Perineuronal net structure as a non-cellular mechanism contributing to affective state: A scoping review.

Affective state encompasses emotional responses to our physiology and influences how we perceive and respond within our environment. In affective disorders such as depression, cognitive adaptability is challenged, and structural and functional brain changes have been identified. However, an incomplete understanding persists of the molecular and cellular mechanisms at play in affective state. An exciting area of newly appreciated importance is perineuronal nets (PNNs); a specialised component of extracellular matrix playing a critical role in neuroprotection and synaptic plasticity. A scoping review found 24 studies demonstrating that PNNs are still a developing field of research with a promising general trend for stress in adulthood to increase the intensity of PNNs, whereas stress in adolescence reduced (potentially developmentally delayed) PNN numbers and intensity, while antidepressants correlated with reduced PNN numbers. Despite promising trends, limited research underscores the need for further exploration, emphasizing behavioral outcomes for validating affective states. Understanding PNNs' role may offer therapeutic insights for depression and inform biomarker development, advancing precision medicine and enhancing well-being.

[Novel surgical techniques for treatment of benign prostatic hyperplasia]. / Neue operative Techniken zur Therapie des benignen Prostatasyndroms.

In recent years new surgical techniques to treat benign prostatic hyperplasia have been introduced into urological practice and evaluated in clinical studies. Complications of standard procedures, e.g. transurethral resection of the prostate (TURP), can be avoided while maintaining equivalent clinical outcomes. The main goal is preservation of erectile and ejaculatory function. Furthermore, outpatient treatment associated with a rapid patient recovery would be desirable. This article presents the course of the interventions, the mechanisms of action and current clinical evidence for novel mechanical approaches of recanalization, water-based ablation as well as prostate artery embolization. Initial study results partially indicate that in the future practically all patients can be offered an individualized surgical technique, which provides optimal symptomatic and functional improvements with a minimized risk of complications.

Dietary influences on cognition.

Obesity is a world-wide crisis with profound healthcare and socio-economic implications and it is now clear that the central nervous system (CNS) is a target for the complications of metabolic disorders like obesity. In addition to decreases in physical activity and sedentary lifestyles, diet is proposed to be an important contributor to the etiology and progression of obesity. Unfortunately, there are gaps in our knowledge base related to how dietary choices impact the structural and functional integrity of the CNS. For example, while chronic consumption of hypercaloric diets (increased sugars and fat) contribute to increases in body weight and adiposity characteristic of metabolic disorders, the mechanistic basis for neurocognitive deficits in obesity remains to be determined. In addition, studies indicate that acute consumption of hypercaloric diets impairs performance in a wide variety of cognitive domains, even in normal non-obese control subjects. These results from the clinical and basic science literature indicate that diet can have rapid, as well as long lasting effects on cognitive function. This review summarizes our symposium at the 2017 Society for the Study of Ingestive Behavior (SSIB) meeting that discussed these effects of diet on cognition. Collectively, this review highlights the need for integrated and comprehensive approaches to more fully determine how diet impacts behavior and cognition under physiological conditions and in metabolic disorders like type 2 diabetes mellitus (T2DM) and obesity.

European otorhinolaryngology training programs: results of a European survey about training satisfaction, work environment and conditions in six countries.

ORL-students and residents have an ongoing debate about the "best" programme in Europe. Aim of this study was to comparatively assess differences among programmes in training, satisfaction, quality of life (QoL) of residents and recent otorhinolaryngologist (ORL) specialists in France, Germany, Spain, Italy, Austria, and Belgium. A self-administered anonymous questionnaire, structured in ten sections including general information, provided guidance, working environment, training structure, teaching of medical students, publication work, QoL, and satisfaction with training, were emailed to residents and recent ORL specialists. 476 returned questionnaires from 6 countries revealed that daily work hours were the highest in France and Belgium with 11 and 10.4 h on average, respectively. QoL, work conditions, and salary were best in Germany followed by Austria in terms of possibility of part-time contracts, better respect for post-duty day off, and compensation for overtime. Satisfaction with training including support and guidance of seniors was lowest in Italy, but, on the other hand, the publication work and support had a more important place than in other countries. In Belgium, there was some gap between the quality of teaching and feedback from seniors as well as apprenticeship. The highest satisfaction with training was in France and Spain followed by Austria. The study results provide guidance before choosing an ORL training programme in Europe. Country-specific strengths could be included into future harmonization efforts to improve all programmes, facilitate professional exchange and, finally, establish standards-of-care carried out by well-trained doctors also looking after a satisfying work-life balance.

Hypervulnerability of the adolescent prefrontal cortex to nutritional stress via reelin deficiency.

Overconsumption of high-fat diets (HFDs) can critically affect synaptic and cognitive functions within telencephalic structures such as the medial prefrontal cortex (mPFC). The underlying mechanisms, however, remain largely unknown. Here we show that adolescence is a sensitive period for the emergence of prefrontal cognitive deficits in response to HFD. We establish that the synaptic modulator reelin (RELN) is a critical mediator of this vulnerability because (1) periadolescent HFD (pHFD) selectively downregulates prefrontal RELN+ cells and (2) augmenting mPFC RELN levels using transgenesis or prefrontal pharmacology prevents the pHFD-induced prefrontal cognitive deficits. We further identify N-methyl-d-aspartate-dependent long-term depression (NMDA-LTD) at prefrontal excitatory synapses as a synaptic signature of this association because pHFD abolishes NMDA-LTD, a function that is restored by RELN overexpression. We believe this study provides the first mechanistic insight into the vulnerability of the adolescent mPFC towards nutritional stress, such as HFDs. Our findings have primary relevance to obese individuals who are at an increased risk of developing neurological cognitive comorbidities, and may extend to multiple neuropsychiatric and neurological disorders in which RELN deficiency is a common feature.

Integration of reward signalling and appetite regulating peptide systems in the control of food-cue responses.

Understanding the neurobiological substrates that encode learning about food-associated cues and how those signals are modulated is of great clinical importance especially in light of the worldwide obesity problem. Inappropriate or maladaptive responses to food-associated cues can promote over-consumption, leading to excessive energy intake and weight gain. Chronic exposure to foods rich in fat and sugar alters the reinforcing value of foods and weakens inhibitory neural control, triggering learned, but maladaptive, associations between environmental cues and food rewards. Thus, responses to food-associated cues can promote cravings and food-seeking by activating mesocorticolimbic dopamine neurocircuitry, and exert physiological effects including salivation. These responses may be analogous to the cravings experienced by abstaining drug addicts that can trigger relapse into drug self-administration. Preventing cue-triggered eating may therefore reduce the over-consumption seen in obesity and binge-eating disorder. In this review we discuss recent research examining how cues associated with palatable foods can promote reward-based feeding behaviours and the potential involvement of appetite-regulating peptides including leptin, ghrelin, orexin and melanin concentrating hormone. These peptide signals interface with mesolimbic dopaminergic regions including the ventral tegmental area to modulate reactivity to cues associated with palatable foods. Thus, a novel target for anti-obesity therapeutics is to reduce non-homeostatic, reward driven eating behaviour, which can be triggered by environmental cues associated with highly palatable, fat and sugar rich foods.

Transgenic expression of the FTDP-17 tauV337M mutation in brain dissociates components of executive function in mice.

Frontotemporal lobe dementia (FTD) is a heterogeneous range of disorders, a subset of which arise from fully penetrant, autosomal dominant point mutations in the gene coding for the microtubule associated protein tau. These genetic tauopathies are associated with complex behavioural/cognitive disturbances, including compromised executive function. In the present study, we modelled the effects of the FTD with Parkinsonism linked to chromosome 17 (FTDP-17) tauV337M mutation (known as the Seattle Family A mutation) expressed in mice on executive processes using a novel murine analogue of the Stroop task. Employing biconditional discrimination procedures, Experiment 1 showed that normal mice, but not mice with excitotoxic lesions of the medial prefrontal cortex, were able to use context cues to resolve response conflict generated by incongruent stimulus compounds. In contrast to predictions, response conflict resolution was not disrupted by the tauV337M mutation (Experiment 2). However, while context appropriate actions were goal-directed in wild-type mice, performance of tauV337M mice was not goal-directed (Experiment 3). The results indicate that the tauV337M mutation in mice disrupts, selectively, a subset of processes related to executive function.

The role of neurexins in schizophrenia and autistic spectrum disorder.

Schizophrenia and autistic spectrum disorder (ASD) are common, chronic mental conditions with both genetic and environmental components to their aetiology. The identification of genes influencing susceptibility to these disorders offers a rational route towards a clearer understanding of the neurobiology, and with this the prospect of treatment and prevention strategies tailored towards the remediation of the altered pathways. Copy number variants (CNVs) underlie many serious illnesses, including neurological and neurodevelopmental syndromes. Recent studies assessing copy number variation in ASD and schizophrenia have repeatedly observed heterozygous deletions eliminating exons of the neurexin-1α gene (but not the neurexin-1ß gene) in patients with ASD and schizophrenia. The neurexins are synaptic adhesion proteins that are known to play a key role in synaptic formation and maintenance. The functional significance of the recurrent deletion is poorly understood, but the availability of mice with deletion of the promoter and first exon of neurexin-1α provides direct access to the biological effects of neurexin-1α disruption on phenotypes relevant to ASD and schizophrenia. We review the evidence for the role of neurexin-1α in schizophrenia and ASD, and consider how genetic disruption of neurexin-1α may underpin the neuropathology contributing to these distinct neurodevelopmental disorders.

Gravity cavernosometry--a simple diagnostic test for cavernosal incompetence.

The papaverine test has been widely used as a diagnostic procedure in erectile impotence. However, when patients do not achieve full erection on the test, it is necessary to differentiate between insufficient inflow and excessive outflow. Gravity cavernosometry is a method designed to evaluate the pressure responses in the corpora when they are subjected to a constant infusion pressure. The infusion flow is of minor significance. The intracavernous pressure (ICP) was measured in cadavers, in psychogenically impotent patients and in patients with arteriogenic impotence, following administration of papaverine and gravity perfusion. During perfusion in cadavers and in psychogenic patients, the ICP showed values above 110 cm H2O, while in arteriogenic patients the values ranged from 30 to 141 cm H2O. In the arteriogenic group, 11/20 patients had an ICP lower than 110 during perfusion. There was no correlation between the pre-perfusion pressure and the final pressure with perfusion. Gravity cavernosometry is a simple, cost-effective and reliable method for the assessment of corporeal competence.

Surgical exclusion of the crural ending of the corpora cavernosa: late results.

Twenty-three patients with corpora cavernosa incompetence responsive to perineal compression were submitted to surgical exclusion of the crural ending of the corpora cavernosa. There were two mild complications: perineal hematoma and incisional pain for 10 days. At the end of the first month, 65% of the patients claimed better erections, and the late good results were 47.7%, with an average follow-up period of 18.9 months. Three of the failed cases were later submitted to a penile prosthesis implantation.

Impact of cigarette smoking on papaverine-induced erection.

Owing to the vasoconstrictive effect of nicotine, smoking may potentially interfere in the results of the drug-induced erection test for papaverine hydrochloride. To investigate the effect of smoking on this test, 12 patients between 22 and 65 years old underwent the following protocol: phase 1--intracavernous injection of 100 mg. papaverine hydrochloride with measurement of intracavernous pressure by puncture with a 19 caliber butterfly needle attached to an aneroid manometer and phase 2--1 week after the initial test the procedure was repeated after the patient smoked 2 cigarettes. In phase 1 all men obtained a full erection, compared to only 4 in phase 2. The average intracavernous pressures were 85.83 and 53.50 mm. Hg, respectively, in phases 1 and 2 (p less than 0.01). We conclude that cigarette smoking, probably through nicotine, interferes with the drug-induced erection test, which might explain some false negative results.

Leakage through the crural edge of corpus cavernosum. Diagnosis and treatment.

Blood drainage of the corpora cavernosa is made by the deep dorsal vein and by the deep crural veins. The root of the corpora can be compressed against the ischium during papaverine test or cavernometry. In a series of patients with cavernosal leakage, this maneuver demonstrated that the crural edge of the corpora is the point of leakage in many of them. Exclusion of the crural edge by ligation of the corpora proximal to the entrance of the arterial supply caused improvement of erections in 7 of 8 patients.