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Janne Evensen,1 Helene Lundgaard Soberg,2,3 Unni Sveen,2,3 Knut A Hestad,4,5 Berit Arnesveen Bronken4 1Department of Physical Medicine and Rehabilitation, Innlandet Hospital Trust, Gjøvik, Norway; 2Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway; 3Department of Physical Medicine and Rehabilitation, Oslo University Hospital, Oslo, Norway; 4Department of Health and Nursing Sciences, Faculty of Health- and Social Sciences, The Inland Norway University of Applied Sciences, Elverum, Norway; 5Department of Research, Innlandet Hospital Trust, Brumunddal, NorwayCorrespondence: Janne EvensenDepartment of Physical Medicine and Rehabilitation, Innlandet Hospital Trust, Gjøvik 2819, NorwayTel +47 61 11 75 00Email janne.evensen@sykehuset-innlandet.noAim: The primary aim of this study was to investigate the applicability of the Patient-Specific Functional Scale (PSFS) in patients with acquired brain injury (ABI) admitted to a specialized rehabilitation unit in a regional hospital. A secondary aim was to identify patient characteristics and functioning that predicted changes in the PSFS.Patients and Methods: In a cohort study, 59 patients with ABI were assessed for the ability to complete the PSFS. A trained multidisciplinary team applied the PSFS as part of a collaborative development of rehabilitation goals. The modified Rankin Scale (mRS), the Functional Ambulation Categories (FAC), the Rivermead Behavioural Memory Test (RBMT), the Norwegian Basic Aphasia Assessment (NBAA) and the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) were used to identify characteristics of the sample. Multivariate regression analyses were performed to investigate associations between changes in the PSFS score from admission to discharge and a selected set of participant baseline characteristics and functioning.Results: Fifty-four patients (92%) of the patients with ABI were able to complete the PSFS. The five (8%) who were unable to complete the PSFS had severe cognitive or language impairment. The PSFS score improved by a mean of 2.6 (SD 2.0) points from admission to discharge. The LOTCA score made the strongest unique contribution to explain the change in the PSFS score (beta = 0.477, p= 0.020).Conclusion: In the present study, most patients with ABI (92%) were able to complete the PSFS. Cognitive function on admission was a predictor of improved functioning on the PSFS.Keywords: multidisciplinary rehabilitation, patient-specific outcome measure, patient-identified goals, shared decision making

Helge Toft,1,2 Jørgen G Bramness,1,3 Lars Lien,1,4 Dawit S Abebe,1,5 Bruce E Wampold,6,7 Terje Tilden,6 Knut Hestad,4,8,9 Sudan Prasad Neupane1,10 1Norwegian National Advisory Unit on Concurrent Substance Abuse and Mental Health Disorders, Innlandet Hospital Trust, Ottestad, Norway; 2Institute of Clinical Medicine, University of Oslo, Oslo, Norway; 3Institute of Clinical Medicine, UiT, Norway's Arctic University, Tromsø, Norway; 4Department of Health Studies, Inland Norway University of Applied Sciences, Elverum, Norway; 5Department of Nursing and Health Promotion, Oslo Metropolitan University, Oslo, Norway; 6Research Institute, Modum Psychiatric Center, Vikersund, Norway; 7Department of Counseling Psychology, University of Wisconsin-Madison, Madison, WI, USA; 8Department of Research, Innlandet Hospital Trust, Brumunddal, Norway; 9Department of Psychology, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; 10Norwegian Center for Addiction Research (SERAF), Institute of Clinical Medicine, University of Oslo, Oslo, Norway Background: A reciprocal relationship between activated innate immune system and changes in mood and behavior has been established. There is still a paucity of knowledge on how the immune system responds during psychiatric treatment. We aimed to explore circulating cytokines and assess psychiatric symptom severity scores during 12 weeks of inpatient psychiatric treatment. Methods: The study was a longitudinal assessment of 124 patients (88 women and 36 men) in treatment at Modum Psychiatric Center, Norway. The patient sample comprised a mixed psychiatric population of whom 39 were diagnosed with posttraumatic stress disorder (PTSD). Serum blood samples for cytokine analysis and measures of mental distress using Global Severity Index were collected at admission (T0), halfway (T1), and before discharge (T2). Other factors assessed were age, gender, and the use of antidepressants and anti-inflammatory drugs. Multilevel modeling was used for longitudinal analyses to assess the repeated cytokine samples within each patient. Results: Overall level of IL-1RA was higher in PTSD patients when compared to those without PTSD (P=0.021). The level of IL-1β, MCP-1, and TNF-α increased over time in PTSD compared to non-PTSD patients (P=0.025, P=0.011 and P=0.008, respectively). All patients experienced reduced mental distress as measured by self-reported Global Severity Index scores. Stratified analysis showed that PTSD patients who used anti-inflammatory drugs had higher levels of IL-1β (P=0.007) and TNF-α (P=0.049) than PTSD patients who did not use such drugs. Conclusion: The study indicates that traumatized patients may have a distinct neuroimmune development during recovery. Their activated immune system shows even further activation during their rehabilitation despite symptom reduction. Keywords: cytokines, trauma, inflammation, PTSD, immune activation

Geir Ogrim,1–3 Knut A Hestad,3,4 Jan Ferenc Brunner,3,5,6 Juri Kropotov3,7,8 1Neuropsychiatric Unit, Østfold Hospital Trust, Fredrikstad, Norway; 2National Resource Center for ADHD, Tourettes' Syndrome and Narcolepsy, Oslo, Norway; 3Institute of Psychology, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; 4Division of Mental Health, Innlandet Hospital Trust, Brumunddal, Norway; 5Department of Physical Medicine and Rehabilitation, St Olav's Hospital, Trondheim, Norway; 6Department of Neuroscience, NTNU, Trondheim, Norway; 7Institute of the Human Brain, Russian Academy of Sciences, Saint Petersburg, Russia; 8Department of Neuropsychology, Andrzej Frycz Modrzewski Krakow University, Krakow, Poland Background: The aim of this study was to search for predictors of acute side effects of stimulant medication in pediatric attention deficit/hyperactivity disorder (ADHD), emphasizing variables from quantitative electroencephalography (QEEG), event-related potentials (ERPs), and behavior data from a visual continuous-performance test (VCPT). Methods: Seventy medication-naïve ADHD patients aged 7–16 years were tested with QEEG, including a go/no-go task condition (VCPT) from which behavior data and ERPs were extracted, followed by a systematic trial on stimulant medication lasting at least 4 weeks. Based on data from rating scales and interviews, two psychologists who were blind to the QEEG/ERP test results independently rated the patients as having no or small side effects (n = 37) or troublesome side effects (n = 33). We determined if the side effects were related to sex, age, IQ, ADHD subtype, comorbidities, clinical outcome, and variables in QEEG, ERPs, and VCPT. Results: There was a moderate negative correlation between clinical outcome and side effects. Three variables were significantly associated with side effects in a multivariate logistic regression analysis. In the ERP independent component – contingent negative variation – which reflected action preparation and time evaluation, patients with high amplitudes (close to normal values) experienced more side effects than patients with lower amplitudes. A faster-than-normal reaction time in VCPT was associated with side effects, as was a high amplitude in an early ERP component (early visual independent component), reported to be influenced by attention, perceptual sensitivity, and anxiety. Conclusion: The group with troublesome side effects had normal action-preparation electrical brain activity, a faster-than-normal reaction time, and an increased level of anxiety (measured by ERP) compared with the no side-effects group. Keywords: ADHD, stimulants, side effects, QEEG, ERP, go/no-go test

This study examined whether there are neuropsychological performance differences between human immunodeficiency virus-seropositive participants being followed at a University of Zambia clinic and demographically comparable seronegative controls being tested for infection in the same setting. All participants were administered a standardized neurocognitive test battery that has been found sensitive to HIV-associated Neurocognitive Disorder in the United States and internationally (e.g., in China, India, Romania, and Cameroon). The test battery was found to be applicable to a Zambian population. A clear HIV effect was seen with a medium to large overall effect size (Cohen d = 0.74). However, it was only the female seropositive participants who showed this HIV effect. HIV can result in neuropsychological deficits in Zambia, where clade C of the virus dominates. It is suggested that the HIV-infected women are more at risk of developing cognitive deficits than are men in this population, possibly because of sex-related social, financial, and healthcare disadvantages. However, further analyses are required regarding this conclusion because the finding was a result of an unplanned subanalysis. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: High and low blood pressure and apolipoprotein (Apo)-E epsilon4 alleles have been shown to be associated with dementia of the Alzheimer's type. The aim of this study was to examine the relationship between Apo-E epsilon4 allele status and the effect of antihypertensive treatment on cognitive performance in persons >/=80 years of age. METHODS: A sample of 258 individuals 80-102 years of age was studied. Associations between the Mini-Mental State Examination (MMSE) score and treatment with antihypertensive medication, blood pressure, Apo-E polymorphism, sex, age and education were assessed. Patients treated with antihypertensive drugs typically used two to ten different medications. RESULTS: Individuals with no Apo-E epsilon4 alleles who were not treated with antihypertensive medications had a significantly higher diastolic blood pressure than other participants in the study but no cognitive deficits. Participants who had at least one Apo-E epsilon4 allele who were not treated with antihypertensive medications scored significantly lower on the MMSE compared with other participants in the study. CONCLUSIONS: Individuals with an Apo-E epsilon4 allele who were not treated with antihypertensive medication showed the poorest cognitive performance. This could suggest that individuals with the Apo-E epsilon4 allele may benefit cognitively from treatment with antihypertensive drugs. [ABSTRACT FROM AUTHOR]

Members of three generations of a Norwegian family (N = 9) with a rare demyelinating disease were studied. Neuropsychological testing was performed using the Mini Mental Status Examination (MMSE), Wechsler Intelligence Scale-III (WAIS-III), and Hopkins Verbal Learning Test-Revised (HVLT-R). EEGs were recorded with grand averaging spectrograms and event-related potentials (ERPs) in rest and cued GO/NOGO task conditions. The results were within the normal range on the MMSE. Full-scale WAIS-III results were in the range of 69-113, with lower scores in verbal understanding than in perceptual organization, and low scores also in indications of working memory and processing speed difficulties. The HVLT-R showed impairment of both immediate and delayed recall. Quantitative EEG showed an increase in low alpha (around 7.5 Hz) activity in the temporofrontal areas, mostly on the left side. There was a deviation in the late (>300 ms) component in response to the NOGO stimuli. A strong correlation (r = 0.78, p = 0.01) between the Hopkins Verbal Learning Test (delayed recall) and the amplitude of the NOGO ERP component was observed. The EEG spectra showed deviations from the healthy controls, especially at frontotemporal deviations. Deviations in the ERP component of the NOGO trials were related to delayed recall in the Hopkins Verbal learning test.

Objectives: To explore the rehabilitation goals measured with the Patient-Specific Functional Scale (PSFS) in patients undergoing acute and subacute stroke rehabilitation. In addition, to assess whether PSFS goals corresponded to impairments and activity limitations, as identified by standardized measures., Design: Observational study., Participants: A total of 71 participants undergoing inpatient stroke rehabilitation., Methods: The PSFS goals were linked to second-level categories in the International Classification of Functioning, Disability and Health (ICF), using established linking rules. Frequencies of the linked ICF categories were calculated. Frequencies of participants with limitations in walking, activities of daily living (ADL), vision, language, and cognition, were calculated, along with goals in corresponding areas of functioning., Results: The participants' goals were linked to 50 second-level ICF categories, comprising areas such as walking and moving, ADL, language, vision, and cognition. The most frequent ICF categories were "Moving around in different locations" (n = 24), "Walking" (n = 23), "Toileting" (n = 16), "Hand and arm use (n = 12) and "Fine hand use (n = 12)". Of participants with limitations in walking, cognition, and vision, 85%, 10%, and 16%, respectively, had goals in these areas., Conclusion: Participants' goals included walking, ADL, language, vision, and cognition. Few with impairments in cognition or vision had goals in these corresponding areas on the PSFS.

Objective: This study investigated the validity, reliability, responsiveness, and interpretability of the Patient-Specific Functional Scale (PSFS) in subacute stroke rehabilitation to determine its suitability to measure patient-identified rehabilitation goals., Methods: A prospective observational study was designed according to the checklist from Consensus-Based Standards for Selecting Health Measurement Instruments. Seventy-one patients diagnosed with stroke were recruited in the subacute phase from a rehabilitation unit in Norway. The International Classification of Functioning, Disability and Health was used to assess the content validity. Assessment of construct validity was based on hypotheses for correlation of the PSFS and comparator measurements. We assessed reliability by calculating the Intraclass Correlation Coefficient (ICC) (3.1) and the standard error of measurement. The assessment of responsiveness was based on hypotheses for the correlation of change scores between the PSFS and the comparator measurements. A receiver operating characteristic analysis was conducted to assess responsiveness. The smallest detectable change and minimal important change were calculated., Results: Eighty percent of the PSFS items were classified as activities and participation in the International Classification of Functioning, Disability and Health, indicating satisfactory content validity. The reliability was satisfactory with an ICC of 0.81 (95% CI = 0.69-0.89). The standard error of measurement was 0.70 point, and the smallest detectable change was 1.94 points. Five of 7 hypotheses were confirmed for construct validity, and 5 of 6 were confirmed for responsiveness, indicating moderate construct validity and high responsiveness. Assessing responsiveness with a criterion approach resulted in an area under the curve of 0.74. A ceiling effect was identified for 25% of the participants 3 months after discharge. The minimal important change was estimated to be 1.58 points., Conclusion: This study demonstrates satisfactory measurement properties for the PSFS in individuals undergoing inpatient stroke rehabilitation., Impact: This study supports the use of the PSFS to document and monitor patient-identified rehabilitation goals in patients receiving subacute stroke rehabilitation when applied using a shared decision approach., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Physical Therapy Association.)

Despite the fact that many coinfections in people with HIV (PWH) are treatable or suppressible, they may still impact neurocognitive (NC) functioning. Here, we aim to evaluate the presence of latent/treated coinfections and their association with NC functioning in a cohort of PWH in Zambia. We carried out a cross-sectional, nested study involving 151 PWH with viral suppression, and a normative sample of 324 adults without HIV. Plasma samples from PWH who underwent a comprehensive NC assessment were evaluated for the presence of treated/latent coinfections that are common in Zambia. Information about treated pulmonary tuberculosis (TB) was obtained from participants' clinical charts. Overall, PWH differed significantly from the HIV seronegatives on all neuropsychological domains except for fine motor control. ANOVA comparisons of all 3 HIV + groups' demographically corrected mean NC T-scores showed that the HIV + /TB + group had the poorest NC functioning in the following domains: executive functioning (F = 4.23, p = 0.02), working memory (F = 5.05, p = 0.002), verbal fluency (F = 4.24, p = 0.006), learning (F = 11.26, p < 0.001), delayed recall (F = 4.56, p = 0.01), and speed of information processing (F = 5.16, p = 0.005); this group also was substantially worse on the total battery (global mean T-scores; F = 8.02, p < 0.001). In conclusion, treated TB coinfection in PWH was associated with worse NC performance compared to both those with antibodies against other coinfections and without. PWH with antibodies for other coinfections (HIV + /CI +) showed somewhat better NC performance compared to those without (HIV + /CI -), which was not expected, although comparisons with the HIV + /CI + group are limited by its lack of specificity regarding type of coinfection being represented., (© 2023. Journal of NeuroVirology, Inc.)

Bovine mastitis infection in dairy cattle is a significant economic burden for the dairy industry globally. To reduce the use of antibiotics in treatment of clinical mastitis, new alternative treatment options are needed. Antimicrobial peptides from bacteria, also known as bacteriocins, are potential alternatives for combating mastitis pathogens. In search of novel bacteriocins against mastitis pathogens, we screened samples of Norwegian bovine raw milk and found a Streptococcus uberis strain with potent antimicrobial activity toward Enterococcus , Streptococcus, Listeria , and Lactococcus . Whole-genome sequencing of the strain revealed a multibacteriocin gene cluster encoding one class IIb bacteriocin, two class IId bacteriocins, in addition to a three-component regulatory system and a dedicated ABC transporter. Isolation and purification of the antimicrobial activity from culture supernatants resulted in the detection of a 6.3-kDa mass peak by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry, a mass corresponding to the predicted size of one of the class IId bacteriocins. The identification of this bacteriocin, called ubericin K, was further confirmed by in vitro protein synthesis, which showed the same inhibitory spectrum as the purified antimicrobial compound. Ubericin K shows highest sequence similarity to the class IId bacteriocins bovicin 255, lactococcin A, and garvieacin Q. We found that ubericin K uses the sugar transporter mannose phosphotransferase (PTS) as a target receptor. Further, by using the pHlourin sensor system to detect intracellular pH changes due to leakage across the membrane, ubericin K was shown to be a pore former, killing target cells by membrane disruption. IMPORTANCE Bacterial infections in dairy cows are a major burden to farmers worldwide because infected cows require expensive treatments and produce less milk. Today, infected cows are treated with antibiotics, a practice that is becoming less effective due to antibiotic resistance. Compounds other than antibiotics also exist that kill bacteria causing infections in cows; these compounds, known as bacteriocins, are natural products produced by other bacteria in the environment. In this work, we discover a new bacteriocin that we call ubericin K, which kills several species of bacteria known to cause infections in dairy cows. We also use in vitro synthesis as a novel method for rapidly characterizing bacteriocins directly from genomic data, which could be useful for other researchers. We believe that ubericin K and the methods described in this work will aid in the transition away from antibiotics in the dairy industry.

Objective : The aim of the study was to determine if systolic blood pressure (SBP), total-tau (t-tau), and beta-amyloid (Aβ) in the cerebral spinal fluid (CSF) were associated with the results on the Consortium to Establish a Registry for Alzheimer's Disease Word List (CERAD-WL) immediate and delayed recall, and the Mini Mental State Examination (MMSE) in "younger" older adults, controlling for age and sex. Method : We included 72 participants, mean age: 62.9 (SD 8.6, range 41-76) from a Norwegian memory clinic; eight were diagnosed with subjective cognitive decline, 32 with mild cognitive impairment (MCI), 30 with dementia of the Alzheimer's type (DAT), and two with combined DAT and vascular dementia (VaD). Data were examined in three fitted multiple linear regression models using the CERAD-WL immediate and delayed recall, and MMSE as dependent variables; and SBP, t-tau, and Aβ as independent variables, controlling for age and sex. Results : The strongest associations were found in the model using CERAD-WL delayed recall as the dependent variable, where 45% of the variance was explained (standardized Beta = -0.313, p = 0.004 for t-tau and standardized Beta -0.238, p = 0.01 for SBP). The unique contribution of age was close to 8%, t-tau close to 7%, and SBP above 5%. When cardiovascular medication was entered into the analysis, the explained variance increased to 51% and Aβ became significant (standardized Beta = 0.216, p = 0.03). Participants on this medication exhibited worse performance on CERAD-WL delayed recall than those who were not on medication. Age (7%), t-tau (6%), and SBP (5%) showed the same unique contribution, whereas medication contributed 6% and Aβ contributed 4%. CERAD-WL immediate recall, and MMSE yielded similar findings, but explained variance was poorer for these two variables. Conclusions : Both elevated SBP and t-tau were associated with poorer cognitive performance, especially delayed recall. Those on cardiovascular medication were more impaired than were participants who were not on this medication-a finding that probably reflected cerebral incidents in the medicated group., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hestad, Horndalsveen and Engedal.)

Objective: It is unknown whether systolic blood pressure (SBP) drop is part of the normal aging process or due to the onset of dementia for some people. SBP drop is referring to the decrease in blood pressure often seen before death. Thus, the aim of this study was to examine whether SBP at time of diagnosis of dementia, mild cognitive impairment, or subjective cognitive decline was associated with years prior to death, and whether these associations were modified by diagnoses, age, and sex., Methods: Participants were 2,236 patients from the Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog), who died during follow-up (2009-2017) for whom we had valid blood pressure measurements. Mean age at diagnosis was 77.5 years (SD 8.3), and patients were followed for an average of 3.9 years (SD 2.2, maximum 10.5 years). The patients had subjective cognitive decline (95), mild cognitive impairment (573), dementia (1,401), or no diagnoses related to cognitive deficits (167). SBP as dependent variable was regressed against years prior to death., Results: In men, SBP was 1.8 mmHg lower per year closer to death (p < .01), and this trend was linear without any acceleration. This association between years prior to death and SBP in men was not modified by age, year of diagnosis, or diagnosis. There was no such association in women., Conclusion: SBP was significantly lower for those diagnosed close to death in men, but not in women. This association was not modified by either age or onset of diagnosis. Thus, the lowering of SBP is more related to closeness to death and sex than to dementia or age. The downward trend was linear all 10 years prior to death, with no acceleration closer to death., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: HIV infection may result in neurocognitive deficits, but the effects of pulmonary tuberculosis (TB+), a common comorbid condition in HIV infection, on cognition in HIV infections are unknown. Accordingly, we examined the effects of TB+, on neurocognitive functioning in HIV-infected (HIV+) Zambian adults., Setting: All participants were drawn from HIV clinics in and around Lusaka, the capital of Zambia., Methods: Participants were 275 HIV+, of whom 237 were HIV+ and TB-negative (HIV+/TB-), and 38 also had pulmonary TB+ (HIV+/TB+). Controls were 324 HIV- and TB-uninfected (HIV-) healthy controls. All HIV+ participants were prescribed combination antiretroviral treatment (cART). Published, demographically corrected Zambian neuropsychological norms were used to correct for effects of age, education, sex, and urban/rural residence., Results: Neuropsychological deficits, assessed by global deficit scores, were more prevalent in this order: 14% (46 of 324) of HIV- controls, 34% (80 of 237) of HIV+/TB-, and 55% (21 of 38) of HIV+/TB+ group. Thus, both HIV-infected groups evidenced more impairment than HIV- controls, and the HIV+/TB+ group had a higher rate of neurocognitive impairment than the HIV+/TB- group. HIV+/TB+ patients were more likely to be male, younger, less-educated, and have lower CD4 counts and detectable HIV RNA in blood compared with the HIV+/TB- patients., Conclusions: In HIV infection, TB may contribute to cognitive impairment, even after controlling for lower CD4 counts and viral load. Thus, systemic inflammation from HIV and TB and more advanced immune deficiency at diagnosis of HIV may contribute to impaired cognition in HIV+/TB+ patients.

Objective: Older age and lower education levels are known to be associated with worse neurocognitive (NC) performance in healthy adults, and individuals with HIV infection may experience accelerated brain/cognition aging. However, higher education may possibly protect against HIV-associated neurocognitive disorders (HAND). The aim of the current cross-sectional study was to assess the effect of age and education in an HIV-1 clade C infected adult population in urban Zambia., Method: Demographically corrected Zambian norms on a neuropsychological (NP) test battery were used to correct for normal age and education effects. The study assessed 286 HIV positive (+) males (37.1%) and females (62.9%) with a mean age of 41.35 (SD = 8.56) and mean years of education = 10.16 (SD = 2.18). A comprehensive NP test battery was used to assess cognitive domains frequently affected by HIV: attention/working memory, learning/and delayed recall, executive function, verbal fluency, processing speed, verbal and visual episodic memory, and fine motor skills., Results: In younger HIV+ Zambians, higher education evidenced protective effects against NC impairments overall, and for the specific domains of executive functions, learning and speed of information processing. Impairment scores did not support accelerated overall brain aging although the restricted age range and relative youth of our total sample may have precluded detection of such tendencies., Conclusions: The present study raises the need to investigate factors that could be implicated in the poor neurocognitive performance among the younger, less educated HIV+ individuals in Zambia. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

It has been suggested that the metabolic enzyme indoleamine 2,3-dioxygenase (IDO) is a biological mediator of inflammation related to the psychopathology of depression, with a Kynurenine (KYN) increase in the Tryptophan (TRP) metabolic pathway, resulting in reduced Serotonin. In this study, we examined KYN, TRP, and the ratio of KYN to TRP concentrations × 10 3 (KT Ratio) in serum and cerebrospinal fluid (CSF) in (a) a group of depressed patients and (b) a control group of patients referred to a neurologic outpatient clinic for whom no specific diagnosis could be established. The KT Ratio is considered an index that represents IDO. The participants were examined with the Beck Depression Inventory II (BDI-II), the Montgomery Aasberg Depression Rating Scale (MADRS), and a neuropsychological test battery. We found no significant differences between the two study groups with respect to TRP, KYN, or KT Ratio in serum or CSF. Differences in neuropsychological performance between the two patient groups could be seen in the following tests: Animal Fluency, Digit Symbol, the DKEFS Color-Interference Test (Naming Part), Trail Making Test A and B, and the Grooved Pegboard Non-dominant Hand. KYN in serum correlated highly with KYN in CSF. KYN in serum correlated significantly with both age and gender. When analyzing males and females separately, we found that women had a lower level of TRP in both serum (Mann-Whitney U -test: TRP in Serum; p = 0.001) and CSF (Mann-Whitney U -test: TRP in CSF; p = 0.003). Women had a lower level of KYN in serum ( p = 0.029) than men did. Age was positively associated with KYN. KYN in CSF correlated only with age, however; there were no gender differences. No significant relationship was seen between BDI-II and MADRS on the one hand, and KYN and TRP on the other. KYN in CSF as the KT Ratio in both serum and CSF was associated with neuropsychological performance. Thus, we suggest that KYN and KT Ratio are related more strongly to neuropsychological performance than to affective symptoms in depression.

This is a study of neuroAIDS in sub-Saharan Africa, involving 266 Zambian adults infected with the human immunodeficiency virus (HIV), clade C. All HIV+ participants were receiving combination antiretroviral therapy (CART), and were administered a comprehensive neuropsychological (NP) test battery covering seven ability domains that are frequently affected by neuroAIDS. The battery was developed in the U.S. but has been validated in other international settings and has demographically-corrected normative standards based upon 324 healthy Zambian adults. Compared to the healthy Zambian controls, the HIV+ sample performed worse on the NP battery with a medium effect size (Cohen's d = 0.64). 34.6 % of the HIV+ individuals had global NP impairment and met criteria for HIV associated neurocognitive disorder (HAND). The results indicate that the Western-developed NP test battery is appropriate for use in Zambia and can serve as a viable HIV and AIDS management tool.

Objective: To conduct a blind study of quantitative electroencephalogram-band amplitudes in patients with anorexia nervosa (AN) and healthy controls., Methods: Twenty-one patients with AN and 24 controls were examined with eyes-closed 16-channel electroencephalogram. Main variables were absolute alpha, theta, and delta amplitudes in frontal, temporal, and posterior regions., Results: There were no significant differences between the AN patients and controls regarding absolute regional band amplitudes in μV. Borderline significance was found for anterior theta ( P =0.051). Significantly increased left and right frontal electrode theta amplitude was found in AN patients (F3, P =0.014; F4, P =0.038) compared to controls. Significant differences were also observed for secondary variables: lower values for relative parietooccipital delta and frontocentral alpha activity among AN patients than among controls., Conclusion: We observed slight excess frontal theta and lower relative alpha and delta amplitudes among AN patients than among controls. This pattern is possibly related to a slight frontal lobe dysfunction in AN, or it may reflect increased attention/vigilance or another state-related change in patients with AN compared to healthy controls.

Objective: Human depression is a major burden, both on the individuals who suffer from the disease and on society at large. Traditionally, depression has been linked to psychological and biological causes, but there has been increasing interest in the gut-brain axis. In this regard, we have recently shown that specific bacteria are correlated with human depression, and we hypothesize that volatile fatty acids (VFAs) are mediators., Methods: Here, we analyzed the direct correlation between VFAs, depression and cortisol in a cohort consisting of 34 depressed patients and 17 controls., Results: We found statistically significant correlations between depression and the VFA isovaleric acid, as well as between isovaleric acid and cortisol. Furthermore, bacteria that previously have been identified as being correlated with depression were also correlated with isovaleric acid. Isovaleric acid showed a bimodal distribution in which the depressed patients were overrepresented in the high level group (P < 0.00005, binominal test)., Discussion: It has recently been shown that gut-derived VFAs can cross the blood-brain barrier, where isovaleric acid interferes with synaptic neurotransmitter release. The multiple correlation patterns, in addition to a potential mechanistic model, point towards a potential causal relationship between depression and isovaleric acid.

Human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) are frequently associated with neurocognitive impairment (NCI). However, few studies have examined the interrelationship between gender and NCI in the HIV and AIDS population. This cross-sectional study examined the neurocognitive (NC) functioning of HIV-infected male and female adults from urban Zambia. The participants included 266 HIV seropositive (HIV+) adults (males [n=107] and females [n=159]). Participants completed NC assessment by means of a comprehensive test battery using normative data from 324 HIV-seronegative (HIV-) controls. The norms corrected for effects of age, education, and gender in the general population, and the test battery measures domains of attention/working memory (learning and delayed recall), executive function, verbal fluency, processing speed, verbal and visual episodic memory, and fine motor skills. An overall comparison of the HIV+ male and female participants yielded no statistically significant differences. Analysis of covariance results controlling for disease characteristics showed that HIV+ female participants had worse delayed recall scores than males, F(1,117) =9.70, P=0.002, partial η(2)=0.077. The females also evidenced a trend toward greater impairment on learning efficiency (P=0.015). The findings suggest that there are gender-related differences in NCI after controlling for disease characteristics. It was observed that although the HIV+ females enjoyed better health compared to their HIV+ male counterparts, they still had worse performance on the neuropsychological tests. This implies that HIV may have more NC consequences for Zambian females than males.

Introduction: Depression is considered an independent risk factor for hypertension, particularly for people with recurrent episodes or a long history of depression. Another risk factor for cardiovascular disease is the Apolipoprotein E e4 allele (ApoE e4). The aim of this study was to examine how ApoE e4 was related to blood pressure (BP) in patients with depression and a control group., Methods: A total of 78 patients, 49 with depression and 29 without, all recruited from the same hospital, underwent ApoE e genotyping (24 had at least one ApoE e4 allele) and examination of BP., Results: In the depression group, but not in the control group, both systolic and diastolic BP were significantly higher in patients with ApoE e4 than in those without. The effect of ApoE e4 on BP differed significantly between the two groups., Conclusion: Our findings showed that the effect of ApoE e4 on BP differed between the patients with depression and the control group. In patients with depression, ApoE e4 was associated with an increase in BP. We suggest that patients with depression and ApoE e4-positive status are particularly prone to develop BP elevation.

Introduction: Several reports indicate that inflammation may play a role in depression and demonstrate enhanced systemic levels of inflammatory mediators. We hypothesized that 44 patients with a diagnosis of depression would present with a specific and different serum and cerebrospinal fluid (CSF) cytokine profile compared to 21 patients with diffuse neurological symptoms, of whom 15 had fatigue as a major symptom, but no change in emotional state., Methods: The diagnoses of the patients with depression were according to the International Classification of Diseases, tenth edition (F32-34 spectra). Cytokine profiles in serum and CSF were determined by multiplex analysis, including 27 cytokines, chemokines, and growth factors., Results: No differences could be found between the two groups studied regarding cytokine levels in serum or CSF except for serum interleukin (IL)-1 receptor antagonist that was lower in the depression group. There were only four high correlations (>0.4) between serum and CSF levels of the cytokines, reflecting independent synthesis and turnover in these two compartments. In the control group, fatigue was associated with increased IL-1 receptor antagonist, IL-10, granulocyte-colony stimulating factor, and interferon-γ (all P<0.01)., Conclusion: Patients with depression had a similar cytokine profile as nondepressive patients, both systemically and in CSF. Fatigue was associated with higher levels of some inflammatory markers in the control group. It is possible that the presence of fatigue in a large proportion of patients and controls could contribute to the lack of difference in cytokine levels between these two groups.

Healthy Zambian adults (N = 324) were evaluated to determine to what degree a Western neuropsychological (NP) test battery, with African American norms adjusted for age, gender, and education could be used in healthy Zambians, including 157 men (48.46%) and 167 women (51.54%) with an average age of 38.48 (SD = 12.80) years and an average education level of 11.02 (SD = 2.58) years. The NP battery included tests of attention/working memory, executive function, verbal fluency, processing speed, verbal and visual episodic memory, and fine motor skills. The Zambian Achievement Test (ZAT) and the U.S. Wide Range Achievement Test-4 (WRAT-4) reading subtest also were administered to assess literacy and quality of education. Similar to findings in Western countries, the Zambian results show substantial age and education effects on most tests and smaller, less consistent effects of gender. Beyond the basic demographic effects, urban/rural background had small effects on some cognitive variables, and the ZAT (but not WRAT-4) reading level was a robust predictor of performance on many NP tests, even when other background characteristics were controlled. Women in the United States tend to outperform men on tests of processing speed and episodic memory. However, Zambian women showed modest but statistically significant disadvantages versus their male counterparts. The results show that tests developed in the United States may be used in Zambia. Nevertheless, development and use of local cultural norms remains very important and is a must. New demographically corrected norms were developed for the cohort that was examined., ((c) 2016 APA, all rights reserved).)

Background: We searched for predictors of the clinical outcome of stimulant medication in pediatric attention-deficit/hyperactivity disorder (ADHD), emphasizing variables from quantitative electroencephalography, event-related potentials (ERPs), and behavioral data from a visual go/no-go test., Methods: Nineteen-channel electroencephalography (EEG) was recorded during the resting state in eyes-open and eyes-closed conditions and during performance of the cued go/no-go task in 98 medication-naïve ADHD patients aged 7-17 years and in 90 controls with the same age and sex distribution as the patients. For patients, the recording was followed by a systematic trial on stimulant medication lasting at least 4 weeks. Based on data from rating scales and interviews, two psychologists who were blind to the electrophysiological results independently rated the patients as responders (REs) (N=74) or non-responders (non-REs) (N=24). Using a logistic regression model, comparisons were made between REs and non-REs on the EEG spectra, ERPs (cue P3, contingent negative variation, and P3 no-go of the ERP waves and independent components [ICs] extracted from these waves), reaction time, reaction time variability, number of commission and omission errors, intelligence quotient, age, sex, ADHD subtype, and comorbidities., Results: The two groups differed significantly on eight of the variables, with effect sizes (Cohen's d) ranging from 0.49 to 0.76. In the multivariate logistic regression analysis, only three of these variables were significantly associated with clinical outcome. The amplitude of the IC cue P3, which has a parietal-occipital distribution, was normal in REs but significantly smaller in non-REs, whereas the centrally distributed IC P3 no-go early was smaller in REs than in non-REs and controls. In addition, the REs had more power in the EEG theta band. A quartile-based index was calculated using these three variables. The group with the lowest scores comprised only 36% REs; response rates in the three other groups were 83%, 86%, and 89%., Conclusion: The clinical outcome of stimulant medication was best predicted by electrophysiological parameters. The brain dysfunctions of the REs appear to be primarily associated with prefrontal lobe hypoactivation. The non-REs were deviant from the controls in parietal-occipital functions.

Objective: The purpose of this pilot study was to compare the effects of 30 sessions of neurofeedback (NF) with stimulant medication on attention-deficit/hyperactivity disorder (ADHD) patients., Methods: Thirty-two medication-naïve ADHD patients, ages 7-16, from a neuropsychiatric clinic, were randomized to NF (n=16) or drug treatment (n=16). Other actions, such as parent management training, information, or support in school were given as needed, with no differences between the groups. All participants were assessed before treatment on two rating scales, each with parent and teacher forms. In addition, quantitative electroencephalogram (QEEG) and event-related potentials (ERPs), which included behavioral data from a go/no go test were administered. NF training took place in the clinic over a period of 7-11 months, and was followed by a repeat of the same assessment tools. The mean time interval between pre- and postassesment was not significantly different in the two groups. The 18 symptoms of ADHD (American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV)) were used as the primary outcome measure., Results: Analysis of covariance revealed a significant difference between the groups at evaluation in favor of medication, with a large effect size. This picture was confirmed by other outcome measures. The QEEG spectral power in the theta and beta bands did not change in either group. In ERP, the P3 no go component increased significantly in 8 of 12 patients who had a clinically relevant medication effect, but did not increase in the medication nonresponders or the NF group., Conclusions: Our study supports effects for stimulants, but not for NF. Effects of NF may require thorough patient selection, frequent training sessions, a system for excluding nonresponders, and active transfer training. The P3 no go ERP component may be a marker for treatment response.

Various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis, spondyloarthritis, vasculitis and systemic lupus erythematosus, are associated with premature atherosclerosis. However, premature atherosclerosis has not been uniformly observed in systemic sclerosis. Furthermore, although experimental models of atherosclerosis support the role of antiphospholipid antibodies in atherosclerosis, there is no clear evidence of premature atherosclerosis in antiphospholipid syndrome (APA). Ischemic events in APA are more likely to be caused by pro-thrombotic state than by enhanced atherosclerosis. Cardiovascular disease (CVD) in ARDs is caused by traditional and non-traditional risk factors. Besides other factors, inflammation and immunologic abnormalities, the quantity and quality of lipoproteins, hypertension, insulin resistance/hyperglycemia, obesity and underweight, presence of platelets bearing complement protein C4d, reduced number and function of endothelial progenitor cells, apoptosis of endothelial cells, epigenetic mechanisms, renal disease, periodontal disease, depression, hyperuricemia, hypothyroidism, sleep apnea and vitamin D deficiency may contribute to the premature CVD. Although most research has focused on systemic inflammation, vascular inflammation may play a crucial role in the premature CVD in ARDs. It may be involved in the development and destabilization of both atherosclerotic lesions and of aortic aneurysms (a known complication of ARDs). Inflammation in subintimal vascular and perivascular layers appears to frequently occur in CVD, with a higher frequency in ARD than in non-ARD patients. It is possible that this inflammation is caused by infections and/or autoimmunity, which might have consequences for treatment. Importantly, drugs targeting immunologic factors participating in the subintimal inflammation (e.g., T- and B-cells) might have a protective effect on CVD. Interestingly, vasa vasorum and cardiovascular adipose tissue may play an important role in atherogenesis. Inflammation and complement depositions in the vessel wall are likely to contribute to vascular stiffness. Based on biopsy findings, also inflammation in the myocardium and small vessels may contribute to premature CVD in ARDs (cardiac ischemia and heart failure). There is an enormous need for an improved CVD prevention in ARDs. Studies examining the effect of DMARDs/biologics on vascular inflammation and CV risk are warranted., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: The therapeutic alliance is related to better course and outcome of treatment in schizophrenia. This study explores predictors and characteristics of the therapeutic alliance in recent-onset schizophrenia spectrum disorders including the agreement between patient and therapist alliance ratings., Methods: Forty-two patients were assessed with demographic, neurocognitive, and clinical measures including the Positive and Negative Syndrome Scale (PANSS). The therapeutic alliance was measured with the Working Alliance Inventory - Short Form (WAI-S)., Results: Patient WAI-S total scores were predicted by age and PANSS excitative symptoms. Therapist WAI-S total scores were predicted by PANSS insight. Patient and therapist WAI-S total scores were moderately associated. Neurocognition was not associated with working alliance., Conclusion: Working alliance is associated with specific demographic and symptom characteristics in patients with recent-onset schizophrenia spectrum disorders. There is moderate agreement between patients and therapists on the total quality of their working alliance. Findings highlight aspects that may increase therapists' specificity in the use of alliance-enhancing strategies.

Aims/hypothesis: In diabetic children and adolescents, a history of severe hypoglycaemia (SH) has been associated with increased slow EEG activity and reduced cognition, possibly due to harmful effects of SH on the developing brain. In a group of type 1 diabetic patients with early exposure to SH, who had EEG abnormalities and reduced cognition in childhood, we have recently demonstrated that the reduced cognition may persist into adulthood. We have now assessed whether the reduced cognition was accompanied by lasting EEG abnormalities., Methods: In 1992-1993, we studied EEG and cognition in 28 diabetic children and 28 matched controls. 16 years later, we re-investigated the same participants, with 96% participation rate. Diabetic participants were classified as with (n = 9) or without (n = 18) early SH, defined as episodes with convulsions or loss of consciousness by 10 years of age. For each EEG band (delta, theta, alpha and beta) and cerebral region (frontocentral, temporal, and parietooccipital), we calculated relative amplitudes and amplitude asymmetry. We also calculated occipital alpha mean frequency, alpha peak frequency at maximum amplitude, alpha peak width, and theta regional mean frequencies. We examined whether these EEG measures, relative to age- and sex-matched controls, differed between diabetic participants with and without early SH., Results: We found no association of early SH with any of the EEG measures., Conclusions/interpretation: Childhood SH was not associated with EEG abnormalities in young type 1 diabetic adults. Our findings suggest that the reduced adulthood cognition associated with childhood exposure to SH is not accompanied by lasting EEG abnormalities.