Serum Serotonin Abnormality in Depression

Background

Serotonin plays an important role in treatment of depression. We evaluated the clinical correlates of plasma serotonin levels in depressed patients before and after treatment.

Methods

Study sample comprised of 40 patients diagnosed on ICD-10 diagnostic criteria, and an equal number of healthy matched controls. Subjects were evaluated on Beck''s Depression Inventory (BDI) and Suicide Ideation Scale (SIS), before and after the treatment. Blood samples were collected from all the cases and controls before starting the antidepressant medication with selective serotonin reuptake inhibitors (SSRI''s). Serum serotonin levels were measured before and after treatment.

Result

Significant differences in scores before and after the intervention on BDI, SIS and serotonin levels of cases and controls (p<.000) were noted. Correlation between the serum serotonin levels before and after the treatment, and between the rating scales did not reveal significant association (p > 0.05). Patients with suicidal intentions had lower levels of serotonin. The scores changed after intervention.

Conclusion

Treatment with SSRI''s had shown significant changes in clinical conditions. However these changes did not relate significantly with serum serotonin levels.Key Words: Serotonin, Depression, Selective serotonin reuptake inhibitors     

Validation of MCADD newborn screening

Medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD) represents a potentially fatal fatty acid β‐oxidation disorder. Newborn screening (NBS) by tandem mass spectrometry (MS/MS) has been implemented worldwide, but is associated with unresolved questions regarding population heterogeneity, burden on healthy carriers, cut‐off policies, false‐positive and negative rates. In a retrospective case‐control study, 333 NBS samples showing borderline acylcarnitine patterns but not reaching recall criteria were genotyped for the two most common mutations (c.985A>G/c.199C>T) and compared with genotypes and acylcarnitines of 333 controls, 68 false‐positives, and 34 patients. c.985A>G was more frequently identified in the study group and false‐positives compared to controls (1:4.3/1:2.3 vs. 1:42), whereas c.199C>T was found more frequently only within the false‐positives (1:23). Biochemical criteria were devised to differentiate homozygous (c.985A>G), compound heterozygous (c.985A>G/c.199C>T), and heterozygous individuals. Four false‐negatives were identified because our initial algorithm required an elevation of octanoylcarnitine (C₈) and three secondary markers in the initial and follow‐up sample. The new approach allowed a reduction of false‐positives (by defining high cut‐offs: 1.4 μmol/l for C₈; 7 for C₈/C₁₂) and false‐negatives (by sequencing the ACADM gene of few suspicious samples). Our validation strategy is able to differentiate healthy carriers from patients doubling the positive predictive value (42→88%) and to target NBS to MCADD‐subsets with potentially higher risk of adverse outcome. It remains controversial, if NBS programs should aim at identifying all subsets of all diseases included. Because the natural course of milder variants cannot be assessed by observational studies, our strategy could serve as a general model for evaluation of MS/MS‐based NBS.     

Italian healthcare workers' views on mandatory vaccination

Background  

Mandatory vaccination has contributed to the success of immunisation programmes but voluntary vaccination allows people to be responsible for their own health. There are benefits from both policies and the arguments between them remain subject to debate within and without the scientific community, both nationally and internationally. The aim of this study is to assess the opinions of those who actually work in the Vaccination Service.     

The use of chemokine antagonists in EAE models

Multiple sclerosis is believed to be an autoimmune disease with an end-point of neuro-degeneration, but in which inflammation plays a predominant role. Therefore therapies which target inhibition of the excessive recruitment of leukocytes into the central nervous system (CNS) are actively sought after by medical research. Drug discovery relies heavily on animal models used for such research, called Experimental Autoimmune Encephalomyelitis (EAE). Several chemokines and their receptors have been shown to play a role in this recruitment into the CNS, and we have investigated several strategies which antagonize this system in EAE models. We will discuss these strategies and their successes and failures to prevent disease symptoms and the insights they have provided.     

Advantages of routine next-generation sequencing over standard genetic testing in the amyotrophic lateral sclerosis clinic

Background

Next-generation sequencing has enhanced our understanding of amyotrophic lateral sclerosis (ALS) and its genetic epidemiology. Outside the research setting, testing is often restricted to those who report a family history. The aim of this study was to explore the added benefit of offering routine genetic testing to all patients in a regional ALS centre.

Methods

C9ORF72 expansion testing and exome sequencing was offered to consecutive patients (150 with ALS and 12 with primary lateral sclerosis [PLS]) attending the Oxford Motor Neuron Disease Clinic within a defined time period.

Results

A total of 17 (11.3%) highly penetrant pathogenic variants in C9ORF72, SOD1, TARDBP, FUS and TBK1 were detected, of which 10 were also found through standard clinical genetic testing pathways. The systematic approach resulted in five additional diagnoses of a C9ORF72 expansion (number needed to test [NNT] = 28), and two further missense variants in TARDBP and SOD1 (NNT = 69). Additionally, 3 patients were found to carry pathogenic risk variants in NEK1, and 13 patients harboured common missense variants in CFAP410 and KIF5A, also associated with an increased risk of ALS. We report two novel non-coding loss-of-function splice variants in TBK1 and OPTN. No relevant variants were found in the PLS patients. Patients were offered double-blinded participation, but >80% requested disclosure of the results.

Conclusions

This study provides evidence that expanding genetic testing to all patients with a clinical diagnosis of ALS enhances the potential for recruitment to clinical trials, but will have direct resource implications for genetic counselling.     

Detection and viability of tumor cells in peripheral blood stem cell collections from breast cancer patients using immunocytochemical and clonogenic assay techniques [see comments]

Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and BM from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 x 10(5) mononuclear cells. Immunostained tumor cells were detected in 9.8% (13/133) PBSC specimens from 9/48 (18.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < .005). The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/10(5) mononuclear cells (range 0.33 to 2.0/10(5)) compared with 22.9/10(5) mononuclear cells in BM (range 1 to 3,000/10(5), P < .0001). In culture experiments, clonogenic tumor colonies grew in 21/26 immunocytochemically positive specimens. No tumor colony growth was detected in 30/32 immunocytochemically negative specimens. Immunocytochemical detection of tumor involvement in BM and PBSC correlated significantly with in vitro clonogenic growth (P < .0001). We conclude that PBSC contain fewer tumor cells than paired BM specimens from patients with advanced breast cancer and that these tumor cells appear to be capable of clonogenic growth in vitro.     

Social and Self-Reflective Use of a Web-Based Personally Controlled Health Management System

Background

Personally controlled health management systems (PCHMSs) contain a bundle of features to help patients and consumers manage their health. However, it is unclear how consumers actually use a PCHMS in their everyday settings.

Objective

To conduct an empirical analysis of how consumers used the social (forum and poll) and self-reflective (diary and personal health record [PHR]) features of a Web-based PCHMS designed to support their physical and emotional well-being.

Methods

A single-group pre/post-test online prospective study was conducted to measure use of a Web-based PCHMS for physical and emotional well-being needs during a university academic semester. The PCHMS integrated an untethered PHR with social forums, polls, a diary, and online messaging links with a health service provider. Well-being journeys additionally provided information to encourage engagement with clinicians and health services. A total of 1985 students and staff aged 18 and above with access to the Internet were recruited online, of which 709 were eligible for analysis. Participants’ self-reported well-being, health status, health service utilization, and help-seeking behaviors were compared using chi-square, McNemar’s test, and Student’s t test. Social networks were constructed to examine the online forum communication patterns among consumers and clinicians.

Results

The two PCHMS features that were used most frequently and considered most useful and engaging were the social features (ie, the poll and forum). More than 30% (213/709) of participants who sought well-being assistance during the study indicated that other people had influenced their decision to seek help (54.4%, 386/709 sought assistance for physical well-being; 31.7%, 225/709 for emotional well-being). Although the prevalence of using a self-reflective feature (diary or PHR) was not as high (diary: 8.6%, 61/709; PHR: 15.0%, 106/709), the proportion of participants who visited a health care professional during the study was more than 20% greater in the group that did use a self-reflective feature (diary: P=.03; PHR: P<.001).

Conclusions

There was variation in the degree to which consumers used social and self-reflective PCHMS features but both were significantly associated with increased help-seeking behaviors and health service utilization. A PCHMS should combine both self-reflective as well as socially driven components to most effectively influence consumers’ help-seeking behaviors.