To suppress enzymatic reduction of nitroxyl group of spin probes, this study designed two new nitroxyl probes, 4-hydroxy and 4-oxopiperidine-N-oxyls having 4'-hydroxyspirocyclohexyl groups at the 2- and 6-positions of the piperidine ring (hydroxy-DICPO and oxo-DICPO, respectively). The decay of the EPR signal of these probes in mouse liver homogenates was significantly suppressed compared with that of 4-hydroxy- and 4-oxo-2,2,6,6-tetramethylpiperidine-N-oxyl (hydroxy-TEMPO and oxo-TEMPO, respectively), although hydroxy-DICPO and oxo-DICPO showed no difference in the reactivities with ascorbic acid. While both hydroxy- and oxo-DICPO reacted with hydroxyl radicals, only hydoxy-DICPO lost its EPR signal by the reaction with superoxide anion radical in the presence of cysteine. This feature is similar to that observed for hydroxy- and oxo-TEMPO. These results suggest that the introduction of spirocyclohexyl groups to nitroxyl spin probes is effective for protecting the nitroxyl group against enzymatic reduction without changing the characteristics of the reaction with oxygen radicals.
The present study was conducted to investigate the predictability of early serum bilirubin levels on the subsequent development of neonatal hyperbilirubinemia. For this purpose 84 healthy newborn infants were enrolled and followed up for first 5 days of life. Study subjects were divided into two groups. Group-I consisted of 71 subjects, who did not develop significant hyperbilirubinemia (bilirubin <17mg/dl); Group-II consisted of 13 newborns, who developed significant hyperbilirubinemia (bilirubin >17 mg/dl) during the follow up. Of the enrolled subjects, 46 (55%) were male and rest 38 (45%) were female; 64 (76%) were term babies and 20 (24%) were pre-term babies. Significantly higher percentage of pre-term babies developed hyperbilirubinemia. ROC (receiver operating characteristic) analysis demonstrates that the critical value of cord blood bilirubin >2.5mg/dl had the high sensitivity (77%) and specificity (98.6%) to predict the newborn who would develop significant hyperbilirubinemia. At this level the negative predictive value was 96% and positive predictive value 91%. In our setting infants having umbilical cord blood total serum bilirubin (TSB) >2.5 mg/dl should be followed up strictly either in hospital or as an outpatient department on day 5 if practicable. Infants having TSB <2.5mg/dl in cord blood can be discharged early.
Facility-based sentinel testing for COVID-19 was implemented in May 2020 to monitor the prevalence of COVID-19 amongst the Rohingya and host community in Cox’s Bazar, Bangladesh. In response both to low uptake of testing across all camps, and rumours of an outbreak of an influenza-like illness in May/June 2020, the International Organization for Migration (in partnership with ACAPS) undertook a qualitative study to collect accounts from the Rohingya relating to testing and treatment, and to explore the possibility that what was thought to be an outbreak of influenza may have been COVID-19. The report provided rich descriptions of the apprehension around testing and offered some clear recommendations for addressing these. We developed a testing ‘script’ in response to these recommendations, deploying it alongside a survey to determine reasons for declining a test. We compared testing uptake before deploying the testing script, and after (controlling for the total number of consultations), to generate a crude measure of the impact of the script on testing uptake. We coded reasons for declining a test thematically, disaggregated by status (Rohingya and host community) and sex. Despite the small sample size our results suggest an increase in testing uptake following the implementation of the script. Reasons provided by patients for declining a test included: 1) fear, 2) the belief that COVID-19 does not exist, that Allah will prevent them from contracting it, or that their symptoms are not caused by COVID-19, 3) no permission from husband/family, and 4) a preference to return at a later time for a test. Our findings largely mirror the qualitative accounts in the International Organization for Migration/ACAPS report and suggest that further testing amongst both populations will be complicated by fear, and a lack of clarity around testing. Our data lend force to the recommendations in the International Organization for Migration/ACAPS report and emphasise that contextual factors play a key role and must be considered in designing and implementing a health response to a novel disease.
Teaching Veterinary Hospital (TVH) in Chittagong Veterinary and Animal Sciences University (CVASU) plays an important role of public service to animal welfare since the period of 1996. There are lots of goats and cattle are recorded in this hospital every year but previously no report published on it. So this research was conducted to determine the prevalence of clinical diseases and manifestations of goats and cattle recorded at TVH in CVASU during the period of January to December 2012. A total of 3090 clinical cases (goats 2778 and cattle 312) were registered. Diagnosis of these clinical diseases and disorders were based on clinical history, clinical sign and different lab test. Medicinal cases constituted highest percentage (goats 74.66% and cattle 66.35%) in comparison to surgical (goats 16.84% and cattle 24.04 %) cases and gynae-obstetrical (goats 8.50% and cattle 9.62%) cases. Among the (1) medicinal cases, highest percentage was recorded with the diseases of digestive system (goats 16.85% and cattle 20.83%) followed by parasitic diseases (goats 15.22% and cattle 12.82%), infectious diseases (goats 11.95% and cattle 12.18%), general systemic states (goats 7.91% and cattle 6.73%), disease of the respiratory system (goats 9.57% and cattle 4.16%), urinary system(goats 3.31% and cattle 1.28%), special sense organs (goats 3.99% and cattle 1.28%) and noninfectious diseases (goats 5.83% and cattle 4.17%). Among of the (2) surgical cases, general surgery (goats 11.77 and cattle 16.58%) was higher in percentage than special (goats 3.31% and cattle 3.20%) and orthopedic (goats 1.76% and cattle 3.85%) surgery. Among of the gynae-obstetrical cases, gynaecological disorders were recorded higher (goats 6.98% and cattle 8.33%) than obstetrical disorders (goats 1.51% and cattle 1.28%). Prevalence of clinical diseases and disorders were analyzed on the basis of age, sex, breed and season. P-value (P≤0.05) was considered as significant. So that an appropriate control strategy has to be designed and applied, which helps to prevent of these disease conditions in study area.
These results suggest that loss of specific PP2A regulatory subunits is functionally important in breast tumourigenesis, and support strategies to enhance PP2A activity as a therapeutic approach in breast cancer.
Mannan A, Hahn-Stro¨mberg V. K-ras mutations are correlated to lymph node metastasis and tumor stage, but not to the growth pattern of colon carcinoma. APMIS 2012; 120: 459-68.In colorectal carcinoma, pathological assessment of tumors is essential for determining therapy and prognosis of the disease. Molecular associations of tumor complexity index and genetic alternations can be helpful to understand the tumor progression mechanism. Oncogenic K-ras is one of the major colorectal cancer associated genes, and is mutated in up to 50% of colorectal cancers. In this current study, we correlated tumor complexity index with mutations in K-ras codon 12, 13, and 61 in association with different clinicopathological parameters such as TNM stage, localization, sex, and age. Formalin-fixed paraffin embedded tissue blocks from colon cancer samples was selected from 88 patients diagnosed with adenocarcinoma. Mutations in the K-ras gene were detected using pyrosequencing technique. Tumor complexity index was calculated using immunohistochemically stained images of the tumor outline of the specimens and then analyzing these pictures using Photoshop CS, Fovea Pro, and Image J computer programs. Statistical analysis was performed with SPSS. K-ras mutations were detected in 17 (19.3%) colon cancer samples. Most of the samples were at a lower complexity index. No correlation was observed between K-ras mutations and complexity index. However, K-ras mutations were correlated with regional lymph node metastasis and tumor stages and complexity index with tumor wall penetration. In conclusion, complexity index and K-ras mutations are independent events; however, both correlate with tumor progression and are important in the biologic development of colon carcinoma.
Acute lymphoblastic leukaemia (ALL) is the most common cancer diagnosed in children and adolescents. Approximately 70% of patients survive >5-years following diagnosis, however, for those that fail upfront therapies, survival is poor. Reactive oxygen species (ROS) are elevated in a range of cancers and are emerging as significant contributors to the leukaemogenesis of ALL. ROS modulate the function of signalling proteins through oxidation of cysteine residues, as well as promote genomic instability by damaging DNA, to promote chemotherapy resistance. Current therapeutic approaches exploit the pro-oxidant intracellular environment of malignant B and T lymphoblasts to cause irreversible DNA damage and cell death, however these strategies impact normal haematopoiesis and lead to long lasting side-effects. Therapies suppressing ROS production, especially those targeting ROS producing enzymes such as the NADPH oxidases (NOXs), are emerging alternatives to treat cancers and may be exploited to improve the ALL treatment. Here, we discuss the roles that ROS play in normal haematopoiesis and in ALL. We explore the molecular mechanisms underpinning overproduction of ROS in ALL, and their roles in disease progression and drug resistance. Finally, we examine strategies to target ROS production, with a specific focus on the NOX enzymes, to improve the treatment of ALL.
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