Clinical and Pathological Features of Pilomatrixoma in Children: A Retrospective Study.

INTRODUCTION: Pilomatrixoma is a benign skin neoplasm that is common in children and is often misdiagnosed. This study aimed to summarize the clinical and pathological features of pilomatrixoma in children. METHODS: Data on demographic information, clinical and pathological features, diagnosis, and treatment of 171 patients with pilomatrixoma from Shenzhen Baoan Women's and Children's Hospital were collected and analyzed retrospectively. RESULTS: The mean age of the patients was 5.7 (standard deviation [SD] = 3.9) years old, and there were 2 age peaks (≤1 year old, 5-11 years old) and 2 age valleys (2-4 years old, ≥12 years old). The mean disease course was 9.3 (SD = 14.1) months, 69.0%, 86.5%, and 95.3% of the patients' disease course in 6 months, 12 months, and 24 months, respectively. The mean tumor volume was 0.6 (SD = 1.0) cm3, and 81.3% of the patients' tumor volume ≤1.0 cm3. Tumors were distributed sequentially in the head and neck (77.2%), upper limbs (12.9%), trunk (7.6%), and lower limbs (2.3%). The correct rates of clinical and ultrasonic diagnosis were 50.9% and 38.6%, respectively. The two most common pathological features of pilomatrixoma were shadow cells (99.4%) and basaloid cells (94.7%). There were no significant differences in age, disease course, or tumor volume between the male and female patients (p > 0.05). The age and tumor volume of the patients in different body parts were significantly different (P1 = 3.10E-05 and P2 = 5.60E-05, respectively). The correlation between the disease course and tumor volume was positively significant (p ≤ 0.05). There was a significant correlation between the disease course and tumor volume in patients with tumors at upper limbs (p = 0.03). CONCLUSION: The age of children with pilomatrixoma presented 2 peaks and 2 valleys. Most patients had disease courses in 24 months and with tumor volumes ≤1.0 cm3. The correct rates of clinical and ultrasonic diagnosis were relatively low. The head and neck were the most common distribution sites of pilomatrixoma, and shadow cells and basaloid cells were the most common pathological features. The tumor volume was positively correlated with disease course in patients with pilomatrixoma.

Effect of ciliary sulcus angle on the prediction of the vault for phakic implantable collamer lens in the KS formula.

PURPOSE: We aimed to explore the effects of the ciliary sulcus angle (CSA) on accurate prediction of the vault after phakic implantable collamer lens (EVO ICL Model V4c) using the KS formula. METHODS: Patients were classified according to the size of CSA: group A, narrow angle (CSA < 30°); group B, normal angle (CSA = 30-90°); and group C, wide angle (CSA > 90°). Further, differences between the actual vault dimensions at 3 months postoperatively and the preoperatively predicted vault dimensions in the three groups were analyzed. RESULTS: This study included 223 eyes of 223 individuals. In groups A-C, the difference in the preoperative vault dimensions of the three groups predicted with the KS formula was not statistically significant (P = 0.056). The actual vault dimensions at 3 months postoperatively were significantly different between the three groups (P < 0.001). Moreover, the difference between the actual and predicted vaults by the KS formula was statistically significant (P < 0.001). In the 3 months, after surgery, the percentages of patients with a low vault (< 250 µm) were 0%, 3%, and 29% in groups A, B, and C, respectively. Further, the percentages of patients with an ideal vault (250-750 µm) in the postoperative period were 66%, 84%, and 71% in groups A, B, and C, respectively. Finally, the percentages of patients with a high vault (> 750 µm) in the postoperative period were 34%, 13%, and 0% in groups A, B, and C, respectively. Notably, the distribution of the vault among the three groups was statistically significant (P < 0.001). CONCLUSION: The size of CSA significantly affects the predictiveness of the vault by the KS formula, with the most pronounced effect on the angles < 30° and > 90°. Therefore, CSA should be considered when selecting the lens size using the KS formula preoperatively. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2200065501.

The impact of temperature, humidity and closing school on the mumps epidemic: a case study in the mainland of China.

BACKGROUND: To control resurging infectious diseases like mumps, it is necessary to resort to effective control and preventive measures. These measures include increasing vaccine coverage, providing the community with advice on how to reduce exposure, and closing schools. To justify such intervention, it is important to understand how well each of these measures helps to limit transmission. METHODS: In this paper, we propose a simple SEILR (susceptible-exposed-symptomatically infectious-asymptomatically infectious-recovered) model by using a novel transmission rate function to incorporate temperature, humidity, and closing school factors. This new transmission rate function allows us to verify the impact of each factor either separately or combined. Using reported mumps cases from 2004 to 2018 in the mainland of China, we perform data fitting and parameter estimation to evaluate the basic reproduction number  R 0 . As a wide range of one-dose measles, mumps, and rubella (MMR) vaccine programs in China started only in 2008, we use different vaccination proportions for the first Stage I period (from 2004 to 2008) and the second Stage II period (from 2009 to 2018). This allows us to verify the importance of higher vaccine coverage with a possible second dose of MMR vaccine. RESULTS: We find that the basic reproduction number  R 0  is generally between 1 and 3. We then use the Akaike Information Criteria to assess the extent to which each of the three factors contributed to the spread of mumps. The findings suggest that the impact of all three factors is substantial, with temperature having the most significant impact, followed by school opening and closing, and finally humidity. CONCLUSION: We conclude that the strategy of increasing vaccine coverage, changing micro-climate (temperature and humidity), and closing schools can greatly reduce mumps transmission.

An Overview of Millimeter-Wave Radar Modeling Methods for Autonomous Driving Simulation Applications.

Autonomous driving technology is considered the trend of future transportation. Millimeter-wave radar, with its ability for long-distance detection and all-weather operation, is a key sensor for autonomous driving. The development of various technologies in autonomous driving relies on extensive simulation testing, wherein simulating the output of real radar through radar models plays a crucial role. Currently, there are numerous distinctive radar modeling methods. To facilitate the better application and development of radar modeling methods, this study first analyzes the mechanism of radar detection and the interference factors it faces, to clarify the content of modeling and the key factors influencing modeling quality. Then, based on the actual application requirements, key indicators for measuring radar model performance are proposed. Furthermore, a comprehensive introduction is provided to various radar modeling techniques, along with the principles and relevant research progress. The advantages and disadvantages of these modeling methods are evaluated to determine their characteristics. Lastly, considering the development trends of autonomous driving technology, the future direction of radar modeling techniques is analyzed. Through the above content, this paper provides useful references and assistance for the development and application of radar modeling methods.

Interfacial Engineering of Zn Metal via a Localized Conjugated Layer for Highly Reversible Aqueous Zinc Ion Battery.

Aqueous zinc-ion batteries are regarded as promising and efficient energy storage systems owing to remarkable safety and satisfactory capacity. Nevertheless, the instability of zinc metal anodes, characterized by issues such as dendrite growth and parasitic side reactions, poses a significant barrier to widespread applications. Herein, we address this challenge by designing a localized conjugated structure comprising a cyclic polyacrylonitrile polymer (CPANZ), induced by a Zn2+-based Lewis acid (zinc trifluoromethylsulfonate) at a temperature of 120 °C. The CPANZ layer on the Zn anode, enriched with appropriate pyridine nitrogen-rich groups (conjugated cyclic -C=N-), exhibits a notable affinity for Zn2+ with ample deposition sites. This zincophilic skeleton not only serves as a protective layer to guide the deposition of Zn2+ but also functions as proton channel blocker, regulating the proton flux to mitigate the hydrogen evolution. Additionally, the strong adhesion strength of the CPANZ layer guarantees its sustained protection to the Zn metal during long-term cycling. As a result, the modified zinc electrode demonstrates long cycle life and high durability in both half-cell and pouch cells. These findings present a feasible approach to designing high performance aqueous anodes by introducing a localized conjugated layer.

A facile approach for sulphur and nitrogen co-doped carbon nanodots to improve photothermal eradication of drug-resistant bacteria.

In this study, we produced S, N co-doped CNDs (SN@CNDs) by using dimethyl sulfoxide (DMSO) and formamide (FA) as single sources of S and N, respectively. We varied the S/N ratios by adjusting the volume ratios of DMSO and FA and investigated their effect on the red-shift of the CNDs' absorption peak. Our findings demonstrate that SN@CNDs synthesized using a volume ratio of 5:6 between DMSO and FA exhibit the most significant absorption peak redshift and enhanced near-infrared absorption performance. Based on comparative analysis of the particle size, surface charge, and fluorescence spectrum of the S@CNDs, N@CNDs, and SN@CNDs, we propose a possible mechanism to explain the change of optical properties of CNDs due to S, N doping. Co-doping creates a more uniform and smaller band gap, resulting in a shift of the Fermi level and a change in energy dissipation from radioactive to non-radiative decay. Importantly, the as-prepared SN@CNDs exhibited a photothermal conversion efficiency of 51.36% at 808 nm and demonstrated exceptional photokilling effects against drug-resistant bacteria in both in vitro and in vivo experiments. Our facile method for synthesizing S and N co-doped CNDs can be extended to the preparation of other S and N co-doped nanomaterials, potentially improving their performance.

Surface-Diluted LiMn6 Superstructure Units Utilizing PO4 3- Confined Ni-Doping Sites to Stabilize Li-Rich Layered Oxides.

Serious capacity and voltage degradation of Li-rich layered oxides (LLOs) caused by severe interfacial side reactions (ISR), structural instability, and transition metal (TM) dissolution during charge/discharge need to be urgently resolved. Here, it is proposed for the inaugural time that the confinement effect of PO4 3- dilutes the LiMn6 superstructure units on the surface of LLOs, while deriving a stable interface with phosphate compounds and spinel species. Combining theoretical calculations, diffraction, spectroscopy, and micrography, an in-depth investigation of the mechanism is performed. The results show that the modified LLO exhibits excellent anionic/cationic redox reversibility and ultra-high cycling stability. The capacity retention is increased from 72.4% to 95.4%, and the voltage decay is suppressed from 2.48 to 1.29 mV cycle-1 after 300 cycles at 1 C. It also has stable long cycling performance, with capacity retention improved from 40.2% to 81.9% after 500 cycles at 2 C. The excellent electrochemical performance is attributed to the diluted superstructure units on the surface of LLO inhibiting the TM migration in the intralayer and interlayer. Moreover, the stable interfacial layers alleviate the occurrence of ISR and TM dissolution. Therefore, this strategy can give some important insights into the development of highly stable LLOs.

Synthesis of Ni3 B/Ni via Vacuum-Induced for Ultrahigh Stable and Efficient Methanol Oxidation.

Designing efficient catalysts to promote the electrochemical oxidation of anodes is the core of the development of electrochemical synthesis technologies, such as HER and CO2 RR. Here, a novel vacuum induction strategy is used to synthesize nickel boride/nickel (Ni3 B/Ni) heterostructure catalyst for electrochemical oxidation of methanol into formic acid. The catalyst has extremely high reactivity (only 146.9 mV overpotential at 10 mA cm-2 , the maximum current density reaches 555.70 mA mg-1 and 443.87 mA cm-2 ), ultra-high selectivity (Faraday efficiency of methanol conversion to formic acid is close to 100%), and ultra-long life (over 50 h at 100 mA cm-2 ). In-suit electrochemical impedance spectroscopy proved that MeOH is oxidized first and inhibits the phase transition of the electrocatalyst to the high-valent electrooxidation products, which not only enables the high selectivity of MeOH oxidation but also ensures high stability of the catalyst. The mechanism studies by density functional theory calculations show that the potential determining step, the formation of *CH2 O, occurs most favorably in the Ni3 B/Ni heterostructure. These results provide references for the development of MeOH oxidation catalysts with high activity, high stability, high selectivity, and low cost.

Distinguishable Influence of the Delivery Mode, Feeding Pattern, and Infant Sex on Dynamic Alterations in the Intestinal Microbiota in the First Year of Life.

The delivery mode, the feeding pattern and infant sex significantly influence the development of the infant gut flora. However, the extent to which these factors contribute to the establishment of the gut microbiota at different stages has rarely been studied. The factors that play a dominant role in determining microbial colonization of the infant gut at specific time points are unknown. The purpose of this study was to assess the different contributions of the delivery mode, the feeding pattern and infant sex to the composition of the infant gut microbiome. Here, 213 fecal samples from 55 infants at five ages (0, 1, 3, 6, and 12 months postpartum) were collected, and the composition of the gut microbiota via 16S rRNA sequencing was analyzed. The results showed that the average relative abundances of four genera, Bifidobacterium, Bacteroides, Parabacteroides, and Phascolarctobacterium, were increased in vaginally delivered infants versus cesarean section-delivered infants, while those of ten genera, such as Salmonella and Enterobacter, were reduced. The relative proportions of Anaerococcus and Peptostreptococcaceae were higher in exclusive breastfeeding than in combined feeding, while those of Coriobacteriaceae, Lachnospiraceae and Erysipelotrichaceae were lower. The average relative abundances of two genera, Alistipes and Anaeroglobus, were increased in male infants compared with female infants, whereas those of the phyla Firmicutes and Proteobacteria were reduced. During the first year of life, the average UniFrac distances revealed that the individual difference in the gut microbial composition in vaginally delivered infants was greater than that in cesarean section-delivered infants (P < 0.001) and that infants who received combined feeding had greater individual microbiota differences than exclusively breastfed infants (P < 0.01). The delivery mode, infant sex, and the feeding pattern were the dominant factors determining colonization of the infant gut microbiota at 0 months, from 1 to 6 months, and at 12 months postpartum, respectively. This study demonstrated for the first time that infant sex accounted for the dominant contribution to infant gut microbial development from 1 to 6 months postpartum. More broadly, this study effectively established the extent to which the delivery mode, the feeding pattern and infant sex contribute to the development of the gut microbiota at various time points during the first year of life.

Development of a rapid simultaneous assay of two urinary tetrasaccharide metabolites using differential ion mobility and tandem mass spectrometry and its application to patients with glycogen storage disease (type Ib and II).

Glucose tetrasaccharide (Glc4) and maltotetraose (M4) are important biomarkers for Pompe disease and other glycogen storage diseases (GSDs). With the development of new treatments for GSDs, more specific and sensitive bioanalytical methods are needed to determine biomarkers. In recent years, differential mobility spectrometry (DMS) has become an effective analytical technique with high selectivity and specificity. This study aimed to develop an efficient analytical method for the two urinary tetrasaccharide metabolites using DMS and apply it to patients with GSDs (type Ib and II). Urine samples were directly diluted and injected into liquid chromatography-differential mobility spectrometry tandem mass spectrometry (LC-DMS-MS/MS). Chromatographic separation was performed on an Acquity™ UPLC BEH Amide column (2.1 × 50 mm, 1.7 µm) with a short gradient elution of 2.6 min. DMS-MS/MS was used to detect two urinary tetrasaccharide metabolites in a negative multiple reaction monitoring mode with isopropanol as a modifier. A total of 20 urine samples from 6 healthy volunteers and 10 patients with GSDs (type Ib and II) were collected for analysis. The method was linear over a concentration range of 0.5~100.0 µg/mL for each urinary tetrasaccharide (r≥0.99). The intra- and inter-day precision RSD% were less than 14.3%, and the accuracy RE% were in the range of -14.3~13.4%. The relative matrix effect was between 86.6 and 114.3%. No carryover or interference was observed. Patients with GSDs (type Ib and II) had significantly higher median urinary Glc4 (P=0.001) and M4 (P=0.012) excretion than healthy subjects. The developed method was simple, rapid, sensitive, and specific. It was successfully applied to healthy volunteers and patients with GSDs (type Ib and II). DMS technology greatly improved analysis efficiency and provided high sensitivity and specificity.

Internalizing Symptoms in Adolescents With Sickle Cell Disease.

OBJECTIVE: Sickle cell disease (SCD) is a genetic blood disorder that may affect patients' mood and behavior. However, measuring the prevalence of internalizing symptoms (anxiety and depression) in patients with SCD has been elusive. We assessed internalizing symptoms in adolescents with SCD to evaluate prevalence and to test whether neurocognitive performance and frequency of pain-related episodes were associated with internalizing concerns. METHODS: One hundred eighty-five patients (57% HbSS/HbSß0-thalassemia, 43% HbSC/HbSß+-thalassemia), ages 12-18 years, received a neuropsychological evaluation as a part of a larger cohort study. Internalizing symptoms were measured using the Behavior Assessment System for Children, Second or Third Edition. Scores on the depression and anxiety scales were compared to normative values using Wilcoxon signed rank test. Spearman correlations examined associations between neurocognitive performances and internalizing symptoms. Robust multivariable regression models measured associations between internalizing symptoms and age, sex, sickle genotype, total hemoglobin, fetal hemoglobin, socioeconomic status, and frequency of pain episodes. RESULTS: Parent- and self-reported ratings of internalizing symptoms were not elevated compared to normative expectations. Overall, 1.8% and 6.3% of the sample displayed clinically elevated symptoms of anxiety and depression based on self-report, respectively. There were no associations between internalizing symptoms and neurocognitive performance (all p > .05). In multivariable analyses, the frequency of pain episodes was positively associated with self-reported anxiety (p = .006) and parent-reported depressive symptoms (p = .017). CONCLUSIONS: Adolescents with SCD do not report elevated internalizing symptoms compared to normative expectations. Further research is needed to examine the trajectory of internalizing symptoms and the bidirectional relationship between pain and psychosocial functioning in SCD.

Benign and Malignant Ovarian Teratomas: Multimodality Imaging Findings With Histopathologic Correlation.

ABSTRACT: The purpose of this article is to provide a comprehensive review of the imaging findings along with histopathologic correlation of mature (benign) teratomas and malignant ovarian teratomas, which include both immature teratomas and malignant degeneration of mature teratomas. The radiologist's ability to provide an accurate diagnosis plays an essential role in guiding the interdisciplinary care of patients with malignant teratomas and improving their outcomes.

Harnessing the plenoptic function for a directionally illuminated autostereoscopic display.

The plenoptic function is ideal to describe three-dimensional displays. We propose and demonstrate in this work that plenoptic function is a particularly suitable scenario in the directionally illuminated autostereoscopic display. Guided by this function, backlight structures and functional thin films are designed and applied for wave-vector and amplitude control so that homogeneous viewing is achieved in large viewing volume while display functionality with optical focusing and diverting can be fulfilled. The demonstration of high-quality displays by cloaking various optical defects in an otherwise severely distorted radiance distribution introduced by lens array is presented. We conclude that the scenario adopted in this work is immediately applicable to enhance general performance for autostereoscopy.

Adenosine A2A receptor antagonism protects against hyperoxia-induced retinal vascular loss via cellular proliferation.

Retinopathy of prematurity (ROP) remains one of the major causes of blindness in children worldwide. While current ROP treatments are mostly disruptive to reduce proliferative neovascularization by targeting the hypoxic phase, protection against early hyperoxia-induced retinal vascular loss represents an effective therapeutic window, but no such therapeutic strategy is available. Built upon our recent demonstration that the protection against oxygen-induced retinopathy by adenosine A2A receptor (A2A R) antagonists is most effective when administered at the hyperoxia (not hypoxic) phase, we here uncovered the cellular mechanism underlying the A2A R-mediated protection against early hyperoxia-induced retinal vascular loss by reversing the inhibition of cellular proliferation via possibly multiple signaling pathways. Specifically, we revealed two distinct stages of the hyperoxia phase with greater cellular proliferation and apoptosis activities and upregulation of adenosine signaling at postnatal 9 day (P9) but reduced cellular activities and adenosine-A2A R signaling at P12. Importantly, the A2A R-mediated protection at P9 was associated with the reversal of hyperoxia-induced inhibition of progenitor cells at the peripheral retina at P9 and of retinal endothelial proliferation at P9 and P12. The critical role of cellular proliferation in the hyperoxia-induced retinal vascular loss was validated by the increased avascular areas by siRNA knockdown of the multiple signaling molecules involved in modulation of cellular proliferation, including activin receptor-like kinase 1, DNA-binding protein inhibitor 1, and vascular endothelial growth factor-A.

Enuresis and Hyperfiltration in Children With Sickle Cell Disease.

Nocturnal enuresis is a common symptom in children with sickle cell disease (SCD). Risk factors for development of enuresis are currently unknown. An early manifestation of SCD-associated kidney damage is glomerular hyperfiltration. We test the hypothesis that in a pediatric SCD cohort, individuals with hyperfiltration are more likely to have nocturnal enuresis when compared to children without hyperfiltration. To assess the relationship between nocturnal enuresis and hyperfiltration, we retrospectively evaluated children with SCD enrolled in the Evaluation of Nocturnal Enuresis and Barriers to Treatment among Pediatric Patients with SCD study and prospectively identified children who reported nocturnal enuresis and were enrolled in the longitudinal cohort study Sickle Cell Clinical Research and Intervention Program. Nocturnal enuresis occurred in 46.5% of Pediatric Patients with Sickle Cell Disease participants and was more frequent in participants with HbSS/HbSß 0 thalassemia and in male participants. We did not identify an association between hyperfiltration from 3 to 5 years of age with the later development of enuresis. Severe SCD genotypes and male sex were associated with nocturnal enuresis after age 5 years. We could not identify additional renal or hematologic predictors associated with the diagnosis of nocturnal enuresis. Future studies should incorporate nonrenal risk factors into studies that predict development of enuresis.

Propofol protects against high glucose-mediated endothelial injury via inhibition of COX2 and iNOS expressions.

Perioperative hyperglycemia is a common metabolic disorder in the clinic. Hyperglycemia, via upregulation of E74-like ETS transcription factor 3 (ELF3), induces cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS) expressions, thus leading to endothelial apoptosis and vascular endothelial injury. Propofol is a widely used anesthetic. In the present study, we explored whether and how propofol protects against high glucose-induced COX2 and iNOS expressions in human umbilical vein endothelial cells (HUVECs). We found that high glucose level decreases cell viability and increases COX2 and iNOS expressions in HUVECs. Our data also indicated that ELF3 overexpression participates in high glucose-mediated cell viability reduction and high glucose-induced COX2 and iNOS expressions. Moreover, propofol treatment improves high glucose-mediated reduction in cell viability and decreases COX2 and iNOS expressions via inhibition of ELF3 expressions. Furthermore, specificity protein 1 (SP1) was found to regulate ELF3 expression, thus mediating endothelial injury. Propofol inhibits high glucose-induced SP1 expression. High glucose increases the abundance of SP1 bound to the ELF3 promoter, which can be reversed by propofol treatment. The protective effect of propofol is reversed by SP1 overexpression. In conclusion, propofol downregulates high glucose-induced SP1 expression, thus attenuating high glucose-induced ELF3 expression, inhibiting high glucose-induced COX2 and iNOS expressions, and improving high glucose-mediated cell viability reduction in HUVECs.

A Prospective Study of the Effect of Tinnitus Sound Matching Degree on the Efficacy of Customized Sound Therapy in Patients with Chronic Tinnitus.

OBJECTIVES: The aim of this study was to explore and compare the customized sound therapy effect between tinnitus sound matching and nonmatching patients in tinnitus customized sound therapy and therapy-related influencing factors. METHODS: This prospective study investigated a total of 100 patients with unilateral chronic tinnitus who received customized sound therapy. The participants were dichotomously divided into matching (group A) and nonmatching (group B) groups after 4 stages of tinnitus matching via the tinnitus assistant app (provided by Sound Ocean Company, SuZhou, China). Each group consists of 50 participants. Before and 6 months after the treatment, Hospital Anxiety and Depression Scale (HADS), tinnitus handicap inventory (THI), and tinnitus loudness Visual Analog Scale (VAS) were used to evaluate the customized sound therapy effect and explore other related influencing factors. RESULTS: (1) The HADS-A, HADS-D, THI, and VAS scores of 2 groups were both significantly decreased after treatment. (2) The HADS-A and THI scores improved markedly in group A than that in group B, which could be related to the hearing loss of the tinnitus side ear before treatment; the lighter the degree of hearing loss, the better the improvement. No statistically significant differences were detected in HADS-D and VAS scores between the 2 groups, and also, these were not related to the degree of hearing loss. The differences in age, gender, and tinnitus duration did not show any statistically significant effect on the improvement of the 2 groups. CONCLUSIONS: Both tinnitus sound matching and nonmatching of the customized sound therapy brought a significant effect to tinnitus participants. Our study also suggests that THI and HADS-A scores of those with tinnitus matching participants improved markedly as compared to those of nonmatching participants, and the customized sound therapy effect is negatively correlated with the severity of hearing loss.

What drives transcranial Doppler velocity improvement in paediatric sickle cell anaemia: analysis from the Sickle Cell Clinical Research and Intervention Program (SCCRIP) longitudinal cohort study.

Children with sickle cell anaemia (SCA) and conditional transcranial Doppler (TCD) flow velocities (conditional: 170-199 cm/s; normal: <170 cm/s) have an increased risk of stroke. The Sickle Cell Clinical Research and Intervention Program (SCCRIP), a lifetime observational study, assessed the influence of haematological markers on TCD velocities. In children (≤16 years) with SCA (HbSS/HbSß0 -thalassaemia) and conditional TCD velocities (n = 32), increases in haemoglobin and in fetal haemoglobin after hydroxyurea initiation were significantly associated with decreases in TCD velocities. The benefit of pharmacological intervention to increase haemoglobin and fetal haemoglobin and normalise TCD velocities was demonstrated in this real-world dataset.

Comparative influence of differentiation and proliferation on gene expression in human meibomian gland epithelial cells.

We recently discovered that by changing environmental signals, differentiated immortalized human meibomian gland epithelial cells (IHMGECs) de-differentiate into proliferating cells. We also discovered that following exposure to appropriate stimuli, these proliferative cells re-differentiate into differentiated IHMGECs. We hypothesize that this plasticity of differentiated and proliferative IHMGECs is paralleled by very significant alterations in cellular gene expression. To begin to test this hypothesis, we compared the gene expression patterns of IHMGECs during differentiation and proliferation. IHMGECs were cultured for four days in either differentiating or proliferating media. After four days of culture, cells were processed for the analysis of gene expression by using Illumina BeadChips and bioinformatic software. Our study identified significant differences in the expression of more than 9200 genes in differentiated and proliferative IHMGECs. Differentiation was associated with significant increases in the expression of specific genes (e.g. S100 calcium binding protein P; 7,194,386-fold upregulation) and numerous ontologies (e.g. 83 biological process [bp] ontologies with ≥100 genes were upregulated), such as those related to development, transport and lysosomes. Proliferation also led to a significant rise in specific gene expressions (e.g. cathelicidin antimicrobial peptide; 859,100-fold upregulation) and many ontologies (115 biological process [bp] ontologies with ≥100 genes were upregulated), with most of the highly significant ontologies related to cell cycle (z scores > 13.9). Our findings demonstrate that gene expression in differentiated and proliferative IHMGECs is extremely different. These results may have significant implications for the regeneration of HMGECs and the reversal of MG dropout in MG dysfunction.

Eltrombopag in children with severe aplastic anemia.

BACKGROUND: Immunosuppressive therapy with horse antithymocyte globulin and cyclosporine currently remains the standard therapy for children with severe aplastic anemia (SAA) who lack human leukocyte antigen (HLA)-identical sibling. The thrombopoietin receptor agonist eltrombopag has been recently approved for SAA patients 2 years and older. However, there are limited data on its safety and efficacy in pediatric cohorts. METHODS: We conducted a retrospective study of patients ≤18 years old consecutively diagnosed with SAA between 2000 and 2018. Patients received either standard immunosuppressive therapy (IST-Std) or IST with eltrombopag (IST-Epag). The primary outcome was the objective response (OR), including partial and complete response (CR), at 6 and 12 months after starting therapy. RESULTS: We identified 16 patients receiving IST-Std and nine IST-Epag treatment (seven of nine as upfront therapy and two of seven after previously failed IST). The OR at 6 and 12 months in IST-Std arm was 71% and 100%, with CR in 29% and 58%, respectively. Seven patients receiving upfront IST-Epag had OR at 6 and 12 months, with two of seven (29%) achieving CR at 6 and 12 months. Two patients who previously failed standard IST did not respond to eltrombopag. No significant differences were observed in both cohorts with regard to infections. One IST-Epag-treated patient developed transient grade 3 transaminitis. Finally, no changes in paroxysmal nocturnal hemoglobinuria (PNH) clone size and cytogenetic abnormalities were seen in either cohort. CONCLUSION: The addition of eltrombopag to standard IST was well tolerated and resulted in satisfactory hematological response at 6 and 12 months in this single-institution experience. A larger cohort with longer follow-up is required to assess response durability.