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Public health preparedness for coronavirus (CoV) disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal CoVs (sCoVs) and other cocirculating viruses in the West of Scotland, United Kingdom. We analyzed routine diagnostic data for >70 000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43, and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently, and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.

BB0405 is a surface exposed Borrelia burgdorferi protein and its vaccination protected mice against B. burgdorferi infection. As BB0405 is highly conserved across different B. burgdorferi sensu lato species, we investigated whether vaccination with recombinant BB0405 or through intradermal bb0405 DNA tattoo vaccination could provide protection against different Borrelia species, specifically against Borrelia afzelii, the predominant B. burgdorferi sensu lato genospecies causing Lyme borreliosis across Eurasia. We immunized C3H/HeN mice with recombinant BB0405 or with a codon-optimized bb0405 DNA vaccine using the pVAC plasmid and immunized corresponding control groups mice with only adjuvant or empty vectors. We subsequently subjected these immunized mice to a tick challenge with B. afzelii CB43-infected Ixodes ricinus nymphs. Upon vaccination, recombinant BB0405 induced a high total IgG response, but bb0405 DNA vaccination did not elicit antibody responses. Both vaccine formulations did not provide protection against Borrelia afzelii strain CB43 after tick challenge. In an attempt to understand the lack of protection of the recombinant vaccine, we determined expression of BB0405 and showed that B. afzelii CB43 spirochetes significantly and drastically downregulate the expression of BB0405 protein at 37 °C compared to 33 °C, where as in B. burgdorferi B31 spirochetes expression levels remain unaltered. Vaccination with recombinant BB0405 was previously shown to protect against B. burgdorferi sensu stricto. Here we show that vaccination with either recombinant BB0405 (or non-immunogenic bb0405 DNA), despite being highly conserved among B. burgdorferi sl genospecies, does not provide cross-protection against B. afzelii, mostly likely due to downregulation of this protein in B. afzelii in the mammalian host.

Modelling the small-area spatio-temporal dynamics of the Covid-19 pandemic is of major public health importance, because it allows health agencies to better understand how and why the virus spreads. However, in Scotland during the first wave of the pandemic testing capacity was severely limited, meaning that large numbers of infected people were not formally diagnosed as having the virus. As a result, data on confirmed cases are unlikely to represent the true infection rates, and due to the small numbers of positive tests these data are not available at the small-area level for confidentiality reasons. Therefore to estimate the small-area dynamics in Covid-19 incidence this paper analyses the spatio-temporal trends in telehealth data relating to Covid-19, because during the first wave of the pandemic the public were advised to call the national telehealth provider NHS 24 if they experienced symptoms of the virus. Specifically, we propose a multivariate spatio-temporal correlation model for modelling the proportions of calls classified as either relating to Covid-19 directly or having related symptoms, and provide software for fitting the model in a Bayesian setting using Markov chain Monte Carlo simulation. The model was developed in partnership with the national health agency Public Health Scotland, and here we use it to analyse the spatio-temporal dynamics of the first wave of the Covid-19 pandemic in Scotland between March and July 2020, specifically focusing on the spatial variation in the peak and the end of the first wave.

Aim: The aim of this Systematic Review is to compare the survival rate of teeth autotransplantation with immediate implant placement in cases of singular loss of teeth and obtain a clinical recommendation for similar cases. Materials And Methods: The research will be conducted by two independent reviewers in PubMed search and it will include studies from January 2017 to December 2020.The survival rate of both immediate implant placement and tooth autotransplantation will be evaluated in different follow-up times and the information compiled in several metaanalyses.

The I‐MOVE‐COVID‐19 network has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement no 101003673. Background : Claims of influenza vaccination increasing COVID-19 risk are circulating. Within the I-MOVE-COVID-19 primary care multicentre study, we measured the association between 2019-20 influenza vaccination and COVID-19. Methods : We conducted a multicentre test-negative case-control study at primary care level, in study sites in five European countries, from March to August 2020. Patients presenting with acute respiratory infection were swabbed, with demographic, 2019-20 influenza vaccination and clinical information documented. Using logistic regression, we measured the adjusted odds ratio (aOR), adjusting for study site and age, sex, calendar time, presence of chronic conditions. The main analysis included patients swabbed ≤7 days after onset from the three countries with

2018/19 was the first season of introduction of a newly licensed adjuvanted influenza vaccine (aTIV) for adults aged 65 years and over and the sixth season in the roll-out of a childhood influenza vaccination programme with a quadrivalent live attenuated influenza vaccine (LAIV). The season saw mainly A(H1N1)pdm09 and latterly A(H3N2) circulation. End-of-season adjusted vaccine effectiveness (aVE) estimates against laboratory confirmed influenza infection in primary care were calculated using the test negative case control method adjusting for key confounders. End-of-season aVE was 44.3% (95% CI: 26.8, 57.7) against all laboratory-confirmed influenza; 45.7% (95% CI: 26.0, 60.1) against influenza A(H1N1)pdm09 and 35.1% (95% CI: −3.7,59.3) against A(H3N2). Overall aVE was 49.9% (95%CI: −13.7, 77.9) for all those ≥ 65 years of age and 62.0% (95% CI: 3.4, 85.0) for those who received aTIV. Overall aVE for 2–17 year olds receiving LAIV was 48.6% (95% CI: −4.4, 74.7). The paper provides evidence of overall significant influenza VE in 2018/19, most notably against influenza A(H1N1)pdm09, however, as seen in 2017/18, there was reduced, non-significant VE against A(H3N2). aTIV provided significant protection for those 65 years of age and over.

Public health preparedness for coronavirus disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal human coronaviruses (sCoVs) and other cocirculating viruses in the West of Scotland, UK. We analyzed routine diagnostic data for >70,000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43 and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.

The Brazilian state of Goias, untouched by spotted fever (SF) until 2012, has subsequently reported cases of the disease in several regions. This study aimed to survey the diversity of potential vectors and rickettsia in areas of Goias under environmental surveillance or case investigation for SF. Collected specimens were assayed with molecular biology technology using DNA extraction, amplification and sequencing of fragments of the genes gltA, ompA, ompB and sca4 to detect rickettsia in ticks and fleas. Amplification of cytochrome oxidase subunit II and 16S rRNA was performed to assist tick identification. Rickettsia felis (Rickettsiales: Rickettsiaceae) was found in Ctenocephalides felis (Bouche, 1835) (Siphonaptera: Pulicidae). Rickettsia bellii was found in Amblyomma rotundatum Koch, 1844 (Ixodida: Ixodidae) and in Amblyomma cajennense sensu lato. Rickettsia sp. strain NOD was found in Amblyomma nodosum Neumann, 1899. Of the Amblyomma cajennense complex, Amblyomma sculptum Berlese, 1888 was confirmed in the northern, northeast, midwest and southeast regions of Goias, whereas Amblyomma cajennense sensu stricto (Fabricius, 1787) was found only in the northern region of the state. Amblyomma dubitatum Neumann, 1899 associated with a species of the A. cajennense complex was the most common epidemiological finding, although Rickettsia rickettsii was not detected. This is the first report of Rickettsia sp. strain NOD in Goias.

Cardiovascular complications, in particular perioperative myocardial infarctions, are central contributors to morbidity and mortality after non-cardiac surgery. We present a case of a 41-year-old male, smoker and dyslipidemic, who underwent bimaxillary orthognathic jaw surgery with the development of an acute coronary syndrome in the immediate postoperative period. We managed to early diagnose the myocardial infarction and promptly performed a percutaneous transluminal coronary angioplasty, resulting in a positive outcome.

Resumen Las complicaciones cardiovasculares, en particular el infarto de miocardio perioperatorio, contribuyen significativamente a la morbimortalidad tras la cirugia no cardiaca. Presentamos el caso de un hombre de 41 anos de edad, fumador, con dislipidemia, sometido a una cirugia ortognatica bimaxilar, que desarrollo un sindrome coronario agudo en el periodo postoperatorio inmediato. El infarto agudo de miocardio se diagnostico de manera temprana, realizandose de inmediato una angioplastia coronaria transluminal percutanea, que se tradujo en un resultado y evolucion favorables.

Background During the 2017/18 and 2018/19 influenza seasons, molecular amplification-based point-of-care tests (mPOCT) were introduced in Scotland to aid triaging respiratory patients for hospital admission, yet communication of results to national surveillance was unaccounted for. Aim This retrospective study aims to describe steps taken to capture mPOCT data and assess impact on influenza surveillance. Methods Questionnaires determined mPOCT usage in 2017/18 and 2018/19. Searches of the Electronic Communication of Surveillance in Scotland (ECOSS) database were performed and compared with information stored in laboratory information management systems. Effect of incomplete data on surveillance was determined by comparing routine against enhanced data and assessing changes in influenza activity levels determined by the moving epidemic method. Results The number of areas employing mPOCT increased over the two seasons (6/14 in 2017/18 and 8/14 in 2018/19). Analysis of a small number of areas (n = 3) showed capture of positive mPOCT results in ECOSS improved between seasons and remained high (> 94%). However, capture of negative results was incomplete. Despite small discrepancies in weekly activity assessments, routine data were able to identify trend, start, peak and end of both influenza seasons. Conclusion This study has shown an improvement in capture of data from influenza mPOCT and has highlighted issues that need to be addressed for results to be accurately captured in national surveillance. With the clear benefit to patient management we suggest careful consideration should be given to the connectivity aspects of the technology in order to ensure minimal impact on national surveillance.

Background In the United Kingdom (UK), in recent influenza seasons, children are offered a quadrivalent live attenuated influenza vaccine (LAIV4), and eligible adults mainly trivalent inactivated vaccine (TIV). Aim To estimate the UK end-of-season 2017/18 adjusted vaccine effectiveness (aVE) and the seroprevalence in England of antibodies against influenza viruses cultured in eggs or tissue. Methods This observational study employed the test-negative case–control approach to estimate aVE in primary care. The population-based seroprevalence survey used residual age-stratified samples. Results Influenza viruses A(H3N2) (particularly subgroup 3C.2a2) and B (mainly B/Yamagata/16/88-lineage, similar to the quadrivalent vaccine B-virus component but mismatched to TIV) dominated. All-age aVE was 15% (95% confidence interval (CI): −6.3 to 32) against all influenza; −16.4% (95% CI: −59.3 to 14.9) against A(H3N2); 24.7% (95% CI: 1.1 to 42.7) against B and 66.3% (95% CI: 33.4 to 82.9) against A(H1N1)pdm09. For 2–17 year olds, LAIV4 aVE was 26.9% (95% CI: −32.6 to 59.7) against all influenza; −75.5% (95% CI: −289.6 to 21) against A(H3N2); 60.8% (95% CI: 8.2 to 83.3) against B and 90.3% (95% CI: 16.4 to 98.9) against A(H1N1)pdm09. For ≥ 18 year olds, TIV aVE against influenza B was 1.9% (95% CI: −63.6 to 41.2). The 2017 seroprevalence of antibody recognising tissue-grown A(H3N2) virus was significantly lower than that recognising egg-grown virus in all groups except 15–24 year olds. Conclusions Overall aVE was low driven by no effectiveness against A(H3N2) possibly related to vaccine virus egg-adaption and a new A(H3N2) subgroup emergence. The TIV was not effective against influenza B. LAIV4 against influenza B and A(H1N1)pdm09 was effective.

Alzheimer's disease (AD) is a severe neurodegenerative disorder and the most common type of dementia in the elderly. The clinical symptoms of AD include a progressive loss of memory and impairment of cognitive functions interfering with daily life activities. The main neuropathological features consist in extracellular amyloid-β (Aβ) plaque deposition and intracellular Neurofibrillary tangles (NFTs) of hyperphosphorylated Tau. Understanding the pathophysiological mechanisms that underlie neurodegeneration in AD is essential for rational design of neuroprotective agents able to prevent disease progression. According to the “Amyloid Cascade Hypothesis” the critical molecular event in the pathogenesis of AD is the accumulation of Aβ neurotoxic oligomers. Since the proteolytic processing of Amyloid Precursor Protein (APP) by β-secretase (beta-site APP cleaving enzyme 1, BACE1) is the rate-limiting step in the production of Aβ, this enzyme is considered a major therapeutic target and BACE1 inhibitors have the potential to be disease-modifying drugs for AD treatment. Therefore, intensive efforts to discover and develop inhibitors that can reach the brain and effectively inhibit BACE1 have been pursued by several groups worldwide. The aim of this review is to highlight the progress in the discovery of potent and selective small molecule BACE1 inhibitors over the past decade.

Scotland observed an unusual influenza A(H3N2)-\ud dominated 2017/18 influenza season with healthcare\ud services under significant pressure. We report the\ud application of the moving epidemic method (MEM) to\ud virology data as a tool to predict the influenza peak\ud activity period and peak week of swab positivity in the\ud current season. This novel MEM application has been\ud successful locally and is believed to be of potential use\ud to other countries for healthcare planning and building\ud wider community resilience.

Background Increased serum IgE levels are characteristic but not specific for allergic diseases. Particularly, severe atopic dermatitis (AD) overlaps with hyper-IgE syndromes (HIES) regarding eczema, eosinophilia, and increased serum IgE levels. HIES are primary immunodeficiencies due to monogenetic defects such as in the genes DOCK8 and STAT3. As it is not known to date why allergic manifestations are not present in all HIES entities, we assessed the specificity of serum IgE of AD and HIES patients in the context of clinical and immunological findings. Methods Clinical data, skin prick tests, specific IgE to aero- and food allergens, and T helper (Th) subpopulations were compared in AD and molecularly defined HIES patients. Results Total serum IgE levels were similarly increased in STAT3-HIES, DOCK8-HIES, and AD patients. The ratio of aeroallergen-specific IgE to total IgE was highest in AD, whereas DOCK8-HIES patients showed the highest specific serum IgE against food allergens. Overall, clinical allergy and skin prick test results complied with the specific IgE results. Th2-cell numbers were significantly increased in DOCK8-HIES and AD patients compared to STAT3-HIES patients and controls. AD patients showed significantly higher nTreg-cell counts compared to STAT3-HIES and control individuals. High Th17-cell counts were associated with asthma. Specific IgE values, skin prick test, and T-cell subsets of STAT3-HIES patients were comparable with those of healthy individuals except decreased Th17-cell counts. Conclusion Hyper-IgE syndromes and atopic dermatitis patients showed different sensitization pattern of serum IgE corresponding to the allergic disease manifestations and Th-cell subset data, suggesting a key role of DOCK8 in the development of food allergy.

Approximately 10-15% of all pregnancies end in spontaneous abortions. Many factors can lead to embryonic loss; however, it has been well established that over 50% of all miscarriages result from chromosomal abnormalities, primarily aneuploidies (>96%). Identifying the cause of miscarriage can significantly reduce the psychological stress in women, and enable better genetic counseling for a future pregnancy. Quantitative fluorescent polymerase chain reaction (QF-PCR) has been previously used in the study of chromosomal abnormalities. In this retrospective study, the frequency of aneuploidy in samples of 130 miscarriages undergone by patients (age average: 34.1 ± 4.6 years) at our institution was determined by QF-PCR using short tandem repeat markers. The gender of the miscarriage cases was determined by amplifying the amelogenin locus (70 males and 60 females). Seventy-one of these cases (54.6%) presented aneuploidies such as trisomy, monosomy, triploidy, and double trisomy. Trisomy 22 was the most common aneuploidy (present in 14 cases), followed by trisomy 15, trisomy 16, and monosomy X. We also observed monosomy at chromosomes X and 21 and a case with multiple aneuploidies at chromosomes 16 and 22. The most common aneuploidies associated with miscarriages were detected by QF-PCR; therefore, we concluded that QF-PCR is a rapid and reliable method for the detection of aneuploidy, and can be used as an accessory to the widely used karyotype analysis.

This project aims to analyze and describe the potential of using crushed seed oleifera Moringa and chitosan in the treatment of industrial waste water, based on the samples of the effluent in the wash tanks of an electroplating industry, located in the city of Mossoro -RN. These samples were made in the laboratory using parameters such as turbidity, color, pH, temperature and conductivity. If Consisting in the preparation of solutions with different types of ground seeds dosages of Moringa, chitosan, aluminum sulfate, ferric chloride comparing the efficiency of these solutions in the industrial wastewater treatment and to determine the volume of the solutions that were more efficient each coagulant. The best turbidity reduction and color occurred with the use of the following dosages of each coagulant: Moringa (7.5 ml and 12.5 ml); chitosan (2.5 ml and 7.5 ml); Aluminum sulfate (2.5 ml and 1 ml) and ferric chloride (1 ml and 1.5 ml). Pointing the possibility of reuse of this effluent to be treated with organic coagulants as an alternative easily accessible and affordable, especially in the Northeast where access to water is scarce in times of drought.

Issue/problem Physical activity is widely recognized as a cornerstone of type 2 diabetes treatment and control. However most individuals with type 2 diabetes do not engage in physical activity on a regular basis. This work aims to present Diabetes em Movimento® a community-based exercise program for lifestyle intervention in patients with type 2 diabetes and the major results of a 4-year experience in Portugal. Description …

The 2014/15 influenza season in the United Kingdom (UK) was characterised by circulation of predominantly antigenically and genetically drifted influenza A(H3N2) and B viruses. A universal paediatric influenza vaccination programme using a quadrivalent live attenuated influenza vaccine (LAIV) has recently been introduced in the UK. This study aims to measure the end-of-season influenza vaccine effectiveness (VE), including for LAIV, using the test negative case–control design. The overall adjusted VE against all influenza was 34.3% (95% confidence interval (CI) 17.8 to 47.5); for A(H3N2) 29.3% (95% CI: 8.6 to 45.3) and for B 46.3% (95% CI: 13.9 to 66.5). For those aged under 18 years, influenza A(H3N2) LAIV VE was 35% (95% CI: −29.9 to 67.5), whereas for influenza B the LAIV VE was 100% (95% CI:17.0 to 100.0). Although the VE against influenza A(H3N2) infection was low, there was still evidence of significant protection, together with moderate, significant protection against drifted circulating influenza B viruses. LAIV provided non-significant positive protection against influenza A, with significant protection against B. Further work to assess the population impact of the vaccine programme across the UK is underway.

The purpose of this study was to analyze the prevalence of overuse syndrome in classical and flamenco guitarists from Andalucia (Spain). Of the 64 professional guitarists who participated in the study, 75% showed symptoms of overuse syndrome. Considering the fact that classical and flamenco are two distinct styles of guitar playing, 62.5% of the classical guitarists who took part in the study were affected by some kind of overuse syndrome, versus 87.5% of the flamenco guitarists (p = 0.021). Among the guitarists affected by overuse syndrome, a total of 50% of the classical and 82.1% of the flamenco guitarists reported deterioration in their playing ability (p = 0.018). The specific symptom for which there was a difference in distribution in the two groups was tension in the upper extremities, reported more frequently by the flamenco guitarists. The higher incidence of problems and the greater perception of tension among the flamenco guitarists are attributed mainly to the plucking technique they use, which requires greater effort from the extensor muscles of the fingers, as well as the need to produce a higher volume of sound due to the nature of playing in groups.

Positron Emission Tomography (PET) is a powerful functional imaging technique targeted for in vivo quantification and localization of physiological and pathophysiological functions. The possibility to develop a vast number of diseases in transgenic and knockout mice, and the chance to follow the onset of the diseases and the evolution of the treatment efficacy in an individual basis, made PET the third preferred preclinical imaging technique (20%) in research and development of new drug therapies [1]. Two features are mandatory in a preclinical PET system: a high Full Width at Half Maximum (FWHM) Spatial Resolution (SR), comprised between 0.40 and 0.27 mm for mice, so as to achieve the same level of detail of current state-of-the art PET scanners for humans [2], and a sensitivity as high as possible, to allow to differentiate and quantify a subtle signal in the presence of significant background counts [3]. Commercially available state-of-the-art preclinical PET systems make use of detectors based on segmented inorganic scintillation crystals coupled to photodetectors [2]. To reduce the complexity and cost, light multiplexing is used to decode the position of interaction of annihilation photons [3]. This scheme poses some limitations to the sensitivity and SR attained by preclinical PET systems, due to, among other problems, the difficulty of measuring efficiently the Depth-Of-Interaction [3]. The best reported values for the sensitivity and SR of current commercially available preclinical PET systems, are of, respectively, ∼10% and ∼1 mm FWHM [2]. Timing Resistive Plate Chambers (RPCs) are gaseous detectors with resistive parallel plate electrodes (made of glass) separated by small (∼300 μm thick) and precise amplification gaps filled with an appropriate gas mixture. For the detection of photons, these are first converted into electrons in the resistive plates in an electronic cascade process. Some of the originated electrons will eventually escape to the amplification gap, where they will be accelerated by a uniform electric field, leading to a Townsend avalanche, which induces a current in a set of signal pickup strips. These low cost detectors have an excellent time resolution of 300 ps FWHM for 511 keV photon pairs, an excellent intrinsic SR, the readout being in almost full 3D mode. Recently, we developed a first fully functional prototype of a preclinical RPC-PET scanner for mice, which revealed a SR of 0.4 mm FWHM after image reconstruction by a Maximum Likelihood Expectation Maximization type algorithm. Preliminary tests with mice, preformed at the Institute of Nuclear Sciences Applied to Health (ICNAS — Instituto de Ciencias Nucleares Aplicada as Saude) of the University of Coimbra, shown the capability of the system to clearly identify the very small brain structures of mice, as well as the heart walls. The results obtained thus far are very promising, revealing unprecedented SR.

The presence of toxic substances in the workplace environment requires systematic evaluation of exposure and health status in exposed subjects. Cadmium is a highly toxic element found in water. Although free mediated cellular damage and reactive oxygen species (ROS), had been theorized as contributing to the cadmium mechanism of toxicity, and recent investigations have established that free radicals may be important contributors to cardiac dysfunction, there is little information on the effect of cadmium exposure on markers of oxidative stress in cardiac tissue. Cadmium exposure (Cd 2+ - 100 mg/l - from CdCl 2 ) in drinking water, during 15 days, significantly increased lipoperoxide and decreased the activities of superoxide dismutase and glutathione peroxidase. No alterations were observed in catalase activity in heart of rats with cadmium exposure. We also observed decreased glycogen and glucose concentration and increased total lipid content in cardiac tissue of rats with cadmium exposure. The decrease...

The applications and variety of ionic liquids (ILs) have increased during the last few years, and their use at a large scale will require their removal/recovery from wastewater streams. Adsorption on activated carbons (ACs) has been recently proposed for this aim and this work presents a systematic analysis of the influence of the IL chemical structures (cation side chain, head group, anion type and the presence of functional groups) on their adsorption onto commercial AC from water solution. Here, the adsorption of 21 new ILs, which include imidazolium-, pyridinium-, pyrrolidinium-, piperidinium-, phosphonium- and ammonium-based cations and different hydrophobic and hydrophilic anions, has been experimentally measured. This contribution allows an expansion of the range of IL compounds studied in previous works, and permits a better understanding of the influence of the IL structures through the adsorption on AC. In addition, the COSMO-RS method was used to analyze the measured adsorption isotherms, allowing the understanding of the role of the cationic and anionic structures in the adsorption process, in terms of the different interactions between the IL compound and AC surface/water solvent. The results of this work provide new insights for the development of adsorption as an effective operation to remove/recover ILs with very different chemical nature from water solution, The authors are grateful to the Spanish “Ministerio de Ciencia e Innovación (MICINN)” and “Comunidad de Madrid” for financial support (projects CTQ2011-26758 and S2009/PPQ-1545). We are very grateful to “Centro de Computación Científica de la Universidad Autónoma de Madrid” for computational facilities. The authors also acknowledge FCT – Fundaçao para a Ciencia e a Tecnologia, through the projects Pest-C/CTM/LA0011/2011 and PTDC/AAC-AMB/119172/2010. Catarina M. S. S. Neves also acknowledges FCT for the doctoral grant SFRH/BD/70641/2010

Hyperchloremia is one of the multiple etiologies of metabolic acidosis in hemodialysis (HD) patients. The aim of the present study was to determine the influence of chloride dialysate on metabolic acidosis control in this population. We enrolled 30 patients in maintenance HD program with a standard base excess (SBE) ≤2 mEq/L and urine output of less than 100 mL/24 h. The patients underwent dialysis three times per week with a chloride dialysate concentration of 111 mEq/L for 4 weeks, and thereafter with a chloride dialysate concentration of 107 mEq/L for the next 4 weeks. Arterial blood was drawn immediately before the second dialysis session of the week at the end of each phase, and the Stewart physicochemical approach was applied. The strong ion gap (SIG) decreased (from 7.5 ± 2.0 to 6.2 ± 1.9 mEq/L, P = 0.006) and the standard base excess (SBE) increased after the use of 107 mEq/L chloride dialysate (from -6.64 ± 1.7 to -4.73 ± 1.9 mEq/L, P < 0.0001). ∆SBE was inversely correlated with ∆SIG during the phases of the study (Pearson r = -0.684, P < 0.0001) and there was no correlation with ∆chloride. When we applied the Stewart model, we demonstrated that the lower concentration of chloride dialysate interfered with the control of metabolic acidosis in HD patients, surprisingly, through the effect on unmeasured anions.

Water contaminants have a high potential risk for the health of populations. Protection from toxic effects of environmental water pollutants primarily involves considering the mechanism of low level toxicity and likely biological effects in organisms who live in these polluted waters. The biomarkers assessment of oxidative stress and metabolic alterations to cadmium exposure were evaluated in Nile tilapia, Oreochromis niloticus. The fish were exposed to 0.35, 0.75, 1.5, and 3.0 mg/l concentrations of Cd2+ (CdCl2) in water for 60 days. Fish that survived cadmium exposure showed a metabolic shift and a compensatory development for maintenance of the body weight gain. We observed a decreased glycogen content and decreased glucose uptake in white muscle. Lactate dehydrogenase (LDH) and creatine phosphokinase (CK) activities were also decreased, indicating that the glycolytic capacity was decreased in this tissue. No alterations were observed in total protein content in white muscle due to cadmium exposure suggesting a metabolic shift of carbohydrate metabolism to maintenance of the muscle protein reserve. There was an increase in glucose uptake, CK increased activity, and a clear increase of LDH activity in red muscle of fish with cadmium exposure. Since no alterations were observed in lipoperoxide concentration, while antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were changed in the liver and the red and white muscle of fish with cadmium exposure, we can conclude that oxygen free radicals are produced as a mediator of cadmium toxicity. Resistance development is related with increased activities of antioxidant enzymes, which were important in the protection against cadmium damage, inhibiting lipoperoxide formation. Keywords: Cadmium, Oxidative stress, Metabolic responses, Fish, Oreochromis niloticus

Introduction Harmful effects of medicines should be reviewed with similar rigour as therapeutic benefits. Most evidence on harms is obtained from post marketing surveillance, so the use of meta-analysis to pool safety information presents challenges of inherent biases and differences in study designs. Yet, it9s crucial to provide an accurate safety profile of pharmacological interventions. We aimed to describe the data sources of published meta-analysis of adverse drug effects. Method We searched meta-analysis published in the last 5 years in six medical journals with the highest impact factor. All the meta-analysis focussing primarily on adverse effects of pharmacological interventions, with pooled results, were included and the characteristics assessed. Results A total of 61 meta-analysis were included, 16 were published in JAMA, 13 in Lancet, 11 in BMJ, 10 in Ann Intern Med, nine in Arch Intern Med and two in NEJM. Of these 90.2% (n=55) included only experimental studies, two included only observational studies and four meta-analysis comprised both type of studies. Less than half (47.5%; n=29) of the meta-analysis assessed the quality of the included studies according to specified recommendation statements, and only 18 (29.5%) considered unpublished studies. Conclusion The majority of meta-analysis of adverse drug effects included only experimental studies, less than half assessed their quality and few considered unpublished studies. These results reinforce the need for methodological research to clarify the role of meta-analysis in Pharmacovigilance and evaluate how to pool safety information from different surveillance methods, to provide an accurate safety profile of pharmacological interventions.