Functional and anatomical evaluation of the effect of nepafenac in prevention of macular edema after phacoemulsification in diabetic patients

AIM: To evaluate the effect of prophylactic administration of nepafenac in prevention of macular edema occurring in diabetic patients after phacoemulsification and to investigate the correlation between optical coherence tomography (OCT) foveal thickness and multifocal electroretinogram (MF-ERG) parameters. METHODS: The study included two groups. Group 1 included 50 diabetic patients with senile cataract (50 eyes, 30 females, 20 males, aged 55±7y) received nepafenac 0.1% eye drop. Group 2 included another 50 diabetic patients with senile cataract (50 eyes, 22 female, 28 males, aged 53.8±8y) did not receive nepafenac. All patients were followed up for 3mo postoperatively. OCT and MF-ERG were done preoperative and at 1wk, 1, 2 and 3mo. RESULTS: The mean foveal thickness was statistically significantly lower in Group 1. Five eyes in Group 2 developed clinical cystoid macular oedema (CMO) (10%), and no patients in Group 1 developed central macular thickening more than 50 μm. There were insignificant differences in MF-ERG amplitudes and latencies between the two groups except in the five eyes that developed CMO, there statistically significant reduction of MF-ERG amplitude with increase in foveal thickness. CONCLUSION: Perioperative nepafenac reduces the incidence of CMO following uncomplicated phacoemulsification significantly. Nepafenac has no side effects.     

Chronic neuroprotective effects of low concentration lithium on SH-SY5Y cells:possible involvement of stress proteins and gene expression

To investigate the molecular mechanism underlying the neuroprotective effect of lithium on cells, in this study, we exposed SH-SY5Y cells to 0.5 mmol/L lithium carbonate(Li2CO2) for 25–50 weeks and then detected the expression levels of some neurobiology related genes and post-translational modifications of stress proteins in SH-SY5Y cells. cDNA arrays showed that pyruvate kinase 2(PKM2) and calmodulin 3(CaM 3) expression levels were significantly down-regulated, phosphatase protein PP2A expression was lightly down-regulated, and casein kinase II(CK2), threonine/tyrosine phosphatase 7(PYST2), and dopamine beta-hydroxylase(DBH) expression levels were significantly up-regulated. Besides, western blot analysis of stress proteins(HSP27, HSP70, GRP78 and GRP94) showed an over-expression of two proteins: a 105 kDa protein which is a hyper-phosphorylated isoform of GRP94, and a 108 kDa protein which is a phosphorylated tetramer of HSP27. These results suggest that the neuroprotective effects of lithium are likely related to gene expressions and post-translational modifications of proteins cited above.     

A Basomedial Amygdala to Intercalated Cells Microcircuit Expressing PACAP and Its Receptor PAC1 Regulates Contextual Fear

Trauma can cause dysfunctional fear regulation leading some people to develop disorders, such as post-traumatic stress disorder (PTSD). The amygdala regulates fear, whereas PACAP (pituitary adenylate activating peptide) and PAC1 receptors are linked to PTSD symptom severity at genetic/epigenetic levels, with a strong link in females with PTSD. We discovered a PACAPergic projection from the basomedial amygdala (BMA) to the medial intercalated cells (mICCs) in adult mice. In vivo optogenetic stimulation of this pathway increased CFOS expression in mICCs, decreased fear recall, and increased fear extinction. Selective deletion of PAC1 receptors from the mICCs in females reduced fear acquisition, but enhanced fear generalization and reduced fear extinction in males. Optogenetic stimulation of the BMA-mICC PACAPergic pathway produced EPSCs in mICC neurons, which were enhanced by the PAC1 receptor antagonist, PACAP 6-38. Our findings show that mICCs modulate contextual fear in a dynamic and sex-dependent manner via a microcircuit containing the BMA and mICCs, and in a manner that was dependent on behavioral state.SIGNIFICANCE STATEMENT Traumatic stress can affect different aspects of fear behaviors, including fear learning, generalization of learned fear to novel contexts, how the fear of the original context is recalled, and how fear is reduced over time. While the amygdala has been studied for its role in regulation of different aspects of fear, the molecular circuitry of this structure is quite complex. In addition, aspects of fear can be modulated differently in males and females. Our findings show that a specific circuitry containing the neuropeptide PACAP and its receptor, PAC1, regulates various aspects of fear, including acquisition, generalization, recall, and extinction in a sexually dimorphic manner, characterizing a novel pathway that modulates traumatic fear.     

Primary and secondary hyperoxaluria: Understanding the enigma

Hyperoxaluria is characterized by an increased urinary excretion of oxalate. Primary and secondary hyperoxaluria are two distinct clinical expressions of hyperoxaluria. Primary hyperoxaluria is an inherited error of metabolism due to defective enzyme activity. In contrast, secondary hyperoxaluria is caused by increased dietary ingestion of oxalate, precursors of oxalate or alteration in intestinal microflora. The disease spectrum extends from recurrent kidney stones, nephrocalcinosis and urinary tract infections to chronic kidney disease and end stage renal disease. When calcium oxalate burden exceeds the renal excretory ability, calcium oxalate starts to deposit in various organ systems in a process called systemic oxalosis. Increased urinary oxalate levels help to make the diagnosis while plasma oxalate levels are likely to be more accurate when patients develop chronic kidney disease. Definitive diagnosis of primary hyperoxaluria is achieved by genetic studies and if genetic studies prove inconclusive, liver biopsy is undertaken to establish diagnosis. Diagnostic clues pointing towards secondary hyperoxaluria are a supportive dietary history and tests to detect increased intestinal absorption of oxalate. Conservative treatment for both types of hyperoxaluria includes vigorous hydration and crystallization inhibitors to decrease calcium oxalate precipitation. Pyridoxine is also found to be helpful in approximately 30% patients with primary hyperoxaluria type 1. Liver-kidney and isolated kidney transplantation are the treatment of choice in primary hyperoxaluria type 1 and type 2 respectively. Data is scarce on role of transplantation in primary hyperoxaluria type 3 where there are no reports of end stage renal disease so far. There are ongoing investigations into newer modalities of diagnosis and treatment of hyperoxaluria. Clinical differentiation between primary and secondary hyperoxaluria and further between the types of primary hyperoxaluria is very important because of implications in treatment and diagnosis. Hyperoxaluria continues to be a challenging disease and a high index of clinical suspicion is often the first step on the path to accurate diagnosis and management.     

Counselor skill influences outcomes of brief motivational interventions

The aim of this study was to estimate the influence of counselor skills during brief motivational interventions (BMIs) on patient alcohol use 12 months later. Ninety-five BMIs delivered by five counselors of similar background and training were recorded and coded using the Motivational Interviewing Skills Code (MISC). Baseline alcohol measures and sociodemographics of patients did not differ across counselors, whereas MISC scores and outcome at 12 months did. Multilevel models showed that counselors with better motivational interviewing (MI) skills achieved better outcomes overall and maintained efficacy across all levels of an important predictor (patient ability to change), whereas counselors with poorer MI skills were effective mostly at high levels of ability to change. Findings indicated that avoidance of MI-inconsistent skills was more important than frequency of using MI-consistent skills and that training and selection of counselors should be based more on the overall MI-consistent gestalt than on particular MI techniques.