Pattern of childhood and adolescent malignancies at a tertiary health institution in South-east Nigeria : A ten year study

Background: Cancer remains a major cause of death in children and adolescents, and differs in adults in nature, distribution and prognosis1. A culture of case documentation is lacking in our environment and many cases go unreported.Study objectives: To document the pattern of childhood and adolescent malignancies at a tertiary health institution in south-east Nigeria over a ten year period (January 2004 to December 2013)Methodology: Details of all children and adolescents aged 18 years and below treated for malignancy were extracted from the cancer registry and the records unit of the histopathology department for the period beginning at January 2004 to December 2013 at Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi, Nigeria. Information retrieved was verified against the hospital admission register, as well as the medical and histopathology records for all cancer patients over the period of interest.Results: Eighty-five cases of childhood and adolescent malignancy were treated at NAUTH, Nnewi between January 2004 and December 2013. Median age of the study population was 9years, with a range of 0.1– 18years, more males (56.50%) than females (43.50%). Commonest tumours were the Lymphomas (11.76%) comprising Non- Hodgkin’s lymphoma (80%), Hodgkin’s lymphoma (10%) and Large-cell lymphoma (10%), the Leukaemias (11.76%) comprising Acute myeloblastic leukaemia (80%) and Acute lymphoblastic leukaemia (20%). Others were Rhabdomyosarcoma (11.76%), Nephroblastoma (11.76%), Retinoblastoma (5.88%), Ovarian tumours (4.71%), the Soft tissue sarcomas-excluding rhabdomyosarcoma (3.53%) and Osteogenic sarcoma (3.35%)’.Conclusion: Study findings suggest that lymphoma, leukaemia, rhabdomyosarcoma and nephroblastoma are the commonest childhood and adolescent malignancies in south-east Nigeria.Keywords: Childhood, Adolescent, Malignanc

EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 9, Revision 4 (FGE.09Rev4): Secondary alicyclic saturated and unsaturated alcohols, ketones and esters containing secondary alicyclic alcohols from chemical group 8 and 30, and an ester of a phenol derivative from chemical group 25

<p>The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate 21 flavouring substances in the Flavouring Group Evaluation 9, Revision 4, using the Procedure in Commission Regulation (EC) No 1565/2000. The present revision of FGE.09 includes the assessment of four additional flavouring substances, p-menthan-3-one [FL-no: 07.059], 2,6,6-trimethylcyclohex-2-en-1-one [FL-no: 07.202], l-piperitone [FL-no: 07.255] and menthol 1-and 2-propylene glycol carbonate [FL-no: 09.843]. None of the substances were considered to have genotoxic potential. The substances were evaluated through a stepwise approach (the Procedure) that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel concluded that the 20 substances [FL-no: 02.070, 02.075, 02.135, 02.167, 06.136, 07.059, 07.202, 07.203, 07.255, 09.154, 09.355, 09.520, 09.618, 09.619, 09.621, 09.843, 09.870, 09.929, 09.935 and 09.949] do not give rise to safety concerns at their levels of dietary intake, estimated on the basis of the MSDI approach. For the remaining candidate substance [FL-no: 07.207], additional toxicity data are requested (further metabolism and/or toxicity studies). Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have been considered. Specifications including complete purity criteria and identity for the materials of commerce have been provided for all candidate substances.</p&gt

Twisted fallopian tube in pregnancy: a case report

BACKGROUND: Isolated twisted fallopian tube is an uncommon event, isolated twisted fallopian tube in pregnancy is also very rare. The diagnosis is often difficult and established during the operation. The right fallopian tube is most common affected. CASE PRESENTATION: We report an uncommon twisted left fallopian tube in pregnancy. A 34-year-old G(3)P(2) 28 weeks pregnant woman presented with acute left lower abdominal pain. The clinical and ultrasonographic findings led to diagnosis of twisted left ovarian cyst. Emergency exploratory laparotomy was performed. A twisted left fallopian tube and paratubal cyst was noted and left salpingectomy was performed. The postoperative course was uneventful and the pregnancy continued until term without complication. CONCLUSIONS: Although isolated twisted fallopian tube during pregnancy is very rare, it should be included in the differential diagnosis of acute abdomen in pregnancy. Early surgical intervention will decrease obstetric morbidity and may allow preservation of the fallopian tube

Chern-Simons black holes: scalar perturbations, mass and area spectrum and greybody factors

We study the Chern-Simons black holes in d-dimensions and we calculate analytically the quasi-normal modes of the scalar perturbations and we show that they depend on the highest power of curvature present in the Chern-Simons theory. We obtain the mass and area spectrum of these black holes and we show that they have a strong dependence on the topology of the transverse space and they are not evenly spaced. We also calculate analytically the reflection and transmission coefficients and the absorption cross section and we show that at low frequency limit there is a range of modes which contributes to the absorption cross section.Comment: 19 pages, 18 figures, the title has been changed to reflect the addition of an another section on the reflection, transmission coefficients and absorption cross sections of the Chern-Simons black holes. Version to be published in JHE

Surfactant protein D modulates HIV infection of both T-cells and dendritic cells

Surfactant Protein D (SP-D) is an oligomerized C-type lectin molecule with immunomodulatory properties and involvement in lung surfactant homeostasis in the respiratory tract. SP-D binds to the enveloped viruses, influenza A virus and respiratory syncytial virus and inhibits their replication in vitro and in vivo. SP-D has been shown to bind to HIV via the HIV envelope protein gp120 and inhibit infectivity in vitro. Here we show that SP-D binds to different strains of HIV (BaL and IIIB) and the binding occurs at both pH 7.4 and 5.0 resembling physiological relevant pH values found in the body and the female urogenital tract, respectively. The binding of SP-D to HIV particles and gp120 was inhibited by the presence of several hexoses with mannose found to be the strongest inhibitor. Competition studies showed that soluble CD4 and CVN did not interfere with the interaction between SP-D and gp120. However, soluble recombinant DC-SIGN was shown to inhibit the binding between SP-D and gp120. SP-D agglutinated HIV and gp120 in a calcium dependent manner. SP-D inhibited the infectivity of HIV strains at both pH values of 7.4 and 5.0 in a concentration dependent manner. The inhibition of the infectivity was abolished by the presence of mannose. SP-D enhanced the binding of HIV to immature monocyte derived dendritic cells (iMDDCs) and was also found to enhance HIV capture and transfer to the T-cell like line PM1. These results suggest that SP-D can bind to and inhibit direct infection of T-cells by HIV but also enhance the transfer of infectious HIV particles from DCs to T-cells in vivo

Defects in the Outer Limiting Membrane Are Associated with Rosette Development in the Nrl−/− Retina

The neural retinal leucine zipper (Nrl) knockout mouse is a widely used model to study cone photoreceptor development, physiology, and molecular biology in the absence of rods. In the Nrl−/− retina, rods are converted into functional cone-like cells. The Nrl−/− retina is characterized by large undulations of the outer nuclear layer (ONL) commonly known as rosettes. Here we explore the mechanism of rosette development in the Nrl−/− retina. We report that rosettes first appear at postnatal day (P)8, and that the structure of nascent rosettes is morphologically distinct from what is seen in the adult retina. The lumen of these nascent rosettes contains a population of aberrant cells protruding into the subretinal space that induce infolding of the ONL. Morphologically adult rosettes do not contain any cell bodies and are first detected at P15. The cells found in nascent rosettes are photoreceptors in origin but lack inner and outer segments. We show that the adherens junctions between photoreceptors and Müller glia which comprise the retinal outer limiting membrane (OLM) are not uniformly formed in the Nrl−/− retina and thus allow protrusion of a population of developing photoreceptors into the subretinal space where their maturation becomes delayed. These data suggest that the rosettes of the Nrl−/− retina arise due to defects in the OLM and delayed maturation of a subset of photoreceptors, and that rods may play an important role in the proper formation of the OLM

Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium

Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. © 2013 Mishra et al

HPV16 Oncoproteins Induce MMPs/RECK-TIMP-2 Imbalance in Primary Keratinocytes: Possible Implications in Cervical Carcinogenesis

Cervical cancer is the third most common cancer in women worldwide. Persistent infection with high-risk HPV types, principally HPV16 and 18 is the main risk factor for the development of this malignancy. However, the onset of invasive tumor occurs many years after initial exposure in a minority of infected women. This suggests that other factors beyond viral infection are necessary for tumor establishment and progression. Tumor progression is characterized by an increase in secretion and activation of matrix metalloproteinases (MMPs) produced by either the tumor cells themselves or tumor-associated fibroblasts or macrophages. Increased MMPs expression, including MMP-2, MMP-9 and MT1-MMP, has been observed during cervical carcinoma progression. These proteins have been associated with degradation of ECM components, tumor invasion, metastasis and recurrence. However, few studies have evaluated the interplay between HPV infection and the expression and activity of MMPs and their regulators in cervical cancer. We analyzed the effect of HPV16 oncoproteins on the expression and activity of MMP-2, MMP-9, MT1-MMP, and their inhibitors TIMP-2 and RECK in cultures of human keratinocytes. We observed that E7 expression is associated with increased pro-MMP-9 activity in the epithelial component of organotypic cultures, while E6 and E7 oncoproteins co-expression down-regulates RECK and TIMP-2 levels in organotypic and monolayers cultures. Finally, a study conducted in human cervical tissues showed a decrease in RECK expression levels in precancer and cancer lesions. Our results indicate that HPV oncoproteins promote MMPs/RECK-TIMP-2 imbalance which may be involved in HPV-associated lesions outcome

Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: A pivotal interplay in the pathogenesis of Atopic Dermatitis

Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials

High nutrient-use efficiency during early seedling growth in diverse Grevillea species (Proteaceae)

Several hypotheses have been proposed to explain the rich floristic diversity in regions characterised by nutrient-impoverished soils; however, none of these hypotheses have been able to explain the rapid diversification over a relatively short evolutionary time period of Grevillea, an Australian plant genus with 452 recognised species/subspecies and only 11 million years of evolutionary history. Here, we hypothesise that the apparent evolutionary success of Grevillea might have been triggered by the highly efficient use of key nutrients. The nutrient content in the seeds and nutrient-use efficiency during early seedling growth of 12 species of Grevillea were compared with those of 24 species of Hakea, a closely related genus. Compared with Hakea, the Grevillea species achieved similar growth rates (root and shoot length) during the early stages of seedling growth but contained only approximately half of the seed nutrient content. We conclude that the high nutrient-use efficiency observed in Grevillea might have provided a selective advantage in nutrient-poor ecosystems during evolution and that this property likely contributed to the evolutionary success in Grevillea