Vector design influences hepatic genotoxicity after adeno-associated virus gene therapy.

The use of adeno-associated virus (AAV) as a gene therapy vector has been approved recently for clinical use and has demonstrated efficacy in a growing number of clinical trials. However, the safety of AAV as a vector has been challenged by a single study that documented hepatocellular carcinoma (HCC) after AAV gene delivery in mice. Most studies have not noted genotoxicity following AAV-mediated gene delivery; therefore, the possibility that there is an association between AAV and HCC is controversial.

Leading-process actomyosin coordinates organelle positioning and adhesion receptor dynamics in radially migrating cerebellar granule neurons.

Background: During brain development, neurons migrate from germinal zones to their final positions to assemble neural circuits. A unique saltatory cadence involving cyclical organelle movement (e.g.

Best practice guidelines for stroke in Cameroon: An innovative and participatory knowledge translation project.

Background: Although the adherence to stroke guidelines in high-income countries has been shown to be associated with improved patient outcomes, the research, development and implementation of rehabilitation related guidelines in African countries is lacking.

Objectives: The purpose of this article is to describe how a group of front-line practitioners collaborated with academics and students to develop best practice guidelines (BPG) for the management and rehabilitation of stroke in adult patients in Cameroon.

Method: A working group was established and adapted internationally recognised processes for the development of best practice guidelines.

Reducing maternal mortality from preeclampsia and eclampsia in low-resource countries--what should work?

Objective: Preeclampsia/eclampsia (PE/E) remains a major cause of maternal death in low-income countries. We evaluated interventions to reduce PE/E-related maternal mortality in sub-Saharan Africa.

Design: Mathematical model to assess impact of interventions on PE/E-related maternal morbidity and mortality.

X-linked Hyper-IgM Syndrome with Bronchiectasis.

The X-linked hyper-immunoglobulin M syndrome (HIGM-1) is a rare genetic disorder characterized by elevated serum IgM levels and low to undetectable levels of serum IgG, IgA and IgE. These patients characteristically present with recurrent sinopulmonary infections and recurrent diarrhea. They also have high susceptibility for Pneumocystis jiroveci (PJ) pneumonia.

Studies on in vitro interaction of ampicillin and fresh garlic extract against Staphylococcus aureus by checkerboard method.

Objective: Staphylococcus aureus has largely developed resistance to the multiple antimicrobial agents. Garlic (Allium sativum) is claimed to retard development of resistance and produce synergy with conventional antimicrobial agents. The aim of the present study was to evaluate the effect of combination of ampicillin with fresh garlic extract (FGE) against S.

Molecular basis of photoperiodic control of reproductive cycle in a subtropical songbird, the Indian weaver bird (Ploceus philippinus).

Less is known about genetic basis of photoperiodic regulation of reproductive cycle in subtropical birds. This study measured the expression levels of DIO2, DIO3, GnRH, and GnIH genes in Indian weaver birds subjected to short days (8h light:16h darkness, 8L:16D) and long days (16L:8D) for 48weeks. Whereas small, reproductively inactive testes were maintained under short days, weaver birds underwent testis recrudescence - regression cycle under long days.

Tuberculosis of the adrenal gland: a case report and review of the literature of infections of the adrenal gland.

Infections of the adrenal glands remain an important cause of adrenal insufficiency, especially in the developing world. Indeed, when Thomas Addison first described the condition that now bears his name over 150 years ago, the vast majority of cases were attributable to tuberculosis. Here we describe a classic, but relatively uncommon, presentation in the United States of adrenal insufficiency followed by a review of the current literature pertaining to adrenal infections.

Versatility of adipofascial anterolateral thigh flap for reconstruction of maxillary defects with infratemporal fossa extension.

Tumors arising from the posterior hard palate or posterolateral maxilla may extend to involve the infratemporal fossa (ITF). Resection of these tumors results in infrastructural maxillectomy with ITF defects. In this study, we describe the use of an adipofascial anterolateral thigh flap (ALT) specifically for such defects.

Targeted correction of RUNX1 mutation in FPD patient-specific induced pluripotent stem cells rescues megakaryopoietic defects.

Familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML) is an autosomal dominant disease of the hematopoietic system that is caused by heterozygous mutations in RUNX1. FPD/AML patients have a bleeding disorder characterized by thrombocytopenia with reduced platelet numbers and functions, and a tendency to develop AML. No suitable animal models exist for FPD/AML, as Runx11/2 mice and zebra fish do not develop bleeding disorders or leukemia.

Metastasis-associated protein ribosomal RNA processing 1 homolog B (RRP1B) modulates metastasis through regulation of histone methylation.

Unlabelled: Overexpression of ribosomal RNA processing 1 homolog B (RRP1B) induces a transcriptional profile that accurately predicts patient outcome in breast cancer. However, the mechanism by which RRP1B modulates transcription is unclear. Here, the chromatin-binding properties of RRP1B were examined to define how it regulates metastasis-associated transcription.

Factors predicting outcome after salvage treatment for stage IV oral squamous cell carcinoma: Evidence of the potential importance of the cyclooxygenase-2-prostaglandin E2 pathway.

Background: We determined the clinicopathological factors that predicted outcome after salvage treatment for stage IV oral squamous cell carcinoma (OSCC). Additionally, the prognostic significance of the cyclooxygenase-2 (COX-2)/microsomal prostaglandin-E synthase-1 (mPGES-1) pathway was evaluated.

Methods: Thirty-one patients who underwent salvage surgery were included.

Distinct microRNA expression signatures are associated with melanoma subtypes and are regulated by HIF1A.

The complex genetic changes underlying metastatic melanoma need to be deciphered to develop new and effective therapeutics. Previously, genome-wide microarray analyses of human melanoma identified two reciprocal gene expression programs, including transcripts regulated by either transforming growth factor, beta 1 (TGFβ1) pathways, or microphthalmia-associated transcription factor (MITF)/SRY-box containing gene 10 (SOX10) pathways. We extended this knowledge by discovering that melanoma cell lines with these two expression programs exhibit distinctive microRNA (miRNA) expression patterns.

Bronchoalveolar lavage cell immunophenotyping facilitates diagnosis of lung allograft rejection.

Supplementary methods to identify acute rejection and to distinguish rejection from infection may improve clinical outcomes for lung allograft recipients. We hypothesized that distinct bronchoalveolar lavage (BAL) cell profiles are associated with rejection and infection. We retrospectively compared 2939 BAL cell counts and immunophenotypes against concomitantly obtained transbronchial biopsies and microbiologic studies.

Photon counting as a probe of superfluidity in a two-band Bose-Hubbard system coupled to a cavity field.

We show that photon number measurement can be used to detect superfluidity for a two-band Bose-Hubbard model coupled to a cavity field. The atom-photon coupling induces transitions between the two internal atomic levels and results in entangled polaritonic states. In the presence of a cavity field, we find different photon numbers in the Mott-insulating versus superfluid phases, providing a method of distinguishing the atomic phases by photon counting.

Age does not adversely affect sperm retrieval in men undergoing microdissection testicular sperm extraction.

Objective: To evaluate the effect of male age on the outcome of microdissection testicular sperm extraction (micro-TESE) and assisted reproductive technology.

Design: Clinical retrospective study.

Setting: Center for reproductive medicine at a tertiary university hospital.

Enzymatic hydrolysis and production of bioethanol from common macrophytic green alga Ulva fasciata Delile.

The green seaweed Ulva which proliferates fast and occurs abundantly worldwide was used as a feedstock for production of ethanol following enzymatic hydrolysis. Among the different cellulases investigated for efficient saccharification, cellulase 22119 showed the highest conversion efficiency of biomass into reducing sugars than Viscozyme L, Cellulase 22086 and 22128. Pre-heat treatment of biomass in aqueous medium at 120°C for 1h followed by incubation in 2% (v/v) enzyme for 36 h at 45°C gave a maximum yield of sugar 206.

Transient thyrotoxicosis following minimally invasive radio-guided parathyroidectomy.

Objective: We report a case of thyrotoxicosis following minimally invasive parathyroidectomy.

Methods: Case report with literature review.

Results: A 70-year-old woman with primary hyperparathyroidism developed thyrotoxicosis 2 weeks following minimally invasive radio-guided parathyroidectomy.

Microvascular free flap reconstruction for head and neck cancer in a resource-constrained environment in rural India.

Introduction: Reconstruction with free flaps has significantly changed the outcome of patients with head and neck cancer. Microsurgery is still considered a specialised procedure and is not routinely performed in the resource-constrained environment of certain developing parts of India.

Materials And Methods: This article focuses on the practice environment in a cancer clinic in rural India.

Partial restoration of macrophage alteration from diet-induced obesity in response to Porphyromonas gingivalis infection.

Obesity is a chronic inflammatory disease that weakens macrophage innate immune response to infections. Since M1 polarization is crucial during acute infectious diseases, we hypothesized that diet-induced obesity inhibits M1 polarization of macrophages in the response to bacterial infections. Bone marrow macrophages (BMMΦ) from lean and obese mice were exposed to live Porphyromonas gingivalis (P.

Targeting proximal tubule mitochondrial dysfunction attenuates the renal disease of methylmalonic acidemia.

Isolated methylmalonic acidemia (MMA), caused by deficiency of the mitochondrial enzyme methylmalonyl-CoA mutase (MUT), is often complicated by end stage renal disease that is resistant to conventional therapies, including liver transplantation. To establish a viable model of MMA renal disease, Mut was expressed in the liver of Mut(-/-) mice as a stable transgene under the control of an albumin (INS-Alb-Mut) promoter. Mut(-/-);Tg(INS-Alb-Mut) mice, although completely rescued from neonatal lethality that was displayed by Mut(-/-) mice, manifested a decreased glomerular filtration rate (GFR), chronic tubulointerstitial nephritis and ultrastructural changes in the proximal tubule mitochondria associated with aberrant tubular function, as demonstrated by single-nephron GFR studies.

A somatic cell defect is associated with the onset of neurological symptoms in a lysosomal storage disease.

Mutations in individuals with the lysosomal storage disorder Niemann-Pick disease, type C1 (NPC1) are heterogeneous, not localized to specific protein domains, and not correlated to time of onset or disease severity. We demonstrate direct correlation of the time of neurological symptom onset with the severity of lysosomal defects in NPC1 patient-derived fibroblasts. This is a novel assay for NPC1 individuals that may be predictive of NPC1 disease progression and broadly applicable to other lysosomal disorders.