Effect of coinfections on neurocognitive functioning among people with clade C HIV infection in Zambia.

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.

APOE - a genetic marker of comorbidity in subjects with morbid obesity.

BACKGROUND: In population-based studies, the genetic variability of the APOE E alleles have been associated with health outcomes. Health problems are common in subjects with obesity. This study explored associations between the APOE E alleles and comorbidity in subjects with morbid obesity. METHODS: The study included consecutive subjects referred for evaluation of bariatric surgery with morbid obesity (defined as BMI > 40 or > 35 kg/m2 with complications related to obesity). The subjects followed a conservative weight loss program for 6 months before surgery and had a follow-up visit 12 months after surgery. Demographic data and a set psychosomatic scores (musculoskeletal pain, WHO-5 Well-Being Index, Rosenberg Self-Esteem Scale, Hopkins Symptom Check-list 10; Epworth Sleepiness Scale, and Fatigue Severity Scale) were collected, and blood samples were analysed for haematological and biochemical parameters and APOE alleles. RESULTS: One hundred and forty subjects (men/women: 32 (23%)/108 (77%) with mean age 43.0 (SD 8.7) years and BMI 42.1 (SD 3.8) kg/m2 were included. One hundred and eight and 92 subjects had data after conservative treatment and 12 months after surgery, respectively. The prevalence of the APOE alleles were: E2E2: 1 (0.7%), E2E3: 13 (9.3%), E2E4: 4 (2.9%), E3E3: 71 (50.7%), E3E4: 47 (33.6%), and E4E4: 4 (2.9%). The prevalence rates were as anticipated in a Norwegian population. The weight loss during conservative treatment and after bariatric surgery was independent of E allele variability. E2 was associated with a significant or clear trend toward improvement of all psychosomatic disorders. There was a significant fall in CRP during the two treatment periods with weight loss. E2 and E4 were significantly associated with high and low CRP, respectively, but no associations were seen between CRP and comorbidity. CONCLUSIONS: The most marked finding was the association between E2 and improvement of all psychosomatic disorders. The positive and negative associations between CRP and E2 and E4, respectively, could indicate effects on inflammation and immunological reactions.

Use of Western Neuropsychological Test Battery in Detecting HIV-Associated Neurocognitive Disorders (HAND) in Zambia.

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.

Faecal short-chain fatty acids - a diagnostic biomarker for irritable bowel syndrome?

BACKGROUND: The diagnosis of irritable bowel syndrome (IBS) relies on symptom-based criteria. A valid and reliable biomarker that could confirm the diagnosis is desirable. This study evaluated the properties of faecal short-chain fatty acids (SCFA) as diagnostic biomarkers for IBS. METHODS: Twenty-five subjects with IBS and 25 controls were included in this explanatory case-control study. Stool samples were analysed for SCFA (acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and isovaleric acid) with gas chromatography and reported as mmol/l and molar%. In the search for the best way to distinguish between subjects with and without IBS, the total amount and the amount of each of the SCFA were measured, and the proportions and differences between the SCFA were calculated. RESULTS: In the IBS and control group, the mean age was 46.2 (SD 12.9) and 49.2 (SD 14.6), and the number of females was 13/25 (52 %) and 15/25 (60 %) respectively. The difference between propionic and butyric acid (mmol/l) had the best diagnostic properties, the area under the Receiver Operating Characteristic curve was 0.89 (95 % CI: 0.80-0.98) (p < 0.001). With a cut-off value > 0.015 mmol/l indicating IBS, the sensitivity, specificity, positive and negative likelihood ratio, and diagnostic odds ratio were 92 %, 72 %, 3.29, 0.11 and 29.6 respectively. Similar diagnostic properties were shown for all the IBS subgroups. CONCLUSIONS: The study indicated that faecal SCFA could be a non-invasive, valid and reliable biomarker for the differentiation of healthy subjects from subjects with IBS.

Treatment strategies in Alzheimer's disease: a review with focus on selenium supplementation.

Alzheimer's disease (AD) is a neurodegenerative disorder presenting one of the biggest healthcare challenges in developed countries. No effective treatment exists. In recent years the main focus of AD research has been on the amyloid hypothesis, which postulates that extracellular precipitates of beta amyloid (Aß) derived from amyloid precursor protein (APP) are responsible for the cognitive impairment seen in AD. Treatment strategies have been to reduce Aß production through inhibition of enzymes responsible for its formation, or to promote resolution of existing cerebral Aß plaques. However, these approaches have failed to demonstrate significant cognitive improvements. Intracellular rather than extracellular events may be fundamental in AD pathogenesis. Selenate is a potent inhibitor of tau hyperphosphorylation, a critical step in the formation of neurofibrillary tangles. Some selenium (Se) compounds e.g. selenoprotein P also appear to protect APP against excessive copper and iron deposition. Selenoproteins show anti-inflammatory properties, and protect microtubules in the neuronal cytoskeleton. Optimal function of these selenoenzymes requires higher Se intake than what is common in Europe and also higher intake than traditionally recommended. Supplementary treatment with N-acetylcysteine increases levels of the antioxidative cofactor glutathione and can mediate adjuvant protection. The present review discusses the role of Se in AD treatment and suggests strategies for AD prevention by optimizing selenium intake, in accordance with the metal dysregulation hypothesis. This includes in particular secondary prevention by selenium supplementation to elderly with mild cognitive impairment.

Isovaleric acid in stool correlates with human depression.

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.

Central Coherence, Visuoconstruction and Visual Memory in Patients with Eating Disorders as Measured by Different Scoring Methods of the Rey Complex Figure Test.

OBJECTIVE: The aims of this study were to examine the performance of eating disorder (ED) patients on the Rey Complex Figure Test and to investigate the validity of the Q-score as a new method for measuring central coherence (CC). METHOD: Forty-one patients with anorexia nervosa, 40 patients with bulimia nervosa and 40 healthy controls completed the Rey Complex Figure Test, which was scored both quantitatively and qualitatively. RESULTS: Both ED groups scored lower than the healthy controls on copy, recall and the Q-score. For the anorexia nervosa group, performance on the Central Coherence Index was associated with the nadir body mass index. Performance on the recall measures was independently associated with the nadir body mass index and depressive symptoms for the bulimia nervosa group. There was a strong correlation between the Q-score and the Central Coherence Index (r = 0.77). DISCUSSION: The study reveals different levels of CC and suggests that the Q-score might be an applicable method for measuring CC in ED patients.

The relationship of alcohol use disorders and depressive symptoms to tryptophan metabolism: cross-sectional data from a Nepalese alcohol treatment sample.

BACKGROUND: Activation of the kynurenine pathway of tryptophan metabolism results in increased production of potentially depressogenic tryptophan catabolites and a reduction in tryptophan availability for serotonin synthesis. As alcohol consumption affects tryptophan metabolism and disposition, we determined serum levels of tryptophan, kynurenine, and an index of tryptophan degradation (kynurenine/tryptophan ratio) in patients with alcohol-use disorder (AUD) and compared their levels considering abstinence duration, AUD severity, and comorbid depression. METHODS: The study sample included 169 AUD inpatients from 8 alcohol treatment facilities in Kathmandu, Nepal. The Composite International Diagnostic Interview was administered to generate the AUD diagnosis. The Alcohol Use Disorder Identification Test (AUDIT) captured AUD severity and patterns of alcohol use. The Hopkins Symptom Checklist-25 was used to reveal current depressive symptoms. Serum kynurenine and tryptophan levels were determined by high-performance liquid chromatography, and tryptophan degradation was measured by KT ratio (kynurenine/tryptophan × 10(3)). RESULTS: Patients with above average AUDIT scores had higher mean serum levels of kynurenine (2.1 µM ± 0.7 vs. 1.8 µM ± 0.6, p = 0.006) and KT ratios (48.6 ± 17.6 vs. 40.4 ± 14.3, p = 0.002) than those with below average scores. Patients with current depressive symptoms had higher mean tryptophan concentrations (49.9 µM ± 13 vs. 45.7 µM ± 14.1, p = 0.047) and lower KT ratios (41.4 ± 14 vs. 47.5 ± 17.6, p = 0.028) compared to patients whose reported depressive symptoms were below the standard cutoff. Higher tryptophan levels and lower KT ratios in the depressed group were specific to patients with longer abstinence and higher AUD severity. CONCLUSIONS: Depression-related deregulation in tryptophan metabolism was found to depend on length of abstinence and on AUD severity. Together, results suggest that in AUD populations, peripheral tryptophan metabolism is subject to interactions between AUD severity and depressive symptoms.

Neuropsychological function in patients with anorexia nervosa or bulimia nervosa.

OBJECTIVE: This study explored the neuropsychological performance of patients diagnosed with anorexia nervosa (AN) or bulimia nervosa (BN) compared with healthy controls (HCs). An additional aim was to investigate the effect of several possible mediators on the association between eating disorders (EDs) and cognitive function. METHOD: Forty patients with AN, 39 patients with BN, and 40 HCs who were comparable in age and education were consecutively recruited to complete a standardized neuropsychological test battery covering the following cognitive domains: verbal learning and memory, visual learning and memory, speed of information processing, visuospatial ability, working memory, executive function, verbal fluency, attention/vigilance, and motor function. RESULTS: The AN group scored significantly below the HCs on eight of the nine measured cognitive domains. The BN group also showed inferior performance on six cognitive domains. After adjusting for possible mediators, the nadir body mass index (lowest lifetime BMI) and depressive symptoms explained all findings in the BN group. Although this adjustment reduced the difference between the AN and HC groups, the AN group still performed worse than the HCs regarding verbal learning and memory, visual learning and memory, visuospatial ability, working memory, and executive functioning. DISCUSSION: Patients with EDs scored below the HCs on several cognitive function measures, this difference being most pronounced for the AN group. The nadir BMI and depressive symptoms had strong mediating effects. Longitudinal studies are needed to identify the importance of weight restoration and treatment of depressive symptoms in the prevention of a possible cognitive decline.

Intellectual function in patients with anorexia nervosa and bulimia nervosa.

OBJECTIVE: This study aimed to examine cognitive function in individuals with anorexia nervosa (AN) and bulimia nervosa (BN) on the basis of IQ measures, indexes and subtests of the Wechsler Adult Intelligence Scale ­ Third Edition (WAIS-III). METHODS: A total of 41 patients with AN, 40 patients with BN and 40 healthy controls (HC), matched for sex, age and education, were recruited consecutively to complete the WAIS-III. RESULTS: The AN group showed a significantly lower performance than the HC group on most global measures and on eight of the 13 administered subtests. Minor differences in verbal function were detected between the BN group and the HC group. CONCLUSION: The patients with eating disorders showed normal intellectual functions compared with the normative population. However, the AN group displayed a consistently lower performance than the matched HC group, which performed above normative means. The BN group performed at a level between that of the AN and HC groups.

Neuropsychological Characteristics and Quantitative Electroencephalography in Skogholt's Disease-A Rare Neurodegenerative Disease in a Norwegian Family.

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.

Individualized goals expressed by patients undergoing stroke rehabilitation: an observational study.

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.

Personality traits, interpersonal problems and therapeutic alliance in early schizophrenia spectrum disorders.

BACKGROUND: The quality of the therapeutic alliance is associated with engagement in- and thus important to the outcome of- treatment in schizophrenia. In non-psychotic disorders, general personality traits and individual patterns of interpersonal problems have been linked to the formation and quality of the therapeutic alliance. The role of these factors in relation to therapeutic alliance has not previously been explored in schizophrenia spectrum disorders. AIM: To investigate associations between personality traits, interpersonal problems and the quality of the therapeutic alliance in early schizophrenia spectrum disorders. METHODS: Demographic and clinical characteristics including Positive and Negative Syndrome Scale (PANSS) scores were assessed in 42 patients. Personality traits and interpersonal problems were assessed with the NEO Five factor Inventory (NEO-FFI) and the circumplex model of the Inventory of Interpersonal Problems (IIP-64C). Therapeutic alliance was measured with the Working Alliance Inventory - short form (WAI-S). RESULTS: Patient WAI-S scores were predicted by IIP-64C Submissive/Hostile interpersonal problems, age and PANSS excitative symptoms. Therapist WAI-S scores were predicted by NEO-FFI Agreeableness and the PANSS insight item. CONCLUSION: Core traits of personality and dimensions of interpersonal problems are associated with both patients' and therapists' perceptions of the quality of the working alliance.

Therapeutic alliance in early schizophrenia spectrum disorders: a cross-sectional study.

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.

APOE Polymorphism Is Associated with Changes in the Kynurenine Pathway.

BACKGROUND: APOE polymorphism and the Kynurenine pathway (KP) are associated with many disorders, but little is known about associations between APOE polymorphism and the KP. This study explored the associations between the KP and APOE polymorphism in disorders associated with APOE polymorphism and changes in the KP. METHODS: Subjects with morbid obesity before and after bariatric surgery (numbers 139 and 95, respectively), depression (number 49), and unspecified neurological symptoms (number 39) were included. The following grouping of the APOE genotypes was used: E2 = ɛ2ɛ2 + ɛ2ɛ3, E3 = ɛ3ɛ3 + ɛ2ɛ4, and E4 = ɛ3ɛ4 + ɛ4ɛ4. The KP metabolites Tryptophan, Kynurenine, Kynurenic acid, Quinolinic acid, and Xanthurenic acid were quantified in serum. RESULTS: The main findings were a significant positive association between E3 and Quinolinic acid (difference between E3 and E2E4: 12.0 (3.5; 18.6) ng/mL); p = 0.005), and a negative association between E4 and Kynurenine (difference between E4 and E2E3: -31.3 (-54.2; -3.2) ng/mL; p = 0.008). Quinolinic acid has been ascribed neurotoxic and inflammatory effects, and Kynurenine is a marker of inflammation. CONCLUSIONS: The findings indicate that APOE polymorphism might cause changes in the KP that contribute to the disease. Inflammation could be the link between APOE and the KP.

The Kynurenine Pathway in Healthy Subjects and Subjects with Obesity, Depression and Chronic Obstructive Pulmonary Disease.

BACKGROUND: Changes in tryptophan metabolism through the kynurenine pathway (KP) are observed in several disorders and coupled with pathophysiological deviations. METHODS: This study retrospectively compared the KP in serum in healthy subjects (108) with subjects with obesity (141), depression (49), and chronic obstructive pulmonary disease (COPD) (22) participating in four clinical studies and explored predictors of the changes in the KP metabolites. RESULTS: Compared with the healthy group, the KP was upregulated in the disease groups with high kynurenine, quinolinic acid (QA), kynurenine/tryptophan-ratio and QA/xanthurenic acid-ratio and low kynurenic acid/QA-ratio. Tryptophan and xanthurenic acid were upregulated in the depressed group compared with the groups with obesity and COPD. The covariates BMI, smoking, diabetes, and C-reactive protein explained the significant differences between the healthy group and the group with obesity but not between the healthy group and the groups with depression and COPD, indicating that different pathophysiological conditions result in the same changes in the KP. CONCLUSIONS: The KP was significantly upregulated in the disease groups compared with the healthy group, and there were significant differences between the disease groups. Different pathophysiological abnormalities seemed to result in the same deviations in the KP.

Measurement Properties of the Patient-Specific Functional Scale in Rehabilitation for Patients With Stroke: A Prospective Observational Study.

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.

Sex differences in neuropsychological performance as an effect of human immunodeficiency virus infection: a pilot study in Zambia, Africa.

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.

The Role of Tryptophan Dysmetabolism and Quinolinic Acid in Depressive and Neurodegenerative Diseases.

Emerging evidence suggests that neuroinflammation is involved in both depression and neurodegenerative diseases. The kynurenine pathway, generating metabolites which may play a role in pathogenesis, is one of several competing pathways of tryptophan metabolism. The present article is a narrative review of tryptophan metabolism, neuroinflammation, depression, and neurodegeneration. A disturbed tryptophan metabolism with increased activity of the kynurenine pathway and production of quinolinic acid may result in deficiencies in tryptophan and derived neurotransmitters. Quinolinic acid is an N-methyl-D-aspartate receptor agonist, and raised levels in CSF, together with increased levels of inflammatory cytokines, have been reported in mood disorders. Increased quinolinic acid has also been observed in neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and HIV-related cognitive decline. Oxidative stress in connection with increased indole-dioxygenase (IDO) activity and kynurenine formation may contribute to inflammatory responses and the production of cytokines. Increased formation of quinolinic acid may occur at the expense of kynurenic acid and neuroprotective picolinic acid. While awaiting ongoing research on potential pharmacological interventions on tryptophan metabolism, adequate protein intake with appropriate amounts of tryptophan and antioxidants may offer protection against oxidative stress and provide a balanced set of physiological receptor ligands.

Circulating Lipoproteins in Subjects with Morbid Obesity Undergoing Bariatric Surgery with Gastric Bypass or Sleeve Gastrectomy.

The efficacy of various bariatric procedures on the mitigation of the obese dyslipidemia remains debated, and the impact of these measures on lipoprotein(a) (Lp(a)) levels is unknown. In this study we aimed to compare the two most commonly used procedures: gastric bypass (RYGB) and sleeve gastrectomy (SG). Adult patients with morbid obesity were assigned to receive either RYGB or SG. The levels of non-HDL cholesterol, LDL/HDL-ratio and Lp(a) at examinations conducted 6 and 12 months postoperatively were determined and compared to preoperative levels to estimate the efficacy of the two surgical methods. All results 6 and 12 months after surgery were used in the comparisons with the preoperative results. A linear mixed regression model for repeated analyses was used. The Lp(a) and the non-HDL cholesterol levels were considerably reduced in the RYGB group, in contrast to the minor changes in the SG group. In addition, the LDL/HDL ratio was significantly more reduced in the RYGB group when compared to the SG group. Conclusively, RYGB was found to be more efficient than SG for the mitigation of obese dyslipidemia, including preoperative high Lp(a)-levels. This might have important individual and societal implications, especially regarding the potential to reduce the risk of cardiovascular disease and the related societal costs.