GSK3β phosphorylates Six1 transcription factor and regulates its APC/C mediated proteosomal degradation.

Sine oculis homeobox homolog 1 (Six1) is a developmentally important transcription factor that regulates cellular proliferation, apoptosis, and dissemination during embryogenesis. Six1 overexpression as reported in multiple cancers modulates expression of a repertoire of its target genes causing an increase in proliferation, metastasis and survival of cancer cells. Six1 exists as a cell cycle regulated nuclear phosphoprotein and its cellular turnover is regulated by APC/C (Anaphase promoting complex / Cyclosome) complex mediated proteolysis.

Serum MicroRNAs as Predictors for HCV Progression and Response to Treatment in Pakistani Patients.

Hepatitis is one of the common liver diseases, imposing a heavy health burden worldwide. Acute hepatitis may develop into chronic hepatitis, progressing to cirrhosis and hepatocellular carcinoma. In the present study, the expression of miRNAs was quantified by real-time PCR, such as miRNA-182, 122, 21, 150, 199, and 222.

Molecular Characterization, Purification, and Mode of Action of KAE01 from Lactic Acid Bacteria and Its In Silico Analysis against MDR/ESBL .

Bacteriocins are gaining immense importance in therapeutics since they show significant antibacterial potential. This study reports the bacteriocin KAE01 from along with its characterization, molecular modeling, and antibacterial potency, by targeting the matrix protein of . The bacteriocin was purified by using ammonium sulfate precipitation and fast protein liquid chromatography (FPLC), and its molecular weight was estimated as 55 kDa by means of SDS-PAGE.

Neuroprotective effects of Bhilawanol and Anacardic acid during glutamate-induced neurotoxicity.

Bhilawanol (Bh) and anacardic acid (AA) are two lipid-soluble compounds mostly found in the nut of Semecarpus anacardium (SA). This herb has many medicinal properties including enhancing learning and memory, yet its active compounds have not been studied for neuroprotective effects. We investigated the neuroprotective effects of Bh and AA against glutamate induced cell death in the adrenal pheochromocytoma cell line of rats (PC12 cells).

Stress level assessment among health care workers involved in the management of critically ill COVID-19 patients.

Background: Intensive care health care workers (HCWs) are frontlines of this crisis as they deal with critically ill COVID-19 patients which can potentially affect their mental well-being and causes different levels of stress.

Aim: To determine the prevalence of stress among HCWs involved in the management of critically ill COVID-19 patient, identify the factors associated with stress, and highlight the availability of psychological support provided to HCWs.

Methods: A cross-sectional multicenter, international study using a web-based questionnaire of 27 questions including the Perceived Stress Scale-10 (PSS-10) for assessment of stress level.

Development of a novel, sensitive translational immunoassay to detect plasma glial fibrillary acidic protein (GFAP) after murine traumatic brain injury.

Background: Glial fibrillary acidic protein (GFAP) has emerged as a promising fluid biomarker for several neurological indications including traumatic brain injury (TBI), a leading cause of death and disability worldwide. In humans, serum or plasma GFAP levels can predict brain abnormalities including hemorrhage on computed tomography (CT) scans and magnetic resonance imaging (MRI). However, assays to quantify plasma or serum GFAP in preclinical models are not yet available.

Improved Detection of Postoperative Residual Meningioma with [Ga]Ga-DOTA-TOC PET Imaging Using a High-resolution Research Tomograph PET Scanner.

Purpose: PET with somatostatin receptor ligand [Ga]Ga-DOTA-D-Phe-Tyr-octreotide ([Ga]Ga-DOTA-TOC) is an established method in radiotherapy planning because of the improved detection and delineation of meningioma tissue. We investigated the diagnostic accuracy of supplementary [Ga]Ga-DOTA-TOC PET in patients with a 3-month postoperative MRI reporting gross-total resection (GTR).

Experimental Design: Thirty-seven patients with a histologically proven meningioma and GTR on postoperative MRI were prospectively referred to [Ga]Ga-DOTA-TOC PET.

PET imaging of meningioma with 18F-FLT: a predictor of tumour progression.

We have previously reported that PET with 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) provides a non-invasive assessment of cell proliferation in vivo in meningiomas. The purpose of this prospective study was to evaluate the potential of 18F-FLT PET in predicting subsequent tumour progression in asymptomatic meningiomas. Forty-three adult patients harbouring 46 MRI-presumed (n = 40) and residual meningiomas from previous surgery (n = 6) underwent a 60-min dynamic 18F-FLT PET scan prior to radiological surveillance.

Somatostatin Receptor-Targeted Radiopeptide Therapy in Treatment-Refractory Meningioma: Individual Patient Data Meta-analysis.

Somatostatin receptor (SSTR)-targeted peptide receptor radionuclide therapy (PRRT) represents a promising approach for treatment-refractory meningiomas. We performed an individual patient data meta-analysis, including all published data on meningioma patients treated with SSTR-targeted PRRT. The main outcomes were toxicity, response to treatment, progression-free survival (PFS), and overall survival (OS).

Pearls and Pitfalls in Interpretation of 68Ga-DOTATOC PET Imaging.

DOTA-D-Phe-Tyr-octreotide labeled with Ga (Ga-DOTATOC) is the commonly used PET tracer for imaging meningioma because of its high affinity to somatostatin receptor subtype 2 (SSTR2) and an established imaging modality for planning radiation and radionuclide therapy. However, SSTR2 is not an exclusive marker for meningioma, and not all meningiomas express high levels of SSTR2. The SSTR2 expression has been reported in other intracranial tumors, for example, glioma, pituitary adenoma, medullablastoma, primitive neuroectodermal tumors, and hemangioblastoma leading to a significant risk of misinterpretation of PET/CT findings.

Pharmacokinetic analysis of [Ga]Ga-DOTA-TOC PET in meningiomas for assessment of in vivo somatostatin receptor subtype 2.

Purpose: DOTA-D-Phe-Tyr-octreotide with gallium-68 ([Ga]Ga-DOTA-TOC) is one of the PET tracers that forms the basis for peptide receptor radionuclide therapy based on somatostatin receptor subtype 2 (SSTR2) expression in meningiomas. Yet, the quantitative relationship between [Ga]Ga-DOTA-TOC accumulation and SSTR2 is unknown. We conducted a correlative analysis of a range of [Ga]Ga-DOTA-TOC PET metric(s) as imaging surrogate(s) of the receptor binding in meningiomas by correlating the PET results with SSTR2 expression from surgical specimens.

In vivo imaging of cell proliferation in meningioma using 3'-deoxy-3'-[F]fluorothymidine PET/MRI.

Purpose: Positron emission tomography (PET) with 3'-deoxy-3'-[F]fluorothymidine ([F]FLT) provides a noninvasive assessment of tumour proliferation in vivo and could be a valuable imaging modality for assessing malignancy in meningiomas. We investigated a range of static and dynamic [F]FLT metrics by correlating the findings with cellular biomarkers of proliferation and angiogenesis.

Methods: Seventeen prospectively recruited adult patients with intracranial meningiomas underwent a 60-min dynamic [F]FLT PET following surgery.

An Automated Kinematic Measurement System for Sagittal Plane Murine Head Impacts.

Mild traumatic brain injuries are typically caused by nonpenetrating head impacts that accelerate the skull and result in deformation of the brain within the skull. The shear and compressive strains caused by these deformations damage neural and vascular structures and impair their function. Accurate head acceleration measurements are necessary to define the nature of the insult to the brain.

Increased severity of the CHIMERA model induces acute vascular injury, sub-acute deficits in memory recall, and chronic white matter gliosis.

Traumatic brain injury (TBI) is a leading cause of death and disability in modern societies. Diffuse axonal and vascular injury are nearly universal consequences of mechanical energy impacting the head and contribute to disability throughout the injury severity spectrum. CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) is a non-surgical, impact-acceleration model of rodent TBI that reliably produces diffuse axonal injury characterized by white matter gliosis and axonal damage.

Recurrent glioblastoma versus late posttreatment changes: diagnostic accuracy of O-(2-[18F]fluoroethyl)-L-tyrosine positron emission tomography (18F-FET PET).

Background: Diagnostic accuracy in previous studies of O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) PET in patients with suspected recurrent glioma may be influenced by prolonged dynamic PET acquisitions, heterogeneous populations, different non-standard-of-care therapies, and PET scans performed at different time points post radiotherapy. We investigated the diagnostic accuracy of a 20-minute 18F-FET PET scan in MRI-suspected recurrent glioblastoma 6 months after standard radiotherapy and its ability to prognosticate overall survival (OS).

Methods: In total, 146 glioblastoma patients with 168 18F-FET PET scans were reviewed retrospectively.

Cerebral Microvascular Injury: A Potentially Treatable Endophenotype of Traumatic Brain Injury-Induced Neurodegeneration.

Traumatic brain injury (TBI) is one the most common human afflictions, contributing to long-term disability in survivors. Emerging data indicate that functional improvement or deterioration can occur years after TBI. In this regard, TBI is recognized as risk factor for late-life neurodegenerative disorders.

Repetitive closed-head impact model of engineered rotational acceleration (CHIMERA) injury in rats increases impulsivity, decreases dopaminergic innervation in the olfactory tubercle and generates white matter inflammation, tau phosphorylation and degeneration.

Traumatic brain injury (TBI) affects at least 3 M people annually. In humans, repetitive mild TBI (rmTBI) can lead to increased impulsivity and may be associated with chronic traumatic encephalopathy. To better understand the relationship between repetitive TBI (rTBI), impulsivity and neuropathology, we used CHIMERA (Closed-Head Injury Model of Engineered Rotational Acceleration) to deliver five TBIs to rats, which were continuously assessed for trait impulsivity using the delay discounting task and for neuropathology at endpoint.

CHIMERA repetitive mild traumatic brain injury induces chronic behavioural and neuropathological phenotypes in wild-type and APP/PS1 mice.

Background: The annual incidence of traumatic brain injury (TBI) in the United States is over 2.5 million, with approximately 3-5 million people living with chronic sequelae. Compared with moderate-severe TBI, the long-term effects of mild TBI (mTBI) are less understood but important to address, particularly for contact sport athletes and military personnel who have high mTBI exposure.

An End-to-end System for Automatic Characterization of Iba1 Immunopositive Microglia in Whole Slide Imaging.

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Detailed studies of the microglial response after TBI require high throughput quantification of changes in microglial count and morphology in histological sections throughout the brain. In this paper, we present a fully automated end-to-end system that is capable of assessing microglial activation in white matter regions on whole slide images of Iba1 stained sections.

Contrast-induced nephropathy following CT scan for trauma is not rare and is associated with increased mortality in South African trauma patients.

Purpose: Acute trauma patients are at risk for the development of acute kidney injury (AKI). One potential nephrotoxic agent, which a trauma patient may be exposed to, is iodinated contrast media (ICM). We aim to review the incidence and outcome of contrast-induced nephropathy (CIN) in trauma patients in a busy trauma service, and to identify potentially modifiable risk factors.

Scandinavian Multicenter Acute Subdural Hematoma (SMASH) Study: Study Protocol for a Multinational Population-Based Consecutive Cohort.

Background: Traumatic acute subdural hematomas (ASDHs) are associated with high rate of morbidity and mortality, especially in elderly individuals. However, recent reports indicate that the morbidity and mortality rates might have improved.

Objective: To evaluate postoperative (30-d) mortality in younger vs elderly (≥70 yr) patients with ASDH.