Low-temperature processing of screen-printed piezoelectric KNbO3 with integration onto biodegradable paper substrates.

The development of fully solution-processed, biodegradable piezoelectrics is a critical step in the development of green electronics towards the worldwide reduction of harmful electronic waste. However, recent printing processes for piezoelectrics are hindered by the high sintering temperatures required for conventional perovskite fabrication techniques. Thus, a process was developed to manufacture lead-free printed piezoelectric devices at low temperatures to enable integration with eco-friendly substrates and electrodes. A printable ink was developed for screen printing potassium niobate (KNbO3) piezoelectric layers in microns of thickness at a maximum processing temperature of 120 °C with high reproducibility. Characteristic parallel plate capacitor and cantilever devices were designed and manufactured to assess the quality of this ink and evaluate its physical, dielectric, and piezoelectric characteristics; including a comparison of behaviour between conventional silicon and biodegradable paper substrates. The printed layers were 10.7-11.2 µm thick, with acceptable surface roughness values in the range of 0.4-1.1 µm. The relative permittivity of the piezoelectric layer was 29.3. The poling parameters were optimised for the piezoelectric response, with an average longitudinal piezoelectric coefficient for samples printed on paper substrates measured as d 33, eff, paper = 13.57 ± 2.84 pC/N; the largest measured value was 18.37 pC/N on paper substrates. This approach to printable biodegradable piezoelectrics opens the way forward for fully solution-processed green piezoelectric devices.

EZH2 mutations at diagnosis in follicular lymphoma: a promising biomarker to guide frontline treatment.

EZH2 is mutated in nearly 25% of follicular lymphoma (FL) cases. Little is known about how EZH2 affects patients' response to therapy. In this context, the aim of this study was to retrospectively analyze the frequency of mutations in EZH2 at diagnosis in tissue and ctDNA in patients with FL and to assess the patients' outcomes after receiving immunochemotherapy, depending on the EZH2 mutation status. Among the 154 patients included in the study, 27% had mutated EZH2 (46% with high-grade and 26% with low-grade FL). Of the mutated tissue samples, the mutation in ctDNA was identified in 44% of cases. EZH2 mutation in ctDNA was not identified in any patient unmutated in the tissue.Unmutated patients who received R-CHOP had significantly more relapses than patients who received R-Bendamustine (16/49 vs. 2/23, p = 0.040). Furthermore, our results show that patients with mutated EZH2 treated with R-CHOP vs. those treated with R-Bendamustine present a lower incidence of relapse (10% vs. 42% p = 0.09 at 4 years), a higher PFS (92% vs. 40% p = 0.039 at 4 years), and higher OS (100% vs. 78% p = 0.039 at 4 years). Based on these data, RCHOP could be a more suitable regimen for mutated patients, and R-bendamustine for unmutated patients. These findings could mean the first-time identification of a useful biomarker to guide upfront therapy in FL.

Hydro-climatic changes of wetlandscapes across the world.

Assessments of ecosystem service and function losses of wetlandscapes (i.e., wetlands and their hydrological catchments) suffer from knowledge gaps regarding impacts of ongoing hydro-climatic change. This study investigates hydro-climatic changes during 1976-2015 in 25 wetlandscapes distributed across the world's tropical, arid, temperate and cold climate zones. Results show that the wetlandscapes were subject to precipitation (P) and temperature (T) changes consistent with mean changes over the world's land area. However, arid and cold wetlandscapes experienced higher T increases than their respective climate zone. Also, average P decreased in arid and cold wetlandscapes, contrarily to P of arid and cold climate zones, suggesting that these wetlandscapes are located in regions of elevated climate pressures. For most wetlandscapes with available runoff (R) data, the decreases were larger in R than in P, which was attributed to aggravation of climate change impacts by enhanced evapotranspiration losses, e.g. caused by land-use changes.

The Cumulative and Differential Relation of Adverse Childhood Experiences and Substance Use During Emerging Adulthood.

Adverse childhood experiences (ACEs) have far-reaching effects on a wide range of health outcomes in adulthood, however, less is known about their consequences in emerging adulthood or in a geographically distinct sample. We examined the cumulative and individual relation of ACEs and two risky behaviors: alcohol and illegal drugs consumed by 490 Spanish emerging adults (mean age = 18.9). Participants answered the ACEs questionnaire, and two items about alcohol and illegal drugs consumption. Results showed that the overall experience of suffering different ACEs was a significant predictor of drug but not of alcohol consumption. Moreover, ACEs subtypes presented differential effects on substance use. Whereas some increased the likelihood of either drug or alcohol use, others reduced it. This study supports the importance of examining specific adverse experiences rather than only using an overall measure and provides some counterintuitive results that may be linked to resilient mechanisms.

Predictive Validity of the YLS/CMI in a Sample of Spanish Young Offenders of Arab Descent.

This study was conducted to assess the predictive validity of the Youth Level of Service/Case Management Inventory (YLS/CMI) in young offenders of Arab descent, living in Spain. To address this subject, the Inventory was administered to a sample of Arab minor offenders (N = 116), and results were compared to a sample of non-Arab minor offenders (N = 140), who were all aged between 14 and 17 years. The charges filed after the date of the first assessment carried out by the Youth Offending Team were coded during the follow-up period (2012-2017). The Inventory showed a similar predictive validity for both groups. However, the values were always slightly higher in the non-Arab group than in the Arab group. With subtle cultural differences, the YLS/CMI seems to be a risk instrument capable of predicting recidivism among Arab young offenders.

Hallazgos de neuroimagen en una serie de 14 pacientes con cefalea tratados con parche hemático epidural / Neuroimaging findings in a series of 14 patients witch headache for spontaneous intracranial hypotension treated with epidural blood patch

No disponible

Exome sequencing reveals three homozygous missense variants in SNRPA in two sisters with syndromic intellectual disability.

Splicing-related gene mutations might affect the expression of a single gene or multiple genes and cause clinically heterogeneous diseases. With the advent of next-generation sequencing, several splicing gene mutations have been exposed, yet most major spliceosome genes have no reports of germline mutations and therefore, their effects are largely unknown. We describe the previously unreported concurrence of intellectual disability, short stature, poor speech, and minor craniofacial and hand anomalies in 2 female siblings with 3 homozygous missense variants in SNRPA (a component of the U1 small nuclear ribonucleoprotein complex) characterized by homozygosity mapping and whole exome sequencing. Combined, c.97A>G, c.98T>C, and c.100T>A, in exon 2 of SNRPA lead to p.Ile33Ala and p.Phe34Ile exchanges, which were predicted in silico to be deleterious. Although both patients exhibited some clinical features seen in other spliceosomal disorders, their complete clinical phenotype appears to be rather uncommon, a finding that may further support the notion that mutations in components of the major spliceosome do not strictly lead to the same syndromes/phenotypes.

Clinical features of Mexican patients with Mucopolysaccharidosis type I.

Mucopolysaccharidosis type I (MPS-I) is an autosomal recessive lysosomal storage disorder caused by a deficiency or absence of α--iduronidase, which is involved in the catabolism of glycosaminoglycans (GAGs). This deficiency leads to the accumulation of GAGs in several organs. Given the wide spectrum of the disease, MPS-I has historically been classified into 3 clinical subtypes - severe (Hurler syndrome), intermediate (Hurler-Scheie syndrome), and mild (Scheie syndrome) - none of which is determined by residual enzyme activity. Eleven Mexican patients with MPS-I from northwestern México were evaluated. Diagnoses were confirmed through quantification of GAGs in urine and enzyme assay for α--iduronidase. Regardless of phenotype, all patients had various degrees of infiltrated facies, short stature, dysostosis multiplex, joint contractures, and corneal opacity typical of the disease. A better understanding of the spectrum of this disease can assist in diagnosis, treatment, and improvement in the quality of life for these patients.

Turning the screw even further to increase microparticle retention and ocular bioavailability of associated drugs: The bioadhesion goal.

Ocular drug delivery is one of the most fascinating and challenging tasks facing pharmaceutical researchers. Improving drug ocular residence time and/or penetration is complex. Microparticles (MP) provide interesting opportunities to increase ocular bioavailability of drugs and patient compliance brought about by decreased frequency of dosing. However, sustained-release microsphere formulation would fail to accomplish the task of long-lasting drug release unless microspheres remained for a prolonged period at the site of action. Some strategies have been assessed to retain MP at the target site. Among them, improving bioadhesion properties is possibly the one that offers the best technical features to date. In this review, we present the latest scientific communications in the field of MP development and coating to increase bioavailability when MP are destined for ocular treatment. All of these are more or less useful tools that must be considered as an important part of the development process for ocular medication optimization.

Role of the spinal TrkB-NMDA receptor link in the BDNF-induced long-lasting mechanical hyperalgesia in the rat: A behavioural study.

BACKGROUND: Intrathecal/intracisternal BDNF in rodents produces long-lasting hyperalgesia/allodynia, which implies BDNF plays a role in the establishment and maintenance of central sensitization. Both self-regeneration of endogenous BDNF and neuroplastic modifications of spinal NMDA receptors downstream TrkB signalling could be involved in such enduring hyperalgesia. We investigated to what extent BDNF by itself could participate in the generation and maintenance of mechanical hyperalgesia using pharmacological tools. METHODS: We studied sensitivity of mechanical hyperalgesia induced by a single intrathecal (i.t.) injection of BDNF (3 ng/10 µL i.t.) administered at time zero, for: (1) chronic NMDA receptor inhibition with subcutaneously implanted 7-day delivery osmotic pumps loaded with ketamine; (2) TrkB receptor inhibition with intraperitoneal (i.p.) cyclotraxine-B; and (3) chronic glial inhibition with repeated propentofylline i.t. injections. Nociceptive threshold to paw pressure, tested on days -3, 0, 3, 7, 10 and 14, was used as the index of central sensitization. Locomotor patterns and food and water consumption were assessed with LABORAS. RESULTS: Chronic ketamine prevented the mechanical hyperalgesia induced by BDNF, without affecting locomotion and food and water consumption. After pump depletion, a late hyperalgesic response to paw pressure stimulation emerged, which can be lastingly antagonized by cyclotraxine-B. Chronic propentofylline treatment irreversibly suppressed BDNF-induced hyperalgesia. CONCLUSION: Activation of NMDA receptors downstream to TrkB signalling is essential for behavioural expression of the mechanical hyperalgesia induced by intrathecal BDNF. However, maintenance of the hyperalgesia depends mainly from self-regenerating glial BDNF rather than from a NMDA receptor-dependent form of neuroplasticity. SIGNIFICANCE: Intrathecal BDNF induces long-lasting central sensitization via a glial-likely BDNF self-regenerating mechanism, whose behavioural expression depends on downstream activation of NMDA receptors. This knowledge suggests that TrkB antagonists could represent an interesting lead for the development of novel therapeutic strategies for some chronic pain conditions.

Hedgehog Pathway-Mediated Vascular Alterations Following Trigeminal Nerve Injury.

Whereas neurovascular interactions in spinal neuropathic pain models have been well characterized, little attention has been given to such neurovascular interactions in orofacial neuropathic pain models. This study investigated in male Sprague-Dawley rats the vascular changes following chronic constriction injury (CCI) of the infraorbital nerve (IoN), a broadly validated preclinical model of orofacial neuropathic pain. Following IoN-CCI, an early downregulation of tight junction proteins Claudin-1 and Claudin-5 was observed within the endoneurium and perineurium, associated with increased local accumulation of sodium fluorescein (NaFlu) within the IoN parenchyma, as compared with sham animals. These events were evidence of local blood-nerve barrier disruption and increased vascular permeability. A significant upregulation of immunocytes (CD3, CD11b) and innate immunity (TLR2, TLR4) mRNA markers was also observed, suggestive of increased local inflammation. Finally, a significant downregulation of Hedgehog pathway readouts Patched-1 and Gli-1 was observed within the IoN after CCI and local injections of cyclopamine, a Hedgehog pathway inhibitor, replicated in naïve rats the molecular, vascular, and behavioral changes observed following IoN-CCI. These results suggest a major role of Hedgehog pathway inhibition in mediating local increased endoneurial and perineurial vascular permeability following trigeminal nerve injury, thus facilitating immunocytes infiltration, neuroinflammation development, and neuropathic pain-like aversive behavior.

Colagenosis perforante reactiva: A propósito de dos casos / Reactive perforating colagenosis: Report of two cases

Los desórdenes perforantes actualmente incluyen a la enfermedad de Kyrle, la elastosis perforante adquirida serpiginosa, la colagenosis perforante reactiva adquirida y la foliculitis perforante. Antes se consideraban entidades diferentes, pero debido a los hallazgos similares en la clínica e histopatología, se engloban dentro de este término unificador. Se manifiestan como pápulas y/o nódulos que presentan un tapón queratósico central. Su causa es desconocida, sin embargo, se las ha relacionado con distintas patologías sistémicas como la diabetes mellitus y la enfermedad renal crónica, entre otras. Se presentan dos casos de dermatosis perforante adquirida tipo colagenosis perforante reactiva, en un hombre de 69 años con antecedentes de diabetes mellitus tipo II y cirrosis hepática secundaria a infección por virus de hepatitis C y una paciente de 62 años con antecedente de diabetes mellitus tipo II.

Perforating disorders currently include Kyrle's disease, serpiginous perforating elastosis acquired, the acquired reactive perforating colagenosis and perforating folliculitis. Previously they were considered different entities, but due to similar findings in clinical and histopathology are now included within this umbrella term. The clinical findings are papules and / or nodules with a central keratotic plug and pruritus is the predominant symptom. It causes are still unknown; however they have been associated with various systemic diseases such as diabetes mellitus and chronic renal disease, among others. We report two cases of reactive perforating collagenosis one in a 69-year-old man with a history of type II diabetes mellitus and liver cirrhosis secondary to infection with hepatitis C and the other one in a 62-year-old woman with type II diabetes mellitus.

Earlier menarcheal age in Spanish girls is related with an increase in body mass index between pre-pubertal school age and adolescence.

BACKGROUND: Higher body mass index (BMI) has been associated with earlier pubertal development. OBJECTIVE: The aim of this longitudinal study was to determine menarcheal age in a Spanish cohort and to assess its association with anthropometric variables at birth, childhood and adolescence. We also analyse whether the tracking of weight between different ages could affect the timing of menarche. METHODS: The sample population included 195 randomly selected 6-8-year-old girls who participated in the baseline of the Four Provinces Study and in the follow-up of this study at 13-16 years old. Anthropometrical variables were measured and BMI and BMI z-score were calculated. Information regarding birth weight and menarche was obtained by means of self-report questionnaire. RESULTS: Correlation analysis showed a significant negative association of age at menarche with weight, BMI and BMI z-score in the baseline and follow-up groups but not with weight at birth. Fat mass at adolescence is related to a significantly earlier menarcheal age. When comparing weight categories, earliest menarcheal age is associated with an increase of BMI between 6-8-year-old and 13-16-year-old girls. CONCLUSION: In our study, high weight in girls is associated with the earliest age at menarche. This becomes a major influence when weight gain occurs between pre-pubertal school age and adolescence.

Evidence of Surface Loss as Ubiquitous Limiting Damping Mechanism in SiN Micro- and Nanomechanical Resonators.

Silicon nitride (SiN) micro- and nanomechanical resonators have attracted a lot of attention in various research fields due to their exceptionally high quality factors (Qs). Despite their popularity, the origin of the limiting loss mechanisms in these structures has remained controversial. In this Letter we propose an analytical model combining acoustic radiation loss with intrinsic loss. The model accurately predicts the resulting mode-dependent Qs of low-stress silicon-rich and high-stress stoichiometric SiN membranes. The large acoustic mismatch of the low-stress membrane to the substrate seems to minimize radiation loss and Qs of higher modes (n∧m≥3) are limited by intrinsic losses. The study of these intrinsic losses in low-stress membranes reveals a linear dependence with the membrane thickness. This finding was confirmed by comparing the intrinsic dissipation of arbitrary (membranes, strings, and cantilevers) SiN resonators extracted from literature, suggesting surface loss as ubiquitous damping mechanism in thin SiN resonators with Q_{surf}=ßh and ß=6×10^{10}±4×10^{10} m^{-1}. Based on the intrinsic loss the maximal achievable Qs and Qf products for SiN membranes and strings are outlined.

Confusión como síntoma de presentación de una pseudomigraña con pleocitosis en un paciente pediátrico / Confusion as a presentation symptom of pseudomigraine with pleocytosis in a paediatric patient

La cefalea con déficits neurológicos transitorios con pleocitosis linfocitaria en el líquido cefalorraquídeo (HaNDL) es una entidad poco frecuente y de etiología desconocida caracterizada por episodios de cefalea intensa, déficits neurológicos transitorios recurrentes durante 3 meses y pleocitosis linfocitaria. Presentamos el caso de una niña de 14 años con cefalea y vómitos de 4 días de evolución, asociando posteriormente confusión, disminución de conciencia, afasia, paresia facial periférica, ataxia y febrícula durante 24 h. El análisis del LCR mostró pleocitosis (110 leucocitos/ml) y proteinorraquia (87 mg/dl). El electroencefalograma mostraba enlentecimiento generalizado en el momento agudo y posteriormente actividad lenta focalizada izquierda. En los siguientes 2 meses presentó 7 nuevos episodios de cefalea migrañosa permaneciendo asintomática después. Es el primer caso pediátrico de HaNDL que se presenta como agitación y/o estado confusional. Esta entidad debe incluirse en el diagnóstico diferencial ante cuadros de cefalea y alteración de conciencia para evitar tratamientos prolongados o pruebas invasivas innecesarias

Transient headache and neurological deficits with cerebrospinal fluid lymphocytic pleocytosis (Handl) syndrome is a rare condition of unknown origin that is characterized by episodes of severe headache, transient neurological deficits that recur over less than 3 months, and lymphocytic pleocytosis in CSF. We report the case of a 14 year-old girl who presented with headache and vomiting that lasted 4 days, later combined with a clinical presentation of confusion, with a decrease in the level of consciousness, aphasia, peripheral facial paralysis, ataxia and fever for 24 hours. CSF analysis showed pleocytosis (110 cells/ml) and proteinorrachia (87 mg/dl). Electroencephalogram in the acute time showed generalized slowing, and later a focal slowing in the left hemisphere. She suffered 7 episodes of migraine (severe headache and vomiting) in the following two months, remaining asymptomatic thereafter. This is the first pediatric case published in the literature that presents with an agitated and/or confused state. This condition must be considered in the differential diagnosis of patients with headache and acute altered level of consciousness, in order to avoid prolonged treatments or unnecessary invasive testing

Optical detection of radio waves through a nanomechanical transducer.

Low-loss transmission and sensitive recovery of weak radio-frequency and microwave signals is a ubiquitous challenge, crucial in radio astronomy, medical imaging, navigation, and classical and quantum communication. Efficient up-conversion of radio-frequency signals to an optical carrier would enable their transmission through optical fibres instead of through copper wires, drastically reducing losses, and would give access to the set of established quantum optical techniques that are routinely used in quantum-limited signal detection. Research in cavity optomechanics has shown that nanomechanical oscillators can couple strongly to either microwave or optical fields. Here we demonstrate a room-temperature optoelectromechanical transducer with both these functionalities, following a recent proposal using a high-quality nanomembrane. A voltage bias of less than 10 V is sufficient to induce strong coupling between the voltage fluctuations in a radio-frequency resonance circuit and the membrane's displacement, which is simultaneously coupled to light reflected off its surface. The radio-frequency signals are detected as an optical phase shift with quantum-limited sensitivity. The corresponding half-wave voltage is in the microvolt range, orders of magnitude less than that of standard optical modulators. The noise of the transducer--beyond the measured 800 pV Hz-1/2 Johnson noise of the resonant circuit--consists of the quantum noise of light and thermal fluctuations of the membrane, dominating the noise floor in potential applications in radio astronomy and nuclear magnetic imaging. Each of these contributions is inferred to be 60 pV Hz-1/2 when balanced by choosing an electromechanical cooperativity of ~150 with an optical power of 1 mW. The noise temperature of the membrane is divided by the cooperativity. For the highest observed cooperativity of 6,800, this leads to a projected noise temperature of 40 mK and a sensitivity limit of 5 pV Hz-1/2. Our approach to all-optical, ultralow-noise detection of classical electronic signals sets the stage for coherent up-conversion of low-frequency quantum signals to the optical domain.

[Confusion as a presentation symptom of pseudomigraine with pleocytosis in a paediatric patient]. / Confusión como síntoma de presentación de una pseudomigraña con pleocitosis en un paciente pediátrico.

Transient headache and neurological deficits with cerebrospinal fluid lymphocytic pleocytosis (Handl) syndrome is a rare condition of unknown origin that is characterized by episodes of severe headache, transient neurological deficits that recur over less than 3 months, and lymphocytic pleocytosis in CSF. We report the case of a 14 year-old girl who presented with headache and vomiting that lasted 4 days, later combined with a clinical presentation of confusion, with a decrease in the level of consciousness, aphasia, peripheral facial paralysis, ataxia and fever for 24 hours. CSF analysis showed pleocytosis (110 cells/ml) and proteinorrachia (87 mg/dl). Electroencephalogram in the acute time showed generalized slowing, and later a focal slowing in the left hemisphere. She suffered 7 episodes of migraine (severe headache and vomiting) in the following two months, remaining asymptomatic thereafter. This is the first pediatric case published in the literature that presents with an agitated and/or confused state. This condition must be considered in the differential diagnosis of patients with headache and acute altered level of consciousness, in order to avoid prolonged treatments or unnecessary invasive testing.

Association of the tumor necrosis factor-alpha -308G>A polymorphism with breast cancer in Mexican women.

The tumor necrosis factor-alpha (TNF-α) gene plays an important role in cell proliferation, differentiation, apoptosis, lipid metabolism, coagulation, insulin resistance, and endothelial function. Polymorphisms of TNF-α have been associated with cancer. We examined the role of the -308G>A polymorphism in this gene by comparing the genotypes of 294 healthy Mexican women with those of 465 Mexican women with breast cancer. The observed genotype frequencies for controls and breast cancer patients were 1 and 14% for AA, 13 and 21% for GA, and 86 and 65% for GG, respectively. We found that the odds ratio (OR) for AA genotype was 2.4, with a 95% confidence interval (95%CI) of 5.9-101.1 (P = 0.0001). The association was also evident when comparing the distribution of the AA-GA genotype in patients in the following categories: 1) premenopause and obesity I (OR = 3.5, 95%CI = 1.3-9.3, P = 0.008), 2) Her-2 neu and tumor stage I-II (OR = 2.5, 95%CI = 1.31-4.8, P = 0.004), 3) premenopause and tumor stage III-IV (OR = 1.7, 95%CI = 1.0-2.9, P = 0.034), 4) chemotherapy non-response and abnormal hematocrit (OR = 2.4, 95%CI = 1.2-4.8, P = 0.015), 5) body mass index and Her-2 neu and III-IV tumor stage (OR = 2.8, 95%CI = 1.2- 6.6, P = 0.016), and 6) nodule metastasis and K-I67 (OR = 4.0, 95%CI = 1.01-15.7, P = 0.038). We concluded that the genotypes AA-GA of the -308G>A polymorphism in TNF-α significantly contribute to breast cancer susceptibility in the analyzed sample from the Mexican population.