Risk factors, biomarkers, and mechanisms for persistent inflammation, immunosuppression, and catabolism syndrome (PICS): a systematic review and meta-analysis.

INTRODUCTION: Persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has been proposed as an endotype of chronic critical illness (CCI). The aim of this systematic review is to synthesise the available evidence of risk factors, biomarkers, and biological mechanisms underlying PICS. METHODS: MEDLINE, CENTRAL, and EMBASE were searched on June 2, 2023. Our population of interest was adult intensive care unit survivors. The exposure group was patients with PICS and the comparator group was patients with no PICS, CCI, or rapid recovery. Mean differences were pooled for each biomarker using a random effects DerSimonian-Laird method. Risk of bias assessment was done using the Newcastle-Ottawa Scale. RESULTS: Six papers were included. Five were single-centre retrospective cohort studies, and one was a prospective cohort study, with sample sizes ranging from 22 to 391 patients. Two studies showed an increased incidence of PICS with age, and two studies showed an association between PICS and Charlson Comorbidity Index scores. PICS was associated with requiring mechanical ventilation in four studies. Meta-analysis showed a 34.4 mg L-1 higher C-reactive protein (95% confidence interval [CI] 12.7-56.2 mg L-1; P<0.01), a 4.4 g L-1 lower albumin (95% CI 0.5-8.3 g L-1; P<0.01), and a 0.36×109 L-1 lower lymphocyte count (95% CI 0.25-0.47×109 L-1; P=0.01) in the PICS compared with the non-PICS group. There are a large variety of other potential biomarkers but limited validation studies. The overall quality of evidence is limited, and these results should be interpreted accordingly. CONCLUSIONS: While older patients and those with co-morbidities could be at greater risk for PICS, acquired risk factors, such as injury severity, are potentially more predictive of PICS than intrinsic patient characteristics. There are many potential biomarkers for PICS, but limited validation studies have been conducted. Persistent myeloid-derived suppressor cell expansion, the continual release of danger-associated molecular patterns and pathogen-associated molecular patterns propagating inflammation, and bioenergetic failure are all mechanisms underlying PICS that could offer potential for novel biomarkers and therapeutic interventions. CLINICAL TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO; CRD42023427749).

Creatine supplementation for optimization of physical function in the patient at risk of functional disability: A systematic review and meta-analysis.

BACKGROUND: The efficacy of creatine replacement through supplementation for the optimization of physical function in the population at risk of functional disability is unclear. METHODS: We conducted a systematic literature search of MEDLINE, EMBASE, the Cochrane Library, and CINAHL from inception to November 2022. Studies included were randomized controlled trials (RCTs) comparing creatine supplementation with placebos in older adults and adults with chronic disease. The primary outcome was physical function measured by the sit-to-stand test after pooling data using random-effects modeling. We also performed a Bayesian meta-analysis to describe the treatment effect in probability terms. Secondary outcomes included other measures of physical function, muscle function, and body composition. The risk of bias was assessed using the Cochrane risk-of-bias tool. RESULTS: We identified 33 RCTs, comprising 1076 participants. From six trials reporting the primary outcome, the pooled standardized mean difference (SMD) was 0.51 (95% confidence interval [CI]: 0.01-1.00; I2 = 62%; P = 0.04); using weakly informative priors, the posterior probability that creatine supplementation improves physical function was 66.7%. Upper-body muscle strength (SMD: 0.25; 95% CI: 0.06-0.44; I2 = 0%; P = 0.01), handgrip strength (SMD 0.23; 95% CI: 0.01-0.45; I2 = 0%; P = 0.04), and lean tissue mass (MD 1.08 kg; 95% CI: 0.77-1.38; I2 = 26%; P < 0.01) improved with creatine supplementation. The quality of evidence for all outcomes was low or very low because of a high risk of bias. CONCLUSION: Creatine supplementation improves sit-to-stand performance, muscle function, and lean tissue mass. It is crucial to conduct high-quality prospective RCTs to confirm these hypotheses (PROSPERO number, CRD42023354929).

Dental morphology in Homo habilis and its implications for the evolution of early Homo.

The phylogenetic position of Homo habilis is central to debates over the origin and early evolution of the genus Homo. A large portion of the species hypodigm consists of dental remains, but they have only been studied at the often worn enamel surface. We investigate the morphology of the H. habilis enamel-dentine junction (EDJ), which is preserved in cases of moderate tooth wear and known to carry a strong taxonomic signal. Geometric morphometrics is used to characterise dentine crown shape and size across the entire mandibular and maxillary tooth rows, compared with a broad comparative sample (n = 712). We find that EDJ morphology in H. habilis is for the most part remarkably primitive, supporting the hypothesis that the H. habilis hypodigm has more in common with Australopithecus than later Homo. Additionally, the chronologically younger specimen OH 16 displays a suite of derived features; its inclusion in H. habilis leads to excessive levels of variation.

Variation and covariation of external shape and cross-sectional geometry in the human metacarpus.

OBJECTIVES: Analyses of external bone shape using geometric morphometrics (GM) and cross-sectional geometry (CSG) are frequently employed to investigate bone structural variation and reconstruct activity in the past. However, the association between these methods has not been thoroughly investigated. Here, we analyze whole bone shape and CSG variation of metacarpals 1-5 and test covariation between them. MATERIALS AND METHODS: We analyzed external metacarpal shape using GM and CSG of the diaphysis at three locations in metacarpals 1-5. The study sample includes three modern human groups: crew from the shipwrecked Mary Rose (n = 35 metacarpals), a Pre-industrial group (n = 50), and a Post-industrial group (n = 31). We tested group differences in metacarpal shape and CSG, as well as correlations between these two aspects of metacarpal bone structure. RESULTS: GM analysis demonstrated metacarpus external shape variation is predominately related to changes in diaphyseal width and articular surface size. Differences in external shape were found between the non-pollical metacarpals of the Mary Rose and Pre-industrial groups and between the third metacarpals of the Pre- and Post-industrial groups. CSG results suggest the Mary Rose and Post-industrial groups have stronger metacarpals than the Pre-industrial group. Correlating CSG and external shape showed significant relationships between increasing external robusticity and biomechanical strength across non-pollical metacarpals (r: 0.815-0.535; p ≤ 0.05). DISCUSSION: Differences in metacarpal cortical structure and external shape between human groups suggest differences in the type and frequency of manual activities. Combining these results with studies of entheses and kinematics of the hand will improve reconstructions of manual behavior in the past.

Early Homo erectus lived at high altitudes and produced both Oldowan and Acheulean tools.

In Africa, the scarcity of hominin remains found in direct association with stone tools has hindered attempts to link Homo habilis and Homo erectus with particular lithic industries. The infant mandible discovered in level E at Garba IV (Melka Kunture) on the highlands of Ethiopia is critical to this issue due to its direct association with an Oldowan lithic industry. Here, we use synchrotron imaging to examine the internal morphology of the unerupted permanent dentition and confirm its identification as Homo erectus. Additionally, we utilize new palaeomagnetic ages to show that (i) the mandible in level E is ca. 2 million-years-old, and represents one of the earliest Homo erectus fossils, and (ii) that overlying level D, ca. 1.95 million-years-old, contains the earliest known Acheulean assemblage.

Impacts of artificial light at night on the early life history of two ecosystem engineers.

Sessile marine invertebrates play a vital role as ecosystem engineers and in benthic-pelagic coupling. Most benthic fauna develop through larval stages and the importance of natural light cycles for larval biology and ecology is long-established. Natural light-dark cycles regulate two of the largest ocean-scale processes that are fundamental to larvae's life cycle: the timing of broadcast spawning for successful fertilization and diel vertical migration for foraging and predator avoidance. Given the reliance on light and the ecological role of larvae, surprisingly little is known about the impacts of artificial light at night (ALAN) on the early life history of habitat-forming species. We quantified ALAN impacts on larval performance (survival, growth, development) of two cosmopolitan ecosystem engineers in temperate marine ecosystems, the mussel Mytilus edulis and the barnacle Austrominius modestus. Higher ALAN irradiance reduced survival in both species (57% and 13%, respectively). ALAN effects on development and growth were small overall, and different between species, time-points and parentage. Our results show that ALAN adversely affects larval survival and reiterates the importance of paternal influence on offspring performance. ALAN impacts on the early life stages of ecosystem engineering species have implications not only for population viability but also the ecological communities that these species support. This article is part of the theme issue 'Light pollution in complex ecological systems'.

Global disruption of coral broadcast spawning associated with artificial light at night.

Coral broadcast spawning events - in which gametes are released on certain nights predictably in relation to lunar cycles - are critical to the maintenance and recovery of coral reefs following mass mortality. Artificial light at night (ALAN) from coastal and offshore developments threatens coral reef health by masking natural light:dark cycles that synchronize broadcast spawning. Using a recently published atlas of underwater light pollution, we analyze a global dataset of 2135 spawning observations from the 21st century. For the majority of genera, corals exposed to light pollution are spawning between one and three days closer to the full moon compared to those on unlit reefs. ALAN possibly advances the trigger for spawning by creating a perceived period of minimum illuminance between sunset and moonrise on nights following the full moon. Advancing the timing of mass spawning could decrease the probability of gamete fertilization and survival, with clear implications for ecological processes involved in the resilience of reef systems.

Can pioglitazone be used for optimization of nutrition in critical illness? A systematic review.

BACKGROUND: Skeletal muscle wasting is a determinant of physical disability in survivors of critical illness. Intramuscular bioenergetic failure, altered substrate metabolim, and inflammation are likely underpinning mechanisms. We examined the effect of pioglitazone, a peroxisome proliferator-activated receptor γ agonist, on muscle-related outcomes in adults. METHODS: We included randomized controlled trials in which pioglitazone was administered (no dose/dosage restrictions) and muscle-related outcomes were reported. We searched MEDLINE, CENTRAL, EMBASE, CINAHL, and trial registries. Risk of bias was assessed using RoB 2. Primary outcomes were physical function and symptoms, muscle mass and function, or body composition and muscular compositional change. Secondary outcomes included muscle insulin sensitivity, mitochondrial effects, and intramuscular inflammation. RESULTS: Fourteen studies over 19 publications (n = 474 patients) were included. Lean body mass was unaffected in three studies (n = 126) and increased by 1.8-1.92 kg in two studies (P = 0.02 and 0.003, respectively; n = 48). Pioglitazone was associated with increased peripheral insulin sensitivity (+23%-72%, standardized mean difference of 0.97 from trial start point to end point [95% CI, 0.36-1.58; n = 213]). Treatment reduced intramuscular tumor necrosis factor-α (TNF-α) levels (-30%; P = 0.02; n = 29), with mixed effects on serum TNF-α and intramyocellular lipid concentrations. Treatment increased intramuscular markers of adenosine triphosphate (ATP) biosynthesis (ATP5A [+33%, P ≤ 0.05], ETFA [+60%, P ≤ 0.05], and CX6B1 [+ 33%, P = 0.01] [n = 24]), PGC1α and PGC1ß messenger RNA expression (P < 0.05; n = 26), and AMPK phosphorylation (+38%, P < 0.05; n = 26). These data have low-quality evidence profiles owing to risk of bias. CONCLUSIONS: Pioglitazone therapy increases skeletal muscle insulin sensitivity and can decrease intramuscular inflammation.

Long-term effects of artificial nighttime lighting and trophic complexity on plant biomass and foliar carbon and nitrogen in a grassland community.

The introduction of artificial nighttime lighting due to human settlements and transport networks is increasingly altering the timing, intensity, and spectra of natural light regimes worldwide. Much of the research on the impacts of nighttime light pollution on organisms has focused on animal species. Little is known about the impacts of daylength extension due to outdoor lighting technologies on wild plant communities, despite the fact that plant growth and development are under photoperiodic control. In a five-year field experiment, artificial ecosystems ("mesocosms") of grassland communities both alone or in combination with invertebrate herbivores and predators were exposed to light treatments that simulated street lighting technologies (low-pressure sodium, and light-emitting diode [LED]-based white lighting), at ground-level illuminance. Most of the plant species in the mesocosms did not exhibit changes in biomass accumulation after 5 years of exposure to the light treatments. However, the white LED treatment had a significant negative effect on biomass production in the herbaceous species Lotus pedunculatus. Likewise, the interaction between the white LED treatment and the presence of herbivores significantly reduced the mean shoot/root ratio of the grass species Holcus lanatus. Artificial nighttime lighting had no effect on the foliar carbon or nitrogen in most of the grassland species. Nevertheless, the white LED treatment significantly increased the leaf nitrogen content in Lotus corniculatus in the presence of herbivores. Long-term exposure to artificial light at night had no general effects on plant biomass responses in experimental grassland communities. However, species-specific and negative effects of cool white LED lighting at ground-level illuminance on biomass production and allocation in mixed plant communities are suggested by our findings. Further studies on the impacts of light pollution on biomass accumulation in plant communities are required as these effects could be mediated by different factors, including herbivory, competition, and soil nutrient availability.

Artificial light at night reverses monthly foraging pattern under simulated moonlight.

Mounting evidence shows that artificial light at night (ALAN) alters biological processes across levels of organization, from cells to communities. Yet, the combined impacts of ALAN and natural sources of night-time illumination remain little explored. This is in part due the lack of accurate simulations of the complex changes moonlight intensity, timing and spectra throughout a single night and lunar cycles in laboratory experiments. We custom-built a novel system to simulate natural patterns of moonlight to test how different ALAN intensities affect predator-prey relationships over the full lunar cycle. Exposure to high intensity ALAN (10 and 50 lx) reversed the natural lunar-guided foraging pattern by the gastropod mesopredator Nucella lapillus on its prey Semibalanus balanoides. Foraging decreased during brighter moonlight in naturally lit conditions. When exposed to high intensity ALAN, foraging increased with brighter moonlight. Low intensity ALAN (0.1 and 0.5 lx) had no impact on foraging. Our results show that ALAN alters the foraging pattern guided by changes in moonlight brightness. ALAN impacts on ecosystems can depend on lunar light cycles. Accurate simulations of night-time light cycle will warrant more realistic insights into ALAN impacts and also facilitate advances in fundamental night-time ecology and chronobiology.

Dental data challenge the ubiquitous presence of Homo in the Cradle of Humankind.

The origins of Homo, as well as the diversity and biogeographic distribution of early Homo species, remain critical outstanding issues in paleoanthropology. Debates about the recognition of early Homo, first appearance dates, and taxonomic diversity within Homo are particularly important for determining the role that southern African taxa may have played in the origins of the genus. The correct identification of Homo remains also has implications for reconstructing phylogenetic relationships between species of Australopithecus and Paranthropus, and the links between early Homo species and Homo erectus. We use microcomputed tomography and landmark-free deformation-based three-dimensional geometric morphometrics to extract taxonomically informative data from the internal structure of postcanine teeth attributed to Early Pleistocene Homo in the southern African hominin-bearing sites of Sterkfontein, Swartkrans, Drimolen, and Kromdraai B. Our results indicate that, from our sample of 23 specimens, only 4 are unambiguously attributed to Homo, 3 of them coming from Swartkrans member 1 (SK 27, SK 847, and SKX 21204) and 1 from Sterkfontein (Sts 9). Three other specimens from Sterkfontein (StW 80 and 81, SE 1508, and StW 669) approximate the Homo condition in terms of overall enamel-dentine junction shape, but retain Australopithecus-like dental traits, and their generic status remains unclear. The other specimens, including SK 15, present a dominant australopith dental signature. In light of these results, previous dietary and ecological interpretations can be reevaluated, showing that the geochemical signal of one tooth from Kromdraai (KB 5223) and two from Swartkrans (SK 96 and SKX 268) is consistent with that of australopiths.

Accessory cusp expression at the enamel-dentine junction of hominin mandibular molars.

Studies of hominin dental morphology frequently consider accessory cusps on the lower molars, in particular those on the distal margin of the tooth (C6 or distal accessory cusp) and the lingual margin of the tooth (C7 or lingual accessory cusp). They are often utilized in studies of hominin systematics, where their presence or absence is assessed at the outer enamel surface (OES). However, studies of the enamel-dentine junction (EDJ) suggest these traits may be more variable in development, morphology and position than previously thought. Building on these studies, we outline a scoring procedure for the EDJ expression of these accessory cusps that considers the relationship between these accessory cusps and the surrounding primary cusps. We apply this scoring system to a sample of Plio-Pleistocene hominin mandibular molars of Paranthropus robustus, Paranthropus boisei, Australopithecus afarensis, Australopithecus africanus, Homo sp., Homo habilis and Homo erectus from Africa and Asia (n = 132). We find that there are taxon-specific patterns in accessory cusp expression at the EDJ that are consistent with previous findings at the OES. For example, P. robustus M1s and M2s very often have a distal accessory cusp but no lingual accessory cusp, while H. habilis M1s and M2s show the opposite pattern. The EDJ also reveals a number of complicating factors; some apparent accessory cusps at the enamel surface are represented at the EDJ only by shouldering on the ridges associated with the main cusps, while other accessory cusps appear to have little or no EDJ expression at all. We also discuss the presence of double and triple accessory cusps, including the presence of a double lingual accessory cusp on the distal ridge of the metaconid in the type specimen of H. habilis (OH 7-M1) that is not clear at the OES due to occlusal wear. Overall, our observations, as well as our understanding of the developmental underpinnings of cusp patterning, suggest that we should be cautious in our comparisons of accessory cusps for taxonomic interpretations.

The morphology of the Late Pleistocene hominin remains from the site of La Cotte de St Brelade, Jersey (Channel Islands).

Thirteen permanent fully erupted teeth were excavated at the Paleolithic site of La Cotte de St Brelade in Jersey in 1910 and 1911. These were all found in the same location, on a ledge behind a hearth in a Mousterian occupation level. They were originally identified as being Neanderthal. A fragment of occipital bone was found in a separate locality in a later season. Recent dating of adjacent sediments gives a probable age of <48 ka. The purpose of this article is to provide an updated description of the morphology of this material and consider its likely taxonomic assignment from comparison with Neanderthal and Homo sapiens samples. One of the original teeth has been lost, and we identify one as nonhominin. At least two adult individuals are represented. Cervix shape and the absence of common Neanderthal traits in several teeth suggest affinities with H. sapiens in both individuals, while crown and root dimensions and root morphology of all the teeth are entirely consistent with a Neanderthal attribution, pointing toward a possible shared Neanderthal and H. sapiens ancestry (the likely date of this material corresponds with the time in which both Neanderthals and H. sapiens were present in Europe). The occipital fragment is stratigraphically more recent and does not exhibit any diagnostic Neanderthal features.

Distinct mandibular premolar crown morphology in Homo naledi and its implications for the evolution of Homo species in southern Africa.

Homo naledi displays a combination of features across the skeleton not found in any other hominin taxon, which has hindered attempts to determine its placement within the hominin clade. Using geometric morphometrics, we assess the morphology of the mandibular premolars of the species at the enamel-dentine junction (EDJ). Comparing with specimens of Paranthropus, Australopithecus and Homo (n = 97), we find that the H. naledi premolars from the Dinaledi chamber consistently display a suite of traits (e.g., tall crown, well-developed P3 and P4 metaconid, strongly developed P3 mesial marginal ridge, and a P3 > P4 size relationship) that distinguish them from known hominin groups. Premolars from a second locality, the Lesedi Chamber, are consistent with this morphology. We also find that two specimens from South Africa, SK 96 (usually attributed to Paranthropus) and Stw 80 (Homo sp.), show similarities to the species, and we discuss a potential evolutionary link between H. naledi and hominins from Sterkfontein and Swartkrans.

Biologically important artificial light at night on the seafloor.

Accelerating coastal development is increasing the exposure of marine ecosystems to nighttime light pollution, but is anthropogenic light reaching the seafloor in sufficient quantities to have ecological impacts? Using a combination of mapping, and radiative transfer modelling utilising in situ measurements of optical seawater properties, we quantified artificial light exposure at the sea surface, beneath the sea surface, and at the sea floor of an urbanised temperate estuary bordered by an LED lit city. Up to 76% of the three-dimensional seafloor area was exposed to biologically important light pollution. Exposure to green wavelengths was highest, while exposure to red wavelengths was nominal. We conclude that light pollution from coastal cities is likely having deleterious impacts on seafloor ecosystems which provide vital ecosystem services. A comprehensive understanding of these impacts is urgently needed.

Cannulation of the subclavian vein using real-time ultrasound guidance.

Cannulation of the subclavian vein has many advantages when compared to other anatomical sites for central venous access. Difficulty in its ultrasonic visualisation, and the perceived consequent 'higher' complication rate, mean that this approach has fallen out of favour. This barrier, however, may now have disappeared. In this article, we discuss the indications, contraindications and complications associated with subclavian vein cannulation, and present an ultrasound-guided approach to infraclavicular subclavian cannulation.

Observational study of the microcirculation in patients with liver cirrhosis.

BACKGROUND AND AIM: Liver cirrhosis is associated with widespread microcirculatory dysfunction and hemodynamic derangement, which may play a role in the pathogenesis of multiple organ failure. Little is known, however, about the progression of microvascular alterations as the severity of liver disease worsens. Therefore, our aim is to quantify the peripheral systemic microcirculatory changes associated with increasing severity of liver cirrhosis. METHODS: Forty patients with liver cirrhosis were studied and divided into groups based on Child-Pugh classes A (n = 9), B (n = 18), and C (n = 13) for comparison. Incident dark field imaging was used to evaluate the sublingual microcirculation and near-infrared spectroscopy at the thenar eminence to assess microvascular reactivity and function. RESULTS: There was no difference in microcirculatory flow index (P = 0.655), heterogeneity index (P = 0.702), or vessel density (P = 0.923) between the different Child-Pugh groups. Microvascular reactivity did not change as the severity of liver disease worsened. CONCLUSIONS: This study showed no association between peripheral systemic microcirculatory alterations and the severity of liver disease. Further research with larger study cohorts are needed to clarify the relationship between microcirculatory abnormalities and disease progression and to establish if the peripheral microcirculation is affected by the pathophysiology of worsening cirrhosis.

Endostructural morphology in hominoid mandibular third premolars: Discrete traits at the enamel-dentine junction.

The mandibular third premolar (P3) exhibits substantial differences in size and shape among hominoid taxa, and displays a number of discrete traits that have proven to be useful in studies of hominin taxonomy and phylogeny. Discrete traits at the enamel-dentine junction (EDJ) can be accurately assessed on moderately worn specimens, and often appear sharper than at the outer-enamel surface (OES). Here we use microtomography to image the P3 EDJ of a broad sample of extant apes, extinct hominins and modern humans (n = 100). We present typologies for three important premolar discrete traits at the EDJ (transverse crest, marginal ridge and buccal grooves), and score trait frequencies within our sample. We find that the transverse crest is variable in extant apes, while the majority of hominins display a transverse crest which runs directly between the two major premolar cusps. Some Neanderthals display a unique form in which the transverse crest fails to reach the protoconid. We find that mesial marginal ridge discontinuity is common in Australopithecus anamensis and Australopithecus afarensis while continuous marginal ridges largely characterize Australopithecus africanus and Paranthropus. Interrupted mesial and distal marginal ridges are again seen in Homo sapiens and Neanderthals. Premolar buccal grooves, previously identified at the OES as important for hominin systematics, are again found to show a number of taxon-specific patterns at the EDJ, including a clear difference between Australopithecus and Paranthropus specimens. However, their appearance may be dependent on the morphology of other parts of the crown such as the protoconid crest, and the presence of accessory dentine horns. Finally, we discuss rare variations in the form of dentine horns that underlie premolar cusps, and their potential homology to similar morphologies in other tooth positions.