Gastrointestinal neuromuscular disease: methodological and ontological issues in histopathological analysis

The term gastrointestinal neuromuscular disease comprises a heterogeneous group of chronic conditions associated with impaired bowel motility. Gastrointestinal motor dysfunctions, differening for etiopathogenic mechanisms, pathologic lesions, and region of gut involvement (e.g., irritable bowel syndrome, slow transit constipation, inflammatory bowel disease, diverticular disease), represent a relevant matter for public health: in fact, they are very common, can be disabling, and induce major social and economic burdens. These motor disturbances are presumed or proven to arise as a result of dysfunctional enteric neuromuscular apparatus set up by myenteric ganglionic cells, interstitial cells of Cajal and smooth muscle cells of the muscularis propria. Despite the presence of intestinal dysmotility in the clinical phenotype of these patients, scarce attention has been paid to the morphological arrangements of the enteric neuromuscular apparatus. Furthermore, standards for histopathological reports remain relatively neglected resulting in significant differences in applied methodologies which confound the reliable delineation of normality and, as a consequence, the specificity of particular pathological changes for disease. Thus, in order to overcome the lack or heterogeneity of current data, to get normative data and delineation of abnormality, careful morphological examinations and development of standardized procedures are particularly required in the field of gastrointestinal neuromuscular pathology, as recently suggested

The clinical effectiveness of an integrated multidisciplinary evidence-based program to prevent intraoperative pressure injuries in high-risk children undergoing long-duration surgical procedures: a quality improvement study

The prevention of hospital-acquired pressure injuries (HAPIs) in children undergoing long-duration surgical procedures is of critical importance due to the potential for catastrophic sequelae of these generally preventable injuries for the child and their family. Long-duration surgical procedures in children have the potential to result in high rates of HAPI due to physiological factors and the difficulty or impossibility of repositioning these patients intraoperatively. We developed and implemented a multi-modal, multi-disciplinary translational HAPI prevention quality improvement program at a large European Paediatric University Teaching Hospital. The intervention comprised the establishment of wound prevention teams, modified HAPI risk assessment tools, specific education, and the use of prophylactic dressings and fluidized positioners during long-duration surgical procedures. As part of the evaluation of the effectiveness of the program in reducing intraoperative HAPI, we conducted a prospective cohort study of 200 children undergoing long-duration surgical procedures and compared their outcomes with a matched historical cohort of 200 children who had undergone similar surgery the previous year. The findings demonstrated a reduction in HAPI in the intervention cohort of 80% (p < 0.01) compared to the comparator group when controlling for age, pathology, comorbidity, and surgical duration. We believe that the findings demonstrate that it is possible to significantly decrease HAPI incidence in these highly vulnerable children by using an evidence-based, multi-modal, multidisciplinary HAPI prevention strategy

Effects of Extreme Dilutions of Preparations on Gene Expression Profiles of Human Cells

Gene expression analysis has been employed in the past to test the effects of high dilutions on cell systems. However, most of the previous studies were restricted to the investigation of few dilutions, making it difficult to explore underlying mechanisms of action. Using whole-genome transcriptomic analysis, we investigated the effects of a wide range of Apis mellifica dilutions on gene expression profiles of human cells. RWPE-1 cells, a nonneoplastic adult human epithelial prostate cell line, were exposed to Apis mellifica preparations (3C, 5C, 7C, 9C, 12C, 15C, and 30C) or to the reference solvent solutions for 24 hours; nonexposed cells were also checked for gene expression variations. Our results showed that even the most diluted solutions retained the ability to trigger significant variations in gene expression. Gene pathway analysis revealed consistent variations in gene expression induced by Apis mellifica when compared to nonexposed reference cells but not to reference solvent solutions. Since the effects of Apis Mellifica at extreme dilutions did not show dose–effect relationships, the biological or functional interpretation of these results remains uncertain

Integration between orthodox medicine, homeopathy and acupuncture for inpatients: Three years experience in the first hospital for Integrated Medicine in Italy

The hospital in Pitigliano (Tuscany) is the first hospital in Italy to put into practice a model of Integrated Medicine. This clinical setting caters for the use of complementary medicine (homeopathy and acupuncture (針灸 zhēn jiǔ)) alongside orthodox therapies (conventional medicine). The therapeutic model implicates doctors who are experts in complementary and alternative medicine (CAM; 補充與替代醫學 bǔ chōng yǔ tì dài yī xué) and the rest of the hospital personnel working together as equals. This contribution explains the difficulties, critical aspects and potential of this innovative setting. The clinical setting for Integrated Medicine was evaluated in part through observation and in part through the analysis of approval questionnaires. The writers of the questionnaires were the orthodox medical personnel and the hospital patients. The project is still evolving today in spite of the initial partial contrariety of some doctors in the hospital and some external doctors in the area. However, it can already be considered a positive experience, as confirmed by the high approval gained from many health workers and most of the hospital patients. Moreover, the follow-up carried out through specific surgeries dedicated to CAM is extremely positive. Up to now 532 inpatients suffering from acute illnesses, relapse of a chronic illness or neurological or orthopaedic rehabilitation following strokes, brain haemorrhage, neurological illness or limb prosthesis operations have been treated. This work has tried to illustrate the innovative and positive experience for the Italian public health authorities so that it may also be useful to anyone who would like to promote similar initiatives within its public health Institution

Collision tumors: A diagnostic challenge

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The sieve-element endoplasmic reticulum: A focal point of phytoplasma-host plant interaction?

The rough endoplasmic reticulum (r-ER) is of paramount importance for adaptive responses to biotic stresses due to an increased demand for de novo synthesis of immunity-related proteins and signaling components. In nucleate cells, disturbance of r-ER integrity and functionality leads to the “unfolded protein response” (UPR), which is an important component of innate plant immune signalling. In contrast to an abundance of reports on r-ER responses to biotic challenges, sieve-element endoplasmic reticulum (SE-ER) responses to phytoplasma infection have not been investigated. We found that morphological SE-ER changes, associated with phytoplasma infection, are accompanied by differential expression of genes encoding proteins involved in shaping and anchoring the reticulum. Phytoplasma infection also triggers an increased release of bZIP signals from the (SE-ER)/r-ER and consequent differential expression of UPR-related genes. The modified expression patterns seem to reflect a trade-off between survival of host cells, needed for the phytoplasmic biotrophic lifestyle, and phytoplasmas. Specialized plasmodesmata between sieve element and companion cell may provide a corridor for transfer of phytoplasma effectors inducing UPR-related gene expression in companion cells

Thyroid dysfunction in megalin deficient mice

Megalin mediates transcytosis of thyroglobulin (Tg), the thyroid hormone precursor, resulting in its passage into the bloodstream. The process involves especially hormone-poor Tg, which may favour hormone secretion by preventing competition with hormone-rich Tg for proteolytic degradation. To gain more insight into the role of megalin, here we studied thyroid function and histology in megalin deficient mice compared with WT mice. As expected from the knowledge that megalin mediates Tg transcytosis, serum Tg levels were significantly reduced in homozygous (megalin-/-) mice, which, more importantly, were found to be hypothyroid, as demonstrated by significantly reduced serum free thyroxine and significantly increased serum thyroid stimulating hormone (TSH) levels. In heterozygous (megalin+/-) mice, in which megalin expression was normal, thyroid function was unaffected. Although the serological phenotype in megalin-/- mice was not associated with histological alterations or goiter, our results support a major role of megalin in thyroid hormone secretion

TSH-Dependent Expression of the LDL Receptor-Associated Protein (RAP) in Thyroid Epithelial Cells

The low density lipoprotein (LDL) receptor-associated protein (RAP) is an endoplasmic reticulum (ER)-resident molecular chaperone for several LDL receptor family members and it also binds to thyroglobulin (Tg), the thyroid hormone precursor. Disruption of the RAP gene in thyrocytes results in impaired Tg secretion. To gain further insights into the function of RAP in the thyroid, we investigated whether its expression in thyrocytes is regulated by thyroid-stimulating hormone (TSH), a feature common to all proteins involved in thyroid hormone secretion. We found by immunofluorescence that in FRTL-5 cells cultured in the presence of TSH, RAP is expressed intracellularly. The levels of expression increased after exposure to TSH, beginning at 48 hours, in a concentration-dependent manner as observed by immunofluorescence and Western blotting. Expression of RAP was also increased by TSH in primary cultures of human thyrocytes as observed by Western blotting. In hypothyroid mice with high serum TSH, RAP was markedly increased compared with euthyroid mice as observed by immunohistochemistry and Western blotting. Based on these findings, we concluded that RAP is expressed by thyrocytes in a TSH-dependent manner, both in cultured thyroid cells and in vivo