Validation of a non-motor fluctuations questionnaire in Parkinson's disease.

INTRODUCTION: Non-motor fluctuations (NMF) in Parkinson's disease (PD) remain poorly recognized but have a high impact on patients' quality of life. The lack of assessment tools limits our understanding of NMF, compromising appropriate management. Our objective was to validate a hetero-questionnaire for NMF in PD patients at different stages of the disease: without treatment, without motor fluctuations, with motor fluctuations. METHODS: We included patients in 15 centers in France. Our questionnaire, NMF-Park, resulted from previous studies, allowing us to identify the more pertinent NMF for evaluation. Patients reported the presence (yes or no) of 22 selected NMF, and their link with dopaminergic medications. The assessment was repeated at one and two years to study the progression of NMF. We performed a metrological validation of our questionnaire. RESULTS: We included 255 patients (42 without treatment, 88 without motor fluctuations and 125 with motor fluctuations). After metrological validation, three dimensions of NMF were found: dysautonomic; cognitive; psychiatric. The sensory/pain dimension described in the literature was not statistically confirmed by our study. DISCUSSION: Our questionnaire was validated according to clinimetric standards, for different stages of PD. It was clinically coherent with three homogeneous dimensions. It highlighted a link between fatigue, visual accommodation disorder, and cognitive fluctuations; and the integration of sensory/pain fluctuations as part of dysautonomic fluctuations. It focused exclusively on NMF, which is interesting considering the described differences between non-motor and motor fluctuations. CONCLUSION: Our study validated a hetero-questionnaire of diagnosis for NMF for different stages of PD.

Cancer-related fatigue and its determinants in a cohort of women with breast cancer: the DAMA Cohort.

Cancer-related fatigue (CRF) is one of the most prolonged discomforts suffered by people who have had cancer. Seventy-eight to ninety-six percent of cancer patients experience fatigue, especially while undergoing treatment. CRF is related to insomnia, anxiety, depression, and also varies depending on age. However, little is known about the factors contributing to CRF and better understanding of determinants of CRF makes it easier to identify early patients at risk and in designing intervention planning. The aim of this study was to assess the influence of precipitating factors (diagnosis of breast cancer and other clinical aspects) and perpetuating factors (social network, quality of life, mental disorders) on the presence of chronic fatigue in women from our cultural context, by social class each other determinants. METHODS: It was carried out a mixed cohort study (prospective and retrospective) using a convenience sample of women diagnosed with breast cancer. The information sources were data from the Brief Fatigue Inventory questionnaire and hospital medical records. The dependent variable was fatigue and the independent variables were age, social class, time since diagnoses, cohabitation, comorbidity, relapse, body mass index, mental health (anxiety and depression), social network, social support, and quality of life. RESULTS: Seventy-two percent of the women in the DAMA cohort reported moderate to severe fatigue. Risk of suffering from severe fatigue was greatest among individuals with low social class, those aged under 50 years, those with chronic disorders who had relapsed, and those with symptoms of anxiety and depression. In our study, CRF did not appear to be related to the stage of the cancer at diagnosis, or to the time since diagnosis. CONCLUSIONS: CRF is an element that the professionals responsible for the control and monitoring of women should take into account as another element to be taken into consideration.

Historical reflections on neurosyphilis based on the 1826 treatise on general paralysis in demented patients by Louis Florentin Calmeil (1798-1895).

General paralysis is a neurological symptom of tertiary syphilis that was first identified in asylums as paralytic madness. The enlightened discussion of 60 clinicopathological cases provided by Louis Florentin Calmeil in his 1826 treatise greatly improved our knowledge of general paralysis. However, Calmeil was unable to relate this symptom to syphilis, although the latter was quite widespread at that time. Following a detailed reanalysis of Calmeil's observations with special attention to his clinical and demographic data, we conclude that this eminent clinician was unable to define the cause of general paralysis because his early 19th century mind was still under the influence of traditional knowledge and moral prejudices. For Calmeil, general paralysis belonged entirely to the realm of psychiatry.

Direct Observation of a Localized Magnetic Soliton in a Spin-Transfer Nanocontact.

We report the direct observation of a localized magnetic soliton in a spin-transfer nanocontact using scanning transmission x-ray microscopy. Experiments are conducted on a lithographically defined 150 nm diameter nanocontact to an ultrathin ferromagnetic multilayer with perpendicular magnetic anisotropy. Element-resolved x-ray magnetic circular dichroism images show an abrupt onset of a magnetic soliton excitation localized beneath the nanocontact at a threshold current. However, the amplitude of the excitation ≃25° at the contact center is far less than that predicted (⪅180°), showing that the spin dynamics is not described by existing models.

Singlet-to-triplet interconversion using hyperfine as well as ferromagnetic fringe fields.

Until recently the important role that spin-physics ('spintronics') plays in organic light-emitting devices and photovoltaic cells was not sufficiently recognized. This attitude has begun to change. We review our recent work that shows that spatially rapidly varying local magnetic fields that may be present in the organic layer dramatically affect electronic transport properties and electroluminescence efficiency. Competition between spin-dynamics due to these spatially varying fields and an applied, spatially homogeneous magnetic field leads to large magnetoresistance, even at room temperature where the thermodynamic influences of the resulting nuclear and electronic Zeeman splittings are negligible. Spatially rapidly varying local magnetic fields are naturally present in many organic materials in the form of nuclear hyperfine fields, but we will also review a second method of controlling the electrical conductivity/electroluminescence, using the spatially varying magnetic fringe fields of a magnetically unsaturated ferromagnet. Fringe-field magnetoresistance has a magnitude of several per cent and is hysteretic and anisotropic. This new method of control is sensitive to even remanent magnetic states, leading to different conductivity/electroluminescence values in the absence of an applied field. We briefly review a model based on fringe-field-induced polaron-pair spin-dynamics that successfully describes several key features of the experimental fringe-field magnetoresistance and magnetoelectroluminescence.

Spin wave excitation patterns generated by spin torque oscillators.

Spin torque nano-oscillators (STNO) are nanoscale devices that can convert a direct current into short wavelength spin wave excitations in a ferromagnetic layer. We show that arrays of STNO can be used to create directional spin wave radiation similarly to electromagnetic antennas. Combining STNO excitations with planar spin waves also creates interference patterns. We show that these interference patterns are static and have information on the wavelength and phase of the spin waves emitted from the STNO. We describe a means of actively controlling spin wave radiation patterns with the direct current flowing through STNO, which is useful in on-chip communication and information processing and could be a promising technique for studying short wavelength spin waves in different materials.

Onset of a propagating self-sustained spin reversal front in a magnetic system.

The energy released in a magnetic material by reversing spins as they relax toward equilibrium can lead to a dynamical instability that ignites self-sustained rapid relaxation along a deflagration front that propagates at a constant subsonic speed. Using a trigger heat pulse and transverse and longitudinal magnetic fields, we investigate and control the crossover between thermally driven magnetic relaxation and magnetic deflagration in single crystals of Mn(12)-acetate.

[Acute axonal polyneuropathy and Gougerot-Sjögren syndrome]. / Polyneuropathie axonale aiguë et syndrome de Gougerot-Sjögren.

INTRODUCTION: Gougerot-Sjögren syndrome (GSS) is an autoimmune disease characterized by a lymphocytic infiltration and destruction of saliva and lachrymal glands. About 20% of patients develop a neurological involvement. CASE REPORT: A 29-year-old woman was admitted with a dysautonomic and sensorial neuropathy. Clinical manifestations (dry syndrome and positive Schirmer's test), blood (anti-SSA and anti-SSB antibodies) and histological (chronic sialadenitis) tests linked this neuropathy to a primary GSS. The characteristics of this case were acute onset (within a few days), severe clinical presentation (continued confinement to bed and malnutrition) and non-responsiveness to all treatments (intravenous immunoglobulins, corticosteroids, plasmapheresis, rituximab). CONCLUSION: This case illustrates various clinical signs and inconstant responsiveness to treatment of neuropathy associated with primary GSS.

Detection of incident breast and colorectal cancer cases from an administrative healthcare database in Catalonia, Spain.

OBJECTIVE: To validate the Catalan minimum basic data set (MBDS) of hospital discharges as an information source for detecting incident breast (BC) and colorectal cancer (CRC), against the Hospital del Mar Cancer Registry (RTHMar) in Barcelona (Spain) as the gold standard. METHODS: Using ASEDAT software (Analysis, Selection and Extraction of Tumour Data), we identified Catalan public hospital discharge abstracts in patients with a first-time diagnosis of BC and CRC in the years 2005, 2008, and 2011, aggregated by unique patient identifiers and sorted by date. Once merged with the RTHMar database and anonymized, tumour-specific algorithms were validated to extract data on incident cases, tumour stage, surgical treatment, and date of incidence. RESULTS: MBDS had a respective sensitivity and positive predictive value (PPV) of 78.0% (564/723) and 90.5% (564/623) for BC case detection; and 83.9% (387/461) and 94.9% (387/408) for CRC case detection. The staging algorithms overestimated the proportion of local-stage cases and underestimated the regional-stage cases in both cancers. When loco-regional stage and surgery were combined, sensitivity and PPV reached 98.3% and 99.8%, respectively, for BC and 96.4% and 98.4% for CRC. The differences between dates of incidence between RTHMar and MBDS were greater for BC cases without initial surgery, whereas they were generally smaller and homogeneous for CRC cases. CONCLUSIONS: The MBDS is a valid and efficient instrument to improve the completeness of a hospital-based cancer registry (HBCR), particularly in BC and CRC, which require hospitalization and are predominantly surgical.

[Surgical treatment of prolapse using laparoscopic promontofixation: technical principles and results]. / Traitement chirurgical du prolapsus par promontofixation par laparotomie: principes techniques et résultats.

UNLABELLED: Abdominal sacrofixation is the gold standard for the treatment of the prolapse. There are many ways to do it: technical, meshes, dissection, fixation of the mesh, associated procedures. Laparotomy is the classical procedure for sacrofixation. The basis of sacrofixation is to dissect the weak vesicovaginal and rectovaginal fascias and to replace with meshes spread out on the entire dissected surface. PROCEDURE: Suprapubic abdominal incision, dissection of the anterior vertebral ligament on the right of the promontory, dissection of the vesicovaginal and rectovaginal spaces; meshes are fixed anteriorly on the vagina, posteriorly on the levator ani and uterosacral ligaments. The peritoneum on the meshes is carefully closed to avoid later ileus. RESULTS: Redux is globally 10% (74-98%); the redux occur in the two years. Meshes exposure, spondilodiscitis, ileus are uncommon. In comparison with the vaginal procedures, there is less redux, less dyspareunia. But the drawbacks are postoperative pains, scars, eventration, low dissection difficult and some contraindications to the abdominal sacrofixation: respiratory insufficiency, morbid obesity, multi-operated abdomen, ascitis, aortoiliac aneurysms.

Anxiety and depression in women with breast cancer: Social and clinical determinants and influence of the social network and social support (DAMA cohort).

BACKGROUND: Anxiety and depression are the most prevalent mental health pathologies among women with breast cancer. Social, clinical and contextual variables may influence emotional stress among women with breast cancer. The aim of this work is to study anxiety and depression in a cohort of women diagnosed with breast cancer between 2003 and 2013 in Barcelona. We evaluate social and clinical determinants. METHODS: We performed a mixed cohort study (prospective and retrospective) using a convenience sample of women diagnosed with breast cancer. The information sources were the Hospital Anxiety and Depression questionnaire and hospital medical records. Dependent variables were anxiety and depression; independent variables were social class, age, employment status, tumour stage at diagnosis, time since diagnosis, social network and social support. We performed a descriptive analysis, a bivariate analysis, and a multivariate logistic regression analysis. RESULTS: A total of 1086 (48.6%) women had some degree of anxiety-related problem. As for depression. In the case of depression, 225 (15%) women had some degree of depression-related problem. Low emotional support and social isolation were clear risk factors for having more anxiety and depression. Low social class was also a risk factor, and age also played a role. DISCUSSION: Our results show that women long period of cancer survival have high prevalences of anxiety than depression, and this prevalence of anxiety is higher than the general population. In addition, we found inequalities between social classes and the isolation and social support are worse too in low social class.

The X-ray structure of the FMN-binding protein AtHal3 provides the structural basis for the activity of a regulatory subunit involved in signal transduction.

BACKGROUND: The Arabidopsis thaliana HAL3 gene product encodes for an FMN-binding protein (AtHal3) that is related to plant growth and salt and osmotic tolerance. AtHal3 shows sequence homology to ScHal3, a regulatory subunit of the Saccharomyces cerevisae serine/threonine phosphatase PPz1. It has been proposed that AtHal3 and ScHal3 have similar roles in cellular physiology, as Arabidopsis transgenic plants that overexpress AtHal3 and yeast cells that overexpress ScHal3 display similar phenotypes of improved salt tolerance. The enzymatic activity of AtHal3 has not been investigated. However, the AtHal3 sequence is homologous to that of EpiD, a flavoprotein from Staphylococcus epidermidis that recognizes a peptidic substrate and subsequently catalyzes the alpha, beta-dehydrogenation of its C-terminal cysteine residue. RESULTS: The X-ray structure of AtHal3 at 2 A resolution reveals that the biological unit is a trimer. Each protomer adopts an alpha/beta Rossmann fold consisting of a six-stranded parallel beta sheet flanked by two layers of alpha helices. The FMN-binding site of AtHal3 contains all the structural requirements of the flavoenzymes that catalyze dehydrogenation reactions. Comparison of the amino acid sequences of AtHal3, ScHal3 and EpiD reveals that a significant number of residues involved in trimer formation, the active site, and FMN binding are conserved. This observation suggests that ScHal3 and EpiD might also be trimers, having a similar structure and function to AtHal3. CONCLUSIONS: Structural comparisons of AtHal3 with other FMN-binding proteins show that AtHal3 defines a new subgroup of this protein family that is involved in signal transduction. Analysis of the structure of AtHal3 indicates that this protein is designed to interact with another cellular component and to subsequently catalyze the alpha,beta-dehydrogenation of a peptidyl cysteine. Structural data from AtHal3, together with physiological and biochemical information from ScHal3 and EpiD, allow us to propose a model for the recognition and regulation of AtHal3/ScHal3 cellular partners.

Arginine Decarboxylase Is Localized in Chloroplasts.

Plants, unlike animals, can use either ornithine decarboxylase or arginine decarboxylase (ADC) to produce the polyamine precursor putrescine. Lack of knowledge of the exact cellular and subcellular location of these enzymes has been one of the main obstacles to our understanding of the biological role of polyamines in plants. We have generated polyclonal antibodies to oat (Avena sativa L.) ADC to study the spatial distribution and subcellular localization of ADC protein in different oat tissues. By immunoblotting and immunocytochemistry, we show that ADC is organ specific. By cell fractionation and immunoblotting, we show that ADC is localized in chloroplasts associated with the thylakoid membrane. The results also show that increased levels of ADC protein are correlated with high levels of ADC activity and putrescine in osmotically stressed oat leaves. A model of compartmentalization for the arginine pathway and putrescine biosynthesis in active photosynthetic tissues has been proposed. In the context of endosymbiote-driven metabolic evolution in plants, the location of ADC in the chloroplast compartment may have major evolutionary significance, since it explains (a) why plants can use two alternative pathways for putrescine biosynthesis and (b) why animals do not possess ADC.

[Lung cancer at a university hospital: epidemiological and histological characteristics of a recent and a historical series]. / Características del cáncer de pulmón en un hospital universitario. Cambios epidemiológicos e histológicos en relación con una serie histórica.

OBJECTIVE: To describe the clinical, histological, and epidemiological characteristics of patients diagnosed with lung cancer in our hospital over a period of 5 years and compare them with those of historical cases treated at the same hospital. PATIENTS AND METHODS: The cases of patients diagnosed with lung cancer from January 1998 through December 2002 were studied retrospectively and compared with data published for the period from 1978 through March 1981. RESULTS: A total of 678 patients (89% men, mean age 67 years) were studied. Fifty-six percent of the men and 38% of the women were smokers (P<.001). The most common histological types were squamous cell carcinoma (33%) and adenocarcinoma (30%): squamous carcinoma in men (36%) and adenocarcinoma in women (56%). Metastasis was present in 42% of the patients with non-small cell lung cancer and in 55% of those with small cell lung cancer. In patients with a history of neoplastic disease, laryngeal tumors were most common in patients with squamous carcinoma whereas bladder tumors were the most frequent in patients with adenocarcinoma. The ratio of men to women was lower in the recent series than in the historical one. The percentage of squamous carcinoma was lower and that of adenocarcinoma higher (P<.001). The percentage of patients diagnosed with regional involvement was greater in the recent series (P<.001). CONCLUSIONS: Squamous cell carcinoma continues to be the most frequent histological type. Male sex and smoking are associated with squamous carcinoma and female sex is associated with adenocarcinoma. Epidemiological and histological patterns have changed, possibly in relation to changes in smoking habits.

Direct observation and imaging of a spin-wave soliton with p-like symmetry.

Spin waves, the collective excitations of spins, can emerge as nonlinear solitons at the nanoscale when excited by an electrical current from a nanocontact. These solitons are expected to have essentially cylindrical symmetry (that is, s-like), but no direct experimental observation exists to confirm this picture. Using a high-sensitivity time-resolved magnetic X-ray microscopy with 50 ps temporal resolution and 35 nm spatial resolution, we are able to create a real-space spin-wave movie and observe the emergence of a localized soliton with a nodal line, that is, with p-like symmetry. Micromagnetic simulations explain the measurements and reveal that the symmetry of the soliton can be controlled by magnetic fields. Our results broaden the understanding of spin-wave dynamics at the nanoscale, with implications for the design of magnetic nanodevices.

Utilization of screening mammography as a preventive practice prior to initiating a population-based breast cancer screening program.

Factors associated with the level of utilization of screening mammography as a preventive practice were analyzed prior to initiating a population-based breast cancer screening program. A questionnaire was used to collect information about screening mammography utilization during the last 4 years among women invited to enroll in the program. Sociodemographic and health factors, and health services utilization were studied. A screening mammography in the last 4 years had been performed on 59.3% of the 8867 women interviewed. The utilization of mammography was higher among women who were younger, had a higher education level, or had previous visits to a physician (P < 0.001). The variables more strongly associated with use of screening mammography were: visit to a gynecologist and performance of a pap smear. Also associated with the utilization of screening mammography were: personal history of breast pathology, family history of breast cancer, breast self-examination, and recent visit to a general practitioner. Self-perceived health presented an inverse relation with screening mammography use (P < 0.001). The use of screening mammography appears to have increased in recent years, although inequalities persist which the breast cancer screening programs help to modulate. Mammographic frequency only would be deemed appropriate by the European guidelines in fewer than one-half of the cases.

Participation in a colorectal cancer screening programme: influence of the method of contacting the target population.

We assessed the effect of two different methods of contacting the target population on the rate of participation in a colorectal cancer screening programme. All individuals aged between 50 and 74 years enlisted in one primary health care centre in Barcelona (Spain) were included in a prospective randomized controlled trial. An invitation letter signed by a doctor together with two containers for faecal sample collection were sent by post to subjects in the 'standard' group (n = 1060), while subjects in the 'study' group (direct contact, n = 965) were visited by a trained non-health professional who supplied them with the same documentation as the standard group. The screening test consisted of an immunological method for the detection of faecal blood which does not require any prior specific dietary measures. Specimens were collected on two successive days. A significantly higher participation was observed in the study group (557/965, 57.7%) compared with the standard group (388/1060, 36.5%, P < 0.005). Specimen collection correctness was also higher in the study group (419/557, 75.1%) compared with the standard group (262/388, 67.5%, P < 0.014). There were no differences in terms of either age group or sex for the participation, nor for degree of correctness of specimen collection. Participation and specimen collection can be raised in colorectal cancer screening programmes by means of an invitation made through direct contact by a suitably trained non-health professional.

[Progressive supranuclear palsy: a clinical, natural history and disability study]. / Paralysie supranucléaire progressive: étude clinique, histoire naturelle et progression du handicap.

We studied the clinical features, the natural history and disability in 47 progressive supranuclear palsy patients and brain imaging aspects by routinely performed MRI in a subgroup of 25. Unexplained falls together with atypical parkinsonism (symmetric, levodopa unresponsive without resting tremor) are good clinical pointers of the early diagnosis, since they occurred within the first year. Cognitive slowness and unspecific visual complains are also early symptoms, while usual cardinal signs such as supranuclear palsy are more delayed. Blepharospasm and eyelid opening apraxia as well as deep sighs are also quite characteristic clinical features (1/3 of cases). Cardinal signs (falls, pseudobulbar signs, supranuclear gaze palsy) worsened rapidly (20 to 30 months) towards a major disability. In the 20 patients deceased during follow-up, the mean survival time was about 5 years. The MRI study showed typical cortical fronto-temporo-parietal atrophy, mesencephalic and quadrigeminal plate atrophy with third ventricle dilatation. In conclusion, unexplained falls associated with atypical parkinsonism are contributive for the early clinical diagnosis. Non specific visual complains could be useful pointers in the absence of supranuclear ophthalmoplegia. MRI contributes to the clinical diagnosis even in the first 3 years of the disease course.

[Development and validation of an algorithm to identify cancer recurrences from hospital data bases]. / Desarrollo y validación de un algoritmo para identificar recidivas de cáncer a partir de bases de datos hospitalarias.

OBJECTIVES: Hospital cancer registries and hospital databases are valuable and efficient sources of information for research into cancer recurrences. The aim of this study was to develop and validate algorithms for the detection of breast cancer recurrence. METHODS: A retrospective observational study was conducted on breast cancer cases from the cancer registry of a third level university hospital diagnosed between 2003 and 2009. Different probable cancer recurrence algorithms were obtained by linking the hospital databases and the construction of several operational definitions, with their corresponding sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: A total of 1,523 patients were diagnosed of breast cancer between 2003 and 2009. A request for bone gammagraphy after 6 months from the first oncological treatment showed the highest sensitivity (53.8%) and negative predictive value (93.8%), and a pathology test after 6 months after the diagnosis showed the highest specificity (93.8%) and negative predictive value (92.6%). The combination of different definitions increased the specificity and the positive predictive value, but decreased the sensitivity. CONCLUSIONS: Several diagnostic algorithms were obtained, and the different definitions could be useful depending on the interest and resources of the researcher. A higher positive predictive value could be interesting for a quick estimation of the number of cases, and a higher negative predictive value for a more exact estimation if more resources are available. It is a versatile and adaptable tool for other types of tumors, as well as for the needs of the researcher.