Another case of use of the ProSealTM laryngeal mask airway in a difficult obstetric airway

Editor—We read with interest the case report by Awan andcolleagues,¹ describing successful use of the ProSeal^TM laryngealmask airway (PLMA) after failed tracheal intubation in a parturientundergoing Caesarean section. After securing the airway withthe PLMA, the authors removed it and tried again to performtracheal intubation. We think that the PLMA can be left in placeand used as a definitive airway after failed intubation in Caesareansection. We report another case where the PLMA     

Photochemistry of aqueous pyruvic acid

The study of organic chemistry in atmospheric aerosols and cloud formation is of interest in predictions of air quality and climate change. It is now known that aqueous phase chemistry is important in the formation of secondary organic aerosols. Here, the photoreactivity of pyruvic acid (PA; CH₃COCOOH) is investigated in aqueous environments characteristic of atmospheric aerosols. PA is currently used as a proxy for α-dicarbonyls in atmospheric models and is abundant in both the gas phase and the aqueous phase (atmospheric aerosols, fog, and clouds) in the atmosphere. The photoreactivity of PA in these phases, however, is very different, thus prompting the need for a mechanistic understanding of its reactivity in different environments. Although the decarboxylation of aqueous phase PA through UV excitation has been studied for many years, its mechanism and products remain controversial. In this work, photolysis of aqueous PA is shown to produce acetoin (CH₃CHOHCOCH₃), lactic acid (CH₃CHOHCOOH), acetic acid (CH₃COOH), and oligomers, illustrating the progression from a three-carbon molecule to four-carbon and even six-carbon molecules through direct photolysis. These products are detected using vibrational and electronic spectroscopy, NMR, and MS, and a reaction mechanism is presented accounting for all products detected. The relevance of sunlight-initiated PA chemistry in aqueous environments is then discussed in the context of processes occurring on atmospheric aerosols.     

Association of VEGFA,TIMP-3, and IL-6 gene polymorphisms with predisposition to optic neuritis and optic neuritis with multiple sclerosis

ABSTRACT

Background

The etiology of the inflammatory ON is multifactorial. Much attention is paid to the inflammatory and immune processes that are likely to contribute to the demyelination and MS development. IL-6, VEGFA, and TIMP-3 genes are thought to be involved in the inflammatory processes and manifestation of CNS demyelination, so we aimed to determine the relationship between VEGFA rs1413711, TIMP-3 rs9621532, IL-6 rs1800796 gene polymorphisms and ON, and ON with MS.     

Functional outcomes of the failed plate fixation in distal tibial fractures salvaged by hexapod external fixator

European Journal of Orthopaedic Surgery & Traumatology - The purpose of this study was to evaluate the clinical and functional outcomes of failed plate fixation in distal tibia fractures...     

Swimming induced pulmonary oedema in athletes – a systematic review and best evidence synthesis

Background

Swimming induced pulmonary oedema is an uncommon occurrence and usually presents during strenuous distance swimming in cold water. The prevalence is most likely underreported and the underlying mechanisms are controversial. The purpose of this study was to summarize the evidence with regards to prevalence, pathophysiology and treatment of swimming induced pulmonary oedema in endurance athletes.

Methods

Medline, Embase, Scopus and Google Scholar were searched and level I-IV from 1970 to 2017 were included. For clinical studies, only publications reporting on swimming-induced pulmonary oedema were considered. Risk of bias was assessed with the ROBINS-I tool, and the quality of evidence was assessed with the Cochrane GRADE system. For data synthesis and analysis, a best evidence synthesis was used.

Results

A total of 29 studies were included (174 athletes). The most common symptom was cough, dyspnoea, froth and haemoptysis. The risk of bias for the clinical studies included 13 with moderate risk, 3 with serious, and 4 with critical. Four of the pathophysiology studies had a moderate risk, 3 a serious risk, and 1 a critical risk of bias. A best evidence analysis demonstrated a strong association between cold water immersion and in increases of CVP (central venous pressure), MPAP (mean pulmonary arterial pressure), PVR (peripheral vascular resistance) and PAWP (pulmonary arterial wedge pressure) resulting in interstitial asymptomatic oedema.

Conclusion

The results of this study suggest a moderate association between water temperature and the prevalence of SIPE. The presence of the clinical symptoms cough, dyspnoea, froth and haemoptysis are strongly suggestive of SIPE during or immediately following swimming. There is only limited evidence to suggest that there are pre-existing risk factors leading to SIPE with exposure to strenuous physical activity during swimming. There is strong evidence that sudden deaths of triathletes are often associated with cardiac abnormalities.

     

In situ observation of peptide bond formation at the water–air interface

We report unambiguous spectroscopic evidence of peptide bond formation at the air–water interface, yielding a possible mechanism providing insight into the formation of modern ribosomal peptide bonds, and a means for the emergence of peptides on early Earth. Protein synthesis in aqueous environments, facilitated by sequential amino acid condensation forming peptides, is a ubiquitous process in modern biology, and a fundamental reaction necessary in prebiotic chemistry. Such reactions, however, are condensation reactions, requiring the elimination of a water molecule for every peptide bond formed, and are thus unfavorable in aqueous environments both from a thermodynamic and kinetic point of view. We use the hydrophobic environment of the air–water interface as a favorable venue for peptide bond synthesis, and demonstrate the occurrence of this chemistry with in situ techniques using Langmuir-trough methods and infrared reflection absorption spectroscopy. Leucine ethyl ester (a small amino acid ester) first partitions to the water surface, then coordinates with Cu²⁺ ions at the interface, and subsequently undergoes a condensation reaction selectively forming peptide bonds at the air–water interface.Protein synthesis (condensation of amino acids through sequential peptide bond formation) is a fundamental and ubiquitous reaction in biology. Aqueous media are the required environments in which this chemistry takes place; however, protein synthesis is unfavorable in aqueous solution. In modern biology, the condensation reactions necessary in the formation of peptide bonds are facilitated catalytically by the large subunit of the ribosome. The mechanism of this catalyzed reaction originally proposed by Nissen et al. in 2000 (1) involved favorable orientation of peptide precursors, acid-base catalysis and transition-state stabilization, and the altered pK_a of the functional groups of the precursors caused by the reaction environment provided by the active site; such pK_a shifts had previously been seen in the active sites of other proteins (2). Since then, the original mechanism has been contested (3, 4). The acknowledged mechanistic function of the ribosome’s active site is its ability to bring the precursors in close proximity and orient them for reaction, with further mechanistic details remaining unresolved (4). Studies of peptide bond formation in the absence of modern biological machinery can give insight into the mechanism employed by the ribosome’s active site, as well as yield important information in the prebiotic route to the first peptides in the origin of life. The formation of a peptide bond (reaction R1 shown below) is a condensation reaction, eliminating a water molecule for each peptide bond formed, and thus faces both thermodynamic and kinetic constraints in bulk aqueous solution (5).5, 6). Amino acid monomers have the added kinetic disadvantage of existing primarily as zwitterions at environmentally and physiologically relevant pH values in bulk aqueous solution (5, 7). Insightful experiments have been performed, yielding peptide bonds in anhydrous solvents with amino acid ester starting materials and copper(II) ion catalysis (8, 9). Transition metal ions are thought to have been components of the early ocean (10), with one source being the heavy meteoritic and cometary bombardment experienced by the early Earth, but the anhydrous solvents used in these studies are neither physiologically relevant nor likely to have been present on early Earth. The same mechanism was attempted in aqueous solution, but no peptide formation was detected (9). Polymer formation in aqueous environments would most likely have been necessary on early Earth because the liquid ocean would have been the reservoir of amino acid precursors needed for protein synthesis. In this work, the air–water interface is utilized as the auspicious environment for peptide bond formation, coupling the water surface with the bulk water reservoir of monomers. In situ surface-sensitive techniques are used here to observe the condensation reaction of a model system composed of a small, water-soluble amino acid ester (leucine ethyl ester) through Cu²⁺ coordination.Air–water interfaces are found now, as on prebiotic Earth, at the surfaces of lakes, oceans, and atmospheric aerosols. The air–water interface (atmospheric aerosols in particular) has previously been proposed to be important in prebiotic chemistry (11–14) because it provides a unique environment for chemistry through its ability to concentrate and align biochemical precursors and to alter the state of ionization of surface species (15–19). Contemporary marine aerosols have been found to contain the amino acid precursors necessary for peptide bond chemistry (20), enabling the possibility for their use in such reactions. Further, the fluctuating conditions experienced by aerosols throughout their atmospheric lifetime, including evaporation of water, coagulation, and possibly reentry into the ocean, would naturally provide the compression of the surface layer shown in this work to be necessary for Cu²⁺ coordination leading to peptide bond chemistry (12).In addition, the unfavorable equilibrium constant for peptide bond formation in bulk aqueous solution is shifted when the molecules experience a water-restricted reaction environment at the water surface. Although the exact surface pH of water is debated (21–23), the surface is known to alter the pK_a of surface-active molecules toward their neutral form (24, 25), which aids in the promotion of peptide bond chemistry at the interface by reducing zwitterion formation and alleviating the kinetic constraint on peptide bond synthesis. The air–water interface has been reported in the literature to have a catalytic role in peptide bond formation (26–29) using synthetic long-chain amino acid esters that are anchored to the surface by the polar groups attached to their 18-carbon-long hydrocarbon tails, thus forced to reside solely at the surface of the water. Reaction amongst the surface monomers was promoted in these studies (27–29) through surface compression, and supported by subsequent collection, drying, and analysis of the surface products. In the work presented here, infrared reflection absorption spectroscopy (IRRAS) and Langmuir trough methods were used to observe, in situ, complex formation with a metal cation followed by condensation chemistry leading to peptide bond formation occurring at the air–water interface. The observation of such condensation reactions in situ at the interface and with such a small activation group (an ethyl ester) on the starting amino acid precursor in an aqueous environment is unique.     

HIV clades B and C are associated with reduced brain volumetrics

The human immunodeficiency virus (HIV) has multiple genetic clades with varying prevalence throughout the world. Both HIV clade C (HIV-C) and HIV clade B (HIV-B) can cause cognitive impairment, but it is unclear if these clades are characterized by similar patterns of brain dysfunction. We examined brain volumetrics and neuropsychological performance among highly active antiretroviral therapy (HAART)-naïve HIV-B and HIV-C participants. Thirty-four HAART-naïve HIV-infected (HIV+) participants [17 HIV-B (USA); 17 HIV-C (South Africa)] and 34 age- and education-matched HIV-uninfected (HIV?) participants were evaluated. All participants underwent similar laboratory, neuropsychological, and neuroimaging studies. Brain volume measures were assessed within the caudate, putamen, amygdala, thalamus, hippocampus, corpus callosum, and cortical (gray and white matter) structures. A linear model that included HIV status, region, and their interaction assessed the effects of the virus on brain volumetrics. HIV? and HIV+ individuals were similar in age. On laboratory examination, HIV-C participants had lower CD4 cell counts and higher plasma HIV viral loads than HIV-B individuals. In general, HIV+ participants performed significantly worse on neuropsychological measures of processing speed and memory and had significantly smaller relative volumetrics within the thalamus, hippocampus, corpus callosum, and cortical gray and white matter compared to the respective HIV? controls. Both HIV-B and HIV-C are associated with similar volumetric declines when compared to matched HIV? controls. HIV-B and HIV-C were associated with significant reductions in brain volumetrics and poorer neuropsychological performance; however, no specific effect of HIV clade subtype was evident. These findings suggest that HIV-B and HIV-C both detrimentally affect brain integrity.     

Approaches to identifying appropriate medication adherence assessments for HIV infected individuals with comorbid bipolar disorder

Assessing medication adherence in already difficult-to-treat HIV-infected subpopulations presents a unique challenge. The objective of this study was to compare different approaches to assessing medication adherence: (1) electronic medication monitoring, (2) standardized self-report questionnaire, and (3) self-report visual analogue scale, and to determine whether antiretroviral therapy (ART) adherence measures differed for HIV-infected persons with bipolar disorder (HIV+?/BD+) as compared to HIV-infected persons without bipolar disorder (HIV+?/BD-). ART adherence was assessed for 74 HIV-positive participants using the Medication Event Monitoring System (MEMS), AIDS Clinical Trials Group (ACTG) adherence questionnaire, and visual analogue scale (VAS). Participants were classified as adherent or nonadherent on each measure by previously validated cutscores. Correlations and logistic regressions were used to examine associations between adherence measures and demographic and clinical variables. In the HIV+?/BD- group, significant correlations existed between each self-report measure and the MEMS. Males comprised 81% of the study population. Participants averaged 44 years of age and 13 years of education. No significant correlations were found among adherence measures in the HIV+?/BD+ group. Among participants reporting adherence on either self-report measure but classified as nonadherent based on MEMS, 94% had a diagnosis of bipolar disorder. Bipolar disorder was a significant predictor of adherence classification discordance among self-report measures. Our findings suggest that it remains difficult to assess ART adherence among HIV-positive individuals with bipolar disorder. Combined approaches of self-report and objective measures may be the best way to estimate adherence, and may provide the best basis for interventions designed to improve adherence in difficult-to-treat populations.