Factors influencing interprofessional collaboration in long-term care from a multidisciplinary perspective: a case study approach.

Systematic assessments of interprofessional collaboration barriers and enablers in long-term care settings are critical for delivering person-centered healthcare. However, research on factors influencing interprofessional collaboration in long-term care settings is limited. For this study, 65 healthcare professionals across multiple facilities experienced in long-term care in Japan participated in online focus group discussions and individual interviews to discuss cases. The qualitative data were analyzed using qualitative content analysis. Seven themes emerged: coordination, the need for care manager training, hierarchy among healthcare professionals, specialization but not the mind-set of overspecialization, casual conversations, electronic group communication tools, and excessive fear of personal information protection. These findings highlight the need to develop coordinator roles and for interprofessional education on the proper approach to personal information protection laws. Furthermore, daily casual conversations, the use of online platforms, and the prevention of patients being left behind due to overspecialization are required.

Efficacy and safety of fixed doses of intranasal Esketamine as an add-on therapy to Oral antidepressants in Japanese patients with treatment-resistant depression: a phase 2b randomized clinical study.

BACKGROUND: Esketamine nasal spray (Spravato) in conjunction with oral antidepressants (ADs) is approved in the European Union, United States, and other markets for treatment-resistant depression (TRD). Efficacy, safety, and tolerability of esketamine nasal spray in Japanese patients with TRD needs to be assessed. METHODS: This Phase 2b, randomized, double-blind (DB), placebo-controlled study was conducted in adult Japanese patients with TRD meeting the Diagnostic and Statistical Manual of Mental Disorders (fifth edition) criteria of major depressive disorder with nonresponse to ≥ 1 but < 5 different ADs in the current episode at screening. Patients were treated with a new oral AD for 6 weeks (prospective lead-in phase); nonresponders were randomized (2:1:1:1) to placebo or esketamine (28-, 56-, or 84-mg) nasal spray along with the continued use of AD for 4 weeks (DB induction phase). Responders (≥50% reduction from baseline in the Montgomery-Asberg Depression Rating Scale [MADRS] total score) from the DB induction phase continued into the 24-week posttreatment phase and patients who relapsed could participate in a 4-week open-label (OL) second induction (flexibly-dosed esketamine). The primary efficacy endpoint, change from baseline in the MADRS total score at Day 28 in the DB induction phase, was based on mixed-effects model using repeated measures pairwise comparisons using a Dunnett adjustment. RESULTS: Of the 202 patients randomized in the DB induction phase (esketamine [n = 122] or placebo [n = 80]), the MADRS total scores decreased from baseline to Day 28 of the DB induction phase (- 15.2, - 14.5, - 15.1, and - 15.3 for esketamine 28 mg, 56 mg, 84 mg, and placebo groups, respectively), indicating an improvement in depressive symptoms; however, the difference between the esketamine and placebo groups was not statistically significant. The most common treatment-emergent adverse events during the DB induction phase in the combined esketamine group (incidences ranging from 12.3 to 41.0%) were blood pressure increased, dissociation, dizziness, somnolence, nausea, hypoaesthesia, vertigo, and headache; the incidence of each of these events was > 2-fold higher than the corresponding incidence in the placebo group. CONCLUSIONS: Efficacy of esketamine plus oral AD in Japanese TRD patients was not established; further investigation is warranted. All esketamine doses were safe and tolerated. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02918318 . Registered: 28 September 2016.

Role of the Transcription Factor BTB and CNC Homology 1 in a Rat Model of Acute Liver Injury Induced by Experimental Endotoxemia.

Hepatic oxidative stress plays an important role in the pathogenesis of several acute liver diseases, and free heme is thought to contribute to endotoxemia-induced acute liver injury. The heme oxygenase 1 (HO-1) gene is upregulated and the δ-aminolevulinate synthase (ALAS1) gene is downregulated in the rat liver following lipopolysaccharide (LPS) treatment. BTB and CNC homology 1 (Bach1) is a heme-responsive transcription factor that normally represses HO-1 expression. In this study, we evaluated the changes in HO-1, ALAS1, and Bach1 expression and nuclear Bach1 expression in rat livers following intravenous LPS administration (10 mg/kg body weight). LPS significantly upregulated HO-1 mRNA and downregulated ALAS1 mRNA in the rat livers, suggesting that hepatic free heme concentrations are increased after LPS treatment. Bach1 mRNA was strongly induced after LPS injection. In contrast, nuclear Bach1 was significantly but transiently decreased after LPS treatment. Rats were also administered hemin (50 mg/kg body weight) intravenously to elevate heme concentrations, which decreased nuclear Bach1 levels. Our results suggest that elevated hepatic free heme may be associated with a decline of nuclear Bach1, and induction of Bach1 mRNA may compensate for the decreased nuclear Bach1 after LPS treatment in the rat liver.

[A Case of Advanced Gastric Cancer with Bone Marrow Metastasis Treated with Low-Dose Combination Chemotherapy Containing S-1 and Docetaxel].

A 77-year-old woman was admitted to our hospital with complaints of lumbago. Based on MRI, bone marrow biopsy, and upper endoscopy, she was diagnosed as having advanced gastric cancer accompanied by bone marrow metastasis and multiple bone metastases. She underwent combination chemotherapycontaining S-1 and docetaxel(TXT). However, during the first course of chemotherapy, she developed Grade 4 neutropenia and sepsis, and her ADL worsened. The anticancer agent doses were reduced drasticallyto 40% of the initial dose from the next course of chemotherapy. She was able to continue treatment without developing severe adverse events, and the disease did not progress for 11 months. However, during the 6 course of chemotherapy, she developed Grade 4 neutropenia and sepsis again, and it became difficult to continue treatment. Subsequent S-1 monotherapywas not efficacious, and she died 17 months after diagnosis. From the view of persistence and efficacy, we believe that low-dose combination chemotherapycontaining S-1 and TXT maybe a suitable regimen for advanced gastric cancer with bone marrow metastasis.

Challenges to Successful Community-based Integrated Approach to Dementia: A Qualitative Study.

The aim of this study is to identify key challenges to successful community-based integrated team approach to the management of older adults with dementia. A nationwide community-based qualitative research strategy was applied. We purposively recruited 24 health-care providers and 13 family caregivers from selected 8 prefectures among 47 prefectures. Face to face interviews were conducted from May to September 2017. Qualitative content analysis was used to analyze the qualitative data. Ten themes regarding the challenges were emerged: Ignored wishes, Family caregivers' full responsibilities, Encouragement, Practical and easy-to-understand information, Essential skills of dementia diagnosis and assessment, Gratitude by helping others, Difference between being kind and overly-kind, Legal barrier against information sharing, Coordination between volunteers and clients, and Conflict avoidance in multidisciplinary collaboration. The findings highlight the need to provide practical and easy-to-understand information for family caregivers, educate physicians in dementia diagnosis and assessment, share personal dementia care information among health-care providers, promote platforms which aim to match dementia care volunteers with older adults with dementia and their families in need of help, and raise awareness of advance care planning among both older individuals and health-care providers.

Comprehensive mutation profiling of mucinous gastric carcinoma.

Mucinous gastric carcinoma (MGC) is a unique subtype of gastric cancer with a poor survival outcome. Comprehensive molecular profiles and putative therapeutic targets of MGC remain undetermined. We subjected 16 tumour-normal tissue pairs to whole-exome sequencing (WES) and an expanded set of 52 tumour-normal tissue pairs to subsequent targeted sequencing. The latter focused on 114 genes identified by WES. Twenty-two histologically differentiated MGCs (D-MGCs) and 46 undifferentiated MGCs (U-MGCs) were analysed. Chromatin modifier genes, including ARID1A (21%), MLL2 (19%), MLL3 (15%), and KDM6A (7%), were frequently mutated (47%) in MGC. We also identified mutations in potential therapeutic target genes, including MTOR (9%), BRCA2 (9%), BRCA1 (7%), and ERBB3 (6%). RHOA mutation was detected only in 4% of U-MGCs and in no D-MGCs. MYH9 was recurrently (13%) mutated in MGC, with all these being of the U-MGC subtype (p = 0.023). Three U-MGCs harboured MYH9 nonsense mutations. MYH9 knockdown enhanced cell migration and induced intracytoplasmic mucin and cellular elongation. BCOR mutation was associated with improved survival. In U-MGCs, the MLH1 expression status and combined mutation status (TP53/BCL11B or TP53/MLL2) were prognostic factors. A comparative analysis of driver genes revealed that the mutation profile of D-MGC was similar to that of intestinal-type gastric cancer, whereas U-MGC was a distinct entity, harbouring a different mutational profile to intestinal- and diffuse-type gastric cancers. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

PHLDA3 is a novel tumor suppressor of pancreatic neuroendocrine tumors.

The molecular mechanisms underlying the development of pancreatic neuroendocrine tumors (PanNETs) have not been well defined. We report here that the genomic region of the PHLDA3 gene undergoes loss of heterozygosity (LOH) at a remarkably high frequency in human PanNETs, and this genetic change is correlated with disease progression and poor prognosis. We also show that the PHLDA3 locus undergoes methylation in addition to LOH, suggesting that a two-hit inactivation of the PHLDA3 gene is required for PanNET development. We demonstrate that PHLDA3 represses Akt activity and Akt-regulated biological processes in pancreatic endocrine tissues, and that PHLDA3-deficient mice develop islet hyperplasia. In addition, we show that the tumor-suppressing pathway mediated by MEN1, a well-known tumor suppressor of PanNETs, is dependent on the pathway mediated by PHLDA3, and inactivation of PHLDA3 and MEN1 cooperatively contribute to PanNET development. Collectively, these results indicate the existence of a novel PHLDA3-mediated pathway of tumor suppression that is important in the development of PanNETs.

Improvement of heme oxygenase-1-based heme sensor for quantifying free heme in biological samples.

We recently reported a novel heme sensor using fluorescently labeled heme oxygenase-1; however, its inherent enzyme activity would be a potential obstacle in quantifying heme in biological samples. Here, we found that mutation of the catalytically important residue, Asp140, with histidine in the sensor not only diminished the heme degradation activity but also increased heme binding affinity. The sensor with a visible fluorophore was also found to be beneficial to avoid background emission from endogenous substance in biological samples. By using the improved heme sensor, we succeeded in quantifying free heme in rat hepatic samples for the first time.

Axitinib (AG-013736), an oral specific VEGFR TKI, shows potential therapeutic utility against cholangiocarcinoma.

OBJECTIVE: Cholangiocarcinoma is a refractory cancer whose incidence has been increasing worldwide in recent years. Neoangiogenesis plays an important role in the growth of various solid cancers, including cholangiocarcinoma. Vascular endothelial growth factor plays an important role in tumor-induced angiogenesis and its expression is associated with the progression and prognosis of cholangiocarcinoma. This study examined whether axitinib (AG-013736, INLYTA(®)), a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2 and 3, could be a potentially useful therapeutic agent for cholangiocarcinoma. METHODS: We performed expression profiling of angiogenesis-related molecules in eight cholangiocarcinoma cell lines and found that three of them showed high vascular endothelial growth factor expression. Among them, we examined the in vivo anti-tumor effect of axitinib on NCC-BD1 (a gemcitabine-sensitive extra-hepatic cholangiocarcinoma cell line) and TKKK (a gemcitabine-resistant intra-hepatic cholangiocarcinoma cell line) using subcutaneous xenograft models. RESULTS: Oral administration of axitinib significantly inhibited the growth of TKKK xenografts at a dose of 6 mg kg(-1) day(-1) (P<0.05), and the growth of NCC-BD1 xenografts at 30 mg kg(-1)day(-1) (P<0.05). Treated tumors showed a significant decrease of microvessel density and the tumor cell proliferation index and a mild but significant increase of the apoptotic index in comparison with untreated tumors. CONCLUSIONS: Our results suggest that axitinib should be a promising therapy for vascular endothelial growth factor-expressing cholangiocarcinoma, irrespective of tumor origin and gemcitabine sensitivity.

Downregulation of the microRNA biogenesis components and its association with poor prognosis in hepatocellular carcinoma.

Genetic alterations and deregulation of the miRNA biogenesis pathway components have been reported in human tumors. Tissue-specific deletion of the Dicer gene, which encodes an essential miRNA processing enzyme, promotes carcinogenesis in animal models. These features indicate that aberrant miRNA biogenesis components are directly associated with cancer. For the present study, we conducted quantitative RT-PCR of 14 genes that are related to the miRNA biogenesis pathway in 47 paired samples of primary hepatocellular carcinoma (HCC) and matched non-cancerous liver. Expression of seven genes (Dgcr8, p68, p72, Dicer, Ago3, Ago4 and Piwil4) was significantly decreased in primary HCC, especially in non-viral HCC subtypes, compared to the non-cancerous liver. Combinations of decreased expression of the miRNA biogenesis components in non-cancerous liver were related to cigarette smoking, alcohol intake and diabetes, which are known to be risk factors for HCC, and were also associated with the occurrence of multicentric tumors. Reduction of two of these genes (Dicer and p68) in HCC was associated with poor prognosis. Trimethylation of histone H3 lysine 27 in the promoters is implicated in the deregulation of these miRNA-biogenesis-related genes in non-HBV genome integrated HCC cell lines. In conclusion, deregulation of the miRNA biogenesis pathway components is frequently observed in non-viral-associated HCC and is linked to etiological risk factors and poor prognosis. Our study further showed that epigenetic regulation could be implicated in the deregulation of these genes during hepatocarcinogenesis.

Evaluation of Ethnicity Effect on Intranasal Esketamine Pharmacokinetics by Population Pharmacokinetic Modeling Using Data From a Japanese Phase 2b Study.

Esketamine is used for the treatment of treatment-resistant depression in many countries. A population pharmacokinetic (popPK) model of esketamine and its metabolite (noresketamine) has been previously developed, which included Asian race and Japanese ethnicity as covariates on their exposures. The present study aimed to update the popPK model by adding new data from a phase 2b study in Japanese patients and reassess intrinsic and extrinsic factors on esketamine and noresketamine exposures. The updated model identified the effects of body weight on the fraction of the esketamine dose absorbed in the nasal cavity and elimination rate constant of esketamine, and Asian race on the apparent clearance of noresketamine. The model predicted that an increase of 30 kg of body weight would decrease esketamine exposures by ≈20%. Noresketamine exposures would be affected by Asian race and body weight. However, those newly identified covariates were not considered to have clinically relevant impacts, and therefore dose adjustments were not necessary. In conclusion, the popPK model of esketamine and noresketamine was successfully updated and suggested that interindividual variability of esketamine exposures can be better explained by body weight, rather than by race/ethnicity. The new findings obtained in this study should be useful information for the further development of esketamine and for clinical practice in the future.

Nano-Tactile Scanner with Dust-Proof and Drip-Proof Structure for High-Resolution Measurement of Skin Surface Textures.

In this study, we have successfully developed a scanner-type measurement device with a built-in nano-tactile sensor for measuring living organisms and skin surface. A complete sensor protection structure for sensitive tactile sensor device has been developed to achieve a sensing system that is capable of measuring texture changes on the skin surface. By using a highly flexible organic ultra-thin film (film adhesive bandage) as the protective structure, it is possible to prevent deterioration of sensor performance and the intrusion of droplets and dust present on the surface to be measured. This system was used in a clinical experiment at the university's medical faculty, and succeeded in accurately extracting changes in the properties of the patient's skin caused by different wiping methods. As a result, the measurement of tactile texture of the skin surface in various states between dry and wet could be accurately done. Finally, in addition to the ability to measure tactile characteristics of the skin surface, a new function has been realized to measure skin hardness distribution caused by skin changes due to blisters, moles, etc.Clinical Relevance- The developed micron scale was the first to explain the changes in the skin surface structure according to the type of skin surface stimulus and the time of its appearance. It is clinically useful to interpret the protective function of the skin and the function of sensory reception.

Efficacy of an Algorithm-Based Nursing Intervention to Promote a Balance Between Cancer Patients' Social Roles and Outpatient Treatment: A Quasi-Experimental Study.

BACKGROUND: Cancer patients undergoing treatment are often unable to balance treatment and work because of the time required for care at the hospital and a desire to avoid problems at work. OBJECTIVE: The aim of this study was to elucidate the efficacy of an algorithm-based nursing intervention (ANI) to promote balance between social roles and outpatient treatment in cancer patients. METHODS: Participants were outpatients receiving cancer therapy and randomly assigned to a control or an intervention group, the latter to receive ANI for 2 months. The outcomes were assessed using the Distress and Impact Thermometer and changes in employment status. Data from 54 evaluable participants in each group were analyzed. RESULTS: Distress and Impact Thermometer scores in the intervention group were significantly lower than those in the control group ( P < .001). In addition, 2 months later, 20 participants had resigned from their employment or were on leave in the control group (37.0%); this was twice the number in the intervention group, a significant difference ( χ2 = 4.573, P < .05). Logistic regression analysis showed that the odds ratio in the control group was 3.6 times that of the intervention group of having resigned. CONCLUSION: The ANI appears to have reduced distress and impact scores associated with the course of treatment and to have reduced the likelihood of resignations at 2 months after implementation. IMPLICATIONS FOR PRACTICE: The intervention appears to be effective and may be a new tool for use by outpatient oncology nurses.

Dexmedetomidine improves acute lung injury by activating autophagy in a rat hemorrhagic shock and resuscitation model.

Dexmedetomidine (DEX) can reduce lung injury in a hemorrhagic shock (HS) resuscitation (HSR) model in rats by inhibiting inflammation. Here, we aimed to investigate if these effects of DEX are due to autophagy activation. Therefore, we established HSR rat models and divided them into four groups. HS was induced using a blood draw. The rats were then resuscitated by reinjecting the drawn blood and saline. The rats were sacrificed 24 h after resuscitation. Lung tissues were harvested for histopathological examination, determination of wet/dry lung weight ratio, and detection of the levels of autophagy-related marker proteins LC3, P62, Beclin-1, and the ATG12-ATG5 conjugate. The morphological findings of hematoxylin and eosin staining in lung tissues and the pulmonary wet/dry weight ratio showed that lung injury improved in HSR + DEX rats. However, chloroquine (CQ), an autophagy inhibitor, abolished this effect. Detecting the concentration of autophagy-related proteins showed that DEX administration increased LC3, ATG12-ATG5, and Beclin-1 expression and decreased P62 expression. The expression levels of these proteins were similar to those in the HSR group after CQ + DEX administration. In summary, DEX induced autophagic activation in an HSR model. These findings suggest that DEX administration partially ameliorates HSR-induced lung injury via autophagic activation.

Human epidermal growth factor 2 overexpressed alpha-fetoprotein-producing-gastric cancer.

PURPOSE: This study aimed to elucidate the clinicopathological characteristics of α-fetoprotein (AFP)-producing gastric carcinoma (AFP-GC) with human epidermal growth factor receptor (HER)2 overexpression to extend the treatment strategy for AFP-GC. METHODS: We analyzed 41 patients with AFP-GC who underwent surgical resection or chemotherapy from 1989 to 2019, and who had over 20ng/mL of serum AFP or positive immunohistochemical AFP expression. HER2 expression status was investigated by immunohistochemistry (IHC) for all patients and by fluorescence in situ hybridization (FISH) for cases with an IHC score of 2+. AFP-GC with an IHC score of 3 + or 2 + and FISH positivity was defined as HER2 overexpressed AFP-GC. The correlation between HER2 status and clinicopathological characteristics and prognosis in AFP-GC was analyzed. RESULTS: HER2 overexpression was detected in 17.1% of AFP-GC patients. The prognosis of the patients with HER2 overexpressed AFP-GC was not significantly different compared to HER2 non-overexpressed AFP-GC. HER2 overexpressed AFP-GC consisted of heterogeneous histology with a higher proportion of mixed-type tumors (p = 0.002). The clinical outcome of AFP-GC with mixed-type of histology tended to be better than other intestinal or diffuse types (p = 0.05). CONCLUSION: HER2 overexpressed AFP-GC consisted of a mixed type of histology, which showed a better prognosis. The results presented that HER2 status in AFP-GC is one of the molecular candidates to improve the prognosis.

Protective effect of tin chloride on rhabdomyolysis-induced acute kidney injury in rats.

The heme component of myoglobin plays a crucial role in the pathogenesis of rhabdomyolysis-associated acute kidney injury (RM-AKI). Heme oxiganenase-1 (HO-1) is the rate-limiting enzyme of heme catabolism, and its metabolites, iron, biliverdin, and carbon monoxide, have antioxidant properties. Tin chloride (SnCl2) is a kidney specific HO-1 inducer. In this study, we examined whether the induction of HO-1 in the kidney by SnCl2 pretreatment ameliorates RM-AKI in rats and if the effect is due to the degradation of excess renal free heme. We developed an RM-AKI rat (male Sprague-Dawley rats) model by injecting glycerol (Gly) in the hind limbs. RM-AKI rats were pretreated with saline or SnCl2 or additional SnMP (tin mesoporphyrin, a specific HO inhibitor) followed by Gly treatment. Serum blood urea nitrogen (BUN) and creatinine (Crea) were measured as indicators of renal function. Renal free heme level was assessed based on the levels of δ-aminolevulinate synthase (ALAS1), a heme biosynthetic enzyme, and nuclear BTB and CNC homology 1 (Bach1), an inhibitory transcription factor of HO-1. Elevated free heme levels lead to decreases in ALAS1 and nuclear Bach1. After 24 h of Gly injection, serum BUN and Crea levels in saline-pretreated rats were significantly higher than those in untreated control rats. In contrast, SnCl2-pretreated rats showed no significant increase in the indices. However, additional treatment of SnMP abolished the beneficial effect of SnCl2. Renal ALAS1 mRNA levels and renal nuclear Bach1 protein levels in the saline pretreated rats were significantly lower than those in control rats 3 h after Gly injection. In contrast, the levels in SnCl2-pretreated rats were not altered. The findings indicate that SnCl2 pretreatment confers protection against RM-AKI by virtue of HO-1 induction in the renal system, at least in part through excess free heme degradation.

[Prevalence of psychiatric disorders among homeless people in one area of Tokyo].

OBJECTIVES: This study is the first ever field survey in Japan of the prevalence of psychiatric disorders among homeless people in one area of Tokyo. The main aim of was to make accurate diagnoses by a psychiatrist to give an accurate picture. METHODS: The survey period was from December 30, 2008 to January 4, 2009. The people covered by the survey were people living on the streets within a one-kilometer radius ofJR Ikebukuro Station in this period. The survey area was selected within Toshima City as a district where it would be possible to roughly grasp the total number of homeless people. The definition of homeless people in this study was the same as that which was stipulated in the Ministry of Health, Labor and Welfare national survey. A total of 115 people living on the streets received the written request to participate in the survey and 80 agreed to do so, beiung enrolled as the subjects of this study. Mini International Neuropsychiatric Interview (MINI) questionnaires and a separately created questionnaire that asked about the subjects' living circumstances were used in the interviews and finally, a psychiatrist made diagnoses of psychiatric disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnosis standards. RESULTS: The average age of the subjects was 50.5 (standard deviation; 12.3) and there were 75 men (93.8%) and 5 women (6.3%). 50 people (62.5%) were diagnosed with psychiatric disorders which included 33 people (41.3%) who had depression, 12 (15%) who were dependent on alcohol and 12 (15%) who had psychotic disorders such as hallucinations or delusions. Using the degree of risk in the MINI classification, 45 (57.0%) were at risk of committing suicide and 25 people (31.6%) had already attempted suicide in the past. CONCLUSION: The representativeness of homeless people in Japan who have psychiatric disorders in this study is limited but that the finding of 62.5% of homeless people suffering from some symptoms and a high risk of suicide suggestss that this is an urgent issue for medical support.

Perceptions and behaviors related to noncommunicable diseases in Palau: a qualitative study.

The increasing burden of noncommunicable diseases (NCDs) is a major public health concern in Palau. This study aims to identify social and psychological factors related to NCDs among Palauan people using a qualitative approach. We conducted eight key informant interviews and eight focus group discussions, which were audio-recorded, transcribed and translated into English. Ideas of the respondents were extracted and labeled, and the labels were analyzed using an inductive multistage approach referred to as qualitative content analysis. Three themes emerged: (1) home education, (2) traditional local community, and (3) modernization and westernization of lifestyle. Respondents believed that the influence of the family on lifestyle was significant, but that disciplining children at home had become difficult. They considered that the traditional lifestyle was mostly healthy, and were reluctant to abandon certain unhealthy customs, such as serving abundant food to guests as a sign of fraternity. They also thought that they overate because of their stressful modernized lifestyle. This is the first qualitative study to analyze perception and behavior of the Palauan people in relation to NCDs. We found that the increase in NCDs was related to two concurrent trends: preserving certain traditional customs unfavorable to good health, and abandoning time-consuming healthy traditional lifestyle to adopt a modernized one. We also found that Palauan people were not confident in their ability to prevent NCDs. Therefore, health promotion activities should be designed to empower people to make positive changes.

Establishment of six new human biliary tract carcinoma cell lines and identification of MAGEH1 as a candidate biomarker for predicting the efficacy of gemcitabine treatment.

The aim of this study was to establish new biliary tract carcinoma (BTC) cell lines and identify predictive biomarkers for the potential effectiveness of gemcitabine therapy. Surgical specimens of BTC were transplanted directly into immunodeficient mice to establish xenografts, then subjected to in vitro cell culture. The gemcitabine sensitivity of each cell line was determined and compared with the genome-wide gene expression profile. A new predictive biomarker candidate was validated using an additional cohort of gemcitabine-treated BTC cases. From 55 BTC cases, we established 19 xenografts and six new cell lines. Based on their gemcitabine sensitivity, 10 BTC cell lines (including six new and four publicly available ones) were clearly categorized into two groups, and MAGEH1 mRNA expression in the tumor cells showed a significant negative correlation with their sensitivity to gemcitabine. Immunohistochemically, MAGEH1 protein was detected in three (50%) out of six sensitive cell lines, and four (100%) out of four resistant cell lines. In the validation cohort of gemcitabine-treated recurrence cases, patients were categorized into "effective" and "non-effective" groups according to the RECIST guidelines for assessment of chemotherapeutic effects. MAGEH1 protein expression was detected in two (40%) out of five "effective" cases and all four (100%) "non-effective" cases. We have established a new BTC bioresource that covers a wide range of biological features, including drug sensitivity, and is linked with clinical information. Negative expression of MAGEH1 protein serves as a potential predictive marker for the effectiveness of gemcitabine therapy in BTC.

Protective effect of carbon monoxide inhalation on lung injury after hemorrhagic shock/resuscitation in rats.

BACKGROUND: Hemorrhagic shock and resuscitation (HSR) induces pulmonary inflammation that leads to acute lung injury. Carbon monoxide (CO), a by-product of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. The aim of this study was to examine the effects of CO inhalation at low concentration on lung injury induced by HSR in rats. METHODS: Rats were subjected to HSR by bleeding to achieve mean arterial pressure of 30 mm Hg for 60 minutes followed by resuscitation with shed blood and saline as needed to restore blood pressure. HSR animals were either maintained in room air or were exposed to CO at 250 ppm for 1 hour before and 3 hours after HSR. RESULTS: HSR caused an increase in the DNA binding activity of nuclear factor-kappaB and activator protein-1 in the lung followed by the up-regulation of pulmonary gene expression of tumor necrosis factor-alpha, inducible nitric oxide synthase, and interleukin (IL)-10. HSR also resulted in an increase in myeloperoxidase activity and wet weight to dry weight ratio in the lung, and more prominent histopathologic changes including congestion, edema, cellular infiltration, and hemorrhage. In contrast, CO inhalation significantly ameliorated these inflammatory events as judged by fewer histologic changes, less up-regulation of inflammatory mediators, and less activation of nuclear factor-kappaB and activator protein-1. Interestingly, the protective effects against lung injury afforded by CO were associated with further increases in mRNA expression of IL-10 in the lung. CONCLUSIONS: These findings suggest that inhaled CO at a low concentration ameliorated HSR-induced lung injury and attenuated inflammatory cascades by up-regulation of anti-inflammatory IL-10.