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International audience ; Quantum dots (QDs) are colloidal fluorescent semiconductor nanocrystals with exceptional optical properties. Their widespread use, particularly in light-emitting diodes (LEDs), displays, and photovoltaics, is questioning their potential toxicity. The most widely used QDs are CdSe and CdTe QDs, but due to the toxicity of cadmium (Cd), their use in electrical and electronic equipment is now restricted in the European Union through the Restriction of hazardous substances in electrical and electronic equipment (RoHS) directive. This has prompted the development of safer alternatives to Cd-based QDs; among them, InP QDs are the most promising ones. We recently developed RoHS-compliant QDs with an alloyed core composed of InZnP coated with a Zn(Se,S) gradient shell, which was further coated with an additional ZnS shell to protect the QDs from oxidative surface degradation. In this study, the toxicity of single-shelled InZnP/Zn(Se,S) core/gradient shell and of double-shelled InZnP/Zn(Se,S)/ZnS core/shell/shell QDs was evaluated both in their pristine form and after aging in a climatic chamber, mimicking a realistic environmental weathering. We show that both pristine and aged QDs, whatever their composition, accumulate in the cytoplasm of human primary keratinocytes where they form agglomerates at the vicinity of the nucleus. Pristine QDs do not show overt toxicity to cells, while aged QDs show cytotoxicity and genotoxicity and significantly modulate the mRNA expression of proteins involved in zinc homeostasis, cell redox response, and inflammation. While the three aged QDs show similar toxicity, the toxicity of pristine gradient-shell QD is higher than that of pristine double-shell QD, confirming that adding a second shell is a promising safer-by-design strategy. Taken together, these results suggest that end-of-life degradation products from InP-based QDs are detrimental to skin cells in case of accidental exposure and that the mechanisms driving this effect are oxidative stress, ...

International audience ; Quantum dots (QDs) are colloidal fluorescent semiconductor nanocrystals with exceptional optical properties. Their widespread use, particularly in light-emitting diodes (LEDs), displays, and photovoltaics, is questioning their potential toxicity. The most widely used QDs are CdSe and CdTe QDs, but due to the toxicity of cadmium (Cd), their use in electrical and electronic equipment is now restricted in the European Union through the Restriction of hazardous substances in electrical and electronic equipment (RoHS) directive. This has prompted the development of safer alternatives to Cd-based QDs; among them, InP QDs are the most promising ones. We recently developed RoHS-compliant QDs with an alloyed core composed of InZnP coated with a Zn(Se,S) gradient shell, which was further coated with an additional ZnS shell to protect the QDs from oxidative surface degradation. In this study, the toxicity of single-shelled InZnP/Zn(Se,S) core/gradient shell and of double-shelled InZnP/Zn(Se,S)/ZnS core/shell/shell QDs was evaluated both in their pristine form and after aging in a climatic chamber, mimicking a realistic environmental weathering. We show that both pristine and aged QDs, whatever their composition, accumulate in the cytoplasm of human primary keratinocytes where they form agglomerates at the vicinity of the nucleus. Pristine QDs do not show overt toxicity to cells, while aged QDs show cytotoxicity and genotoxicity and significantly modulate the mRNA expression of proteins involved in zinc homeostasis, cell redox response, and inflammation. While the three aged QDs show similar toxicity, the toxicity of pristine gradient-shell QD is higher than that of pristine double-shell QD, confirming that adding a second shell is a promising safer-by-design strategy. Taken together, these results suggest that end-of-life degradation products from InP-based QDs are detrimental to skin cells in case of accidental exposure and that the mechanisms driving this effect are oxidative stress, ...

International audience ; Quantum dots (QDs) are colloidal fluorescent semiconductor nanocrystals with exceptional optical properties. Their widespread use, particularly in light-emitting diodes (LEDs), displays, and photovoltaics, is questioning their potential toxicity. The most widely used QDs are CdSe and CdTe QDs, but due to the toxicity of cadmium (Cd), their use in electrical and electronic equipment is now restricted in the European Union through the Restriction of hazardous substances in electrical and electronic equipment (RoHS) directive. This has prompted the development of safer alternatives to Cd-based QDs; among them, InP QDs are the most promising ones. We recently developed RoHS-compliant QDs with an alloyed core composed of InZnP coated with a Zn(Se,S) gradient shell, which was further coated with an additional ZnS shell to protect the QDs from oxidative surface degradation. In this study, the toxicity of single-shelled InZnP/Zn(Se,S) core/gradient shell and of double-shelled InZnP/Zn(Se,S)/ZnS core/shell/shell QDs was evaluated both in their pristine form and after aging in a climatic chamber, mimicking a realistic environmental weathering. We show that both pristine and aged QDs, whatever their composition, accumulate in the cytoplasm of human primary keratinocytes where they form agglomerates at the vicinity of the nucleus. Pristine QDs do not show overt toxicity to cells, while aged QDs show cytotoxicity and genotoxicity and significantly modulate the mRNA expression of proteins involved in zinc homeostasis, cell redox response, and inflammation. While the three aged QDs show similar toxicity, the toxicity of pristine gradient-shell QD is higher than that of pristine double-shell QD, confirming that adding a second shell is a promising safer-by-design strategy. Taken together, these results suggest that end-of-life degradation products from InP-based QDs are detrimental to skin cells in case of accidental exposure and that the mechanisms driving this effect are oxidative stress, ...

Quantum dots (QDs) are colloidal fluorescent semiconductor nanocrystals with exceptional optical properties. Their widespread use, particularly in light-emitting diodes (LEDs), displays, and photovoltaics, is questioning their potential toxicity. The most widely used QDs are CdSe and CdTe QDs, but due to the toxicity of cadmium (Cd), their use in electrical and electronic equipment is now restricted in the European Union through the Restriction of hazardous substances in electrical and electronic equipment (RoHS) directive. This has prompted the development of safer alternatives to Cd-based QDs; among them, InP QDs are the most promising ones. We recently developed RoHS-compliant QDs with an alloyed core composed of InZnP coated with a Zn(Se,S) gradient shell, which was further coated with an additional ZnS shell to protect the QDs from oxidative surface degradation. In this study, the toxicity of single-shelled InZnP/Zn(Se,S) core/gradient shell and of double-shelled InZnP/Zn(Se,S)/ZnS core/shell/shell QDs was evaluated both in their pristine form and after aging in a climatic chamber, mimicking a realistic environmental weathering. We show that both pristine and aged QDs, whatever their composition, accumulate in the cytoplasm of human primary keratinocytes where they form agglomerates at the vicinity of the nucleus. Pristine QDs do not show overt toxicity to cells, while aged QDs show cytotoxicity and genotoxicity and significantly modulate the mRNA expression of proteins involved in zinc homeostasis, cell redox response, and inflammation. While the three aged QDs show similar toxicity, the toxicity of pristine gradient-shell QD is higher than that of pristine double-shell QD, confirming that adding a second shell is a promising safer-by-design strategy. Taken together, these results suggest that end-of-life degradation products from InP-based QDs are detrimental to skin cells in case of accidental exposure and that the mechanisms driving this effect are oxidative stress, inflammation, and disturbance of cell ...

IntroductionThe costs of combination antiretroviral therapy (cART) consisting of separate, particularly generic, components are generally much lower than of a single tablet regimen (STR) including the same active ingredients. Our aim was to evaluate whether patients in care in the Netherlands would be willing to take separate component regimens (SCR) instead of an STR and to examine whether willingness was associated with particular patient characteristics.Materials and MethodsData from the HIV Monitoring Foundation of all adult HIV‐1‐infected patients in care taking cART>6 months were used to randomly select 1000 patients. As part of a questionnaire developed for a study assessing patient experience, patients were asked whether they were willing to take an SCR instead of an STR. Logistic regression was used to examine associations between age, gender, region of origin, mode of HIV transmission, socioeconomic status, duration of cART and answering "yes" to the question versus "maybe" or "no." Variables with p<0.1 in the univariate analysis were entered in a multivariate model.ResultsOf the 300 patients who completed the questionnaire, 49% answered "yes," 24% "maybe" and 27% "no" to the question whether they would be willing to use a SCR. Reasons for answering "no" included difficulties swallowing pills, convenience of STR (especially when travelling/at work), and concerns about side effects. Respondents who answered "maybe" often indicated that they preferred STRs, emphasized the importance of taking the pills once daily, and pointed out that efficacy/safety of an SCR should not be less. Having to pay for medication was reported as a reason to consider switching to an SCR. In the multivariate analysis, respondents who were born outside the Netherlands were less likely; and those with cART use ≥15 yrs were more likely to answer "yes" (Table 1).ConclusionsHalf of the respondents were willing to take SCRs instead of an STR. The likelihood of accepting to switch to SCR seems less for migrants and for those who have commenced treatment more recently. Duration of cART use and region of origin may therefore be factors to take into account when considering to prescribe SCR. Future studies should investigate whether an expressed willingness to switch will translate into maintained high levels of adherence and viral suppression.

IntroductionA recent meta‐analysis of 4 RCTs showed an increased rate of suicidality events (suicidal ideation or attempted/completed suicide) associated with efavirenz (EFV) compared to other regimens, but only a trend towards a higher rate of completed/attempted suicides, as only 17 events occurred. We investigated the association between EFV use and completed suicide.Materials and MethodsAll D:A:D participants were followed from study entry to the first of death, last study visit or 1 February 2013. Deaths are centrally validated using cause of death methodology, which assigns underlying, immediate and up to four contributing causes of death. Two endpoints were considered: 1) suicide or psychiatric disease as the underlying cause, and 2) suicide or psychiatric disease mentioned as an underlying, immediate or contributing cause of death (anywhere). Adjusted rate ratios were calculated using Poisson regression.ResultsA total of 4420 deaths occurred in 49,717 people over 371,333 person‐years (PY) (rate 11.9 per 1000 PY; 95% CI 11.6–12.3). A total of 193 deaths (rate 0.52; 0.45–0.59) had an underlying cause of suicide or psychiatric disease, and 482 deaths (1.30; 1.18–1.41) had suicide or psychiatric disease mentioned anywhere. A strong association with current CD4 count was seen: for suicide or psychiatric disease mentioned anywhere, rates were: 3.18 (2.55–3.80) for <200 cells/uL, 1.60 (1.29–1.90) for 201–350 cells/uL, 1.07 (0.86–1.29) for 351–500 cells/uL, 0.95 (0.80–1.09) for >500 cells/uL and 1.30 (1.18–1.41) for unknown. Highest rate of suicide or psychiatric deaths were seen in ART‐experienced people currently off ART, but no differences were seen according to current ART regimen, which remained after adjustment (Table 1). Consistent results were obtained when considering additional endpoints of suicide alone as the underlying cause and death from suicide or any possibly related cause (psychiatric disease, drug overdose, alcohol related, accidental or violent), as well as considering recent EFV use in the previous 3 and 6 months.ConclusionsThe finding of no higher death rates from suicide amongst those receiving EFV is reassuring. However, there is likely confounding by indication in our observational study. In light of conflicting results from RCTs, this potentially could suggest that in clinical practice EFV may be less frequently prescribed in those with underlying psychiatric conditions.

IntroductionProteinuria (PTU) is an important marker for the development and progression of renal disease, cardiovascular disease and death, but there is limited information about the prevalence and factors associated with confirmed PTU in predominantly white European HIV+ persons, especially in those with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2.Patients and methodsBaseline was defined as the first of two consecutive dipstick urine protein (DPU) measurements during prospective follow‐up >1/6/2011 (when systematic data collection began). PTU was defined as two consecutive DUP >1+ (>30 mg/dL) >3 months apart; persons with eGFR <60 at either DPU measurement were excluded. Logistic regression investigated factors associated with PTU.ResultsA total of 1,640 persons were included, participants were mainly white (n=1,517, 92.5%), male (n=1296, 79.0%) and men having sex with men (n=809; 49.3%). Median age at baseline was 45 (IQR 37–52 years), and CD4 was 570 (IQR 406–760/mm3). The median baseline date was 2/12 (IQR 11/11–6/12), and median eGFR was 99 (IQR 88–109 mL/min/1.73 m2). Sixty‐nine persons had PTU (4.2%, 95% CI 3.2–4.7%). Persons with diabetes had increased odds of PTU, as were those with a prior non‐AIDS [1] or AIDS event and those with prior exposure to indinavir. Among females, those with a normal eGFR (>90) and those with prior abacavir use had lower odds of PTU (Figure 1).There was no significant association between past or current use of tenofovir, lopinavir, atazanvir (boosted or unboosted) or any other boosted PI and PTU (p>0.2). During 688.2 person‐years of follow up (PYFU), three persons developed chronic kidney disease (CKD; confirmed [>3 months apart] eGFR<60); 2/685 (0.3%) without PTU and 1/38 (2.8%) with PTU (p=0.032). The crude incidence of CKD in those with baseline PTU and eGFR>60 was almost 10 times higher than in those without baseline PTU and eGFR>60 (rate ratio 9.61; 95% CI 0.87–105.9, p=0.065).ConclusionsOne in 25 persons with eGFR>60 had confirmed proteinuria at baseline. Factors associated with PTU were similar to those associated with CKD. The lack of association with antiretrovirals, particularly tenofovir, may be due to the cross‐sectional design of this study, and additional follow‐up is required to address progression to PTU in those without PTU at baseline. It may also suggest other markers are needed to capture the deteriorating renal function associated with antiretrovirals may be needed at higher eGFRs. Our findings suggest PTU is an early marker for impaired renal function.

IntroductionEuroSIDA has previously reported a poorer clinical prognosis for HIV‐positive individuals in Eastern Europe (EE) as compared with patients from other parts of Europe, not solely explained by differences in patient characteristics. We explored regional variability in self‐reported HIV management at individual EuroSIDA clinics, with a goal of identifying opportunities to reduce the apparent inequalities in health.MethodsA survey (www.chip.dk/eurosida/csurvey) on HIV management was conducted in early 2014 in all currently active EuroSIDA clinics. Responders in EE were compared with clinics in all other EuroSIDA regions combined (non‐EE). Characteristics were compared between regions using Fishers exact test.ResultsA total of 80/97 clinics responded (82.5%, 12/15 in EE, 68/82 in non‐EE). Participating clinics reported seeing a total of 133,532 patients [a median of 1300 per clinic (IQR 700–2399)]. The majority of clinics requested viral load and CD4 measurements at least every six months for patients on as well as off ART (EE 66.7%, non‐EE 75%, p=0,72). Significantly fewer EE clinics performed resistance tests before ART as well as upon treatment failure (Figure 1). Half of the EE clinics indicated following WHO guidelines (EE 50%, non‐EE 7.4%, p<0.0001), whereas most non‐EE clinics followed EACS guidelines (non‐EE 76.5%, EE 41.7%, p=0.017). The majority of EE clinics and ¼ non‐EE clinics indicated deferral of ART initiation in asymptomatic individuals until CD4 ≤350 cells/mm3 (Figure 1). There were no significant regional differences in screening haematology, liver or renal function, which the majority of clinics reported to do routinely. However, EE clinics reported screening significantly less for cardiovascular disease (CVD), and only about half screened for tobacco use, alcohol consumption and drug use (Figure 1). Screening for cervical cancer and for anorectal cancer was low in both regions (Figure 1).ConclusionsWe found significant regional variability in self‐reported HIV management across Europe, with less resistance testing, screening for CVD and substance use in EE. EE clinics indicated deferral of ART initiation for longer than non‐EE clinics. Adherence to international guidelines for cervical cancer screening was poor in both regions. Whether differences in HIV management are reflected in clinical outcomes deserves further investigation.

IntroductionThere is a lack of data on potential gender differences in the use of interventions to prevent and treat cardiovascular disease (CVD) in HIV‐positive individuals. We investigated whether such differences exist in the D:A:D study.Materials and MethodsFollow‐up was from 01/02/99 until the earliest of death, 6 months after last visit or 01/02/13. Rates of initiation of lipid‐lowering drugs (LLDs), angiotensin‐converting enzyme inhibitors (ACEIs), anti‐hypertensives and receipt of invasive cardiovascular procedures (ICPs; bypass, angioplasty, endarterectomy) were calculated in those without a myocardial infarction (MI) or stroke at baseline, overall and in groups known to be at higher CVD risk: (i) age >50, (ii) total cholesterol >6.2 mmol/l, (iii) triglyceride >2.3 mmol/l, (iv) hypertension, (v) previous MI, (vi) diabetes, or (vii) predicted 10‐year CVD risk >10%. Poisson regression was used to assess whether rates of initiation were higher in men than women, after adjustment for these factors.ResultsAt enrolment, women (n=13,039; median (interquartile range) 34 (29–40) years) were younger than men (n=36,664, 39 (33–46) years, p=0.001), and were less likely to be current smokers (29% vs. 39%, p=0.0001), to have diabetes (2% vs. 3%, p=0.0001) or to have hypertension (7% vs. 11%, p=0.0001). Of 49,071 individuals without a MI/stroke at enrolment, 0.6% women vs. 2.1% men experienced a MI while 0.8% vs. 1.3% experienced a stroke. Overall, women received ICPs at a rate of 0.07/100 person‐years (PYRS) compared to 0.29/100 PYRS in men. Similarly, the rates of initiation of LLDs (1.28 vs. 2.46), anti‐hypertensives (1.11 vs. 1.38) and ACEIs (0.82 vs. 1.37) were all significantly lower in women than men (Table 1). As expected, initiation rates of each intervention were higher in the groups determined to be at moderate/high CVD risk; however, within each high‐risk group, initiation rates of most interventions (with the exception of anti‐hypertensives) were generally lower in women than men. These gender differences persisted after adjustment for potential confounders (Table 1).ConclusionUse of most CVD interventions was lower among women than men in the D:A:D study. Our findings suggest that actions should be taken to ensure that both men and women are monitored for CVD and, if eligible, receive appropriate CVD interventions.