Molecular mechanism of caloric restriction mimetics-mediated neuroprotection of age-related neurodegenerative diseases: an emerging therapeutic approach.

Aging-induced neurodegenerative diseases (NDs) are significantly increasing health problem worldwide. It has been well documented that oxidative stress is one of the potential causes of aging and age-related NDs. There are no drugs for the treatment of NDs, therefore there is an immediate necessity for the development of strategies/treatments either to prevent or cure age-related NDs. Caloric restriction (CR) and intermittent fasting have been considered as effective strategies in increasing the healthspan and lifespan, but it is difficult to adhere to these routines strictly, which has led to the development of calorie restriction mimetics (CRMs). CRMs are natural compounds that provide similar molecular and biochemical effects of CR, and activate autophagy process. CRMs have been reported to regulate redox signaling by enhancing the antioxidant defense systems through activation of the Nrf2 pathway, and inhibiting ROS generation through attenuation of mitochondrial dysfunction. Moreover, CRMs also regulate redox-sensitive signaling pathways such as the PI3K/Akt and MAPK pathways to promote neuronal cell survival. Here, we discuss the neuroprotective effects of various CRMs at molecular and cellular levels during aging of the brain. The CRMs are envisaged to become a cornerstone of the pharmaceutical arsenal against aging and age-related pathologies.

Attractor-like Dynamics in the Subicular Complex.

Distinct computations are performed at multiple brain regions during the encoding of spatial environments. Neural representations in the hippocampal, entorhinal, and head direction (HD) networks during spatial navigation have been clearly documented, while the representational properties of the subicular complex (SC) are relatively underexplored, although it has extensive anatomic connections with various brain regions involved in spatial information processing. We simultaneously recorded single units from different subregions of the SC in male rats while they ran clockwise on a centrally placed textured circular track (four different textures, each covering a quadrant), surrounded by six distal cues. The neural activity was monitored in standard sessions by maintaining the same configuration between the cues, while in cue manipulation sessions, the distal and local cues were either rotated in opposite directions to create a mismatch between them or the distal cues were removed. We report a highly coherent neural representation of the environment and a robust coupling between the HD cells and the spatial cells in the SC, strikingly different from previous reports of coupling between cells from co-recorded sites. Neural representations were (1) originally governed by the distal cues under local-distal cue-conflict conditions, (2) controlled by the local cues in the absence of distal cues, and (3) governed by the cues that are perceived to be stable. We propose that such attractor-like dynamics in the SC might play a critical role in the orientation of spatial representations, thus providing a "reference map" of the environment for further processing by other networks.SIGNIFICANCE STATEMENT The subicular complex (SC) receives major inputs from the entorhinal cortex and the hippocampus, and head direction (HD) information directly from the HD system. Using cue-conflict experiments, we studied the hierarchical representation of the local and distal cues in the SC to understand its role in the cognitive map, and report a highly coherent neural representation with robust coupling between the HD cells and the spatial cells in different subregions of the SC exhibiting attractor-like dynamics unaffected by the cue manipulations, strikingly different from previous reports of coupling between cells from co-recorded sites. This unique feature may allow the SC to function as a single computational unit during the representation of space, which may serve as a reference map of the environment.

The shear bond strength of MTA with three different types of adhesive systems: An in vitro study.

AIM: To evaluate the shear bond strength of MTA with three different types of adhesive systems- self-adhering flowable composite, etch and rinse adhesive system and self etch adhesive system. METHODOLOGY: MTA specimens (n = 60) were prepared using cylindrical acrylic blocks, having a central cavity with 4 mm diameter and 2 mm depth. MTA was mixed and placed in the prepared cavity, and was covered with a moist cotton pellet and temporary filling material. The specimens were divided into 3 groups which were further divided into 2 sub-groups (45 Minutes and 24 hours). After the application of bonding agents composite resin was placed over the MTA surface. The specimens were tested for shear bond strength and readings were statically analyzed. RESULT: After 24 hrs the mean value of etch and rinse group was significantly higher than self etch and the self adhering composite groups. Among the 45 minutes groups there were no significant difference. CONCLUSION: In single visit after 45 minutes self adhering flowable can be used successfully as a final restorative material in place of conventional flowable composite without using any alternative adhesive system over MTA.

Trichobezoar Causing Gastric Perforation: A Case Report.

Trichobezoars are impactions of swallowed hairs in the stomach and occasionally in the intestine. They occur in emotionally disturbed, depressed, or mentally retarded patients who have trichotillomania and trichophagia. Trichobezoars are usually diagnosed on CT scan or upper GI endoscopy. They can give rise to complications like gastroduodenal ulceration, haemorrhage, perforation, peritonitis, or obstruction, with a high rate of mortality. The treatment is endoscopic, laparoscopic, or surgical removal and usually followed by psychiatric opinion. Herein, we report a case of gastric trichobezoar presenting as gastric perforation in a patient of trichotillomania and trichophagia that was accidentally found on laparotomy. As the patient was in shock on admission, relevant history of trichophagia could not be elicited. Henceforth, she was operated for perforation peritonitis. Trichobezoar was discovered intraoperatively and removed. The perforation was repaired with Graham's omental patch. Postoperatively, history of trichophagia was corroborated with scarring alopecia of scalp. Trichobezoars is usually seen in adolescent girls, often with an underlying psychiatric or social problem. Laparotomy is the gold standard treatment. Surgical treatment should be followed by behavioral and psychiatric treatment. The patient should be vigilantly monitored for this impulsive disorder, as recurrences are common.