Assessment of Microbial Reduction by Cage Washing and Thermal Disinfection using Quantitative Biologic Indicators for Spores, Viruses and Vegetative Bacteria.

Cage washing is a key process of the biosecurity program in rodent facilities. For the current study, we developed systems (i. e., magnet attachments, quantitative biologic indicators (Q-BI), and measurement of thermal disinfection at equipment level) to assess the microbial decontamination achieved by a rodent equipment washer with and without thermal disinfection. 99% of the magnets remained in position to hold Q-BI and temperature probes inside cages, water bottles or at equipment level across a cabinet washer chamber with loads dedicated to either housing or drinking devices. Various types of Q-BI for Bacillus atrophaeus, Enterococcus hirae and minute virus of mice were tested. To simulate potential interference from biologic material and animal waste during cage processing, Q-BI contained test soil: bovine serum albumin with or without feces. As a quantitative indicator of microbial decontamination, the reduction factor was calculated by comparing microbial load of processed Q-BI with unprocessed controls. We detected variation between Q-BI types and assessed the washer's ability to reduce microbial load on equipment. Reduction factor results were consistent with the Q-BI type and showed that the washing and thermal disinfection cycle could reduce loads of vegetative bacteria, virus and spore by 5 log10 CFU/TCID50 and beyond. Thermal disinfection was monitored with temperature probes linked to data loggers recording live. We measured the period of exposure to temperatures above 82.2 °C, to calculate A0, the theoretical indicator for microbial lethality by thermal disinfection, and to assess whether the cabinet washer could pass the minimum quality standard of A0 = 600. Temperature curves showed an A0 > 1000 consistently across all processed equipment during thermal disinfection. These data suggest that, when sterilization is not required, a cabinet washer with thermal disinfection could replace an autoclave and reduce environmental and financial waste.

Federation of European Laboratory Animal Science Associations recommendations of best practices for the health management of ruminants and pigs used for scientific and educational purposes.

Most ruminants and pigs used for scientific and educational aims are bred not for these purposes but in a farm environment. Given the wide range of diseases that these species might have, ensuring that the animals' health status is appropriate can be complex and challenging. The Federation of European Laboratory Animal Science Associations has previously published recommendations for the health monitoring of experimental colonies of pigs (1998) and, respectively, calves, sheep and goats (2000). Unfortunately, the uptake of those recommendations was poor and insufficiently reported in scientific publications. These new recommendations for best practice focus on the main species of ruminants (cattle, sheep and goats) and pigs. They provide general and specific information helpful for designing a health management programme for the suppliers and for the user establishments, as well as guidance on animal procurement. Critical thinking based on the fields of use of the animals is promoted, aiming to help in taking informed decisions rather than establishing an exhaustive exclusion list for pathogens. Implementing the best health and welfare management practices should be done under the guidance of a competent attending veterinarian, with expertise and sufficient authority to take the appropriate action, doubled by excellent communication skills. It is strongly recommended that the user establishment's veterinarian works in close collaboration with the supplier's veterinarian.

Comparison of burnout, anxiety and depressive syndromes in hospital psychiatrists and other physicians: Results from the ESTEM study.

AIMS: To compare prevalence and risk factors for burnout, anxiety and depression among hospital psychiatrists and non-psychiatrists. METHOD: Regional online survey of psychiatric and non-psychiatric hospital physicians was performed including: a job-stress scale, the Hospital Anxiety and Depression Scale (HADS), the Copenhagen Burnout Inventory (CBI), a stressful work relationships list and a six items scale about work-related psychosocial risk factors (PRFs). The client-related burnout scale of the CBI has been changed to an interpersonal burnout scale. Cases were defined by a score of 8+ for the HADS-A/HADS-D and 50+ for the three CBI subscales. RESULTS: 285 psychiatrists and 326 non-psychiatrists participated. The prevalence of depression, personal burnout and work-related burnout did not differ between physicians. Anxiety was lower in psychiatrists and interpersonal burnout was higher in senior psychiatrists. Multivariate analysis showed two main PRFs, common to both groups of physicians: "work intensity and time" was associated with four of the five syndromes and "emotional demands" with the three burnout syndromes. Interpersonal burnout was associated with stressful relationships with leaders, but not with patients. CONCLUSION: Reducing the workload, improving the management of emotions and increasing managerial skills are important approaches for prevention.

Enhancing laboratory capacity during Ebola virus disease (EVD) heightened surveillance in Liberia: lessons learned and recommendations.

INTRODUCTION: Following a declaration by the World Health Organization that Liberia had successfully interrupted Ebola virus transmission on May 9th, 2015; the country entered a period of enhanced surveillance. The number of cases had significantly reduced prior to the declaration, leading to closure of eight out of eleven Ebola testing laboratories. Enhanced surveillance led to an abrupt increase in demand for laboratory services. We report interventions, achievements, lessons learned and recommendations drawn from enhancing laboratory capacity. METHODS: Using archived data, we reported before and after interventions that aimed at increasing laboratory capacity. Laboratory capacity was defined by number of laboratories with Ebola Virus Disease (EVD) testing capacity, number of competent staff, number of specimens tested, specimen backlog, daily and surge testing capacity, and turnaround time. Using Stata 14 (Stata Corporation, College Station, TX, USA), medians and trends were reported for all continuous variables. RESULTS: Between May and December 2015, interventions including recruitment and training of eight staff, establishment of one EVD laboratory facility, implementation of ten Ebola GeneXpert diagnostic platforms, and establishment of working shifts yielded an 8-fold increase in number of specimens tested, a reduction in specimens backlog to zero, and restoration of turn-around time to 24 hours. This enabled a more efficient surveillance system that facilitated timely detection and containment of two EVD clusters observed thereafter. CONCLUSION: Effective enhancement of laboratory services during high demand periods requires a combination of context-specific interventions. Building and ensuring sustainability of local capacity is an integral part of effective surveillance and disease outbreak response efforts.

Comparison of two prevalent individually ventilated caging systems for detection of murine infectious agents via exhaust air particles.

We compared the efficacies of two different individually ventilated cage systems (Allentown and Tecniplast) for health monitoring (HM) of murine infectious agents using exhaust air particle (EAP) capture and real-time PCR. After three months of monitoring, both EAP capture media allowed detection of Helicobacter, Pasteurella and Entamoeba. Use of the EAP real-time PCR for HM reduces the number of mice used.

Smaller hippocampal volumes predict lower antidepressant response/remission rates in depressed patients: A meta-analysis.

OBJECTIVES: Whether hippocampal volume predicts response and/or remission after antidepressant treatment of major depressive episodes (MDE) in major depressive disorder (MDD) remains unclear. We meta-analysed prospective studies comparing baseline hippocampal volume in patients with or without response/remission after antidepressant treatment. METHODS: Pubmed, Embase and Google Scholar were searched for studies of patients with current MDE in MDD, with hippocampal volume assessments at baseline, initiation of antidepressant drug treatment, and prospective assessment of response/remission after treatment. RESULTS: Six studies (374 patients), of which two were positive and four negative, were meta-analysed. Compared to responders/remitters, patients who failed to achieve response/remission had smaller total hippocampus volumes at baseline (mean volume difference = 260 mm3, 95% CI [93; 427], P = 0.002). These results remained significant in patients under 60 years of age (P = 0.02), in those over 60 years old (P = 0.04), and for right (P = 0.006) and left (P = 0.02) hippocampi. The probability of non-response/non-remission was 68.6% for patients with a total hippocampal volume at least 10% lower than the average, and 47.1% for patients with a total hippocampal volume 10% higher than the average. CONCLUSIONS: In depressed patients treated with antidepressant drugs, smaller hippocampal volumes predict lower response/remission rates.

Rapid Laboratory Identification of Neisseria meningitidis Serogroup C as the Cause of an Outbreak - Liberia, 2017.

On April 25, 2017, a cluster of unexplained illness and deaths among persons who had attended a funeral during April 21-22 was reported in Sinoe County, Liberia (1). Using a broad initial case definition, 31 cases were identified, including 13 (42%) deaths. Twenty-seven cases were from Sinoe County (1), and two cases each were from Grand Bassa and Monsterrado counties, respectively. On May 5, 2017, initial multipathogen testing of specimens from four fatal cases using the Taqman Array Card (TAC) assay identified Neisseria meningitidis in all specimens. Subsequent testing using direct real-time polymerase chain reaction (PCR) confirmed N. meningitidis in 14 (58%) of 24 patients with available specimens and identified N. meningitidis serogroup C (NmC) in 13 (54%) patients. N. meningitidis was detected in specimens from 11 of the 13 patients who died; no specimens were available from the other two fatal cases. On May 16, 2017, the National Public Health Institute of Liberia and the Ministry of Health of Liberia issued a press release confirming serogroup C meningococcal disease as the cause of this outbreak in Liberia.

Outpatient treatment engagement after suicidal attempt: A multisite prospective study.

After suicidal attempt, the rate of specialized out treatment engagement (SOTE) does not exceed 30-50%. We designed a multisite prospective naturalistic study, in order to investigate predictive factors of SOTE after emergency department discharge among 107 suicidal attempters without current psychiatric ambulatory care. Both bivariate and multivariate analyses highlighted that booking an appointment with a mental health professional before discharge was significantly associated with higher SOTE rate. Psychiatric caregivers of emergency departments should be informed that this approach is a simple, fast way to improve SOTE among this population.

Plasma BDNF Level in Major Depression: Biomarker of the Val66Met BDNF Polymorphism and of the Clinical Course in Met Carrier Patients.

AIMS: Despite the involvement of the brain-derived neurotrophic factor (BDNF) in the physiopathology of major depressive disorder (MDD), the coherence between the components of the BDNF pathway and their link with the clinical features of MDD are insufficiently studied. We aimed to assess in Caucasian depressed patients the impact of the BDNF Val66Met polymorphism on plasma BDNF levels taking into account the clinical characteristics of MDD. METHODS: A total of 328 Caucasian adult MDD patients with a current major depressive episode (MDE) were assessed for the BDNF Val66Met polymorphism, plasma BDNF levels and clinical characteristics of the MDD. RESULTS: Plasma BDNF levels were linearly associated with the BDNF Val66Met genotypes (ValVal: 1,525.9 ± 1,183.3 pg/mL vs. ValMet: 1,248.7 ± 1,081.8 vs. MetMet: 1,004.9 ± 952.8; p = 0.04), Met carriers having lower BDNF levels than ValVal ones. Significant interactions between the Val66Met polymorphism and 3 clinical characteristics - age at onset (p = 0.03), MDD duration (p = 0.04), and number of previous MDE (p = 0.04) - were evidenced for plasma BDNF levels. Indeed, in Met carriers, but not in ValVal ones, plasma BDNF levels were negatively correlated with age at onset and positively correlated with MDD duration and number of previous MDE. CONCLUSION: Our results show a measurable, coherent, and functional BDNF pathway based on the BDNF Val66Met polymorphism and plasma BDNF levels in patients with a current MDE. This pathway is related to the clinical course of major depression, plasma BDNF levels being associated with the long-term history of MDD in Met carriers. Further studies assessing central BDNF are needed to understand the underlying mechanisms of this association.

Development, Use, and Impact of a Global Laboratory Database During the 2014 Ebola Outbreak in West Africa.

Background: The international impact, rapid widespread transmission, and reporting delays during the 2014 Ebola outbreak in West Africa highlighted the need for a global, centralized database to inform outbreak response. The World Health Organization and Emerging and Dangerous Pathogens Laboratory Network addressed this need by supporting the development of a global laboratory database. Methods: Specimens were collected in the affected countries from patients and dead bodies meeting the case definitions for Ebola virus disease. Test results were entered in nationally standardized spreadsheets and consolidated onto a central server. Results: From March 2014 through August 2016, 256343 specimens tested for Ebola virus disease were captured in the database. Thirty-one specimen types were collected, and a variety of diagnostic tests were performed. Regular analysis of data described the functionality of laboratory and response systems, positivity rates, and the geographic distribution of specimens. Conclusion: With data standardization and end user buy-in, the collection and analysis of large amounts of data with multiple stakeholders and collaborators across various user-access levels was made possible and contributed to outbreak response needs. The usefulness and value of a multifunctional global laboratory database is far reaching, with uses including virtual biobanking, disease forecasting, and adaption to other disease outbreaks.

Risk for Autism Spectrum Disorders According to Period of Prenatal Antidepressant Exposure: A Systematic Review and Meta-analysis.

Importance: Several studies have examined the links between prenatal exposure to antidepressants and autism spectrum disorders (ASDs) in children, with inconsistent results, especially regarding the impact of the trimester of exposure. Objective: To perform a systematic review of the literature and a meta-analysis of published studies to assess the association between ASDs and fetal exposure to antidepressants during pregnancy for each trimester of pregnancy and preconception. Data Sources: PubMed, EMBASE, and PsycINFO databases up to May 2016 were searched in June 2016 for observational studies. For the meta-analyses, data were analyzed on RevMan version 5.2 using a random-effect model. For the review, studies were included if they had been published and were cohort or case-control studies, and for the meta-analysis, studies were included if they were published studies and the data were not derived from the same cohorts. Study Selection: We included all the studies that examined the association between ASDs and antenatal exposure to antidepressants. Data Extraction and Synthesis: Three reviewers independently screened titles and abstracts, read full-text articles, and extracted data. The quality of the studies was also assessed. Main Outcomes and Measures: Primary outcome was the association between antidepressants during pregnancy and ASDs. Secondary outcomes were the associations between antidepressants in each individual trimester or before pregnancy and ASDs. Results: Our literature search identified 10 relevant studies with inconsistent results. For prenatal exposure, the meta-analysis on the 6 case-control studies (117 737 patients) evidenced a positive association between antidepressant exposure and ASDs (odds ratio [OR], 1.81; 95% CI, 1.49-2.20). The association was weaker when controlled for past maternal mental illness (OR, 1.52; 95% CI, 1.09-2.12). A similar pattern was found whatever the trimester of exposure considered (first trimester: OR, 2.09, 95% CI,1.66-2.64; second: OR, 2.00, 95% CI, 1.55-2.59; and third: OR, 1.90, 95% CI, 1.20-3.02. Controlled for past maternal mental illness: first trimester: OR, 1.79; 95% CI, 1.27-2.52, second: OR, 1.67, 95% CI, 1.14-2.45; and third: OR, 1.54, 95% CI, 0.82-2.90). No association was found when the 2 cohort studies were pooled (772 331 patients) for the whole pregnancy (hazard ratio, 1.26; 95% CI, 0.91-1.74) or for the first trimester. In addition, preconception exposure to antidepressants was significantly associated with an increased risk for ASDs (OR controlled for past maternal illness, 1.77; 95% CI, 1.49-2.09). Conclusions and Relevance: There is a significant association between increased ASD risk and maternal use of antidepressants during pregnancy; however, it appears to be more consistent during the preconception period than during each trimester. Maternal psychiatric disorders in treatment before pregnancy rather than antenatal exposure to antidepressants could have a major role in the risk for ASDs. Future studies should address the problem of this potential confounder.

No impact of eight NTRK2 genetic polymorphisms on 6-month antidepressant efficacy in depressed patients.

AIM: NTRK2 is the main receptor of the brain derived neurotrophic factor, which is involved in antidepressant efficacy. We assessed the impact of eight NTRK2 SNPs pertaining to response and remission after antidepressant treatment in depressed patients. PATIENTS & METHODS: In a naturalistic study, 569 patients with a major depressive episode requiring a new antidepressant treatment were genotyped for eight NTRK2 SNPs (rs1187352, rs1439050, rs1778933 rs2289656, rs2289657, rs2289658, rs3824519, rs56142442) and prospectively assessed for response and remission after 6 months of treatment. RESULTS: No association was shown between the NTRK2 SNPs and response/remission. CONCLUSION: There is no benefit to assess these eight TRKB SNPs to predict response/remission after antidepressant treatment in depressed patients.

Early life adversity is associated with a smaller hippocampus in male but not female depressed in-patients: a case-control study.

BACKGROUND: Three studies assessed the association of early life adversity (ELA) and hippocampal volumes in depressed patients, of which one was negative and the two others did not control for several potential confounding variables. Since the association of ELA and hippocampal volumes differ in male and female healthy volunteers, we investigated the association of ELA and hippocampal volumes in depressed patients, while focusing specifically on sex and controlling for several relevant socio-demographic and clinical variables. METHODS: Sixty-three depressed in-patients treated in a psychiatric setting, with a current Major Depressive Episode (MDE) and a Major Depressive Disorder (MDD) were included and assessed for ELA. Hippocampal volumes were measured with brain magnetic resonance imaging (MRI) and automatic segmentation. They were compared between patients with (n = 28) or without (n = 35) ELA. After bivariate analyses, multivariate regression analyses tested the interaction of sex and ELA on hippocampal volume and were adjusted for several potential confounding variables. The subgroups of men (n = 26) and women (n = 37) were assessed separately. RESULTS: Patients with ELA had a smaller hippocampus than those without ELA (4.65 (±1.11) cm3 versus 5.25 (±1.01) cm3), bivariate: p = 0.03, multivariate: HR = 0.40, 95%CI [0.23;0.71], p = 0.002), independently from other factors. This association was found in men (4.43 (±1.22) versus 5.67 (±0.77) cm3), bivariate: p = 0.006, multivariate HR = 0.23, 95%CI [0.06;0.82], p = 0.03) but not in women. CONCLUSION: ELA is associated with a smaller hippocampus in male but not female depressed in-patients. The reasons for this association should be investigated in further studies.

Pioglitazone could induce remission in major depression: a meta-analysis.

BACKGROUND: Pioglitazone, a selective agonist of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ), prescribed for the treatment of type 2 diabetes, could have antidepressant properties. However, its potential to induce remission of major depressive episodes, the optimal clinical target for an antidepressant drug, is a matter of concern. Indeed, only one out of four double-blind randomized controlled trials show higher remission rates with pioglitazone than with control treatments. Hence, the main aim of this study was to perform a meta-analysis of the efficacy of pioglitazone for the treatment of MDE, focusing on remission rates. METHODS: Four double-blind randomized controlled trials, comprising 161 patients with an MDE, were included in this meta-analysis. Pioglitazone was studied either alone (one study) or as add-on therapy to conventional treatments (antidepressant drugs or lithium salts). It was compared either to placebo (three studies) or to metformin (one study). Remission was defined by a Hamilton Depression Rating Scale score <8 after treatment. RESULTS: Pioglitazone could induce higher remission rates than control treatments (27% versus 10%, I2=17.3%, fixed-effect model: odds ratio [OR] =3.3, 95% confidence interval [95% CI; 1.4; 7.8], P=0.008). The OR was even higher in the subgroup of patients with major depressive disorder (n=80; 23% versus 8%, I2=0.0%; fixed-effect model: OR =5.9, 95% CI [1.6; 22.4], P=0.009) and in the subgroup of patients without metabolic comorbidities (n=84; 33% versus 10%, I2=0.0%; fixed-effect model: OR =5.1, 95% CI [1.5; 17.9], P=0.01). As compared to control treatments, results suggest six patients would need to be treated with pioglitazone in order to achieve the possibility of one more remission. CONCLUSION: Pioglitazone, either alone or as add-on therapy to conventional treatments, could induce remission of MDE, suggesting that drugs with PPAR-γ agonist properties may be true and clinically relevant antidepressants, even in patients without metabolic comorbidities.

Hippocampal volume predicts antidepressant efficacy in depressed patients without incomplete hippocampal inversion.

BACKGROUND: Incomplete hippocampal inversion (IHI), also called malrotation, is a frequent atypical anatomical pattern of the hippocampus. Because of the crucial implication of the hippocampus in Major Depressive Disorder (MDD) and the neurodevelopmental hypothesis of MDD, we aimed to assess the prevalence of IHI in patients with MDD, the link of IHI with hippocampal volume (HV) and the impact of IHI on the predictive value of HV for response and remission after antidepressant treatment. METHODS: IHI (right and left, partial and total and IHI scores) and HV were assessed in 60 patients with a current Major Depressive Episode (MDE) in a context of MDD and 60 matched controls. Patients were prospectively assessed at baseline and after one, three and six months of antidepressant treatment for response and remission. RESULTS: The prevalence of IHI did not significantly differ between MDD patients (right = 23.3%; left = 38.3%) and controls (right = 16.7%; left = 33.3%). IHI was not significantly associated with MDD clinical characteristics. IHI alone did not predict response and remission after antidepressant treatment. However, an interaction between left HV and left IHI predicted six-month response (p = 0.04), HDRS score decrease (p = 0.02) and both three-month (p = 0.04) and six-month (p = 0.03) remission. A case-control design in 30 matched patients with or without left IHI confirmed that interaction. In patients without left IHI, left HV at baseline were smaller in six-month non-remitters as compared to remitters (2.2(± 0.43) cm3 vs 2.97(± 0.5) cm3 p = 0.02), and in six-month non-responders as compared to responders (2.18(± 0.42) cm3 vs 2.86(± 0.54) cm3, p = 0.03). In patients with left IHI, no association was found between left HV at baseline and antidepressant response and remission. CONCLUSION: IHI is not more frequent in MDD patients than in controls, is not associated with HV, but is a confounder that decreases the predictive value of hippocampal volume to predict response or remission after antidepressant treatment. IHI should be systematically assessed in future research studies assessing hippocampal volume in MDD.

Tobacco use is associated with increased plasma BDNF levels in depressed patients.

Since serum Brain Derived Neurotrophic Factor (BDNF) levels are higher in tobacco smokers than in non-smokers and since Major Depressive Disorder (MDD) is associated with a 2-fold increased risk of smoking, we assessed the association of smoking and plasma BDNF levels in 359 depressed MDD patients. Plasma BDNF levels were positively correlated with the magnitude of tobacco consumption (current number of cigarettes/day and number of packs/year). Accordingly, current tobacco users had significantly higher plasma BDNF levels than non-users. In further studies of MDD, peripheral measures of BDNF should take into account tobacco use.