Miracle-dz/UniFAR-FTUs huggingface dataset:
Letter regarding the role of radical surgery in the management of CEAP C5/6 and lipodermatosclerosis

Dear Editor, I read with interest the paper, ‘‘The role of radical surgery in the management of CEAP C5/6 and lipodermatosclerosis’’ by Gábor Martis and Renáta Laczik. I would like to congratulate the authors on bringing a very useful technique to the literature which mirrors, and greatly adds to, a presentation of our early results of a similar approach that we used to follow and that we presented at the UK Venous Forum in 2000. However, we subsequently moved to a more conservative interventional approach by correcting underlying venous reflux in truncal veins using endovenous thermoablation and in perforating veins using the TRLOP technique. Using these endovenous techniques, under local anaesthetic only since 2005, we have reported long-term healing of 85% in these C6 patients, 52% not needing any further compression at all. Similar results have now been reported for endovenous foam sclerotherapy. As the authors of this current study have shown 100% healing at one year with their radical surgery with long post-operative recovery, but simple endovenous techniques performed as ambulatory outpatient procedures as referenced above can show healing in 70 to 85% of the same sort of cases, do the authors think that their radical surgery should be reserved for those 15 to 30% of patients who fail the less invasive and less expensive endovenous techniques? This would lead to a logical treatment strategy for patients with venous leg ulcers starting with minimally invasive ambulatory techniques for patients with reflux in their truncal veins and/or perforating veins, with radical surgery such as the authors described held in reserve for those patients failing this approach.
Transported biofilms and their influence on subsequent macrofouling colonization

Abstract Biofilm organisms such as diatoms are potential regulators of global macrofouling dispersal because they ubiquitously colonize submerged surfaces, resist antifouling efforts and frequently alter larval recruitment. Although ships continually deliver biofilms to foreign ports, it is unclear how transport shapes biofilm microbial structure and subsequent macrofouling colonization. This study demonstrates that different ship hull coatings and transport methods change diatom assemblage composition in transported coastal marine biofilms. Assemblages carried on the hull experienced significant cell losses and changes in composition through hydrodynamic stress, whereas those that underwent sheltered transport, even through freshwater, were largely unaltered. Coatings and their associated biofilms shaped distinct macrofouling communities and affected recruitment for one third of all species, while biofilms from different transport treatments had little effect on macrofouling colonization. These results demonstrate that transport conditions can shape diatom assemblages in biofilms carried by ships, but the properties of the underlying coatings are mainly responsible for subsequent macrofouling. The methods by which organisms colonize and are transferred by ships have implications for their distribution, establishment and invasion success.
MicroRNA-544 promotes colorectal cancer progression by targeting forkhead box O1

Dysregulation of microRNAs has been confirmed to serve an important role in cancer development and progression. However, the role of microRNA (miR)-544 in colorectal cancer progression remains unknown. In the present study, it was observed that the expression level of miR-544 was increased in breast cancer cell lines and tissues using the quantitative polymerase chain reaction. Overexpression of miR-544 promoted cell proliferation and invasion in colorectal cancer, whereas inhibition of miR-544 suppressed colorectal cancer progression as determined using MTT, colony formation and Transwell assays. Furthermore, forkhead box O1 (FOXO1) was a direct target of miR-544. FOXO1 mediated miR-544-regulated colorectal cancer progression and cell cycle distribution. In conclusion, the results of the present study revealed that miR-544 serves an important role in promoting human colorectal cancer cell progression.
Doxorubicin, mesenchymal stem cell toxicity and antitumour activity: implications for clinical use

The use of doxorubicin, an antineoplastic medication used for the treatment of cancers via mechanisms that prevent replication of cells or lead to their death, can result in damage to healthy cells as well as malignant. Among the affected cells are mesenchymal stem cells (MSCs), which are involved in the maintenance and repair of tissues in the body. This review explores the mechanisms of biological effects and damage attributed to doxorubicin on MSCs. The PubMed database was used as a source of literature for this review.
Six-year surveillance of Newcastle disease virus in wild birds in north-eastern Spain (Catalonia)

ABSTRACT Given that Newcastle disease (ND) is one of the major threats for the poultry industry, testing of Newcastle disease virus (NDV) has been carried out since 2010 in cases of mortality in wild birds (passive surveillance) in Catalonia. The objective is to provide an early warning system to prevent the infection of poultry. Since 2010, 35 episodes of mortality in wild birds were attributed to NDV infection. Throughout this period there was a progressive expansion of NDV to new areas, with an increase in the episodes of mortality, although it is not clear whether they were the result of the spread of the virus, or of the improvement of the surveillance. Phylogenetic analyses indicate that two distinct sublineages of NDV, 4a and 4b, were circulating in Catalonia. Both sublineages seem to be endemic in the wild bird population, affecting mainly Eurasian-collared doves, with a clear pattern in relation to its spatial distribution (coincident with the distribution of this species), and its temporal distribution (with the majority of cases between September and February). So far, endemicity in wild birds has not resulted in ND outbreaks in poultry. However, there are still many uncertainties about, for example, whether NDV may expand to new areas of Catalonia (with higher poultry density), or about the threat that the apparently more novel sublineage 4a may represent. Hence, efforts should be made so that measures to prevent infection of poultry farms (particularly in high-risk areas and periods) are encouraged, and surveillance is maintained.
Workload and costs of audiological assessment on tertiary settings: Data analysis and audit

presented as pharyngeal tumor in an acquired immune deficiency syndrome patient. Zhong hua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2011;46:690–692. 7. Maria C, Khuanchai S. Penicillium marneffei Infection immunocompromised Host. Curr Fungal Infect Rep. 2013;7:44–50. 8. Yousukh A, Jutavijittum P, Pisetpongsa P, et al. Clinicopathologic study of hepatic Penicillium marneffei in Northern Thailand. Arch Pathol Lab Med. 2004;128:191–194. 9. Wong SY, Wong KF. Penicillium marneffei Infection in AIDS. Patholog Res Int. 2011;10:764293.
Neuronal NOS Inhibitor That Reduces Oxidative DNA Lesions and Neuronal Sensitivity Increases the Expression of Intact c-fos Transcripts after Brain Injury

In response to oxidative stress, the ischemic brain induces immediate early genes when its nuclear genes contain gene damage. Antioxidant that reduces gene damage also reduces cell death. To study the mechanism of neuronal sensitivity, we investigated the transcription of the c-fos gene after brain injury of the ischemia-reperfusion type using focal cerebral ischemia-reperfusion in Long-Evans hooded rats. We observed a significant (p < 0.01) increase in c-fos mRNA in the ischemic cortex immediately after brain injury. However, the c-fos transcript was sensitive to RNase A protection assay (RPA) upon reperfusion. The transcript became significantly resistant to RPA (42%, p < 0.03) when 3-bromo-7-nitroindazole (25 mg/kg, i.p.), known to abolish nitric oxide, gene damage and neuronal sensitivity, was injected. Our data suggest that neuronal nitric oxide synthase and aberrant mRNA from genes with oxidative damage could be associated with neuronal sensitivity.
Pediatric Pituitary Adenoma: Case Series, Review of the Literature, and a Skull Base Treatment Paradigm

Abstract Background Pediatric pituitary adenoma is a rare skull base neoplasm, accounting for 3% of all intracranial neoplasms in children and 5% of pituitary adenomas. Compared with pituitary tumors in adults, secreting tumors predominate and longer disease trajectories are expected due to the patient age resulting in a natural history and treatment paradigm that is complex and controversial. Objectives The aims of this study were to describe a large, single-institution series of pediatric pituitary adenomas with extensive long-term follow-up and to conduct a systematic review examining outcomes after pituitary adenoma surgery in the pediatric population. Methods The study cohort was compiled by searching institutional pathology and operative reports using diagnosis and site codes for pituitary and sellar pathology, from 1956 to 2016. Systematic review of the English language literature since 1970 was conducted using PubMed, MEDLINE, Embase, and Google Scholar. Results Thirty-nine surgically managed pediatric pituitary adenomas were identified, including 15 prolactinomas, 14 corticotrophs, 7 somatotrophs, and 4 non-secreting adenomas. All patients underwent transsphenoidal resection (TSR) as the initial surgical treatment. Surgical cure was achieved in 18 (46%); 21 experienced recurrent/persistent disease, with secondary treatments including repeat surgery in 10, radiation in 14, adjuvant pharmacotherapy in 11, and bilateral adrenalectomy in 3. At the last follow-up (median 87 months, range 3–581), nine remained with recurrent/persistent disease (23%). Thirty-seven publications reporting surgical series of pediatric pituitary adenomas were included, containing 1,284 patients. Adrenocorticotropic hormone (ACTH)-secreting tumors were most prevalent (43%), followed by prolactin (PRL)-secreting (37%), growth hormone (GH)-secreting (12%), and nonsecreting (7%). Surgical cure was reported in 65%. Complications included pituitary insufficiency (23%), permanent visual dysfunction (6%), chronic diabetes insipidus (DI) (3%), and postoperative cerebrospinal fluid (CSF) leak (4%). Mean follow-up was 63 months (range 0–240), with recurrent/persistent disease reported in 18% at the time of last follow-up. Conclusion Pediatric pituitary adenomas are diverse and challenging tumors with complexities far beyond those encountered in the management of routine adult pituitary disease, including nuanced decision-making, a technically demanding operative environment, high propensity for recurrence, and the potentially serious consequences of hypopituitarism with respect to fertility and growth potential in a pediatric population. Optimal treatment requires a high degree of individualization, and patients are most likely to benefit from consolidated, multidisciplinary care in highly experienced centers.
Sleep deprivation and cerebrospinal fluid biomarkers for Alzheimer’s disease

Study Objectives To investigate the cumulative effect of five consecutive nights of partial sleep deprivation (PSD) on a panel of cerebrospinal fluid (CSF) biomarkers in healthy adults. Methods A randomized, cross-over study conducted at the University of Gothenburg. The participants (N = 13) were healthy adults (20-40 years of age) with a normal sleeping pattern. The participants underwent a baseline sleep period consisting of five nights with 8 hr spent in bed. A subsequent period with PSD consisted of five nights of maximum 4 hr of sleep per night. Four participants were also subjected to a prolonged period of PSD consisting of eight nights with 4 hr of sleep per night. Sleep was monitored by means of observation, actigraphy, and continuous polysomnographic recordings. CSF samples were collected by routine lumbar puncture after each period. CSF biomarkers included the 38, 40, and 42 amino acid-long Aβ isoforms, total-τ, phospho-τ, orexin, monoamine metabolites (3-methoxy-4-hydroxyphenylglycol, homovanillinic acid, and 5-hydroxyindoleacetic acid), neuron-derived biomarkers (neurofilament light, neuron-specific enolase, and fatty acid-binding protein), and astro- and microglia-derived biomarkers (glial fibrillary acidic protein, S-100B, and YKL-40). Results PSD was associated with a 27 per cent increase in CSF orexin concentrations (p = 0.001). No PSD-related changes in CSF biomarkers for amyloid build-up in the brain, Alzheimer's disease (AD)-type neurodegeneration, or astroglial activation were observed. PSD led to a shortening of time spent in all sleep stages except slow-wave sleep (SWS). Conclusion Five to eight consecutive nights of PSD, with preserved SWS, increased CSF orexin but had no effect on CSF biomarkers for amyloid deposition, neuronal injury, and astroglial activation.
Leukotriene Receptor Antagonists – A Novel Therapeutic Approach in Atopic Dermatitis?

Cysteinyl leukotrienes have been shown to be important in the pathogenesis of both asthma and rhinitis. Improvement of skin manifestations in atopic dermatitis has been reported with leukotriene receptor antagonists. This article reviews current data on the experimental evidence and clinical efficacy of leukotriene receptor antagonists in the treatment of atopic dermatitis.
Correlation between Cosyntropin Stimulation Study and Disease Severity in Children with Fluid- and Catecholamine-Refractory Shock in the Pediatric and Cardiovascular Intensive Care Unit

Background: The cosyntropin stimulation study (CSS) measures the patient’s ability to adequately mount a cortisol response. Clinically, CSS results may not be used to guide hydrocortisone use. The objective of this study was to examine how the CSS results are associated with clinical parameters, mortality/disease severity, and use of glucocorticoids in pediatric patients with catecholamine- and fluid-resistant shock. Methods: This was a retrospective cohort study of patients who had a CSS during 2009–2014 in the intensive care unit at a children’s hospital. Data collected included clinical variables, mortality, biochemical studies, and glucocorticoid use. PRISM III scores were used to determine the association between CSS results and disease severity. Adequate response to cosyntropin was defined as peak cortisol of 18 µg/dL or higher. Results: Of the 76 patients that underwent CSS, 68 (89%) had an adequate response to cosyntropin. There was a positive correlation between peak cortisol and PRISM III score (r = 0.45, r2 = 0.2). Glucocorticoid was administered in 52/76 (68%) despite several patients with normal CSS results. Conclusions: Sicker patients were more likely to have an adequate response to CSS. Clinically, glucocorticoid supplementation was not based on CSS results. Further prospective studies are needed to elucidate if CSS is a valuable clinical tool.
Age-Dependent Decline in Fate Switch from NG2 Cells to Astrocytes After Olig2 Deletion

NG2 cells are a resident glial progenitor cell population that is uniformly distributed throughout the developing and mature mammalian CNS. Those in the postnatal CNS generate exclusively myelinating and non-myelinating oligodendrocytes and are thus equated with oligodendrocyte precursor cells. Prenatally, NG2 cells in the ventral gray matter of the forebrain generate protoplasmic astrocytes as well as oligodendrocytes. The fate conversion from NG2 cells into protoplasmic astrocytes is dependent on downregulation of the key oligodendrocyte transcription factor Olig2. We showed previously that constitutive deletion of Olig2 in NG2 cells converts NG2 cells in the neocortex into protoplasmic astrocytes at the expense of oligodendrocytes. In this study, we show that postnatal deletion of Olig2 caused NG2 cells in the neocortex but not in other gray matter regions to become protoplasmic astrocytes. However, NG2 cells in the neocortex became more resistant to astrocyte fate switch over the first 3 postnatal weeks. Fewer NG2 cells differentiated into astrocytes and did so with longer latency after Olig2 deletion at postnatal day 18 (P18) compared with deletion at P2. The high-mobility group transcription factor Sox10 was not downregulated for at least 1 month after Olig2 deletion at P18 despite an early transient upregulation of the astrocyte transcription factor NFIA. Furthermore, inhibiting cell proliferation in slice culture reduced astrocyte differentiation from Olig2-deleted perinatal NG2 cells, suggesting that cell division might facilitate nuclear reorganization needed for astrocyte transformation. SIGNIFICANCE STATEMENT NG2 cells are glial progenitor cells that retain a certain degree of lineage plasticity. In the normal postnatal neocortex, they generate mostly oligodendrocyte lineage cells. When the oligodendrocyte transcription factor Olig2 is deleted in NG2 cells in the neocortex, they switch their fate to protoplasmic astrocytes. However, the efficiency of the fate switch decreases with age over the first 3 postnatal weeks and is reduced when cell proliferation is inhibited. As the neocortex matures, sustained expression of the oligodendrocyte lineage-specific key transcription factor Sox10 becomes less dependent on Olig2. Together, our findings suggest a gradual stabilization of the oligodendrocyte lineage genes and loss of lineage plasticity during the first 3 weeks after birth, possibly due to nuclear reorganization.
Cutting Edge: c-Maf Is Required for Regulatory T Cells To Adopt RORγt+ and Follicular Phenotypes

Regulatory T cells (Tregs) adopt specialized phenotypes defined by coexpression of lineage-defining transcription factors, such as RORγt, Bcl-6, or PPARγ, alongside Foxp3. These Treg subsets have unique tissue distributions and diverse roles in maintaining organismal homeostasis. However, despite extensive functional characterization, the factors driving Treg specialization are largely unknown. In this article, we show that c-Maf is a critical transcription factor regulating this process in mice, essential for generation of both RORγt+ Tregs and T follicular regulatory cells, but not for adipose-resident Tregs. c-Maf appears to function primarily in Treg specialization, because IL-10 production, expression of other effector molecules, and general immune homeostasis are not c-Maf dependent. As in other T cells, c-Maf is induced in Tregs by IL-6 and TGF-β, suggesting that a combination of inflammatory and tolerogenic signals promote c-Maf expression. Therefore, c-Maf is a novel regulator of Treg specialization, which may integrate disparate signals to facilitate environmental adaptation.
Suggestions for a Guideline for Cochlear Implantation in CHARGE Syndrome

Objective: Identifying aspects for establishing cochlear implantation guidelines for patients with ocular coloboma, heart defects, atresia of the choanae, retardation (of growth and/or of development), genital anomalies, and ear anomalies (CHARGE) syndrome (CS). Study Design: Explorative retrospective study. Setting: Cochlear implant (CI)-centers of tertiary referral centers in The Netherlands. Patients: Ten patients with CS who received a CI between 2002 and 2012. Interventions: Describing the challenges and benefits of cochlear implantation in CS. Main Outcome Measures: Imaging and surgical findings, language development, and Quality-of-life (QoL), compared with two control groups: 1) 34 non-syndromic CI-users and 2) 13 patients with CS without CI because of sufficient hearing. Results: Subjective and objective audiometry and magnetic resonance imaging were necessary to confirm the presence of the cochlear nerve. Surgery in CS was challenging because of enlarged emissary veins, semi-circular-canal aplasia, aberrant facial nerve, and dysplastic cochlear windows, making computed tomography indispensable in surgical preparations. No major intraoperative complications occurred. Despite additional handicaps, all patients showed auditory benefit and improvement in disease-specific QoL. Patients implanted at a relatively young age (⩽37 months) followed by a long period of CI-use (>5 years) and with minor additional problems, developed spoken language at a basic level comparable to that of the control group of CS patients. Conclusion: A CI should be considered in all patients with CS and severe sensorineural hearing loss. A careful work-up is required, comprising computed tomography, magnetic resonance imaging, objective, and subjective audiometry and assessment by a specialized multidisciplinary team. Cochlear implantation in CS might be complicated by syndrome-related temporal-bone anatomy, and the outcome of the CI is more individually determined. Early implantation should be aimed for.
Malnutrition and Developmental Defects of Enamel in 2- to 6 -Year-Old Saudi Boys

Three hundred and ninety boys aged 2, 4 or 6 years from Riyadh, Saudi Arabia, took part in a survey in 1993/94. The main aims of the study were first, to identify factors related to malnutrition in young children since a study of older children from the same area 1 year before had shown malnutrition to be strongly related to prevalence of developmental defects of enamel (DDE) of permanent teeth and, second, to identify factors related to the prevalence of developmental defects of primary teeth. Enamel defects were recorded by clinical examination of the buccal surfaces of all primary teeth by 1 examiner using the DDE index. A questionnaire to parents provided information on socio-economic status, illness in the mother and child, infant feeding, trauma to teeth and toothbrushing. A 24-hour dietary record, to estimate water and milk intake, and a 24-hour urine collection were obtained for each child twice. Nutritional status was calculated from height for age using WHO methods. Multiple regression analyses revealed four variables related (p < 0.05) to malnourished status: low birth-weight, low volume of water drunk, child stopped breast- and bottle-feeding before 1 year of age, and low class urban or rural area of residence. Birth-weight was itself related to area of residence (p = 0.02), parental education (p = 0.02) and maternal illness during pregnancy (p = 0.06). Malnutrition (p < 0.001), low birth-weight (p < 0.001), childhood illness (p < 0.001), brushing of child’s teeth (p = 0.003) and swallowing toothpaste (p < 0.001) were related to the prevalence of developmental defects of primary teeth. This study indicated several independent variables which may be related to the prevalence of enamel defects in primary and permanent teeth, but longitudinal studies are required to determine which are causes and which are markers of these developmental defects.
Recommendations for the detection and diagnosis of Niemann-Pick disease type C

Abstract Purpose of review: Niemann-Pick disease type C (NP-C) is a neurovisceral disorder that may be more prevalent than earlier estimates. Diagnosis of NP-C is often delayed; a key aim for clinical practice is to reduce this delay. Recently, substantial progress has been made in the field of NP-C screening and diagnosis, justifying an update to the existing recommendations for clinical practice. Recent findings: New biomarker profiling and genetic analysis technologies are included as first-line diagnostic tests for NP-C. Most diagnoses can now be confirmed by combination of biomarker and genetic analyses. Filipin staining may facilitate diagnosis in uncertain cases. Recommendations are provided for psychiatrists, neuro-ophthalmologists, and radiologists, and on screening within specific at-risk patient cohorts. The NP-C diagnostic algorithm has been updated and simplified. Summary: This publication provides expert recommendations for clinicians who may see patients presenting with the signs and symptoms of NP-C, including general practitioners, pediatricians, neurologists, and psychiatrists.