Background
Chronic constipation (CC) is a common and severe gastrointestinal complaint in Parkinson's disease (PD), but its pathogenesis remains poorly understood. This study evaluated functionally ...distinct submucosal neurons in relation to colonic motility and anorectal function in PD patients with constipation (PD/CC) vs both CC and controls.
Methods
Twenty‐nine PD/CC and 10 Rome III‐defined CC patients were enrolled. Twenty asymptomatic age‐sex matched subjects served as controls. Colonic transit time measurement and conventional anorectal manometry were evaluated in PD/CC and CC patients. Colonoscopy was performed in all three groups. Colonic submucosal whole mounts from PD/CC, CC, and controls were processed for immunohistochemistry with antibodies for vasoactive intestinal polypeptide (VIP) and peripheral choline acetyltransferase, markers for functionally distinct submucosal neurons. The mRNA expression of VIP and its receptors were also assessed.
Key Results
Four subgroups of PD/CC patients were identified: delayed colonic transit plus altered anorectal manometry (65%); delayed colonic transit (13%); altered manometric pattern (13%); and no transit and manometric impairment (9%). There were no differences in the number of neurons/ganglion between PD/CC vs CC or vs controls. A reduced number of submucosal neurons containing VIP immunoreactivity was found in PD/CC vs controls (P<.05). VIP, VIPR1, and VIPR2 mRNA expression was significantly reduced in PD/CC vs CC and controls (P<.05).
Conclusions and Inferences
Colonic motor and rectal sensory functions are impaired in most PD/CC patients. These abnormalities are associated with a decreased VIP expression in submucosal neurons. Both sensory‐motor abnormalities and neurally mediated motor and secretory mechanisms are likely to contribute to PD/CC pathophysiology.
Chronic constipation is usually a severe gastrointestinal dysfunction in patients with Parkinson's disease, but its pathogenesis remains poorly understood. This study evaluated functionally distinct submucosal neurons in relation to colonic motility and anorectal function in PD patients with constipation (PD/CC) vs both CC and controls.
Colonic motor and rectal sensory functions resulted impaired in most parkinsonian constipated patients. Compared with controls, they display a decreased number of submucosal secretomotor neurons containing VIP immunoreactivity accompanied by a reduced mRNA expression of VIP and VIP receptors.
The main challenge in the management of indeterminate incidentally discovered adrenal tumours is to differentiate benign from malignant lesions. In the absence of clear signs of invasion or ...metastases, imaging techniques do not always precisely define the nature of the mass. The present pilot study aimed to determine whether radiomics may predict malignancy in adrenocortical tumours.
CT images in unenhanced, arterial, and venous phases from 19 patients who had undergone resection of adrenocortical tumours and a cohort who had undergone surveillance for at least 5 years for incidentalomas were reviewed. A volume of interest was drawn for each lesion using dedicated software, and, for each phase, first-order (histogram) and second-order (grey-level colour matrix and run-length matrix) radiological features were extracted. Data were revised by an unsupervised machine learning approach using the K-means clustering technique.
Of operated patients, nine had non-functional adenoma and 10 carcinoma. There were 11 patients in the surveillance group. Two first-order features in unenhanced CT and one in arterial CT, and 14 second-order parameters in unenhanced and venous CT and 10 second-order features in arterial CT, were able to differentiate adrenocortical carcinoma from adenoma (P < 0.050). After excluding two malignant outliers, the unsupervised machine learning approach correctly predicted malignancy in seven of eight adrenocortical carcinomas in all phases.
Radiomics with CT texture analysis was able to discriminate malignant from benign adrenocortical tumours, even by an unsupervised machine learning approach, in nearly all patients.
Pelvic floor rehabilitation is frequently recommended for defecation disorders, in both constipation and fecal incontinence. However, the lack of patient selection, together with the variety of ...rehabilitation methods and protocols, often jeopardize the results of this approach, causing difficulty in evaluating outcomes and addressing proper management, and above all, in obtaining scientific evidence for the efficacy of these methods for specific indications. The authors represent different gastroenterological and surgical scientific societies in Italy, and their aim was to identify the indications and agree on treatment protocols for pelvic floor rehabilitation of patients with defecation disorders. This was achieved by means of a modified Delphi method, utilizing a working team (10 members) which developed the statements and a consensus group (15 members, different from the previous ones) which voted twice also suggesting modifications of the statements.
Background
Achalasia is a rare motility disorder characterized by myenteric neuron and interstitial cells of Cajal (ICC) abnormalities leading to deranged/absent peristalsis and lack of relaxation of ...the lower esophageal sphincter. The mechanisms contributing to neuronal and ICC changes in achalasia are only partially understood. Our goal was to identify novel molecular features occurring in patients with primary achalasia.
Methods
Esophageal full‐thickness biopsies from 42 (22 females; age range: 16‐82 years) clinically, radiologically, and manometrically characterized patients with primary achalasia were examined and compared to those obtained from 10 subjects (controls) undergoing surgery for uncomplicated esophageal cancer (or upper stomach disorders). Tissue RNA extracted from biopsies of cases and controls was used for library preparation and sequencing. Data analysis was performed with the “edgeR” option of R‐Bioconductor. Data were validated by real‐time RT‐PCR, western blotting and immunohistochemistry.
Key Results
Quantitative transcriptome evaluation and cluster analysis revealed 111 differentially expressed genes, with a P ≤ 10−3. Nine genes with a P ≤ 10−4 were further validated. CYR61, CTGF, c‐KIT, DUSP5, EGR1 were downregulated, whereas AKAP6 and INPP4B were upregulated in patients vs controls. Compared to controls, immunohistochemical analysis revealed a clear increase in INPP4B, whereas c‐KIT immunolabeling resulted downregulated. As INPP4B regulates Akt pathway, we used western blot to show that phospho‐Akt was significantly reduced in achalasia patients vs controls.
Conclusions & Inferences
The identification of altered gene expression, including INPP4B, a regulator of the Akt pathway, highlights novel signaling pathways involved in the neuronal and ICC changes underlying primary achalasia.
Primary achalasia is a disorder due to neuronal defects supplying the esophagus leading to altered peristalsis and lack of sphincter relaxation. Nonetheless, the molecular mechanisms involved in this condition are poorly understood.
Transcriptomic analysis of achalasic tissues identified a dysregulated expression of different genes, in particular c‐KIT (downregulated) and INPP4B (upregulated), the latter being linked to Akt pathway regulation.
Our results unravel novel signaling pathways involved in the neuronal and interstitial cells of Cajal abnormalities in primary achalasia.
The aim of this work is to report the effect of the solvent polarity on the adsorption of CdSe quantum dots (QDots) over the surface of TiO2 nanotubes and the influence of the coverage gained on the ...efficiency of photoanodes based on these materials. Particularly, it is shown that the amount of QDots adsorbed on TiO2 nanotubes can be tuned by using solvent mixtures of different polarity and volume ratios. An increase on QDots coverage was found when the polarity increases. What is noticeable is that the photoanode efficiency increased at a higher rate than the QDots coverage. For instance, a two-fold increase of coverage at a 50% acetone – 50% toluene ratio induces up to a seven-fold increase of the photocurrent values with respect to those obtained when the adsorption is performed from toluene. This effect is explained in terms of a different distribution of QDots along the nanotube walls depending on the solvent polarity used for the adsorption.
•Higher coverage of nanotubes with Qdots achieved by increasing solvent polarity.•Qdots coat nanotubes further along the length when adsorbed from polar solvents.•Photoanode efficiency increases more than expected by enhancing Qdots adsorbed.
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