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Water quality, Endocrine disruptors, Marine pollution, and Sewage disposal plants

Endocrine disrupting compounds (EDCs) can be found in domestic sewage, wastewater treatment plant effluents, natural water, rivers, lakes and in the marine environment. Jurujuba Sound, located in the state of Rio de Janeiro, Southeastern Brazil, receives untreated sewage into its waters, one the main sources of aquatic contamination in this area. In this context, the aim of the present study was to evaluate the estrogenic potential of water sampled from different depths and from areas with differential contamination levels throughout Jurujuba Sound. Water quality was evaluated and acute toxicity assays using Allviibrio fischeri were conducted, while estrogenic activity of the water samples was determined by a Yeast Estrogen Screening assay (YES). Water quality was mostly within the limits established for marine waters by the Brazilian legislation, with only DOC and ammoniacal nitrogen levels above the maximum permissible limits. No acute toxicity effects were observed in the Allivibrio fisheri assay. The YES assay detected moderate estrogenic activity in bottom water samples from 3 sampling stations, ranging from 0.5 to 3.2 ng L −1 , as well as in one surface water sample. Estrogenic activity was most frequently observed in samples from the bottom of the water column, indicating adsorption of estrogenic compounds to the sediment. [ABSTRACT FROM AUTHOR]

Water treatment plants, Ozonization, Estrogen, Hydrological research, and Yeast

The estrogenicity of waters collected from an important hydrological system in Brazil (Paraiba do Sul and Guandu Rivers) was assessed using the yeast estrogen screen (YES) assay. Sampling was performed in rivers and at the outlets of conventional water treatment plants (WTP). The removal of estrogenic activity by ozonation and chlorination after conventional water treatment (clarification and sand filtration) was investigated employing samples of the Guandu River spiked with estrogens and bisphenol A (BPA). The results revealed a preoccupying incidence of estrogenic activity at levels higher than 1 ng L −1 along some points of the rivers. Another matter of concern was the number of samples from WTPs presenting estrogenicity surpassing 1 ng L −1 . The oxidation techniques (ozonation and chlorination) were effective for the removal of estrogenic activity and the combination of both techniques led to good results using less amounts of oxidants. [ABSTRACT FROM AUTHOR]

Pollination, Agricultural productivity, Crop yields, Sustainable agriculture, Pollinators, Apple orchards, Factorial experiment designs, and Orchards

The alarming loss of pollinator diversity world‐wide can reduce the productivity of pollinator‐dependent crops, which could have economic impacts. However, it is unclear to what extent the loss of a key native pollinator species affects crop production and farmer's profits.By experimentally manipulating the presence of colonies of a native bumblebee species Bombus pauloensis in eight apple orchards in South Argentina, we evaluated the impact of losing natural populations of a key native pollinator group on (a) crop yield, (b) pollination quality, and (c) farmer's profit. To do so, we performed a factorial experiment of pollinator exclusion (yes/no) and hand pollination (yes/no).Our results showed that biotic pollination increased ripe fruit set by 13% when compared to non‐biotic pollination. Additionally, fruit set and the number of fruits per apple tree was reduced by less than a half in those orchards where bumblebees were absent, even when honeybees were present at high densities. Consequently, farmer's profit was 2.4‐fold lower in farms lacking bumblebees than in farms hosting both pollinator species. The pollination experiment further suggested that the benefits of bumblebees could be mediated by improved pollen quality rather than quantity.Synthesis and applications. This study highlights the pervasive consequences of losing key pollinator functional groups, such as bumblebees, for apple production and local economies. Adopting pollinator‐friendly practices such as minimizing the use of synthetic inputs or restoring/maintaining semi‐natural habitats at farm and landscape scales, will have the double advantage of promoting biodiversity conservation, and increasing crop productivity and profitability for local farmers. Yet because the implementation of these practices can take time to deliver results, the management of native pollinator species can be a provisional complementary strategy to increase economic profitability of apple growers in the short term. [ABSTRACT FROM AUTHOR]

The contamination of water sources by pharmaceutically active compounds (PhACs) and their effect on aquatic communities and human health have become an environmental concern worldwide. Membrane bioreactors (MBRs) are an alternative to improve biological removal of recalcitrant organic compounds from municipal sewage. Their efficiency can be increased by using high retention membranes such as forward osmosis (FO) and membrane distillation (MD). Thus, this research aimed to evaluate the performance of an anaerobic osmotic MBR coupled with MD (OMBR-MD) in the treatment of municipal sewage containing PhACs and estrogenic activity. A submerged hybrid FO-MD module was integrated into the bioreactor. PhACs removal was higher than 96% due to biological degradation, biosorption and membrane retention. Biological removal of the PhACs was affected by the salinity build-up in the bioreactor, with reduction in biodegradation after 32 d. However, salinity increment had little or no effect on biosorption removal. The anaerobic OMBR-MD removed >99.9% of estrogenic activity, resulting in a distillate with 0.14 ng L−1 E2-eq, after 22 d, and 0.04 ng L−1 E2-eq, after 32 d. OMBR-MD treatment promoted reduction in environmental and human health risks from high to low, except for ketoprofen, which led to medium acute environmental and human health risks. Carcinogenic risks were reduced from unacceptable to negligible, regarding estrogenic activity. Thus, the hybrid anaerobic OMBR-MD demonstrated strong performance in reducing risks, even when human health is considered. [Display omitted] • Biological removal of estrogenic compounds was governed mainly by biodegradation. • Biological removal of micropollutants (MP) was affected by the salinity build-up. • MgCl 2 as draw solute reduced the negative impacts on biological removal of MP. • Ketoprofen in distillate led to medium acute environmental and human health risks. • Carcinogenic risk, regarding estrogenicity, reduced from unacceptable to negligible. [ABSTRACT FROM AUTHOR]

ATHLETES, FATIGUE (Physiology), PHYSICAL education, QUESTIONNAIRES, and SPORTS medicine

Abstract: Objective. – The group of consensus of the French Society of Sport Medicine prepared a questionnaire in order to detect early stage of overtraining. This questionnaire includes 54 items which the subjects have to answer by “yes” or by “not”. A score is then established by summing the “yes”. Taking into account the formulation of the questions, this score will increase with the training load. The aim of our study is to propose a score of overtraining, and also to highlight the importance of some items or groups of items. Methods. – Our population consisted of French sportsmen of both sexes, from different geographical origins, age, sporting practice and level. A multicentric analysis was carried out on the basis of 1984 collected questionnaires. We analysed the evolution of the percentage of subjects, the weight of various parameters (age, overtraining) and the evolution of the frequency of each item as a function of the score. Results. – A score of 20 was proposed as an overtraining state threshold, which has to be confirmed on the basis of correlations with biological indices, in particular with a state of clinically established overtraining. Sixteen items present a linear evolution traducing an increase of tiredness according to the overload. Six items have a logarithmic increase, traducing a kind of “background noise”. The others items (N =32) presenting a non-linear increase are sign of a decompensation phenomenon. Conclusion. – This analysis by item make possible an improve of the questionnaire, by selecting items groups which may give an orientation on the type of tiredness. It also confirms the usefulness of this questionnaire as a tool for the follow-up of the training state of sportsmen, a score equal to or higher than 20 constituting the overtraining threshold. [Copyright &y& Elsevier]

Wastewater treatment, Sewage purification, Sewage disposal plants, Yeast-free diet, Leavening agents, and Fire assay

Effluents from wastewater treatment plants (WWTPs) are responsible for the input of estrogenic contaminants into aquatic ecosystems, leading to widespread effects in wildlife. In the present work, levels of estrone (E1), 17α- and 17β-estradiol (E2), 17α-ethinylestradiol (EE2), bisphenol A (BPA), and nonylphenol (NP) were quantified in effluents from WWTPs located in Ria de Aveiro (NW Portugal), as well as in the final effluent discharged into the Atlantic Ocean through the S. Jacinto submarine outfall. Reference sites, located at the entrance of the estuarine system and at the seaside, were also included. Samples were collected under summer (June 2005) and winter (February 2006) conditions. For the summer survey samples, estrogenicity and androgenicity were evaluated using the yeast estrogen screen (YES) and the yeast androgen screen (YAS) assay. Estrone levels varied from 0.5 to 85 ng/L in the summer survey and between L in winter; estradiol levels ranged from L in summer and were always L up to 2,350 ng/L in summer and from 10 to 2,410 ng/L in winter; BPA levels varied from 2.8 to 897 ng/L in summer and from 2.6 up to 316 ng/L in winter. Biological assays disclosed estrogenic levels at reference sites lower than the ones reported to pose risk for wildlife. However, the S. Jacinto outfall effluent released high concentrations of NP and BPA into the marine environment. [ABSTRACT FROM AUTHOR]

BIPOLAR disorder, MENTAL depression, DEPRESSED persons, ANTIPSYCHOTIC agents, and MENTAL health

Abstract: Introduction: Although depressive moods are recognised as a very broad condition, there is still only one definition in international classifications for describing a major depressive episode (MDE). However, there is currently some controversy surround the treatment of depressive states. This includes SSRIs and suicide in adolescents, and more specifically in bipolar disorders where some depressions are made worse by antidepressants. New data has suggested that depressive states in BP patients can be improved by atypical antipsychotics. Aim: We aimed to assess 1) whether it is possible to distinguish different forms of bipolar depression using a dimensional approach, and 2) if, yes, whether there are different patterns of treatment response. Method: We characterised 60 bipolar patients with a Major Depressive Episode (DSM-IV) using a new tool (MATHYS: Multidimensional Assessment of Thymic States) assessing five fundamental dimensions (emotional reactivity, cognitive speed, psycho-motricity, motivation and senses perception) of mood states (full description elsewhere). Results: A cluster analysis using the items of the dimensional scale revealed two types of depressive states. One group (G1; N =38), which had a low score, is characterised by an inhibition in all dimensions, whereas the other group (G2; N =22) is characterised by an over-activation. Emotional reactivity is a useful dimension for discriminating these two types of depression (G1: hyporeactivity; G2: hyperreactivity) whereas sadness is not. A lower score on the MAThyS scale at day 1 was associated with a good response to antidepressant treatment, whereas higher scores were linked to a good response to a mood stabilizers alone or in combination with an antipsychotic. Conclusion: Bipolar depressive states are not homogeneous and this heterogeneity can explain various patterns of treatment response. A dimensional approach could be useful for discriminating the different forms of bipolar depression and to help manage treatment. [Copyright &y& Elsevier]

ETHICS, PSYCHIATRISTS, MENTAL health personnel, PSYCHIATRY, and PSYCHOTHERAPISTS

Abstract: In legal proceedings the expert witness testimony may be considered a medical act only if the expert conducts his clinical observations within the limits established by the medical code of ethics. This will then allow the psychiatrist to help the judge reach a more informed legal decision. The difficulty inherent in this process is for the expert to give an exact answer (“yes” or “no”) to the questions formulated in order for the judge to arrive at an accurate decision. To better understand the evidence presented, the judge may ask empirical questions that require the expert witness to give testimony going beyond the information directly gathered through clinical observations. It is the expert witness'' responsibility to determine what amount of interpretation of material drawn from a clinical observation is appropriate to help the judge make a legal decision. This requires defining legal standards such as credibility, truth, and suggestibility. One must also recognize that the clinical observation of a victim is often the person''s first contact with a psychiatrist. [Copyright &y& Elsevier]

Health risk assessment, Endocrine disruptors, Water purification, Water supply, and Drinking water quality

Endocrine disrupting chemicals (EDCs) are ubiquitous in the environment and have been detected in drinking water from various countries. Although various water treatment processes can remove EDCs, chemicals can also migrate from pipes that transport water and contaminate drinking water. This study investigated the estrogenic activity in drinking water from various distribution points in Pretoria (City of Tshwane) (n = 40) and Cape Town (n = 40), South Africa, using the recombinant yeast estrogen screen (YES) and the T47D-KBluc reporter gene assay. The samples were collected seasonally over four sampling periods. The samples were also analysed for bisphenol A (BPA), nonylphenol (NP), di(2-ethylhexyl) adipate (DEHA), dibutyl phthalate (DBP), di(2-ethylhexyl) phthalate (DEHP), diisononylphthalate (DINP), 17β-estradiol (E 2 ), estrone (E 1 ) and ethynylestradiol (EE 2 ) using ultra-performance liquid chromatography-tandem mass spectrophotometry (UPLC-MS/MS). This was followed by a scenario based health risk assessment to assess the carcinogenic and toxic human health risks associated with the consumption of distribution point water. None of the water extracts from the distribution points were above the detection limit in the YES bioassay, but the EEq values ranged from 0.002 to 0.114 ng/L using the T47D-KBluc bioassay. BPA, DEHA, DBP, DEHP, DINP E 1 , E 2, and EE 2 were detected in distribution point water samples. NP was below the detection limit for all the samples. The estrogenic activity and levels of target chemicals were comparable to the levels found in other countries. Overall the health risk assessment revealed acceptable health and carcinogenic risks associated with the consumption of distribution point water. [ABSTRACT FROM AUTHOR]

For the development of the subject we first need the concept of constitutional state -aluding to its substantive distancing with the old rule of law-, and seeking its direct entanglement with a broad democratic order, yes, in Colombia, impaired with the continuity of the everlasting reformist custom of the Political Charter, basically along the way of art. 375 constitutional (and mainly on initiative or with the endorsement of the executive in office), which, for that task, the referred rule empowers the Congress of the Republic through the figure of legislative acts. Next (point 2), we alluded to tht' theme of the different constitutional reforms that have cracked the text of the Charter, and on them we need and develop (point 3), in our opinion, one of the most reactionary reforms, if not the most, altering the precarious state legitimacy achieved with the issuance of the Constitution itself. We refer here to the detriment that, by different legal paths, the democratic figure of the administrative career has suffered. In this last aspect we specify the obstinacy of the Uribe Velez period for depreciating and despising the importance of the institution of merit in the public service; inheritance received by the Santos government, trying to give continuity. [ABSTRACT FROM AUTHOR]

Environmental monitoring, Water pollution measurement, Water quality monitoring, Biological assay, Xenoestrogens, Analytical chemistry techniques, In vitro toxicity testing, and Evaluation

Bioassays are well established in the pharmaceutical industry and single compound analysis, but there is still uncertainty about their usefulness in environmental monitoring. We compared the responses of five bioassays designed to measure estrogenic activity (the yeast estrogen screen, ER-CALUX, MELN, T47D-KBluc, and E-SCREEN assays) and chemical analysis on extracts from four different water sources (groundwater, raw sewage, treated sewage, and river water). All five bioassays displayed similar trends and there was good agreement with analytical chemistry results. The data from the ER-CALUX and E-SCREEN bioassays were robust and predictable, and well-correlated with predictions from chemical analysis. The T47D-KBluc appeared likewise promising, but with a more limited sample size it was less compelling. The YES assay was less sensitive than the other assays by an order of magnitude, which resulted in a larger number of nondetects. The MELN assay was less predictable, although the possibility that this was due to laboratory-specific difficulties cannot be discounted. With standardized bioassay data analysis and consistency of operating protocols, bioanalytical tools are a promising advance in the development of a tiered approach to environmental water quality monitoring. [ABSTRACT FROM AUTHOR]

Sewage disposal plants, Sewage purification, Refuse disposal facilities, Environmental impact charges, Water quality management, Water utilities, Hospitals, Steroids, and Hormones

Influent and effluent samples originating from two wastewater treatment plants (WWTPs) (treating hospital wastewater and domestic wastewater, Belgium) have been analyzed in order to estimate their steroid hormone content. The natural estrogens estrone (E1), 17β-estradiol (E2), and the synthetic 17α-ethinylestradiol (EE2) together with other steroid hormones progesterone (P) and testosterone (T) metabolites were detected in these samples. The hormone concentrations in both the hospital and the domestic WWTP samples were not significantly different and ranged from <0.2 ng EE2/L to 114 ng EE2/L, from <0.2 ng E1/L to 58 ng E1/L and from <0.2 ng P/L to >100 ng P/L. E2 was detected once at a concentration of 17 ng/L. In the domestic WWTP which comprises a conventional activated sludge treatment in parallel with a membrane bioreactor, no differences in estrogen removal efficiency could be observed for both treatments. In comparison to chemical analysis data, the Yeast Estrogen Screen (YES) appears to underestimate the influent estrogen concentrations, probably due to influent toxicity for the YES. Effluent estrogen concentrations, on the other hand, were overestimated by the YES test, probably due to the presence of other estrogenic compounds in the effluent. [ABSTRACT FROM AUTHOR]

Organic water pollutants, Particulate matter, Endocrine disruptors, Sewage disposal plants, and Estrogen

Trace emerging contaminants (ECs) occur in both waste and surface waters that are rich in particulates that have been found to sorb several organic contaminants. An analytical method based on off-line solid-phase extraction (SPE) followed by liquid chromatography-mass spectrometry (LC-MS) analysis was developed for the detection and quantification of 31 ECs from surface water, wastewater, suspended particulate matter (SPM) as well as sediments. Lyophilized sediments and air-dried SPM were subjected to ultrasonic extraction. Water samples and extracts were then concentrated and cleaned-up by off-line SPE. Quantification was realized using a Q Exactive mass spectrometer in both full scan (FS) and MS 2 modes. These two modes were optimized and compared to determine which one was the most suitable for each matrix studied. Yeast estrogen screen assay (YES-assay) adapted from the direct measurement of estrogenic activity without sample extraction was tested on filtered wastewater samples. An endocrine disrupting effect was detected in all effluent samples analyzed with estradiol equivalent concentrations ranging from 4.4 to 720 ng eq E2 L −1 for the WWTP-1 and 6.5–42 ng eq E2 L −1 for the WWTP-2. The analytical methods were also applied on six samples of surface water, the corresponding SPM, the sediments and thirty-nine effluent samples from two wastewater treatment plants (WWTPs) sampled over a period of five months (February to June 2014). [ABSTRACT FROM AUTHOR]

ANESTHESIA, PLACEBOS, ETOMIDATE, and HEART beat

Abstract: Objective: Various drugs including hydroxyzine are preoperatively administered to facilitate the induction of general anaesthesia. We investigated the effect of hydroxyzine premedication on BIS-based etomidate induction of general anaesthesia. Patients and methods: Sixty-seven ASA I–II consecutive patients were randomly allocated to receive oral hydroxyzine 1.5 mg/kg or placebo, 90 min prior to inducing general anaesthesia using intravenous etomidate alone 0.3 mg/kg. BIS values were continuously recorded. The times for the BIS to decrease to 50 and to loss of eyelid reflex; the evolution of arterial pressure and heart rate; and myoclonia rate and grade were investigated and compared. Results: The results for the hydroxyzine and placebo groups were similar with respect to: a) time [median (range) (seconds)] to a BIS decrease to 50 [100 (21–266) versus 113 (30–510), P =0.1] and to loss of eyelid reflex [83 (21–210) versus 97 (30–300), P =0.1]; b) myoclonia frequency (yes/no) (9/26 versus 4/28, P =0.2) and grade (P =0.3); the evolution of mean arterial pressure and heart rate (P =0.3). Conclusion: Oral weight-related hydroxyzine premedication does not alter BIS-based etomidate induction of GA. [Copyright &y& Elsevier]

Corbicula fluminea, Caffeine, Ibuprofen, Carbamazepine, Novobiocin, Tamoxifen, DNA damage, and Oxidative stress

Reports indicating the presence of pharmaceutical in fresh water environment in the ng L −1 to µg L −1 range are occurring with increasing frequency. It is also a fact that pharmaceuticals may produce adverse effects on aquatic organisms. Nevertheless, there is still a lack of knowledge regarding how these emergent contaminants may affect aquatic biota. The goal of this research was to evaluate the sublethal responses in Corbicula fluminea such as, general stress (lysosomal membrane stability [LMS]), biomarkers of phase I and II (etoxyresorufin O-deethylase [EROD], dibenzylfluorescein dealkylase [DBF], gluthathione-S-transferase [GST]), oxidative stress (gluthathione reductase [GR], gluthathione peroxidase [GPX], lipid peroxidation [LPO]), and biomarkers of effect (DNA damage) after 21 days of exposure to caffeine, ibuprofen, carbamazepine, novobiocin and tamoxifen at 0.1, 1, 5, 10, 15, 50 µg L −1 . Environmental concentrations tested in this study caused general stress and produced changes on biomarkers tested. LMS, responses from phase I and II enzymatic activity, oxidative stress, and biomarker of effect represent important ecotoxicological information, and will provide a useful reference for the assessment of selected drugs and the effects which these compounds may have on aquatic invertebrates, using C. fluminea as a bioindicator species. [ABSTRACT FROM AUTHOR]

Humic acid, Pollutants, Sewage disposal plants, Endocrine disruptors, Humus, Complex matrices, and Xenoestrogens

The presence of estrogenic endocrine disruptors in aquatic environments has been a concern and bioassays are recommended tools for their monitoring. However, the physicochemical properties of contaminants and the environmental matrix features may influence the resultant response. This study aimed to assess this influence on the Yeast Estrogen Screen (YES) assay. Mixtures of 17β-estradiol (E2) and humic acid (HA) were evaluated through the Schild approach aiming to investigate the interactions between estrogens and dissolved organic matter (DOM). Moreover, environmental samples from municipal landfill leachate and wastewater treatment plant (WWTP) influents and effluents were screened for (anti)estrogenic activity at both dissolved and particulate phases. Finally, results were statistically confronted with physicochemical parameters through principal component analysis (PCA). The HA test concentrations strongly reduced the E2 response, even at low levels. Humic substances may not only reduce estrogen bioavailability, but also interfere with the assay mechanism through enzymatic inhibition thus masking the sample estrogenic potential. Landfill leachate had total E2-Eq in the range 1282–2591 ng L−1, while WWTP influent and effluent were in the range 12.1–41.4 and L−1, so estrogenicity was reduced 92% in average. Particulate phase was responsible for 33–100% of measured E2-Eq between matrices, though cytotoxicity occurred in some extracts. Antiestrogenic activity was observed in both phases and might also have masked the estrogenicity of samples. PCA did not resulted in positive correlations supporting a multiphase distribution pattern of estrogenic compounds. Nevertheless, the solids and organic matter characteristics supported the data interpretation. In conclusion, the in vitro YES assay is subjected to factors intrinsic to the environmental sample that can influence on the measured estrogenic response. Therefore, results interpretation should be performed together with organic matter characterization parameters, cytotoxicity and antiestrogenic activity evaluation. [Display omitted] • Humic acid induces strong antagonistic effect in the Yeast Estrogen Screen. • Landfill leachate, WWTP influents and effluents were highly estrogenic. • Cytotoxicity was recurrently associated with particles >0.7 μm. • DOM, antiestrogenic activity and phase distribution influenced on estrogenic response. [ABSTRACT FROM AUTHOR]

Environmental monitoring, Environmental quality, Sediments, Extraction (Chemistry), Atmospheric chemistry, and Mixtures

Aquatic environments are often contaminated with complex mixtures of chemicals that may pose a risk to ecosystems and human health. This contamination cannot be addressed with target analysis alone but tools are required to reduce this complexity and identify those chemicals that might cause adverse effects. Effect-directed analysis (EDA) is designed to meet this challenge and faces increasing interest in water and sediment quality monitoring. Thus, the present paper summarizes current experience with the EDA approach and the tools required, and provides practical advice on their application. The paper highlights the need for proper problem formulation and gives general advice for study design. As the EDA approach is directed by toxicity, basic principles for the selection of bioassays are given as well as a comprehensive compilation of appropriate assays, including their strengths and weaknesses. A specific focus is given to strategies for sampling, extraction and bioassay dosing since they strongly impact prioritization of toxicants in EDA. Reduction of sample complexity mainly relies on fractionation procedures, which are discussed in this paper, including quality assurance and quality control. Automated combinations of fractionation, biotesting and chemical analysis using so-called hyphenated tools can enhance the throughput and might reduce the risk of artifacts in laboratory work. The key to determining the chemical structures causing effects is analytical toxicant identification. The latest approaches, tools, software and databases for target-, suspect and non-target screening as well as unknown identification are discussed together with analytical and toxicological confirmation approaches. A better understanding of optimal use and combination of EDA tools will help to design efficient and successful toxicant identification studies in the context of quality monitoring in multiply stressed environments. [ABSTRACT FROM AUTHOR]

ANTIBIOTICS, MOLECULES, PHARMACEUTICAL industry, SCIENCE, and CLINICAL trials

Abstract: The golden age of antibacterial antibiotics extend from year 1941 to the 1990s decade. At that time, something like an earth quake occurred: from the thirty molecules or so whose development was being achieved or was already marketed, only three were put on the French market, and faced the greatest difficulties to be prescribed by practicians, because: [-] the knights of good practice want a strict limitation of their use to precise indications; [-] the pharmaceutical companies find that the return on investment is almost impossible; [-] the prescribers are stunned by the inconsistency between the MAs, the advances in science and the health economic authorities advices which claim that these products are not very interesting; [-] the research for new antibiotics is stalling; [-] thus, for the first time in 60 years, an iconoclastic question arises: do we need new antibiotics? However, while the debate is raging, many of us think “yes we do”, as it is a duty to anticipate today the consequences of tomorrow''s bacterial resistances. This paper presents three types of propositions to optimise the development of future molecules: [-] sharpening of the data concerning preclinical security for a better predicting both the activity and the toxicity; [-] improvement in performances and organization of clinical trials, which implicates to reconsider some of the present methodological rules; [-] inclusion in the evaluation data of some relevant and new features measuring the anti-bacterial activity while taking into account the present and future bacterial resistances. The development of new concepts to develop new drugs which would be active against tomorrow''s bacteria compels us to manage in a new fashion today''s systems, which have reached their own limits. [Copyright &y& Elsevier]