Metformin and the gastrointestinal tract

Metformin is an effective agent with a good safety profile that is widely used as a first-line treatment for type 2 diabetes, yet its mechanisms of action and variability in terms of efficacy and side effects remain poorly understood. Although the liver is recognised as a major site of metformin pharmacodynamics, recent evidence also implicates the gut as an important site of action. Metformin has a number of actions within the gut. It increases intestinal glucose uptake and lactate production, increases GLP-1 concentrations and the bile acid pool within the intestine, and alters the microbiome. A novel delayed-release preparation of metformin has recently been shown to improve glycaemic control to a similar extent to immediate-release metformin, but with less systemic exposure. We believe that metformin response and tolerance is intrinsically linked with the gut. This review examines the passage of metformin through the gut, and how this can affect the efficacy of metformin treatment in the individual, and contribute to the side effects associated with metformin intolerance

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children <18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p<0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p<0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p<0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

Preliminary evaluation of some aspects of the ecology (growth pattern, condition factor and reproductive biology) of African pike, Hepsetus odoe (Bloch 1794), in Lake Eleiyele, Ibadan, Nigeria

Abstract A preliminary investigation of length-weight relationship, condition factor and reproductive ecology of African pike fish, Hepsetus odoe, was conducted between June to August 2010 in Lake Eleiyele. A total of 90 samples of the fish species were caught by fishermen using gill nets. The results obtained showed that fish species had isometric growth pattern (contrary to negative allometry expected) with the growth exponent, b value of 2.64, that is not statistically different from 3 and with high statistical power of 0.866 when tested. The mean condition factor, K, was found to be 2.6, indicating that the fish species were in good condition in the study area. For reproductive biology, mean fecundity and gonadosomatic index were found to be 1349 eggs and 3.53% respectively. This study was necessary to fill the knowledge gap and provide information for management and conservation of the investigated species in the lake system. This study recommended that further research needs to be conducted because the sampling was carried out in the rainy season period and within a quarter of a year

Measurement of the cross-section for the process gamma*gamma* -> hadrons at LEP

Measurements of the two-photon interaction e(+)e(-) --> e(+)e(-) + hadrons at root s similar or equal to 91 GeV and root s similar or equal to 183 GeV are presented. The double-tag events, collected with the L3 detector, correspond to integrated luminosities of 140 pb(-1) at 91 GeV and 52 ph(-1) at 183 GeV. The cross-section of gamma*gamma* collisions has been measured at [Q(2)] = 3.5 GeV2 and [Q(2)] = 14 GeV2. The data agree well with predictions based on perturbative QCD, while the Quark Parton Model alone is insufficient to describe the data. (C) 1999 Published by Elsevier Science B.V. All rights reserved

Study of neutral-current four-fermion and ZZ production in e(+)e(-) collisions at root s=183GeV RID C-2983-2009 RID C-4549-2008 RID C-5719-2008

A study of neutral-current four-fermion processes is performed using a data sample corresponding to 55.3 pb(-1) of integrated luminosity collected by the L3 detector at LEP at an average centre-of-mass energy of 183 GeV. The neutral-current four-fermion cross sections for final slates with a pair of charged leptons plus jets and with four charged leptons are measured to be consistent with the Standard Model predictions. Events with fermion pair masses close to the Z boson mass are selected in all observable final states and the ZZ production cross section is measured to be sigma ZZ = 0.30(-0.16-0.03)(+0.22 + 0.07) pb, in agreement with the Standard Model expectation. No evidence for the existence of anomalous triple gauge boson ZZZ and ZZ gamma couplings is found and limits on these couplings are set. (C) 1999 Elsevier Science B.V. All rights reserved

Measurement of W-pair cross sections in e(+)e(-) interactions at root s = 183 GeV and W-decay branching fractions

We report on the measurement of W-boson pair-production with the L3 detector at LEP, In a data sample corresponding to a total luminosity of 55.47 pb(-1) collected at an average centre-of-mass energy of 182.68 GeV, we select 824 four-fermion events with pairs of hadronic jets or pairs of leptons with high invariant masses. Branching fractions of W decays into different fermion-antifermion pairs are determined, Assuming charged-current lepton universality, the branching fraction for hadronic W decays is measured to be: B(W --> hadrons) = 70.1 +/- 1.3(stat.) +/- 0.4(syst.) %. Combining all final states the total cross section for W-pair production is measured to be: sigma(WW) = 16.53 +/- 0.67(stat.) +/- 0.26(syst.) pb. (C) 1998 Elsevier Science B.V, All rights reserved