Predictors of overload in parents of children with neuromuscular diseases.

Introduction: Parents of children with neuromuscular diseases experience multiple difficulties in their daily lives that affect their physical and psychological health. The risk factors for these health issues have not been sufficiently investigated. Therefore, the aim of this study was to analyze the potential predictors of overload in these parents, including QoL, somatic symptomatology, life satisfaction, psychological adjustment and certain sociodemographic variables. Methods: A cross-sectional research study was conducted among parents who are caregivers for children with NMD in Spain. A convenience sample of 110 parents who were contacted by associations and hospitals was used. Variables were evaluated using the sociodemographic questionnaire, CarerQol-7D, PHQ-15, Barthel Index, Psychological Adaptation Scale, Zarit Overload Scale and Satisfaction with Life Scale. Results: One of the most relevant findings of the present study is the identification of 3 overload groups (mild to moderate, moderate to severe, and severe overload) based on life satisfaction and somatic symptom scores within the predictive model of the discriminate analysis. Wilk's lambda of the discriminant function was 0.568, χ2 (2, n = 55) = 8.815, p < 0.001. Discussion: This study presents a model that reveals the influence of unemployment, having a child with a severe level of dependency, the presence of somatic symptomatology and life satisfaction on caregiver overload. Likewise, the caregiver's self-esteem could be a protective factor against overload.

Cognitive Functioning in Adults with Phenylketonuria in a Cohort of Spanish Patients.

The early introduction of a low phenylalanine (Phe) diet has been demonstrated to be the most successful treatment in subjects with phenylketonuria (PKU), especially for preventing severe cognitive and neurological damages. However, it still concerns that even if treated in the first months of life with supplements and following a diet, they can show slight scores below people without PKU in neuropsychological assignments. We investigated 20 adults with classical PKU aged 19-48 years (mean age 29 years) and 20 heathy controls matched by age, gender, and years of education. Patients and controls were assessed with an extended neuropsychological battery, as well as psychological aspects and quality of life, also the last Phe level result was obtained. Results showed that the most affected cognitive domains are processing speed, executive functioning, memory, and also theory of mind, but very well-preserved verbal fluency, language, and visuospatial functioning. In quality of life, some significant results were seen specially in anxiety of Phe levels, anxiety of Phe levels during pregnancy, guilt if poor adherence to supplements, and if dietary protein restriction not followed. No significant results were obtained for the psychological variables. In conclusion, it has been shown that a combination of a low Phe diet, supplement intake, and keeping Phe levels in a low range seems appropriate to have the most normal and alike cognitive performance to persons without PKU.

Biallelic KITLG variants lead to a distinct spectrum of hypomelanosis and sensorineural hearing loss.

BACKGROUND: Pathogenic variants in KITLG, a crucial protein involved in pigmentation and neural crest cell migration, cause non-syndromic hearing loss, Waardenburg syndrome type 2, familial progressive hyperpigmentation and familial progressive hyper- and hypopigmentation, all of which are inherited in an autosomal dominant manner. OBJECTIVES: To describe the genotypic and clinical spectrum of biallelic KITLG-variants. METHODS: We used a genotype-first approach through the GeneMatcher data sharing platform to collect individuals with biallelic KITLG variants and reviewed the literature for overlapping reports. RESULTS: We describe the first case series with biallelic KITLG variants; we expand the known hypomelanosis spectrum to include a 'sock-and-glove-like', symmetric distribution, progressive repigmentation and generalized hypomelanosis. We speculate that KITLG biallelic loss-of-function variants cause generalized hypomelanosis, whilst variants with residual function lead to a variable auditory-pigmentary disorder mostly reminiscent of Waardenburg syndrome type 2 or piebaldism. CONCLUSIONS: We provide consolidating evidence that biallelic KITLG variants cause a distinct auditory-pigmentary disorder. We evidence a significant clinical variability, similar to the one previously observed in KIT-related piebaldism.

Design of a compact off-axis four-mirror objective system for a thermal camera.

The optical design of a compact off-axis four-mirror objective system (OFOS) of a thermal camera for a syndromic surveillance system that captures bioclinical signals, like temperature, directly related to the physical symptoms of the COVID-19 disease through thermal images is presented. The OFOS design works on wavelengths of 7.5-14 µm, with an f-number of 4, and a field of view (FOV) of 24×4 deg.

Music therapy and Sanfilippo syndrome: an analysis of psychological and physiological variables of three case studies.

INTRODUCTION: Mucopolysaccharidosis type III (MPS III) or Sanfilippo syndrome is a neurodegenerative disease caused by the accumulation of mucopolysaccharides in the body. As the symptoms are wide ranging, it is a challenge to provide a diagnosis and psychological treatment for affected children. METHOD: The main objective of this study was to describe a form of music therapy treatment applied to three children diagnosed with MPS III. The psychological variables were evaluated by an ad hoc observation recording template, and the physiological variables were measured with a digital meter before and after each session. The perception of the parents was also considered through a semi-structured interview. RESULTS: An improvement in the psychological variables was shown in all cases. Changes in the physiological variables were also noted, although they varied according to each child. The parents report some benefit of music therapy and they share difficulty in assessing the extent of benefits of the music therapy. DISCUSSION: Findings indicate that music therapy can be a useful form of treatment with multiple benefits for children with conditions such as MPS III or similar conditions. However, further research is needed in this area and in the development of specific ways of evaluating music therapy.

Ketogenic diet and cognition in neurological diseases: a systematic review.

CONTEXT: In recent years, the ketogenic diet has gained special relevance as a possible therapeutic alternative to some neurological and chronic diseases. OBJECTIVE: The aim of this systematic review was to answer the following question: Does a ketogenic diet improve cognitive skills in patients with Alzheimer's disease, Parkinson's disease, refractory epilepsy, and type 1 glucose deficiency syndrome? To define the research question, the PICOS criteria were used, following the guidelines of the PRISMA method. DATA SOURCES: Medline/PubMed, Elsevier Science Direct, Dialnet, EBSCOhost, Mediagraphic, Sage Journals, ProQuest, and Wiley Online Library databases were used. DATA EXTRACTION: After applying inclusion and exclusion criteria in accordance with the PRISMA method, a total of 63 entries published between 2004 and 2019 were used. DATA ANALYSIS: The records extracted were analyzed from a qualitative approach, so no statistical analysis was carried out. CONCLUSION: Although scientific literature on the subject is scarce and there has tended to be a lack of scientific rigor, the studies reviewed confirmed the effectiveness of this diet in improving the cognitive symptomatology of the aforementioned diseases.

Leishmania mexicana: promastigotes and amastigotes secrete protein phosphatases and this correlates with the production of inflammatory cytokines in macrophages.

Phosphatase activity of Leishmania spp. has been shown to deregulate the signalling pathways of the host cell. We here show that Leishmania mexicana promastigotes and amastigotes secrete proteins with phosphatase activity to the culture medium, which was higher in the Promastigote Secretion Medium (PSM) as compared with the Amastigote Secretion Medium (ASM) and was not due to cell lysis, since parasite viability was not affected by the secretion process. The biochemical characterization showed that the phosphatase activity present in PSM was higher in dephosphorylating the peptide END (pY) INASL as compared with the peptide RRA (pT)VA. In contrast, the phosphatase activity in ASM showed little dephosphorylating capacity for both peptides. Inhibition assays demonstrated that the phosphatase activity of both PSM and ASM was sensible only to protein tyrosine phosphatases inhibitors. An antibody against a protein phosphatase 2C (PP2C) of Leishmania major cross-reacted with a 44·9 kDa molecule in different cellular fractions of L. mexicana promastigotes and amastigotes, however, in PSM and ASM, the antibody recognized a protein about 70 kDa. By electron microscopy, the PP2C was localized in the flagellar pocket of amastigotes. PSM and ASM induced the production of tumor necrosis factor alpha, IL-1ß, IL-12p70 and IL-10 in human macrophages.

Field- and temperature-dependent 13C NMR studies of the EDTA-Zn2+ complex: insight into structure and dynamics via relaxation measurements.

The relaxation rates for the three different carbon types in EDTA (carbonyl, CH2 central, and CH2 lateral) were measured with and without Zn(2+) as a function of field strength and temperature. The use of different field strengths in combination with NOE measurements allowed for the contribution of each relaxation mechanism (chemical shift anisotropy; spin rotation; dipole-dipole) to the total relaxation rate for each carbon to be determined. Temperature studies allowed for determination of the activation energy (Ea) for the motions of each carbon type. The most surprising result was the observation that the τ(c) decreases significantly for the lateral carbon upon addition of Zn(2+) at neutral pH, going from 54 to 8.6 ps at 298 K. This appears to be a pH-dependent phenomenon as other reports indicate that τ(c) increases for the lateral carbon upon addition of Zn(2+) under strongly basic conditions.

Graph-based symbolic technique and its application in the frequency response bound analysis of analog integrated circuits.

A new graph-based symbolic technique (GBST) for deriving exact analytical expressions like the transfer function H(s) of an analog integrated circuit (IC), is introduced herein. The derived H(s) of a given analog IC is used to compute the frequency response bounds (maximum and minimum) associated to the magnitude and phase of H(s), subject to some ranges of process variational parameters, and by performing nonlinear constrained optimization. Our simulations demonstrate the usefulness of the new GBST for deriving the exact symbolic expression for H(s), and the last section highlights the good agreement between the frequency response bounds computed by our variational analysis approach versus traditional Monte Carlo simulations. As a conclusion, performing variational analysis using our proposed GBST for computing the frequency response bounds of analog ICs, shows a gain in computing time of 100x for a differential circuit topology and 50x for a 3-stage amplifier, compared to traditional Monte Carlo simulations.

Population-based comparison of prognostic factors in invasive micropapillary and invasive ductal carcinoma of the breast.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) is a variant of breast carcinoma with a higher propensity for lymph node metastases compared with invasive ductal carcinoma (IDC). METHODS: Retrospective analysis of 636 IMPC and 297 735 IDC cases in the Surveillance, Epidemiology and End RESULTS database comparing disease-specific survival (DSS) and overall survival (OS) between IMPC and IDC. RESULTS: A higher percentage of IMPC cases (52.0%) had nodal metastases compared with IDC cases (34.6%). The 5-year DSS and OS for IMPC was 91.8% and 82.9%, respectively compared with 88.6% and 80.5% for IDC, respectively. For both IMPC and IDC, oestrogen-receptor positivity was associated with better survival, while having four or more positive lymph nodes or larger tumour size correlated with worse survival. Radiotherapy provided a survival benefit for both histological types. CONCLUSIONS: Despite IMPC's higher propensity for lymph node metastasis, IMPC has DSS and OS that compare favourably with IDC.

[Validity of airway predictors in outpatient medicine]. / Validez de los predictores de vía aérea difícil en medicina extrahospitalaria.

Isolation of the airway sometimes determines the survival or death of the patient. To anticipate the presence of a difficult airway (DA) there are a number of indicators that are validated for hospitals: Mallampati, sternum and thyromental distance, interdental distance and Cormack grade. The aim of this study is to evaluate the use of these indicators in the ambulatory setting and to know the incidence of DA. This data was collected from 324 intubations. Most patients were males (65.2%). The average age of the population was 63 years and no significant difference in age between DA and DA was found. A DA presence of 20.7% was objectified and an alternative device utilization of 21.4%. The thyromental distance was abnormal in 59% of patients and sternomentonal distance in 56.4% but neither showed an association with the presence of DA (p = 0.681 and p = 0.415 respectively). Interdental distance was less than 3 cm if presence is associated with DA (p = 0.005). The sensitivity and specificity of all measures are low. According to our series the sternum and thyromental distance are not useful in the ambulatory setting, but interdental distance is useful for predicting a DA.

Clinical and pathological aspects of multicentric hemangiosarcoma in a Pinscher dog / Sinais neurológicos multifocais devido ao hemangiossarcoma multicêntrico em um cão Pinscher: aspectos clínicos e patológicos

A 3-year-old female Pinscher dog was presented with a history of lameness and pain in hind limbs for one week which acutely progressed to non-ambulatory paraparesis. The dog had been apathetic and anorexic during the six days prior to presentation. The neurological findings were compatible with upper motor neuron signs to the left hind limb due to a spinal cord compressive mass on the twelfth thoracic vertebral body. On the other hand, signs of lower motor neurons to the right hind limb were due to a mass with a pathological fracture in the right proximal femur, compressing the sciatic nerve. A histopathological analysis of all organs revealedthe proliferation of endothelial cells showingin filtrative growth and organization into vascular structures with a solid pattern. In addition, immunohistochemycal analysis revealed low proliferation index and citoplasmatic positivity for CD-31, confirming the vascular nature of the neoplasm. Clinical, histopathological and immunophenotipical findings were consistent with hemangiosarcoma.

Uma cadela Pinscher de três anos de idade foi atendida em Hospital Veterinário Escola com histórico de dor nos membros pélvicos com progressão aguda para paraparesia não ambulatória. O animal estava apático e anoréxico há seis dias. Os achados neurológicos foram compatíveis com sinais de lesão de neurônios motores superiores para o membro pélvico esquerdo devido a uma massa no 12º corpo vertebral comprimindo a medula espinhal. Por outro lado, foram observados sinais de lesão de neurônios motores inferiores para o membro pélvico direito devido a uma fratura patológica no colo proximal do fêmur direito que comprimiu o nervo isquiático. Análises histopatológicas de todos os órgãos revelaram proliferação de células endoteliais com crescimento infiltrativo e organização sólida em estruturas vasculares. Adicionalmente, a análise imuno-histoquímica revelou baixa proliferação e marcação citoplasmática positiva para CD-31, confirmando a natureza vascular da neoplasia. Os achados clínicos, histopatológicos e imuno-histoquímicos foram consistentes com hemangiossarcoma.

DNA repair signature is associated with anthracycline response in triple negative breast cancer patients.

We hypothesized that a subset of sporadic triple negative (TN) breast cancer patients whose tumors have defective DNA repair similar to BRCA1-associated tumors are more likely to exhibit up-regulation of DNA repair-related genes, anthracycline-sensitivity, and taxane-resistance. We derived a defective DNA repair gene expression signature of 334 genes by applying a previously published BRCA1-associated expression pattern to three datasets of sporadic TN breast cancers. We confirmed a subset of 69 of the most differentially expressed genes by quantitative RT-PCR, using a low density custom array (LDA). Next, we tested the association of this DNA repair microarray signature expression with pathologic response in neoadjuvant anthracycline trials of FEC (n = 50) and AC (n = 16), or taxane-based TET chemotherapy (n = 39). Finally, we collected paraffin-fixed, formalin-embedded biopsies from TN patients who had received neoadjuvant AC (n = 28), and tested the utility of the LDA to discriminate response. Correlation between RNA expression measured by the microarrays and 69-gene LDA was ascertained. This defective DNA repair microarray gene expression pattern was significantly associated with anthracycline response and taxane resistance, with the area under the ordinary receiver operating characteristic curve (AUC) of 0.61 (95% CI = 0.45-0.77), and 0.65 (95% CI = 0.46-0.85), respectively. From the FFPE samples, the 69-gene LDA could discriminate AC responders, with AUC of 0.79 (95% CI = 0.59-0.98). In conclusion, a promising defective DNA repair gene expression signature appears to differentiate TN breast cancers that are sensitive to anthracyclines and resistant to taxane-based chemotherapy, and should be tested in clinical trials with other DNA-damaging agents and PARP-1 inhibitors.

Relación entre los niveles de ácido fólico, vitamina B12 y homocisteína materna y los defectos de tubo neural y labio hendido / Relation between levels of folic acid, vitamin B12 and maternal homocysteine with neural tube defects and cleft lip

El objetivo del trabajo fue determinar la asociación entre los niveles de ácido fólico, vitamina B (Vit B12) y homocisteína (Hci) maternos, con defectos del tubo neural (DTN) y labio hendido (LH) con y sin paladar hendido (c/s PH). Se realizó un estudio tipo casos y controles. Casos, con diagnóstico de DTN y LH c/s PH (n=36) y cuatro controles hospitalarios por caso (n=141). Se incluyeron recién nacidos (RN) y lactantes hasta 12 meses de edad. Las variables de pareamiento fueron: edad del RN o lactante, etnia y hospital. Un 23 por ciento de etnia Tarahumara y 77 por ciento mestizos. Se determinó ácido fólico intraeritrocitario (AFI), plasmático (AFP) y Vit B12 por radioinmunoensayo, la Hci por inmunoensayo de fluorescencia polarizada. Se consideró deficiencia si el AFI fue <160 ng/mL, AFP <3.5 ng/ mL y la Vit B12 <200 pg/mL e hiperhomocisteinemia, si Hci >15 J.mol/L. El análisis estadístico se realizó a través de regresión logística condicionada. Se identificó deficiencia de AFI en el 22 por ciento de las mujeres cuyos recién nacidos o lactantes presentaron algún tipo de defecto congénito y en el 12 por ciento de los controles. La relación entre AFI y DTN, LH c/s PH ajustada por edad materna, exposición a plaguicidas y zona de residencia fue RM 2,96 (IC 95 por ciento 0,92-9,46). No se encontraron diferencias en los niveles de Hci ni de Vit B12. Conclusiones: Nuestros resultados sugieren que RN cuyas madres cursan con una deficiencia de AFI tienen mayor riesgo de presentar DTN y LH c/s PH.

Objective: To determine the association between maternal folate deficiency, neural tube defects (NTDs), and cleft lip, with and without cleft palate (CL/P). Material and methods: A case/control study was conducted. The cases included subjects with diagnoses of NTD and CL/P (n=36) and four hospital controls per case (n=141); the study included newborns (NBs) and nursing babies up to 12monthsof age. The parameter variables were the following: the age of the NB or nursing baby, the ethnic group, and the hospital of origin. The Tarahumara ethnic group made up 23 percent of the cases, while 77 percent were mestizos. The red cell folate (RCF), the plasma folie acid (PFA), and the vitamin B12 levels were determined by radioimmunoassay and the homocysteine levels by polarized fluorescence immunoassay. A deficiency was considered to be present if the RCF were <160 ng/mL, the PFA <3.5 ng/mL and the vitamin B <200 pg/ mL; hyperhomocysteinemia was defined as HC >15 J,mol/L. The statistical analysis was carried out through of conditional logistic regression. Results: An RCF deficiency was identified in 22 percent of the women whose newborn or nursing babies presented with some type of congenital defect and in 12 percent of the controls. The correlation adjusted by maternal age, exposure to pesticides and zone of residence was OR 2.96 (CI 95 percent 0.92-9.46). There was no difference in vitamin B12 or homocysteine levels between groups. Conclusions: Our results suggest that newborns whose mothers present with an RCF deficiency have an increased risk of displaying NTD and CL/P.

Experimental and theoretical analysis of the reorientational dynamics of fullerene C70 in various aromatic solvents.

A previous study of C70 in deuterated chlorobenzene generated evidence suggesting C70 was experiencing unique reorientational behavior at given temperatures. The present study explores the possibility that this behavior is present across other solvents. The 13C spin-lattice relaxation rates for four carbon resonances in C70 were analyzed in benzene-d6, chlorobenzene-d5, and o-dichlorobenzene-d4, and as a function of temperature, to probe the reorientational dynamics of this fullerene. Anisotropic behavior was observed at the lowest (283 K) and highest temperatures (323 K), isotropic diffusion was seen between 293 and 303 K, and quasi-isotropic at 313 K. When anisotropic motion was present, diffusion about the figure axis was seen to be higher than diffusion of the figure axis. Experimentally obtained diffusion coefficients generated reorientational correlation times that were in excellent agreement with experimental values. Theoretical predictions generated by a modified Gierer-Wirtz model provided acceptable predictions of the diffusion constants; with DX usually being more closely reproduced and DZ values generally being underestimated. Overall, the results indicate that the factors affecting rotational behavior are complex and that multiple solvent factors are necessary to characterize the overall motion of C70 in these solvents. Although a solvent's viscosity is normally sufficient to characterize the tumbling motion, the spinning motion is less sensitive to solvent viscosity but more responsive to solvent structure. The balance and collective influence of these factors ultimately determines the overall rotational behavior.

Un acercamiento a los discos duros / An Approach to Hard Disks

Se denomina disco duro o disco rígido (en inglés hard disk, abreviado con frecuencia HD o HDD) al dispositivo encargado de almacenar información de forma permanente en una computadora. Los discos duros generalmente utilizan un sistema de grabación magnética analógica, que graba la información sobre el soporte cuando este pasa delante del electroimán, el soporte puede ser un carrete de hilo, cinta de papel o cinta magnética. El electroimán reorienta las partículas del material ferromagnético (óxidos de hierro o de cromo) que recubren el soporte; la reproducción recorre el camino opuesto. Esta cinta magnética es un tipo de soporte de almacenamiento de información que se graba en pistas sobre una banda de un material magnético, generalmente óxido de hierro o algún cromato, el tipo de información que se puede almacenar en las cintas magnéticas es variado: vídeo, audio y datos.

Effects of cyanobacterial extracellular products and gibberellic acid on salinity tolerance in Oryza sativa L.

Salt stress is one of the most serious factors limiting the productivity of rice, the staple diet in many countries. Gibberellic acid has been reported to reduce NaCl-induced growth inhibition in some plants including rice. Most paddy soils have a natural population of Cyanobacteria, prokaryotic photosynthethic microorganisms, which synthesize and liberate plant growth regulators such as gibberellins that could exert a natural beneficial effect on salt stressed rice plants. The aim of this work was to evaluate the effect of the cyanobacterium Scytonema hofmanni extracellular products on the growth of rice seedlings inhibited by NaCl and to compare it with the effect of the gibberellic acid in the same stress condition. Growth (length and weight of the seedlings) and biochemical parameters (5-aminolevulinate dehydratase activity, total free porphyrin and pigments content) were evaluated. Salt exposure negatively affected all parameters measured, with the exception of chlorophyll. Chlrorophyll concentrations nearly doubled upon exposure to high salt. Gibberellic acid counteracted the effect of salt on the length and dry weight of the shoot, and on carotenoid and chlorophyll b contents. Extracellular products nullified the salt effect on shoot dry weight and carotenoid content; partially counteracted the effect on shoot length (from 54% to 38% decrease), root dry weight (from 59% to 41% decrease) and total free porphyrin (from 31 to 13% decrease); reduced by 35% the salt increase of chlorophyll a; had no effect on root length and chlorophyll b. Gibberellic acid and extracellular products increased 5-aminolevulinate dehydratase activity over the control without salt. When coincident with high salinity, exposure to either EP or GA3, resulted in a reversal of shoot-related responses to salt stress. We propose that Scytonema hofmanni extracellular products may counteract altered hormone homeostasis of rice seedlings under salt stress by producing gibberellin-like plant growth regulators.