Post-discharge mortality among patients hospitalised with severe acute respiratory infection, Bangladesh, 2012-2019: a prospective observational study.

Background: Enhancing outcomes post-hospitalisation requires an understanding of predictive factors for adverse events. This study aimed to estimate post-discharge mortality rates among patients with severe acute respiratory infection (SARI) in Bangladesh, identify associated factors, and document reported causes of death. Methods: From January 2012 to December 2019, we conducted follow-up calls to patients or their families 30 days after discharge to assess the status of patients with SARI. Proportions of deaths within 30 days of discharge were estimated, and a comparative analysis of demographics, clinical characteristics, and influenza illness between decedents and survivors was performed using multivariable Cox regression models. Findings: Among 23,360 patients with SARI (median age: 20 years, IQR: 1.5-48, 65% male), 351 (1.5%) died during hospitalisation. Of 23,009 patients alive at discharge, 20,044 (87%) were followed, with 633 (3.2%) deaths within 30 days of discharge. In children (<18 years), difficulty breathing (adjusted hazard ratio [aHR] 1.8; 95% CI 1.1-3.0), longer hospital stay (aHR 1.1; 95% CI 1.1-1.1), and heart diseases (aHR 8.5; 95% CI 3.2-23.1) were associated with higher post-discharge death risk. Among adults (≥18 years), difficulty breathing (aHR 2.3; 95% CI 1.7-3.0), chronic obstructive pulmonary disease (aHR 1.7; 95% CI 1.4-2.2), and intensive care unit admission (aHR 5.2; 95% CI 1.9-14.0) were linked to elevated post-discharge death risk. Influenza virus was detected in 13% (46/351) of in-hospital SARI deaths and 10% (65/633) of post-discharge SARI deaths. Interpretation: Nearly one in twenty patients with SARI died during hospitalisation or within 1 month of discharge, with two-thirds of deaths occurring post-discharge. Seasonal influenza vaccination is recommended to mitigate influenza-associated mortality. To enhance post-discharge outcomes, hospitals should consider developing safe-discharge algorithms, reinforcing post-discharge care plans, and establishing outpatient monitoring for recently discharged patients. Funding: Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA [U01GH002259].

Oral cholera vaccine coverage evaluation survey: Forcibly Displaced Myanmar Nationals and host community in Cox's Bazar, Bangladesh.

Introduction: Cholera remains a significant public health concern in many parts of the world, particularly in areas with poor sanitation and hygiene. Bangladesh and other impoverished nations have been severely affected by cholera outbreaks, especially in areas with a high population density. In order to mitigate the spread of cholera, oral cholera vaccines (OCVs) are recommended as a prophylactic measure. In May 2018, 775,666 of the Forcibly Displaced Myanmar Nationals (FDMN) in the registered and makeshift camps and 103,605 of the residents in the host community received two doses of OCV ShancholTM in Cox's Bazar, Bangladesh, because the conditions in the area favored the transmission of cholera and other waterborne diseases. This study aimed to assess the coverage of OCV among the FDMN and the host community in Cox's Bazar. Methods: In August 2018, we enrolled 4,240 respondents for this study following the "World Health Organization (WHO) Vaccination Coverage Cluster Surveys: Reference Manual (2018)." The coverage survey was conducted with three strata of the population: the host community from the Teknaf Upazila, the registered camp, and the makeshift camp from the Ukhia Upazila. We collected information regarding OCV coverage, demographic characteristics, and knowledge and behaviors of people toward the vaccine. The data were analyzed using descriptive statistics. Results: According to our study, the overall OCV coverage was 85%, with 68% in the host community, 91% in the registered camp, and 98% in the makeshift camp. The lower coverage in the host community was due to residents unaware of the vaccination campaign, the unavailability of vaccines, and unaware where to go for vaccination. Discussion: Our findings demonstrate that the OCV campaign in the FDMN camps was successful, reaching over 90% coverage, while coverage in the host community was much lower. In order to make sure that OCV vaccination efforts are reaching the target population and having the desired impact, our study emphasizes the need to inform the target population of when and where to get vaccinated.

Recent Progress, Challenges, and Opportunities of Membrane Distillation for Heavy Metals Removal.

Water is essential for the presence of life on this earth. However, water contamination due to the presence of heavy/toxic metals is one of the serious environmental issues for living beings. Several methods have been devoted to separating or removing those heavy metals from wastewater. Among them, membrane distillation (MD) has become one of the most attractive approaches due to its higher rejection rate than processes driven by pressure, lower energy consumption than traditional distillation processes. MD has gained significant attention for removing heavy metals than other techniques like ion exchange and adsorption in the last two decades. This review provides insight knowledge to the reader and focuses on how heavy metals impact humans and the environment, sources of heavy metals, current and especially removal methods using the MD method. Moreover, recent studies, challenges, and opportunities on MD membrane modules and heavy metal removal systems are discussed. More importantly, in this review, we have identified the gaps and opportunities that are required for enhancing the MD approach and its practical suitability for heavy metal removals. MD module and system showed high performance, proving their possible applications to remove heavy metal ions in water/wastewater treatment.

Acute Watery Diarrhea Surveillance During the Rohingya Crisis 2017-2019 in Cox's Bazar, Bangladesh.

BACKGROUND: Forcibly Displaced Myanmar Nationals (FDMNs) fled into Cox's Bazar, Bangladesh due to internal conflict. Considering the public health situation, a surveillance network was established to identify the enteric pathogens and early detection of cholera epidemics. The purpose of this manuscript is to report the clinical, epidemiological determinants of cholera and other enteric pathogens among hospitalized diarrheal patients from FDMNs and host community. METHODS: A total of 11 sentinel surveillance sites were established around the camps in Ukhia and Teknaf Upazila, Cox's Bazar. Rapid diagnostic testing was conducted for immediate detection of cholera cases. Stool samples were transferred to the Infectious Diseases Division, International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b) laboratory for culture. RESULTS: A total of 8134 participants with diarrhea were enrolled from 2017 to 2019: 4881 were FDMNs and 3253 were from the Bangladeshi host community. Among the FDMNs, the proportion of Vibrio cholerae was 0.7%, the proportion of enterotoxigenic Escherichia coli (ETEC) was 4.9%, and the proportion of Shigella was 1.5%. The distributions from host community were 1.2% V cholerae, 1.8% ETEC, and 1.1% Shigella. Similar risk factors have been identified for the diarrheal pathogens for both communities. CONCLUSIONS: This surveillance helped to monitor the situation of diarrheal diseases including cholera in refugee camps as well as in the neighboring host community. These findings lead policymakers to take immediate preventive measures.

No Serological Evidence of Trachoma or Yaws Among Residents of Registered Camps and Makeshift Settlements in Cox's Bazar, Bangladesh.

Successful achievement of global targets for elimination of trachoma as a public health problem and eradication of yaws will require control efforts to reach marginalized populations, including refugees. Testing for serologic evidence of transmission of trachoma and yaws in residents of registered camps and a Makeshift Settlement in Cox's Bazar District, Bangladesh, was added to a serosurvey for vaccine-preventable diseases (VPDs) conducted April-May 2018. The survey was primarily designed to estimate remaining immunity gaps for VPDs, including diphtheria, measles, rubella, and polio. Blood specimens from 1- to 14-year-olds from selected households were collected and tested for antibody responses against antigens from Treponema pallidum and Chlamydia trachomatis using a multiplex bead assay to evaluate for serologic evidence of the neglected tropical diseases (NTDs) yaws and trachoma, respectively. The prevalence of antibodies against two C. trachomatis antigens in children ranged from 1.4% to 1.5% for Pgp3 and 2.8% to 7.0% for CT694. The prevalence of antibody responses against both of two treponemal antigens (recombinant protein17 and treponemal membrane protein A) tested was 0% to 0.15% in two camps. The data are suggestive of very low or no transmission of trachoma and yaws, currently or previously, in children resident in these communities. This study illustrates how integrated serologic testing can provide needed data to help NTD programs prioritize limited resources.

Vaccination coverage survey and seroprevalence among forcibly displaced Rohingya children, Cox's Bazar, Bangladesh, 2018: A cross-sectional study.

BACKGROUND: During August 2017-January 2018, more than 700,000 forcibly displaced Rohingyas crossed into Cox's Bazar, Bangladesh. In response to measles and diphtheria cases, first documented in September and November 2017, respectively, vaccination campaigns targeting children <15 years old were mobilized during September 2017-March 2018. However, in a rapidly evolving emergency situation, poor sanitation, malnutrition, overcrowding, and lack of access to safe water and healthcare can increase susceptibility to infectious diseases, particularly among children. We aimed to estimate population immunity to vaccine-preventable diseases (VPDs) after vaccination activities in the camps to identify any remaining immunity gaps among Rohingya children. METHODS AND FINDINGS: We conducted a cross-sectional serologic and vaccination coverage survey in Nayapara Registered Refugee Camp ("Nayapara") and makeshift settlements (MSs) April 28, 2018 to May 31, 2018, among 930 children aged 6 months to 14 years. MSs are informal, self-settled areas with a population of more than 850,000, the majority of whom arrived after August 2017, whereas Nayapara is a registered camp and has better infrastructure than MSs, including provision of routine immunization services. Households were identified using simple random sampling (SRS) in Nayapara and multistage cluster sampling in MSs (because household lists were unavailable). Dried blood spots (DBSs) were collected to estimate seroprotection against measles, rubella, diphtheria, and tetanus, using Luminex multiplex bead assay (MBA). Caregiver interviews assessed vaccination campaign participation using vaccination card or recall. In Nayapara, 273 children aged 1 to 6 years participated; 46% were female and 88% were registered refugees. In MSs, 358 children aged 1 to 6 years and 299 children aged 7 to 14 years participated; 48% of all children in MSs were female, and none were registered refugees. In Nayapara, estimated seroprotection among 1- to 6-year-olds was high for measles, rubella, diphtheria, and tetanus (91%-98%; 95% confidence interval [CI] 87%-99%); children >6 years were not assessed. In MSs, measles seroprotection was similarly high among 1- to 6-year-olds and 7- to 14-year-olds (91% [95% CI 86%-94%] and 99% [95% CI 96%-100%], respectively, p < 0.001). Rubella and diphtheria seroprotection in MSs were significantly lower among 1- to 6-year-olds (84% [95% CI 79%-88%] and 63% [95% CI 56%-70%]) compared to 7- to 14-year-olds (96% [95% CI 90%-98%] and 77% [95% CI 69%-84%]) (p < 0.001). Tetanus seroprevalence was similar among 1- to 6-year-olds and 7- to 14-year-olds (76% [95% CI 69%-81%] and 84% [95% CI 77%-89%], respectively; p = 0.07). Vaccination campaign coverage was consistent with seroprotection in both camps. However, nonresponse, the main limitation of the study, may have biased the seroprotection and campaign coverage results. CONCLUSIONS: In this study, we observed that despite multiple vaccination campaigns, immunity gaps exist among children in MSs, particularly for diphtheria, which requires serial vaccinations to achieve maximum protection. Therefore, an additional tetanus-diphtheria campaign may be warranted in MSs to address these remaining immunity gaps. Rapid scale-up and strengthening of routine immunization services to reach children and to deliver missed doses to older children is also critically needed to close immunity gaps and prevent future outbreaks.

Screening for malaria antigen and anti-malarial IgG antibody in forcibly-displaced Myanmar nationals: Cox's Bazar district, Bangladesh, 2018.

BACKGROUND: Several refugee settlements in Bangladesh have provided housing and medical care for the forcibly-displaced Myanmar nationals (FDMN, also known as Rohingya) population. The identification of malaria infection status in the refugee settlements is useful in treating infected persons and in developing malaria prevention recommendations. Assays for Plasmodium antigens and human IgG against Plasmodium parasites can be used as indicators to determine malaria infection status and exposure. METHODS: Dried blood spot (DBS) samples (N = 1239) from a household survey performed April-May 2018 in three settlements in Cox's Bazar district, Bangladesh were utilized for a sample population of children from ages 1-14 years of age. The samples were tested using a bead-based multiplex antigen assay for presence of the pan-Plasmodium antigen aldolase as well as Plasmodium falciparum histidine rich protein 2 (HRP2). A bead-based multiplex assay was also used to measure human IgG antibody response to P. falciparum, Plasmodium malariae, and Plasmodium vivax merozoite surface protein 1 antigen (MSP1) isoforms, and P. falciparum antigens LSA1, CSP, and GLURP-R0. RESULTS: There were no detectable Plasmodium antigens in any samples, suggesting no active malaria parasite infections in the tested children. IgG seroprevalence was highest to P. vivax (3.1%), but this was not significantly different from the percentages of children antibody responses to P. falciparum (2.1%) and P. malariae (1.8%). The likelihood of an anti-Plasmodium IgG response increased with age for all three malaria species. Evidence of exposure to any malaria species was highest for children residing 8-10 months in the settlements, and was lower for children arriving before and after this period of time. CONCLUSIONS: Absence of Plasmodium antigen in this population provides evidence that children in these three Bangladeshi refugee settlements did not have malaria at time of sampling. Higher rates of anti-malarial IgG carriage from children who were leaving Myanmar during the malaria high-transmission season indicate these migrant populations were likely at increased risk of malaria exposure during their transit.

Hepatitis E as a cause of adult hospitalization in Bangladesh: Results from an acute jaundice surveillance study in six tertiary hospitals, 2014-2017.

In the absence of reliable data on the burden of hepatitis E virus (HEV) in high endemic countries, we established a hospital-based acute jaundice surveillance program in six tertiary hospitals in Bangladesh to estimate the burden of HEV infection among hospitalized acute jaundice patients aged ≥14 years, identify seasonal and geographic patterns in the prevalence of hepatitis E, and examine factors associated with death. We collected blood specimens from enrolled acute jaundice patients, defined as new onset of either yellow eyes or skin during the past three months of hospital admission, and tested for immunoglobulin M (IgM) antibodies against HEV, HBV and HAV. The enrolled patients were followed up three months after hospital discharge to assess their survival status; pregnant women were followed up three months after their delivery to assess pregnancy outcomes. From December'2014 to September'2017, 1925 patients with acute jaundice were enrolled; 661 (34%) had acute hepatitis E, 48 (8%) had hepatitis A, and 293 (15%) had acute hepatitis B infection. Case fatality among hepatitis E patients was 5% (28/589). Most of the hepatitis E cases were males (74%; 486/661), but case fatality was higher among females-12% (8/68) among pregnant and 8% (7/91) among non-pregnant women. Half of the patients who died with acute hepatitis E had co-infection with HAV or HBV. Of the 62 HEV infected mothers who were alive until the delivery, 9 (15%) had miscarriage/stillbirth, and of those children who were born alive, 19% (10/53) died, all within one week of birth. This study confirms that hepatitis E is the leading cause of acute jaundice, leads to hospitalizations in all regions in Bangladesh, occurs throughout the year, and is associated with considerable morbidity and mortality. Effective control measures should be taken to reduce the risk of HEV infections including improvements in water quality, sanitation and hygiene practices and the introduction of HEV vaccine to high-risk groups.

Genome-wide scan reveals divergent selection among taurine and zebu cattle populations from different regions.

In this study, to identify genomic signatures of divergent selection, we genotyped 10 cattle breeds/populations (n = 275), representing eight Ethiopian cattle populations (n = 229) and two zebu populations (n = 46) adapted to tropical and sub-tropical environments, using the high-density single-nucleotide polymorphisms (SNPs) derived mainly from Bos indicus breeds, and using five reference taurine breeds (n = 212). Population genetic differentiation (FST ) values across sliding windows were estimated between zebu and reference combined taurine breeds. The most differentiated regions (FST  ≥ 0.53), representing the top 1% smoothed FST values, were considered to represent regions under diversifying selection. In total, 285 and 317 genes were identified in the comparisons of Ethiopian cattle with taurine and Asian zebu with taurine respectively. Some of these genes are involved in stress responses/thermo-tolerance and DNA damage repair (HSPA4, HSF1, CMPK1 and EIF2AK4), pigmentation (ERBB3 and MYO1A), reproduction/fertility (UBE2D3, ID3 and PSPC1), immune response (PIK3CD and AKIRIN2) and body stature and size (MBP2, LYN and NPM1). Additionally, the candidate genes were associated with functional terms (e.g. cellular response to stress, DNA repair, inflammatory response) important for physiological adaptation to environmental stresses. The results of our study may shed light on the influence of artificial and natural selection in shaping the genomic diversity of modern cattle breeds and also may serve as a basis for further genetic investigation of traits of tropical adaptation in cattle.

Economic costs of hospitalized diarrheal disease in Bangladesh: a societal perspective.

BACKGROUND: Diarrheal diseases are a major threat to human health and still represent a leading cause of morbidity and mortality worldwide. Although the burden of the diarrheal diseases is much lower in developed countries, it is a significant public health problem in low and middle-income countries like Bangladesh. Though diarrhea is preventable and managed with low-cost interventions, it is still the leading cause of morbidity according to the patient who sought care from public hospitals in Bangladesh indicating that significant resources are consumed in treating those patients. The aim of the study is to capture the inpatients and outpatient treatment cost of diarrheal disease and to measure the cost burden and coping mechanisms associated with diarrheal illness. METHODS: This study was conducted in six randomly selected district hospitals from six divisions (larger administrative units) in Bangladesh. The study was performed from the societal perspective which means all types of costs were identified, measured and valued no matter who incurred them. Cost analysis was estimated using the guideline proposed by the World Health Organization for estimating the economic burden of diarrheal diseases. The study adopted quantitative techniques to collect the household and hospital level data including structured and semi-structured questionnaires, observation checklists, analysis of hospital database, telephone interviews and compilation of service statistics. RESULTS: The average total societal cost of illness per episode was BDT 5274.02 (US $ 67.18) whereas the average inpatient and outpatient costs were BDT 8675.09 (US $ 110.51) and BDT 1853.96 (US $ 23.62) respectively. The cost burden was significantly highest for poorest households, 21.45% of household income, compared to 4.21% of the richest quintile. CONCLUSIONS: Diarrheal diseases continue to be an overwhelming problem in Bangladesh. The economic impact of any public health interventions (either preventive or promotive) that can reduce the prevalence of diarrheal diseases can be estimated from the data generated from this study.

Computed tomography findings of bowel wall thickening: its significance and relationship to endoscopic abnormalities.

INTRODUCTION: The aim of this study was to conduct retrospective analysis of abdominopelvic computed tomography (CT) reports, identifying those patients in whom bowel wall thickening (BWT) was observed, and to correlate these reports with subsequent endoscopic evaluation. METHODS: Formal reports for all patients undergoing abdominopelvic CT between February 2007 and September 2009 were reviewed. Where patients were identified as having colorectal 'wall thickening', results of subsequent endoscopic evaluations were documented. Only those patients with a report of BWT who had follow-up endoscopy (colonoscopy, sigmoidoscopy) were included in the analysis. RESULTS: A total of 165 patients were included. Abnormalities on endoscopy at the exact site of the BWT on CT were found in 95 patients (57.58%); in 36 cases (21.82%) this was a malignant lesion. BWT of the transverse colon was significantly more likely to correspond to an endoscopic finding of cancer than other sites (p=0.034). Rectal bleeding was reported significantly more often in patients with BWT and neoplastic disease on endoscopy compared with those with normal endoscopy (p=0.04). Excluding patients with inflammatory/diverticular lesions, 59.02% of Caucasians had a neoplastic lesion at the site of reported BWT, significantly higher than the other ethnic groups (p=0.008). There were 38 patients (23.03%) who did not present with bowel symptoms and, of these, 6 were diagnosed subsequently with colorectal cancer. CONCLUSIONS: This study supports endoscopic evaluation to investigate patients with CT evidence of BWT, especially in cases involving the transverse colon, in Caucasian patients or in association with symptoms of rectal bleeding.

Meta-analysis of randomized controlled trials comparing lightweight and heavyweight mesh for Lichtenstein inguinal hernia repair.

PURPOSE: Lichtenstein inguinal hernia repair is associated with a low incidence of recurrence; however, the use of heavyweight mesh has been linked with chronic pain and foreign body sensation. It is hypothesized that the use of lightweight mesh may reduce these problems. This study aims to use meta-analysis to compare lightweight and heavyweight mesh for Lichtenstein inguinal hernia repair. METHODS: Information was gathered from randomized controlled trials that compared lightweight and heavyweight mesh for Lichtenstein inguinal hernia repair. The Cochrane Library, Medline, EMBASE, trial registries, conference proceedings and reference lists were searched. Primary outcome measures were chronic pain, foreign body sensation and hernia recurrence. Secondary outcome measures were duration of surgery, mean visual analogue scale (VAS) pain scores, surgical-site infection, testicular atrophy and haematoma/seroma. The pooled Peto odds ratio (OR) was calculated for categorical data and weighted mean difference (WMD) for continuous data. RESULTS: Six trials with 1936 hernias were included. Lightweight mesh was associated with reduced chronic pain (OR = 0.67, 95% CI = 0.50-0.90; p < 0.01) and foreign body sensation (OR = 0.43, 95% CI = 0.21-0.93; p < 0.05). Lightweight mesh was also associated with lower VAS pain scores at 3 months after surgery (WMD = -0.35, 95% CI = -0.39 to -0.31; p < 0.0001). There were no differences in hernia recurrence (OR = 1.19, 95% CI = 0.54-2.64; p = 0.66) or other post-operative complications between the two groups. CONCLUSIONS: The use of lightweight mesh in Lichtenstein inguinal hernia repair is associated with less chronic pain, and foreign body sensation compared with heavyweight mesh without any difference in recurrence.

The role of ultrasound scan in the diagnosis of occult inguinal hernias.

AIMS: The aim of this study is to examine the role of ultrasound in conjunction with clinical judgment in diagnosing occult inguinal hernias in patients with groin pain. METHODS: The study involved a retrospective analysis of 297 patients who presented over an 18 month period from January 2007 to August 2008. All the patients presented to outpatient clinic with groin pain but a normal or equivocal clinical examination. Data was obtained from hospital records, radiology system and operation notes. RESULTS: 167 examinations (56%) were positive for a hernia, as a result of which 116 patients underwent surgery. At surgery, a hernia was found in 85 cases and no hernia was found in 31 cases. 130 examinations (44%) were negative for hernia. Six patients proceeded to surgery despite a negative ultrasound due to ongoing pain and a hernia was found in 5 cases. Overall, correlation with surgical findings showed ultrasound to have a sensitivity of 94%. Ultrasound used with clinical judgment has a positive predictive value of 73%. CONCLUSIONS: Ultrasound scan alone in diagnosing groin hernias is not effective when correlated with operative findings. However in conjunction with clinical judgment it is a useful tool in diagnosing occult inguinal groin hernias and aiding in further management.

Meta-analysis of the use of glyceryl trinitrate ointment after haemorrhoidectomy as an analgesic and in promoting wound healing.

INTRODUCTION: Glyceryl Trinitrate (GTN) ointment has been used to treat anal fissure and pain relief in haemorrhoids, but the value of its use post-haemorrhoidectomy as an analgesic and in wound healing is unclear. The side effect of headache has often been an associated problem. Therefore, a meta-analysis of randomised controlled trials was carried out investigating the role of GTN post-haemorrhoidectomy as an analgesic, its role in would healing and the unwanted incidence of headache. METHOD: A structured literature search from 1966 to 2009, both paper and online, with no language barrier was carried out. 760 papers were identified and 5 randomised control trials which met the entry criteria were included in this study. RESULTS: A total of 333 patients were included in the meta-analysis. The results revealed that GTN ointment was statistically significant in reducing pain on Day 3 and 7 compared to the placebo group. Day 3 shows a pain score of - 1.51 (p value of 0.029) and Day 7 by - 1.66 (p value of 0.014) respectively. However, it was not significant in reducing pain on Day 1. The Odds ratio for wound healing after GTN treatment at 3 weeks was 3.57 (P < 0.0001) when compared to the placebo group. Side effect of headache was not statistically significant. CONCLUSION: This meta-analysis has shown that GTN ointment used post-haemorrhoidectomy has a significant analgesic effect in the intermediate time period (ie. Days 3-7). It also significantly improved wound healing at 3 weeks.

Embryonic stem cell (ESC)-mediated transgene delivery induces growth suppression, apoptosis and radiosensitization, and overcomes temozolomide resistance in malignant gliomas.

High-grade gliomas are among the most lethal of all cancers. Despite considerable advances in multimodality treatment, including surgery, radiotherapy and chemotherapy, the overall prognosis for patients with this disease remains dismal. Currently available treatments necessitate the development of more effective tumor-selective therapies. The use of gene therapy for malignant gliomas is promising, as it allows in situ delivery and selectively targets brain tumor cells while sparing the adjacent normal brain tissue. Viral vectors that deliver proapoptotic genes to malignant glioma cells have been investigated. Although tangible results on patients' survival remain to be further documented, significant advances in therapeutic gene transfer strategies have been made. Recently, cell-based gene delivery has been sought as an alternative method. In this paper, we report the proapoptotic effects of embryonic stem cell (ESC)-mediated mda-7/IL-24 delivery to malignant glioma cell lines. Our data show that these are similar to those observed using a viral vector. In addition, acknowledging the heterogeneity of malignant glioma cells and their signaling pathways, we assessed the effects of conventional treatment for high-grade gliomas, ionizing radiation and temozolomide, when combined with ESC-mediated transgene delivery. This combination resulted in synergistic effects on tumor cell death. The mechanisms involved in this beneficial effect included activation of both apoptosis and autophagy. Our in vitro data support the concept that ESC-mediated gene delivery might offer therapeutic advantages over standard approaches to malignant gliomas. Our results corroborate the theory that combined treatments exploiting different signaling pathways are needed to succeed in the treatment of malignant gliomas.

Incarcerated inguinal hernia: atypical presentation of an abdominal aortic aneurysm.

The diagnosis of an inguinal hernia, be it complicated or uncomplicated, is often simple and straight forward. Rarely, this simple presentation may be the external manifestation of a distant pathology, which is in communication with the inguinal canal through its anatomic relationship. We report a case of ruptured abdominal aortic aneurysm (AAA) that presented as a strangulated left inguinal hernia. To the best of our knowledge, this is the first reported case where the patient was stable on initial presentation, both clinically and biochemically. The only clue for our patient that pointed towards a potential aneurysm was the presence of intra-operative blood in the spermatic cord. We conclude that any patient presenting with symptoms suggestive of a hernia, particularly on the left side, should have a thorough assessment to rule out AAA.

Shear bond strength of tooth-colored indirect restorations bonded to coronal and cervical enamel.

This study evaluated the shear bond strength of resin inlays bonded with resin cement to cervical and mid-coronal enamel. Two regions of enamel, cervical and mid-coronal, were chosen from the buccal surface of extracted molars. Composite "inlays" (Estenia, Kuraray Medical Inc) were fabricated indirectly and cemented with a dual-cured resin cement (Panavia Fluoro Cement II, Kuraray Medical Inc). The resin cement was cured with or without light irradiation for 30 seconds. After 24-hours or one-week's storage in 37 degrees C water, the bonded inlays were subjected to a microshear bond test, whereby a shear force was applied to the inlays at a crosshead speed of 1 mm/minute. The data were statistically analyzed using ANOVA and Fisher's PLSD test, with significance defined as p<0.05. Observations using confocal laser scanning microscopy were also performed after debonding the specimens. The light-cure method showed significantly higher bond strengths to both enamel regions compared with self-cure, especially at 24 hours (p<0.05). However, bond strength of the self-cured resin cement significantly improved after one week's storage (p<0.05; cervical enamel: p=0.022, midcoronal enamel: p=0.0024). The cervical enamel showed significantly lower bonding than midcoronal enamel (p<0.05), except for the self-cured specimens at 24 hours. Light curing of resin cement is a better choice than self-curing for luting of indirect restorations. The bond strength of indirect restorations to cervical enamel was lower than mid-coronal enamel.

Pulpal response to a hybrid composite resin inlay bonded with a newly developed resin-modified glass ionomer luting cement.

This study evaluated the pulpal response of hybrid composite resin inlay luted with a resin-modified glass ionomer cement, and compared it with a glass ionomer cement and an amalgam. Cervical cavities were prepared in monkey teeth. A resin-modified glass ionomer luting cement (Ionotite F, Tokuyama Dental Corp.) was applied to the teeth in one of the experimental groups, and then hybrid composite resin inlays (Estenia, Kuraray Medical Inc.) were bonded to the cavities. The teeth were extracted after 3, 30, and 90 days and stained with Hematoxylin and Eosin staining or Brown and Brenn gram stain for bacterial observation. No serious inflammatory reaction of the pulp, such as necrosis or abscess formation, was observed in any of the experimental groups. No bacterial penetration along the cavity walls was detected in the resin-modified glass ionomer luting cement group. Hence, the resin-modified glass ionomer luting cement showed an acceptable biological compatibility with monkey pulp.

Gap junction remodeling in hypertrophied left ventricles of aortic-banded rats: prevention by angiotensin II type 1 receptor blockade.

Remodeling of gap-junctional organization in hypertrophied left ventricle (LV) in response to pressure overload in rats induced by abdominal aorta banding was investigated by immunoconfocal and electron microscopy. Eight to 12 weeks after banding, rats developed significant LV hypertrophy. In contrast to control LV myocytes, which showed connexin43 (Cx43) labeling largely confined to the intercalated disks, LV myocytes from aortic-banded rats showed dispersion of punctate Cx43 labeling over the entire cell surface. In LV tissues sectioned longitudinally, the proportion of Cx43 label at the intercalated disk decreased significantly (control, 0.87 v aortic-banded, 0.62). En-face views of intercalated disks of hypertrophied myocardium revealed a reduction of Cx43 gap junctions in the disk center, giving rise to a significant decrease in the proportion of the disk occupied by gap-junctional membrane (control, 0.32 v aortic-banded, 0.24). Electron microscopy of hypertrophied LV tissue revealed that Cx43-containing gap junctions were frequently displaced from their usual locations to form side-to-side contacts distant from the disk, and also appeared as annular profiles. In aortic-banded rats treated with the angiotensin II (AII) type 1 receptor (AT1) antagonist, losartan (10 mg/kg/day, 11 weeks) not only LV hypertrophy, but also the gap junction disorganization was markedly reduced. These results suggest that LV hypertrophy induced by pressure overload is associated with Cx43 gap junction disorganization and that AII may play an important role either directly or indirectly in gap-junctional remodeling.