A computational approach for structural and functional analyses of disease-associated mutations in the human CYLD gene.

Tumor suppressor cylindromatosis protein (CYLD) regulates NF-κB and JNK signaling pathways by cleaving K63-linked poly-ubiquitin chain from its substrate molecules and thus preventing the progression of tumorigenesis and metastasis of the cancer cells. Mutations in CYLD can cause aberrant structure and abnormal functionality leading to tumor formation. In this study, we utilized several computational tools such as PANTHER, PROVEAN, PredictSNP, PolyPhen-2, PhD-SNP, PON-P2, and SIFT to find out deleterious nsSNPs.

A Review on Saliva-Based Health Diagnostics: Biomarker Selection and Future Directions.

The human body has a unique way of saying when something is wrong with it. The molecules in the body fluids can be helpful in the early detection of diseases by enabling health and preventing disease progression. These biomarkers enabling better healthcare are becoming an extensive area of research interest.

Adolescent HIV-related behavioural prediction using machine learning: a foundation for precision HIV prevention.

Background: Precision prevention is increasingly important in HIV prevention research to move beyond universal interventions to those tailored for high-risk individuals. The current study was designed to develop machine learning algorithms for predicting adolescent HIV risk behaviours.

Methods: Comprehensive longitudinal data on adolescent risk behaviours, perceptions, peer and family influence, and neighbourhood risk factors were collected from 2564 grade-10 students at baseline followed for 24 months over 2008-2012.

In Vivo Generation of Post-infarct Human Cardiac Muscle by Laminin-Promoted Cardiovascular Progenitors.

Regeneration of injured human heart muscle is limited and an unmet clinical need. There are no methods for the reproducible generation of clinical-quality stem cell-derived cardiovascular progenitors (CVPs). We identified laminin-221 (LN-221) as the most likely expressed cardiac laminin.

Utility of cord blood culture in early onset neonatal sepsis.

Background: Neonatal sepsis is a major cause of neonatal mortality. The clinical outcome mainly depends on the early diagnosis and peripheral venous blood culture (PVBC) is the most widely practiced diagnostic method.

Aims: This study aimed to evaluate the utility of umbilical cord blood culture (UCBC) in neonates at high risk of early onset neonatal sepsis (EONS) in comparison to peripheral venous blood culture.

A comparative encyclopedia of DNA elements in the mouse genome.

The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways. To gain greater insights into both shared and species-specific transcriptional and cellular regulatory programs in the mouse, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types. By comparing with the human genome, we not only confirm substantial conservation in the newly annotated potential functional sequences, but also find a large degree of divergence of sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization.

Evaluation of healthcare professionals' understanding of eponymous maneuvers and mnemonics in emergency obstetric care provision.

Objective: To evaluate whether eponymous maneuvers and mnemonics taught for the management of shoulder dystocia, vaginal breech delivery, and uterine inversion were remembered and understood in practice.

Methods: A questionnaire was distributed to obstetricians and midwives collecting information about the HELPERR and PALE SISTER mnemonics. Three extended matching questions evaluated participants' knowledge of the correct maneuvers, with their matching eponyms, used in the management of shoulder dystocia, vaginal breech delivery, and uterine inversion.

Pregnancy outcomes in severe hyperemesis gravidarum in a multi-ethnic population.

We evaluated pregnancy outcomes among women with hyperemesis gravidarum (HG) in a North London multi-ethnic population. A retrospective case-control study was performed on records of obstetric admissions during a 4-year period, at North Middlesex University Hospital in North London. A total of 208 women with HG were identified according to Fairweather's criteria occurring in the first 20 weeks of pregnancy, which is severe enough to require admission to hospital.

DNA hypomethylation at the ZNF206-exon 5 CpG island associated with neuronal differentiation in mice and development of neuroblastoma in humans.

Differentiation of human neuroblastoma recapitulates neural crest development. In our whole genome DNA methylation screening of tissue-specific differentially methylated regions (T-DMRs) and developmental stage specific differentially methylated regions (DS-DMRs) we reported that the exon 5 CpG island (CpGi) of Zfp206 (human: ZNF206), which was required to maintain embryonic stem cells in a pluripotent state, was one of potent brain and testis-specific T-DMRs in mice. In this study methylation level of the CpG sites at Zfp206-exon 5 CpGi in mouse brain samples at three different developmental stages (15-day-old embryo; E15, new born; NB, 12-week adult; AD) were quantitatively analyzed and it was identified that Zfp206-exon 5 CpGi was the DS-DMRs in mouse brain.

Zoledronic acid in metastatic bone disease: an audit based discussion.

Background: Metastatic bone disease is a common problem in patients with advanced cancer causing significant morbidity and poor quality of life. Effective and less toxic treatments, like bisphophonates, can reduce morbidity in such cases.

Objectives: The objectives of this study were to determine whether Zoledronic acid was administered in accordance with current recommendations for its prescribing and to produce protocols for improved patient outcomes.

Beta1-integrin circumvents the antiproliferative effects of trastuzumab in human epidermal growth factor receptor-2-positive breast cancer.

Resistance to trastuzumab, the monoclonal antibody targeting human epidermal growth factor receptor 2 (HER-2), is a major concern for HER-2-positive metastatic breast cancer (MBC) patients. To date, HER-2 status is the only available biomarker for selecting patients for trastuzumab-based therapy. Beta(1)-integrin, an adhesion molecule involved in cell survival and drug resistance, shares common downstream signaling elements with HER-2, such as the phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase-1/2 (ERK1/2) pathways.

Multiple triphenylphosphonium cations shuttle a hydrophilic peptide into mitochondria.

A variety of diseases are related to mitochondrial dysfunction. Hence, the ability to transport drugs to mitochondria that are otherwise cell impermeable would be of great therapeutic potential. Triphenylphosphonium (TPP) cations have been shown to accumulate in mitochondria when attached to small molecules.

Colutellin A, an immunosuppressive peptide from Colletotrichum dematium.

Colletotrichum dematium is an endophytic fungus recovered from a Pteromischum sp. growing in a tropical forest in Costa Rica. This fungus makes a novel peptide antimycotic, colutellin A, with a MIC of 3.

How we do it: Switching from mechanical perforation to the CO2 laser; audit results of primary small-fenestra stapedotomy in a district general hospital.

The use of laser for stapedotomy was introduced in our department in the year 2002, and since then has taken over the mechanical technique. A total of 85 patients who had undergone primary stapedotomy with either technique are reported with regards to effectiveness and rate of side effects. Although footplate complications were reduced with the laser, short-term hearing outcomes were similar between the two techniques.

Imprint cytology of needle core-biopsy specimens of breast lesions: is it a useful adjunt to rapid assessment breast clinics?

This study aimed at assessing the practicability of imprint cytology (IC) of core biopsy (CB) specimens in order to achieve one-stop diagnosis of breast lesions. In total, 199 symptomatic patients underwent free-hand CB of the suspected breast lesions. The slides were stained by Diff-QuikO and reported independently of histological reporting.

Can heterotopic gastric mucosa present as globus pharyngeus?

We present a series of four patients presenting with symptoms leading to a provisional diagnosis of globus pharyngeus. On further investigation, they were all found to have small areas of abnormal mucosa in either their hypopharynx or proximal oesophagus, which on biopsy were reported as containing gastric-type mucosa. Following anti-reflux treatment, all patients eventually reported a cessation of symptoms.

A novel TEAD1 mutation is the causative allele in Sveinsson's chorioretinal atrophy (helicoid peripapillary chorioretinal degeneration).

Sveinsson's chorioretinal atrophy (SCRA), also referred to as helicoid peripapillary chorioretinal degeneration or atrophia areata, is an autosomal dominant eye disease, characterized by symmetrical lesions radiating from the optic disc involving the retina and the choroid. Genome-wide linkage analysis mapped the SCRA gene to chromosome 11p15 in 81 patients from a large founder pedigree in Iceland. The parametric LOD score obtained was 18.

Effect of aldrin on accessory sex glands and plasma testosterone levels in rats.

The effects of aldrin, an organochlorine insecticide, on accessory sex glands and plasma testosterone levels in rats were studied. The aldrin was administered i.p.

Studies on membrane ATPase activity and lipid level in vibrio el tor under normal and nitrofurantoin resistant conditions.

Nitrofurantoin resistance brought about decreased level of membrane bound ATPase activity in Vibrio el tor as compared to the normal strain while phospholipid as well as total lipid levels in the membrane fraction was increased. Mg++ was found to be the mose effective co-factor for ATPase. At higher concentrations of sodium and potassium ions, ATPase of normal and nitrofurantoin resistant Vibrio el tor responded quite differently.