Effects of acute and chronic methylphenidate on prepulse inhibition: A sex difference study in Wistar rats.

BACKGROUND: The utilization of methylphenidate (MPH) is experiencing a notable surge within the adult population. This growth can be attributed to two key factors: its recreational and cognitive enhancement purposes, as well as the rising prevalence of ADHD diagnoses within this population. This study examined acute and chronic oral MPH effects on attention in male and female Wistar rats. To this end, we used a prepulse inhibition (PPI) task, which is widely used to assess psychoactive drug effects in both humans and rodents. This task allowed us to evaluate changes in attention by analyzing sensorimotor gating associated with stimulus selection process. METHODS: Animals were administered a clinically relevant dose of MPH (5 mg/kg) daily for seven days. The estrous cycle phases of the female rats were measured during behavioral sessions. The PPI task was conducted 20 min after drug administration on day 1 (acute), day 7 (chronic), and 48 h post-treatment. RESULTS: Results indicated that both acute and chronic MPH treatment impaired PPI expression in male rats, but not in female rats, regardless of their estrous cycle phase. Furthermore, a differential effect of chronic MPH treatment on the PPI task was found in male rats. Specifically, on the seventh treatment day, the PPI effect was observed when animals undertook the PPI task for the first time but was impaired in those animals in which the initial PPI session occurred under the acute influence of the drug (day 1). CONCLUSIONS: These findings suggest that the impact of MPH on sensorimotor gating responses may vary based on sex and task experience, possibly leading to state-dependent effects in healthy individuals.

Positioning of Tezepelumab in Severe Asthma.

Asthma is one of the most common chronic diseases and is estimated to be severe in 3%-10% of affected patients. There is a need for additional biologic treatments that are highly efficacious across the spectrum of severe uncontrolled asthma. Currently available drugs inhibit 1 or 2 specific cytokines or IgE antibodies and thus only partially suppress the complex type 2 (T2) inflammatory cascade. Biologics targeting more upstream molecules in the pathophysiological pathway of asthma could treat asthma more effectively. Tezepelumab is a human monoclonal immunoglobulin G2λ antibody that targets the cytokine thymic stromal lymphopoietin (TSLP). It is the first marketed biologic against an epithelial cell-derived cytokine, preventing binding of TSLP to its receptor and reducing the immune stimuli that TSLP can trigger in different asthma endotypes. Tezepelumab reduces downstream biomarkers of inflammation, such as blood and airway eosinophils, FeNO, IgE, IL-5, and IL-13. Tezepelumab provides a clinical benefit in severe asthma, reducing the annualized asthma exacerbation rate in patients with either high or low levels of biomarkers of T2 inflammation, although the effect is greater among those with high levels. The drug has been shown to improve asthma control, quality of life, and lung function and reduce airway hyperresponsiveness. Therefore, tezepelumab can be used across the spectrum of patients with severe uncontrolled asthma, especially in T2-high patients. This review includes a positioning statement by the authors, all of whom are members of the SEAIC Asthma Committee.

Obscure digestive bleeding.

A 50-year-old woman presented to the emergency department with several episodes of melena in the last week. The patient was not hemodynamically compromised and was conservatively managed. Urgent upper gastrointestinal endoscopy and colonoscopy showed no source of bleeding. Abdominal CT demonstrated three mural nodular lesions up to 2cm in the mid jejunum with hypervascular characteristics in arterial phase without active bleeding in venous phase. Angiography (Figure 1A) revealed three tumours with neo-angiogenesis and no active bleeding. Each lesion was stained with methylene blue and followed by embolization with coils. Exploratory laparotomy (Figure 1B) showed the three nodules marked by angiography. Intestinal resection of the affected segment was performed. Histopathological study proved the diagnosis of suspicion (Figure 2).

Increased synovial immunohistochemistry reactivity of TGF-ß1 in erosive peripheral psoriatic arthritis.

BACKGROUND: Immune and non-immune cells contribute to the pathology of chronic arthritis, and they can contribute to tissue remodeling and repair as well as disease pathogenesis. The present research aimed to analyze inflammation and bone destruction/regeneration biomarkers in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), osteoarthritis (OA), and ankylosing spondylitis (AS). METHODS: Samples were obtained from the inflamed knee of patients with knee arthritis who had been referred for undergoing arthroscopies. The synovial membrane was processed for pathological description, IHC analysis, and quantification of mRNA expression ratio by qRT-PCR. Serum levels of TGF-ß1, IL-23, IL-6, IL-17 A, IL-22, Dkk1, Sclerostin, BMP2, BMP4, Wnt1, and Wnt5a were measured by ELISA. All these data were analyzed and compared with the demographic, clinical, blood tests, and radiological characteristics of the patients. RESULTS: The synovial membrane samples were obtained from 42 patients for IHC, extraction, and purification of RNA for synovial mRNA expression analysis, and serum for measuring protein levels from 38 patients. IHC reactivity for TGF-ß1 in the synovial tissue was higher in patients with psoriatic arthritis (p 0.036) and was positively correlated with IL-17 A (r = 0.389, p = 0.012), and Dkk1 (r = 0.388, p = 0.012). Gene expression of the IL-17 A was higher in PsA patients (p = 0.018) and was positively correlated with Dkk1 (r = 0.424, p = 0.022) and negatively correlated with BMP2 (r = -0.396, p = 0.033) and BMP4 (r = -0.472, p = 0.010). It was observed that IHC reactivity for TGF-ß1 was higher in patients with erosive PsA (p = 0.024). CONCLUSIONS: The IHC reactivity of TGF-ß1 in synovial tissue was higher in patients with erosive psoriatic arthritis, and TGF-ß1 was in relation to higher levels of gene expression of IL-17 A and Dkk1.

Dupilumab to induce tolerance to SLIT-Melocotón®.

Summary: Introduction. Food allergy is an increasing problem for population and treatments inducing tolerance using sublingual immunotherapy is currently under study. Case presentation. Our aim as allergists is to achieve tolerance to sublingual allergen specific immunotherapy with sublingual immunotherapy (SLIT-peach). We present a case report consisting of a 40 year old woman with anaphylactic reactions after eating fruit and other plant-foods due to sensitization to nonspecific lipid transfer proteins (nsLTP). Her diagnose, LTP-syndrome. This protein is the main panallergen in our area and causes crossed reaction to multiple plant foods. The principal allergen in this syndrome is rPru p3, present in peach and most vegetables, fruits, nuts and grains. Serum specific IgE levels were performed using microarrays and positive for seven nsLTPs: rAra h9, rCor a8, nJug r3, rPru p3, rTri a 14, nArt v3 and rPla a3. Immediate reaction to SLIT in the fourth month of maintenance-dose led us to interrupt pru p3 immunotherapy. Immediate reaction to Omalizumab in the fourth dose in Hospital consisting in anaphylaxis prompted us to switch to Dupilumab. After four months with this monoclonal antibody we reintroduced sublingual immunotherapy with pru p3 SLIT-peach® achieving maintenance dose of four drops a day with no clinical reactions. SLIT-peach® in our patient is crucial for her due to her restricted diet, the severity of reactions and lack of quality of life measured by Europevall questionnaire. Conclusions in our case our aim is to achieve SLIT. We report a case of compassionate use with Dupilumab in a patient with multiple food allergy syndrome mediated by nsLTP. There are no cases reported for Dupilumab in this use.

Probing intra- and inter-molecular interactions through rotational spectroscopy: The case of the odorant 2'-aminoacetophenone and its 1:1 water and neon complexes.

The chirped-pulse Fourier transform microwave spectrum of 2'-aminoacetophenone, an aromatic chemical species with odorant properties, has been recorded in the 2-8 GHz frequency range and analyzed, obtaining precise information on the structure of the monomer and its neon and water complexes. The conformation of the monomer is determined by the formation of a resonance-assisted hydrogen bond (RAHB) between the carbonyl and amino groups, which leads to the formation of a bicyclic-like aromatic structure. Accordingly, the cycle formed by the non-covalent bond is preferred to the phenyl ring as the interaction site for neon. In the 1:1 complex, water lies in the molecular plane and forms a strong hydrogen bond with the carbonyl group coupled to an ancillary interaction with the methyl group, leaving the intramolecular RAHB unchanged. The experimental findings are supported by atoms in molecules and symmetry-adapted perturbation theory, which allowed for determining the hydrogen bond and intermolecular interaction energies, respectively.

Update on smoking. Alternatives for the management of patients with cardiovascular risk.

Smoking is the leading cause of morbidity and mortality worldwide and is clearly involved as a cardiovascular risk factor. Smoking has different effects on the cardiovascular system, such as a decrease in nitric oxide, increased inflammatory response, increased adhesion of pro-atherogenic molecules, lipid disturbances, generation of oxidative stress and endothelial dysfunction as can be shown in different biomarkers modifications. Despite the aids currently available for smoking cessation, many smokers are unwilling or unable to achieve this. So alternative tools with potential harm reduction, such as non-combustion tobacco products, could be an option due to the better results they had shown on cardiovascular risk factors. This has led these devices to be taken into account as a risk-modifying tobacco product according to the FDA.

Potentially inappropriate medications in older adults living with HIV.

OBJECTIVES: We assessed the prevalence of potentially inappropriate medication (PIM) among older (≥ 65 years) people living with HIV (O-PLWH) in the region of Madrid. METHODS: We analysed the dispensation registry of community and hospital pharmacies from the Madrid Regional Health Service (SERMAS) for the period between 1 January and 30 June 2017, looking specifically at PIMs according to the 2019 Beers criteria. Co-medications were classified according to the Anatomical Therapeutic Chemical (ATC) classification system. RESULTS: A total of 6 636 451 individuals received medications. Of these individuals, 22 945 received antiretrovirals (ARVs), and of these 1292 were O-PLWH. Overall, 1135 (87.8%) O-PLWH were taking at least one co-medication, and polypharmacy (at least five co-medications) was observed in 852 individuals (65.9%). A PIM was identified in 482 (37.3%) O-PLWH. Factors independently associated with PIM were polypharmacy [adjusted odds ratio (aOR) 7.08; 95% confidence interval (CI) 5.16-9.72] and female sex (aOR 1.75; 95% CI 1.30-2.35). The distribution of PIMs according to ATC drug class were nervous system drugs (n = 369; 28.6%), musculoskeletal system drugs (n = 140; 10.8%), gastrointestinal and metabolism drugs (n = 72; 5.6%), cardiovascular drugs (n = 61; 4.7%), respiratory system drugs (n = 13; 1.0%), antineoplastic and immunomodulating drugs (n = 10; 0.8%), and systemic anti-infectives (n = 2; 0.2%). Five drugs accounted for 84.8% of the 482O PLWH with PIMs: lorazepam (38.2%), ibuprofen (18.0%), diazepam (10.2%), metoclopramide (9.9%), and zolpidem (8.5%). CONCLUSIONS: Prescription of PIMs is highly prevalent in O-PLWH. Consistent with data in uninfected elderly people, the most frequently observed PIMs were benzodiazepines and nonsteroidal anti-inflammatory drugs . Targeted interventions are warranted to reduce inappropriate prescribing and polypharmacy in this vulnerable population.

Population and breast cancer patients' analysis reveals the diversity of genomic variation of the BRCA genes in the Mexican population.

Interpretation of variants of unknown significance (VUS) in genetic tests is complicated in ethnically diverse populations, given the lack of information regarding the common spectrum of genetic variation in clinically relevant genes. Public availability of data obtained from high-throughput genotyping and/or exome massive parallel sequencing (MPS)-based projects from several thousands of outbred samples might become useful tools to evaluate the pathogenicity of a VUS, based on its frequency in different populations. In the case of the Mexican and other Latino populations, several thousands of samples have been genotyped or sequenced during the last few years as part of different efforts to identify common variants associated to common diseases. In this report, we analyzed Mexican population data from a sample of 3985 outbred individuals, and additional 66 hereditary breast cancer patients were analyzed in order to better define the spectrum of common genomic variation of the BRCA1 and BRCA2 genes. Our analyses identified the most common genetic variants in these clinically relevant genes as well as the presence and frequency of specific pathogenic mutations present in the Mexican population. Analysis of the 3985 population samples by MPS identified three pathogenic mutations in BRCA1, only one population sample showed a BRCA1 exon 16-17 deletion by MLPA. This resulted in a basal prevalence of deleterious mutations of 0.10% (1:996) for BRCA1 and 11 pathogenic mutations in BRCA2, resulting in a basal prevalence of deleterious mutations of 0.276% (1:362) for BRCA2, combined of 0.376% (1:265). Separate analysis of the breast cancer patients identified the presence of pathogenic mutations in 18% (12 pathogenic mutations in 66 patients) of the samples by MPS and 13 additional alterations by MLPA. These results will support a better interpretation of clinical studies focused on the detection of BRCA mutations in Mexican and Latino populations and will help to define the general prevalence of deleterious mutations within these populations.

Differential interference contrast microscopy for cells using hard x-ray holography.

We propose a differential interference contrast method for cells using hard x-ray Gabor holography and knife-edge filtering in the spatial frequency domain, without relying on beam shearing. A phase object is holographically recorded and reconstructed by computer. Interference between the wavefronts of zeroth order weighted by ejπ/2 in the positive frequency region produces a dark image. Similarly, interference between the wavefronts of the zeroth order weighted by ej3π/2 in the negative frequency region produces a bright image. By adding these two intensity distributions, good quality phase-contrast images of 8-µm-diameter polystyrene beads and human HeLa cells were obtained.

Microsolvated complexes of ibuprofen as revealed by high-resolution rotational spectroscopy.

Hydrogen-bonded complexes between ibuprofen and water generated in a supersonic expansion were characterized using chirped-pulse Fourier transform microwave spectroscopy in the 2-8 GHz frequency range. Four spectra were observed allowing the determination of their rotational parameters. Comparison with quantum-chemical calculations led to their identification as the lowest energy 1 : 1 ibuprofen-water complexes. These correspond to the complexes between water and the four different conformers of ibuprofen previously detected in the gas phase, owing to their similar stabilization energies and abundances. Water seems to not change the conformational distribution of ibuprofen.

[The relationship between unemployment rates and lost work time due to sickness absence in an economic recession]. / Relación entre las tasas de desempleo y los indicadores de absentismo por incapacidad temporal durante periodos de crisis económica.

INTRODUCTION: Different countries have shown an inverse relationship between unemployment rates (UR) and indicators of sickness absence during periods of economic recession. OBJECTIVE: To evaluate the relationship between indicators of sickness absence and unemployment in Spain during 2009-2015. METHODS: We obtained incidence and absenteeism rates of non-work related sickness absence (NWSA) from Social Security data, and UR from the National Institute of Statistics. The relationship between indicators of NWSA and UR in the period 2009 to 2015 was graphically described using time trend plots. Scatter plots of NWSA indicators were also made against UR. Finally, we fitted linear regression models. RESULTS: Incidence (IR) and absenteeism rates (AR) of NWSA showed downward trends in 2009-2013 (IR 2009=28.07%, IR 2013=20.41%; AR 2009=2.53% and AR 2013=1.86%), changing to an upward trend up to 2015 (IR 2015=22.52%, AR 2015=2.12%). Unemployment rates trended upward in 2009-2013 (UR 2009=17.86%, UR 2013=26.10%), and then changed to a downward trend through 2015 (UR 2015=22.06%). There was an inverse relationship between UR and NWSA indicators. CONCLUSIONS: As in previous international studies, we found an inverse relationship between unemployment rates and indicators of sickness absence in Spain. More detailed studies are needed to evaluate explanatory hypotheses, such as those associated with the effects of discipline, selection and/or changes in the workforce.

INTRODUCCIÓN: Estudios realizados en varios países presentan una relación inversa entre las tasas de desempleo (TD) y los indicadores de absentismo por incapacidad temporal (IT) durante periodos de crisis económica. OBJETIVO: Evaluar la relación entre indicadores de absentismo y el desempleo en España (2009-2015). MÉTODOS: Se obtuvieron tasas de incidencia (TI) y absentismo (TA) por IT de origen común (ITcc) a partir de datos de la Seguridad Social, así como las TD según datos del Instituto Nacional de Estadística. Se describió gráficamente la evolución temporal de los indicadores de ITcc y el desempleo en el periodo 2009-2015. Para explorar dicha relación también se realizaron gráficos de dispersión de los indicadores frente a las TD. Posteriormente, se ajustaron modelos de regresión lineal simple. RESULTADOS: Las TI y TA descienden en 2009-2013 (TI 2009=28,07%, TI 2013=20,41%, TA 2009=2,53%, TA 2013=1,86%) momento en que cambia su tendencia, iniciando una fase ascendente hasta 2015 (TI 2015=22,52%, TA 2015=2,12%). La TD asciende en 2009-2013 (TD 2009=17,86%, TD 2013=26,10%), pasando a descender hasta 2015 (TD 2015=22,06%). Las TD y los indicadores de absentismo presentan una relación lineal inversa. CONCLUSIONES: Se observó una relación inversa entre el desempleo y los indicadores de absentismo en España. Son necesarios estudios específicos para poder evaluar hipótesis explicativas como las asociadas a los efectos de disciplina, selección y/o cambios en la fuerza de trabajo.

Influence of supplemental canola or soybean oil on milk yield, fatty acid profile and postpartum weight changes in grazing dairy goats.

OBJECTIVE: This experiment was designed to evaluate the effect of supplementation with soybean or canola oil on milk production and the composition of long chain fatty acids as well as weight changes in the goats and their kids. METHODS: Thirty nine mulitparous crossed Alpine×Nubian goats (initial body weight [BW] 43.5±1.7 kg) from the day of parturition were assigned to the treatments: grazing control (n = 15); grazing plus 20 mL/goat/d of supplemental soybean oil (n = 12); and grazing plus 20 mL/goat/d of supplemental canola oil (n = 12) from November 26, 2014 to March 7, 2015. The planned contrasts were: CI (control vs supplemented with oils); CII (soybean vs canola oil) to compare the treatment effects. RESULTS: The vegetable oil supplementation reduced weight losses in lactating goats (CI: -0.060 vs 0.090 kg/d; p = 0.03) but did not improve milk production or affect kids' growth. The content of C4, C6, C8, C10, C11, C14, and C18:1n9t in the milk was increased (p<0.05) with respect to control. However, C12, C14, C16, C18, C18:1n9c, C18:2n6c, and C18:3n3 were reduced (p<0.05) in supplemented goats. Conjugated linoleic acid (CLA) was increased (p<0.05) in goats supplemented with oils compared to the control group. CONCLUSION: Supplementation with 20 mL/d of soybean or canola oil did not affect milk production or kids' performance; however, it increased CLA concentration and reduced the reduced weight losses in lactating goats.

Sevoflurane anaesthesia for nasal surgery in a patient with multiple chemical sensitivity. / Anestesia con sevoflurano para cirugía de senos paranasales en un paciente con sensibilidad química múltiple.

Multiple chemical sensitivity syndrome is a group of complex disorders that include psychiatric disorders, chronic fatigue and/or respiratory problems. This syndrome could be triggered by specific allergens and toxins that cause neurophysiological sensitization and the appearance of the clinical symptomatology. Anaesthesia for these patients always poses a challenge for the anaesthetist, because they need to find and use drugs that do not trigger or aggravate the symptoms of the disease. Therefore, sevoflurane in these circumstances might be "the ideal anaesthetic". Performing general anaesthesia with sevoflurane as the sole anaesthetic agent, together with a series of environmental measures formed the basis for successful anaesthesia and surgery in our patient with a multiple chemical sensitivity syndrome.