Relapse and Outcome of Lupus Nephritis After Renal Transplantation in the Modern Immunosuppressive Era.

Background Recurrence of lupus nephritis in the graft is a concern in lupus patients with end-stage renal disease undergoing renal transplantation. The recurrence of lupus nephritis has been variable among different studies depending on the patient characteristics, immunosuppressive regimen, and indications of renal biopsy. Therefore, we investigated the recurrence of lupus nephritis among our patients to see if the new post-transplant regimen has impacted the recurrence. Methods We collected data on all recipients with end-stage renal disease secondary to lupus nephritis, who received renal transplants between 2006-2017 in our center. Patient demographics, transplant, and dialysis-related information have been recorded including kidney biopsy, graft loss, and survival were recorded. An association between recurrent lupus nephritis with survival and/or graft loss was examined using survival models. Results The overall mean±SD age at baseline was 42±13 years; 89% were female; 89% were African American; the previous time on dialysis was a median of 4 years (IQR: 2-8 years), 81% received hemodialysis and 31% received living donor transplantation in the cohort. Our patients received the standard immunosuppressive regimen consisting of prednisone, tacrolimus, and mycophenolate mofetil. Four (10.5%) of the 38 patients had biopsy-proven lupus nephritis recurrence. A total of 10 patients (26%) had graft loss or died during the median follow-up time of 1,230 days (IQR: 460-2,227 days). Recurrence of lupus nephritis showed a trend for increased risk of graft loss or patient death (Hazard Ratio: 3.14, 95%Confidence Interval: 0.65-15.24) compared to the recipient without recurrence in our unadjusted proportional Cox regression model. Conclusion The recurrence rate of lupus nephritis in our patient population is much lower compared to past studies from different immunosuppressive eras. Patients with recurrent lupus nephritis showed an increased risk of graft loss or death.

PD-L1 recruits phospholipase C and enhances tumorigenicity of lung tumors harboring mutant forms of EGFR.

Cancer immunotherapy focuses on inhibitors of checkpoint proteins, such as programmed death ligand 1 (PD-L1). Unlike RAS-mutated lung cancers, EGFR mutant tumors have a generally low response to immunotherapy. Because treatment outcomes vary by EGFR allele, intrinsic and microenvironmental factors may be involved. Among all non-immunological signaling pathways surveyed in patients' datasets, EGFR signaling is best associated with high PD-L1. Correspondingly, active EGFRs stabilize PD-L1 transcripts and depletion of PD-L1 severely inhibits EGFR-driven tumorigenicity and metastasis in mice. The underlying mechanisms involve the recruitment of phospholipase C-γ1 (PLC-γ1) to a cytoplasmic motif of PD-L1, which enhances PLC-γ1 activation by EGFR. Once stimulated, PLC-γ1 activates calcium flux, Rho GTPases, and protein kinase C, collectively promoting an aggressive phenotype. Anti-PD-L1 antibodies can inhibit these intrinsic functions of PD-L1. Our results portray PD-L1 as a molecular amplifier of EGFR signaling and improve the understanding of the resistance of EGFR+ tumors to immunotherapy.

Common paraverbal errors during hypnosis intervention training.

There is growing literature to support the use of hypnosis as an evidence-based behavioral medicine intervention to manage a wide variety of symptoms and side effects associated with cancer and its treatment (e.g., pain, nausea, fatigue). However, formal training in hypnosis is often lacking among cancer care providers. The purpose of this study is to identify common paraverbal errors among hypnosis trainees in order to inform future training efforts. In a sample of 196 hypnosis trainees, paraverbal errors (i.e., tone, pacing, and phrasing) were tracked across hypnotic intervention components. Results revealed that trainees had most difficulty with hypnotic tone, particularly during the Induction, Deepening, and Alerting components. Individual trainee characteristics were unrelated to paraverbal errors.

A Multifaceted Hypnosis Smoking-Cessation Program: Enhancing Motivation and Goal Attainment.

Smoking cessation remains a major health priority. Despite public campaigns against smoking and widespread availability of smoking-cessation treatments, many people continue to smoke. The authors argue that the "problem of motivation," that is, suboptimal or fluctuating motivation to resist smoking urges and to comply with the demands of treatment, commonly undermines treatment seeking and adherence, appreciably reducing the success rates of smoking-cessation programs. The authors describe the history of the Winning Edge smoking-cessation program and discuss ways to enhance motivation before, during, and after formal treatment. They illustrate how hypnotic suggestions, administered in the context of their program, can promote cognitive, behavioral, and emotional commitment to treatment and enhance motivation to live a smoke-free life.

Consumption of Lake Ontario sport fish and the incidence of colorectal cancer in the New York State Angler Cohort Study (NYSACS).

Fish consumption is hypothesized to reduce the risk of colorectal cancer. Nonetheless, consuming sport fish from the Great Lakes increases exposure to certain persistent organic pollutants, namely polychlorinated biphenyls (PCBs) and organochlorine insecticides, which may increase the risk of cancer. Evidence that exposure to persistent organic pollutants is associated with colorectal cancer is sparse. We examined colorectal cancer incidence in the New York State Angler Cohort Study (NYSACS), a prospective cohort of 17,110 anglers and spouses age 18-40 years at enrollment. In 1991, participants completed a mailed self-administered questionnaire that ascertained the number of years that fish from Lake Ontario were consumed, as well as potential confounders. Forty-one histologically confirmed first primary incident colorectal cancers diagnosed as of December 31, 2008 were identified via the New York State Cancer Registry. Vital status was ascertained by linkage with the Social Security Administration Death File. Rate ratios (RR) and 95% confidence intervals (CI) were calculated with Poisson regression, adjusting for age, pack-years of smoking, and sex. Compared with never consumers, colorectal cancer incidence was statistically non-significantly lower among consumers of Lake Ontario sport fish (RR=0.66; 95% CI: 0.35; 1.24). Incidence of colon cancer was lower among Lake Ontario sport fish consumers (RR=0.45, 95%CI: 0.20; 1.00). We did not observe any evidence of effect measure modification by sex or age. Although consumption of Lake Ontario sport fish may have an inverse association with colorectal cancer risk, inferences are complicated by a small number of cases and a lack of information regarding potential confounders including other dietary factors. However, our results do not provide support for the hypothesis that consumption of contaminated sport fish increases the risk of colorectal cancer.

A cross sectional study on fertility knowledge in Japan, measured with the Japanese version of Cardiff Fertility Knowledge Scale (CFKS-J).

BACKGROUND: A recent survey of 79 countries showed that fertility knowledge was lower in Japan than in any other developed country. Given the fertility decline in Japan and the importance of fertility knowledge, we conducted an online survey to examine fertility knowledge and the related factors for effective public education. METHODS: We studied people aged 18-59 years old, n = 4,328 (the "General" group), and also people who had been trying to conceive for at least six months, 18-50 years old, n = 618 (the "Triers" group). Fertility knowledge was assessed using the Japanese version of the 13-item Cardiff Fertility Knowledge Scale (CFKS-J). All participants provided socio-demographic and fertility information. Participants also completed a 14-item health literacy scale and an 11-item health numeracy scale. We asked participants who were aware of age-related decline in fertility when and where they first acquired that knowledge. RESULTS: The average percentages of CFKS-J items answered correctly were 53.1% in the Triers group and 44.4% in the General group (p < 0.001). Multivariate linear regression models showed in the Triers group greater fertility knowledge was associated with greater health literacy and prior medical consultation regarding their fertility. In the General group greater fertility knowledge was associated with being female, younger, university educated, currently trying to conceive, non-smoking, having higher household income, having higher health literacy and having higher health numeracy. Of those who were aware of the age-related decline in fertility, around 3% first learned the fact "at school", and around 65% first learned it "through mass media" or "via the Internet". More than 30% of the respondents first learned it "less than 5 years before" the survey. CONCLUSIONS: Although fertility knowledge had improved since a previous study, possibly due to recent media coverage of age-related infertility, it was still low. Educational interventions, both in schools and in the community, may be needed to increase fertility knowledge in the general population because most people obtain fertility knowledge from mass media, which has been shown to often present distorted and inaccurate fertility information.

Development of a short version of the visual function questionnaire using item-response theory.

PURPOSE: In clinical ophthalmology as in other fields, measuring patient-reported outcomes imposes a burden on patients. To decrease that burden, we used item-response theory (IRT) to develop and test a short version of the National Eye Institute's Visual Function Questionnaire (VFQ). METHODS: We analyzed VFQ data from 276 adults in Japan. Most of them had glaucoma, cataract, or macular degeneration. Their visual acuity (Snellen fraction) averaged 20/120 (range: 20/13 to 20/2000) for the better eye, and 20/200 (range: 20/13 to 20/2000) for the worse eye. We used a polytomous IRT model, the Generalized Partial Credit Model as implemented in software for parameter scaling of rating data (PARSCALE). To select items for inclusion in the short version we examined each item's location on the latent-trait continuum, its slope, and its frequency of missing data. We also ensured representation of all 7 domains that are important in Japan. To examine the characteristics of the resulting scale, we computed its test information (an index of precision that can vary with the value of the latent trait), and carried out validation testing. RESULTS: From 32 of the original VFQ items, we selected 11. The scale comprising those 11 items (the VFQ-J11) had test information greater than 9 for values of the latent trait between -2.0 and +0.8. The item thresholds were well-targeted for patients with vision problems. Scores on the VFQ-J11 correlated strongly and in the expected direction with measures of visual field and corrected visual acuity. As expected for a valid measure, those scores also improved by a large amount (almost one standard deviation) after cataract surgery. CONCLUSION: This 11-item instrument can provide reliable and the valid data on visual functioning in patients with ophthalmic problems. It is expected to be less of a burden on respondents, while it maintains good psychometric properties.

Gender-related differences in hypnosis-based treatments for smoking: a follow-up meta-analysis.

In an earlier meta-analysis of 12 studies using hypnosis-based treatments for smoking cessation, we provided preliminary evidence that males fare better than females when trying to quit smoking (Green, Lynn, & Montgomery, 2006). By excluding studies that reported no gender differences, but failed to report final outcome-statistics-by-gender, our previous conclusion may have overestimated the role of gender in hypnosis-based smoking cessation treatment. In the present analysis, we included 12 additional studies that reported no gender differences, but failed to report final outcome-by-gender statistics. Across each of these studies, we calculated identical success rates for male and female participants and then added these results to our database. Among all 24 groups of participants who completed hypnosis-based treatment for smoking, we found a small but significant effect for male participants being more successful in quitting smoking relative to females. Specific suggestions for tailoring hypnosis smoking cessation programs to take gender differences into account are discussed.

A meta-analysis of gender, smoking cessation, and hypnosis:a brief communication.

Results of a meta-analysis showed that males were more likely to report smoking abstinence than female participants following hypnosis-based treatments for smoking. Across 12 studies that used hypnosis in the treatment of smoking and reported outcome statistics by gender, the authors found that the odds of achieving smoking abstinence were 1.37 times greater for male than female participants. The results are consistent with the nonhypnosis literature suggesting that females have a more difficult time achieving smoking abstinence compared to males.

Psychometric properties of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25), Japanese version.

BACKGROUND: The importance of evaluating the outcomes of health care from the standpoint of the patient is now widely recognized. The purpose of this study is to develop and test a Japanese version of the National Eye Institute Visual Function Questionnaire (NEI VFQ-25). METHODS: A Japanese version was developed with a previously standardized method. The questionnaire and optional items were completed by 245 patients with cataracts, glaucoma, or age-related macular degeneration, by 110 others before and after cataract surgery, and by a reference group (n = 31). We computed rates of missing data, measured reproducibility and internal consistency reliability, and tested for convergent and discriminant validity, concurrent validity, known-groups validity, factor structure, and responsiveness to change. RESULTS: Based on information from the participants, some items were changed to 2-step items (asking if an activity was done, and if it was done, then asking how difficult it was). The near-vision and distance-vision subscales each had 1 item that was endorsed by very few participants, so these items were replaced with items that were optional in the English version. For example, more than 60% of participants did not drive, so the driving question was excluded. Reliability and validity were adequate for all subscales except driving, ocular pain, color vision, and peripheral vision. With cataract surgery, most scores improved by at least 20 points. CONCLUSION: With minor modifications from the English version, the Japanese NEI VFQ-25 can give reliable, valid, responsive data on vision-related quality of life, for group-level comparisons or for tracking therapeutic outcomes.

Usefulness of five-item and three-item Mental Health Inventories to screen for depressive symptoms in the general population of Japan.

BACKGROUND: The five-question Mental Health Inventory (MHI-5) is a brief questionnaire that can be used to screen for depressive symptoms. Removing the 2 anxiety-related items from the MHI-5 yields the MHI-3. We assessed the performance of the Japanese versions of the MHI-5 and MHI-3 in detecting depressive symptoms in the general population of Japan. METHODS: From the population of Japan, 4500 people 16 years old or older were selected by stratified-random sampling. The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36, which includes the MHI-5) and the Zung Self-rating Depression Scale (ZSDS) were included in a self-administered questionnaire. ZSDS scores of 48 and above were taken to indicate the presence of moderate or severe depressive symptoms, and scores of 56 and above were taken to indicate the presence of severe depressive symptoms. We computed the correlation coefficient between the ZSDS score and the scores on the MHI-5 and MHI-3. We also computed the sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve. RESULTS: Of the 3107 subjects (69% of the 4500 initially selected), 14.0% had moderate or severe depressive symptoms, and 2.0% had severe depressive symptoms as measured with the ZSDS. The correlations of ZSDS scores with MHI-5 scores and with MHI-3 scores were similar: -0.63 and -0.61, respectively. These correlation coefficients were almost the same whether or not the data were stratified by age and sex. For detecting severe depressive symptoms with the MHI-5, the area under the ROC curve was 0.942 (95%CI: 0.919 - 0.965); for the MHI-3, it was 0.933 (95%CI: 0.904 - 0.962). CONCLUSION: The MHI-5 and MHI-3 scores were correlated with the ZSDS score, and can be used to identify people with depressive symptoms in the general population of Japan.

Validation of the care notebook for measuring physical, mental and life well-being of patients with cancer.

To measure patients' QOL in the daily practice of clinical oncology, we developed and tested the Care Notebook. This instrument has 24 questions expressed in single words or short phrases to make it more acceptable to patients. The Care Notebook, EORTC QLQ-C30 and FACIT-Sp-12 were administered to 249 outpatients with cancer. Construct validity was investigated by cluster analysis and multitrait scaling analysis. The results showed that three scales (physical well-being, mental well-being, and life well-being) could explain 55% of the variance in scores. The life well-being scale could be divided into subscales of Daily Functioning, Social Functioning, and Subjective QOL. Multitrait scaling analysis confirmed convergent and discriminant validity of these scales and subscales. Internal consistency and test-retest reliability were favorable. Differences in Care Notebook scores were also consistent with differences in performance status rating (known-groups validity), and Care Notebook scores correlated with EORTC QLQ-C30 and FACT-Sp-12 scores (concurrent validity). The Care Notebook allows clinical oncologists to easily collect valid and reliable QOL information of physical, mental, and life well-being repeatedly and with minimal burden on patients.

Suramin sensitizing cells to ionizing radiation by inactivating DNA-dependent protein kinase.

Here we report that suramin sensitizes LM217, MDA-MB-468, T98G and A431 cells to ionizing radiation. Suramin sensitized cells to X radiation in a dose-dependent fashion, and longer exposure to suramin before X irradiation resulted in more efficient sensitization. The dose-modifying factors calculated from the survival curves were 1.18 in LM217 cells and 1.37 in MDA-MB-468 cells. Suramin did not sensitize Scid cells that had no DNA-dependent protein kinase activity. Suramin inhibited DNA-dependent protein kinase activity in vitro and in vivo. The concentration of suramin resulting in 50% inhibition in vitro was 1.7 microM in LM217 cells and 2.4 microM in MDA-MB-468 cells. Exposure of LM217 and MDA-MB-468 cells to suramin did not affect the level of Ku70 (G22P1) or Ku80 (XRCC5), but it increased the level of DNA-PKcs(PRKDC). Suramin did not sensitize LM217 or MDA-MB-468 cells to UV radiation. Suramin's effects were not caused by accumulation of cells in a specific phase of the cell cycle. These results suggest that suramin sensitizes cells to ionizing radiation by inhibiting DNA-dependent protein kinase activity.

Brain reorganization after stroke.

After a stroke, recovery that continues beyond 3 or 4 weeks has been attributed to plasticity, a reorganization of the brain in which functions previously performed by the ischemic area are assumed by other ipsilateral or contralateral brain areas. Neuronal plasticity has been variously attributed to redundancy (parallel distributed pathways), changes in synaptic strength, axonal sprouting with formation of new synapses, assumption of function by contralateral homologous cortex, and substitution of uncrossed pathways. Transcranial magnetic stimulation, positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and 128-electrode high-resolution electroencephalography have been successfully applied to demonstrate cortical reorganization after hemiplegia. Recording the motor potential is a promising noninvasive method for the localization of motor control after hemispheric lesions. Most patients with hemiparetic stroke show some improvement, usually during the first 3 to 6 months after the ictus. Improvement and prognosis depend on a number of variables including volume and location of the infarction, age of the patient, and the elimination of risk factors to avoid future episodes (i.e., dietary control of lipids, the elimination of tobacco, and the control of diabetes and hypertension). Currently, emphasis has been placed on fibrinolytic treatment in the first 3 hours to prevent or minimize neurological deficit. Aside from the above listed factors, improvement after stroke may be due to reorganization of the brain, particularly the cerebral cortex, and repair of damaged tissue and recanalization. It is also important to relate such changes to functional improvement and successful rehabilitation.

Reliability, validity, and responsiveness of the Japanese version of the Inflammatory Bowel Disease Questionnaire.

BACKGROUND: Inflammatory bowel disease affects the quality of a patient's life in many ways, but no validated instrument for measuring disease-specific quality of life in these patients is available in Japan. We developed a Japanese version of the Inflammatory Bowel Disease Questionnaire (IBDQ), together with the author of the original English-language version. METHODS: Translation and cross-cultural adaptation followed an accepted process. The reliability, validity, and responsiveness of the IBDQ's four subscales were then assessed in a prospective cohort of Crohn's disease patients who underwent hospitalization. RESULTS: Internal consistency was acceptable for all four subscales. Concurrent validity (with the Short Form [SF]36 as a reference) was as expected. Scores on the IBDQ could be used to discriminate patient subgroups with different levels of disease activity. Responsiveness was comparable to that of the SF36. CONCLUSIONS: This Japanese version of the IBDQ is reliable, valid, and responsive for assessing disease-specific quality of life in patients with Crohn's disease.