Impaired delay and trace eyeblink conditioning performance in major depressive disorder

BACKGROUND: Preliminary evidence obtained in our lab has revealed that depressive symptoms impair associative learning, as measured by acquisition of eyeblink classical conditioning (EBCC) tasks. The current study assesses EBCC acquisition in individuals with major depressive disorder (MDD). METHODS: The 17-item Hamilton Rating Scale for Depression (HAM-D(17)) and the 30-item Inventory for Depressive Symptomatology, Self-Report (IDS-SR(30)) were used to quantify severity of depressive symptoms. Participants received 60 trials each in delay 500, trace 500, and trace 1000 conditioning paradigms. A 150-ms, 5-7 psi air puff served as the unconditioned stimulus (US), and an 80-dB, 1-kHz tone as the conditioned stimulus (CS). Mean percent conditioned responses (CRs) served as the primary measure of task acquisition. RESULTS: The MDD group generated significantly fewer CRs on delay 500 and trace 500 tasks, and approached significance on the trace 1000 task compared to healthy controls. Furthermore, presentation of successive trials did not increase CR production in the depressed group, in contrast to progressive increases observed in the control group. LIMITATIONS: The presentation of multiple EBCC tasks precludes some detailed analyses of task-specific performance. Future studies may also benefit from including sufficient numbers of subjects to assess differential characteristics of depression (e.g., length of episode, depressive subtype) and treatment effects. CONCLUSIONS: These data suggest that MDD impairs acquisition of EBCC, providing behavioral support for cerebellar and hippocampal dysfunction in depression. Delineating the neural substrates involved in MDD may aid in future treatment approaches for this pervasive disorder.     

Carbetocin versus oxytocin to reduce additional uterotonic use at non-elective caesarean section: a double-blind,randomised trial*

Objective: We compared the efficacy of Carbetocin (long-acting oxytocin receptor agonist) versus Oxytocin given at non-elective caesarean section.

Method: We performed a double-blind, randomised, single-centre study. Eligible women were?≥37 weeks of gestation undergoing emergency caesarean section. Participants received either carbetocin of 100?μg or oxytocin 5 international units. The primary outcome was the need to administer additional uterotonics, as determined by the clinician. Secondary outcomes included estimated blood loss, haemoglobin drop pre–post operation and the need for a blood transfusion

Results: From August 2012 to February 2013, 114 women were enroled. Two were excluded from analysis as they received a general anaesthetic. Fifty-nine patients received 100-μg carbetocin; 53 received 5 international units oxytocin. There was no statistically significant difference in the number of women requiring additional uterotonics between the two groups: Carbetocin group 22% and Oxytocin group 13% (p?=?0.323). There were no significant differences in the fall in haemoglobin, estimated blood loss, rates of post-partum haemorrhage or blood transfusions.

Conclusion: Oxytocin and carbetocin have similar requirements for additional uterotonics, estimated blood loss, haemoglobin drop and blood transfusions. There was a trend towards requiring additional uterotonics in patients receiving Carbetocin which was not statistically significant. This study found no benefits in using carbetocin over oxytocin.     

Pseudomonas aeruginosa biofilms perturb wound resolution and antibiotic tolerance in diabetic mice

Diabetic patients are more susceptible to the development of chronic wounds than non-diabetics. The impaired healing properties of these wounds, which often develop debilitating bacterial infections, significantly increase the rate of lower extremity amputation in diabetic patients. We hypothesize that bacterial biofilms, or sessile communities of bacteria that reside in a complex matrix of exopolymeric material, contribute to the severity of diabetic wounds. To test this hypothesis, we developed an in vivo chronic wound, diabetic mouse model to determine the ability of the opportunistic pathogen, Pseudomonas aeruginosa, to cause biofilm-associated infections. Utilizing this model, we observed that diabetic mice with P. aeruginosa-infected chronic wounds displayed impaired bacterial clearing and wound closure in comparison with their non-diabetic littermates. While treating diabetic mice with insulin improved their overall health, it did not restore their ability to resolve P. aeruginosa wound infections or speed healing. In fact, the prevalence of biofilms and the tolerance of P. aeruginosa to gentamicin treatment increased when diabetic mice were treated with insulin. Insulin treatment was observed to directly affect the ability of P. aeruginosa to form biofilms in vitro. These data demonstrate that the chronically wounded diabetic mouse appears to be a useful model to study wound healing and biofilm infection dynamics, and suggest that the diabetic wound environment may promote the formation of biofilms. Further, this model provides for the elucidation of mechanistic factors, such as the ability of insulin to influence antimicrobial effectiveness, which may be relevant to the formation of biofilms in diabetic wounds.     

Clinical differences among depressed patients with and without a history of suicide attempts: findings from the STAR*D trial

BACKGROUND: This study sought to determine whether a history of suicide attempts among outpatients diagnosed with nonpsychotic major depressive disorder (MDD) is correlated with any difference in clinical presentation that should influence patient care. METHODS: Baseline data from the Sequenced Treatment Alternatives to Relieve Depression (STAR()D) trial on outpatients with MDD treated in primary and specialty care settings were used to model significant demographic and clinical correlates of suicide attempter status. RESULTS: Altogether, 16.5% of participants (n=667) reported prior suicide attempts. Controlling for age, gender, and depressive symptom severity, previous attempters had more current general medical conditions (micro=3.2 vs. 2.9, p<.0001), more current alcohol/substance abuse (p<.0001), and more work hours missed in the past week (26.2% vs. 18.2%, p<.0001) than non-attempters. On average, for the previously suicidal, the onset of MDD occurred 8.9 years earlier in life (p<.0001) and had included 1.2 additional depressive episodes (p=0.001) compared to those without prior suicidal behavior. Previous attempters also reported more current suicidal ideation (61.3% of previous attempters, adjusted OR 1.6, vs. 45.5% of nonattempters, p<.0001). LIMITATIONS: Presence or absence of a history of suicide attempts was determined only through self report. CONCLUSIONS: Those with a history of suicidal behavior suffer a greater burden of depressive illness. Earlier intervention and ongoing, aggressive care, including maintenance-phase pharmacotherapy, may be critical to mitigating the long-term consequences associated with this increased disease burden.     

A case of autoimmune myopathy in pregnancy

Autoimmune diseases are not found frequently with pregnancy in clinical practice. Polymyositis Dermatomyositis have a prevalence of 2.4-10.7/ 100,000 in general population. This is further low in pregnant women. It is associated with 57% perinatal morbidity and increased maternal and fetal mortality. Literature suggests that pregnancy outcomes are poorer if it manifests early in gestation while development or exacerbation in second or third trimester is associated with a better fetal prognosis. Not many case reports are published where the disease was diagnosed in third trimester. We present a case detected in third trimester, which was initially mistaken as a case of allergic reaction, however timely diagnosis and adequate management resulted in good fetal and maternal outcome.     

Structure and genetic relationship of five populations from central India based on 15 autosomal STR loci

Aim: To estimate population parameters based on allele frequencies obtained for 15 polymorphic autosomal STR loci investigated in caste and tribal populations of central India (n?=?419).

Methods: Multiplexed PCR amplifications of the 15 Autosomal STR Loci were performed and amplified products were genotyped using multi-capillary electrophoresis on an ABI 3100 genetic analyser. Parameters of population genetics and forensic interest based on the allele frequencies were calculated. Genetic affinity of the studied populations among themselves and with previously reported populations of India was also analysed using distance-based NJ tree and using PCA plot.

Results: All the 15 STR loci were highly informative and discriminating, with CPD of 0.999 99. Except for Brahmins and Rajput, all other studied populations were in Hardy–Weinberg equilibrium (HWE). The only tribe (Gond) population studied showed significant variation with the other four caste populations (Brahmin, Yadav, Rajput and Muslim) studied and formed a cluster with other previously reported tribal populations of India. Nei’s genetic distance based clustering pattern of the NJ tree and the PCA plot showed the same pattern of genetic relationship, i.e. caste and tribal populations formed a distinct cluster.

Conclusions: With respect to the distribution of alleles at each STR locus, the studied loci were found to be substantially polymorphic in all the studied populations, indicating good informativeness of all 15 STR markers. The population data generated in this study are useful for forensic, anthropological and demographic studies.     

Emergency Department Visit Data for Rapid Detection and Monitoring of Norovirus Activity,United States

Noroviruses are the leading cause of gastroenteritis in the United States, but timely measures of disease are lacking. BioSense, a national-level electronic surveillance system, assigns data on chief complaints (patient symptoms) collected during emergency department (ED) visits to 78 subsyndromes in near real-time. In a series of linear regression models, BioSense visits mapped by chief complaints of diarrhea and nausea/vomiting subsyndromes as a monthly proportion of all visits correlated strongly with reported norovirus outbreaks from 6 states during 2007–2010. Higher correlations were seen for diarrhea (R = 0.828–0.926) than for nausea/vomiting (R = 0.729–0.866) across multiple age groups. Diarrhea ED visit proportions exhibited winter seasonality attributable to norovirus; rotavirus contributed substantially for children <5 years of age. Diarrhea ED visit data estimated the onset, peak, and end of norovirus season within 4 weeks of observed dates and could be reliable, timely indicators of norovirus activity.     

Randomized comparison of selective serotonin reuptake inhibitor (escitalopram) monotherapy and antidepressant combination pharmacotherapy for major depressive disorder with melancholic features: a CO-MED report

Background

The clinical effects of antidepressant combinations vs. monotherapy as initial treatment for major depression with melancholic features (MDD-MF) are unknown.

Methods

Outpatients with chronic or recurrent major depression (MDD) were randomized to initial treatment with escitalopram + placebo (the MONO condition), bupropion-sustained release + escitalopram, or venlafaxine-extended release + mirtazapine (the COMB conditions) in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial. Secondary data analyses were conducted to compare demographic and clinical characteristics, and contrast clinical responses according to drug treatment, in patients with MDD-MF (n = 124) and non-melancholic MDD (n = 481).

Results

While numerically lower, remission rates in MDD-MF did not differ significantly from those with non-melancholic MDD either at 12 (33.1% vs. 41.0%, aOR 1.16, p = 0.58) or 28 (39.5% vs. 46.8%, aOR = 1.02, p = 0.93) weeks of treatment. Remission rates did not differ significantly between combination and monotherapy groups in either MDD-MF or non-melancholic MDD patients at either time point. Similar conclusions were reached for response rates, premature study discontinuation, and self-rated depression symptom severity.

Limitations

This is a secondary analysis of data from the CO-MED trial, which was not designed to address differential treatment response in melancholic and non-melancholic MDD.

Conclusions

We found no evidence of differential remission or response rates to antidepressant combination or monotherapy between melancholic/non-melancholic MDD patients, or according to antidepressant treatment group, after 12 and 28 weeks. Melancholic features may not be a valid predictor of more favorable response to antidepressant combination therapy as initial treatment.