Accelerated Screening of Alternative DNA Base-Organic Molecule-Base Architectures via Integrated Theory and Experiment.

Organic molecule-mediated noncanonical DNA self-assembly expands the standard DNA base-pairing alphabets. However, only a very limited number of small molecules have been recognized as mediators because of the tedious and complicated experiments like crystallization and microscopy imaging. Here we present an integrative screening protocol incorporating molecular dynamics (MD) for fast theoretical simulation and native polyacrylamide gel electrophoresis for convenient experimental validation. Melamine, the molecule that was confirmed mediating noncanonical DNA base-pairing, and 38 other candidate molecules were applied to demonstrate the feasibility of this protocol. We successfully identified seven stable noncanonical DNA duplex structures, and another eight novel structures with sub-stability. In addition, we discovered that hairpins at both ends can significantly stabilize the noncanonical DNA structures, providing a guideline to design small organic molecule-incorporated DNA structures. Such an efficient screening protocol will accelerate the design of alternative DNA-molecule architectures beyond Watson-Crick pairs. Considering the wide range of potential mediators, it will also facilitate applications such as noncovalent, highly dense loading of drug molecules in DNA-based delivery system and probe design for sensitive detection of certain molecules.

Antiretroviral Therapy Intensification for Neurocognitive Impairment in Human Immunodeficiency Virus.

BACKGROUND: Neurocognitive impairment (NCI) in people with HIV (PWH) on antiretroviral therapy (ART) is common and may result from persistent HIV replication in the central nervous system. METHODS: A5324 was a randomized, double-blind, placebo-controlled, 96-week trial of ART intensification with dolutegravir (DTG) + MVC, DTG + Placebo, or Dual - Placebo in PWH with plasma HIV RNA <50 copies/mL on ART and NCI. The primary outcome was the change on the normalized total z score (ie, the mean of individual NC test z scores) at week 48. RESULTS: Of 357 screened, 191 enrolled: 71% male, 51% Black race, 22% Hispanic ethnicity; mean age 52 years; mean CD4+ T-cells 681 cells/µL. Most (65%) had symptomatic HIV-associated NC disorder. Study drug was discontinued due to an adverse event in 15 (8%) and did not differ between arms (P = .17). Total z score, depressive symptoms, and daily functioning improved over time in all arms with no significant differences between them at week 48 or later. Adjusting for age, sex, race, study site, efavirenz use, or baseline z score did not alter the results. Body mass index modestly increased over 96 weeks (mean increase 0.32 kg/m2, P = .006) and did not differ between arms (P > .10). CONCLUSIONS: This is the largest, randomized, placebo-controlled trial of ART intensification for NCI in PWH. The findings do not support empiric ART intensification as a treatment for NCI in PWH on suppressive ART. They also do not support that DTG adversely affects cognition, mood, or weight.

The bacterial communities in vagina of different Candida species-associated vulvovaginal candidiasis.

The incidence of vaginal infection caused by Candida species has considerably increased over the past two decades. Candida albicans is the main cause of vulvovaginal candidiasis (VVC); however, non-albicans Candida (NAC) species, such as Candida glabrata and Candida tropicalis, are now frequently identified in VVC patients. Although the vaginal microbiome (VMB) was well studied in Candida albicans-associated VVC patients, the fungal influence on bacterial communities of NAC species-associated VVC and potential microbial interplay contributing to VVC pathology remain elusive. We characterized VMB via Candida albicans and NAC species-associated VVC patients, as Candida albicans (CA, n = 16), Candida glabrata (CG, n = 16), Candida tropicalis (CT, n = 4), and recruiting healthy (CON, n = 20) women as references of dysbiosis and eubiosis. The bacterial diversity of the vagina in the CG group significantly declined. Further, all VVC patients have a higher abundance of Lactobacillus iners, especially for the CG group. Meanwhile, the predicted functions in all VVC are toned which may be associated with a disruption in the bacterial network. In conclusion, according to the taxonomic analysis, we found that the vaginal microbiome in C. glabrata-associated VVC women is different from that of other Candida species-associated VVC women, implying a different pathogenesis.

Using molecular network analysis to understand current HIV-1 transmission characteristics in an inland area of Yunnan, China.

HIV-1 molecular surveillance provides a new approach to explore transmission risks and targeted interventions. From January to June 2021, 663 newly reported HIV-1 cases were recruited in Zhaotong City, Yunnan Province, China. The distribution characteristics of HIV-1 subtypes and HIV-1 molecular network were analysed. Of 542 successfully subtyped samples, 12 HIV-1 strains were identified. The main strains were CRF08_BC (47.0%, 255/542), CRF01_AE (17.0%, 92/542), CRF07_BC (17.0%, 92/542), URFs (8.7%, 47/542), and CRF85_BC (6.5%, 35/542). CRF08_BC was commonly detected among Zhaotong natives, illiterates, and non-farmers and was mostly detected in Zhaoyang County. CRF01_AE was frequently detected among married and homosexual individuals and mostly detected in Weixin and Zhenxiong counties. Among the 516 pol sequences, 187 (36.2%) were clustered. Zhaotong natives, individuals aged ≥60 years, and illiterate individuals were more likely to be found in the network. Assortativity analysis showed that individuals were more likely to be genetically associated when stratified by age, education level, occupation, and reporting area. The genetic diversity of HIV-1 reflects the complexity of local HIV epidemics. Molecular network analyses revealed the subpopulations to focus on and the characteristics of the risk networks. The results will help optimise local prevention and control strategies.

A Randomized Clinical Trial of Human Papillomavirus Test-and-Treat as Compared to Cytology-Based Screening for Prevention of Cervical Cancer Among Women With Human Immunodeficiency Virus: AIDS Clinical Trials Group Protocol A5282.

BACKGROUND: Cytology-based cervical cancer screening followed by confirmation and treatment of biopsy-proven high-grade squamous intraepithelial lesions (bHSIL) is difficult to implement in resource-constrained settings. We hypothesized that high-risk human papillomavirus (hrHPV) testing followed by immediate cryotherapy of women with hrHPV (HPV screen-and-treat) may improve outcomes. METHODS: Randomized, open-label, phase 2, multinational clinical trial enrolling women with human immunodeficiency virus (HIV) age 18 or older with cervical hrHPV and having no cervical lesions or lesions appropriate for cryotherapy. Women were randomized to immediate cryotherapy (Arm A) or cytology-based screening (Arm B). For Arm A, cervical biopsies were obtained followed by cervical cryotherapy, and in Arm B, women with abnormal cytology underwent colposcopy followed by loop electroexcision procedure (LEEP) if bHSIL was detected. Women were followed through 30 months. The primary outcome was time to bHSIL detected from Month 6 through study completion. RESULTS: In total, 288 women (145 in Arm A, 143 in Arm B) were randomized: median age 35 years, 84% on antiretroviral therapy, median CD4 501 cells/mm3. In Arm A, 39 (27%) of women had bHSIL at entry, and in Arm B, 88 (62%) had abnormal cytology, 22 (15%) were diagnosed with bHSIL, 12 (8%) underwent LEEP. In follow-up, 30 (21%) and 31 (22%) developed bHSIL; time to bHSIL was similar between arms (P=.94). The prevalence of hrHPV at Month 6 was similar between arms (61% and 70%, P=.13). CONCLUSIONS: HPV test-and-treat was not associated with improved bHSIL outcomes as compared to cytology-based screening. More effective treatment options are required to improve outcomes from screen-and-treat programs. CLINICAL TRIALS REGISTRATION: NCT01315363.

HIV-1 pretreatment drug resistance and genetic transmission network in the southwest border region of China.

BACKGROUND: HIV drug resistance increased with the widespread use of antiretroviral drugs, and posed great threat to antiretroviral therapy (ART). Pu'er Prefecture, lying in the southwest of Yunnan Province, China, borders Myanmar, Laos and Vietnam, is also the area where AIDS was discovered earlier, however, in which there has been no information on HIV drug resistance. METHODS: A cross-sectional survey of pretreatment drug resistance (PDR) was conducted in Pu'er Prefecture in 2021. Partial pol gene sequences were obtained to analyze drug resistance and construct genetic transmission network. HIV drug resistance was analyzed using the Stanford University HIVdb algorithm. RESULTS: A total of 295 sequences were obtained, among which 11 HIV-1 strain types were detected and CRF08_BC (62.0%, 183/295) was the predominant one. Drug resistance mutations (DRMs) were detected in 42.4% (125/295) of the sequences. The prevalence of PDR to any antiretroviral drugs, nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 10.8% (32/295), 9.5% (28/295), 1.0% (3/295) and 0.3% (1/295), respectively. The risk of PDR occurrence was higher among individuals with CRF01_AE strain types. HIV-1 molecular network was constructed, in which 56.0% (42/75) of links were transregional, and 54.7% (41/75) of links were associated with Lancang County. Among the sequences in the network, 36.8% (35/95) harbored DRMs, and 9.5% (9/95) were drug resistance strains. Furthermore, 8 clusters had shared DRM. CONCLUSION: The overall prevalence of PDR in this study was in a moderate level, but NNRTIs resistance was very approaching to the threshold of public response initiation. PDR was identified in the transmission network, and DRMs transmission was observed. These findings suggested that the consecutive PDR surveillance should be conducted in this region.

Human health risk identification of petrochemical sites based on extreme gradient boosting.

Petrochemical industry is a key industry of soil pollution, which presents great effects on human health and the ecological environment. It is of great significance to achieve rapid, economic and efficient health risk identification for petrochemical industry in China. In this work, an efficient method was developed based on extreme gradient boosting (XGBoost) algorithm for human health risk identification, which is different from the traditional health risk assessment with complicated procedures. In this methodology, an index system of 13 indicators was established from the perspective of "sources - pathways - receptors" for risk identification. The 10-fold cross validation was used to assess the generalization performance, and the accuracy, precision and recall were employed to evaluate the performance of the algorithms. Wilcoxon signed-rank test was conducted to analyze the differences between XGBoost and other models for statistical support. The results showed that XGBoost significantly presented a better performance for health risk identification over multilayer perceptron neural network with error backpropagation training (BPNN), support vector machine (SVM), gradient boosting decision tree (GBDT) and light gradient boosting machine (LightGBM), with an accuracy of 0.783. The most important features contributing to the risk identification were determined with the sequence of site location (in the industrial zone or not), site planning and production period. Great attention should be given to the petrochemical sites that are not located in the industrial zone with long production period and sensitive receptors in the health risk identification. This method has important reference significance for relevant departments to carry out soil contamination screening and health risk assessment of petrochemical sites.

The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China.

HIV-1 drug resistance can compromise the effectiveness of antiretroviral therapy (ART). A survey of pretreatment HIV-1 drug resistance (PDR) was conducted in Lincang Prefecture of Yunnan Province. From 372 people living with HIV/AIDS initiating ART for the first time during 2017-2018, 322 pol sequences were obtained, of which 11 HIV-1 strain types were detected. CRF08_BC (70.2%, 226/322) was the predominant strain, followed by URF strains (10.6%, 34/322). Drug resistance mutations (DRMs) were detected among 34.2% (110/322) of the participants. E138A/G/K/R (14.3%, 46/322) and V179E/D/T (13.7%, 47/322) were the predominant DRMs. Specifically, E138 mutations commonly occurred in CRF08_BC (19.9%, 45/226). Among the DRMs detected, some independently conferred resistance, such as K65R (1.6%, 5/322), Y188C/F/L (0.9%, 3/322), K103N (0.6%, 2/322) and G190A (0.3%, 1/322), which conferred high-level resistance. The prevalence of PDR was 7.5% (95% CI: 4.6-10.3%) and the prevalence of non-nucleotide reverse transcriptase inhibitor (NNRTI) resistance was 5.0% (95% CI: 2.6-7.4%), which is below the threshold (⩾10%) of initiating a public health response. In conclusion, HIV-1 genetic diversity and an overall moderate level of PDR prevalence were found in western Yunnan. PDR surveillance should be continually performed to decide whether a public health response to NNRTI resistance should be initiated.

Spatial clusters of HIV-1 genotypes in a recently infected population in Yunnan, China.

BACKGROUND: As a gateway for HIV-1 in China, Yunnan has experienced dramatic changes in HIV-1 epidemics, during which HIV-1 genotypes have become complex. To track dynamic changes in HIV-1 genotypes, an HIV-1 molecular epidemiological study was implemented in the recently infected population in Yunnan. METHODS: From 6,357 HIV-1-positive samples diagnosed during the first half of 2015 in Yunnan, 586 samples were identified as recent infections with BED-capture enzyme immunoassay (CEIA) and were subjected to phylogenetic analyses. Spatial scanning analyses for the main HIV-1 genotypes were also performed. RESULTS: Among the 439 specimens successfully genotyped, more than ten genotypes were detected, including CRF08_BC (45.3%), CRF07_BC (19.4%), unique recombinant forms (URFs) (18.2%), CRF01_AE (11.4%), subtype C (2.1%), CRF85_BC (1.1%), CRF55_01B (0.9%), subtype B (0.5%), CRF64_BC (0.5%), CRF59_01B (0.2%), CRF83_cpx (0.2%) and CRF87_cpx (0.2%). Females, Chinese, heterosexual contact and intravenous drug injection were significantly associated with CRF08_BC infection; homosexual contact was significantly associated with CRF01_AE and CRF07_BC infection; males and non-Chinese had a higher risk of URF infection than females. Among all HIV-1 genotypes, the geographic coverage of CRF08_BC was the largest. For CRF08_BC, CRF07_BC, URFs and CRF01_AE, spatial clusters were detected. The two CRF08_BC clusters and one URF cluster were associated with heterosexual transmission, and two of CRF01_AE clusters were associated with homosexual transmission. Transmitted drug resistance (TDR)-associated mutations were detected in 2.4% of individuals. CONCLUSIONS: The diversity of HIV-1 genotypes increased in recent infections because of a long-term HIV-1 epidemic in Yunnan. The predominant HIV-1 strains showed distinct demographic characteristics and formed spatial clusters. These findings improved our understanding of the evolution of HIV-1 in Yunnan and provided information for further HIV-1 control and prevention.

Demographic characteristics and spatial clusters of recent HIV-1 infections among newly diagnosed HIV-1 cases in Yunnan, China, 2015.

BACKGROUND: The characteristics of recent HIV infections can provide the information about the dynamics of HIV transmission. Yunnan is one of the provinces hardest-hit by HIV-1 in China. To further understand the characteristics of the HIV-1 epidemic in Yunnan, we analyzed the prevalence of recent HIV-1 infections among newly diagnosed cases, identified the associated factors and explored the spatial distribution of recent HIV-1 infections. METHODS: Residual plasma samples from HIV-1 diagnostic tests were preserved. The associated information was collected from China HIV/AIDS case reporting system. Recent HIV-1 infections were estimated by combining the information about disease progression and BED- capture enzyme immunoassay (CEIA). The proportions of recent HIV-1 infections among newly diagnosed cases stratified by demographic characteristics were analyzed. The spatial clusters of recent HIV-1 infections were investigated by spatial scan statistics. RESULTS: Among 6119 HIV/AIDS cases were newly reported between January 2015 and June 2015 in Yunnan Province, 9.3% (570/6119) were estimated as recent infections. Female, aged below 25 years and homosexual contact were more associated with the higher proportion of recent HIV-1 infections. Among the different demographic sub-groups, men who have sex with men (MSM) aged < 25 years and ≥ 50 years had a higher chance of being diagnosed as recent infections, heterosexually infected men aged ≥25 years had a lower chance of being diagnosed as recent infections. In the sub-groups with different screening approaches, the highest proportion of recent infections (16.1%) was found among women diagnosed by testing during pregnancy and childbirth. In the sub-groups with different contact histories, the higher proportion of recent infections was found among the female cases having commercial heterosexual contacts (16.4%) and MSM (19.7%). The statistically significant spatial clusters of recent infections attributed to heterosexual contact, homosexual contact and intravenous drug injection were identified, respectively. CONCLUSIONS: The investigation of recent HIV infections among newly diagnosed cases supplements the routine HIV surveillance, and reveals the characteristics of ongoing HIV transmission. Our finding identified the potential sub-populations and geographic areas in need of services or improved interventions.

A Randomized, Placebo-Controlled Trial of the Quadrivalent Human Papillomavirus Vaccine in Human Immunodeficiency Virus-Infected Adults Aged 27 Years or Older: AIDS Clinical Trials Group Protocol A5298.

Background: Adults living with human immunodeficiency virus (HIV) are at increased risk for anal and oropharyngeal cancer caused by human papillomavirus (HPV). The efficacy of HPV vaccines in this population is unknown. Methods: In this phase 3, double-blind, randomized, controlled trial, we assigned HIV-infected adults aged ≥27 years to the quadrivalent HPV (types 6, 11, 16, 18) vaccine or placebo (1:1) stratified by sex and presence of anal high-grade squamous intraepithelial lesions on biopsy (bHSIL). The primary endpoint was vaccine efficacy against incident persistent anal infection with quadrivalent vaccine types or single detection at the final visit that were not present at baseline. Secondary endpoints included vaccine efficacy for anal bHSIL after week 52, persistent oral HPV infection. Results: A total of 575 participants were randomized. The Data and Safety Monitoring Board stopped the study early due to futility. Vaccine efficacy was 22% (95.1% confidence interval [CI], -31%, 53%) for prevention of persistent anal infection or single detection at the final visit, 0% (95% CI -44%, 31%) for improving bHSIL outcomes and 88% (95.1% CI 2%, 98%) for preventing persistent oral HPV infection, but was 32% (95.1% CI -80%, 74%) for 6-month persistent oral HPV infection or single detection at the final visit. Conclusions: These results do not support HPV vaccination of HIV-infected adults aged ≥27 years to prevent new anal HPV infections or to improve anal HSIL outcomes. However, our data suggest a role for prevention of oral HPV infections, but this finding should be confirmed in future studies. Clinical Trials Registration: NCT01461096.

Attapulgite suspension mitigates fine particulate matter (PM2.5) emission from coal combustion in fluidized bed.

To reduce fine particulate matter emission from coal burning sources especially fossil fuel fired energy generation facility is critical to improve air quality. Attapulgite suspension was attempted to spray in a 6 kW fluidized bed facility and reduce fine particulate matter emission during coal combustion. The key parameters such as attapulgite mass, flowrate and spraying zone were investigated to determine the optimal and critical conditions that influence fine particulate matter emission. Exciting results indicate that both fine particle number and mass concentrations are largely decreased due to the physical/chemical absorption with the suitable mass ratio of 3 wt%. The spray of attapulgite suspension in both dense bed and dilute bed effectively mitigates fine particle emission based on the agglomeration and absorption. The most excellent result is achieved at a flowrate of 38 ml/min in dense bed with particle number reduction up to 93.5% in PM2.5 (fine particles is equal to/less than 2.5 µm), 93.6% in PM1.0 (fine particles is equal to/less than 1.0 µm) and 93.7% in PM0.1 (fine particles is equal to/less than 0.1 µm), respectively. The work highlights the potential of spraying attapulgite suspension as an effective process to reduce fine particle emission during coal combustion in fluidized bed system.

The changing trends of HIV-1 prevalence and incidence from sentinel surveillance of five sub-populations in Yunnan, China, 2001-2010.

BACKGROUND: Yunnan is one of the provinces hardest-hit by HIV in China. To understand HIV epidemic dynamics and evaluate prevention effectiveness, we studied the changing trends in HIV-1 prevalence and incidence among five sub-populations in Yunnan. METHODS: Consecutive sentinel surveillances were conducted among people who inject drugs (PWID), male sexually transmitted diseases (STD) clinic attendees, and pregnant women for 2001-2010,female sex workers (FSWs) for 2007-2010, men who have sex with men (MSM) for 2008-2010. For the newly diagnosed HIV-seropositive samples, the recent infections were determined with BED-capture enzyme immunoassay (BED-CEIA), based on which HIV incidence was calculated for each sub-population using McDougal algorithm. RESULTS: From 231,117 individuals, 6,107 HIV-positive samples were tested with BED-CEIA, among which 964 samples were identified as recent infections. In PWID, HIV prevalence for 2001-2010 was between 27.16% and 18.35%, while the estimated incidence rate significantly decreased from 11.68% in 2001 to 1.70% in 2010. Among male STD clinic attendees, both the HIV prevalence (from 3.62% in 2001 to 1.73% in 2010) and incidence (from 1.10% in 2001 to 0.40% in 2010) showed a significant decreasing trend. In FSWs, the HIV prevalence for 2007-2010 kept stable (between 2.46% and 1.95%), while the HIV incidence significantly decreased (from 0.71% in 2007 to 0.31% in 2010). In MSM, the HIV prevalence (between 11.78% and 9.42%) and incidence (between 6.01% and 8.38%) remained stable at a relatively high level for 2008-2010. In pregnant women, the HIV prevalence (between 0.44% and 0.30%) and incidence (between 0.15% and 0.08%) remained stable for 2001-2010. CONCLUSION: The HIV incidences in PWID, male STD clinic attendees and FSWs showed the decreasing trend, supporting a positive effect of prevention strategies for these sub-populations. MSM with the highest HIV incidence have become the sub-population most at risk. In most sub-populations, the HIV prevalence did not decline, suggesting the disease burden is still heavy. These findings are valuable for developing HIV prevention strategies in Yunnan.

In vivo splenic clearance correlates with in vitro deformability of red blood cells from Plasmodium yoelii-infected mice.

Recent experimental and clinical studies suggest a crucial role of mechanical splenic filtration in the host's defense against malaria parasites. Subtle changes in red blood cell (RBC) deformability, caused by infection or drug treatment, could influence the pathophysiological outcome. However, in vitro deformability measurements have not been directly linked in vivo with the splenic clearance of RBCs. In this study, mice infected with malaria-inducing Plasmodium yoelii revealed that chloroquine treatment could lead to significant alterations to RBC deformability and increase clearance of both infected and uninfected RBCs in vivo. These results have clear implications for the mechanism of human malarial anemia, a severe pathological condition affecting malaria patients.

HIV-1 molecular networks and pretreatment drug resistance at the frontier of Yunnan Province, China.

The border areas of Yunnan Province in China are severely affected by human immunodeficiency virus (HIV). To investigate the risk of HIV transmission and assess the prevalence of pretreatment drug resistance (PDR) in the border area, blood samples were collected from individuals with newly reported HIV in 2021 in three border counties (Cangyuan, Gengma, and Zhenkang) in Yunnan Province. Among the 174 samples successfully genotyped, eight circulating recombinant forms (CRFs), two subtypes, and several unique recombinant forms (URFs) were identified. CRF08_BC (56.9%, 99/174), URFs (14.4%, 25/174), CRF01_AE (10.9%, 19/174) and CRF07_BC (8.0%, 14/174) were the main genotypes. CRF08_BC and URFs were detected more frequently in Chinese and Burmese individuals, respectively. CRF07_BC was found more frequently in men who have sex with men (MSM). The proportion of individuals detected in HIV-1 networks was only associated with case-reporting counties. When stratified by county, individuals aged ≤40 years in Cangyuan and ≥41 years in Gengma were more likely to be found in these networks. Furthermore, 93.8% (15/16) of the links in Cangyuan and 79.4% (50/63) of those in Gengma were located within their own counties. The prevalence of PDR to any antiretroviral drug, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) were 10% (17/170), 0.6% (1/170) and 9.4% (16/170), respectively. The most frequent resistance-associated mutations (RAMs) were V179D/VD/E/T (22.9%, 39/170) and E138A/G/K/R (13.5%, 23/170). In the molecular networks, six clusters shared common RAMs. HIV-1 genetics has become more diverse in border areas. HIV-1 molecular network analysis revealed the different characteristics of the HIV-1 epidemic in the border counties. The prevalence of PDR showed an upward trend, and the PDR to NNRTIs was close to the public response threshold. These findings provide information for the development of AIDS prevention and treatment strategies.

Peripheral neuropathy in ART-experienced patients: prevalence and risk factors.

Peripheral neuropathy (PN) is a common neurological complication of HIV infection that has debilitating effects on quality of life. While there has been a comprehensive evaluation of the prevalence of neuropathic signs/symptoms and risk factors (RFs) for PN or symptomatic PN (SPN) with initiation of combination antiretroviral therapy (cART) in ART-naïve patients, similar evaluation in ART-experienced patients is limited. This study investigated the prevalence and RFs for PN/SPN in ART-experienced patients enrolled in clinical salvage therapy studies. Between February 2000 and June 2007, 522 ART-experienced participants who experienced virologic failure with a prior regimen and started new regimens were followed longitudinally and annually screened for signs and symptoms of PN. Rates of PN/SPN at 3 years since parent study entry were 52.8 and 24.0 %, respectively. Aging, taller height, protease inhibitor use, and female sex were significant RFs for PN/SPN. The use of statin drugs was significantly associated with lower odds of SPN, and it may prevent progression from no SPN to SPN.

Retrospective study of pemetrexed as salvage therapy for central nervous system lymphoma.

There is currently no standard therapy for recurrent or chemotherapy-refractory central nervous system lymphoma (CNSL). Pemetrexed has been reported to have activity in patients with primary CNSL (PCNSL). The use of pemetrexed in secondary CNS lymphoma (SCNSL) has not previously been reported. Here we retrospectively review the outcomes and toxicities of standard and modified doses of pemetrexed as salvage therapy in 18 PCNSL and 12 SCNSL patients. The overall response rate for PCNSL patients was 64.7 %, all of whom achieved a complete response (CR). The median progression-free survival (PFS) was 5.8 months. For the SCNSL patients, RR was 58.3 % with 2 CR (16.7 %); the median PFS was 2.5 months. Grade ≥3 adverse events included leukopenia in 5 patients (16.7 %), neutropenia in 1 patient (3.3 %), and fatigue in 3 patients (10.0 %). 3 patients died while on treatment, 2 due to infections and 1 due to pulmonary embolism. Our results indicate that pemetrexed has activity as salvage therapy in recurrent PCNSL, even with modified dosing, but outcomes trend towards less favorable in SCNSL.

[Evaluation of PIMA analyzer detecting CD4 cell count of venous and capillary blood in HIV-infected individuals].

OBJECTIVE: This study is aimed at evaluating the utility of the portable CD4 analyzers (PIMA). METHODS: The paired finger prick blood (25 µl) and 5 ml venous blood samples were collected from 196 HIV infected patients, who came to Yunnan CDC voluntary counseling and testing (VCT) clinic for CD4 test services, from May to August, 2012. The absolute CD4 cell counts were measured by PIMA (using venous and finger-prick blood) and by Calibur (using venous blood) as the reference. The PIMA and Calibur CD4 results were compared using the Wilcoxon matched-pairs test, and the Spearman's rank correlation coefficients were estimated. The Bland-Altman plots were used to assess the consistency of the two methods. RESULTS: The median absolute CD4 counts of 196 venous blood samples obtained by PIMA and by Calibur were 268 (range:169-403) cells/µl and 302 (range:181-474) cells/µl respectively, which showed significant difference (Z = -7.31, P < 0.01). The median absolute CD4 counts measured by PIMA and by Calibur (using 188 finger-prick and venous blood samples respectively) were 271 (range: 165-450) cells/µl and 304 (range:188-476) cells/µl, which also showed significant difference (Z = -7.60, P < 0.01). The CD4 counts obtained by PIMA CD4 analyzer (using venous and finger-prick blood) showed strong positive correlation with the CD4 counts obtained by the reference method (using venous blood), and the r values were 0.94 and 0.92 respectively (P < 0.01) . The mean biases (limit of agreement) were -38.7 (-210.9-133.5)cells/µl and -45.4 (-221.8-131.0) cells/µl, respectively.Using 350 CD4 counts as the threshold for ART treatment initiation, the sensitivity and specificity of PIMA were 99.1% and 79.3% for venous blood samples, and 97.2%and 78.5% for finger-prick blood samples, respectively. CONCLUSION: The CD4 counts obtained by PIMA are lower than that obtained by Calibur, while the sensitivity is high.

Carbon dioxide capture using polyethylenimine-loaded mesoporous carbons.

A high efficiency sorbent for CO2 capture was developed by loading polyethylenimine (PEI) on mesoporous carbons which possessed well-developed mesoporous structures and large pore volume. The physicochemical properties of the sorbent were characterized by N2 adsorption/desorption, scanning electron microscopy (SEM), thermal gravimetric analysis (TG) and Fourier transform infrared spectroscopy (FT-IR) techniques followed by testing for CO2 capture. Factors that affected the sorption capacity of the sorbent were studied. The sorbent exhibited extraordinary capture capacity with CO2 concentration ranging from 5% to 80%. The optimal PEI loading was determined to be 65 wt.% with a CO2 sorption capacity of 4.82 mmol-CO2/g-sorbent in 15% CO2/N2 at 75 degrees C, owing to low mass-transfer resistance and a high utilization ratio of the amine compound (63%). Moisture had a promoting effect on the sorption separation of CO2. In addition, the developed sorbent could be regenerated easily at 100 degrees C, and it exhibited excellent regenerability and stability. These results indicate that this PEI-loaded mesoporous carbon sorbent should have a good potential for CO2 capture in the future.

Mechanochemical treatment of hexachlorobenzene-contaminated soil with additives.

The use of mechanochemistry for the remediation of hexachlorobenzene (HCB)-contaminated soil was investigated. Additives such as alkaline materials, neutral materials, natural minerals, and solid waste were studied to explore their effect on the degradation of hexachlorobenzene in soil with single or combined addition by mechanochemical method. The best combination of materials were determined based on HCB destruction percentage by considering the impact on soil quality, the treatment cost, and the availability of additives. Scanning electron microscope (SEM) images and X-ray photoelectron spectrometer (XPS) analysis were conducted for the mechanism studies. The combination of albite and ferric oxide (Fe3O4) was found to achieve the best performance in the degradation of HCB with the destruction percentage from 74.3 to 92.5% after 2-h and 6-h reaction, respectively. The developed fracture structure and complex compositions of albite provided abundant reaction sites for mechanochemical degradation of HCB in soil.