Upregulation of serine metabolism enzyme PSAT1 predicts poor prognosis and promotes proliferation, metastasis and drug resistance of clear cell renal cell carcinoma.

Serine metabolic reprogramming is known to be associated with oncogenesis and tumor development. The key metabolic enzyme PSAT1 has been identified as a potential prognostic marker for various cancers, but its role in ccRCC remains unkown. In this study, we investigated expression of PSAT1 in ccRCC using the TCGA database and clinical specimens. Our results showed that PSAT1 exhibited lower expression in tumor tissue compared to adjacent normal tissue, but its expression level increased with advancing stages and grades of ccRCC. Patients with elevated expression level of PSAT1 exhibited an unfavorable prognosis. Functional experiments have substantiated that the depletion of PSAT1 shows an effective activity in inhibiting the proliferation, migration and invasion of ccRCC cells, concurrently promoting apoptosis. RNA sequencing analysis has revealed that the attenuation of PSAT1 can diminish tumor resistance to therapeutic drugs. Furthermore, the xenograft model has indicated that the inhibition of PSAT1 can obviously impact the tumorigenic potential of ccRCC and mitigate lung metastasis. Notably, pharmacological targeting PSAT1 by Aminooxyacetic Acid (AOA) or knockdown of PSAT1 increased the susceptibility of sunitinib-resistant cells. Inhibition of PSAT1 increased the sensitivity of drug-resistant tumors to sunitinib in vivo. Collectively, our investigation identifies PSAT1 as an independent prognostic biomarker for advanced ccRCC patients and as a prospective therapeutic target.

Prognostic value and model construction of preoperative inflammatory markers in patients with metastatic renal cell carcinoma.

BACKGROUND: Inflammation is considered to be one of the driving factors of cancer, and chronic inflammation plays a crucial role in tumor growth and metastasis. The aim of this study was to examine the predictive value of preoperative inflammatory biomarkers for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC), including preoperative neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and aspartate aminotransferase-to-lymphocyte ratio (ALR), a novel inflammatory biomarker. METHOD: This study included 198 patients with mRCC from a single center from 2006 to 2022. The optimal cut-off levels for the three biomarkers were derived using the receiver operating characteristic curve (ROC). Cox univariate and multivariate analyses were used to assess independent prognostic inflammatory biomarkers. Finally, independent prognostic inflammatory biomarkers were incorporated into the prognostic model to establish a nomogram to predict the postoperative survival of patients with mRCC. RESULT: The area under the ROC curve for NLR, LMR, and ALR, respectively, is 0.71 (CI: 0.635-0.784), 0.68 (CI: 0.604-0.755), and 0.75 (CI: 0.680-0.819). The optimal LMR, NLR, and ALR cut-off levels as evaluated by the ROC curve were 3.836, 3.106, and 68.056, respectively. Patients with NLR and ALR higher than the cut-off level and LMR lower than the cut-off level had a significant relationship with OS. Multivariate analysis revealed that tumor necrosis, lower LMR, and higher ALR were independent risk factors for OS. In addition, a nomogram that includes independent prognostic inflammatory biomarkers can accurately predict the OS in patients with mRCC. CONCLUSION: ALR and LMR are independent risk factors for the prognosis of individuals with mRCC. By monitoring ALR and LMR postoperatively, the prognosis of patients with mRCC can be better evaluated.

Genome-wide analysis of genomic imprinting in the endosperm and allelic variation in flax.

Genomic imprinting is an epigenetic phenomenon that causes biased expression of maternally and paternally inherited alleles. In flowering plants, genomic imprinting predominantly occurs in the triploid endosperm and plays a vital role in seed development. In this study, we identified 248 candidate imprinted genes including 114 maternally expressed imprinted genes (MEGs) and 134 paternally expressed imprinted genes (PEGs) in flax (Linum usitatissimum L.) endosperm using deep RNA sequencing. These imprinted genes were neither clustered in specific chromosomal regions nor well conserved among flax and other plant species. MEGs tended to be expressed specifically in the endosperm, whereas the expression of PEGs was not tissue-specific. Imprinted single nucleotide polymorphisms differentiated 200 flax cultivars into the oil flax, oil-fiber dual purpose flax and fiber flax subgroups, suggesting that genomic imprinting contributed to intraspecific variation in flax. The nucleotide diversity of imprinted genes in the oil flax subgroup was significantly higher than that in the fiber flax subgroup, indicating that some imprinted genes underwent positive selection during flax domestication from oil flax to fiber flax. Moreover, imprinted genes that underwent positive selection were related to flax functions. Thirteen imprinted genes related to flax seed size and weight were identified using a candidate gene-based association study. Therefore, our study provides information for further exploration of the function and genomic variation of imprinted genes in the flax population.

Identification and verification of genes related to pollen development and male sterility induced by high temperature in the thermo-sensitive genic male sterile wheat line.

MAIN CONCLUSION: Bioinformatic analysis identified the function of genes regulating wheat fertility. Barley stripe mosaic virus-induced gene silencing verified that the genes TaMut11 and TaSF3 are involved in pollen development and related to fertility conversion. Environment-sensitive genic male sterility is of vital importance to hybrid vigor in crop production and breeding. Therefore, it is meaningful to study the function of the genes related to pollen development and male sterility, which is still not fully understand currently. In this study, YanZhan 4110S, a new thermo-sensitive genic male sterility wheat line, and its near-isogenic line YanZhan 4110 were analyzed. Through comparative transcriptome basic bioinformatics and weighted gene co-expression network to further identify some hub genes, the genes TaMut11 and TaSF3 associated with pollen development and male sterility induced by high-temperature were identified in YanZhan 4110S. Further verification through barley stripe mosaic virus-induced gene silencing elucidated that the silencing of TaMut11 and TaSF3 caused pollen abortion, finally resulting in the declination of fertility. These findings provided data on the abortive mechanism in environment-sensitive genic male sterility wheat.

Identification and validation of genetic locus Rfk1 for wheat fertility restoration in the presence of Aegilops kotschyi cytoplasm.

KEY MESSAGE: Major fertility restorer locus for Aegilops kotschyi cytoplasm in wheat, Rfk1, was mapped to chromosome arm 1BS. Most likely candidate gene is TraesCS1B02G197400LC, which is predicted to encode a pectinesterase/pectinesterase inhibitor. Cytoplasmic male sterility (CMS) is widely used for heterosis and hybrid seed production in wheat. Genes related to male fertility restoration in the presence of Aegilops kotschyi cytoplasm have been reported, but the fertility restoration-associated gene loci have not been investigated systematically. In this study, a BC1F1 population derived from a backcross between KTP116A, its maintainer line TP116B, and its restorer line LK783 was employed to map fertility restoration by bulked segregant RNA-Seq (BSR-Seq). A major fertility allele restorer locus for Ae. kotschyi cytoplasm in wheat, Rfk1, was mapped to chromosome arm 1BS, and it was contributed by LK783. Morphological and cytological studies showed that male fertility restoration occurred mainly after the late uninucleate stage. Based on simple sequence repeat and single-nucleotide polymorphism genotyping, the gene locus was located between Xnwafu_6 and Xbarc137 on chromosome arm 1BS. To further isolate the specific region, six Kompetitive allele-specific polymerase chain reaction markers derived from BSR-Seq were developed to delimit Rfk1 within physical intervals of 26.0 Mb. After searching for differentially expressed genes within the candidate interval in the anthers and sequencing analysis, TraesCS1B02G197400LC was identified as a candidate gene for Rfk1 and it was predicted to encode a pectinesterase/pectinesterase inhibitor. Expression analysis also confirmed that it was specifically expressed in the anthers, and its expression level was higher in fertile lines compared with sterile lines. Thus, TraesCS1B02G197400LC was identified as the most likely candidate gene for Rfk1, thereby providing insights into the fertility restoration mechanism for K-type CMS in wheat.

Blocked synthesis of sporopollenin and jasmonic acid leads to pollen wall defects and anther indehiscence in genic male sterile wheat line 4110S at high temperatures.

Environment-sensitive genic male sterility is a valid tool for hybrid production and hybrid breeding, but there are no previous reports of the molecular mechanism of fertility conversion. In this study, RNA-seq, phenotypic and cytological observations, and physiological indexes were applied to analyze thermo-sensitive genic male sterility line 4110S under different temperature conditions to explore the fertility transformation mechanism. In total, 3420 differentially expressed genes (DEGs) were identified comprising 2331 upregulated genes and 1089 downregulated genes. The DEGs were apparently distributed among 54 Gene Ontology functional groups. The phenylpropanoid, long-chain fatty acid, and jasmonic acid (JA) biosynthesis pathways were related to male sterility, where their downregulation blocked the synthesis of sporopollenin and JA. Phenotypic and cytological analyses showed that pollen wall defects and anther indehiscence at high temperatures induced sterility. Moreover, enzyme-linked immunosorbent assay results indicated that the abundance of JA was lower in 4110S under restrictive conditions (high temperature) than permissive conditions (low temperature). A possible regulated network of pathways associated with male sterility was suggested. These results provided insights into the molecular mechanism of fertility conversion in the thermosensitive male sterility system.

Comprehensive analysis of polygalacturonase gene family highlights candidate genes related to pollen development and male fertility in wheat (Triticum aestivum L.).

MAIN CONCLUSION: Four polygalacturonase gene family members were highlighted that contribute to elucidate the roles of polygalacturonase during the fertility conversion process in male-sterile wheat. Polygalacturonase (PG) belongs to a large family of hydrolases with important functions in cell separation during plant growth and development via the degradation of pectin. Specific expressed PGs in anthers may be significant for male sterility research and hybrid wheat breeding, but they have not been characterized in wheat (Triticum aestivum L.). In this study, we systematically studied the PG gene family using the latest published wheat reference genomic information. In total, 113 wheat PG genes were identified, which could be classified into six categories A-F according to their structure characteristics and phylogenetic comparisons with Arabidopsis and rice. Polyploidy and segmental duplications in wheat were proved to be mainly responsible for the expansion of the wheat PG gene family. RNA-seq showed that TaPGs have specific temporal and spatial expression characteristics, in which 12 TaPGs with spike-specific expression patterns were detected by qRT-PCR in different fertility anthers of KTM3315A, a thermo-sensitive cytoplasmic male-sterile wheat. Four of them specific upregulated (TaPG09, TaPG95, and TaPG93) or downregulated (TaPG87) at trinucleate stage of fertile anthers, and further aligning with the homologous in Arabidopsis revealed that they may undertake functions such as anther dehiscence, separation of pollen, pollen development, and pollen tube elongation, thereby inducing male fertility conversion in KTM3315A. These findings facilitate function investigations of the wheat PG gene family and provide new insights into the fertility conversion mechanism in male-sterile wheat.

Genome-Wide Investigation of Heat Shock Transcription Factor Family in Wheat (Triticum aestivum L.) and Possible Roles in Anther Development.

Heat shock transcription factors (HSFs) play crucial roles in resisting heat stress and regulating plant development. Recently, HSFs have been shown to play roles in anther development. Thus, investigating the HSF family members and identifying their protective roles in anthers are essential for the further development of male sterile wheat breeding. In the present study, 61 wheat HSF genes (TaHsfs) were identified in the whole wheat genome and they are unequally distributed on 21 chromosomes. According to gene structure and phylogenetic analyses, the 61 TaHsfs were classified into three categories and 12 subclasses. Genome-wide duplication was identified as the main source of the expansion of the wheat HSF gene family based on 14 pairs of homeologous triplets, whereas only a very small number of TaHsfs were derived by segmental duplication and tandem duplication. Heat shock protein 90 (HSP90), HSP70, and another class of chaperone protein called htpG were identified as proteins that interact with wheat HSFs. RNA-seq analysis indicated that TaHsfs have obvious period- and tissue-specific expression patterns, and the TaHsfs in classes A and B respond to heat shock, whereas the C class TaHsfs are involved in drought regulation. qRT-PCR identified three TaHsfA2bs with differential expression in sterile and fertile anthers, and they may be candidate genes involved in anther development. This comprehensive analysis provides novel insights into TaHsfs, and it will be useful for understanding the mechanism of plant fertility conversion.

Analysis of metabolic pathways related to fertility restoration and identification of fertility candidate genes associated with Aegilops kotschyi cytoplasm in wheat (Triticum aestivum L.).

BACKGROUND: Thermo-sensitive male-sterility based on Aegilops kotschyi cytoplasm (K-TCMS) plays an important role in hybrid wheat breeding. This has important possible applications in two-line hybrid wheat breeding but the genetic basis and molecular regulation mechanism related to fertility restoration are poorly understood. In this study, comparative transcriptome profiling based on RNA sequencing was conducted for two near-isogenic lines comprising KTM3315R and its sterile counterpart KTM3315A, a total of six samples (3 repetitions per group), in order to identify fertility restoration genes and their metabolic pathways. RESULTS: In total, 2642 significant differentially expressed genes (DEGs) were detected, among which 1238 were down-regulated and 1404 were up-regulated in fertile anthers. Functional annotation enrichment analysis identified important pathways related to fertility restoration, such as carbohydrate metabolism, phenylpropanoid metabolism and biosynthesis, as well as candidate genes encoding pectin methylesterase and flavanone 3-hydroxylase. Moreover, transcription factor analysis showed that a large number of DEGs were mainly involved with the WRKY, bHLH, and MYB transcription factor families. Determination of total soluble sugar and flavonoid contents demonstrated that important metabolic pathways and candidate genes are associated with fertility restoration. Twelve DEGs were selected and detected by quantitative reverse-transcribed PCR, and the results indicated that the transcriptome sequencing results were reliable. CONCLUSIONS: Our results indicate that identified DEGs were related to the fertility restoration and they proved to be crucial in Aegilops kotschyi cytoplasm. These findings also provide a basis for exploring the molecular regulation mechanism associated with wheat fertility restoration as well as screening and cloning related genes.

iTRAQ-Based Proteomics Analyses of Sterile/Fertile Anthers from a Thermo-Sensitive Cytoplasmic Male-Sterile Wheat with Aegilops kotschyi Cytoplasm.

A “two-line hybrid system” was developed, previously based on thermo-sensitive cytoplasmic male sterility in Aegilops kotschyi (K-TCMS), which can be used in wheat breeding. The K-TCMS line exhibits complete male sterility and it can be used to produce hybrid wheat seeds during the normal wheat-growing season; it propagates via self-pollination at high temperatures. Isobaric tags for relative and absolute quantification-based quantitative proteome and bioinformatics analyses of the TCMS line KTM3315A were conducted under different fertility conditions to understand the mechanisms of fertility conversion in the pollen development stages. In total, 4639 proteins were identified, the differentially abundant proteins that increased/decreased in plants with differences in fertility were mainly involved with energy metabolism, starch and sucrose metabolism, phenylpropanoid biosynthesis, protein synthesis, translation, folding, and degradation. Compared with the sterile condition, many of the proteins that related to energy and phenylpropanoid metabolism increased during the anther development stage. Thus, we suggest that energy and phenylpropanoid metabolism pathways are important for fertility conversion in K-TCMS wheat. These findings provide valuable insights into the proteins involved with anther and pollen development, thereby, helping to further understand the mechanism of TCMS in wheat.

Identification of Proteins Involved in Carbohydrate Metabolism and Energy Metabolism Pathways and Their Regulation of Cytoplasmic Male Sterility in Wheat.

Cytoplasmic male sterility (CMS) where no functional pollen is produced has important roles in wheat breeding. The anther is a unique organ for male gametogenesis and its abnormal development can cause male sterility. However, the mechanisms and regulatory networks related to plant male sterility are poorly understood. In this study, we conducted comparative analyses using isobaric tags for relative and absolute quantification (iTRAQ) of the pollen proteins in a CMS line and its wheat maintainer. Differentially abundant proteins (DAPs) were analyzed based on Gene Ontology classifications, metabolic pathways and transcriptional regulation networks using Blast2GO. We identified 5570 proteins based on 23,277 peptides, which matched with 73,688 spectra, including proteins in key pathways such as glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase and 6-phosphofructokinase 1 in the glycolysis pathway, isocitrate dehydrogenase and citrate synthase in the tricarboxylic acid cycle and nicotinamide adenine dinucleotide (NADH)-dehydrogenase and adenosine-triphosphate (ATP) synthases in the oxidative phosphorylation pathway. These proteins may comprise a network that regulates male sterility in wheat. Quantitative real time polymerase chain reaction (qRT-PCR) analysis, ATP assays and total sugar assays validated the iTRAQ results. These DAPs could be associated with abnormal pollen grain formation and male sterility. Our findings provide insights into the molecular mechanism related to male sterility in wheat.

Public Health Employees' Perception of Workplace Environment and Job Satisfaction: The Role of Local Health Departments' Engagement in Accreditation.

OBJECTIVES: To examine the association between local health departments' (LHDs') engagement in accreditation and their staffs' perceptions of workplace environment and the overall satisfaction with their jobs. DESIGN: Data from the 2014 Public Health Workforce Interests and Needs Survey (PH WINS) (local data only) and the 2014 Forces of Change survey were linked using LHDs' unique ID documented by the National Association of County & City Health Officials. The Forces of Change survey assessed LHDs' accreditation status. Local health departments were classified as "formally engaged" in the Public Health Accreditation Board accreditation process if they had achieved accreditation, submitted an application, or submitted a statement of intent. The PH WINS survey measured employees' perception of 3 aspects of workplace environment, including supervisory support, organizational support, and employee engagement. The overall satisfaction was measured using the Job in General Scale (abridged). There are 1884 LHD employees who completed PH WINS and whose agencies responded to the question on the accreditation status of the Forces of Change survey. RESULTS: When compared with employees from LHDs less engaged in accreditation, employees from LHDs that were formally engaged in accreditation gave higher ratings to all 3 aspects of workplace environment and overall job satisfaction. Controlling for employee demographic characteristics and LHD jurisdiction size, the agency's formal engagement in accreditation remained related to a higher score in perceived workplace environment and job satisfaction. After controlling for perceived workplace environment, accreditation status was marginally associated with job satisfaction. CONCLUSION: The findings provide support for previous reports by LHD leaders on the benefits of accreditation related to employee morale and job satisfaction. The results from this study allow us to further catalog the benefits of accreditation in workforce development and identify factors that may moderate the extent of the benefits. Findings from this study show that engagement in public health accreditation is associated with overall job satisfaction. This link may be explained by the hypotheses that meeting accreditation standards could increase staff satisfaction or that having higher job satisfaction could lead to a higher likelihood that a health department would apply for accreditation. Further research to explore this relationship is critical as many health departments are weighing the value of accreditation as they face constrained financial resources.

Local Boards of Health Characteristics Influencing Support for Health Department Accreditation.

BACKGROUND: Local boards of health (LBoHs) serve as the governance body for 71% of local health departments (LHDs). PURPOSE: To assess the impact of LBoH governance functions and other characteristics on the level of LBoH support of LHD accreditation. METHODS: Data from 394 LHDs that participated in the 2015 Local Boards of Health Survey were used for computing summative scores for LBoHs for domains of taxonomy and performing logistic regression analyses in 2016. RESULTS: Increased odds of an LBoH directing, encouraging, or supporting LHD accreditation activities were significantly associated with (a) a higher overall combined score measuring performance of governance functions and presence of other LBoH characteristics (adjusted odds ratio [AOR] = 1.05; P < .001); (b) a higher combined score for the Governance Functions subscale (AOR = 1.06; P < .01); (c) the "continuous improvement" governance function (AOR = 1.15; P < .001); and (d) characteristics and strengths such as board composition (eg, LBoH size, type of training, elected vs nonelected members), community engagement and input, and the absence of an elected official on the board (AOR = 1.14; P = .02). CONCLUSIONS: LBoHs are evenly split by thirds in their attention to Public Health Accreditation Board accreditation among the following categories: (a) encouraged or supported, (b) discussed but made no recommendations, and (c) did not discuss. This split might indicate that they are depending on the professional leadership of the LHD to make the decision or that there is a lack of awareness. The study findings have policy implications for both LBoHs and initiatives aimed at strengthening efforts to promote LHD accreditation.

Creating a Taxonomy of Local Boards of Health Based on Local Health Departments' Perspectives.

OBJECTIVES: To develop a local board of health (LBoH) classification scheme and empirical definitions to provide a coherent framework for describing variation in the LBoHs. METHODS: This study is based on data from the 2015 Local Board of Health Survey, conducted among a nationally representative sample of local health department administrators, with 394 responses. The classification development consisted of the following steps: (1) theoretically guided initial domain development, (2) mapping of the survey variables to the proposed domains, (3) data reduction using principal component analysis and group consensus, and (4) scale development and testing for internal consistency. RESULTS: The final classification scheme included 60 items across 6 governance function domains and an additional domain-LBoH characteristics and strengths, such as meeting frequency, composition, and diversity of information sources. Application of this classification strongly supports the premise that LBoHs differ in their performance of governance functions and in other characteristics. CONCLUSIONS: The LBoH taxonomy provides an empirically tested standardized tool for classifying LBoHs from the viewpoint of local health department administrators. Future studies can use this taxonomy to better characterize the impact of LBoHs.

Challenges and Innovations in Surveying the Governmental Public Health Workforce.

Surveying governmental public health practitioners is a critical means of collecting data about public health organizations, their staff, and their partners. A greater focus on evidence-based practices, practice-based systems research, and evaluation has resulted in practitioners consistently receiving requests to participate in myriad surveys. This can result in a substantial survey burden for practitioners and declining response rates for researchers. This is potentially damaging to practitioners and researchers as well as the field of public health more broadly. We have examined recent developments in survey research, especially issues highly relevant for public health practice. We have also proposed a process by which researchers can engage with practitioners and practitioner groups on research questions of mutual interest.

Assessment of Staffing, Services, and Partnerships of Local Health Departments - United States, 2015.

Beginning in 2008, the National Association of County and City Health Officials (NACCHO) periodically surveyed local health departments (LHDs) to assess the impact of the economic recession on jobs and budgets (1). In 2014, the survey was expanded to assess a wider range of factors affecting programs, services, and infrastructure in LHDs and renamed the Forces of Change survey (2). The survey was administered in to January-February 2015 to 948 LHDs across the United States to assess budget changes, job losses, changes in services, and collaboration with health care partners; 690 (73%) LHDs responded. Findings indicated a change in LHD infrastructure: compared with the previous fiscal year.* Overall, LHDs reported 3,400 jobs lost; 25% of LHDs reported budget decreases; 36% reported a reduction in at least one service area; and 35% reported serving fewer patients in clinics. In addition, up to 24% of LHDs reported expanding population-based prevention services, and LHDs reported exploring new collaborations with nonprofit hospitals and primary care providers (PCPs).

Local Health Departments' Approaches to Deal With Recession: What Strategies Are Used to Minimize the Negative Impact on Public Health Services to Community?

CONTEXT: Local health departments (LHDs) are crucial components in the public health system. As with their state counterparts, operating since the 2008 recession has proven financially difficult for the majority of the nation's 2800 LHDs. These health departments have elected to employ a variety of strategies to maintain operations and public-facing services and programs. OBJECTIVES: This study aimed to assess strategies used by LHDs to minimize the negative impact on services to community and to examine variation in these strategies by the size of population in LHD jurisdiction. DESIGN AND PARTICIPANTS: The design of this research brief report is observational, based on cross-sectional data from a nationally representative sample of 957 LHDs that enumerates and characterizes the nature of their responses to austerity. OUTCOMES MEASURES: The main outcome measures included 19 strategies. We used descriptive and bivariate analyses to highlight our study findings. RESULTS: LHDs use a variety of strategies to mitigate negative impacts on the public health services in their communities, focusing on workforce, funding, service referral, and several other areas. The most frequently used strategies include cross-training staff, increasing work hours, pursuing new funding, resource sharing, and seeking fees for services provided. Some minor variation by the size of jurisdiction population existed in frequency of top 10 strategies used by LHDs. CONCLUSIONS: Some of the LHD strategies to deal with the impact of recession address immediate issues caused by budget cuts and might be short-term fixes, including increasing workload of employees, and pay freezes. Other strategies, such as seeking new sources of revenues and resource sharing, can have potentially positive effects in the long run.

National Voluntary Public Health Accreditation: Are More Local Health Departments Intending to Take Part?

OBJECTIVE: This article examines local health department (LHD) participation and intentions to participate in national voluntary accreditation and reasons for not seeking accreditation. Specifically, it compares the results of national surveys among LHDs in 2010, 2013, and 2014. DESIGN: Longitudinal cohort study. SETTING: United States. PARTICIPANTS: LHDs that responded to the 2014 Forces of Change Survey and the 2010 and 2013 National Association of County and City Health Officials Profile studies. MAIN OUTCOME MEASURES: LHD level of engagement in Public Health Accreditation Board (PHAB) accreditation. RESULTS: Data of 2014 indicated that 1% of LHDs achieved accreditation and 11% had submitted an application or a statement of intent, compared with 6% of LHDs that submitted an application or a statement of intent in 2013. The percent of LHDs that indicated they planned to apply for accreditation but had not submitted a statement of intent declined from 27% in 2013 to 22% in 2014. In multivariate models, controlling for governance category and jurisdiction population size, LHDs in states where the state health department (SHD) participated in e-PHAB had higher odds of being favorably inclined toward accreditation than those located in states where the SHD was not in the e-PHAB system (odds ratio = 2.82, 95% confidence interval: 1.81-4.41). Across 2013 and 2014, and across small and large LHDs, the top 2 reasons for deciding not to apply for accreditation were the time/effort required exceeded the benefits (67%) and fees were too high (46%). CONCLUSIONS: SHDs are powerful mediators of LHDs' perceptions of the PHAB accreditation program. Health department governance structure and jurisdiction population size are associated with LHD accreditation participation decisions. With the launch of PHAB's program, fewer LHDs are undecided about accreditation participation and many have taken affirmative steps to become accredited. The top 2 reasons LHDs indicated for not proceeding with accreditation were time/effort exceed benefit and fees perceived as too high.

[Crystal structure and crystal form stability of trelagliptin succinate].

In order to investigate trelagliptin succinate's stability in solution, recrystallization and suspension methods in polar solvent (mainly in water and 95% alcohol) were used to study the crystal form transformation of trelagliptin succinate. Single crystal X-ray diffraction, powder X-ray diffraction and thermalgravimetric analysis, and differential scanning calorimetry were used to characterize the structure of the solid state form before and after transformation. The results showed that trelagliptin succinate can easily convert to trelagliptin hemi-succinate mediated by solvent, especially by polar solvent, namely trelagliptin hemi-succinate is more stable than trelagliptin succinate in solution.

Reductions of budgets, staffing, and programs among local health departments: results from NACCHO's economic surveillance surveys, 2009-2013.

OBJECTIVES: To provide an overview of budget cuts, job losses, and program reductions among local health departments (LHDs) and to examine the association between LHD infrastructure characteristics and the likelihood of budget cuts. DESIGN: Data from 4 waves of the economic surveillance survey (July-August 2009, September-November 2010, January-February 2012, and January-March 2013) conducted by the National Association of County & City Health Officials were analyzed to assess cuts to budgets, jobs, and programs since 2009. Data from the 2013 National Profile of Local Health Departments survey were used to assess the infrastructural characteristics associated with budget cuts. RESULTS: When asked in early 2013, more than a quarter of LHDs (26.9%) reported a reduced budget, continuing the trend of a substantial proportion of LHDs experiencing financial hardship in recent years. The percentages of LHDs that made cuts to programmatic areas fluctuated from year to year but have never been lower than 40%. Maternal and child health services were among areas most often cut during all 4 time points of the survey. Governance type, total expenditures, and percentage of revenues from local sources were significantly associated with LHD budget cuts. CONCLUSIONS: Cuts in LHD budgets, staff, and activities have been widespread for a period that lasted long after the official end of the Great Recession. There is a great need for substantive and consistent funding to ensure the retention of the workforce and the delivery of essential public health services.