At room temperature, poly(N-isopropylacrylamide) (PNIPAM) is soluble in water and methanol, but it is not soluble in certain water/methanol mixtures. This phenomenon, known as cononsolvency, has been explored in great detail experimentally and theoretically in an attempt to understand the complex interactions occurring in the ternary PNIPAM/water/co-nonsolvent system. Yet little is known about the effects of the polymer structure on cononsolvency. To address this point, we investigated the temperature-dependent solution properties in water, methanol, and mixtures of the two solvents of poly(2-cyclopropyl-2-oxazoline) (PcyPOx) and two structural isomers of PNIPAM (M n ∼ 11 kg/mol): poly(2-isopropyl-2-oxazoline) (PiPOx) and poly(2-n-propyl-2-oxazoline) (PnPOx). The phase diagram of the ternary water/methanol/poly(2-propyl-2-oxazolines) (PPOx) systems, constructed based on cloud point (T CP) measurements, revealed that PnPOx exhibits cononsolvency in water/methanol mixtures. In contrast, methanol acts as a cosolvent for PiPOx and PcyPOx in water. The enthalpy, ΔH, and temperature, T max, of the coil-to-globule transition of the three polymers in various water/methanol mixtures were measured by high-sensitivity differential scanning calorimetry. T max follows the same trends as T CP, confirming the cononsolvency of PnPOx and the cosolvency of PiPOx and PcyPOx. ΔH decreases linearly as a function of the methanol content for all PPOx systems. Ancillary high-resolution 1H NMR spectroscopy studies of PPOx solutions in D2O and methanol-d 4, coupled with DOSY and NOESY experiments revealed that the n-propyl group of PnPOx rotates freely in D2O, whereas the rotation of the isopropyl and cyclopropyl groups of PiPOx and PcyPOx, respectively, is limited due to steric restriction. This factor appears to play an important role in the case of the PPOxs/water/methanol ternary system.

Enterococcus faecalis is a Gram-positive, facultative anaerobic coccus that can survive under harsh conditions. Studies have shown a positive relationship between biofilm formation and gelE gene expression in E. faecalis. The production of gelatinase (MMP 2) has been detected in 50% of E. faecalis isolates from endodontic and periodontal infections, which suggests its role in the pathogenesis of apical and marginal periodontitis. Although E. faecalis is not considered a periodontopathogen, this species has been more frequently detected in subgingival samples with periodontitis than from periodontally healthy subjects, suggesting that the local conditions in periodontitis may favor its colonization. Hence, the aim of the current study was to detect and compare the presence of E. faecalis in subgingival biofilms of healthy, gingivitis, and periodontitis subjects.

Smokers are at a higher risk of contracting periodontitis. This association is established and reported in many studies. Periodontitis is a polymicrobial disease, wherein smoking is an environmental factor which aggravates the damage caused to the tissues. Procalcitonin (ProCT) is a well-known marker for inflammatory and other infectious diseases and has been assessed in this study. It has been observed that the release of reactive oxygen species (ROS) is exaggerated in smokers. Antioxidants are administered to combat the harmful effects caused by the ROS, and Oxitard™ is a powerful herbal antioxidant that can counteract the action of free radicals.

Understanding the association between fertility histories and health later in life is necessary in the context of ageing societies. Past literature has generally found a U-shaped relationship between parity, age at first birth, and several health-related outcomes. However, these findings differed to some extent depending on the country under analysis and on the measures of health considered. As such, using wave 3 (2008-2009) and 5 (2013) of the Survey of Health, Ageing and Retirement in Europe (SHARE), this work aimed to answer the question: "Are fertility histories associated with the presence of chronic conditions later in life in Europe?" The analysis included 11 European countries and compared results using two different measures of chronic conditions: self-reported chronic or long-term illness and chronic diseases diagnosed by a doctor. Results showed that age at first birth is more relevant than parity for health outcomes at older ages. Moreover, in socio-democratic and continental countries, the association between fertility and chronic conditions-in particular between age at first birth and long-term illnesses-is statistically significant among women, but not among men. Finally, the association between fertility history and health was similar when using self-reported measures and chronic diseases diagnosed by a doctor.

Students' perception of their educational environment has a significant impact on their behavior and academic progress.

No abstract available

The brain is the most functionally organized structure of all organs. It manages behavior, perception and higher cognitive functions. The WWOX gene is non-classical tumor suppressor gene, which has been shown to have an impact on proliferation, apoptosis and migration processes. Moreover, genetic aberrations in WWOX induce severe neuropathological phenotypes in humans and rodents. The aim of the present study was to investigate in detail the impact of WWOX on human neural progenitor cell (hNPC) maintenance and how depletion of WWOX disturbs signaling pathways playing a pivotal role in neuronal differentiation and central nervous system (CNS) organogenesis. hNPC with a silenced WWOX gene exhibited lowered mitochondrial redox potential, enhanced adhesion to fibronectin and extracellular matrix protein mixture, downregulation of MMP2/9 expression and impaired 3D growth. Global transcriptome analysis using cap analysis of gene expression (CAGE) found that WWOX downregulation significantly changes the expression of multiple genes engaged in cytoskeleton organization, adhesion, cell signaling and chromatin remodeling. The massive changes in gene expression caused by WWOX silencing may strongly affect the differentiation and migration of neurons in organogenesis, brain injury, cancerogenesis or neurodifferentiation. WWOX gene appears to be an important regulator of neural tissue architecture and function.

The cytokine transforming growth factor β (TGFβ) plays a crucial role in the induction of both epithelial-to-mesenchymal transition (EMT) program and fibro-cirrhotic process in the liver, where it contributes also to organ inflammation following several chronic injuries. All these pathological situations greatly increase the risk of hepatocellular carcinoma (HCC) and contribute to tumor progression. In particular, late-stage HCCs are characterized by constitutive activation of TGFβ pathway and by an EMT molecular signature leading to the acquisition of invasive and metastatic properties. In these pathological conditions, the cytokine has been shown to induce the transcriptional downregulation of HNF1α, a master regulator of the epithelial/hepatocyte differentiation and of the EMT reverse process, the mesenchymal-to-epithelial transition (MET). Therefore, the restoration of HNF1α expression/activity has been proposed as targeted therapeutic strategy for liver fibro-cirrhosis and late-stage HCCs. In this study, TGFβ is found to trigger an early functional inactivation of HNF1α during EMT process that anticipates the effects of the transcriptional downregulation of its own gene. Mechanistically, the cytokine, while not affecting the HNF1α DNA-binding capacity, impaired its ability to recruit CBP/p300 acetyltransferases on target gene promoters and, consequently, its transactivating function. The loss of HNF1α capacity to bind to CBP/p300 and HNF1α functional inactivation have been found to correlate with a change of its posttranslational modification profile. Collectively, the results obtained in this work unveil a new level of HNF1α functional inactivation by TGFβ and contribute to shed light on the early events triggering EMT in hepatocytes. Moreover, these data suggest that the use of HNF1α as anti-EMT tool in a TGFβ-containing microenvironment may require the design of new therapeutic strategies overcoming the TGFβ-induced HNF1α inactivation.

Prevention and treatment of osteoporosis are an issue of great concern in public health so that the increase/maintenance of whole-body bone mineral density (BMD) is clinically relevant and could reduce the financial burden. Whole-body vibration (WBV) has been recently proposed as a potential alternative to bone stimulation, which combined with therapies, could provide a new treatment for osteoporosis prevention. In this sense, moderate cyclic hypoxia protocols may help to restrain osteoclastic activity and/or stimulate osteoblastic activity, enhance the effects of whole-body vibration alone. So, the present study investigated the effects of cyclic hypoxic exposure combined with WBV training on BMD of the elderly. Healthy elderly persons (n = 30) were randomly assigned to a (1) Hypoxia-Whole Body Vibration group (HWBV; n = 10), (2) Normoxic-Whole Body Vibration group (NWBV; n = 10) or (3) Control group (CON; n = 10). During 18 weeks, HWBV performed WBV treatment under normobaric hypoxic conditions (16.1% FiO2). A vibration session included 4 bouts of 30 s (12.6 Hz-4 mm) with 1 min rest between bouts. NWBV performed the same vibration treatment as HWBV but under normoxic conditions. Whole-body and proximal femur BMD (g⋅cm-2) were measured using dual-energy X-ray absorptiometry. Two-way ANOVA indicated a borderline significant (p = 0.07) time x group interaction for total BMD; post hoc analysis revealed a slight but significant (p = 0.021) increase of BMD after treatment in the HWBV group. In conclusion, 18-week WBV training with hypoxic stimuli has shown positive effects for the participants of the current study. As changes did not differ significantly between groups, future large-scale studies will be necessary to confirm these findings.

Generalized anxiety disorder (GAD) is one of the most common anxiety disorders. The brain's dysfunctional processing of interoceptive information is increasingly recognized as an important component of anxiety disorders. However, the neural mechanisms remain insufficiently understood. In the present study, patients with GAD and healthy control participants underwent an eyes-closed (EC) resting state (interoception) and eyes-open (EO) resting state (exteroception) without paying conscious attention to heartbeat. Electrocardiography (ECG) and electroencephalography (EEG) signals were recorded at the same time. The results show that in healthy controls, the heartbeat-evoked brain potential (HEP) was modulated by the conditions, with a significantly higher amplitude under EC than EO, while this was not the case in GAD patients. Further analysis revealed that the dysfunction of HEP modulation in GAD patients may be attributed to excessive interoceptive processing under EO, with a marginally higher HEP in GAD than in the healthy controls. Finally, the right prefrontal HEP amplitude during EC condition was significantly correlated with the severity of the patients' anxiety symptoms. Our results suggest that altered cortical processing of interoceptive signals may play an important role in the pathophysiology of generalized anxiety disorder.

Introduction: Major symptoms of Gilles de la Tourette syndrome (GTS) are tics, but in 90% of cases, psychiatric comorbidities occur. Self-harm behaviors (SHBs) could result from deliberate action and unintentional injury from tics. Methods: We examined 165 consecutive GTS patients aged 5 to 50 years (75.8% males). The median duration of GTS was 14 years (interquartile range, 9-22 years). The patients were evaluated for GTS and comorbid mental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Self-harm behavior was diagnosed during the interview. To determine a direct relationship between SHB and clinical variables, we conducted two analyses, at the time of evaluation and lifetime. We also compared the group of children and adults with SHB. We also tried to distinguish between deliberate (non-tic-related SHB) and accidental (tic-related SHB). Results: Lifetime SHB was reported by 65 patients (39.4%), and in 55 of the cases, it was present at the time of evaluation. The age at the onset of SHB was reported in 55 of the cases (84.6%), and the median was 10 years (interquartile range, 7-13 years). In 30 of the patients (46.2%), SHB was evaluated as mild; in 26 (40%), as moderate; and in only 9 cases (13.9%), as severe. In the multivariable analysis for the predictor of lifetime SHB, attention-deficit/hyperactivity disorder (p = 0.016) and obsessive-compulsive disorder (OCD; p = 0.042) were determined as risk factors, while for current SHB, only tic severity (p < 0.0001) was statistically significant. When comparing predictors of SHB for children and adults, tic severity was determined as predictor for lifetime SHB in children (p < 0.0001), while the anxiety disorder was associated with lifetime SHB in adults (p = 0.05). Similarly, tic severity was a predictor of current SHB in the children group (p = 0.001), but this was not confirmed for adults. The group of patients with tic-related and non-tic-related SHB did not differ. Conclusions: Self-harm behavior appears mostly in children and adolescents and rarely begins in adulthood. Self-harm behavior is associated mainly with tic severity, obsessive-compulsive disorder, and attention-deficit/hyperactivity disorder. Clinical correlates of SHB are age related and differ at different points of life. Tic severity is the main factor associated with SHB in children. In the adult group, anxiety disorder and other psychiatric comorbidities may play the most important role.

Accurate prediction of the early stage of Alzheimer's disease (AD) is important but very challenging. The goal of this study was to utilize predictors for diagnosis conversion to AD based on integrating resting-state functional MRI (rs-fMRI) connectivity analysis and structural MRI (sMRI). We included 177 subjects in this study and aimed at identifying patients with mild cognitive impairment (MCI) who progress to AD, MCI converter (MCI-C), patients with MCI who do not progress to AD, MCI non-converter (MCI-NC), patients with AD, and healthy controls (HC). The graph theory was used to characterize different aspects of the rs-fMRI brain network by calculating measures of integration and segregation. The cortical and subcortical measurements, e.g., cortical thickness, were extracted from sMRI data. The rs-fMRI graph measures were combined with the sMRI measures to construct input features of a support vector machine (SVM) and classify different groups of subjects. Two feature selection algorithms [i.e., the discriminant correlation analysis (DCA) and sequential feature collection (SFC)] were used for feature reduction and selecting a subset of optimal features. Maximum accuracy of 67 and 56% for three-group ("AD, MCI-C, and MCI-NC" or "MCI-C, MCI-NC, and HC") and four-group ("AD, MCI-C, MCI-NC, and HC") classification, respectively, were obtained with the SFC feature selection algorithm. We also identified hub nodes in the rs-fMRI brain network which were associated with the early stage of AD. Our results demonstrated the potential of the proposed method based on integration of the functional and structural MRI for identification of the early stage of AD.

Adoptive cell transfer therapy is currently one of the most promising approaches for cancer treatment. This therapy has some limitations, however, such as the dispersion of in vivo-administered cells, causing only a small proportion to reach the tumor. Nanotechnological approaches could offer a solution for this drawback, as they can increase cell retention and accumulation in a region of interest. In particular, strategies employing magnetic nanoparticles (MNPs) to improve targeting of adoptively transferred T or NK cells have been explored in mice. In vivo magnetic retention is reported using the human NK cell line NK-92MI transfected with MNPs. Primary NK cells are nonetheless highly resistant to transfection, and thus we explore in here the possibility of attaching the MNPs to the NK cell surface to overcome this issue, and examine whether this association would affect NK effector functions. We assessed the attachment of MNPs coated with different polymers to the NK cell surface, and found that APS-MNP attached more efficiently to the NK-92MI cell surface. In association with MNPs, these cells preserved their main functions, exhibiting a continued capacity to degranulate, conjugate with and lyse target cells, produce IFN-γ, and respond to chemotactic signals. MNP-loaded NK-92MI cells were also retained in an in vitro capillary flow system by applying an EMF. A similar analysis was carried out in primary NK cells, isolated from mice, and expanded in vitro. These primary murine NK cells also maintained their functionality intact after MNP treatment and were successfully retained in vitro. This work therefore provides further support for using MNPs in combination with EMFs to favor specific retention of functional NK cells in a region of interest, which may prove beneficial to adoptive cell-therapy protocols.

In alkaline soils in arid and semi-arid areas toxic concentrations of the micronutrient boron (B) are problematic for many cereal and legume crops. Molecular markers have been developed for B toxicity in cereals and Medicago. There is a need for such tools in clovers-Trifolium. To this end, we undertook a genome-wide association study (GWAS) with a diversity panel of subterranean clover (Trifolium subterraneum L.), an established model pasture legume for genetic and genomic analyses for the genus. The panel comprised 124 T. subterraneum genotypes (97 core collection accessions and 27 Australian cultivars). Substantial and useful diversity in B toxicity tolerance was found in T. subterraneum. Such variation was continuously distributed and exhibited a high broad sense heritability H 2 = 0.92. Among the subspecies of T. subterraneum, ssp. brachycalycinum was most susceptible to B toxicity (P < 0.05). From the GWAS, the most important discoveries were single-nucleotide polymorphisms (SNPs) located on Chr 1, 2, and 3, which mapped to haplotype blocks providing potential genes for a B toxicity tolerance assay and meriting further investigation. A SNP identified on Chr 1 aligned with Medicago truncatula respiratory burst oxidase-like protein (TSub_ g2235). This protein is known to respond to abiotic and biotic stimuli. The identification of these novel potential genes and their use to design markers for marker-assisted selection offer a pathway in pasture legumes to manage B toxicity by exploiting B tolerance.

In the present work, we performed a comparative genome-wide analysis of 22 species representative of the main clades and lifestyles of the phylum Platyhelminthes. We selected a set of 700 orthologous genes conserved in all species, measuring changes in GC content, codon, and amino acid usage in orthologous positions. Values of 3rd codon position GC spanned over a wide range, allowing to discriminate two distinctive clusters within freshwater turbellarians, Cestodes and Trematodes respectively. Furthermore, a hierarchical clustering of codon usage data differs remarkably from the phylogenetic tree. Additionally, we detected a synonymous codon usage bias that was more dramatic in extreme GC-poor or GC-rich genomes, i.e., GC-poor Schistosomes preferred to use AT-rich terminated synonymous codons, while GC-rich M. lignano showed the opposite behavior. Interestingly, these biases impacted the amino acidic usage, with preferred amino acids encoded by codons following the GC content trend. These are associated with non-synonymous substitutions at orthologous positions. The detailed analysis of the synonymous and non-synonymous changes provides evidence for a two-hit mechanism where both mutation and selection forces drive the diverse coding strategies of flatworms.

Purpose: To clarify the mutation spectrum and frequency of ABCA4 in a Chinese cohort with Stargardt disease (STGD1). Methods: A total of 153 subjects, comprising 25 families (25 probands and their family members) and 71 sporadic cases, were recruited for the analysis of ABCA4 variants. All probands with STGD1 underwent a comprehensive ophthalmologic examination. Overall, 792 genes involved in common inherited eye diseases were screened for variants by panel-based next-generation sequencing (NGS). Variants were filtered and analyzed to evaluate possible pathogenicity. Results: The total variant detection rate of at least one ABCA4 mutant allele was 84.3% (129/153): two or three disease-associated variants in 86 subjects (56.2%), one mutant allele in 43 subjects (28.1%), and no variants in 24 subjects (15.7%). Ninety-six variants were identified in the total cohort, which included 62 missense (64%), 15 splicing (16%), 11 frameshift (12%), 6 nonsense (6%), and 2 small insertion or deletion (2%) variants. Thirty-seven novel variants were found, including a de novo variant, c.4561delA. The most prevalent variant was c.101_106delCTTTAT (10.5%), followed by c.2894A > G (6.5%) and c.6563T > C (4.6%), in STGD1 patients from eastern China. Conclusion: Thirty-seven novel variants were detected using panel-based NGS, including one de novo variant, further extending the mutation spectrum of ABCA4. The common variants in a population from eastern China with STGD1 were also identified.

Several recurrent microdeletions and microduplications in the proximal, central, and distal regions of chromosomal 22q11.2 have been identified. However, due to a limited number of patients reported in the literature, highly variable clinical phenotypes, and incomplete penetrance, the pathogenicity of some microdeletions/microduplications in 22q11.2 central and distal regions is unclear. Hence, the genetic counseling and subsequent pregnancy decision are extremely challenging, especially when they are found in structurally normal fetuses. Here, we reported 27 consecutive cases diagnosed prenatally with 22q11.2 microdeletions or microduplications by chromosomal microarray analysis in our center. The prenatal ultrasound features, inheritance of the microdeletions/microduplications, and their effects on the pregnancy outcome were studied. We found that fetuses with 22q11.2 microdeletions were more likely to present with structure defects in the ultrasound, as compared with fetuses with 22q11.2 microduplications. Both the prenatal ultrasound findings and the inheritance of the microdeletions/microduplications affected the parent's decision of pregnancy. Those with structure defects in prenatal ultrasound or occurred de novo often resulted in termination of the pregnancy, whereas those with normal ultrasound and inherited from healthy parent were likely to continue the pregnancy and led to normal birth. Our study emphasized that proximal, central, and distal 22q11.2 deletions or duplications were different from each other, although some common features were shared among them. More studies are warranted to demonstrate the underlying mechanisms of different clinical features of these recurrent copy-number variations, thereby to provide more information for genetic counseling of 22q11.2 microdeletions and microduplications when they are detected prenatally.

Dogs can act as reservoirs of canine leishmaniasis, caused by Leishmania species. The aims of this study were to determine the prevalence of canine leishmaniasis using a PCR technique among stray dogs living in three provinces of Saudi Arabia, Riyadh, Al-Ahsa Oasis and Al-Qaseem, where the disease is endemic; and to identify and document different Leishmania to species levels.

Cystic echinococcosis, a major public health and economic concern, is a zoonotic helminth infection with worldwide distribution. This study was conducted to investigate the genetic characteristics of hydatid cysts isolated from human and livestock in Hamadan region, western Iran during 2016-2017.

The present study aimed to evaluate the prevalence of intestinal parasitic infection among mentally retarded individuals and the staff of the center in Bandar Abbas, south of Iran.