Changes in the gastric enteric nervous system and muscle: A case report on two patients with diabetic gastroparesis

<p>Abstract</p> <p>Background</p> <p>The pathophysiological basis of diabetic gastroparesis is poorly understood, in large part due to the almost complete lack of data on neuropathological and molecular changes in the stomachs of patients. Experimental models indicate various lesions affecting the vagus, muscle, enteric neurons, interstitial cells of Cajal (ICC) or other cellular components. The aim of this study was to use modern analytical methods to determine morphological and molecular changes in the gastric wall in patients with diabetic gastroparesis.</p> <p>Methods</p> <p>Full thickness gastric biopsies were obtained laparoscopically from two gastroparetic patients undergoing surgical intervention and from disease-free areas of control subjects undergoing other forms of gastric surgery. Samples were processed for histological and immunohistochemical examination.</p> <p>Results</p> <p>Although both patients had severe refractory symptoms with malnutrition, requiring the placement of a gastric stimulator, one of them had no significant abnormalities as compared with controls. This patient had an abrupt onset of symptoms with a relatively short duration of diabetes that was well controlled. By contrast, the other patient had long standing brittle and poorly controlled diabetes with numerous episodes of diabetic ketoacidosis and frequent hypoglycemic episodes. Histological examination in this patient revealed increased fibrosis in the muscle layers as well as significantly fewer nerve fibers and myenteric neurons as assessed by PGP9.5 staining. Further, significant reduction was seen in staining for neuronal nitric oxide synthase, heme oxygenase-2, tyrosine hydroxylase as well as for c-KIT.</p> <p>Conclusion</p> <p>We conclude that poor metabolic control is associated with significant pathological changes in the gastric wall that affect all major components including muscle, neurons and ICC. Severe symptoms can occur in the absence of these changes, however and may reflect vagal, central or hormonal influences. Gastroparesis is therefore likely to be a heterogeneous disorder. Careful molecular and pathological analysis may allow more precise phenotypic differentiation and shed insight into the underlying mechanisms as well as identify novel therapeutic targets.</p

Concurrent system programming with effect handlers

© Springer International Publishing AG, part of Springer Nature 2018. Algebraic effects and their handlers have been steadily gaining attention as a programming language feature for composably expressing user-defined computational effects. While several prototype implementations of languages incorporating algebraic effects exist, Multicore OCaml incorporates effect handlers as the primary means of expressing concurrency in the language. In this paper, we make the observation that effect handlers can elegantly express particularly difficult programs that combine system programming and concurrency without compromising performance. Our experimental results on a highly concurrent and scalable web server demonstrate that effect handlers perform on par with highly optimised monadic concurrency libraries, while retaining the simplicity of direct-style code

The Neuropeptide PDF Acts Directly on Evening Pacemaker Neurons to Regulate Multiple Features of Circadian Behavior

Animals use distinct sets of clock neurons to time behaviors in the morning and evening. In this article, the direct neural targets for morning neurons and the neuropeptide pigment dispersing factor are revealed in the fruit fly

Large cell neuroendocrine lung carcinoma: consensus statement from The British Thoracic Oncology Group and the Association of Pulmonary Pathologists

Over the past 10 years, lung cancer clinical and translational research has been characterised by exponential progress, exemplified by the introduction of molecularly targeted therapies, immunotherapy and chemo-immunotherapy combinations to stage III and IV non-small cell lung cancer. Along with squamous and small cell lung cancers, large cell neuroendocrine carcinoma (LCNEC) now represents an area of unmet need, particularly hampered by the lack of an encompassing pathological definition that can facilitate real-world and clinical trial progress. The steps we have proposed in this article represent an iterative and rational path forward towards clinical breakthroughs that can be modelled on success in other lung cancer pathologies

Breathing adapted radiotherapy: a 4D gating software for lung cancer

<p>Abstract</p> <p>Purpose</p> <p>Physiological respiratory motion of tumors growing in the lung can be corrected with respiratory gating when treated with radiotherapy (RT). The optimal respiratory phase for beam-on may be assessed with a respiratory phase optimizer (RPO), a 4D image processing software developed with this purpose.</p> <p>Methods and Materials</p> <p>Fourteen patients with lung cancer were included in the study. Every patient underwent a 4D-CT providing ten datasets of ten phases of the respiratory cycle (0-100% of the cycle). We defined two morphological parameters for comparison of 4D-CT images in different respiratory phases: tumor-volume to lung-volume ratio and tumor-to-spinal cord distance. The RPO automatized the calculations (200 per patient) of these parameters for each phase of the respiratory cycle allowing to determine the optimal interval for RT.</p> <p>Results</p> <p>Lower lobe lung tumors not attached to the diaphragm presented with the largest motion with breathing. Maximum inspiration was considered the optimal phase for treatment in 4 patients (28.6%). In 7 patients (50%), however, the RPO showed a most favorable volumetric and spatial configuration in phases other than maximum inspiration. In 2 cases (14.4%) the RPO showed no benefit from gating. This tool was not conclusive in only one case.</p> <p>Conclusions</p> <p>The RPO software presented in this study can help to determine the optimal respiratory phase for gated RT based on a few simple morphological parameters. Easy to apply in daily routine, it may be a useful tool for selecting patients who might benefit from breathing adapted RT.</p

"May I Buy a Pack of Marlboros, Please?" A Systematic Review of Evidence to Improve the Validity and Impact of Youth Undercover Buy Inspections

Most smokers become addicted to tobacco products before they are legally able to pur- chase these products. We systematically reviewed the literature on protocols to assess underage purchase and their ecological validity. We conducted a systematic search in May 2015 in PubMed and PsycINFO. We independently screened records for inclusion. We con- ducted a narrative review and examined implications of two types of legal authority for proto- cols that govern underage buy enforcement in the United States: criminal (state-level laws prohibiting sales to youth) and administrative (federal regulations prohibiting sales to youth). Ten studies experimentally assessed underage buy protocols and 44 studies assessed the association between youth characteristics and tobacco sales. Protocols that mimicked real-world youth behaviors were consistently associated with substantially greater likelihood of a sale to a youth. Many of the tested protocols appear to be designed for compliance with criminal law rather than administrative enforcement in ways that limited ecological validity. This may be due to concerns about entrapment. For administrative enforcement in particular, entrapment may be less of an issue than commonly thought. Commonly used underage buy protocols poorly represent the reality of youths' access to tobacco from retailers. Compliance check programs should allow youth to present them- selves naturally and attempt to match the community’s demographic makeup

Angiographically borderline left main coronary artery lesions: correlation of transthoracic doppler echocardiography and intravascular ultrasound: a pilot study

<p>Abstract</p> <p>Background</p> <p>the clinical decision making could be difficult in patients with borderline lesions (visually assessed stenosis severity of 30 to 50%) of the left main coronary artery (LM). The aim of the study was to evaluate the relationship between transthoracic Doppler (TTDE) peak diastolic flow velocity (PDV) and intravascular ultrasound (IVUS) measurements in the assessment of angiographically borderline LM lesions.</p> <p>Methods</p> <p>27 patients (mean age 64 ± 8 years, 21 males) with borderline LM stenosis referred for IVUS examination were included in the study. We performed standard IVUS with minimal lumen area (MLA) and plaque burden (PB) measurement and routine quantitative coronary angiography (QCA) with diameter stenosis (%DS) and area stenosis (%AS) assessment in all. During TTDE, resting PDV was measured in the LM.</p> <p>Results</p> <p>interpretable Doppler signal could be obtained in 24 patients (88% feasibility); therefore these patients entered the final analysis. MLA was 7.1 ± 2.7 mm². TTDE measured PDV correlated significantly with IVUS-derived MLA (r = -0.46, p < 0.05) and plaque burden (r = 0.51, p < 0.05). Using a velocity cut-off of 112 cm/sec TTDE showed a 92% sensitivity and 62% specificity to identify IVUS-significant (MLA < 6 mm²) LM stenosis.</p> <p>Conclusion</p> <p>In angiographically borderline LM disease, resting PDV from transthoracic echocardiography is increased in presence of increased plaque burden by IVUS. TTDE evaluation might be a useful adjunct to other invasive and non-invasive methods in the assessment of borderline LM lesions. Further, large scale studies are needed to establish the exact cut-off value of PDV for routine clinical application.</p