Is a tiered restrictions system an effective intervention for COVID-19 control? Results from Portugal, November-December 2020.

BACKGROUND: In November 2020, similar to other European countries, Portugal implemented a tiered restrictions system to control the COVID-19 pandemic. We aimed to compare the COVID-19 growth rate across tiers to assess the effect of a tiered restrictions system in Portugal, using models with different times between tiers assessment. Our hypothesis was that being in a higher tier brings a faster deceleration in the growth rate than being in a lower tier. METHODS: The national database of notified COVID-19 cases and publicly available data were used to analyse the effect of the tiered restrictions system on the COVID-19 incidence growth rate. The tiers were based on the European Centre for Disease Control risk classification: moderate, high, very and extremely high. We used a generalised mixed-effects regression model to estimate the growth rate ratio (GRR) for each tier, comparing the growth rates of higher tiers using moderate tier as reference. Three models were fitted using different times between tiers assessment, separated by 14 days. RESULTS: We included 156 034 cases. Very high tier was the most frequent combination in all the three moments assessed (21.2%), and almost 50% of the municipalities never changed tier during the study period. Immediately after the tiers implementation, a reduction was identified in the municipalities in high tier (GRR high tier: 0.90 [95%CI: 0.79; 1.02]) and very high tier (GRR very high tier: 0.68 [95%CI: 0.61; 0.77]), however with some imprecision in the 95% confidence interval for the high tier. A reduction in very high tier growth rate was identified two weeks (GRR: 0.79 [95%CI: 0.71; 0.88]) and four weeks (GRR: 0.77 [95%CI: 0.74; 0.82]) after the implementation, compared to moderate tier. In high tier, a reduction was also identified in both times, although smaller. CONCLUSIONS: We observed a reduction in the growth rate in very high tier after the tiered restriction system was implemented, but we also observed a lag between tiered restriction system implementation and the onset of consequent effects. This could suggest the importance of early implementation of stricter measures for pandemic control. Thus, studies analysing a broader period of time are needed.

Sickle cell trait in São Tomé e Príncipe: a population-based prevalence study in women of reproductive age.

BACKGROUND: Sickle Cell Disorder is Africa's most prevalent genetic disease. Yet, it remains a neglected condition, with high mortality under-five, and a lack of population-based studies in the region. This is the first of its kind in São Tomé e Príncipe, aiming to estimate the prevalence of sickle cell trait and other haemoglobin variants in women of reproductive age and its associated factors. METHODS: We conducted a cluster survey in 35 neighbourhoods. Haemoglobin was assessed through point-of-care capillary electrophoresis or high-performance liquid chromatography, and sociodemographic data through questionnaires. The weighted prevalence of sickle cell trait (HbAS) and HbC carriers was estimated with a 95% confidence interval (95% CI). We calculated weighted prevalence ratios (95% CI) through robust Poisson regression for its association with age and individual and collective genetic heritage. FINDINGS: The prevalence of sickle cell trait in women of reproductive age in São Tomé e Príncipe (n = 376) was 13.45% (95% CI: 9.05-19.00). The prevalence of HbC carriers was 8.00% (95% CI: 4.71-12.00). Older age and speaking Forro or Angolar were positively associated with having sickle cell trait. INTERPRETATION: The prevalence of sickle cell trait in São Tomé e Príncipe ranks high in the West African region. The country should follow international guidelines, implementing newborn screening and comprehensive healthcare management.

Microfluidic Paper-Based Device Incorporated with Silica Nanoparticles for Iodide Quantification in Marine Source Dietary Supplements.

Iodine is an essential micronutrient for humans due to its fundamental role in the biosynthesis of thyroid hormones. As a key parameter to assess health conditions, iodine intake needs to be monitored to ascertain and prevent iodine deficiency. Iodine is available from various food sources (such as seaweed, fish, and seafood, among others) and dietary supplements (multivitamins or mineral supplements). In this work, a microfluidic paper-based analytical device (µPAD) to quantify iodide in seaweed and dietary supplements is described. The developed µPAD is a small microfluidic device that emerges as quite relevant in terms of its analytical capacity. The quantification of iodide is based on the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by hydrogen peroxide in the presence of iodine, which acts as the catalyst to produce the blue form of TMB. Additionally, powder silica was used to intensify and uniformize the colour of the obtained product. Following optimization, the developed µPAD enabled iodide quantification within the range of 10-100 µM, with a detection limit of 3 µM, and was successfully applied to seaweeds and dietary supplements. The device represents a valuable tool for point-of-care analysis, can be used by untrained personnel at home, and is easily disposable, low-cost, and user-friendly.

Investigating the role of symptom valorisation in tuberculosis patient delay in urban areas in Portugal.

BACKGROUND: Diagnosis delay contributes to increased tuberculosis (TB) transmission and morbimortality. TB incidence has been decreasing in Portugal, but median patient delay (PD) has risen. Symptom valorisation may determine PD by influencing help-seeking behaviour. We aimed to analyse the association between symptom valorisation and PD, while characterising individuals who disregarded their symptoms. METHODS: A cross-sectional study was conducted among TB patients in Lisbon and Oporto in 2019 - 2021. Subjects who delayed seeking care because they did not value their symptoms or thought these would go away on their own were considered to have disregarded their symptoms. PD was categorised using a 21-day cut-off, and a 30-day cut-off for sensitivity analysis. We estimated the effect of symptom valorisation on PD through a directed acyclic graph. Then, a multivariable regression analysis characterised patients that disregarded their symptoms, adjusting for relevant variables. We fitted Poisson regression models to estimate crude and adjusted prevalence ratios (PR). RESULTS: The study included 75 patients. Median PD was 25 days (IQR 11.5-63.5), and 56.0% of participants had PD exceeding 21 days. Symptom disregard was reported by 38.7% of patients. Patients who did not value their symptoms had higher prevalence of PD exceeding 21 days compared to those who valued their symptoms [PR 1.59 (95% CI 1.05-2.42)]. The sensitivity analysis showed consistent point estimates but wider confidence intervals [PR 1.39 (95% CI 0.77-2.55)]. Being a smoker was a risk factor for symptom disregard [PR 2.35 (95% CI 1.14-4.82)], while living in Oporto [PR 0.35 (95% CI 0.16-0.75)] and having higher household incomes [PR 0.39 (95% CI 0.17-0.94)] were protective factors. CONCLUSIONS: These findings emphasise the importance of symptom valorisation in timely TB diagnosis. Patients who did not value their symptoms had longer PD, indicating a need for interventions to improve symptom recognition. Our findings also corroborate the importance of the socioeconomic determinants of health, highlighting tobacco as a risk factor both for TB and for PD.

Biogenic Amine Sensing Based on Rosamine a N-Methylpyridinium Derivative Supported on Silica Materials from Rice Husk.

In this work new rosamine-silica composites were prepared and their sensing ability towards different amines was assessed. Rice husk wastes were used as a biogenic silica source. Silica was extracted by thermal treatment, before rice husk ash and after acid leaching with citric acid-treated rice husk ash. Mesoporous material (SBA-15) was also prepared using the extracted silica. The prepared materials were characterized by several techniques such as FTIR, XRD, SEM and N2 adsorption. The materials were then used as adsorbents of the chromophore N-methylpyridinium rosamine (Ros4PyMe). The obtained loaded composites were tested in solution for amines sensing (n-butylamine, aniline, putrescine and cadaverine). The detection studies were analyzed by fluorescence and revealed 40% and 48% quenching in fluorescence intensity for the composite Ros4PyMe@SBA in the presence of the biogenic amines cadaverine and putrescine, respectively. The composite was also sensitive in the powder form, changing the color from violet to pale pink in the presence of putrescine vapors with a fast response (around 2 min), the process being reversible by exposure to air.

Functionalization of Rhodamine Platforms with 3-Hydroxy-4-pyridinone Chelating Units and Its Fluorescence Behavior towards Fe(III).

Functionalization of xanthene fluorophores with specific receptor units is an important topic of research aiming for the development of new analytical tools for biological sciences, clinical diagnosis, food and environmental monitoring. Herein, we report a new dihydrorosamine containing two active amino groups, which was functionalized with 3-benzyloxy-1-(3'-carboxypropyl)-2-methyl-4-pyridinone through an amide coupling strategy. Benzylated mono- and di-functionalized dihydrorosamine derivatives (H in position 9 of the xanthene) were obtained, but with modest reaction yields, requiring long and laborious purification procedures. Looking for a more efficient approach, rhodamine 110 was selected to react with the carboxypropyl pyridinone, enabling the isolation of the corresponding mono- and di-functionalized derivatives in amounts that depend on the excess of pyridinone added to the reaction. The structure of all compounds was established by 1H and 13C NMR, MS (ESI) and their absorption and emission properties were evaluated in dichloromethane. The fluorescence behavior of the debenzylated mono-rhodamine 110 derivative in the presence of Fe(III) was studied, making it an interesting fluorogenic dye for future optical sensing applications.

Synthesis of Novel Diketopyrrolopyrrole-Rhodamine Conjugates and Their Ability for Sensing Cu2+ and Li.

The search for accurate and sensitive methods to detect chemical substances, namely cations and anions, is urgent and widely sought due to the enormous impact that some of these chemical species have on human health and on the environment. Here, we present a new platform for the efficient sensing of Cu2+ and Li+ cations. For this purpose, two novel photoactive diketopyrrolopyrrole-rhodamine conjugates were synthesized through the condensation of a diketopyrrolopyrrole dicarbaldehyde with rhodamine B hydrazide. The resulting chemosensors 1 and 2, bearing one or two rhodamine hydrazide moieties, respectively, were characterized by 1H and 13C NMR and high-resolution mass spectrometry, and their photophysical and ion-responsive behaviours were investigated via absorption and fluorescence measurements. Chemosensors 1 and 2 displayed a rapid colorimetric response upon the addition of Cu2+, with a remarkable increase in the absorbance and fluorescence intensities. The addition of other metal ions caused no significant effects. Moreover, the resulting chemosensor-Cu2+ complexes revealed to be good probes for the sensing of Li+ with reversibility and low detection limits. The recognition ability of the new chemosensors was investigated by absorption and fluorescence titrations and competitive studies.

Foliar application of 3-hydroxy-4-pyridinone Fe-chelate [Fe(mpp)3 ] induces responses at the root level amending iron deficiency chlorosis in soybean.

Iron (Fe) deficiency chlorosis (IDC) affects the growth of several crops, especially when growing in alkaline soils. The application of synthetic Fe-chelates is one of the most commonly used strategies in IDC amendment, despite their associated negative environmental impacts. In a previous work, the Fe-chelate tris(3-hydroxy-1-(H)-2-methyl-4-pyridinonate) iron(III) [Fe(mpp)3 ] has shown great potential for alleviating IDC in soybean (Glycine max) in the early stages of plant development under hydroponic conditions. Herein, its efficacy was verified under soil conditions in soybean grown from seed to full maturity. Chlorophyll levels, plant growth, root and shoot mineral accumulation (K, Mg, Ca, Na, P, Mn, Zn, Ni, and Co) and FERRITIN expression were accessed at V5 phenological stage. Compared to a commonly used Fe chelate, FeEDDHA, supplementation with [Fe(mpp)3 ] led to a 29% higher relative chlorophyll content, 32% higher root biomass, 36% higher trifoliate Fe concentration, and a twofold increase in leaf FERRITIN gene expression. [Fe(mpp)3 ] supplementation also resulted in increased accumulation of P, K, Zn, and Co. At full maturity, the remaining plants were harvested and [Fe(mpp)3 ] application led to a 32% seed yield increase when compared to FeEDDHA. This is the first report on the use of [Fe(mpp)3 ] under alkaline soil conditions for IDC correction, and we show that its foliar application has a longer-lasting effect than FeEDDHA, induces efficient root responses, and promotes the uptake of other nutrients.

Tuberculosis amongst foreign-born and nationals: different delays, different risk factors.

BACKGROUND: Delay in Tuberculosis (TB) diagnosis affects foreign-born and nationals in different ways, especially in low-incidence countries. This study characterises total delay and its components amongst foreign-born individuals in Portugal. Additionally, we identify risk factors for each type of delay and compare their effects between foreign-born and nationals. METHODS: We analysed data from the Portuguese TB surveillance system and included individuals with pulmonary TB (PTB), notified between 2008 and 2017. We described patient, healthcare, and total delays. Cox regression was used to identify factors associated with each type of delay. All analyses were stratified according to the origin country: nationals (those born in Portugal) and foreign-born. RESULTS: Compared with nationals, foreign-born persons presented statistically significant and longer median total and patient delays (Total: 67 vs. 63; Patient: 44 vs. 36 days), and lower healthcare services delays (7 vs. 9 days). Risk factors for delayed diagnosis differed between foreign-born and nationals. Being unemployed, having drug addiction, and having comorbidities were identified as risk factors for delayed diagnosis in national individuals but not in foreigners. Alcohol addiction was the only factor identified for healthcare delay for both populations: foreign-born (Hazard Ratio 1.34 [95% confidence interval 1.17;1.53]); nationals (Hazard Ratio 1.20 [95% confidence interval 1.13;1.27]). CONCLUSIONS: Foreign-born individuals with PTB take longer to seek health care. While no specific risk factors were identified, more in-depth studies are required to identify barriers and support public health intervention to address PTB diagnosis delay in foreign-born individuals.

No effect modification of influenza virus vaccine effectiveness by age or chronic condition was observed in the 2010/11 to 2017/18 seasons.

PURPOSE: Most European influenza vaccine strategies target individuals at higher risk of complications, which include, among others, individuals aged ≥65 years and with chronic conditions. These individuals not only have a high-risk of post-infection complications but also could have lower capacity of acquiring adequate vaccine-induced protection. As such, chronic conditions and age could modify the effect of vaccines. This study aimed at assessing the potential effect modification of influenza vaccine effectiveness (IVE) by age and chronic conditions. METHODS: We used eight-season data from the Portuguese vaccine effectiveness study. Every season, physicians at primary care units recruited patients with influenza-like illness. Clinical data and swabs were collected for Reverse Transverse Polymerase Chain Reaction (RT-PCR) detection of influenza. Trivalent inactivated IVE was estimated as 1 - odds ratio (OR) of being vaccinated in cases (RT-PCR positive for influenza) versus negative controls. ORs were obtained using a multivariable conditional logistic regression model, paired by week of onset within each season. Confounders were assessed by designing a specific causal diagram. Age (< 65 or ≥65 years) and chronic conditions (diabetes, cardiovascular disease, chronic renal disease, chronic hepatic disease, obesity, chronic respiratory disease, and congenital or acquired immunodeficiency) were studied as effect modifiers by including an interaction term in the regression models. Significance was established at 5%. RESULTS: Point estimates indicate a higher IVE in the chronic condition strata compared to that in the no chronic condition strata. Regarding age, different results were obtained considering the virus type and (sub)type. When comparing the ≥65 years with the <65 years of age strata, we observed a higher IVE against A(H1N1)pdm09, an equal IVE against A(H3N2) and a lower IVE against B virus. However, all interaction terms were statistically insignificant, and this may be due to a small sample size. CONCLUSION: The potential effect modification of age or chronic condition was not observed within our study.

Delayed diagnosis of active pulmonary tuberculosis - potential risk factors for patient and healthcare delays in Portugal.

BACKGROUND: Early diagnosis and treatment of pulmonary tuberculosis (PTB) is essential for an effective control of the tuberculosis (TB) epidemic. Delayed diagnosis and treatment of TB increases the chance of complications and mortality for the patients, and enhances TB transmission in the population. Therefore, the aim of this study was to characterize patient, healthcare and total delay in diagnosing PTB and assess the effect of clinical and sociodemographic factors on the time until first contact with healthcare or reaching a PTB diagnosis. METHODS: Retrospective cohort study that included active PTB patients notified in the National Tuberculosis Surveillance System (SVIG-TB), between 2008 and 2017. Descriptive statistics, Kaplan-Meier estimates, logrank test and Cox proportional hazards model were used to characterize patient, healthcare and total delay and estimate the effect of clinical and sociodemographic variables on these delays. Significance level was set at 0.05. RESULTS: Median patient, healthcare and total delays was 37 days (Interquartile range (IQR): 19-71), 8 days (IQR: 1-32) and 62 days (IQR: 38-102), respectively. The median patient delay showed a constant increase, from 33 days in 2008 to 44 days in 2017. The median total delay presented a similar trend, increasing from 59 days in 2008 to 70 days in 2017. Healthcare delay remained constant during the study period. More than half of the PTB cases (82.9%) had a delay > 1 month between symptom onset and diagnosis. In the final Cox model, alcohol abuse, unemployment and being from a high TB incidence country were factors significantly associated with longer patient delay, while being female, having more than 45 years, oncologic and respiratory diseases were associated with longer healthcare delay. Being female, having more than 45 years and being from a high TB incidence country were associated with longer total delay. CONCLUSIONS: Patient delay and total delay have increased in recent years. Older patients, patients with alcohol problems, other comorbidities, unemployed or from countries with high TB incidence would benefit from the development of specific public health strategies that could help reduce the delay in TB diagnosis observed in our study. This study emphasizes the need to promote awareness of TB in the general population and among the healthcare community, especially at ambulatory care level, in order to reduce the gap between beginning of symptoms and TB diagnosis.

Synthesis of Catechol Derived Rosamine Dyes and Their Reactivity toward Biogenic Amines.

Functional organic dyes play a key role in many fields, namely in biotechnology and medical diagnosis. Herein, we report two novel 2,3- and 3,4-dihydroxyphenyl substituted rosamines (3 and 4, respectively) that were successfully synthesized through a microwave-assisted protocol. The best reaction yields were obtained for rosamine 4, which also showed the most interesting photophysical properties, specially toward biogenic amines (BAs). Several amines including n- and t-butylamine, cadaverine, and putrescine cause spectral changes of 4, in UV-Vis and fluorescence spectra, which are indicative of their potential application as an effective tool to detect amines in acetonitrile solutions. In the gas phase, the probe response is more expressive for spermine and putrescine. Additionally, we found that methanolic solutions of rosamine 4 and n-butylamine undergo a pink to yellow color change over time, which has been attributed to the formation of a new compound. The latter was isolated and identified as 5 (9-aminopyronin), whose solutions exhibit a remarkable increase in fluorescence intensity together with a shift toward more energetic wavelengths. Other 9-aminopyronins 6a, 6b, 7a, and 7b were obtained from methanolic solutions of 4 with putrescine and cadaverine, demonstrating the potential of this new xanthene entity to react with primary amines.

Synthesis of Pyridyl and N-Methylpyridinium Analogues of Rosamines: Relevance of Solvent and Charge on Their Photophysical Properties.

A series of pyridyl analogues of rosamines was prepared by employing two methodologies: (i) the conventional-heating condensation of a pyridinecarboxaldehyde with 3-(diethylamino)phenol in propionic acid, and (ii) the novel ohmic-heating assisted condensation under "on water" conditions, followed by oxidation. The 4-pyridyl substituted rosamine was further converted into the N-methylpyridinium derivative through N-alkylation using methyl iodide. The influence of the position and cationization of the nitrogen atom of the pyridyl ring in the physicochemical properties of fluorophores was investigated by 1 H, 13 C, 15 N NMR spectral analysis, UV/Vis and fluorescence spectroscopy, single-crystal X-ray diffraction (4-pyridyl and N-methylpyridinium derivatives) and thermal-behavior analysis. Curiously, for ethanolic solutions of 4-pyridyl and N-methylpyridinium derivatives an extinction of color and fluorescence over time was observed. This phenomenon was further studied and the data revealed that it is the result of nucleophilic addition of ethoxide ion to the central 9-position of the xanthene. The kinetics of the process is slower for the 4-pyridyl rosamine, which emphasizes the importance of the charge in the N-methylpyridinium analogue in the reactivity of the molecule towards a nucleophile agent. This phenomenon is reversible, meaning that the compounds can be rapidly recovered by decreasing the pH, opening new avenues in the sensing applications of this class of rosamines.

Do delays in data availability limit the implementation of near real-time vaccine safety surveillance using the Clinical Practice Research Datalink?

PURPOSE: Near real-time vaccine safety surveillance (NRTVSS) using electronic health records has been used to detect timely vaccine safety signals. Trial implementation of NRTVSS using the Clinical Practice Research Datalink (CPRD) has shown that there is limited power to detect safety signals for rare events. Delays in recording outcomes and receiving data influence the power and timeliness to identify a signal. Our work aimed to compare how different sources of delays influence power and expected time to signal to implement NRTVSS using CPRD. METHODS: We studied seasonal influenza vaccine/Guillain-Barré syndrome and performed power and expected time to signal calculations for the 2013-2014/2014-2015 seasons. We used the Poisson-based maximised sequential probability ratio test, which compares observed-to-expected events. For each study season, we obtained an average Guillain-Barré syndrome/seizures age-sex-adjusted rate from the 5 previous seasons and then used this rate to calculate the expected number of events, assuming a 42-day risk-window. Calculations were performed for detecting rate ratios of 1.5 to 10. We compared power and timeliness considering combinations of the presence/absence of delays in recording outcomes and in receiving data. The R-package Sequential was used. RESULTS: In general, there was ≥80% power to detect increases in risk of ≥4 at the end of the season. Assuming absence of delays slightly improved power (a maximum increase of 4%) but did not noticeably reduce time to detect a signal. CONCLUSION: Removing delays in data availability is insufficient to significantly improve the performance of a NRTVSS system using CPRD. Expansion of CPRD data is required. KEY POINTS The Clinical Practice Research Datalink (CPRD) can be used to implement near real-time vaccine safety surveillance, but there is limited power to detect signals for rare outcomes. Delays in recording outcomes and in receiving data might limit power and timeliness of a system. We assessed the influence of these sources of delays to inform data providers of the steps required to improve a system using CPRD data. Removing delays in recording outcomes and receiving data is unlikely to significantly improve the performance of a system using CPRD data. Expansion of the data available is needed.

Assessing recording delays in general practice records to inform near real-time vaccine safety surveillance using the Clinical Practice Research Datalink (CPRD).

PURPOSE: Near real-time vaccine safety surveillance (NRTVSS) is an option for post-licensure vaccine safety assessment. NRTVSS requires timely recording of outcomes in the database used. Our main objective was to examine recording delays in the Clinical Practice Research Datalink (CPRD) for outcomes of interest for vaccine safety to inform the feasibility of NRTVSS using these data. We also evaluated completeness of recording and further assessed reporting delays for hospitalized events in CPRD. METHODS: We selected Guillain-Barré syndrome (GBS), Bell's palsy (BP), optic neuritis (ON) and febrile seizures (FS), from January 2005 to June 2014. We assessed recording delays (e.g. due to feedback from specialist referral) in stand-alone CPRD by comparing the event and system dates and excluding delays >1 year. We used linked CPRD-hospitalization data to further evaluate delays and completeness of recording in CPRD. RESULTS: Among 51 220 patients for the stand-alone CPRD analysis (GBS: n = 830; BP: n = 12 602; ON: n = 1720; and FS: n = 36 236), most had a record entered within 1 month of the event date (GBS: 73.6%; BP: 93.4%; ON: 76.2%; and FS: 85.6%). A total of 13 482 patients, with a first record in hospital, were included for the analysis of linked data (GBS: n = 678; BP: n = 4060; ON: n = 485; and FS: n = 8321). Of these, <50% had a record in CPRD after 1 year (GBS: 41.3%; BP: 22.1%; ON: 22.4%; and FS: 41.8%). CONCLUSION: This work shows that most diagnoses in CPRD for the conditions examined were recorded with delays of ≤30 days, making NRTVSS possible. The pattern of delays was condition-specific and could be used to adjust for delays in the NRTVSS analysis. Despite low sensitivity of recording, implementing NRTVSS in CPRD is worthwhile and could be carried out, at least on a trial basis, for events of interest. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

Design of a Water Soluble Fluorescent 3-Hydroxy-4-Pyridinone Ligand Active at Physiological pH Values.

In the present work we report the structure and the spectroscopic characterization of a new fluorescent 3-hydroxy-4-pyridinone ligand D-3,4-HPO. The synthesis of the compound was performed in two steps, which involve the reaction of the commercially available fluorophore dansyl chloride with a 3-hydroxy-4-pyridinone chelating unit and further deprotection. The new fluorescent chelator was characterized in the solid state by single-crystal X-ray diffraction and in solution by NMR, MS, absorption and fluorescence spectroscopies. The analysis of the variation of the absorption spectrum with pH allowed the determination of four pK a values (pK a1  = 3.50, pK a2  = 4.50, pK a3  = 9.60, pK a4  = 10.20) and establishment of the corresponding distribution diagram. The study of the fluorescence properties of the ligand show that in the pH range between 4 and 9 the fluorescence intensity is constant and has its maximum value thus allowing its further use at physiological pH values. The interaction of the ligand with copper(II) was accessed by fluorescence spectroscopy in MOPS buffer and the results show that the presence of copper(II) quenches the fluorescence of the ligand in ca 94 % at a ligand: metal ratio of 2:1. The latter result is consistent with the formation of a copper(II) complex with the bidentate ligand, as confirmed by the EPR spectroscopy. Graphical Abstract New water soluble fluorescent ligand active at physiological pH values.

Near real-time vaccine safety surveillance using electronic health records-a systematic review of the application of statistical methods.

PURPOSE: Pre-licensure studies have limited ability to detect rare adverse events (AEs) to vaccines, requiring timely post-licensure studies. With the increasing availability of electronic health records (EHR) near real-time vaccine safety surveillance using these data has emerged as an option. We reviewed methods currently used to inform development of similar systems for countries considering their introduction. METHODS: Medline, EMBASE and Web of Science were searched, with additional searches of conference abstract books. Questionnaires were sent to organizations worldwide to ascertain unpublished studies. Eligible studies used EHR and regularly assessed pre-specified AE to vaccine(s). Key features of studies were compared descriptively. RESULTS: From 2779 studies, 31 were included from the USA (23), UK (6), and Taiwan and New Zealand (1 each). These were published/conducted between May 2005 and April 2015. Thirty-eight different vaccines were studied, focusing mainly on influenza (47.4%), especially 2009 H1N1 vaccines. Forty-six analytic approaches were used, reflecting frequency of EHR updates and the AE studied. Poisson-based maximized sequential probability ratio test was the most common (43.5%), followed by its binomial (23.9%) and conditional versions (10.9%). Thirty-seven of 49 analyses (75.5%) mentioned control for confounding, using an adjusted expected rate (51.4% of those adjusting), stratification (16.2%) or a combination of a self-controlled design and stratification (13.5%). Guillain-Barré syndrome (11.9%), meningitis/encephalitis/myelitis (11.9%) and seizures (10.8%) were studied most often. CONCLUSIONS: Near real-time vaccine safety surveillance using EHR has developed over the past decade but is not yet widely used. As more countries have access to EHR, it will be important that appropriate methods are selected, considering the data available and AE of interest.

The Influence of the Amide Linkage in the Fe(III) -Binding Properties of Catechol-Modified Rosamine Derivatives.

The two new fluorescent ligands RosCat1 and RosCat2 contain catechol receptors connected to rosamine platforms through an amide linkage and were synthesized by using microwave-assisted coupling reactions of carboxyl- or amine-substituted rosamines with the corresponding catechol units and subsequent deprotection. RosCat1 possesses a reverse amide, whereas RosCat2 has the usual oriented amide bond (HNCO vs. CONH, respectively). The ligands were characterized by means of NMR spectroscopy, mass-spectrometry, and DFT calculations and X-ray crystallography studies for RosCat1. The influence of the amide linkage on the photophysical properties of the fluorescent ligands was assessed in different solvents and showed a higher fluorescence quantum yield for RosCat1. The coordination chemistry of these ligands with a Fe(III) center has been rationalized by mass-spectrometric analysis and semiempirical calculations. Octahedral Fe(III) complexes were obtained by the chelation of three RosCat1 or RosCat2 ligands. Interestingly, the unconventional amide connectivity in RosCat1 imposes the formation of an eight-membered ring on the chelate complex through a "salicylate-type" mode of coordination.

Isoxazolidine-fused meso-tetraarylchlorins as key tools for the synthesis of mono- and bis-annulated chlorins.

The microwave-assisted catalytic hydrogenation of the isoxazolidine-fused meso-tetrakis(pentafluorophenyl)chlorin afforded directly a mono-annulated chlorin with a singular 1-methyl-2,3-dihydro-1H-benzo[b]azepine ring that resulted from the cleavage of the isoxazolidine N-O bond followed by an intramolecular nucleophilic aromatic substitution of an o-F atom. The subsequent treatment of the mono-annulated chlorin with NaH induced a second intramolecular nucleophilic aromatic substitution, generating a bis-annulated chlorin having an additional 2H-pyran ring.

Optimizing Antimicrobial Efficacy: Investigating the Impact of Zinc Oxide Nanoparticle Shape and Size.

Zinc oxide nanoparticles (ZnO NPs) have been investigated due to their distinct properties, variety of structures and sizes, and mainly for their antimicrobial activity. They have received a positive safety evaluation from the European Food Safety Authority (EFSA) for packaging applications as transparent ultraviolet (UV) light absorbers based on the absence of significant migration of zinc oxide in particulate form. ZnO NPs with different morphologies (spherical, flower, and sheet) have been synthesized via different sol-gel methods and extensively characterized by several solid-state techniques, namely vibrational spectroscopy, powder X-ray diffraction (XRD), scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS), Fourier Transform Infrared Spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-VIS), electron paramagnetic resonance (EPR), and nitrogen adsorption-desorption isotherms. The ZnO NPs were assessed for their antibacterial activity against Escherichia coli (gram-negative bacteria) and Staphylococcus aureus (gram-positive bacteria) to study the influence of morphology and size on efficacy. ZnO NPs with different morphologies and sizes demonstrated antimicrobial activity against both bacteria. The highest microbial cell reduction rate (7-8 log CFU mL-1 for E. coli and 6-7 log CFU mL-1 for S. aureus) was obtained for the sheet- and spherical-shaped NPs as a result of the high specific surface area. In fact, the higher surface areas of the sheet- and spherical-shaped nanoparticles (18.5 and 13.4 m2 g-1, respectively), compared to the flower-shaped NPs (5.3 m2g-1), seem to promote more efficient bacterial cell reduction. The spherical-shaped particles were also smaller (31 nm) compared with the flower-shaped (233 × 249 nm) ones. The flower ZnO NP resulted in a 4-5 log CFU mL-1 reduction for E. coli and 3-4 log CFU mL-1 reduction for S. aureus. The lower apparent antibacterial activity of the flower-shaped could be associated with either the lack of defects on the particle core or the shape shielding effect. Compared to S. aureus, E. coli seems to be less resistant to ZnO NPs, which may be explained by the characteristics of its cell membrane. With simple synthesis techniques, which do not allow the size and shape of the nanoparticles to be controlled simultaneously, it is a challenge to elucidate the effect of each of these two parameters on antibacterial performance.