Enhancing phytoremediation of hazardous metal(loid)s using genome engineering CRISPR-Cas9 technology.

Rapid and drastic changes in the global climate today have given a strong impetus to developing newer climate-resilient phytoremediation approaches. These methods are of great public and scientific importance given the urgency of this environmental crisis. Climate change has adverse effects on the growth, outputs, phenology, and overall productivity of plants. Contamination of soil with metal(loid)s is a major worldwide problem. Some metal(loids) are carcinogenic pollutants that have a long half-life and are non-degradable in the environment. There are many instances of the potential link between chronic heavy metal exposure and human disease. The adaptation of plants in the changing environment is, however, a major concern in phytoremediation practice. The creation of climate-resistant metal hyperaccumulation plants using molecular techniques could provide new opportunities to mitigate these problems. Consequently, advancements in molecular science would accelerate our knowledge of adaptive plant remediation/resistance and plant production in the context of global warming. Genome modification using artificial nucleases has the potential to enhance phytoremediation by modifying genomes for a sustainable future. This review focuses on biotechnology to boost climate change tolerant metallicolous plants and the future prospects of such technology, particularly the CRISPR-Cas9 genome editing system, for enhancing phytoremediation of hazardous pollutants.

Serum Iron Profile and Red Cell Indices in Children with Severe Acute Malnutrition in A Tertiary Level Hospital.

This cross-sectional analytical study was conducted in the department of Paediatrics, Mymensingh Medical College Hospital (MMCH), Mymensingh, Bangladesh from March 2017 to August 2018 to assess the pattern of serum iron profile and red cell indices in children with severe acute malnutrition. Seventy children having severe acute malnutrition were compared with 70 age matched children those had normal growth. Age range of the studied children was 6 months to 59 completed months. Male was found predominant (54.3%) in both study group and comparison group. Mean serum iron, serum ferritin, serum total iron binding capacity and transferrin saturation in severely malnourished children were 45.3±19.3µg/dl, 26.5±20.0ng/ml, 246.3±47.5µg/dl and 16.4±2.0% respectively which were significantly lower than that of healthy children (p<0.05). Mean Hb level in children with severe acute malnutrition was found 8.3±1.6gm/dl which was also found significantly lower than that of normal children (p<0.05). Anaemia was found in all (100%) severely malnourished children compared to 25.7% of children in comparison group. Mean MCV, MCH and MCHC in children with severe acute malnutrition was found 71.7±13.5fl, 24.0±5.8pg and 31.4±4.0gm/dl respectively which were significantly lower than that of comparison group (p<0.05). Serum iron profile and red cell indices should be routinely done in severely malnourished children for early intervention and management of iron deficiency anaemia.

Gail model utilization in predicting breast cancer risk in Egyptian women: a cross-sectional study.

PURPOSE: Herein, our purpose was to calculate the 5-year and lifetime risk of breast cancer and to assess new breast cancer potential contributors among Egyptian women utilizing the modified Gail model, while presenting a global comparison of risk assessment. METHODS: This study included 7009 women from both urban and rural areas scattered across 40% of the Egyptian provinces. The 5-year risk categories were defined as low risk (≤ 1.66%) or high risk (> 1.66%), whereas the lifetime risk categories were defined as low risk (≤ 20%) or high risk (> 20%). Pearson's Chi-squared test was performed to determine the association between participants' characteristics and distinct risk categories. Binary logistic regression was carried out for correlation analysis. RESULTS: The mean estimated risk for developing invasive breast cancer over 5 years was 0.86 (± 0.67), whereas the mean lifetime breast cancer risk score was 11.26 (± 5.7). Accordingly, only 614 (8.75%) and 470 (6.7%) women were categorized as individuals with high risk of breast cancer incidence in 5-year and lifetime, respectively. Only 192 participants (2.7%) conferred both high 5-year and high lifetime risk scores. Marital status, method of feeding, physical activity behavior, contraceptive use, menopause and number of children were found to have a statistically significant association with both 5-year and lifetime breast cancer risk categories. CONCLUSION: We revealed that modified Gail model had a well-fitting and discrimination accuracy in Egyptian women when compared with other countries.

Deletion of Thioredoxin-Interacting Protein (TXNIP) Abrogates High Fat Diet-induced Retinal Leukostasis, Barrier Dysfunction and Microvascular Degeneration in a Mouse Obesity Model.

We have shown that a high fat diet (HFD) induces the activation of retinal NOD-like receptor protein (NLRP3)-inflammasome that is associated with enhanced expression and interaction with thioredoxin-interacting protein (TXNIP). Here, the specific contribution of TXNIP and the impact of HFD on retinal leukostasis, barrier dysfunction and microvascular degeneration were investigated. Wild-type (WT) and TXNIP knockout (TKO) mice were fed with normal diet or 60% HFD for 8-18 weeks. TXNIP was overexpressed or silenced in human retinal endothelial cells (REC). At 8 weeks, HFD significantly induced retinal leukostasis and breakdown of the blood-retina barrier in WT mice, but not in TKO mice. In parallel, HFD also induced retinal expression of adhesion molecules and cleaved IL-1ß in WT mice, which were also abrogated in TKO mice. In culture, TXNIP overexpression induced NLRP3, IL-1b, and adhesion molecules expression, while TXNIP silencing inhibited them. Blocking the IL-1ß receptor significantly suppressed TXNIP-induced expression of NLRP3-inflammasome and adhesion molecules in HREC. Ex-vivo assay showed that leukocytes isolated from WT-HFD, but not from TKO-HFD, induced leukostasis and cell death. At 18 weeks, HFD triggered development of degenerated (acellular) capillaries and decreased branching density in WT but not in TKO mice. Together, HFD-induced obesity triggered early retinal leukostasis and microvascular dysfunction at least in part via TXNIP-NLRP3-inflammasome activation.

Evaluation of Preoperative Ultrasonography in Gall Stone Disease to Predict Technical Difficulties during Laparoscopic Cholecystectomy.

Laparoscopic cholecystectomy is the gold standard in the treatment of gallstones. This study was carried out to determine the technical difficulties that can be encountered during laparoscopic cholecystectomy and to evaluate the role of ultrasonography in identifying patients at risk of conversion returning to open surgery. The objective of this study was to evaluate the efficacy of preoperative ultrasonography in assessing technical difficulty faced during laparoscopic cholecystectomy in gallstone disease. This was an observational comparative study which was conducted in the Department of Surgery of Shaheed Suhrawardy Medical College & Hospital, Dhaka, Bangladesh from January 2016 to January 2017. A purposive sampling method was applied to select the study sample. A total of 160 patients were included this study. Data processing and analysis were done using SPSS (statistical package for social sciences), version 20. The summarized data were presented in the form of figures and tables with due statistical interpretation. In this study, there was a total of 160 cases, among which 90(56.25%) turned out to have undergone normal laparoscopic cholecystectomies. Seventy (43.75%) were difficult, among which 6(3.75%) were converted to open cholecystectomies. Among 160 patients, 120(75%) were female and 40(25%) were male. There is a total of 136/160 (85%) patients with gallbladder wall thickness <3mm and 24/160 (15%) patients >3mm. Among the 136 patients with gallbladder wall thickness <3mm, there was difficulty in holding the gallbladder in 28(25%) cases, 28(20.6%) had undergone gallbladder perforation, 32(23.5%) had undergone moderate bleeding and only 2(1.5%) had undergone severe bleeding. Among the 24 patients with gallbladder wall thickness >3mm, there was difficulty in holding the gallbladder in 22(91.7%) cases, 18(75%) had undergone gallbladder perforation, 18(75%) had undergone moderate bleeding and only 2(8.33%) had undergone severe bleeding. It shows a total of 124/160 (77.5%) patients with normal gall bladder, 26/160 (16.25%) patients with contracted gallbladder and 10/160 (6.25%) patients with distended gallbladder. Among the 124 patients with normal gallbladder, 16(12.9%) had undergone difficult Calot's dissection, 26(21%) had undergone difficult gallbladder bed dissection, 26(21%) had undergone moderate bleeding and none had undergone severe bleeding. Among 26 patients with contracted gallbladder, 20(76.9%) underwent difficult Calot's dissection, 24(92.3%) had undergone difficult gallbladder bed dissection, 18(69.2%) had undergone moderate bleeding and 4(15.4%) had undergone severe bleeding. Among 10 patients with distended gallbladder, 4(40%) underwent difficult Calot's dissection, 6(60%) underwent difficult gallbladder bed dissection, 6(60%) had undergone moderate bleeding and none had undergone severe bleeding. From this study, we conclude that preoperative ultrasonography is a good predictor of difficulty in laparoscopic cholecystectomy in the majority of cases and should be used as a screening procedure.

Skin Biopsy and Histopathological Diagnosis of Dermatological Diseases.

Microscopic examination of skin and mucous membrane is an established investigation in diagnosis and follow up of many dermatological conditions frequently encountered during practice. Histopathological examination is performed with biopsied specimen from skin and or mucous membrane where required. However neither do all skin biopsies produce neither a conclusive diagnosis nor the dermatologists routinely perform this procedure to every patient they consult. This cross sectional descriptive study conducted by reviewing the records of all biopsied cases studied for histopathology in Mymensingh Medical College, Mymensingh and Shaheed Mansur Ali Medical College, Dhaka, Bangladesh from January 2012 to December 2016. The aim of this study was to investigate the favourable clinical diagnoses set by dermatologists when performing skin biopsy, the diagnoses reached by the dermatopathologists after microscopic examination, and the relationship between them and finally to comment on the instances that skin biopsy fails to fulfill the diagnostic task. Fourteen hundred and thirty six (1436) cases of skin biopsy were reviewed and descriptive statistics were performed. Maximum cases 39.1% (562) were in 2nd decade with almost equal sex distribution. The most frequently proposed clinical diagnoses included papulosquamous dermatoses 28.6% (410), whereas histological confirmation was in 13.1% (188). Histological diagnosis was more as nonspecific dermatitis 31.6% (454). After microscopic examination, a specific histological diagnosis was found in 83.5% (1199) of the cases and a consensus between clinical and histological diagnoses was observed in 69.2% (994). Neither histological diagnosis nor any feature consistent with clinical suspicion was observed in 10.1% (145) cases. Histopathological examination of skin biopsy is still a valuable diagnostic tool in many skin diseases and dermatoses with diagnostic dilemma. There are cases in which diagnostic inefficiency are being faced even after skin biopsy examination.

Embryo cell allocation patterns are not altered by biopsy but can be linked with further development.

It has been suggested that first embryo cleavage can be related with the embryonic-abembryonic axis at blastocyst stage in mice. Thus, cells of the 2-cell embryo might be already biased to form the inner cell mass or trophectoderm. This study was conducted to observe the possible effects of embryo biopsy on cell allocation patterns during embryo preimplantation in two different mouse strains and the effects of these patterns on further development. First, one blastomere of the 2-cell embryo was injected with a lipophilic tracer and cell allocation patterns were observed at blastocyst stage. Blastocysts were classified into orthogonal, deviant or random pattern. For the first experiment, embryos were biopsied at 8-cell stage and total cell counts (TCC) were annotated. Furthermore, non-biopsied blastocysts were transferred into foster mothers. Then, pups and their organs were weighed two weeks after birth. Random pattern was significantly recurrent (≈60%), against orthogonal (<22%) and deviant (<22%) patterns among groups. These patterns were not affected by biopsy procedure. However, TCC on deviant embryos were reduced after biopsy. Moreover, no differences were found between patterns for implantation rates, litter size, live offspring and organ weights (lungs, liver, pancreas and spleen). However, deviant pups presented heavier hearts and orthogonal pups presented lighter kidneys among the group. In conclusion, these results suggest that single blastomere removal does not disturb cell allocation patterns during pre-implantation. Nonetheless, the results suggest that embryos following different cell allocation patterns present different coping mechanisms against in vitro manipulations and further development might be altered.

Prevalence and Correlates of Smoking among Low-Income Adults Residing in New York City Public Housing Developments-2015.

To guide targeted cessation and prevention programming, this study assessed smoking prevalence and described sociodemographic, health, and healthcare use characteristics of adult smokers in public housing. Self-reported data were analyzed from a random sample of 1664 residents aged 35 and older in ten New York City public housing developments in East/Central Harlem. Smoking prevalence was 20.8%. Weighted log-binomial models identified to be having Medicaid, not having a personal doctor, and using health clinics for routine care were positively associated with smoking. Smokers without a personal doctor were less likely to receive provider quit advice. While most smokers in these public housing developments had health insurance, a personal doctor, and received provider cessation advice in the last year (72.4%), persistently high smoking rates suggest that such cessation advice may be insufficient. Efforts to eliminate differences in tobacco use should consider place-based smoking cessation interventions that extend cessation support beyond clinical settings.

Plant-microbial association in petroleum and gas exploration sites in the state of Assam, north-east India-significance for bioremediation.

The state of Assam in north-east India gained popularity in Asia because of discovery of oil. Pollution due to petroleum and gas exploration is a serious problem in Assam. Oil and gas exploration by various agencies in Assam resulted in soil pollution due to hydrocarbons (HCs) and heavy metals (HMs). Bioremediation gained considerable significance in addressing petroleum hydrocarbon polluted sites in various parts of the world. In this investigation, we have observed 15 species of plants belonging to grass growing on the contaminated soils. Among 15 species of grasses, 10 species with high important value index (IVI) were found to be better adapted. The highest IVI is exhibited by Axonopus compressus (21.41), and this grass can be identified as key ecological tool in the rehabilitation of the degraded site. But no definite correlation between the IVI and the biomass of the various grass existed in the study sites. Chemical study of rhizosphere (RS) and non-rhizosphere (NRS) soil of these grasses revealed both aromatic and aliphatic compounds (M.W. 178-456). Four-ring pyrene was detected in NRS soil but not in RS soil. Microbiological study of RS and NRS soil showed high colony-forming unit (CFU) of HC-degrading microbes in RS compared to NRS. The increased microbial catabolism in RS soil established the fact that pyrene is transformed to aliphatic compounds. Metals in RS soil ranged from (in mg kg-1) 222.6 to 267.3 (Cr), 854 to 956 (Pb) and 180 to 247 (Ni), but despite the very high total metal concentration in RS and NRS soil, the CaCl2-extracted metals were relatively low in RS soil (1.04 for Cr, 0.56 for Pb, 0.35 for Ni). Plants with the highest uptake of metals were Leersia hexandra (36.43 mg Cr kg-1) and Kyllinga brevifolia (67.73 mg Pb kg-1 and 40.24 mg Ni kg-1). These plant species could be potentially exploited for biomonitoring and bioremediation. Out of 15 plant species, 8 of them have high percentages of cellulose, crude fibres, lignin and holocellulose (14-16%). The explored species thus qualify as energy crops since they have high bioproductivity and are more resilient and adaptable in HM/HC-contaminated sites.

Shift in disparities in hepatitis C treatment from interferon to DAA era: A population-based cohort study.

We evaluated the shift in the characteristics of people who received interferon-based hepatitis C virus (HCV) treatments and those who received recently introduced direct-acting antivirals (DAAs) in British Columbia (BC), Canada. The BC Hepatitis Testers Cohort includes 1.5 million individuals tested for HCV or HIV, or reported cases of hepatitis B and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalization, cancer, prescription drugs and mortality data. This analysis included all patients who filled at least one prescription for HCV treatment until 31 July 2015. HCV treatments were classified as older interferon-based treatments including pegylated interferon/ribavirin (PegIFN/RBV) with/without boceprevir or telaprevir, DAAs with RBV or PegIFN/RBV, and newer interferon-free DAAs. Of 11 886 people treated for HCV between 2000 and 2015, 1164 (9.8%) received interferon-free DAAs (ledipasvir/sofosbuvir: n=1075; 92.4%), while 452 (3.8%) received a combination of DAAs and RBV or PegIFN/RBV. Compared to those receiving interferon-based treatment, people with HIV co-infection (adjusted odds ratio [aOR]: 2.96, 95% CI: 2.31-3.81), cirrhosis (aOR: 1.77, 95% CI: 1.45-2.15), decompensated cirrhosis (aOR: 1.72, 95% CI: 1.31-2.28), diabetes (aOR: 1.30, 95% CI: 1.10-1.54), a history of injection drug use (aOR: 1.34, 95% CI: 1.09-1.65) and opioid substitution therapy (aOR: 1.30, 95% CI: 1.01-1.67) were more likely to receive interferon-free DAAs. Socio-economically marginalized individuals were significantly less likely (most deprived vs most privileged: aOR: 0.71, 95% CI: 0.58-0.87) to receive DAAs. In conclusion, there is a shift in prescription of new HCV treatments to previously excluded groups (eg HIV-co-infected), although gaps remain for the socio-economically marginalized populations.

Thioredoxin-interacting protein: a novel target for neuroprotection in experimental thromboembolic stroke in mice.

Redox imbalance in the brain significantly contributes to ischemic stroke pathogenesis, but antioxidant therapies have failed in clinical trials. Activation of endogenous defense mechanisms may provide better protection against stroke-induced oxidative injury. TXNIP (thioredoxin-interacting protein) is an endogenous inhibitor of thioredoxin (TRX), a key antioxidant system. We hypothesize that TXNIP inhibition attenuates redox imbalance and inflammation and provides protection against a clinically relevant model of embolic stroke. Male TXNIP-knockout (TKO), wild-type (WT), and WT mice treated with a pharmacological inhibitor of TXNIP, resveratrol (RES; 5 mg/kg body weight), were subjected to embolic middle cerebral artery occlusion (eMCAO). Behavior outcomes were monitored using neurological deficits score and grip strength meter at 24 h after eMCAO. Expression of oxidative, inflammatory, and apoptotic markers was analyzed by Western blot, immunohistochemistry, and slot blot at 24 h post-eMCAO. Our result showed that ischemic injury increases TXNIP in WT mice and that RES inhibits TXNIP expression and protects the brain against ischemic damage. TKO and RES-treated mice exhibited a 39.26 and 41.11 % decrease in infarct size and improved neurological score and grip strength compared to WT mice after eMCAO. Furthermore, the levels of TRX, nitrotyrosine, NOD-like receptor protein (NLRP3), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and activations of caspase-1, caspase-3, and poly-ADP-ribose polymerase (PARP) were significantly (P < 0.05) attenuated in TKO and RES-treated mice. The present study suggests that TXNIP is contributing to acute ischemic stroke through redox imbalance and inflammasome activation and inhibition of TXNIP may provide a new target for therapeutic interventions. This study also affirms the importance of the antioxidant effect of RES on the TRX/TXNIP system.

Clinical and haemato-pathological characteristics of adult acute lymphoblastic leukaemia.

Acute lymphoblastic leukaemia (ALL) is a heterogeneous group of disorders. It varies with respect to the morphologic, cytogenetic, molecular and immunologic features of the neoplastic cells reflecting the variable clinical-pathologic presentations and outcome of the patients. The aim of the study was to observe the clinical and haemato-pathological characteristics in newly diagnosed adult ALL patients. A total number of 61 patients morphologically diagnosed as acute lymphoblastic leukaemia aged 15 and above assigned for this observational study. The study was carried out in the Department of Haematology, BSMMU from January 2007 to December 2008. Among 61 patients, aged 15 to 80 years with median age 25 years, 79% were male and 21% were female. Most of the patients presented with anaemia (67%), fever (66%), lymphadenopathy (64%) and splenomegaly (57%). Other common clinical findings were hepatomegaly (39%), bone tenderness (44%) and bleeding manifestations (34%). Among haemato-pathological findings 67% patients had Hb level ≤10gm/dl, 46% patients had WBC count ≥30×109/L, 67% patients had platelet count ≤100×109/L, 93% patients had blast in peripheral blood and 61% patients had ≥90 % blasts in the bone marrow at the time of diagnosis. In this study adult ALL patients were analyzed only for their clinical and haemato-pathological characteristics. But their biologic characteristics were not analyzed due to lack of availability of facility. A progressive understanding of the biologic and genetic characteristics of ALL will allow us to identify different prognostic subgroups with specific molecular and cellular features. All the necessary measures have to be developed in our country in order to identify prognostically distinct subgroups of patients.

Post-traumatic immunosuppression is reversed by anti-coagulated salvaged blood transfusion: deductions from studying immune status after knee arthroplasty.

Major trauma increases vulnerability to systemic infections due to poorly defined immunosuppressive mechanisms. It confers no evolutionary advantage. Our objective was to develop better biomarkers of post-traumatic immunosuppression (PTI) and to extend our observation that PTI was reversed by anti-coagulated salvaged blood transfusion, in the knowledge that others have shown that non-anti-coagulated (fibrinolysed) salvaged blood was immunosuppressive. A prospective non-randomized cohort study of patients undergoing primary total knee arthroplasty included 25 who received salvaged blood transfusions collected post-operatively into acid-citrate-dextrose anti-coagulant (ASBT cohort), and 18 non-transfused patients (NSBT cohort). Biomarkers of sterile trauma included haematological values, damage-associated molecular patterns (DAMPs), cytokines and chemokines. Salvaged blood was analysed within 1 and 6 h after commencing collection. Biomarkers were expressed as fold-changes over preoperative values. Certain biomarkers of sterile trauma were common to all 43 patients, including supranormal levels of: interleukin (IL)-6, IL-1-receptor-antagonist, IL-8, heat shock protein-70 and calgranulin-S100-A8/9. Other proinflammatory biomarkers which were subnormal in NSBT became supranormal in ASBT patients, including IL-1ß, IL-2, IL-17A, interferon (IFN)-γ, tumour necrosis factor (TNF)-α and annexin-A2. Furthermore, ASBT exhibited subnormal levels of anti-inflammatory biomarkers: IL-4, IL-5, IL-10 and IL-13. Salvaged blood analyses revealed sustained high levels of IL-9, IL-10 and certain DAMPs, including calgranulin-S100-A8/9, alpha-defensin and heat shock proteins 27, 60 and 70. Active synthesis during salvaged blood collection yielded increasingly elevated levels of annexin-A2, IL-1ß, Il-1-receptor-antagonist, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IFN-γ, TNF-α, transforming growth factor (TGF)-ß1, monocyte chemotactic protein-1 and macrophage inflammatory protein-1α. Elevated levels of high-mobility group-box protein-1 decreased. In conclusion, we demonstrated that anti-coagulated salvaged blood reversed PTI, and was attributed to immune stimulants generated during salvaged blood collection.

Food Intake Recording Software System, version 4 (FIRSSt4): a self-completed 24-h dietary recall for children.

The Food Intake Recording Software System, version 4 (firsst4), is a web-based 24-h dietary recall (24 hdr) self-administered by children based on the Automated Self-Administered 24-h recall (ASA24) (a self-administered 24 hdr for adults). The food choices in firsst4 are abbreviated to include only those reported by children in US national surveys; and detailed food probe questions are simplified to exclude those that children could not be expected to answer (e.g. questions regarding food preparation and added fats). ASA24 and firsst4 incorporate 10 000+ food images, with up to eight images per food, to assist in portion size estimation. We review the formative research conducted during the development of firsst4. When completed, firsst4 will be hosted and maintained for investigator use on the National Cancer Institute's ASA24 website.

A multicenter phase II study incorporating high-dose rituximab and liposomal doxorubicin into the CODOX-M/IVAC regimen for untreated Burkitt's lymphoma.

BACKGROUND: Despite improvement with intensive multi-agent chemotherapy, 2-year progression-free survival (PFS) rates for adults with high-risk Burkitt's lymphoma (BL) remains <55%. PATIENTS AND METHODS: We conducted a phase II trial for newly diagnosed classic BL utilizing liposomal doxorubicin (Adriamycin) in lieu of doxorubicin and incorporating intravenous rituximab (at 500 mg/m(2) twice/cycle) into the CODOX-M/IVAC regimen. Correlative analyses included paired serum and cerebrospinal fluid (CSF) rituximab levels and close examination of cardiac function. RESULTS: Among 25 BL patients, the median age was 44 years (23-70) and 4 patients were HIV positive. There were 20 high-risk and 5 low-risk patients. At baseline, 40% of high-risk patients had bone marrow involvement, 35% had bulky disease and 15% had central nervous system involvement. The overall response rate was 100% (complete remission 92%). At 34-month median follow-up, the 2-year PFS and overall survival (OS) rates for all patients were 80% and 84%, respectively (low-risk: both 100%; high-risk: 76% and 81%, respectively). Furthermore, the 2-year PFS, OS, and disease-specific survival (DSS) rates for high-risk, HIV-negative patients were 84%, 89% and 100%, respectively. Adverse events (AEs) appeared to be consistent with prior CODOX-M/IVAC data, although there were several grade 3 cardiac events noted (all declined ejection fraction without clinical symptoms). The mean serum rituximab levels at 24 h after cycles 1 and 3 for patients without relapse were 258 and 306 µg/ml, respectively, versus 131 and 193 µg/ml, respectively, for patients with early progression (P = 0.002 and 0.002, respectively). The mean CSF rituximab levels for all patients were 0.11 and 0.24 µg/ml, respectively, at cycle 1 (24/72 h), which equated to serum:CSF ratios of 0.05% and 0.20%, respectively. CONCLUSIONS: The integration of rituximab into CODOX-M/IVAC for adult BL was feasible and tolerable, while changes in cardiac function warrant continued examination. This regimen was associated with excellent survival rates for HIV-negative BL. Further investigation of the predictive value of serum rituximab is needed. Clinicaltrials.gov NCT00392990.

Outcome of adult acute lymphoblastic leukaemia following induction chemotherapy with modified MRC UKALL XII/ECOG E2993 protocol.

Cure rates for adult acute lymphoblastic leukaemia (ALL) in developing countries are significantly lower because of problems unique to these countries. Recent studies have reported complete response rates for any induction regimen of more than 90% in adult ALL patients. This study was conducted to evaluate the response rate of induction chemotherapy in adult ALL patients in the Department of Haematology, Bangabandhu Sheikh Mujib Medical University, from January 2007 to December 2008. In this observational study, 35 newly diagnosed ALL patients classified either as L1/L2 according to French-American-British (FAB) classification, aged between 15 to 60 years were assigned for induction therapy with modified MRC UKALL XII/ECOG E2993 protocol. But ultimately 30 patients completed therapy and available for statistical analysis. Among the studied 30 cases 12(40%) patients after phase 1 and overall 24 (80%) patients after phase 2 induction therapy, achieved morphologic complete remission (CR). After phase 2 therapy 6 (20%) patients fell in the group of non responders (NR) as the blast percentage was > or = 5% at the time of bone marrow evaluation. This study shows the response rates in adult ALL with induction therapy slightly below the anticipated response rates of developed countries which may be due to little modification of the original protocol.

Diabetes exacerbates retinal oxidative stress, inflammation, and microvascular degeneration in spontaneously hypertensive rats.

PURPOSE: Hypertension and diabetes are known risk factors for retinal microvascular damage. However, the combined effects of diabetes with early and established stages of hypertension on retinal microvascular degeneration remain incompletely understood. METHODS: Male spontaneously hypertensive rats (SHR) were compared to SHR with streptozotocin-induced diabetes (SHR+D) for 6 or 10 weeks and Wistar rats as controls. RESULTS: Hypertension alone (the SHR group) or in combination with diabetes (the SHR+D group) for 6 weeks induced additive increases in total retinal cell death, compared to the Wistar controls. This increase was associated with significant increases in phosphorylated-Jun N-terminal kinase (pJNK) activation, phosphorylated-Akt inhibition, plasma and retinal lipid peroxides, and soluble intracellular adhesion molecule-1 (sICAM-1) levels. After 10 weeks, a similar trend was still observed in retinal nitrotyrosine, nuclear factor kappaB p65, and tumor necrosis factor-α expression, associated with exacerbated pJNK activation and formation of acellular capillaries. CONCLUSIONS: In conclusion, combining diabetes and hypertension-potentiated retinal oxidative/inflammatory stress promoted imbalance between the JNK stress and survival Akt pathways resulting in accelerated retinal cell death and acellular capillary formation.

Noninvasive diagnosis of cardiac allograft rejection using echocardiography indices of systolic and diastolic function.

BACKGROUND: Limited and conflicting data exist on the diagnosis of cardiac allograft rejection with the use of echocardiography. The purpose of our study was to evaluate various systolic and diastolic indices, including newer tissue Doppler imaging techniques, in diagnosing cardiac allograft rejection. METHODS: We prospectively performed 426 echocardiography studies at the time of endomyocardial biopsy in 54 cardiac transplant patients. We measured left ventricular (LV) systolic and diastolic dimensions, mitral inflow pattern and annular velocities, and the myocardial performance index. Biopsies were assessed for cellular rejection and antibody-mediated rejection (AMR). RESULTS: Mild cellular rejection was diagnosed in 74 biopsy specimens and significant cellular rejection in 10 biopsy specimens. AMR was diagnosed in 30 biopsy specimens. In patients with mild or significant cellular rejection, no significant differences in echocardiographic parameters were observed. In patients with AMR, LV fractional shortening was significantly reduced compared with those with no AMR (mean±SD 31.8±8.9% vs 36.0±7.1%; P=.02). CONCLUSIONS: Although 1 echocardiographic parameter was statistically different in the setting of rejection, lack of consistency and overlap between nonrejection and rejection groups does not permit definitive noninvasive diagnosis of cardiac allograft rejection using this imaging modality.