Immigration and access to dementia diagnostics and treatment: A nationwide study in Sweden.

•Compared to Swedish-born people, foreign-born people were less likely to receive dementia diagnostic tests.•Being born in Africa or Europe was associated with lower chance of receiving cholinesterase inhibitors.•Asian-born people had higher chance of receiving cholinesterase inhibitors, but were less likely to receive memantine.•Disparities existed in dementia diagnostics and treatment between Swedish-born and foreign-born people, but were not consistent after adjusting for MMSE scores.

Respiratory and circulatory insufficiency during emergent long-distance critical care interhospital transports to tertiary care in a sparsely populated region: a retrospective analysis of late mortality risk.

OBJECTIVES: To test if impaired oxygenation or major haemodynamic instability at the time of emergency intensive care transport, from a smaller admitting hospital to a tertiary care centre, are predictors of long-term mortality. DESIGN: Retrospective observational study. Impaired oxygenation was defined as oxyhaemoglobin %-inspired oxygen fraction ratio (S/F ratio)<100. Major haemodynamic instability was defined as a need for treatment with norepinephrine infusion to sustain mean arterial pressure (MAP) at or above 60 mm Hg or having a mean MAP <60. Logistic regression was used to assess mortality risk with impaired oxygenation or major haemodynamic instability. SETTING: Sparsely populated Northern Sweden. A fixed-wing interhospital air ambulance system for critical care serving 900 000 inhabitants. PARTICIPANTS: Intensive care cases transported in fixed-wing air ambulance from outlying hospitals to a regional tertiary care centre during 2000-2016 for adults (16 years old or older). 2142 cases were included. PRIMARY AND SECONDARY OUTCOME MEASURES: All-cause mortality at 3 months after transport was the primary outcome, and secondary outcomes were all-cause mortality at 1 and 7 days, 1, 6 and 12 months. RESULTS: S/F ratio <100 was associated with increased mortality risk compared with S/F>300 at all time-points, with adjusted OR 6.3 (2.5 to 15.5, p<0.001) at 3 months. Major haemodynamic instability during intensive care unit (ICU) transport was associated with increased adjusted OR of all-cause mortality at 3 months with OR 2.5 (1.8 to 3.5, p<0.001). CONCLUSION: Major impairment of oxygenation and/or major haemodynamic instability at the time of ICU transport to get to urgent tertiary intervention is strongly associated with increased mortality risk at 3 months in this cohort. These findings support the conclusion that these conditions are markers for many fold increase in risk for death notable already at 3 months after transport for patients with these conditions.

Differences in Dementia Care Between Swedish-Born and Foreign-Born from Countries with Different Country Level Socioeconomic Position: A Nationwide Register-Based Study.

BACKGROUND: With a growing elderly population worldwide, the prevalence of dementia is rapidly increasing. Studies from high income countries have shown that belonging to a minority ethnic group increases the risk of health disadvantages. OBJECTIVE: The aim of the present registry-based study was to identify potential differences in diagnostics, treatment, and care of individuals with dementia focusing on foreign-born in Sweden and the impact of country level socioeconomic position (SEP). METHODS: The study was based on a large dataset from the Swedish Dementia Registry (SveDem) and the Swedish Tax Agency's population registry. Data on demographic variables, cognitive tests, clinical assessments, medication, diagnosis, and interventions initiated at diagnosis were collected. Country level SEP was determined by country of birth as classified by World Bank Country and Lending groups. RESULTS: Of 57,982 patients with dementia registered in SveDem, 7,171 (12.4%) were foreign-born. The foreign-born were significantly younger at diagnosis (p < 0.001), had a lower MMSE score (p < 0.001), lower odds of receiving a specific dementia diagnosis (p < 0.001), lower use of acetylcholinesterase inhibitors (p < 0.001), and overall a higher use of neuroleptics compared with the Swedish-born group. The lower SEP, the greater differences to Swedish-born were seen in many of the examined variables. CONCLUSION: There were significant differences in dementia diagnostics, treatment, and care between foreign-born and Swedish-born, a lower SEP indicating greater differences. Further research should focus on various socioeconomic aspects and health care outcomes for a more profound analysis of equity in dementia care.

Inactivation of the budding yeast cohesin loader Scc2 alters gene expression both globally and in response to a single DNA double strand break.

Genome integrity is fundamental for cell survival and cell cycle progression. Important mechanisms for keeping the genome intact are proper sister chromatid segregation, correct gene regulation and efficient repair of damaged DNA. Cohesin and its DNA loader, the Scc2/4 complex have been implicated in all these cellular actions. The gene regulation role has been described in several organisms. In yeast it has been suggested that the proteins in the cohesin network would effect transcription based on its role as insulator. More recently, data are emerging indicating direct roles for gene regulation also in yeast. Here we extend these studies by investigating whether the cohesin loader Scc2 is involved in regulation of gene expression. We performed global gene expression profiling in the absence and presence of DNA damage, in wild type and Scc2 deficient G2/M arrested cells, when it is known that Scc2 is important for DNA double strand break repair and formation of damage induced cohesion. We found that not only the DNA damage specific transcriptional response is distorted after inactivation of Scc2 but also the overall transcription profile. Interestingly, these alterations did not correlate with changes in cohesin binding.

The impact of genetics and hormonal contraceptives on the steroid profile in female athletes.

The steroid module of the Athlete Biological Passport, the newest innovation in doping testing, is currently being finalized for implementation. Several factors, other than doping, can affect the longitudinal steroid profile. In this study, we investigated the effect of hormonal contraceptives (HC) as well as the effect of three polymorphisms on female steroid profiles in relation to doping controls. The study population consisted of 79 female elite athletes between the ages of 18 and 45. HC were used by 32% of the subjects. A full urinary steroid profile was obtained using World Anti-Doping Agency accredited methods. In addition all subjects were genotyped for copy number variation of UGT2B17 and SNPs in UGT2B7 and CYP17. Subjects using HC excreted 40% less epitestosterone as compared to non-users (p = 0.005) but showed no difference in testosterone excretion. When removing individuals homozygous for the deletion in UGT2B17, the testosterone to epitestosterone (T/E) ratio was 29% higher in the HC group (p = 0.016). In agreement with previous findings in men, copy number variation of UGT2B17 had significant effect on female urinary testosterone excretion and therefore also the T/E ratio. Subjects homozygous for the T allele of CYP17 showed a lower urinary epitestosterone concentration than the other CYP17 genotypes. It is of great importance that the athlete's steroidal passport can compensate for all possible normal variability in steroid profiles from women. Therefore, considering the large impact of HC on female steroid profiles, we suggest that the use of HC should be a mandatory question on the doping control form.

The age and genomic integrity of neurons after cortical stroke in humans.

It has been unclear whether ischemic stroke induces neurogenesis or neuronal DNA rearrangements in the human neocortex. Using immunohistochemistry; transcriptome, genome and ploidy analyses; and determination of nuclear bomb test-derived (14)C concentration in neuronal DNA, we found neither to be the case. A large proportion of cortical neurons displayed DNA fragmentation and DNA repair a short time after stroke, whereas neurons at chronic stages after stroke showed DNA integrity, demonstrating the relevance of an intact genome for survival.

A regulatory role for the cohesin loader NIPBL in nonhomologous end joining during immunoglobulin class switch recombination.

DNA double strand breaks (DSBs) are mainly repaired via homologous recombination (HR) or nonhomologous end joining (NHEJ). These breaks pose severe threats to genome integrity but can also be necessary intermediates of normal cellular processes such as immunoglobulin class switch recombination (CSR). During CSR, DSBs are produced in the G1 phase of the cell cycle and are repaired by the classical NHEJ machinery. By studying B lymphocytes derived from patients with Cornelia de Lange Syndrome, we observed a strong correlation between heterozygous loss-of-function mutations in the gene encoding the cohesin loading protein NIPBL and a shift toward the use of an alternative, microhomology-based end joining during CSR. Furthermore, the early recruitment of 53BP1 to DSBs was reduced in the NIPBL-deficient patient cells. Association of NIPBL deficiency and impaired NHEJ was also observed in a plasmid-based end-joining assay and a yeast model system. Our results suggest that NIPBL plays an important and evolutionarily conserved role in NHEJ, in addition to its canonical function in sister chromatid cohesion and its recently suggested function in HR.

Importance of Polη for damage-induced cohesion reveals differential regulation of cohesion establishment at the break site and genome-wide.

Genome integrity depends on correct chromosome segregation, which in turn relies on cohesion between sister chromatids from S phase until anaphase. S phase cohesion, together with DNA double-strand break (DSB) recruitment of cohesin and formation of damage-induced (DI) cohesion, has previously been shown to be required also for efficient postreplicative DSB repair. The budding yeast acetyltransferase Eco1 (Ctf7) is a common essential factor for S phase and DI-cohesion. The fission yeast Eco1 ortholog, Eso1, is expressed as a fusion protein with the translesion synthesis (TLS) polymerase Polη. The involvement of Eso1 in S phase cohesion was attributed to the Eco1 homologous part of the protein and bypass of UV-induced DNA lesions to the Polη part. Here we describe an additional novel function for budding yeast Polη, i.e. formation of postreplicative DI genome-wide cohesion. This is a unique Polη function not shared with other TLS polymerases. However, Polη deficient cells are DSB repair competent, as Polη is not required for cohesion locally at the DSB. This reveals differential regulation of DSB-proximal cohesion and DI genome-wide cohesion, and challenges the importance of the latter for DSB repair. Intriguingly, we found that specific inactivation of DI genome-wide cohesion increases chromosomal mis-segregation at the entrance of the next cell cycle, suggesting that S phase cohesion is not sufficient for correct chromosome segregation in the presence of DNA damage.