Treatment Objectives, Memory, and Desire.

This article explores the problems of the frequent loss, in the course of treatment, of the initial goals and motivation for treatment by both patient and therapist, and the connected lack of clarity of the real initial motivation for treatment on the part of both participants. It is strongly proposed that a true coincidence of at least one important initial motivational goal of patient and therapist is essential to assure the success of psychotherapy and that particular care is required to establish such agreement. On this basis, the goals of therapy may be expanded in the course of the therapist's experience, countertransference, and the patient's changing reality during treatment, and the existential and philosophical value systems of the therapist may play an important role in such widening of the therapist's expectations for the patient.

Severe hypoxaemic hypercapnia compounds cerebral oxidative-nitrosative stress during extreme apnoea: Implications for cerebral bioenergetic function.

We examined the extent to which apnoea-induced extremes of oxygen demand/carbon dioxide production impact redox regulation of cerebral bioenergetic function. Ten ultra-elite apnoeists (six men and four women) performed two maximal dry apnoeas preceded by normoxic normoventilation, resulting in severe end-apnoea hypoxaemic hypercapnia, and hyperoxic hyperventilation designed to ablate hypoxaemia, resulting in hyperoxaemic hypercapnia. Transcerebral exchange of ascorbate radicals (by electron paramagnetic resonance spectroscopy) and nitric oxide metabolites (by tri-iodide chemiluminescence) were calculated as the product of global cerebral blood flow (by duplex ultrasound) and radial arterial (a) to internal jugular venous (v) concentration gradients. Apnoea duration increased from 306 ± 62 s during hypoxaemic hypercapnia to 959 ± 201 s in hyperoxaemic hypercapnia (P ≤ 0.001). Apnoea generally increased global cerebral blood flow (all P ≤ 0.001) but was insufficient to prevent a reduction in the cerebral metabolic rates of oxygen and glucose (P = 0.015-0.044). This was associated with a general net cerebral output (v > a) of ascorbate radicals that was greater in hypoxaemic hypercapnia (P = 0.046 vs. hyperoxaemic hypercapnia) and coincided with a selective suppression in plasma nitrite uptake (a > v) and global cerebral blood flow (P = 0.034 to <0.001 vs. hyperoxaemic hypercapnia), implying reduced consumption and delivery of nitric oxide consistent with elevated cerebral oxidative-nitrosative stress. In contrast, we failed to observe equidirectional gradients consistent with S-nitrosohaemoglobin consumption and plasma S-nitrosothiol delivery during apnoea (all P ≥ 0.05). Collectively, these findings highlight a key catalytic role for hypoxaemic hypercapnia in cerebral oxidative-nitrosative stress. KEY POINTS: Local sampling of blood across the cerebral circulation in ultra-elite apnoeists determined the extent to which severe end-apnoea hypoxaemic hypercapnia (prior normoxic normoventilation) and hyperoxaemic hypercapnia (prior hyperoxic hyperventilation) impact free radical-mediated nitric oxide bioavailability and global cerebral bioenergetic function. Apnoea generally increased the net cerebral output of free radicals and suppressed plasma nitrite consumption, thereby reducing delivery of nitric oxide consistent with elevated oxidative-nitrosative stress. The apnoea-induced elevation in global cerebral blood flow was insufficient to prevent a reduction in the cerebral metabolic rates of oxygen and glucose. Cerebral oxidative-nitrosative stress was greater during hypoxaemic hypercapnia compared with hyperoxaemic hypercapnia and coincided with a lower apnoea-induced elevation in global cerebral blood flow, highlighting a key catalytic role for hypoxaemia. This applied model of voluntary human asphyxia might have broader implications for the management and treatment of neurological diseases characterized by extremes of oxygen demand and carbon dioxide production.

Borderline personality disorder: a comprehensive review of diagnosis and clinical presentation, etiology, treatment, and current controversies.

Borderline personality disorder (BPD) was introduced in the DSM-III in 1980. From the DSM-III to the DSM-5, no major changes have occurred in its defining criteria. The disorder is characterized by instability of self-image, interpersonal relationships and affects. Further symptoms include impulsivity, intense anger, feelings of emptiness, strong abandonment fears, suicidal or self-mutilation behavior, and transient stress-related paranoid ideation or severe dissociative symptoms. There is evidence that BPD can be reliably diagnosed and differentiated from other mental disorders by semi-structured interviews. The disorder is associated with considerable functional impairment, intensive treatment utilization, and high societal costs. The risk of self-mutilation and suicide is high. In the general adult population, the lifetime prevalence of BPD has been reported to be from 0.7 to 2.7%, while its prevalence is about 12% in outpatient and 22% in inpatient psychiatric services. BPD is significantly associated with other mental disorders, including depressive disorders, substance use disorders, post-traumatic stress disorder, attention-deficit/hyperactivity disorder, bipolar disorder, bulimia nervosa, and other personality disorders. There is convincing evidence to suggest that the interaction between genetic factors and adverse childhood experiences plays a central role in the etiology of BPD. In spite of considerable research, the neurobiological underpinnings of the disorder remain to be clarified. Psychotherapy is the treatment of choice for BPD. Various approaches have been empirically supported in randomized controlled trials, including dialectical behavior therapy, mentalization-based therapy, transference-focused therapy, and schema therapy. No approach has proved to be superior to others. Compared to treatment as usual, psychotherapy has proved to be more efficacious, with effect sizes between 0.50 and 0.65 with regard to core BPD symptom severity. However, almost half of the patients do not respond sufficiently to psychotherapy, and further research in this area is warranted. It is not clear whether some patients may benefit more from one psychotherapeutic approach than from others. No evidence is available consistently showing that any psychoactive medication is efficacious for the core features of BPD. For discrete and severe comorbid anxiety or depressive symptoms or psychotic-like features, pharmacotherapy may be useful. Early diagnosis and treatment of BPD can reduce individual suffering and societal costs. However, more high-quality studies are required, in both adolescents and adults. This review provides a comprehensive update of the BPD diagnosis and clinical characterization, risk factors, neurobiology, cognition, and management. It also discusses the current controversies concerning the disorder, and highlights the areas in which further research is needed.

Differential Expression of Vascular-Related MicroRNA in Circulating Endothelial Microvesicles in Adults With Spinal Cord Injury: A Pilot Study.

Background: Spinal cord injury (SCI) is associated with an increased risk and prevalence of cardiopulmonary and cerebrovascular disease-related morbidity and mortality. The factors that initiate, promote, and accelerate vascular diseases and events in SCI are poorly understood. Clinical interest in circulating endothelial cell-derived microvesicles (EMVs) and their microRNA (miRNA) cargo has intensified due to their involvement in endothelial dysfunction, atherosclerosis, and cerebrovascular events. Objectives: The aim of this study was to determine whether a subset of vascular-related miRNAs is differentially expressed in EMVs isolated from adults with SCI. Methods: We assessed eight adults with tetraplegia (7 male/1 female; age: 46±4 years; time since injury: 26±5 years) and eight uninjured (6 male/2 female; age: 39±3 years). Circulating EMVs were isolated, enumerated, and collected from plasma by flow cytometry. The expression of vascular-related miRNAs in EMVs was assessed by RT-PCR. Results: Circulating EMV levels were significantly higher (~130%) in adults with SCI compared with uninjured adults. The expression profile of miRNAs in EMVs from adults with SCI were significantly different than uninjured adults and were pathologic in nature. Expression of miR-126, miR-132, and miR-Let-7a were lower (~100-150%; p < .05), whereas miR-30a, miR-145, miR-155, and miR-216 were higher (~125-450%; p < .05) in EMVs from adults with SCI. Conclusion: This study is the first examination of EMV miRNA cargo in adults with SCI. The cargo signature of vascular-related miRNAs studied reflects a pathogenic EMV phenotype prone to induce inflammation, atherosclerosis, and vascular dysfunction. EMVs and their miRNA cargo represent a novel biomarker of vascular risk and a potential target for intervention to alleviate vascular-related disease after SCI.

Borderline Personality Disorder: A Review.

Importance: Borderline personality disorder (BPD) affects approximately 0.7% to 2.7% of adults in the US. The disorder is associated with considerable social and vocational impairments and greater use of medical services. Observations: Borderline personality disorder is characterized by sudden shifts in identity, interpersonal relationships, and affect, as well as by impulsive behavior, periodic intense anger, feelings of emptiness, suicidal behavior, self-mutilation, transient, stress-related paranoid ideation, and severe dissociative symptoms (eg, experience of unreality of one's self or surroundings). Borderline personality disorder is typically diagnosed by a mental health specialist using semistructured interviews. Most people with BPD have coexisting mental disorders such as mood disorders (ie, major depression or bipolar disorder) (83%), anxiety disorders (85%), or substance use disorders (78%). The etiology of BPD is related to both genetic factors and adverse childhood experiences, such as sexual and physical abuse. Psychotherapy is the treatment of choice for BPD. Psychotherapy such as dialectical behavior therapy and psychodynamic therapy reduce symptom severity more than usual care, with medium effect sizes (standardized mean difference) between -0.60 and -0.65. There is no evidence that any psychoactive medication consistently improves core symptoms of BPD. For discrete and severe comorbid mental disorders, eg, major depression, pharmacotherapy such as the selective serotonin reuptake inhibitors escitalopram, sertraline, or fluoxetine may be prescribed. For short-term treatment of acute crisis in BPD, consisting of suicidal behavior or ideation, extreme anxiety, psychotic episodes, or other extreme behavior likely to endanger a patient or others, crisis management is required, which may include prescription of low-potency antipsychotics (eg, quetiapine) or off-label use of sedative antihistamines (eg, promethazine). These drugs are preferred over benzodiazepines such as diazepam or lorazepam. Conclusions and Relevance: Borderline personality disorder affects approximately 0.7% to 2.7% of adults and is associated with functional impairment and greater use of medical services. Psychotherapy with dialectical behavior therapy and psychodynamic therapy are first-line therapies for BPD, while psychoactive medications do not improve the primary symptoms of BPD.

Common carotid artery responses to the cold-pressor test are impaired in individuals with cervical spinal cord injury.

Cervical spinal cord injury (SCI) leads to autonomic cardiovascular dysfunction that underlies the three- to fourfold elevated risk of cardiovascular disease in this population. Reduced common carotid artery (CCA) dilatory responsiveness during the cold-pressor test (CPT) is associated with greater cardiovascular disease risk and progression. The cardiovascular and CCA responses to the CPT may provide insight into cardiovascular autonomic dysfunction and cardiovascular disease risk in individuals with cervical SCI. Here, we used CPT to perturb the autonomic nervous system in 14 individuals with cervical SCI and 12 uninjured controls, while measuring cardiovascular responses and CCA diameter. The CCA diameter responses were 55% impaired in those with SCI compared with uninjured controls (P = 0.019). The CCA flow, velocity, and shear response to CPT were reduced in SCI by 100% (P < 0.001), 113% (P = 0.001), and 125% (P = 0.002), respectively. The association between mean arterial pressure and CCA dilation observed in uninjured individuals (r = 0.54, P = 0.004) was absent in the SCI group (r = 0.22, P = 0.217). Steady-state systolic blood pressure (P = 0.020), heart rate (P = 0.003), and cardiac contractility (P < 0.001) were reduced in those with cervical SCI, whereas total peripheral resistance was increased compared with uninjured controls (P = 0.042). Relative cerebral blood velocity responses to CPT were increased in the SCI group and reduced in controls (middle cerebral artery, P = 0.010; posterior cerebral artery, P = 0.026). The CCA and cardiovascular responsiveness to CPT are impaired in those with cervical SCI.NEW & NOTEWORTHY This is the first study demonstrating that CCA responses during CPT are suppressed in SCI. Specifically, CCA diameter, flow, velocity, and shear rate were reduced. The relationship between changes in MAP and CCA dilatation in response to CPT was absent in individuals with SCI, despite similar cardiovascular activation between SCI and uninjured controls. These findings support the notion of elevated cardiovascular disease risk in SCI and that the cardiovascular responses to environmental stimuli are impaired.

Hypoxemia increases blood-brain barrier permeability during extreme apnea in humans.

Voluntary asphyxia imposed by static apnea challenges blood-brain barrier (BBB) integrity in humans through transient extremes of hypertension, hypoxemia and hypercapnia. In the present study, ten ultra-elite breath-hold divers performed two maximal dry apneas preceded by normoxic normoventilation (NX: severe hypoxemia and hypercapnia) and hyperoxic hyperventilation (HX: absence of hypoxemia with exacerbating hypercapnia) with measurements obtained before and immediately after apnea. Transcerebral exchange of NVU proteins (ELISA, Single Molecule Array) were calculated as the product of global cerebral blood flow (gCBF, duplex ultrasound) and radial arterial to internal jugular venous concentration gradients. Apnea duration increased from 5 m 6 s in NX to 15 m 59 s in HX (P = <0.001) resulting in marked elevations in gCBF and venous S100B, glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase-L1 and total tau (all P < 0.05 vs. baseline). This culminated in net cerebral output reflecting mildly increased BBB permeability and increased neuronal-gliovascular reactivity that was more pronounced in NX due to more severe systemic and intracranial hypertension (P < 0.05 vs. HX). These findings identify the hemodynamic stress to which the apneic brain is exposed, highlighting the critical contribution of hypoxemia and not just hypercapnia to BBB disruption.

Passive leg cycling increases activity of the cardiorespiratory system in people with tetraplegia.

Individuals with cervical spinal cord injury (SCI) are at an increased risk for cardiovascular disease. Exercise is well-established for preventing cardiovascular disease; however, there are limited straightforward and safe exercise approaches for increasing the activity of the cardiorespiratory system after cervical SCI. The objective of this study was to investigate the cardiorespiratory response to passive leg cycling in people with cervical SCI. Beat-by-beat blood pressure, heart rate, and cerebral blood flow were measured before and throughout 10 minutes of cycling in 11 people with SCI. Femoral artery flow-mediated dilation was also assessed before and immediately after passive cycling. Safety was monitored throughout all study visits. Passive cycling elevated systolic blood pressure (5 ± 2 mm Hg), mean arterial pressure (5 ± 3 mm Hg), stroke volume (2.4 ± 0.8 mL), heart rate (2 ± 1 beats/min) and cardiac output (0.3 ± 0.07 L/min; all p < 0.05). Minute ventilation (0.67 ± 0.23 L/min), tidal volume (70 ± 30 mL) and end-tidal PO2 (2.6 ± 1.23 mm Hg) also increased (all p < 0.05). Endothelial function was improved immediately after exercise (1.62 ± 0.13%, p < 0.01). Passive cycling resulted in an incidence of autonomic dysreflexia. Therefore, passive leg cycling increased the activity of the cardiorespiratory system and improved endothelial function, indicating it may be a beneficial exercise intervention for the cardiovascular and respiratory systems in people with cervical SCI. Novelty: Passive leg cycling increases the activity of the cardiorespiratory system and improves markers of cardiovascular health in cervical SCI. Passive leg cycling exercise is an effective, low-cost, practical, alternative exercise modality for people with cervical SCI.

Differential neural response to psychoanalytic intervention techniques during structural interviewing: A single-case analysis using EEG.

Background: Previous studies detected changes in the electroencephalographic (EEG) signal as an effect of psychoanalytic interventions. However, no study has investigated neural correlates of specific psychoanalytic interventions in the EEG power spectrum yet. In the present case study, we contrasted three types of interventions (clarification, confrontation, and interpretation) and a neutral control condition during a structural psychoanalytic interview conducted while EEG was recorded. Methods: A 27-year-old male patient diagnosed with major depressive disorder and borderline personality disorder with recurrent suicidal and self-injurious behavior underwent a structural interview while recording EEG. Two independent experts selected by consensus the characteristic episodes of the four conditions (clarification, confrontation, interpretation, and neutral control) within the interview, which were included in the EEG analyses. Fast Fourier transformation (FFT) was applied to subsegments of the intervention type to analyze the EEG power spectra. Alpha and beta power from central, frontal, and parietal sites were considered in linear mixed-effects models with segments as a random factor with maximum-likelihood estimates due to the lack of balance in the length of the interview segments. Results: The interventions "interpretation" and "confrontation" showed a significantly lower alpha power compared with the control condition in the central electrodes. In the frontal and parietal sites of the alpha power and all beta power sites, the omnibus tests (full model/model without intervention) and comparisons relative to control conditions showed no significant overall result or failed significance after alpha error correction. Conclusion: Incisive interventions, such as confrontation with discrepancies and interpretation of unconscious intrapsychic conflicts, may have provoked temporary emotional lability, leading to a change in psychic processing akin to interference from external stimuli. This conclusion is consistent with the finding that interpretations, which are potentially the most concise interventions, had the strongest effects on alpha power. Using EEG during therapeutic psychoanalytic intervention techniques might be a helpful tool to evaluate differential responses to the psychotherapeutic process on a neural level. However, this single-case result has to be replicated in a larger sample and does not allow generalizations.

Extensions of Psychoanalytic Technique: The Mutual Influences of Standard Psychoanalysis and Transference-Focused Psychotherapy.

The author describes the differences between standard psychoanalysis and transference-focused psychotherapy (TFP) and reviews particular difficulties that psychodynamically trained clinicians have in learning TFP. In delineating differences between standard psychoanalysis and TFP, the author discusses mutual influences between standard psychoanalytic techniques and techniques of TFP. TFP is an extension and modification of standard psychoanalysis, but with quantitative modifications geared to the treatment of the most severe segment of personality disorders that tend not to be treatable by standard analysis. TFP includes some features that are directly facilitated by psychoanalytic education, such as the importance of free association and the organization of interpretations in terms of the analysis of defense, motivation, and impulse. On the other hand, TFP provides new strategies, enhancing standard psychoanalytic treatment, when it modifies technical neutrality under certain circumstances, allows for the analysis of "incompatible realities," and accelerates interventions under conditions of severe acting out when technical neutrality is not possible to maintain. The author demonstrates the advantages of systematic training in TFP within psychoanalytic institutes as a true enrichment of technical training. He proposes that psychoanalysis as a profession consists of a broad spectrum of treatment approaches based upon the combined utilization of psychoanalytic techniques, with specific modifications to be organized in specific forms of psychoanalytic psychotherapy. TFP may be the closest modification to standard psychoanalysis proper and is clearly defined and manualized. This has permitted empirical research that has already demonstrated the effectiveness of TFP.

An alternative route towards the fabrication of 2D blue phosphorene.

Blue phosphorene (BlueP) is a novel two-dimensional material that shares properties with black phosphorene and is potentially even more interesting for opto-electronic applications because of its layer dependent wide band gap of ≈ 2 to 3 eV and superior charge carrier mobility. It was first fabricated on Au(111), where, however, a network consisting of BlueP subunits and Au-linker atoms is formed. The physical properties of such an arrangement strongly differ from a freestanding BlueP monolayer. Here, we report on the growth of epitaxial BlueP on the Au(100) surface, which is an interesting alternative when aiming at quasi-freestanding BlueP domains. We find two different phosphorus phases by means of scanning tunneling microscopy and distortion-corrected low-energy electron diffraction. In the low coverage regime, we observe a commensurate (2 × 2) phase, whereas for higher coverage, a nearly hexagonal structure is formed. For the latter, the lattice parameters measured via atomically resolved scanning tunneling hydrogen microscopy closely resemble those of freestanding BlueP, and the typical height modulation of the phosphorus atoms is verified in our layers by means of x-ray photoelectron diffraction. We further analyze the chemical and electronic properties of these films by means of x-ray and (angle resolved) ultraviolet photoelectron spectroscopy.

Challenges for the Future of Psychoanalysis.

This paper summarizes the current crisis of psychoanalysis in its relations to the scientific and cultural environment. It proposes tasks to assure the survival and contributions of psychoanalysis as science, profession, and humanistic discipline. It proposes emphasis on empirical research in the boundaries with the neurosciences and social psychology, and the development of an infrastructure for research linked to its educational program. It proposes renovation in training, abolishment of the training analysis system, and systematic teaching and research on the psychoanalytic psychotherapies focused on specific pathologies. This overall proposal stresses the need to collaborate and potentially integrate psychoanalytic institutions within university settings, and the development of active interdisciplinary engagements with other sciences and the community at large. Finally, it stresses the role of contemporary object relations theory to reunify the presently diverging schools of psychoanalytic theory and technique.

Thoughts on Transference Analysis in Transference-Focused Psychotherapy.

Transference-focused psychotherapy (TFP) represents a specific extension of psychoanalytic therapy for treatment of individuals with personality disorders, who may be helped without the more significant time investment required of a standard psychoanalysis. The treatment represents a contemporary formulation of psychoanalytic psychotherapy, updated in light of both empirical research and scientific developments in boundary fields close to the psychodynamic endeavor, particularly affective neuroscience and the psychology of couples and small groups. In TFP, the transference signifies the enactment in the here and now of a specific affective relationship between patient and therapist that reflects one aspect, defensive or impulsive, of a pathogenic dynamic unconscious conflict. This conflict needs to be analyzed, interpreted, and resolved. Various elements of transference analysis in TFP are discussed in this article.

Development and Validation of the Interview of Personality Organization Processes in Adolescence (IPOP-A).

The assessment of personality and personality pathology in adolescence represents a critical topic to understand adolescent's difficulties, predict long-term outcome in adulthood, and indicate adequate treatment. Personality Organization, and its underlying dimensions, plays an essential role in shaping how adolescents face their developmental tasks as they are connected with psychosocial functioning and psychopathological severity. However, few measures are available to assess personality organization during adolescence. The aim of the present research is to investigate the psychometric properties of the Interview of Personality Organization Processes in Adolescence (IPOP-A), a semi-structured interview designed for the assessment of the main personality organization dimensions in adolescence. Three studies were performed to explore the psychometric properties of the IPOP-A, in terms of factor structure, reliability, convergent, and discriminant validity. Exploratory and confirmatory factor analysis supported the IPOP-A construct validity. Furthermore, IPOP-A showed good reliability and evidenced a convergent and discriminant validity with DSM-oriented personality patterns, emotion dysregulation, identity disturbance, and psychopathology. Our results provide evidence of IPOP-A validity to assess emerging personality organization in adolescence. Furthermore, the IPOP-A is a promising tool to use in the clinical consultation and treatment planning for the adolescent.

Assessment of the applicability of HLB values for natural phospholipid emulsifiers for preparation of stable emulsions.

Natural phospholipid (PL) excipients are native, biocompatible and relatively inexpensive alternatives to synthetic emulsifiers. A well-known PL excipient is lecithin, which primarily contains phosphatidylcholine (PC) and (depending on the purity grade) also contains a well-defined mixture of other PLs with a fatty acid composition, which reflects their natural source. Since all of these lipid species are emulsifiers, natural PLs can be considered as a mixture of (co-) emulsifiers. Many different HLB values for lecithins are given in the literature, which is why this needs to be clarified. To assess this, HLB values of thirteen different plant derived PLs differing in PC content were determined using a centrifugation stress method to determine the relative stability of an emulsion with the respective emulsifier and different oil phases. It could be shown that the studied PLs can be characterized by a broad HLB range, which may be linked to the composition of the PLs and the oil used. In order to emphasize the results of the HLB determination, it could be demonstrated that stable emulsions could be prepared with a wide range of oils using the plant-based PLs and that the preparation method of the emulsions is important in order to obtain stable emulsions. Therefore, assigning a specific exact HLB value to natural PLs instead of a wider range is inappropriate. The broad HLB ranges indicate the suitability of the studied PL emulsifiers for the preparation of oil-in-water emulsions for a wide range of oils: It is recommended to experimentally evaluate the suitability of these natural emulsifiers for the preparation of stable emulsions and to benefit from the wide range of HLB values of these emulsifiers instead of relying on inaccurate and confusing HLB values in the literature.

Alterations in resting cerebrovascular regulation do not affect reactivity to hypoxia, hyperoxia or neurovascular coupling following a SCUBA dive.

NEW FINDINGS: What is the central question of this study? What are the characteristics of cerebral blood flow (CBF) regulation following a single SCUBA dive to a depth of 18 m sea water with a 47 min bottom time. What is the main finding and its importance? Acute alterations in CBF regulation at rest, including extra-cranial vasodilatation, reductions in shear patterns and elevations in intra-cranial blood velocity were observed at rest following a single SCUBA dive. These subtle changes in CBF regulation did not translate into any functional changes in cerebrovascular reactivity to hypoxia or hyperoxia, or neurovascular coupling following a single SCUBA dive. ABSTRACT: Reductions in vascular function during a SCUBA dive - due to hyperoxia-induced oxidative stress, arterial and venous gas emboli and altered endothelial integrity - may also extend to the cerebrovasculature following return to the surface. This study aimed to characterize cerebral blood flow (CBF) regulation following a single SCUBA dive to a depth of 18 m sea water with a 47 min bottom time. Prior to and following the dive, participants (n = 11) completed (1) resting CBF in the internal carotid (ICA) and vertebral (VA) arteries (duplex ultrasound) and intra-cranial blood velocity (v) of the middle and posterior cerebral arteries (MCAv and PCAv, respectively) (transcranial Doppler ultrasound); (2) cerebrovascular reactivity to acute poikilocapnic hypoxia (i.e. FIO2 , 0.10) and hyperoxia (i.e. FIO2 , 1.0); and (3) neurovascular coupling (NVC; regional CBF response to local increases in cerebral metabolism). Global CBF, cerebrovascular reactivity to hypoxia and hyperoxia, and NVC were unaltered following a SCUBA dive (all P > 0.05); however, there were subtle changes in other cerebrovascular metrics post-dive, including reductions in ICA (-13 ± 8%, P = 0.003) and VA (-11 ± 14%, P = 0.021) shear rate, lower ICAv (-10 ± 9%, P = 0.008) and VAv (-9 ± 14%, P = 0.028), increases in ICA diameter (+4 ± 5%, P = 0.017) and elevations in PCAv (+10 ± 19%, P = 0.047). Although we observed subtle alterations in CBF regulation at rest, these changes did not translate into any functional changes in cerebrovascular reactivity to hypoxia or hyperoxia, or NVC. Whether prolonged exposure to hyperoxia and hyperbaria during longer, deeper, colder and/or repetitive SCUBA dives would provoke changes to the cerebrovasculature requires further investigation.

Effects of circulating extracellular microvesicles from spinal cord-injured adults on endothelial cell function.

People with spinal cord injury (SCI) have three- to four-fold greater risk of cardiovascular disease (CVD) compared with those without SCI. Although circulating extracellular microvesicles are key effectors of vascular health and disease, how their functional phenotype might be altered with SCI is unknown. The aim of the present study was to determine the effects of microvesicles isolated from SCI adults on endothelial cell inflammation and oxidative stress as well as endothelial nitric oxide (NO) synthase (eNOS) activation and tissue-type plasminogen activator (t-PA) expression. Eighteen young and middle-aged adults were studied: 10 uninjured (7M/3F; age: 39 ± 3 years) and 8 cervical level spinal cord injured (SCI; 7M/1F; 46 ± 4 years; cervical injury: C3: n=1; C5: n=4; C6: n=3). Circulating microvesicles were isolated, enumerated and collected from plasma by flow cytometry. Human umbilical vein endothelial cells (HUVECs) were cultured and treated with microvesicles from either the uninjured or SCI adults. Microvesicles from SCI adults did not affect cellular markers or mediators of inflammation and oxidative stress. However, microvesicles from the SCI adults significantly blunted eNOS activation, NO bioavailability and t-PA production. Intercellular expression of phosphorylated eNOS at Ser1177 and Thr495 sites, specifically, were ∼65% lower and ∼85% higher, respectively, in cells treated with microvesicles from SCI compared with uninjured adults. Decreased eNOS activity and NO production as well as impaired t-PA bioavailability renders the vascular endothelium highly susceptible to atherosclerosis and thrombosis. Thus, circulating microvesicles may contribute to the increased risk of vascular disease and thrombotic events associated with SCI.

Malignant Narcissism and Large Group Regression.

This paper explores the mutual relationship between large group regression and leadership with the characteristic of the syndrome of malignant narcissism. Regressed large groups intuitively search for such leadership and personalities with these characteristics are prone to aspire to the correspondent role. The underlying dynamics of groups and leaders are complementary and determine a mutually reinforcing psychopathology. This paper will explore these dynamics, their social consequences, and discuss potential preventive and therapeutic interventions that protect society from this psychosocial psychopathology.

Vascular dysfunction following breath-hold diving.

The pathogenesis of predominantly neurological decompression sickness (DCS) is multifactorial. In SCUBA diving, besides gas bubbles, DCS has been linked to microparticle release, impaired endothelial function, and platelet activation. This study focused on vascular damage and its potential role in the genesis of DCS in breath-hold diving. Eleven breath-hold divers participated in a field study comprising eight deep breath-hold dives with short surface periods and repetitive breath-hold dives lasting for 6 h. Endothelium-dependent vasodilation of the brachial artery, via flow-mediated dilation (FMD), and the number of microparticles (MPs) were assessed before and after each protocol. All measures were analyzed by two-way within-subject ANOVA (2 × 2 ANOVA; factors: time and protocol). Absolute FMD was reduced following both diving protocols (p < 0.001), with no interaction (p = 0.288) or main effect of protocol (p = 0.151). There was a significant difference in the total number of circulating MPs between protocols (p = 0.007), where both increased post-dive (p = 0.012). The number of CD31+/CD41- and CD66b+ MP subtypes, although different between protocols (p < 0.001), also increased by 41.0% ± 56.6% (p = 0.050) and 60.0% ± 53.2% (p = 0.045) following deep and repetitive breath-hold dives, respectively. Both deep and repetitive breath-hold diving lead to endothelial dysfunction that may play an important role in the genesis of neurological DCS.

Network analysis identifies consensus physiological measures of neurovascular coupling in humans.

Intimate communication between neural and vascular structures is required to match neuronal metabolism to blood flow, a process termed neurovascular coupling. The number of laboratories assessing neurovascular coupling in humans is increasing due to clinical interest in disease states, and basic science interest in a non-anesthetized, non-craniotomized, unrestrained, in vivo model. However, there is a lack of knowledge regarding how best to characterize the neurovascular response. To address this knowledge gap, we have amassed a highly powered human neurovascular coupling dataset, and deployed a network-based approach to reveal the most powerful and consistent metrics for quantifying neurovascular coupling. Using dimensionality reduction, community-based clustering, and majority-voting of traditional metrics (e.g. peak response, time to peak) and non-traditional metrics (e.g. varying time windows, pulsatility), we have identified which of the existing metrics predominantly characterize the neurovascular coupling response, are stable within and across participants, and explain the vast majority of the variance within our dataset of over 300 trials. We then harnessed our empirical approach to generate powerful novel metrics of neurovascular coupling, termed iAmplitude, iRate, and iPulsatility, which increase sensitivity when capturing population differences. These metrics may be useful to optimally understand neurovascular coupling in health and disease.