In eukaryotic cells, about one-third of the synthesized proteins are translocated into the endoplasmic reticulum; they are membrane or lumen resident proteins and proteins direct to the Golgi ...apparatus. The co-translational translocation takes place through the heterotrimeric protein-conducting channel Sec61 which is associated with the ribosome and many accessory components, such as the heterotetrameric translocon-associated protein (TRAP) complex. Recently, microscopic techniques, such as cryo-electron microscopy and cryo-electron tomography, have enabled the determination of the translocation machinery structure. However, at present, there is a lack of understanding regarding the roles of some of its components; indeed, the TRAP complex function during co-translational translocation needs to be established. In addition, TRAP may play a role during unfolded protein response, endoplasmic-reticulum-associated protein degradation and congenital disorder of glycosylation (ssr4 CDG). In this article, I describe the current understanding of the TRAP complex in the light of its possible function(s).
Context: Gastric emptying (GE) is a major determinant of postprandial glycemia. Because the presence of fat in the small intestine inhibits GE, ingestion of fat may attenuate the glycemic response to ...carbohydrate.
Objective: The objective of this study was to evaluate the effect of patterns of fat consumption on GE and glucose, insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) concentrations after a carbohydrate meal in type 2 diabetes.
Design: This was a randomized, cross-over study in which GE of a radioisotopically labeled potato meal was measured on 3 d.
Setting: The study was performed at the Royal Adelaide Hospital.
Patients: Six males with type 2 diabetes were studied.
Intervention: Subjects ingested 1) 30 ml water 30 min before the mashed potato (water), 2) 30 ml olive oil 30 min before the mashed potato (oil), or 3) 30 ml water 30 min before the mashed potato meal that contained 30 ml olive oil (water and oil).
Main Outcome Measures: GE, blood glucose, plasma insulin, GLP-1, and GIP concentrations were the main outcome measures.
Results: GE was much slower with oil compared with both water (P < 0.0001) and water and oil (P < 0.05) and was slower after water and oil compared with water (P < 0.01). The postprandial rise in blood glucose was markedly delayed (P = 0.03), and peak glucose occurred later (P = 0.04) with oil compared with the two other meals. The rises in insulin and GIP were attenuated (P < 0.0001), whereas the GLP-1 response was greater (P = 0.0001), after oil.
Conclusions: Ingestion of fat before a carbohydrate meal markedly slows GE and attenuates the postprandial rises in glucose, insulin, and GIP, but stimulates GLP-1, in type 2 diabetes.
it Tre dei sei ospedali medievali di Sciacca furono fondati da esponenti del ceto mercantile e nobiliare catalano e valenzano trapiantato in Sicilia. Questo dato permette di mostrare il ruolo svolto ...dalle famiglie iberiche a Sciacca. Attraverso lo studio dei testamenti, in cui oltre ai legati pro anima, veniva disposta la fondazione di chiese, monasteri e strutture assistenziali, il saggio ricostruisce le espressioni della sensibilità religiosa e devozionale di queste famiglie, soffermandosi, in particolar modo, sull’istituzione dei tre ospedali e sulle diverse forme di carità praticate.
The COVID-19 pandemic propelled immunology into global news and social media, resulting in the potential for misinterpreting and misusing complex scientific concepts.
To study the extent to which ...immunology is discussed in news articles and YouTube videos in English and Italian, and if related scientific concepts are used to support specific political or ideological narratives in the context of COVID-19.
In English and Italian we searched the period 11/09/2019 to 11/09/2022 on YouTube, using the software Mozdeh, for videos mentioning COVID-19 and one of nine immunological concepts: antibody-dependent enhancement, anergy, cytokine storm, herd immunity, hygiene hypothesis, immunity debt, original antigenic sin, oxidative stress and viral interference. We repeated this using MediaCloud for news articles.Four samples of 200 articles/videos were obtained from the randomised data gathered and analysed for mentions of concepts, stance on vaccines, masks, lockdown, social distancing, and political signifiers.
Vaccine-negative information was higher in videos than news (8-fold in English, 6-fold in Italian) and higher in Italian than English (4-fold in news, 3-fold in videos). We also observed the existence of information bubbles, where a negative stance towards one intervention was associated with a negative stance to other linked ideas. Some immunological concepts (immunity debt, viral interference, anergy and original antigenic sin) were associated with anti-vaccine or anti-NPI (non-pharmacological intervention) views. Videos in English mentioned politics more frequently than those in Italian and, in all media and languages, politics was more frequently mentioned in anti-guidelines and anti-vaccine media by a factor of 3 in video and of 3-5 in news.
There is evidence that some immunological concepts are used to provide credibility to specific narratives and ideological views. The existence of information bubbles supports the concept of the "rabbit hole" effect, where interest in unconventional views/media leads to ever more extreme algorithmic recommendations.
Predictors of Delayed Gastric Emptying in Diabetes
Karen L. Jones , PHD ,
Antonietta Russo , MSC ,
Julie E. Stevens , BSC ,
Judith M. Wishart , BSC ,
Melanie K. Berry , B MED RAD and
Michael Horowitz ..., PHD
Department of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, Australia
Abstract
OBJECTIVE —To define the predictors of the rate of gastric emptying in patients with diabetes.
RESEARCH DESIGN AND METHODS —A total of 101 outpatients with diabetes (79 type 1 and 22 type 2) underwent measurements of gastric emptying of a solid/liquid
meal (scintigraphy), upper gastrointestinal symptoms (questionnaire), glycemic control (blood glucose concentrations during
gastric emptying measurement), and autonomic nerve function (cardiovascular reflexes).
RESULTS —The gastric emptying of solid and/or liquid was delayed in 66 (65%) patients. Solid (retention at 100 min 64 ± 3.2 vs. 50.2
± 3.6%, P < 0.005) and liquid (retention at 100 min 22.7 ± 1.7 vs. 16.0 ± 1.8%, P < 0.001) gastric emptying was slower in women than in men. Of all upper gastrointestinal symptoms (including nausea and vomiting),
only abdominal bloating/fullness was associated with slower gastric emptying ( P < 0.005). A multiple regression analysis demonstrated that both abdominal bloating/fullness and female sex were predictors
of slower gastric emptying of both solids and liquids.
CONCLUSIONS —We conclude that the presence of abdominal bloating/fullness but not any other upper gastrointestinal symptom is associated
with diabetic gastroparesis and that gastric emptying is slower in diabetic women than in diabetic men.
T50, time taken for 50% of the liquid to empty
Footnotes
Address correspondence and reprint requests to Dr. Karen Jones, Department Medicine, University of Adelaide, Royal Adelaide
Hospital, North Terrace, Adelaide, South Australia, 5000, Australia. E-mail: karen.jones{at}adelaide.edu.au .
Received for publication 24 October 2000 and accepted in revised form 16 March 2001.
M.H. is a member of an advisory board for Janssen-Cilag Australia and has received honoraria from Janssen Pharmaceutical/Janssen-Cilag.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
The herbal preparation Iberogast has been reported to improve upper abdominal symptoms in functional dyspepsia (FD) and to decrease fundic tone, increase antral contractility, and decrease afferent ...nerve sensitivity in experimental animals. The effects of Iberogast on the human gastrointestinal tract have not been evaluated.
We investigated the effects of oral control and Iberogast, each administered as a single dose (1.1 mL), in a double-blind randomized fashion, on proximal gastric volume (part A), antropyloroduodenal motility (part B), and gastric emptying and intragastric distribution of a solid/liquid meal (part C) for 120 minutes, in nine (part A), 12 (part B), and eight (part C) healthy men.
Iberogast increased proximal gastric volume (max volume; control 104+/-12 mL, Iberogast 174+/-23 mL, P<0.05) (part A), increased the motility index of antral pressure waves in the first 60 minutes (P<0.05) without affecting pyloric or duodenal pressures (part B), and slightly increased the retention of liquid in the total stomach between 10 and 50 minutes (P<0.01), but had no effect on gastric emptying of solids or intragastric distribution (part C).
Iberogast affects gastric motility in humans, probably in a region-dependent manner. The stimulation of gastric relaxation and antral motility may contribute to the reported therapeutic efficacy of Iberogast in FD.
Delayed gastric emptying occurs frequently in critically ill patients and has the potential to adversely affect both the rate, and extent, of nutrient absorption. However, there is limited ...information about nutrient absorption in the critically ill, and the relationship between gastric emptying (GE) and absorption has hitherto not been evaluated. The aim of this study was to quantify glucose absorption and the relationships between GE, glucose absorption and glycaemia in critically ill patients.
Studies were performed in nineteen mechanically-ventilated critically ill patients and compared to nineteen healthy subjects. Following 4 hours fasting, 100 ml of Ensure, 2 g 3-O-methyl glucose (3-OMG) and 99mTc sulphur colloid were infused into the stomach over 5 minutes. Glucose absorption (plasma 3-OMG), blood glucose levels and GE (scintigraphy) were measured over four hours. Data are mean +/- SEM. A P-value < 0.05 was considered significant.
Absorption of 3-OMG was markedly reduced in patients (AUC240: 26.2 +/- 18.4 vs. 66.6 +/- 16.8; P < 0.001; peak: 0.17 +/- 0.12 vs. 0.37 +/- 0.098 mMol/l; P < 0.001; time to peak; 151 +/- 84 vs. 89 +/- 33 minutes; P = 0.007); and both the baseline (8.0 +/- 2.1 vs. 5.6 +/- 0.23 mMol/l; P < 0.001) and peak (10.0 +/- 2.2 vs. 7.7 +/- 0.2 mMol/l; P < 0.001) blood glucose levels were higher in patients; compared to healthy subjects. In patients; 3-OMG absorption was directly related to GE (AUC240; r = -0.77 to -0.87; P < 0.001; peak concentrations; r = -0.75 to -0.81; P = 0.001; time to peak; r = 0.89-0.94; P < 0.001); but when GE was normal (percent retention240 < 10%; n = 9) absorption was still impaired. GE was inversely related to baseline blood glucose, such that elevated levels were associated with slower GE (ret 60, 180 and 240 minutes: r > 0.51; P < 0.05).
In critically ill patients; (i) the rate and extent of glucose absorption are markedly reduced; (ii) GE is a major determinant of the rate of absorption, but does not fully account for the extent of impaired absorption; (iii) blood glucose concentration could be one of a number of factors affecting GE.
Some practitioners advocate hyperbaric oxygen (HBO2) for sequelae following brain injury. This study assessed recruitment, tolerance and safety in preparation for a randomized clinical trial.
...Prospective, open-label feasibility study.
Hyperbaric medicine department of a tertiary academic hospital.
Participatory adult outpatients with problems from stroke (n=22), anoxia (13) or trauma (28) that occurred at least 12 months before enrollment, without contraindications to HBO2. Sixty-three participants enrolled in the study (21 females,42 males). Age was 45 +/- 16 years (18-76) and time from injury was 6.9 +/- 7.1 years (1.0-29.3). Fifty-three completed the study intervention, and 55 completed the assessment battery.
PARTICIPANTS underwent 60 daily HBO2 sessions (1.5 atm abs, 100% oxygen, 60 minutes). Assessments were conducted at baseline, after the HBO2 course, and six months later.
The prime outcome was feasibility. To estimate the immediate and long-term effects of HBO2, we assessed neuropsychological measures, questionnaires, neurologic exam and physical functioning measures. Some participants also had pre- and post-HBO2 speech evaluation (n=27) and neuroimaging (n=17).
The study met our a priori definition for feasibility for recruitment, but 44% required additional time to complete the 60 sessions (up to 105 days). HBO2-related adverse events were rare and not serious. Although many participants reported improvement in symptoms (51% memory, 51% attention/concentration, 48% balance/coordination, 45% endurance, 20% sleep) post-HBO2, and 93% reported that they would participate in the study again, no standardized testing showed clinically important improvement. In the small subset of those undergoing neuroimaging, apparent improvement was observed in auditory functional MRI (8/13), MR spectroscopy (9/17) and brain perfusionby CT angiography (5/9).
Conducting an HBO2 clinical trial in this population was feasible. Although many participants reported improvement, the lack of concurrent controls limits the strength of inferences from this trial, especially considering lack of change in standardized testing. The clinical relevance of neuroimaging changes is unknown. The findings of this study may indicate a need for caution when considering the broad application of HBO2 more than one year after brain injury due to stroke, severe TBI and anoxia, until there is more compelling evidence from carefully designed sham-controlled, blinded clinical trials.
Developmental DNA elimination in Paramecium tetraurelia occurs through a trans-nuclear comparison of the genomes of two distinct types of nuclei: the germline micronucleus (MIC) and the somatic ...macronucleus (MAC). During sexual reproduction, which starts with meiosis of the germline nuclei, MIC-limited sequences including Internal Eliminated Sequences (IESs) and transposons are eliminated from the developing MAC in a process guided by noncoding RNAs (scnRNAs and iesRNAs). However, our current understanding of this mechanism is still very limited. Therefore, studying both genetic and epigenetic aspects of these processes is a crucial step to understand this phenomenon in more detail. Here, we describe the involvement of homologs of classical meiotic proteins, Spo11, Msh4-1, and Msh5 in this phenomenon. Based on our analyses, we propose that proper functioning of Spo11, Msh4-1, and Msh5 during Paramecium sexual reproduction are necessary for genome reorganization and viable progeny. Also, we show that double-strand breaks (DSBs) in DNA induced during meiosis by Spo11 are crucial for proper IESs excision. In summary, our investigations show that early sexual reproduction processes may significantly influence later somatic genome integrity.
•SPO11, MSH4-1 and MSH5 knockdowns affect DNA elimination.•SPO11, MSH4-1 and MSH5 knockdowns cause slight reduction of scnRNA and significant reduction of iesRNAs.•No apparent morphological effect on meiosis and mitosis•Spo11 induces double-strand breaks (DSBs) during meiosis which are essential for further IES excision.
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