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Background Reflex and spontaneous movements are not uncommon in brain death patients. However, most studies have been conducted in adults, while reports in infants and children are rare. Thus, we aimed to evaluate the frequency and characteristics of these movements in pediatric patients declared as brain death. Methods Records of pediatric patients who were diagnosed as brain death from 15 hospitals in the Yeongnam region, South Korea, between January 2013 and September 2016 were analyzed. All body movements in patients who met the criteria for brain death as established by the Korea Medical Association were assessed by medical doctors and trained organ transplant coordinators. The frequency and characteristics of these movements were identified. Additionally, the demographic and clinical factors of the brain death patients with and without these movements were compared. Results A total of 31 patients who met the criteria for brain death were enrolled. Seven patients (22.6%) showed either reflex or spontaneous movements; six of them (85.7%) showed reflex movements only, and one patient (14.3%) showed both types of movements. The most common types of reflex movements were the flexor/extensor plantar response and isolated finger jerk. Four of seven patients (57.1%) showed a single movement pattern, while three (42.9%) showed two different movement patterns. Conclusion It is essential for physicians who perform pediatric brain death examinations to recognize the frequency and characteristics of reflex and spontaneous movements, and this article may help in the accurate and prompt diagnosis of brain death.

Background and purpose The increased demand for donor organs has made it crucial to keep the organs of patients with impending brain death (PWIBDs) suitable for transplantation during the process of determining brain death. This study aimed to identify the time taken to determine brain death (TT-BD) in PWIBDs and the associated influencing factors. Methods This study analyzed data collected by the Korean Organ Donation Agency from 15 hospitals in the Yeongnam region of South Korea. There were 414 PWIBDs eligible for inclusion in this study. The data consisted of the TT-BD for PWIBDs and the potential variables influencing the TT-BD. Results The mean age of the 414 PWIBDs was 48.9 years, and 120 of them were female (29.0%). The mean TT-BD was 8.5 days. The presence of spontaneous movements (SMs) and craniotomy significantly affected the TT-BD. The mean TT-BDs were 13.9 and 8.2 days in the PWIBDs with and without SMs, respectively, and 9.8 and 8.0 days in the PWIBDs with and without craniotomy, respectively. Conclusions The SMs in PWIBDs and a craniotomy performed immediately before starting the process of determining brain death seem to be related to lengthening the TT-BD.

Background Brain death is a clinical diagnosis that implies irreversible loss of function of the entire brain, including the brainstem and both hemispheres. Based on previous reports, it is not rare for reflex and spontaneous movements to occur in patients during the process of determining brain death. However, reports of the frequency and common types of these movements vary from study to study. Thus, we evaluated adult patients with impending brain death in Korea to determine the frequency and characteristics of reflex and spontaneous movements. Methods Brain dead patients who were admitted to 15 hospitals in the Yeongnam region (Southeast) of Korea were recruited prospectively from January 2013 to September 2016. All patients met the criteria for brain death as established by the Korea Medical Association. All body movements occurred during the process of diagnosing brain death and were assessed by physicians and trained organ transplant coordinators. The frequency and characteristics of these movements were identified and the demographic and clinical factors of impending brain dead patients with and without these movements were compared. Results A total of 436 patients who met the criteria for brain death were enrolled during the study period. Of these patients, 74 (17.0%) exhibited either reflex or spontaneous movements. Of this subset, 45 (60.8%) exhibited reflex movements only, 18 (24.3%) exhibited spontaneous movements only, and 11 (14.9%) exhibited both reflex and spontaneous movements. The most common reflex movements were the flexor/extensor plantar response and spinal myoclonus. Of the 74 patients, 52 (70.3%) exhibited one movement of the same pattern and 22 (29.7%) exhibited two or more different movement patterns. In addition, 45 (60.8%) exhibited these movements only on a limited area of the body with the leg being most common (n = 26, 57.8%). Patients with hypoxic brain damage and a higher systolic blood pressure exhibited significantly more reflex or spontaneous movements. Conclusion Movements associated with brain dead patients are not rare and thus an awareness of these movements is important to brain death diagnosis. Physicians who perform brain death examinations should understand the frequency and characteristics of these movements to reduce delays in determining brain death., Graphical Abstract

Background: The number of deceased donors that have increased annually until 2016 has started to decline in the last three years. This study therefore intends to analyze the trend of potential brain death reported to Korea Organ Donation Agency (KODA) and use the analysis results as a basic data for the activation of organ donation. Methods: A comparative analysis was performed for the first period (P1: 2014 to 2016) where the number of donations continued to increase and the second period (P2: 2017 to 2019) that showed decline in donations compared to 2016. Results: The cases of potential brain death reported to KODA was 5,548 in P1 and 7,126 in P2, a 28.4% increase from the previous period. Among these, the cases of medically suitable for organ donation increased by 36.5%, from 4,053 in P1 to 5,534 in P2. Decreased the consent rate from 52.9% in P1 to 37.2% in P2. The discontinuation of donation process even after family consent increased by 17.6% (from 74 cases in P1 to 87 cases in P2), mostly due to legal issues and death before the judgment of brain death. Conclusions: The decrease in families’ consent for organ donation turned out to be the biggest cause of declining donation. The major reasons for refusal to donation such as can be attributed to the lack of understanding of the medical state of brain death, a negative image of sharing and donation that is pervasive in Korean society, and the distrust between community members. Therefore, there is a need for education and promotion at a national level to enhance the awareness of the value of life and to en courage the public to practice the value of sharing.

Background: According to the statistics of the National Agency for Management of Life-Sustaining Treatment, 85,000 end of life care patients have been withdrawn life sustaining treatment over two years since the implementation of law in February 2018. However, according to annual report of Korea Organ Donation Agency (KODA), there were a considerable number of patients who requested to withdraw life sustaining treatment among the referred potential brain death to the call center of KODA. Their family consent rate was lower than the group that didn’t mentioned about interrupting the end of life care. Methods: The study was designed using the referred cases of potential brain death to KODA during 2018 and 2019. Demographic findings of requesting withdrawn life sustaining treatment among the referred cases and their result of donation progress in each step were evaluated. Results: Within the research period, there were a total of 4,910 cases (2,426 in 2018, 2,484 in 2019) of brain death, and among them, 569 (193 in 2018 and 376 in 2019) cases requested to withdraw life sustaining treatment. This means a 94.8% increase in requesting family compared to the previous year. In terms of gender, 63% of the cases were male, and the most common age group was the fifties (23.4%). Among 569 requested donors, 475 (83.5%) were appropriate for organ donation, out of which, 394 (82.9%) families were interviewed about organ donation, and accepted organ donation in 45 cases (9.5%). Only 29 cases (6.1%) were succeeded in organ procurement. Conclusions: It is estimated that there will be more families who wish to withdraw life sustaining treatment among potential brain death referred to KODA for organ donation in the future. Therefore, in order to activate organ donations, we need a system revision about end of life care process, first to the donor coordinator and then explain all the options by that coordinator.

There is no effective treatment for cocaine addiction despite extensive knowledge of the neurobiology of drug addiction. Here we show that a selective aldehyde dehydrogenase-2 (ALDH-2) inhibitor, ALDH2i, suppresses cocaine self-administration in rats and prevents cocaine- or cue-induced reinstatement in a rat model of cocaine relapse-like behavior. We also identify a molecular mechanism by which ALDH-2 inhibition reduces cocaine-seeking behavior: increases in tetrahydropapaveroline (THP) formation due to inhibition of ALDH-2 decrease cocaine-stimulated dopamine production and release in vitro and in vivo. Cocaine increases extracellular dopamine concentration, which activates dopamine D2 autoreceptors to stimulate cAMP-dependent protein kinase A (PKA) and protein kinase C (PKC) in primary ventral tegmental area (VTA) neurons. PKA and PKC phosphorylate and activate tyrosine hydroxylase, further increasing dopamine synthesis in a positive-feedback loop. Monoamine oxidase converts dopamine to 3,4-dihydroxyphenylacetaldehyde (DOPAL), a substrate for ALDH-2. Inhibition of ALDH-2 enables DOPAL to condense with dopamine to form THP in VTA neurons. THP selectively inhibits phosphorylated (activated) tyrosine hydroxylase to reduce dopamine production via negative-feedback signaling. Reducing cocaine- and craving-associated increases in dopamine release seems to account for the effectiveness of ALDH2i in suppressing cocaine-seeking behavior. Selective inhibition of ALDH-2 may have therapeutic potential for treating human cocaine addiction and preventing relapse.

A sensitive, specific, and robust method to simultaneously determine enantiomeric salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, SAL), a potential biomarker implicated in alcohol-related neurotoxicity in a stereoselective manner, and its precursor dopamine (DA) has been developed using simple chemical derivatization and chiral separation coupled with electrospray ionization-tandem mass spectrometry (ESI-MS/MS). SAL enantiomers and DA were converted to stable pentafluorobenzyl (PFB) derivatives directly from aqueous media. Bulky PFB groups introduced into the SAL structure enabled baseline separation of SAL stereoisomers on a chiral column without cumbersome chiral derivatization to unstable SAL diastereomers. Subsequent analysis by ESI-MS/MS with multiple reaction monitoring (MRM) in the presence of deuterium-labeled internal standards allowed specific detection of both derivatives with a wide dynamic range (SAL, 0.5-5000 pg; DA, 0.02-20 ng). The limit of quantitation assayed in the plasma matrix was below 10 pg for each SAL enantiomer and 100 pg for DA. Both coefficient of variance and error for inter- and intraday measurements in the blank plasma were less than 10% for SAL and DA in the concentration range of 10-4000 pg/mL and 0.1-8 ng/mL, respectively. This strategy enabled routine and specific determination of both SAL enantiomers and DA from 0.5 mL of human plasma and cerebrospinal fluid, which has not been possible using existing methodologies.

To maintain an optimum dynamic range, membranes of living systems must have the ability to regulate their translational and vibrational motion in the face of environmental changes that might offset them. This is done through structural modifications of the lipids. Sarcina ventriculi was used as a case study to explore membrane structural reorganizations which allow some organisms to adapt to extreme environmental changes. It is capable of a variety of unusual and dramatic chemical processes including lipid alkyl chain tail-to-tail and lipid head-to-head coupling. There is also interlipid headgroup transfer or shuffling. The tail-to-tail coupling activity is capable of joining foreign (exogenously added) hydrocarbon chains to the native chains. The adaptative processes occur dynamically and instantaneously and render this organism tolerant to low and high pH, moderately high temperatures, the presence of organic solvents, and a wide spectrum of antibiotics at concentrations as high as 200 μg/mL. Chemical a...

The structure of peptidoglycan extracted from the Gram-positive bacterium Sarcina ventriculi grown at pH 3 was characterized by amino acid analysis, mass spectrometry, and two-dimensional NMR spectroscopy. The basic muropeptide subunit consisted of an N -acetylglucosamine- β -1,4- N -acetylmuramic acid disaccharide substituted with an oligopeptide with the sequence Ala- iso Gln-A 2 pm(-Gly)-Ala. The dimeric muropeptide was also characterized as a cross-linked bis-disaccharide-penta-hexapeptide with the structure, GlcNAc-MurNAc-Ala- iso Gln-A 2 pm(-Gly)-Ala → GlcNAc-MurNAc-Ala- iso Gln-A 2 (-Gly)-Ala-Ala. These results are consistent with a structure proposed based on enzymatic degradation and chemical modifications but with no use of spectroscopic information [O. Kandler, D. Claus, and A. Moore, Arch. Mikrobiol. , 82 (1972) 140–146]. The cell wall of this organism is very tightly cross-linked and is much more rigid than that of most other Gram-positive bacteria. There is, however, a large degree of conservation in the general structure compared to peptidoglycan in other bacteria that are not well adaptable to extremes, indicating that the membrane plays a more important role in adaptation.

A new β-1-O-acyl-β-1,2-diglucosyl glycoside has been isolated from the membranes of the gram positive bacterium Sarcina ventriculi. Its levels are regulated by environmental conditions such as pH and temperature. The structure was determined by 2-D-NMR spectroscopy and by mass spectrometry.

DHA (docosahexaenoic acid, C22:6,n−3) has been shown to promote neurite growth and synaptogenesis in embryonic hippocampal neurons, supporting the importance of DHA known for hippocampus-related learning and memory function. In the present study, we demonstrate that DHA metabolism to DEA (N-docosahexaenoylethanolamide) is a significant mechanism for hippocampal neuronal development, contributing to synaptic function. We found that a fatty acid amide hydrolase inhibitor URB597 potentiates DHA-induced neurite growth, synaptogenesis and synaptic protein expression. Active metabolism of DHA to DEA was observed in embryonic day 18 hippocampal neuronal cultures, which was increased further by URB597. Synthetic DEA promoted hippocampal neurite growth and synaptogenesis at substantially lower concentrations in comparison with DHA. DEA-treated neurons increased the expression of synapsins and glutamate receptor subunits and exhibited enhanced glutamatergic synaptic activity, as was the case for DHA. The DEA level in mouse fetal hippocampi was altered according to the maternal dietary supply of n–3 fatty acids, suggesting that DEA formation is a relevant in vivo process responding to the DHA status. In conclusion, DHA metabolism to DEA is a significant biochemical mechanism for neurite growth, synaptogenesis and synaptic protein expression, leading to enhanced glutamatergic synaptic function. The novel DEA-dependent mechanism offers a new molecular insight into hippocampal neurodevelopment and function.

The involvement of morphine-like alkaloids in alcoholism has been extensively studied ever since the formation of dopamine-derived alkaloids, SAL (1-methyl-1,2,3,4-tetrahydro-6,7-dihydroxy-isoquinolines) and tetrahydropapaveroline (THP), was observed in vitro after rat brain homogenate was treated with ethanol or acetaldehyde (Davis and Walsh, 1970; Yamanaka et al., 1970). Subsequent identification of increased in vivo production of SAL in parkinsonian patients on L-DOPA treatment after ethanol ingestion (Sandler et al., 1973) further prompted studies of SAL as a potential biomarker for alcoholism. SAL is formed from dopamine (DA) either by nonenzymatic Pictet-Spengler condensation with acetaldehyde, a metabolite of ethanol, yielding racemic (R/S)-SAL, or with pyruvic acid followed by enzymatic decarboxylation and reduction, producing (R)-SAL. It has been also reported that enantio-selective (R)-SAL can be synthesized from DA and acetaldehyde by (R)-SAL synthase in human brain (Naoi et al., 1996). (R/S)-SAL is present in urine, plasma, cerebrospinal fluid and postmortem brains of both alcoholics and nonalcoholics (Haber et al., 1996; Sjoquist et al., 1982). The SAL is also contained in alcoholic beverages and variety of foods such as cheese, banana, beef, and milk (Duncan et al., 1984; Riggin et al., 1976). Attempts to correlate the SAL levels in biological fluids and brain tissues to ethanol intake or to alcohol addiction behavior have been reported even though the results are controversial. Acute ethanol ingestion by nonalcoholics showed unchanged, decreased, or increased SAL levels in human biological fluids (Adachi et al., 1986; Haber et al., 1996; Sjoquist et al., 1985). A role of SAL in alcohol addiction has been suggested, as SAL infusion into rat brain ventricles promoted alcohol consumption or self-administration (Duncan and Deitrich, 1980; Melchior and Myers, 1977; Rodd et al., 2003). The SAL concentrations in plasma and urine were shown to be elevated in chronic alcoholics in comparison to nonalcoholics (Collins et al., 1979; Faraj et al., 1989; Sjoquist et al., 1981), supporting SAL as a potential clinical marker for alcohol addiction. However, others reported that SAL levels in urine (Feest et al., 1991; Musshoff et al., 1997) or in the postmortem brains (Musshoff et al., 2005; Sjoquist et al., 1983) were not different between alcoholics and controls. These controversial results prompted further studies to evaluate possible stereoselective contributions of SAL to alcoholism. Advances in analytical methods for the enantiomeric determination of SAL isomers have proved changes in R/S ratio in the brain regions of alcohol-preferring (P) rats after ethanol consumption (Haber et al., 1999; Rojkovicova et al., 2008). However, enantiomeric distribution of SAL isomers was neither changed in human urine and plasma by acute alcohol ingestion (Haber et al., 1996) nor different in postmortem brains between alcoholics and controls (Musshoff et al., 2005). The variability in the reported levels of SAL in healthy subjects and conflicting results on the influence of ethanol on SAL levels and enantiomeric distribution might be partly due to analytical problems and experimental variables including dietary conditions and genetic factors. In this study, we examined the effect of SAL-containing foods, ethanol or genetic predisposition to high alcohol drinking on the levels of SAL enantiomers and DA in humans and rats using a newly developed method (Lee et al., 2007).

We have developed an MR method to measure the volumes of renal cysts and parenchyma in patients with polycystic kidney disease. Phantoms were designed to simulate polycystic kidneys. Four patients were recruited. MR scans were performed on the phantoms and patients. A stereology technique was applied for image segmentation and volume measurement. Volumetric measurement of renal cysts and parenchyma was accurate in phantom studies and reliable in both phantom and patient studies in these limited examples.

The structure of a family of unusual glucans from Sarcina ventriculi has been characterized by NMR spectroscopy, methylation analysis, and mass spectrometry. One is a trisaccharide containing a β -(1 → 3) and a β -(1 → 4)-linkage. The other is a hexasaccharide that is simply a 1,4-linked dimer of the trisaccharide unit. This is the first report of β-glucan biosynthesis in a Gram-positive organism. Their occurrence in these organisms supports an even more general link between their synthesis and the adaptability of bacteria.

Several common links between the structural chemistry of the chitolipooligosaccharides of Rhizobium and the general rhizobial membrane lipid and lipopolysaccharide chemistry of these bacteria have been uncovered. Aspects of common chemistry include sulfation, methylation, and the position and extent of fatty acyl chain unsaturation. We find that bacteria which are known to synthesize sulfated chitolipooligosaccharides (such as Rhizobium meliloti strains and the broad-host-range Rhizobium species strain NGR234) also have sulfated lipopolysaccharides. Their common origins of sulfation have been demonstrated by using mutants which are known to be impaired in sulfating their chitolipooligosaccharides. In such cases, there is a corresponding diminution or complete lack of sulfation of the lipopolysaccharides. The structural diversity of the fatty acids observed in the chitolipooligosaccharides is also observed in the other membrane lipids. For instance, the doubly unsaturated fatty acids which are known to be predominant components of R. meliloti chitolipooligosaccharides were also found in the usual phospholipids and glycolipids. Also, the known functionalization of the chitolipooligosaccharides of R. sp. NGR234 by O- and N-methylation was also reflected in the lipopolysaccharide of this organism. The common structural features of chitolipooligosaccharides and membrane components are consistent with a substantial degree of biosynthetic overlap and a large degree of cellular, spatial overlap between these molecules. The latter aspect is clearly demonstrated here since we show that the chitolipooligosaccharides are, in fact, normal membrane components of Rhizobium. This increases the importance of understanding the role of the bacterial cell surface chemistry in the Rhizobium/legume symbiosis and developing a comprehensive understanding of the highly integrated membrane lipid and glycolipid chemistry of Rhizobium.