Computer-aided X-ray screening for tuberculosis and HIV testing among adults with cough in Malawi (the PROSPECT study): A randomised trial and cost-effectiveness analysis

BackgroundSuboptimal tuberculosis (TB) diagnostics and HIV contribute to the high global burden of TB. We investigated costs and yield from systematic HIV-TB screening, including computer-aided digital chest X-ray (DCXR-CAD).Methods and findingsIn this open, three-arm randomised trial, adults (≥18 years) with cough attending acute primary services in Malawi were randomised (1:1:1) to standard of care (SOC); oral HIV testing (HIV screening) and linkage to care; or HIV testing and linkage to care plus DCXR-CAD with sputum Xpert for high CAD4TBv5 scores (HIV-TB screening). Participants and study staff were not blinded to intervention allocation, but investigator blinding was maintained until final analysis. The primary outcome was time to TB treatment. Secondary outcomes included proportion with same-day TB treatment; prevalence of undiagnosed/untreated bacteriologically confirmed TB on day 56; and undiagnosed/untreated HIV. Analysis was done on an intention-to-treat basis. Cost-effectiveness analysis used a health-provider perspective. Between 15 November 2018 and 27 November 2019, 8,236 were screened for eligibility, with 473, 492, and 497 randomly allocated to SOC, HIV, and HIV-TB screening arms; 53 (11%), 52 (9%), and 47 (9%) were lost to follow-up, respectively. At 56 days, TB treatment had been started in 5 (1.1%) SOC, 8 (1.6%) HIV screening, and 15 (3.0%) HIV-TB screening participants. Median (IQR) time to TB treatment was 11 (6.5 to 38), 6 (1 to 22), and 1 (0 to 3) days (hazard ratio for HIV-TB versus SOC: 2.86, 1.04 to 7.87), with same-day treatment of 0/5 (0%) SOC, 1/8 (12.5%) HIV, and 6/15 (40.0%) HIV-TB screening arm TB patients (p = 0.03). At day 56, 2 SOC (0.5%), 4 HIV (1.0%), and 2 HIV-TB (0.5%) participants had undiagnosed microbiologically confirmed TB. HIV screening reduced the proportion with undiagnosed or untreated HIV from 10 (2.7%) in the SOC arm to 2 (0.5%) in the HIV screening arm (risk ratio [RR]: 0.18, 0.04 to 0.83), and 1 (0.2%) in the HIV-TB screening arm (RR: 0.09, 0.01 to 0.71). Incremental costs were US$3.58 and US$19.92 per participant screened for HIV and HIV-TB; the probability of cost-effectiveness at a US$1,200/quality-adjusted life year (QALY) threshold was 83.9% and 0%. Main limitations were the lower than anticipated prevalence of TB and short participant follow-up period; cost and quality of life benefits of this screening approach may accrue over a longer time horizon.ConclusionsDCXR-CAD with universal HIV screening significantly increased the timeliness and completeness of HIV and TB diagnosis. If implemented at scale, this has potential to rapidly and efficiently improve TB and HIV diagnosis and treatment.Trial registrationclinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03519425","term_id":"NCT03519425"}}NCT03519425.

In a randomised trial, Peter MacPherson and colleagues investigate the costs, timeliness, and completeness of computer-aided X-ray screening for tuberculosis and HIV testing in adults with cough in Malawi.     

A role of hexokinases in plant resistance to oxidative stress and pathogen infection

Previously, we reported that mitochondria-associated hexokinases are active in controlling programmed cell death in plants (Plant Cell 18, 2341-2355). Here, we investigated their role under abiotic- and biotic-stress conditions. Expression ofNbHxk1, aNicotiana benthamiana hexokinase gene, was stimulated by treatment with salicylic acid or methyl viologen (MV), and was also up-regulated by pathogen infection. In response to MV-induced oxidative stress, NbHxk1-silenced plants exhibited increased susceptibility, while the HXK1— and HXK2-overexpressingArabidopsis plants had enhanced tolerance. Moreover, those overexpressing plants showed greater resistance to the necrotrophic fungal pathogenAlternaria brassicicola. HXK-over-expression also mildly protected plants against the bacterial pathogenPseudomonas syringae pv.tomato DC3000, a response that was accompanied by increased H₂O₂ production and elevatedPR1 gene expression. These results demonstrate that higher levels of hexokinase confer improved resistance to MV-induced oxidative stress and pathogen infection.     

小麦黄色素合成途径中Psy基因的克隆及分子特性

对普通小麦(Ttiticum aestivum)黄色素(YP)合成途径中的首要限速酶——八氢番茄红素合成酶(Psy)基因进行克隆和测序,并和玉米Psy基因进行序列比对。结果表明,在高和低YP含量小麦品种中均扩增出一条长1192bp的Psy基因片段,该片段包含一条可编码78个氨基酸的小麦Psy基因的外显子,与玉米Psy基因第4外显子的核苷酸序列同源率为80.74,同源区域内有47个SNPs,但仅11个SNPs导致氨基酸编码序列的改变,二者氨基酸序列的同源率达85.89,推测Psy基因在不同物种中的表达具有较高的保守性。BLAST聚类分析表明,禾谷类植物Psy基因的分类与物种的亲缘关系存在明显的相关性,小麦Psy基因在系统进化中比禾谷类其他植物更为高级。     

尼氟灭酸通过钙库钙释放引起豚鼠耳蜗螺旋动脉平滑肌细胞超极化

本研究旨在观察氯离子通道阻断剂尼氟灭酸（niflumic acid,NFA）引起豚鼠耳蜗螺旋动脉平滑肌细胞产生超极化的机制。以豚鼠为实验动物,运用细胞内微电极和全细胞膜片钳记录技术,观察NFA和其它药物对急性分离的耳蜗螺旋动脉平滑肌细胞的作用。结果显示：NFA、indanyloxyacetic acid94（LAh-94）和diSOdium4,4’-diisothiocyanatostilbene-2,2’-disulfonate（DIDS）可使低静息膜电位的细胞产生超极化,但对高静息膜电位的细胞无明显作用。低静息膜电位细胞的平均静息电位为（-42．47±1．38）mV（n=24）,100μmol／LNFA、10μmol／LIAA-94和200μmol／LDIDS分别使细胞超极化至（13．7±4．3）mV=9,P〈0．01）,（11．4±4．2）mV（n=7,P〈0．01）和（12．3±3．7）mV（n=8,P〈0．01）,这种氯离子通道阻断剂引起细胞超极化反应的效应呈浓度依赖性。NFA引起的超极化和外向电流几乎完全被100nmol／L iberiotoxin、100nmol／L charybdotoxin、10mmol／L tetraethylammonium、50μmol／LBAPTA—AM、10μmol／Lryanodine和0．1-10mmol／Lcaffeine阻断,但不能被100μmol／Lnifedipine、100μmol／LCdCI,和无Ca^2＋灌流外液阻断。结果捉示：氯离_了通道的阻断剂NFA可通过平滑肌细胞内钙库的钙释放增加细胞内钙,进而激活钙依赖的钾通道,产生耳蜗螺旋动脉平滑肌细胞的超极化反应。     

幼虫密度和温度对水芹叶象甲未成熟阶段生长发育的影响

[目的]为明确不同幼虫密度和不同温度条件对水芹叶象甲Hypera sp.未成熟阶段生长发育的影响.[方法]在室内条件下对不同幼虫饲养密度和不同温度条件饲养的水芹叶象甲未成熟阶段(卵、幼虫、预蛹和蛹)的存活和生长发育进行研究.[结果]幼虫密度对水芹叶象甲幼虫、预蛹和蛹的存活和生长发育均具有显著影响.水芹叶象甲幼虫、预蛹和蛹在50头/盒的密度条件下的存活率均显著高于其它密度条件,且发育历期显著短于其它密度条件.此外,各密度条件下的雌蛹重均显著重于雄蛹重,但性比(♀/♂)不受密度条件的影响.温度条件对水芹叶象甲卵、幼虫、预蛹和蛹的存活和生长发育亦均具有显著影响.27℃条件下的幼虫和蛹的存活率均显著高于其它温度条件,1龄幼虫在30℃条件下的存活率显著高于其它温度条件,而3龄幼虫在27℃条件下的存活率显著高于其它温度条件,但温度条件对2龄幼虫的存活率无显著影响.水芹叶象甲各龄期幼虫及各虫态的发育历期随着温度升高而显著缩短.[结论]幼虫饲养密度和温度是影响水芹叶象甲种群变化的重要因子,这将为分析水芹叶象甲种群动态变化规律,以 及提高该虫的预测预报和综合防控水平提供依据.     

Will an Unsupervised Self-Testing Strategy for HIV Work in Health Care Workers of South Africa? A Cross Sectional Pilot Feasibility Study

Background

In South Africa, stigma, discrimination, social visibility and fear of loss of confidentiality impede health facility-based HIV testing. With 50% of adults having ever tested for HIV in their lifetime, private, alternative testing options are urgently needed. Non-invasive, oral self-tests offer a potential for a confidential, unsupervised HIV self-testing option, but global data are limited.

Methods

A pilot cross-sectional study was conducted from January to June 2012 in health care workers based at the University of Cape Town, South Africa. An innovative, unsupervised, self-testing strategy was evaluated for feasibility; defined as completion of self-testing process (i.e., self test conduct, interpretation and linkage). An oral point-of-care HIV test, an Internet and paper-based self-test HIV applications, and mobile phones were synergized to create an unsupervised strategy. Self-tests were additionally confirmed with rapid tests on site and laboratory tests. Of 270 health care workers (18 years and above, of unknown HIV status approached), 251 consented for participation.

Findings

Overall, about 91% participants rated a positive experience with the strategy. Of 251 participants, 126 evaluated the Internet and 125 the paper-based application successfully; completion rate of 99.2%. All sero-positives were linked to treatment (completion rate:100% (95% CI, 66.0–100). About half of sero-negatives were offered counselling on mobile phones; completion rate: 44.6% (95% CI, 38.0–51.0). A majority of participants (78.1%) were females, aged 18–24 years (61.4%). Nine participants were found sero-positive after confirmatory tests (prevalence 3.6% 95% CI, 1.8–6.9). Six of nine positive self-tests were accurately interpreted; sensitivity: 66.7% (95% CI, 30.9–91.0); specificity:100% (95% CI, 98.1–100).

Interpretation

Our unsupervised self-testing strategy was feasible to operationalize in health care workers in South Africa. Linkages were successfully operationalized with mobile phones in all sero-positives and about half of the sero-negatives sought post-test counselling. Controlled trials and implementation research studies are needed before a scale-up is considered.     

强光照和全黑暗条件下荒漠沙蜥视网膜内GAP-43表达的免疫组织化学

采用免疫组织化学技术研究了在强光照和全黑暗条件下荒漠沙蜥(Phrynocephalus prezewalskic)视网膜内生长相关蛋白GAP-43的表达变化。结果表明,在正常光照条件下,视网膜内GAP-43阳性表达部位主要存在于内网层;强光照条件下,GAP-43免疫染色部位主要出现在内网层、节细胞层和内核层的部分细胞核。在全黑暗条件下,在视纤维层和内网层呈阳性染色;提示视网膜在不同环境条件下GAP-43的不同定位,可能与其在相应的环境下参与不同的视觉功能有关。     

新疆蓝刺头化学成分研究

以新疆蓝刺头(Echinops ritro L.)全草为研究材料,通过硅胶柱色谱,Sephadex LH-20柱色谱,重结晶等技术对新疆蓝刺头化学成分进行分离纯化,通过理化性质分析及1H-NMR,13C-NMR等技术对化合物结构进行鉴定.结果表明,共分离出5个化合物,分别是三萜类化合物蒲公英甾醇乙酰酯(化合物1)、蒲公英甾醇(化合物2)、黄酮苷类化合物金丝桃苷(化合物3)、胡萝卜苷(化合物4)与β-豆甾醇葡萄糖苷(化合物5).其中化合物1,2,5首次从该种植物中分离,化合物3为首次从该属植物中分离.