Telomerase, p53 and human papillomavirus infection in the uterine cervix

Human papillomavirus infection is postulated to be a major risk factor for cervical cancer, while more recent data have stressed the clinical significance of telomerase expression during tumorigenesis. This study therefore looked for any relationship between telomerase expression, presence of human papillomavirus (HPV) and expression of the high-risk HPV E6 protein at various phases of tumor progression in the uterine cervix. In addition, accumulation of the p53 protein and total tissue proliferative fraction were also studied. Telomerase was detected using a modified TRAP (telomerase repeat amplification protocol) assay. Expression of p53, Ki 67 and E6 protein was evaluated by immunocytochemistry. Presence of mutant p53 was detected using a mutant-specific ELISA. Type of HPV infection was determined by polymerase chain reaction and Southern blot using type-specific primers and probes. There was a significant correlation between the expression of telomerase with histological grade (r=0.646, p=0.00003). Fisher's exact test analysis revealed that the odds ratio of a tissue sample expressing telomerase being a case (high-grade squamous intraepithelial lesion or invasive cancer) was 28.93 (p=0.0001, 95% CI: 7.22, to 115.94). High-risk HPV-infected tissues and those expressing E6 showed increased telomerase expression (r=0.555, p=0.00001). Similarly, accumulation of p53 protein and increased cell proliferation (Ki 67 index) also correlated to the presence of telomerase (r=0.661, p=0.000004 for p53 and r=0.647, p=0.000003 for Ki 67). There was no correlation between telomerase expression and presence of p53 mutation. Activation of telomerase thus appears to be associated with high-risk-HPV infection, accumulation of inactive p53 protein and increased cell proliferation in cervical lesions.     

A flexible Ti3C2Tx (MXene)/paper membrane for efficient oil/water separation

The scalable fabrication of flexible membranes for efficient oil/water separation is in high demand but still significantly underdeveloped. Here, we present a flexible membrane using Ti₃C₂T_x (MXene) as the functional layer on conventional print paper as the substrate. With a simple coating process using MXene ink, we developed a highly hydrophilic and oleophobic membrane with an underwater oil contact angle of 137°. Such a simple membrane shows outstanding flexibility and robustness, and demonstrates a facile approach for membrane scale-up using MXene ink on low-cost print paper. The membrane shows high separation efficiency for oil/water emulsions, of over 99%, and a high water permeation flux of over 450 L per m² per h per bar. We demonstrate the excellent anti-fouling property of this membrane by cleaning the membranes without chemicals. These low-cost, highly efficient, anti-fouling membranes can provide new opportunities for industrial oil/water separation applications.

A highly hydrophilic and oleophobic membrane based on Ti₃C₂T_x (MXene) coated paper demonstrated high separation efficiency for oil/water emulsions with excellent antifouling properties.     

Systemic review on drug related hospital admissions – A pubmed based search

Background

Drug related admissions have significantly increased over the past few decades. According to various studies on drug related hospital admissions, it was estimated that around 5–10% of hospital admissions were due to drug related problems (DRP), in which 50% of them are avoidable.

Objective

The objective of the study was to derive results from various studies conducted on drug related hospital admissions and have an overall view about the incidence, frequency, cost of treatment, major causative drugs, problems for drug related hospital admissions, and preventable drug related admissions and summarize the factors responsible for the occurrence of DRP.

Method

Relevant literatures related to ‘drug related hospital admissions’ were obtained from PubMed database. Articles that were published from October 2007 to September 2012 were collected. All the studies being shown in the search results were considered for the study irrespective of the specialty department.

Results

A total of 366 articles were found based on the keyword ‘drug related hospital admission’, ‘drug related problem admission’, and ‘adverse drug event admissions’ search. Out of which 49 articles were identified to be showing relevance to the study. Non-English, abstract-only articles, and out-patient adverse drug reaction (ADR) studies were filtered from 49 articles. Finally 15 articles were taken up for the study. Systemic analysis was made on these articles and the results were summarized.

Conclusion

Most of DRP studies were retrospective, multicenter studies conducted in general populations in Europe. The main objective of the studies was to estimate DRP frequency, incidence, risk factors and trends of DRP hospital admissions. Anti-neoplastic agents, CVS drugs and CNS drugs were related to most of the drug related problems. These studies concluded polypharmacy and older age were the major risk factors for developing drug related problems. It was found that the cost for the management of DRP was directly proportional to severity.     

Management of synchronous adenocarcinoma of the esophago-gastric junction and ampulla of Vater: case report of a surgically challenging condition

We report herein a case of a synchronous presentation of an adenocarcinoma of esophagago-gastric junction type II and an ampullary tumor that was treated by combined Whipple's pancreaticoduodenectomy, total gastrectomy and esophagectomy. The magnitude of this operation was safely achieved with meticulous surgical techniques and perioperative care without any major short or long term complications. Patient returned to a good quality of life at six-month follow up with no further gastrointestinal symptoms or evidence of disease recurrence.     

The role of phagocytosis,oxidative burst and neutrophil extracellular traps in the interaction between neutrophils and the periodontal pathogen Porphyromonas gingivalis

Neutrophils are regarded as the sentinel cells of innate immunity and are found in abundance within the gingival crevice. Discovery of neutrophil extracellular traps (NETs) within the gingival pockets prompted us to probe the nature of the interactions of neutrophils with the prominent periopathogen Porphyromonas gingivalis. Some of the noted virulence factors of this Gram‐negative anaerobe are gingipains: arginine gingipains (RgpA/B) and lysine gingipain (Kgp). The aim of this study was to evaluate the role of gingipains in phagocytosis, formation of reactive oxygen species, NETs and CXCL8 modulation by using wild‐type strains and isogenic gingipain mutants. Confocal imaging showed that gingipain mutants K1A (Kgp) and E8 (RgpA/B) induced extracellular traps in neutrophils, whereas ATCC33277 and W50 were phagocytosed. The viability of both ATCC33277 and W50 dwindled as the result of phagocytosis and could be salvaged by cytochalasin D, and the bacteria released high levels of lipopolysaccharide in the culture supernatant. Porphyromonas gingivalis induced reactive oxygen species and CXCL8 with the most prominent effect being that of the wild‐type strain ATCC33277, whereas the other wild‐type strain W50 was less effective. Quantitative real‐time polymerase chain reaction revealed a significant CXCL8 expression by E8. All the tested P. gingivalis strains increased cytosolic free calcium. In conclusion, phagocytosis is the primary neutrophil response to P. gingivalis, although NETs could play an accessory role in infection control. Although gingipains do not seem to directly regulate phagocytosis, NETs or oxidative burst in neutrophils, their proteolytic properties could modulate the subsequent outcomes such as nutrition acquisition and survival by the bacteria.     

Symptomatic and asymptomatic Cryptosporidium infections in children in a semi-urban slum community in southern India

Cryptosporidium is a leading cause of childhood diarrhea in developing countries. We investigated symptomatic and asymptomatic cryptosporidiosis in 20 children less than two years of age in a semi-urban slum in southern India. All surveillance (conducted every two weeks) and diarrheal samples from 20 children (n = 1,036) with cryptosporidial diarrhea previously identified by stool microscopy were tested by polymerase chain reaction-restriction fragment length polymorphism for species and subgenotype determination. Thirty-five episodes of cryptosporidiosis were identified in 20 children, of which 25 were diarrheal. Fifteen episodes were associated with prolonged oocyst shedding. Multiple episodes of cryptosporidiosis occurred in 40% of the children. Most infections were with C. hominis, subtype Ia. Children with multiple infections had significantly lower weight-for-age and height-for-age Z scores at 24 months but had scores comparable with children with a single episode by 36 months. Multiple symptomatic Cryptosporidium infections associated with prolonged oocyst shedding occur frequently in this disease-endemic area and may contribute to the long-term effects of cryptosporidiosis on physical growth in these children.     

Changes in adiponectin and inflammatory genes in response to hormonal imbalances in female mice and exacerbation of depot selective visceral adiposity by high-fat diet: implications for insulin resistance

Early obesity and late onset of insulin resistance associated with hormonal imbalances occur in FSH receptor-deficient follitropin receptor knockout female mice. This study tests the hypothesis that chronic high-fat diet aggravates obesogenic changes in a depot-specific manner and explores some molecular links of hormone imbalances with insulin resistance. In SV 129 mice, hormonal imbalances seem obligatory for exacerbation of diet-induced obesity. Visceral adiposity, glucose intolerance, and lipid disturbances in 9-month follitropin receptor knockout females were associated with decrease in adiponectin signaling. High-molecular-weight plasma adiponectin and adipose tissue adiponectin mRNA were decreased. Adiponectin receptors R1 and R2 mRNA was selectively altered in mesenteric fat but not periuterine fat. R2 decreased in the liver and R1 was higher in muscle. Whereas hepatic adenosine monophosphate T-activated protein kinase activity was down-regulated, both phosphoenolpyruvate carboxykinase and glucose-6-phosphatase enzymes were up-regulated. Longitudinally, diminishing sex hormone signaling in adipose tissue was associated with progressive down-regulation of adiponectin activity and gradual impaired glucose tolerance. Chronic high-fat diet in SV129 wild-type mice did not produce overt obesity but induced visceral fat depot changes accompanied by liver lipid accumulation, high cholesterol, and up-regulation of inflammation gene mRNAs. Thus, TNF-alpha, C-C motif chemokine receptor-2, and C-C motif chemokine ligand-2 were selectively elevated in mesenteric fat without altering glucose tolerance and adiponectin signaling. Our study highlights adiponectin signaling and regulation to be involved in hormone imbalance-induced insulin resistance and demonstrates selective visceral adipose depot alterations by chronic high-fat diet and induction of inflammatory genes.     

Endoscopic injection sclerotherapy with doxycycline for mediastinal and esophageal lymphangiohemangioma

BACKGROUND: Lymphangiohemangioma, also called lymphatic-venous or venolymphatic malformation, is a rare malformation of the lymphatics, with vascular elements. These are low-flow vascular lesions. OBJECTIVE: To evaluate the feasibility and efficacy of endoscopic injection sclerotherapy with doxycycline for low-flow vascular malformations in the GI tract. DESIGN: Case report. SETTING: Academic center. PATIENTS: An adult man with lymphangiohemangioma that involved the mediastinum and the esophagus. The esophageal involvement caused dysphagia and chest pain. INTERVENTIONS: We characterized the lesion with EUS and successfully treated the esophageal and paraesophageal lesions with endoscopic injection sclerotherapy by using doxycycline. MAIN OUTCOME MEASUREMENT: Symptom resolution and complications. RESULTS: The patient's esophageal symptoms resolved with sclerotherapy. This is the first reported case of lymphangiohemangioma with esophageal involvement and the first reported case of endoscopic injection sclerotherapy by using doxycycline in the GI tract. LIMITATIONS: Case report and short follow-up period. CONCLUSIONS: Endoscopic injection sclerotherapy with doxycycline for lymphatic and low-flow vascular malformations in the GI tract is feasible, easy, safe, and effective.