Frequency of Retinopathy of Prematurity in Premature Neonates with a Birth Weight below 1500 Grams and a Gestational Age Less than 32 Weeks: A Study from a Tertiary Care Hospital in a Lower-Middle Income Country…

Introduction

Retinopathy of prematurity (ROP) is a treatable cause of blindness in neonates. In Pakistan, ROP is often not recognized early because screening and treatment programs are not yet in place in most neonatal units, even in tertiary care hospitals. It is hoped that this report will help inform medical professionals of the magnitude of the problem and help to design appropriate management strategies.

Objectives

The aim was to determine the frequency of ROP in premature and very low birth weight (BW) neonates (BW<1500 g and gestational age (GA) <32 weeks).

Study Design

Cross-sectional study.

Study Setting

Neonatal intensive care unit (NICU) of a tertiary care hospital in Karachi, Pakistan.

Study Duration

From June 2009 to May 2010.

Subjects and Methods

Neonates with a Birth weight (BW) <1500 g and Gestational Age (GA) <32 weeks who were admitted to the NICU and received an eye examination, or were referred for a ROP eye examination as an outpatient, were included in the study. GA was estimated from intrauterine ultrasound findings. Neonates with major congenital malformations, syndromes or congenital cataracts or tumors of the eyes, and those that died before the eye examination or did not attend the out patients department for an eye examination, were excluded. The neonatal eye examination was performed by a trained ophthalmologist at 4 or 6 weeks of age.

Results

Out of 86 neonates, ROP was identified in nine neonates (10.5%) at the first eye examination. ROP was significantly associated with BW (P = 0.037), GA (P = 0.033), and chronological age (P<0.001).

Conclusions

we identified ROP in 10.5% of neonates at first eye examination. Significant associations between ROP and a GA<32 weeks and a BW<1500 g were also observed.we also stress that serial follow-up of neonates at risk for ROP is important when making a final diagnosis.     

Defining the identity of mouse embryonic dermal fibroblasts

Embryonic dermal fibroblasts in the skin have the exceptional ability to initiate hair follicle morphogenesis and contribute to scarless wound healing. Activation of the Wnt signaling pathway is critical for dermal fibroblast fate selection and hair follicle induction. In humans, mutations in Wnt pathway components and target genes lead to congenital focal dermal hypoplasias with diminished hair. The gene expression signature of embryonic dermal fibroblasts during differentiation and its dependence on Wnt signaling is unknown. Here we applied Shannon entropy analysis to identify the gene expression signature of mouse embryonic dermal fibroblasts. We used available human DNase‐seq and histone modification ChiP‐seq data on various cell‐types to demonstrate that genes in the fibroblast cell identity signature can be epigenetically repressed in other cell‐types. We found a subset of the signature genes whose expression is dependent on Wnt/β‐catenin activity in vivo. With our approach, we have defined and validated a statistically derived gene expression signature that may mediate dermal fibroblast identity and function in development and disease. genesis 54:415–430, 2016. © 2016 Wiley Periodicals, Inc.     

Foxp3 and IL-10 expression correlates with parasite burden in lesional tissues of post kala azar dermal leishmaniasis (PKDL) patients

Background

Post kala-azar dermal leishmaniasis (PKDL), a sequel to visceral leishamaniasis (VL) in 5–15% cases, constitutes a parasite reservoir important in disease transmission. The precise immunological cause of PKDL outcome remains obscure. However, overlapping counter regulatory responses with elevated IFN-γ and IL-10 are reported.

Methodology/Principal Findings

Present study deals with ex-vivo mRNA and protein analysis of natural regulatory T cells (nTreg) markers (Foxp3, CD25 and CTLA-4) and IL-10 levels in lesion tissues of PKDL patients at pre and post treatment stages. In addition, correlation of nTreg markers and IL-10 with parasite load in tissue lesions was investigated. mRNA levels of nTreg markers and IL-10 were found significantly elevated in pre-treatment PKDL cases compared to controls (Foxp3, P = 0.0009; CD25 & CTLA-4, P<0.0001; IL-10, P<0.0001), and were restored after treatment. Analysis of nTreg cell markers and IL-10 in different clinical manifestations of disease revealed elevated levels in nodular lesions compared to macules/papules. Further, Foxp3, CD25 and IL-10 mRNA levels directly correlated with parasite load in lesions tissues.

Conclusion/Significance

Data demonstrated accumulation of nTreg cells in infected tissue and a correlation of both IL-10 and nTreg levels with parasite burden suggesting their role in disease severity in PKDL.     

Structure of the chromo barrel domain from the MOF acetyltransferase

We report here the structure of the putative chromo domain from MOF, a member of the MYST family of histone acetyltransferases that acetylates histone H4 at Lys-16 and is part of the dosage compensation complex in Drosophila. We found that the structure of this domain is a beta-barrel that is distinct from the alpha + beta fold of the canonical chromo domain. Despite the differences, there are similarities that support an evolutionary relationship between the two domains, and we propose the name "chromo barrel." The chromo barrel domains may be divided into two groups, MSL3-like and MOF-like, on the basis of whether a group of conserved aromatic residues is present or not. The structure suggests that, although the MOF-like domains may have a role in RNA binding, the MSL3-like domains could instead bind methylated residues. The MOF chromo barrel shares a common fold with other chromatin-associated modules, including the MBT-like repeat, Tudor, and PWWP domains. This structural similarity suggests a probable evolutionary pathway from these other modules to the canonical chromo domains (or vice versa) with the chromo barrel domain representing an intermediate structure.     

Constructing and testing the thermodynamic limits of synthetic NAD(P)H:H2 pathways

NAD(P)H:H₂ pathways are theoretically predicted to reach equilibrium at very low partial headspace H₂ pressure. An evaluation of the directionality of such near‐equilibrium pathways in vivo, using a defined experimental system, is therefore important in order to determine its potential for application. Many anaerobic microorganisms have evolved NAD(P)H:H₂ pathways; however, they are either not genetically tractable, and/or contain multiple H₂ synthesis/consumption pathways linked with other more thermodynamically favourable substrates, such as pyruvate. We therefore constructed a synthetic ferredoxin‐dependent NAD(P)H:H₂ pathway model system in Escherichia coli BL21(DE3) and experimentally evaluated the thermodynamic limitations of nucleotide pyridine‐dependent H₂ synthesis under closed batch conditions. NADPH‐dependent H₂ accumulation was observed with a maximum partial H₂ pressure equivalent to a biochemically effective intracellular NADPH/NADP⁺ ratio of 13:1. The molar yield of the NADPH:H₂ pathway was restricted by thermodynamic limitations as it was strongly dependent on the headspace : liquid ratio of the culture vessels. When the substrate specificity was extended to NADH, only the reverse pathway directionality, H₂ consumption, was observed above a partial H₂ pressure of 40 Pa. Substitution of NADH with NADPH or other intermediates, as the main electron acceptor/donor of glucose catabolism and precursor of H₂, is more likely to be applicable for H₂ production.     

Oral delivery of curcumin bound to chitosan nanoparticles cured Plasmodium yoelii infected mice

Curcumin has been shown to have anti malarial activity, but poor bioavailability and chemical instability has hindered its development as a drug. We have bound curcumin to chitosan nanoparticles to improve its bioavailability and chemical stability. We found that curcumin bound to chitosan nanoparticles did not degrade that rapidly in comparison to free curcumin when such particles were incubated in mouse plasma in vitro at room temperature. The uptake of bound curcumin from chitosan nanoparticles by mouse RBC was much better than from free curcumin. Oral delivery of curcumin bound chitosan nanoparticles to normal mice showed that they can cross the mucosal barrier intact and confocal microscopy detected the nanoparticles in the blood. Curcumin loaded chitosan nanoparticles when delivered orally improved the bioavailability of curcumin in the plasma and RBC. While mice infected with a lethal strain of Plasmodium yoelii (N-67) died between 8 and 9 days post infection, feeding of chitosan nanoparticles alone made them to survive for five more days. Feeding 1mg of native curcumin to infected mice per day for seven days resulted in survival of one third of mice but under the same condition when 1mg of curcumin bound to chitosan nanoparticles was fed all the mice survived. Like chloroquine, curcumin inhibited parasite lysate induced heme polymerization in vitro in a dose dependent manner and curcumin had a lower IC(50) value than chloroquine. We believe that binding of curcumin to chitosan nanoparticles increases its chemical stability and enhances its bioavailability when fed to mice. In vitro data suggest that it can inhibit hemozoin synthesis which is lethal for the parasite.     

A decade of molecular cell biology: achievements and challenges

Nature Reviews Molecular Cell Biology celebrated its 10-year anniversary during this past year with a series of specially commissioned articles. To complement this, here we have asked researchers from across the field for their insights into how molecular cell biology research has evolved during this past decade, the key concepts that have emerged and the most promising interfaces that have developed. Their comments highlight the broad impact that particular advances have had, some of the basic understanding that we still require, and the collaborative approaches that will be essential for driving the field forward.     

Patient navigation pathway and barriers to treatment seeking in cancer in India: A qualitative inquiry

Cancer is a leading cause of mortality worldwide. Early diagnosis and treatment of cancer may curb the growing burden of the disease. Understanding cancer patients’ navigation pathways for seeking treatment is important in order to facilitate early diagnosis and treatment. With this background we conducted a hospital-based cross-sectional study comprising 68 randomly selected cancer inpatients in a tertiary cancer specialty hospital in Odisha, India, to explore the treatment-seeking pathways of the cancer patients and the barriers and enablers in seeking treatment. Financial constraint is one of the major reasons for the delay in accessing treatment, even when patients are suspected of or diagnosed with cancer. Low awareness of the presenting signs and symptoms of cancer and limited knowledge of the availability of cancer diagnosis and treatment facilities are major factors contributing to delay. Family and friends’ support is found to be the major enabling factor toward seeking treatment. Generation of awareness of cancer among the general population and primary-care practitioners – including those in alternative systems of medicine – is important. Information on diagnostic and treatment services appears to be a felt need.