1,333 research outputs found
Chronic constipation: improved understanding offers a new therapeutic approach
No full textThe author currently receives funding from The Dunhill Medical Trust; The Research into Ageing Fund, set up and managed by Age UK; the BBSRC (Case award with GlaxoSmithKline); and Takeda pharmaceuticals
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GJ 3929: High-precision Photometric and Doppler Characterization of an Exo-Venus and Its Hot, Mini-Neptune-mass Companion
No full textWe detail the follow-up and characterization of a transiting exo-Venus identified by TESS, GJ 3929b (TOI-2013b), and its nontransiting companion planet, GJ 3929c (TOI-2013c). GJ 3929b is an Earth-sized exoplanet in its star’s Venus zone (P b = 2.616272 ± 0.000005 days; Sb = 17.3 − 0.7 + 0.8 S ⊕) orbiting a nearby M dwarf. GJ 3929c is most likely a nontransiting sub-Neptune. Using the new, ultraprecise NEID spectrometer on the WIYN 3.5 m Telescope at Kitt Peak National Observatory, we are able to modify the mass constraints of planet b reported in previous works and consequently improve the significance of the mass measurement to almost 4σ confidence (M b = 1.75 ± 0.45 M ⊕). We further adjust the orbital period of planet c from its alias at 14.30 ± 0.03 days to the likely true period of 15.04 ± 0.03 days, and we adjust its minimum mass to m sin i = 5.71 ± 0.92 M ⊕. Using the diffuser-assisted ARCTIC imager on the ARC 3.5 m telescope at Apache Point Observatory, in addition to publicly available TESS and LCOGT photometry, we are able to constrain the radius of planet b to R p = 1.09 ± 0.04 R ⊕. GJ 3929b is a top candidate for transmission spectroscopy in its size regime (TSM = 14 ± 4), and future atmospheric studies of GJ 3929b stand to shed light on the nature of small planets orbiting M dwarfs. © 2022. The Author(s). Published by the American Astronomical Society.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
Why is motilin active in some studies with mice, rats, and guinea pigs, but not in others? Implications for functional variability among rodents
No full textThe Optimization of the Performance Management for Operators in GJ Company Xiamen
No full text本文以绩效管理的基本理论和GJ厦门厂的实际情况为基础，分析了GJ厦门厂一线作业员绩效管理的问题点，并结合公司目前的实际情况提出一线作业员的绩效管理改善方案。该方案以平衡计分卡的绩效管理体系为逻辑，将公司的战略目标分解到制造处，再分解至一线作业员，让作业员的绩效也能从财务面、客户面、内部运营面、学习成长面四个维度上对公司的战略发展起到支撑作用，以促进组织战略目标的实现。 在绩效管理改进方案中，作者特别强调沟通在绩效管理过程中的重要作用，它贯穿了绩效管理的整个过程。沟通有助于促进员工个人绩效的提升和员工个人的成长，从而提升组织的整体效益。 根据GJ厦门厂的实际情况，将一线作业员的绩效考核结...In this paper, operators’ performance management problems in GJ Company are analyzed based on the basic theory of performance management and the real situation of the company. The author propose to break down the company’s strategic targets to lower levels with balanced scorecard system by four levels of financial, customer, internal operation, learning and developing. So that operators’ performa...学位：管理学硕士院系专业：管理学院_工商管理硕士(工商管理硕士)学号：1792012115103
The human colon: Evidence for degenerative changes during aging and the physiological consequences.
No full textBACKGROUND: The incidence of constipation increases among the elderly (>65 years), while abdominal pain decreases. Causes include changes in lifestyle (e.g., diet and reduced exercise), disease and medications affecting gastrointestinal functions. Degenerative changes may also occur within the colo-rectum. However, most evidence is from rodents, animals with relatively high rates of metabolism and accelerated aging, with considerable variation in time course. In humans, cellular and non-cellular changes in the aging intestine are poorly investigated. PURPOSE: To examine all available studies which reported the effects of aging on cellular and tissue functions of human isolated colon, noting the region studied, sex and age of tissue donors and study size. The focus on human colon reflects the ability to access full-thickness tissue over a wide age range, compared with other gastrointestinal regions. Details are important because of natural human variability. We found age-related changes within the muscle, in the enteric and nociceptor innervation, and in the submucosa. Some involve all regions of colon, but the ascending colon appears more vulnerable. Changes can be cell- and sublayer-dependent. Mechanisms are unclear but may include development of "senescent-like" and associated inflammaging, perhaps associated with increased mucosal permeability to harmful luminal contents. In summary, reduced nociceptor innervation can explain diminished abdominal pain among the elderly. Degenerative changes within the colon wall may have little impact on symptoms and colonic functions, because of high "functional reserve," but are likely to facilitate the development of constipation during age-related challenges (e.g., lifestyle, disease, and medications), now operating against a reduced functional reserve
The Ageing of the Human Lower Bowel
No full textOlder people suffer a greater number of disorders of the gastrointestinal tract, including chronic constipation and faecal incontinence. In this review, we examine the age-related degenerative changes that have been identified in the lower bowel of humans. Firstly, older individuals may experience less abdominal pain and a lower incidence of gut-brain disorders that are defined partly by abdominal pain (e.g., irritable bowel syndrome); the causes are unclear. Secondly, an age-dependent reduction in mucosal barrier functions may follow a decline in intestinal stem cell activity, a reduced density of tight junction proteins linking epithelial cells and a decline in mucus layer thickness. This allows antigenic and toxic material to enter the wall of the colon. Thirdly, degenerative changes within the wall of the colon occur in both the ascending and descending regions, but the ascending colon appears most vulnerable. Here, there is reduced cholinergic neuromuscular function (potentially reducing colonic motility), perhaps because of dysfunctional nerve axon transport, and associated senescence-like activity. These changes lower the ‘intestinal reserve’, that is the capacity of neuromuscular functions to absorb other ‘life events’ that affect bowel motility (e.g., changes in lifestyle or eating habits, medications that affect neuromuscular functions and diseases such as diverticulosis) without generating symptoms such as constipation. When combined, symptoms are more likely to develop
Investigational drug therapies for the treatment of gastroparesis
No full textIntroduction: Gastroparesis is defined by nausea, vomiting, pain, early satiety and bloating, and characterized by delayed gastric emptying without obvious structural abnormalities. Metoclopramide is widely used, increasing gastric emptying and inhibiting nausea and vomiting. Other drugs are available in certain countries and some are used ‘off-label’ because they increase gastric emptying or inhibit emesis. However, correlation between gastroparesis symptoms and rates of gastric emptying is poor. For anti-emetic drugs, dose-ranging and Phase III trials in gastroparesis are lacking.
Areas covered: Gastric motility may still be disordered, leading to nausea, even though gastric emptying is unchanged. One hypothesis is that interstitial cells of Cajal (ICC) are damaged by diabetes leading to gastric dysrhythmia and nausea. Novel approaches to treatment of nausea also include the use of ghrelin receptor agonists, highlighting a link between appetite and nausea.
Expert opinion: There is an urgent need to diversify away from historical drug targets. In particular, there is a need to control nausea by regulating ICC functions and/or by facilitating appetite via ghrelin receptor agonists. It is also important to note that different upper gastrointestinal disorders (gastroparesis, chronic unexplained nausea and vomiting, functional dyspepsia) are difficult to distinguish apart, suggesting wider therapeutic opportunity
Review article: An analysis of the pharmacological rationale for selecting drugs to inhibit vomiting or increase gastric emptying during treatment of gastroparesis.
No full textBACKGROUND: Drugs which can inhibit nausea/vomiting and/or increase gastric emptying are used to treat gastroparesis, mostly 'off-label'. Within each category, they act at different targets and modulate different physiological mechanisms. AIMS: Address the questions: In gastroparesis, why should blocking one pathway causing vomiting, be more appropriate than another? Why might increasing gastric emptying via one mechanism be more appropriate than another? METHODS: Drugs used clinically were identified via consensus opinions and reviews, excluding the poorly characterised. Their pharmacology was defined, mapped to mechanisms influencing vomiting and gastric emptying, and rationale developed for therapeutic use. RESULTS: Vomiting: Rationale for 5-HT3 , D2 , H1 or muscarinic antagonists, and mirtazapine, amitriptyline, nortriptyline, are poor. Arguments for inhibiting central consequences of vagal afferent transmission by NK1 antagonism are complicated by doubts over effects on nausea. Gastric emptying: Confusion emerges because of side-effects of drugs increasing gastric emptying: Metoclopramide (5-HT4 agonist, D2 and 5-HT3 antagonist; also blocks some emetic stimuli and causes tardive dyskinesia) and Erythromycin (high-efficacy motilin agonist, requiring low doses to minimise side-effects). Limited trials with selective 5-HT4 agonists indicate variable efficacy. CONCLUSIONS: Several drug classes inhibiting vomiting have no scientific rationale. NK1 antagonism has rationale but complicated by limited efficacy against nausea. Studies must resolve variable efficacy of selective 5-HT4 agonists and apparent superiority over motilin agonists. Overall, lack of robust activity indicates a need for novel approaches targeting nausea (e.g., modulating gastric pacemaker or vagal activity, use of receptor agonists or new targets such as GDF15) and objective assessments of nausea
Age-related decline in goblet cell numbers and mucin content of the human colon: Implications for lower bowel functions in the elderly.
No full textBACKGROUND & AIMS: Older people experience a greater incidence of lower bowel disorders, including constipation. Causes can include factors associated with growing older, such as use of medications or disease, but compounded by degenerative changes within the bowel wall. It has been suggested that the latter is exacerbated by loss of an effective mucosal barrier to luminal contents. In human colon, little is known about the impact of ageing on key components of this barrier, namely the goblet cells and mucin content. METHODS: Changes in the number of goblet cells and density of mucin content were investigated in macroscopically normal human ascending (AC; n = 13) and descending (DC; n = 14) colon from elderly (≥ 67 years) and younger adults (60 years and below). Samples were serially sectioned and stained for haematoxylin and eosin to assess tissue morphology, and alcian blue periodic acid Schiff (ABPAS) and MUC-2 antibody to identify goblet cells producing mucins. New procedures in visualization and identification of goblet cells and mucin contents were employed to ensure unbiased counting and densitometric analysis. RESULTS: Compared with the younger adults, the numbers of goblet cells per crypt were significantly lower in the elderly AC (72 ± 1.2 vs 51 ± 0.5) and DC (75 ± 2.6 vs. 54 ± 1.9), although this reduction did not reach statistical significance when assessed per mucosal area (AC: P = 0.068; DC: P = 0.096). In both regions from the elderly, numerous empty vesicles (normally containing mucins) were observed, and some areas of epithelium were devoid of goblet cells. Thus, the density of mucin content per unit mucosal area were significantly reduced with age. CONCLUSIONS: Ageing could result in a reduced number of goblet cells and development of degenerative changes in mucin production. Together, these have implications for the mucus barrier function in the colon of elderly individuals
Gastrointestinal pharmacology: challenges ahead
No full textThis is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credite
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