Multicenter Registry of Adenomas of the Pituitary and Related Disorders: Initial Description of Cushing Disease Cohort, Surgical Outcomes, and Surgeon Characteristics.

BACKGROUND AND OBJECTIVES: To address the lack of a multicenter pituitary surgery research consortium in the United States, we established the Registry of Adenomas of the Pituitary and Related Disorders (RAPID). The goals of RAPID are to examine surgical outcomes, improve patient care, disseminate best practices, and facilitate multicenter surgery research at scale. Our initial focus is Cushing disease (CD). This study aims to describe the current RAPID patient cohort, explore surgical outcomes, and lay the foundation for future studies addressing the limitations of previous studies. METHODS: Prospectively and retrospectively obtained data from participating sites were aggregated using a cloud-based registry and analyzed retrospectively. Standard preoperative variables and outcome measures included length of stay, unplanned readmission, and remission. RESULTS: By July 2023, 528 patients with CD had been treated by 26 neurosurgeons with varying levels of experience at 9 academic pituitary centers. No surgeon treated more than 81 of 528 (15.3%) patients. The mean ± SD patient age was 43.8 ± 13.9 years, and most patients were female (82.2%, 433/527). The mean tumor diameter was 0.8 ± 2.7 cm. Most patients (76.6%, 354/462) had no prior treatment. The most common pathology was corticotroph tumor (76.8%, 381/496). The mean length of stay was 3.8 ± 2.5 days. The most common discharge destination was home (97.2%, 513/528). Two patients (0.4%, 2/528) died perioperatively. A total of 57 patients (11.0%, 57/519) required an unplanned hospital readmission within 90 days of surgery. The median actuarial disease-free survival after index surgery was 8.5 years. CONCLUSION: This study examined an evolving multicenter collaboration on patient outcomes after surgery for CD. Our results provide novel insights on surgical outcomes not possible in prior single-center studies or with national administrative data sets. This collaboration will power future studies to better advance the standard of care for patients with CD.

Detection of Cerebrospinal Fluid Leaks Using the Endoscopic Fluorescein Test in the Postoperative Period following Pituitary and Ventral Skull Base Surgery.

Objective Diagnosis of cerebrospinal fluid (CSF) leaks is sometimes challenging in the postoperative period following pituitary and ventral skull base surgery. Intrathecal fluorescein (ITF) may be useful in this setting. Design Retrospective chart review. Setting Tertiary care center. Methods and Participants All patients who underwent pituitary and ventral skull base surgery performed by a single rhinologist between January 2017 and March 2020 were included. There were 103 patients identified. Eighteen patients received 20 ITF injections due to clinical suspicion for CSF leak during the postoperative period without florid CSF rhinorrhea on clinical exam. Computed tomography scans with new or increasing intracranial air and intraoperative findings were used to confirm CSF leaks. Clinical courses were reviewed for at least 6 months after initial concern for leak as the final determinate of CSF leak. Main Outcome Measures Specificity and safety of ITF. Results Eleven (61%) ITF patients were female and 7 (39%) were male. Average patient age was 52.50 ± 11.89. There were six patients with confirmed postoperative CSF leaks, 3 of whom had evaluations with ITF. ITF use resulted in 2 true positives, 1 false negative, 17 true negatives, and 0 false positives. ITF sensitivity was 67%, specificity was 100%, and positive and negative predictive values were 100 and 94.4%, respectively. There were no adverse effects from ITF use. Conclusions Existing modalities for detecting postoperative CSF leaks suffer from suboptimal sensitivity and specificity, delayed result reporting, or limited availability. ITF represents a specific and safe test with potential utility in the postoperative setting.

Rapid Automated Analysis of Skull Base Tumor Specimens Using Intraoperative Optical Imaging and Artificial Intelligence.

BACKGROUND: Accurate specimen analysis of skull base tumors is essential for providing personalized surgical treatment strategies. Intraoperative specimen interpretation can be challenging because of the wide range of skull base pathologies and lack of intraoperative pathology resources. OBJECTIVE: To develop an independent and parallel intraoperative workflow that can provide rapid and accurate skull base tumor specimen analysis using label-free optical imaging and artificial intelligence. METHODS: We used a fiber laser-based, label-free, nonconsumptive, high-resolution microscopy method (<60 seconds per 1 × 1 mm2), called stimulated Raman histology (SRH), to image a consecutive, multicenter cohort of patients with skull base tumor. SRH images were then used to train a convolutional neural network model using 3 representation learning strategies: cross-entropy, self-supervised contrastive learning, and supervised contrastive learning. Our trained convolutional neural network models were tested on a held-out, multicenter SRH data set. RESULTS: SRH was able to image the diagnostic features of both benign and malignant skull base tumors. Of the 3 representation learning strategies, supervised contrastive learning most effectively learned the distinctive and diagnostic SRH image features for each of the skull base tumor types. In our multicenter testing set, cross-entropy achieved an overall diagnostic accuracy of 91.5%, self-supervised contrastive learning 83.9%, and supervised contrastive learning 96.6%. Our trained model was able to segment tumor-normal margins and detect regions of microscopic tumor infiltration in meningioma SRH images. CONCLUSION: SRH with trained artificial intelligence models can provide rapid and accurate intraoperative analysis of skull base tumor specimens to inform surgical decision-making.

Pulmonary, liver and cerebral paragonimiasis: An unusual clinical case in Colombia.

BACKGROUND: Mainly affecting poorer populations in remote (sub)tropical areas, paragonimiasis is considered one of the world's most neglected tropical diseases by the World Health Organization. It is usually acquired by consuming undercooked freshwater crustaceans and primarily affects the lungs, but may ectopically migrate to other organs to produce a multisystemic clinical presentation. This study details what appears to be the first documented case in South America and particularly in Colombia of cerebral paragonimiasis and infection by the crab Moreirocarcinus emarginatus. CASE PRESENTATION: After consuming this crab, a 32-year-old Colombian male developed dyspnea and headache. A chest X-ray revealed tension pneumothorax (TPT) and a thoracoscopic lung biopsy bronchiolitis, eosinophilia, and granulomatous reaction due to Paragonimus parasites. RESULTS: Brain tomography and MRI also showed a configuration typical of Paragonimus parasites, namely a predominantly cystic area near the left cuneus with diffusion restriction, a hemosiderin halo, and linear enhancement characteristic of the tunnel sign, indicating an adult worm moving in the brain. CONCLUSIONS: Cerebral paragonimiasis can occur in the Colombian population and Moreirocarcinus emarginatus can be its cause. In rural areas, education about raw crab consumption would be beneficial, and physicians addressing lung-related complaints should bear paragonimiasis in mind and ask about raw crab consumption.

An in silico model using prognostic genetic factors for ovarian response in controlled ovarian stimulation: A systematic review.

PURPOSE: To study the use of in silica model to better understand and propose new markers of ovarian response to controlled ovarian stimulation before IVF. METHODS: A systematic review and in silica model using bioinformatics. After the selection of 103 papers from a systematic review process, we performed a GRADE qualification of all included papers for evidence-based quality evaluation. We included 57 genes in the silica model using a functional protein network interaction. Moreover, the construction of protein-protein interaction network was done importing these results to Cytoscape. Therefore, a cluster analysis using MCODE was done, which was exported to a plugin BINGO to determine Gene Ontology. A p value of < 0.05 was considered significant, using a Bonferroni correction test. RESULTS: In silica model was robust, presenting an ovulation-related gene network with 87 nodes (genes) and 348 edges (interactions between the genes). Related to the network centralities, the network has a betweenness mean value = 102.54; closeness mean = 0.007; and degree mean = 8.0. Moreover, the gene with a higher betweenness was PTPN1. Genes with the higher closeness were SRD5A1 and HSD17B3, and the gene with the lowest closeness was GDF9. Finally, the gene with a higher degree value was UBB; this gene participates in the regulation of TP53 activity pathway. CONCLUSIONS: This systematic review demonstrated that we cannot use any genetic marker before controlled ovarian stimulation for IVF. Moreover, in silica model is a useful tool for understanding and finding new markers for an IVF individualization. PROSPERO: CRD42020197185.

Prosopagnosia associated with brain metastasis near the inferior longitudinal fasciculus in the nondominant temporal lobe: illustrative case.

BACKGROUND: Disruptions of the inferior longitudinal fasciculus (ILF) in the nondominant temporal lobe can lead to the rare but significant higher visual-processing disturbance of prosopagnosia. Here, the authors describe a 57-year-old right hand-dominant female with a large breast cancer brain metastasis in the right temporal lobe who underwent resection and subsequent Gamma Knife radiosurgery. She presented with difficulty with facial recognition, but following surgical intervention, the prosopagnosia became more profound. OBSERVATIONS: Even in nondominant cortex, significant deficits can arise when operating near higher visual-processing centers, including the ILF. LESSONS: This case highlights the utility of imaging-based tractography obtained from preoperative imaging for resective surgical planning even when operating in areas that do not involve what is traditionally considered elegant areas of the brain. To optimize neurological outcomes in metastatic tumor resection, awareness and diffusion tensor imaging of neighboring, displaced white matter tracts may prevent permanent deficits in higher visual processing.

What to do in an oncology department to face the new COVID-19 era challenges?

Italy was the first European country to be hit by COVID-19 pandemic. As a consequence, Italian oncologists had to guarantee essential treatments although minimizing exposure to the virus, and accidental infection, of patients and healthcare professionals. As Department of Medical Oncology of the University Hospital of Udine, in this short report, we describe the measures that we have taken, and gradually updated, since February 26, 2020. All accesses to our Oncology facilities are currently regulated by entrance check-points where patients are screened for infections following dedicated algorithms. Up to date, after 6 weeks of systematic execution of swabs no physician, nurse or other individual of the staff has been found positive to COVID-19. Only one patient admitted for therapy has been identified as COVID-19 positive. The aim of our work is to propose a model, made up of a set of operative procedures, that may be adopted by all the oncologists that daily struggle to guarantee safety and care in Oncology during this COVID-19 emergency.

Variación espacio-temporal de macroinvertebrados acuáticos en la Lindosa, Guayana colombiana

Introducción: Describir los patrones de biodiversidad y los mecanismos que los subyacen es indispensable para afrontar las desenfrenadas presiones sobre los ecosistemas de agua dulce en el trópico. Esto es particularmente relevante en regiones escasamente estudiadas como el escudo guayanés colombiano Objetivo: Describir la estructura taxonómica y funcional de las comunidades de macroinvertebrados, y evaluar su variación a lo largo de escalas espaciales y temporales Métodos: Las comunidades de macroinvertebrados de cuatro ríos fueron muestreadas durante la época seca del 2017 y 2018. Adicionalmente, se evaluaron los patrones de diversidad dentro y entre los ríos y entre diferentes meses de muestreo en uno de los cursos hídricos. Los patrones de diversidad fueron evaluados mediante la comparación de los patrones entre y dentro de los ríos de la diversidad alfa (diferencias en la riqueza y abundancia de taxones entre comunidades) y de la diversidad beta (diferencias en la composición de taxones entre comunidades). La diversidad alfa fue estimada usando los números de Hill, mientras que la diversidad beta se estimó usando los índices de Sørensen y Morisita-Horn y comparada usando un análisis de similaridad (ANOSIM). Resultados: La composición de taxones fue distinta dentro (escala de mesohábitat) y entre los ríos (escala regional). Sin embargo, la composición de FFG cambió entre, pero no dentro de los ríos. La comparación de los números de Hill y de la composición de taxones sugiere que el tipo de mesohábitat es un factor determinante de la diversidad taxonómica pero no de la diversidad de FFG en distintas escalas. En la escala temporal, la diversidad alfa fue baja para los meses con altas precipitaciones (febrero-abril) y alta para la temporada seca (enero). La diversidad beta temporal fue alta para los periodos muestreados y los procesos de anidamiento fueron el componente más notable de la diversidad beta a lo largo del año. Conclusión: Los ríos de la Serranía de la Lindosa albergan una alta diversidad de macroinvertebrados acuáticos. La estacionalidad y las diferencias en la heterogeneidad del hábitat dentro de los ríos parecen determinar los patrones de diversidad observados a diferentes escalas temporales y espaciales. Profundizar en su estudio es necesario para entender el funcionamiento de estos ecosistemas y mejorar la habilidad para generar estrategias de manejo y conservación.

Introduction: Describing biodiversity patterns and the underlying drivers is relevant for tackling the rampant pressures on tropical freshwaters. This is particularly relevant in scarcely studied regions, such as in the Colombian Guiana shield. Objective: To describe the taxonomic and functional structure of macroinvertebrate communities and assess their variability across spatial and temporal scales. Methods: We sampled the invertebrate communities in four streams during the dry seasons of 2017 and 2018. Additionally, we assessed diversity patterns within and among streams and between different sampling months in one stream. To assess diversity patterns, we compared alpha (differences in taxon richness and abundance within communities) and beta (differences in taxon composition among communities) diversity patterns among and within rivers. Alpha diversity was estimated using the numbers of Hill, while beta diversity was estimated using the Sørensen and Morisita-Horn indices and compared using a similarities analysis (ANOSIM). Results: The taxon composition of the communities was different within (mesohabitat scale) and among streams (regional scale). However, the composition of FFGs changed among but not within streams. The comparison of the numbers of Hill and the taxon composition suggested that the mesohabitat type is a determining factor of the taxonomic but not FFG diversity across scales. At the temporal scale, alpha diversity was low for months with high precipitation (February-April) and high for the dry season (January). The temporal beta diversity was high among sampling periods, being nestedness processes driving beta diversity among years and turnover processes driving beta diversity within years. Conclusion: Streams from Serranía de la Lindosa host a high diversity of freshwater macroinvertebrates. Seasonality and differences in the in-stream habitat heterogeneity seem to determine the diversity patterns observed at different temporal and spatial scales. A deeper study is needed to understand the functioning of these ecosystems and improve the ability to generate management and conservation strategies.

Demolition activities in a healthcare facility: results from a fungal surveillance after extraordinary preventive measures.

OBJECTIVES: Aspergillus spp could be responsible of nosocomial aspergillosis in immunocompromised patients. In 2018, it was decided to demolish a building of Careggi Hospital (Florence, Italy), the Chief Medical Officer ordered a 9-months-long air and surface microbiological sampling and extraordinary preventive measures. STUDY DESIGN: A 9-months-long prospective study. METHODS: After mapping the at-risk areas, air and surface samples were collected in different locations: in corridors, in rooms (high efficiency particulate air filter (HEPA) filtered or not), and outdoors. The samples were collected during the critical phases of the demolition. Air temperature and weather conditions were determined and recorded at the beginning of each sampling. RESULTS: Seventy-eight air samples and 72 surface samples were collected. The results showed highest contamination at time zero (before extraordinary preventive measures) and in the wards without HEPA filtered air. No specific prophylaxis strategy was implemented at our hospital for immunocompromised patients, and no cases of aspergillosis were recorded. CONCLUSIONS: Our results showed that extraordinary protective measures, the use of air treatment systems, and a continuous monitoring could be associated with decreased Aspergillus air contamination during construction, renovation, or demolition works.

Sertoli cells for cell transplantation: pre-clinical studies and future perspectives.

Sertoli cells are located in the testes where they control several key functions in spermatogenesis. Over the past 30 years, Sertoli cells have been upgraded from a simple scaffold-like structural system to a dynamic functional system of intercellular support that delivers potent immunomodulatory and trophic factors. Since the discovery of new Sertoli cell secretory products, these cells have been utilized in experimental cell transplantation and co-transplantation protocols aimed at treating both chronic inflammatory and degenerative disorders. For these reasons, this work reviews the application of both naked and microencapsulated Sertoli cells used in cell transplantation studies of several chronic or autoimmune diseases such as diabetes mellitus, Laron dwarfism, and Duchenne muscular dystrophy and in studies aimed at the prevention of skin allograft rejection.

Secondary prophylaxis of hepatocellular carcinoma: the comparison of direct-acting antivirals with pegylated interferon and untreated cohort.

During the past two decades, several studies showed reduced rates of hepatocellular carcinoma recurrence in patients with HCV-related cirrhosis after interferon-based antiviral therapies respect to untreated controls, even without reaching viral clearance. The recent development of new all-oral regimens with direct-acting antivirals has radically improved the therapeutic management of hepatitis C. Nevertheless, paradoxical, or at least unexpected, high rates of both occurrence and recurrence of hepatocellular carcinoma after a treatment with direct-acting antivirals, have been reported in the recent literature. These findings generated a strong rebound in the hepatology community and are at present still controversial. We sought to compare the hepatocellular carcinoma recurrence-free survival of a historical cohort treated with pegylated interferon/ribavirin and an untreated cohort with a cohort treated with direct-acting antivirals.

Quilotórax. Actualización en pediatría: Presentación de casos / Chylothorax Update in pediatrics: Presentation of cases

El quilotórax es el acúmulo de quilo en el espacio pleural como resultado de una lesión del conducto torácico. Es una causa relativamente rara de derrame pleural en los niños y ocurre más frecuentemente como una complicación de una cirugía cardiotorácica pero puede deberse a diferentes condiciones en las que haya alteración de los linfáticos. Causa una morbilidad respiratoria importante y puede llevar a desnutrición e inmunodeficiencia por lo que es necesario su diagnóstico y manejo oportuno. El diagnóstico se basa en el análisis bioquímico del líquido pleural que contiene quilomicrones y niveles elevados de triglicéridos y linfocitos. En esta revisión se presentará la anatomía y la fisiología del sistema linfático y diferentes causas que pueden llevar al desarrollo de quilotórax en los niños. Se revisan sus manifestaciones clínicas y los métodos diagnósticos y las opciones terapéuticas.

Chylothorax is the accumulation of chyle in the pleural space as a result of damage of the thoracic duct. It is a relatively rare cause of pleural effusion in children is most commonly seen as a complication of cardiothoracic surgery but also may occur in conditions associated with abnormal lymphatics. It can cause significant respiratory morbidity, as well as lead to malnutrition and immunodeficiency. The diagnostic is base on biochemical analysis of the pleural fluid, which contains chylomicrons, high levels of triglycerides and lymphocytes. This review will first discuss the anatomy and physiology of the lymphatic system and discuss various causes that can lead to development of a chylothorax in children. Then, clinical manifestations, methods of diagnosis and treatment will be reviewed.

Assessing an imidazolium salt's performance as antifungal agent on a mouthwash formulation.

AIMS: This study demonstrates the development of a mouthwash formulation containing the imidazolium salt (IMS) 1-n-hexadecyl-3-methylimidazolium chloride (C16 MImCl), considering its stability and efficacy against Candida sp. Biofilm formation. METHODS AND RESULTS: A variety of in vitro test methods were applied, assessing contaminated acrylic resin strip specimens before and after applying the mouthwash formulations. The formulation using C16 MImCl presented a similar antibiofilm activity to cetylpyridinium chloride one and a commercial mouthwash, but at a 10 times lower concentration. Scanning electron microscopy imaging demonstrated that the selected mouthwash preparation fully destroys the biofilm cells, while with the hypoallergenicity test no irritant effect was observed in ex vivo model. CONCLUSIONS: The results presented herein indicate a high potential for imidazolium salts application as mouthwash agents that can eliminate Candida biofilm growth at very low concentrations. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates a new and effective antibiofilm formulation containing the IMS C16 MImCl. These findings suggest the IMS' use as mouthwash formulations active ingredient against Candida biofilms on oral surfaces, as it outperforms the often used cetylpyridinium chloride at a 10 times lower concentration.

Imidazolium salts with antifungal potential for the control of head blight of wheat caused by Fusarium graminearum.

AIMS: Evaluate the in vitro effect of imidazolium salts (IMS) on the conidia germination and mycelial growth of Fusarium graminearum and their in vivo efficacy for suppressing the symptoms of the disease and infection of kernels in wheat plants. METHODS AND RESULTS: The minimum inhibitory concentrations (MIC) of three IMS (C16 MImCl, C16 MImMeS and C16 MImNTf2 ) were determined for four F. graminearum isolates using serial broth dilution method. The MICs found for all IMS were either 3·12 or 6·25 µg ml(-1) across the isolates, with the former as the most frequent. In the mycelial growth assay on potato dextrose agar media, only the C16 MImCl among the IMS reduced 50% of mycelial growth of one isolate at an estimated concentration of 0·32 mg ml(-1) . The time-kill curves showed a strong fungicidal effect starting 1 h after incubation at a concentration of 12·5 µg ml(-1) , representing a fourfold increase in the most frequent MIC. The C16 MImCl sprayed onto the spikes of potted wheat plants during the flowering stage reduced disease intensity at levels comparable to the commercial fungicide when applied preventatively (1 h prior to fungal inoculation), rather than curatively, and at the higher dosage (2 mg ml(-1) ) rather than lower dosage (0·5 mg ml(-1) ). CONCLUSIONS: C16 MImCl proved to be a potent inhibitor of F. graminearum growth and provided good levels of control of the disease at levels comparable to a commercial fungicide, in wheat plants treated prior to fungal infection during flowering stages. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests the potential of using IMS as alternative to the hazardous standard fungicides in the management of Fusarium head blight of wheat.

1-n-Hexadecyl-3-methylimidazolium methanesulfonate and chloride salts with effective activities against Candida tropicalis biofilms.

UNLABELLED: Although the use of catheters in critically ill patients is mostly inevitable, this invasive procedure comes together with several health risks. Within this context, the contamination with Candida tropicalis is a primary concern as this highly prevalent pathogenic yeast can develop an extensive polymeric matrix that hinders the drugs' penetration and its effective treatment. This study addresses the potential for the 1-n-hexadecyl-3-methylimidazolium methanesulfonate (C16 MImMeS) and chloride (C16 MImCl) salts for eliminating the viable cells of biofilms of Candida tropicalis, compared to the performance of chlorhexidine (CHX) and fluconazole (FLZ). The minimum concentration required of C16 MImMeS, C16 MImCl, CHX and FLZ for elimination of the biofilm's viable cells (MBEC) was evaluated through microtitre plate biofilm exposure with different concentrations of these substances. These concentrations were determined at 80% of effective activity against the biofilm's viable cells by using the MTT reduction assay. C16 MImMeS and C16 MImCl were able to eliminate the viable cells at much lower concentrations (15·6 and 0·45 µg ml(-1) respectively) than CHX (1250 µg ml(-1) ) and FLZ (resistance of the viable cells). This demonstrates the high potential of these substances for nosocomial infections control. SIGNIFICANCE AND IMPACT OF THE STUDY: The 1-n-hexadecyl-3-methylimidazolium methanesulfonate (C16 MImMeS) and chloride (C16 MImCl) salts are extremely effective in eliminating the viable cells of Candida tropicalis biofilms, which allows the use of much lower concentrations than with the antimicrobial of choice (chlorhexidine) in hospital practices. These findings indicate these imidazolium salts as high-potential candidates for asepsis of medical environments and materials, including implants.

Imidazolium salts with antifungal potential against multidrug-resistant dermatophytes.

AIMS: To investigate the antidermatophytic action of a complementary set imidazolium salts (IMS), determining structure-activity relationships and characterizing the IMS toxicological profiles. METHODS AND RESULTS: The susceptibility evaluation of 45 dermatophytic clinical isolates, treated in vitro with eleven different IMS (ionic compounds) and commercial antifungals (nonionic compounds), was performed by broth microdilution, following the standard norm of CLSI M38-A2. All dermatophytes were inhibited by IMS, where the lowest minimum inhibitory concentration (MIC) values were observed for salts with n-hexadecyl segment in the cation side chain, containing either the chloride or methanesulfonate anion. 1-n-Hexadecyl-3-methylimidazolium chloride (C16 MImCl) and 1-n-hexadecyl-3-methylimidazolium methanesulfonate (C16 MImMeS) acted as fungicides, even in extremely low concentrations, wherein C16 MImMeS exerted this effect on 100% of the tested dermatophytes. Some of these IMS provoked evident alterations on the fungi cell morphology, causing a total cell damage of ≥ 70%. Importantly, none of the screened IMS were cytotoxic, mutagenic or genotoxic to human leucocyte cells. CONCLUSIONS: This report demonstrates for the first time the strong antifungal potential of IMS against multidrug-resistant dermatophytes, without presenting toxicity to human leucocyte cells at MIC. SIGNIFICANCE AND IMPACT OF THE STUDY: The expressive antifungal activity of IMS, combined with the in vitro nontoxicity, makes them promising compounds for the safe and effective treatment of dermatophytoses, mainly when this skin mycosis is unresponsive to conventional drugs.

Congenital diaphragmatic hernia: focus on abnormal muscle formation.

BACKGROUND: CDH is a major birth defect, characterized by high mortality. How the initial defective mesenchymal substructures affects muscle malformation is unclear. Defects of genes involved in diaphragmatic development, such as friend-of-GATA2 (Fog2), may play an important role in its pathogenesis. We investigated the expression of Fog2 and proteins of myogenesis in a series of CDH and in diaphragms at different fetal ages, in order to clarify the role of muscular components during diaphragmatic development in cases with CDH. MATERIAL AND METHODS: Specimen were obtained from seven diaphragms of CDH cases undergoing surgery, 3 entire diaphragms from non repaired CDH, 5 control diaphragms at different gestational ages (16, 17, 22, 32, and 40g.w.), and 3 biopsy samples of normal voluntary muscle. The thickness of diaphragms at the edge of the defect in CDH and in developing diaphragms was measured. All samples were processed for HE staining and immunohistochemistry. Immunohistochemical expression of MyoD, Myf4, Pax7, Mib1 and Fog2 was evaluated. RESULTS: Mean thickness at the edge of the defect was 4.14mm. Contralateral hemi-diaphragm in 3 autopsies and in controls at 32 and 40weeks measured 2.25mm; histology showed a higher density of desmin-positive muscular cells at the edge of defect. CDH displayed scattered Myf4-positive cells (range 0%-10%, mean 2.4%), numerous Pax7-positive cells (range 0%-24%, mean 12.1%) and less than 1% Mib1-positive cells. Controls showed a reduction of positive cell with the progression of gestational age for Myf4 (30% at 16 weeks, 20% at 17 weeks, 5% at 22 weeks, 1% at 32 and 40 weeks), Pax7 (85% at 16 weeks and 17 weeks, 35% at 22 weeks, 11% at 32 weeks) and Mib1 (20% at 16 weeks, 8% at 17 weeks, 7% at 22weeks, 2% at 32 weeks). Fog-2 was diffusely positive in mesenchymal, mesothelial and muscular cells, in diaphragms from 16 to 22 weeks, decreasing to 20% of positive muscular cells in 32-week diaphragm. In CDH only mesothelial and mesenchymal cells were positive. Stem cell markers were negative in cases and controls. COMMENT: CDH shows a thick muscular border, with high number of mature muscle cells and significant increase of quiescent satellite cells (PAX7+, Mib1-). Abnormal architecture may affect the normal process of myogenesis and thus signaling and cell-cell interactions of myocytes. The expression of Fog2 in mesothelial and mesenchymal cells in CDH demonstrates the absence of a genetic defect involving Fog2 in our cases. Being Fog2 expressed in muscle cells at early stage supports the hypothesis that the altered diaphragmatic genesis may undermine also the muscular component instead of the only mesenchymal one.

Imidazolium salts as antifungal agents: strong antibiofilm activity against multidrug-resistant Candida tropicalis isolates.

UNLABELLED: The in vitro activity of the imidazolium salt C16 MImCl against planktonic and biofilm cells of multidrug-resistant isolates of Candida tropicalis was evaluated, both in solution and applied on a commercial catheter surface. This was determined by inhibition and susceptibility assays of biofilm and planktonic cells. In both cases, C16 MImCl prevented in vitro biofilm formation of C. tropicalis strains, including multidrug-resistant ones. Outstanding performances were observed, even at extremely low concentrations. Furthermore, this is the first report of the antifungal lock property of C16 MImCl, using a tracheal catheter as the test specimen to mimic a clinical in vivo condition. As such, C16 MImCl has been identified as a promising antimicotic pharmaceutical candidate for the treatment of candidiasis infections. SIGNIFICANCE AND IMPACT OF THE STUDY: The imidazolium salt 1-n-hexadecyl-3-methylimidazolium chloride (C16 MImCl) strongly prevents, in concentrations as low as 0·028 µg ml(-1) , the biofilm formation of multidrug-resistant Candida tropicalis isolates, either in solution or applied on the surface of commercial catheters. This presents an effective antimicotic candidate and alternative for invasive clinical procedure toolset asepsis.