Orofacial clefts are among the most prevalent birth defects, with severe medical and psychosocial consequences. Cleft lip with or without cleft palate (CL ± P) and cleft palate only (CPO) affect on average nearly 1/700 births worldwide. The cause of most non-syndromic cases is unknown.
View Article and Find Full Text PDFOutcome prediction in prolonged disorders of consciousness (DOC) remains challenging. This can result in either inappropriate withdrawal of treatment or unnecessary prolongation of treatment. Electroencephalography (EEG) is a cheap, portable, and non-invasive device with various opportunities for complex signal analysis.
View Article and Find Full Text PDFBackground: Lymph node and resection margin status are associated with oncologic outcomes after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. However, surgical radicality at the portomesenteric axis in case of suspected infiltration remains controversial.
Methods: Clinicopathological data of patients who underwent a partial or total pancreaticoduodenectomy for PDAC between 2012 to 2019 in 2 major hepato-pancreato-biliary centers in Germany and Switzerland were assessed.
Objective: Most patients with pancreatic ductal adenocarcinoma (PDAC) will experience recurrence after resection. Here, we investigate spatially organised immune determinants of PDAC recurrence.
Design: PDACs (n=284; discovery cohort) were classified according to recurrence site as liver (n=93/33%), lung (n=49/17%), local (n=31/11%), peritoneal (n=38/13%) and no-recurrence (n=73/26%).
Aim: Tumor mutational burden (TMB: somatic mutations per megabase, mut/Mb) predicts the efficacy of immunotherapy. Here, we link TMB levels with the activation of immune pathways and intratumoral immune responses in pancreatic adenocarcinoma (PDAC) to explore immunoarchitectural patterns associated with high TMB.
Methods: We assessed TMB in 161 resected, microsatellite stable (MSS) PDACs, including 41 long-term survivors (LTS).
Leech hearts are hybrids; they are myogenic but need entrainment by a heartbeat central pattern generator (CPG) to execute functional constriction patterns. Leech hearts are modular: two lateral segmented heart tubes running the length of the animal. Moving blood through the segmented heart tubes of leeches requires sequential constrictions, timed by a heartbeat CPG and relayed to each heart segment by likewise segmental motor neurons.
View Article and Find Full Text PDFBackground & Aims: Intestinal epithelial homeostasis depends on a tightly regulated balance between intestinal epithelial cell (IEC) death and proliferation. While the disruption of several IEC death regulating factors result in intestinal inflammation, the loss of the anti-apoptotic BCL2 family members BCL2 and BCL2L1 has no effect on intestinal homeostasis in mice. We investigated the functions of the antiapoptotic protein MCL1, another member of the BCL2 family, in intestinal homeostasis in mice.
View Article and Find Full Text PDFClimate change challenges forest vitality both directly by increasing drought and heat periods and indirectly, e.g., by creating favorable conditions for mass outbreaks of phyllophagous insects.
View Article and Find Full Text PDFRhythmic behaviors vary across individuals. We investigated the sources of this output variability across a motor system, from the central pattern generator (CPG) to the motor plant. In the bilaterally symmetric leech heartbeat system, the CPG orchestrates two coordinations in the bilateral hearts with different intersegmental phase relations (Δ) and periodic side-to-side switches.
View Article and Find Full Text PDFThe neurogenic heartbeat of certain invertebrates has long been studied both as a way of understanding how automatic functions are regulated and for how neuronal networks generate the inherent rhythmic activity that controls and coordinates this vital function. This review focuses on the heartbeat of decapod crustaceans and hirudinid leeches, which remain important experimental systems for the exploration of central pattern generator networks, their properties, network and cellular mechanisms, modulation, and how animal-to-animal variation in neuronal and network properties are managed to produce functional output.
View Article and Find Full Text PDFBackground: Insulinomas are rare tumors, in the majority of cases best treated by surgical resection. Preoperative localization of insulinoma is challenging. The more precise the preoperative localization the less invasive and safer is the resection.
View Article and Find Full Text PDFSmall-intestine adhesiolysis can be very time consuming and may be associated with bowel wall damage. The risk for injuries to the small or large bowel resulting in increased morbidity and costs is considerable. Both efficient and gentle dissection of adhesions is important in order to avoid intraoperative perforation or, worse, postoperative intestinal leaks.
View Article and Find Full Text PDFCentral pattern generators (CPGs) produce motor patterns that ultimately drive motor outputs. We studied how functional motor performance is achieved, specifically, whether the variation seen in motor patterns is reflected in motor performance and whether fictive motor patterns differ from those in vivo. We used the leech heartbeat system in which a bilaterally symmetrical CPG coordinates segmental heart motor neurons and two segmented heart tubes into two mutually exclusive coordination modes: rear-to-front peristaltic on one side and nearly synchronous on the other, with regular side-to-side switches.
View Article and Find Full Text PDFBackground: The conservative treatment of acute necrotizing pancreatitis has greatly improved due to broad antibiotic treatment and improved organ support in intensive care units. Nevertheless, infected necrosis or persistent multi-organ dysfunction are predictors of poor outcome. In these patients, there is still a need to perform necrosectomy.
View Article and Find Full Text PDFCentral pattern generators (CPGs) pace and pattern many rhythmic activities. We have uncovered a new module in the heartbeat CPG of leeches that creates a regional difference in this segmentally distributed motor pattern. The core CPG consists of seven identified pairs and one unidentified pair of heart interneurons of which 5 pairs are premotor and inhibit 16 pairs of heart motor neurons.
View Article and Find Full Text PDFExperimental and corresponding modeling studies indicate that there is a 2- to 5-fold variation of intrinsic and synaptic parameters across animals while functional output is maintained. Here, we review experiments, using the heartbeat central pattern generator (CPG) in medicinal leeches, which explore the consequences of animal-to-animal variation in synaptic strength for coordinated motor output. We focus on a set of segmental heart motor neurons that all receive inhibitory synaptic input from the same four premotor interneurons.
View Article and Find Full Text PDFExperimental and corresponding modeling studies have demonstrated a twofold to fivefold variation of intrinsic and synaptic parameters across animals, whereas functional output is maintained. These studies have led to the hypothesis that correlated, compensatory changes in particular parameters can at least partially explain the biological variability in parameters. Using the leech heartbeat central pattern generator (CPG), we selected three different segmental motor neurons that fire in a functional phase progression but receive input from the same four premotor interneurons.
View Article and Find Full Text PDFTRP proteins form ion channels which are activated following receptor stimulation. In T-cell lines, expression data of TRP proteins have been published. However, almost no data about TRP expression is available in primary human T-cells.
View Article and Find Full Text PDFBackground: To determine the incidence and significance of vascular malformations in a varicose vein surgery patient cohort in a prospective cohort study.
Patients And Methods: During a ten year time span we prospectively searched for patients with vascular malformations within a varicose vein surgery cohort. All patients underwent colour duplex sonography and surgery for symptomatic chronic venous disease or chronic venous insufficiency corresponding to clinical classes C2 to C6 according to CEAP.
Costimulation is a fundamental principle of T-cell activation. In addition to T-cell receptor engagement, the interaction between CD80 and/or CD86 with CD28 and/or cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptors is required to regulate T-cell activation and tolerance. While the importance of costimulation is clearly established, the exact molecular mechanism is unknown.
View Article and Find Full Text PDFClonal T cell expansion through proliferation is a central process of the adaptive immune response. Apoptosis of activated T cells is required to avoid chronic inflammation. T cell proliferation and apoptosis are often analyzed with stimuli that do not induce formation of a functional immunological synapse.
View Article and Find Full Text PDFThe central pattern generator (CPG) for heartbeat in medicinal leeches consists of seven identified pairs of segmental heart interneurons and one unidentified pair. Four of the identified pairs and the unidentified pair of interneurons make inhibitory synaptic connections with segmental heart motor neurons. The CPG produces a side-to-side asymmetric pattern of intersegmental coordination among ipsilateral premotor interneurons corresponding to a similarly asymmetric fictive motor pattern in heart motor neurons, and asymmetric constriction pattern of the two tubular hearts, synchronous and peristaltic.
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