The time course of blood lactate levels could be helpful to assess a patient's response to therapy. Although the focus of published studies has been largely on septic patients, many other studies ...have reported serial blood lactate levels in different groups of acutely ill patients.
We performed a systematic search of PubMed, Science Direct, and Embase until the end of February 2016 plus reference lists of relevant publications. We selected all observational and interventional studies that evaluated the capacity of serial blood lactate concentrations to predict outcome. There was no restriction based on language. We excluded studies in pediatric populations, experimental studies, and studies that did not report changes in lactate values or all-cause mortality rates. We separated studies according to the type of patients included. We collected data on the number of patients, timing of lactate measurements, minimum lactate level needed for inclusion if present, and suggested time interval for predictive use.
A total of 96 studies met our criteria: 14 in general ICU populations, five in general surgical ICU populations, five in patients post cardiac surgery, 14 in trauma patients, 39 in patients with sepsis, four in patients with cardiogenic shock, eight in patients after cardiac arrest, three in patients with respiratory failure, and four in other conditions. A decrease in lactate levels over time was consistently associated with lower mortality rates in all subgroups of patients. Most studies reported changes over 6, 12 or 24 hrs, fewer used shorter time intervals. Lactate kinetics did not appear very different in patients with sepsis and other types of patients. A few studies suggested that therapy could be guided by these measurements.
The observation of a better outcome associated with decreasing blood lactate concentrations was consistent throughout the clinical studies, and was not limited to septic patients. In all groups, the changes are relatively slow, so that lactate measurements every 1-2 hrs are probably sufficient in most acute conditions. The value of lactate kinetics appears to be valid regardless of the initial value.
Abstract
South America is home to one of the most culturally diverse present-day native populations. However, the dispersion pattern, genetic substructure, and demographic complexity within South ...America are still poorly understood. Based on genome-wide data of 58 native populations, we provide a comprehensive scenario of South American indigenous groups considering the genomic, environmental, and linguistic data. Clear patterns of genetic structure were inferred among the South American natives, presenting at least four primary genetic clusters in the Amazonian and savanna regions and three clusters in the Andes and Pacific coast. We detected a cline of genetic variation along a west-east axis, contradicting a hard Andes-Amazon divide. This longitudinal genetic variation seemed to have been shaped by both serial population bottlenecks and isolation by distance. Results indicated that present-day South American substructures recapitulate ancient macroregional ancestries and western Amazonia groups show genetic evidence of cultural exchanges that led to language replacement in precontact times. Finally, demographic inferences pointed to a higher resilience of the western South American groups regarding population collapses caused by the European invasion and indicated precontact population reductions and demic expansions in South America.
Protein arginine methyltransferases (PRMTs) are a family of enzymes involved in gene regulation and protein/histone modifications. PRMT8 is primarily expressed in the central nervous system, ...specifically within the cellular membrane and synaptic vesicles. Recently, PRMT8 has been described to play key roles in neuronal signaling such as a regulator of dendritic arborization, synaptic function and maturation, and neuronal differentiation and plasticity. Here, we examined the role of PRMT8 in response to hypoxia-induced stress in brain metabolism. Our results from liquid chromatography mass spectrometry, mitochondrial oxygen consumption rate, and protein analyses indicate that PRMT8(-/-) knockout mice presented with altered membrane phospholipid composition, decreased mitochondrial stress capacity, and increased neuroinflammatory markers, such as tumor necrosis factor alpha and ionized calcium binding adaptor molecule 1 (Iba1, a specific marker for microglia/macrophage activation) after hypoxic stress. Furthermore, adenovirus-based overexpression of PRMT8 reversed the changes in membrane phospholipid composition, mitochondrial stress capacity, and neuroinflammatory markers. Together, our findings establish PRMT8 as an important regulatory component of membrane phospholipid composition, short-term memory function, mitochondrial function, and neuroinflammation in response to hypoxic stress.
We delve into the first principles of quantum field theory to prove that the so-called spin-1/2 “bosons” and the fermions with mass dimension 1, including ELKO, cannot represent physical particle ...states with spin 1/2. Specifically, we first demonstrate that both aforementioned fields are not invariant under rotational symmetry, which implies that the particles created for these fields are not eigenstates of the spin operator in the
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representation of the Lorentz group, nor is it possible to construct a Hamiltonian density scalar under the rotational group from them. Furthermore, following Weinberg’s approach to local causal fields, we prove that regardless of any discrete symmetry or adjoint structure, the relativistic fields in the
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representation satisfy the Fermi-Dirac statistics in complete agreement with the well-established spin-statistics theorem and experimental results.
•We previously discovered palmitic acid methyl ester (a C16:0 saturated fatty acid) is a novel and potent vasodilator.•We investigated the therapeutic potential of palmitic acid methyl ester against ...cardiac arrest-induced brain injury and neurological deficits.•We found that post-treatment of palmitic acid methyl ester after cardiac arrest can enhance cerebral blood flow and neuronal cell survival ultimately improving functional learning/memory.
We previously discovered that palmitic acid methyl ester (PAME) is a potent vasodilator first identified and released from the superior cervical ganglion and remain understudied. Thus, we investigated PAME's role in modulating cerebral blood flow (CBF) and neuroprotection after 6 min of cardiac arrest (model of global cerebral ischemia). Our results suggest that PAME can enhance CBF under normal physiological conditions, while administration of PAME (0.02 mg/kg) immediately after cardiopulmonary resuscitation can also enhance CBF in vivo. Additionally, functional learning and spatial memory assessments (via T-maze) 3 days after asphyxial cardiac arrest (ACA) suggest that PAME-treated rats have improved learning and memory recovery versus ACA alone. Furthermore, improved neuronal survival in the CA1 region of the hippocampus were observed in PAME-treated, ACA-induced rats. Altogether, our findings suggest that PAME can enhance CBF, alleviate neuronal cell death, and promote functional outcomes in the presence of ACA.
Objetivo: Esse estudo tem como objetivo mensurar o impacto da profilaxia antibiótica combinada nas taxas de Infecção de Sítio Cirúrgico (ISC) de pacientes submetidos à Redução Aberta de Fratura (RAF) ...e avaliar o impacto dessa medida no perfil de resistência antimicrobiana dos pacientes com diagnóstico de Infecção Relacionadas a Fraturas (IRF). Métodos: Estudo de coorte retrospectivo, unicêntrico, realizado em um hospital universitário, utilizando banco de dados do Serviço de Controle de Infecção Hospitalar (SCIH) de pacientes submetidos a RAF no período de janeiro a dezembro de 2022. Foram excluídos da análise pacientes com fratura exposta e menores de 18 anos. IRF foi definido de acordo com os critérios de ISC do Centers for Disease Control and Prevention. Paciente de elevado risco para ISC foi definido como índice de comorbidades de Charlson maior ou igual a cinco. Os pacientes foram seguidos por três meses do pós-operatório. De janeiro a março de 2022 foi utilizado cefalotina como profilaxia cirúrgica (grupo pré-intervenção) e de abril a dezembro o grupo intervenção utilizou cefuroxima + gentamicina para os pacientes de risco elevado ou cefuroxima em monoterapia para os demais. Resultados: No total, 1.901 pacientes foram incluídos no estudo, 864 pré-intervenção e 1.037 no grupo intervenção. As taxas de ISC do grupo pré vs. intervenção foram 6,9% (72) e 2,8% (24), respectivamente (RR=0,4; 95% IC 0,22‒0,58; p=0,000). No ano de 2022, os microrganismos mais frequentemente identificados na FRI foram S. aureus (28%), S. coagulase negativo (14%), Klebsiella aerogenes (13%) e Pseudomonas aeruginosa (9%). A profilaxia antibiótica estendida aplicada para pacientes com elevado risco de ISC não alterou a epidemiologia microbiana da IRF, enquanto não aumentou as taxas de microrganismos Multirresistentes (MDR) (p=0,784). Paralelamente, houve aumento na sensibilidade à oxacilina para Gram-positivos (pré-40% vs. 67%) e aumento na sensibilidade aos carbapenêmicos aos Gram-negativos (pré-82% e pós-100%). Conclusão: A profilaxia antibiótica estendida aplicada para um grupo selecionado de pacientes com maior risco de desenvolverem IRF não elevou as taxas de ISC por microrganismos multirresistentes, porém, contribuiu para redução significativa das taxas de ISC. Estratégias individualizadas de prevenção de ISC e mais estudos multicêntricos, especialmente para infecções associadas a biofilme são necessárias.
We present the detections of 18 solar flares detected in high-energy gamma-rays (above 100 MeV) with the Fermi Large Area Telescope (LAT) during its first 4 yr of operation. This work suggests that ...particle acceleration up to very high energies in solar flares is more common than previously thought, occurring even in modest flares, and for longer durations. We then describe the detailed temporal, spatial, and spectral characteristics of the first two long-lasting events; the 2011 March 7 flare, a moderate (M3.7) impulsive flare followed by slowly varying gamma-ray emission over 13 hr, and the 2011 June 7 M2.5 flare. We compare the Fermi LAT data with X-ray and proton data measurements from GOES and RHESSI. We argue that the gamma-rays are more likely produced through pion decay than electron bremsstrahlung, and we find that flic energy spectrum of the proton distribution softens during the extended emission of the 2011 March 7 flare.
Cerebral ischemia is one of the leading causes of morbidity and mortality worldwide. Although stroke (a form of cerebral ischemia)-related costs are expected to reach 240.67 billion dollars by 2030, ...options for treatment against cerebral ischemia/stroke are limited. All therapies except anti-thrombolytics (i.e., tissue plasminogen activator) and hypothermia have failed to reduce neuronal injury, neurological deficits, and mortality rates following cerebral ischemia, which suggests that development of novel therapies against stroke/cerebral ischemia are urgently needed. Here, we discuss the possible mechanism(s) underlying cerebral ischemia-induced brain injury, as well as current and future novel therapies (i.e., growth factors, nicotinamide adenine dinucleotide, melatonin, resveratrol, protein kinase C isozymes, pifithrin, hypothermia, fatty acids, sympathoplegic drugs, and stem cells) as it relates to cerebral ischemia.
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