The usage and costs of national drug price-negotiated anticancer medicines in a first-tier city in Northeast China: a study based on health insurance data.

BACKGROUND: The National Drug Price Negotiation (NDPN) policy has entered a normalisation stage, aiming to alleviate, to some extent, the disease-related and economic burdens experienced by cancer patients. This study analysed the use and subsequent burden of anticancer medicines among cancer patients in a first-tier city in northeast China. METHODS: We assessed the usage of 64 negotiated anticancer medicines using the data on the actual drug deployment situation, the frequency of medical insurance claims and actual medication costs. The affordability of these medicines was measured using the catastrophic health expenditure (CHE) incidence and intensity of occurrence. Finally, we used the defined daily doses (DDDs) and defined daily doses cost (DDDc) as indicators to evaluate the actual use of these medicines in the region. RESULTS: During the study period, 63 of the 64 medicines were readily available. From the perspective of drug usage, the frequency of medical insurance claims for negotiated anticancer medicines and medication costs showed an increasing trend from 2018 to 2021. Cancer patients typically sought medical treatment at tertiary hospitals and purchased medicines at community pharmacies. The overall quantity and cost of medications for patients covered by the Urban Employee Basic Medical Insurance (UEBMI) were five times higher than those covered by the Urban and Rural Resident Medical Insurance (URRMI). The frequency of medical insurance claims and medication costs were highest for lung and breast cancer patients. Furthermore, from 2018 to 2021, CHE incidence showed a decreasing trend (2.85-1.60%) under urban patients' payment capability level, but an increasing trend (11.94%-18.42) under rural patients' payment capability level. The average occurrence intensities for urban (0.55-1.26 times) and rural (1.27-1.74 times) patients showed an increasing trend. From the perspective of drug utilisation, the overall DDD of negotiated anticancer medicines showed an increasing trend, while the DDDc exhibited a decreasing trend. CONCLUSION: This study demonstrates that access to drugs for urban cancer patients has improved. However, patients' medical behaviours are affected by some factors such as hospital level and type of medical insurance. In the future, the Chinese Department of Health Insurance Management should further improve its work in promoting the fairness of medical resource distribution and strengthen its supervision of the nation's health insurance funds.

Production of single cell protein rich in potassium by Nectaromyces rattus using biogas slurry and molasses.

Single-cell protein (SCP) is a vital supplement for animal protein feed. This study utilized biogas slurry and sugarcane molasses to ferment Nectaromyces rattus for the production of SCP. The optimal batch fermentation conditions were obtained in a 5L jar with a tank pressure of 0.1 MPa, an initial speed of 300 rpm, and an inoculum volume of 30%. The highest cell dry weight concentrations of the fed-batch fermentation without reflux and the fed-batch fermentation with reflux were 46.33 g/L and 29.71 g/L, respectively. The nitrogen conversion rates (47.05% and 44.12%) and the cell yields of total organic carbon (1 g/g and 1.17 g/g) of both fermentation modes were compared. The SCP contained 42.32% amino acids. Its high concentrations of potassium (19859.96 mg/kg) and phosphorus (7310.44 mg/kg) present a novel approach for the extraction of these essential nutrients from biogas slurry. The enrichment of K was related to the H+ efflux and sugar transport.

The molecular chaperone Hsp90 regulates heterochromatin assembly through stabilizing multiple complexes in fission yeast.

In the fission yeast Schizosaccharomyces pombe, both RNAi machinery and RNAi-independent factors mediate transcriptional and posttranscriptional silencing and heterochromatin formation. Here, we show that the silencing of reporter genes at major native heterochromatic loci (centromeres, telomeres, mating-type locus and rDNA regions) and an artificially induced heterochromatin locus is alleviated in a fission yeast hsp90 mutant, hsp90-G84C Also, H3K9me2 enrichment at heterochromatin regions, especially at the mating-type locus and subtelomeres, is compromised, suggesting heterochromatin assembly defects. We further discovered that Hsp90 is required for stabilization or assembly of the RNA-induced transcriptional silencing (RITS) and Argonaute siRNA chaperone (ARC) RNAi effector complexes, the RNAi-independent factor Fft3, the shelterin complex subunit Poz1 and the Snf2/HDAC-containing repressor complex (SHREC). Our ChIP data suggest that Hsp90 regulates the efficient recruitment of the methyltransferase/ubiquitin ligase complex CLRC by shelterin to chromosome ends and targeting of the SHREC and Fft3 to mating type locus and/or rDNA region. Finally, our genetic analyses demonstrated that increased heterochromatin spreading restores silencing at subtelomeres in the hsp90-G84C mutant. Thus, this work uncovers a conserved factor critical for promoting RNAi-dependent and -independent heterochromatin assembly and gene silencing through stabilizing multiple effectors and effector complexes.

Overexpression of PeNAC122 gene promotes wood formation and tolerance to osmotic stress in poplars.

Finding the adequate balance between wood formation and abiotic stress resistance is still an important challenge for industrial woody crops. In this study, PeNAC122, a member of the NAC transcription factor (TF) family highly expressed in xylem, was cloned from Populus euphratica. Tissue expression and ß-glucuronidase (GUS) staining showed that PeNAC122 was exclusively expressed in phloem fiber and secondary xylem of stems. Subcellular and yeast transactivation assays confirmed that PeNAC122 protein existed in the nucleus and did not have transcriptional activation and inhibitory activity. Overexpression of PeNAC122 poplar lines exhibited reduced plant height, thickened xylem, and accumulated lignin content in stems, and also upregulates the expression of secondary cell wall biosynthetic genes. Moreover, overexpression of PeNAC122 lines displayed more tolerance to PEG6000-induced osmotic stress, with stronger photosynthetic performance, higher antioxidant enzyme activity, and less accumulation of reactive oxygen species in leaves, and higher expression levels of stress response genes DREB2A, RD29, and NCED3. These results indicate that PeNAC122 plays a crucial role in wood formation and abiotic stress tolerance, which, in addition to potential use in improving wood quality, provides further insight into the role of NAC family TFs in balancing wood development and abiotic stress resistance.

Comparing Public Perceptions and Preventive Behaviors During the Early Phase of the COVID-19 Pandemic in Hong Kong and the United Kingdom: Cross-sectional Survey Study.

BACKGROUND: Given the public health responses to previous respiratory disease pandemics, and in the absence of treatments and vaccines, the mitigation of the COVID-19 pandemic relies on population engagement in nonpharmaceutical interventions. This engagement is largely driven by risk perception, anxiety levels, and knowledge, as well as by historical exposure to disease outbreaks, government responses, and cultural factors. OBJECTIVE: The aim of this study is to compare psychobehavioral responses in Hong Kong and the United Kingdom during the early phase of the COVID-19 pandemic. METHODS: Comparable cross-sectional surveys were administered to adults in Hong Kong and the United Kingdom during the early phase of the epidemic in each setting. Explanatory variables included demographics, risk perception, knowledge of COVID-19, anxiety level, and preventive behaviors. Responses were weighted according to census data. Logistic regression models, including effect modification to quantify setting differences, were used to assess the association between the explanatory variables and the adoption of social distancing measures. RESULTS: Data from 3431 complete responses (Hong Kong, 1663; United Kingdom, 1768) were analyzed. Perceived severity of symptoms differed by setting, with weighted percentages of 96.8% for Hong Kong (1621/1663) and 19.9% for the United Kingdom (366/1768). A large proportion of respondents were abnormally or borderline anxious (Hong Kong: 1077/1603, 60.0%; United Kingdom: 812/1768, 46.5%) and regarded direct contact with infected individuals as the transmission route of COVID-19 (Hong Kong: 94.0%-98.5%; United Kingdom: 69.2%-93.5%; all percentages weighted), with Hong Kong identifying additional routes. Hong Kong reported high levels of adoption of various social distancing measures (Hong Kong: 32.6%-93.7%; United Kingdom: 17.6%-59.0%) and mask-wearing (Hong Kong: 98.8% (1647/1663); United Kingdom: 3.1% (53/1768)). The impact of perceived severity of symptoms and perceived ease of transmission of COVID-19 on the adoption of social distancing measures varied by setting. In Hong Kong, these factors had no impact, whereas in the United Kingdom, those who perceived their symptom severity as "high" were more likely to adopt social distancing (adjusted odds ratios [aORs] 1.58-3.01), and those who perceived transmission as "easy" were prone to adopt both general social distancing (aOR 2.00, 95% CI 1.57-2.55) and contact avoidance (aOR 1.80, 95% CI 1.41-2.30). The impact of anxiety on adopting social distancing did not vary by setting. CONCLUSIONS: Our results suggest that health officials should ascertain baseline levels of risk perception and knowledge in populations, as well as prior sensitization to infectious disease outbreaks, during the development of mitigation strategies. Risk should be communicated through suitable media channels-and trust should be maintained-while early intervention remains the cornerstone of effective outbreak response.

F-box proteins Pof3 and Pof1 regulate Wee1 degradation and mitotic entry in fission yeast.

The key cyclin-dependent kinase Cdk1 (Cdc2) promotes irreversible mitotic entry, mainly by activating the phosphatase Cdc25 while suppressing the tyrosine kinase Wee1. Wee1 needs to be downregulated at the onset of mitosis to ensure rapid activation of Cdk1. In human somatic cells, one mechanism of suppressing Wee1 activity is mediated by ubiquitylation-dependent proteolysis through the Skp1/Cul1/F-box protein (SCF) ubiquitin E3 ligase complex. This mechanism is believed to be conserved from yeasts to humans. So far, the best-characterized human F-box proteins involved in recognition of Wee1 are ß-TrCP (BTRCP) and Tome-1 (CDCA3). Although fission yeast Wee1 was the first identified member of its conserved kinase family, the F-box proteins involved in recognition and ubiquitylation of Wee1 have not been identified in this organism. In this study, our screen using Wee1-Renilla luciferase as the reporter revealed that two F-box proteins, Pof1 and Pof3, are required for downregulating Wee1 and are possibly responsible for recruiting Wee1 to SCF. Our genetic analyses supported a functional relevance between Pof1 and Pof3 and the rate of mitotic entry, and Pof3 might play a major role in this process.

Effect of integrating maternal health services and family planning services on postpartum family planning behavior in Ethiopia: results from a longitudinal survey.

BACKGROUND: Very few postpartum women want to become pregnant within the next 2 years, but approximately 60% of postpartum women in low- and middle-income countries are not using contraceptive methods. The World Health Organization recommends that women receive postpartum family planning (PPFP) counseling during antenatal, immediate postpartum, and postnatal services. Our objective was to establish whether PPFP counseling is being provided in antenatal and postnatal care services in SNNPR, Ethiopia and whether receipt of PPFP counseling improved uptake of postpartum family planning use by 6 months postpartum. METHODS: Longitudinal data from the Performance Monitoring for Accountability 2020 - Maternal and Newborn Health study were used. At screening, 329 women were identified as six or more months pregnant; 307 completed the survey at 6 months postpartum. We used weighted parametric survival analysis with Weibull distribution to assess the effect of receipt of postpartum counseling in antenatal and/or postnatal care by 6 weeks postpartum on contraceptive uptake, after adjusting for intention to use family planning, wantedness of the index pregnancy, delivery location, amenorrhea, exclusive breastfeeding, residence, parity, and education. RESULTS: Coverage of PPFP counseling is low; by six-weeks postpartum only 20% of women had received counseling. Women who received counseling in postnatal care only and postnatal care and antenatal care took up contraception at significantly higher rates than women who did not receive any counseling (HR: 3.4, p < .01 and HR: 2.5, p = .01, respectively). There was no difference between women who received PPFP counseling only in ANC and women who did not receive counseling at all. Women who did not want the child at all took up contraception at significantly lower rates than women who wanted the child at that time (HR: 0.3, p = .04). Women who had four or more children took up contraception at significantly lower rates than woman with 1-3 children (HR: 0.3, p = .01). There were no significant differences by delivery location, exclusive breastfeeding, residence, or education. CONCLUSION: Integration of postpartum family planning counseling into postnatal care services is an effective means to increase postpartum contraceptive uptake, but significant gaps in coverage, particularly in the delivery and postnatal period, remain.

New acrylamide-substituted quinazoline derivatives with enhanced potency for the treatment of EGFR T790M-mutant non-small-cell lung cancers.

A new class of acrylamide-substituted quinazoline derivatives with enhanced inhibitory activity against mutant EGFR T790M enzyme were synthesized. Among them, compound 10b displayed the strongest inhibitory potency to block the phosphorylation of the EGFR T790M enzyme, with an IC50 value of 4.3 nM. Compared with the lead compound gefitinib, compound 10b significantly strengthened the activity against EGFR T790M (194 times higher). Furthermore, compound 10b only exhibited moderate activity against wild type EGFR, with an IC50 of 105.0 nM, suggesting its improved selectivity over the T790M-mutated EGFR. In addition, compound 10b also showed stronger activity against H1975 cells harboring the EGFR T790M mutation than gefitinib. Moreover, compound 10b has low inhibitory activity toward the normal HBE cells (IC50 > 34.04 µM), indicating its low cell cytotoxicity. Overall, this modification provided a new insight to design covalent binding EGFRT790M inhibitors to prevent NSCLC resistance.

Assessment of the Risk of Malnutrition or Frailty Among Patients Undergoing Liver Transplantation: A Hospital-Based Prospective Study.

Objective: We aimed to explore the status of nutritional and frailty in patients undergoing liver transplantation and the associated influencing factors. Methods: We conducted a follow-up analysis of 44 patients who underwent liver transplantation between 2021 and 2022. We followed up and recorded the nutritional status and risk of weakness at different time-points (days 1, 2, 3, 6, 9, and 12) postoperatively. Patient information regarding demographics, physical examination, medical history, and perioperative blood tests were collected. Binary logistic regression was applied to identify risk factors for weakness after liver transplantation. Results: The cohort comprised 44 liver transplant recipients, with a mean age of 47.66 years (standard deviation=9.49 years). Initial analysis revealed that, compared to the group without nutritional risks, the group with nutritional risks displayed elevated age and preoperative blood ammonia levels one week post-surgery. Moreover, this group had reduced levels of albumin and total bile acid preoperatively. Patients with preoperative nutritional risks were also prone to similar risks 2 weeks postoperatively. Further, a correlation was observed between preoperative pulmonary infections and increased frailty risk 6 days postoperatively. At both 9 and 12 days postoperatively, patients with frailty risk exhibited higher preoperative white blood cell counts and ammonia levels than those without. Multivariable analysis, controlling for confounding factors, indicated a significant association between preoperative nutritional status and nutritional risk 2 weeks postoperatively, as well as a link between preoperative white blood cell count and frailty risk at 12 days postoperatively. Conclusion: There was a significant correlation between preoperative nutritional status and nutritional risk 2 weeks after liver transplantation, and preoperative white blood cell count was an independent risk factor for weakness 12 days postoperatively. Preoperative nutritional management for patients could potentially mitigate the likelihood of adverse clinical outcomes.

A Qualitative Study on Nutritional Awareness Among Parents of Pediatric Recipients of Liver or Kidney Transplants.

Objective: The primary aim of this study was to examine the extent of nutritional awareness concerning dietary requisites within a cohort comprising pediatric recipients of liver and kidney transplants, along with their respective caregivers. The overarching goal was to establish a foundation for enhancing the dietary nutrition of this specific population. Methods: This was a qualitative research study, involving in-depth interviews and subsequent qualitative data analysis. Our sample included pediatric patients in a specific age range who had undergone a liver or kidney transplant, as well as their parents. The data analysis technique we used was content analysis. Results: The survey focused on knowledge of dietary requirements and restrictions, nutritional needs, and adherence to daily dietary requirements among pediatric patients and their respective caregivers. Approximately 30% of the parents lacked relevant nutritional awareness, 30% relied on a single source for acquiring nutritional knowledge, and 40% expressed a considerable need for nutritional guidance. Our findings revealed a deficiency in the understanding of nutritional and dietary requirements for children who have undergone a liver or kidney transplant. Their nutrient intake was unbalanced, and their dietary habits were irregular, highlighting the need for better nutritional guidance and monitoring. Conclusion: The nutritional awareness and knowledge of dietary requirements among pediatric liver and kidney transplant recipients and their care providers are inadequate. Medical professionals are urged to tackle this concern by imparting comprehensive education to parents regarding the nutritional prerequisites essential for their children post-transplant. This approach empowers parents to implement requisite dietary modifications effectively. Furthermore, healthcare institutions should augment the nutritional proficiency of their medical staff through meticulously structured training initiatives.

Association between apolipoprotein E gene polymorphism and the risk of recurrent pregnancy loss: a meta-analysis.

PURPOSE: The association between apolipoprotein E (ApoE) gene polymorphism and the risk of recurrent pregnancy loss (RPL) remains controversial. The present meta-analysis was performed to derive a precise estimate of the relationship. METHOD(S): We searched the PubMed, Embase, and Web of Science data- bases for studies related to the association between the ApoE genotype and the risk of RPL. We estimated the summary odds ratio (OR) with 95% confidence interval (CI) to assess the association. RESULT(S): Seven studies, including 2,090 RPL cases and 742 control samples, were identified. The results showed a significant association between ApoE E4 mutation and RPL risk (for E4 allele: OR =1.98, 95 %CI =1.14-3.43, P=0.499; for E2E3 vs. E3E3: OR =1.33, 95%CI =1.12-1.42, P=0.008; for E2E4 vs. E3E3: OR =1.26, 95 % CI =1.07-1.49, P=0.005). CONCLUSION(S): The meta-analysis suggests an association between ApoE E4 mutation and increased risk of RPL.

Resveratrol protects against postmenopausal atherosclerosis progression through reducing PCSK9 expression via the regulation of the ERα-mediated signaling pathway.

Elevated circulating proprotein convertase subtilisin/kexin 9 (PCSK9) levels are an important contributor to postmenopausal atherosclerosis (AS). We have previously reported that resveratrol (RSV), as a phytoestrogen, reduces hepatocyte steatosis and PCSK9 expression in L02 cells. This study aimed to investigate how RSV reduces PCSK9 expression to inhibit postmenopausal AS progression. Here, we found that treatment of Ovx/ApoE -/- mice with RSV significantly reduced dyslipidemia, plasma PCSK9 concentration and aortic plaque area. In addition, RSV significantly inhibited liver fat accumulation and improved the hepatocyte ultrastructure. Further studies showed that RSV upregulated estrogen receptor α (ERα) expression, while reduced the liver X receptor α (LXRα) expression and sterol regulatory-element-binding protein-1c (SREBP-1c) transcriptional activity. In vitro, RSV inhibited insulin-induced elevated intracellular/extracellular PCSK9 levels, enhanced receptor-mediated uptake of low-density lipoproteins in HepG2 cells. Furthermore, RSV attenuated the activity of the SRE-dependent PCSK9 promoter. However, these effects can be partially reversed by the antiestrogen ICI 182,780. Attenuation of these changes with ERα inhibition suggest that RSV may prevent the progression of postmenopausal AS by reducing PCSK9 expression in hepatocytes through ERα-mediated signaling.

Mechanism of bio-electrokinetic remediation of pyrene contaminated soil: Effects of an electric field on the degradation pathway and microbial metabolic processes.

In this study, the mechanism of bio-electrokinetic (BIO-EK) remediation to improve the degradation of pyrene was evaluated based on an analysis of the intermediate products and the microbial community. The results show that BIO-EK remediation has a higher pyrene degradation efficiency on pyrene and its intermediate products than the bioremediation and electrokinetic (EK) remediation processes. A series of intermediate products were detected. According to the type of the intermediate products, two degradation pathways, biological metabolism and electrochemical oxidation, are proposed in the BIO-EK remediation of pyrene. Furthermore, the primary microbial taxa involved in the pollutant degradation changed, which led to variations in the functional gene components. The abundant and functional genes related to metabolism were specifically analyzed. The results indicate that the electric field promotes the expression of metabolisms associated with 14 carbohydrates, 13 lipids, 13 amino acids, five energies, and in particular, 11 xenobiotics. These results suggest that in addition to the promotion effect on the microbial metabolism caused by the electric field, BIO-EK remediation can promote the degradation of pollutants due to the coexistence of a microbial metabolic pathway and an electrochemical oxidation pathway.

Xiaoyao San attenuates hepatic steatosis through estrogen receptor α pathway in ovariectomized ApoE-/- mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoyao San (XYS) is a famous prescription in traditional Chinese medicine, which is used in the treatment of "liver depression and spleen deficiency" syndrome. It is often used clinically to treat chronic hepatitis, liver cirrhosis, various symptoms of postmenopausal women, especially mental disorders and digestive system diseases. However, the effect of XYS on hepatic steatosis in postmenopausal women remains unclear. In this research, we investigated the effects of XYS on hepatic steatosis in ovariectomized (OVX) apolipoprotein E knockout (ApoE-/-) mice, as well as the molecular mechanisms in vitro and in vivo. MATERIALS AND METHODS: Fifty female ApoE-/- mice were divided into 5 groups: control group (Sham), model group (OVX), OVX + ß-estradiol (E2, 0.4 mg/kg) group, OVX + XYS (13.0 g/kg) group, and OVX + XYS (6.5 g/kg) group. The control group received a standard diet, while the other groups received a high-fat diet (HFD). The hepatic pathologies of the mice were examined with Oil red O staining and HE staining after 12 week treatment. Blood and liver variables were determined enzymatically. Transmission electron microscopy was used to examine the ultrastructure of hepatocytes. The expression of estrogen receptor α (ERα) and lipid metabolism genes was analyzed by real-time PCR and/or Western blot. In in vitro studies, we investigated the effect of XYS-medicated serum on the expression and activity of ERα in L02 cells by immunofluorescence and luciferase reporter assays, and examined the protection of XYS-medicated serum against free fatty acid (FFA)-induced steatosis of L02 cells. Intracellular lipid accumulation were measured by Oil red O staining and Nile red staining assay. Finally, the influence of ICI 182,780, a specific antagonist of ERα, on the protective effect of XYS-medicated serum on FFA-induced steatosis of L02 cells was investigated. RESULTS: Treatment of Ovx/ApoE-/- mice with XYS significantly decreased HFD-induced increases in hepatic steatosis and triglyceride (TG) content, accompanied by inhibition of liver X receptor α (LXRα), sterol regulatory element binding protein (SREBP)-1c and its target lipogenic genes transcription. Similarly, XYS-medicated serum reduced the size and number of lipid droplets and the cellular TG content in FFA-induced L02 cells. In addition, XYS significantly increased the ERα expression in hepatocytes in vivo and in vitro and enhanced the transcriptional activity of ERα promoter in L02 cells. And these effects could be partly reversed by the antiestrogen ICI 182,780. CONCLUSIONS: These findings suggest that XYS has an estrogen-like effect and inhibits steatosis in postmenopausal animal models by reducing the expression of genes related to TG synthesis through ERα pathway.

Ubiquitination of CLIP-170 family protein restrains polarized growth upon DNA replication stress.

Microtubules play a crucial role during the establishment and maintenance of cell polarity. In fission yeast cells, the microtubule plus-end tracking proteins (+TIPs) (including the CLIP-170 homologue Tip1) regulate microtubule dynamics and also transport polarity factors to the cell cortex. Here, we show that the E3 ubiquitin ligase Dma1 plays an unexpected role in controlling polarized growth through ubiquitinating Tip1. Dma1 colocalizes with Tip1 to cortical sites at cell ends, and is required for ubiquitination of Tip1. Although the absence of dma1+ does not cause apparent polar growth defects in vegetatively growing cells, Dma1-mediated Tip1 ubiquitination is required to restrain polar growth upon DNA replication stress. This mechanism is distinct from the previously recognized calcineurin-dependent inhibition of polarized growth. In this work, we establish a link between Dma1-mediated Tip1 ubiquitination and DNA replication or DNA damage checkpoint-dependent inhibition of polarized growth in fission yeast.

Evaluating consistency of recall of maternal and newborn care complications and intervention coverage using PMA panel data in SNNPR, Ethiopia.

BACKGROUND: There is recognition that effective interventions are available to prevent neonatal and maternal deaths but providing reliable and valid coverage estimates remains a challenge. Household surveys rely on recall of self-reported events that may span up to 5 years, raising concerns of recall bias. OBJECTIVE: This study assessed the reliability of maternal recall of pregnancy, delivery, and postpartum events over a six-month period and identified relevant individual characteristics associated with inconsistent reporting. METHODOLOGY: A longitudinal household survey was conducted with 321 pregnant women in 44 enumeration areas in Southern Nationals, Nationalities and People's Region in Ethiopia. Women who were six or more months pregnant were enrolled and interviewed at seven days, six weeks, and six months post-partum using an identical set of questions regarding maternal and neonatal health and receipt of select neonatal care interventions. We compared responses given at 7 days to those reported at 6 weeks and 6 months and conducted sensitivity, specificity, area under receiving operative curve, and Kappa analyses of selected indicators. RESULTS: We find that reporting complications is higher at the first interview after birth than at either the six-week or six-month interview. The specificity of the majority of complications is high, however sensitivity is generally much lower. The sensitivity of reporting any complication during pregnancy, delivery, or post-partum ranged from 54.5% to 67.6% at the 6-week interview and from 39.2% to 63.2% at the 6-month interview. Though sensitivity of receipt of neonatal interventions was high, specificity and kappa demonstrate low consistency. CONCLUSION: As with childbirth, it may be that during the first seven days women note symptoms with higher scrutiny, but if these do not later develop into serious health issues, they may be forgotten over time. Maternal complications and care are likely to be under-reported by women if interviewed for distant events.

Structural optimization of diphenylpyrimidine scaffold as potent and selective epidermal growth factor receptor inhibitors against L858R/T790M resistance mutation in nonsmall cell lung cancer.

A new class of thiodiphenylpyrimidine analogs (Thio-DPPY) were synthesized as potent and selective EGFR T790M inhibitors to overcome gefitinib resistance in nonsmall cell lung cancer (NSCLC). This structural optimization led to the identification of two potent EGFRT790M/L858R inhibitors, 14a and 14e, which possess IC50 values of 27.5 and 9.1 nM, respectively. Moreover, compounds 14a (SI > 36.4) and 14e (SI > 109.9) exhibited high selectivity and low activity against the wild-type EGFR (IC50  > 1,000 nM). In particular, compound 14a also displayed strong potency against EGFRT790M -mutated H1975 cells (IC50  = 0.074 µM), but weak activity toward normal cells HBE (IC50  > 40 µM) and LO-2 (IC50  = 9.891 µM). It is important that compound 14a (SI = 52.6) significantly improved the selectivity against mutant H1975 cells over wild-type A431 cells than rociletinib (SI = 6.0), thus revealing its slight cell cytotoxicity. This study provides a promising Thio-DPPY derivative as enhanced EGFR T790M inhibitor, and also revealed valuable clues for further optimization of DPPY scaffold to overcome NSCLC resistance.