Short communication: Daily intake of 125 g of cheese for 2 weeks did not alter amount or distribution of serum lipids or desaturase indexes in healthy adults in an exploratory pilot study.

Regular cheese contains saturated fat, consumption of which may negatively influence the amount of serum lipids. The American Dietary Guidelines (https://health.gov/dietaryguidelines/2015/guidelines/) recommend consumption of low-fat food. However, we observed a negative association between cheese intake and serum triglycerides and a positive association with high-density lipoprotein cholesterol. Cheese intake was also inversely related to metabolic syndrome and blunted the harmful association of intake of soft drinks with serum lipids. Cheese contains calcium and factors that may inhibit desaturases, thereby partly explaining why cheese might not have negative effects on serum lipids. Thus, opposing forces seem to govern the cheese effect but will any of these prevail? In an exploratory pilot study, 17 healthy subjects participated in a 4-wk crossover trial without washout. During the first 2 wk, 9 subjects were randomly assigned to add 125 g/d of regular cheese to their habitual diet. After 2 wk, cheese intake was discontinued and the subjects were instructed to return to their habitual diet. The other 8 subjects followed their habitual diet during the first 2 wk, and then added 125 g/d of cheese for the next 2 wk. Mean values (mmol/L) before and after 2 wk on habitual (cheese) diet were as follows: serum triglycerides: 0.91 (0.89) and 0.95 (0.91); total cholesterol: 5.25 (5.16) and 5.08 (5.24); low-density lipoprotein cholesterol: 3.18 (3.17) and 3.09 (3.22); and high-density lipoprotein cholesterol: 1.71 (1.64) and 1.61 (1.66). The fatty acid pattern in total serum lipids and desaturase indexes did not change significantly in response to high cheese intake. Thus, an appreciable increase in daily cheese intake for 2 wk may not alter concentrations of serum lipids, estimates of desaturases, or the distribution of serum fatty acids.

Maintained superiority of chronotherapeutics vs. exercise in a 20-week randomized follow-up trial in major depression.

OBJECTIVE: To investigate the long-term antidepressant effect of a chronotherapeutic intervention. METHOD: In this randomized controlled trial 75 patients with major depression were allocated to fixed duloxetine and either a chronotherapeutic intervention (wake group) with three initial wake therapies, daily bright light therapy, and sleep time stabilization or to a group using daily exercise. Patients were followed 29 weeks. We report the last 20 weeks, a follow-up phase, where medication could be altered. Patients were assessed every 4 weeks. Remission rates were primary outcome. RESULTS: Patients in the wake group had a statistically significant higher remission rate of 61.9% vs. 37.9% in the exercise group at week 29 (OR = 2.6, CL = 1.3-5.6, P = 0.01). This indicated continued improvement compared with the 9 weeks of treatment response (44.8% vs. 23.4%) with maintenance of the large difference between groups. HAM-D17 endpoint scores were statistically lower in the wake group with endpoint scores of 7.5 (SE = 0.9) vs. 10.1 (SE = 0.9) in the exercise group (difference 2.7, CL = 0.5-4.8, P = 0.02). CONCLUSION: In this clinical study patients continued to improve in the follow-up phase and obtained very high remission rates. This is the first study to show adjunct short-term wake therapy and long-term bright light therapy as an effective and feasible method to attain and maintain remission.

Psychometric evaluation of the Major Depression Inventory (MDI) as depression severity scale using the LEAD (Longitudinal Expert Assessment of All Data) as index of validity.

BACKGROUND: The Major Depression Inventory (MDI) was developed to cover the universe of depressive symptoms in DSM-IV major depression as well as in ICD-10 mild, moderate, and severe depression. The objective of this study was to evaluate the standardization of the MDI as a depression severity scale using the Visual Analogue Scale (VAS) as index of external validity in accordance with the LEAD approach (Longitudinal Expert Assessment of All Data). METHODS: We used data from two previously published studies in which the patients had a MINI Neuropsychiatric Interview verified diagnosis of DSM-IV major depression. The conventional VAS scores for no, mild, moderate, and severe depression were used for the standardization of the MDI. RESULTS: The inter-correlation for the MDI with the clinician ratings (VAS, MES, HAM-D17 and HAM-D6) increased over the rating weeks in terms of Pearson coefficients. After nine weeks of therapy the coefficient ranged from 0.74 to 0.83. Using the clinician-rated VAS depression severity scale, the conventional MDI cut-off scores for no or doubtful depression, and for mild, moderate and severe depression were confirmed. CONCLUSIONS: Using the VAS as index of external, clinical validity, the standardization of the MDI as a measure of depression severity was accepted, with an MDI cut-off score of 21 for mild depression, 26 for moderate depression severity, and 31 for severe depression. TRIAL REGISTRATION: Martiny et al. Acta Psychiatr Scand 112:117-25, 2005: None - due to trial commencement date. Straaso et al. Acta Neuropsychiatr 26:272-9; 2014: ClinicalTrials.gov ID NCT01353092 .

Relapse Prevention in Major Depressive Disorder After Successful Acute Electroconvulsive Treatment: a 6-month Double-blind Comparison of Three Fixed Dosages of Escitalopram and a Fixed Dose of Nortriptyline - Lessons from a Failed Randomised Trial of the Danish University Antidepressant Group (DUAG-7).

INTRODUCTION: Electroconvulsive treatment (ECT) is an effective treatment for severe depression but carries a risk of relapse in the following months. METHODS: Major depressive disorder patients in a current episode attaining remission from ECT (17-item Hamilton Depression Rating Scale (HAM-D17) score≤9) received randomly escitalopram 10 mg, 20 mg, 30 mg or nortriptyline 100 mg as monotherapies and were followed for 6 months in a multicentre double-blind set-up. Primary endpoint was relapse (HAM-D17≥16). RESULTS: As inclusion rate was low the study was prematurely stopped with only 47 patients randomised (20% of the planned sample size). No statistically significant between-group differences could be detected. When all patients receiving escitalopram were compared with those receiving nortriptyline, a marginal superiority of nortriptyline was found (p=0.08). One third of patients relapsed during the study period, and one third completed. DISCUSSION: Due to small sample size, no valid efficacy inferences could be made. The outcome was poor, probably due to tapering off of non-study psychotropic drugs after randomisation; this has implications for future study designs. ClinicalTrials.gov Identifier: NCT00660062.

Identifying patients with therapy-resistant depression by using factor analysis.

INTRODUCTION: Attempts to identify the factor structure in patients with treatment-resistant depression have been very limited. METHODS: Principal component analysis was performed using the baseline datasets from 3 add-on studies [2 with repetitive transcranial magnetic stimulation and one with transcranial pulsed electromagnetic fields (T-PEMF)], in which the relative effect as percentage of improvement during the treatment period was analysed. RESULTS: We identified 2 major factors, the first of which was a general factor. The second was a dual factor consisting of a depression subscale comprising the negatively loaded items (covering the pure depression items) and a treatment resistant subscale comprising the positively loaded items (covering lassitude, concentration difficulties and sleep problems). These 2 dual subscales were used as outcome measures. Improvement on the treatment resistant subscale was 40% in the active treatment group compared to 17-30% improvement in the sham treatments. DISCUSSION: It is possible to describe patients with therapy-resistant depression by a factor structure. Both rTMS and T-PEMF had a clinical effect on the factor-derived scales when compared to sham treatment.

Toxoplasma gondii and cytomegalovirus: mixed infection by a parasite and a virus.

Human fibroblasts infected in vitro with cytomegalovirus are relatively resistant to infection by Toxoplasma gondii during the first 4 days of virus infection. After 5 days, however, the cytomegalovirus-infected cells become susceptible to the parasites. The toxoplasmas replicate in paracentral rosettes surrounded by host cell mitochondria. This growth configuration differs from that seen in human fibroblasts infected in vitro with toxoplasma only but resembles the pattern seen in doubly infected cells found in human necropsy tissue.

Construction of synthetic immunogen: use of new T-helper epitope on malaria circumsporozoite protein.

The circumsporozoite (CS) protein of Plasmodium falciparum is the focus of intense efforts to develop an antisporozoite malaria vaccine. Localization of sites for T-cell recognition on this molecule is critical for vaccine design. By using an algorithm designed to predict T-cell sites and a large panel of H-2 congenic mice, a major nonrepetitive T-cell site was located. When a synthetic peptide corresponding to this site was covalently linked to the major B-cell site on the molecule, an immunogen capable of eliciting a high-titer antibody response was formed. This peptide sequence could prime helper T cells for a secondary response to the intact CS protein. The new helper T-cell site is located outside the repetitive region of the CS protein and appears to be the immunodominant T site on the molecule. This approach should be useful in the rational design and construction of vaccines.

A validation analysis of two self-reported HAM-D6 versions.

OBJECTIVE: The six items of the clinician-administrated Hamilton Depression Scale (HAM-D(6)) cover the core items of depressive states reflecting the antidepressive effect of medication. In this study, the two self-reported versions of the HAM-D(6) have been psychometrically validated to ensure the unidimensionality of this administration form in patients with mild-to-moderate depression. METHOD: The item response theory analysis of Mokken was used to test the unidimensionality of both the Interactive Voice Recording System (IVRS) version of the HAM-D(6) and a paper-and-pencil self-reported version (S-HAM-D(6)). Patients with typical major depression and with seasonal affective disorder were included. RESULTS: The Mokken analysis showed that the two self-reported versions of the HAM-D(6) obtained coefficients of homogeneity above 0.40, similar to the clinician-rated HAM-D(6) and thus implying unidimensionality. By contrast, the full HAM-D(17) versions (self-reported as well as clinician-rated) obtained coefficients of homogeneity below 0.40, implying that the HAM-D(17) is a multidimensional scale. CONCLUSION: The analysis show that both the IVRS version and the S-HAM-D(6) version are unidimensional self-rating scales for the measurement of depressive states.

High cortisol awakening response is associated with an impairment of the effect of bright light therapy.

OBJECTIVE: We investigated the predictive validity of the cortisol awakening response (CAR) in patients with non-seasonal major depression. METHOD: Patients were treated with sertraline in combination with bright or dim light therapy for a 5-week period. Saliva cortisol levels were measured in 63 patients, as an awakening profile, before medication and light therapy started. The CAR was calculated by using three time-points: awakening and 20 and 60 min after awakening. RESULTS: Patients with low CAR had a very substantial effect of bright light therapy compared with dim light therapy, whereas patients with a high CAR had no effect of bright light therapy compared with dim light therapy. CONCLUSION: High CAR was associated with an impairment of the effect of bright light therapy. This result raises the question of whether bright light acts through a mechanism different from that of antidepressants.

Chronic lymphadenopathic toxoplasmosis. A case with marked hyperglobulinemia and impaired delayed hypersensitivity responses during active infection.

A patient with lymphadenopathic toxoplasmosis characterized by prolonged symptoms and repeated relapses with isolation of toxoplasma from lymph nodes is described. As the disease persisted and progressed, striking immunologic changes occurred that ultimately resulted in a state of extreme hyperglobulinemia associated with impaired delayed hypersensitivity responses. The case in question illustrates that progressive infection may occur in the face of high antibody levels of all immunoglobulin types whereas the only demonstrable immunologic impairment was of delayed hypersensitivity.

Post-stroke depression: combined treatment with imipramine or desipramine and mianserin. A controlled clinical study.

In a 6-week study the efficacy of combined treatment of imipramine plus mianserin was compared to combined treatment of desipramine plus mianserin in patients with post-stroke depression. Patients were required to have a minimum baseline total score of 15 on the 17-item Hamilton Depression Scale (HAMD). The Melancholia Scale (MES) was also used to measure severity of depressive states to show that somatic symptoms had little influence on the evaluation of depression. Out of 120 stroke patients screened, 20 patients fulfilled the inclusion criteria. The doses of the drugs were flexible, using side-effects as a guide during treatment. Both intention to treat analysis and efficacy data (excluding patients who had dropped out during the first 2 weeks of treatment) showed that imipramine (mean dose 75 mg daily) plus mianserin (mean dose 25 mg daily) was superior to desipramine (mean dose 66 mg daily) plus mianserin (27 mg daily). The MES was found to be more sensitive than the HAMD for measuring change in depressive states during treatment. The assessment of side-effects using the UKU scale showed good tolerance in general. The only difference between the two treatment groups was seen in micturition disturbances, where the imipramine treated patients had most complaints after 14 days of treatment, but the symptoms disappeared despite continuous treatment.

A C1Q enzyme-linked immunosorbent assay (ELISA) using polyethylene glycol for immune complexes.

A C1q-ELISA for the detection of immune complexes is described in which the sensitivity was increased by the addition of polyethylene glycol (PEG). Although the ELISA without PEG adequately detected immune complexes in sera from patients with autoimmune disorders, when sera from patients with filariasis were tested, there was little correlation between values obtained with ELISA and the 125I-C1q binding assays. The addition of PEG to the filariasis sera before reacting the bound complexes to the enzyme conjugated anti-IgG increased the sensitivity to allow detection of immune complexes in those sera. This could be done without adversely affecting the reaction with normal sera or sera from patients with systemic lupus erythematosus. The solid phase C1q-ELISA with the PEG modification can be used for the detection of immune complexes in filariasis and should be adaptable for use with sera from other parasitic infections.

Enzyme-linked immunosorbent assay (ELISA) for detecting IgM and IgE antibodies in human schistosomiasis.

Sera from patients with acute or early and chronic schistosomiasis were examined for IgG, IgM, and IgE antibody by an enzyme-linked immunosorbent assay technique, using soluble egg antigen from Schistosoma mansoni. Cercarial/adult IgG antibody ratios were determined, using soluble cercarial and adult worm antigens. Sera with cercarial/adult ratios indicative of acute or early schistosomiasis also contained specific IgM antibodies. Schistosome IgE antibody was found in sera from patients with acute schistosomiasis, but in only 1 of 10 sera from patients with chronic schistosomiasis. The inability of ELISA to detect IgE antibodies in chronic sera indicates that it may be a relatively insensitive measure of IgE antibodies in those patients with chronic schistosomiasis.

Filarial antigen in circulating immune complexes from patients with Wuchereria bancrofti filariasis.

Detection of filarial antigen in circulating immune complexes from patient sera was performed by an enzyme immunoassay in which the immune complexes were precipitated in the cold with polyethylene glycol and then dissociated in an acid pH buffer before being added to an ELISA plate. The dissociated antigen bound to the plate where it could be detected by peroxidase-labeled polyclonal rabbit antifilarial antiserum. Control sera used for defining the specificity of the assay included sera with immune complexes not related to parasite infection with and without free parasite antigen added prior to polyethylene glycol precipitation as well as sera from normal individuals. Filarial antigen was detected in the circulating immune complexes from 10 of 28 patients with bancroftian filariasis residing in either the Cook Islands (subperiodic Wuchereria bancrofti) or India (periodic W. bancrofti). By immunoblotting, the most frequently identified filarial antigen in these complexes was an approximately equal to 200 kDa circulating antigen.

Cellular hypersensitivity to toxoplasmal and retinal antigens in patients with toxoplasmal retinochoroiditis.

To investigate the possible role of hypersensitivity to toxoplasmal and retinal antigens in patients with toxoplasmal retinochoroiditis, we examined their in vitro lymphoproliferative responses to antigens prepared from Toxoplasma gondii and human retina. The magnitude of patients' responses, determined by incorporation of [3H]-thymidine, was compared to those of Toxoplasma seropositive and seronegative controls. Patients were indistinguishable from seropositive controls in terms of antitoxoplasmal antibody titer (dye test, indirect hemagglutination and enzyme-linked immunosorbent assay) and in vitro lymphoproliferative responses to toxoplasmal antigens. Furthermore, there was no relationship between antibody titer and the magnitude of proliferative responses in seropositive individuals. Four of four patients with active eye disease and six of 13 with inactive disease, but none of the seropositive or seronegative controls, had significant lymphoproliferative responses to human retinal antigens. These observations raise the possibility of an autoimmune component in the pathogenesis of relapses in toxoplasmal retinochoroiditis.

Serological differences between acute and chronic schistosomiasis mansoni detected by enzyme-linked immunosorbent assay (ELISA).

Sera from patients with acute and chronic schistosomiasis mansoni, and from laboratory-infected monkeys, were examined by an enzyme-linked immunosorbent assay technique using antigens prepared from eggs, cercariae, and adult worms. Sera from patients with acute schistosomiasis and from monkeys 2 months post-infection reacted more positively to cercarial antigen than to adult worm antigen whereas sera from both patients with chronic schistosomiasis and monkeys infected for longer than 4 months reacted more positively to adult worm antigen. These differential responses to antigen serologically differentiated between acute and chronic schistosome infections.

Endemic filariasis on a Pacific Island. II. Immunologic aspects: immunoglobulin, complement, and specific antifilarial IgG, IgM, and IgE antibodies.

Sixty-eight individuals from a Pacific island hyperendemic for subperiodic bancroftian filariasis were selected from a larger study population to include the entire clinical spectrum of filarial infection in that region and also an "endemic control" group without clinical or parasitologic evidence of filarial infection. Analysis of their blood leukocyte and humoral immune responses yielded the following major findings: 1) levels of specific antifilarial antibodies of three different immunoglobulin class (IgG and IgM measured by ELISA and IgE determined by radioimmunoassay) were significantly greater in the "endemic control" population than in the patients with filariasis, an observation true for both children and adults; 2) the endemic controls also had significantly higher levels of serum IgM and C3 than did the filariasis patients 3) while individuals with "filarial fevers" and "chronic (lymphatic) pathology" did have significantly lower IgG antibody responses to filarial antigen than the controls, the lowest antibody levels were found in the patients with microfilaremia; 4) symptomatic patients (i.e., those with filarial fevers or lymphatic obstruction) regularly showed higher specific antibody responses to filarial antigens than asymptomatic, infected individuals, although the difference did not reach statistical significance. These findings are in concert with our previously reported, intriguing observation that lymphocyte proliferative responsiveness to filarial antigens was much greater in individuals of the "non-infected" endemic control population than in patients with filariasis; furthermore, they indicate the important issues that must be approached and resolved to define the immunologic determinants leading both to the various filarial clinical syndromes and to protective immunity.

Development of antibodies to Plasmodium vivax as measured by two different serologic techniques.

Sera from individuals infected with Plasmodium vivax were tested for the presence of malarial antibodies using the indirect fluorescent antibody (IFA) and the indirect hemagglutination (IGA) tests. The primary infection resulted in the conversion of all sera to a positive response in the IFA test, whereas only 50% gave a positive IGA response. There was a direct relationship between the duration of the primary parasitemia and percentage giving positive IGA response. Relapse resulted in high level positive IFA and IGA responses.

Toxoplasma encephalitis in patients with acquired immune deficiency syndrome: diagnosis and response to therapy.

Although Toxoplasma gondii is the most commonly recognized cause of central nervous system mass lesions in patients with acquired immune deficiency syndrome, published investigations have provided little information about criteria for diagnosis of toxoplasmosis or the response to therapy. In this series the method of diagnosis and response to therapy were assessed in 14 patients who had evidence for toxoplasmosis based on routine histopathology, immunoperoxidase staining, or mouse inoculation. These patients presented with clinical and radiologic findings that did not clearly distinguish them from patients with other infectious or neoplastic processes. Excisional biopsies usually showed tachyzoites on routine histology, but needle biopsies were usually negative unless mouse inoculation or immunoperoxidase staining was employed. Response to pyrimethamine and sulfadiazine therapy was often prompt, but therapy had to be continued for long periods of time to maintain a clinical response, and no alternative regimen of one or more drugs appeared to be effective in patients unable to tolerate both pyrimethamine and sulfadiazine.

The life cycles of the temperate lactococcal bacteriophage phiLC3 monitored by a quantitative PCR method.

We present here a new and general approach for monitoring the life cycles of temperate bacteriophages which establish lysogeny by inserting their genomes site-specifically into the bacterial host chromosome. The method is based on quantitative amplification of specific DNA sites involved in various cut-and-join events during the life cycles of the phages (i.e. the cos, attP, attB, attL and attR sites) with the use of sequence-specific primers. By comparing the amounts of these specific DNA sites at different intervals, we were able to follow the development of the lytic and lysogenic life cycles of the temperate lactococcal bacteriophage phiLC3 after infection of its bacterial host Lactococcus lactis ssp. cremoris IMN-C18.