Clinical, imaging, and molecular findings in a sample of Mexican families with pantothenate kinase-associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder characterized by iron accumulation in the brain, because of mutations in the PANK2 gene. Phenotypic and genotypic characteristics of 11 patients from five Mexican families with PKAN disease are reported. Sequencing of PANK2 confirmed the diagnosis. The 11 patients had dysarthria associated with dystonia and Parkinsonism in six. Brain magnetic resonance imaging (MRI) showed the 'eye-of-the-tiger' sign in all patients. Three different mutations were identified, a novel one (p.A469P) and two (p.G219V and p.N404I) very rare. Homozygous sibs for the p.G219V mutation had a severe disease progression with early death. Dystonia predominated in the p.A469P/p.N404I compound heterozygous patients. Homozygous for p.N404I showed Parkinsonism, tics and personality and speech disorders. Early and late disease onset and variable expression was present in carriers of the different identified mutations. The 'eye-of-the-tiger' is an excellent neuroimaging hallmark to predict PANK2 mutations. We detected a 'cluster' of patients harboring the p.N404I mutation, strongly suggesting a founder effect for this mutation. This is the first familial clinical-genetic PKAN disease study accomplished in Mexico.

Factors associated with the quality of life of subjects with Parkinson's disease and burden on their caregivers.

INTRODUCTION: Parkinson's disease affects the quality of life of the individual with the disease in addition to creating a burden on the caregiver. Factors related to these effects include motor and non-motor aspects of the disease, as well as traits inherent to the caregiver. METHODS: We evaluated subjects with Parkinson's disease using the following instruments: Quality of Life Questionnaire PDQ-8, Movement Disorders Society Unified Parkinson's disease Rating Scale part i to iv (MDS-UPDRS), and Hoehn and Yahr staging. The Zarit Burden Inventory was used to assess all primary caregivers. Major demographic and clinical variables were also recorded. RESULTS: A total of 250 subjects with Parkinson's disease were included, of whom 201 had a primary caregiver. In the multivariate analysis, predictors of poor quality of life for a subject with Parkinson's disease were the MDS-UPDRS I score (ß=.39, P<.001), MDS-UPDRS II score (ß=.21, P<.001), and MDS-UPDRS III score (ß=.07, P=.004). Regarding caregiver burden, the MDS-UPDRS II score (ß=.54, P=.007) was the most influential factor. CONCLUSIONS: The present study shows a relationship between quality of life for the subject with Parkinson's disease and the caregiver's perceived burden. However, the factors that determine each situation appear to be distinct.

Establishment of local diagnostic reference levels for abdomen and chest radiographies in the region of Algarve, Portugal.

PURPOSE: To assess doses variabilities in the same abdomen and chest RX exams for adults, to check the need for dose harmonization. To calculate Diagnostic Reference Levels (DRL), mandatory in the European Union, for the Algarve district in Portugal. Our results can be a valuable reference for the Portuguese official determination of DRLs, still in progress. METHOD: We considered 4,936 abdomen and 41,320 chest radiographs of adults, covering 7 health centres and 35 radiographers in Algarve. Entrance skin dose (ESD) was calculated for each radiograph and the corresponding uncertainty estimated. Mean doses per centre and per technician, and their uncertainties, were calculated to access dose variabilities. DRLs, set at the 3rd quartile of the total ESD distribution, were determined for a standard patient and for intervals of body mass index (BMI) to study their correlation with patient anatomical variations. Standard quartile errors were estimated. RESULTS: Our results suggest significant dispersion in applied ESDs among different centres and radiographers. Estimates of DRLs also show small fluctuations across years and an important dependence on BMI intervals. For a standard patient, they are 8.7 ± 0.1 (abdomen) and 0.44 ± 0.01 (chest), while the European DRLs are, respectively, 5.1 and 0.2 (all in mGy). CONCLUSIONS: Results suggest that there is room for dose optimization and harmonization with European DRLs, urging a national dose survey and the establishment of official national DRLs. Official DRLs in intervals of BMI would be quite beneficial, to avoid unnecessary dose exposures.

Determinants and impact of alexithymia on quality of life in Parkinson's disease.

INTRODUCTION: Alexithymia is a neuropsychiatric symptom conceptualized as difficulty identifying and describing feelings. Although associated with other non-motor symptoms, mainly neuropsychiatric, alexithymia may present as an isolated symptom in persons with Parkinson's Disease (PwP). The objective of the study is to identify determinants of alexithymia and its association with quality of life (QoL) in Parkinson's disease. METHODS: Subjects with Parkinson's disease were recruited. The following instruments were applied: Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Non-Motor Symptoms Scale (NMSS), Montreal Cognitive Assessment (MoCA), Toronto alexithymia scale (TAS-20) and Parkinson's Disease Questionnaire (PDQ-8). Matched healthy controls were screened using TAS-20. Clinical and demographical variables were compared between alexithymic and non-alexithymic. Regression models were used to find determinants of alexithymia. Impact of alexithymia on QoL was estimated with a linear regression model. RESULTS: 98 patients were included. 56.1% PwP and 28.8% controls were alexithymic (p<0.001). Education level (OR 0.86) and NMSS urinary score (OR 1.09) determined alexithymia as well as TAS-20 score. Alexithymia was an independent determinant of QoL. CONCLUSIONS: Alexithymia is a prevalent independent non-motor symptom in PwP with impact on QoL. Low education level and urinary symptoms are important determinants of alexithymia.

Relationship between the type and side of motor symptoms with the prevalence of non-motor symptoms in Parkinson's disease.

INTRODUCTION: the relationship between laterality and asymmetry of Parkinson's disease and non-motor dysfunction has been studied mainly from the perspective of cognitive functions, and the few studies that have included other symptoms have mixed reports. The relationship between non-motor symptoms and the type of onset of the disease has not been studied in detail. OBJECTIVE: to analyse the association between the side and type of motor onset and the prevalence of non-motor symptoms. PATIENTS AND METHODS: we included 232 patients diagnosed with Parkinson's disease. Type of onset and the side initially affected were documented. The presence of non-motor symptoms was determined by applying the non-motor symptom questionnaire (NMSQuest). RESULTS: when analysing the side of onset and presence of each non-motor symptom explored, statistically significant differences were found in the frequency of hallucinations (P=0.04) and sleep behaviour disorder (P<0.01) in subjects with right side onset. The motor type of onset differences were not statistically significant. CONCLUSIONS: subjects with right side onset seem to have a higher risk of having hallucinations and sleep behaviour disorders. These symptoms should be intentionally sought in order to provide treatment and improve the patient's quality of life.

Determinants and impact of alexithymia on quality of life in Parkinson's disease.

INTRODUCTION: Alexithymia is a neuropsychiatric symptom conceptualized as difficulty identifying and describing feelings. Although associated with other non-motor symptoms, mainly neuropsychiatric, alexithymia may present as an isolated symptom in persons with Parkinson's Disease (PwP). The objective of the study is to identify determinants of alexithymia and its association with quality of life (QoL) in Parkinson's disease. METHODS: Subjects with Parkinson's disease were recruited. The following instruments were applied: Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Non-Motor Symptoms Scale (NMSS), Montreal Cognitive Assessment (MoCA), Toronto alexithymia scale (TAS-20) and Parkinson's Disease Questionnaire (PDQ-8). Matched healthy controls were screened using TAS-20. Clinical and demographical variables were compared between alexithymic and non-alexithymic. Regression models were used to find determinants of alexithymia. Impact of alexithymia on QoL was estimated with a linear regression model. RESULTS: 98 patients were included. 56.1% PwP and 28.8% controls were alexithymic (p<0.001). Education level (OR 0.86) and NMSS urinary score (OR 1.09) determined alexithymia as well as TAS-20 score. Alexithymia was an independent determinant of QoL. CONCLUSIONS: Alexithymia is a prevalent independent non-motor symptom in PwP with impact on QoL. Low education level and urinary symptoms are important determinants of alexithymia.

Unequivocal assignments of flavonoids from Tephrosia sp. (Fabaceae).

(1)H and (13)C NMR chemical shifts of praecansone B, pongaflavone and dehydrorotenone isolated from Tephrosia egregia Sandw and obovatin from T. toxicaria Pers. were unambiguously assigned by 1D and 2D NMR experiments including (1)H, (1)H COSY, gHMQC and gHMBC, allowing the correction of literature assignments.

Effect of neuraxial technique after inadvertent dural puncture on obstetric outcomes and anesthetic complications.

BACKGROUND: The aim of this study was to evaluate labor and delivery outcomes in parturients with inadvertent dural puncture managed by either insertion of an intrathecal catheter or a resited epidural catheter. METHODS: This was a retrospective cohort review of 235 parturients who had an inadvertent dural puncture during epidural placement over a six-year period. The primary outcome was the proportion of women with a delayed second stage of labor. Secondary outcomes were the proportion of cesarean deliveries, the proportion of cases resulting in post-dural puncture headache, and the incidence of failed labor analgesia. RESULTS: Baseline characteristics such as age, body mass index and parity were similar between the two groups. Among the 236 cases of inadvertent dural puncture, 173 women (73%) had an intrathecal catheter placed while 63 women (27%) had the epidural catheter resited. Comparing intrathecal with epidural catheters, there was no observed difference in the proportion of cases of prolonged second stage of labor (13% vs. 16%, P=0.57) and the overall rate of cesarean deliveries (17% vs. 16%, P=0.78). However, we observed a lower rate of post-dural puncture headache in women who had cesarean delivery compared to vaginal delivery (53% vs. 74%, P=0.007). A greater proportion of failed labor analgesia was observed in the intrathecal catheter group (14% vs. 2%, P=0.005). CONCLUSION: The choice of neuraxial technique following inadvertent dural puncture does not appear to alter the course of labor and delivery. Cesarean delivery decreased the incidence of post-dural puncture headache by 35%. Intrathecal catheters were associated with a higher rate of failed analgesia.

Plasmid transcriptional repressor CopG oligomerises to render helical superstructures unbound and in complexes with oligonucleotides.

CopG is a 45 amino acid residue transcriptional repressor involved in the copy number control of the streptococcal plasmid pMV158. To do so, it binds to a DNA operator that contains a 13 bp pseudosymmetric DNA element. Binding of CopG to its operator results in repression, at the transcriptional level, of its own synthesis and that of the initiator of replication protein, RepB. Biochemical experiments have shown that CopG co-operatively associates to its target DNA at low protein:DNA ratios, completely protecting four helical turns on the same face of the double helix in both directions from the inverted repeat that constitutes the CopG primary target. This has been correlated with a CopG-mediated DNA bend of about 100 degrees. Here, we show that binding of CopG to DNA fragments containing the inverted repeat just at one end led to nucleation of the protein initiating from the inverted repeat. Nucleation extended to the entire fragment, with CopG-DNA contacts occurring on the same face of the DNA helix. The protein, the prototype for a family of homologous plasmid repressors, displays a homodimeric ribbon-helix-helix arrangement. It polymerises within the unbound crystal to render a continuous right-handed protein superhelix of homodimers, around which a bound double-stranded (ds) DNA could wrap. We have solved the crystal structure of CopG in complex with a 22 bp dsDNA oligonucleotide encompassing the cognate pseudosymmetric element. In the crystal, one protein tetramer binds at one face of the DNA with two parallel beta-ribbons inserted into the major groove. The DNA is bent about 50 degrees under compression of both major and minor grooves. A continuous right-handed complex helix made up mainly by protein-protein and some protein-DNA interactions is observed. The protein-protein interactions involve regions similar to those observed in the oligomerisation of the native crystals and those employed to set up the functional tetramer. A previously solved complex structure of the protein with a 19 bp dsDNA had unveiled a left-handed helical superstructure just made up by DNA interactions.

Assessment of therapeutic response of Plasmodium falciparum to chloroquine and sulfadoxine-pyrimethamine in an area of low malaria transmission in Colombia.

Although chloroquine (CQ) resistance was first reported in Colombia in 1961 and sulfadoxine-pyrimethamine (SP) resistance in 1981, the frequency of treatment failures to these drugs in Colombia is unclear. A modified World Health Organization 14-day in vivo drug efficacy test for uncomplicated Plasmodium falciparum malaria in areas with intense malaria transmission was adapted to reflect the clinical and epidemiologic features of a low-intensity malaria transmission area in the Pacific Coast Region of Colombia. Patients > or =1 year of age with a parasite density > or =1,000 asexual parasites per microliter were enrolled in this study. Forty-four percent (24 of 54) of the CQ-treated patients were therapeutic failures, including 7 early treatment failures (ETFs) and 17 late treatment failures (LTFs). Four (6%) of 67 SP-treated patients were therapeutic failures (2 ETFs and 2 LTFs). Therapeutic failure in the CQ-treated group was associated with an age <15 years old (P < 0.01), but was not associated with initial parasite density, the presence of CQ or sulfa-containing drugs in urine, or a history of malaria. The high level of therapeutic failures to CQ detected in this study underscores the need and importance of drug efficacy evaluation in the development of a rational national antimalarial drug policy. The relatively low level of therapeutic failures to SP compared with other South American countries raises further questions regarding factors that might have prevented the rapid development of in vivo resistance to this drug combination.

Evaluation of L1 and L2 minimum norm performances on EEG localizations.

OBJECTIVE: In this work we study the performance of minimum norm methods to estimate the localization of brain electrical activity. These methods are based on the simplest forms of L(1) and L(2) norm estimates and are applied to simulated EEG data. The influence of several factors like the number of electrodes, grid density, head model, the number and depth of the sources and noise levels was taken into account. The main objective of the study is to give information about the dependence, on these factors, of the localization sources, to allow for proper interpretation of the data obtained in real EEG records. METHODS: For the tests we used simulated dipoles and compared the localizations predicted by the L(1) and L(2) norms with the location of these point-like sources. We varied each parameter separately and evaluated the results. RESULTS: From this work we conclude that, the grid should be constructed with approximately 650 points, so that the information about the orientation of the sources is preserved, especially for L(2) norm estimates; in favorable noise conditions, both L(1) and L(2) norm approaches are able to distinguish between more than one point-like sources. CONCLUSIONS: The critical dependence of the results on the noise level and source depth indicates that regularized and weighted solutions should be used. Finally, all these results are valid both for spherical and for realistic head models.

Constituents of Bowdichia virgilioides.

The isolation and (13)C-NMR data of flavone derivatives from Bowdichia virgilioides roots are reported.

A structural and immunocytochemical study of palatine and labial salivary glands from chronic alcoholics.

In the present study we investigated tissue changes in palatine (PG) and labial (LG) minor salivary glands from individuals who had died of alcoholic hepatic cirrhosis, to characterize histopathological parameters of alcoholic sialosis, that may be used for differential diagnosis. Samples obtained from autopsies were processed using cytochemical techniques for mucosubstances and immunocytochemical labelling for cytokeratines, PS 100 and T-cells. Both PG and LG showed dilated excretory ducts with atrophic epithelium, which contained PAS+ metachromatic material and detached cells. Intra and interlobular ductal hyperplasia was present in some areas, mainly in PG. CK expression was heterogeneous in ductal cells, and negative in acinar cells. Most of the acinar cell nuclei were normal, but some of them were atypical in shape and distribution. Myoepithelial cells, serous demilunes and the basal region of the cells of the striated ducts expressed PS 100. In PG, 85% of the mononuclear infiltrates expressed T-cell markers, whereas in LG only 40% of these cells were T-cells. These findings, in addition to other histopathological parameters seen in previous studies, may be used as indicators for differential diagnosis with other gland pathologies.

Histological study of parotid, submaxillary and von Ebner salivary glands in chronic alcoholics.

Samples from parotid, submaxillary, and von Ebner salivary glands of six chronic alcoholic individuals who had died of alcoholic hepatic cirrhosis were analyzed by topographic and histochemical routine stains and marked for cytokeratins; two normal adult individuals were used as control. Modifications in the acinar cells were found, but the most evident changes were observed in the ductal system: enlargement of major ducts, heterogeneous expression of cytokeratins and athrophy in epithelial cells, desquamated cells and stasis of content, and ductal hyperplasia in von Ebner glands. The lymphoplasmocytic infiltration does not represent the typical lymphocytic focus on Sjögren's syndrome or other connective tissue pathologies. Our findings indicate that functional and structural variations are produced both in serous acini and ducts parotid, submaxilar and von Ebner glands affected by alcoholic sialosis.

Human papillomavirus in carcinomas of the tongue: clinical and prognostic implications.

It is not clear whether the presence of human papillomavirus (HPV) in squamous cell carcinomas of the tongue (SCCT) is of etiopathogenic and clinical significance. This study was designed to establish the incidence of HPV in SCCT and to determine the influence of HPV detection on clinical parameters and the prognosis. Clinical and histopathological data of 64 patients with SCCT were collected. Thirty benign lesions of the tongue were analyzed in parallel, in order to compare the HPV incidence and genotypes in these lesions with those of SCCT. Paraffin blocks of all cases were collected and PCR was carried out using SPF10 primers and the INNO-LiPA genotyping methodology. HPV was detected in 26.2% of the patients. Hybridization results showed that all patients except one had high-risk (HR)-HPV. HPV56 was the most common (42.1%), followed by HPV18 (26.3%), HPV16 (10.5%), HPV66 (10.5%), HPV39 (5.3%), and HPV51 (5.3%). The odds ratio of HR-HPV infection in cases vs. controls was statistically significant (9.45, 95% confidence interval 1.18-75.46). Among the results of the univariate analysis correlating the presence of HR-HPV with different clinical parameters, only mortality showed a statistically significant correlation, being higher in HR-HPV patients (odds ratio 3.97, 95% confidence interval 1.07-14.7).

Tephrosia toxicaria†Pers. reduces temporomandibular joint inflammatory hypernociception: the involvement of the HO-1 pathway.

BACKGROUND: We investigated both the efficacy and the sub-chronic toxicity of Tephrosia toxicaria Pers. in the zymosan-induced temporomandibular joint (TMJ) inflammatory hypernociception in rats evaluating the possible role of heme oxygenase-1 (HO-1). METHODS: Rats were pretreated with T. toxicaria (0.2, 2.0 or 20 mg/kg) 60 min before the intra-articular injection of zymosan (2 mg, 40 µL) in the left TMJ. In another series of experiments, rats were treated with ZnPP-IX (3 mg/kg), a specific HO-1 inhibitor, before T. toxicaria (20 mg/kg). Von Frey test was used to evaluate inflammatory hypernociception (g) 4 h after zymosan injection. Six hours after zymosan injection, the synovial lavage was collected for total cell count and myeloperoxidase (MPO) activity, and joint tissue for histopathological analysis and immunohistochemistry for HO-1. To evaluate the sub-chronic toxicity, mice received T. toxicaria (20 mg/kg) or saline once a day for 14 days to analyse body mass, organ weight and biochemical parameters. RESULTS: T. toxicaria partially reversed the zymosan-induced head withdrawal threshold, the number of cells and the MPO activity. T. toxicaria reduced the inflammatory cell influx in the synovial membrane. TMJ immunohistochemical analyses treated with T. toxicaria showed increased HO-1 expression. These effects of T. toxicaria were not observed in the presence of ZnPP-IX. T. toxicaria treatment for 14 days did not show significant signs of toxicity when administrated to mice. CONCLUSIONS: T. toxicaria did not produce any signs of toxicity and effectively decreased zymosan-induced TMJ inflammatory hypernociception dependent, at least in part, upon the HO-1 pathway integrity.

Functional restructured meat: applications of ingredients derived from plants / Reestructurados cárnicos funcionales: aplicación de ingredientes derivados de plantas

Background: Meat is an important source of nutrients. However, in recent years their consumption is associated with chronic-degenerative diseases giving it the perception of "unhealthy food" Given that meat is an affordable source of quality protein; its improvement entails a huge challenge for the industry and science. Methods: The search and structured review of the literature in the last ten years in the scientific databases of articles related to the elaboration of restructured meat products with functional ingredients derived from plants. Objective: This work presents a general overview, as well as the most representative studies on the elaboration of restructured meat with ingredients from plants considered functional. Conclusions: The present review is intended to emphasize the use of plant natural ingredients in the elaboration of functional restructured meat products as an alternative for consumers allowing the inclusion of functional compounds beneficial to human health in their daily diet

Antecedentes: La carne es una fuente importante de nutrientes. Sin embargo, en los últimos años su consumo se asocia a enfermedades crónico-degenerativas dando la percepción de alimento poco saludable. Dado a que es una fuente accesible de proteína de calidad, su mejoramiento implica un enorme desafío para la industria y la ciencia de la carne. Método: La revisión estructurada de diversos artículos de investigación encontrados en bases de datos científicas, durante los últimos 10 años, relacionados a la elaboración de reestructurados cárnicos con derivados de plantas considerados funcionales. Objetivo: Este trabajo presenta una revisión general, de los estudios más representativos sobre la elaboración reestructurados cárnicos elaborados con derivados de plantas considerados como funcionales. Conclusión: La elaboración de productos reestructurados cárnicos funcionales con la utilización de derivados vegetales, puede considerarse una alternativa para los consumidores a fin de incluir compuestos funcionales beneficiosos para la salud humana en la dieta diaria