Background. In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk ...reduction was higher for infection-related cancer and determined by differences in CD4 cell counts and human immunodeficiency virus (HIV) RNA between the study arms. Methods. Incident malignancies in START were categorized into infection-related and infection-unrelated cancer. We used Cox models to assess factors associated with both cancer categories. We used sequential adjustment for baseline covariates, cancer risk factors, and HIV-specific variables to investigate potential mediators of cancer risk reduction with immediate cART. Results. There were 14 cancers among persons randomized to immediate cART (6 infection-related and 8 infection-unrelated) and 39 cancers in the deferred arm (23 infection-related and 16 infection-unrelated); hazard ratios of immediate vs deferred cART initiation were 0.26 (95% confidence interval CI, .11-.64) for infection-related and 0.49 (95% CI, .21-1.15) for infection-unrelated cancer. Independent predictors of infection-related cancer were older age, higher body mass index, low- to middle-income region, HIV RNA, and baseline CD8 cell count. Older age and baseline CD8 cell count were independent predictors of infection-unrelated cancer. Adjustment for latest HIV RNA level had little impact on the protective effect of immediate cART on infection-related cancer. Adjustment for latest HIV RNA level, but not for CD4 cell count or cancer risk factors, attenuated the effect of immediate cART on infection-unrelated cancer. Conclusions. Immediate cART initiation significantly reduces risk of cancer. Although limited by small sample size, this benefit does not appear to be solely attributable to HIV RNA suppression and may be also mediated by other mechanisms.
We validate the Transiting Exoplanet Survey Satellite (TESS) object of interest TOI-2266.01 (TIC 348911) as a small transiting planet (most likely a super-Earth) orbiting a faint M5 dwarf ...(\(V=16.54\)) on a 2.33~d orbit. The validation is based on an approach where multicolour transit light curves are used to robustly estimate the upper limit of the transiting object's radius. Our analysis uses SPOC-pipeline TESS light curves from Sectors 24, 25, 51, and 52, simultaneous multicolour transit photometry observed with MuSCAT2, MuSCAT3, and HiPERCAM, and additional transit photometry observed with the LCOGT telescopes. TOI-2266 b is found to be a planet with a radius of \(1.54\pm\0.09\,R_\oplus\), which locates it at the edge of the transition zone between rocky planets, water-rich planets, and sub-Neptunes (the so-called M~dwarf radius valley). The planet is amenable to ground-based radial velocity mass measurement with red-sensitive spectrographs installed in large telescopes, such as MAROON-X and Keck Planet Finder (KPF), which makes it a valuable addition to a relatively small population of planets that can be used to probe the physics of the transition zone. Further, the planet's orbital period of 2.33 days places it inside a `keystone planet' wedge in the period-radius plane where competing planet formation scenarios make conflicting predictions on how the radius valley depends on the orbital period. This makes the planet also a welcome addition to the small population of planets that can be used to test small-planet formation scenarios around M~dwarfs.
Because the liver plays a major role in metabolic homeostasis and secretion of clotting factors and inflammatory innate immune proteins, there is interest in understanding the mechanisms of hepatic ...cell activation under hyperglycaemia and whether this can be attenuated pharmacologically. We have previously shown that hyperglycaemia stimulates major changes in chromatin organization and metabolism in hepatocytes, and that the histone deacetylase inhibitor valproic acid (VPA) is able to reverse some of these metabolic changes. In this study, we have used RNA-sequencing (RNA-seq) to investigate how VPA influences gene expression in hepatocytes. Interesting, we observed that VPA attenuates hyperglycaemia-induced activation of complement and coagulation cascade genes. We also observe that many of the gene activation events coincide with changes to histone acetylation at the promoter of these genes indicating that epigenetic regulation is involved in VPA action.
Ivermectin (IVM) resistance of Cooperia spp. in cattle has become an increasing and global problem. The early detection of anthelmintic resistance (AR) is important to propose strategies to slow down ...the development of resistance and requires sensitive, reliable, economic high-throughput and practical tests. The purpose of the present study was to apply a larval migration inhibition test (LMIT) for evaluating IVM and MOX efficacy against well-characterized field isolates of Cooperia spp. infecting cattle in Brazil. Eight isolates were used for IVM and seven for MOX. The following EC50 values of IVM were observed for the isolates: susceptible, 1.16ηmol; Nova Alvorada do Sul I, 4.09ηmol (RF=3.52); Campo Grande BNA, 3.57ηmol (RF=3.07); Campo Grande TBR, 4.09ηmol (RF=3,52); Nova Alvorada do Sul II, 2.50ηmol (RF=2.15); Bandeirantes, 11.35ηmol (RF=9.78); Campo Grande II, 6.03ηmol (RF=5.20); and Porto Mortinho, 8.63ηmol (RF=7.44). For MOX, the following EC50 values were observed: susceptible, 0.75ηmol; Campo Grande BNA, 0.93ηmol (RF=1.24); Campo Grande TBR, 0.36ηmol (RF=0.48); Nova Alvorada do Sul II, 2.57ηmol (RF=3.42); Bandeirantes, 1.43ηmol (RF=1.90); Campo Grande II, 1.08ηmol (RF=1.44); and Porto Mortinho, 0.49ηmol (RF=0.65). The LMIT used in the present study can be a useful tool for in vitro evaluation of IVM, but not of MOX. However, such methodology cannot be used in large-scale studies yet. The isolates of Cooperia spp. showed various degrees of resistance to IVM, though remaining susceptible to MOX.
Abstract
The relative rarity of giant planets around low-mass stars compared with solar-type stars is a key prediction from the core-accretion planet formation theory. In this paper we report on the ...discovery of four gas giant planets that transit low-mass late K and early M dwarfs. The planets HATS-74Ab (TOI 737b), HATS-75b (TOI 552b), HATS-76b (TOI 555b), and HATS-77b (TOI 730b) were all discovered from the HATSouth photometric survey and follow-up using TESS and other photometric facilities. We use the new ESPRESSO facility at the VLT to confirm systems and measure their masses. We find that these planets have masses of 1.46 ± 0.14
M
J, 0.491 ± 0.039
M
J, 2.629 ± 0.089
M
J, and
1.374
−
0.074
+
0.100
M
J, respectively, and radii of 1.032 ± 0.021
R
J, 0.884 ± 0.013
R
J, 1.079 ± 0.031
R
J, and 1.165 ± 0.021
R
J, respectively. The planets all orbit close to their host stars with orbital periods ranging from 1.7319 days to 3.0876 days. With further work, we aim to test core-accretion theory by using these and further discoveries to quantify the occurrence rate of giant planets around low-mass host stars.
International Consensus on drug allergy Demoly, P.; Adkinson, N. F.; Brockow, K. ...
Allergy,
April 2014, Letnik:
69, Številka:
4
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions (DHRs) before showing the evidence of either drug‐specific antibodies or T cells. DHRs may be allergic or ...nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life‐threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under‐reporting) and overdiagnosis (due to an overuse of the term ‘allergy’) are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more‐expensive or less‐effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class‐induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the World Allergy Organization (WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of DHRs.
Abstract Background We report prospective associations of baseline risk factors with the first onset and persistence of suicide-related outcomes (SROs; ideation, plans, gestures, and attempts) over a ...10-year interval among respondents who participated in both the 1990–02 National Comorbidity Survey (NCS) and the 2000–02 National Comorbidity Survey follow-up (NCS-2). Methods A total of 5001 NCS respondents were re-interviewed (87.6% of baseline sample) in the NCS-2. Three sets of baseline (NCS) risk factors were considered as predictors of the first onset and persistence of SROs: socio-demographics, lifetime DSM-III-R disorders, and SROs. Results New onsets included 6.2% suicide ideation, 2.3% plan, 0.7% gesture, and 0.9% attempts. More than one-third of respondents with a baseline history of suicide ideation continued to have suicide ideation at some time over the intervening decade. Persistence was lower for other SROs. The strongest predictors of later SROs were baseline SROs. Prospective associations of baseline mental disorders with later SROs were largely limited to the onset and persistence of ideation. Limitations Although data were gathered prospectively, they were based on retrospective reports at both baseline and follow-up. Conclusions Baseline history of SROs explained much of the association of mental disorders with later SROs. It is important clinically to note that many of the risk factors known to predict onset of SROs also predict persistence of SROs.
Treatment of suicidal people around the world Bruffaerts, Ronny; Demyttenaere, Koen; Hwang, Irving ...
British journal of psychiatry,
07/2011, Letnik:
199, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Suicide is a leading cause of death worldwide; however, little information is available about the treatment of suicidal people, or about barriers to treatment.
To examine the receipt of mental health ...treatment and barriers to care among suicidal people around the world.
Twenty-one nationally representative samples worldwide (n=55 302; age 18 years and over) from the World Health Organization's World Mental Health Surveys were interviewed regarding past-year suicidal behaviour and past-year healthcare use. Suicidal respondents who had not used services in the past year were asked why they had not sought care.
Two-fifths of the suicidal respondents had received treatment (from 17% in low-income countries to 56% in high-income countries), mostly from a general medical practitioner (22%), psychiatrist (15%) or non-psychiatrist (15%). Those who had actually attempted suicide were more likely to receive care. Low perceived need was the most important reason for not seeking help (58%), followed by attitudinal barriers such as the wish to handle the problem alone (40%) and structural barriers such as financial concerns (15%). Only 7% of respondents endorsed stigma as a reason for not seeking treatment.
Most people with suicide ideation, plans and attempts receive no treatment. This is a consistent and pervasive finding, especially in low-income countries. Improving the receipt of treatment worldwide will have to take into account culture-specific factors that may influence the process of help-seeking.
•Palm oil and β-carotene were encapsulated in chitosan/CMC by complex coacervation.•Palm oil and β-carotene were encapsulated in chitosan/TPP by ionic gelation.•Release profile was evaluated ...simulating gastric and intestinal conditions.•The microparticles were applied in bread and yogurt.•When applied in the foods the release of carotenoids was increased.
Carotenoids are susceptible to isomerization and oxidation upon exposure to oxygen, light and heat, which can result in loss of color, antioxidant activity, and vitamin activity. Microencapsulation helps retain carotenoid stability and promotes their release under specific conditions. Thus, the aim of the study was to encapsulate palm oil and β-carotene with chitosan/sodium tripolyphosphate or chitosan/carboxymethylcellulose and to assess the performance of these microparticles in food systems by analyzing their release profile under simulated gastric and intestinal conditions. Encapsulation efficiency was greater than 95%, and the yield of microparticles coated with chitosan/sodium tripolyphosphate was approximately 55%, while that of microparticles coated with chitosan/carboxymethylcellulose was 87%. Particles encapsulated with chitosan/carboxymethylcellulose exhibited ideal release behavior in water and gastric fluid, but showed low release in the intestinal fluid. However, when applied to food systems these particles showed enhanced carotenoid release but showed low release of carotenoids upon storage.
Context. Exoplanets with orbital periods of less than one day are known as ultra-short period (USP) planets. They are relatively rare products of planetary formation and evolution processes, but ...especially favourable for characterisation with current planet detection methods. At the time of writing, 125 USP planets have already been confirmed. Aims. Our aim is to validate the planetary nature of two new transiting planet candidates around M dwarfs announced by the NASA Transiting Exoplanet Survey Satellite (TESS), registered as TESS Objects of Interest (TOIs) TOI-1442.01 and TOI-2445.01. Methods. We used TESS data, ground-based photometric light curves, and Subaru/IRD spectrograph radial velocity (RV) measurements to validate both planetary candidates and to establish their physical properties. Results. TOI-1442 b is a validated exoplanet with an orbital period of \(P\)=0.4090682+/-0.0000004 d, a radius of \(R_p\)=1.15+/-0.06\(R_{\oplus}\), and equilibrium temperature of \(T_{p,eq}\)=1357\(_{-42}^{+49}\)K. TOI-2445 b is also validated with an orbital period of \(P\)=0.3711286+/-0.0000004 d, a radius of \(R_p\)= 1.33+/-0.09\(R_{\oplus}\), and equilibrium temperature of \(T_{p,eq}\)=1330\(_{-56}^{+61}\)K. Their physical properties align with current empirical trends and formation theories of USP planets. Based on the RV measurements, we set 3\(\sigma\) upper mass limits of 8\(M_{\oplus}\) and 20\(M_{\oplus}\), thus confirming the non-stellar, sub-Jovian nature of both transiting objects. More RV measurements will be needed to constrain the planetary masses and mean densities, and the predicted presence of outer planetary companions. These targets extend the small sample of USP planets orbiting around M dwarfs up to 21 members. They are also among the 20 most suitable terrestrial planets for atmospheric characterisation via secondary eclipse with the JWST, according to a widespread emission spectroscopy metric.
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