Metformin use in pregnancy: promises and uncertainties

Metformin has been prescribed in pregnancy for over 40 years; for much of this time, use has been limited both in numbers and geographically, and the evidence base has been confined to observational studies. In early years, perceived safety concerns and lack of availability of the drug in many countries acted as a barrier to use. More recently, RCTs have begun to examine the role of metformin in pregnancy in much-needed detail. However, this evidence base has been interpreted differently in different countries, leading to very wide variation in its current application in pregnancy. In this short review, we will discuss the history of metformin in pregnancy and highlight some of the key clinical trials. We will then consider some of the remaining controversies associated with metformin use in pregnancy, most important of these being the potential for long-term ‘programming’ effects on the fetus as a result of metformin being able to cross the placenta. We will also consider clinical situations where metformin might be avoided. Finally, we will discuss some future directions for this drug as it reaches its sixtieth anniversary

Impact of ambient oxygen on the surface structure of α-Cr2O3(0001)

Surface x-ray diffraction has been employed to quantitatively assess the surface structure of α-Cr2O3(0001) as a function of oxygen partial pressure at room temperature. In ultrahigh vacuum, the surface is found to exhibit a partially occupied double layer of chromium atoms. At an oxygen partial pressure of 1×10−2 mbar, the surface is determined to be terminated by chromyl species (CrO), clearly demonstrating that the presence of oxygen can significantly influence the structure of α-Cr2O3(0001)

The Rab5 Effector Rabankyrin-5 Regulates and Coordinates Different Endocytic Mechanisms

The small GTPase Rab5 is a key regulator of clathrin-mediated endocytosis. On early endosomes, within a spatially restricted domain enriched in phosphatydilinositol-3-phosphate [PI(3)P], Rab5 coordinates a complex network of effectors that functionally cooperate in membrane tethering, fusion, and organelle motility. Here we discovered a novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity. In addition to early endosomes, however, Rabankyrin-5 localises to large vacuolar structures that correspond to macropinosomes in epithelial cells and fibroblasts. Overexpression of Rabankyrin-5 increases the number of macropinosomes and stimulates fluid-phase uptake, whereas its downregulation inhibits these processes. In polarised epithelial cells, this function is primarily restricted to the apical membrane. Rabankyrin-5 localises to large pinocytic structures underneath the apical surface of kidney proximal tubule cells, and its overexpression in polarised Madin-Darby canine kidney cells stimulates apical but not basolateral, non-clathrin-mediated pinocytosis. In demonstrating a regulatory role in endosome fusion and (macro)pinocytosis, our studies suggest that Rab5 regulates and coordinates different endocytic mechanisms through its effector Rabankyrin-5. Furthermore, its active role in apical pinocytosis in epithelial cells suggests an important function of Rabankyrin-5 in the physiology of polarised cells

Sizing the association between lifestyle behaviours and fatness in a large, heterogeneous sample of youth of multiple ethnicities from 4 countries

Background:&nbsp;The magnitude of the relationship between lifestyle risk factors for obesity and adiposity is not clear.&nbsp;The aim of this study was to clarify this in order to determine the level of importance of lifestyle factors in obesity&nbsp;aetiology.Methods: A cross-sectional analysis was carried out on data on youth who were not trying to change weight&nbsp;(n = 5714), aged 12 to 22 years and from 8 ethnic groups living in New Zealand, Australia, Fiji and Tonga.&nbsp;Demographic and lifestyle data were measured by questionnaires. Fatness was measured by body mass index (BMI),&nbsp;BMI z-score and bioimpedance analysis, which was used to estimate percent body fat and total fat mass (TFM).&nbsp;Associations between lifestyle and body composition variables were examined using linear regression and forest plots.Results: TV watching was positively related to fatness in a dose-dependent manner. Strong, dose-dependent&nbsp;associations were observed between fatness and soft drink consumption (positive relationship), breakfast consumption&nbsp;(inverse relationship) and after-school physical activity (inverse relationship). Breakfast consumption-fatness associations&nbsp;varied in size across ethnic groups. Lifestyle risk factors for obesity were associated with percentage differences in body&nbsp;composition variables that were greatest for TFM and smallest for BMI.Conclusions: Lifestyle factors were most strongly related to TFM, which suggests that studies that use BMI alone to&nbsp;quantify fatness underestimate the full effect of lifestyle on adiposity. This study clarifies the size of lifestyle-fatness&nbsp;relationships observed in previous studies.</div

Energy Neutral Activity Monitoring:Wearables Powered by Smart Inductive Charging Surfaces

Wearable technologies play a key role in the shift of traditional healthcare services towards eHealth and self-monitoring. Maintenance overheads, such as regular battery recharging, impose a limitation on the applicability of such technologies in some groups of the population. In this paper, we propose an activity monitoring system that is based on wearable sensors that are powered by textile inductive charging surfaces. By strategically positioning these surfaces on pieces of furniture that are routinely used, the system passively charges the wearable sensor whilst the user is present. As a proof-of-concept example, experiments conducted on a prototype implementation of the system suggest that 36 minutes of daily desktop computer usage are on average sufficient to maintain a wearable sensor energy neutral

Risk of cardiovascular disease and total mortality in adults with type 1 diabetes: Scottish registry linkage study

&lt;p&gt;Background: Randomized controlled trials have shown the importance of tight glucose control in type 1 diabetes (T1DM), but few recent studies have evaluated the risk of cardiovascular disease (CVD) and all-cause mortality among adults with T1DM. We evaluated these risks in adults with T1DM compared with the non-diabetic population in a nationwide study from Scotland and examined control of CVD risk factors in those with T1DM.&lt;/p&gt; &lt;p&gt;Methods and Findings: The Scottish Care Information-Diabetes Collaboration database was used to identify all people registered with T1DM and aged ≥20 years in 2005–2007 and to provide risk factor data. Major CVD events and deaths were obtained from the national hospital admissions database and death register. The age-adjusted incidence rate ratio (IRR) for CVD and mortality in T1DM (n = 21,789) versus the non-diabetic population (3.96 million) was estimated using Poisson regression. The age-adjusted IRR for first CVD event associated with T1DM versus the non-diabetic population was higher in women (3.0: 95% CI 2.4–3.8, p&#60;0.001) than men (2.3: 2.0–2.7, p&#60;0.001) while the IRR for all-cause mortality associated with T1DM was comparable at 2.6 (2.2–3.0, p&#60;0.001) in men and 2.7 (2.2–3.4, p&#60;0.001) in women. Between 2005–2007, among individuals with T1DM, 34 of 123 deaths among 10,173 who were &#60;40 years and 37 of 907 deaths among 12,739 who were ≥40 years had an underlying cause of death of coma or diabetic ketoacidosis. Among individuals 60–69 years, approximately three extra deaths per 100 per year occurred among men with T1DM (28.51/1,000 person years at risk), and two per 100 per year for women (17.99/1,000 person years at risk). 28% of those with T1DM were current smokers, 13% achieved target HbA1c of &#60;7% and 37% had very poor (≥9%) glycaemic control. Among those aged ≥40, 37% had blood pressures above even conservative targets (≥140/90 mmHg) and 39% of those ≥40 years were not on a statin. Although many of these risk factors were comparable to those previously reported in other developed countries, CVD and mortality rates may not be generalizable to other countries. Limitations included lack of information on the specific insulin therapy used.&lt;/p&gt; &lt;p&gt;Conclusions: Although the relative risks for CVD and total mortality associated with T1DM in this population have declined relative to earlier studies, T1DM continues to be associated with higher CVD and death rates than the non-diabetic population. Risk factor management should be improved to further reduce risk but better treatment approaches for achieving good glycaemic control are badly needed.&lt;/p&gt

Carbon Fiber Insoles Enhance Perception of Performance Despite Variable Objective Outcomes: Specific to the Moderately Active Individual

International Journal of Exercise Science 16(4): 885-897, 2023. Carbon fiber insoles (CFIs) may benefit performance in elite athletes, however, their use in moderately active individuals has been adopted without evidence supporting such enhancements in this population. Fifteen male subjects performed vertical jump (VJ) and repeat treadmill sprint tests before and after a VO2peak while wearing 1) CFIs and 2) control insoles (CON). Subjects completed a subjective survey regarding their perceived performance abilities for both conditions. There were no significant differences between CFIs and CON in VJ height, sprint distance, heart rate following sprints; and rate of oxygen consumption, perceived fatigue, and perceived exertion at 85% of maximal speed (p \u3e 0.05) during the VO2peak. At maximal speed, although there was no difference between conditions in peak rate of oxygen consumption (95%CI [-4.85, 0.21]) and respiratory exchange ratio (95%CI [-0.01, 0.03]), CFIs resulted in a reduced level of perceived fatigue (95%CI [-1, 0]) and perceived exertion (95%CI [-2, 0]) compared to CON. Subjects subjectively reported increased feelings of “propulsion or explosiveness” (p = 0.026) and being able to “perform better while jumping” (p = 0.029) while wearing CFIs. Heightened perceptions of performance enhancements when wearing CFIs indicate, in the moderately active, perceptual benefits could be more influential for determining CFI use

Serum Zinc Correlates with Parent- and Teacher-Rated Inattention in Children with Attention-Deficit/Hyperactivity Disorder

Objective: The aim of this study was to explore the relationship of zinc nutrition to the severity of attentiondeficit/ hyperactivity disorder (ADHD) symptoms in a middle-class American sample with well-diagnosed ADHD. Previous reports of zinc in ADHD, including two positive clinical trials of supplementation, have come mainly from countries and cultures with different diets and/or socioeconomic realities. Method: Children 5–10 years of age with DISC- and clinician-diagnosed ADHD had serum zinc determinations and parent and teacher ratings of ADHD symptoms. Zinc levels were correlated (Pearson’s and multiple regression) with ADHD symptom ratings. Results: Forty-eight children (37 boys, 11 girls; 33 combined type, 15 inattentive) had serum zinc levels with a median/mode at the lowest 30% of the laboratory reference range; 44 children also had parent/teacher ratings. Serum magnesium levels were normal. Nutritional intake by a parent-answered food frequency questionnaire was unremarkable. Serum zinc correlated at r = -0.45 (p = 0.004) with parent-teacher-rated inattention, even after controlling for gender, age, income, and diagnostic subtype, but only at r = -0.20 (p = 0.22) with CPT omission errors. In contrast, correlation with parent-teacher-rated hyperactivity-impulsivity was nonsignificant in the opposite direction. Conclusion: These findings add to accumulating evidence for a possible role of zinc in ADHD, even for middle-class Americans, and, for the first time, suggest a special relationship to inattentive symptoms. They do not establish either that zinc deficiency causes ADHD nor that ADHD should be treated with zinc. Hypothesis-testing clinical trials are needed

Multi-instrument comparison and compilation of non-methane organic gas emissions from biomass burning and implications for smoke-derived secondary organic aerosol precursors

Multiple trace-gas instruments were deployed during the fourth Fire Lab at Missoula Experiment (FLAME- 4), including the first application of proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOFMS) and comprehensive two-dimensional gas chromatography-time-offlight mass spectrometry (GC×GC-TOFMS) for laboratory biomass burning (BB) measurements. Open-path Fourier transform infrared spectroscopy (OP-FTIR) was also deployed, as well as whole-air sampling (WAS) with onedimensional gas chromatography-mass spectrometry (GCMS) analysis. This combination of instruments provided an unprecedented level of detection and chemical speciation. The chemical composition and emission factors (EFs) determined by these four analytical techniques were compared for four representative fuels. The results demonstrate that the instruments are highly complementary, with each covering some unique and important ranges of compositional space, thus demonstrating the need for multi-instrument approaches to adequately characterize BB smoke emissions. Emission factors for overlapping compounds generally compared within experimental uncertainty, despite some outliers, including monoterpenes. Data from all measurements were synthesized into a single EF database that includes over 500 non-methane organic gases (NMOGs) to provide a comprehensive picture of speciated, gaseous BB emissions. The identified compounds were assessed as a function of volatility; 6-11% of the total NMOG EF was associated with intermediate-volatility organic compounds (IVOCs). These atmospherically relevant compounds historically have been unresolved in BB smoke measurements and thus are largely missing from emission inventories. Additionally, the identified compounds were screened for published secondary organic aerosol (SOA) yields. Of the total reactive carbon (defined as EF scaled by the OH rate constant and carbon number of each compound) in the BB emissions, 55-77% was associated with compounds for which SOA yields are unknown or understudied. The best candidates for future smog chamber experiments were identified based on the relative abundance and ubiquity of the understudied compounds, and they included furfural, 2-methyl furan, 2-furan methanol, and 1,3- cyclopentadiene. Laboratory study of these compounds will facilitate future modeling efforts