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Purpose: The purpose of our study was to evaluate the usefulness of the BiofireFilmArray Meningitis/Encephalitis (FA ME) panel and identify factors associated with positive FA ME panel results. Methods: We retrospectively analyzed the medical records of 129 patients (45 children, 84 adults) with central nervous system infections and FA ME panel test results. We compared the results of the FA ME panel and the diagnostic yield between pediatric and adult patients with positive and negative FA ME panel results. Positive FA ME panel results were compared with conventional microbiological testing. Results: Forty-three patients (33.3%) had positive results on the FA ME panel. The detected pathogens were enterovirus (n=17, 39.5%), varicella zoster virus (n=10, 23.3%), herpes simplex virus-2 (n=2, 16.3%), herpes simplex virus-1 (n=2, 4.7%), human parechoviruses (n=2), Cryptococcus neoformans/gattii (n=2), Streptococcus agalactiae (n=1, 2.3%), Streptococcus pneumoniae (n=1), and Haemophilus influenzae (n=1). The time to detection of the FA ME panel (4.9±6.6 hours) was significantly shorter than that of conventional culture (77.4±48.2 hours) (P=0.005). Fever was more common in the positive FA ME group than in the negative FA ME group (81.4% vs. 41.9%) and in pediatric patients than in the adult patients (93.3% vs. 34.5%) (P

Purpose: The aim of this study was to examine whether gonadotropin-releasing hormone (GnRH) agonist treatment is effective in preserving final height in patients with central precocious puberty (CPP) or early puberty (EP).Methods: The medical records of 40 patients with CPP and 206 patients with EP who completed GnRH agonist treatment following diagnosis were analyzed retrospectively. Height and height standard deviation (height SDS) scores based on bone age (BA) were measured and calculated at baseline, after treatment completion, and at final follow-up to compare changes within and between groups. Predicted adult height (PAH) was estimated by the height corresponding to height SDS for BA in girls at 18 years 11 months of age based on the growth chart.Results: PAH at baseline did not differ significantly between the CPP group (153.67±4.95) and the EP group (154.77±3.72). In the CPP group, PAH significantly increased at treatment completion (156.01±4.61) and at final follow-up (158.52±6.04) compared to baseline. In the EP group, PAH significantly increased at treatment completion (157.7±3.60) and at final follow-up (159.31±4.26) compared to baseline. The increase in PAH at all timepoints compared to baseline did not significantly differ between the CPP and EP groups.Conclusion: Both CPP and EP groups had significantly greater PAH after treatment, with no difference in the amount of increase between groups. These results show that GnRH agonist treatment can help increase final height even in patients diagnosed with EP after the age of 8 years.

Pediatric nondysraphic intramedullary lipoma is very rare, and only limited cases have been reported. In the present case, we present two infant patients with these pathologies who were surgically treated. Previous literature on 20 patients with these diseases who had undergone surgical treatments was analyzed. Surgical treatment should be considered in most symptomatic patients, and laminoplastic laminotomy and internal debulking of the lipoma under intraoperative neurophysiological monitoring are mostly recommended.

Twenty compounds were isolated from Morus alba using a PCSK9 expression monitoring assay. For the first time, it is found that betulinic acid may inherit a new role as a PCSK9 inhibitor.

Mucoepidermoid carcinoma (MEC) and sclerosing MEC with eosinophilia (SMECE) are rare primary thyroid carcinomas. In this study, we aimed to present our multicenter series of MEC and SMECE and integrated our data with published literature to further investigate the clinicopathological characteristics and prognoses of these tumors. We found 2 MECs and 4 SMECEs in our multicenter archives. We performed fluorescence in situ hybridization (FISH) to determine the MAML2 gene rearrangement. We screened for mutations in BRAF, TERT promoter, and RAS mutations using Sanger sequencing and digital polymerase chain reaction. Histopathologically, MECs and SMECEs were composed of two main cell types including epidermoid and mucin-secreting cells, arranged in cords, nests, and tubules. SMECEs were characterized by a densely sclerotic stroma with abundant eosinophils. We did not detect any MAML2 fusion in any of our cases. Two MEC cases harbored concomitant BRAF p.V600E and TERT C228T mutations. RAS mutations were absent in all cases. Concurrent foci of another thyroid malignancy were more commonly seen in MECs (p 0.001), whereas SMECEs were associated with chronic lymphocytic thyroiditis (p 0.001). MECs and SMECEs had equivalent recurrence-free survival (RFS) but MECs conferred significantly dismal disease-specific survival (DSS) as compared to SMECEs (p = 0.007). In conclusion, MECs and SMECEs not only shared some similarities but also demonstrated differences in clinicopathological characteristics, prognoses, and molecular profiles. SMECEs had a superior DSS in comparison to MECs, suggesting that they are low-grade cancers. This could help clinicians better evaluate patient outcomes and decide appropriate treatment plans.

The World Health Organization identified men as an essential group to target with HIV testing and treatment strategies;: men who have sex with men (MSM) and male clients of female sex workers (CFSW) account for 35% of new HIV infections globally. Using a cross-sectional design from a community-based HIV prevention project in Tanzania (October 2015–September 2018) and multivariable logistic regression, we identified predictors of HIV seropositivity among men. Of 1,041,343 men on their initial visit to the project, 36,905 (3.5%) were MSM; 567,005 (54.5%) were CFSW; and 437,343 (42.0%) were other men living near hotspots (OMHA). Three predictors of HIV seropositivity emerged across all three groups: being uncircumcised, having sexually transmitted infection symptoms, and harmful drinking of alcohol before sex. Any reported form of gender-based violence among MSM and OMHA and inconsistent condom use among CFSW were associated with HIV seropositivity. These findings may inform community HIV strategies like self-testing, delivery of pre-exposure prophylaxis and antiretroviral therapy, and behavioral change communication targeting men at higher risk of infection.

Background Respectful maternity care (RMC) remains a key challenge in Afghanistan, despite progress on improving maternal and newborn health during 2001–2021. A qualitative study was conducted in 2018 to provide evidence on the situation of RMC in health facilities in Afghanistan. The results are useful to inform strategies to provide RMC in Afghanistan in spite of the humanitarian crisis due to Taliban’s takeover in 2021.Methods Focus group discussions were conducted with women (4 groups, 43 women) who had used health facilities for giving birth and with providers (4 groups, 21 providers) who worked in these health facilities. Twenty key informant interviews were conducted with health managers and health policy makers. Motivators for, deterrents from using, awareness about and experiences of maternity care in health facilities were explored.Results Women gave birth in facilities for availability of maternity care and skilled providers, while various verbal and physical forms of mistreatment were identified as deterrents from facility use by women, providers and key informants. Low awareness, lack of resources and excessive workload were identified among the reasons for violation of RMC.Conclusion Violation of RMC is unacceptable. Awareness of women and providers about the rights of women to respectful maternity care, training of providers on the subject, monitoring of care to prevent mistreatment, and conditioning any future technical and financial assistance to commitments to RMC is recommended.

Introduction Tanzania had an estimated 5.400 maternal deaths in 2020. Suboptimal quality of antenatal care (ANC) presents a major challenge. It is not known what precisely the uptake of the various ANC components is, such as counseling on birth preparedness and complication readiness, preventive measures and screening tests. We assessed the level of receiving the various ANC components and associated factors in order to identify opportunities to improve ANC. Methods A cross-sectional household survey using a structured questionnaire through face-to-face interviews, was conducted in April 2016 in Mara and Kagera regions, Tanzania, applying a two-stage, stratified-cluster sampling design. The analysis included 1,162 women aged 15–49 years who attended ANC during their last pregnancy and had given birth not longer than two years prior to the survey. To account for inter- and intra-cluster variations, we used mixed-effect logistic regression to examine factors associated with receiving essential ANC components: counseling around birth preparedness and complication readiness (with presumed effects on knowledge about danger signs) and preventive measures. Results About In 878 (76.1%) women preparedness for birth and its complications was observed to exist. Overall counseling was low where 902 (77.6%) women received adequate counseling. Overall knowledge of danger signs was low in 467 women (40.2%). Uptake of preventive measures was low, with presumptive malaria treatment in 828 (71.3%) and treatment of intestinal worms in 519 (44.7%) women. Screening test levels varied for HIV in 1,057 (91.2%), any blood pressure measurement in 803 (70.4%), syphilis in 367 (32.2%) and tuberculosis in 186 (16.3%) women. After adjusting for age, wealth and parity, the likelihood of receiving adequate counseling on essential topics was less in women without education versus primary education (aOR 0.64; 95% CI 0.42–0.96) and in women who had Conclusion Overall uptake of various essential ANC components was low. Frequent ANC visits and ensuring privacy are all essential to improve the uptake of ANC.

Non-tumor mesenchymal cell lines and Rb-WT/p53-deficient MFS/UPS cell lines are less sensitive to SKP2 knockdown

Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are highly genetically complex soft tissue sarcomas. Up to 50% of patients develop distant metastases, but current systemic therapies have limited efficacy. MFS and UPS have recently been shown to commonly harbor copy number alterations or mutations in the tumor suppressor genes RB1 and TP53. As these alterations have been shown to engender dependence on the oncogenic protein Skp2 for survival of transformed cells in mouse models, we sought to examine its function and potential as a therapeutic target in MFS/UPS. Comparative genomic hybridization and next-generation sequencing confirmed that a significant fraction of MFS and UPS patient samples (n = 94) harbor chromosomal deletions and/or loss-of-function mutations in RB1 and TP53 (88% carry alterations in at least one gene; 60% carry alterations in both). Tissue microarray analysis identified a correlation between absent Rb and p53 expression and positive expression of Skp2. Downregulation of Skp2 or treatment with the Skp2-specific inhibitor C1 revealed that Skp2 drives proliferation of patient-derived MFS/UPS cell lines deficient in both Rb and p53 by degrading p21 and p27. Inhibition of Skp2 using the neddylation-activating enzyme inhibitor pevonedistat decreased growth of Rb/p53-negative patient-derived cell lines and mouse xenografts. These results demonstrate that loss of both Rb and p53 renders MFS and UPS dependent on Skp2, which can be therapeutically exploited and could provide the basis for promising novel systemic therapies for MFS and UPS.Significance:Loss of both Rb and p53 renders myxofibrosarcoma and undifferentiated pleomorphic sarcoma dependent on Skp2, which could provide the basis for promising novel systemic therapies.See related commentary by Lambert and Jones, p. 2437

Skp2 knockdown causes cell cycle arrest and reduces Akt activation

Comparison of rates of RB1 and TP53 copy number alterations in MFS and UPS samples across 3 large genomic databases

Pevonedistat increases p21 and p27 expression and apoptosis in Rb/p53-deficient MFS and UPS xenografts with negligible toxicity.

Supplementary tables and figure legends. Supplementary Table 1. siRNA targeting sequences; Supplementary Table 2. pLKO.1 shRNA sequences; Supplementary Table 3. Antibodies Supplementary Table 4. PCR primers

RB1 and TP53 deletion or loss-of-function mutation associates with negative protein expression

The Skp2-specific inhibitor C1 is cytotoxic to 8000s cells and increases their expression of p21 and p27

Fingerprint-inspired elastomeric grating meta-skin (EGMS) is herein fabricated to investigate the chirality of fingerprints. The EGMS is made by a facile nanoimprinting method with a diffraction grating as a template using polydimethylsiloxane, followed by gold deposition. The chirality of the surface is caused by symmetry breaking, induced by the pattern (biP/i/b) and curvature (biT/i/b). Furthermore, the chiroptical properties of EGMS are reconfigurable through the control of the skew angle (θ), which is the angle betweenbiP/i/bandbiT/i/b. The chiroptical properties of a fingerprint are also shown and interpreted in this perspective. On the basis of the results, we suggest the strategy to impart chirality on the surface, which is reconfigurable by controllingbiP/i/bandbiT/i/b. It will be a useful method to produce chirality in membranes, thin films, metasurfaces, and 2D nanomaterials, as well as advance biometric recognition.

Purpose: Epilepsy is one of the most common neurological disorders in both adults and children. After detailed history-taking, electroencephalography (EEG) is the most important investigation in the evaluation of epilepsy patients. Polyspikes, defined as a sequence of two or more spikes, are among the findings that can be seen on EEGs of epilepsy patients, but the literature on their significance in focal epilepsy patients is scarce. Therefore, in the current study, we investigated the significance of polyspikes on EEG in childhood focal epilepsy. Methods: A retrospective analysis was conducted of data from children who were diagnosed with focal epilepsy and received anti-seizure medications at Pusan National University Children’s Hospital. Results: Among the 1,125 children included in this study, 468 (41.6%) showed interictal polyspikes on their EEGs. In the multivariate analysis, only the presence of brain magnetic resonance imaging (MRI) abnormalities was significantly associated with the presence of interictal polyspikes on EEGs. Among patients with brain MRI abnormalities, localized polyspikes were significantly associated with focal cortical dysplasia, while multifocal polyspikes were significantly associated with perinatal insults (hypoxic-ischemic encephalopathy and destructive encephalomalacia). Conclusion: Focal epilepsy patients with interictal polyspikes were more likely to have a structural etiology. Furthermore, patients with localized polyspikes were more likely to have focal cortical dysplasia as the structural etiology, while patients with multifocal polyspikes were more likely to have perinatal insults as the structural etiology. This study demonstrates that focal polyspikes can be used as markers of the possible presence of a structural etiology in routine practice.

Fractionation of a methanol extract of

BACKGROUND Little information exists regarding the incidence of chronic spontaneous urticaria (CSU) or differences in its characteristics according to age. OBJECTIVE To evaluate the incidence, clinical characteristics and treatment response of CSU according to age. METHODS The relevance of gender, age, history of allergic disease, pre-diagnosis duration, and treatment response were retrospectively evaluated in patients diagnosed with CSU at Pusan National University Hospital between 2011 and 2018. RESULTS A total of 970 patients were included in the study, consisting of 198 children and 772 adults. The CSU incidence increased during the study period in children, but not in adults. CSU was more common in adults than in children and the peak age of occurrence was 20-59 years. Increased female incidence was noted in adults, whereas patient and family allergic history was frequently observed in children than in adults. The overall rate of improvement was remarkably higher in children than in adults (P < 0.01), with pre-diagnosis duration and treatment duration both shorter in children than in adults. (P = 0.001). The proportion of men was higher and treatment duration was shorter in adolescence than in the other age groups, whereas the treatment duration was shorter in patients greater or equal to 60 years than in adults under 60 years, and the step 1 treatment rate was higher. CONCLUSION CSU incidence increased annually in children, but not in adults. The clinical characteristics and treatment response of CSU may differ depending on age and clinicians should be made aware of this fact.