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ystems become even more financially constrained, recognising how PFM reforms can influence organisational culture, and how the negative effects can be mitigated, is of international importance. We highlight the importance of a participatory culture that encourages shared decision making and coproduction, particularly as countries grapple with how to achieve UHC with limited funds.
The sustainable development goals (SDGs) have generated momentum for global health, aligning efforts from governments and international organisations toward a set of goals that are expected to reflect improvements in life conditions across the globe. Mexico has huge social inequalities that can affect access to quality care and health outcomes. The objective of this study is to analyse inequalities among Mexico's 32 states on the health-related SDG indicators (HRSDGIs) from 1990 to 2017.
These analyses rely on the estimation of HRSDGIs as part of the Global Burden of Disease study 2017. We estimated the concentration index for 40+3 HRSDGI stratified by Socio-demographic Index and marginalisation index, and then for indicators where inequalities were identified, we ran decomposition analyses using structural variables such as gross domestic product per capita, poverty and health expenditure.
Mexico has made progress on most HRSDGIs, but current trends in improvement do not appear to fast enough to meet 2but also for communities and other subnational levels.
Several previous studies have reported the incidence of new-onset diabetes mellitus (NODM) after pancreatectomy. Nevertheless, the results were inconsistent. The true rate of NODM after distal pancreatectomy (DP) is still unknown.
The aim of this study was to investigate the incidence of and the risk factors for NODM after DP. This study enrolled patients who underwent DP between January 2004 and February 2016 at Peking Union Medical College Hospital. Patients with preoperative diabetes mellitus or diagnosed with pancreatic cancer were excluded. The primary outcome was NODM.
A total of 485 patients were enrolled. The median (IQR) of follow-up duration was 30.95 (9.26-180.30) months. The accumulative incidence of NODM was 8.9% at postoperative 6 months, 14.0% at postoperative year one, 22.3% at year three, 27.1% at year five, and 35.5% at year ten. Multivariate analysis showed that the risk of postoperative NODM was positively correlated with age (HR 1.029 (1.013-1.045), p<0.001), preoperative body mass index (BMI) (HR 1.042 (1.003-1.083), p=0.001), operative blood loss (HR 1.0003 (1.0002-1.0010), p<0.001), and length of resected pancreas (HR 1.079 (1.013-1.148), p
0.017). Moreover, concomitant splenectomy (HR 2.001 (1.202-3.331), p=0.008) was associated with significantly higher risk of postoperative NODM.
NODM incidence increased with postoperative time progression. Age, BMI, surgical blood loss, length of resected pancreas and splenectomy were independent risk factors for NODM after DP.
NCT03030209.
NCT03030209.Most eukaryotic pre-mRNAs must undergo 3'-end cleavage and polyadenylation prior to their export from the nucleus. A large number of proteins in several complexes participate in this 3'-end processing, including cleavage and polyadenylation specificity factor (CPSF) in mammals. The CPSF30 subunit contains five CCCH zinc fingers (ZFs), with ZF2-ZF3 being required for the recognition of the AAUAAA poly(A) signal. ZF4-ZF5 recruits the hFip1 subunit of CPSF, although the details of this interaction have not been characterized. Here we report the crystal structure of human CPSF30 ZF4-ZF5 in complex with residues 161-200 of hFip1 at 1.9 Å resolution, illuminating the molecular basis for their interaction. Unexpectedly, the structure reveals one hFip1 molecule binding to each ZF4 and ZF5, with a conserved mode of interaction. Our mutagenesis studies confirm that the CPSF30-hFip1 complex has 12 stoichiometry in vitro. Mutation of each binding site in CPSF30 still allows one copy of hFip1 to bind, while mutation of both sites abrogates binding. Our fluorescence polarization binding assays show that ZF4 has higher affinity for hFip1, with a Kd of 1.8 nM. We also demonstrate that two copies of the catalytic module of poly(A) polymerase (PAP) are recruited by the CPSF30-hFip1 complex in vitro, and both hFip1 binding sites in CPSF30 can support polyadenylation.Mutations in the telomere-binding protein POT1 are associated with solid tumors and leukemias. POT1 alterations cause rapid telomere elongation, ATR kinase activation, telomere fragility, and accelerated tumor development. Here, we define the impact of mutant POT1 alleles through complementary genetic and proteomic approaches based on CRISPR interference and biotin-based proximity labeling, respectively. These screens reveal that replication stress is a major vulnerability in cells expressing mutant POT1, which manifests as increased telomere mitotic DNA synthesis at telomeres. Our study also unveils a role for the nuclear pore complex in resolving replication defects at telomeres. Depletion of nuclear pore complex subunits in the context of POT1 dysfunction increases DNA damage signaling, telomere fragility and sister chromatid exchanges. Furthermore, we observed telomere repositioning to the nuclear periphery driven by nuclear F-actin polymerization in cells with POT1 mutations. In conclusion, our study establishes that relocalization of dysfunctional telomeres to the nuclear periphery is critical to preserve telomere repeat integrity.Interacting morphogens produce periodic patterns in developing tissues. Such patterning can be modelled as reaction-diffusion (RD) processes (as originally formulated by Alan Turing), and although these models have been developed and refined over the years, they often tend to oversimplify biological complexity by restricting the number of interacting morphogens. A new paper in Development reports how perturbation analysis can guide multi-morphogen modelling of the striped patterning the roof of the mouse mouth. To hear more about the story, we caught up with first author Andrew Economou and his former supervisor Jeremy Green, Professor of Developmental Biology at King's College, London.
Although diabetic kidney disease is the leading cause of ESKD in the United States, identifying those patients who progress to ESKD is difficult. Efforts are under way to determine if plasma biomarkers can help identify these high-risk individuals.
In our case-cohort study of 894 Chronic Renal Insufficiency Cohort Study participants with diabetes and an eGFR of <60 ml/min per 1.73 m
at baseline, participants were randomly selected for the subcohort; cases were those patients who developed progressive diabetic kidney disease (ESKD or 40% eGFR decline). Using a multiplex system, we assayed plasma biomarkers related to tubular injury, inflammation, and fibrosis (KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40). Weighted Cox regression models related biomarkers to progression of diabetic kidney disease, and mixed-effects models estimated biomarker relationships with rate of eGFR change.
Median follow-up was 8.7 years. Higher concentrations of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were each as the highest risk after accounting for the other biomarkers. OSS_128167 mouse These findings validate previous literature on TNFR-1, TNFR-2, and KIM-1 in patients with prevalent CKD and provide new insights into the influence of suPAR and YKL-40 as plasma biomarkers that require validation.
Cultured cell lines are widely used for research in the physiology, pathophysiology, toxicology, and pharmacology of the renal proximal tubule. The lines that are most appropriate for a given use depend upon the genes expressed. New tools for transcriptomic profiling using RNA sequencing (RNA-Seq) make it possible to catalog expressed genes in each cell line.
Fourteen different proximal tubule cell lines, representing six species, were grown on permeable supports under conditions specific for the respective lines. RNA-Seq followed standard procedures.
Transcripts expressed in cell lines variably matched transcripts selectively expressed in native proximal tubule. Opossum kidney (OK) cells displayed the highest percentage match (45% of proximal marker genes [TPM threshold =15]), with pig kidney cells (LLC-PK1) close behind (39%). Lower-percentage matches were seen for various human lines, including HK-2 (26%), and lines from rodent kidneys, such as NRK-52E (23%). Nominally, identical OK cells from different sources differed substantially in expression of proximal tubule markers. Mapping cell line transcriptomes to gene sets for various proximal tubule functions (sodium and water transport, protein transport, metabolic functions, endocrine functions) showed that different lines may be optimal for experimentally modeling each function. An online resource (https//esbl.nhlbi.nih.gov/JBrowse/KCT/) has been created to interrogate cell line transcriptome data. Proteomic analysis of NRK-52E cells confirmed low expression of many proximal tubule marker proteins.
No cell line fully matched the transcriptome of native proximal tubule cells. However, some of the lines tested are suitable for the study of particular metabolic and transport processes seen in the proximal tubule.
No cell line fully matched the transcriptome of native proximal tubule cells. However, some of the lines tested are suitable for the study of particular metabolic and transport processes seen in the proximal tubule.This study investigated parental factors and beliefs supporting aggression as predictors of physical aggression by adolescents. The participants were 2,443 junior high school students from Ankara, Turkey, who completed measures of parental support for aggression, family conflict, parental monitoring, beliefs supporting aggression, and physical aggression. The findings showed both direct and indirect effects of parental factors on physical aggression through beliefs supporting aggression. Furthermore, a multigroup model comparison indicated invariance of the structural relationships among variables in the model across gender and that the hypothesized structural model was a close fit for both the girl and the boy data. The findings suggest that it might be beneficial to consider beliefs supporting aggression and parental factors as risk factors when designing interventions to target physical aggression among adolescents.Unarousable child with short bowelA 4-year-old boy was admitted with progressive lethargy of a few hours' duration and no other symptoms. His medical history was relevant for short bowel syndrome (SBS), following neonatal volvulus, with residual bowel length of 23 cm and intact ileocecal valve. He had similar self-limiting episodes in the past, after weaning parenteral nutrition, especially after eating large meals. The day before, he had consumed a large amount of apples.Arterial blood gas (ABG) analysis showed metabolic acidosis with normal lactacidaemia (pH 7.09, pCO2 19 mm Hg, pO2 101 mm Hg, HCO3 5.8 mmol/L, BE -24, anion gap 29.4, chloride 116 mmol/L, L-lactate level 4 mmol/L).On admission, the child could be awakened, but he was confused with slurred speech (Glasgow Coma Scale 14), with a body temperature of 37 C°, a heart rate of 125 beats/min and a respiratory rate of 38 breaths/min. The abdomen was distended, without guarding and with normal bowel sounds. Blood glucose levels were normal, as well as white blood cell count, liver and kidney function test and C reactive protein.
