Accelerated long-term forgetting reveals everyday memory deficits in early-stage multiple sclerosis.

BACKGROUND: Patients with multiple sclerosis (MS) patients report subjective memory impairment (SMI) escaping routine neuropsychological testing. Accelerated long-term forgetting (ALF) refers to above average loss of information over an extended period of time (e.g., 7 days). This study investigates ALF in mildly affected MS patients and relates long-term memory performance to SMI. METHODS: This prospective study included 30 patients with early MS (mean EDSS ± SD = 1.1 ± 0.9) and 30 healthy controls (HC) matched for age and education. Participants underwent ALF testing [word list (RAVLT), geometric figure (RCF), logical memory (WMS)] at three time points (baseline, 30 min, 7 days). Cognition (Montreal Cognitive Assessment), depression, SMI and fatigue were assessed. The primary outcome (PO) was defined as the quotient of the 7-day score and the 30-min memory score for the verbal (RAVLT, WMS) and figural (RCF) memory tests. The study was approved by the local ethics committee and is registered in the German Register of Clinical Studies (DRKS00025791). RESULTS: MS patients showed impairments in PORAVLT (MS 0.66 ± 0.13 vs HC 0.82 ± 0.16; p < 0.001), whereas POWMS (MS 0.88 ± 0.15 vs HC 1.01 ± 0.12; p = 0.02) showed only a tendency. Regression analysis revealed significant associations for PORAVLT and fatigue (p = 0.034), and PORAVLT and SMI (p = 0.01) in patients but not in HC. CONCLUSION: The ALF test quantifies SMI in MS-patients. With fatigue as a relevant associated factor, this fills the gap in objectifying SMI in MS for diagnostic purposes.

Comparison of sulfolane effects in Sprague Dawley rats, B6C3F1/N mice, and Hartley guinea pigs after 28 days of exposure via oral gavage.

Sulfolane is a solvent used in industrial refining with identified environmental exposure in drinking water. Due to potential large species differences, the National Toxicology Program (NTP) conducted 28-day toxicity studies in male and female Hsd:Sprague Dawley® SD® rats, B6C3F1/N mice, and Hartley guinea pigs. A wide dose range of 0, 1, 10, 30, 100, 300, and 800 mg/kg was administered via gavage. Histopathology, clinical pathology, and organ weights were evaluated after 28 days of exposure. In addition, plasma concentrations of sulfolane were evaluated 2 and 24 h after the last dose. Increased mortality was observed in the highest dose group of guinea pigs and mice while decreased body weight was observed in rats compared to controls. Histopathological lesions were observed in the kidney (male rat), stomach (male mice), esophagus (male and female guinea pigs), and nose (male guinea pigs). Plasma concentrations were generally higher in rats and guinea pigs compared to mice with evidence of saturated clearance at higher doses. Male rats appear to be the most sensitive with hyaline droplet accumulation occurring at all doses, although the human relevance of this finding is questionable.

Babesia gibsoni infection in dogs in Poland.

Canine babesiosis is a tickborne, protozoal, haemoparasitic disease. Babesia organisms are frequently classified as either large (B. canis) or small (B. gibsoni). The aim of this study was an attempt to detect B. gibsoni DNA in blood samples taken from dogs suspected of suffering from tick-borne diseases. 216 samples were tested using PCR, of which, in 99 of them B. canisDNA was detected, whereas in 3 of them B. gibsoni was detected. Positive PCR results for B. gibsoni were confirmed using a Qube MDx real-time analyzer. The results indicate that infec-tions with this B. gibsoni should be taken into account and included in the differential diagnosis of vector-borne diseases in dogs in Poland, and that the accurate identification of the species of parasite causing the infection is crucial for developing the correct treatment regimen and prognosis.

A systematic review on the effect of work-related stressors on mental health of young workers.

PURPOSE: There is no review on the effect of work-related stressors on mental health of young workers. We systematically reviewed epidemiological evidence on this relationship. METHODS: The review searched eight databases: Embase, PubMed, Web of Science, Cinahl, Cochrane Library, Informit, PsycINFO, and Scopus from their respective start dates until May 2017. Studies that have examined a mental health outcome in relation to a work-related stressor as exposure in young workers were included. The review was reported based on the PRISMA statement. RESULTS: Three cross-sectional studies and six longitudinal cohort studies were included. Cross-sectional evidence showed that adverse work conditions including working overtime, job boredom, low skill variety, low autonomy, high job insecurity, and lack of reward were associated with poor mental health of young workers. Longitudinal evidence showed that high job demands, low job control, effort-reward imbalance, and low work support (men only) were associated with poor mental health. There was evidence on the contemporaneous relationship between two or more adverse work conditions and poor mental health. CONCLUSIONS: Although more research (particularly high-quality longitudinal studies) is warranted in this area, our review indicates that work-related stressors have a negative impact on the mental health of young workers. The current review suggests that workplace interventions and policy are required to improve the quality of work for young workers.

The relationship between an electronic mental health stigma campaign and suicidal thoughts and behaviours: a two-arm randomized controlled trial in the Australian construction industry.

Males employed in the construction industry are at greater risk of suicide than other employed males. It is plausible that a high level of stigma against mental health problems explains the elevated rates of suicide among this group. This study sought to test the effectiveness of an electronic mental health stigma intervention on suicide ideation, communication about suicide and attempts. Participants were randomly assigned to receive either a series of brief contact interventions over a 6-week period or a wait list control. Suicidal ideation, communication about suicide and suicide attempts were assessed using the Suicidal Behaviors Questionnaire-Revised at post-intervention. We used linear regression to assess effectiveness at post-intervention, adjusting for relevant covariates using both conventional methods and a propensity score approach. Results indicate that the intervention had no significant impact on suicidal thoughts, communication or suicide attempts. There was some indication that individuals in the intervention group reported a slight increase in attempts and communication about suicide. These observations underscore an urgent need for more research to understand the complex and nuanced relationship between stigma and suicide in non-clinical populations.

Simultaneous removal of a locking plate and implantation of a reversed shoulder prosthesis in elderly patients suffering from fracture sequelae of the proximal humerus.

PURPOSE: Open reduction and internal fixation with a locking plate are performed frequently to treat fractures of the proximal humerus. Avascular necrosis and non-union or malunion are potential complications of this procedure, which lead to specific fracture sequelae. The aim of this study was to investigate the clinical and radiological results of patients treated by removal of a failed locking plate of the proximal humerus and simultaneous implantation of a reverse total shoulder prosthesis. METHODS: Twenty-one patients (f = 17, m = 4; mean age 70 years) out of 29 patients were available for follow-up after a mean period of 45 (30-65) months. At follow-up, all patients were assessed with the constant score and the ASES score as well as plain radiographs. RESULTS: In comparison with the preoperative values, abduction (31° vs. 115°; p < 0.001) and forward flexion (34° vs. 121°; p < 0.001) improved until follow-up, while the pain score on a visual analog scale decreased (6.7 vs. 0.9; p < 0.001). At follow-up, the mean ASES score rated 73 and the constant score rated 62. The radiologic findings included scapular notching (n = 7; 33%), radiolucency (n = 4; 19%), heterotopic ossifications (n = 3; 14%), and stress shielding (n = 4; 19%). CONCLUSION: Reverse total shoulder arthroplasty is a useful instrument for the treatment of failed locking plate osteosynthesis of the proximal humerus in elderly patients. The patients benefit from both pain relief and improved shoulder function. The rate of radiologic changes like scapular notching, radiolucency, stress-shielding and heterotopic ossifications at follow-up is notable.

Adverse events associated with deep brain stimulation in patients with childhood-onset dystonia.

BACKGROUND: Data on pediatric DBS is still limited because of small numbers in single center series and lack of systematic multi-center trials. OBJECTIVES: We evaluate short- and long-term adverse events (AEs) of patients undergoing deep brain stimulation (DBS) during childhood and adolescence. METHODS: Data collected by the German registry on pediatric DBS (GEPESTIM) were analyzed according to reversible and irreversible AEs and time of occurrence with relation to DBS-surgery: Intraoperative, perioperative (<4 weeks), postoperative (4 weeks < 6 months) and long term AEs (>6 months). RESULTS: 72 patients with childhood-onset dystonia from 10 DBS-centers, who received 173 DBS electrodes and 141 implantable pulse generators (IPG), were included in the registry. Mean time of postoperative follow-up was 4.6 ±â€¯4 years. In total, 184 AEs were documented in 53 patients (73.6%). 52 DBS-related AEs in 26 patients (36.1%) required 45 subsequent surgical interventions 4.7 ±â€¯4.1 years (range 3 months-15 years) after initial implantation. The total risk of an AE requiring surgical intervention was 7.9% per electrode-year. Hardware-related AEs were the most common reason for surgery. There was a tendency of a higher rate of AEs in patients aged 7-9 years beyond 6 months after implantation. DISCUSSION: The intraoperative risk of AEs in pediatric patients with dystonia undergoing DBS is very low, whereas the rate of postoperative hardware-related AEs is a prominent feature with a higher occurrence compared to adults, especially on long-term follow-up. CONCLUSION: Factors leading to such AEs must be identified and patient management has to be focused on risk minimization strategies in order to improve DBS therapy and maximize outcome in pediatric patients.

Life-threatening DBS withdrawal syndrome in Parkinson's disease can be treated with early reimplantation.

INTRODUCTION: The deep brain stimulation (DBS) withdrawal syndrome (DBS-WDS) is a rare, life-threatening complication in Parkinson's disease (PD) patients with long disease duration and stimulation when stimulation is terminated for extended periods mostly due to infection of the DBS-hardware. METHODS, RESULTS: In five patients explantation became necessary because of infection after a mean of 11.4 years (range 4-15 years) of DBS and a mean disease duration of 24.6 years (range 3-22 years). Mean UPDRS motor-score pre-explantation was 38 points (range 24-55 points) which increased to a mean of 78.4 points (range 58-90 points) after explantation, despite optimal Levodopa dosing. Reimplantation of the hardware after 23 days (range 3-45 days) under antibiotic treatment led to an improvement to a mean of 40 points (range 25-73 points) and a complication free survival. CONCLUSION: Early reimplantation of the DBS-hardware is a treatment option of the DBS-WDS when the life-threatening urgency overrides surgical standards. Observation of the syndrome indicates pharmacological unresponsiveness of the dopaminergic system in advanced PD and long-term DBS.

Five-year outcome after conversion of a hemiarthroplasty when used for the treatment of a proximal humeral fracture to a reverse total shoulder arthroplasty.

Aims: The reasons for failure of a hemirthroplasty (HA) when used to treat a proximal humeral fracture include displaced or necrotic tuberosities, insufficient metaphyseal bone-stock, and rotator cuff tears. Reverse total shoulder arthroplasty (rTSA) is often the only remaining form of treatment in these patients. The aim of this study was to evaluate the clinical outcome after conversions from a failed HA to rTSA. Material and Methods: A total of 35 patients, in whom a HA, as treatment for a fracture of the proximal humerus, had failed, underwent conversion to a rTSA. A total of 28 were available for follow-up at a mean of 61 months (37 to 91), having been initially reviewed at a mean of 20 months (12 to 36) postoperatively. Having a convertible design, the humeral stem could be preserved in nine patients. The stem was removed in the other 19 patients and a conventional rTSA was implanted. At final follow-up, patients were assessed using the American Shoulder and Elbow Surgeons (ASES) score, the Constant Score, and plain radiographs. Results: At final follow-up, the mean ASES was 59 (25 to 97) and the mean adjusted Constant Score was 63% (23% to 109%). Both improved significantly (p < 0.001). The mean forward flexion was 104° (50° to 155°) and mean abduction was 98° (60° to 140°). Nine patients (32%) had a complication; two had an infection and instability, respectively; three had a scapular fracture; and one patient each had delayed wound healing and symptomatic loosening. If implants could be converted to a rTSA without removal of the stem, the operating time was shorter (82 minutes versus 102 minutes; p = 0.018). Conclusion: After failure of a HA in the treatment of a proximal humeral fracture, conversion to a rTSA may achieve pain relief and improved shoulder function. The complication rate is considerable. Cite this article: Bone Joint J 2018;100-B:761-6.

Suicidio entre los trabajadores agrícolas, forestales y pesqueros: una revisión sistemática de la literatura y un metaanálisis / Suicide agricultural, forestry and fishery workers: a systematic literature review and meta-analysis

Objetivos: Cuantificar el riesgo de suicidio entre los trabajadores agrícolas, forestales y pesqueros, y analizar las posibles variaciones del riesgo dentro de esta población. Métodos: Revisión sistemática de la literatura y un metaanálisis de los años 1995 al 2016 utilizando MEDLINE y siguiendo las recomendaciones de PRISMA. Se calculó el efecto agrupado del riesgo de suicidio entre la población de interés mediante la técnica del metaanálisis. Se realizaron análisis de subgrupos para evaluar si el tamaño del efecto difería según la población o las características del estudio. La meta regresión se utilizó para identificar fuentes de heterogeneidad. Resultados: La revisión sistemática identificó 65 estudios, de los cuales se incluyeron 32 en el metaanálisis. El tamaño del efecto agrupado fue de 1,48 (IC95% 1,30-1,68). El análisis de subgrupos mostró que el efecto varió según el área geográfica, por ejemplo, en Japón mostró un riesgo más alto. Las siguientes características contribuyeron a la varianza entre los estudios: grupo de referencia, medida del tamaño del efecto y diseño del estudio. Conclusiones: Los hallazgos sugieren un exceso de riesgo de suicidio entre los trabajadores agrícolas, forestales y pesqueros, y demostraron que este exceso puede ser incluso mayor para estos grupos de trabajadores en Japón. Esta revisión destaca la necesidad de implementar políticas de prevención del suicidio enfocado a esta población específica de trabajadores. También se necesita más investigación para comprender los factores fundamentales que pueden aumentar el riesgo de suicidio en este colectivo

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A smart-phone intervention to address mental health stigma in the construction industry: A two-arm randomised controlled trial.

BACKGROUND: High levels of self-stigma are associated with a range of adverse mental health, treatment, and functional outcomes. This prospective study examined the effects of an electronic mental health stigma reduction intervention on self-stigma (self-blame, shame, and help-seeking inhibition) among male construction workers in Australia. METHOD: Male construction workers (N = 682) were randomly assigned to receive either the intervention condition or the wait list control over a six-week period. Self-stigma was assessed using the Self-Stigma of Depression Scale at post-intervention. We conducted linear regression to assess the effectiveness of the intervention on self-stigma, adjusting for relevant covariates. RESULTS: Self-stigma was relatively low in the sample. The intervention had no significant effect on self-stigma, after adjusting for confounders. There were reductions in stigma in both the intervention and control groups at 6-week follow-up. Process evaluation indicated that participants generally enjoyed the program and felt that it was beneficial to their mental health. CONCLUSIONS: These observations underscore the need for further research to elucidate understanding of the experience of self-stigma among employed males.

Spatial orientation and postural control in patients with Parkinson's disease.

Postural instability is one of the most disabling and risky symptoms of advanced Parkinson's disease (PD). The purpose of this study was to investigate whether and how this is mediated by a centrally impaired spatial orientation. Therefore, we performed a spatial orientation study in 21 PD patients (mean age 68years, SD 8.5 years, 9 women) in a medically on condition and 21 healthy controls (mean age 68.9years, SD 5.5years, 14 women). We compared their spatial responses to the horizontal axis (Sakashita's visual target cancellation task), the vertical axis (bucket-test), the sagittal axis (tilt table test) and postural stability using the Fullerton Advanced Balance Scale (FAB). We found larger deviations on the vertical axis in PD patients, although the direct comparisons of performance in PD patients and healthy controls did not reveal significant differences. While the total scores of the FAB Scale were significantly worse in PD (25.9 points, SD 7.2 points) compared to controls (35.1 points, SD 2.3 points, p<0.01), the results from the spatialorientation task did not correlate with the FAB Scale. In summary, our results argue against a relation between perceptional deficits of spatial information and postural control in PD. These results are in favor of a deficit in higher order integration of spatial stimuli in PD that might influence balance control.

Suicide among emergency and protective service workers: A retrospective mortality study in Australia, 2001 to 2012.

BACKGROUND: Emergency and protective services personnel (e.g., police, ambulance, fire-fighters, defence, prison and security officers) report elevated levels of job stress and health problems. While population-level research is lacking, there has been some research suggesting suicide rates may be elevated in emergency and protective services. OBJECTIVES: This paper compares suicide rates between emergency and protective services occupational groups over a 12-year period (2001-2012) in Australia. METHOD: Labour force data was obtained from the 2006 Australian Census. Suicide data was obtained from the National Coroners Information System (NCIS). Negative binomial regression was used to estimate the association between suicide and employment as an emergency or protective service worker (including prison and security officers) over the period 2001-2012, as compared to all other occupations. Information on suicide method was extracted from the NCIS. RESULTS: The age-adjusted suicide rate across all emergency and protective service workers was 22.4 (95% CI 19.5 to 25.2) per 100,000 in males and 7.8 in females (95% CI 4.6 to 11.00), compared to 15.5 per 100,000 (95% CI 15.2 to 15.9) for males and 3.4 (95% CI 3.2 to 3.6) for females in other occupations. The highest risk by subgroup was observed among those employed in the defence force, prison officers, and ambulance personnel. The major method of death for all occupational groups was hanging. CONCLUSIONS: Our results clearly highlight the need for suicide prevention among emergency and protective service occupations.

Access to means of suicide, occupation and the risk of suicide: a national study over 12 years of coronial data.

BACKGROUND: Availability of lethal means is a significant risk factor for suicide. This study investigated whether occupations with greater access to lethal means had higher suicide rates than those without access, and further, whether this relationship differed for females versus males. METHODS: A retrospective mortality study was conducted across the Australian population over the period 2001 to 2012. Data from the Australian Bureau of Statistics, which collects Census information on occupation for the Australian population, and the National Coroners Information System, which records information on suicide deaths, were combined. Employed suicide records were coded by occupation and work-related access to lethal means. Descriptive analysis and negative binomial regression were used to assess the relationship between access to means and suicide. RESULTS: Persons in occupations with access to firearms, medicines or drugs, and carbon monoxide more frequently used these methods to end their lives than those without access to means. Females employed in occupations with access to means had suicide rates that were 3.02 times greater (95% CI 2.60 to 3.50, p < 0.001) than those employed in occupations without access. Males in occupations with access had suicide rates that were 1.24 times greater than those without access (95% CI 1.16 to 1.33, p < 0.001). CONCLUSION: Work-related access to means is a risk factor for suicide in the employed population, but is associated with a greater risk for females than males. The findings of this study suggest the importance of controlling access to lethal methods in occupations where these are readily available.

[Nonpharmacological treatment procedures for Parkinson's disease]. / Nichtmedikamentöse Therapieverfahren beim Morbus Parkinson.

Nonpharmacological treatment strategies in Parkinson' disease include heterogeneous treatment modalities, such as physiotherapy, occupational therapy, speech therapy, cognitive training and deep brain stimulation as well as noninvasive brain stimulation strategies. Even in the early stages of Parkinson's disease nonpharmacological interventions, such as active exercise therapy and speech therapy can be indicated taking the individual symptoms of a patient into account. Mild cognitive deficits are frequently detected in the course of the disease and progression of these disorders to dementia in the advanced stages of the disease is not uncommon. The starting point for a cognitive training, training strategy and training frequency is unknown and currently under investigation. Deep brain stimulation is an established treatment modality, which should be considered when motor fluctuations cannot be adequately controlled by pharmacological treatment. This therapeutic option depends on patient-specific needs and has to be managed by a multiprofessional team. Non-invasive neurostimulation techniques, such as transcranial magnetic stimulation and transcranial direct current stimulation are experimental tools and cannot currently be recommended for general use.

Is reverse total shoulder arthroplasty a feasible treatment option for failed shoulder arthroplasty? A retrospective study of 44 cases with special regards to stemless and stemmed primary implants.

Is reverse total shoulder arthroplasty a feasible treatment option for failed shoulder arthroplasty? A retrospective study of 44 cases with special regards to stemless and stemmed primary implants. BACKGROUND: Due to humeral or glenoid bone-loss and rotator cuff insufficiency reverse total shoulder arthroplasty often means the only remaining treatment option in revision shoulder arthroplasty. This study investigates the clinical outcome of patients treated with a reverse total shoulder in revision cases with special regard to stemless and stemmed primary implants. MATERIALS AND METHODS: From 2010 to 2012 60 failed shoulder arthroplasties were converted to reverse total shoulder arthroplasty. Forty-four patients were available for follow-up after a mean of 24 months. Patients were assessed with X-rays, Constant- and ASES Score and a questionnaire about their subjective satisfaction. RESULTS: The total number of observed complications was seven (16%). Ninety-eight percent of the patients were satisfied with their clinical result. Patients achieved a mean normalized constant score of 70.2% and a mean ASES Score of 65.3. Patients with stemless primary implants achieved a higher normalized constant score than patients with stemmed primary implants (82 vs. 61.8%; p = 0009). CONCLUSION: Reverse total shoulder arthroplasty provides satisfactory clinical results and a high patient satisfaction in revision shoulder arthroplasty. The complication rate needs to be considered and discussed with the patient prior to surgery. Presence or absence of a stem of revised shoulder arthroplasties interferes with the outcome. LEVEL OF EVIDENCE IV: (Retrospective study).

Effect of high-frequency subthalamic neurostimulation on gait and freezing of gait in Parkinson's disease: a systematic review and meta-analysis.

The aim of this meta-analysis was to summarize the short- and long-term effects of bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) on gait and freezing of gait (FOG) in Parkinson's disease and to detect predictors of post-stimulation outcome. A comprehensive review of the literature was conducted up to October 2015 using Medline Ovid databases for studies analyzing the effect of bilateral STN-DBS on FOG and/or gait. Sixteen studies with available data for the gait item (no. 29) of the Unified Parkinson's Disease Rating Scale (UPDRS) and six studies with the FOG item (no. 14) were included. Data were summarized for the following follow-up periods: 6-15, 24-48 and >48 months. For the medication (Med)-Off/stimulation(Stim)-On condition compared with baseline Med-Off, STN-DBS significantly improved gait on average from 2.43 to 0.96, 2.53 to 1.31 and 2.56 to 1.40 points at 6-15, 24-48 and >48 months, respectively (P < 0.05). Pre-operative levodopa responsiveness of UPDRS-III and Med-Off severity of gait were the predictors of this beneficial effect. STN-DBS significantly improved FOG for the Med-Off/Stim-On condition compared with baseline on average from 2.26 to 0.82, 2.43 to 1.13 and 2.48 to 1.38 points at 6-15, 24-48 and >48 months, respectively (P < 0.05). There was no significant effect in the Med-On/Stim-On condition. This meta-analysis showed a robust improvement of gait and FOG by STN-DBS for more than 4 years in the Med-Off/Stim-On condition. No beneficial effect was found for the On state of medication. Pre-operative levodopa responsiveness of global motor performance (UPDRS-III) is the strongest predictor of the effect of deep brain stimulation on gait.

Hyaluronic Acid Binding Sperm Selection for assisted reproduction treatment (HABSelect): study protocol for a multicentre randomised controlled trial.

INTRODUCTION: The selection of a sperm with good genomic integrity is an important consideration for improving intracytoplasmic sperm injection (ICSI) outcome. Current convention selects sperm by vigour and morphology, but preliminary evidence suggests selection based on hyaluronic acid binding may be beneficial. The aim of the Hyaluronic Acid Binding Sperm Selection (HABSelect) trial is to determine the efficacy of hyaluronic acid (HA)-selection of sperm versus conventionally selected sperm prior to ICSI on live birth rate (LBR). The mechanistic aim is to assess whether and how the chromatin state of HA-selected sperm corresponds with clinical outcomes-clinical pregnancy rate (CPR), LBR and pregnancy loss (PL). METHODS AND ANALYSIS: Couples attending UK Centres will be approached, eligibility screening performed and informed consent sought. Randomisation will occur within 24 hours prior to ICSI treatment. Participants will be randomly allocated 1:1 to the intervention arm (physiological intracytoplasmic sperm injection, PICSI) versus the control arm using conventional methods (ICSI). The primary clinical outcome is LBR ≥37 weeks' gestation with the mechanistic study determining LBR's relationship with sperm DNA integrity. Secondary outcomes will determine this for CPR and PL. Only embryologists performing the procedure will be aware of the treatment allocation. Steps will be taken to militate against biases arising from embryologists being non-blinded. Randomisation will use a minimisation algorithm to balance for key prognostic variables. The trial is powered to detect a 5% difference (24-29%: p=0.05) in LBR ≥37 weeks' gestation. Selected residual sperm samples will be tested by one or more assays of DNA integrity. ETHICS AND DISSEMINATION: HABSelect is a UK NIHR-EME funded study (reg no 11/14/34; IRAS REF. 13/YH/0162). The trial was designed in partnership with patient and public involvement to help maximise patient benefits. Trial findings will be reported as per CONSORT guidelines and will be made available in lay language via the trial web site (http://www.habselect.org.uk/). TRIAL REGISTRATION NUMBER: ISRCTN99214271; Pre-results.

Cripto-1 vaccination elicits protective immunity against metastatic melanoma.

Metastatic melanoma is a fatal disease that responds poorly to classical treatments but can be targeted by T cell-based immunotherapy. Cancer vaccines have the potential to generate long-lasting cytotoxic CD8(+) T cell responses able to eradicate established and disseminated tumors. Vaccination against antigens expressed by tumor cells with enhanced metastatic potential represents a highly attractive strategy to efficiently target deadly metastatic disease. Cripto-1 is frequently over-expressed in human carcinomas and melanomas, but is expressed only at low levels on normal differentiated tissues. Cripto-1 is particularly upregulated in cancer-initiating cells and is involved in cellular processes such as cell migration, invasion and epithelial-mesenchymal transition, which are hallmarks of aggressive cancer cells able to initiate metastatic disease. Here, we explored the potential of Cripto-1 vaccination to target metastatic melanoma in a preclinical model. Cripto-1 was overexpressed in highly metastatic B16F10 cells as compared to poorly metastatic B16F1 cells. Moreover, B16F10 cells grown in sphere conditions to enrich for cancer stem cells (CSC) progressively upregulated cripto1 expression. Vaccination of C57Bl/6 mice with a DNA vaccine encoding mouse Cripto-1 elicited a readily detectable/strong cytotoxic CD8(+) T cell response specific for a H-2 Kb-restricted epitope identified based on its ability to bind H-2(b) molecules. Remarkably, Cripto-1 vaccination elicited a protective response against lung metastasis and subcutaneous challenges with highly metastatic B16F10 melanoma cells. Our data indicate that vaccination against Cripto-1 represents a novel strategy to be tested in the clinic.

Verbal memory declines more in female patients with Parkinson's disease: the importance of gender-corrected normative data.

BACKGROUND: Data on gender-specific profiles of cognitive functions in patients with Parkinson's disease (PD) are rare and inconsistent, and possible disease-confounding factors have been insufficiently considered. METHOD: The LANDSCAPE study on cognition in PD enrolled 656 PD patients (267 without cognitive impairment, 66% male; 292 with mild cognitive impairment, 69% male; 97 with PD dementia, 69% male). Raw values and age-, education-, and gender-corrected Z scores of a neuropsychological test battery (CERAD-Plus) were compared between genders. Motor symptoms, disease duration, l-dopa equivalent daily dose, depression - and additionally age and education for the raw value analysis - were taken as covariates. RESULTS: Raw-score analysis replicated results of previous studies in that female PD patients were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.03), while men outperformed women in visuoconstruction (p = 0.002) and figural memory (p = 0.005). In contrast, gender-corrected Z scores showed that men were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.02; recognition, p = 0.04), while no difference was found for visuospatial tests. This picture could be observed both in the overall analysis of PD patients as well as in a differentiated group analysis. CONCLUSIONS: Normative data corrected for gender and other sociodemographic variables are relevant, since they may elucidate a markedly different cognitive profile compared to raw scores. Our study also suggests that verbal memory decline is stronger in women than in men with PD. Future studies are needed to replicate these findings, examine the progression of gender-specific cognitive decline in PD and define different underlying mechanisms of this dysfunction.