Efectividad de la respiración glosofaríngea en pacientes con enfermedades neuromusculares y lesión medular: Revisión sistemática exploratoria / Effectiveness of glossopharyngeal breathing in patients with neuromuscular diseases and spinal cord injury: Scoping review

Antecedentes Las enfermedades neuromusculares y las lesiones medulares comprometen los músculos respiratorios y función pulmonar ocasionando complicaciones respiratorias. La insuficiencia respiratoria aguda y el compromiso respiratorio crónico ocasionan alto riesgo de morbilidad y mortalidad. Se ha descrito el uso de la respiración glosofaríngea para mejorar variables de función pulmonar y muscular respiratoria que promueven la tos más efectiva y aumento del tiempo libre de ventilación mecánica. Objetivo Describir y presentar la evidencia actual de la efectividad de la respiración glosofaríngea en mejorar la función pulmonar y muscular respiratoria en pacientes adultos y pediátricos con enfermedades neuromusculares o lesión medular con o sin ventilación mecánica. Diseño Revisión exploratoria con la metodología PRISMA-ScR. Se realizó una búsqueda en las bases de datos PEDro, Web of Science, Scopus, PubMed, ScienceDirect, Springer, Medline, Cochrane, SciELO, Lilacs, Google Académico, se usaron palabras claves y términos MeSH en idiomas español, inglés y portugués, entre los años 2000-2020. Los resultados se presentan de forma descriptiva. Resultados Se identificaron 491 estudios y fueron incluidos 12. El 58,3% fueron realizados en países europeos. El 41,6% de los estudios fueron valorados y ninguno cumplió totalmente los criterios de calidad. La efectividad de la respiración glosofaríngea en la función pulmonar y muscular respiratoria estuvo relacionada con mejoría de capacidad vital en 66,6% y pico flujo de tos en 33,3% de los estudios. Se reportó mejoría en expansión torácica en 66,6% de los estudios y complicaciones como síncope, mareo en 33,3%. Conclusión La efectividad de respiración glosofaríngea en pacientes con enfermedades neuromusculares y lesión medular está relacionada con aumento de capacidad vital y pico flujo de tos. Se recomienda la realización de estudios con más rigurosidad científica para soportar la validez de estos resultados (AU)

Background Neuromuscular diseases and spinal cord injuries compromise respiratory muscles and lung function, causing respiratory complications. Acute respiratory failure and chronic respiratory compromise cause high risk of morbidity and mortality. The use of glossopharyngeal respiration has been described to improve pulmonary and respiratory muscle function variables that promote more effective coughing and increased time off mechanical ventilation. Objective Describe and present the current evidence of the effectiveness of glossopharyngeal respiration in improving lung and respiratory muscle function in adult and pediatric patients with neuromuscular diseases or spinal cord injury with or without mechanical ventilation. Design Exploratory review with the PRISMA-ScR methodology. A search was carried out in the PEDro, Web of Science, Scopus, PubMed, ScienceDirect, Springer, Medline, Cochrane, SciELO, Lilacs, Google Academic databases, keywords and MeSH terms were used in Spanish, English and Portuguese languages, among the years 2000–2020. The results are presented in a descriptive way. Results 491 studies were identified and 12 were included. 58.3% were conducted in European countries. 41.6% of the studies were critically appraised and none fully met the quality criteria. The effectiveness of glossopharyngeal breathing in lung and respiratory muscle function was related to an improvement in vital capacity in 66.6% and peak cough flow in 33.3% of the studies. Improvement in thoracic expansion was reported in 66.6% of the studies and complications such as syncope, dizziness in 33.3%. Conclusion The effectiveness of glossopharyngeal respiration in patients with neuromuscular diseases and spinal cord injury is related to increased vital capacity and peak flow of cough. Studies with more scientific rigor are recommended to support the validity of these results (AU)

Clinicopathological features, MCPyV status and outcomes of Merkel cell carcinoma in solid-organ transplant recipients: a retrospective, multicentre cohort study.

BACKGROUND: The proportion of Merkel cell carcinomas (MCCs) in solid-organ transplant recipients (SOTR) harbouring Merkel cell polyomavirus (MCPyV) is unknown, as are factors affecting their outcomes. OBJECTIVE: To describe clinicopathological features of MCC in SOTR, investigate the tumoral MCPyV-status and identify factors associated with tumour outcomes. METHODS: Retrospective, international, cohort-study. MCPyV-status was investigated by immunohistochemistry and polymerase chain reaction. RESULTS: A total of 30 SOTR and 44 consecutive immunocompetent patients with MCC were enrolled. SOTR were younger at diagnosis (69 vs. 78 years, P < 0.001). Thirty-three percent of SOTR MCCs were MCPyV-positive vs. 91% of immunocompetent MCCs (P = 0.001). Solid-organ transplantation was associated with an increased cumulative incidence of progression (SHR: 3.35 [1.57-7.14], P = 0.002), MCC-specific mortality (SHR: 2.55 [1.07-6.06], P = 0.034) and overall mortality (HR: 3.26 [1.54-6.9], P = 0.002). MCPyV-positivity and switching to an mTOR inhibitor (mTORi) after MCC diagnosis were associated with an increased incidence of progression (SHR: 4.3 [1.5-13], P = 0.008 and SHR: 3.6 [1.1-12], P = 0.032 respectively) in SOTR. LIMITATIONS: Retrospective design and heterogeneity of SOTR cohort. CONCLUSIONS: MCPyV appears to play a less prominent role in the aetiopathogenesis of MCC in SOTR. SOTR have a worse prognosis than their immunocompetent counterparts and switching to an mTORi after the diagnosis of MCC does not improve progression.

Awake prone positioning in nonintubated spontaneous breathing ICU patients with acute hypoxemic respiratory failure (PRONELIFE)-protocol for a randomized clinical trial.

BACKGROUND: It is uncertain whether awake prone positioning can prevent intubation for invasive ventilation in spontaneous breathing critically ill patients with acute hypoxemic respiratory failure. Awake prone positioning could benefit these patients for various reasons, including a reduction in direct harm to lung tissue, and prevention of tracheal intubation-related complications. DESIGN AND METHODS: The PRONELIFE study is an investigator-initiated, international, multicenter, randomized clinical trial in patients who may need invasive ventilation because of acute hypoxemic respiratory failure. Consecutive patients admitted to participating ICUs are randomly assigned to standard care with awake prone positioning, versus standard care without awake prone positioning. The primary endpoint is a composite of tracheal intubation and all-cause mortality in the first 14 days after enrolment. Secondary endpoints include time to tracheal intubation and effects of awake prone positioning on oxygenation parameters, dyspnea sensation, and complications. Other endpoints are the number of days free from ventilation and alive at 28 days, total duration of use of noninvasive respiratory support, total duration of invasive ventilation, length of stay in ICU and hospital, and mortality in ICU and hospital, and at 28, 60, and 90 days. We will also collect data regarding the tolerance of prone positioning. DISCUSSION: The PRONELIFE study is among the first randomized clinical trials investigating the effect of awake prone positioning on intubation rate in ICU patients with acute hypoxemic failure from any cause. The PRONELIFE study is sufficiently sized to determine the effect of awake prone positioning on intubation for invasive ventilation-patients are eligible in case of acute hypoxemic respiratory failure without restrictions regarding etiology. The PRONELIFE study is a pragmatic trial in which blinding is impossible-however, as around 35 ICUs worldwide will participate in this study, its findings will be highly generalizable. The findings of the PRONELIFE study have the potential to change clinical management of patients who may need invasive ventilation because of acute hypoxemic respiratory failure. TRIAL REGISTRATION: ISRCTN ISRCTN11536318 . Registered on 17 September 2021. The PRONELIFE study is registered at clinicaltrials.gov with reference number NCT04142736 (October, 2019).

Diethyl sinapate-grafted cellulose nanocrystals as nature-inspired UV filters in cosmetic formulations.

Inspired by nature's photoprotection mechanisms, we report an effective UV-blocking nanomaterial based on diethyl sinapate-grafted cellulose nanocrystals (CNC-DES). The colloidal stability and UV-blocking performance of CNC-DES in aqueous glycerol (a common humectant in petroleum-free cosmetic formulations) and in a commercially available moisturizing cream were studied. Grafting the water-insoluble DES onto CNCs renders it dispersible in these water-based formulations, thanks to the excellent water-dispersibility of CNC nanoparticles. Glycerol dispersions containing 0.1 to 1.5 wt% CNC-DES display very high UV-blocking activity owing to the anti-UV DES moieties anchored onto CNCs. A facial cream blended with 1.5 wt% CNC-DES exhibits an SPF of 5.03, which is higher than a commercially available sunscreen with the same active ingredient concentration (SPF = 3.84). DPPH radical scavenging assay also showed the antioxidant potential of CNC-DES, albeit coinciding with a significant reduction in antioxidant activity after grafting DES onto CNCs. Cytotoxicity measurements revealed the CNC-DES not to cause significant cytotoxicity to murine fibroblast cells after 24 h of exposure. Overall, CNC-DES exhibits strong anti-UV and antioxidant properties and is water-dispersible, biocompatible, non-greasy, and lightweight. This study demonstrates the exceptional potential of DES-grafted CNCs as nature-inspired UV filters in the next generation of cosmetic formulations, including those for sensitive skins.

Columnar nitrogen-doped ZnO nanostructured thin films obtained through atomic layer deposition.

The present study was aimed to develop nitrogen-doped nanostructured ZnO thin films. These films were produced in a sequential procedure involving the atomic layer deposition technique, and a hydrothermal process supported by microwave heating. Employing the atomic layer deposition technique, through self-limited reactions of diethylzinc (DEZn) and H2O, carried out at 3.29 × 10-4atm and 190 °C, a high-quality ZnO seed was grown on a Si (100) substrate, producing a textured film. In a second stage, columnar ZnO nanostructures were grown perpendicularly oriented to the silicon substrate on those films, using a solvothermal process in a microwave heating facility, employing Zn(NO3)2as zinc precursor, while hexamethylenetetramine (HMTA) was used to produce the bridging of Zn2+ions. The consequence of N-doping concentration on the physicochemical properties of ZnO thin films was studied. The manufactured films were structurally analyzed by scanning electron microscopy and x-ray diffraction. Also, x-ray photoelectron spectroscopy, Raman, and UV-vis spectroscopies were used to provide further insight on the effect of nitrogen doping. The N-doped films displayed textured wurtzite-like structures that changes their preferential growth from the (002) to the (100) crystallographic plane, apparently promoted by the increase of nitrogen precursor. It is also shown that nitrogen-doped films undergo a reduction in their bandgap, compared to ZnO. The methodology presented here provides a viable way to perform high-quality N-ZnO nanostructured thin films.

Antimicrobial activity of ceftolozane-tazobactam against Enterobacterales and Pseudomonas aeruginosa recovered during the Study for Monitoring Antimicrobial Resistance Trends (SMART) program in Spain (2016-2018).

OBJECTIVE: To analyse the susceptibility to ceftolozane-tazobactam and comparators in Enterobacterales and Pseudomonas aeruginosa isolates recovered from intraabdominal (IAI), urinary (UTI), respiratory (RTI) and bloodstream infection (BSI) in the SMART (Study for Monitoring Antimicrobial Resistance Trends) study. METHODS: The susceptibility of 5,351 isolates collected in 11 Spanish hospitals (2016-2018) were analysed (EUCAST-2020 criteria) by broth microdilution and were phenotypically studied for the presence of extended-spectrum beta-lactamases (ESBL). Ceftolozane-tazobactam and/or carbapenem resistant isolates were genetically characterized for ESBL and carbapenemases. RESULTS: Escherichia coli was the most frequent pathogen (49.3% IAI, 54.9% UTI, 16.7% RTI and 50% BSI), followed by Klebsiella pneumoniae (11.9%, 19.1%, 13.1% and 15.4%, respectively). P. aeruginosa was isolated in 9.3%, 5.6%, 32% and 9%, respectively. The frequency of isolates with ESBLs (2016-2017) was: 30.5% K. pneumoniae, 8.6% E. coli, 2.3% Klebsiella oxytoca and 0.7% Proteus mirabilis. Ceftolozane-tazobactam was very active against non-ESBL-(99.3% susceptible) and ESBL-(95.2%) producing E. coli being less active against K. pneumoniae (98% and 43.1%, respectively) isolates. CTX-M-15 was the most prevalent ESBL in E. coli (27.5%) and K. pneumoniae (51.9%) frequently associated with OXA-48-like carbapenemase. Overall, 93% of P. aeruginosa isolates were susceptible to ceftolozane-tazobactam, preserving this activity (>75%) in isolates resistant to other beta-lactams except in those resistant to meropenen or ceftazidime-avibactam. GES-5, PER-1, VIM-1/2 were the most prevalent enzymes in isolates resistant to ceftolozane-tazobactam. CONCLUSIONS: Ceftolozane-tazobactam showed high activity rates against isolates recovered in the SMART study although it was affected in K. pneumoniae and P. aeruginosa isolates with ESBL and/or carbapenemases.

Severity of Chest Imaging is Correlated with Risk of Acute Neuroimaging Findings among Patients with COVID-19.

BACKGROUND AND PURPOSE: Severe respiratory distress in patients with COVID-19 has been associated with higher rate of neurologic manifestations. Our aim was to investigate whether the severity of chest imaging findings among patients with coronavirus disease 2019 (COVID-19) correlates with the risk of acute neuroimaging findings. MATERIALS AND METHODS: This retrospective study included all patients with COVID-19 who received care at our hospital between March 3, 2020, and May 6, 2020, and underwent chest imaging within 10 days of neuroimaging. Chest radiographs were assessed using a previously validated automated neural network algorithm for COVID-19 (Pulmonary X-ray Severity score). Chest CTs were graded using a Chest CT Severity scoring system based on involvement of each lobe. Associations between chest imaging severity scores and acute neuroimaging findings were assessed using multivariable logistic regression. RESULTS: Twenty-four of 93 patients (26%) included in the study had positive acute neuroimaging findings, including intracranial hemorrhage (n = 7), infarction (n = 7), leukoencephalopathy (n = 6), or a combination of findings (n = 4). The average length of hospitalization, prevalence of intensive care unit admission, and proportion of patients requiring intubation were significantly greater in patients with acute neuroimaging findings than in patients without them (P < .05 for all). Compared with patients without acute neuroimaging findings, patients with acute neuroimaging findings had significantly higher mean Pulmonary X-ray Severity scores (5.0 [SD, 2.9] versus 9.2 [SD, 3.4], P < .001) and mean Chest CT Severity scores (9.0 [SD, 5.1] versus 12.1 [SD, 5.0], P = .041). The pulmonary x-ray severity score was a significant predictor of acute neuroimaging findings in patients with COVID-19. CONCLUSIONS: Patients with COVID-19 and acute neuroimaging findings had more severe findings on chest imaging on both radiographs and CT compared with patients with COVID-19 without acute neuroimaging findings. The severity of findings on chest radiography was a strong predictor of acute neuroimaging findings in patients with COVID-19.

Uso intraluminal de stent de nitinol dual para colapso completo de tráquea en un canino de raza maltés / Intraluminal use of dual nitinol stent for complete collapse of trachea in a Canine Maltese breed

RESUMEN Paciente canino, de raza maltés, género femenino, castrado, de 4 años y 5 Kg de peso. El motivo principal de consulta fue tos y dificultad respiratoria grave. Durante la evaluación clínica, el paciente presentó cianosis, estridor inspiratorio y espiratorio severo, tos en graznido especialmente después de un estímulo emocional. Se realizó una broncoscopia que reveló una disminución dinámica en el diámetro de la luz traqueal, un colapso severo en las porciones cervicales y torácicas. Debido a la gravedad del colapso traqueal, se decidió la implantación de un stent de nitinol. La elección del stent es fundamental y por tanto fue necesario realizar una medición del diámetro y la longitud de la tráquea para minimizar los efectos secundarios y los rechazos. La tráquea presentó variabilidad del diámetro a nivel torácico, razón por la cual se decidió utilizar un stent dual, el cual se colocó mediante observación directa a través de un broncoscopio pediátrico. Se presenta un caso en el que se usó un stent dual, indicado en casos en que el diámetro de la tráquea varía en su trayecto. Se obtuvieron excelentes resultados ya que se ajustó a los diferentes diámetros que presentó la tráquea en los niveles cervical y torácico.

ABSTRACT Canine patient, Maltese breed, female gender, castrated, 4 years old and 5 Kg of weight. The main reason for consultation was cough and severe respiratory distress. During the clinical evaluation, the patient presented cyanosis, severe inspiratory and expiratory stridor, squawking cough, especially after emotional stimulation. A bronchoscopy was performed that revealed a dynamic decrease in the diameter of the tracheal lumen, a severe collapse in the cervical and thoracic portions. Due to the severity of the tracheal collapse, the implantation of a nitinol stent was decided. The choice of stent is essential and therefore it was necessary to perform a measurement of the diameter and length of the trachea to minimize side effects and rejections. The trachea presented diameter variability at the thoracic level, which is why it was decided to use a dual stent, which was placed by direct observation through a pediatric bronchoscope. We present a case in which a dual stent was used, indicated in cases in which the diameter of the trachea varies along its path. Excellent results were obtained since it was adjusted to the different diameters that the trachea presented at the cervical and thoracic levels.

Análisis del potencial de innovación en apósitos para tratar heridas crónicas en la ciudad de Lima, Perú / Analysis Of The Potential Of Innovation In Dressings To Treat Chronic Wounds In The City Of Lima, Peru

Objetivo: Analizar el potencial de innovación en apósitos para tratar heridas crónicas en la Ciudad de Lima. Métodos: Se realizó un estudio cualitativo mediante una encuesta y análisis de las entrevistas realizadas a expertos médicos y gestores de compras en insumos para el tratamiento de heridas de difícil resolución en 8 instituciones representativas de salud pública con categorías 1 ­ 4 dentro de las 54 existentes solo en Lima Metropolitana, Perú - 2018. Resultados: Se determinó que en las instituciones de salud pública son atendidos un promedio 17 pacientes mensualmente (60% provenientes de hospitalización y 40% de consultorio externo). Equivale decir que 11,016 pacientes presentan heridas crónicas de difícil resolución al año, los cuales requerirán de tratamiento especializado y una demanda anual promedio de 110,160 apósitos en stock. Los apósitos con mayor demanda corresponden a los Hidrogeles e Hidrocoloides, respectivamente que son utilizados por los resultados positivos que ofrecen en la curación de las heridas, aunque en ocasiones la limitante es el aspecto económico. En el mercado, el precio unitario oscila entre los 20 y 90 soles, esto representa una inversión económica de 1500 soles en promedio por paciente, produciendo en algunos casos complicaciones o abandono del tratamiento cuando los recursos son escasos. Conclusiones: La demanda de pacientes con heridas crónicas de difícil resolución en las instituciones de salud públicas de Lima metropolitana es alta. Es importante promover e incentivar la investigación de nuevas alternativas terapéuticas y/o dispositivos biomédicos que favorezcan su curación.

Objective: To analyze the potential for innovation in dressings to treat chronic wounds in the City of Lima. Methods: A qualitative study was carried out by means of interviews to medical experts and purchasing managers of medical supplies for the treatment of difficult-to-resolve wounds in 8 representative public health institutions with categories 1-4 within the only 54 of Lima, Peru - 2018. Results: It was determined that an average of 17 patients is treated in public health institutions on a monthly basis (60% from hospitalization and 40% from an outpatient office). It is equivalent to say that 11,016 patients present chronic wounds of difficult resolution each year, which will require specialized treatment and an average annual demand of 110,160 dressings in stock. The dressings with the highest demand correspond to the Hydrogels and Hydrocolloids, respectively; used because of the positive results they offer in wound healing, despite economic limitations. The market price per unit ranges between 20 and 90 soles (S/.), representing an economic investment of 1500 soles on average per patient, in some cases causing complications or abandonment of treatment when resources are scarce. Conclusions: There is a high demand for patients with chronic wounds of difficult resolution in the public health institutions of Lima. It is important to promote and incentivize the investigation of new therapeutic alternatives and / or biomedical devices that favor its treatment.

Allergic sensitization increases contractile responses to 5-HT in guinea pig aorta.

Epidemiological and clinical studies suggest that asthma is associated with adverse cardiovascular outcomes, but its mechanism is uncertain. 5-Hydroxytryptamine (5-HT) is a mediator involved in asthma and in cardiovascular functioning. Thus, in the present study, we explored whether allergic sensitization in guinea pigs modifies 5-HT-induced contractile responses and 5-HT2A receptor expression in thoracic aorta rings. We found that sensitization produced a significant increase of 100 microM 5-HT-induced contractions of aorta rings (~27 % greater contraction than in non-sensitized animals, p<0.05). Preincubation with 10 nM ketanserin (a 5-HT2A receptor antagonist) reduced by ~30 % (p=0.003) and ~36 % (p=0.005) the area under the curve of 5-HT-induced contractions in aortas from non-sensitized and sensitized animals, respectively. There were no differences between sensitized and non-sensitized animals with respect to mRNA (qPCR) and protein (Western blot) expression of 5-HT2A receptor in thoracic aortas. We concluded that in this guinea pig model of asthma, allergic sensitization is not confined to airways, but also affects arterial contractile responses to 5-HT; changes in the expression of the 5-HT2A receptor appear not to be involved in this phenomenon.

Sequencing of a 'mouse azoospermia' gene panel in azoospermic men: identification of RNF212 and STAG3 mutations as novel genetic causes of meiotic arrest.

STUDY QUESTION: What is the diagnostic potential of next generation sequencing (NGS) based on a 'mouse azoospermia' gene panel in human non-obstructive azoospermia (NOA)? SUMMARY ANSWER: The diagnostic performance of sequencing a gene panel based on genes associated with mouse azoospermia was relatively successful in idiopathic NOA patients and allowed the discovery of two novel genes involved in NOA due to meiotic arrest. WHAT IS KNOWN ALREADY: NOA is a largely heterogeneous clinical entity, which includes different histological pictures. In a large proportion of NOA, the aetiology remains unknown (idiopathic NOA) and yet, unknown genetic factors are likely to play be involved. The mouse is the most broadly used mammalian model for studying human disease because of its usefulness for genetic manipulation and its genetic and physiological similarities to man. Mouse azoospermia models are available in the Mouse Genome Informatics database (MGI: http://www.informatics.jax.org/). STUDY DESIGN, SIZE, DURATION: The first step was to design of a 'mouse azoospermia' gene panel through the consultation of MGI. The second step was NGS analysis of 175 genes in a group of highly selected NOA patients (n = 33). The third step was characterization of the discovered gene defects in human testis tissue, through meiotic studies using surplus testicular biopsy material from the carriers of the RNF212 and STAG3 pathogenic variants. The final step was RNF212 and STAG3 expression analysis in a collection of testis biopsies. PARTICIPANTS/MATERIALS, SETTING, METHODS: From a total of 1300 infertile patients, 33 idiopathic NOA patients were analysed in this study, including 31 unrelated men and 2 brothers from a consanguineous family. The testis histology of the 31 unrelated NOA patients was as follows: 20 Sertoli cell-only syndrome (SCOS), 11 spermatogenic arrest (6 spermatogonial arrest and 5 spermatocytic arrest). The two brothers were affected by spermatocytic arrest. DNA extracted from blood was used for NGS on Illumina NextSeq500 platform. Generated sequence data was filtered for rare and potentially pathogenic variants. Functional studies in surplus testicular tissue from the carriers included the investigation of meiotic entry, XY body formation and metaphases by performing fluorescent immunohistochemical staining and immunocytochemistry. mRNA expression analysis through RT-qPCR of RNF212 and STAG3 was carried out in a collection of testis biopsies with different histology. MAIN RESULTS AND THE ROLE OF CHANCE: Our approach was relatively successful, leading to the genetic diagnosis of one sporadic NOA patient and two NOA brothers. This relatively high diagnostic performance is likely to be related to the stringent patient selection criteria i.e. all known causes of azoospermia were excluded and to the relatively high number of patients with rare testis histology (spermatocytic arrest). All three mutation carriers presented meiotic arrest, leading to the genetic diagnosis of three out of seven cases with this specific testicular phenotype. For the first time, we report biallelic variants in STAG3, in one sporadic patient, and a homozygous RNF212 variant, in the two brothers, as the genetic cause of NOA. Meiotic studies allowed the detection of the functional consequences of the mutations and provided information on the role of STAG3 and RNF212 in human male meiosis. LIMITATIONS, REASONS FOR CAUTION: All genes, with the exception of 5 out of 175, included in the panel cause azoospermia in mice only in the homozygous or hemizygous state. Consequently, apart from the five known dominant genes, heterozygous variants (except compound heterozygosity) in the remaining genes were not taken into consideration as causes of NOA. We identified the genetic cause in approximately half of the patients with spermatocytic arrest. The low number of analysed patients can be considered as a limitation, but it is a very rare testis phenotype. Due to the low frequency of this specific phenotype among infertile men, our finding may be considered of low clinical impact. However, at an individual level, it does have relevance for prognostic purposes prior testicular sperm extraction. WIDER IMPLICATIONS OF THE FINDINGS: Our study represents an additional step towards elucidating the genetic bases of early spermatogenic failure, since we discovered two new genes involved in human male meiotic arrest. We propose the inclusion of RNF212 and STAG3 in a future male infertility diagnostic gene panel. Based on the associated testis phenotype, the identification of pathogenic mutations in these genes also confers a negative predictive value for testicular sperm retrieval. Our meiotic studies provide novel insights into the role of these proteins in human male meiosis. Mutations in STAG3 were first described as a cause of female infertility and ovarian cancer, and Rnf212 knock out in mice leads to male and female infertility. Hence, our results stimulate further research on shared genetic factors causing infertility in both sexes and indicate that genetic counselling should involve not only male but also female relatives of NOA patients. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the Spanish Ministry of Health Instituto Carlos III-FIS (grant number: FIS/FEDER-PI14/01250; PI17/01822) awarded to CK and AR-E, and by the European Commission, Reproductive Biology Early Research Training (REPROTRAIN, EU-FP7-PEOPLE-2011-ITN289880), awarded to CK, WB, and AE-M. The authors have no conflict of interest.

Impact and safety of open lung biopsy in patients with acute respiratory distress syndrome (ARDS) / Impacto y seguridad de la biopsia abierta de pulmón en pacientes con síndrome de distrés respiratorio agudo

Introduction: Acute respiratory distress syndrome (ARDS) is an inflammatory lung disorder, and its pathological hallmark is diffuse alveolar damage (DAD). Given that open lung biopsy (OLB) can sometimes result in severe side effects, it is rarely performed in patients with ARDS. Aim: The aims of this study were to describe: (a) the rate of treatment change associated with the histological result; and (b) the incidence of side effects induced by OLB. Design and patients: A retrospective, single-center, descriptive observational study was carried out in Hospital Santa Clara (Bogotá, Colombia) from February 2007 to January 2014. Inclusion criteria: Critically ill patients over 18 years of age, undergoing invasive mechanical ventilation, diagnosed with ARDS of unknown etiology, and with OLB performed at the bedside. ARDS was diagnosed according to the Berlin definition. DAD was defined by the presence of a hyaline membrane plus at least one of the following: intra-alveolar edema, alveolar type I cell necrosis, alveolar type II cell (cuboidal cells) proliferation progressively covering the denuded alveolar-capillary membrane, interstitial proliferation of fibroblasts and myofibroblasts, or organizing interstitial fibrosis. The rate of treatment change (RTC) was established according to whether the OLB pathology report resulted in: a) the prescription or discontinuation of an antimicrobial; b) the indication of new procedures; c) medical interconsultation; or d) limitation of therapeutic effort. Patients were followed-up until death or hospital discharge. This study was approved by the Ethics Committee. Results: A total of 32 OLBs were performed during the study period; 17 were ruled out as they did not involve ARDS, and 15 were considered for further analysis. A histological diagnosis was reached in 14 of the 15 patients (12 DAD, one case of bronchiolitis obliterans organizing pneumonia and one case of Wegener's granulomatosis with alveolar hemorrhage). The RTC rate was 0.73. The most frequent intervention was discontinuation of antimicrobial or corticosteroid treatment. No deaths but four side effects (3 airway leaks and one hemothorax) were associated with the OLB procedure. All were resolved before ICU discharge. Conclusion: The information provided by OLB performed at the bedside in ARDS patients of unknown etiology could be relevant, as it may optimize treatment. The risk associated with OLB seems to be acceptable

Introducción: El síndrome de dificultad respiratoria aguda (ARDS, acute respiratory distress syndrome) es una enfermedad pulmonar inflamatoria y su característica distintiva patológica es el daño alveolar difuso (DAD, diffuse alveolar damage). Dado que la biopsia pulmonar abierta (OLB, open lung biopsy) a veces puede dar lugar a efectos secundarios graves, rara vez se realiza en pacientes con SDRA. Objetivos: Los objetivos de este estudio fueron describir: a) la tasa de cambio de tratamiento asociado con el resultado histológico y b) la tasa de efectos secundarios inducidos por la OLB. Diseño: Estudio observacional, descriptivo, unicéntrico y retrospectivo realizado en el Hospital Santa Clara, Bogotá (Colombia) desde febrero de 2007 a enero de 2014. Criterios de inclusión: Pacientes críticamente enfermos mayores de 18 años sometidos a ventilación mecánica invasiva, diagnosticados con SDRA de etiología desconocida en quienes se realizó la OLB al lado de la cama. El SDRA fue diagnosticado según la definición de Berlín. El DAD se definió por la presencia de membrana hialina y al menos uno de los siguientes criterios: edema intraalveolar, necrosis de células alveolares tipo I, proliferación de células alveolares tipo II (células cuboidales) con denudación progresiva de la membrana alveolar-capilar, proliferación intersticial de fibroblastos y miofibroblastos o fibrosis intersticial organizada. La tasa de cambio de tratamiento asociada con el resultado de la biopsia pulmonar abierta (RTC) se definió si, basándose en el análisis patológico de la biopsia de pulmón abierto: a) se prescribió o suspendió un antimicrobiano, b) se indicó un nuevo procedimiento, o c) interconsulta médica, o d) limitado el esfuerzo terapéutico. Los pacientes fueron seguidos hasta la muerte o el alta hospitalaria. Este estudio fue aprobado por el comité de ética. Resultados: Durante el período de estudio, se realizaron 32 OLB; 17 pacientes fueron descartados, ya que no tenían ARDS y 15 fueron considerados para análisis. Se llegó a diagnóstico histológico en 14 (12 casos con DAD, un caso con bronquiolitis obliterante con neumonía de organización y un caso con granulomatosis de Wegener asociada a hemorragia alveolar) de los 15 pacientes; RTC: 0,73. La intervención más frecuente fue la interrupción del tratamiento con antimicrobianos o esteroides. No hubo muertes, pero 4 acontecimientos adversos (3 neumotórax y un hemotórax) se asociaron con el procedimiento de OLB. Todos fueron resueltos antes del alta de la UCI. Conclusión: La OLB constituye un procedimiento de diagnóstico de alto rendimiento que determina un impacto relevante en el tratamiento de pacientes con SDRA. El riesgo asociado a este procedimiento es aceptable. La información proporcionada por la OLB, realizada junto a la cama en la UCI, en pacientes con SDRA de etiología desconocida es relevante, ya que puede optimizar el tratamiento. El riesgo asociado con la OLB parece ser aceptable

Monitoring the antimicrobial susceptibility of Gram-negative organisms involved in intraabdominal and urinary tract infections recovered during the SMART study (Spain, 2016 and 2017).

OBJECTIVE: Continuous antimicrobial resistance surveillance is recommended by Public Health authorities. We up-dated data from the SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance study in Spain. METHODS: The antimicrobial susceptibility data and extended-spectrum beta-lactamase (ESBL) production in isolates recovered from intra-abdominal (IAI) (n=1,429) and urinary tract (UTI) (n=937) infections during the 2016- 2017 SMART study in 10 Spanish hospitals were analysed. RESULTS: Escherichia coli was the most frequently microorganism isolated (48.3% and 53.7%) followed by Klebsiella spp. (11.5% and 21.9%) in IAIs and UTIs, respectively. Figures for Pseudomonas aeruginosa were 9.0% and 6.1%, being more frequently recovered from patients with nosocomial infections. Overall, 9.9% (IAI) and 14.0% (UTI) of E. coli, Klebsiella spp. and Proteus mirabilis isolates were ESBL-producers, being Klebsiella pneumoniae (34.5%) from UTI of nosocomial origin the most frequent. ESBL-producers were higher in patients >60 years in both IAIs and UTIs. As in previous years, amikacin (96.3%-100% susceptibility), ertapenem (84.2%-100%) and imipenem (70.3%- 100%) were the most active antimicrobials tested among Enterobacterales species. The activity of amoxicillin-clavulanic, piperacillin-tazobactam, and ciprofloxacin susceptibility was lower, particularly among ESBL-producers. Ertapenem susceptibility (88.9%-100%) was retained in ESBL-E. coli isolates that were resistant to these antimicrobials but decreased (28.6%-100%) in similar isolates of K. pneumoniae. CONCLUSIONS: Continuous antimicrobial resistance surveillance from the SMART study reveals overall maintenance of ESBL-producers in Spain, although with higher presence in isolates from UTIs than from IAIs. Moreover, ertapenem activity was high in E. coli irrespective of ESBL production but decreased in K. pneumoniae, particularly among ESBL-producers.

Impact and safety of open lung biopsy in patients with acute respiratory distress syndrome (ARDS).

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is an inflammatory lung disorder, and its pathological hallmark is diffuse alveolar damage (DAD). Given that open lung biopsy (OLB) can sometimes result in severe side effects, it is rarely performed in patients with ARDS. AIM: The aims of this study were to describe: (a) the rate of treatment change associated with the histological result; and (b) the incidence of side effects induced by OLB. DESIGN AND PATIENTS: A retrospective, single-center, descriptive observational study was carried out in Hospital Santa Clara (Bogotá, Colombia) from February 2007 to January 2014. INCLUSION CRITERIA: Critically ill patients over 18 years of age, undergoing invasive mechanical ventilation, diagnosed with ARDS of unknown etiology, and with OLB performed at the bedside. ARDS was diagnosed according to the Berlin definition. DAD was defined by the presence of a hyaline membrane plus at least one of the following: intra-alveolar edema, alveolar type I cell necrosis, alveolar type II cell (cuboidal cells) proliferation progressively covering the denuded alveolar-capillary membrane, interstitial proliferation of fibroblasts and myofibroblasts, or organizing interstitial fibrosis. The rate of treatment change (RTC) was established according to whether the OLB pathology report resulted in: a) the prescription or discontinuation of an antimicrobial; b) the indication of new procedures; c) medical interconsultation; or d) limitation of therapeutic effort. Patients were followed-up until death or hospital discharge. This study was approved by the Ethics Committee. RESULTS: A total of 32 OLBs were performed during the study period; 17 were ruled out as they did not involve ARDS, and 15 were considered for further analysis. A histological diagnosis was reached in 14 of the 15 patients (12 DAD, one case of bronchiolitis obliterans organizing pneumonia and one case of Wegener's granulomatosis with alveolar hemorrhage). The RTC rate was 0.73. The most frequent intervention was discontinuation of antimicrobial or corticosteroid treatment. No deaths but four side effects (3 airway leaks and one hemothorax) were associated with the OLB procedure. All were resolved before ICU discharge. CONCLUSION: The information provided by OLB performed at the bedside in ARDS patients of unknown etiology could be relevant, as it may optimize treatment. The risk associated with OLB seems to be acceptable.

Antimicrobial susceptibility trends and evolution of isolates with extended spectrum ß-lactamases among Gram-negative organisms recovered during the SMART study in Spain (2011-2015).

OBJECTIVE: The SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance study monitors antimicrobial susceptibility and extended spectrum ß-lactamases (ESBLs) in Gram-negative bacilli recovered from intra-abdominal infections (IAI). METHODS: Antimicrobial susceptibility of 5,343 isolates from IAI recovered in 11 centres during the 2011-2015 SMART-Spain program was analysed by standard microdilution (EUCAST criteria) and compared with that from 2002-2010. ESBLs were phenotypically detected. RESULTS: Escherichia coli, the most common isolate, significantly decreased in community acquired IAI (60.9% 2002-2010 vs. 56.1% 2011-2015, P=0.0003). It was followed in prevalence by Klebsiella pneumoniae that increased both in the community (8.9% vs. 10.8%, P=0.016) and nosocomial (9.2% vs. 10.8%, P=0.029) IAI and P. aeruginosa, which significantly increased in community acquired IAI (5.6% vs. 8.0%, P=0.0003). ESBLs were more prevalent in K. pneumoniae (16.3%) than in E. coli (9.5%) of nosocomial origin and were more frequently isolated from elderly patients (>60 years). Considering all Enterobacteriaceae, ertapenem (92.3-100%) and amikacin (95.5%-100%) were the most active antimicrobials. Ertapenem activity, unlike amoxicillin-clavulanate or piperacillin-tazobactam, remained virtually unchanged in ESBL (100%) and non-ESBL (98.8%) E. coli producers. Its activity decreased in ESBL-K. pneumoniae (74.7%) but was higher than that of amoxicillin-clavulanate (14.0%) and piperacillin-tazobactam (24.0%). Interestingly, ertapenem susceptibility was maintained in >60% of ESBL isolates that were resistant to amoxicillin-clavulanate, piperacillin-tazobactam or fluoroquinolones. CONCLUSIONS: SMART-Spain results support current guidelines which include ertapenem as empiric treatment in mild-moderate community-acquired IAI, particularly with ESBL producers. These recommendations will need to be updated with the recently introduction of new antimicrobials.

Plasmonic resonances in hybrid systems of aluminum nanostructured arrays and few layer graphene within the UV-IR spectral range.

The size-controllable and ordered Al nanocavities and nanodomes arrays were synthesized by electrochemical anodization of aluminum using phosphoric acid, citric acid and mixture both acids. Few layer graphene (FLG) was transferred directly on top of Al nanostructures and their morphology were evaluated by scanning electron microscopy. The interaction between FLG and the plasmonic properties of Al nanostructures arrays were investigated based on specular reflectivity in the ultraviolet-visible-infrared range and Raman spectroscopy. We found that their optical reflectivity was dramatically reduced as compared with unstructured Al. At the same time pronounced reflectivity dips were detectable in the 200-896 nm wavelength range, which were ascribed to plasmonic resonances. The plasmonic properties of these nanostructures do not exhibit evident changes by the presence of FLG in the UV-vis range of the electromagnetic spectrum. By contrast, the surface-enhanced Raman spectroscopy of FLG was observed in nanocavities and nanodomes structures that result in an intensity increase of the characteristic G and 2D bands of FLG induced by the plasmonic properties of Al nanostructures.

Expression of metallothionein type 2 and 3 genes in Prosopis glandulosa leaves treated with copper.

For a better understanding of the strategies that are used by Prosopis glandulosa in heavy metal tolerance, the present study evaluated the gene expression of three metallothioneins (MTs; PgMt2-1, PgMt2, and PgMt3) in plants exposed to sub-lethal concentrations of copper. The PgMt2-1, PgMt2, and PgMt3 sequences were homologous to the MT type 2 (isoform 1), Mt2, and Mt3 sequences of other plant species found in GenBank. A reverse transcriptase-polymerase chain reaction showed that treatment with 100 mM Cu2+ induced a significant increase in PgMt2 and PgMt3 expression during the first 4 h of exposure compared to that of PgMt2-1. However, after 8 h of exposure, the expression levels of PgMt2 and PgMt3 were significantly lower than those of PgMt2-1. PgMt transcript levels only increased significantly during the first hour after exposure to copper, suggesting that PgMts could play a key role in the plant's detoxification mechanism. However, additional studies are required to confirm MTs as a mechanism of heavy metal tolerance and accumulation in this species.

Comparison of bacteriological conversion and treatment outcomes among MDR-TB patients with and without diabetes in Mexico: Preliminary data.

Diabetes mellitus (DM) is a well-known risk factor for tuberculosis (TB). However, it is not known to what extent DM affects the outcome in patients with multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB) treated with second-line anti-TB drugs. The objective of this study was to compare the microbiological evolution (sputum smear and culture conversion) and final outcomes of MDR/XDR-TB patients with and without DM, managed at the national TB reference centre in Mexico City. RESULTS: Ninety patients were enrolled between 2010 and 2015: 73 with MDR-TB (81.1%), 11 with pre-XDR-TB (e.g. MDR-TB with additional resistance to one injectable drug or a fluoroquinolone, 12.2%) and 6 (6.7%) with XDR-TB. Out of these, 49 (54.4%) had DM and 42 (86%) were undergoing insulin treatment. No statistically significant differences were found in treatment outcomes comparing DM vs. non-DM MDR-TB cases: 18/32 (56.3%) of DM cases and 19/24 (79.2%) non DM patients achieved treatment success (p=0.07). The time to sputum smear and culture conversion was longer (although not statistically) in patients without DM, as follows: the mean (±SD) time to sputum smear conversion was 53.9 (±31.4) days in DM patients and 65.2 (±34.8) days in non-DM ones (p=0.15), while the time to culture conversion was 66.2 (±27.6) days for DM and 81.4 (±37.7) days for non-DM MDR-TB cases (p=0.06). CONCLUSIONS: The study results support the Mexican National TB programme to strengthen its collaboration with the DM programme, as an entry point for TB (and latent TB infection) screening and management.

Activity of linezolid and tedizolid against clinical isolates of methicillin-resistant and methicillin and linezolid resistant Staphylococcus aureus: an in vitro comparison.

OBJECTIVE: The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in Spain is approximately 20-30%. However, resistance to linezolid is rare, and the main reports are from nosocomial outbreaks. The objective of the present study was to compare the in vitro susceptibility of linezolid with that of tedizolid against MRSA isolates and methicillin-and linezolid-resistant isolates (MLRSA) mediated by the cfr gene. METHODS: The in vitro susceptibility of linezolid and tedizolid was determined using the E-test with 18 MRSA strains and 18 cfr-mediated MLRSA strains obtained from clinical isolates in the microbiology service of a tertiary university hospital. RESULTS: All MRSA strains were susceptible to both antibiotics. Analysis of the MRSA isolates revealed that the MIC50 and MIC90 of linezolid were 1.5 and 2 mg/L, respectively; those of tedizolid were 0.25 and 0.4 mg/L. The MIC50 and MIC90 of tedizolid remained at 0.75 and 1 mg/L against the MLRSA strains (MIC90 ≥ 8 mg/L). CONCLUSIONS: Both for MRSA and for MLRSA, the MICs obtained for tedizolid were at least 2 dilutions lower than those of linezolid, thus demonstrating between 2 and 4 times greater activity in vitro than linezolid.