GPR177 promotes gastric cancer proliferation by suppressing endoplasmic reticulum stress-induced cell death.

Gastric cancer is the fourth most common cancer worldwide. Despite the high incidence of gastric cancer, efficient chemotherapy treatments still need to be developed. In this study, we examined the anticancer effects of endoplasmic reticulum (ER) stress inducer tunicamycin in gastric cancer. Previously, we found that overexpression of WLS1/GPR177 correlated with poor prognosis in patients with gastric cancer. Furthermore, tunicamycin treatment downregulated GPR177 expression in a dose-dependent manner. GPR177 transports WNT ligand from ER to the plasma membrane, mediating its secretion to the extracellular matrix. In gastric cancer cells, GPR177 preferentially localizes to the ER. Small interfering RNA-mediated knockdown of GPR177 leads to sensitization to ER stress and induces apoptosis of cancer cells along with tunicamycin treatment. GPR177 suppression promoted the ER stress-mediated proapoptotic pathway, such as PERK-CHOP cascade. Furthermore, fluorouracil treatment combined with tunicamycin dramatically reduced cancer cell proliferation. Efficacy of tunicamycin chemotherapy treatments depended on GPR177 expression in gastric cancer cell lines. Together, our results indicate that ER stress can potentiate anticancer effects and suggest GPR177 as a potential gastric cancer therapeutic target.

The quality of doctoral nursing education in South Africa.

BACKGROUND: The number of doctoral programmes in nursing has multiplied rapidly throughout the world. This has led to widespread concern about nursing doctoral education, specifically with regard to the quality of curricula and faculty, as well as to the availability of appropriate institutional resources. In South Africa, no study of these issues has been conducted at a national level. OBJECTIVE: To explore and describe the quality of nursing doctoral education in South Africa from the perspectives of deans, faculty, doctoral graduates and students. METHOD: A cross-sectional survey design was used. All deans (N = 15; n = 12), faculty (N = 50; n = 26), doctoral graduates (N = 43; n = 26) and students (N = 106; n = 63) at South African nursing schools that offer a nursing doctoral programme (N = 16; n = 15) were invited to participate. Data were collected by means of structured email-mediated Quality of Nursing Doctoral Education surveys. RESULTS: Overall, the graduate participants scored their programme quality most positively of all the groups and faculty scored it most negatively. All of the groups rated the quality of their doctoral programmes as good, but certain problems related to the quality of resources, students and faculty were identified. CONCLUSION: These evaluations, by the people directly involved in the programmes, demonstrated significant differences amongst the groups and thus provide valuable baseline data for building strategies to improve the quality of doctoral nursing education in South Africa.

Collagenous micronodules in prostate cancer revisited: are they solely associated with Gleason pattern 3 adenocarcinomas?

Collagenous micronodules (CMs) are microscopic stromal nodular eosinophilic fibrillar collagen deposition of uncertain histogenesis seen in prostatic adenocarcinoma. Per the 2005 International Society of Urologic Pathology (ISUP) consensus conference, they are categorized as Gleason pattern 3. This study analyzes morphological and clinical features of CMs from a large series of radical prostatectomies. Hematoxylin and eosin stained slides for 129 radical prostatectomies for adenocarcinoma of prostate with CMs and for 93 prostatic adenocarcinoma cases without CMs as comparison were examined out of a total of 667 cases performed from January 2010 to December 2011 at Houston Methodist Hospital. CMs were identified in 19% of all radical prostatectomies (129/667 cases). Almost all tumors with CMs were located in the peripheral zone (98%) as single or multiple foci of prostatic cancer glands. The vast majority of cases (96%) were identified in association with mucinous secretion. A cribriform Gleason pattern 4 was associated in 86 cases (67%). The CMs were associated with glomerulation (42%) and amphophilic luminal secretion (59%). 88 cases (68%) showed tumor foci with Gleason pattern ≥ 4 in close association with CMs. Multivariate analysis revealed CMs of the prostatic adenocarcinoma are closely related to mucinous secretion, cribriform growth pattern, and Gleason pattern 4. This study suggests that CMs are more frequently associated with Gleason pattern 4 cancer warranting morphologic reappraisal of CMs, rather than the consensus assignment of Gleason pattern 3.

Sustained release of amnion-derived cellular cytokine solution facilitates achilles tendon healing in rats.

OBJECTIVE: In the United States, around 50% of all musculoskeletal injuries are soft tissue injuries including ligaments and tendons. The objective of this study is to assess the role of amnion-derived cellular cytokine solution (ACCS) in carboxy-methyl cellulose (CMC) gel in the healing of Achilles tendon in a rat model, and to examine its effects on mechanical properties and collagen content. METHODS: Achilles tendons of Sprague-Dawley rats were exposed and transected. The distal and proximal ends were injected with either saline or ACCS in CMC, in a standardized fashion, and then sutured using a Kessler technique. Tendons from both groups were collected at 1, 2, 4, 6, and 8 weeks postoperatively and assessed for material properties. Collagen studies were performed, including collagen content, collagen cross-linking, tendon hydration, and immunohistochemistry. Tendons were also evaluated histologically for cross-sectional area. RESULTS: Mechanical testing demonstrated that treatment with ACCS in CMC significantly enhances breaking strength, ultimate tensile strength, yield strength, and Young's modulus in the tendon repair at early time points. In context, collagen content, as well as collagen cross-linking, was also significantly affected by the treatment. CONCLUSION: The application of ACCS in CMC has a positive effect on healing tendons by improving mechanical properties at early time points. Previous studies on onetime application of ACCS (not in CMC) did not show significant improvement on tendon healing at any time point. Therefore, the delivery in a slow release media like CMC seems to be essential for the effects of ACCS demonstrated in this study.

Periodic alternating nystagmus of peripheral vestibular origin.

OBJECTIVES/HYPOTHESIS: Periodic alternating nystagmus (PAN) is most commonly found either in its congenital form or after cerebellar/pontomedullary lesions. However, we identified PAN in 10 patients with peripheral vestibular disorders and will try to describe their characteristics to aid in the differential diagnosis between peripheral and central etiologies. STUDY DESIGN: Observation of a case series. METHOD: Peripheral vestibular lesions were confirmed by neurological examinations, vestibular function tests, and brain magnetic resonance imaging (MRIs). Eye movements of the patients were recorded using electronystagmography or video nystagmography for a minimum of 10 minutes to confirm the nystagmus change in direction. RESULTS: The final diagnoses of the patients included Meniere's disease (n = 3), acute labyrinthitis (n = 4), sudden sensorineural hearing loss with vertigo (n = 2), and vestibular schwannoma (n = 1). Direction-changing spontaneous horizontal nystagmus with quiescent intervals was observed in all patients under dark conditions. The nystagmus was suppressed by visual fixation; and the results of oculomotor tests were normal for saccadic and smooth pursuit eye movements and optokinetic nystagmus. All patients showed mild to complete canal paresis on a bithermal caloric test. PAN progressed into unidirectional nystagmus of the contra-lesion side in all patients within 48 hours. CONCLUSION: PAN can be observed in patients with peripheral vestibular disorders, but detecting PAN in this subpopulation is difficult because of its transitory nature. The absence of central symptoms and signs, the visual suppression of PAN, normal oculomotor tests, and transient persistence are important diagnostic clues for differentiating peripheral from central PAN. LEVEL OF EVIDENCE: 4.

Subsets of microsatellite-unstable colorectal cancers exhibit discordance between the CpG island methylator phenotype and MLH1 methylation status.

Although the presence of MLH1 methylation in microsatellite-unstable colorectal cancer generally indicates involvement of the CpG island methylator phenotype (CIMP) in the development of the tumor, these two conditions do not always correlate. A minority of microsatellite-unstable colorectal cancers exhibit discordance between CIMP and MLH1 methylation statuses. However, the clinicopathological features of such microsatellite-unstable colorectal cancers with discrepant MLH1 methylation and CIMP statuses remain poorly studied. Microsatellite-unstable colorectal cancers (n=220) were analyzed for CIMP and MLH1 methylation statuses using the MethyLight assay. Based on the combinatorial CIMP and MLH1 methylation statuses, the microsatellite-unstable colorectal cancers were grouped into four subtypes (CIMP-high (CIMP-H) MLH1 methylation-positive (MLH1m+), CIMP-H MLH1 methylation-negative, CIMP-low/0 (CIMP-L/0) MLH1m+, and CIMP-L/0 MLH1 methylation-negative), which were compared in terms of their associations with clinicopathological and molecular features. The CIMP-L/0 MLH1 methylation-negative and CIMP-H MLH1m+ subtypes were predominant, comprising 63.6 and 24.1% of total microsatellite-unstable colorectal cancers, respectively. The discordant subtypes, CIMP-H MLH1 methylation-negative and CIMP-L/0 MLH1m+, were found in 5 and 7% of microsatellite-unstable colorectal cancers, respectively. The CIMP-H MLH1 methylation-negative subtype exhibited elevated incidence rates in male patients and was associated with larger tumor size, more frequent loss of MSH2 expression, increased frequency of KRAS mutation, and advanced cancer stage. The CIMP-L/0 MLH1m+ subtype was associated with onset at an earlier age, a predominance of MLH1 loss, and earlier cancer stage. None of the CIMP-L/0 MLH1m+ subtype patients succumbed to death during the follow-up. Our findings suggest that the discordant subtypes of colorectal cancers exhibit distinct clinicopathological and molecular features, although the proportion of discordant subtypes is low. The microsatellite-unstable colorectal cancers of the same CIMP status tended to exhibit different clinicopathological features depending on MLH1 methylation status.

Multilocus variable-number tandem-repeat analysis for subtyping Salmonella enterica serovar Gallinarum.

Salmonella enterica serovar Gallinarum causes a severe systemic disease, fowl typhoid, primarily in chickens and turkeys, and it remains a disease of worldwide significance. Multilocus variable-number tandem-repeat analysis (MLVA) has proved to be very useful for subtyping other Salmonella serovars. We describe the development of a simple MLVA assay for S. enterica serovar Gallinarum that is comparable with pulsed-field gel electrophoresis (PFGE) in resolution. The genome sequence of S. enterica serovar Gallinarum strain 287/91 was analysed for potential variable-number tandem repeats (VNTRs) and then polymerase chain reaction assays were developed to assess the variability of the loci. Four VNTR markers were selected and used in a multiplex fragment analysis assay. The stability of the VNTR markers was assessed by conducting in vitro passage experiments with two strains (95 clones per strain) over a 30-day period. A MLVA of 68 strains of S. enterica serovar Gallinarum based on the four VNTR loci distinguished 26 allelic profiles. The MLVA assay showed a Simpson's diversity index of 0.918, whereas PFGE analysis produced 23 patterns and had a diversity index of 0.874. Most importantly, the MLVA further discriminated strains having the same PFGE pattern. The MLVA assay is a highly discriminatory genotyping method for S. enterica serovar Gallinarum. Therefore, MLVA can be a useful addition to routine PFGE analysis for molecular epidemiological investigation of fowl typhoid.

Provocative lumbar discography versus functional anesthetic discography: a comparison of the results of two different diagnostic techniques in 52 patients with chronic low back pain.

BACKGROUND CONTEXT: There is mounting evidence that the currently available techniques for the diagnosis of discogenic low back pain are insufficiently accurate-this may explain some of the variability in outcomes of surgery for this important clinical problem. New diagnostic methods are needed to address this diagnostic issue; improvements here may do as much to improve overall patient outcomes as improvements in surgical treatment methods. PURPOSE: To compare the results of standard pressure-controlled provocative discography (PD) to those of the functional anesthetic discogram (FAD) in a series of patients presenting with chronic low back pain and considering surgical treatment. STUDY DESIGN: Prospective clinical series in an academic spinal surgical practice. PATIENT SAMPLE: Fifty-two patients presenting with chronic low back pain; mean age 45 years (range, 24-70 years); 28 women, 24 men; and 25% in workman's compensation program. OUTCOME MEASURES: Oswestry, visual analog scale for back pain, distress and risk assessment method psychometric analysis, demographic data, magnetic resonance imaging scan of lumbar spine. During provocative discogram: pressurization at pain, pain level, and concordancy. During FAD: position or activity used to elicit typical pain, baseline pain level before injection, during injection, at 5, 10, and 20 minutes after the injection, and substance injected. METHODS: Standard pressure-controlled PD was performed, followed by (in positive cases or in patients with clinical features and imaging studies felt to be highly suggestive of symptomatic disc degeneration) the FAD test-an assessment of the response to injection of a low dose of local anesthetic into the disc during a position productive of the patient's typical pain. RESULTS: Discordant results of the two tests were noted in 46% of the patients in the series. Of them, 26% of patients with positive PD had negative findings on the FAD test; 16% had positive findings at a single level only, whereas the provocative discogram had been positive at two or more levels; 4% had new positive findings on the FAD test. CONCLUSIONS: We have presented the results of a new diagnostic technique in 52 patients with chronic low back pain presumed discogenic in origin that was designed to help differentiate between symptomatic and asymptomatic disc degeneration. The findings of the test differed from those of standard pressure-controlled PD in 46% of the cases reported on here. Further studies are needed to demonstrate the clinical utility of the test.

Lateralized effects of unilateral thalamotomy and thalamic stimulation in patients with essential tremor.

BACKGROUND AND PURPOSE: Stereotactic thalamotomy has been an effective surgical procedure in the treatment of medically refractory essential tremor (ET), however, little is known about the bilateral effects of unilateral ventralis intermedius (Vim) thalamotomy and Vim deep brain stimulation (DBS). We studied the lateralized effects of unilateral Vim thalamotomy and Vim DBS in ET patients. METHODS: Vim thalamotomy was performed in 6 patients and Vim DBS in 6. Patients were evaluated preoperatively and at 3 and 6 months postoperatively using the Clinical Rating Scale for Tremor (CRST). RESULTS: The contralateral Part A (tremor localization/severity rating) and Part B (specific motor tasks/function rating) subscores, and axial subscores of CRST significantly improved after unilateral Vim thalamotomy or Vim DBS. On the side ipsilateral to surgery, ET patients demonstrated no significant improvements in the Part A and Part B subscores of CRST. The Part C (functional disabilities resulting from tremor) subscores and total scores of CRST were significantly improved after surgery. CONCLUSIONS: Vim thalamotomy and DBS may be equally effective for the management of contralateral and axial tremor in ET patients, but both interventions may not improve tremor on the side ipsilateral to surgery.

Comparing adolescents' adjustment and family resilience in divorced families depending on the types of primary caregiver.

AIMS: This study compared three different types of primary caregiver in divorced families: father, mother and grandparent(s) and aimed to (1) compare adolescents' perception of their level of adjustment and family resilience and (2) identify the family resilience predictors of adolescents' adjustment. BACKGROUND: The Resiliency Model of Family Stress, Adjustment and Adaptation guided this study. DESIGN: Survey. METHOD: Adolescents in divorced families in Korea (n = 178) completed self-administered questionnaires. Family resilience was measured by Family Hardiness Index, Family Crisis Oriented Personal Evaluation Scale, Parent-Adolescent Communication Inventory, Social Support Appraisal Scale, Belief about Parental Divorce and Self-Esteem Scale. Korean-Child Behaviour Checklist was used to assess adolescents' adjustment. Descriptive statistics, chi-square test, anova, ancova and multiple regression analysis were used for data analysis. RESULTS: The level of adolescents' adjustment was not statistically different among the three groups. However, statistically significant differences were found in family hardiness, family communication and problem-solving/coping skill-seeking help among the family resilience measurements. Adolescents living with mothers reported the highest scores in family hardiness and family communication. The grandparent(s) group sought and accepted help outside of the family more often than did the other groups. Regardless of the types of primary caregiver, a common significant predictor for adolescents' adjustment was their positive belief about parental divorce; whereas high self-esteem and low level of seeking help were additional predictors for the father group and grandparent(s) group, respectively. CONCLUSIONS: Adolescents' belief about parental divorce is a major predictor for adolescents' adjustment to divorced family life. Nursing services that maximise the family resilience predictors found in this study would enhance adolescents' adjustment in divorced families. RELEVANCE TO CLINICAL PRACTICE: This study provides empirical evidence for nursing care of adolescents who live with differing primary caregivers in divorced families and enhances nurses' understanding of family resilience predictors that influence adolescents' adjustment in divorced families.

Levosulpiride-induced movement disorders.

Levosulpiride is a substituted benzamide that is widely used for the management of dyspepsia and emesis. However, little is known about levosulpiride-induced movement disorders (LIM). The aim of this study was to investigate the clinical characteristics of patients with LIM. Among 132 consecutive patients who were diagnosed with drug-induced movement disorders between January 2002 and March 2008, 91 patients with LIM were identified and their medical records reviewed. Seventy-eight (85.7%) patients were aged more than 60 years. The most common LIM was parkinsonism (LIP) (n = 85, 93.4%), followed by tardive dyskinesia (n = 9, 9.9%) and isolated tremor (n = 3, 3.3%). Twenty-one (24.7%) of the 85 patients with LIP were rated as Hoehn and Yahr stage III-V. The oro-lingual area was the only body part that was involved by tardive dyskinesia. LIM persisted after withdrawal of levosulpiride in 48.1% of patients with LIP, 66.7% with dyskinesia, and none with isolated tremor. None of clinical and MRI features predicted the reversibility of LIP. Levosulpiride frequently causes drug-induced movement disorders, presenting mainly with LIP followed by lower face dyskinesia. The symptoms are often severe, and irreversible even after the withdrawal of levosulpiride. Physicians should be cautious in using levosulpiride, especially in elderly patients.

Functional brain imaging in pure akinesia with gait freezing: [18F] FDG PET and [18F] FP-CIT PET analyses.

Pure akinesia with gait freezing (PAGF) has characteristic features, including freezing of gait and prominent speech disturbance without rigidity or tremor. The purpose of this study was to investigate changes in brain glucose metabolism and presynaptic dopaminergic function in PAGF. By using [(18)F] fluorodeoxyglucose (FDG) PET, 11 patients with PAGF were compared with 14 patients with probable progressive supranuclear palsy (PSP), 13 patients with Parkinson's disease (PD), and 11 normal controls. [(18)F] N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane (FP-CIT) PET was performed in 11 patients with PAGF and with 10 normal controls. The PAGF patients showed decreased glucose metabolism in the midbrain when compared with normal controls. PSP patients showed a similar topographic distribution of glucose hypometabolism with additional areas, including the frontal cortex, when compared with normal controls. The FP-CIT PET findings in patients with PAGF revealed severely decreased uptake bilaterally in the basal ganglia. These findings suggest that both PAGF and PSP may be part of the same pathophysiologic spectrum of disease. However, the reason why PAGF manifests clinically in a different manner needs to be further elucidated.

Effect of thalamotomy on focal hand dystonia in a family with DYT1 mutation.

We report the clinical and molecular features of a family with focal hand dystonia caused by DYT1 mutation. Four members of a family who underwent thalamotomy showed a marked and sustained therapeutic benefit that lasted for up to 12 years without recurrence of dystonia or any significant surgical complication. The hand dystonia caused by DYT1 mutation may be successfully managed by thalamotomy.

Effects of a Web-based teaching method on undergraduate nursing students' learning of electrocardiography.

This study examined the effects of a Web-based teaching method (versus a traditional lecture method) on undergraduate nursing students' learning of electrocardiography (ECG). The Web-based learning program was developed by the authors and implemented for 4 weeks. The study used a pretest-posttest experimental design. A total of 105 senior nursing students were recruited at a university in Korea. Fifty-four students were assigned to an experimental group in 2002, and 51 were assigned to a control group in 2003. Knowledge about ECG among students in the Web-based group was significantly lower than that of students in the control group (p < .01). Conversely, the ability to interpret ECG recordings was significantly higher among students in the Web-based group (p < .05). No significant differences were found between the two groups in level of motivation or satisfaction with learning. The self-directed, Web-based ECG learning program appears to be effective in helping nursing students to interpret ECG recordings.