OBJECTIVE
To report the clinical spectrum seen in young abusers of street‐ketamine (regular recreational abusers of street‐ketamine, for its hallucinogenic effects) in Hong Kong, presenting with ...significant lower urinary tract symptoms (LUTS) but with no evidence of bacterial infection.
PATIENTS AND METHODS
We retrospectively analysed the clinical presentations, pelvic pain and urgency/frequency scores, video‐urodynamic studies, cystoscopy findings, histological features of bladder biopsies and radiological findings of 59 ketamine abusers who were referred to the urology units of Princess Margaret and Tuen Mun Hospital, Hong Kong, from March 2000 to December 2007.
RESULTS
Of the 59 patients, all had moderate to severe LUTS, i.e. frequency, urgency, dysuria, urge incontinence and occasionally painful haematuria. Forty‐two (71%) patients had a cystoscopy that showed various degrees of epithelial inflammation similar to that seen in chronic interstitial cystitis. All of 12 available bladder biopsies had histological features resembling those of interstitial cystitis. Urodynamically, either detrusor overactivity or decreased bladder compliance with or without vesico‐ureteric reflux was detected to some degree in all of 47 patients. Thirty patients (51%) had unilateral or bilateral hydronephrosis on renal ultrasonography, and four (7%) showed features suggestive of papillary necrosis on radiological imaging. Eight patients had a raised serum creatinine level.
CONCLUSION
A syndrome of cystitis and contracted bladder can be associated with street‐ketamine abuse. Secondary renal damage can occur in severe cases which might be irreversible, rendering patients dependent on dialysis. The present data do not establish the precise cause nor the incidence. Street‐ketamine abuse is not only a drug problem, but might be associated with a serious urological condition causing a significant burden to healthcare resources.
In December 2019, a few coronavirus disease (COVID-19) cases were first reported in Wuhan, Hubei, China. Soon after, increasing numbers of cases were detected in other parts of China, eventually ...leading to a disease outbreak in China. As this dreadful disease spreads rapidly, the mass media has been active in community education on COVID-19 by delivering health information about this novel coronavirus, such as its pathogenesis, spread, prevention, and containment.
The aim of this study was to collect media reports on COVID-19 and investigate the patterns of media-directed health communications as well as the role of the media in this ongoing COVID-19 crisis in China.
We adopted the WiseSearch database to extract related news articles about the coronavirus from major press media between January 1, 2020, and February 20, 2020. We then sorted and analyzed the data using Python software and Python package Jieba. We sought a suitable topic number with evidence of the coherence number. We operated latent Dirichlet allocation topic modeling with a suitable topic number and generated corresponding keywords and topic names. We then divided these topics into different themes by plotting them into a 2D plane via multidimensional scaling.
After removing duplications and irrelevant reports, our search identified 7791 relevant news reports. We listed the number of articles published per day. According to the coherence value, we chose 20 as the number of topics and generated the topics' themes and keywords. These topics were categorized into nine main primary themes based on the topic visualization figure. The top three most popular themes were prevention and control procedures, medical treatment and research, and global or local social and economic influences, accounting for 32.57% (n=2538), 16.08% (n=1258), and 11.79% (n=919) of the collected reports, respectively.
Topic modeling of news articles can produce useful information about the significance of mass media for early health communication. Comparing the number of articles for each day and the outbreak development, we noted that mass media news reports in China lagged behind the development of COVID-19. The major themes accounted for around half the content and tended to focus on the larger society rather than on individuals. The COVID-19 crisis has become a worldwide issue, and society has become concerned about donations and support as well as mental health among others. We recommend that future work addresses the mass media's actual impact on readers during the COVID-19 crisis through sentiment analysis of news data.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The elementary mechanism of radical‐mediated peptide tyrosine nitration, which is a hallmark of post‐translational modification of proteins under nitrative stress in vivo, has been elucidated in ...detail by using an integrated approach that combines the gas‐phase synthesis of prototypical molecular tyrosine‐containing peptide radical cations, ion–molecule reactions, and isotopic labeling experiments with DFT calculations. This reaction first involves the radical recombination of .NO2 towards the prerequisite phenoxyl radical tautomer of a tyrosine residue, followed by proton rearrangements, finally yielding the stable and regioselective 3‐nitrotyrosyl residue product. In contrast, nitration with the π‐phenolic radical cation tautomer is inefficient. This first direct experimental evidence for the elementary steps of the radical‐mediated tyrosine nitration mechanism in the gas phase provides a fundamental insight into the regioselectivity of biological tyrosine ortho‐nitration.
Determining elementary steps: The elementary mechanism of radical‐mediated peptide tyrosine nitration has been elucidated in detail. Peptide tyrosine nitration resulting in the regioselective 3‐nitrotyrosyl residue requires the availability of the prerequisite phenoxyl radical. By contrast, the π‐phenolic radical cation structure is nonreactive.
The metazoan-specific acetyltransferase p300/CBP is involved in activating signal-induced, enhancer-mediated transcription of cell-type-specific genes. However, the global kinetics and mechanisms of ...p300/CBP activity-dependent transcription activation remain poorly understood. We performed genome-wide, time-resolved analyses to show that enhancers and super-enhancers are dynamically activated through p300/CBP-catalyzed acetylation, deactivated by the opposing deacetylase activity, and kinetic acetylation directly contributes to maintaining cell identity at very rapid (minutes) timescales. The acetyltransferase activity is dispensable for the recruitment of p300/CBP and transcription factors but essential for promoting the recruitment of TFIID and RNAPII at virtually all enhancers and enhancer-regulated genes. This identifies pre-initiation complex assembly as a dynamically controlled step in the transcription cycle and reveals p300/CBP-catalyzed acetylation as the signal that specifically promotes transcription initiation at enhancer-regulated genes. We propose that p300/CBP activity uses a “recruit-and-release” mechanism to simultaneously promote RNAPII recruitment and pause release and thereby enables kinetic activation of enhancer-mediated transcription.
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•p300/CBP and deacetylase activities regulate dynamic (de)activation of enhancers•p300/CBP-catalyzed acetylation promotes PIC assembly and RNAPII recruitment•BRD4 acts as a p300/CBP downstream effector to promote RNAPII pause release•Coupling of RNAPII recruitment and pause release enables rapid enhancer activation
A systems-wide analysis reveals that enhancers are activated by p300/CBP-catalyzed acetylation and deactivated by deacetylation. p300/CBP activity promotes pre-initiation complex assembly and RNAPII recruitment independently of its previously known function in BRD4-dependent pause release. By simultaneously promoting transcription initiation and elongation, p300/CBP activity drives the rapid activation of enhancers and super-enhancers.
The contributory roles of vitamin D in ocular and visual health have long been discussed, with numerous studies pointing to the adverse effects of vitamin D deficiency. In this paper, we provide a ...systematic review of recent findings on the association between vitamin D and different ocular diseases, including myopia, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), dry eye syndrome (DES), thyroid eye disease (TED), uveitis, retinoblastoma (RB), cataract, and others, from epidemiological, clinical and basic studies, and briefly discuss vitamin D metabolism in the eye. We searched two research databases for articles examining the association between vitamin D deficiency and different ocular diseases. One hundred and sixty-two studies were found. There is evidence on the association between vitamin D and myopia, AMD, DR, and DES. Overall, 17 out of 27 studies reported an association between vitamin D and AMD, while 48 out of 54 studies reported that vitamin D was associated with DR, and 25 out of 27 studies reported an association between vitamin D and DES. However, the available evidence for the association with other ocular diseases, such as glaucoma, TED, and RB, remains limited.
DNA replication fork perturbation is a major challenge to the maintenance of genome integrity. It has been suggested that processing of stalled forks might involve fork regression, in which the fork ...reverses and the two nascent DNA strands anneal. Here, we show that FBH1 catalyzes regression of a model replication fork in vitro and promotes fork regression in vivo in response to replication perturbation. Cells respond to fork stalling by activating checkpoint responses requiring signaling through stress-activated protein kinases. Importantly, we show that FBH1, through its helicase activity, is required for early phosphorylation of ATM substrates such as CHK2 and CtIP as well as hyperphosphorylation of RPA. These phosphorylations occur prior to apparent DNA double-strand break formation. Furthermore, FBH1-dependent signaling promotes checkpoint control and preserves genome integrity. We propose a model whereby FBH1 promotes early checkpoint signaling by remodeling of stalled DNA replication forks.
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•FBH1 helicase plays a major role in remodeling of stalled DNA replication forks•FBH1 is required for DNA replication fork reversal in vivo•FBH1 helicase directly catalyzes fork reversal in vitro•ATM checkpoint signaling following replication fork stalling depends on FBH1
It is unclear how stalling DNA replication forks are being processed in order to preserve genome stability. Here, Fugger et al. demonstrate that FBH1, through its helicase activity, catalyzes the reversal of stalling DNA replication forks in vivo and in vitro and promotes checkpoint signaling to promote genome integrity.
Retinoblastoma is the most common intraocular cancer in childhood. Loss of function in both copies of the RB1 gene is the causal mutation of retinoblastoma. Current treatment for retinoblastoma ...includes the use of chemotherapeutic agents, such as the DNA damaging agent etoposide, which is a topoisomerase II poison that mainly generates DNA double-strand breaks (DSBs) and genome instability. Unfaithful repairing of DSBs could lead to secondary cancers and serious side effects. Previously, we found that RB knocked-down mammalian cells depend on a highly mutagenic pathway, the micro-homology mediated end joining (MMEJ) pathway, to repair DSBs. Poly ADP ribose polymerase 1 (PARP1) is a major protein in promoting the MMEJ pathway. In this study, we explored the effects of olaparib, a PARP inhibitor, in killing retinoblastoma cells. Retinoblastoma cell line Y79 and primary retinoblastoma cells expressed the cone-rod homeobox protein (CRX), a photoreceptor-specific marker. No detectable RB expression was found in these cells. The co-treatment of olaparib and etoposide led to enhanced cell death in both the Y79 cells and the primary retinoblastoma cells. Our results demonstrated the killing effects in retinoblastoma cells by PARP inhibitor olaparib after inducing DNA double-strand breaks. The use of olaparib in combination with etoposide could improve the cell-killing effects. Thus, lower dosages of etoposide can be used to treat retinoblastoma, which would potentially lead to a lower level of DSBs and a relatively more stable genome.
Artificial intelligence (AI) methods can potentially be used to relieve the pressure that the COVID-19 pandemic has exerted on public health. In cases of medical resource shortages caused by the ...pandemic, changes in people's preferences for AI clinicians and traditional clinicians are worth exploring.
We aimed to quantify and compare people's preferences for AI clinicians and traditional clinicians before and during the COVID-19 pandemic, and to assess whether people's preferences were affected by the pressure of pandemic.
We used the propensity score matching method to match two different groups of respondents with similar demographic characteristics. Respondents were recruited in 2017 and 2020. A total of 2048 respondents (2017: n=1520; 2020: n=528) completed the questionnaire and were included in the analysis. Multinomial logit models and latent class models were used to assess people's preferences for different diagnosis methods.
In total, 84.7% (1115/1317) of respondents in the 2017 group and 91.3% (482/528) of respondents in the 2020 group were confident that AI diagnosis methods would outperform human clinician diagnosis methods in the future. Both groups of matched respondents believed that the most important attribute of diagnosis was accuracy, and they preferred to receive combined diagnoses from both AI and human clinicians (2017: odds ratio OR 1.645, 95% CI 1.535-1.763; P<.001; 2020: OR 1.513, 95% CI 1.413-1.621; P<.001; reference: clinician diagnoses). The latent class model identified three classes with different attribute priorities. In class 1, preferences for combined diagnoses and accuracy remained constant in 2017 and 2020, and high accuracy (eg, 100% accuracy in 2017: OR 1.357, 95% CI 1.164-1.581) was preferred. In class 2, the matched data from 2017 were similar to those from 2020; combined diagnoses from both AI and human clinicians (2017: OR 1.204, 95% CI 1.039-1.394; P=.011; 2020: OR 2.009, 95% CI 1.826-2.211; P<.001; reference: clinician diagnoses) and an outpatient waiting time of 20 minutes (2017: OR 1.349, 95% CI 1.065-1.708; P<.001; 2020: OR 1.488, 95% CI 1.287-1.721; P<.001; reference: 0 minutes) were consistently preferred. In class 3, the respondents in the 2017 and 2020 groups preferred different diagnosis methods; respondents in the 2017 group preferred clinician diagnoses, whereas respondents in the 2020 group preferred AI diagnoses. In the latent class, which was stratified according to sex, all male and female respondents in the 2017 and 2020 groups believed that accuracy was the most important attribute of diagnosis.
Individuals' preferences for receiving clinical diagnoses from AI and human clinicians were generally unaffected by the pandemic. Respondents believed that accuracy and expense were the most important attributes of diagnosis. These findings can be used to guide policies that are relevant to the development of AI-based health care.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Dysregulation of Th17 cell differentiation and pathogenicity contributes to multiple autoimmune and inflammatory diseases. Previously growth hormone releasing hormone receptor (GHRH-R) deficient mice ...have been reported to be less susceptible to the induction of experimental autoimmune encephalomyelitis. Here, we show GHRH-R is an important regulator of Th17 cell differentiation in Th17 cell-mediated ocular and neural inflammation. We find that GHRH-R is not expressed in naïve CD4
T cells, while its expression is induced throughout Th17 cell differentiation in vitro. Mechanistically, GHRH-R activates the JAK-STAT3 pathway, increases the phosphorylation of STAT3, enhances both non-pathogenic and pathogenic Th17 cell differentiation and promotes the gene expression signatures of pathogenic Th17 cells. Enhancing this signaling by GHRH agonist promotes, while inhibiting this signaling by GHRH antagonist or GHRH-R deficiency reduces, Th17 cell differentiation in vitro and Th17 cell-mediated ocular and neural inflammation in vivo. Thus, GHRH-R signaling functions as a critical factor that regulates Th17 cell differentiation and Th17 cell-mediated autoimmune ocular and neural inflammation.
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