Hepatoprotective effect of aqeous methanolic extract of Rumex dentatus in paracetamol induced hepatotoxicity in mice

Rumex dentatus is well known plant of Polygonaceae family which is widely used in traditional medicine to treat gastrointestinal tract. R. dentatus at doses 250 and 500 mg/kg significance decreased (p<0.001) the elevated level of ALT, AST, ALP and bilirubin induced by paracetamol and results are comparable (p<0.001) with silymarin. The results were supported by histopathological investigations, phytochemical screening and detection of hepatoprotective active constituents e.g quercetin, kaempferol, myricetin by HPLC. So, it is concluded that R. dentatus has hepatoprotective effect against paracetamol liver damage in mice

Big Data Analytics for Wireless and Wired Network Design: A Survey

Currently, the world is witnessing a mounting avalanche of data due to the increasing number of mobile network subscribers, Internet websites, and online services. This trend is continuing to develop in a quick and diverse manner in the form of big data. Big data analytics can process large amounts of raw data and extract useful, smaller-sized information, which can be used by different parties to make reliable decisions. In this paper, we conduct a survey on the role that big data analytics can play in the design of data communication networks. Integrating the latest advances that employ big data analytics with the networks’ control/traffic layers might be the best way to build robust data communication networks with refined performance and intelligent features. First, the survey starts with the introduction of the big data basic concepts, framework, and characteristics. Second, we illustrate the main network design cycle employing big data analytics. This cycle represents the umbrella concept that unifies the surveyed topics. Third, there is a detailed review of the current academic and industrial efforts toward network design using big data analytics. Forth, we identify the challenges confronting the utilization of big data analytics in network design. Finally, we highlight several future research directions. To the best of our knowledge, this is the first survey that addresses the use of big data analytics techniques for the design of a broad range of networks

Crystallographic substrate binding studies of Leishmania mexicana SCP2-thiolase (type-2):unique features of oxyanion hole-1

Abstract Structures of the C123A variant of the dimeric Leishmania mexicana SCP2-thiolase (type-2) (Lm-thiolase), complexed with acetyl-CoA and acetoacetyl-CoA, respectively, are reported. The catalytic site of thiolase contains two oxyanion holes, OAH1 and OAH2, which are important for catalysis. The two structures reveal for the first time the hydrogen bond interactions of the CoA-thioester oxygen atom of the substrate with the hydrogen bond donors of OAH1 of a CHH-thiolase. The amino acid sequence fingerprints (CxS, NEAF, GHP) of three catalytic loops identify the active site geometry of the well-studied CNH-thiolases, whereas SCP2-thiolases (type-1, type-2) are classified as CHH-thiolases, having as corresponding fingerprints CxS, HDCF and GHP. In all thiolases, OAH2 is formed by the main chain NH groups of two catalytic loops. In the well-studied CNH-thiolases, OAH1 is formed by a water (of the Wat-Asn(NEAF) dyad) and NE2 (of the GHP-histidine). In the two described liganded Lm-thiolase structures, it is seen that in this CHH-thiolase, OAH1 is formed by NE2 of His338 (HDCF) and His388 (GHP). Analysis of the OAH1 hydrogen bond networks suggests that the GHP-histidine is doubly protonated and positively charged in these complexes, whereas the HDCF histidine is neutral and singly protonated

Neonatal Hyperbilirubinemia in infants with <it>G6PD c.563C > T</it><it>Variant</it>

<p>Abstract</p> <p>Background</p> <p>There is a strong correlation between glucose-6-phosphate dehydrogenase (G6PD) deficiency and neonatal hyperbilirubinemia with a rare but potential threat of devastating acute bilirubin encephalopathy. G6PD deficiency was observed in 4–14% of hospitalized icteric neonates in Pakistan. <it>G6PD c.563C > T</it> is the most frequently reported variant in this population. The present study was aimed at evaluating the time to onset of hyperbilirubinemia and the postnatal bilirubin trajectory in infants having <it>G6PD c.563C > T.</it></p> <p>Methods</p> <p>This was a case–control study conducted at The Aga Khan University, Pakistan during the year 2008. We studied 216 icteric male neonates who were re-admitted for phototherapy during the study period. No selection was exercised. Medical records showed that 32 were G6PD deficient while 184 were G6PD normal. Each infant was studied for birth weight, gestational age, age at the time of presentation, presence of cephalhematoma, sepsis and neurological signs, peak bilirubin level, age at peak bilirubin level, days of hospitalization, whether phototherapy or exchange blood transfusion was initiated, and the outcome. During hospital stay, each baby was tested for complete blood count, reticulocyte count, ABO and Rh blood type, direct antiglobulin test and quantitative G6PD estimation [by kinetic determination of G6PDH]. <it>G6PDgenotype</it> was analyzed in 32 deficient infants through PCR-RFLP analysis and gene sequencing.</p> <p>Results</p> <p><it>G6PD variants c.563C > T</it> and <it>c.131 C > G</it> were observed in 21 (65%) and three (9%) of the 32 G6PD deficient infants, respectively. DNA of eight (25%) newborns remained uncharacterized. In contrast to G6PD normal neonates, infants with <it>c.563C > T</it> variant had significantly lower enzyme activity (mean ± 1SD; 0.3 ± 0.2 U/gHb vs. 14.0 ± 4.5 U/gHb, <it>p</it> < 0.001) experienced higher peak levels of total serum bilirubin (mean ± 1SD; 16.8 ± 5.4 mg/dl vs. 13.8 ± 4.6 mg/dl, <it>p =</it> 0.008) which peaked earlier after birth (mean ± 1SD 2.9 ± 1.6 vs. 4.3 ± 2.3 days, <it>p =</it> 0.007). No statistically significant difference was observed in mean weight, age at presentation, hemoglobin, reticulocyte count, TSH level, hospital stay or in the frequency of initiation of phototherapy or blood exchange between the two groups.</p> <p>Conclusions</p> <p>We concluded that infants with <it>G6PD c.563C > T</it> variant developed jaundice earlier than infants with normal G6PD enzyme levels. Compared to G6PD normal infants, <it>G6PD c.563C > T</it> carrying infants had significantly low G6PD activity.</p

Impact of the COVID-19 pandemic on patients with paediatric cancer in low-income, middle-income and high-income countries: a multicentre, international, observational cohort study

OBJECTIVES: Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs. DESIGN: A multicentre, international, collaborative cohort study. SETTING: 91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020. PARTICIPANTS: Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, Wilms' tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer. MAIN OUTCOME MEASURE: All-cause mortality at 30 days and 90 days. RESULTS: 1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p<0.001). After adjusting for confounders, patients with paediatric cancer in LMICs had 15.6 (95% CI 3.7 to 65.8) times the odds of death at 30 days (p<0.001). CONCLUSIONS: The COVID-19 pandemic has affected paediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, many patients with paediatric cancer continued to receive their normal standard of care. This speaks to the adaptability and resilience of healthcare systems and healthcare workers globally