Little is known about the capacity, mechanisms, or timing of growth in beta-cell mass in humans. We sought to establish if the predominant expansion of beta-cell mass in humans occurs in early ...childhood and if, as in rodents, this coincides with relatively abundant beta-cell replication. We also sought to establish if there is a secondary growth in beta-cell mass coincident with the accelerated somatic growth in adolescence.
To address these questions, pancreas volume was determined from abdominal computer tomographies in 135 children aged 4 weeks to 20 years, and morphometric analyses were performed in human pancreatic tissue obtained at autopsy from 46 children aged 2 weeks to 21 years.
We report that 1) beta-cell mass expands by severalfold from birth to adulthood, 2) islets grow in size rather than in number during this transition, 3) the relative rate of beta-cell growth is highest in infancy and gradually declines thereafter to adulthood with no secondary accelerated growth phase during adolescence, 4) beta-cell mass (and presumably growth) is highly variable between individuals, and 5) a high rate of beta-cell replication is coincident with the major postnatal expansion of beta-cell mass.
These data imply that regulation of beta-cell replication during infancy plays a major role in beta-cell mass in adult humans.
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•Mass transfer of gas-liquid Taylor flow in milli channels is analysed.•Small scale convection by Taylor vortices in the liquid slugs plays a key role.•Periodical nature of liquid ...mass transfer is directly linked to global transfer rate.•kLa is proportional to circulation frequency in liquid slugs in most conditions.•Influence of flow behavior at T-mixer on the concentration patterns is discussed.
The results of the recent experimental work performed by Butler et al. (2016, 2018) are analysed based on the dominant phenomena: (i) small scale convection by means of Taylor vortices in the liquid slugs and (ii) diffusion in lubrication film. A main result shown here is that the Taylor circulation frequency is able to reflect the global mass transfer rate in gas-liquid Taylor flow through an almost linear relationship, which emphasizes the interest of the circulating motion in the slug, and gives a very simple correlation to predict the kLa value (at large Schmidt number). A mechanism of flow behavior during the bubble formation at the T-mixer is proposed as a possible explanation of unexpected concentration areas (called “islands”). However, despite of these unusual concentration field structures in these cases, the mass transfer rate coefficient kLa is still accurately predicted by the Taylor circulation frequency in the slug.
Type 2 diabetes (T2DM) is characterized by insulin resistance, defective insulin secretion, loss of β-cell mass with increased β-cell apoptosis and islet amyloid. The islet amyloid is derived from ...islet amyloid polypeptide (IAPP, amylin), a protein coexpressed and cosecreted with insulin by pancreatic β-cells. In common with other amyloidogenic proteins, IAPP has the propensity to form membrane permeant toxic oligomers. Accumulating evidence suggests that these toxic oligomers, rather than the extracellular amyloid form of these proteins, are responsible for loss of neurons in neurodegenerative diseases. In this review we discuss emerging evidence to suggest that formation of intracellular IAPP oligomers may contribute to β-cell loss in T2DM. The accumulated evidence permits the amyloid hypothesis originally developed for neurodegenerative diseases to be reformulated as the toxic oligomer hypothesis. However, as in neurodegenerative diseases, it remains unclear exactly why amyloidogenic proteins form oligomers in vivo, what their exact structure is, and to what extent these oligomers play a primary or secondary role in the cytotoxicity in what are now often called unfolded protein diseases.
Iron limits primary productivity in vast regions of the ocean. Given that marine phytoplankton contribute up to 40% of global biological carbon fixation, it is important to understand what parameters ...control the availability of iron (iron bioavailability) to these organisms. Most studies on iron bioavailability have focused on the role of siderophores; however, eukaryotic phytoplankton do not produce or release siderophores. Here, we report on the pivotal role of saccharides—which may act like an organic ligand—in enhancing iron bioavailability to a Southern Ocean cultured diatom, a prymnesiophyte, as well as to natural populations of eukaryotic phytoplankton. Addition of a monosaccharide (>2 nM of glucuronic acid, GLU) to natural planktonic assemblages from both the polar front and subantarctic zones resulted in an increase in iron bioavailability for eukaryotic phytoplankton, relative to bacterioplankton. The enhanced iron bioavailability observed for several groups of eukaryotic phytoplankton (i.e., cultured and natural populations) using three saccharides, suggests it is a common phenomenon. Increased iron bioavailability resulted from the combination of saccharides forming highly bioavailable organic associations with iron and increasing iron solubility, mainly as colloidal iron. As saccharides are ubiquitous, present at nanomolar to micromolar concentrations, and produced by biota in surface waters, they also satisfy the prerequisites to be important constituents of the poorly defined "ligand soup," known to weakly bind iron. Our findings point to an additional type of organic ligand, controlling iron bioavailability to eukaryotic phytoplankton—a key unknown in iron biogeochemistry.
Point-of-care testing of C-reactive protein (CRP) may be a way to reduce unnecessary use of antibiotics without harming patients who have acute exacerbations of chronic obstructive pulmonary disease ...(COPD).
We performed a multicenter, open-label, randomized, controlled trial involving patients with a diagnosis of COPD in their primary care clinical record who consulted a clinician at 1 of 86 general medical practices in England and Wales for an acute exacerbation of COPD. The patients were assigned to receive usual care guided by CRP point-of-care testing (CRP-guided group) or usual care alone (usual-care group). The primary outcomes were patient-reported use of antibiotics for acute exacerbations of COPD within 4 weeks after randomization (to show superiority) and COPD-related health status at 2 weeks after randomization, as measured by the Clinical COPD Questionnaire, a 10-item scale with scores ranging from 0 (very good COPD health status) to 6 (extremely poor COPD health status) (to show noninferiority).
A total of 653 patients underwent randomization. Fewer patients in the CRP-guided group reported antibiotic use than in the usual-care group (57.0% vs. 77.4%; adjusted odds ratio, 0.31; 95% confidence interval CI, 0.20 to 0.47). The adjusted mean difference in the total score on the Clinical COPD Questionnaire at 2 weeks was -0.19 points (two-sided 90% CI, -0.33 to -0.05) in favor of the CRP-guided group. The antibiotic prescribing decisions made by clinicians at the initial consultation were ascertained for all but 1 patient, and antibiotic prescriptions issued over the first 4 weeks of follow-up were ascertained for 96.9% of the patients. A lower percentage of patients in the CRP-guided group than in the usual-care group received an antibiotic prescription at the initial consultation (47.7% vs. 69.7%, for a difference of 22.0 percentage points; adjusted odds ratio, 0.31; 95% CI, 0.21 to 0.45) and during the first 4 weeks of follow-up (59.1% vs. 79.7%, for a difference of 20.6 percentage points; adjusted odds ratio, 0.30; 95% CI, 0.20 to 0.46). Two patients in the usual-care group died within 4 weeks after randomization from causes considered by the investigators to be unrelated to trial participation.
CRP-guided prescribing of antibiotics for exacerbations of COPD in primary care clinics resulted in a lower percentage of patients who reported antibiotic use and who received antibiotic prescriptions from clinicians, with no evidence of harm. (Funded by the National Institute for Health Research Health Technology Assessment Program; PACE Current Controlled Trials number, ISRCTN24346473.).
Abstract Objectives: To better understand reasons for antibiotics being prescribed for sore throats despite well known evidence that they are generally of little help. Design: Qualitative study with ...semi-structured interviews. Setting: General practices in South Wales. Subjects: 21 general practitioners and 17 of their patients who had recently consulted for a sore throat or upper respiratory tract infection. Main outcome measures: Subjects' experience of management of the illness, patients' expectations, beliefs about antibiotic treatment for sore throats, and ideas for reducing prescribing. Results: Doctors knew of the evidence for marginal effectiveness yet often prescribed for good relationships with patients. Possible patient benefit outweighed theoretical community risk from resistant bacteria. Most doctors found prescribing “against the evidence” uncomfortable and realised this probably increased workload. Explanations of the distinction between virus and bacterium often led to perceived confusion. Clinicians were divided on the value of leaflets and national campaigns, but several favoured patient empowerment for self care by other members of the primary care team. Patient expectations were seldom made explicit, and many were not met. A third of patients had a clear expectation for antibiotics, and mothers were more likely to accept non-antibiotic treatment for their children than for themselves. Satisfaction was not necessarily related to receiving antibiotics, with many seeking reassurance, further information, and pain relief. Conclusions: This prescribing decision is greatly influenced by considerations of the doctor-patient relationship. Consulting strategies that make patient expectations explicit without damaging relationships might reduce unwanted antibiotics. Repeating evidence for lack of effectiveness is unlikely to change doctors' prescribing, but information about risk to individual patients might. Emphasising positive aspects of non-antibiotic treatment and lack of efficacy in general might be helpful.
There remains public misconception about antibiotic use and resistance. Preschool children are at particular risk of receiving unnecessary antibiotics because they commonly present in primary care ...and many childhood infections are self-limiting.
The aim of our study was to explore parents' perceptions and understanding of antibiotic use and resistance in the context of their young child with an acute respiratory tract infection (RTI) and to explore strategies parents would find acceptable to minimize antibiotic resistance for their families.
Semi-structured interviews were conducted with 23 parents of preschool children who recently had an acute RTI across greater Oxfordshire, UK (2016-17 winter). We explored their beliefs about antibiotics, understanding of antibiotic resistance and views on current public antibiotic awareness campaigns at the time. Thematic analysis was used to analyse the data.
Parents had a sense of optimism and considered their families to be at low risk of antibiotic resistance because their families were 'low users' of antibiotics. Very few parents considered antibiotic resistance as a possible harm of antibiotics. Parents thought they were acting morally responsibly by following campaign messages. They wanted future campaigns to have a relevant, accessible message for families about the impact of antibiotic resistance.
Future communication about the potential impact of unnecessary antibiotic use and antibiotic resistance needs to focus on outcomes that parents of young children can relate to (e.g. infection recurrence) and in a format that parents will engage with (e.g. face-to-face dissemination at playgroups and parent/child community events) to make a more informed decision about the risks and benefits of antibiotics for their child.
This paper investigated the mackinawite (FeS)-associated products formed during reaction between FeS and carbon tetrachloride (CT) at pH 7 and 8. At pH 8, reaction of FeS with CT led to formation of ...abundant spherical particles with diameters between 50 and 400 nm on the FeS surface and in solution; far fewer such particles were observed at pH 7. Analysis of the FeS surface by energy dispersive X-ray spectroscopy after reaction with CT at pH 8 showed decreased sulfur and elevated oxygen compared to unreacted FeS. The spherical particles that formed upon FeS reaction with CT were mostly amorphous with localized areas of poorly crystalline two-line ferrihydrite. X-ray photoelectron spectroscopy indicated that the predominant Fe surface species after reaction with CT at pH 8 was Fe(III)O, consistent with ferrihydrite and other amorphous iron (hydr)oxides as major products. Powder X-ray diffraction analysis suggested formation of greigite upon reaction of FeS with CT at pH 7. Both ferrihydrite and Fe2+, which is a product of greigite dissolution, can react with dissolved HS– to form FeS, suggesting that, after oxidation by chlorinated aliphatics, FeS can be regenerated by addition or microbial generation of sulfide.
The islet in type 2 diabetes (T2D) is characterized by amyloid deposits derived from islet amyloid polypeptide (IAPP), a protein co-expressed with insulin by β-cells. In common with amyloidogenic ...proteins implicated in neurodegeneration, human IAPP (hIAPP) forms membrane permeant toxic oligomers implicated in misfolded protein stress. Here, we establish that hIAPP misfolded protein stress activates HIF1α/PFKFB3 signaling, this increases glycolysis disengaged from oxidative phosphorylation with mitochondrial fragmentation and perinuclear clustering, considered a protective posture against increased cytosolic Ca
characteristic of toxic oligomer stress. In contrast to tissues with the capacity to regenerate, β-cells in adult humans are minimally replicative, and therefore fail to execute the second pro-regenerative phase of the HIF1α/PFKFB3 injury pathway. Instead, β-cells in T2D remain trapped in the pro-survival first phase of the HIF1α injury repair response with metabolism and the mitochondrial network adapted to slow the rate of cell attrition at the expense of β-cell function.
The NASA Langley Research Center (LaRC) airborne High Spectral Resolution Lidar (HSRL) on the NASA B200 aircraft has acquired extensive datasets of aerosol extinction (532 nm), aerosol optical depth ...(AOD) (532 nm), backscatter (532 and 1064 nm), and depolarization (532 and 1064 nm) profiles during 18 field missions that have been conducted over North America since 2006. The lidar measurements of aerosol intensive parameters (lidar ratio, depolarization, backscatter color ratio, and spectral depolarization ratio) are shown to vary with location and aerosol type. A methodology based on observations of known aerosol types is used to qualitatively classify the extensive set of HSRL aerosol measurements into eight separate types. Several examples are presented showing how the aerosol intensive parameters vary with aerosol type and how these aerosols are classified according to this new methodology. The HSRL-based classification reveals vertical variability of aerosol types during the NASA ARCTAS field experiment conducted over Alaska and northwest Canada during 2008. In two examples derived from flights conducted during ARCTAS, the HSRL classification of biomass burning smoke is shown to be consistent with aerosol types derived from coincident airborne in situ measurements of particle size and composition. The HSRL retrievals of AOD and inferences of aerosol types are used to apportion AOD to aerosol type; results of this analysis are shown for several experiments.
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