EuCd_{2}As_{2}: A Magnetic Semiconductor.

EuCd_{2}As_{2} is now widely accepted as a topological semimetal in which a Weyl phase is induced by an external magnetic field. We challenge this view through firm experimental evidence using a combination of electronic transport, optical spectroscopy, and excited-state photoemission spectroscopy. We show that the EuCd_{2}As_{2} is in fact a semiconductor with a gap of 0.77 eV. We show that the externally applied magnetic field has a profound impact on the electronic band structure of this system. This is manifested by a huge decrease of the observed band gap, as large as 125 meV at 2 T, and, consequently, by a giant redshift of the interband absorption edge. However, the semiconductor nature of the material remains preserved. EuCd_{2}As_{2} is therefore a magnetic semiconductor rather than a Dirac or Weyl semimetal, as suggested by ab initio computations carried out within the local spin-density approximation.

Semi-automatic quantification of mosaic perfusion of lung parenchyma and its correlation with haemodynamic parameters in patients with chronic thromboembolic pulmonary hypertension.

AIM: To investigate the feasibility of semiautomatic quantification of mosaic perfusion and the associations between mosaic perfusion on computed tomography (CT; the ratio of hypoperfused parenchyma to the whole lung volume) and haemodynamic parameters through linear regression analysis. MATERIALS AND METHODS: Fifty-eight consecutive patients (mean age 66 years, 28 females) diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH) in General University Hospital, Prague, in 2021 were evaluated retrospectively and underwent both right heart catheterisation and CT pulmonary angiography. The parameters derived from the CT examinations were correlated with the recorded haemodynamic parameters. RESULTS: A method was developed for semiautomatic detection of hypoperfused tissue from CT using widely available software and a statistically significant correlation was found between the proportion of hypoperfused parenchyma and the mean pulmonary artery pressure (mPAP; R2 0.22; p<0.01) and pulmonary vascular resistance (PVR; R2 0.09; p<0.05). CONCLUSIONS: The developed method facilitates the quantification of mosaic perfusion, which is associated with important haemodynamic parameters (mPAP and PVR) in patients with CTEPH.

A rare case of diagnosed absent aortic valve and severely hypoplastic pulmonary valve with double outlet right ventricle: A case report.

Agenesis of the aortic and pulmonary valves is a very rare congenital malformation of the semilunar valves. The literature describes no more than thirty cases of such anomaly in combination with congenital heart disease. Most descriptions include aplasia of either the aortic or pulmonic valve. The combination of such defect in both valves has been described in a much smaller number of scientific papers. In this article, we present a clinical case of the treatment of a patient with agenesis of aortic valve and severely hypoplastic pulmonary valve. As a result circulatory arrest occurred immediately after birth, which required the implementation of cardiopulmonary resuscitation. The child was resuscitated and transferred to the intensive care unit for further examination and treatment.

The Impact of Diet and Photoperiodism on the Life History of Thanatophilus sinuatus (Coleoptera: Silphidae).

The forensically important genus Thanatophilus Leach, 1815 (Coleoptera: Silphidae) is a widespread group of carrion beetles that occupies the Holarctic and Afrotropical realms. It has recently received more recognition, as its species are frequently detected on large carrion, including humans, and can be useful in estimating the time of colonization (TOC) and the post-mortem interval (PMI). The immature stages of Thanatophilus sinuatus (Fabricius, 1775) were reared on three different meat diets (pork liver, pork muscle, and chicken muscle). Diet influence on some of the essential life history traits of the species was examined for different populations. Our findings indicated an accelerated development on pork muscle followed closely by pork liver and a prolonged development on chicken muscle. The diet significantly affected the size, and the body condition (weight/ size) as both pork muscle and liver produced individuals in better physical condition (larger and heavier). The impact of two cyclic photoperiod regimes (16 h Light (L): 8 h Dark (D) and 12 h L: 12 h D) was further evaluated and indicated no significant variability.

UHPLC-Orbitrap study of the first phase tacrine in vitro metabolites and related Alzheimer's drug candidates using human liver microsomes.

Tacrine was the first drug used in the therapy of Alzheimer's disease (AD) and is one of the leading structures frequently pursued in the drug discovery of novel candidates for tackling AD. However, because tacrine has been withdrawn from the market due to its hepatotoxicity, ascribed to specific metabolites, concerns are high about the toxicity profile of newly developed compounds related to tacrine. From the point of view of drug safety, the formation of metabolites must be uncovered and analyzed. Bearing in mind that the main culprit of tacrine hepatotoxicity is its biotransformation to hydroxylated metabolites, human liver microsomes were used as a biotransformation model. Our study aims to clarify phase I metabolites of three potentially non-toxic tacrine derivatives (7-methoxytacrine, 6-chlorotacrine, 7-phenoxytacrine) and to semi-quantitatively determine the relative amount of individual metabolites as potential culprits of tacrine-based hepatotoxicity. For this purpose, a new selective UHPLC-Orbitrap method has been developed. Applying UHPLC-Orbitrap method, two as yet unpublished tacrine and 7-methoxytacrine monohydroxylated metabolites have been found and completely characterized, and the separation of ten dihydroxylated tacrine and 7-methoxytacrine metabolites was achieved for the first time. Moreover, the structures of several new metabolites of 7-phenoxytacrine and 6-chlorotacrine have been identified. In addition, the relative amount of these newly observed metabolites was determined. Based on the results and known facts about the toxicity of tacrine metabolites published so far, it appears that 7-phenoxytacrine and 6-chlorotacrine could be substantially less hepatotoxic compared to tacrine, and could potentially pave the way for metabolically safe molecules applicable in AD therapy.

Investigation of Cellular Interactions of Lipid-Structured Nanoparticles With Oral Mucosal Epithelial Cells.

Lipid-based nanosystems enable intracellular delivery of drugs in the oral cavity for the treatment of local diseases. To rationally design such systems, suitable matrix compositions and particle properties need to be identified, and manufacturing technologies that allow reproducible production have to be applied. This is a prerequisite for the reliable and predictable performance of in-vitro biological studies. Here, we showed that solid lipid nanoparticles (SLN, palmitic acid) and nanostructured lipid carriers (NLC, palmitic acid and oleic acid in different ratios) with a size of 250 nm, a negative zeta potential, and a polydispersity index (PdI) of less than 0.3 can be reproducibly prepared by high-pressure homogenization using quality by design and a predictive model. SLN and NLC were colloidally stable after contact with physiological fluid and did not form agglomerates. The in-vitro studies clearly showed that besides particle size, surface charge and hydrophobicity, matrix composition had a significant effect. More specifically, the addition of the liquid lipid oleic acid increased the cellular uptake capacity without changing the underlying uptake mechanism. Regardless of the matrix composition, caveolin-mediated endocytosis was the major route of uptake, which was confirmed by particle localization in the endoplasmic reticulum. Thus, this work provides useful insights into the optimal composition of lipid carrier systems to enhance the intracellular uptake capacity of drugs into the oral mucosa.

Developmental models of the carrion beetle Thanatophilus rugosus (Linnaeus, 1758) (Coleoptera: Silphidae).

Coleoptera are currently considered a fundamental tool to help solve criminal investigations, allowing forensic entomologists to estimate post-mortem intervals and obtain other ecology-related information. Thanatophilus rugosus (Linnaeus, 1758) is an important necrophagous beetle distributed through most of the Palaearctic region, where it is readily found on human bodies and animal carcasses. In this study, the new thermal summation models for all the developmental stages of Thanatophilus rugosus are provided. Beetles were reared at six different constant and ecologically relevant temperatures (12, 14, 16, 18, 20, and 22 °C), and their developmental times were measured. Thermal summation constants were calculated for each developmental stage (egg, three larval instars, post-feeding stage, and pupa).

Alveolar Echinococcosis of the Liver with a Rare Infiltration of the Adrenal Gland.

Human alveolar echinococcosis (AE) is a silently-progressing disorder that has become a threat in many countries. Since 2000, when the first case was recorded, the number of human AE patients in Slovakia is on continuous raise. The article presents a rare case of alveolar echinococcosis with infiltration in the adrenal gland and discusses the problems associated with differential diagnosis of the disease. In 2016, abdominal ultrasound performed due abdominal pain complaint showed the presence of cystic lesions in the right liver lobe of 54-year old female patient. During surgery, another lesion in the right adrenal gland was found, and neoplastic processes or echinococcosis were considered in the differential diagnosis. Due to unclear correlation between radiology, serology and histopathology results and endemic situation in Slovakia, molecular examination was recommended. Subsequently E. multilocularis was confirmed as etiological agent of infection. Alveolar echinococcosis is considered as a rare disease, with very few patients referred to clinicians or hospitals that sometimes have almost none existing experience with the diagnosis and treatment of the disease. Therefore, the establishment of networks or reference centres specialized on management of the disease would be suitable way to provide the patients with the best care and improve the disease diagnosis, treatment and prognosis.

Report on G4-Med, a Geant4 benchmarking system for medical physics applications developed by the Geant4 Medical Simulation Benchmarking Group.

BACKGROUND: Geant4 is a Monte Carlo code extensively used in medical physics for a wide range of applications, such as dosimetry, micro- and nanodosimetry, imaging, radiation protection, and nuclear medicine. Geant4 is continuously evolving, so it is crucial to have a system that benchmarks this Monte Carlo code for medical physics against reference data and to perform regression testing. AIMS: To respond to these needs, we developed G4-Med, a benchmarking and regression testing system of Geant4 for medical physics. MATERIALS AND METHODS: G4-Med currently includes 18 tests. They range from the benchmarking of fundamental physics quantities to the testing of Monte Carlo simulation setups typical of medical physics applications. Both electromagnetic and hadronic physics processes and models within the prebuilt Geant4 physics lists are tested. The tests included in G4-Med are executed on the CERN computing infrastructure via the use of the geant-val web application, developed at CERN for Geant4 testing. The physical observables can be compared to reference data for benchmarking and to results of previous Geant4 versions for regression testing purposes. RESULTS: This paper describes the tests included in G4-Med and shows the results derived from the benchmarking of Geant4 10.5 against reference data. DISCUSSION: Our results indicate that the Geant4 electromagnetic physics constructor G4EmStandardPhysics_option4 gives a good agreement with the reference data for all the tests. The QGSP_BIC_HP physics list provided an overall adequate description of the physics involved in hadron therapy, including proton and carbon ion therapy. New tests should be included in the next stage of the project to extend the benchmarking to other physical quantities and application scenarios of interest for medical physics. CONCLUSION: The results presented and discussed in this paper will aid users in tailoring physics lists to their particular application.

Eye-background contrast as a quantitative marker for pupal age in a forensically important carrion beetle Necrodes littoralis L. (Silphidae).

Insect pupae sampled at a death scene may be used to estimate the post-mortem interval. The pupal age is however difficult to estimate, as there are no good quantitative markers for the age of a pupa. We present a novel method for pupal age estimation based on the quantification of contrast in intensity between the eyes of a pupa and the middle grey photography card as a standard background. The intensity is measured on a standardized scale from 0 (perfect black) to 255 (perfect white) using computer graphical software and pictures of the eye and the background taken with a stereomicroscope. Eye-background contrast is calculated by subtracting the average intensity of the eye from the average intensity of the background. The method was developed and validated using pupae of Necrodes littoralis (Linnaeus, 1758) (Coleoptera: Silphidae), one of the most abundant beetle species on human cadavers in Central Europe. To develop the model, pupae were reared in 17, 20 and 23 °C, with a total of 120 specimens. The method was validated by three raters, using in total 182 pupae reared in 15, 17, 20, 23 and 25 °C. We found a gradual increase in eye-background contrast with pupal age. Changes followed generalized logistic function, with almost perfect fit of the model. Using our method pupal age was estimated with the average error of 8.1 accumulated degree-days (ADD). The largest error was 27.8 ADD and 95% of age estimates had errors smaller than 20 ADD. While using the method, different raters attained similar accuracy. In conclusion, we have demonstrated that eye-background contrast is a good quantitative marker for the age of N. littoralis pupae. Contrast measurements gave accurate estimates for pupal age. Our method is thus proven to be a candidate for a reliable approach to age insect pupae in forensic entomology.

Ribotypes in isolates and testing algorithm of C. difficile infections in the studied sample.

BACKGROUND: Clostridium (Clostridioides) difficile is the most common pathogen of nosocomial and antibiotic-related diarrhea in health-care facilities. The aim of the analysis was to show the testing algorithm and to identify hypervirulent strains (suspected RT 027). METHODS: The retrospective analysis of patient samples suspected on CDI was carried out by a two-step algorithm. Biological specimens were analysed by GDH or culture, immunoenzymatic assay on toxins A/B and selected samples also by a real-time PCR. RESULTS: In 1006 specimen suspected on CDI, 202 specimens were evaluated as positive in the two-step algorithm. Conflicting results (64 C. difficile isolates) were tested in a three-step algorithm by a real-time PCR and revealed 59 toxigenic and non RT 027 ribotypes. Statistically significant dependence among the independent variables, such as: diagnostic parameters and length of hospitalization (p = 0.175) and C. difficile (suspected RT027) ribotypes was not found. CONCLUSION: The results of PCR ribotyping showed a high prevalence of hypervirulent and toxigenic ribotypes in the studied sample. A resistance to vancomycin was found in one isolate. The PCR method contributed to the rapid laboratory diagnosis and thus treatment of high risk patients or was used as a third step in in the case of unclear results of standard diagnostic methods(Tab. 1, Fig. 4, Ref. 18). Text in PDF www.elis.sk.

In-hospital management of elderly patients undergoing myocardial perfusion scintigraphy.

OBJECTIVE: To investigate the impact of myocardial perfusion scintigraphy results on the decision for invasive coronary angiography in elderly patients (≥75 years) with suspected coronary artery disease hospitalized in a single tertiary medical center. SUBJECTS AND METHODS: In the retrospective study, data of 276 (136 elderly) consecutive hospitalized patients referred to myocardial perfusion imaging were analyzed. The clinical characteristics, myocardial perfusion scintigraphy results, invasive coronary angiography and revascularization rates and in-hospital adverse events were identified by manually reviewing the patients' records. RESULTS: Ischemia was found in 40.2% of patients. There was no significant difference in the proportion of ischemia between elderly and younger patients (38.2% vs. 42.1%, P=0.508). Invasive coronary angiography was performed in 64.0% of patients with ischemia and in 6.8% of patients with normal myocardial perfusion imaging (P<0.001). The referral rate for invasive coronary angiography was not different between elderly and younger patients with ischemia (63.5% vs. 64.4%, P=0.848). Ischemia on myocardial perfusion imaging was the most predictive variable for a referral to invasive coronary angiography (odds ratio 31.8, 95% confidence interval 14.6-69.5, P<0.001). There was no significant difference between the younger and elderly patients in revascularization rate and adverse events until discharge (39% vs. 40%, P=0.99 and 7.1% vs. 8.8%, P=0.6, respectively). CONCLUSION: Ischemia on myocardial perfusion scintigraphy is a powerful predictor for in-hospital invasive coronary angiography independent of the patient's age. Elderly patients with ischemia received invasive coronary angiography equally as their younger counterparts and have similar rates of adverse events until discharge.

Comparative Analysis of Gene Expression Patterns for Oral Epithelium-Related Functions with Aging.

Epithelial cells and functions of the epithelium are critical to the health of the oral cavity. We used a nonhuman primate model to profile the transcriptome of gingival tissues in health across the lifespan and hypothesized that in older animals, epithelial-related transcriptome patterns would reflect epithelial cells that are aggressively responsive to the surrounding environment and less able to modulate and resolve the noxious challenge from the bacteria. Rhesus monkeys (n = 34) with a healthy periodontium were distributed into four groups: ≤3 years (young), 3-7 years (adolescent), 12-16 years (adult), and 18-23 years (aged), and a buccal gingival sample from the premolar/molar region of each animal was obtained. RNA was subjected to a microarray analysis (GeneChip® Rhesus Macaque Genome Array, Affymetrix), and 336 genes examined that are linked to epithelium and epithelial cell functions categorized into 9 broad functional groups: extracellular matrix and cell structure; extracellular matrix remodeling enzymes; cell adhesion molecules, cytoskeleton regulation; inflammatory response; growth factors; kinases/cell signaling; cell surface receptors; junction associated molecules; autophagy/apoptosis; antimicrobial peptides; and transcription factors. Total of 255 genes displayed a normalized signal >100, and differences across the age groups were observed primarily in extracellular matrix and cell structure, cell adhesion molecules, and cell surface receptor gene categories with elevations in the aged tissues. Keratins 2, 5, 6B, 13, 16, 17 were all significantly increased in healthy-aged tissues versus adults, and keratins 1 and 2 were significantly decreased in young animals. Approximately 15 integrins are highly expressed in the gingival tissues across the age groups with only ITGA8, ITGAM (CD11b), and ITGB2 significantly increased in the aged tissues. Little impact of aging on desmosomal/hemidesmosomal genes was noted. These results suggest that healthy gingival aging has a relatively limited impact on the broader functions of the epithelium and epithelial cells, with some effects on genes for extracellular matrix and cell adhesion molecules (e.g., integrins). Thus, while there is a substantial impact of aging on immune system targets even in healthy gingiva, it appears that the epithelial barrier remains reasonably molecularly intact in this model system.

Wirelessly Powered Endoscopically Implantable Devices into the Submucosa as the Possible Treatment of Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is a rather common disease with a prevalence reaching up to 10 or 20% in the western world. The most specific symptoms which point to the diagnosis of GERD are feelings of heartburn and the regurgitation of acidic stomach contents into the esophagus. However, a certain number of patients do not respond to standard therapy, and in these cases, it is necessary to resort to other treatment methods, such as laparoscopic fundoplication or electrostimulation of the lower esophageal sphincter. The aim of our work was to design and manufacture a miniature, battery-less stimulator to provide electric stimulation of the lower esophageal sphincter, which could be implanted deep into the submucosa of the distal esophagus. The main goal was to provide a battery-less system as opposed to traditional battery neurostimulators to reduce the size and weight of the device. An electronic prototype of a wirelessly powered implantable device was developed. We used animal models for the experiments. The device is designed to treat GERD via electrical stimulation of the muscularis propria. It is implanted into the submucosal pocket by the lower esophageal sphincter with an endoscope. This method of implantation is superior to esophageal stimulators used today because of very low invasiveness of the surgery. Bipolar neurostimulation via two gold-plated leads is provided. The device does not have any source of energy; it is powered wirelessly which reduces the risk of potential battery leakage and reduces the overall dimensions.

Comparative analysis of expression of microbial sensing molecules in mucosal tissues with periodontal disease.

Host-derived pattern recognition receptors (PRRs) are necessary for effective innate immune engagement of pathogens that express microbial-associated molecular patterns (MAMP) ligands for these PRRs. This study used a nonhuman primate model to evaluate the expression of these sensing molecules in gingival tissues. Macaca mulatta aged 12-24 with a healthy periodontium (n = 13) or periodontitis (n = 11) provided gingival tissues for assessment of naturally-occurring periodontitis. An additional group of animals (12-23 years; n = 18) was subjected to a 5 month longitudinal study examining the initiation and progression of periodontitis, RNA was isolated and microarray analysis conducted for gene expression of the sensing PRRs. The results demonstrated increased expression of various PRRs in naturally-occurring established periodontitis. Selected PRRs also correlated with both bleeding on probing (BOP) and pocket depth (PD) in the animals. The longitudinal model demonstrated multiple TLRs, as well as selected other PRRs that were significantly increased by 2 weeks during initiation of the lesion. While gene expression levels of various PRRs correlated with BOP and PD at baseline and resolution of disease, few correlated with these clinical parameters during initiation and progression of the lesion. These findings suggest that the levels of various PRRs are affected in established periodontitis lesions, and that PRR expression increased most dramatically during the initiation of the disease process, presumably in response to the juxtaposed microbial challenge to the tissues and goal of reestablishing homeostasis.

Social stability influences the association between adrenal responsiveness and hair cortisol concentrations in rhesus macaques.

Hair cortisol concentrations are increasingly being used in both humans and nonhuman animals as a biomarker of chronic stress. However, many details regarding how hair cortisol concentrations relate to the dynamic activity and regulation of the HPA axis are still unknown. The current study explores 1) how the regulation of the HPA axis in infancy relates to hair cortisol concentrations (HCC) in infancy 2) whether this relationship persists into adulthood under conditions of social stability, and 3) how social instability impacts these relationships. All subjects were rhesus monkeys housed in large social groups at the California National Primate Research Center, and all had participated in a 25-hr. long BioBehavioral Assessment (BBA) at 3-4 months of age when four plasma samples were taken to assess HPA regulation, in particular cortisol responses to 1) 2-hour social separation and relocation, 2) sustained challenge, 3) dexamethasone and 4) ACTH administration. In Study 1, hair samples were collected at the end of the BBA testing from 25 infant rhesus monkeys from 2 different stable social groups. In Study 2, hair samples were obtained at three timepoints from 108 adults from 3 different stable social groups (1 in the Spring/Summer and 2 in the Fall/Winter) to examine the temporal stability of the relationship between HCC and HPA axis regulation. In Study 3, subjects included 31 infants and 33 adults from a single social group experiencing social instability following the same procedures as in Studies 1 and 2. Generalized linear models were used to determine if infants' HPA axis activity and regulation predicted HCC in infancy (Study 1), in adulthood with animals living in stable social conditions (Study 2) or in animals living in an unstable social group (Study 3). Results indicated that for both infants and adults living in stable social groups, HCC are associated with the adrenal response to ACTH in infancy. Samples collected in the winter also had higher HCC than those collected in summer. In the unstable social group, adult hair cortisol levels were higher than in the stable social groups. Additionally, there were no consistent relationships between HCC and infant HPA axis regulation among adults or infants living in a group experiencing social instability. These results suggest that the aspects of the HPA axis that drive HCC may differ depending on context. Under stable, non-stressed conditions there seems to be a trait-like association between adrenal responsivity and HCC in infancy and adulthood. However, this association may be reduced or eliminated under conditions of social stress.

Genotoxic effects of the cyanobacterial pentapeptide nodularin in HepG2 cells.

The cyanobacterial pentapeptide nodularin (NOD), mainly produced by genus Nodularia, is a potent inhibitor of protein phosphatases PP1 and PP2A, and causes animal mortality. The few studies available indicate that NOD is a potential non-genotoxic carcinogen. In the present study we evaluated NOD (0.01, 0.1 and 1 µg/ml) genotoxic activity in human hepatoma (HepG2) cells with the comet, γH2AX and cytokinesis block micronucleus cytome assays. In addition, induction of oxidative stress was studied. Moreover changes in the expression of selected genes from the P53 pathway, involved in the response to DNA damage (P53, GADD45α, CDKN1A, MDM2), apoptosis (BAX, BCL2) and oxidative stress (GPX1, GSR, GCLC, CAT, SOD1) were determined using qPCR. Non-cytotoxic concentrations induced time and dose dependant increase in reactive oxygen species (ROS) production and substantially increased the formation of oxidative DNA damage. In addition, elevated formation of micronuclei was detected. For the first time it has been shown that NOD deregulated the mRNA level of DNA damage (CDKN1A, GADD45α) and oxidative stress (GPX1, GSR, GCLC, CAT and SOD1) responsive genes and anti-apoptotic gene BCL2. Our results provide new evidence that NOD genotoxic effects are mediated through ROS production, already at low environmentally relevant concentrations.

AADvac1, an Active Immunotherapy for Alzheimer's Disease and Non Alzheimer Tauopathies: An Overview of Preclinical and Clinical Development.

Neurofibrillary tau protein pathology is closely associated with the progression and phenotype of cognitive decline in Alzheimer's disease and other tauopathies, and a high-priority target for disease-modifying therapies. Herein, we provide an overview of the development of AADvac1, an active immunotherapy against tau pathology, and tau epitopes that are potential targets for immunotherapy. The vaccine leads to the production of antibodies that target conformational epitopes in the microtubule-binding region of tau, with the aim to prevent tau aggregation and spreading of pathology, and promote tau clearance. The therapeutic potential of the vaccine was evaluated in transgenic rats and mice expressing truncated, non mutant tau protein, which faithfully replicate of human tau pathology. Treatment with AADvac1 resulted in reduction of neurofibrillary pathology and insoluble tau in their brains, and amelioration of their deleterious phenotype. The vaccine was highly immunogenic in humans, inducing production of IgG antibodies against the tau peptide in 29/30 treated elderly patients with mild-to-moderate Alzheimer's. These antibodies were able to recognise insoluble tau proteins in Alzheimer patients' brains. Treatment with AADvac1 proved to be remarkably safe, with injection site reactions being the only adverse event tied to treatment. AADvac1 is currently being investigated in a phase 2 study in Alzheimer's disease, and a phase 1 study in non-fluent primary progressive aphasia, a neurodegenerative disorder with a high tau pathology component.

The interplay between single particle anisotropy and interparticle interactions in ensembles of magnetic nanoparticles.

This paper aims to analyze the competition of single particle anisotropy and interparticle interactions in nanoparticle ensembles using a random anisotropy model. The model is first applied to ideal systems of non-interacting and strongly dipolar interacting ensembles of maghemite nanoparticles. The investigation is then extended to more complex systems of pure cobalt ferrite CoFe2O4 (CFO) and mixed cobalt-nickel ferrite (Co,Ni)Fe2O4 (CNFO) nanoparticles. Both samples were synthetized by the polyol process and exhibit the same particle size (DTEM ≈ 5 nm), but with different interparticle interaction strengths and single particle anisotropy. The implementation of the random anisotropy model allows investigation of the influence of single particle anisotropy and interparticle interactions, and sheds light on their complex interplay as well as on their individual contribution. This analysis is of fundamental importance in order to understand the physics of these systems and to develop technological applications based on concentrated magnetic nanoparticles, where single and collective behaviors coexist.

Gene expression analysis of neuropeptides in oral mucosa during periodontal disease in non-human primates.

BACKGROUND: Neuropeptides (NPs) are innate pivotal regulators of the immunoinflammatory response. Nevertheless, their role in the pathogenesis of periodontal disease remains unknown. Changes in gene expression of 10 NPs and 16 NP receptors (NPRs) coincident with the initiation, progression, and resolution of periodontitis were determined. METHODS: The ligature-induced periodontitis model was used in rhesus monkeys (n = 18). Gingival tissue samples were taken at baseline (preligatures), at 2 weeks and at 1 month (initiation), and at 3 months (progression) postligation. Ligatures were removed and samples taken 2 months later (resolution). Total RNA was isolated from tissues and NP/NPR gene expression microarray analysis was performed. Gene expression changes were validated by quantitative polymerase chain reaction and immunohistochemistry. RESULTS: Unexpectedly, the expression of pro-inflammatory NPs/NPRs did not change during periodontitis or with resolution. However, increased expression of the anti-inflammatory NPs adrenomedullin (ADM) and galanin (GAL), and the NPRs calcitonin receptor-like (CALCRL) and receptor activity-modifying protein-2 and -3 (RAMP2 and RAMP3) were observed during initiation and progression of disease. The expression of the same NPs/NPRs exhibited a significant positive correlation with both molecular (interleukin-1ß, matrix mettaloproteinase-9, and receptor activator of nuclear factor-kappa B ligand) and clinical measures of gingival inflammation and tissue destruction. CONCLUSION: Initiation and progression of periodontitis involve significant overexpression of ADM, GAL, CALCRL, RAMP2, and RAMP3. These anti-inflammatory NPs/NPRs could play a role in the unresolved infection and inflammation that normally drives tissue destruction in periodontitis. Both ADM and GAL potentially are new candidates to consider as biomolecules associated with periodontal disease activity.