Monoaminergic system and depression.

Major depressive disorder is a severe, disabling disorder that affects around 4.7% of the population worldwide. Based on the monoaminergic hypothesis of depression, monoamine reuptake inhibitors have been developed as antidepressants and nowadays, they are used widely in clinical practice. However, these drugs have a limited efficacy and a slow onset of therapeutic action. Several strategies have been implemented to overcome these limitations, including switching to other drugs or introducing combined or augmentation therapies. In clinical practice, the most often used augmenting drugs are lithium, triiodothyronine, atypical antipsychotics, buspirone, and pindolol, although some others are in the pipeline. Moreover, multitarget antidepressants have been developed to improve efficacy. Despite the enormous effort exerted to improve these monoaminergic drugs, they still fail to produce a rapid and sustained antidepressant response in a substantial proportion of depressed patients. Recently, new compounds that target other neurotransmission system, such as the glutamatergic system, have become the focus of research into fast-acting antidepressant agents. These promising alternatives could represent a new pharmacological trend in the management of depression.

Oral mucosal peeling related to dentifrices and mouthwashes: A systematic review.

BACKGROUND: The aim of this systematic review was to summarise the clinical information available about oral mucosal peeling (OMP) and to explore its aetiopathogenic association with dentifrices and mouthwashes. MATERIAL AND METHODS: PICOS outline. Population, subjects diagnosed clinically and/or pathologically. Intervention, exposition to oral hygiene products. Comparisons, patients using products at different concentrations. Outcomes, clinicopathological outcomes (primary) and oral epithelial desquamation (secondary) after use. Study design, any. Exclusion criteria, reports on secondary or unpublished data, in vitro studies. Data were independently extracted by two reviewers. RESULTS: Fifteen reports were selected from 410 identified. Descriptive studies mainly showed low bias risk, experimental studies mostly an "unclear risk". Dentifrices or mouthwashes were linked to OMP, with an unknown origin in 5 subjects. Sodium lauryl-sulphate (SLS) was behind this disorder in 21 subjects, tartar-control dentifrices in 2, and flavouring agents in 1 case. Desquamation extension was linked to SLS concentration. Most cases were painless, leaving normal mucosa after desquamation. Tartar-control dentifrices caused ulcerations more frequently. CONCLUSIONS: OMP management should consider differential diagnosis with oral desquamative lesions, particularly desquamative gingivitis, with a guided clinical interview together with pathological confirmation while discouraging the use of the product responsible for OMP.

NDUFA9 point mutations cause a variable mitochondrial complex I assembly defect.

Mitochondrial respiratory chain complex I consists of 44 different subunits and contains 3 functional modules: the Q-, the N- and the P-module. NDUFA9 is a Q-module subunit required for complex I assembly or stability. However, its role in complex I biogenesis has not been studied in patient fibroblasts. So far, a single patient carrying an NDUFA9 variant with a severe neonatally fatal phenotype has been reported. Via exome sequencing, we identified a novel homozygous NDUFA9 missense variant in another patient with a milder phenotype including childhood-onset progressive generalized dystonia and axonal peripheral neuropathy. We performed complex I assembly analysis using primary skin fibroblasts of both patients. Reduced complex I abundance and an accumulation of Q-module subassemblies were present in both patients but more pronounced in the severe clinical phenotype patient. The latter displayed additional accumulation of P-module subassemblies, which was not present in the milder-phenotype patient. Lentiviral complementation of both patient fibroblast cell lines with wild-type NDUFA9 rescued complex I deficiency and the assembly defects. Our report further characterizes the phenotypic spectrum of NDUFA9 deficiency and demonstrates that the severity of the clinical phenotype correlates with the severity of the effects of the different NDUFA9 variants on complex I assembly.

A Dramatic Case of Odynophagia.

We report the case of a 77-year-old male with a history of aortic stenosis and interstitial lung disease, who debuted 3 years ago with an outbreak of necrotic and very painful canker sores. The severity of the lesions and their refractory response to treatment led to several hospital admissions and multiple consultations to different specialists (ENT, rheumatology, dermatology, ophthalmology, cardiology, and internal medicine). During this time, the patient received central parenteral nutrition with an episode of catheter-related septicemia, and he came to require psychiatric assistance for autolytic ideation. Numerous diagnostic tests were performed with inconclusive results, including biopsy of the lesion (histological study, immunohistochemistry for CD68 + , CD4 + , CD8 + , CD20 + , MCT +, and cytomegalovirus, PAS, Grocott-Gomori and Zielh-Neelsen staining, and in situ hybridization for Epstein Barr virus). Numerous treatments were unsuccessfully tested until thalidomide was administered, thus completely remitting lesions but leaving retractable scarring sequelae. Since then, the patient has had two recurrences, coinciding with the reduction of thalidomide dosages, which were controlled by increasing the dose of the immunomodulator. Recurrent necrotizing major aphthous stomatitis (Sutton's disease) is a clinical variant of recurrent aphthous stomatitis that may have a dramatic course. Unfortunately, the lack of etiopathogenetic uniformity precludes any specific treatment. In severe cases, immunomodulators, including thalidomide, may represent a valid therapeutic option.

Early responses to deep brain stimulation in depression are modulated by anti-inflammatory drugs.

Deep brain stimulation (DBS) in the subgenual cingulated gyrus (SCG) is a promising new technique that may provide sustained remission in resistant major depressive disorder (MDD). Initial studies reported a significant early improvement in patients, followed by a decline within the first month of treatment, an unexpected phenomenon attributed to potential placebo effects or a physiological response to probe insertion that remains poorly understood. Here we characterized the behavioural antidepressant-like effect of DBS in the rat medial prefrontal cortex, focusing on modifications to rodent SCG correlate (prelimbic and infralimbic (IL) cortex). In addition, we evaluated the early outcome of DBS in the SCG of eight patients with resistant MDD involved in a clinical trial. We found similar antidepressant-like effects in rats implanted with electrodes, irrespective of whether they received electrical brain stimulation or not. This effect was due to regional inflammation, as it was temporally correlated with an increase of glial-fibrillary-acidic-protein immunoreactivity, and it was blocked by anti-inflammatory drugs. Indeed, inflammatory mediators and neuronal p11 expression also changed. Furthermore, a retrospective study indicated that the early response of MDD patients subjected to DBS was poorer when they received anti-inflammatory drugs. Our study demonstrates that electrode implantation up to the IL cortex is sufficient to produce an antidepressant-like effect of a similar magnitude to that observed in rats receiving brain stimulation. Moreover, both preclinical and clinical findings suggest that the use of anti-inflammatory drugs after electrode implantation may attenuate the early anti-depressive response in patients who are subjected to DBS.

Accuracy of systolic aortic regurgitation in the diagnosis of heart failure: a predictive approach.

BACKGROUND: Systolic aortic regurgitation (SAR) is a curious phenomenon that has been found to be associated with heart failure (HF). We aimed to determine de diagnostic value of SAR as a black box predictive tool in patients with suspected HF admitted to hospital with dyspnea as leading symptom. METHODS AND RESULTS: Cross-sectional study including 269 consecutive patients admitted to hospital with dyspnea as leading symptom without definite clinical diagnosis. SAR was defined by echocardiography as the presence of blood flow from the aorta to the left ventricular outflow tract during a complete systole. The reference standard was the presence of HF diagnosis at discharge. SAR was present in 9 (3.3%) patients. Prevalence of HF was 40.3%. Specificity of SAR in the diagnosis of HF was high at 99.4% (95% CI 96.5-99.9%). Sensitivity was 7.5% (95% CI 3.9-14.2%). Positive predictive value (PPV) was 88.9% (95% CI 56.5-98.0%). Positive likelihood ratio was 11.85. Estimated PPV of SAR was significantly higher than 50% for any hypothetical prevalence of HF. CONCLUSION: In patients admitted to hospital with dyspnea, the finding of systolic aortic regurgitation in echocardiography has a high PPV for HF diagnosis at discharge.

Er,Cr:YSGG laser therapy for oral leukoplakia minimizes thermal artifacts on surgical margins: a pilot study.

Laser use for biopsy of suspicious lesions may simulate cytological atypia at the margin of the incisions, challenging pathological diagnosis. Erbium, chromium: yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser has shown promising results in experimental models by inducing fewer artifacts. The aims of this study were to examine the thermal wounds induced by Er,Cr:YSGG laser in a short series of oral leukoplakias in terms of cytological and epithelial architectural changes and also to assess the width of the thermal damage lateral to the incision. Four oral leukoplakia patients entered the study and underwent complete surgical excision of their lesions by using Er,Cr:YSGG laser. Patients were weekly controlled until complete healing was accomplished. The patients were included on the existing follow-up program for these lesions thereafter. Study samples were routinely processed by the same technician and double-blindedly studied by two pathologists until a consensus was reached for each case. The pathological analysis of the samples revealed no autolysis and no fixation- or handling-related artifacts. However, cellular and nuclear polymorphism could be observed in two samples. Loss of intercellular adherence was the most frequent thermal artifact in this series; all pseudodysplastic artifacts recognized in the study were of low intensity and located at the basal and suprabasal layers of the leukoplakias' epithelium. The width of the thermal damage at the edge of the incision scored an average of 26.60 ± 25.3 µm. It is concluded that irradiation with Er,Cr:YSGG laser induces a minimal amount of thermal artifacts at the surgical margins of oral leukoplakias and avoids diagnostic interferences with real dysplastic borders.

Design and evaluation of the MAMMI dedicated breast PET.

PURPOSE: A breast dedicated positron emission tomography (PET) scanner has been developed based on monolithic LYSO crystals coupled to position sensitive photomultiplier tubes (PSPMTs). In this study, we describe the design of the PET system and report on its performance evaluation. METHODS: MAMMI is a breast PET scanner based on monolithic LYSO crystals. It consists of 12 compact modules with a transaxial field of view (FOV) of 170 mm in diameter and 40 mm axial FOV that translates to cover up to 170 mm. The patient lies down in a prone position that facilitates maximum breast elongation. Quantitative performance analysis of the calculated method for the attenuation correction specifically developed for MAMMI, and based on PET image segmentation, has also been conducted in this evaluation. In order to fully determine the MAMMI prototype's performance, we have adapted the measurements suggested for National Electrical Manufacturers Association (NEMA) NU 2-2007 and NU 4-2008 protocol tests, as they are defined for whole-body and small animal PET scanners, respectively. RESULTS: Spatial resolutions of 1.6, 1.8, and 1.9 mm were measured in the axial, radial, and tangential directions, respectively. A scatter fraction of 20.8% was obtained and the maximum NEC was determined to be 25 kcps at 44 MBq. The average sensitivity of the system was observed to be 1% for an energy window of (250 keV-750 keV) and a maximum absolute sensitivity of 1.8% was measured at the FOV center. CONCLUSIONS: The overall performance of the MAMMI reported on this evaluation quantifies its ability to produce high quality PET images. Spatial resolution values below 3 mm were measured in most of the FOV. Only the radial component of spatial resolution exceeds the 3 mm at radial positions larger than 60 mm. This study emphasizes the need for standardized testing methodologies for dedicated breast PET systems similar to NEMA standards for whole-body and small animal PET scanners.

Ewing-like sarcoma bladder primary tumour: A case report and literature review.

Bladder primitive neuroectodermal tumors are extremely rare but are most frequent in older adult. 59-year-old man that complained of hematuria for the previous 24 h, urethral syndrome, and pain in the right renal fossa over the previous two weeks. No definitive management or treatment guidelines have been established. Hematuria is the most frequent symptom. Advanced age, metastasis, and incomplete tumor resection are determinants of a poor prognosis. Ewing-like bladder primary tumor is a rare entity with a poor prognosis, hence an aggressive treatment combining surgery and chemotherapy must be considered from the beginning.

[Invasive mechanical ventilation in COPD and asthma]. / Ventilación mecánica invasiva en EPOC y asma.

COPD and asthmatic patients use a substantial proportion of mechanical ventilation in the ICU, and their overall mortality with ventilatory support can be significant. From the pathophysiological standpoint, they have increased airway resistance, pulmonary hyperinflation, and high pulmonary dead space, leading to increased work of breathing. If ventilatory demand exceeds work output of the respiratory muscles, acute respiratory failure follows. The main goal of mechanical ventilation in this kind of patients is to improve pulmonary gas exchange and to allow for sufficient rest of compromised respiratory muscles to recover from the fatigued state. The current evidence supports the use of noninvasive positive-pressure ventilation for these patients (especially in COPD), but invasive ventilation also is required frequently in patients who have more severe disease. The physician must be cautious to avoid complications related to mechanical ventilation during ventilatory support. One major cause of the morbidity and mortality arising during mechanical ventilation in these patients is excessive dynamic pulmonary hyperinflation (DH) with intrinsic positive end-expiratory pressure (intrinsic PEEP or auto-PEEP). The purpose of this article is to provide a concise update of the most relevant aspects for the optimal ventilatory management in these patients.

Clinical guideline for the treatment of dual pathology in the adult population.

Editorial del vol 28-1.

Sustained escitalopram administration affects glucose metabolism in the rat brain.

Escitalopram is a selective serotonin reuptake inhibitor (SSRIs) antidepressant, drug that is currently used as first-line agents for the treatment of depression and it is also used in the treatment of other psychiatric disorders. The main goal of this study was to identify which brain areas are affected by escitalopram administration. This study was carried out on male Wistar rats that received escitalopram daily over 14 days and that were studied by 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG)-PET on the last day of treatment. Computed tomography (CT) images were acquired immediately before each PET scan and the main effects of drug administration were elucidated by Statistical Parametric Mapping. The results obtained indicated that repeated exposure to escitalopram increased metabolic activity in the retrosplenial and posterior cingulate cortices, while it decreased such activity in the ventral hippocampus, cerebellum, brainstem and midbrain regions, including the raphe nuclei and ventral tegmental area. Therefore, repeated exposure to escitalopram alters the activity of several brain areas closely related to the serotonergic system, and previously identified as key regions in the antidepressant effect induced by SSRIs. Furthermore, some of the changes found, such as the dampened metabolism in the ventral tegmental area, are similar to changes that have been described after treating with other fast-acting antidepressant approaches.

[Mild encephalitis/encephalopathy with a reversible splenial corpus callosum lesion (MERS)]. / Encefalitis/encefalopatía leve con lesión reversible del esplenio del cuerpo calloso (MERS).

INTRODUCTION: Mild encephalitis/encephalopathy with a reversible isolated splenial corpus callosum lesion (MERS) is a clinical-radiological syndrome characterized by a lesion in the center of the splenium identified by magnetic resonance imaging (MRI), the imaging test of choice. CASE REPORT: A 31-year-old man is admitted with fever, intense hemicranial headache, disorientation, dysarthria and paresthesia in the lips and both upper extremities is presented; and that he is admitted for a suspected diagnosis of viral encephalitis. The cerebrospinal fluid analysis shows an elevation of proteins and the electroencephalogram shows generalized slowing, predominantly on the left. MRI shows a well-defined ovoid lesion, isolated in the splenium of the corpus callosum, homogeneous and hyperintense on T2 and FLAIR, with restriction to fluid diffusion and without uptake after gadolinium administration. The patient received empirical treatment with acyclovir and corticosteroids, with good subsequent evolution and disappearance of the lesion described in the control MRI at 3 weeks. CONCLUSION: MERS is a benign, infrequent entity of unknown pathogenesis, which must be differentiated from other pathologies that present with lesions of the corpus callosum, but with an unfavorable prognosis.

TITLE: Encefalitis/encefalopatía leve con lesión reversible del esplenio del cuerpo calloso (MERS).Introducción. La encefalitis/encefalopatía leve con lesión reversible aislada del esplenio del cuerpo calloso (MERS) es un síndrome clinicorradiológico caracterizado por una lesión en el centro del esplenio identificada por resonancia magnética, prueba de imagen de elección. Caso clínico. Se presenta el caso de un varón de 31 años con cuadro de fiebre, cefalea intensa hemicraneal, desorientación, disartria y parestesias en los labios y en ambas extremidades superiores, y que ingresa por sospecha diagnóstica de encefalitis vírica. El análisis del líquido cefalorraquídeo muestra una elevación de proteínas y el electroencefalograma manifiesta una lentificación generalizada de predominio izquierdo. La resonancia magnética evidencia una lesión ovoidea, bien delimitada, aislada en el esplenio del cuerpo calloso, homogénea e hiperintensa en T2 y FLAIR, con restricción a la difusión hídrica y sin captación tras la administración de gadolinio. El paciente recibe tratamiento de forma empírica con aciclovir y corticoesteroides, con buena evolución posterior y desaparición de la lesión descrita en la resonancia magnética de control a las tres semanas. Conclusión. La MERS es una entidad benigna, infrecuente y de patogenia desconocida, que debe diferenciarse de otras patologías que cursan con lesiones del cuerpo calloso en las que el pronóstico es desfavorable.

Sex differences in fear memory consolidation via Tac2 signaling in mice.

Memory formation is key for brain functioning. Uncovering the memory mechanisms is helping us to better understand neural processes in health and disease. Moreover, more specific treatments for fear-related disorders such as posttraumatic stress disorder and phobias may help to decrease their negative impact on mental health. In this line, the Tachykinin 2 (Tac2) pathway in the central amygdala (CeA) has been shown to be sufficient and necessary for the modulation of fear memory consolidation. CeA-Tac2 antagonism and its pharmacogenetic temporal inhibition impair fear memory in male mice. Surprisingly, we demonstrate here the opposite effect of Tac2 blockade on enhancing fear memory consolidation in females. Furthermore, we show that CeA-testosterone in males, CeA-estradiol in females and Akt/GSK3ß/ß-Catenin signaling both mediate the opposite-sex differential Tac2 pathway regulation of fear memory.

High-flow priapism in pediatric population: Case series and review of the literature.

INTRODUCTION: Priapism is a prolonged erection that lasts longer than four hours. It is a rare pathology in the pediatric population, with an estimation of 0.3-1.5 per 100,000 children per year. The diagnostic sequence includes clinical history, physical examination and penile Doppler ultrasound (PDUS). Puncture of corpora cavernosa is not always necessary to establish the differential diagnosis between high-flow and low-flow priapism. The treatment of choice in pediatric age is not well defined. PATIENTS AND METHODS: Multicentric, retrospective and descriptive study including patients under 14 years with high-flow priapism between 2010 and 2020. RESULTS: A total of seven patients were diagnosed with high-flow priapism. None of them required puncture of the corpora cavernosa. Patients were treated with a conservative management, two patients required superselective arterial embolization due to persistent symptoms. CONCLUSIONS: High-flow priapism is a very rare entity in pediatric age; therefore, knowing the proper diagnosis and management is crucial. Currently, penile doppler ultrasound is enough for diagnosis in most cases and allows obviating the use of blood gas analysis. Children should be initially treated with a conservative management, reserving embolization for refractory cases.

High-flow Priapism in Pediatric Population: Case Series and Review of the Literature. / Priapismo de alto flujo en población pediátrica: serie de casos y revisión de la literatura.

INTRODUCTION: Priapism is a prolonged erection that lasts longer than four hours. It is a rare pathology in the pediatric population, with an estimation of 0.3-1.5 per 100,000 children per year. The diagnostic sequence includes clinical history, physical examination and penile Doppler ultrasound (PDUS). Puncture of corpora cavernosa is not always necessary to establish the differential diagnosis between high-flow and low-flow priapism. The treatment of choice in pediatric age is not well defined. PATIENTS AND METHODS: Multicentric, retrospective and descriptive study including patients under 14 years with high-flow priapism between 2010 and 2020. RESULTS: A total of seven patients were diagnosed with high-flow priapism. None of them required puncture of the corpora cavernosa. Patients were treated with a conservative management, two patients required superselective arterial embolization due to persistent symptoms. CONCLUSIONS: High-flow priapism is a very rare entity in pediatric age; therefore, knowing the proper diagnosis and management is crucial. Currently, penile doppler ultrasound is enough for diagnosis in most cases and allows obviating the use of blood gas analysis. Children should be initially treated with a conservative management, reserving embolization for refractory cases.

Migration of nuclear shell gaps studied in the d(24Ne,pγ)25Ne reaction.

The transfer of neutrons onto 24Ne has been measured using a reaccelerated radioactive beam of 24Ne to study the (d,p) reaction in inverse kinematics. The unusual raising of the first 3/2+ level in 25Ne and its significance in terms of the migration of the neutron magic number from N=20 to N=16 is put on a firm footing by confirmation of this state's identity. The raised 3/2+ level is observed simultaneously with the intruder negative parity 7/2- and 3/2- levels, providing evidence for the reduction in the N=20 gap. The coincident gamma-ray decays allowed the assignment of spins as well as the transferred orbital angular momentum. The excitation energy of the 3/2+ state shows that the established USD shell model breaks down well within the sd model space and requires a revised treatment of the proton-neutron monopole interaction.

Reactor decay heat in 239Pu: solving the γ discrepancy in the 4-3000-s cooling period.

The ß feeding probability of (102,104,105,106,107)Tc, 105Mo, and 101Nb nuclei, which are important contributors to the decay heat in nuclear reactors, has been measured using the total absorption technique. We have coupled for the first time a total absorption spectrometer to a Penning trap in order to obtain sources of very high isobaric purity. Our results solve a significant part of a long-standing discrepancy in the γ component of the decay heat for 239Pu in the 4-3000 s range.

[Male androgenetic alopecia and cardiovascular risk factors: A case-control study]. / Alopecia androgénica masculina y factores de riesgo cardiovascular: estudio de casos y controles.

BACKGROUND AND OBJECTIVES: The relationship between androgenetic alopecia and cardiovascular disease has been studied by some authors in the past, although the results of epidemiological studies have been variable. The objective of this study was to determine the prevalence of metabolic syndrome and carotid arteriosclerosis in patients with early-onset androgenetic alopecia. PATIENTS AND METHODS: Seventy men were studied, 35 with diagnosis of early-onset (before 35 years of age) androgenetic alopecia and 35 control subjects who consulted for other skin conditions. In both groups, the criteria for metabolic syndrome according to the Adult Treatment Panel-III were studied (obesity, triglycerides, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, and blood glucose), presence of atheromatous plaques, and carotid intima-media thickness using Doppler ultrasonography. Other cardiovascular risk factors, hormones, and acute-phase reactants were also analyzed. RESULTS: Criteria for metabolic syndrome were met by 57.1% of the patients with androgenetic alopecia compared to 14.3% of the controls (P<0001). Thirty-four percent of the patients with androgenetic alopecia had atheromatous plaques compared to 8.6% of the controls (P=.018). In an independent correlation analysis, abdominal obesity, systolic blood pressure, triglycerides, and blood glucose levels were significantly greater among patients with androgenetic alopecia. Testosterone and sex hormone binding globulin levels were similar in the 2 groups whereas insulin and aldosterone levels were higher in patients with androgenetic alopecia (P<05). CONCLUSIONS: The high frequency of metabolic syndrome and carotid atheromatous plaques in patients with androgenetic alopecia suggests cardiovascular screening should be done to enable early detection of individuals at risk and initiation of preventive treatment before cardiovascular disease becomes established.