Hepatitis B Virus x Protein Increases Cellular OCT3/4 and MYC and Facilitates Cellular Reprogramming.

Hepatitis B virus x (HBx) is a multifunctional protein coded by the Hepatitis B virus that is involved in various cellular processes such as proliferation, cell survival/apoptosis, and histone methylation. HBx was reported to be associated with liver "cancer stem cells." The stemness inducing properties of HBx could also facilitate the generation of pluripotent stem cells from somatic cells. It is well established that somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) using a cocktail of transcription factors called Yamanaka's factors (YFs) (OCT4, SOX2, KLF4, and MYC). The reprogramming process proceeds step-by-step with reprogramming factor chromatin interactions, transcription, and chromatin states changing during transitions. HBx is a "broad spectrum trans-activator" and therefore could facilitate these transitions. We electroporated low passage and high passage (difficult to reprogram) fibroblasts using YFs with and without HBx and evaluated the reprogramming efficiency. We also investigated the tri-lineage and terminal differentiation potential of iPSC derived using HBx. We found that the addition of HBx to YF improves iPSC derivation, and it increases the efficiency of iPSC generation from "difficult or hard-to-reprogram samples" such as high passage/senescent fibroblasts. Further, we show that HBx can substitute the key transcription factor MYC in the YF cocktail to generate iPSC. The cellular levels of OCT3/4 and MYC were increased in HBx expressing cells. Our results have practical value in improving the efficiency of pluripotent stem cell derivation from "difficult to reprogram" somatic cells, in addition to providing some insights into the mechanisms of liver carcinogenesis in chronic hepatitis B. To conclude, HBx improves the reprogramming efficiency of YFs. HBx increases the cellular levels of OCT3/4 and MYC.

Outcome in 32 cases of tethered cord in adults-is intervention justified?

INTRODUCTION: Adults rarely present with tethered cord syndrome, and this review examines whether it is justifiable to perform surgical intervention in this group. METHODS: Between 2003 and 2017, we performed surgical intervention in 32 adults with tethered cord syndrome. The age range varied from 22 to 65 years. Twenty-six had pain, 20 had motor deficits, and 18 had sensory deficits, whereas 17 presented with sphincter disturbances. Three had undergone surgery for meningomyelocele as infants. Six patients had major spinal deformity in the shape of kyphosis or scoliosis. All patients underwent digital radiographs and MR scans of the whole spine. The oldest with a leaking open meningocele was 41 years old. RESULTS: The mean follow-up was 3.2 years. Twenty-one out of 26 patients presenting with pain had their VAS scores improve significantly; 14 had motor deficits which improved. However, sensory deficits got better in only 7 out of 18 patients, and sphincter improvement was documented (via urodynamics studies and bladder ultrasound) in only 4 out of 17 patients. In 15 cases, surgery was performed under neurophysiological monitoring, and overall improvement was documented in 11 of these patients compared with 7 of the remaining 17 patients. Surgery for spinal deformity was performed in 6 patients, and deformity correction as well as pain reduction was achieved in all. CONCLUSION: Surgery leads to significant reduction of pain by untethering and in those with spinal deformity by correction of the same. Improvement in sensory changes and sphincter problems occurred in few patients. Neuromonitoring certainly has improved our results.

Sphenoid Wing Meningioma Presenting as Cognitive Impairment.

Frontal meningioma may present solely withpsychological symptoms that resemble dementia. We present the case of a 42-year-old man who initially was thought to have dementia, but he was eventually diagnosed with dementia caused by a sphenoid wing meningioma. Diagnosis of this illness is often delayed due to the insidious nature of the symptoms, which may be mistaken as symptoms of dementia. As cognitive impairment is complex and easily overlooked, it is important to accurately assess neuropsychological function in patients with large brain tumors.

Obsessive slowness presenting as catatonia in a patient with Borderline Intelligence.

Obsessive slowness is described to be a syndrome of extreme slowness in ways various tasks are performed. Its existence as an independent syndrome is challenged by authors, who regard it to be a part of obsessive compulsive disorder. We describe here a case of a 24-year-old male patient who presented with catatonic symptoms. Diagnostic difficulties and management issues are highlighted.

Oligodendroglioma presenting as chronic mania.

SUMMARY: Oligodendrogliomas may present with a variety of psychological symptoms but it only rarely presents with mania. The patient described in this case report is a 55-year-old man with a three year history of progressive mania who was initially diagnosed as chronic mania but a subsequent MRI identified a brain tumor. This report highlights the importance of considering differential organic diagnosis when patients present with atypical presentations of psychiatric disorders. A brain tumor should be considered and brain imaging studies conducted for patients with a late age of onset who do not respond to appropriate medication.

Foxo3a transcriptionally upregulates AQP4 and induces cerebral edema following traumatic brain injury.

Increased cranial pressure due to development of edema contributes significantly to the pathology of traumatic brain injury (TBI). Induction of an astrocytic water channel protein, Aquaporin 4 (AQP4), is known to predominantly contribute to cytotoxic edema following TBI. However, the mechanism for the increase in AQP4 following 24 h of TBI is poorly understood. Here we show that transcriptional activation of a ubiquitously expressed mammalian forkhead transcription factor, Foxo3a, induces cerebral edema by increasing the AQP4 level in the controlled cortical impact model of TBI in mice. TBI stimulates nuclear translocation of Foxo3a in astrocytes and subsequently augments its binding to AQP4 promoter in pericontusional cortex. Nuclear accumulation of Foxo3a is augmented by a decrease in phosphorylation at its Ser256 residue due to inactivation of Akt after TBI. Depletion of Foxo3a in mice rescues cytotoxic edema by preventing induction of AQP4 as well as attenuates memory impairment after TBI in mice.

Psychiatric aspects of burn.

Burn injuries and their subsequent treatment cause one of the most excruciating forms of pain imaginable. The psychological aspects of burn injury have been researched in different parts of the world, producing different outcomes. Studies have shown that greater levels of acute pain are associated with negative long-term psychological effects such as acute stress disorder, depression, suicidal ideation, and post-traumatic stress disorder for as long as 2 years after the initial burn injury. The concept of allostatic load is presented as a potential explanation for the relationship between acute pain and subsequent psychological outcomes. A biopsychosocial model is also presented as a means of obtaining better inpatient pain management and helping to mediate this relationship.