How Society Changes: Sociological Enlightenment and a Theory of Social Evolution for Freedom.

This article clarifies the relationship between individual freedom and social order by relying on Niklas Luhmann's social systems theory and thereby defines sociology's contribution to social evolution as sociological enlightenment, which seeks otherwiseness in living experience and action. For this purpose, Luhmann's theory will specifically be compared with Emile Durkheim's and Alfred Schutz's sociological theories. Durkheim, a "child of the Enlightenment," considered freedom a collective ideal of moral individualism and conceived that the rational state realizes freedom by spreading the civil-religious human ideal for modern social order. In contrast, Schutz, following Henri Bergson, who criticized rationality for spatially fixing inner time, regarded freedom as a given in the individual's underlying duration, not as a shared ideal. Yet, unlike Bergson, he continued relying on rationalism, and he thought that the sociological observer observes how something appears to people with the epoché of natural attitude, not what it objectively is. Inheriting this phenomenological subjectivism, Luhmann showed that the self-referentiality of consciousness also applies to society: A social system, which path-dependently emerges itself from a double contingency, observes the world in its own way based on its self-referentially constituted eigen-time. On account of this system closure, and contrary to Durkheim's illuminist belief, there is no controlling entity in a highly evolved society, where freedom results from the enlarged, diversified possibilities of living experience and action (contingency). Thus, sociological enlightenment doubts self-evidence so that society brackets the taken-for-granted social order or social reality and amplifies individuals' deviations to evolve toward freedom.

Comparison of emotional processing assessed with fear conditioning by interpersonal conflicts in patients with depression and schizophrenia.

AIM: While emotional processing is implicated in various psychiatric illnesses, its differences among diagnoses are unclear. We compared associative learning of social values in patients with depression and schizophrenia by measuring skin conductance response to interpersonal stimuli. METHODS: We included 20 female outpatients each with depression and schizophrenia. They underwent Pavlovian conditioning experiments in response to a classical aversive sound, and an interpersonal stimulus that was designed to cause aversive social conditioning with actors' faces coupled with negative verbal messages. Multiple regression analysis was performed to examine the associations between the degree of conditioned response and the clinical characteristics of the participants. RESULTS: Conditioned responses during the acquisition phase in both conditions were higher in depression compared to schizophrenia. Patients with depression successfully showed fear conditioning in both conditions, and they exhibited slower extinction in the interpersonal condition. The conditioned response during the extinction phase showed a positive association with Emotion Regulation Questionnaire Expressive Suppression score, and a negative association with the Emotion Regulation Questionnaire Cognitive Reappraisal score and the use of antidepressants. Patients with schizophrenia did not become conditioned in either of the conditions. The Positive and Negative Syndrome Scale Negative Syndrome score was negatively associated with the degree of conditioned response during the acquisition phase in the interpersonal condition. CONCLUSION: Female patients with schizophrenia, especially those who prominently demonstrated negative symptoms, suggested their intrinsic impairments in the associative learning of social context. Antidepressants and adaptive emotional regulation strategy may enhance the extinction learning of aversive social conditioning in depression.

[THE MINIMUM NUMBER OF SPUTUM SMEAR SAMPLES NEEDED FOR THE DIAGNOSIS OF TUBERCULOSIS].

[Objective] To determine whether three sputum examinations with fluorescent staining are necessary to diag- nose tuberculosis (TB) in our hospital. [Patients] From April 2005 to December 2012, 379 TB patients were admitted and received anti-TB therapy in our hospital. [Methods] A retrospective study was conducted to assess the positivity rates of sputum smears based on three exami- nations. The positivity rate of first sputum smear and the cumulative smear-positive rates in the second and third were determined. Then, we also determined difference of positivity rates in sputum properties, sampling procedures and cavity formation. [Results] Of the 379 patients who met the screening criteria, 300 tested positive based on the first sputum smear (79.2%). The positivity rate of the first sputum smears was higher in the purulent sputum group than in the mucous sputum group (91.2% vs. 72.3%). Cavity formation, and sputum extraction procedures were not related to the positivity rate of the first sputum smears. In the mucous sputum group, the cumulative smear-positive rate in the second test significantly rose, but did not rise in the third test. [Conclusions] Three sputum smear examinations were necessary in patients who submitted mucous sputum samples. It is important to get purulent sputum.

Evaluation of the Japanese Metabolic Syndrome Risk Score (JAMRISC): a newly developed questionnaire used as a screening tool for diagnosing metabolic syndrome and insulin resistance in Japan.

OBJECTIVES: To prevent the onset of lifestyle-related diseases associated with metabolic syndrome (MetS) in Japan, research into the development of a useful screening method is strongly desired. We developed a new screening questionnaire (JAMRISC) utilizing a logistic regression model and evaluated its ability to predict the development of MetS, type 2 diabetes and other lifestyle-related diseases in Japanese populace. METHODS: JAMRISC questionnaire was sent to 1,850 individuals in Rumoi, a small city in Hokkaido. We received a total of 1,054 valid responses. To maximize the target individuals accurately diagnosed with MetS, logistic regression analysis was used to generate a unique metabolic syndrome score calculation formula as taking into consideration the clinical relevance of each question item as individual coefficients. RESULTS: The results of our comparative research utilizing both JAMRISC and Finnish Diabetes Risk Score (FINDRISC) questionnaires revealed the usefulness of JAMRISC for its ability to detect risks for MetS, pre-MetS, diabetes, and pre-diabetes. Study of disease risk detection via JAMRISC questionnaire targeting the 4283 residents of Rumoi indicated a high detection rate for pre-MetS (98.8 %), MetS (94.2 %), pre-diabetes (85.1 %) and type 2 diabetes (94.9 %). In addition, JAMRISC was useful not only as a MetS risk score test, but also as a screening tool for diagnosing insulin resistance. CONCLUSIONS: JAMRISC questionnaire is a useful instrument for the detection of early risk of not only MetS and type 2 diabetes but also insulin resistance.

[AN OUTBREAK OF PULMONARY TUBERCULOSIS DUE TO DEFINITE EXOGENOUS REINFECTION AMONG ELDERLY INDIVIDUALS IN WELFARE FACILITIES].

PURPOSE: We report an outbreak of 64 cases of tuberculosis (TB) that spread in a welfare facility for elderly individuals. OBJECTIVE AND METHODS: First, 64 TB patients who had contact with the source patient were screened at our hospital. We examined the time course up to the discovery of symptoms and analyzed the results for variable numbers of tandem repeats (VNTR) and the drug susceptibility tests. Second, we performed chest computed tomography to examine lesions due to a previous TB infection. RESULT: The source patient had recurrent aspiration pneumonia. The delay in doctor consultation was considered day 0, and the delay of diagnosis was 267 days. On examining the contacts, we found that 29 patients had TB while 35 had a latent TB infection. Results of the VNTR and the drug susceptibility tests showed that all the patients who developed TB had the same pattern as that of the source patient. Chest computed tomography showed lesions due to a previous TB infection in 8 patients. CONCLUSION: Based on the results of the VNTR and drug susceptibility tests, we concluded that the outbreak was due to an exogenous infection from the same source. All 8 patients who showed lesions due to a previous TB infection were aged > 81 years, and TB in these patients was found to be due to exogenous re-infection.

[[CASE OF TUBERCULOSIS COMPLICATIONS DURING PREGNANCY LEADING TO AN INFECTION OUTBREAK].]

A 31-year-old woman developed a constant cough during the 8th week of pregnancy and was diagnosed with bronchial asthma. She was prescribed prednisolone and inhaled corticosteroids. At 28 weeks of pregnancy, she showed worsening weight loss, fever, night sweats, hoarseness, and coughs. At 31 weeks of pregnancy, a scatter shadow and cavitary lesions were detected on the chest radiograph. Acid- fast bacilli smear test and tuberculosis (TB) polymerase chain reaction tests yielded positive results (G-8), and she was diagnosed with TB. Contact tracing and screening indicated 3 patients with TB onset and 18 patients with latent TB infec- tion attributed to the initial patient, who infected a total of 36 people. In the present case, physicians were reluctant to order a chest radiograph for fear of harming the fetus and did not order sputum or interferon gamma release (IGRA) assay tests either. The diagnosis was delayed by 152 days, which was considered as a factor that caused the outbreak. The diag- nosis of TB in a pregnant patient may be very challenging because symptoms may initially be ascribed to the pregnan- cy, and delayed diagnosis and treatment of military TB can lead to the death of the mother and fetus. Consequently, to ensure early diagnosis and treatment, chest radiography and sputum and IGRA tests are recommended for pregnant women who have TB symptoms or are at high risk for TB.

Comparison of clinical management of young and elderly asthmatics by respiratory specialists and general practitioners.

BACKGROUND: Asthmatic death in the elderly is a serious problem worldwide. Differences in clinical skill between respiratory specialists (RS) and general practitioners (GP) are important in asthma control. The aim of this study was to compare asthma management between RS and GP. METHODS: A cross-sectional survey was carried out in Shimane, Japan, in February 2009 using a questionnaire about patient background, treatment, asthma control test (ACT) and adherence to treatment. We secured the cooperation of 48 clinics (39 private clinics and 9 general hospitals). Asthmatics were divided into the elderly and young groups, and also into the RS and GP groups. RESULTS: Clinical data of 779 patients were available for analysis. Elderly patients constituted 464 (RS group: 192, GP group: 272), while those of the young group were 315 (RS group: 207, GP group: 108). RS prescribed inhaled corticosteroids (ICSs) to their elderly and young patients more than GP. The total ACT score was higher in young RS group than in young GP group, but no such difference was noted in the elderly. Despite more asthma-related symptoms, the ACT showed that elderly GP asthmatics used fewer rescue inhalers than elderly RS. Self-assessment was higher in elderly GP than elderly RS asthmatics. Adherence to therapy was better in elderly patients than young patients. CONCLUSIONS: Elderly asthmatics treated by GPs underestimated the severity of their asthma and asthmatics seen by GPs were undertreated. The results stress the need to engage patients in educational activities, to adhere to guidelines, and to improve the coordination between GP and RS.

Evaluation of the efficacy and safety of biapenem against pneumonia in the elderly and a study on its pharmacokinetics.

Although biapenem is used in the treatment of pneumonia, the clinical data on elderly patients are yet insufficient. Therefore, the purpose of this study was evaluating the efficacy and safety of biapenem against pneumonia in the elderly and its pharmacokinetics. The subjects were patients 65 years of age or older with pneumonia. Biapenem (300 mg) was administered once to three times per day. For some cases, the drug concentrations in plasma were measured chronologically. The clinical efficacy was evaluated in reference to the improvement in subjective symptoms and objective opinion. The primary outcome was efficacy rate at the end of treatment. Biapenem was effective in 17 of 20 subject cases (85.0 %). Regarding safety, although 4 cases experienced hepatic dysfunction and 1 case had nausea, these effects were not severe in all cases and administration was continued. There was no deterioration of renal function associated with biapenem. In 13 cases in which the trough value of biapenem was measured, there were no unacceptable side effects and the trough values were generally low. It is believed that biapenem (300 mg once to three times a day), even when taken by elderly people, does not accumulate and that the dosage is safe and appropriate. The changes in the predicted concentrations calculated with the pharmacokinetic-pharmacodynamic (PK-PD) software, which is based on previously reported population pharmacokinetic parameters, and those in the measured concentrations approximately matched. It is useful to plan biapenem administration using the PK-PD software when performing antibiotic chemical treatment.

Efficacy and safety of piperacillin/tazobactam versus biapenem in late elderly patients with nursing- and healthcare-associated pneumonia.

Pneumonia is associated with an extremely high mortality rate in patients of late elderly age. Piperacillin/tazobactam and carbapenems are drugs of first choice for hospitalized patients with potentially resistant bacteria. We compared the efficacy and safety of piperacillin/tazobactam and biapenem. Among elderly patients with nursing- and healthcare-associated pneumonia, we extracted 53 patients treated with piperacillin/tazobactam and 53 patients treated with biapenem who were matched for sex, age, and severity of pneumonia. The average age was more than 80 years; most of the patients were middle- to oldest old in age. Although clinical efficacy was equally good, patients in the piperacillin/tazobactam group achieved significantly faster improvements on chest X-ray and body temperature on day 7. However, in the piperacillin/tazobactam group, nephrotoxicity frequently led to a need for a reduction in the dose or complete discontinuation of treatment. The average age of patients who developed significant nephrotoxicity was high, at 83.2 years. The biapenem group exhibited significantly better continuation of treatment than the piperacillin/tazobactam group. Toxicity profiles were different between the two groups. Hepatic toxicity was significantly higher in the biapenem group, whereas nephrotoxicity was significantly more common in the piperacillin/tazobactam group. Rate of decrease in bacteria was equally good between the two groups. Providing careful follow-up and conducting more detailed examinations, including studies to determine optimal dose and timing of administration, are necessary for the treatment of late elderly patients with numerous underlying diseases and potential organ dysfunctions.

BlotGlycoABCTM, an integrated glycoblotting technique for rapid and large scale clinical glycomics.

Recent progress in mass spectrometry has led to new challenges in glycomics, including the development of rapid glycan enrichment techniques. A facile technique for exploration of a carbohydrate-related biomarker is important because proteomics research targets glycosylation, a posttranslational modification. Here we report an "all-in-one" protocol for high throughput clinical glycomics. This new technique integrates glycoblotting-based glycan enrichment onto the BlotGlycoABC bead, on-bead stabilization of sialic acids, and fluorescent labeling of oligosaccharides in a single workflow on a multiwell filter plate. The advantage of this protocol and MALDI-TOF MS was demonstrated through differentiation of serum N-glycan profiles of subjects with congenital disorders of glycosylation and hepatocellular carcinoma and healthy donors. The method also permitted total cellular glycomics analysis of human prostate cancer cells and normal human prostate epithelial cells. These results demonstrate the potentials of glycan enrichment/processing for biomarker discovery.

Language and imagined Gesellschaft: Émile Durkheim's civil-linguistic nationalism and the consequences of universal human ideals.

When Thomas Luckmann, a pioneer of the "linguistic turn" in sociology, regarded Émile Durkheim as a source for the sociology of language, he had lifeworldly community-building in mind. However, the French sociologist himself understood language in the context of civil society-building. To Durkheim, language was a "social thing in the highest degree" that enabled general ideas and intermediated them to people. Abstract human ideals like the civil religion since the French Revolution could be shared through (a common) language. Thus, Durkheim took the exclusive use of French in the Third Republic's laic public education for granted, ignoring the patois in the country: This "child of the Enlightenment" considered French to be a universal language of Gesellschaft and, beyond ethno-communal elements, to work as a basis for the organic solidarity of French national civil society where the social division of labor was progressing. Durkheim's theory was predicated on civil-linguistic, not ethnolinguistic, nationalism.

Dominant-negative p53 mutant R248Q increases the motile and invasive activities of oral squamous cell carcinoma cells.

The tumor suppressor gene TP53 (gene) codes for a transcription factor which transactivates its target genes responsible for cell cycle arrest, DNA repair, apoptosis, and senescence. TP53 is well known to be the most frequent target of genetic mutations in nearly half of human cancers including oral squamous cell carcinoma (OSCC). Many p53 mutants including R248Q and R248W not only lose its tumor-suppressor activities, but also interfere with the functions of wild-type p53; this is so-called dominant-negative (DN) mutation. The DN p53 mutation is a predictor of poor outcome in patients with various cancers, and also a risk factor for metastatic recurrence in patients with OSCC. Recently it has been reported that DN p53 mutants acquire new oncogenic activities, which is named gain-of-function (GOF). This study aimed at determining whether R248Q and R248W were involved in OSCC cells' acquiring aggressive phenotypes, using SAS, HSC4 and Ca9-22 cell lines. First, two mutants p53, R248Q and R248W, were respectively transfected into SAS cells harboring recessive-type p53 (E336X). As a result, SAS cells expressing R248Q showed highly spreading, motile and invasive activities compared to parent or mock-transfected cells whereas those expressing R248W did not increase those activities. Secondly, in HSC4 cells harboring R248Q and Ca9-22 cells harboring R248W, expressions of the mutants p53 were inhibited by the transfection with siRNAs targeting p53. The inhibition of the mutants p53 decreased spreading, motile and invasive activities of HSC4 cells whereas it did not affect those activities of Ca9-22 cells. These findings suggest that R248Q p53 mutation, but not R248W p53 mutation, induces more motile and invasive potentials in human OSCC cells.

PAX4 has the potential to function as a tumor suppressor in human melanoma.

We hypothesize that dysregulated expression levels of the developmental regulatory genes in the adult body result in tumor development and malignant progression. PAX genes discovered as human orthologous genes of Drosophila 'paired' encode transcription factors, which control the expression of target genes to go on along the program of development. In this study, we first quantified expression of 9 PAX genes in human nevus pigmentosus tissues, melanoma tissues and melanoma cell lines by the real-time reverse transcription-PCR method. As a result, we found that the expression levels of PAX4 and PAX9 were extremely low in melanoma tissues and cell lines compared to nevus pigmentosus tissues. We then established melanoma cells overexpressing PAX4 and examined roles of PAX4 in cell growth. PAX4-overexpression reduced in vitro cell growth of human melanoma C8161 and MeWo cells. BrdU-uptake assay and cell cycle analysis by flow cytometry indicated that the retardation of cell proliferation by PAX4-overexpression was due to decreased DNA synthesis and cell cycle arrest at the G0/G1 phase. Furthermore, treatment of C8161 and MeWo cells with 5-azacytidine, a DNA demethylating agent, induced the expression of PAX4, suggesting that DNA methylation repressed the PAX4 gene expression in human melanoma. These results suggest that PAX4 functions as a potent tumor suppressor.

Infiltration of Epstein-Barr virus-harboring lymphocytes occurs in a large subset of bladder cancers.

OBJECTIVE: Epstein-Barr virus (EBV) has been implicated in the genesis of a variety of human cancers. We aimed to confirm the presence and define the role of EBV in bladder cancer. METHODS: A total of 39 bladder cancer specimens were analyzed. Ten urinary bladder tissues obtained at autopsy were used as a normal control. EBV-encoded RNA (EBER) was evaluated by in situ hybridization (ISH). Frozen material available from 18 EBER-positive cases was analyzed by using reverse transcription-polymerase chain reaction for BZLF1, an early lytic gene product. The expression of CD20, CD3, ZEBRA (BZLF1 product) and transforming growth factor beta1 (TGFbeta-1) was assessed using an immunohistochemical technique. RESULTS: Infiltration of EBER-expressing lymphocytes was detected in 26 of 39 bladder cancer cases (66.7%). A small fraction of the tumor cells as well as the infiltrating lymphocytes were positive in two cases. All normal urinary bladder specimens showed negative results. The incidence of EBV-positive lymphocyte infiltration was significantly higher for advanced stage cancers than those in earlier stages (Ta-152% vs T2-4 93%, P = 0.013). The presence of BZLF1 mRNA was demonstrated in seven out of the 18 EBER-positive cases. CONCLUSIONS: Infiltration of EBV-harboring lymphocytes occurs in a large subset of bladder cancers cases. It is more frequently associated with advanced stages. EBV infection in tumor cells is very limited. Our findings suggest that EBV-positive lymphocytes might play a role in bladder cancer progression.

Effects of dietary supplementation with milk fat globule membrane on the physical performance of community-dwelling Japanese adults: a randomised, double-blind, placebo-controlled trial.

We conducted a randomised, double-blind, placebo-controlled trial to elucidate the effects of dietary milk fat globule membrane (MFGM) on the physical performance of community-dwelling Japanese adults. For this 24-week study, 115 middle-aged subjects (range 50-70 years old) were invited, of whom 113 (seventy-two women, forty-one men) completed the trial. Participants were then divided into either the placebo control or MFGM group. Measurements of physical performance (without undertaking any mandatory exercise) examining muscle strength, agility and balance were tested every 6 weeks until 24 weeks. Analyses were performed using the intention-to-treat method for all participants. Although the effects of MFGM on muscle strength and agility were not significant, we noted that the parameter for balance (such as the ability to stand on one leg with eyes closed for longer durations) increased in the MFGM group (mean 10·1 (95 % CI 8·25, 12·4) s) compared with the placebo (mean 7·53 (95 % CI 6·11, 9·30) s) (P = 0·046). Similarly, application of the mixed-effect model for repeated measures under unstructured covariance also revealed that the effect of MFGM was significant when compared with the placebo (10·2 (95 % CI 8·33, 12·4) v. 7·61 (95 % CI 6·17, 9·30) s) (P = 0·045). In conclusion, we demonstrated that MFGM had an effect on the physical performance of community-dwelling Japanese adults despite mandatory exercise. However, studies using larger cohorts of individuals from different demographic backgrounds are required to further elucidate the mechanisms underlying these effects and to extend the application of MFGM.

p53 dominant-negative mutant R273H promotes invasion and migration of human endometrial cancer HHUA cells.

Dominant negative (DN) mutations of tumor suppressor p53 (TP53) are clinically associated with cancer progression and metastasis of endometrial malignancy. To investigate the DN effect on tumor migration and invasion, we generated cells that stably co-expressed wild-type (wt) and R273H DN mutant TP53 (273H cells), and wt and R213Q recessive mutant TP53 (213Q cells), by transfection in endometrial cancer cells HHUA that expressed wt p53. R273H, but not R213Q, repressed wt p53-stimulated transcription of p21, Bax, and MDM2. 273H cells also showed markedly increased in vitro invasion and migration potentials, and displayed reduced Maspin, PAI-1, and KAI1 mRNA expressions as compared with 213Q and wt cells. The induction of wt p53 function by use of Adriamycin resulted in the inhibition of the invasion/migration capacity in association with the up-regulation of p53 target genes to a far greater degree in 213Q and wt cells than in 273H cells. R273H expression in p53-null cancer cell SK-OV-3 and Saos-2 did not significantly affect cell invasion and migration activities. Taken together, these results suggest that transdominance of R273H mutant over wt p53 rather than a gain-of-function promotes tumor metastasis by increasing invasion and migration in HHUA cells.

Low expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) indicates a shorter survival after resection in patients with adenocarcinoma of the lung.

It has been reported that an endogenous matrix metalloproteinase (MMP) inhibitor, reversion-inducing cysteine-rich protein with Kazal motifs (RECK), is able to inhibit tumour angiogenesis, invasion, and metastasis through inhibition of MMP-2, MMP-9, and membrane type-1 (MT1)-MMP (MMP-14) secretion and activity. In this study, using quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR), we have analysed RECK expression levels in resected non-small-cell lung cancer (NSCLC) tissue and compared these data with the clinicopathological features of these patients to investigate the role of RECK in NSCLC. We have also analysed the expression of MMP-2, MMP-9, and MMP-14 and compared the data with those for RECK expression. Tissue samples of primary lung cancers were obtained from a total of 83 patients [46 with adenocarcinomas (ADC) and 37 with squamous cell carcinomas (SCC)] who underwent curative resection. The samples were taken from 83 tumours and 20 matched normal lung tissue samples as controls. Expressions of RECK in ADC and SCC were significantly lower than in the control. In ADC tissue, the expression of RECK was higher in stage IA than in stage IB-IIIA. There was no such a correlation in SCC. In ADC, univariate analysis for relapse-free survival using Cox regression analysis identified low RECK expression (p=0.036), low MMP-14 expression (p=0.038), and tumour T2 (p=0.034) as significant negative prognostic predictors. However, in SCC, none of the clinicopathological factors assessed, including RECK expression, had prognostic value. In conclusion, our study suggests that suppression of RECK expression is involved in the progression of ADC of the lung and that RECK expression in resected ADC of the lung is a favorable predictor of patients' prognosis.

Dysregulated expression of HOX and ParaHOX genes in human esophageal squamous cell carcinoma.

Homeobox genes function as master regulators in embryonic morphogenesis. We hypothesized that homeobox genes are essential to maintain tissue- or organ-specificity even in adult body and that the dysregulated expression of homeobox genes results in tumor development and progression. To better understand the roles of homeobox genes in development and progression of esophageal cancer, we analyzed the expression patterns of 39 HOX genes and 4 ParaHOX (CDX1, CDX2, CDX4 and PDX1) genes in esophageal squamous cell carcinoma (ESCC) and normal esophageal mucosa tissues. A total of 48 primary ESCC tissues and 7 normal esophageal mucosa tissues were resected from patients who underwent radical surgery without any preoperative chemotherapy or radiotherapy. The expression of HOX and ParaHOX genes were analyzed by a quantitative real-time RT-PCR method and immunohistochemistry. The expression levels of 24 HOX genes, CDX1, CDX2 and PDX1 were significantly higher in ESCC compared to normal mucosa (p<0.01, Mann-Whitney U test). The Immunohistochemical study revealed that HOXA5 and D9 proteins were more cytoplasmic in ESCC than normal mucosa cells. Our data indicate that the disordered expression of HOX and ParaHOX genes are involved in the development of ESCC or its malignancy.

Early Improvement of Specific Symptoms Predicts Subsequent Recovery in Bipolar Depression: Reanalysis of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Data.

OBJECTIVE: The aim of this post hoc analysis was to evaluate which specific depressive items could predict subsequent durable recovery in patients with bipolar depression. METHODS: The study population was at least 18 years old and met DSM-IV criteria for a major depressive episode associated with either bipolar I or II disorder. The data were derived from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), in which patients with bipolar depression were randomly assigned to treatment for acute depression with a mood stabilizer plus an adjunctive antidepressant drug or placebo. The primary and secondary outcomes were durable recovery (ie, 8 consecutive weeks of euthymia) and treatment-emergent affective switch (ie, transition to mania or hypomania), respectively. Binary logistic regression analysis was performed to identify specific symptoms whose improvement during the first 2 weeks predicted those outcomes; the score change of each individual symptom in the continuous symptom subscales for depression (SUM-D) from week 0 to week 2 was used as an independent variable. RESULTS: In the evaluable 188 participants who took placebo and active drugs, the improvement in loss of self-esteem (P = .037) or loss of energy (P = .040) at week 2 was significantly associated with higher chances of subsequent durable recovery. For participants taking active drugs (n = 91), solely the improvement in loss of energy at week 2 was significantly associated with subsequent durable recovery (P = .027). There was a significant association between the improvement of psychomotor retardation at week 2 and subsequent affective switch (P = .008). CONCLUSIONS: These findings imply that focusing on individual symptoms is important in bipolar depression, rather than relying solely on a summed score in rating scales. TRIAL REGISTRATION: The original STEP-BD dataset is registered on ClinicalTrials.gov (identifier: NCT00012558).