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Nitrated α-syn (nitro-α-syn) is a biomarker for Parkinson's desease (PD), and its sensitive detection in serum is of great importance for early PD diagnosis. Silver-coated copper MOF (Cu-MOF@Ag) with outstanding oxidase activity and electrochemical response property was designed and synthesized. Cu-MOF@Ag exhibited excellent oxidase activity with a low Km value (0.568 mM), avoiding the addition of strong oxidant to catalyze chromogenic substrate, which enhanced the colorimetric stability. Silver nanoparticles as an electrochemical signal reporter can be easily decorated on the surface of Cu-MOF with bifunctional groups (-SH and -NH2) material, which can increase the electrochemical signal output. The α-syn antibody modified Cu-MOF@Ag and nitro-α-syn modified magnetic nanoparticle were used as immunoprobes to specifically capture nitro-α-syn. A dual-modal immunosensor was fabricated for the simple and reliable detection of nitro-α-syn based on Cu-MOF@Ag. Combing colorimetric and electrochemical detection, nitro-α-syn can be determined quantitatively within a wide linear range (10–350 ng/mL) with low detection limit (0.5 ng/mL). The ability of the sensor with magnetic separation and dual signal analysis allowed to successfully detect nitro-α-syn and distinguish PD patients from healthy people (P < 0.005). Thanks to its excellent selectivity, stability, and the precision of 2.69%, the dual-modal sensor has potential clinical application for nitro-α-syn detection and paves a new way for PD diagnosis at its early stage. [ABSTRACT FROM AUTHOR]

The photonic band structures of waves in configuration-periodic equilateral polygonal networks (EPNs) are studied in the paper. The results indicate that comb-like optical transmission spectrum can be realized by EPNs.The number, width, and range of continuous equidistant frequency bands can be controlled conveniently by adjusting the waveguide length and the unit cell numbers of upper arm. Those comb-like frequency bands have potential in the design optical narrowband filters, multichannel filters, and optical switching. [ABSTRACT FROM AUTHOR]

Background OsWRKY62 and OsWRKY76, two close members of WRKY transcription factors, function together as transcriptional repressors. OsWRKY62 is predominantly localized in the cytosol. What are the regulatory factors for OsWRKY62 nuclear translocation? Results In this study, we characterized the interaction of OsWRKY62 and OsWRKY76 with rice importin, OsIMα1a and OsIMα1b, for nuclear translocation. Chimeric OsWRKY62.1-GFP, which is predominantly localized in the cytoplasm, was translocated to the nucleus of Nicotiana benthamiana leaf cells in the presence of OsIMα1a or OsIMαΔIBB1a lacking the auto-inhibitory importin β-binding domain. OsIMαΔIBB1a interacted with the WRKY domain of OsWRKY62.1, which has specific bipartite positively charged concatenated amino acids functioning as a nuclear localization signal (NLS). Similarly, we found that OsIMαΔIBB1a interacted with the AvrPib effector of rice blast fungus Magnaporthe oryzae, which contains a scattered distribution of positively charged amino acids. Furthermore, we identified a nuclear export signal (NES) in OsWRKY62.1 that inhibited nuclear transportation. Overexpression of OsIMα1a or OsIMα1b enhanced resistance to M. oryzae, whereas knockout mutants decreased resistance to the pathogen. However, overexpressing both OsIMα1a and OsWRKY62.1 were slightly more susceptible to M. oryzae than OsWRKY62.1 alone. Ectopic overexpression of OsWRKY62.1-NES fused gene compromised the enhanced susceptibility of OsWRKY62.1 to M. oryzae. Conclusion These results revealed the existence of NLS and NES in OsWRKY62. OsWRKY62, OsWRKY76, and AvrPib effector translocate to nucleus in association with importin α1s through new types of nuclear localization signals for negatively regulating defense responses. [ABSTRACT FROM AUTHOR]

In this study, we investigate reaction-diffusion complex-valued neural networks with mixed delays. The mixed delays include both time-varying and infinite distributed delays. Criteria are derived to ensure the existence, uniqueness, and exponential stability of the equilibrium state of the addressed system on the basis of the M-matrix properties and homeomorphism mapping theories as well as the vector Lyapunov function method. The results demonstrate the positive effect of reaction-diffusion on the stability, which further improves the existing conditions. Finally, the analysis of several examples is compared to the present results to verify the correctness and reduced conservatism of the primary results. [ABSTRACT FROM AUTHOR]

Purpose: NSCLC is the most common type of lung cancers. The purpose of this study is to screen cancer-related mutations in early LUAD in China through NGS technology, determine their correlation with clinical characteristics and provide basis for treatment decisions. Methods: In this study, we performed a 583 gene panel to detect the mutational spectrum of the tumors which were collected from 98 LUAD patients. The sequencing data and clinical characteristics were analyzed. Results: Mutations were identified in 94.9% of patients. EGFR had the highest mutation frequency which was detected in 66% of the patients and was significantly associated with female gender and non-smoking history. Other genes with high mutation frequency were TP53 (37%), ERBB2 (24%), BCOR (22%), ZFHX3 (19%), BTG1 (17%), ATR (16%), WWTR1 (15%), etc. TP53 mutations were significantly associated with medium and low differentiation of tumors; BCOR and BLM mutations with gender; WWTR1 mutations with age; and ATR mutations with visceral pleura invasion were observed. 61% of the patients harbored at less one actionable alteration associated with FDA-recognized or investigational drugs. Conclusion: Multiple mutations in LUAD patients in this study have not previously been reported in NSCLC. Moreover, mutations in driver genes including EGFR, TP53, BCOR, BLM, WWTR1, and ATR were significantly related to clinical features. The panel used in this study is an effective approach for molecular analysis and can be applied in personalized treatment decision-making and drug development. [ABSTRACT FROM AUTHOR]

The development of self-regulation is influenced by children’s experiences at home, with parenting styles and parenting stress being important contextual factors. However, little is known about how parenting styles and stress are related to the emotional (hot) and cognitive (cool) aspects of self-regulation. This study examined the relationships between different parenting styles (authoritative, authoritarian, and permissive) and children’s performance on hot and cool self-regulation tasks and the role of parenting stress in moderating this relationship in Chinese households. The participants included 310 preschoolers (51% girls/49% boys; Mage = 4.96 years; SD = 0.96) enrolled in four kindergartens in Beijing, China. The hierarchical regression results showed that after controlling for demographic variables, the level of authoritative parenting positively predicted children’s cognitive flexibility performance, while parenting stress moderated the relationship between authoritative parenting and children’s inhibitory control performance. The positive association between authoritative parenting and children’s inhibitory control was found only among children who experienced a lower level of parenting stress. Parenting styles were not associated with children’s hot self-regulation or working memory performance. These findings provide nuanced evidence on the relationships between parents’ parenting style, parenting stress, and children’s performance on hot and cool self-regulation. The implications for parenting education and future studies are discussed. [ABSTRACT FROM AUTHOR]

Using the first-principles calculations within density functional theory (DFT), we investigated magnetism, electronic structures, and half-metallicity stability of Heusler compound Co2Cr1−xTixAl. Besides, the origin of the half-metallic energy gap of Co2CrAl is also revealed. With Ti concentration increases, the magnetic moment of the Cr atom linearly increases, while that of Co and Cr atoms linearly decreases The total magnetic moment of Co2Cr1−x TixAl agrees with the Slater-Pauling rule very well. The Fermi level shifts from a low energy zone of the minority spin gap to a highenergy zone with increasing Ti concentration x, and it lies in the middle of the gap when x = 0.5. The corresponding doped compound Co2Cr0.5Ti0.5Al therefore possesses the most stable half metallicity. [ABSTRACT FROM AUTHOR]

Context: Glypican-4 (GPC-4) has been identified as a novel adipokine capable of enhancing insulin signaling. A significant association between circulating GPC-4 levels and nonalcoholic fatty liver disease and cardiometabolic risk factors has been found in women. Objective: The aim of the present study was to investigate the relationship between GPC-4 and insulin resistance in cross-sectional and interventional studies. Patients and design: We measured circulating GPC-4 (determined with ELISA) in subjects with NGT, IGT, and nT2DM. Euglycemic-hyperinsulinemic clamps were performed in healthy and T2DM subjects. Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of GPC-4. Results: Circulating GPC-4 levels were significantly higher in IGT subjects and lower in nT2DM subjects compared to controls. Circulating GPC-4 was positively correlated with BMI, WHR, HOMA-IS, and FAT%, while it was inversely correlated with FBG and HbA1c. Excluding diabetic subjects, increasing GPC-4 levels were associated with HOMA-IR and M values. Significantly lower GPC-4 mRNA and protein levels were found in muscle and fat of nT2DM patients, compared to controls. GPC-4 levels were significantly increased upon an oral glucose intake. The secretion of GPC-4 exhibited a characteristic diurnal rhythm in humans, with a major rise occurring between afternoon and midnight. Conclusions: Circulating GPC-4 is elevated in prediabetic subjects and is reduced in nT2DM patients. The elevated GPC-4 appears to be associated with insulin resistance and obesity in IGT subjects. [ABSTRACT FROM AUTHOR]

Purpose: The air health index (AHI) captures the combined effects of air pollution and non-optimal temperatures and helps assess the atmospheric environment's overall health risk. Shandong Province is a crucial industrial base in China, and the health effects of air pollution and non-optimal temperature cannot be ignored. To construct an AHI for Shandong Province and assess the district-level mortality burden due to AHI in the study area. Methods: Daily district-specific mortality, meteorological, and air pollution data over 2013–2018 were collected in Shandong Province, China. The AHI construction eventually incorporated PM2.5 and NO2, O3, and non-optimal temperatures. Attributable fraction (AF) and attributable number (AN) were used to estimate the district-specific mortality burden attributable to AHI. Results: The average AHI value observed in Shandong Province was 6. Our research revealed a positive association between the total AHI and total mortality, with an overall trend of a slow increase followed by a rapid increase. The exposure–response curves, when stratified by gender, age, and cause of death, were approximately consistent with the overall trend. The provincial attributable fraction (AF) was 5.31% (95% CI 4.58%, 5.91%), and the attributable number (AN) was 188,246 (95% CI 162,396, 209,533). Overall, higher ANs mainly appeared in the southwestern area, while higher values of AF were observed in the central-eastern and central-northern areas. Conclusions: The air health index performs well in predicting death burden and can convey health risks related to exposure to the ambient environment to the public. [ABSTRACT FROM AUTHOR]

This pilot study aimed to determine if a biophilic Green Therapy or Virtual Reality environment can decrease an oncology patient's pain and distress while receiving chemotherapy. A case-crossover pilot study was conducted in a comprehensive cancer infusion center. 33 participants with breast, gynecologic, gastrointestinal, pancreatic and prostate cancers were all included in three rooms in a random order at different cycles: control room, Green Therapy room, and Virtual Reality room to receive chemotherapy, respectively. Participants' pain, distress, heart rate, blood pressure, and saliva cortisol were measured before and after infusion in each room. No statistical significance differences were shown in the changes of heart rate, systolic, or diastolic blood pressure, saliva cortisol, pain, or distress before and after infusion between the control, Green Therapy, and Virtual Reality rooms. However, more patients reported the experience as "fun" and "enjoyable" when they were in Green Therapy or Virtual reality room as compared to in the control room. Additionally, since participating in the study, 14 patients reported spending at least 30 min or more outside in nature. In this study, we found that patients' heart rate, blood pressure, and self-reported distress levels were reduced after each biophilic intervention although results are not statistically significant. The study also suggested that biophilic interventions are safe and feasible and may complement the standard of care for oncology patients. [ABSTRACT FROM AUTHOR]

Multiple morphological abnormalities of the sperm flagella (MMAF) is a rare disease that causes primary infertility. However, the genetic causes for approximately half of MMAF cases are unknown. Whole exome sequencing analysis of the 27 patients with MMAF identified several CFAP44 mutations (3 homozygous: c.2935_2944del: p.D979*, c.T1769A: p.L590Q, c.2005_2006del: p.M669Vfs*13; and putative compound heterozygous: c.G3262A: p.G1088S and c.C1718A: p.P573H.) and CFAP43 acceptor splice-site deletion (c.3661-2A>-) mutations in 5 and 1 patients, respectively. Real-time quantitative polymerase chain reaction assays also demonstrated that CFAP44 expression was very weak in patient (P)1 and P3, and CFAP43 expression was lower in P6 than in the control. Immunofluorescence analysis of CFAP43 showed lower CFAP43 protein expression levels in P6 than in the normal control. This study demonstrated that biallelic mutations in CFAP44 and CFAP43 cause MMAF. These results provide researchers with a new insight to understand the genetic etiology of MMAF and to identify new loci for genetic counselling of MMAF. [ABSTRACT FROM AUTHOR]

In this paper, we aim to solve the stabilization problem for a large class of fractional-order nonautonomous systems via linear state feedback control and adaptive control. By constructing quadratic Lyapunov functions and utilizing a new property for Caputo fractional derivative we derive some sufficient conditions for the global asymptotical stabilization of a class of fractional-order nonautonomous systems. We give two illustrative examples to validate the effectiveness of the theoretical results. [ABSTRACT FROM AUTHOR]

Liver hepatocellular carcinoma (LIHC) is one of the most common malignancies and places a heavy burden on patients worldwide. HAUS augmin-like complex subunit 5 (HAUS5) is involved in the occurrence and development of various cancers. However, the functional role and significance of HAUS5 in LIHC remain unclear. The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE) and Gene Expression Omnibus (GEO) databases were used to analyze the mRNA expression of HAUS5. The value of HAUS5 in predicting LIHC prognosis and the relationship between HAUS5 and clinicopathological features were assessed by the Kaplan–Meier plotter and UALCAN databases. Functional enrichment analyses and nomogram prediction model construction were performed with the R packages. The LinkedOmics database was searched to reveal co-expressed genes associated with HAUS5. The relationship between HAUS5 expression and immune infiltration was explored by searching the TISIDB database and single-sample gene set enrichment analysis (ssGSEA). The Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas (HPA) databases were used to evaluate HAUS5 protein expression. Finally, the effect of HAUS5 on the proliferation of hepatoma cells was verified by CCK-8, colony formation and EdU assays. HAUS5 is aberrantly expressed and associated with a poor prognosis in most tumors, including LIHC. The expression of HAUS5 is significantly correlated with clinicopathological indicators in patients with LIHC. Functional enrichment analysis showed that HAUS5 was closely related to DNA replication, cell cycle and p53 signaling pathway. HAUS5 may serve as an independent risk factor for LIHC prognosis. The nomogram based on HAUS5 had area under the curve (AUC) values of 0.74 and 0.77 for predicting the 3-year and 5-year overall survival (OS) of LIHC patients. Immune correlation analysis showed that HAUS5 was significantly associated with immune infiltration. Finally, the results of in vitro experiments showed that when HAUS5 was knocked down, the proliferation of hepatoma cells was significantly decreased. The pan-oncogene HAUS5 is a positive regulator of LIHC progression and is closely associated with a poor prognosis in LIHC. Moreover, HAUS5 is involved in immune infiltration in LIHC. HAUS5 may be a new prognostic marker and therapeutic target for LIHC patients. [ABSTRACT FROM AUTHOR]

Purpose: In order to maximise the utility of [C]-PBR28 for use in longitudinal studies and clinical trials in Alzheimer's disease (AD), there is a need to develop non-invasive metrics of tracer binding that do not require arterial cannulation. Recent work has suggested that standardised uptake value (SUV)-based methods may be sensitive to changes in translocator protein (TSPO) levels associated with neurodegeneration. However, the test-retest reliability of these approaches in AD over a time period relevant for clinical trials is unknown. In this study, the test-retest reliability of three SUV-based metrics was assessed in AD patients over 12 weeks. Methods: Five patients with mild AD and the high-affinity binding TSPO genotype underwent two [C]-PBR28 PET scans approximately 12 weeks apart. The test-retest reliability (TRR) of the unadjusted SUV, SUV relative to cerebellar grey matter (SUVR) and SUV normalised to whole brain activity (SUVR) in nine cortical and limbic regions of interest was assessed using the absolute variability and the intraclass correlation coefficient. Results: Of the three measures, SUVR performed best overall, showing low absolute variability (mean −0.13 %, SD 2.47 %) and high reliability (mean ICC = 0.83). Unadjusted SUV also performed well, with high reliability (ICC = 0.94) but also high variability (mean −1.24 %, SD 7.28 %). By comparison, the SUVR showed higher variability (mean −3.98 %, SD 7.07 %) and low reliability (ICC = 0.65). Conclusions: In this AD sample, we found that SUV-derived metrics of [C]-PBR28 binding showed high stability over 12 weeks. These results compare favourably with studies reporting TRR of absolute quantification of [C]-PBR28. Pending further validation of SUV-based measures of [C]-PBR28, semi-quantitative methods of [C]-PBR28 analysis may prove useful in longitudinal studies of AD. [ABSTRACT FROM AUTHOR]

This randomized, double-blind, placebo-controlled, multiple ascending–dose study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of milvexian, an oral small-molecule FXIa inhibitor, in healthy Japanese participants. Participants received oral milvexian daily under fasted (50 mg and 200 mg) or fed conditions (500 mg) or placebo over 14 days; 24 participants (8/cohort: 6 milvexian; 2 placebo) were planned. Due to an unblinding event, participants in one cohort (200 mg daily) were discontinued, and a second cohort enrolled; 32 participants were included in safety and pharmacodynamic analyses, and 24/32 in pharmacokinetic analyses. Milvexian up to 500 mg daily for 14 days was generally well tolerated, with no deaths, serious adverse events, or discontinuations due to adverse events. Milvexian exposure increased between 50-mg and 200-mg doses. Median Tmax was similar with 50-mg and 200-mg doses (2.5–3.0 h) and delayed under fed conditions (500 mg, 7.0–8.0 h). Median T1/2 was similar across doses (8.9–11.9 h). Multiple oral milvexian administrations resulted in concentration-related prolongation of aPTT and decreased FXI clotting activity. Milvexian was generally safe and well tolerated. The pharmacokinetic and pharmacodynamic profile of milvexian demonstrates suitability for further clinical development in Japanese participants. [ABSTRACT FROM AUTHOR]

Objective: The aim of this in vitro study was to compare fluorescence-aided caries excavation with conventional excavation based on the Martens and Vickers hardness of dentin at the cavity floor after caries removal. Materials and methods: In total, 20 extracted human teeth with dentin caries were bisected through the lesion center into two halves, which were assigned to either the fluorescence-aided caries excavation group or the conventional excavation group. After the treatment, embedding, mounting, and polishing, a line of indentations from the dental pulp across the sound dentin to the cavity floor was made on each sample. The data were compared with Student's t and Mann-Whitney U tests. Results: The calculated Vickers hardness of the sound dentin was 57 ± 10 kg/mm in the fluorescence-aided caries excavation group and 59 ± 8 kg/mm in the conventional excavation group, which is consistent with the previous studies. The absolute and relative Martens hardness measurements of the cavity floor were 224 ± 93 N/mm and 46 ± 17 %, respectively, in the fluorescence-aided caries excavation group and 412 ± 75 N/mm and 81 ± 14 %, respectively, in the conventional excavation group. Based on either the Martens or Vickers hardness, both the absolute and relative microhardness measurements of the cavity floor after fluorescence-aided caries excavation were significantly lower than the values obtained by conventional excavation. Conclusion: Fluorescence-aided caries excavation showed the tissue-preserving property and was more conservative than the conventional excavation in this in vitro study. [ABSTRACT FROM AUTHOR]

Background: NRF2, a prime target of cellular defense against oxidative stress, has shown a dark side profile in cancer progression. GRIM-19, an essential subunit of the mitochondrial MRC complex I, was recently identified as a suppressive role in tumorigenesis of human gastric cancer (GC). However, little information is available on the role of GRIM-19 and its cross-talk with NRF2 in GC metastasis. Methods: Online GC database was used to investigate DNA methylation and survival outcomes of GRIM-19. CRISPR/Cas9 lentivirus-mediated gene editing, metastasis mice models and pharmacological intervention were applied to investigate the role of GRIM-19 deficiency in GC metastasis. Quantitative RT-PCR, FACS, Western blot, IHC, IF and reporter gene assay were performed to explore underlying mechanisms. Results: Low GRIM-19 is correlated with poor survival outcome of GC patients while DNA hypermethylation is associated with GRIM-19 downregulation. GRIM-19 deficiency facilitates GC metastasis and triggers aberrant oxidative stress as well as ROS-dependent NRF2-HO-1 activation. Experimental interventions of specific ROS, NRF2 or HO-1 inhibitor significantly abrogate GRIM-19 deficiency-driven GC metastasis in vitro and in vivo. Moreover, HO-1 inhibition not only reverses GRIM-19 deficiency-driven NRF2 activation, but also feedback blocks NRF2 activator-induced NRF2 signaling, resulting in decreased metastasis-associated genes. Conclusions: Our data suggest that GRIM-19 deficiency accelerates GC metastasis through the oncogenic ROS-NRF2-HO-1 axis via a positive-feedback NRF2-HO-1 loop. Therefore, this study not only offers novel insights into the role of oncogenic NRF2 in tumor progression, but also provides new strategies to alleviate the dark side of NRF2 by targeting HO-1. [ABSTRACT FROM AUTHOR]

Background and purpose: Aβ1–42-induced neurotoxicity has been considered as a possible mechanism to aggravate the onset and progression of Alzheimer's disease (AD). In this study, we aim to determine the protective effect of DMDD on the apoptosis of SH-SY5Y cells induced by Aβ1–42 and elucidate potential mechanism of DMDD's protective function in apoptosis. Experimental approach: CCK-8, AnnexinV-FITC/PI flow cytometry, and transmission electron microscopy analysis were used to determine the protection of DMDD on Aβ1–42-evoked apoptosis of SH-SY5Y cells. Cytochrome c release, JC-1 staining, and measuring the protein of Bcl-2 family by Western blot were applied to elucidate the mechanism of DMDD's protective function in apoptosis. Key results: Three concentration of DMDD (5 μmol/L, 10 μmol/L, and 20 μmol/L) rescues the cell viability loss and apoptosis of SH-SY5Y cells cultivated in Aβ1–42. The expressions of cleaved Caspase-3, -8, -9, the cytochrome c release, and mitochondrial membrane potential loss were inhibited by DMDD in Aβ1–42-insulted SH-SY5Y cells. The Western blot analysis showed that DMDD pretreatment clearly downregulated the protein of Bax and upregulated Bcl-2. Moreover, the Bcl-2/Bax ratio was obviously decreased in cells only exposed to Aβ1–42, but, which was suppressed by treated with DMDD. Conclusion and implications: DMDD attenuated the apoptosis of SH-SY5Y cells induced by Aβ1–42 through reversing the Bcl-2/Bax ratio. [ABSTRACT FROM AUTHOR]

Haliotis discus hannai is an important marine economic species in China. Its egg color was found to be associated with economic traits, which provides a new idea for breeding. However, the molecular mechanism of the egg-color formation has not been reported. Thus, the pigment composition and comparative transcriptome analyses of H. discus hannai with green and gray egg color were conducted using high-performance liquid chromatography (HPLC) and RNA-Seq methods. Results show that individuals with green and gray eggs both possess the fucoxanthin. Lutein existed in gray-egged individuals, but not in green-egged individuals. In transcriptome analysis, 272 310 unigenes were received from 461 162 transcripts with a mean length of 985 bp and N50 of 1 524 bp, respectively. A total of 185 unigenes were identified as differentially expressed genes (DEGs). The DEGs involved in "flavin-containing compound metabolic process", "melanosome", "glutathione metabolism", and "cytochrome b6f complex" were likely related to the formation of the egg color. Our results provide foundational information for the functional analysis of egg-color related genes and are beneficial to the selective breeding of H. discus hannai. [ABSTRACT FROM AUTHOR]

Leber hereditary optic neuropathy (LHON) is a degenerative disease of the optic nerve associated with one of three mitochondrial DNA (mtDNA) m.3460G>A, m.11778G>A and m.14484T>C mutations. Although several procedures are available to genotype these mutations, quantitative approaches with rapid, low-cost and easy to handle advantages for three LHON mtDNA mutations are rarely reported. Here, we firstly developed a "one-step" tetra-primer amplification-refractory mutation system (T-ARMS) PCR for qualitative genotyping of three LHON mtDNA mutations. Subsequently, we established single, duplex and triplex TaqMan MGB probe-based fluorescence quantitative PCR (qPCR) assays to perform both qualitative and quantitative analyses of three LHON mtDNA mutations. Standard curves based on tenfold diluted plasmid standard exhibited high specificity and sensitivity, stable repeatability and reliable detectable ability of TaqMan probe qPCR assays without cross-reactivity upon probes combination. Moreover, by comparing with SYBR Green qPCR, we further validated the feasibility of the triplex-probe qPCR assay for the quantitative detection of mtDNA copy number in blood samples. In conclusion, our study describes a rapid, low-cost, easy to-handle, and high-throughput TaqMan-MGB probe qPCR assay to perform both qualitative and quantitative analysis of three primary LHON mtDNA mutations, offering a promising approach for genetic screening and testing of LHON mutations. [ABSTRACT FROM AUTHOR]

Background: Although prostate cancer (PCa) screening is conducted before testosterone replacement therapy (TRT), clinically occult PCa cases may exist. Methods: To evaluate whether the possible inclusion of occult PCa cases distorts the effect of TRT on risk of PCa, we followed 776 hypogonadal males (TRT = 400, non-TRT = 376) from a urology center in Germany from 2004 to 2016, with a mean follow-up period of 7 years. We assumed occult cases might take 1–2 years (latency period) to become clinically detectable after receiving TRT. We selected several latency periods (12/18/24 months) and compared the risk of PCa in the TRT and non-TRT group over the latency period, from the end of latency period till the end of follow-up, and over the whole follow-up time. Results: Overall, 26 PCa cases occurred in the non-TRT group vs 9 cases in the TRT group. Within 18 months of follow-up, 9 cases occurred in the TRT group vs 0 cases in the non-TRT group; from the end of 18 months till the end of follow-up, 26 cases occurred in the non-TRT group vs 0 cases in the TRT group. The adjusted table showed seemingly adverse effects of TRT on PCa development within 18 months (p = 0.0301) and beneficial effects from the end of 18 months till the end of follow-up (p = 0.0069). Similar patterns were observed for 12 or 24 months as the latency period. Conclusions: TRT may make occult PCa cases detectable within early phase of treatment and present a beneficial effect in the long run. Future longitudinal studies are needed to confirm findings from our exploratory analyses. [ABSTRACT FROM AUTHOR]

HIV-infected (HIV+) women may be more vulnerable to neurocognitive impairment (NCI) due to psychological and physiological factors but previous studies show mixed findings. We investigated the neurocognitive performances in HIV+ versus HIV− women and men. This cross-sectional analysis included 669 HIV+ patients (223 women) and 1338 HIV-uninfected (HIV−) controls (446 women) which were frequency matched on sex, education, and 5-year age categories. NCI was screened using the Mini-mental State Examination. Psychomotor speed was assessed using timed alternating hand sequence test. Prevalence of NCI was higher among women versus men in the HIV+ group (16.1% vs 10.5%) but not the HIV− group (4.3% vs 3.5%). HIV+ women performed worse compared to men on psychomotor speed, orientation, attention, and calculation, whereas HIV− women performed worse compared to men on attention and calculation. Adjusted interaction effects of HIV status × sex (women vs men) were significant on orientation, attention, and calculation, and marginally significant on psychomotor speed (p = 0.053). In multivariable models, among both HIV+ women and men, less years of education and depressive symptoms were associated with NCI. Waist-to-hip ratio above the cut-off was strongly associated with NCI among HIV+ women. HIV+ women perform worse on cognitive measures compared to HIV+ men. The association of central obesity with NCI in HIV+ women should be noted. [ABSTRACT FROM AUTHOR]

Objectives: To examine the association between early menarche and gestational diabetes mellitus (GDM). Methods: Data from the National Health and Nutrition Examination Survey 2007-2012 were used to investigate the association between age at menarche and the risk of GDM at first birth among 5914 women. A growth mixture model was used to detect distinctive menarche onset patterns based on self-reported age at menarche. Logistic regression models were then used to examine the associations between menarche initiation patterns and GDM after adjusting for sociodemographic factors, family history of diabetes mellitus, lifetime greatest Body Mass Index, smoking status, and physical activity level. Results: Among the 5914 first-time mothers, 3.4 % had self-reported GDM. We detected three groups with heterogeneous menarche onset patterns, the Early, Normal, and Late Menarche Groups. The regression model shows that compared to the Normal Menarche Group, the Early Menarche Group had 1.75 (95 % CI 1.10, 2.79) times the odds of having GDM. No statistically significant difference was observed between the Normal and the Late Menarche Group. Conclusion: This study suggests that early menarche may be a risk factor of GDM. Future studies are warranted to examine and confirm this finding. [ABSTRACT FROM AUTHOR]

Purpose: Clinically relevant pharmacokinetic interactions exist between gastric acid-reducing agents and certain weakly basic drugs that rely on acidic environments for optimal oral absorption. In this study, we examine whether the administration of betaine hydrochloride under fed conditions can enhance the absorption of atazanavir, an HIV-1 protease inhibitor, during pharmacologically-induced hypochlorhydria. Methods: In this randomized, single-dose, 3 period, crossover study healthy volunteers received ritonavir-boosted atazanavir (atazanavir/ritonavir 300/100 mg) alone, following pretreatment with the proton pump inhibitor rabeprazole (20 mg twice daily), and with 1500 mg of betaine HCl after rabeprazole pretreatment. Atazanavir was administered with a light meal and gastric pH was monitored using the Heidelberg Capsule. Results: Pretreatment with rabeprazole resulted in significant reductions in atazanavir C ( p < 0.01) and AUC ( p < 0.001) (71 and 70%, respectively), and modest decreases in ritonavir C and AUC ( p < 0.01) (40% and 41%, respectively). The addition of betaine HCl restored 13% of ATV C and 12% of AUC lost due to rabeprazole. Conclusions: The co-administration of rabeprazole with atazanavir resulted in significant decreases in atazanavir exposure. The addition of betaine HCl did not sufficiently mitigate the loss of ATV exposure observed during RAB-induced hypochlorhydria. Meal effects lead to a marked difference in the outcome of betaine HCl on atazanavir exposure than we previously reported for dasatanib under fasting conditions. [ABSTRACT FROM AUTHOR]

Two new species, Castanopsis praefissa R.Y. Li et B.N. Sun sp. nov. and Castanopsis praeouonbiensis R.Y. Li et B.N. Sun sp. nov., are described from fossil specimens collected from the upper Miocene Shengxian Formation, Zhejiang Province, Southeast China. The fossil leaves are obovate to elliptical with serration mostly confined to the upper 1/3 of the lamina, pinnate venation, straight anticlinal walls and cyclocytic stomata. The fossil cupule is globose with fasciculate and branched spines, and a broadly ovate nut scar. The fossil leaves and cupule have been compared with those extant and other fossil species hitherto described in this genus. Castanopsis praefissa shows the closest affinity to C. fissa, and C. praeouonbiensis closely resembles C. ouonbiensis. Castanopsis fissa has toothed leaves and scaly cupules, whereas C. ouonbiensis has untoothed leaves and spiny cupules. Furthermore, they were not collected from the same site. So it is reasonable to assign them to two different species, rather than to one. Castanopsis praeouonbiensis and C. praefissa became extinct in this area because of the cooling climate from the late Miocene to the present day in Zhejiang Province. [ABSTRACT FROM AUTHOR]

Purpose: Heat has been known to increase the risk of many health endpoints. However, few studies have examined its effects on stroke. The objective of this case-crossover study is to investigate the effects of high heat and its effect modifiers on the risk of stroke hospitalization in Allegheny County, Pennsylvania. Methods: We obtained data on first stroke hospitalizations among adults ages 65 and older and daily meteorological information during warm seasons (May-September) from 1994 to 2000 in Allegheny County, Pennsylvania. Using conditional multiple logistic regressions, the effects of heat days (any day with a temperature greater than the 95th percentile) and heat wave days (at least two continuous heat days) on the risk of stroke hospitalization were investigated. The potential interactions between high heat and age, type of stroke, and gender were also examined. Results: Heat day and heat wave at lag-2 day were significantly associated with an increased risk for stroke hospitalization (OR 1.121, 95 % CI 1.013-1.242; OR 1.173, 95 % CI 1.047-1.315, respectively) after adjusting for important covariates. In addition, having two or more heat wave days within the 4 day window prior to the event was also significantly associated with an increased risk (OR 1.119, 95 % CI 1.004, 1.246) compared to having no heat wave days during the period. The effect of high heat on stroke was more significant for ischemic stroke, men, and subjects ages 80 years or older. Conclusions: Our study suggests that high heat may have adverse effects on stroke and that some subgroups may be particularly susceptible to heat. [ABSTRACT FROM AUTHOR]

Maternal smoking during pregnancy is a risk factor for attention-deficit/hyperactivity disorder (ADHD), but data on its adverse effects on cognitive functioning are sparse and inconsistent. Since the effect of maternal smoking during pregnancy may be due to correlated genetic risk factors rather than being a pure environmental effect, we examined the effect of prenatal exposure to smoking on attentional control, taking into account the effects of both maternal and paternal smoking, and examined whether these effects were genetically mediated by parental genotypes. We further examined whether the effect of prenatal exposure to smoking on attentional control interacted with genotypes of the child. Participants were 79 children with ADHD, ascertained for the International Multi-centre ADHD Gene project (IMAGE), and 105 normal controls. Attentional control was assessed by a visual continuous performance task. Three genetic risk factors for ADHD ( DRD4 7-repeat allele of the exon 3 variable number of tandem repeats (VNTR), DAT1 10/10 genotype of the VNTR located in the 3′ untranslated region, and the DAT1 6/6 genotype of the intron 8 VNTR) were included in the analyses. Paternal smoking had a negative effect on attentional control in children with ADHD and this effect appeared to be mediated by genetic risk factors. The prenatal smoking effect did not interact with genotypes of the child. Maternal smoking had no main effect on attentional control, which may be due to lower smoking rates. This study suggests that the effects of paternal smoking on attentional control in children with ADHD should be considered a proxy for ADHD and/or smoking risk genes. Future studies should examine if the results can be generalized to other cognitive domains. [ABSTRACT FROM AUTHOR]

A correction to the article "RILP interacts with HOPS complex via VPS41 subunit to regulate endocytic trafficking. " in the December 2, 2014 issue is presented which discusses the role of Rab-interacting lysosomal protein (RILP) on the formation of endosomal membranes.