...we completely agree with the author that organ dysfunction during critical illness is a multilayered problem, and no single component can be pinpointed (i.e., fluids) as the sole determinant of ...its' evolution. ...we count with clinical evidence that support the idea that fluid administration in high-risk patients may deleteriously impact organ function during the resuscitation phase. ...pretending to develop a more granular definition or score of such a complex phenomenon has the inherent risks of oversimplification, reductionism, and rapid obsolescence. Contemporary literature also supports the idea of fluids administration in sepsis, since both early vasopressor studies 11,12, as well as restrictive fluid studies 13, have still administered fluids as an initial resuscitative intervention. ...aiming to provide a more rational and multimodal resuscitation does not imply to pursue a fluid-free strategy, since altered vasomotor tone is not the only pathological determinant of circulatory dysfunction in sepsis.
Rapidly diminishing Arctic summer sea ice is a strong signal of the pace of global climate change. We provide point, interval, and density forecasts for four measures of Arctic sea ice: area, extent, ...thickness, and volume. Importantly, we enforce the joint constraint that these measures must simultaneously arrive at an ice-free Arctic. We apply this constrained joint forecast procedure to models relating sea ice to atmospheric carbon dioxide concentration and models relating sea ice directly to time. The resulting “carbon-trend” and “time-trend” projections are mutually consistent and predict a nearly ice-free summer Arctic Ocean by the mid-2030s with an 80% probability. Moreover, the carbon-trend projections show that global adoption of a lower carbon path would likely delay the arrival of a seasonally ice-free Arctic by only a few years.
An ice sheet model was constrained to reconstruct the evolution of the Greenland Ice Sheet (GrIS) from the Last Glacial Maximum (LGM) to present to improve our understanding of its response to ...climate change. The study involved applying a glaciological model in series with a glacial isostatic adjustment and relative sea-level (RSL) model. The model reconstruction builds upon the work of Simpson et al. (2009) through four main extensions: (1) a larger constraint database consisting of RSL and ice extent data; model improvements to the (2) climate and (3) sea-level forcing components; (4) accounting for uncertainties in non-Greenland ice. The research was conducted primarily to address data-model misfits and to quantify inherent model uncertainties with the Earth structure and non-Greenland ice. Our new model (termed Huy3) fits the majority of observations and is characterised by a number of defining features. During the LGM, the ice sheet had an excess of 4.7 m ice-equivalent sea-level (IESL), which reached a maximum volume of 5.1 m IESL at 16.5 cal ka BP. Modelled retreat of ice from the continental shelf progressed at different rates and timings in different sectors. Southwest and Southeast Greenland began to retreat from the continental shelf by ∼16 to 14 cal ka BP, thus responding in part to the Bølling-Allerød warm event (c. 14.5 cal ka BP); subsequently ice at the southern tip of Greenland readvanced during the Younger Dryas cold event. In northern Greenland the ice retreated rapidly from the continental shelf upon the climatic recovery out of the Younger Dryas to present-day conditions. Upon entering the Holocene (11.7 cal ka BP), the ice sheet soon became land-based. During the Holocene Thermal Maximum (HTM; 9-5 cal ka BP), air temperatures across Greenland were marginally higher than those at present and the GrIS margin retreated inland of its present-day southwest position by 40–60 km at 4 cal ka BP which produced a deficit volume of 0.16 m IESL relative to present. In response to the HTM warmth, our optimal model reconstruction lost mass at a maximum centennial rate of c. 103.4 Gt/yr. Our results suggest that remaining data-model discrepancies are affiliated with missing physics and sub-grid processes of the glaciological model, uncertainties in the climate forcing, lateral Earth structure, and non-Greenland ice (particularly the North American component). Finally, applying the Huy3 Greenland reconstruction with our optimal Earth model we generate present-day uplift rates across Greenland due to past changes in the ocean and ice loads with explicit error bars due to uncertainties in the Earth structure. Present-day uplift rates due to past changes are spatially variable and range from 3.5 to −7 mm/a (including Earth model uncertainty).
•We build on the Simpson et al. (2009) study and model the Greenland Deglaciation.•A constraint dataset of RSL, ice extent, and ice-core observations is established.•We data-constrain a glaciological model and GIA model of RSL change.•We identify a best fitting Greenland reconstruction with respect to the observations.•We quantify the impact of NAIC uncertainties on the Greenland chronology.
How systemic metabolic alterations during acute infections impact immune cell function remains poorly understood. We found that acetate accumulates in the serum within hours of systemic bacterial ...infections and that these increased acetate concentrations are required for optimal memory CD8+ T cell function in vitro and in vivo. Mechanistically, upon uptake by memory CD8+ T cells, stress levels of acetate expanded the cellular acetyl-coenzyme A pool via ATP citrate lyase and promoted acetylation of the enzyme GAPDH. This context-dependent post-translational modification enhanced GAPDH activity, catalyzing glycolysis and thus boosting rapid memory CD8+ T cell responses. Accordingly, in a murine Listeria monocytogenes model, transfer of acetate-augmented memory CD8+ T cells exerted superior immune control compared to control cells. Our results demonstrate that increased systemic acetate concentrations are functionally integrated by CD8+ T cells and translate into increased glycolytic and functional capacity. The immune system thus directly relates systemic metabolism with immune alertness.
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•Serum acetate levels rapidly increase following systemic bacterial infection•Memory CD8+ T cells take up acetate and expand their acetyl-CoA pool•Increased acetyl-CoA levels catalyze functional activity of GAPDH by acetylation•Augmented glycolytic flux rates boost rapid recall responses of memory CD8+ T cells
How systemic metabolic alterations during acute infections impact immune-cell function remains poorly understood. Hess and colleagues demonstrate that acetate rapidly increases during infections, which drives acetylation of GAPDH in memory CD8+ T cells and thereby catalyzes the rapid recall response.
Plasmodium falciparum malaria remains a major public health problem. A vital component of malaria control rests on the availability of good quality artemisinin-derivative based combination therapy ...(ACT) at the correct dose. However, there are increasing reports of poor quality anti-malarials in Africa.
Seven collections of artemisinin derivative monotherapies, ACT and halofantrine anti-malarials of suspicious quality were collected in 2002/10 in eleven African countries and in Asia en route to Africa. Packaging, chemical composition (high performance liquid chromatography, direct ionization mass spectrometry, X-ray diffractometry, stable isotope analysis) and botanical investigations were performed.
Counterfeit artesunate containing chloroquine, counterfeit dihydroartemisinin (DHA) containing paracetamol (acetaminophen), counterfeit DHA-piperaquine containing sildenafil, counterfeit artemether-lumefantrine containing pyrimethamine, counterfeit halofantrine containing artemisinin, and substandard/counterfeit or degraded artesunate and artesunate+amodiaquine in eight countries are described. Pollen analysis was consistent with manufacture of counterfeits in eastern Asia. These data do not allow estimation of the frequency of poor quality anti-malarials in Africa.
Criminals are producing diverse harmful anti-malarial counterfeits with important public health consequences. The presence of artesunate monotherapy, substandard and/or degraded and counterfeit medicines containing sub-therapeutic amounts of unexpected anti-malarials will engender drug resistance. With the threatening spread of artemisinin resistance to Africa, much greater investment is required to ensure the quality of ACTs and removal of artemisinin monotherapies. The International Health Regulations may need to be invoked to counter these serious public health problems.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The college years are stressful for many students. Identifying the sources of stress and their relative importance in leading to clinically significant emotional problems may assist in the ...development of targeted stress management interventions. The current report examines the distribution and associations of perceived stress across major life areas with 12-month prevalence of common mental disorders in a cross-national sample of first-year college students. The 20,842 respondents were from 24 universities in 9 countries that participated in the World Health Organization World Mental Health International College Student Initiative. Logistic regression analysis examined associations of current perceived stress in six life areas (financial situation, health, love life, relationships with family, relationships at work/school, problems experienced by loved ones) with six types of 12-month mental disorders (major depressive disorder, bipolar disorder, generalized anxiety disorder, panic disorder, alcohol use disorder, drug use disorder). Population attributable risk proportions (PARPs) were calculated to estimate the upper-bound potential effects of interventions focused on perceived stress in reducing prevalence of mental disorders. The majority of students (93.7%) reported at least some stress in at least one of the six areas. A significant dose-response association was found between extent of stress in each life area and increased odds of at least one of the six disorders. The multivariable models that included all stress measures were significant for all disorders (
F
= 20.6–70.6,
p
< 0.001). Interpretation of PARPs as representing causal effects of stresses on disorders suggests that up to 46.9–80.0% of 12-month disorder prevalence might be eliminated if stress prevention interventions were developed to block the associations of stress with these disorders.
We constrain a three-dimensional thermomechanical model of Greenland ice sheet (GrIS) evolution from the Last Glacial Maximum (LGM, 21
ka BP) to the present-day using, primarily, observations of ...relative sea level (RSL) as well as field data on past ice extent. Our new model (Huy2) fits a majority of the observations and is characterised by a number of key features: (i) the ice sheet had an excess volume (relative to present) of 4.1
m ice-equivalent sea level at the LGM, which increased to reach a maximum value of 4.6
m at 16.5
ka BP; (ii) retreat from the continental shelf was not continuous around the entire margin, as there was a Younger Dryas readvance in some areas. The final episode of marine retreat was rapid and relatively late (c. 12
ka BP), leaving the ice sheet land based by 10
ka BP; (iii) in response to the Holocene Thermal Maximum (HTM) the ice margin retreated behind its present-day position by up to 80
km in the southwest, 20
km in the south and 80
km in a small area of the northeast. As a result of this retreat the modelled ice sheet reaches a minimum extent between 5 and 4
ka BP, which corresponds to a deficit volume (relative to present) of 0.17
m ice-equivalent sea level. Our results suggest that remaining discrepancies between the model and the observations are likely associated with non-Greenland ice load, differences between modelled and observed present-day ice elevation around the margin, lateral variations in Earth structure and/or the pattern of ice margin retreat.
Current use of vasopressors in septic shock Scheeren, Thomas W. L.; Bakker, Jan; De Backer, Daniel ...
Annals of intensive care,
01/2019, Letnik:
9, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Background
Vasopressors are commonly applied to restore and maintain blood pressure in patients with sepsis. We aimed to evaluate the current practice and therapeutic goals regarding vasopressor use ...in septic shock as a basis for future studies and to provide some recommendations on their use.
Methods
From November 2016 to April 2017, an anonymous web-based survey on the use of vasoactive drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 17 questions focused on the profile of respondents, triggering factors, first choice agent, dosing, timing, targets, additional treatments, and effects of vasopressors. We investigated whether the answers complied with current guidelines. In addition, a group of 34 international ESICM experts was asked to formulate recommendations for the use of vasopressors based on 6 questions with sub-questions (total 14).
Results
A total of 839 physicians from 82 countries (65% main specialty/activity intensive care) responded. The main trigger for vasopressor use was an insufficient mean arterial pressure (MAP) response to initial fluid resuscitation (83%). The first-line vasopressor was norepinephrine (97%), targeting predominantly a MAP > 60–65 mmHg (70%), with higher targets in patients with chronic arterial hypertension (79%). The experts agreed on 10 recommendations, 9 of which were based on unanimous or strong (≥ 80%) agreement. They recommended not to delay vasopressor treatment until fluid resuscitation is completed but rather to start with norepinephrine early to achieve a target MAP of ≥ 65 mmHg.
Conclusion
Reported vasopressor use in septic shock is compliant with contemporary guidelines. Future studies should focus on individualized treatment targets including earlier use of vasopressors.
Current recommendations support guiding fluid resuscitation through the assessment of fluid responsiveness. Recently, the concept of fluid tolerance and the prevention of venous congestion (VC) have ...emerged as relevant aspects to be considered to avoid potentially deleterious side effects of fluid resuscitation. However, there is paucity of data on the relationship of fluid responsiveness and VC. This study aims to compare the prevalence of venous congestion in fluid responsive and fluid unresponsive critically ill patients after intensive care (ICU) admission.
Multicenter, prospective cross-sectional observational study conducted in three medical-surgical ICUs in Chile. Consecutive mechanically ventilated patients that required vasopressors and admitted < 24 h to ICU were included between November 2022 and June 2023. Patients were assessed simultaneously for fluid responsiveness and VC at a single timepoint. Fluid responsiveness status, VC signals such as central venous pressure, estimation of left ventricular filling pressures, lung, and abdominal ultrasound congestion indexes and relevant clinical data were collected.
Ninety patients were included. Median age was 63 45-71 years old, and median SOFA score was 9 7-11. Thirty-eight percent of the patients were fluid responsive (FR+), while 62% were fluid unresponsive (FR-). The most prevalent diagnosis was sepsis (41%) followed by respiratory failure (22%). The prevalence of at least one VC signal was not significantly different between FR+ and FR- groups (53% vs. 57%, p = 0.69), as well as the proportion of patients with 2 or 3 VC signals (15% vs. 21%, p = 0.4). We found no association between fluid balance, CRT status, or diagnostic group and the presence of VC signals.
Venous congestion signals were prevalent in both fluid responsive and unresponsive critically ill patients. The presence of venous congestion was not associated with fluid balance or diagnostic group. Further studies should assess the clinical relevance of these results and their potential impact on resuscitation and monitoring practices.
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