Treatment planning evaluation of sliding window and multiple static segments technique in intensity modulated radiotherapy.

Background: The demand of improved dose conformity of the tumor has been increased in radiation therapy with the advent of recent imaging facilities and efficient computer technologies.

Aim: We compared the intensity modulated radiotherapy (IMRT) plans delivered with the sliding window (SW IMRT) and step and shoot (SS IMRT) techniques.

Materials And Methods: Thirteen patients were planned on 15 MV X-ray for five, seven, nine and thirteen beams direction making the dose constraints analogous.

Altered apoptotic responses in neurons lacking RhoB GTPase.

Caspase 3 activation has been linked to the acute neurotoxic effects of central nervous system damage, as in traumatic brain injury or cerebral ischaemia, and also to the early events leading to long-term neurodegeneration, as in Alzheimer's disease. However, the precise mechanisms activating caspase 3 in neuronal injury are unclear. RhoB is a member of the Rho GTPase family that is dramatically induced by cerebral ischaemia or neurotrauma, both in preclinical models and clinically.

Biological activities of Indian celery, Seseli diffusum (Roxb. ex Sm.) Sant. & Wagh.

In continuation of our work on Indian celery (Seseli diffusum (Roxb. ex Sm.) Santapau & Wagh; Umbelliferae), the fractionation of the 80% MeOH-H(2) O extract of the seeds was performed to identify the principles responsible for its folk use as an antispasmodic and diuretic.

An experimental rat model of sporadic Alzheimer's disease and rescue of cognitive impairment with a neurotrophic peptide.

Alzheimer's disease (AD) is multifactorial and, to date, no single cause of the sporadic form of this disease, which accounts for over 99% of the cases, has been established. In AD brain, protein phosphatase-2A (PP2A) activity is known to be compromised due to the cleavage and translocation of its potent endogenous inhibitor, I2PP2A, from the neuronal nucleus to the cytoplasm. Here, we show that adeno-associated virus vector-induced expression of the N-terminal I2NTF and C-terminal I2CTF halves of I2PP2A , also called SET, in brain reproduced key features of AD in Wistar rats.

Rescue of synaptic failure and alleviation of learning and memory impairments in a trisomic mouse model of down syndrome.

Down syndrome (DS) is caused by the triplication of ∼240 protein-coding genes on chromosome 21 and is the most prevalent form of developmental disability. This condition results in abnormalities in many organ systems, as well as in intellectual retardation. Many previous efforts to understand brain dysfunction in DS have indicated that cognitive deficits are coincident with reduced synaptic plasticity and decreased neuronal proliferation.

Opportunities and challenges in developing Alzheimer disease therapeutics.

Alzheimer disease (AD) is a chronic, progressive disorder with an average disease progression of 7-10 years. However, the histopathological hallmark lesions of this disease, the extracellular Aβ plaques and the intraneuronal neurofibrillary tangles, start as early as childhood in the affected individuals. AD is multifactorial and probably involves many different etiopathogenic mechanisms.

Visual results following intravitreal Bevacizumab in neovascular age-related macular degeneration.

Objective: To determine the visual and anatomic outcome of intravitreal Bevacizumab injection in the treatment of neovascular age-related macular degeneration (AMD).

Study Design: Quasi-experimental study.

Place And Duration Of Study: Layton Rahmatulla Benevolent Trust Eye Hospital (LRBT), Lahore, from January to July 2010.

The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes.

Sperm and eggs carry distinctive epigenetic modifications that are adjusted by reprogramming after fertilization. The paternal genome in a zygote undergoes active DNA demethylation before the first mitosis. The biological significance and mechanisms of this paternal epigenome remodelling have remained unclear.

Regional comparison of the neurogenic effects of CNTF-derived peptides and cerebrolysin in AβPP transgenic mice.

Adult neurogenesis, the production of new neurons in certain brain regions, is known to decrease with age and the loss of neurogenic potential has been implicated in Alzheimer's disease (AD), a leading cause of dementia in the elderly. Cerebrolysin (CBL) has been shown to increase neurogenesis in models of stroke and AD. CBL is composed of small peptides with activity similar to neurotrophic factors including ciliary neurotrophic factor (CNTF), which may mediate its neurogenic effects.

Sexually transmitted infections and hepatitis in men with a history of incarceration.

Background: Men entering correctional facilities have high rates of human immunodeficiency virus, sexually transmitted infections (STI), and hepatitis. Many prisons offer screening, treatment, and vaccination services; however, little is known about the rates of these infections in men after release to the community.

Methods: Young men were recruited from prisons in Mississippi, Rhode Island, and Wisconsin as part of a human immunodeficiency virus/STI/hepatitis intervention study.

Mechanism of inhibition of PP2A activity and abnormal hyperphosphorylation of tau by I2(PP2A)/SET.

Protein phosphatase-2A (PP2A) activity, which is compromised in Alzheimer disease brain, is regulated by two endogenous inhibitors, one of them being I(2)(PP2A), a 277 amino acid long protein also known as SET. Here we report that both the amino terminal fragment (I(2NTF); aa 1-175) and the carboxy terminal fragment (I(2CTF); aa 176-277) of I(2)(PP2A) inhibit PP2A by binding to its catalytic subunit PP2Ac and cause hyperphosphorylation of tau. The C-terminal acidic region in I(2CTF) and Val 92 in I(2NTF) are essential for their association with PP2Ac and inhibition of the phosphatase activity.

The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers.

Background: The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability.

Effect of phacoemulsification on intraocular pressure.

Objective: To evaluate the effect of phacoemulsification on intraocular pressure in normal eyes and glaucomatous eyes.

Study Design: Quasi-experimental study.

Place And Duration Of Study: Layton Rehmatulla Benevolent Trust, Eye and Cancer Hospital, Lahore, from September 2009 to August 2010.

Effects of endocrine disruptors on imprinted gene expression in the mouse embryo.

Environmental endocrine disruptors (EDs) are synthetic chemicals that resemble natural hormones and are known to cause epigenetic perturbations. EDs have profound effects on development and fertility. Imprinted genes had been identified as susceptible loci to environmental insults by EDs because they are functionally haploid, and because the imprints undergo epigenetic resetting between generations.

Deficient brain insulin signalling pathway in Alzheimer's disease and diabetes.

Brain glucose metabolism is impaired in Alzheimer's disease (AD), the most common form of dementia. Type 2 diabetes mellitus (T2DM) is reported to increase the risk for dementia, including AD, but the underlying mechanism is not understood. Here, we investigated the brain insulin-PI3K-AKT signalling pathway in the autopsied frontal cortices from nine AD, 10 T2DM, eight T2DM-AD and seven control cases.

Role of oral clonidine on intraopereative haemodynamic stability for craniotomies of intracranial space occupying lesion.

This was an analytical comparative study. Aim of this study was to observe the effect of oral clonidine on intra operative haemodynamic stability in intracranial space occupying lesion (ICSOL) patients who underwent craniotomy. Total 60 patients were distributed into case and control group.

Blood-cerebrospinal fluid barrier permeability in Alzheimer's disease.

The role of blood-cerebrospinal fluid barrier (BCB) dysfunction in Alzheimer's disease (AD) has been addressed but not yet established. We evaluated the BCB integrity in 179 samples of cerebrospinal fluid (CSF) retrospectively collected from AD patients and control cases using both CSF/serum albumin ratio (QAlb) and CSF secretory Ca2+-dependent phospholipase A2 (sPLA2) activity. These analyses were supplemented with the measurement of total tau, amyloid-β1-42 (Aβ1-42), and ubiquitin CSF levels.

Regulation of the alternative splicing of tau exon 10 by SC35 and Dyrk1A.

Abnormal alternative splicing of tau exon 10 results in imbalance of 3R-tau and 4R-tau expression, which is sufficient to cause neurofibrillary degeneration. Splicing factor SC35, a member of the superfamily of the serine/arginine-rich (SR) proteins, promotes tau exon 10 inclusion. The molecular mechanism by which SC35 participates in tau exon 10 splicing remains elusive.

Classification of suprascapular notch according to anatomical measurements in human scapulae.

The objective of this study was to measure the maximum superior and inferior lengths of the suprascapular notch with the help of a Vernier caliper and to classify the notches accordingly into four types. This is an observational study, conducted from January to December 2009 at Islamic International Medical College, Rawalpindi. Two hundred and fifty dried human scapulae were procured and measured irrespective of age, gender, race, and sidedness.

Cyclic AMP-dependent protein kinase regulates the alternative splicing of tau exon 10: a mechanism involved in tau pathology of Alzheimer disease.

Hyperphosphorylation and deposition of tau into neurofibrillary tangles is a hallmark of Alzheimer disease (AD). Alternative splicing of tau exon 10 generates tau isoforms containing three or four microtubule binding repeats (3R-tau and 4R-tau), which are equally expressed in adult human brain. Dysregulation of exon 10 causes neurofibrillary degeneration.

Splicing factor SC35 promotes tau expression through stabilization of its mRNA.

Altered alternative splicing and accumulation of brain microtubule-associated protein tau are found in several tauopathies and are believed to lead to these neurodegenerative diseases. We found that in addition to promoting tau exon 10 inclusion, splicing factor SC35 also promoted tau expression in HEK-293T cells. The activity of SC35 in promotion of tau expression was limited to exon 10 containing tau isoforms.

Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine.

Genome-wide erasure of DNA cytosine-5 methylation has been reported to occur along the paternal pronucleus in fertilized oocytes in an apparently replication-independent manner, but the mechanism of this reprogramming process has remained enigmatic. Recently, considerable amounts of 5-hydroxymethylcytosine (5hmC), most likely derived from enzymatic oxidation of 5-methylcytosine (5mC) by TET proteins, have been detected in certain mammalian tissues. 5hmC has been proposed as a potential intermediate in active DNA demethylation.

Regulation of alternative splicing of tau exon 10 by 9G8 and Dyrk1A.

Adult human brain expresses 6 isoforms of tau protein as a result of alternative splicing. Alternative splicing of exon 10 (E10) leads to tau isoforms containing either 3 (3R-tau) or 4 (4R-tau) microtubule-binding repeats. Imbalance in the 3R-tau/4R-tau ratio causes neurofibrillary degeneration and dementia.