Heterogeneity of sensitization profiles and clinical phenotypes among patients with seasonal allergic rhinitis in Southern European countries-The @IT.2020 multicenter study.

BACKGROUND: Pollen allergy poses a significant health and economic burden in Europe. Disease patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach. OBJECTIVE: To describe sensitization profiles and clinical phenotypes of pollen allergic patients in nine Southern European cities with a uniform methodological approach. METHODS: Within the @IT.2020 multicenter observational study, pediatric and adult patients suffering from SAR were recruited in nine urban study centers located in seven countries. Clinical questionnaires, skin prick tests (SPT) and specific IgE (sIgE) tests with a customized multiplex assay (Euroimmun Labordiagnostika, Lübeck, Germany) were performed. RESULTS: Three hundred forty-eight children (mean age 13.1 years, SD: 2.4 years) and 467 adults (mean age 35.7 years SD: 10.0 years) with a predominantly moderate to severe, persistent phenotype of SAR were recruited. Grass pollen major allergenic molecules (Phl p 1 and/or Phl p 5) ranged among the top three sensitizers in all study centers. Sensitization profiles were very heterogeneous, considering that patients in Rome were highly poly-sensitized (sIgE to 3.8 major allergenic molecules per patient), while mono-sensitization was prominent and heterogeneous in other cities, such as Marseille (sIgE to Cup a 1: n = 55/80, 68.8%) and Messina (sIgE to Par j 2: n = 47/82, 57.3%). Co-sensitization to perennial allergens, as well as allergic comorbidities also broadly varied between study centers. CONCLUSIONS: In Southern European countries, pollen allergy is heterogeneous in terms of sensitization profiles and clinical manifestations. Despite the complexity, a unique molecular, multiplex, and customized in-vitro IgE test detected relevant sensitization in all study centers. Nevertheless, this geographical diversity in pollen allergic patients imposes localized clinical guidelines and study protocols for clinical trials of SAR in this climatically complex region.

Epidemiology of Non-Tuberculous Mycobacteria isolated from clinical specimens in Madrid, Spain, from 2013 to 2017.

The epidemiology of non-tuberculous mycobacteria (NTM) in Spain is largely unknown because systematic reporting is not compulsory. The aim of our study was to describe the frequency and diversity of NTM species in our region and their distribution according to the source sample, gender, and age of the patients. We performed a multicenter study of all NTM isolated in 24 public hospitals in Madrid from 2013 to 2017. A total of 6.923 mycobacteria were isolated: 4535 (65.5%) NTM, and 2.388 (34.5%) Mycobacterium tuberculosis complex (MTB). Overall, 61 different NTM species were identified. The most frequently isolated species were Mycobacterium avium complex (47.7%), M. lentiflavum (12.2%), M. gordonae (9.2%), M. fortuitum (8.9%), and M. abscessus (3.9%). Whereas MTB cases were stable during the study period, the number of NTM isolates increased considerably from 930 isolates in 2013 to 1012 in 2017; a sharp increase occurred in the last year. The rise in NTM isolates was mostly due to M. lentiflavum, M. kansasii, and M. abscessus mainly isolated from respiratory specimens in patients older than 60. The increase in isolation rate of NTM in our region is consistent with the increasing rates reported worldwide in the last decades. The rise in NTM isolates was mainly attributed to M. lentiflavum but it also should be noted the increasing of species with high pathogenic potential such as M. kansasii and M. abscessus.

[Pregnancy during chronic hemodialysis. A series of cases]. / Embarazo en hemodiálisis crónica: experiencia de un hospital universitario.

BACKGROUND: Pregnancies in women with end stage renal failure are uncommon. However, correction of anemia and improvement in dialysis techniques increases the rate of successful pregnancies. AIM: To describe a 16 years' experience treating pregnant women on hemodialysis and to analyze maternal-fetal outcomes. MATERIALS AND METHODS: Observational study of a dialysis center historical cohort in a university hospital, between 2001 and 2016. RESULTS: Thirteen pregnancies were found in 11 women aged 23 to 32 years, 77% on dialysis prior to pregnancy. Residual diuresis was 1,300 [625-1,575] mL in 24 hrs. The baseline hemoglobin was 9.0 [7.6-9.9] g/dL and 92% of patients did not use contraception. The pre-dialysis blood urea nitrogen was 34 [29-36] mg /dL. An ultrasound to confirm pregnancy was done in all. At 23 [14-25] weeks of pregnancy, dialysis hours were increased, reaching 24 [19.5-24.0] hours per week. The most common complications were severe arterial hypertension (54%), severe anemia (46%), polyhydramnios (31%) and severe intrauterine growth retardation (IUGR) (23%). The median time of pregnancy at delivery was 34 [29-34] weeks. Neonatal median hospitalization length was 4 [4-32] days, with 18% of neonatal deaths. CONCLUSIONS: Pregnancies in dialysis are no longer exceptional. Despite better maternal and fetal outcomes, morbidity and mortality remains higher than in the normal population, which makes multidisciplinary management essential.

Biallelic mutations in mitochondrial tryptophanyl-tRNA synthetase cause Levodopa-responsive infantile-onset Parkinsonism.

Mitochondrial aminoacyl-tRNA synthetases (mtARSs) are essential, ubiquitously expressed enzymes that covalently attach amino acids to their corresponding tRNA molecules during translation of mitochondrial genes. Deleterious variants in the mtARS genes cause a diverse array of phenotypes, many of which involve the nervous system. Moreover, distinct mutations in mtARSs often cause different clinical manifestations. Recently, the gene encoding mitochondrial tryptophanyl tRNA synthetase (WARS2) was reported to cause 2 different neurological phenotypes, a form of autosomal recessive intellectual disability and a syndrome of severe infantile-onset leukoencephalopathy. Here, we report the case of a 17-year-old boy with compound heterozygous mutations in WARS2 (p.Trp13Gly, p.Ser228Trp) who presented with infantile-onset, Levodopa-responsive Parkinsonism at the age of 2 years. Analysis of patient-derived dermal fibroblasts revealed decreased steady-state WARS2 protein and normal OXPHOS content. Muscle mitochondrial studies suggested mitochondrial proliferation without obvious respiratory chain deficiencies at the age of 9 years. This case expands the phenotypic spectrum of WARS2 deficiency and emphasizes the importance of mitochondrial protein synthesis in the pathogenesis of Parkinsonism.

Use of Lymph Node Ultrasound Prior to Sentinel Lymph Node Biopsy in 384 Patients with Melanoma: A Cost-Effectiveness Analysis. / Valor de la ecografía ganglionar previa a la biopsia del ganglio centinela en 384 pacientes con melanoma: análisis de coste-efectividad.

BACKGROUND AND OBJECTIVES: Locoregional lymph node ultrasound is not typically included in guidelines as part of the staging process prior to sentinel lymph node biopsy (SLNB). The objective of the present study was to make a clinical and economic analysis of lymph node ultrasound prior to SLNB. MATERIALS AND METHODS: We performed a retrospective study of 384 patients with clinical stage I-II primary melanoma who underwent locorregional lymph node ultrasound (with or without ultrasound-guided biopsy) prior to SLNB between 2004 and 2015. We evaluated the reliability and cost-effectiveness of the strategy. RESULTS: Use of locorregional lymph node ultrasound avoided SLNB in 23 patients (6%). Ultrasound had a sensitivity of 46% and specificity of 76% for the detection of metastatic lymph nodes that were not clinically palpable. False negatives were significantly more common in patients aged over 60 years and in tumors with a thickness of less than 2mm. The staging process using SLNB and ultrasound with ultrasound-guided biopsy produced an increase of €16.30 in the unit price. Our cost-effectiveness analysis identified the staging protocol with ultrasound and SLNB as the dominant strategy, with a lower cost-effectiveness ratio than the alternative, consisting of SLNB alone (8,095.24 vs. €28,605.00). CONCLUSIONS: Ultrasound with ultrasound-guided biopsy for the diagnostic staging of melanoma prior to SLNB is a useful and cost-effective tool. This procedure does not substitute SLNB, though it does allow to avoid SLNB in a not insignificant proportion of patients.

Low-cost air, noise, and light pollution measuring station with wireless communication and tinyML.

Different types of environmental pollution cause negative consequences to ecosystems throughout the globe, which humanity is now trying to mitigate. It is necessary to know the level of pollution problems in the immediate environment, to evaluate the impact of human activities, and mitigation strategies necessary to ensure habitability. For this reason, in this work, a low-cost pollution measurement station for outdoor or indoor use is proposed and developed that measures air pollution (particulate matter and CO2), noise (level and direction), light pollution (power and multispectral), and also relative humidity and ambient temperature. The system stores the data in an SD memory or transmits data in real-time to the internet via WiFi. The purposes of the system are to be used in environmental studies, to deploy monitoring networks, or to ensure the habitability of a living or working space. The prototype integrates the measurement of the different sources of contamination in a single compact device at USD$ 628.12 without sacrificing measurement accuracy. The system is validated for each variable with reference equipment, obtaining an average error of approximately 2.67% in the measurement of all the variables measured. The system is easy to assemble and has an option for power supply using solar photovoltaic devices and an alternative for connection to 2G/3G mobile networks.

Patients with relapsing polychondritis and previous cartilage trauma present more autoimmunity phenomena.

Relapsing polychondritis (RP) is an autoimmune disease characterized by inflammation and destruction of all type of body cartilage, and the cartilage trauma may be a trigger of the disease in a susceptible person. We describe the clinical and laboratory findings in a group of 18 patients with RP with (7 cases) or without (11 cases) anteceding cartilage trauma. The mean age was 41 years in the group with cartilage trauma and 55 years in the group without cartilage trauma. For both groups, female gender was predominant. All patients presented with auricular chondritis. Systemic manifestations and autoimmunity were more common in patients with anteceding trauma.

[Spurious hypoxemia due to hyperleukocytosis. Report of one case]. / Hipoxemia espuria por hiperleucocitosis. Reporte de un caso y revisión de la literatura.

BACKGROUND: Arterial gasometry is considered the gold standard for establishing a diagnosis of respiratory failure of any etiology. However, there are some circumstances in which it loses specificity, making necessary to consider other tests such as pulse oximetry to adequately determine hypoxemia. We report a 67 years old patient with sudden hypoacusia, right hemiparesis and polypnea. His laboratory exams on admission, showed extreme hypoxemia in several readings, without correlation to the patient's clinical condition nor the pulse oximetry, and a leukocytosis of 800.000 cells x ml, with many immature cells. Chronic myeloid leukemia was diagnosed and treatment with hydroxyurea was initiated, achieving normalization in the arterial gases in accordance with the fall of the white cell count. Interpretation of laboratory findings according to the general clinical context of the patient allowed to suspect a spurious hypoxemia, saving the patient from unnecessary and risky interventions.

[Psychophysiological distress among health care professionals working in Chilean public hospitals]. / Malestar psicofisiológico en profesionales de la salud pública de la Región Metropolitana.

BACKGROUND: The public health reform in Chile resulted in changes in working conditions and organization of health centers. AIM: To examine the presence of psychophysiological symptoms in professionals of public hospitals in the Metropolitan Region and their association with current working conditions. MATERIAL AND METHODS: A questionnaire of quality of working life was applied to a sample of 80 physicians and 110 nurses. The questionnaire considers scales and open questions. RESULTS: Nurses had a higher level of discomfort than physicians (p < 0.01) and had significantly higher scores for emotional distress, physical fatigue, digestive disorders, headache, insomnia, back pain and muscle tension (p < 0.01). There were statistically significant negative correlations between psychophysiological distress and working conditions (r = -0.418), social climate (r = -0.395), satisfaction with the organization (r = -0.337) and psychosocial well-being (r = -0.267). A regression model showed that 21% of the variance in psychophysiological distress was explained by working conditions, psychosocial well-being and adaptation to the organization. CONCLUSIONS: There is a relationship between the high prevalence of psychophysiological symptoms and bad working conditions of public health professionals.

A new multiplex PCR for differential identification of Shigella flexneri and Shigella sonnei and detection of Shigella virulence determinants.

Most of the multiplex PCR (mPCR) used to identify Shigella do not discriminate between Shigella species or serotypes. We designed a mPCR to differentiate between S. flexneri and S. sonnei strains based on the detection of markers associated with the she pathogenicity island described in Shigella. In addition, specific primers were included to detect the Shigella virulence determinants ShET-1 and ShET-2 enterotoxin genes. The analysis of 304 Shigella strains from Chile and 79 Shigella strains from other geographic locations indicated that the mPCR described here detected all Shigella species and specifically differentiated S. flexneri and S. sonnei. The technique was sensitive, reproducible, specific and simple to perform, providing a new tool with the potential to be employed for epidemiological and diagnostic purposes.

"Ears of the Lynx" MRI Sign Is Associated with SPG11 and SPG15 Hereditary Spastic Paraplegia.

BACKGROUND AND PURPOSE: The "ears of the lynx" MR imaging sign has been described in case reports of hereditary spastic paraplegia with a thin corpus callosum, mostly associated with mutations in the spatacsin vesicle trafficking associated gene, causing Spastic Paraplegia type 11 (SPG11). This sign corresponds to long T1 and T2 values in the forceps minor of the corpus callosum, which appears hyperintense on FLAIR and hypointense on T1-weighted images. Our purpose was to determine the sensitivity and specificity of the ears of the lynx MR imaging sign for genetic cases compared with common potential mimics. MATERIALS AND METHODS: Four independent raters, blinded to the diagnosis, determined whether the ears of the lynx sign was present in each of a set of 204 single anonymized FLAIR and T1-weighted MR images from 34 patients with causal mutations associated with SPG11 or Spastic Paraplegia type 15 (SPG15). 34 healthy controls, and 34 patients with multiple sclerosis. RESULTS: The interrater reliability for FLAIR images was substantial (Cohen κ, 0.66-0.77). For these images, the sensitivity of the ears of the lynx sign across raters ranged from 78.8 to 97.0 and the specificity ranged from 90.9 to 100. The accuracy of the sign, measured by area under the receiver operating characteristic curve, ranged from very good (87.1) to excellent (93.9). CONCLUSIONS: The ears of the lynx sign on FLAIR MR imaging is highly specific for the most common genetic subtypes of hereditary spastic paraplegia with a thin corpus callosum. When this sign is present, there is a high likelihood of a genetic mutation, particularly associated with SPG11 or SPG15, even in the absence of a family history.

Osteogenesis distraction and platelet-rich plasma: combined use in restoration of severe atrophic mandible. Long-term results.

OBJECTIVES: The purpose of this paper is to report long-term results on the use of autologous bone graft and platelet-rich plasma in alveolar distraction osteogenesis (DO) for restoration of severe atrophic mandible. We tested the efficacy as to reabsorption of bone volume, peri-implant reabsorption, implant survival and success rate. MATERIALS AND METHODS: Twelve patients were treated. The surgical procedure consisted in mixing autologous bone, harvested from the iliac crest, with autologous platelet concentrate (APC) and in filling the distraction gap with this graft. After a latency of 15 days, a distraction rate of 0.5 mm/day was followed. After a 60-day period of consolidation, the distraction device was removed and implants were placed simultaneously. The abutment connection was accomplished after 6 months. In addition, every patient was evaluated clinically and radiographically annually for 5 years. RESULTS: Planned alveolar height was reached in 11 out of 12 patients. The total number of implants positioned was 47. At the time of implant positioning, the mean decrease of total bone volume was 2.3%. The mean peri-implant resorption was 0.40 mm at the time of abutment connection, 0.61 mm 1 year after implant loading and 1.51 mm after 5 years. After 5 years of follow-up, the mean rate of vertical bone loss was 18.7%. Instead, the implant survival and success rates were 97.9% and 91.5%, respectively. CONCLUSIONS: Long-term results allow us to confirm the combination of autologous bone-platelet gel with alveolar DO as an effective and predictable procedure in restoration of severe atrophic mandible.

Functional endoscopic sinus surgery for the treatment of Aspergillus mycetomas of the maxillary sinus.

AIM: The proper treatment for Aspergillus mycetoma (AM) of the maxillary sinus is a complete removal of the sinus fungal masses and improvement of aeration for the involved sinuses. We report our experience in the treatment of AM of the maxillary sinus by functional endoscopic sinus surgery (FESS). METHODS: Thirteen immunocompetent patients with AM underwent FESS under general anesthesia. Mycotic concretions were endonasally removed through the enlarged maxillary natural ostium. Care was taken to avoid any removal of the maxillary sinus mucosa. Only in one case complete removal could not be achieved and therefore we opened the maxillary sinus via the canine fossa and cleared it of fungal masses. Follow-up has ranged from 6 months to 4 years after surgery. Patients were all closely followed postoperatively with serial endoscopic examinations in order to verify the maintenance of opening of the maxillary natural ostium. RESULTS: Histological examination was positive for Aspergillus in all the patients. Postoperative radiographs and endoscopic examinations revealed maintenance of the antrostomy performed during FESS without mucosal degeneration and no evidence of recurrence. All patients were free of symptoms after a mean follow-up of 31 months. None of the patients required a second procedure. CONCLUSION: Surgical treatment of AM with FESS appears a reliable and safe surgical treatment. Sinus physiology is preserved in the event of a future bone reconstruction for prosthetic purposes.

Hypothalamic epigenetics driving female puberty.

Puberty involves a series of morphological, physiological and behavioural changes during the last part of the juvenile period that culminates in the attainment of fertility. The activation of the pituitary-gonadal axis by increased hypothalamic secretion of gonadotrophin-releasing hormone (GnRH) is an essential step in the process. The current hypothesis postulates that a loss of transsynaptic inhibition and a rise in excitatory inputs are responsible for the activation of GnRH release. Similarly, a shift in the balance in the expression of puberty activating and puberty inhibitory genes exists during the pubertal transition. In addition, recent evidence suggests that the epigenetic machinery controls this genetic balance, giving rise to the tantalising possibility that epigenetics serves as a relay of environmental signals known for many years to modulate pubertal development. Here, we review the contribution of epigenetics as a regulatory mechanism in the hypothalamic control of female puberty.

SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression.

Puberty is regulated by epigenetic mechanisms and is highly sensitive to metabolic and nutritional cues. However, the epigenetic pathways mediating the effects of nutrition and obesity on pubertal timing are unknown. Here, we identify Sirtuin 1 (SIRT1), a fuel-sensing deacetylase, as a molecule that restrains female puberty via epigenetic repression of the puberty-activating gene, Kiss1. SIRT1 is expressed in hypothalamic Kiss1 neurons and suppresses Kiss1 expression. SIRT1 interacts with the Polycomb silencing complex to decrease Kiss1 promoter activity. As puberty approaches, SIRT1 is evicted from the Kiss1 promoter facilitating a repressive-to-permissive switch in chromatin landscape. Early-onset overnutrition accelerates these changes, enhances Kiss1 expression and advances puberty. In contrast, undernutrition raises SIRT1 levels, protracts Kiss1 repression and delays puberty. This delay is mimicked by central pharmacological activation of SIRT1 or SIRT1 overexpression, achieved via transgenesis or virogenetic targeting to the ARC. Our results identify SIRT1-mediated inhibition of Kiss1 as key epigenetic mechanism by which nutritional cues and obesity influence mammalian puberty.

Adult neurogenesis and schizophrenia: a window on abnormal early brain development?

Adult neurogenesis is one of the most rapidly growing areas in neuroscience research and there is great interest in its potential role in the pathophysiology of psychiatric illness. In parallel with early development, adult neurogenesis occurs through the proliferation of precursor cells which migrate to specific regions and differentiate into neurons with characteristics indistinguishable from existing mature neurons. These findings have led to the re-definition of the concept of network plasticity in the adult brain, to include the formation of new neurons as well as new connections. This review examines the idea that adult neurogenesis may be disturbed in schizophrenia. We discuss evidence for abnormal mechanisms of neurogenesis and expression of developmental genes in schizophrenia, the influence of antipsychotic drugs on neurogenesis and the role of candidate schizophrenia susceptibility genes in adult neurogenesis. The recent discovery of molecular markers transiently expressed in newborn neurons within adult neurogenic brain regions could be used to probe whether neurogenesis is disturbed in schizophrenia. Adult neurogenesis could also be used as a unique tool for investigating genes involved in early brain development using post-mortem brains. This is particularly relevant for brain disorders with developmental origins such as schizophrenia.

Sensitivity of cerebellar glutathione system to neonatal ionizing radiation exposure.

Reactive oxygen species (ROS) are relevant components of living organisms that, besides their role in the regulation of different important physiological functions, when present in excess are capable to affect cell oxidative status, leading to damage of cellular molecules and disturbance of normal cell function. ROS accumulation has been associated with a variety of conditions such as neurodegenerative diseases and ionizing radiation exposure. Cell ability to counteract ROS overproduction depends on the capacity of the endogenous antioxidant defenses--which includes the glutathione (GSH) system--to cope with. Since developing central nervous system (CNS) is especially sensitive to ROS-induced damage, the aim of the present work was to evaluate ROS, reduced GSH and oxidized glutathione (GSSG) levels in the cerebellum at different developmental ages after irradiation, in order to test if any changes were induced on these key oxidative stress-related cellular markers that might explain the high cerebellar vulnerability to radiation-induced injury. Since intracellular levels of GSH are maintained by glutathione reductase (GSHr), this enzymatic activity was also evaluated. Newborn Wistar rats were irradiated in their cephalic ends and the different parameters were measured, from 1h to 90 days post-irradiation. Results showed that an early transient increase in ROS levels followed by a decrease in cerebellar weight at 3-5 days post-irradiation were induced. An increase in cerebellar GSH levels was induced at 30 days after irradiation, together with a decrease in GSHr activity. These results support the hypothesis that ROS may represent a marker of damage prior to radiation-induced cell death. In contrast, it would be suggested that GSH system might play a role in the compensatory mechanisms triggered to counteract radiation-induced cerebellar damage.

Femoral nerve palsy after mandibular reconstruction with microvascular iliac flap: a complication under anticoagulation therapy.

Pharmacological prophylaxis and intervention are used extensively in head and neck reconstructions with microvascular flaps. There is no universally accepted protocol, but the microvascular surgery literature recommends intraoperative anticoagulation with heparin. Here is reported a case of iliacus haematoma with subsequent femoral nerve palsy after the harvest of a microvascular iliac flap for mandibular reconstruction in a patient who had been treated with heparin. The association between femoral nerve palsy and anticoagulant therapy has been well described. It remains unclear as to why the iliacus muscle is particularly vulnerable to intramuscular haemorrhage. Femoral nerve neuropathy is also an uncommon but recognized complication after abdominopelvic surgery. Iliacus haematoma secondary to microvascular surgery has not been previously reported. This case illustrates the need to be aware of this type of complication and its clinical manifestations for patients under anticoagulant therapy in the perioperative period during microvascular reconstructions.