The Role of the Medial Prefrontal Cortex in Regulating Social Familiarity-Induced Anxiolysis

Overcoming specific fears and subsequent anxiety can be greatly enhanced by the presence of familiar social partners, but the neural circuitry that controls this phenomenon remains unclear. To overcome this, the social interaction (SI) habituation test was developed in this lab to systematically investigate the effects of social familiarity on anxiety-like behavior in rats. Here, we show that social familiarity selectively reduced anxiety-like behaviors induced by an ethological anxiogenic stimulus. The anxiolytic effect of social familiarity could be elicited over multiple training sessions and was specific to both the presence of the anxiogenic stimulus and the familiar social partner. In addition, socially familiar conspecifics served as a safety signal, as anxiety-like responses returned in the absence of the familiar partner. The expression of the social familiarity-induced anxiolysis (SFiA) appears dependent on the prefrontal cortex (PFC), an area associated with cortical regulation of fear and anxiety behaviors. Inhibition of the PFC, with bilateral injections of the GABA_A agonist muscimol, selectively blocked the expression of SFiA while having no effect on SI with a novel partner. Finally, the effect of D-cycloserine, a cognitive enhancer that clinically enhances behavioral treatments for anxiety, was investigated with SFiA. D-cycloserine, when paired with familiarity training sessions, selectively enhanced the rate at which SFiA was acquired. Collectively, these outcomes suggest that the PFC has a pivotal role in SFiA, a complex behavior involving the integration of social cues of familiarity with contextual and emotional information to regulate anxiety-like behavior.     

The unusual chaperonins of Mycobacterium tuberculosis

Heat shock proteins (Hsps), also known as molecular chaperones, are a diverse set of proteins that mediate the correct folding, assembly, transport and degradation of other proteins. In addition, Hsps have been shown to play a variety of important roles in immunity, thereby representing prominent antigens in the humoral and cellular immune response. Chaperonins form a sub-group of molecular chaperones that are found in all domains of life. Chaperonins in all bacteria are encoded by the essential groEL and groES genes, also called cpn60 and cpn10 arranged on the bicistronic groESL operon. Interestingly, Mycobacterium tuberculosis contains two copies of the cpn60 genes. The existence of a duplicate set of cpn60 genes in M. tuberculosis, however, has been perplexing. Cpn10 and Cpn60s of M. tuberculosis have been shown to be highly antigenic in nature, eliciting strong B- and T-cell immune responses. Recent work has shown intriguing structural, biochemical and signaling properties of the M. tuberculosis chaperonins. This review details the recent developments in the study of the M. tuberculosis chaperonins.     

Alcohol-related acute-on-chronic liver failure—Comparison of various prognostic scores in predicting outcome

Background and Aims

Various prognostic scores are available for predicting outcome in acute-on-chronic liver failure (ACLF). We compared the available prognostic models as predictors of outcome in alcohol-related ACLF patients.

Methods

All consecutive patients with alcohol-related ACLF were included. At admission, prognostic indices-acute physiology and chronic health evaluation score (APACHE II), model for end-stage liver disease (MELD), MELD-Na, Maddrey’s discriminant function (DF), age-bilirubin-INR-creatinine (ABIC), and Chronic Liver Failure Consortium (CLIF-C) ACLF score (CLIF-C ACLF) score were calculated. Receiver operator characteristic (ROC) curves were plotted for all prognostic scores with in-hospital, 90-day, and 1-year mortality as outcome.

Results

Of the 171 patients, 170 were males, and grade 1 ACLF in 20 (11.7%), grade 2 in 52 (30.4%), and grade 3 in 99 (57.9%) patients. One hundred and nineteen (69.6%) died in-hospital. The median (IQR) Maddrey’s score, MELD, MELD-Na, ABIC, APACHE II, and CLIF-C ACLF were 87.8 (66.5–123.0), 33.1 (27.6–40.0), 34.4 (29.5–40.0), 8.5 (7.3–9.6), 15 (12–21), and 51.1 (44.1–56.4), respectively. On multivariate Cox regression analysis, independent predictors of in-hospital outcome were presence of hepatic encephalopathy (early HR, 2.078; 95%CI, 1.173–3.682, p?=?0.012 and advanced, HR, 2.330; 95% CI, 1.270–4.276, p?=?0.006), elevated serum creatinine (HR, 1.140; 95% CI, 1.023–1.270, p?=?0.018), and infection at admission (HR, 1.874; 95% CI, 1.160–23.029, p?=?0.010). On comparison of ROC curves, APACHE II and CLIF-C ACLF AUROC were significantly higher than MELD, MELD-Na, DF, and ABIC (p?<?0.05) for predicting in-hospital, 90-day, and 1-year mortality. The AUROC was highest for APACHE II followed by CLIF-C ACLF (Hanley and McNeil, p?=?0.660).

Conclusions

Alcohol-related ACLF has high in-hospital mortality. Among the available prognostic scores, CLIF-C ACLF and APACHE II perform best.

     

Synthesis of diversely substituted bis-pyrrolizidino/ thiopyrrolizidino oxindolo/acenaphthyleno curcuminoids via sequential azomethine ylide cycloaddition

Curcumin has been transformed to several diversely substituted bis-pyrrolizidino/thiopyrrolizidino oxindolo/acenaphthyleno curcuminoids via a sequential azomethine ylide cycloaddition reaction using isatins/acenaphthoquinone and proline/thioproline as the reagents. The products were separated via extensive chromatography and characterized by 1D/2D NMR and HRMS analysis.

Curcumin has been transformed to several diversely substituted bis-pyrrolizidino/thiopyrrolizidino oxindolo/acenaphthyleno curcuminoids via a sequential azomethine ylide cycloaddition reaction.     

Comparative Evaluation of PCR and Imprint Smear Microscopy Analyses of Skin Biopsy Specimens in Diagnosis of Macular,Papular, and Mixed Papulo-Nodular Lesions of Post-Kala-Azar Dermal Leishmaniasis

Diagnosis of post-kala-azar dermal leishmaniasis (PKDL), particularly the macular form, is difficult when based on microscopy. This study compared the results of nested PCR (91.9% positive samples) with imprint smear microscopy (70.9% positive samples) for 62 PKDL samples. We found that nested PCR, which indicated 87.5% positivity for the macular lesions, compared to 41.6% positivity by imprint smear microscopy, is an efficient method for early diagnosis of PKDL.