Summary Familial gastric cancer comprises at least three major syndromes: hereditary diffuse gastric cancer, gastric adenocarcinoma and proximal polyposis of the stomach, and familial intestinal ...gastric cancer. The risk of development of gastric cancer is high in families affected b-y these syndromes, but only hereditary diffuse gastric cancer is genetically explained (caused by germline alterations of CDH1 , which encodes E-cadherin). Gastric cancer is also associated with a range of several cancer-associated syndromes with known genetic causes, such as Lynch, Li-Fraumeni, Peutz-Jeghers, hereditary breast–ovarian cancer syndromes, familial adenomatous polyposis, and juvenile polyposis. We present contemporary knowledge on the genetics, pathogenesis, and clinical features of familial gastric cancer, and discuss research and technological developments, which together are expected to open avenues for new genetic testing approaches and novel therapeutic strategies.
E-cadherin and P-cadherin are major contributors to cell–cell adhesion in epithelial tissues, playing pivotal roles in important morphogenetic and differentiation processes during development, and in ...maintaining integrity and homeostasis in adult tissues. It is now generally accepted that alterations in these two molecules are observed during tumour progression of most carcinomas. Genetic or epigenetic alterations in E- and P-cadherin-encoding genes (CDH1 and CDH3, respectively), or alterations in their proteins expression, often result in tissue disorder, cellular de-differentiation, increased invasiveness of tumour cells and ultimately in metastasis. In this review, we will discuss the major properties of E- and P-cadherin molecules, its regulation in normal tissue, and their alterations and role in cancer, with a specific focus on gastric and breast cancer models.
Ocean warming and acidification threaten the future growth of coral reefs. This is because the calcifying coral reef taxa that construct the calcium carbonate frameworks and cement the reef together ...are highly sensitive to ocean warming and acidification. However, the global-scale effects of ocean warming and acidification on rates of coral reef net carbonate production remain poorly constrained despite a wealth of studies assessing their effects on the calcification of individual organisms. Here, we present global estimates of projected future changes in coral reef net carbonate production under ocean warming and acidification. We apply a meta-analysis of responses of coral reef taxa calcification and bioerosion rates to predicted changes in coral cover driven by climate change to estimate the net carbonate production rates of 183 reefs worldwide by 2050 and 2100. We forecast mean global reef net carbonate production under representative concentration pathways (RCP) 2.6, 4.5, and 8.5 will decline by 76, 149, and 156%, respectively, by 2100. While 63% of reefs are projected to continue to accrete by 2100 under RCP2.6, 94% will be eroding by 2050 under RCP8.5, and no reefs will continue to accrete at rates matching projected sea level rise under RCP4.5 or 8.5 by 2100. Projected reduced coral cover due to bleaching events predominately drives these declines rather than the direct physiological impacts of ocean warming and acidification on calcification or bioerosion. Presently degraded reefs were also more sensitive in our analysis. These findings highlight the low likelihood that the world's coral reefs will maintain their functional roles without near-term stabilization of atmospheric CO
emissions.
Anorectal malformations are one of the most frequent congenital malformations treated by pediatric surgeons. In low‐income countries, the surgical and anesthetic management of children in need of ...these procedures can be challenging. Limited oxygen supply, lack of equipment, especially pediatric, and intensive care units make the use of regional anesthesia appealing. We present a series of four cases of anorectal malformations corrections in Guinea Bissau, in children up to 13 months of age, under regional anesthesia and sedation with ketodex, a mixture of ketamine and dexmedetomidine (in a proportion of 1 mg to 1 μg). No child developed respiratory depression requiring airway intervention or supplemental oxygen, or had hemodynamic instability.
The pediatric difficult airway is a challenge for the anesthesiologist. In this article, we describe a case where ketamine and dexmedetomidine were used to approach a difficult airway in a ...five-month-old patient with a palatal teratoma. These two drugs have complementary effects, because of which they can be used to maintain ventilation without compromising airway reflexes and are suitable for the management of pediatric difficult airways.
Humans' balance recovery responses to gait perturbations are negatively impacted with ageing. Slip and trip events, the main causes preceding falls during walking, are likely to produce severe ...injuries in older adults. While traditional exercise-based interventions produce inconsistent results in reducing patients' fall rates, perturbation-based balance training (PBT) emerges as a promising task-specific solution towards fall prevention. PBT improves patients' reactive stability and fall-resisting skills through the delivery of unexpected balance perturbations. The adopted perturbation conditions play an important role towards PBT's effectiveness and the acquisition of meaningful sensor data for studying human biomechanical reactions to loss of balance (LOB) events. Hence, this narrative review aims to survey the different methods employed in the scientific literature to provoke artificial slips and trips in healthy adults during treadmill and overground walking. For each type of perturbation, a comprehensive analysis was conducted to identify trends regarding the most adopted perturbation methods, gait phase perturbed, gait speed, perturbed leg, and sensor systems used for data collection. The reliable application of artificial perturbations to mimic real-life LOB events may reduce the gap between laboratory and real-life falls and potentially lead to fall-rate reduction among the elderly community.
Background
Tumour progression relies on the ability of cancer cells to penetrate and invade neighbouring tissues. E-cadherin loss is associated with increased cell invasion in gastric carcinoma, and ...germline mutations of the E-cadherin gene are causative of hereditary diffuse gastric cancer. Although E-cadherin dysfunction impacts cell–cell adhesion, cell dissemination also requires an imbalance of adhesion to the extracellular matrix (ECM).
Methods
To identify ECM components and receptors relevant for adhesion of E-cadherin dysfunctional cells, we implemented a novel ECM microarray platform coupled with molecular interaction networks. The functional role of putative candidates was determined by combining micropattern traction microscopy, protein modulation and in vivo approaches, as well as transcriptomic data of 262 gastric carcinoma samples, retrieved from the cancer genome atlas (TCGA).
Results
Here, we show that E-cadherin mutations induce an abnormal interplay of cells with specific components of the ECM, which encompasses increased traction forces and Integrin β1 activation. Integrin β1 synergizes with E-cadherin dysfunction, promoting cell scattering and invasion. The significance of the E-cadherin-Integrin β1 crosstalk was validated in
Drosophila
models and found to be consistent with evidence from human gastric carcinomas, where increased tumour grade and poor survival are associated with low E-cadherin and high Integrin β1 levels.
Conclusions
Integrin β1 is a key mediator of invasion in carcinomas with E-cadherin impairment and should be regarded as a biomarker of poor prognosis in gastric cancer.
The extracellular matrix (ECM) is a dynamic and highly organized tissue structure, providing support and maintaining normal epithelial architecture. In the last decade, increasing evidence has ...emerged demonstrating that alterations in ECM composition and assembly strongly affect cellular function and behavior. Even though the detailed mechanisms underlying cell-ECM crosstalk are yet to unravel, it is well established that ECM deregulation accompanies the development of many pathological conditions, such as gastric cancer. Notably, gastric cancer remains a worldwide concern, representing the third most frequent cause of cancer-associated deaths. Despite increased surveillance protocols, patients are usually diagnosed at advanced disease stages, urging the identification of novel diagnostic biomarkers and efficient therapeutic strategies. In this review, we provide a comprehensive overview regarding expression patterns of ECM components and cognate receptors described in normal gastric epithelium, pre-malignant lesions, and gastric carcinomas. Important insights are also discussed for the use of ECM-associated molecules as predictive biomarkers of the disease or as potential targets in gastric cancer.
This review aims to recommend directions for future research on robotic biofeedback towards prompt post-stroke gait rehabilitation by investigating the technical and clinical specifications of ...biofeedback systems (BSs), including the complementary use with assistive devices and/or physiotherapist-oriented cues. A literature search was conducted from January 2019 to September 2022 on Cochrane, Embase, PubMed, PEDro, Scopus, and Web of Science databases. Data regarding technical (sensors, biofeedback parameters, actuators, control strategies, assistive devices, physiotherapist-oriented cues) and clinical (participants’ characteristics, protocols, outcome measures, BSs’ effects) specifications of BSs were extracted from the relevant studies. A total of 31 studies were reviewed, which included 660 stroke survivors. Most studies reported visual biofeedback driven according to the comparison between real-time kinetic or spatiotemporal data from wearable sensors and a threshold. Most studies achieved statistically significant improvements on sensor-based and clinical outcomes between at least two evaluation time points. Future research should study the effectiveness of using multiple wearable sensors and actuators to provide personalized biofeedback to users with multiple sensorimotor deficits. There is space to explore BSs complementing different assistive devices and physiotherapist-oriented cues according to their needs. There is a lack of randomized-controlled studies to explore post-stroke stage, mental and sensory effects of BSs.
Understanding the lower limb kinematic, kinetic, and electromyography (EMG) data interrelation in controlled speeds is challenging for fully assessing human locomotion conditions. This paper provides ...a complete dataset with the above-mentioned raw and processed data simultaneously recorded for sixteen healthy participants walking on a 10 meter-flat surface at seven controlled speeds (1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4.0 km/h). The raw data include 3D joint trajectories of 24 retro-reflective markers, ground reaction forces (GRF), force plate moments, center of pressures, and EMG signals from Tibialis Anterior, Gastrocnemius Lateralis, Biceps Femoris, and Vastus Lateralis. The processed data present gait cycle-normalized data including filtered EMG signals and their envelope, 3D GRF, joint angles, and torques. This study details the experimental setup and presents a brief validation of the data quality. The presented dataset may contribute to (i) validate and enhance human biomechanical gait models, and (ii) serve as a reference trajectory for personalized control of robotic assistive devices, aiming an adequate assistance level adjusted to the gait speed and user's anthropometry.
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