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Microglia are the brain’s immunocompetent macrophages with a unique feature that allows surveillance of the surrounding microenvironment and subsequent reactions to tissue damage, infection, or homeostatic perturbations. Thereby, microglia’s striking morphological plasticity is one of their prominent characteristics and the categorization of microglial cell function based on morphology is well established. Frequently, automated classification of microglial morphological phenotypes is performed by using quantitative parameters. As this process is typically limited to a few and especially manually chosen criteria, a relevant selection bias may compromise the resulting classifications. In our study, we describe a novel microglial classification method by morphological evaluation using a convolutional neuronal network on the basis of manually selected cells in addition to classical morphological parameters. We focused on four microglial morphologies, ramified, rod-like, activated and amoeboid microglia within the murine hippocampus and cortex. The developed method for the classification was confirmed in a mouse model of ischemic stroke which is already known to result in microglial activation within affected brain regions. In conclusion, our classification of microglial morphological phenotypes using machine learning can serve as a time-saving and objective method for post-mortem characterization of microglial changes in healthy and disease mouse models, and might also represent a useful tool for human brain autopsy samples.

Background This study assessed the clinical outcomes of graft success rate and early implant survival rate after preprosthetic alveolar ridge reconstruction with autologous bone grafts. Methods A consecutive retrospective study was conducted on all patients who were treated at the military outpatient clinic of the Department of Oral and Plastic Maxillofacial Surgery at the military hospital in Ulm (Germany) in the years of 2009 until 2011 with autologous bone transplantation prior to secondary implant insertion. Intraoral donor sites (crista zygomatico-alveolaris, ramus mandible, symphysis mandible, and anterior sinus wall) and extraoral donor site (iliac crest) were used. A total of 279 patients underwent after a healing period of 3–5 months routinely computer tomography scans followed by virtual implant planning. The implants were inserted using guided oral implantation as described by Naziri et al. All records of all the consecutive patients were reviewed according to patient age, history of periodontitis, smoking status, jaw area and dental situation, augmentation method, intra- and postoperative surgical complications, and surgeon’s qualifications. Evaluated was the augmentation surgical outcome regarding bone graft loss and early implant loss postoperatively at the time of prosthodontic restauration as well a follow-up period of 2 years after loading. Results A total of 279 patients underwent 456 autologous augmentation procedures in 546 edentulous areas. One hundred thirteen crista zygomatico-alveolaris grafts, 104 ramus mandible grafts, 11 symphysis grafts, 116 grafts from the anterior superior iliac crest, and 112 sinus lift augmentations with bone scrapes from the anterior facial wall had been performed. There was no drop out or loss of follow-up of any case that had been treated in our clinical center in this 3-year period. Four hundred thirty-six (95.6%) of the bone grafts healed successfully, and 20 grafts (4.4%) in 20 patients had been lost. Fourteen out of 20 patients with total graft failure were secondarily re-augmented, and six patients wished no further harvesting procedure. In the six patients, a partial graft resorption was detected at the time of implantation and additional simultaneous augmentation during implant insertion was necessary. No long-term nerve injury occurred. Five hundred twenty-five out of 546 initially planned implants in 259 patients could be inserted into successfully augmented areas, whereas 21 implants in 20 patients due to graft loss could not be inserted. A final rehabilitation as preplanned with dental implants was possible in 273 of the 279 patients. The early implant failure rate was 0.38% concerning two out of the 525 inserted implants which had to be removed before the prosthodontic restoration. Two implants after iliac crest augmentation were lost within a period of 2 years after loading, concerning a total implant survival rate after 2 years of occlusal loading rate of 99.6% after autologous bone augmentation prior to implant insertion. Conclusions This review demonstrates the predictability of autologous bone material in alveolar ridge reconstructions prior to implant insertion, independent from donor and recipient site including even autologous bone chips for sinus elevation. Due to the low harvesting morbidity of autologous bone grafts, the clinical results of our study indicate that autologous bone grafts still remain the “gold standard” in alveolar ridge augmentation prior to oral implantation.

Obesity arising from excessive dietary fat intake is a risk factor for cognitive decline, dementia and neurodegenerative diseases, including Alzheimer’s disease. Here, we studied the effect of long-term high-fat diet (HFD) (24 weeks) and return to normal diet (ND) on behavioral features, microglia and neurons in adult male C57BL/6J mice. Consequences of HFD-induced obesity and dietary changes on general health (coat appearance, presence of vibrissae), sensory and motor reflexes, learning and memory were assessed by applying a phenotypic assessment protocol, the Y maze and Morris Water Maze test. Neurons and microglia were histologically analyzed within the mediobasal hypothalamus, hippocampus and frontal motor cortex after long-term HFD and change of diet. Long periods of HFD caused general health issues (coat alterations, loss of vibrissae), but did not affect sensory and motor reflexes, emotional state, memory and learning. Long-term HFD increased the microglial response (increased Iba1 fluorescence intensity, percentage of Iba1-stained area and Iba1 gene expression) within the hypothalamus, but not in the cortex and hippocampus. In neither of these regions, neurodegeneration or intracellular lipid droplet accumulation was observed. The former alterations were reversible in mice whose diet was changed from HFD to ND. Taken together, long periods of excessive dietary fat alone do not cause learning deficits or spatial memory impairment, though HFD-induced obesity may have detrimental consequences for cognitive flexibility. Our data confirm the selective responsiveness of hypothalamic microglia to HFD.

Background: The pancreas develops from two independent buds that fuse to form the adult organ. Ontogeny has largely been neglected in pancreatic surgery. This study aims to demonstrate that the adult pancreas can still be divided into morphogenetic units based on its embryological compartments and connective tissue borders for potential therapeutic purposes. Methods: Ten donor bodies (four female, six male, aged 73–101 years) were used. Manual dissection, guided by the common bile duct to locate the embryological fusion plane, was performed to divide the pancreatic tissue. Immunohistochemical staining for pancreatic polypeptide differentiated the pancreatic tissue by embryological origin and was used to quantify dissection accuracy. Results: Landmark-guided dissection successfully separated the pancreas along a connective tissue plane in seven cases. The resulting compartments were distinctly divided along the dissection plane into an area rich in pancreatic polypeptide and an area with low accumulation. Two cases showed deviations from the dissection plane at the histological level. One case contained tumor tissue, interfering with the utilization of landmarks. Conclusions: Landmark-guided dissection of the pancreas based on its embryological fusion plane allows for reliable separation into morphogenetic compartments. Immunohistochemical staining for pancreatic polypeptide effectively differentiates tissue origins. This approach may enable more precise, differentiated pancreatic resections and tailored treatments, with potential for refinement in routine surgical practice. Approaching the pancreatic tissue with regard to its ontogenetic origin and its clearly distinguishable compartments might even enable tailored treatment beyond refined surgical procedures.

The alterations of subbasal nerve plexus (SBP) innervation and corneal sensation were estimated non-invasively and compared with the values in healthy volunteers. Additionally, this study addressed the relation of SBP changes to the retinal status, glycemic control and diabetes duration. Eighteen eyes of diabetic patients with peripheral diabetic neuropathy aged 68.8±8.8 years and twenty eyes of healthy volunteers aged 66.3±13.3 yrs. were investigated with in vivo confocal laser-scanning microscopy (CLSM). An adapted algorithm for image analysis was used to quantify the morphological and topological properties of SBP. These properties were correlated to incidence of diabetic retinopathy (DR) and corneal sensation (Cochet-Bonnet esthesiometer). The developed algorithm allows a fully automated analysis of pre-segmented SBP structures. Altogether, 10 parameters were analysed, and all of them revealed significant differences between diabetic patients and healthy volunteers. The nerve fibre density, total fibre length and nerve branches were found to be significantly lower in patients with diabetes than those of control subjects (nerve fibre density 0.006±0.002 vs. 0.020±0.007 mm/mm(2); total fibre length 6223±2419 vs. 19961±6553 µm; nerve branches 25.3±28.6 vs. 141.9±85.7 in healthy volunteers). Also the corneal sensation was significantly lower in diabetic group when compared to controls (43±11 vs. 59±18 mm). There was found no difference in SBP morphology or corneal sensation in the subgroups with (DR) or without (NDR) diabetic retinopathy. SBP parameters were significantly reduced in diabetic patients, compared to control group. Interestingly, the SBP impairment could be shown even in the diabetic patients without DR. Although automatic adapted image analysis simplifies the evaluation of in vivo CLSM data, image acquisition and quantitative analysis should be optimised for the everyday clinical practice.

Triple negative breast cancer (TNBC) is the most aggressive molecular subtype and it lacks targetable receptors. Patients have an increased risk of recurrence and poor prognosis. Little is known concerning the characteristics of disseminated tumor cells (DTCs) and their role in TNBC patients. We analyzed the bone marrow aspirates of 80 patients with primary (n = 67) or recurrent (n = 13) TNBC, using a multi-parameter immunofluorescence staining procedure, including Pan-CK as an epithelial marker, vimentin (vim) as a marker of epithelial–mesenchymal transition, Ki67 for cell proliferation, and HER2 as well as PD-L1 as therapy-related markers. The DTC positive rate was 56% (n= 45) among the cohort. We found 20 different DTC subpopulations. The most frequently detected profile was CK+Vim+Ki67+ (n = 75 cells). The occurrence of CK- DTCs (n = 69) was significantly correlated to PD-L1 (r = −0.305, p < 0.01) and HER2 positivity (r = −0.234, p < 0.001). DTC positive patients that received neoadjuvant chemotherapy (NACT) and did not reach pathologic complete response were more likely to have CK- DTCs. Our data indicate that the occurrence of DTC subpopulations positive for Vim, Ki67, and HER2 appear to be markers for bad prognosis and could be therapeutically relevant. Furthermore, our results raise the question of whether DTCs are dormant in TNBC patients and persistent towards chemotherapy.

Cancer research requires models closely resembling the tumor in the patient. Human tissue cultures can overcome interspecies limitations of animal models or the loss of tissue architecture in in vitro models. However, analysis of tissue slices is often limited to histology. Here, we demonstrate that slices are also suitable for whole transcriptome sequencing and present a method for automated histochemistry of whole slices. Tumor and peritumoral tissue from a patient with glioblastoma was processed to slice cultures, which were treated with standard therapy including temozolomide and X-irradiation. Then, RNA sequencing and automated histochemistry were performed. RNA sequencing was successfully accomplished with a sequencing depth of 243 to 368 x 10 6 reads per sample. Comparing tumor and peritumoral tissue, we identified 1888 genes significantly downregulated and 2382 genes upregulated in tumor. Treatment significantly downregulated 2017 genes, whereas 1399 genes were upregulated. Pathway analysis revealed changes in the expression profile of treated glioblastoma tissue pointing towards downregulated proliferation. This was confirmed by automated analysis of whole tissue slices stained for Ki67. In conclusion, we demonstrate that RNA sequencing of tissue slices is possible and that histochemical analysis of whole tissue slices can be automated which increases the usability of this preclinical model.

Background Despite clinical importance and frequent occurrence of sinus disease, little is known about the size of paranasal sinuses and their communication in ponies and small horses. To examine the shape and volume of the paranasal sinuses and evaluate the sinonasal communication, three-dimensional (3D) reconstructions of computed tomography (CT) datasets of 12 healthy adult Shetland ponies were performed and analysed. Linear measurements of head length and width were taken. Using semi-automatic segmentation, 3D-models of all sinus compartments were created. Volumetric measurement of the seven sinus compartments were conducted and statistical analysis was performed. Sinus volumes were compared between the left and right sinuses and the relation to age and head size was evaluated. Results Structure and shape of the paranasal sinus system in Shetland ponies was similar to that of large horses. All seven sinus compartments on each side of the head were identified (rostral maxillary sinus, ventral conchal sinus, caudal maxillary sinus, dorsal conchal sinus, middle conchal sinus, frontal sinus, sphenopalatine sinus). The existence of a bilateral cranial and a caudal system formed by a maxillary septum was visible in all 12 individuals. The volumetric sizes of the left and right sinuses did not differ significantly ( p  > 0.05). A positive correlation between the size of the paranasal sinuses and the head length was shown. A relation between sinus volumes and age could not be proved in adult ponies aged > six years. Communication between single sinus compartments was identified. Furthermore, communication with the nasal cavity over the nasomaxillary aperture (Apertura nasomaxillaris) and a common sinonasal channel (Canalis sinunasalis communis) as well as its splitting up into a rostral and a caudolateral channel could be seen. Examination of the sinonasal communication was challenging and only a descriptive evaluation was possible. Conclusions Our findings concerning the size, shape and volumetric dimensions of Shetland pony CT images could help improve CT interpretation of abnormal clinical cases as well as aiding clinicians to develop and select appropriate instruments for medical inspection and treatments.

The causative agent of Chagas disease, Trypanosoma cruzi , is transmitted by triatomine vectors. The insect is endemic in the Americas, including the United States, where epidemiological studies are limited, particularly in the Southwestern region. Here, we have determined the prevalence of T . cruzi in triatomines, feral cats and dogs, and wild animals, the infecting parasite genotypes and the mammalian host bloodmeal sources of the triatomines at four different geographical sites in the U.S.-Mexico border, including El Paso County, Texas, and nearby cities in New Mexico. Using qualitative polymerase chain reaction to detect T . cruzi infections, we found 66.4% (n = 225) of triatomines, 45.3% (n = 95) of feral dogs, 39.2% (n = 24) of feral cats, and 71.4% (n = 7) of wild animals positive for T . cruzi . Over 95% of T . cruzi genotypes or discrete typing units (DTUs) identified were TcI and some TcIV. Furthermore, Triatoma rubida was the triatomine species most frequently (98.2%) collected in all samples analyzed. These findings suggest a high prevalence of T . cruzi infections among triatomines, and feral and wild animals in the studied sites. Therefore, our results underscore the urgent need for implementation of a systematic epidemiological surveillance program for T . cruzi infections in insect vectors, and feral and wild animals, and Chagas disease in the human population in the southwestern region of the United States.

Diagnosing chronic inflammatory enteropathies (CIE) in cats and differentiation from intestinal lymphoma (IL) using currently available diagnostics is challenging. Intestinally expressed S100/calgranulins, measured in fecal samples, appear to be useful non-invasive biomarkers for canine CIE but have not been evaluated in cats. We hypothesized S100/calgranulins to play a role in the pathogenesis of feline chronic enteropathies (FCE) and to correlate with clinical and/or histologic disease severity. This retrospective case-control study included patient data and gastrointestinal (GI) tissues from 16 cats with CIE, 8 cats with IL, and 16 controls with no clinical signs of GI disease. GI tissue biopsies were immunohistochemically stained using polyclonal α-S100A8/A9 and α-S100A12 antibodies. S100A8/A9+ and S100A12+ cells were detected in all GI segments, with few significant differences between CIE, IL, and controls and no difference between diseased groups. Segmental inflammatory lesions were moderately to strongly correlated with increased S100/calgranulin-positive cell counts. Clinical disease severity correlated with S100A12+ cell counts in cats with IL (ρ = 0.69, p = 0.042) and more severe diarrhea with colonic lamina propria S100A12+ cells with CIE (ρ = 0.78, p = 0.021) and duodenal S100A8/A9+ cells with IL (ρ = 0.71, p = 0.032). These findings suggest a role of the S100/calgranulins in the pathogenesis of the spectrum of FCE, including CIE and IL.