Dynamic changes in endoglin expression in the developing mouse heart.

Endoglin (ENG) is essential for cardiovascular development and is expressed in the heart from its earliest developmental stages. ENG expression has been reported in the cardiac crescent, endocardium, valve mesenchyme and coronary vascular endothelial cells. However, its expression in these cell types is non-uniform and the dynamic changes in ENG expression during heart development have not been systematically studied. Using immunofluorescent staining we tracked ENG protein expression in mouse embryonic hearts aged from 11.5 to 17.5 days, and in postnatal and adult hearts. ENG is expressed in the endocardium and in venous endothelial cells throughout these developmental stages. ENG protein is down-regulated by approximately two-fold as a subset of early coronary veins reprogram to form arteries within the developing myocardium from E13.5. This two-fold higher ratio of ENG protein in veins versus arteries is maintained throughout cardiac development and in the adult heart. ENG is also down-regulated two-fold following mesenchymal transition of endocardial cells to form cardiac valve mesenchyme, whilst expression of the pan-endothelial marker CD31 is completely lost. A subset of epicardial cells (which do not express ENG protein) delaminate and undergo a similar mesenchymal transition to form epicardially derived cells (EPDCs). This transient intra-myocardial mesenchymal cell population expresses low levels of ENG protein, similar to valve mesenchyme. In conclusion, ENG shows dynamic changes of expression in vascular endothelial cells, endocardial cells and mesenchymal cells in the developing heart that vary according to cardiovascular cell type.

The incidence of melanoma in South Africa: An exploratory analysis of National Cancer Registry data from 2005 to 2013 with a specific focus on melanoma in black Africans.

BACKGROUND: Melanoma is an aggressive skin cancer with poor survival when diagnosed late. There are important differences in clinical and histological features of melanoma and disease outcomes in people with darker skin types. METHODS: A retrospective review of data captured by the National Cancer Registry (NCR) of South Africa (SA) was performed for 2005 - 2013. Data on patient numbers, demography, location and biological features were analysed for all records. Closer analysis of melanoma of the limbs reported in black Africans was done after manually collecting this information from original reports. RESULTS: With 11 784 invasive melanomas reported to the NCR, the overall incidence of melanoma for SA was 2.7 per 100 000. Males (51%), individuals aged ≥60 years (48%) and the anatomical sites of lower limb (36%) and trunk (27%) were most commonly affected. Melanoma incidences in the white and black populations were 23.2 and 0.5 per 100 000, respectively. Most cases were diagnosed at private pathology laboratories (73%). Superficial spreading melanoma (47%) and nodular melanoma (20%) predominated. Among 878 black Africans diagnosed in the public sector with melanoma of the limbs, females (68%) and individuals aged ≥60 years (61%) were most commonly affected. Lower-limb lesions (91%) and acral lentiginous melanoma (65%) predominated, with 74% of cases affecting the foot and 62% of cases presenting with a Breslow depth >4 mm. CONCLUSIONS: This study provides up-to-date NCR incidence and demographic data on melanoma and highlights the neglected research gaps in relation to melanoma in black Africans to provide evidence needed to address health disparities in overlooked population groups.

Circulating microRNA's as a diagnostic tool for hepatocellular carcinoma in a hyper endemic HIV setting, KwaZulu-Natal, South Africa: a case control study protocol focusing on viral etiology.

BACKGROUND: A wide range of studies has investigated the diagnostic proficiency of extracellular microRNAs (miRNAs) in hepatocellular cancer (HCC). HCC is expected to increase in Sub-Saharan Africa (SSA), due to endemic levels of viral infection (HBV/HIV), ageing and changing lifestyles. This unique aetiological background provides an opportunity for investigating potentially novel circulating miRNAs as biomarkers for HCC in a prospective study in South Africa. METHODS: This study will recruit HCC patients from two South African cancer hospitals, situated in Durban and Pietermaritzburg in the province of KwaZulu-Natal. These cases will include both HBV mono-infected and HBV/HIV co-infected HCC cases. The control group will consist of two (2) age and sex-matched healthy population controls per HCC case randomly selected from a Durban based laboratory. The controls will exclude patients if they have any evidence of chronic liver disease. A standardised reporting approach will be adopted to detect, quantify and normalize the level of circulating miRNAs in the blood sera of HCC cases and their controls. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) will be employed to quantity extracellular miRNAs. Differences in concentration of relevant miRNA by case/control status will be assessed using the Wilcoxon rank-sum (Mann-Whitney U) test. Adjustment for multiple testing (Bonferroni correction), receiver operating curves (ROC) and optimal breakpoint analyses will be employed to identify potential thresholds for the differentiation of miRNA levels of HCC cases and their controls. DISCUSSION: Although there is a growing base of literature regarding the role of circulating miRNAs as biomarkers, this promising field remains a 'work in progress'. The aetiology of HBV infection in HCC is well understood, as well as it's role in miRNA deregulation, however, the mediating role of HIV infection is unknown. HCC incidence in SSA, including South Africa, is expected to increase significantly in the next decade. A combination of factors, therefore, offers a unique opportunity to identify candidate circulating miRNAs as potential biomarkers for HBV/HIV infected HCC.

The management of pretibial lacerations.

Introduction Pretibial lacerations are common injuries, often presenting in the elderly and infirm. Unclear management pathways often result in inappropriate care. We identify patient demographics, morbidity risk factors, injury severity and management options. Materials and methods This retrospective study involved analysing databases and hardcopy notes for patients admitted with pretibial lacerations to Addenbrooke's Hospital, January to December 2012. Microsoft Excel and Fishers exact test were used to analyse the data with a P-value of less than 0.05 representative of statistical significance. Information on patient demographics, site of lesion, preoperative symptoms, management, operative details and clinical outcomes were collected. Results A total of 36 patients were identified; the mean age was 79 years (± 16 years, 1 standard deviation) with a three to two female to male preponderance; 57% of injuries were caused by mechanical fall, 33% traumatic blunt impact and 7% road traffic accidents. American Society of Anesthesiologists physical status classification was 43% level III, 40% II, 9% I and 9% IV. Dunkin classification of severity was 33% grade III, 30% grade I, 24% grade IV and 12% grade II. Median inpatient duration was 11 days for surgically managed compared with 15 days for conservatively managed patients. Discussion Pretibial lacerations tend to affect the elderly. Management is compounded by polypharmacy and comorbidities. If inadequately managed, such injuries can adopt characteristics of chronic wounds, with lengthy inpatient stays. Surgical intervention may be appropriate where injuries are severe and the patient stable enough for theatre. Conclusions We believe that surgical management with autologous tissue repair, with minimal delay between presentation and theatre, is warranted for extensive injuries wherever possible, with conservative management used for predominantly less extensive pretibial lacerations.

Prevalence of gastrointestinal parasitism in small ruminants in western zone of Punjab, India.

AIM: The aim of this study was to explore the prevalence of gastrointestinal parasitism in small ruminants in relation to various risk factors in the western zone of Punjab. MATERIALS AND METHODS: During the study, 603 fecal samples (391 of sheep and 212 of goats) were examined qualitatively by floatation and sedimentation techniques, and quantitatively by McMaster technique. RESULTS: Out of the 603 fecal (391 sheep and 212 goats) samples examined, 501 were found positive for endoparasitic infection with an overall prevalence of 83.08%, consisting of 85.16% and 79.24% in sheep and goats, respectively. Egg per gram in sheep was apparently more 1441.88±77.72 than goats 1168.57±78.31. The associated risk factors with the prevalence of gastrointestinal tract (GIT) parasites showed that females (85.97%) were significantly more susceptible than males (69.23%). Age wise the adults (>6 months) were significantly more prone to parasitic infection as compared to young ones (<6 months). Seasonal variation was recorded throughout the year and was significantly highest during monsoon (90.10%), followed by winter (83.84%) and summer (78.35%). CONCLUSION: The study revealed an overall prevalence of 83.08% of GIT parasitic infections in small ruminants constituting 85.16% in sheep and 79.24% in goats in the western zone of Punjab. The most relevant risk factors for the prevalence of gastrointestinal parasitism in ruminants were sex, age, and season.

Breast cancer trends differ by ethnicity: a report from the South African National Cancer Registry (1994-2009).

Background: To describe breast cancer (BC) incidence and mortality by ethnicity in South Africa (SA). Methods: Sources of data included the South African National Cancer Registry (NCR) pathology-based reports (1994­2009) and Statistics South Africa (SSA) mortality data (1997­2009). Numbers of cases, age-standardised incidence rates (ASIR) and lifetime risk (LR) were extracted from the NCR database for 1994­2009. Age-specific incidence rates were calculated for five-year age categories. The direct method of standardisation was employed to calculate age-standardised mortality rates (ASMR) using mortality data. Results: Between 1994 and 2009, there were 85 561 female BC. For the Black, Coloured and Asian groups, increases in ASIR and LR were observed between 1994 and 2009. In 2009, the ASIR for the total population, Blacks, Whites, Coloureds and Asians were 26.9, 18.7, 50.2, 40.9 and 51.2 per 100 000, respectively. For Asians, an increase in proportion of BC as a percentage of all female cancers was observed between 1994 and 2002 (11.1%) and continued to increase to 2009 (a further 4.5%). Whites and Asians presented higher incidences of BC at earlier ages compared with Blacks and Coloureds in 2009. In 1998, there were 1618 BC deaths in SA compared with 2784 deaths in 2009. ASMR between 1997 and 2004 increased but stabilised thereafter. Conclusion: This paper demonstrated that SA BC incidence rates are similar to other countries in the region, but lower than other countries with similar health systems. Ethnic differences in BC trends were observed. However, the reasons for observed ethnic differences are unclear.

Fuel wood properties of some oak tree species of Manipur, India.

Five indigenous oak tree species, i.e., Castanopsis indica (Roxb. ex Lindl.) A.DC., Lithocarpus fenestratus (Roxb.) Rehder, Lithocarpus pachyphyllus (Kurz) Rehder, Lithocarpus polystachyus (Wall. ex A.DC.) Rehder and Quercus serrata Murray were estimated for their wood properties such as calorific value, density, moisture content and ash content from a sub-tropical forest of Haraothel hill, Senapati District, Manipur. Wood biomass components were found to have higher calorific value (kJ g(-)) than bark components. The calorific values for tree species were found highest in L. pachyphyllus (17.99 kJ g(-1)) followed by C. indica (17.98 kJ g1), L. fenestratus (17.96 kJ g"), L. polystachyus (17.80 kJ g(-1)) and Q. serrata (17.49 kJ g(-1)). Calorific values for bole bark, bole wood and branch bark were found significantly different (F > 3.48 at p = 0.05) in five oak tree species. Percentage of ash on dry weight basis was found to be highest in Q. serrata (4.73%) and lowest in C. indica (2.19%). Ash content of tree components gives a singnificant factor in determining fuelwood value index (FVI). Of all the five oak tree species, Q. serrata exhibited highest value of wood density (0.78 g cm-) and lowest was observed in C. indica (0.63 g cm(-3)). There was significant correlation between wood density (p<0.05), ash content (p<0.01) with calorific value in oak tree species. Fuelwood value index (FVI) was in the following order: C. indica (1109.70) > L. pachyphyllus (898.41)> L. polystachyus (879.02)> L. fenestratus (824.61)> Q. serrata (792.50). Thus, the present study suggests that C. indica may be considered as a fuelwood oak tree species in Manipur.

South African National Cancer Registry: Effect of withheld data from private health systems on cancer incidence estimates.

BACKGROUND: The National Cancer Registry (NCR) was established as a pathology-based cancer reporting system. From 2005 to 2007, private health laboratories withheld cancer reports owing to concerns regarding voluntary sharing of patient data. OBJECTIVES: To estimate the impact of under-reported cancer data from private health laboratories. METHODS: A linear regression analysis was conducted to project expected cancer cases for 2005-2007. Differences between actual and projected figures were calculated to estimate percentage under-reporting. RESULTS: The projected NCR case total varied from 53,407 (3.8% net increase from actual cases reported) in 2005 to 54,823 (3.7% net increase) in 2007. The projected number of reported cases from private laboratories in 2005 was 26,359 (19.7% net increase from actual cases reported), 27,012 (18.8% net increase) in 2006 and 27,666 (28.4% net increase) in 2007. CONCLUSION: While private healthcare reporting decreased by 28% from 2005 to 2007, this represented a minimal impact on overall cancer reporting (net decrease of <4%).

Swallowing activity assessed by ambulatory impedance-pH monitoring predicts awake and asleep periods at night.

INTRODUCTION: Voluntary muscle activity, including swallowing, decreases during the night. The association between nocturnal awakenings and swallowing activity is under-researched with limited information on the frequency of swallows during awake and asleep periods. AIM: The aim of this study was to assess nocturnal swallowing activity and identify a cut-off predicting awake and asleep periods. METHODS: Patients undergoing impedance-pH monitoring as part of GERD work-up were asked to wear a wrist activity detecting device (Actigraph(®)) at night. Swallowing activity was quantified by analysing impedance changes in the proximal esophagus. Awake and asleep periods were determined using a validated scoring system (Sadeh algorithm). Receiver operating characteristics (ROC) analyses were performed to determine sensitivity, specificity and accuracy of swallowing frequency to identify awake and asleep periods. RESULTS: Data from 76 patients (28 male, 48 female; mean age 56 ± 15 years) were included in the analysis. The ROC analysis found that 0.33 sw/min (i.e. one swallow every 3 min) had the optimal sensitivity (78 %) and specificity (76 %) to differentiate awake from asleep periods. A swallowing frequency of 0.25 sw/min (i.e. one swallow every 4 min) was 93 % sensitive and 57 % specific to identify awake periods. A swallowing frequency of 1 sw/min was 20 % sensitive but 96 % specific in identifying awake periods. Impedance-pH monitoring detects differences in swallowing activity during awake and asleep periods. Swallowing frequency noticed during ambulatory impedance-pH monitoring can predict the state of consciousness during nocturnal periods.

Twice-daily proton pump inhibitor therapy does not decrease the frequency of reflux episodes during nocturnal recumbency in patients with refractory GERD: analysis of 200 patients using multichannel intraluminal impedance-pH testing.

Over half of patients with gastroesophageal reflux disease (GERD) report nocturnal symptoms. Proton pump inhibitors (PPIs) are the main medications used to treat GERD. Multichannel intraluminal impedance with pH (MII-pH) monitoring is the most sensitive method for detection and characterization of GERD. The aim of this study was to assess and compare reflux frequency in patients with refractory GERD symptoms on and off PPI therapy during the nocturnal recumbent period, as assessed by MII-pH testing. We analyzed 24-hour MII-pH studies performed in 200 patients monitored either on twice-daily (n = 100) or off (n = 100) PPI therapy. Demographic analysis of the on-therapy group revealed a mean age of 52 years (24-78 years) with 37% males, and the off-therapy group revealed a mean age of 49 years (18-84 years) with 40% males. All studies were interpreted to assess and characterize the number of acid and nonacid reflux episodes in the nocturnal recumbent period identified by each patient on an overnight recorder (Zephyr, Sandhill Scientific, Inc., Highlands Ranch, CO, USA). The nocturnal recumbent period was the period documented by patients during which they lie in the recumbent period at night to sleep with average periods lasting 456 and 453 minutes for patients on and off PPI therapy. There were more mean recumbent reflux episodes in the on-therapy group in comparison with the off-therapy group (3.76 mean reflux episodes [mre] per patient in the recumbent vs. 2.82 mre); the difference was not statistically significant (P = 0.187). When the reflux events are classified into acid and non-acid reflux episodes, the relative occurrence of acid reflux events is less in the on-therapy group (P = 0.047), while the off-therapy group have fewer nonacid reflux episodes (P = 0.003). PPIs decrease the acidity of esophageal refluxate but do not decrease the relative frequency of reflux episodes in the recumbent position in patients with refractory GERD despite twice-a-day treatment with PPI therapy. The explanation for the finding of numerically increased, although not statistically significant, amount of reflux episodes in the PPI treatment group in this study, and previous studies is unclear and warrants further evaluation.

Effects of elevated ozone on photosynthesis and stomatal conductance of two soybean varieties: a case study to assess impacts of one component of predicted global climate change.

Global climatic change scenarios predict a significant increase in future tropospheric ozone (O(3)) concentrations. The present investigation was done to assess the effects of elevated O(3) (70 and 100 ppb) on electron transport, carbon fixation, stomatal conductance and pigment concentrations in two tropical soybean (Glycine max L.) varieties, PK 472 and Bragg. Plants were exposed to O(3) for 4 h.day(-1) from 10:00 to 14:00 from germination to maturity. Photosynthesis of both varieties were adversely affected, but the reduction was higher in PK 472 than Bragg. A comparison of chlorophyll a fluorescence kinetics with carbon fixation suggested greater sensitivity of dark reactions than light reactions of photosynthesis to O(3) stress. The O(3)-induced uncoupling between photosynthesis and stomatal conductance in PK 472 suggests the reduction in photosynthesis may be attributed to a factor other than reduced stomatal conductance. An increase in internal CO(2) concentration in both O(3)-treated soybean varieties compared suggests that the reduction in photosynthesis was due to damage to the photosynthetic apparatus, leading to accumulation of internal CO(2) and stomatal closure. The adverse impact of O(3) stress increased at higher O(3) concentrations in both soybean varieties leading to large reductions in photosynthesis. This study suggests that O(3)-induced reductions in photosynthesis in tropical and temperate varieties are similar.

A study of knowledge about malaria and treatment seeking behaviour in two tribal communities of Manipur.

The study was conducted on a sample of 250 tribal people of Manipur state, comprised of 125 from the urban valley population and 125 persons from rural tribals settled on hilly area at a higher altitude. The finding shows that knowledge regarding transmission of malaria, self protection and treatment seeking behaviour is still poor among the tribal communities of Manipur. However the urban tribals had better knowledge regarding diagnosis of malaria and prevention of mosquito breeding than their rural counterparts.

Variability in serotonin and enterochromaffin cells in patients with colonic inertia and idiopathic diarrhoea as compared to normal controls.

AIM: To evaluate differences in distribution, density and staining intensity of enterochromaffin cells (EC) and serotonin cells (SC) in the colonic mucosa of patients with colonic inertia (CI), idiopathic diarrhoea (ID) and a control group. METHODS: Three groups were studied: 19 patients' colons after subtotal colectomy for CI, and 17 patients' biopsies for diarrhoea (>3 bowel movements/day) with histological findings of normal mucosa (excluding microscopic, eosinophillic and collagenous colitis). The third group included 15 patients who underwent colonoscopy and biopsy for indications other than constipation, inflammatory bowel disease, diarrhoea or neoplasm (control group). Specimen blocks were obtained in each case from the right and left colon. Immunohistochemical staining for EC and SC were done on 4 micro m sections from Hollandes fixed, paraffin embedded tissues with primary rabbit antibody against chromagranin A or serotonin, and biotynylated secondary antibody and enzyme labelled streptavidin. RESULTS: The number of EC in the mucosa of the left colon in patients with CI (16.8 +/- 10.2) and ID (19.9 +/- 9.7) were significantly higher than they were on the right side (CI: 9.4 +/- 6.0, ID: 12.1 +/- 5.3). However, there were no significant differences between the left and right sides in the control group (L: 10.3 +/- 5.3; R: 13.4 +/- 7.6). Although the quantity of EC in the left colon in both patients with CI (P < 0.05) and ID (P < 0.01) were significantly higher than in the controls, there was no significant difference between CI and ID. In both the right and left colon, the percentage of EC with low positive density was significantly higher (P < 0.01) while those cells with moderate or low staining intensity were significantly lower in patients with CI than in either patients with ID or control group. In patients with CI, the quantity of SC in the mucosa of the left colon (12.1 +/- 6.4) was higher than in the right (CI: 7.9 +/- 3.6; control 4.6 +/- 3.3; ID 4.6 +/- 2.9) (P = 0.0057). In contrast there was no significant difference in SC in either the ID or control groups. The quantity of SC in both sides of the colon was significantly higher both in patients with CI as compared to the control group (P < 0.01) and patients with CI vs. patients with ID (L = P < 0.01; R = P < 0.05). There was a significantly positive correlation between the numbers of EC and SC in patients with CI (L: r = 0.5425, P < 0.05; R: r = 0.745, P < 0.01). CONCLUSION: In patients with CI, EC increases possibly due to an increase in SC. Conversely, in patients with ID, the EC increase results from peptides other than SC. Our results suggest that different aetiological factors contribute to ID and CI.

Conservative management of delayed suprapubic abscess after laparoscopic Burch colposuspension using nonabsorbable polypropylene mesh.

To our knowledge, abscess formation after laparoscopic Burch colposuspension using permanent surgical mesh has not been previously reported. In our patient a suprapubic abscess was identified 4 weeks after the procedure in which polypropylene mesh was used. Conservative management involving drainage under computerized tomographic guidance and antibiotic therapy resulted in complete resolution without necessitating removal of the mesh. (J Am Assoc Gynecol Laparosc 6(2):225-228, 1999)

Tophaceous gout of the thoracic spine presenting as back pain and fever.

Spinal gout has been reported only rarely. We describe a 59-year-old man with a history of gout, who was receiving chronic immunosuppressive therapy after a renal transplant and who presented with fever and back pain. After an extensive work-up and biopsy, the diagnosis was thoracic tophaceous gout. The pain and fever responded to prednisone and allopurinol. Tophaceous gout is a rare cause of fever and back pain but should be considered in the differential diagnosis in the appropriate clinical setting.

Embryo transfer as a means of controlling the transmission of viral infections. XV. Failure to transmit bluetongue virus through the transfer of embryos from viremic sheep donors.

The first experiment involved in vitro exposure of clean embryos to bluetongue virus (BTV) while three subsequent experiments involved the collection of embryos from BTV-infected donor ewes and their transfer to disease-free recipients. In Experiment I, 22 embryos/ova were exposed to BTV type 11 (BTV-11) for 1 h, washed 10 times in PBS and assayed in pairs for BTV. All 11 samples were positive for BTV in the 11-d-old embryonated chicken egg (ECE) assay system and 5/11 samples were positive in baby hamster kidney-21 (BHK-21) cells. In Experiment II, 5 donors were infected with BTV type 10 (BTV-10). All embryos were washed 10 times prior to assay or transfer. Thirty-three embryos/ova were assayed in groups of 2 or 3 and none yielded virus in ECE. Two BTV-seronegative recipients each received 6 embryos and a total of 3 lambs free of BTV antibodies were delivered. In Experiments III and IV, a total of 9 donors were infected with BTV-11. All embryos were washed 10 times prior to assay or transfer. Seventy-four embryos/ova were assayed in groups of 2 or 3 and none yielded virus in ECE, while for each experiment, 6 embryos were transferred into 2 BTV-seronegative recipients. The four recipients and their 3 lambs and 2 aborted fetuses were also seronegative for BTV.