Inter-ictal assay of peripheral circulating inflammatory mediators in migraine patients under adjunctive cervical non-invasive vagus nerve stimulation (nVNS): A proof-of-concept study

Objective

To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.

Improving the international prognostic index score using peripheral blood counts: Results of a large multicenter study involving 520 patients with diffuse large B cell lymphoma

The main purpose of this study was to assess whether it is possible to improve the prognostic impact of international prognostic index (IPI) score by combining it with peripheral blood counts. Thus, we evaluated the prognostic power of lymphocyte, neutrophil, and monocyte counts in 520 patients with diffuse large B cell lymphoma treated with R-CHOP, confirming that these parameters have a strong impact on overall survival (OS). Using revised IPI (R-IPI), 44% of patients were categorized as poor-risk and showed an OS at 5 years of 46%. As OS at 5 years of the 520 patients is 67%, it is clearly evident that R-IPI tends to overestimate the proportion of patients with poor prognosis. Accordingly, in an attempt to improve the discriminating power of R-IPI, we evaluated and compared three different scores by combining the neutrophil lymphocyte ratio (NLR) and absolute monocyte count (AMC) with the following values: (a) IPI score 3-5, (b) age > 60 years and performance status, (c) age ≥ 65 years and LDH > ULN. The three indexes studied, had a similar 5 years OS for the high-risk group (46%-52%), but the proportion of patients classified as poor-risk were 37%, 20%, and 32%, respectively, which are lower than 44% identified with R-IPI. Thus, while R-IPI overestimates the number of high-risk patients, after applying our models, it is possible to recognize patients who are truly at high-risk. Of the three scores, the most accurate appears to be that based on NLR, AMC, LDH > ULN and age ≥ 65 years, which identifies 32% of high-risk patients, correlating well with what is seen in clinical practice.     

CDK12 and HER2 coamplification in two urothelial carcinomas with rapid and aggressive clinical progression

Cyclin‐dependent kinase 12 (CDK12), one of the key factors associated with DNA damage response pathways, is located on chromosome 17 proximal to Erb‐B2 receptor tyrosine kinase 2 (ERBB2). In this report, CDK12 and ERBB2 coamplification was detected by targeted next‐generation sequencing in two urothelial carcinomas. The staining intensity of the CDK12 and human epidermal growth factor receptor‐2 proteins was associated with the prognosis of each urothelial carcinoma case. Our results suggest that CDK12 coamplification with ERBB2 might be associated with tumor aggressiveness and contribution to cancer pathogenesis. Therapies targeting CDK12 should be developed for these patients.     

In vivo kinetics and displacement study of a carbon-11-labeled hallucinogen,N,N-[11C]dimethyltryptamine

The endogenous hallucinogen, N,N-dimethyltryptamine (DMT), was labeled with carbon-11 and its regional distribution in rat brain studied. [¹¹C]DMT showed higher accumulation in the cerebral cortex, caudate putamen, and amygdaloid nuclei. Studies of the subcellular distribution of [¹¹C]DMT revealed the specific localization in the fractions enriched with serotonin receptors only when a very low dose was injected into rats. The proportions of the radioactivity in receptor-rich fractions were greatly enhanced by pretreatment with the monoamine oxidase inhibitor, pargyline. Specific binding of [¹¹C]DMT to serotonin receptors in dog brain was demonstrated by a positron emission tomographic study in which 5-methoxy-N,N-dimethyltryptamine caused approximately 20% displacement of the radioligand from the receptors.     

Motor and non-motor sequence learning in children and adolescents with cerebellar damage.

Cerebellar involvement in motor and non-motor sequence learning was examined with serial reaction time tasks (SRT). Our sample consisted of 8 children and adolescents who had undergone surgical removal of a benign posterior fossa tumor (PFT) during childhood. None of them had undergone chemotherapy or cranial radiation therapy (CRT). Ages ranged from 1-11 years at surgery and 9-17 years at testing. The children were tested not earlier than 2.5 years after surgery (M = 5.9 years), enabling brain plasticity and recovery of functions. Their performance was compared with a matched control sample. The PFT group was not impaired in the implicit learning of sequences, as reflected in their performance in blocks with a repeated sequence, both before and after a random block. However, in the perceptual task, their performance deteriorated more than that of the control group when a random block was introduced, suggesting that it was more difficult for the patients to respond flexibly or change their response set when encountering changing task demands. These results are in line with another study by our group on task switching with the same patients.     

Emergency orthodontic treatment after the traumatic intrusive luxation of maxillary incisors.

Treatment of traumatically intruded teeth is based largely on empirical clinical experience rather than on scientific data. The aim of this qualitative meta-analysis was to provide an evidence base to evaluate the orthodontic repositioning approach. In a MEDLINE search of the literature in English, 14 reported patients involving 22 teeth were found to have been treated by this modality. Additionally, 3 new patients, involving 9 intruded teeth and presented herein, were combined to form a total study sample of 17 subjects (7 girls, 10 boys, aged 8.9 +/- 1.2 years). Orthodontic extrusive forces were applied in the immediate posttrauma period (up to 3 months), with a variety of orthodontic appliances. Repositioning was achieved for 90.3% of the affected teeth but failed in 9.7% because of inflammatory resorption (2 teeth) or a misdiagnosis of root fracture (1 tooth). Early complications included loss of pulp vitality and external root resorption. All intruded teeth with closed root apices lost their vitality regardless of the degree of intrusion, whereas among those with incomplete apices, 45.5% that had been moderately intruded remained vital. External resorption was encountered in 54.8% of the teeth. Loss of marginal bone support was rarely encountered. Late complications included inflammatory root resorption in teeth with closed apices, in which endodontic treatment was not initially performed, and obliteration of the pulp tissue in teeth that remained vital. The results show that this method is superior to other treatment alternatives.     

Overview: Beyond guidelines and guidance—psychosocial perspectives on treatment interventions for young people with substance problems in the United Kingdom

Over the last two decades there has been accumulating evidence that both psychosocial and pharmacological treatment interventions can effect change in substance-misusing adults. Thus, treatment interventions implemented for young people with substance problems largely draw on the adult addiction experience and that of child and adolescent psychiatry and psychology. As young people with problematic drug use have different treatment needs, and require different interventions and services to those of adults, results of adult studies cannot necessarily be directly extrapolated to young people.

Over the last five years evidence has been rapidly mounting that treatment may potentially work in young people, but as yet it is not as extensive as that for adults. The interventions that appear most fruitful are those based on learning theory, e.g. cognitive behavioural therapy and family therapy. Outcome studies in young people demonstrate substantial variability in substance use and misuse following treatment. From the UK perspective, the evidence is almost entirely USA based, and these evaluations of non-UK treatment programmes for young people cannot be simply transferred or transported to UK healthcare settings. This has significant implications for practice and policy.

At this stage, 'guidelines' or 'guidance' that is available is either not directed at young people and/or is largely gleaned from the USA literature. In addition, it does not adequately capture the complexity of cases at front-line specialist settings. The management of young substance misusers in the UK is, in the main, 'beyond guidelines and guidance'.

The restricted treatment service network for young people in the UK makes the potential for undertaking studies on treatment effectiveness extremely limited, but because there is evidence of a growing number of young people requiring treatment, such specialist drug services require evaluation. Serious consideration of the establishment and funding of evaluation of treatment interventions to be delivered to young substance misusers in the UK is urgently needed.     

Neuron transplantation into mice hippocampus alters sensitivity to barbital narcosis

The role of several hippocampal innervations in the sensitivity to barbital-induced narcosis was studied in selected mice strains. The outbred and inbred mouse strains HS/Ibg, SABRA/HUC, C57BL, CBA/LAC, and BALB/c were tested for barbital-induced sleep (315 mg/kg). The relatively short sleeping HS/Ibg (HS) and the longest sleeping BALE/c (BALE) were chosen for further investigation. Cholinergic (ACh), serotonergic (5-HT), and noradrenergic (NE) innervations were studied in HS strain; whereas BALE, which possesses both an unusually high sensitivity to barbital and unique NE innervations in the cortex and hippocampus, was employed in a detailed study of the NE innervations. Transplantation of embryonic NE cells from the mouse embryo into the hippocampus of adult HS mice increased barbital narcosis by 65% (p < 0.05), whereas transplantation of 5-HT cells decreased barbital narcosis by 54% (p < 0.001). Transplantation of ACh cells had no significant effect on barbital-induced narcosis. BALB mice were subjected to NE cell transplantation into the hippocampus and cortex. Similarly to HS, BALB receiving NE transplants into their hippocampus slept 34% longer than control after barbital challenge (p < 0.025). Noradrenergic cell transplantation into frontal cortex had no effect on barbital sleep. The results suggest that (a) enhancement by neural grafting of the NE innervation to the hippocampus accentuates and enhancement of the 5-HT innervations attenuates the sensitivity to barbital narcosis, whereas ACh innervations have no effect on the sensitivity to barbital narcosis, and (b) the unusually high sensitivity of BALB mice to barbital may not be related to its unique NE innervations.