Factors predictive of survival after percutaneous endoscopic gastrostomy in the elderly: is dementia really a risk factor?

OBJECTIVES:  Outcomes, especially survival, after percutaneous endoscopic gastrostomy (PEG) in patients with dementia remain unclear. The aims of this study were to assess the impact of dementia on survival after PEG and to explore the risk factors in elderly patients.
METHODS:  A total of 311 consecutive Japanese patients who underwent PEG were enrolled in this retrospective cohort study. Dementia was defined according to the standard criteria. After the clinical characteristics of patients with and without dementia were compared, the Kaplan-Meier method and Cox proportional-hazards regression analysis were applied to analyze survival rates.
RESULTS:  Survival was not significantly different between the two groups. The 12-month survival rate of patients with dementia (N = 143) was 51%, and that of patients without dementia (N = 168) was 49%. More than 20% of patients with dementia lived more than 3 yr after PEG. The predictors of poor survival after PEG were previous subtotal gastrectomy (odds ratio [OR] 2.619, 95% confidence interval [CI] 1.367–5.019), serum albumin <2.8 g/dL (OR 2.081, 95% CI 1.490–2.905), age >80 yr (OR 1.721, 95% CI 1.234–2.399), chronic heart failure (OR 1.541, 95% CI 1.096–2.168), and male gender (OR 1.407, 95% CI 1.037–1.909).
CONCLUSIONS:  In our series, there was no evidence to support a poorer prognosis after PEG in elderly people with dementia compared with the cognitively preserved elderly. However, if patients are male or of advanced age, have a low serum albumin, chronic heart failure, or subtotal gastrectomy, physicians should inform families that a poor prognosis is expected before performing PEG.     

Arterial Oxygen Saturation in Severely Disabled People: Effect of Oral Feeding in the Sitting Position

Control of the circulatory and respiratory systems is especially important in severely disabled people. The purpose of this study was to clarify the response of hemoglobin oxygen saturation level (SpO₂), pulse rate, and respiratory rate during oral feeding in severely disabled persons. Continuous measurement of these variables was done by pulse oximetry and respiratory inductance plethysmography under two experimental settings in eight severely disabled persons aged 14–28 yrs. Setting I consisted of the following three procedures: (a) a 30-min period in the supine position, (b) a 50-min period in a sitting position, and (c) a 30-min period in the supine position. Setting II consisted of the following four procedures: (a) a 30-min period before the meal in the supine position, (b) a nonspecified period in a sitting position during which the meal was taken, (c) a 30-min period after the meal in the same sitting position, and (d) a 30-min period in the supine position. Results showed that mean SpO₂ level decreased and mean pulse rate increased during the meal in almost all subjects. In many cases, pulse rate and SpO₂ level did not return to baseline values in the sitting position after the meal. These findings indicate that oral feeding of severely disabled persons in a sitting position places considerable stress on the circulatory system, the effects of which may last after the meal in some cases.     

Oral motor function and masticatory performance in the community-dwelling elderly

This study was performed to ascertain the relationships between oral motor functions, such as those of the tongue and lips, and age in the community-dwelling elderly, as well as to investigate the effects of these factors on masticatory performance. The subjects were 268 healthy elderly Japanese living in Kyoto. They were divided into four age groups and further classified into the following two groups by the presence or absence of posterior occlusal support: Eichner A or B1-B3 (group A), and Eichner B4 or C (group B). They were wearing removable or fixed dentures if they had missing teeth. Oral function evaluation items included (1) masticatory performance and (2) oral motor skills. Significant differences were noted among the age groups in tongue pressure within group A (P < 0.01) and group B (P < 0.05), and in the number of repetitions of the syllables /ta/ and /ka/ in group B (/ta/: P < 0.05, /ka/; P < 0.01). The number of natural teeth (β = 0.463, P < 0.001) in group A and tongue pressure (β = 0.436, P < 0.001) in group B were the only predictors of masticatory performance when the data were analyzed by multiple regression analysis. The tongue may compensate for the missing teeth in masticatory performance of those elderly who have lost their natural teeth. The results of this study highlight the importance of tongue function in masticatory performance.     

Differentiation of regioisomeric fluoroamphetamine analogs by gas chromatography–mass spectrometry and liquid chromatography–tandem mass spectrometry

In recent years, a large number of clandestinely produced controlled-substance analogs (designer drugs) of amphetamine with high structural variety have been detected in forensic samples. Analytical differentiation of regioisomers is a significant issue in forensic drug analysis because, in most cases, legal controls are placed only on one or two of the three isomers. In this study, we used gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–tandem mass spectrometry (LC–MS/MS) for the differentiation of regioisomers of fluoroamphetamine analogs (fluoroamphetamines and fluoromethamphetamines), which were synthesized in our laboratories. Free bases and their acylated and silylated derivatives were subjected to GC–MS analysis using DB-1ms, DB-5ms, and DB-17ms capillary columns. The separation of free bases was incomplete on all columns. Trifluoroacetyl derivatives of 3- and 4-positional isomers showed slight separation on DB-1ms and DB-5ms. On the other hand, trimethylsilyl derivatization enabled baseline separation of six fluoroamphetamine analogs on DB-1ms and DB-5ms columns, which was sufficient for unequivocal identification. For LC–MS/MS, a pentafluorophenyl column was able to separate six regioisomeric fluoroamphetamine analogs but a conventional C18 column could not achieve separation between 3- and 4-positional isomers. These results show that a suitable choice of derivatization and analytical columns allows the differentiation of regioisomeric fluoroamphetamine analogs.     

Measurement of bite force variables related to human discrimination of left-right hardness differences of silicone rubber samples placed between the incisors

This study was designed to examine human subjects' ability to discriminate between spatially different bite pressures. We measured actual bite pressure distribution when subjects simultaneously bit two silicone rubber samples with different hardnesses using their right and left incisors. They were instructed to compare the hardness of these two rubber samples and indicate which was harder (right or left). The correct-answer rates were statistically significant at P < 0.05 for all pairs of different right and left silicone rubber hardnesses. Simultaneous bite measurements using a multiple-point sheet sensor demonstrated that the bite force, active pressure and maximum pressure point were greater for the harder silicone rubber sample. The difference between the left and right was statistically significant (P < 0.05) for all pairs with different silicone rubber hardnesses. We demonstrated for the first time that subjects could perceive and discriminate between spatially different bite pressures during a single bite with incisors. Differences of the bite force, pressure and the maximum pressure point between the right and left silicone samples should be sensory cues for spatial hardness discrimination.     

The ATP-hydrolyzing ectoenzyme E-NTPD8 attenuates colitis through modulation of P2X4 receptor–dependent metabolism in myeloid cells

Extracellular adenosine triphosphate (ATP) released by mucosal immune cells and by microbiota in the intestinal lumen elicits diverse immune responses that mediate the intestinal homeostasis via P2 purinergic receptors, while overactivation of ATP signaling leads to mucosal immune system disruption, which leads to pathogenesis of intestinal inflammation. In the small intestine, hydrolysis of luminal ATP by ectonucleoside triphosphate diphosphohydrolase (E-NTPD)7 in epithelial cells is essential for control of the number of T helper 17 (Th17) cells. However, the molecular mechanism by which microbiota-derived ATP in the colon is regulated remains poorly understood. Here, we show that E-NTPD8 is highly expressed in large-intestinal epithelial cells and hydrolyzes microbiota-derived luminal ATP. Compared with wild-type mice, Entpd8^−/− mice develop more severe dextran sodium sulfate–induced colitis, which can be ameliorated by either the depletion of neutrophils and monocytes by injecting with anti–Gr-1 antibody or the introduction of P2rx4 deficiency into hematopoietic cells. An increased level of luminal ATP in the colon of Entpd8^−/− mice promotes glycolysis in neutrophils through P2x4 receptor–dependent Ca²⁺ influx, which is linked to prolonged survival and elevated reactive oxygen species production in these cells. Thus, E-NTPD8 limits intestinal inflammation by controlling metabolic alteration toward glycolysis via the P2X4 receptor in myeloid cells.

The intestinal microbiota contribute to reinforcing epithelial integrity and shaping the immune system via metabolically derived signaling molecules (1–3). However, alterations in microbial metabolites and their translocation following intestinal dysbiosis are implicated in the pathogenesis of chronic disorders, such as inflammatory bowel diseases (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) (4, 5). Extracellular adenosine triphosphate (ATP) is released by microbes and immune cells in the intestine (6–8) and drives immune responses through the P2X_1-7 and P2Y_{1, 2, 11} receptors (9). To avoid inappropriate immune reactions in the intestine, luminal ATP is strictly controlled by epithelial ATP-hydrolyzing ectoenzymes, such as ectonucleotide pyrophosphatase/phosphodiesterases (E-NPPs) and ectonucleoside triphosphate diphosphohydrolases (E-NTPDases). E-NPP3 on the epithelial cells depresses the apoptosis of plasmacytoid dendritic cells (DCs) in the small intestine and Peyer’s patches (10). In addition, E-NTPD7 in small-intestinal epithelial cells hydrolyzes luminal ATP, thus inhibiting excessive T helper 17 (Th17) responses (11). However, how the concentration of luminal ATP produced by commensal bacteria is regulated in the large intestine remains undetermined.Although intestinal phagocytes such as monocytes, macrophages (Mϕ), DCs, and neutrophils have some protective effects, these cells can also function in pathological conditions (12–14). In patients with IBD, inflamed sites of the intestinal mucosa have more inflammatory DCs and Mϕ, many of which are dysfunctional (15). In addition, an enhanced neutrophil accumulation in the intestinal mucosa of UC patients correlates with disease severity (16–18). Accordingly, experimental murine colitis can be abrogated by inhibiting the recruitment of monocytes and neutrophils to the intestinal lamina propria by using anti-CCR2 (19) or -Gr-1 (20–22) antibody or by the targeted deletion of CCR2 (23) or β7-integrin (24). Thus, the number of intestinal phagocytes and their physiological functions must be tightly tuned to prevent the intestinal inflammation. However, the mechanisms by which the activity of monocytes and neutrophils that have infiltrated into the intestinal mucosa are regulated remain poorly understood.Different immune cell populations have distinct nutrient utilizations and cellular metabolisms (25), which are involved in their differentiation, proliferation, functions, longevity, and epigenetic modification (25–27). Microbial components and metabolites, such as lipopolysaccharide (28) and short chain fatty acids (29), can switch to glycolysis in monocytes and T cells, respectively. The small molecule dimethyl fumarate (DMF), which suppresses glycolysis in lymphocytes and myeloid cells (30), abrogates chemically induced colitis in mice (31, 32), which indicates that inadequate glycolysis activation is involved in the pathogenesis of intestinal inflammation. However, the mechanism underlying the adaptation of intestinal myeloid cells to environmental factors that fuel glycolysis is unclear.In this study, we investigated the immunomodulatory function of ATP-hydrolyzing ectoenzyme E-NTPD8 in maintenance of the gut homeostasis. Mice with Entpd8 deficiency had an increased concentration of luminal ATP in their colons, which led to the prolonged survival of neutrophils owing to the facilitation of glycolysis by the P2X4 receptor (P2X4R), thereby exacerbating dextran sodium sulfate (DSS)-induced colitis. Therefore, the clearance of extracellular ATP by E-NTPD8 is essential for the prevention of innate intestinal pathology by inhibiting a metabolic alteration toward glycolysis in myeloid cells.     

31种黄酮、酚酸类化合物和10种中药清除DPPH能力考察

目的:考察中药中黄酮、酚酸类成分清除DPPH自由基活性及构效关系,中药乙醇提取物清除DPPH自由基的活性及其与黄酮、酚酸类成分总量之间的关系.方法:以中药中常见的31种黄酮、酚酸类化合物和10种中药为研究对象,以DPPH法对上述41个样品的抗氧化活性进行评价,以高效液相色谱-库仑阵列检测技术检测黄酮及酚酸类化合物的氧化电位,以Folin-Ciocalteu法测定中药中黄酮和酚酸类成分的总量.结果:31种化合物清除DPPH自由基的能力有很大差别,其中以(-)-EGCg清除DPPH自由基的能力最强,其IC_(50)值为6.7μmol·L~(-1);氧化电位值50 mV;提取物中,茶叶提取物中总黄酮和酚酸类成分的含量最高,为82.9%(以芦丁计),清除DPPH自由基能力最强,IC_(50)值为0.012 g·L~(-1);红花醇提物总黄酮和酚酸类成分的含量最低,为7.01%(以芦丁计),其清除DPPH自由基能力最弱,其IC_(50)值为1.3 g·L~(-1).结论:黄酮、酚酸类成分清除DPPH自由基的能力与化合物中酚羟基的取代个数和位置有关;中药清除DPPH自由基能力(Y)与总黄酮和酚酸类成分含量(X)之间存在相关性,Y=7.779X~(-0.48),r=0.929 5,即总黄酮和酚酸类成分含量高,清除DPPH自由基能力强.     

Single nucleotide variations in genes associated with innate immunity are enriched in Japanese adult cases of face and neck type atopic dermatitis

BackgroundAtopic dermatitis (AD) is heterogenous in terms of phenotype as well as genetic and environmental factors, while its associated genetic factors and pathophysiology are not fully understood.ObjectiveWe identify novel genetic factors enriched in a subgroup of AD patients with characteristic clinical features.MethodsWe clinically subgrouped 18 AD patients who exhibited distinctive characteristic of persistent skin eruption areas on the face and neck from 92 Japanese adult AD patients and identified disease-associated genetic factors enriched within the subgroup. Targeted resequencing and subsequent genetic association analyses were used to identify novel enriched genetic variations in the subgroup compared with the other AD patients.ResultsTargeted resequencing of 648 skin associated genes revealed an enrichment of 12 single nucleotide variations (SNVs) in patients with face and neck AD (n = 18) compared with the general Japanese population in the database. Subsequent allele frequency comparison between the face and neck AD and non - face and neck AD subgroups revealed enrichment of five SNVs. Multivariate analysis using genotype data revealed that three SNVs in theTLR1, TIRAP, and PSAPL1 genes, two of the three genes are involved in the Toll-like receptor pathway, were significantly enriched in patients with face and neck AD.ConclusionThese findings revealed that the SNVs in genes associated with the innate immune pathway are enriched in a subgroup of AD. The combinational approach of clinical subgrouping and genotyping is valuable for detecting novel disease-associated genetic factors.