Identifying a potential biomarker for primary focal segmental glomerulosclerosis and its association with recurrence after transplantation.

BACKGROUND: We investigated circulating levels of individual soluble urokinase plasminogen activation receptor (suPAR) forms to determine if specific circulating fragments of suPAR (II-III) and (I) can better serve as clinical biomarkers for focal segmental glomerulosclerosis (FSGS) and the risk of recurrence after transplantation. MATERIALS AND METHODS: Serum levels of intact suPAR and its cleaved forms were measured with two assays, ELISA and TR-FIA. RESULTS: suPAR levels in healthy controls were significantly lower than those who had glomerular diseases but were not significantly different between FSGS patients and glomerular controls. Intact suPAR (I-II-III) levels were noted to be elevated in glomerular diseases including FSGS. uPAR fragment (I) levels measured with the TR-FIA 4 assay were significantly higher in FSGS (695.4 + 91.29 pMol/L) than glomerular controls (239.1 + 40.45 pMol/L, P = 0.001). However, suPAR(I) levels were not significantly different between recurrent FSGS and nonrecurrent FSGS patients. CONCLUSION: Our analysis of suPAR using the ELISA assay used in all previous studies does not appear to be a useful marker for FSGS nor serve as a predictor for its recurrence after transplantation. The TR-FIA assay results suggest that uPAR(I) is a potential biomarker for FSGS but not of its recurrence.

Effects of kisspeptin on diabetic rat platelets.

Hyperglycemia, hyperlipidemia, and free radicals result in platelet activation and atherogenesis. Kisspeptin (KP) is able to regulate metabolism, hemostasis, and the development of atherosclerosis. We examined whether platelet aggregation of streptozotocin-induced diabetic rats depends on the inducer type and if KP-13 and RF-9 (a kisspeptin receptor modifier) can influence platelet function. We measured the speed and the maximum of aggregation, along with the area under the curve. Serum glucose and calcium levels and urine formation of diabetic animals increased, while the body mass and platelet count decreased. Collagen was the most effective inducer of platelet aggregation. The aggregability of nondiabetic platelets was elevated in the presence of 5 × 10-8 mol/L KP-13. This effect was less expressed in diabetic animals. The effectivity of RF-9 was stronger than that of KP-13 in nondiabetic platelets, however it was ineffective in diabetic animals. RF-9 pre-treatment did not change the effects of 5 × 10-8 mol/L KP-13 in either animal group. The in vivo activation of diabetic platelets, which may be due to elevated serum calcium, induces thrombocytopenia and may lead to reduced in vitro aggregability. We could not demonstrate the antagonistic effect of RF-9 against KP-13 in isolated platelets.

Longitudinal measurement invariance in prospective oral health-related quality of life assessment.

BACKGROUND: Prospective assessments of oral health-related quality of life (OHRQoL) changes are prone to response shift effects when patients reconceptualize, reprioritize, or recalibrate the perceived meanings of OHRQoL test items. If this occurs, OHRQoL measurements are not "invariant" and may reflect changes in problem profiles or perceptions of OHRQoL test items. This suggests that response shift effects must be measured and controlled to achieve valid prospective OHRQoL measurement. The aim of this study was to quantify response shift effects of Oral Health Impact Profile (OHIP) scores in prospective studies of prosthodontic patients. METHODS: Data came from the Dimensions of Oral Health-Related Quality of Life Project. The final sample included 554 patients who completed the OHIP questionnaire on two occasions: pre- and post-treatment. Only items that compose the 14-item OHIP were analyzed. Structural equation models that included pre- and post-treatment latent factors of OHRQoL with different across-occasion constraints for factor loadings, intercepts, and residual variances were fit to the data using confirmatory factor analysis. RESULTS: Data fit both the unconstrained model (RMSEA = .038, SRMR = .051, CFI = .92, TLI = .91) and the partially constrained model with freed residual variances (RMSEA = .037, SRMR = .064, CFI = .92, TLI = .92) well, meaning that the data are well approximated by a one-factor model at each occasion, and suggesting strong factorial across-occasion measurement invariance. CONCLUSIONS: The results provided cogent evidence for the absence of response shift in single factor OHIP models, indicating that longitudinal OHIP assessments of OHRQoL measure similar constructs across occasions.

Oral health-related quality of life after prosthetic rehabilitation: a longitudinal study with the OHIP questionnaire.

BACKGROUND: Aspects of oral health related quality of life (OHRQoL) attracted an increased attention recently. OBJECTIVE: The aim of the study was to assess self-reported oral health related quality of life (OHRQoL) among patients requiring prosthetic rehabilitation and to determine the rate of improvement 1 month and 6-12 months after therapy. In addition, effect of age, gender, oral health indicators and denture types before treatment were assessed on OHRQoL as evaluated and reported by the patients. METHODS: Hungarian version of OHIP-49 (OHIP-49-H) questionnaire was completed before oral rehabilitation (T0-phase) by 389 patients undergoing prosthetic replacement. After 1 month (T1-phase) and 6-12 months (T2-phase) recall periods 235 and 92 patients completed the questionnaire. The median interquartile range (IQR) values of the total OHIP-49-H score were calculated for T0-, T1- and T2-phases. Reliability of the questionnaire was checked by Cronbach's statistics. Age, gender, oral health indicators and denture types of patients before and after treatment were recorded and treatment-associated changes in OHRQoL were evaluated. RESULTS: The study demonstrated the excellent reliability and internal consistency of OHIP-49-H by a high and narrow range of Cronbach's alpha value (0.81-0.93). A median OHIP-49-H score of 52; IQR = 25-83 demonstrated a poor OHRQoL on first admission. Decreasing median total OHIP-49-H scores 1 month (24; IQR = 9-51; p < 0.001) and 6-12 months (20; IQR = 7-37; p = 0,055) after therapy indicated an improvement of OHRQoL. Patients' age and CPI value assessed before treatment proved to be significant factors of OHRQoL. CONCLUSIONS: Here we presented representative data about self-assessed OHRQoL of patients requiring prosthetic treatment from Hungary using OHIP-49-H questionnaire. The results demonstrated that the restoration of oral health was associated with an improvement in patients' OHRQoL. According to the demographical and T0 phase clinical status, the treatment was more effective in the respect of OHIP-49-H score improvement among females (than among males), among younger (than among more aged), and among patients with more serious CPI assessed at T0. The type of prosthetic interventions did not exert a significant effect on total OHIP-49-H score, suggesting that the improvement in OHRQoL is independent from the type of denture applied.

The effect of kisspeptin on the regulation of vascular tone.

Kisspeptin has been implicated in cardiovascular control. Eicosanoids play a crucial role in the activation of platelets and the regulation of vascular tone. In the present study, we investigated the effect of kisspeptins on eicosanoid synthesis in platelets and aorta in vitro. Platelets and aorta were isolated from Wistar-Kyoto rats. After preincubation with different doses of kisspeptin, samples were incubated with [1-(14)C]arachidonic acid (0.172 pmol/mL) in tissue culture Medium 199. The amount of labeled eicosanoids was measured with liquid scintillation, after separation with overpressure thin-layer chromatography. Kisspeptin-13 stimulated the thromboxane synthesis. The dose-response curve was bell-shaped and the most effective concentration was 2.5 × 10(-8) mol/L, inducing a 27% increase. Lipoxygenase products of platelets displayed a dose-dependent elevation up to the dose of 5 × 10(-8) mol/L. In the aorta, kisspeptin-13 induced a marked elevation in the production of 6-keto-prostaglandin F1α, the stable metabolite of prostacyclin, and lipoxygenase products. Different effects of kisspeptin on cyclooxygenase and lipoxygenase products indicate that beyond intracellular Ca(2+) mobilization, other signaling pathways might also contribute to its actions. Our data suggest that kisspeptin, through the alteration of eicosanoid synthesis in platelets and aorta, may play a physiologic and (or) pathologic role in the regulation of vascular tone.

Partial trisomy of the pericentromeric region of chromosome 5 in a girl with binder phenotype.

The patient reported here displayed most characteristic features of Binder syndrome (OMIM: 155050), a rare maxillonasal malformation with unknown etiology. She was sent for genetic evaluation at the age of 10 years because of facial dysmorphism and borderline intellectual disability. Cytogenetic analyses showed a de novo supernumerary small ring chromosome with a pericentromeric region of chromosome 5 in all lymphocytes. Array painting revealed that the marker contains a 20,950-kb genomic region comprising cytogenetic band 5p14.1q11.1. Additionally, 7 reports have been published in the literature with partial trisomy of chromosome 5 overlapping with our case. These 8 cases were analyzed for phenotype/genotype correlation which suggested that the maxillonasal anomalies of Binder phenotype and trisomy of the pericentromeric region of chromosome 5 may be in causal relationship. Future functional annotation studies of genes localized in this genomic region should take this into consideration. To the best of our knowledge, this is the first report on a patient with association of a chromosome abnormality and clinical characteristics of Binder phenotype.

Polarization transition between sunlit and moonlit skies with possible implications for animal orientation and Viking navigation: anomalous celestial twilight polarization at partial moon.

Using full-sky imaging polarimetry, we measured the celestial distribution of polarization during sunset and sunrise at partial (78% and 72%) and full (100%) moon in the red (650 nm), green (550 nm), and blue (450 nm) parts of the spectrum. We investigated the temporal change of the patterns of degree p and angle α of linear polarization of sunlit and moonlit skies at dusk and dawn. We describe here the position change of the neutral points of sky polarization, and present video clips about the celestial polarization transition at moonlit twilight. We found that at partial moon and at a medium latitude (47° 15.481' N) during this transition there is a relatively short (10-20 min) period when (i) the maximum of p of skylight decreases, and (ii) from the celestial α pattern neither the solar-antisolar nor the lunar-antilunar meridian can be unambiguously determined. These meridians can serve as reference directions of animal orientation and Viking navigation based on sky polarization. The possible influence of these atmospheric optical phenomena during the polarization transition between sunlit and moonlit skies on the orientation of polarization-sensitive crepuscular/nocturnal animals and the hypothesized navigation of sunstone-aided Viking seafarers is discussed.

An Enhanced Role of Innate Immunity in the Immune Response After Kidney Transplant in People Living With HIV: A Transcriptomic Analysis.

BACKGROUND: Although kidney transplantation (KT) has become the standard of care for people living with HIV (PLWH) suffering from renal failure, early experiences revealed unanticipated higher rejection rates than those observed in HIV- recipients. The cause of increased acute rejection (AR) in PLWH was assessed by performing a transcriptomic analysis of biopsy specimens, comparing HIV+ to HIV- recipients. METHODS: An analysis of 68 (34 HIV+, 34 HIV-) formalin-fixed paraffin-embedded (FFPE) renal biopsies matched for degree of inflammation was performed from KT recipients with acute T cell-mediated rejection (aTCMR), borderline for aTCMR (BL), and normal findings. Gene expression was measured using the NanoString platform on a custom gene panel to assess differential gene expression (DE) and pathway analysis (PA). RESULTS: DE analysis revealed multiple genes with significantly increased expression in the HIV+ cohort in aTCMR and BL relative to the HIV- cohort. PA of these genes showed enrichment of various inflammatory pathways, particularly innate immune pathways associated with Toll-like receptors. CONCLUSIONS: Upregulation of the innate immune pathways in the biopsies of PLWH with aTCMR and BL is suggestive of a unique immune response that may stem from immune dysregulation related to HIV infection. These findings suggest that these unique HIV-driven pathways may in part be contributory to the increased incidence of allograft rejection after renal transplantation in PLWH.

The Cocktail Effects on the Acute Cytotoxicity of Pesticides and Pharmaceuticals Frequently Detected in the Environment.

Xenobiotics never appear as single, isolated substances in the environment but instead as multi-component mixtures. However, our understanding of the ecotoxicology of mixtures is far from sufficient. In this study, three active pharmaceutical ingredients (carbamazepine, diclofenac, and ibuprofen) and three pesticides (S-metolachlor, terbuthylazine, and tebuconazole) from the most frequently detected emerging micropollutants were examined for their acute cytotoxicity, both individually and in combination, by bioluminescence inhibition in Aliivibrio fischeri (NRRL B-11177). Synergy, additive effects, and antagonism on cytotoxicity were determined using the combination index (CI) method. Additionally, PERMANOVA was performed to reveal the roles of these chemicals in binary, ternary, quaternary, quinary, and senary mixtures influencing the joint effects. Statistical analysis revealed a synergistic effect of diclofenac and carbamazepine, both individually and in combination within the mixtures. Diclofenac also exhibited synergy with S-metolachlor and when mixed with ibuprofen and S-metolachlor. S-metolachlor, whether alone or paired with ibuprofen or diclofenac, increased the toxicity at lower effective concentrations in the mixtures. Non-toxic terbuthylazine showed great toxicity-enhancing ability, especially at low concentrations. Several combinations displayed synergistic effects at environmentally relevant concentrations. The application of PERMANOVA was proven to be unique and successful in determining the roles of compounds in synergistic, additive, and antagonistic effects in mixtures at different effective concentrations.

In vivo estrogenicity of glyphosate, its formulations, and AMPA on transgenic zebrafish (Danio rerio) embryos.

In this study, the disrupting effects of glyphosate (GLY), aminomethylphosphonic acid (AMPA), and three glyphosate-based herbicides (GBHs) on vitellogenesis in a non-concentration-dependent manner are reported for the first time in 120 h of acute exposure of zebrafish at environmentally relevant concentrations. GBHs are commonly used worldwide in weed control management. Due to their extensive application, they frequently occur in aquatic ecosystems and may affect various organisms. The active substance GLY and its major by-product, AMPA, are the most thoroughly studied chemicals; however, the adverse effects of the complex formulas of GBHs with diverse and unknown content of co-formulants are still not sufficiently researched. This study focused on the embryotoxicity, sublethal malformations, and estrogenic potency of GLY, AMPA, and four commonly used GBHs on zebrafish embryos using a wild type and an estrogen-sensitive, transgenic zebrafish line (Tg(vtg1:mCherry)). After 120 h of exposition, AMPA did not cause acute toxicity, while the LC50 of GLY was 160 mg/L. The GBHs were more toxic with LC50 values ranging from 31 to 111 GLY active equivalent (a.e.) mg/L. Exposure to 0.35-2.8 mg/L GBHs led to sublethal abnormalities: typical symptoms were structural deformation of the lower jaw and anomalies in the olfactory region. Deformity rates were 10-30% in the treated groups. In vivo, fluorescently expressed vtg1 mCherry protein in embryonic liver was detected by a non-invasive microscopic method indicating estrogenic action through vitellogenin production by GLY, AMPA, and GBHs. To confirm the in vivo findings, RT-qPCR method was performed to determine the levels of the estrogenicity-related vtg1 mRNA. After 120 h of exposure to GLY, AMPA, and three GBHs at a concentration of 0.35 mg/L, the expression of vtg1 gene was significantly up-regulated. Our results highlight the risk that short-term GLY and GBH exposure can cause developmental malformations and disrupt the hormonal balance in zebrafish embryos.

Tissue-based T cell activation and viral RNA persist for up to 2 years after SARS-CoV-2 infection.

The mechanisms of postacute medical conditions and unexplained symptoms after SARS-CoV-2 infection [Long Covid (LC)] are incompletely understood. There is growing evidence that viral persistence, immune dysregulation, and T cell dysfunction may play major roles. We performed whole-body positron emission tomography imaging in a well-characterized cohort of 24 participants at time points ranging from 27 to 910 days after acute SARS-CoV-2 infection using the radiopharmaceutical agent [18F]F-AraG, a selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the postacute COVID-19 group, which included those with and without continuing symptoms, was higher compared with prepandemic controls in many regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. T cell activation in the spinal cord and gut wall was associated with the presence of LC symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms specifically. Increased T cell activation in these tissues was also observed in many individuals without LC. Given the high [18F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization of SARS-CoV-2 RNA and immunohistochemical studies in a subset of five participants with LC symptoms. We identified intracellular SARS-CoV-2 single-stranded spike protein-encoding RNA in rectosigmoid lamina propria tissue in all five participants and double-stranded spike protein-encoding RNA in three participants up to 676 days after initial COVID-19, suggesting that tissue viral persistence could be associated with long-term immunologic perturbations.

Ghrelin and nicotine stimulate equally the dopamine release in the rat amygdala.

The orexigenic peptide ghrelin plays a prominent role in the regulation of energy balance and in the mediation of reward processes and reinforcement for addictive drugs, such as nicotine. Nicotine is the principal psychoactive component in tobacco, which is responsible for addiction and relapse of smokers. Ghrelin and nicotine activates the mesolimbicocortical dopaminergic pathways via growth hormone secretagogue receptors (GHS-R1A) and nicotinic acetylcholine receptors (nAchR), respectively, resulting in the release of dopamine in the nucleus accumbens, the amygdala and the prefrontal cortex. In the present study an in vitro superfusion of rat amygdalar slices was performed in order to investigate the direct action of ghrelin and nicotine on the amygdalar dopamine release. Ghrelin increased significantly the dopamine release from the rat amygdala following electrical stimulation. This effect was inhibited by both the selective GHS-R1A antagonist GHRP-6 and the selective nAchR antagonist mecamylamine. Under the same conditions, nicotine also increased significantly the dopamine release from the rat amygdala. This effect was antagonized by mecamylamine, but not by GHRP-6. Co-administration of ghrelin and nicotine induced a similar increase of amygdalar dopamine release. This stimulatory effect was partially reversed by both GHRP-6 and mecamylamine. The present results demonstrate that both ghrelin and nicotine stimulates directly the dopamine release in the amygdala, an important dopaminergic target area of the mesolimbicocortical pathway.

Plumage color degradation indicates reproductive effort: an experiment.

Plumage color has traditionally been regarded as a static ornamental trait, but evidence is accumulating for significant color changes without molt that typically reduce the conspicuousness of ornamentation. In some species, the social partner seems to increase its reproductive investment if the color trait is experimentally enhanced, suggesting that color change could act as a signal. However, the information content of this signal is so far unclear. For example, birds in poor condition or making greater effort may deteriorate more severely. We used brood size manipulations to alter the reproductive effort of male and female collared flycatchers Ficedula albicollis. Both sexes showed less severe decline in some reflectance attribute of their white breast when their brood was experimentally reduced. In each sex, greater deterioration of the reflectance trait affected by the manipulation was accompanied by increased feeding rate by the partner. These feeding patterns do not prove, but are consistent with, a compensatory response by the partner to induced degradation. The manipulation effects on color change we detected confirm for the first time that plumage color deterioration can indicate current reproductive effort, thereby providing a potential fitness advantage to social partners that react to such deterioration.

Multimodal Molecular Imaging Reveals Tissue-Based T Cell Activation and Viral RNA Persistence for Up to 2 Years Following COVID-19.

The etiologic mechanisms of post-acute medical morbidities and unexplained symptoms (Long COVID) following SARS-CoV-2 infection are incompletely understood. There is growing evidence that viral persistence and immune dysregulation may play a major role. We performed whole-body positron emission tomography (PET) imaging in a cohort of 24 participants at time points ranging from 27 to 910 days following acute SARS-CoV-2 infection using a novel radiopharmaceutical agent, [18F]F-AraG, a highly selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the post-acute COVID group, which included those with and without Long COVID symptoms, was significantly higher compared to pre-pandemic controls in many anatomical regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. Although T cell activation tended to be higher in participants imaged closer to the time of the acute illness, tracer uptake was increased in participants imaged up to 2.5 years following SARS-CoV-2 infection. We observed that T cell activation in spinal cord and gut wall was associated with the presence of Long COVID symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms. Notably, increased T cell activation in these tissues was also observed in many individuals without Long COVID. Given the high [18F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization SARS-CoV-2 RNA and immunohistochemical studies in a subset of participants with Long COVID symptoms. We identified cellular SARS-CoV-2 RNA in rectosigmoid lamina propria tissue in all these participants, ranging from 158 to 676 days following initial COVID-19 illness, suggesting that tissue viral persistence could be associated with long-term immunological perturbations.

Restraint stress in rats alters gene transcription and protein translation in the hippocampus.

Stress is a relatively new and emerging risk factor for Alzheimer's disease (AD). Severe stress can alter brain characteristics such as neuronal plasticity, due to changes in the metabolism of cytoskeletal proteins. In this study, male Wistar rats were exposed to restraint stress (RS) for 5 h daily for different time periods. At the end of the exposure periods, the amounts of ß-actin, cofilin, amyloid precursor protein (APP) and mitogen-activated protein kinase 1 (MAPK-1) RNAs and proteins were investigated. The mRNA expressions of ß-actin, cofilin and MAPK-1 followed U-shaped time course. Acute (3 days) and chronic (21 days) RS caused a fourfold and tenfold increases, respectively, in hippocampal ß-actin mRNA expression. In the case of cofilin mRNA expression, elevations were detected in the hippocampus on days 3, 7 and 21. The APP mRNA level was increased on day 21. On protein level, chronic stress elevated the levels of ß-actin, cofilin and APP in the hippocampus. These results suggest that stress causes the induction of some genes and proteins that are also elevated in AD selectively in the hippocampal region of the rat brain.

Comparative salivary proteomics of cleft palate patients.

OBJECTIVES: To investigate salivary proteins with proteomic technologies to evaluate protein composition differences between samples with cleft lip and palate and healthy controls. DESIGN, PARTICIPANTS: Matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI TOF/TOF) mass spectrometry was used as a high-throughput analytical technique for identification of nonsyndromic cleft lip and palate stimulated salivary proteins. The samples consisted of two groups: 31 cleft lip and palate patients and a control group with 20 healthy volunteers. RESULTS: The presence of cleft lip and palate stimulated the expression of several proteins, included adaptor-related protein complex 3, dermokine, nidogen 1 precursor, transforming growth factor-ß3, and a zinc finger RAN-binding domain containing 2. CONCLUSIONS: The salivary proteome of cleft lip and palate patients differs from the protein composition of healthy control saliva samples. Several common secreted proteins such as actins, salivary cystatins, and keratins were upregulated by cleft; increased levels of TGF-ß3 and dermokine were detected in the pathologic samples. The current proteomic results suggest keratinocyte activation among patients with cleft lip and palate. The score of our preliminary results suggests the hypothesis that identified salivary proteins are of vital clinical importance in tissue regeneration and the molecular repair mechanism seen in patients with cleft lip and palate.

[The role of immobilization stress and sertindole on the expression of APP, MAPK-1 and beta-actin genes in rat brain]. / Az immobilizációs stressz és a sertindol hatása az APP, MAPK-1 és beta-aktin gének kifejezodésére patkányagyban.

Stress, depending on its level and quality, may cause adaptive and maladaptive alterations in brain functioning. As one of its multiple effects, elevated blood cortisol levels decrease the synthesis of the neuroprotective BDNF, thus leading to hippocampal atrophy and synapse loss, and rendering it a possible cause for the Alzheimer's disease (AD) related neuropathological and cognitive changes. As a result of the stress response, intraneuronal alterations--also affecting the metabolism of beta-actin--can develop. These have a role in the regulation of memory formation (LTP), but in pathological conditions (AD) they could lead to the accumulation of Hirano bodies (actin-cofilin rods). According to the dementia treatment guidelines, the behavioural and psychological symptoms of AD can be treated with certain antipsychotics. Therefore, the aim of our study was to examine the effects of sertindole (currently not used in the standard management of AD) on the transcription of some AD associated genes (amyloid precursor protein [APP], mitogen activated protein kinase-1 [MAPK-1], beta-actin) in the brain of rats exposed to chronic immobilization stress (CIS). Male Wistar rats were exposed to CIS for three weeks. The four groups were: control (n = 16), CIS (n = 10), 10 mg/kg sertindole (n = 5) and 10 mg/kg sertindole + CIS (n = 4). Following transcardial perfusion, the relative levels of hippocampal and cortical mRNA of the previously mentioned genes were measured with real-time PCR. CIS induced hippocampal beta-actin (p < 0.01), MAPK-1 and APP (p < 0.05) mRNA overexpression. The simultaneous administration of sertindole suppressed this increase in beta-actin, MAPK-1 and APP expression (p < 0.05). Ours is the first report about CIS induced beta-actin gene overexpression. This finding, in accordance with the similar results in APP and MAPK-1 expression, underlines the significance of cytoskeletal alterations in AD pathogenesis. The gene expression reducing effect of sertindole suggests that antipsychotic drugs may have a neuroprotective effect.

[Acute and chronic stress induced changes in gene transcriptions related to Alzheimer's disease]. / Az akut es krónikus stressz hatása az Alzheimer- kór patomechanizmusában szerepet játszó gének transzkripciójára.

Preclinical and clinical studies demonstrate that stress may be implicated in the risk of neurodegenerative diseases such as Alzheimer's disease (AD). Our study aimed to investigate the effects of acute and chronic immobilization stress (IS) on the gene transcriptions of beta-actin, amyloid precursor protein (APP) and mitogen activated protein kinase-1 (MAPK-1), proteins related to synaptic plasticity and neuronal degeneration. Male Wistar rats were exposed to IS for five hours daily for 3 days (acute stress) or through 7-14-21 days (chronic stress). At the end of exposure periods, total RNA was purified from the cortex and hippocampus. The amounts of beta-actin, APP and MAPK-1 mRNA were determined with real time PCR method. Our results indicate that the mRNA expression of beta-actin and APP followed a U-shaped time-response curve. Both acute and chronic IS caused a significant increase in beta-actin and MAPK-1 mRNA expression. Significant APP mRNA elevation was observed only by the 3rd week after RS. Our findings demonstrate that both acute and chronic IS lead to gene transcriptional changes of beta-actin, APP and MAPK-1. These proteins maintain the normal function of the cytoskeleton and the synaptic plasticity. The above changes may lead to cognitive deterioration, and the development of AD.

Impaired oral health-related quality of life in Hungary.

OBJECTIVES: To describe the prevalence of impaired oral health-related quality of life (OHRQoL) in the adult Hungarian population and to determine population-based norms for three Hungarian versions of the Oral Health Impact Profile (OHIP-H). MATERIAL AND METHODS: In a survey of 1059 randomly selected subjects, OHIP responses, age, gender, and denture status [natural dentition or fixed partial dentures (FPDs), removable partial dentures (RPDs), or complete dentures (CDs)] were collected. Study outcomes were item prevalence and OHIP summary score frequency ('norms'). RESULTS: The prevalence of OHIP items ranged from 2% to 43%, with a mean item prevalence of 14%. The distribution of summary scores was characterized by decile norms. Median scores for OHIP-H49, the 49-item questionnaire, were 6 OHIP units for subjects with FPDs, 10 OHIP units for subjects with RPDs, and 6 OHIP units for subjects with CDs. The median scores were 0, 0, and 1 OHIP units for the 14-item OHIP-H, and 0, 0, and 0 OHIP units for the five-item OHIP-H. CONCLUSIONS: Our sample demonstrates substantial OHRQoL impact in the Hungarian general population. The derived norms provide a framework for interpretation of data in future studies using the Hungarian OHIP versions, as well as data on how oral conditions and cultural factors affect perceived oral health when compared with international findings.

Kisspeptin-8 Induces Anxiety-Like Behavior and Hypolocomotion by Activating the HPA Axis and Increasing GABA Release in the Nucleus Accumbens in Rats.

Kisspeptins (Kp) are RF-amide neuropeptide regulators of the reproductive axis that also influence anxiety, locomotion, and metabolism. We aimed to investigate the effects of intracerebroventricular Kp-8 (an N-terminally truncated octapeptide) treatment in Wistar rats. Elevated plus maze (EPM), computerized open field (OF), and marble burying (MB) tests were performed for the assessment of behavior. Serum LH and corticosterone levels were determined to assess kisspeptin1 receptor (Kiss1r) activation and hypothalamic-pituitary-adrenal axis (HPA) stimulation, respectively. GABA release from the nucleus accumbens (NAc) and dopamine release from the ventral tegmental area (VTA) and NAc were measured via ex vivo superfusion. Kp-8 decreased open arm time and entries in EPM, and also raised corticosterone concentration, pointing to an anxiogenic effect. Moreover, the decrease in arm entries in EPM, the delayed increase in immobility accompanied by reduced ambulatory activity in OF, and the reduction in interactions with marbles show that Kp-8 suppressed exploratory and spontaneous locomotion. The increase in GABA release from the NAc might be in the background of hypolocomotion by inhibiting the VTA-NAc dopaminergic circuitry. As Kp-8 raised LH concentration, it could activate Kiss1r and stimulate the reproductive axis. As Kiss1r is associated with hyperlocomotion, it is more likely that neuropeptide FF receptor activation is involved in the suppression of locomotor activity.