Expression of Epsin3 and its interaction with Notch signalling in oral epithelial dysplasia and oral squamous cell carcinoma.

BACKGROUND: Most oral squamous cell carcinoma patients present with late-stage disease. Early detection of the disease is considered to be the most effective way of improving patient outcomes. Several biomarkers have been identified as indicators of oral cancer development and progression; however, none have been translated into clinical practice. In this study, we have investigated the role of Epsin3, an endocytic adaptor protein, and Notch1, a transmembrane signalling protein, in oral carcinogenesis with a view to explore their potential as biomarkers. METHODS: Oral cancer cell lines and a normal oral keratinocyte cell line were used together with tissue samples of normal oral mucosa (n = 21), oral epithelial dysplasia (n = 74) and early stage (Stages I and II) oral squamous cell carcinoma (n = 31). Immunocytochemical staining, immunoblotting and real-time quantitative polymerase chain reaction (PCR) were performed to assess protein as well as gene expression levels. RESULTS: The expression levels of Epsin3 and Notch1 mRNA and protein are variable across different oral squamous cell carcinoma derived cell lines. Epsin3 was upregulated in oral epithelial dysplasia and oral squamous cell carcinoma tissues compared with normal epithelium. Overexpression of Epsin3 resulted in a significant reduction of Notch1 expression in oral squamous cell carcinoma. Notch1 was generally downregulated in the dysplasia and oral squamous cell carcinoma samples. CONCLUSION: Epsin3 is upregulated in oral epithelial dysplasia and oral squamous cell carcinoma and has the potential to be used as a biomarker for oral epithelial dysplasia. Notch signalling is downregulated in oral squamous cell carcinoma, possibly through an Epsin3-induced de-activation pathway.

Prevalence, antibiogram and virulence characterization of Vibrio isolates from fish and shellfish in Egypt: a possible zoonotic hazard to humans.

AIMS: Infection of seafood with pathogenic species of the genus Vibrio causes human food-borne illnesses. This study was executed to examine the antimicrobial resistance phenotypes, biofilm-forming capability and virulence-associated genes of Vibrio from fish and shellfishes. METHODS AND RESULTS: Three hundred fresh water and marine fish and shellfish samples were collected from wet markets and supermarkets in Mansoura, Egypt. Bacteriological examination and PCR amplification identified 92 Vibrio spp., including 42 Vibrio parahaemolyticus and 50 Vibrio alginolyticus isolates from the examined fish and shellfish (infection rate: 30·67%). However, V. vulnificus was not found in this study. Vibrio spp. exhibited variable frequencies of antimicrobial resistance with higher percentages to ampicillin and penicillin. Multidrug resistance (MDR) was detected in 69·04 and 38% of V. parahaemolyticus and V. alginolyticus respectively. PCR testing of virulence genes, tdh, trh and tlh revealed the presence of tlh and trh in 100 and 11·9% of V. parahaemolyticus isolates respectively and none of V. alginolyticus carried any of these genes. Biofilm-forming capability was displayed by 76% of V. parahaemolyticus and 73·8% of V. alginolyticus isolates. Both V. parahaemolyticus and V. alginolyticus showed nonsignificant weak positive correlations (r < 0·4) between antimicrobial pairs belonging to different classes; however, a significant positive correlation (P <0·05) between trh and resistance to erythromycin (r = 0·45) and imipenem (r = 0·38) was only identified in V. parahaemolyticus. CONCLUSIONS: This study reports the existence of MDR strains of V. parahaemolyticus and V. alginolyticus from the common types of fishes and shellfishes in Egypt. Furthermore, the presence of virulence genes in these isolates and the ability to produce a biofilm in vitro pose potential health hazards to consumers. SIGNIFICANCE AND IMPACT OF THE STUDY: Frequent monitoring of seafood for the presence of Vibrio spp. and their antimicrobial susceptibility, virulence determinants and biofilm-forming capability is important for assessing the risk posed by these organisms to the public and for improving food safety.

Burden of serious fungal infections in Bangladesh.

In Bangladesh there are several published papers on superficial mycoses. Deep mycoses are also recognized as an important emerging problem. Here, we estimate the annual incidence and prevalence of serious fungal infections in Bangladesh. Demographic data were obtained from world population reports and the data on TB and HIV extracted from the online publications on tuberculosis in Bangladesh and Asia Pacific research statistical data information resources AIDS Data HUB. All the published papers on fungal infections in Bangladesh were identified through extensive search of literature. We estimated the number of affected people from populations at risk and local epidemiological data. Bangladesh has a population of ∼162.6 million, 31% children and only 6% over the age of 60 years. The pulmonary TB caseload reported in 2014 was 119,520, and we estimate a prevalence of 30,178 people with chronic pulmonary aspergillosis, 80% attributable to TB. An anticipated 90,262 and 119,146 patients have allergic bronchopulmonary aspergillosis or severe asthma with fungal sensitization. Only 8,000 people are estimated to be HIV-infected, of whom 2900 are not on ART with a CD4 count <350 µL, Pneumocystis pneumonia and cryptococcal meningitis being rare. Superficial mycoses are very common with Trichophyton rubrum as the predominant etiological agent (80.6%). Numerous cases of mycotic keratitis have been reported from several parts of Bangladesh. Candida bloodstream infection was estimated based on a 5 per 100,000 rate (8100 cases) and invasive aspergillosis based primarily on leukemia and COPD rates, at 5166 cases. Histoplasmosis was documented in 16 cases mostly with disseminated disease and presumed in 21 with HIV infection. This study constitutes the first attempt to estimate the burden of several types of serious fungal infections in Bangladesh.

Metabolic programming of a beige adipocyte phenotype by genistein.

SCOPE: Promoting the development of brown or beige adipose tissue may protect against obesity and related metabolic features, and potentially underlies protective effects of genistein in mice. METHODS AND RESULTS: We observed that application of genistein to 3T3-L1 adipocytes changed the lipid distribution from large droplets to a multilocular distribution, reduced mRNAs indicative of white adipocytes (ACC, Fasn, Fabp4, HSL, chemerin, and resistin) and increased mRNAs that are a characteristic feature of brown/beige adipocytes (CD-137 and UCP1). Transcripts with a role in adipocyte differentiation (Cebpß, Pgc1α, Sirt1) peaked at different times after application of genistein. These responses were not affected by the estrogen receptor (ER) antagonist fulvestrant, revealing that this action of genistein is not through the classical ER pathway. The Sirt1 inhibitor Ex-527 curtailed the genistein-mediated increase in UCP1 and Cebpß mRNA, revealing a role for Sirt1 in mediating the effect. Baseline oxygen consumption and the proportional contribution of proton leak to maximal respiratory capacity was greater for cells exposed to genistein, demonstrating greater mitochondrial uncoupling. CONCLUSIONS: We conclude that genistein acts directly on adipocytes or on adipocyte progenitor cells to programme the cells metabolically to adopt features of beige adipocytes. Thus, this natural dietary agent may protect against obesity and related metabolic disease.

Seronegative neuromyelitis optica after cardiac transplantation.

We report a case of a 42-year-old man who presented with progressive weakness and blindness over the course of several months and met criteria for seronegative neuromyelitis optica. This presentation was in the setting of immunosuppression following cardiac transplant. No infectious causes were found within the neuroaxis, and he ultimately died with complete blindness, quadriplegia, and respiratory failure attributed to panmyelitis and brain stem inflammation despite aggressive therapies.

Basilar artery thrombosis in the setting of antiphospholipid syndrome.

Antiphospholipid syndrome is an autoimmune disorder characterized by arterial or venous thrombosis, recurrent first-trimester pregnancy loss, and multiple additional clinical manifestations. We describe a man with severe atherosclerotic basilar artery stenosis and superimposed in situ thrombus who was found to have antiphospholipid syndrome.

Comparative antioxidant and antiplasmodial activities of 11-O-galloylbergenin and bergenin isolated from Bergenia ligulata.

In the present study, the antioxidant and antiplasmodial activities of bergenin was compared with its natural derivative 11-O-galloylbergenin for the first time. Both compounds were isolated from Bergenia ligulata. 11-O-galloylbergenin was found to be very active in in-vitro antioxidant assay as compared to bergenin, which was found to be almost inactive. The EC50 values of 11-O-galloylbergenin were 7.45±0.2 µg/mL and 5.39±0.28 µg/mL in DPPH antioxidant assay and reducing power assay respectively, while IC50 value for antiplasmodial assay of both compounds were less than 2.5 µM. Interestingly, in the total antioxidant phosphomolybdate assay, 11-O-galloylbergenin was found more potent (CAHT: 940.04±115.30) as compared to α-tocopherol (CAHT: 552.4±27.91).

Beyond photography: evaluation of the consumer digital camera to identify strabismus and anisometropia by analyzing the Bruckner's reflex.

Amblyopia screening is often either costly or laborious. We evaluated the Canon Powershot TX1 (CPTX1) digital camera as an efficient screener for amblyogenic risk factors (ARF). We included 138 subjects: 84-amblyopes and 54-normal. With the red-eye-reduction feature off, we obtained Bruckner reflex photographs of different sized crescents which suggested anisometropia, while asymmetrical brightness indicated strabismus; symmetry implied normalcy. Eight sets of randomly arranged 138 photographs were made. After training, 8 personnel, marked each as normal or abnormal. Of the 84 amblyopes, 42 were strabismus alone (SA), 36 had anisometropia alone (AA) while six were mixed amblyopes (MA). Overall mean sensitivity for amblyopes was 0.86 (95% CI: 0.83-0.89) and specificity 0.85 (95% CI: 0.77-0.93). Sub-group analyses on SA, AA and MA returned sensitivities of 0.86, 0.89 and 0.69, while specificities were 0.85 for all three. Overall Cohen's Kappa was 0.66 (95% CI: 0.62-0.71). The CPTX1 appears to be a feasible option to screen for ARF, although results need to be validated on appropriate age groups.

[Analysis of a new visual field index, the VFI, in Ocular Hypertension and Glaucoma]. / Analyse d'un nouvel indice d'évaluation du champ visuel, le VFI, dans l'hypertonie oculaire et le glaucome.

OBJECTIVE: The Visual Field Index -VFI- is a new perimetric index allowing evaluation of visual function level and progression. In this study, we analysed this new index, that provides a trend analysis of visual field loss progression in Ocular Hypertension and Glaucoma. We also compared results with event analysis. METHODS: Retrospective study on 94 eyes of 54 patients: 35 OHT(ocular hypertension), 34 early POAG (primary open angle glaucoma) (0>MD>-6 dB), 13 moderate POAG (-6>MD>-12 dB) and 12 advanced POAG (MD<-12 dB), with a mean follow-up of 6.5 years (4 to 8 years). Each subject performed a mean number of 10 standard automated perimetry visual field tests (Humphrey SITA Standard 24-2), excluding tests without reliable indices. VFI progression rate was analysed. VFI progression during the first half period of follow up was compared with that during the second half period. VFI progression was confronted with script alert messages delivered by the last GPA (Guided Progression Analysis) event analysis program. RESULTS: VFI values were "stable or with low progression" in 100% of OHT patients, 88% of early POAG, 38.5% of moderate POAG, 33% of advanced POAG. Progression during the first half period (mean of 3 years) of follow-up could be extrapolated for the second half period in 97% of OHT patients, 76% of early POAG, 70% of moderate POAG, 75% of advanced POAG. Results from VFI trend analysis and GPA event analysis corresponded in 97% of OHT patients, 85% of early POAG, 85% of moderate POAG, and 87% of advanced POAG. DISCUSSION: VFI seems to be a useful indicator for glaucoma evaluation and progression follow-up. It completes the event analysis. Some very advanced POAG cannot be analysed by GPA event analysis. VFI should be able to be used for further follow-up. All these results require validation in larger population. The purpose would be to assess if VFI is able to detect different profiles of progression to help treatment decisions.

[Atypical unilateral glaucoma in a young patient]. / Neuropathie optique glaucomateuse unilatérale atypique chez un sujet jeune.

BACKGROUND: Diagnostic and therapeutic problems are common in cases of unilateral optical neuropathy with elevated intraocular pressure (IOP) CASE REPORT: A 17-year-old boy was referred for visual acuity loss and elevated IOP at 40mmHg in his left eye. Juvenile open-angle glaucoma (JOAG) was diagnosed based on the clinical and paraclinical examinations. In spite of a maximal hypotensive treatment, tensional control was insufficient and a filtering surgery procedure was necessary. IOP control was good 6 months after surgery, but functional and anatomical analysis showed neuropathic progression and a bilateralization of the disease. CONCLUSION: The diagnosis of JOAG is difficult and sometimes delayed. Secondary bilateralization commonly causes diagnostic problems which can delay specific and appropriate management. Systematic screening should be performed during infancy when a strong family history of glaucoma is known.

Can depth of tumour invasion predict lymph node positivity in patients undergoing resection for early rectal cancer? A comparative study between T1 and T2 cancers.

OBJECTIVE: The present study investigated the risk of lymph node metastasis according to the depth of tumour invasion in patients undergoing resection for rectal cancer. METHOD: The histology of patients undergoing oncological resection with regional lymphadenectomy for rectal cancer at St Marks Hospital from 1971 to 1996 was reviewed. Of the total number of 1549 patients, 303 patients with T(1) or T(2) rectal cancers were selected. The tumour type, grade, evidence of vascular invasion, depth of submucosal invasion (classed into 'sm1-3') were evaluated as potential predictors of lymph node positivity using univariate and multi-level logistic regression analysis. RESULTS: Tumour stage was classified as T(1) in 55 (18.2%) and T(2) in 248 (81.2%) patients. The incidence of lymph node metastasis in the T(1) group was 12.7% (7/55), compared to 19% (47/247) in the T(2) group. The node positive and negative groups were similar with regard to patient demographics, although the former contained a significantly higher number of poorly differentiated (P = 0.001) and extramural vascular invasion tumours (P = 0.002). There was no significant difference in the number of patients with sm1-3, or T(2) tumour depths within the lymph node positive and negative groups. On multivariate analysis the presence of extramural vascular invasion (odds ratio = 10.0) and tumour grade (odds ratio for poorly vs well-differentiated = 11.7) were independent predictors of lymph node metastasis. CONCLUSION: Whilst the degree of vascular invasion and poor differentiation of rectal tumours were significant risk factors for lymph node metastasis, depth of submucosal invasion was not. This has important implications for patients with superficial early rectal cancers in whom local excision is being considered.

Thrombolytic therapy of acute ischemic stroke during pregnancy.

The authors report eight pregnant women with acute ischemic stroke treated with thrombolysis (rt-PA [recombinant human tissue plasminogen activator] or urokinase). Seven women recovered. Two extracranial and two asymptomatic intracranial hemorrhages complicated treatment; one woman died of arterial dissection complicating angiography. Three patients had therapeutic abortions, two fetuses were miscarried, and two babies were delivered healthy. Although pregnant women may be treated safely with thrombolytics, risks and benefits to mother and fetus must be carefully weighed.

Urethral substitution using vein graft for hypospadias repair.

OBJECTIVE: Complex hypospadias surgery requires abundant and stretchable tissues for urethroplasty. Genital skin is ideal for this purpose but is often unavailable in re-do cases. Extragenital tissues have their drawbacks such as the limited length of buccal and bladder mucosa, and contracture of skin grafts. Tubularization and on-lay techniques comprise one or two longitudinal suture lines that are the source of complications. We investigate the possibility of using a saphenous vein graft to construct a long, wide, stretchable and pre-tubularized neourethra that is not compromised by the longitudinal suture line. PATIENT AND METHOD: A male patient with proximal hypospadias for which surgical correction had failed underwent the operation. The patient had a penoscrotal meatus and was circumcised. A saphenous vein graft was passed through a tunnel created on the ventral aspect of the penis, and was anastomosed to the urethra proximally and the distal opening of the tunnel at the tip of the penis. RESULTS: After 12 months, the patient had a forward stream, no dilatation of the neourethra, and no penile curvature upon morning erection (as reported by the parents). CONCLUSION: This initial experience with saphenous vein urethroplasty shows that the technique is feasible, and may provide a reliable and practical alternative to the current techniques.

Constipation heralding neuroborreliosis: an atypical tale of 2 patients.

This is a report of 2 patients with Lyme disease who initially presented with severe constipation, which progressed to ascending muscular weakness resembling acute idiopathic polyneuritis, with neuropsychiatric symptoms, severe urinary retention, and hyponatremia. These symptoms resolved following proper antibiotic therapy.

Analysis of somatic molecular changes, clinicopathological features, family history, and germline mutations in colorectal cancer families: evidence for efficient diagnosis of HNPCC and for the existence of distinct groups of non-HNPCC families.

OBJECTIVE: To analyse somatic molecular changes, clinicopathological features, family history, and germline mutations in families with colorectal cancer (CRC). METHODS: Molecular changes (K-ras and beta-catenin mutations, chromosome 18q allele loss (LOH), APC LOH, microsatellite instability (MSI), and expression of beta-catenin and p53) were examined in four series of CRC patients with proven or probable hereditary disease: hereditary non-polyposis colon cancer (HNPCC); MYH associated polyposis (MAP); multiple (>5) colorectal adenomas without familial adenomatous polyposis (FAP); and other families/cases referred to family cancer clinics (FCC series). HNPCC was diagnosed using a combination of germline mutation screening and tumour studies. A series of unselected CRC patients was also studied. RESULTS: There was overlap between genetic pathways followed by each type of CRC, but significant differences included: increased frequency of K-ras mutation and reduced frequency of APC LOH in cancers from MAP, but not from multiple adenoma patients; reduced frequency of LOH in HNPCC CRCs; and increased MSI in CRCs from HNPCC, but not from FCC or multiple adenoma patients. HNPCC was apparently detected efficiently by combined germline and somatic analysis. Cancers from the FCC, unselected, and multiple adenoma series shared similar molecular characteristics. In the FCC and multiple adenoma series, hierarchical cluster analysis using the molecular features of the cancers consistently identified two distinct groups, distinguished by presence or absence of K-ras mutation. CONCLUSIONS: While K-ras mutation status is known to differentiate hereditary bowel cancer syndromes such as MAP and FAP, it may also distinguish groups of non-HNPCC, FCC patients whose disease has different, as yet unknown, genetic origins.

Refining the Amsterdam Criteria and Bethesda Guidelines: testing algorithms for the prediction of mismatch repair mutation status in the familial cancer clinic.

PURPOSE: Hereditary nonpolyposis colon cancer (HNPCC) is a Mendelian dominant syndrome of bowel, endometrial, and other cancers and results from germline mutations in mismatch repair (MMR) genes. HNPCC is now best diagnosed on molecular grounds using MMR mutation screening, aided by microsatellite instability (MSI) and immunohistochemistry in tumors. Selection of families for molecular investigation of HNPCC is usually based on suboptimal methods (Amsterdam Criteria or Bethesda Guidelines), but these can be improved using additional clinical data (mean ages of affected persons and presence of endometrial cancer) in a quantitative model. METHODS: We have verified the performance of the Wijnen model and have shown that it remains valid when HNPCC is diagnosed using mutation screening, MSI, and immunohistochemistry. We have also set up and verified our own models (Amsterdam-plus and Alternative), which perform at least as well as the Wijnen model. RESULTS: The Amsterdam-plus model improves on the Amsterdam Criteria by using five extra variables (numbers of colorectal and endometrial cancers in the family, number of patients with five or more adenomas, number with more than one primary cancer of the colorectum or endometrium, and mean age of presentation) and performs better than the Wijnen model. The Alternative model avoids the need to evaluate the Amsterdam Criteria and performs nearly as well as the other models. CONCLUSION: We believe that a quantitative model, such as the Amsterdam-plus model, should be the first choice for selecting families or patients for evaluation of HNPCC using molecular tests. We present an algorithm for this process.

Potent anti-inflammatory activities of hydroalcoholic extract from aerial parts of Stachys inflata on rats.

Extracts obtained from aerial parts of Stachys inflata have been used in Iranian folk medicine in infective, rheumatic and other inflammatory disorders. In the present study, the anti-inflammatory properties of total methanol extract isolated from aerial parts of Stachys inflata were investigated in two well-characterised inflammatory models in rats, carrageenan-induced paw oedema and formalin-induced paw licking. Intraperitoneal injection of the extract, 60 min before induction of inflammation, revealed a dose-related inhibition of carrageenan-induced rat paw oedema over the dose range 50-200 mg/kg. In the formalin test, the extract (50, 100 and 200 mg/kg) had no effect against the first phase (0-5 min) of the formalin-induced pain, but all three doses produced a significant blockade of the second phase (P < 0.001). Myeloperoxidase (MPO) activity was determined, and a histopathological study was carried out in paw tissue 4 h after induction of inflammation. The hydroalcoholic extract (200 mg/kg) substantially reduced MPO activity (P < 0.05), which was increased in the control group. Histological examination showed a marked reduction in tissue injury and inhibition in neutrophil infiltration in rats treated with the extract (200 mg/kg).

Hypernatremia in the elderly.

Hypernatremia is common in elderly persons, who may present with signs that are easily overlooked. Prompt diagnosis and appropriate therapy can sometimes lead to a remarkable recovery. To avoid cerebral edema, rehydration must be accomplished gradually over 48 to 72 hours. The recommended replacement for the first 24 hours is approximately 30 percent of the estimated water loss.

Prevalence of high blood pressure in Qashqai Tribe, Southern Iran, 1973.

On the basis cross sectional health and morbidity survey was conducted in 1973, an attempt was made to measure the prevalence of high blood pressure among Qashqai Tribe. Our study showed that hypertension is by no means a rare condition among nomads and it tends to be a little higher in women than in men age group 35 years and over. Our figures showed that the pattern of increase of prevalence of high blood pressure with the increase of age.