psychopathology did not differ between the hydrocortisone therapies and placebo. CONCLUSIONS: Our results do not show any effect of the hydrocortisone administration on intrusions in complex post-traumatic stress disorder.

Ultrasound-guided stellate ganglion blocks combined with pharmacological and occupational therapy in Complex Regional Pain Syndrome (CRPS): a pilot case series ad interim.

OBJECTIVE: This preliminary and retrospective pilot case series examines a treatment concept consisting of ultrasound-guided stellate ganglion blocks (SGBs) combined with pharmacological and occupational therapy in patients with complex regional pain syndrome (CRPS) of the hand. Efficacy of combined treatment concepts and safety of ultrasound-guided SGB have not been sufficiently investigated yet. METHODS: A total number of 156 blocks were evaluated in 16 patients with CRPS in a retrospective analysis. All patients received pharmacotherapy and a standard regimen of occupational therapy offered simultaneously to the SGBs. Changes in both spontaneous and evoked pain levels were assessed by numerical pain rating score before and after the last blockade of a series. Side effects were documented. RESULTS: The overall mean pain reduction was 63.2% regarding spontaneous and 45.3% regarding evoked pain. Mild complications, such as hoarseness or dysphagia, occurred in 13.5% of the blocks (21 SGBs). Serious complications, such as plexus paresis or accidental puncture of vessels or other structures, did not occur. Time between symptom onset and start of treatment did not affect the extent of pain reduction. CONCLUSIONS: The combination of ultrasound-guided SGB and simultaneous pharmacological and occupational therapy showed encouraging treatment results under conditions of this pilot case series. Assessment of efficacy of this combined treatment concept and safety of ultrasound-guided SGB require further prospective clinical studies with larger number of participants.

Improvements in health-related quality of life by comprehensive cancer pain therapy: a pilot study with breast cancer outpatients under palliative chemotherapy.

BACKGROUND: Cancer-related pain is highly prevalent among outpatients with metastatic breast cancer affecting their health-related quality of life (HRQoL). This study evaluates potential effects of comprehensive pharmacologic cancer pain therapy (CPT) on HRQoL. PATIENTS AND METHODS: 52 outpatients with metastatic breast cancer undergoing palliative chemotherapy participated. 28 patients suffering from moderate to severe cancer pain were offered CPT. 13 patients participated (intervention group), and 15 declined participation (control group). HRQoL was assessed with the Quality of Life Questionnaire (EORTC QLQ-C30) and the breast module QLQ-BR23 at baseline and after 3 weeks. RESULTS: At baseline, 83% of the patients experienced cancer-related pain, of whom 35% were not prescribed any pain medication. HRQoL of all patients was reduced compared to reference scores. After CPT, the intervention group reported significantly alleviated pain and improvement in several HRQoL subscales (Global QoL, Emotional Functioning, Physical Functioning, Future Perspective, Sleeplessness). The control group did not change significantly. CONCLUSION: This study emphasizes the demand for sufficient pain management in palliative breast cancer outpatients. The combination of CPT as a guidance for the pharmacological aspects of cancer pain management and the EORTC QLQ-C30 as an assessment and surveillance tool appears to be a method that warrants further research.

Body image disturbance in patients with borderline personality disorder: impact of eating disorders and perceived childhood sexual abuse.

Body image disturbances occur in women with borderline personality disorder (BPD). Systematic research on these characteristics in well-defined BPD groups is lacking. It is unknown, if the disturbances are related to eating disorders and childhood sexual abuse (CSA), which frequently co-occur in patients with BPD. In the present study, cognitive-affective and behavioral components of body image for 89 female patients with BPD (49 with lifetime eating disorders) and 41 healthy participants were assessed via Body Image Avoidance Questionnaire (BIAQ) and Multidimensional Body-Self Relations Questionnaire (MBSRQ). Within the BPD group, 43 patients reported a history of CSA. Compared to healthy controls, BPD patients reported significantly more negative scores in the BIAQ and the MBSRQ. Both a history of CSA and a comorbid eating disorder were independently associated with an even more negative body image. Results suggest a disturbance of cognitive-affective and behavioral components of body image in female BPD patients.

Body image in patients with posttraumatic stress disorder after childhood sexual abuse and co-occurring eating disorder.

BACKGROUND: Body image is a multidimensional construct with cognitive-affective, behavioral and perceptive components. Survivors of childhood sexual abuse report a disturbance of the cognitive-affective component of their body image but not of the perceptive component. It has not yet been examined whether and how the behavioral component is affected. Also, it is still unknown whether the disturbances might be due to the influence of co-occurring eating disorders. SAMPLING AND METHODS: The cognitive-affective and behavioral components of the body image of 84 female participants with posttraumatic stress disorder (PTSD) after childhood sexual abuse (31 with a co-occurring eating disorder) and 53 healthy participants were assessed via the Dresden Body Image Inventory (Dresdner Körperbildfragebogen-35, DKB-35) and the Body Image Avoidance Questionnaire (BIAQ). RESULTS: PTSD patients reported significantly higher negative scores on all DKB-35 subscales (p < 0.001) and the BIAQ (p = 0.002; p < 0.001). Results remained consistent after accounting for the influence of co-occurring eating disorders (p = 0.021; p = 0.001; p < 0.001). CONCLUSIONS: Results show for the first time that the behavioral component of the body image is impaired in female patients with PTSD in addition to the cognitive-affective component. This is not solely due to a comorbid eating disorder. The effect of established treatments on the body image of PTSD patients should be evaluated and new treatment modules should be developed and tested, if necessary.

[Dialectical Behavior Therapy (DBT) in a patient with factitious disorder: therapist's and patient's perspective]. / Dialektisch-Behaviorale Therapie (DBT) bei einer Patientin mit artifizieller Störung - Behandler- und Patientenperspektive.

OBJECTIVE: Presentation of the disorder model and inpatient psychotherapy of a patient with factitious disorder as seen from the therapist's and patient's perspective. METHOD: Case report including the patient's own notations. RESULTS: The description of her motives by the patient facilitated a concise planning of therapy and its successful progression. CONCLUSIONS: The factitious disorder is based on learning experiences and is maintained, among other things, by the care of the medical personnel. Principles and interventions of DBT could successfully be employed.

Proteome and metabolome alterations in heart and liver indicate compromised energy production during sepsis.

During the course of sepsis, heart and liver dysfunction occurs in 20-30 % of patients. Both septic cardiomyopathy and septic liver dysfunction have a high mortality and the underlying molecular pathophysiology remains unclear. The present study investigated changes in both cardiac and liver protein expression after cecal ligature and puncture (CLP) in a model of rat sepsis during a post-induction time course of 12, 24, and 48 hours. After approval by the local institutional review board, 62 male Wistar rats were investigated and assigned to three sham groups (n=16) and three sepsis groups (n=46). Rats of the sepsis groups and control groups were analyzed at specific time points after sepsis induction. Sepsis was induced by CLP and both heart and liver were removed after decapitation and prepared for proteomics. 2D-gel electrophoresis (2D-GE) and mass spectrometry (MS) as well as bioinformatic network pathway analysis (Ingenuity Pathways Analysis, IPA) were used to identify changes in protein expression between septic and non-septic samples. N=27 rats of the sepsis group died (mortality 59 %) and no rat of the sham group died. More than 1,100 proteins could be discriminated with the proteomic method in both organs, of which 12 and 13 proteins were significantly regulated in heart and liver, respectively. 82 % of the cardiac proteins could be associated with mitochondrial function. Both heart and liver proteins were primarily down-regulated in the course of sepsis. IPA associated the sets of differentially regulated proteins with proteins of heart and liver with compromised energy production. Sepsis induced significant alterations in the cardiac and liver proteome at 12, 24, and 48 hours after sepsis induction. Differentially regulated proteins of both organs mainly play a role in energy production. The diverse protein regulation indicates metabolic derangement and severely compromised cellular energy production following sepsis. Here, protein alterations may reflect septic organ dysfunction.

Isoflurane anesthesia elicits protein pattern changes in rat hippocampus.

Postoperative cognitive dysfunction (POCD) is a known phenomenon occurring after anesthesia with volatile anesthetics (VA), such as isoflurane. Recent reports suggest that VA interact with neurodegenerative disease-associated proteins including compounds with pathogenic relevance in Alzheimer disease (AD) and induce processes that may be linked to AD neuropathology. Unfortunately, our present understanding of the exact anesthetics' molecular mechanisms of action, their side effects on the brain, and their catenation with AD pathology is still limited. The present study analyzes the differential proteome of the hippocampus immediately after and 3 days after a 3-hour 1 minimal alveolar concentration isoflurane anesthesia in rats. Differential 2-dimensional electrophoresis, mass spectrometry, and functional network mapping were used to identify and functionally classify 12 different hippocampal proteins, which were significantly regulated after isoflurane anesthesia (6 up-regulated, 11 down-regulated with P<0.01). Induction of differential expression ranged from 0.05 (25-fold down-regulation) to 4.4 (4.4-fold up-regulation). Ten proteins were regulated immediately after and 7 proteins 3 days after isoflurane exposure. The proteome displays isoflurane-responsive protein candidates, which have also been shown to play a role in AD. They were grouped according to their key biologic activities, which showed that isoflurane affects selected biologic processes including synaptic plasticity, stress response, detoxification, and cytoskeleton in early and late recovery phases after anesthesia. These processes are also affected in AD. Results are discussed in view of AD, the toxicity mechanisms of isoflurane as well as the implications for our present understanding and conduction of clinical anesthesia.

Time-dependent alterations of cerebral proteins following short-term normobaric hyperoxia.

Sufficient oxygenation is indispensable for cognitive performance in mammals. In order to assure adequate oxygenation and to prevent hypoxia in medicine or aviation, different approaches of oxygen delivery are realized. With regard to hyperoxia, it is well known that it increases the risk of tissue toxicity and inflammation by generating radical oxygen species. However, this impact of hyperoxia on the expression of specific brain proteins has not been evaluated in detail yet. The present study analyzes time-dependent changes in protein expression in rat brain after a short-term exposure to normobaric hyperoxia. Thirty-six Wistar rats were randomly assigned to six different groups, three normobaric hyperoxia (NH) groups or three normobaric normoxia (NN) groups, each consisting of n = 6 animals. NH animals were exposed to 100% oxygen, NN rats to 21% oxygen, each group for 3 h. One group of NH and one group of NN were killed immediately after the 3 h, one group each after 3 days and one group each after 7 days. Rat brains were removed for analysis and whole brain detergent protein lysates were separated via two-dimensional gel electrophoresis followed by subsequent identification of protein expression alterations by peptide mass fingerprinting using mass spectrometry. Also, a functional network mapping and molecular pathway analysis were carried out. Statistical analysis was performed using analysis of variance (ANOVA) with Bonferroni correction using P < 0.01. Physiological parameters of the animals did not differ significantly between the two groups except for partial oxygen pressure (580 vs. 89 mmHg; P < 0.05). The expression of nine proteins was found to be significantly altered (five up-regulated: GOT1, CCT2, TCP1, G6PD, and ALB; four down-regulated: PEBP1, PRDX2, ENO1, and MDH1). IPA generated a network with eight focus proteins associated with pathways in "cell death, cancer, and signalling". Although hyperoxia was normobaric and induced for only 3 h, significant changes in brain protein expression were detectable immediately after the 3 h, after 3 days, as well as after 7 days. This may indicate effects on brain protein expression take place in the rat brain following a relatively short period of hyperoxia.

Psycho-pharmacotherapy for anxiety and obsessive-compulsive disorder: the issue of prolonged barbiturate retention.

The authors report the case of a 32-year-old man who had been treated for anxiety and obsessive-compulsive disorder and had received 800 mg methylphenobarbital (MPB). After switching to a barbiturate-free schedule, his condition continued to be unstable for more than 21 MPB half-lives (approx. 30 days) and did not stabilize until MPB-metabolites dropped below their urinary detection limit. Considering that this article provides findings from a single patient, the authors use this experience to discuss and emphasize the importance of clinical control of barbiturates in psychiatry.

Alterations in rat serum proteome and metabolome as putative disease markers in sepsis.

OBJECTIVES: Despite a decreased mortality from sepsis, the absolute number of sepsis-related deaths has actually increased during the last years. At present, there are no biological markers available that can reliably assist early clinical diagnosis and the prompt initiation of therapy. This study investigated the changes in serum protein expression in a coecal ligature and puncture model of rat sepsis at 12, 24, and 48 hours after the induction of sepsis using differential proteomics. METHODS: Sixty-two male Wistar rats were randomly assigned to a sepsis group (coecal ligature and puncture; n = 46) or a sham group (n = 16). Surviving rats were killed 12 hour (n = 6), 24 hour (n = 9), or 48 hour (n = 4) after operation, and their serum lysates were subjected to two-dimensional gel electrophoresis and peptide mass fingerprinting. A systematic functional network mapping and molecular pathway analysis were performed using Ingenuity Pathways Analysis. RESULTS: Septic mortality was 58.7%, but no rat of the sham group was lost. Per gel, an average of 1,082 +/- 10 spots could be discriminated, of which 40 different protein spots were differentially expressed (p < 0.01). From the total of 40, the number of regulated protein spots was 13 (12 hour group) versus 10 (24 hour group) versus 18 (48 hour group). Ingenuity pathways analysis identified 10 of the differential proteins and allocated them to a pathway of tissue inflammation. CONCLUSIONS: The present study quantitatively detected several proteins differentially expressed in acute sepsis. Since a longer time-period was investigated and compared with previous studies, the results may offer new insights into septic organ dysfunction and altered protein pathways. The horizontal analysis of protein expression arrays and systematic biochemical pathways may represent an important new tool for the clinical assessment of septic conditions and support the development of early sepsis markers.