[Diagnostic efficacy of metagenomic next-generation sequencing for intracranial bacterial infection pathogens after neurosurgery].

Objective: To explore the diagnostic efficacy of metagenomicnext-generation sequencing (mNGS) technique for pathogen diagnosis of intracranial infection after neurosurgery. Methods: Patients with suspected intracranial infection after neurosurgery who were treated in Beijing Tiantan Hospital of Capital Medical University from May 2017 to October 2018 were selected. Cerebrospinal fluid samples were collected for mNGS detection and bacterial culture. The sensitivity, specificity, positive predictive value and negative predictive value of these two methods were calculated, and their differences were compared. Results: A total of 80 cerebrospinal fluid samples from patient with suspected intracranial infection after neurosurgery were included, including 53 males and 27 females, with a mean age of (41±19) years old(age range: 2-80 years).After clinical review, a clinical diagnosis was made by two neurosurgery specialists through comprehensively interpretation of the patient's clinical data, laboratory tests and imaging examinations. Finally, 42 cases of intracranial infection and 38 cases of non-infection were clinically diagnosed. The sensitivity and specificity of mNGS detection were 83.33%(35/42) and 76.32%(29/38), and the positive predictive value and negative predictive value were 79.55%(35/44) and 80.56%(29/36). Meanwhile, the sensitivity and specificity of bacterial culture were 59.52%(28/42) and 68.42%(26/38), the positive predictive value and negative predictive value were 68.00% (28/40) and 60.47%(26/40). The sensitivity of mNGS detection washigher than that of bacterial culture, and the difference was statistically significant(χ2=5.83, P=0.015).Compared with bacterial culture, there was no statistically significant difference in the specificity of mNGS detection(χ2=0.59, P=0.441). Conclusion: mNGS detection technique can improve the detection rate of intracranial infection pathogens after neurosurgery, and may become a promising auxiliary diagnostic tool for pathogen detection.

[Effects of statins on mortality and neurologic outcomes in patients with traumatic brain injury: a meta-analysis].

Objective: To systematically evaluate the effects of statins on the mortality and neurologic function prognosis in patients with traumatic brain injury (TBI). Methods: The PubMed, Embase, the Cochrane Library, the Cochrane Clinical Controlled Trial Center Registry Database, Chinese Journal Full-text Database (CNKI), and WanFang database up to 2021.1 were searched to obtain clinical randomized controlled trials (RCTs) and retrospective cohort studies of statins in the treatment of TBI. Inclusion and exclusion criteria were used to screen literature and extract data. Ottawa scale and the RCT bias risk assessment tool was used for quality evaluation. Comprehensive Meta Analysis V3 statistical software for meta-analysis was applied. Results: Thirteen studies were included, with a total of 116, 500 patients, including 46, 933 patients using statins in the intervention group and 69, 567 patients in the control group. Meta-analysis results showed that compared with the control group, statins can reduce the mortality of TBI patients (OR=0.82, 95%CI: 0.74-0.92, P<0.01), significantly improve the neurologic outcomes of TBI patients (OR=0.19, 95%CI: 0.13-0.26, P<0.01), and reduce the levels of TNF-α and IL-1ß after TBI (TNF-α: OR=0.16, 95%CI: 0.07-0.34, P<0.01; IL-1ß: OR=0.08, 95%CI: 0.04-0.18, P<0.01), with statistically significant differences. Conclusion: Statins can reduce the mortality of patients with TBI and improve the neurologic outcomes. Their reduction of inflammation in the body may be the basis of potential treatment, but more high-quality RCTs are still warranted.

[Prevention and treatment of stroke in Chinese and African young adults].

Over the past two decades, with the improvement of living standards and the change of lifestyle, the incidence of stroke in young adults had been increasing year by year. Compared with elderly patients, young patients had a higher proportion of intracranial and subarachnoid hemorrhage. The etiologies of ischemic stroke in young patients were more diverse, with increasing risk factors such as hypertension, diabetes, smoking, alcoholism, and oral contraceptives. Due to the atypical clinical symptoms, various etiologies, the clinical inertia of the receiving physicians and the concerns about the use of statins in young stroke patients, timely diagnosis and standardized treatment are still challenging. China has been providing medical assistance to African countries for nearly 60 years. Considering the regional differences in medical level between China and Africa, in order to help Chinese medical teams to have a deep understanding of the current situation of stroke in young African adults, this paper comprehensively analyzed the epidemiology, etiology, risk factors and prevention measures of stroke in young adults, especially in Chinese and African, which could provide corresponding reference for early identification, treatment, prevention and education of stroke in young people.

Incidence and mortality of nasopharyngeal carcinoma: interim analysis of a cluster randomized controlled screening trial (PRO-NPC-001) in southern China.

BACKGROUND: Previous mass screening studies have shown that IgA antibodies against Epstein-Barr Virus (EBV) can facilitate early detection of nasopharyngeal carcinoma (NPC), but the impact of EBV-antibody screening for NPC-specific mortality remains unknown. PATIENTS AND METHODS: A prospective, cluster randomized, controlled trial for NPC screening (PRO-NPC-001) was conducted in 3 selected towns of Zhongshan City and 13 selected towns of Sihui City in southern China beginning in 2008. Serum samples of the screening group were tested for two previously selected anti-EBV antibodies. Subjects with serological medium risk were subsequently retested annually for 3 years, and those with serological high risk were referred to otorhinolaryngologists for diagnostic check-up. An interim analysis was carried out to evaluate the primary end points of the NPC-specific mortality and the early diagnostic rate, and the secondary end point of the NPC incidence, through linkage with the database of Zhongshan City. RESULTS: Among 70 296 total subjects, 29 413 screened participants (41.8% of the total subjects) in the screening group and 50 636 in the control group, 153 (43.3 per 100 000 person-year), 62 (55.3 per 100 000 person-year) and 99 (33.1 per 100 000 person-year) NPC cases were identified. The early diagnostic rates of NPC were significantly higher in the participants (79.0%, P < 0.0001) and the screening group (45.9%, P < 0.0001) compared with the control group (20.6%). Although no differences were found between NPC-specific mortality of the screening group and the control group [relative risk (RR)= 0.82, 95% confidence interval (CI) 0.37-1.79], lower NPC-specific mortality was noticed among participants from the screening group versus the control group (RR = 0.22, 95% CI 0.09-0.49). CONCLUSION: IgA antibodies against EBV can identify high-risk population and was effective in screening for early asymptomatic NPC. Although the mortality reduction was not significant in the primary end point, we noted encouraging evidence of a mortality reduction in screening participants in this interim analysis. CLINICAL TRIAL NUMBER: NCT00941538.

[Propensity-matched comparison of laparoscopic and open radical cystectomy for female patients with bladder cancer].

OBJECTIVE: To compare the perioperative and oncologic outcomes of female patients receiving laparoscopic radical cystectomy (LRC) and open radical cystectomy (ORC). METHODS: Retrospective review of 91 consecutive female patients with urothelial carcinoma of bladder undergoing radical cystectomy at a single academic institution from 2006 to 2017. Those female patients received open radical cystectomy were matched to the patients who underwent laparoscopic radical cystectomy by using propensity score matching in 1 ∶1 ratio. The matching factors included age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, pathologic stage and pathologic nodal stage. The perioperation and oncology characteristics were compared, and Kaplan-Meier method was used to analyze the overall survival (OS), cancer specific survival (CSS) and progression-free survival (PFS) estimates. Finally, we did a sensitive analysis by using multivariable COX regression of all the patients, adjusting for the matching factors. RESULTS: There were 65 ORC and 26 LRC patients identified in this cohort with urothelial carcinoma of bladder, the median follow-up time was 38 months (interquartile range 18-69). The age (P<0.001) and ASA scores (P=0.018) were less for LRC before being matched. There were 22 LRC and 22 ORC patients matching successfully. Before being matched, the estimate blood loss (P=0.005), transfusion rate (P<0.001) and total complications rate (P=0.015) were less for LRC, and the lymph nodes yield was greater for LRC, but there were no differences in OS (P=0.698), CSS (P=0.942) and PFS (P=0.837) between the two groups. After being matched, the estimate blood loss (P=0.009), transfusion rate (P=0.001) and total complications rate (P=0.040) were less for LRC, but there was no difference in the lymph nodes yield. Besides, there were no statistic differences in OS (P=0.432), CSS (P=0.429) and PFS (P=0.284) between the two groups. In addition, in multivariable COX regression analysis, surgical approaches (LRC/ORC) were not found to be a predictor of OS (HR 1.134, 95%CI 0.335-3.835, P=0.839), CSS (HR 1.051, 95%CI 0.234-4.719, P=0.949) and PFS (HR 0.538, 95%CI 0.138-2.095, P=0.371) of the female patients with urothelial carcinoma of bladder. CONCLUSION: It is advantageous for laparoscopic radical cystectomy in terms of estimating blood loss, transfusion rate and complication rate. But there was no evidence that laparoscopic radical cystectomy for female patients with bladder cancer had a better oncologic prognosis than open radical cystectomy from this study.

[Clinical characteristics of the Wilson disease carrier].

Objective: To study the clinical symptoms, copper metabolism and imaging characteristics of Wilson disease (WD) carriers and to explore the treatment strategy of WD carriers. Methods: Forty WD carriers, 40 WD patients and 20 normal controls from the First Affiliated Hospital of Sun Yat-sen University from July 2007 to May 2018 were included. The modified Young scale was used for neural symptom scoring, and Child grading of liver function, mental symptoms rating scale, magnetic resonance imaging (MRI) scan, susceptibility weighted imaging (SWI) inspection, metal metabolism tests were also applied to all the included subjects. Corrected phase (CP) was measured by SWI. WD carriers were divided into symptomatic group and asymptomatic group. Symptomatic WD carriers were treated with penicillamine for 2 weeks and zinc gluconate for 3 months, then their neurological symptoms, liver function grade, metal metabolism index were rechecked. Results: Six WD carriers presented with some clinical symptoms, including 5 with neurological symptoms and 4 with liver dysfunction. The score of Hamilton anxiety (HAMA) scale of symptomatic WD carriers was higher than that of normal control group (P=0.021). 85% of carriers had ceruloplasmin level less than 0.26 g/L. 80% of carriers had serum copper between normal controls and WD patients. The free copper level of WD carriers was lower than that of WD patients (P=0.012, 0.019). Urinary copper in symptomatic WD carriers was higher than normal controls (P=0.047). The CP values of thalamus, globus pallidus and putamen in symptomatic WD carriers were lower than those in normal control group. After treatment with penicillamine in symptomatic WD carriers, urinary copper was higher than that before treatment (P=0.036). After treatment, the liver enzymes of symptomatic WD carriers returned to normal, and the score of modified Young scale was lower than before treatment (P=0.031). Conclusions: Mild copper metabolism abnormality is seen in WD carriers. A few carriers have neurological symptoms such as limb tremors, or liver symptoms such as abnormal liver enzymes. Abnormal copper metabolism is more serious in symptomatic WD carriers than in asymptomatic WD carriers. Symptomatic WD carriers can be treated with zinc gluconate.

Clinicopathological features and course of cutaneous protothecosis.

BACKGROUND: Protothecosis is an uncommon infection caused by the achlorophyllic algae found more commonly in tropical areas. Only a limited number of cases have been reported. OBJECTIVE: We aimed to evaluate the clinicopathological features and treatment outcomes of cutaneous protothecosis. METHODS: We retrospectively identified 20 pathology-confirmed cases of cutaneous protothecosis based on skin biopsies in two tertiary medical centres in Taiwan from 1997 to 2015. RESULTS: The age of the patients at the time of diagnosis ranged from 48 to 85 years (mean age of 74 years). All lesions developed on the limbs. Twelve (60%) patients had adrenal insufficiency, but no patients had active malignancy at diagnosis. Interestingly, four (20%) patients had concurrent scabies infestation. Clinically, most lesions were erythematous plaques studded with punctate ulcers. Microscopically, the most common finding was granulomatous inflammation. Nineteen (95%) cases were successfully treated with itraconazole for 14-148 days with only one case of recurrence. Concomitant scabies should be suspected if pruritus is recalcitrant despite itraconazole treatment. CONCLUSION: Despite its rarity, cutaneous protothecosis has become more significant due to an increased prevalence of immunocompromised individuals. Steroid overuse or iatrogenic adrenal insufficiency predisposes individuals to high-risk infections. Neglecting the disease leads to a chronic and incurable state. Protothecosis should be suspected in chronic eczematous and ulcerative plaques on the limbs refractory to conventional antibacterial and antiviral treatments, especially in patients with adrenal insufficiency. Clinical suspicion should be confirmed by skin biopsies, and confirmed cases can be successfully treated with itraconazole.

[Difference in imaging and metal metabolism between hepatic and cerebral type Wilson disease].

Objective: To evaluate the difference of metal metabolism, damage to structure and functional activity in brains between hepatic and cerebral type Wilson disease (WD). Methods: Forty patients with WD, including 20 with cerebral type and 20 with hepatic type, and 20 age-matched healthy controls in the First Affiliated Hospital, Sun Yat-sen University between Jul 2013 and May 2016 were enrolled.All study subjects underwent diffusion tensor imaging (DTI), resting state functional MRI (rs-fMRI) and susceptibility weighted imaging (SWI) of the brain.Six regions of interest (ROIs) were chosen.The values of fractional anisotropy (FA), λ in ROIs were determined on DTI, FA and fiber volumes between ROIs were also determined on DTI.The values of amplitude of low frequency fluctuation (ALFF) and regional homogeneity (REHO) in ROIs were determined on rs-fMRI.The values of corrected phase (CP) were calculated on SWI.The copper and iron content were measured.The difference of imaging and metal metrics between cerebral type and hepatic type WD were evaluated. Results: DTI metrics differed between patients with the cerebral and hepatic types of WD.ALFF values in the caudate nucleus, and thalamus were lower (P=0.037, 0.040), and REHO values in the caudate nucleus were lower (P=0.029), in patients of cerebral type than in hepatic type patients.CP values of the right caudate nucleus and left putamen in cerebral type WD patients were lower than in hepatic type patients (P=0.020, 0.23). The serum iron content of hepatic type WD patients was higher than the normal (P=0.013), and the urine copper content was higher than the cerebral type patients (P=0.021). Conclusions: Metal deposition and damage to the structure and functional activity in the brain may occur in hepatic type WD patients.The structural and functional activity damage of the brain in hepatic type is less severe than that in cerebral type patients, while the metal deposition is not significant different between hepatic and cerebral type.

[Effect of mouse nerve growth factor on cognitive impairment in whole brain irradiation rats].

OBJECTIVE: To investigate the positive effects of mouse nerve growth factor(mNGF) on cognitive impairment in whole brain irradiation rats. METHODS: Fifty-five male Sprague-Dawley rats were randomly divided into normal control group, mNGF treated group, saline treated group.mNGF treated group and saline treated group were cranial irradiated at a single dose of 12 Gy by X-ray.30 days after radiation each group were treated with correspondent drugs.60 days after radiation, Morris water maze experiment, EB leakage of the brain, and expressions of neuN, vWF, ZO-1 in hippocampus by immunofluorescence, and expressions of neuN, vWF, ZO-1, VEGF and GFAP in hippocampus by Western blot were tested and analyzed. RESULTS: The escape latencies: normal control group< mNGF treated group< saline treated group; the numbers of crossing hidden platform in these 3 groups were 3.00± 1.08, 1.50± 1.08, 0.38± 0.48 times (P<0.01). EB leakage of these 3 groups were 0.14±0.14, 0.66±0.20 and 1.36±0.27 µg/g (P<0.05). In immunofluorescence, expressions of neuN, vWF and ZO-1: normal control group> mNGF treated group> saline treated group.In Western blot, expressions of neuN, vWF and ZO-1: normal control group> mNGF treated group> saline treated group, yet the expressions of VEGF and GFAP: normal control group< mNGF treated group< saline treated group. CONCLUSION: mNGF ameliorates cognitive impairment after whole brain irradiation.

Footprints of divergent selection in natural populations of Castanopsis fargesii (Fagaceae).

Given predicted rapid climate change, an understanding of how environmental factors affect genetic diversity in natural populations is important. Future selection pressures are inherently unpredictable, so forest management policies should maintain both overall diversity and identify genetic markers associated with the environmental factors expected to change most rapidly, like temperature and rainfall. In this study, we genotyped 648 individuals in 28 populations of Castanopsis fargesii (Fagaceae) using 32 expressed sequence tag (EST)-derived microsatellite markers. After removing six loci that departed from Hardy-Weinberg equilibrium, we measured genetic variation, population structure and identified candidate loci putatively under selection by temperature and precipitation. We found that C. fargesii populations possessed high genetic diversity and moderate differentiation among them, indicating predominant outcrossing and few restrictions to gene flow. These patterns reduce the possible impact of stochastic effects or the influence of genetic isolation. Clear footprints of divergent selection at four loci were discovered. Frequencies of five alleles at these loci were strongly correlated with environmental factors, particularly extremes in precipitation. These alleles varied from being near fixation at one end of the gradient to being completely absent at the other. Our study species is an important forest tree in the subtropical regions of China and could have a major role in future management and reforestation plans. Our results demonstrate that the gene flow is widespread and abundant in natural populations, maintaining high diversity, while diversifying selection is acting on specific genomic regions.

Smoking behaviours of adolescents, influenced by smoking of teachers, family and friends.

BACKGROUND: Smoking tobacco is a global health problem, and this study highlights adolescent smoking in Taiwan. Smoking was completely banned on campuses under the Tobacco Hazards Prevention Act and School Health Regulations. Few have investigated the association between personnel smoking/school smoking policies and adolescent smoking in Taiwan. The smoking rate has gradually increased for senior high school students in Taiwan from 10.7% in 1994 to 14.7% in 2011. AIM: This study examined the influence of family and friends' smoking on the association between the presence of teachers smoking and each stage of adolescents' smoking behaviour. METHODS: A cross-sectional survey was conducted in nine high schools (n = 921). Logistic regression analysis was used to examine the association between smoking stage, father smoking, mother smoking, sibling smoking, friends smoking and the presence of smoking teachers. RESULTS: After adjusting for gender, school type and grade, fathers', siblings' and friends' smoking were significantly associated with adolescents' ever and current smoking behaviours, but mothers' smoking was only associated with adolescents' current smoking behaviours. Friends' smoking was strongly associated with being a smoker. While there was an interaction between friends' smoking and the presence of smoking teachers on current smoking behaviours indicating the effect of the presence of smoking teachers was increased when friends did not smoke. DISCUSSION: The results suggest that teachers smoking on school may increase the likelihood of being a current smoker as their friends do not smoke. Family and friends smoking are associated with adolescent smoking. CONCLUSION: The Taiwanese government has regulated a comprehensive smoking ban in schools to prohibit both student and staff smoking on all school premises. To achieve this, schools should make tobacco control communication efforts. Nurses could address the combined influence of family and friends as well as the effect of school smoking restrictions to help prevent adolescents from smoking.

Scotch Whiskies and Forensic Examinations of Manufacturing-Derived Features for Their Authentication.

With the global whisky market reaching $65.6 billion in 2024 and projected to reach $89.48 billion by the end of 2029, the incentives for fraud in relation to (and adulteration of) this alcoholic beverage are self-evident. Law enforcement agencies worldwide have taken actions against crimes of this nature, with forensic scientists playing crucial roles (mainly through expert testimonies on sample authenticities) during legal proceedings. Important issues associated with Scotch whisky authentication include: (a) understanding the typical manufacturing process; (b) acquisition of reference samples; and (c) effective utilization of instrumentations to characterize features derived from the manufacturing process and strategic approaches for the interpretation of analytical findings. Following a brief review of the definition/classification, manufacturing, and adulteration/counterfeiting of Scotch whiskies, this review focuses on the characterization of manufacturing-derived features and interpretation of analytical findings as grouped into: (a) quantitative analysis of single compounds; (b) qualitative analysis and intensity ratio of multiple compounds; (c) chemometric analysis of selected multi-compounds; and (d) quantitative analysis of selected elements. Finally, a flowchart for conducting the authentication process, from various significantly different perspectives, is proposed.

Toxic effects of two brominated flame retardants BDE-47 and BDE-183 on the survival and protein expression of the tubificid Monopylephorus limosus.

The toxic effects of two brominated diphenyl ethers (BDE), BDE-47, and BDE-183, on a benthic oligochaete tubificid, Monopylephorus limosus were studied under laboratory conditions. Investigated responses included survival, growth, and protein expression profiles, at BDE concentrations of 1, 10, 100, and 700 ng/g on a dry soil weight basis, with isooctane as the carrier solvent. Body weight losses among treatments were insignificant after 8 weeks of exposure. The 8-wk LC(50) of BDE-47 and -183 were 2311 and 169 ng/g, respectively. By applying multivariate analysis techniques, protein expression patterns were compared and correlated with stressful sources of long-term culture, carrier solvent, BDE-47 and -183. The treatment of 8-wk 100 ng/g BDE-47 was most closely clustered to the 10 ng/g BDE-183 treatment, based on the 40 examined protein spots. This indicated that BDE-183 was more potent to M. limosus, than was BDE-47. The 2-wk and 8-wk controls clustered into different groups indicating the occurrence of physiological changes due to long-term laboratory culture. Additionally, solvent effect was shown by grouping the isooctane carrier to different clusters. With further characterization by principle component analysis, it was found that the separation was mainly contributed by the 2nd principal-component. And, the primarily inhibitory variation was at spots 2 (UMP-CMP kinase) and 40 (plasma retinol-binding protein precursor) in the 8-wk groups. On the contrary, protein spots 16 (cell division control protein 2 homolog) and 24 (mitochondrial DNA mismatch repair protein) showed stimulatory variation. In all, the observed proteomic responses suggest that BDEs disrupted metabolic function in M. limosus and multivariate analysis tool offers significant potential for the assessment of various stress sources at biochemical level.

Antinociceptive potentiation and attenuation of tolerance by intrathecal ß-arrestin 2 small interfering RNA in rats.

BACKGROUND: Tolerance to the analgesic effect of opioids complicates the management of persistent pain states. We tested whether the intrathecal infusion of small interfering RNA (siRNA) against ß-arrestin 2 would reduce tolerance to chronic morphine use and the severity of precipitated morphine withdrawal. METHODS: Intrathecal ß-arrestin 2 (2 µg siRNA per 10 µl per rat) was injected once daily for 3 days. Rats then received a continuous intrathecal infusion of morphine (2 nmol h⁻¹) or saline for 7 days. Daily tail-flick (TF) and intrathecal morphine challenge tests were performed to assess the effect of intrathecal ß-arrestin 2 siRNA on antinociception and tolerance to morphine. Naloxone withdrawal (2 mg kg⁻¹) was performed to assess morphine dependence. RESULTS: In the daily TF test, the antinociception of intrathecal morphine was increased and maintained in rats receiving ß-arrestin 2 siRNA compared with the control group (morphine alone). In the probe response test, rats receiving morphine infusion with ß-arrestin 2 siRNA treatment showed a significant left shift in their dose-response curve, as measured by per cent maximal possible effect (MPE), such that the AD50 was significantly decreased by a factor of 5.6 when compared with that of morphine-infused rats. In the naloxone-induced withdrawal tests, rats receiving ß-arrestin 2 siRNA injection with morphine infusion showed a significant reduction in four of the six signs of withdrawal. CONCLUSIONS: We show here that intrathecal ß-arrestin 2 siRNA in rats enhances analgesia and attenuates naloxone-induced withdrawal symptoms. This may warrant further investigation in the context of long-term use of intrathecal opioids for controlling chronic pain.

Influence of angiotensin-converting enzyme insertion/deletion polymorphism on nitric oxide production in hypertensives and hypercholesterolaemics.

UNLABELLED: WHAT IS NEW AND OBJECTIVE: Some evidence suggests that angiotensin-converting enzyme insertion/deletion (I/D) polymorphism may play a role in endothelium-dependent vasodilatation. However, the impact of I/D polymorphism on endogenous nitric oxide production, which may be of great therapeutic significance, has scarcely been studied. This study aimed to investigate this in hypertensives and hypercholesterolaemics. METHODS: Adult Han subjects were recruited by cluster sampling from two communities in Shunde, Guangdong province, China. Plasma nitrite and nitrate (NO(x)) levels were determined by colorimetry assay and angiotensin II and 6-keto-prostaglandin F1-alpha by radioimmunoassay. Angiotensin-converting enzyme gene I/D polymorphism were genotyped by polymer chain reaction-amplified fragment length polymorphism. RESULTS AND DISCUSSION: Of the 779 subjects who met our inclusion criteria, 502 were with normotensive and normocholesterolaemic, 76 had hypertension only, 146 hypercholesterolaemia only, and 55 had both hypertension and hypercholesterolaemia. Among subjects with hypertension only, the plasma levels of NO(x) for genotype DD were significantly lower than those for genotype II (P = 0·034). And the plasma levels of NO(x) for genotype DD was significantly higher than those for genotype II (P = 0·040) in subjects with hypercholesterolaemia only. WHAT IS NEW AND CONCLUSION: Our results suggest that I/D polymorphism has an impact on in vivo NO production in hypertensives and hypercholesterolaemics at the population level. Hypertensives with allele D may be benefit from L-arginine supplementation and hypercholesterolaemics with allele D may respond better to statins or antioxidants.

Novel REST Truncation Mutations Causing Hereditary Gingival Fibromatosis.

Hereditary gingival fibromatosis (HGF) is a rare genetic disorder featured by nonsyndromic pathological overgrowth of gingiva. The excessive gingival tissues can cause dental, masticatory, and phonetic problems, which impose severe functional and esthetic burdens on affected individuals. Due to its high recurrent rate, patients with HGF have to undergo repeated surgical procedures of gingival resection, from childhood to adulthood, which significantly compromises their quality of life. Unraveling the genetic etiology and molecular pathogenesis of HGF not only gains insight into gingival physiology and homeostasis but also opens avenues for developing potential therapeutic strategies for this disorder. Recently, mutations in REST (OMIM *600571), encoding a transcription repressor, were reported to cause HGF (GINGF5; OMIM #617626) in 3 Turkish families. However, the functions of REST in gingival homeostasis and pathogenesis of REST-associated HGF remain largely unknown. In this study, we characterized 2 HGF families and identified 2 novel REST mutations, c.2449C>T (p.Arg817*) and c.2771_2793dup (p.Glu932Lysfs*3). All 5 mutations reported to date are nonsenses or frameshifts in the last exon of REST and would presumably truncate the protein. In vitro reporter gene assays demonstrated a partial or complete loss of repressor activity for these truncated RESTs. When coexpressed with the full-length protein, the truncated RESTs impaired the repressive ability of wild-type REST, suggesting a dominant negative effect. Immunofluorescent studies showed nuclear localization of overexpressed wild-type and truncated RESTs in vitro, indicating preservation of the nuclear localization signal in shortened proteins. Immunohistochemistry demonstrated a comparable pattern of ubiquitous REST expression in both epithelium and lamina propria of normal and HGF gingival tissues despite a reduced reactivity in HGF gingiva. Results of this study confirm the pathogenicity of REST truncation mutations occurring in the last exon causing HGF and suggest the pathosis is caused by an antimorphic (dominant negative) disease mechanism.

Light extraction efficiency enhancement of GaN-based light emitting diodes on n-GaN layer using a SiO2 photonic quasi-crystal overgrowth.

In this paper, GaN-based LEDs with a SiO2 photonic quasi-crystal (PQC) pattern on an n-GaN layer by nano-imprint lithography (NIL) are fabricated and investigated. At a driving current of 20 mA on Transistor Outline (TO)-can package, the better light output power of LED III (d = 1.2 microm) was enhanced by a factor of 1.20. After 1000 h life test (55 degrees C/50 mA) condition, Normalized output power of LED with a SiO2 PQC pattern (LED III (d = 1.2 microm)) on an n-GaN layer only decreased by 5%. This results offer promising potential to enhance the light output power of commercial light-emitting devices using the technique of nano-imprint lithography.

Four-dimensional micro-building blocks.

Four-dimensional (4D) printing relies on multimaterial printing, reinforcement patterns, or micro/nanofibrous additives as programmable tools to achieve desired shape reconfigurations. However, existing programming approaches still follow the so-called origami design principle to generate reconfigurable structures by self-folding stacked 2D materials, particularly at small scales. Here, we propose a programmable modular design that directly constructs 3D reconfigurable microstructures capable of sophisticated 3D-to-3D shape transformations by assembling 4D micro-building blocks. 4D direct laser writing is used to print two-photon polymerizable, stimuli-responsive hydrogels to construct building blocks at micrometer scales. Denavit-Hartenberg (DH) parameters, used to define robotic arm kinematics, are introduced as guidelines for how to assemble the micro-building blocks and plan the 3D motion of assembled chain blocks. Last, a 3D-printed microscaled transformer capable of changing its shape from a race car to a humanoid robot is devised and fabricated using the DH parameters to guide the motion of various assembled compartments.

[Chromosomal aberrations detection in chronic lymphocytic leukemia by conventional cytogenetics using DSP30 and IL-2].

Objective: To study the value of unmethylated cytosine guanine dinucleotide oligodeoxynucleotide (DSP30) and IL-2 in the conventional cytogenetic (CA) detection of the chromosomal aberrations in chronic lymphocytic leukemia (CLL) . Methods: Bone marrow or peripheral blood cells of CLL patients were cultured with DSP30 plus IL-2 for 72 h, following which R-banding analysis was conducted. Fluorescence in situ hybridization (FISH) was performed in 85 patients. CA results were compared with data obtained by FISH. Results: Among 89 CLL patients, the success rate of chromosome analysis was 94.38% (84/89) . Clonal aberrations were detected in 51 patients (51/84, 60.71%) . Of them, 27 (27/51, 52.94%) were complex karyotype. Among 85 CLL patients tested by FISH, chromosomal abnormalities were detected in 74 (74/85, 87.06%) patients, of which 2 (2/74) patients were complex karyotypes, accounting for 2.70%. Of the 85 CLL patients examined by FISH, 50 had abnormal karyotype analysis, 30 had normal karyotype, 5 failed to have chromosome analysis. Among them, 25 cases showed clonal aberrations by FISH assay but normal by CA, and 4 cases were normal by FISH but displayed aberrations in chromosome analysis, and totally 78 (91.76%) cases with abnormality detected by the combination of the two methods. The frequency of 13q- abnormality detected by FISH was significantly higher than that by CA analysis (69.41%vs 16.67%, P<0.001) , while the frequency of 11q-,+12 and 17p- detected by two methods showed no significant difference (P>0.05) . The detection rate of complex abnormalities in conventional karyotype analysis was higher than that in FISH (50.98%vs 2.70%) . In addition, 11 low-risk and 9 intermediate-risk patients according to FISH results showed complex karyotype by cytogenetics, and were classified into high-risk cytogenetic subgroup. Conclusion: DSP30 and IL-2 are effective in improving the detection rate of CA in CLL patients (60.71%) and CA is more effective to detect complex karyotype. However, FISH had a higher overall abnormality detection rate (87.06%) than CA, especially for 13q-. The combination of CA and FISH not only enhanced the detection rate of clonal aberrations to 91.76%, but also provided more precise prognosis stratification for CLL patients, thus to provide more information for clinical implication.

X-ray absorption edge fine structure of potassium ions in various environments: application to frog blood cells.

The edge spectrum is a sensitive probe of local chemistry. Edge spectra of potassium in various chemical environments were measured, and each environment gives a unique edge spectrum. Hydrated potassium has a unique spectrum that is insensitive to counterions. Comparison of the spectra shows that the chemical state of potassium in cells differs appreciably from that in aqueous solutions.