Vaginal Lactobacillus fatty acid response mechanisms reveal a metabolite-targeted strategy for bacterial vaginosis treatment.

Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related lactobacilli, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the vaginal microbiota and enhances bacterial fitness by biochemically sequestering OA in a derivative form only ohyA-harboring organisms can exploit. OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro BV model, suggesting a metabolite-based treatment approach.

Real-world dosing of regorafenib and outcomes among patients with metastatic colorectal cancer: a retrospective analysis using US claims data.

BACKGROUND: The randomized, dose-optimization, open-label ReDOS study in US patients with metastatic colorectal cancer (CRC) showed that, compared with a standard dosing approach, initiating regorafenib at 80 mg/day and escalating to 160 mg/day depending on tolerability increased the proportion of patients reaching their third treatment cycle and reduced the incidence of adverse events without compromising efficacy. Subsequently, the ReDOS dose-escalation strategy was included as an alternative regorafenib dosing option in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines. A retrospective analysis was conducted using a US claims database to assess whether inclusion of this dose-escalation strategy in NCCN Guidelines has influenced the use of flexible dosing in routine US clinical practice, and to describe clinical outcomes pre- and post-inclusion in NCCN Guidelines. METHODS: Patients with CRC in the Optum's de-identified Clinformatics® Data Mart database initiating regorafenib for the first time between January 2016 and June 2020 were stratified based on whether they initiated regorafenib pre- or post-inclusion of ReDOS in NCCN Guidelines, and in two groups: flexible dosing (< 160 mg/day; < 84 tablets in the first treatment cycle) and standard dosing (160 mg/day; ≥ 84 tablets in the first treatment cycle). The primary endpoints were the proportion of patients who initiated their third treatment cycle and the mean number of treatment cycles per group. RESULTS: 703 patients initiated regorafenib during the study period, of whom 310 (44%) initiated before and 393 (56%) initiated after inclusion of ReDOS in NCCN Guidelines. After inclusion in the guidelines, the proportion of patients who received flexible dosing increased from 21% (n = 66/310) to 45% (n = 178/393), the proportion who received standard dosing decreased from 79% (n = 244/310) to 55% (n = 215/393), the proportion who initiated their third treatment cycle increased from 36% (n = 113/310) to 46% (n = 179/393), and the mean (standard deviation) number of treatment cycles increased from 2.6 (2.9) to 3.2 (3.1). CONCLUSIONS: Following inclusion of ReDOS in NCCN Guidelines, real-world data suggest that US clinicians have markedly increased use of flexible dosing in clinical practice, potentially maximizing clinical benefits and safety outcomes for patients with metastatic CRC receiving regorafenib.

Age-related trends in the incidence of metastatic colorectal cancer from 2010 to 2019 in the USA.

Aim: To evaluate temporal changes in metastatic colorectal cancer (mCRC), incidence, and use of chemotherapy treatment by age group using real-world data (RWD) from the USA. Methods: A retrospective, observational study describing temporal trends in mCRC incidence and FOLFOXIRI treatment by age group using a nationwide database of commercially and Medicare Advantage-insured patients from 2010 to 2019. Results: Incidence of mCRC increased by 22.1 and 14.9% in the 18-49 and 50-64 years cohorts, respectively, and decreased by 21.6% in the ≥65 years cohort. Overall, younger patients were more likely to receive FOLFOXIRI treatment versus older patients. Conclusion: The shifting age distribution of mCRC should be considered when recommending screening and treatment. Further research is needed to inform age-specific treatment guidelines.

What is this article about? This article reports the results of a study that used a US database of commercially and Medicare Advantage-insured adults to evaluate how the number of adults with metastatic colorectal cancer (mCRC) in three age groups (18­49 years, 50­64 years and 65 years and over) changed from 2010 to 2019. The study also looked at the use of an aggressive chemotherapy treatment, known as 5-fluorouracil, oxaliplatin, leucovorin calcium and irinotecan (FOLFOXIRI), by age group. What were the results? Overall, 23,970 adults with mCRC were included in the study. From 2010 to 2019, the number of adults with mCRC increased by 22.1% among those aged 18­49 years, increased by 14.9% among those aged 50­64 years, and decreased by 21.6% among those aged 65 years and over. There were some differences between age groups; a higher percentage of younger patients (18­49 years) were Hispanic or Asian, and from the South compared with the older age groups. In comparison, those aged 65 years and over were more likely to be from the West and Northeast of the USA. The study also found that a higher proportion of those aged 18­49 years received FOLFOXIRI (8.4%) compared with adults aged 50­64 years (4.4%) and 65 years and over (1.9%). What do the results of the study mean? Healthcare providers should be aware that early-onset mCRC is becoming more common and consider this when recommending screening and treatment.

Health-related quality of life and medication use among individuals with Angelman syndrome.

PURPOSE: The primary goal of this analysis is to describe the health-related quality of life (HRQoL), medical history, and medication use among adolescents and adults individuals with Angelman syndrome (AS). METHODS: The analysis uses baseline data collected during the STARS study, a double-blind placebo controlled trial of gaboxadol (OV101) in adolescents and adults with AS. The HRQoL was estimated using EuroQoL 5-Dimension 5-Level (EQ-5D) health questionnaire proxy 1 version, which was completed by the caregivers. EQ-5D consists of two parts, a 5-dimension descriptive and a visual analogue scale (VAS) component. The utility score derived from EQ-5D ranges from 0 to 1 (perfect health) and VAS ranges from 0 to 100 (perfect health). RESULTS: 87 individuals with AS were included in the present analysis. The mean utility score was 0.44 ± 0.20 and VAS score was 84 ± 1.5. The EQ-5D data indicated that the self-care, mobility and daily activities were most impacted. All adolescents (100%) and most adults (93%) had at least moderate problems with self-care activities, such as washing or dressing themselves. More than half (55%) of the adolescents and adults had at least moderate issues with mobility and usual activities. Approximately, 30% of adolescents and adults had moderate to extreme problems with anxiety/depression. High baseline concomitant use of medications was observed across both age groups with an average of 5 medications being used per person. CONCLUSION: This study highlights the impact of AS on HRQoL and medication utilization among adolescents and adults individuals with AS.

Dose-response and temporal ergogenic effects of ginseng supplementation in athletes and active participants: A systematic review and meta-analysis.

This review sought to assess the dose-response, i.e., low (<300 mg/day) and high (>300 mg/day), and temporal effects of ginseng, i.e., immediate, short-term (up to 4 weeks) and long-term (>4 weeks) in comparison to placebo on physical performance [visual analogue scale (VAS) level, vertical jump(VJ), rating of perceived exertion (RPE), peak power output (PPO)] and physiological measures [VO2 max, creatine kinase(CK), heart rate(HR)], in athletes and active participants. Search in four databases with English language constraints yielded 492 studies. Fourteen studies were shortlisted through PEDro scale by methodological quality evaluation. Ginseng exhibited significant short-term effect at high dosage for VJ improvement (SMD: -8.17, 95% CI: -16.28 to -0.06, p= 0.05). Ginseng had no effect on VAS (SMD: -0.65, 95% CI: -1.35 to 0.06, p= 0.07), RPE (SMD: -1.11, 95% CI: -2.57 to 0.35, p= 0.14), PPO (SMD: -0.70, 95% CI: -1.78 to 0.38, p= 0.20), HR (SMD: -0.54, 95% CI: -2.05 to 0.96, p= 0.48), CK (SMD: 0.33, 95% CI: -0.18 to 0.84, p= 0.21) and VO2 max (SMD: 0.08, 95% CI: -0.69 to 0.85, p= 0.08).The ginseng supplementation was found to have significant short-term effect at high dose only for VJ in athletic and active participants. Methodologically strong research is warranted to further consolidate these findings.

Bimetallic Fe/Ni nanoparticles derived from green synthesis for the removal of arsenic (V) in mine wastewater.

Since the incidences of arsenicosis have significantly increased worldwide in the last decade, remediation of arsenic (As) pollution is now imperative. In this study, calcined green synthesized Fe/Ni nanoparticles (C-Fe/Ni NPs) were evaluated for their efficacy for As (V) removal from aqueous solution. Under optimal experimental conditions As (V) removal efficiency reached 87.3%. Analysis of changes in the surface properties of C-Fe/Ni NPs before and after interaction with As (Ⅴ) using a range of advanced characterization techniques including IC-AFS, SEM-EDS, XPS and XRD revealed that the As removal mechanism involved only adsorption. Adsorption kinetics followed a pseudo-second order rate model (R2 > 0.986) and adsorption best fit the Langmuir isotherm model (R2 > 0.958). Thermodynamic studies indicated that adsorption was a spontaneous endothermic process. On the basis of these results, a removal mechanism of As (Ⅴ) by C-Fe/Ni NPs was proposed. Finally, the efficacy of the material for practical remediation of As from aqueous solution was assessed, including the influence of coexisting anions. While Cl-, NO3- and SO42- had little influence on As (V) removal, both H2PO4- and HCO3- significantly negatively affected removal.

Removal of low Sb(V) concentrations from mining wastewater using zeolitic imidazolate framework-8.

Wastewater generated during mining remains a significant source of antimony pollution, because techniques to quickly and efficiently remove antimony from wastewater do not exist. In this study, zeolitic imidazolate framework-8 (ZIF-8), a specific type of Metal Organic Frameworks (MOFs), was successfully used to remove trace levels (1 mg L-1) of Sb(V) with a high removal efficiency when the ZIF-8 dose was 0.5 g L-1. Scanning electron microscopy-X-ray energy dispersive spectrometry (SEM-EDS) indicated that Sb(V) was adsorbed onto the ZIF-8surface. The powder X-ray diffraction (XRD) pattern of ZIF-8 before and after adsorption of Sb(V) indicated that ZIF-8 was successfully synthesized, and remained structurally stable after Sb(V) was adsorbed. Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS) both suggested complexation of zinc on ZIF-8 with Sb(V), where removal of Sb(V) by ZIF-8 followed the Langmuir adsorption isotherm with pseudo second-order kinetics. Thus, a possible removal mechanism was proposed which involved Sb(V) complexing with the zinc hydroxyl groups on ZIF-8 (Zn-OH-Sb). Practically, ZIF-8, could remove 78.6% of Sb(V) from a mining wastewater containing 20 µg L-1 Sb(V). Furthermore, ZIF-8 could be remain active after repeated uses and could still remove and 42.3% of Sb(V) from wastewater containing 1 mg L-1) Sb(V) even when the ZIF-8 was reused five time. This indicated that ZIF-8 had potential for practical removal of Sb(V) from mining wastewaters.

Association of Massive Transfusion for Resuscitation in Gastrointestinal Bleeding with Transfusion-related Acute Lung Injury.

BACKGROUND AND AIMS: This study aimed to understand the use of massive transfusion (MT) for gastrointestinal bleeding (GIB). PATIENTS AND METHODS: We performed a retrospective analysis of patients admitted to our medical Intensive Care Unit (ICU) with GIB for the type of bleeding, quantity of blood products transfused, and risk of transfusion-related acute lung injury (TRALI) and death. MT was defined as transfusion of 10 or more units of red blood cell (RBC) within a 24-h period in a 1-unit RBC: 1-unit fresh frozen plasma: and 1-unit platelet ratio. TRALI was defined as development of acute lung injury (ALI), within 6 h of transfusion, with new bilateral pulmonary infiltrates, absence of circulatory overload, or other explanation for ALI. RESULTS: In a 43-month interval, 169 patients were admitted to the ICU with GIB and received blood products, of whom 13 received MT. Ten patients developed TRALI, of whom 7 (70%) had received MT. MT was associated with an increased risk of TRALI (odds ratio [OR]: 17.9, 95% confidence interval [CI]: 2.9-111.2, P = 0.002) after adjusting for age, sex, body mass index, baseline vitals, and laboratory data. Death was predicted by MT (OR: 5.6, 95% CI: 1.6-19.7, P = 0.007), TRALI (OR: 2.3, 95% CI: 1.1-4.6, P = 0.02), and Acute Physiologic Chronic Health Evaluation II score (OR: 1.17 per unit increase, 95% CI: 1.09-1.26, P < 0.001) after adjusting for age and sex. CONCLUSIONS: MT for GIB is associated with an increased risk of TRALI and death. Prospective studies assessing the use of MT in this population are needed to understand and improve outcomes.

Hypertension and Circulating Cytokines and Angiogenic Factors in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma Treated With Sunitinib: Results From a Phase II Trial.

BACKGROUND: We evaluated the significance of hypertension developing during vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor (VEGFR-TKI) treatment and a group of cytokines and angiogenic factors (CAFs) in advanced non-clear cell renal cell carcinoma (nccRCC) patients treated with sunitinib in a phase II study. MATERIALS AND METHODS: Using multiplex assays, we analyzed the levels of 38 CAFs in plasma at baseline and after 4 weeks of sunitinib therapy. Sunitinib benefit was defined as a partial response or stable disease using the Response Evaluation Criteria in Solid Tumors lasting ≥4 months. Cox proportional hazards regression models were used to assess the associations among hypertension, CAFs, and progression-free (PFS) and overall survival (OS). RESULTS: Fifty-seven patients were evaluable; 53 had baseline CAF levels available. The median PFS and OS were 2.9 months (95% confidence interval [CI], 1.4-5.5) and 16.8 months (95% CI, 10.7-27.4), respectively. Sunitinib benefit was observed in 21 patients (37%). However, 33 patients (60%) developed hypertension during treatment, although no association was found with survival or response. Elevated baseline soluble tumor necrosis factor (TNF) receptor I, interleukin-8, growth-regulated oncogene, transforming growth factor-α, and VEGFR-2 levels were associated with an increased risk of death on multivariate analysis. CONCLUSION: We found no association between the development of hypertension and survival or sunitinib benefit in advanced nccRCC. TNF and angiogenic/immunomodulatory mediators were identified for evaluation as markers of prognosis and VEGFR-TKI benefit in future studies.

Arm exercise as an alternative to pharmacologic stress testing: arm exercise stress testing and outcome.

BACKGROUND: Treadmill exercise variables are powerful predictors of all-cause mortality but are unobtainable in at least 50% of patients because of disabilities precluding lower extremity exercise. Arm exercise stress testing is a potentially cost-effective alternative, but no long-term outcome data are available. METHODS: We performed arm ergometer stress tests on 446 veterans aged 64.0 (11.1) years (mean [SD]) between 1997 and 2002 and investigated whether arm exercise capacity in resting metabolic equivalents, heart rate recovery (in beats per minute), delta (peak resting) heart rate (in beats per minute), and other exercise variables predict long-term all-cause mortality, myocardial infarction (MI), or coronary revascularization. RESULTS: During follow-up of 12.0 (1.3) years, 255 patients died (57.2%), 70 had MI (15.7%), and 118 underwent coronary revascularization (26.4%). After adjustment for significant demographic and clinical variables, death was predicted by arm metabolic equivalents (hazard ratio/SD 0.59, 95% CI 0.46-0.75, P < .001), heart rate recovery (hazard ratio/SD 0.64, 95% CI 0.49-0.83, P < .001), and delta heart rate (hazard ratio/SD 0.75, 95% CI 0.63-0.91, P < .001). No exercise variables prognosticated MI, but coronary revascularization was predicted by stress-induced ST-segment deviations (hazard ratio 2.64, 95% CI 1.16-4.33, P < .001), limiting angina (hazard ratio 4.70, 95% CI 1.81-12.22, P < .001), and an abnormal perfusion imaging result (hazard ratio 2.0, 95% CI 1.14-3.51, P < .02). CONCLUSIONS: Arm exercise capacity, heart rate recovery, and delta heart rate predict 12-year all-cause mortality and arm exercise-induced ST changes, limiting angina, and an abnormal nuclear imaging result portend coronary revascularization in lower extremity disabled veterans.

CD8+ T-cell responses to different HIV proteins have discordant associations with viral load.

Selection of T-cell vaccine antigens for chronic persistent viral infections has been largely empirical. To define the relationship, at the population level, between the specificity of the cellular immune response and viral control for a relevant human pathogen, we performed a comprehensive analysis of the 160 dominant CD8(+) T-cell responses in 578 untreated HIV-infected individuals from KwaZulu-Natal, South Africa. Of the HIV proteins targeted, only Gag-specific responses were associated with lowering viremia. Env-specific and Accessory/Regulatory protein-specific responses were associated with higher viremia. Increasing breadth of Gag-specific responses was associated with decreasing viremia and increasing Env breadth with increasing viremia. Association of the specific CD8(+) T-cell response with low viremia was independent of HLA type and unrelated to epitope sequence conservation. These population-based data, suggesting the existence of both effective immune responses and responses lacking demonstrable biological impact in chronic HIV infection, are of relevance to HIV vaccine design and evaluation.

Household's willingness to pay for arsenic safe drinking water in Bangladesh.

This study examines willingness to pay (WTP) in Bangladesh for arsenic (As) safe drinking water across different As-risk zones, applying a double bound discrete choice value elicitation approach. The study aims to provide a robust estimate of the benefits of As safe drinking water supply, which is compared to the results from a similar study published almost 10 years ago using a single bound estimation procedure. Tests show that the double bound valuation design does not suffer from anchoring or incentive incompatibility effects. Health risk awareness levels are high and households are willing to pay on average about 5 percent of their disposable average annual household income for As safe drinking water. Important factors influencing WTP include the bid amount to construct communal deep tubewell for As safe water supply, the risk zone where respondents live, household income, water consumption, awareness of water source contamination, whether household members are affected by As contamination, and whether they already take mitigation measures.

Androgen Receptor Inhibitors in Patients With Nonmetastatic Castration-Resistant Prostate Cancer.

Importance: Novel androgen receptor inhibitors (ARIs; darolutamide, enzalutamide, and apalutamide) are standard-of-care treatments for nonmetastatic castration-resistant prostate cancer (nmCRPC). However, there are sparse data comparing their clinical use and tolerability. Objective: To compare clinical use and outcomes for darolutamide, enzalutamide, and apalutamide in patients with nmCRPC. Design, Setting, and Participants: This retrospective cohort study reviewed electronic medical records from the Precision Point Specialty network of US urology practices. Eligible patients had nmCRPC and no prior novel hormonal therapy and initiated novel ARI treatment between August 1, 2019, and March 31, 2022. Data were analyzed from February 1, 2019, to December 31, 2022. Exposures: Patients were prescribed darolutamide, enzalutamide, or apalutamide as their first novel ARI for nmCRPC. Main Outcomes and Measures: The main outcome was a composite of 2 end points, treatment discontinuation and progression to metastatic CRPC (mCRPC), whichever occurred first. Both end points were also assessed separately. Results: All 870 patients meeting eligibility criteria were included (362 receiving darolutamide [41.6%]; 382, enzalutamide [43.9%]; 126, apalutamide [14.5%]); mean (SD) age was 78.8 (8.7) years. Self-reported race was Black or African American in 187 patients (21.5%), White in 585 (67.2%), and other or unknown in 98 (11.3%). The darolutamide cohort had lower proportions of patients with a composite end point event (134 [37.0%] vs 201 [52.6%] for enzalutamide and 66 [52.4%] for apalutamide), discontinuation (110 [30.4%] for darolutamide vs 156 [40.8%] for enzalutamide and 58 [46.0%] for apalutamide), and progression to mCRPC (64 [17.7%] for darolutamide vs 108 [28.3%] for enzalutamide and 35 [27.8%] for apalutamide) during the study period. After adjusting for baseline covariates, patients receiving darolutamide had a lower risk of a composite end point event compared with enzalutamide (risk reduction, 33.8%; hazard ratio [HR], 0.66 [95% CI, 0.53-0.84]) and apalutamide (risk reduction, 35.1%; HR, 0.65 [95% CI, 0.48-0.88]). Similarly, patients receiving darolutamide had a lower risk of discontinuation compared with enzalutamide (risk reduction, 27.4%; HR, 0.73 [95% CI, 0.56-0.94]) and apalutamide (risk reduction, 39.1%; HR, 0.61 [95% CI, 0.44-0.85]) and a lower risk of progression to mCRPC compared with enzalutamide (risk reduction, 40.6%; HR, 0.59 [95% CI, 0.43-0.82]) and apalutamide (risk reduction, 35.3%; HR, 0.65 [95% CI, 0.42-0.99]). There was no difference between enzalutamide and apalutamide treatment across outcomes. Conclusions and Relevance: In this large cohort study of patients with nmCRPC treated with novel ARIs, results suggest better tolerability for darolutamide compared with enzalutamide and apalutamide, which may be associated with a clinical effectiveness advantage. Comparative clinical studies are needed to guide treatment decisions in the absence of head-to-head clinical trials.

Integration of population genetics with oceanographic models reveals strong connectivity among coral reefs across Seychelles.

Many countries with tropical reef systems face hard choices preserving coral reefs in the face of climate change on limited budgets. One approach to maximising regional reef resilience is targeting management efforts and resources at reefs that export large numbers of larvae to other reefs. However, this requires reef connectivity to be quantified. To map coral connectivity in the Seychelles reef system we carried out a population genomic study of the Porites lutea species complex using 241 sequenced colonies from multiple islands. To identify oceanographic drivers of this connectivity and quantify variability, we further used a 2 km resolution regional ocean simulation coupled with a larval dispersal model to predict the flow of coral larvae between reef sites. Patterns of admixture and gene flow are broadly supported by model predictions, but the realised connectivity is greater than that predicted from model simulations. Both methods detected a biogeographic dispersal barrier between the Inner and Outer Islands of Seychelles. However, this barrier is permeable and substantial larval transport is possible across Seychelles, particularly for one of two putative species found in our genomic study. The broad agreement between predicted connectivity and observed genetic patterns supports the use of such larval dispersal simulations in reef system management in Seychelles and the wider region.

The large key space image encryption algorithm based on modulus synchronization between real and complex fractional-order dynamical systems.

This paper constructs and analyzes the dynamical properties of a new fractional-order real hyper-chaotic system and its corresponding complex variable system. A thorough analysis was done by employing stability of equilibrium points, phase plots, Lyapunov spectrum, and bifurcation analysis for the consequences of varying fractional-order derivative and parameter values on the system. For the first time, a modulus synchronization scheme is proposed to synchronize real and complex fractional-order dynamical systems. Based on Lyapunov stability theory, non-linear controllers are designed to achieve the proposed modulus synchronization scheme. A new modulus synchronization encryption algorithm with a large key space size for digital images is introduced for the application. The experimental results and analysis validate the desired algorithm. Also, we compare our result of the new encryption algorithm with the previously published literature and verify the efficacy of the considered scheme. Numerical simulations are given to validate the theoretical analysis.

Arsenic speciation, oxidation and immobilization in an unsaturated soil in the presence of green synthesized iron oxide nanoparticles and humic acid.

While the availability of arsenic (As) in soil is well known to be highly correlated with the presence of iron (Fe) oxides and humic acid (HA) in the soil, the relationship between Fe oxides and HA and As species in the soil is less well understood. In this study, As speciation in an unsaturated soil in the presence of external HA and green synthesized Fe oxide nanoparticles (FeNPs) showed that As(V) was mainly distributed to the specifically-bound (F2), amorphous and poorly-crystalline hydrous oxides of Fe, Al (F3) and the well-crystallized hydrous oxides of Fe and Al (F4). While As(III). This was the major component in unsaturated soil, and was mainly distributed to F4 and the residual fraction (F5). As bound to F3 and F5 was most sensitive to the addition of HA and FeNPs, while HA/FeNPs treatment increased the F3-bound As(V); however, it decreased the F5-bound As(III). Nonetheless the effect of HA on As is completely different to the HA/FeNPs treatment. The increase of As(V) in F3 resulted from F5-bound As(III) oxidation when treated by HA/FeNPs. Cyclic voltammetry confirmed that HA and Fe3+/Fe2+ redox enhanced As(III) oxidation, while FTIR revealed that HA-bound As(III) was the least available fraction in the soil. Finally, a mechanism involving a combination of HA and FeNPs was proposed for explaining the redistribution of As species in the soil.

Differing natural killer cell, T cell and antibody profiles in antiretroviral-naive HIV-1 viraemic controllers with and without protective HLA alleles.

Previous work suggests that HIV controllers with protective human leukocyte antigen class I alleles (VC+) possess a high breadth of Gag-specific CD8+ T cell responses, while controllers without protective alleles (VC-) have a different unknown mechanism of control. We aimed to gain further insight into potential mechanisms of control in VC+ and VC-. We studied 15 VC+, 12 VC- and 4 healthy uninfected individuals (UI). CD8+ T cell responses were measured by ELISpot. Flow cytometry was performed to analyse surface markers for activation, maturation, and exhaustion on natural killer (NK) cell and T cells, as well as cytokine secretion from stimulated NK cells. We measured plasma neutralization activity against a panel of 18 Env-pseudotyped viruses using the TZM-bl neutralization assay. We found no significant differences in the magnitude and breadth of CD8+ T cell responses between VC+ and VC-. However, NK cells from VC- had higher levels of activation markers (HLA-DR and CD38) (p = 0.03), and lower cytokine expression (MIP-1ß and TNF-α) (p = 0.05 and p = 0.04, respectively) than NK cells from VC+. T cells from VC- had higher levels of activation (CD38 and HLA-DR co-expression) (p = 0.05), as well as a trend towards higher expression of the terminal differentiation marker CD57 (p = 0.09) when compared to VC+. There was no difference in overall neutralization breadth between VC+ and VC- groups, although there was a trend for higher neutralization potency in the VC- group (p = 0.09). Altogether, these results suggest that VC- have a more activated NK cell profile with lower cytokine expression, and a more terminally differentiated and activated T cell profile than VC+. VC- also showed a trend of more potent neutralizing antibody responses that may enhance viral clearance. Further studies are required to understand how these NK, T cell and antibody profiles may contribute to differing mechanisms of control in VC+ and VC-.

Vaginal Lactobacillus fatty acid response mechanisms reveal a novel strategy for bacterial vaginosis treatment.

Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related species, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the human vaginal microbiota and sequesters OA in a derivative form that only ohyA-harboring organisms can exploit. Finally, OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro model of BV, suggesting a novel approach for treatment.

Smoking cessation and its predictors: results from a community-based pharmacy tobacco cessation program in New Mexico.

BACKGROUND: The New Mexico Pharmaceutical Care Foundation received funding through the Tobacco Use Prevention and Control Program (TUPAC) to provide support for pharmacist-delivered tobacco cessation services. The goal of the program was to increase the availability of tobacco cessation services to residents of New Mexico. Program outcomes are presented, using data from the first 2 fiscal years. OBJECTIVE: To assess tobacco quit rates among smokers who participated in the community pharmacist-based program and identify the predictors of quitting at the end of a 6-month program. METHODS: Pharmacists, who had received Rx for Change training, provided tobacco cessation services. Patients were scheduled for an initial visit and then were seen at regularly scheduled follow-up visits at 1 month, 3 months, and 6 months from the initial visit. Data collected at the initial visit included demographics, smoking history, and readiness for quitting. Smoking status was collected at each of the follow-up visits. Data were analyzed using SAS (SAS Institute) and STATA (StataCorp LP) statistical software. Tobacco quit rates were calculated at 1, 3, and 6 months. Multivariate regression analysis was performed to assess predictors of quitting. Standard errors were adjusted for repeated observation. RESULTS: Data were available for 346 participants. The average quit rate at the end of 6 months was 25%. Significant predictors of quitting were high confidence levels in quitting at baseline, individuals who had first cigarettes at least 30 minutes after waking up, first cessation attempt, and nonwhite patients. CONCLUSIONS: A smoking cessation program delivered through trained community pharmacists with prescriptive authority is an effective approach to reducing smoking. Further research should be conducted to compare the effectiveness of pharmacists with that of other providers of tobacco cessation services.