Chemical interference with DSIF complex formation lowers synthesis of mutant huntingtin gene products and curtails mutant phenotypes.

Earlier work has shown that siRNA-mediated reduction of the SUPT4H or SUPT5H proteins, which interact to form the DSIF complex and facilitate transcript elongation by RNA polymerase II (RNAPII), can decrease expression of mutant gene alleles containing nucleotide repeat expansions differentially. Using luminescence and fluorescence assays, we identified chemical compounds that interfere with the SUPT4H-SUPT5H interaction and then investigated their effects on synthesis of mRNA and protein encoded by mutant alleles containing repeat expansions in the huntingtin gene (HTT), which causes the inherited neurodegenerative disorder, Huntington's Disease (HD). Here we report that such chemical interference can differentially affect expression of HTT mutant alleles, and that a prototypical chemical, 6-azauridine (6-AZA), that targets the SUPT4H-SUPT5H interaction can modify the biological response to mutant HTT gene expression. Selective and dose-dependent effects of 6-AZA on expression of HTT alleles containing nucleotide repeat expansions were seen in multiple types of cells cultured in vitro, and in a Drosophila melanogaster animal model for HD. Lowering of mutant HD protein and mitigation of the Drosophila "rough eye" phenotype associated with degeneration of photoreceptor neurons in vivo were observed. Our findings indicate that chemical interference with DSIF complex formation can decrease biochemical and phenotypic effects of nucleotide repeat expansions.

Targeted protein quantitation in human body fluids by mass spectrometry.

Human body fluids (biofluids) contain various proteins, some of which reflect individuals' physiological conditions or predict diseases. Therefore, the analysis of biofluids can provide substantial information on novel biomarkers for clinical diagnosis and prognosis. In the past decades, mass spectrometry (MS)-based technologies have been developed as proteomic strategies not only for the identification of protein biomarkers but also for biomarker verification/validation in body fluids for clinical applications. The main advantage of targeted MS-based methodologies is the accurate and specific simultaneous quantitation of multiple biomarkers with high sensitivity. Here, we review MS-based methodologies that are currently used for the targeted quantitation of protein components in human body fluids, especially in plasma, urine, cerebrospinal fluid, and saliva. In addition, the currently used MS-based methodologies are summarized with a specific focus on applicable clinical sample types, MS configurations, and acquisition modes.

Validation of the Chinese Version of the Speech, Spatial, and Qualities of Hearing Scale for Parents and Children.

OBJECTIVES: To translate and validate the Chinese version of the Speech, Spatial, and Qualities of Hearing Scale (SSQ) for children with hearing impairment (C-SSQ-C) and for their parents (C-SSQ-P). DESIGN: We translated the SSQ for children into Chinese and verified its readability and comprehensibility. A total of 105 participants with moderate-to-profound hearing loss (HL) and 54 with normal hearing were enrolled in the validation process. The participants with HL were fitted with bilateral hearing aids, bimodal hearing, or bilateral cochlear implants. The C-SSQ-P was administered to the parents of participants aged 3 to 6.9 years, and the C-SSQ-C was administered to participants aged 7 to 18 years. The internal consistency, test-retest reliability, and validity were evaluated for both questionnaires. RESULTS: Both C-SSQ-P and C-SSQ-C demonstrated high internal consistency (Cronbach's α >0.8) and good validity (generalized linear model revealed significant negative relationships between the C-SSQ-P subscales with aided better-hearing threshold [ß = -0.08 to -0.12, p ≤ 0.001] and between the C-SSQ-C subscales with worse-hearing threshold [ß = -0.13 to -0.14, p < 0.001]). Among the children with HL, the participants with bilateral cochlear implants had demonstrated better performance than those with bimodal hearing and bilateral hearing aids, as evidenced by the highest mean scores in three subscales. CONCLUSIONS: Both C-SSQ-P and C-SSQ-C are reliable and valid for assessing HL in children and adolescents. The C-SSQ-P is applicable in evaluating young children aged 3 to 6.9 years after a 7-day observation period, while the C-SSQ-C is appropriate for children and adolescents aged 7 to 18 years.

Serum selenium and fasting blood glucose: a cross-sectional study in women of different menopause status.

BACKGROUND: This cross-sectional study aims to explore whether there exists an interaction between selenium and menopause concerning type 2 diabetes (T2D) prevalence and its related indicators such as fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR). METHODS: 150 women aged 35-60 years old were finally analyzed in this study. Multivariate linear or logistic regression modeling was conducted to explore the association of selenium and the prevalence of T2D besides its related indicators. Subgroup analyses were conducted based on menopause status to assess the potential impact on the relationship. RESULTS: In the fully adjusted model, serum selenium was positively associated with FBG (ß: 0.03, CI: 0.01-0.05) and the prevalence of T2D (OR: 1.04, CI: 1.00-1.08). After stratifying the data by menopause status, compared with the postmenopausal women group, as the serum selenium concentrations increased, the FBG concentrations were significantly higher in the premenopausal women group (p for interaction = 0.0020). CONCLUSIONS: The present study found serum selenium was positively associated with FBG and the prevalence of T2D. Furthermore, the relationship between serum selenium and FBG was different in the premenopausal and postmenopausal women. More studies are still needed in the future to verify the relationship as well as to explore the specific mechanisms.

Association between serum vitamin E and bacterial vaginitis in women: a cross-sectional study.

INTRODUCTION: Bacterial vaginitis (BV) is a common vaginal disease. Vitamin E has been shown to reduce BV by enhancing immune function, but no studies have analyzed the relationship between vitamin E and BV at different BMIs and ages. METHOD: This study used 2242 participants from four cycles of NHANES 1999-2006 in American. Participants' vitamin E levels were divided into four groups, and analyses such as study population description, stratified analysis, multiple logistic regression analysis, and curve fitting were performed. To perform data processing, the researchers used the statistical package R (The R Foundation; http://www.r-project.org ; version 3.6.3) and Empower Stats software ( www.empowerstats.net , X&Y solutions, Inc. Boston, Massachusetts). RESULT: The concentrations of serum vitamin E were negatively correlated with the risk of BV, especially when vitamin E were at 1198-5459ug/dL with (OR = -0.443, 95%CI = 0.447-0.923, P = 0.032) or without (OR = -0.521, 95%CI = 0.421-0.837, P = 0.006) adjustment for variables. At the same time, at lower levels, there was no significant association. Vitamin E supplementation may significantly reduce the risk of BV (p < 0.001). In addition, the risk of having BV decreased and then increased with increasing vitamin E concentrations at high BMI levels (p < 0.01). CONCLUSION: Vitamin E at moderate to high concentrations may significantly reduce BV risk, says the study, providing clinical evidence for the prevention and the treatment of BV.

Impact of age, sex, and thyroid autoimmunity on the association between selenium intake and type 2 diabetes mellitus.

BACKGROUND: The association between dietary selenium(Se) intake and type 2 diabetes mellitus (T2DM) remains controversial. The present study aimed to investigate this association using data from the National Health and Nutrition Examination Survey (NHANES) database for the years 2007-2012. METHODS: Three thousand seventy three individuals aged 20 years and above were eligible for inclusion in this cross-sectional study. The average age of the participants was 50.74 years and the proportions of males and females were nearly equal (49.12% vs. 50.88%). The odds ratios (OR) of the association between dietary Se intake (log2-transformed) and T2DM were examined through the multivariate logistic regression model. Subgroup analyses were conducted based on age, sex, and thyroid autoimmunity to assess the potential impact of these variables on the relationship. Fitted smoothing curves and threshold effect analysis were conducted to describe the nonlinear relationship. RESULTS: In the fully adjusted model, a significant positive association between Se intake and T2DM was observed (OR = 1.49, 95% CI: 1.16, 1.90, p = 0.0017). After stratifying the data by age, sex, and thyroid autoimmunity, a significant positive association between Se intake and T2DM was observed in individuals under 65 years of age, males, and those with negative thyroid autoimmunity. A two-segment linear regression model was analyzed for sex stratification, revealing a threshold effect in males with an inflection point of 90.51 µg, and an inverted U-shaped relationship in females with an inflection point of 109.90 µg, respectively. CONCLUSIONS: The present study found a positive relationship between Se intake and the prevalence of T2DM. This association is particularly significant in younger individuals, males, and those with negative thyroid autoimmunity. Our results should be validated in future large prospective studies in different populations.

RAGE potentiates EGFR signaling and interferes with the anticancer effect of gefitinib on NSCLC cells.

The receptor for advanced glycation end-products (RAGE) has been implicated in tumorigenesis, whereas epidermal growth factor receptor (EGFR) signaling plays a vital role in lung cancer progression. Both RAGE and EGFR are transmembrane receptors that transmit intracellular signals through ligand binding, and their downstream signaling cascades show substantial overlap. However, the interplay between these two molecules remains poorly understood. In the present study, we evaluated the correlation between RAGE and EGFR in the tumorigenesis of non-small cell lung cancer (NSCLC) and evaluated the impact of RAGE on the response of NSCLC cells to gefitinib, an EGFR-tyrosine kinase inhibitor (TKI). The expression and activation of EGFR and the phosphorylation of its downstream molecules, signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase (Erk), were increased in RAGE-overexpressed A549 (A549-RAGE) cells. Notably, ligand-triggered activation of EGFR signaling was significantly greater in A549-RAGE compared with A549-parental cells. In addition, gefitinib had less effect on the inhibition of EGFR signaling in A549-RAGE cells. These findings were validated in other NSCLC cell lines, H1299 and H1975. Furthermore, upon gefitinib administration, the antiapoptotic marker B-cell lymphoma 2 (Bcl-2) expression was upregulated in A549-RAGE cells, whereas the apoptotic markers Bcl-2 associated X protein (Bax) and Bcl-2 interacting mediator (Bim) remained at lower levels compared with A549-parental cells. Importantly, our findings provide evidence that RAGE interferes with the anticancer effect of gefitinib by modulating the activation of EGFR-STAT3 and EGFR-Erk pathways. Overall, these significant findings deepen our understanding of the intricate relationship between RAGE and EGFR signaling in NSCLC tumorigenesis and provide new considerations for the clinical treatment of NSCLC.NEW & NOTEWORTHY This study represents a pioneering endeavor in comprehending the intricate interplay between RAGE and EGFR signaling within NSCLC. The findings reveal that RAGE serves to enhance EGFR phosphorylation and activation, consequently modulating apoptosis regulators through the EGFR-STAT3 and EGFR-Erk1/2 signaling pathways. Through this mechanism, RAGE potentially imparts resistance to the toxicity induced by EGFR-TKIs in NSCLC cells.

Associations Between Aldosterone-Renin-Ratio and Bone Parameters Derived from Peripheral Quantitative Computed Tomography and Impact Microindentation in Men.

Components of the renin-angiotensin-aldosterone system (RAAS) are present on bone cells. One measure of RAAS activity, the aldosterone-renin-ratio (ARR), is used to screen for primary aldosteronism. Associations between ARR and bone mineral density are conflicting. This study investigated associations between ARR and peripheral quantitative computed tomography (pQCT) and impact microindentation (IMI). Male participants (n = 431) were from the Geelong Osteoporosis Study. "Likely" primary aldosteronism was defined as ARR ≥ 70 pmol/mIU. Another group, "possible" primary aldosteronism, was defined as either ARR ≥ 70 pmol/mIU or taking a medication that affects the RAAS, but not a beta blocker, and renin < 15 mU/L. Using pQCT, images at 4% and 66% of radial (n = 365) and tibial (n = 356) length were obtained. Using IMI measurements, bone material strength index (BMSi; n = 332) was determined. Associations between ARR or likely/possible primary aldosteronism and IMI or pQCT-derived bone parameters were tested using median regression. ARR and aldosterone values were not associated with any of the pQCT-derived bone variables in either unadjusted or adjusted analyses. Men with likely primary aldosteronism (n = 16), had lower adjusted total bone area (radial 66% site, - 12.5%). No associations were observed for men with possible primary aldosteronism (unadjusted or adjusted). No associations with BMSi were observed (p > 0.05). There were no associations between ARR or aldosterone and pQCT-derived bone parameters. Men with likely primary aldosteronism had lower bone area, suggesting clinically high levels of ARR may have a negative impact on bone health.

The hepatoprotective effects of plant-based foods based on the "gut-liver axis": a prospective review.

The importance of the "gut-liver axis" in the pathogenesis of liver diseases has been revealed recently; which promotes the process of developing preventive and therapeutic strategies. However, considering that there are still many challenges in the medical treatment of liver diseases, potential preventive dietary intervention may be a good alternative choice. Plant-based foods have received much attention due to their reported health-promoting effects in targeting multiple pathways involved in the pathogenesis of liver diseases as well as the relative safety for general use. Based on the PubMed and Web of Science databases, this review emphatically summarizes the plant-based foods and their chemical constituents with reported effects to impact the LPS/TLR4 signaling pathway of gut-liver axis of various liver diseases, reflecting their health benefits in preventing/alleviating liver diseases. Moreover, some plant-based foods with potential gut-liver effects are specifically analyzed from the reported studies and conclusions. This review intends to provide readers an overview of the current progress in the field of this research topic. We expect to see more hepatoprotective measures for alleviating the current prevalence of liver diseases.

Association between red blood cell folate and Trichomonas vaginalis infection among women.

BACKGROUND: Increased folic acid has been found to be latently protective against gynecological infection, including several kinds of vaginosis. In this study, we laid emphasis on whether RBC (Red Blood Cell) folate was associated with the infectious ratio of Trichomonas vaginalis, a kind of anaerobic parasitic protozoan. METHODS: We set RBC folate as the exposure variable and Trichomonas vaginalis as the outcome variable. Other subsidiary variables were regarded as covariates that may work as potential effect modifiers. The cross-sectional study was conducted with two merged waves of the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2004, and a sample of 1274 eligible women (1212 negative and 62 positive in Trichomonas vaginalis infection) was integrated for the exploration of the association between RBC folate and Trichomonas vaginalis infection. Multivariate regression analyses, subgroup analyses, and subsequent smooth curve fittings were conducted to estimate the relationship between RBC folate and Trichomonas vaginalis in women. RESULTS: In the multivariable logistic regression analyses, a negative association was observed between stratified RBC folate status and Trichomonas vaginalis infection with all confounders adjusted. Referencing the lowest RBC folate concentration quartile, the higher concentration quartiles reported a relatively lower infection ratio, while there was a weak correlation between total RBC folate concentration and T. vaginalis (Trichomonas vaginalis) infection. In subgroup analyses stratified by BMI and age, this association was only found significant in high age and BMI groups. CONCLUSIONS: The cross-sectional study indicated a negative association between RBC folic acid and Trichomonas vaginalis infection, and latent effects of BMI and age on the association were also found.

Negative associations between folate and bacterial vaginosis in the NHANES 2001 to 2004.

BACKGROUND: Bacterial vaginosis (BV) is one of the most common infections among women of reproductive age and accounts for 15-50% of infections globally. The role played by folate in the pathogenesis and progression of BV is poorly understood. The aim of this study was to investigate the association between serum folate, red blood cell (RBC) folate, and BV in American women. METHODS: 1,954 participants from the 2001-2004 National Health and Nutrition Examination Survey (NHANES) program were included in this study. Multiple logistic regression was used to analyze the association between serum folate, RBC folate, and BV, and covariates including race, age, education level, and body mass index were used to construct adjusted models. Stratified analysis was used to explore the stability of the above associations in different populations. RESULTS: In the present cross-sectional study, we found that serum folate and RBC folate were inversely associated with the risk of BV. In the fully adjusted model, the risk of BV was reduced by 35% (OR=0.65, 95% CI: 0.51~0.83, p=0.0007) in the highest serum folate group and 32% (OR=0.68, 95% CI: 0.53~0.87, p=0.0023) in the highest RBC folate group compared to the lowest group. CONCLUSIONS: The results of this study indicated that serum folate and RBC folate were inversely associated with the risk of BV folate supplementation may play an important role in the prevention and management of BV.

In Situ Construction of Nitrogen-Doped and Zinc-Confined Microporous Carbon Enabling Efficient Na+-Storage Abilities.

Benefiting from the additional active sites for sodium-ion (Na+) adsorption and porous architecture for electrolyte accessibility, nitrogen-doped porous carbon has been considered the alternative anode material for Na+-storage applications. In this study, nitrogen-doped and zinc-confined microporous carbon (N,Z-MPC) powders are successfully prepared by thermally pyrolyzing the polyhedral ZIF-8 nanoparticles under an argon atmosphere. Following the electrochemical measurements, the N,Z-MPC not only delivers good reversible capacity (423 mAh/g at 0.02 A/g) and comparable rate capability (104 mAh/g at 1.0 A/g) but also achieves a remarkable cyclability (capacity retention: 96.6% after 3000 cycles at 1.0 A/g). Those can be attributed to its intrinsic characteristics: (a) 67% of the disordered structure, (b) 0.38 nm of interplanar distance, (c) a great proportion of sp2-type carbon, (d) abundant microporosity, (e) 16.1% of nitrogen doping, and (f) existence of sodiophilic Zn species, synergistically enhancing the electrochemical performances. Accordingly, the findings observed here support the N,Z-MPC to be a potential anode material enabling exceptional Na+-storage abilities.

Supersaturation and Precipitation Applicated in Drug Delivery Systems: Development Strategies and Evaluation Approaches.

Supersaturation is a promising strategy to improve gastrointestinal absorption of poorly water-soluble drugs. Supersaturation is a metastable state and therefore dissolved drugs often quickly precipitate again. Precipitation inhibitors can prolong the metastable state. Supersaturating drug delivery systems (SDDS) are commonly formulated with precipitation inhibitors, hence the supersaturation is effectively prolonged for absorption, leading to improved bioavailability. This review summarizes the theory of and systemic insight into supersaturation, with the emphasis on biopharmaceutical aspects. Supersaturation research has developed from the generation of supersaturation (pH-shift, prodrug and SDDS) and the inhibition of precipitation (the mechanism of precipitation, the character of precipitation inhibitors and screening precipitation inhibitors). Then, the evaluation approaches to SDDS are discussed, including in vitro, in vivo and in silico studies and in vitro-in vivo correlations. In vitro aspects involve biorelevant medium, biomimetic apparatus and characterization instruments; in vivo aspects involve oral absorption, intestinal perfusion and intestinal content aspiration and in silico aspects involve molecular dynamics simulation and pharmacokinetic simulation. More physiological data of in vitro studies should be taken into account to simulate the in vivo environment. The supersaturation theory should be further completed, especially with regard to physiological conditions.

Genomic Analysis of Group B Streptococcus from Neonatal Sepsis Reveals Clonal CC17 Expansion and Virulence- and Resistance-Associated Traits After Intrapartum Antibiotic Prophylaxis.

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of invasive neonatal infections. This study aimed to investigate the trend of GBS serotype and genotype change and their correlation with antimicrobial resistance before and after implementation of intrapartum antibiotic prophylaxis (IAP). METHODS: We performed serotyping, whole-genome sequencing, antimicrobial susceptibility testing, and single-nucleotide polymorphism (SNP)-based phylogenetic analysis on 238 invasive GBS isolates collected from October 1998 to February 2020 in Taiwan. RESULTS: There were 7 serotypes and 6 clonal complexes (CCs) among the 238 GBS isolates, and more than half of the isolates carried multiple antimicrobial resistance genes. The expansion of CC17 strains and the increase in late-onset disease occurred synchronously after the implementation of IAP. Analysis of the carriage isolates from pregnant women showed diverse serotype distribution in the IAP era. The antimicrobial susceptibility testing showed that all 238 strains were susceptible to ampicillin and penicillin, while the number of various resistance genes in GBS genomes was found increased with the expansion of CC17. Compared with reference genomes, 697 nonsynonymous SNPs in 443 protein-coding genes were CC17 specific. CONCLUSIONS: The study revealed the expansion of GBS CC17 and the increase of late-onset disease that occurred simultaneously with the implementation of IAP. Although the susceptibility of CC17 to antimicrobial agents is not different from that of other sequence types at present, GBS with phenotypic resistance to antimicrobials may emerge in the future, given the environmental selection pressure and the continued accumulation of SNP mutations.

Fracture Risk and Use of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II Receptor Blockers.

Medications used to treat hypertension may affect fracture risk. This study investigated fracture risk for users of angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB). Participants (899 men, median age 70.3 yr (59.9-79.1), range 50.0-96.6 yr; 574 women, median age 65.5 yr (58.1-75.4), range 50.1-94.6 yr) were from the Geelong Osteoporosis Study. Medication use was self-reported and incident fractures were ascertained using radiological reports. Bone mineral density (BMD) was measured at the femoral neck. Participants were divided into four groups: (1) non-users without hypertension, (2) non-users with hypertension, (3) ACEI users and (4) ARB users. Dosage was calculated using the defined daily dose (DDD) criteria. Participants were followed from date of visit to first fracture, death or 31 December 2016, whichever occurred first. Cox proportional hazards models were used for analyses. At least one incident fracture was sustained by 156 men and 135 women over a median(IQR) of 11.5(6.2-13.2) and 10.9(6.3-11.6) years of follow-up, respectively. In unadjusted analyses, compared to non-users without hypertension, men in all three other groups had a higher risk of fracture (Hazard Ratio (HR, 95%CI) 1.54, 1.00-2.37; 1.90, 1.18-3.05; 2.15, 1.26-3.66), for non-users with hypertension, ACEI and ARB users, respectively). Following adjustment for age, prior fracture and BMD, these associations became non-significant. A dose effect for ARB use was observed; men using lower doses had a higher risk of fracture than non-users without hypertension, in both unadjusted (2.66, 1.34-5.29) and adjusted (2.03, 1.01-4.08) analyses, but this association was not observed at higher doses. For women, unadjusted analyses showed a higher risk for ACEI users compared to non-users without hypertension (1.74, 1.07-2.83). This was explained after adjustment for age, alcohol consumption, prior fracture and BMD (1.28, 0.74-2.22). No other differences were observed. In men, lower dose (0 < DDD ≤ 1) ARB use was associated with an increased risk of fracture. ACEI or ARB use was not associated with increased risk of incident fracture in women. These findings may be important for antihypertensive treatment decisions in individuals with a high risk of fracture.

Modulation of adenine phosphoribosyltransferase-mediated salvage pathway to accelerate diabetic wound healing.

Adenine phosphoribosyltransferase (APRT) is the key enzyme involved in purine salvage by the incorporation of adenine and phosphoribosyl pyrophosphate to provide adenylate nucleotides. To evaluate the role of APRT in the repair processes of cutaneous wounds in healthy skin and in diabetic patients, a diabetic mouse model (db/db) and age-matched wild-type mice were used. Moreover, the topical application of adenine was assessed. In vitro studies, analytical, histological, and immunohistochemical methods were used. Diabetic mice treated with adenine exhibited elevated ATP levels in organismic skin and accelerated wound healing. In vitro studies showed that APRT utilized adenine to rescue cellular ATP levels and proliferation from hydrogen peroxide-induced oxidative damage. HPLC-ESI-MS/MS-based analysis of total adenylate nucleotides in NIH-3T3 fibroblasts demonstrated that adenine addition enlarged the cellular adenylate pool, reduced the adenylate energy charge, and provided additional AMP for the further generation of ATP. These data indicate an upregulation of APRT in skin wounds, highlighting its role during the healing of diabetic wounds through regulation of the nucleotide pool after injury. Furthermore, topical adenine supplementation resulted in an enlargement of the adenylate pool needed for the generation of ATP, an important molecule for wound repair.

Habitat effects on reproductive phenotype, pollinator behavior, fecundity, and mating outcomes of a bumble bee-pollinated herb.

PREMISE: Fecundity and mating outcomes commonly differ among plant populations occupying contrasting environments. If self-pollination occurs primarily among flowers within plants, contrasting reproductive outcomes among populations must reflect environmental effects on plant-pollinator interactions. Specifically, local conditions could affect features of plant phenotypes that influence pollinator behavior, in turn modifying plant reproductive outcomes. METHODS: We compared phenotypes, pollinator abundance and behavior, and female fecundity and mating in two meadow populations and two forest populations of Aconitum kusnezoffii within 3 km of each other. Mating outcomes were assessed using microsatellites. RESULTS: Meadow plants generally produced more, shorter ramets with more, larger flowers, but less nectar per flower than forest plants. These differences likely largely represent phenotypic plasticity. Individual bumble bees visited more flowers on forest plants, likely because the more abundant bees in the meadows depleted nectar availability, as indicated by briefer visits to individual flowers. Despite similar fruit set in both habitats, forest plants set more seeds per fruit. Nevertheless, meadow plants produced more seeds overall, owing to sevenfold greater flower production. Consistent with individual bees visiting fewer flowers on meadow plants, more of their seeds were outcrossed. However, the outcrossed seeds of forest plants included more male mates. CONCLUSIONS: Reproductive outcomes can vary among populations of animal-pollinated plants as a result of differences in the availability of effective pollinators and environmental effects on plant phenotypes, and their functional consequences for pollinator behavior that governs pollen dispersal.

Horizontal root fracture in posterior teeth without dental trauma: A diseased condition with special characteristics.

Horizontal root fractures (HRF) were observed mostly in the anterior teeth of young adults due to dental injury. However, HRFs in posterior teeth (PHRF) without dental trauma cannot be neglected. The etiology and risk factors of PHRF were unclear. Lower premolars and palatal root of maxillary molars were particularly affected, indicating the specificity of this diseased entity. PHRF were mainly reported in Asian population, suggesting possible racial difference. Whereas most PHRF teeth showed symptoms mimicking endodontic and periodontal lesions, some affected teeth were asymptomatic. Periodontal pocket, soft tissue swelling, chronic pain or discomfort during mastication were commonly noted. Diagnosis of PHRF depended on thorough clinical examination, radiographic images or exploratory surgery. Intracanal bleeding and electronic apex locator confirmation during endodontic treatment were also useful for diagnosis. Flexible splinting, endodontic/periodontal treatment or root amputation were treatment strategies to preserve the fractured teeth. The aim of this narrative review is to summarize the demography, tooth and root distribution, diagnostic methods, etiology and possible related factors, clinical features, radiographic characteristics, and the treatment schemes of PHRF without dental trauma. A better understanding and identification of this particular root fracture could be achieved. The diagnostic tools and practical management are useful for clinical guides.

Cracked teeth: Distribution and survival at 6 months, 1 year and 2 years after treatment.

BACKGROUND/PURPOSE: The unpredictable condition of cracked teeth warrants further investigation and clinical experiences. The purpose of this study was to collect and record data on demographics, clinical characteristics, different treatment modalities and survival of cracked teeth at 6-month, 1-year and 2-year recalls. METHODS: 77 cracked teeth from 65 patients were included. Data on demographics, clinical parameters, treatment modalities and recall were collected. Binomial, multinomial and chi square tests were used for statistical analysis. RESULTS: Most cracked teeth occurred in patients greater than 40 years old (p < 0.01). Cracked teeth themselves were most often molars (79.22%; p < 0.01), a non-terminal tooth in the arch (62.34%; p < 0.05) and nonendodontically-treated teeth (94.81%; p < 0.01). Cracked teeth exhibited pain to percussion (63.64%, p < 0.05) or biting (74.03%; p < 0.01), and no or only positive mobility (76.62%; p < 0.01). Cracks were most often oriented in the mesiodistal direction (68.83%; p < 0.01). Higher survival rates were noted in cracked teeth lacking pre-operative pain to palpation or spontaneous pain, and with no or only positive mobility at 6-month and 1-year recalls. In vital cracked teeth, higher survival rates were noted in teeth lacking pre-operative pain to palpation and with no or only positive mobility at 2-year recalls. CONCLUSION: The absence of pre-operative palpation discomfort, spontaneous pain and minimal mobility, as well as the presence of pulp vitality were associated with higher survival rates of cracked teeth at all recall times. Results are useful for diagnosis and outcomes-based treatment planning of cracked teeth.

Baseline Global Cognitive Function Affects Cognitive and Functional Outcomes of Combined Physical and Cognitive Training Among Older Adults With Cognitive Decline.

IMPORTANCE: Baseline global cognitive function may affect cognitive and functional outcomes during combined physical and cognitive training; however, how it influences the effects of combined training remains uncertain. OBJECTIVE: To determine the impact of baseline global cognitive function on cognitive and functional outcomes after combined physical and cognitive training among older adults with cognitive decline. DESIGN: Observational. SETTING: Local communities and senior centers. PARTICIPANTS: Older adults with mild cognitive decline (MCD; n = 51) and moderate to severe cognitive decline (MSCD; n = 40). INTERVENTION: Participants received 45 to 55 min of physical exercise training followed by 45 to 55 min of cognitive training in one session per week for 12 wk. Outcomes and Measures: Montreal Cognitive Assessment (MoCA), Lawton-Brody Instrumental Activities of Daily Living Scale (Lawton-Brody IADL), Word Recall Test (WRT), Stroop Color and Word Test (SCWT), Digital Symbol Substitution Test (DSST), and Trail Making Test (TMT) scores were assessed and compared between the MCD and MSCD groups. RESULTS: Significant interaction effects were found for the WRT, SCWT, MoCA, and Lawton-Brody IADL. WRT and SCWT scores significantly improved in the MCD group, whereas MoCA and Lawton-Brody IADL scores significantly improved in the MSCD group. DSST scores increased among all participants, but TMT scores improved only in the MCD group. CONCLUSIONS AND RELEVANCE: Older adults' baseline global cognitive function affected cognitive and instrumental activities of daily living (IADL) outcomes regarding combined training. High-level cognitive function, including inhibition and shifting abilities and working memory capacity, improved among older adults with MCD, whereas general cognitive function and IADLs improved among older adults with MSCD. What This Article Adds: Findings revealed domain-specific changes with respect to baseline cognitive function, which may help to refine current combined training protocols and facilitate development of personalized combined training programs for older adults with cognitive impairments.