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The article profiles the issue of suicide in the state of Rio Grande do Sul. Rio Grande do Sul evidenced the highest rates for suicide in Brazil during the period under study. The standardized coefficients went from levels around 9/100000 in the 1980s to 11/100000 in 1999. The study points to suicide as a collective health problem in Rio Grande do Sul and reveals characteristics that could contribute to preventative action. The monitoring of violent events in the community is one of the strategies in health promotion and allows the identification of potential factors for early intervention.

We report the direct detection of two metastable H(22S) atoms coming from the dissociation of a single cold H2 molecule, in coincidence measurements. The molecular dissociation was induced by electron impact in order to avoid limitations by the selection rules governing radiative transitions. Two detectors, placed close to the collision center, measure the neutral metastable H(22S) through a localized quenching process, which mixes the H(22S) state with the H(22P), leading to a Lyman-a detection. Our data show the accomplishment of a coincidence measurement which proves for the first time the existence of the H(22S)-H(22S) dissociation channel. [ABSTRACT FROM AUTHOR]

The article discusses the public health emergency of national concern declared by the Brazilian Ministry of Health looking at the rising number of neurologic disorders in newborns in the country. It also discusses the potential connection between the Zika virus infection with that of the neurologic disorders like microcephaly and the public health emergency of international concern declared by the organization World Health Organization in February 2016.

Human mobility is an important driver of geographic spread of infectious pathogens. Detailed information about human movements during outbreaks are, however, difficult to obtain and may not be available during future epidemics. The Ebola virus disease (EVD) outbreak in West Africa between 2014–16 demonstrated how quickly pathogens can spread to large urban centers following one cross-species transmission event. Here we describe a flexible transmission model to test the utility of generalised human movement models in estimating EVD cases and spatial spread over the course of the outbreak. A transmission model that includes a general model of human mobility significantly improves prediction of EVD's incidence compared to models without this component. Human movement plays an important role not only to ignite the epidemic in locations previously disease free, but over the course of the entire epidemic. We also demonstrate important differences between countries in population mixing and the improved prediction attributable to movement metrics. Given their relative rareness, locally derived mobility data are unlikely to exist in advance of future epidemics or pandemics. Our findings show that transmission patterns derived from general human movement models can improve forecasts of spatio-temporal transmission patterns in places where local mobility data is unavailable. [ABSTRACT FROM AUTHOR]

The polyphenol resveratrol (3,5,4′-trihydroxystilbene) is a well-known plant secondary metabolite, commonly used as a medical ingredient and a nutritional supplement. Due to its health-promoting properties, the demand for resveratrol is expected to continue growing. This stilbene can be found in different plants, including grapes, berries (blackberries, blueberries and raspberries), peanuts and their derived food products, such as wine and juice. The commercially available resveratrol is usually extracted from plants, however this procedure has several drawbacks such as low concentration of the product of interest, seasonal variation, risk of plant diseases and product stability. Alternative production processes are being developed to enable the biotechnological production of resveratrol by genetically engineering several microbial hosts, such as Escherichia coli, Corynebacterium glutamicum, Lactococcus lactis, among others. However, these bacterial species are not able to naturally synthetize resveratrol and therefore genetic modifications have been performed. The application of emerging metabolic engineering offers new possibilities for strain and process optimization. This mini-review will discuss the recent progress on resveratrol biosynthesis in engineered bacteria, with a special focus on the metabolic engineering modifications, as well as the optimization of the production process. These strategies offer new tools to overcome the limitations and challenges for microbial production of resveratrol in industry. [ABSTRACT FROM AUTHOR]

Epigenetic dysregulation has emerged as an important etiological mechanism of neurodevelopmental disorders (NDDs). Pathogenic variation in epigenetic regulators can impair deposition of histone post-translational modifications leading to aberrant spatiotemporal gene expression during neurodevelopment. The male-specific lethal (MSL) complex is a prominent multi-subunit epigenetic regulator of gene expression and is responsible for histone 4 lysine 16 acetylation (H4K16ac). Using exome sequencing, here we identify a cohort of 25 individuals with heterozygous de novo variants in MSL complex member MSL2. MSL2 variants were associated with NDD phenotypes including global developmental delay, intellectual disability, hypotonia, and motor issues such as coordination problems, feeding difficulties, and gait disturbance. Dysmorphisms and behavioral and/or psychiatric conditions, including autism spectrum disorder, and to a lesser extent, seizures, connective tissue disease signs, sleep disturbance, vision problems, and other organ anomalies, were observed in affected individuals. As a molecular biomarker, a sensitive and specific DNA methylation episignature has been established. Induced pluripotent stem cells (iPSCs) derived from three members of our cohort exhibited reduced MSL2 levels. Remarkably, while NDD-associated variants in two other members of the MSL complex (MOF and MSL3) result in reduced H4K16ac, global H4K16ac levels are unchanged in iPSCs with MSL2 variants. Regardless, MSL2 variants altered the expression of MSL2 targets in iPSCs and upon their differentiation to early germ layers. Our study defines an MSL2-related disorder as an NDD with distinguishable clinical features, a specific blood DNA episignature, and a distinct, MSL2-specific molecular etiology compared to other MSL complex-related disorders., Competing Interests: Declaration of interests B.S. is a shareholder in EpiSign Inc, involved in commercial uses of EpiSign(TM) technology D.A.C. and K.G.M. are employees of GeneDx, LLC., (Copyright © 2024. Published by Elsevier Inc.)

Carbapenem-resistant Klebsiella pneumoniae (CR-KP) are a public health concern, causing infections with a high mortality rate, limited therapeutic options and challenging infection control strategies. In Portugal, the CR-KP rate has increased sharply, but the factors associated with this increase are poorly explored. In order to address this question, phylogenetic and resistome analysis were used to compare the draft genomes of 200 CR-KP isolates collected in 2017-2019 from five hospitals in the Lisbon region, Portugal. Most CR-KP belonged to sequence type (ST) 13 (29%), ST17 (15%), ST348 (13%), ST231 (12%) and ST147 (7%). Carbapenem resistance was conferred mostly by the presence of KPC-3 (74%) or OXA-181 (18%), which were associated with IncF/IncN and IncX plasmids, respectively. Almost all isolates were multi-drug resistant, harbouring resistance determinants to aminoglycosides, beta-lactams, trimethoprim, fosfomycin, quinolones and sulphonamides. In addition, 11% of isolates were resistant to colistin. Colonizing and infecting isolates were highly related, and most colonized patients (89%) reported a previous hospitalization. Moreover, among the 171 events of cross-dissemination identified by core genome multi-locus sequence typing data analysis (fewer than five allelic differences), 41 occurred between different hospitals and 130 occurred within the same hospital. The results suggest that CR-KP dissemination in the Lisbon region results from acquisition of carbapenemases in mobile genetic elements, influx of CR-KP into the hospitals by colonized ambulatory patients, and transmission of CR-KP within and between hospitals. Prudent use of carbapenems, patient screening at hospital entry, and improvement of infection control are needed to decrease the burden of CR-KP infection in Portugal., (Copyright © 2024 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

The gold standard for coronavirus disease 2019 diagnostic testing relies on RNA extraction from naso/oropharyngeal swab followed by amplification through reverse transcription-polymerase chain reaction (RT-PCR) with fluorogenic probes. While the test is extremely sensitive and specific, its high cost and the potential discomfort associated with specimen collection made it suboptimal for public health screening purposes. In this study, we developed an equally reliable, but cheaper and less invasive alternative test based on a one-step RT-PCR with the DNA-intercalating dye SYBR Green, which enables the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly from saliva samples or RNA isolated from nasopharyngeal (NP) swabs. Importantly, we found that this type of testing can be fine-tuned to discriminate SARS-CoV-2 variants of concern. The saliva RT-PCR SYBR Green test was successfully used in a mass-screening initiative targeting nearly 4500 asymptomatic children under the age of 12. Testing was performed at a reasonable cost, and in some cases, the saliva test outperformed NP rapid antigen tests in identifying infected children. Whole genome sequencing revealed that the antigen testing failure could not be attributed to a specific lineage of SARS-CoV-2. Overall, this work strongly supports the view that RT-PCR saliva tests based on DNA-intercalating dyes represent a powerful strategy for community screening of SARS-CoV-2. The tests can be easily applied to other infectious agents and, therefore, constitute a powerful resource for an effective response to future pandemics., (© The Author(s) 2024. Published by Oxford University Press.)

Importance: Endoscopes are paramount to the practice of otolaryngology. To provide physicians in low-middle-income countries with adequate tools to treat otolaryngologic problems, it is necessary to create a low-cost sustainable option., Objective: To describe the design and usability of an open-source, low-cost flexible laryngoscope that addresses the lack of affordable and accessible methods for otolaryngologic visualization in resource-limited settings., Design, Setting, and Participants: This quality improvement study used a mixed-methods approach, including a technical description of device design as well as quantitative and qualitative survey evaluation of device usability. Engineering involved device design, sourcing or manufacturing individual components, fabricating a prototype, and iterative testing. Key assumptions and needs for the device were identified in collaboration with otolaryngologists in Zimbabwe, and designed and simulated by biomedical engineers in a US university laboratory. Board-certified otolaryngologists at a single US university hospital trialed a completed prototype on simulated airways between May 2023 and June 2023., Main Outcomes and Measures: Technical details on the design of the device are provided. Otolaryngologist gave feedback on device characteristics, maneuverability, and visualization using the System Usability Scale, a customized Likert-scale questionnaire (5-point scale), and semistructured interviews., Results: A functional prototype meeting requirements was completed consisting of a distal-chip camera, spring bending tip, handle housing the control mechanism and electronics, and flexible polyether block amide-coated silicone sheath housing the camera and control wires; an external monitor provided real-time visualization and ability to store data. A total of 14 otolaryngologists participated in the device review. The mean (SD) System Usability Scale score was 88.93 (10.08), suggesting excellent usability. The device was rated highly for ease of set up, physical attributes, image quality, and functionality., Conclusions and Relevance: This quality improvement study described the design of a novel open-source low-cost flexible laryngoscope that external review with otolaryngologists suggests was usable and feasible in various resource-limited environments. Future work is needed to translate the model into a clinical setting.

Background: Undiagnosed cases of hepatitis C virus (HCV) infection result in significant morbidity and mortality, further transmission, and increased public health costs. Testing in emergency departments (EDs) is an opportunity to expand HCV screening. The goal of this project was to increase the proportion of eligible patients screened for HCV in urban areas., Methods: An opportunistic automated HCV screening program was implemented in the EDs of 4 public hospitals in Spain and Portugal at different periods between 2018 and 2023. HCV prevalence was prospectively evaluated, and single-step or reflex testing was used for confirmation in the same sample., Results: More than 90% of the population eligible for testing were screened in the participating centers. We found HCV antibody seroprevalence rates ranging from 0.6 to 3.9%, with between 19 and 53% of viremic individuals., Conclusions: Opportunistic HCV screening in EDs is feasible, does not disrupt ED activities, is highly effective in increasing diagnosis, and contributes to WHO's HCV elimination goals., (© 2023. The Author(s).)

Introduction: Exacerbations are common in individuals with alpha-1 antitrypsin deficiency (AATD)-related lung disease. This study intended to identify independent predictive factors for exacerbations in AATD using the Portuguese European Alpha-1 Research Collaboration (EARCO) registry., Methods: This study includes patients from the Portuguese EARCO registry, a prospective multicenter cohort (NCT04180319). From October 2020 to April 2023, this registry enrolled 137 patients, 14 of whom were excluded for analysis for either missing 12 months of follow-up or baseline pulmonary function., Results: Among the 123 AATD patients, 27 (22.0%) had at least one exacerbation in the last 12 months of follow-up. Patients with Pi*ZZ phenotype were three times more likely than the rest of the population to experience any exacerbation (32.7 vs. 14.1%, p = 0.014; OR 3.0). BODE index was significantly higher in exacerbators than in non-exacerbators (3.9 ± 2.4 vs. 1.3 ± 1.2; p < 0.001), including on multivariate analysis (p = 0.002). Similar results were found for BODEx (multivariate p < 0.001). DLCO was the only functional parameter independently associated with exacerbations (p = 0.024)., Conclusions: DLCO, BODE, and BODEx were independent predictors of exacerbations at 12 months in AATD patients. Understanding these risk factors can aid decision-making on AATD-related lung disease management and improve patient outcomes., (© 2024 S. Karger AG, Basel.)

Introduction: Accurate and early staging of lung cancer has a critical impact on its prognosis. EBUS-TBNA is often the procedure of choice for mediastinal staging. Comprehension of the likelihood of malignancy of each lymph node (LN) can assist puncture decision-making during EBUS and offer insight of the procedure expected diagnostic yield., Methods: Prospective analysis of mediastinal LN of patients undergoing EBUS-TBNA from April 2021 to May 2022. The relationship between PET-CT SUV max levels, EBUS features, and malignancy on LN was investigated. For statistical analysis, patients were assigned to 3 groups: suspected malignancy (diagnosis and/or staging), confirmed malignancy (staging) or suspected benign disease., Results: A total of 363 LN from 132 patients (71% male, mean 62 years old) were analyzed. Among those with suspected benign disease, no LN puncture resulted in a diagnosis of malignancy. PET-CT SUV max and short axis size were independent factors for malignancy in LN of patients who underwent EBUS for suspected (p < .001 and p = .047, respectively) or confirmed malignancy (p < .001 and p < .001, respectively). All malignant LN presented SUV max ≥1.85 (≥2.85 for staging EBUS cases) and/or short axis size ≥4.28mm. Vascularized LN were more often malignant in either those with suspected (p = .087) or confirmed (p = .095) malignancy, although not statistically significant. LN that were simultaneously vascularized and lacked central hilar structure were also more commonly malignant (p = .013)., Conclusion: LN that has higher SUV max and are larger should be prioritized for puncture, followed by those vascularized and lacking central hilar structure. In staging EBUS cases, a systematic sampling (N3-N2-N1) is required and must precede any malignancy yield rationale., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A common basis to address the dynamics of directly transmitted infectious diseases, such as COVID-19, are compartmental (or SIR) models. SIR models typically assume homogenous population mixing, a simplification that is convenient but unrealistic. Here we validate an existing model of a scale-free fractal infection process using high-resolution data on COVID-19 spread in São Caetano, Brazil. We find that transmission can be described by a network in which each infectious individual has a small number of susceptible contacts, of the order of 2-5. This model parameter correlated tightly with physical distancing measured by mobile phone data, such that in periods of greater distancing the model recovered a lower average number of contacts, and vice versa. We show that the SIR model is a special case of our scale-free fractal process model in which the parameter that reflects population structure is set at unity, indicating homogeneous mixing. Our more general framework better explained the dynamics of COVID-19 in São Caetano, used fewer parameters than a standard SIR model and accounted for geographically localized clusters of disease. Our model requires further validation in other locations and with other directly transmitted infectious agents., (© 2023 Published by Elsevier Inc.)

Objective: To analyze the relationship between one-minute sit-to-stand test (1MSTST) parameters and a diagnosis of post COVID-19 condition in a cohort of patients who previously had COVID-19., Methods: This was a prospective cohort study of patients with post COVID-19 condition referred for body plethysmography at a tertiary university hospital. Post COVID-19 condition was defined in accordance with the current WHO criteria., Results: Fifty-three patients were analyzed. Of those, 25 (47.2%) met the clinical criteria for post COVID-19 condition. HR was lower in the patients with post COVID-19 condition than in those without it at 30 s after initiation of the 1MSTST (86.2 ± 14.3 bpm vs. 101.2 ± 14.7 bpm; p < 0.001) and at the end of the test (94.4 ± 18.2 bpm vs. 117.3 ± 15.3 bpm; p < 0.001). The ratio between HR at the end of the 1MSTST and age-predicted maximal HR (HRend/HRmax) was lower in the group of patients with post COVID-19 condition (p < 0.001). An HRend/HRmax of < 62.65% showed a sensitivity of 78.6% and a specificity of 82.0% for post COVID-19 condition. Mean SpO2 at the end of the 1MSTST was lower in the patients with post COVID-19 condition than in those without it (94.9 ± 3.6% vs. 96.8 ± 2.4%; p = 0.030). The former group of patients did fewer repetitions on the 1MSTST than did the latter (p = 0.020)., Conclusions: Lower SpO2 and HR at the end of the 1MSTST, as well as lower HR at 30 s after initiation of the test, were associated with post COVID-19 condition. In the appropriate clinical setting, an HRend/HRmax of < 62.65% should raise awareness for the possibility of post COVID-19 condition.

Background: Iron deficiency anaemia (IDA) is the leading cause of years lost to disability in most sub-Saharan African countries and is especially common in young children. The IHAT-GUT trial assessed the efficacy and safety of a novel nano iron supplement, which is a dietary ferritin analogue termed iron hydroxide adipate tartrate (IHAT), for the treatment of IDA in children under 3 years of age., Methods: In this single-country, randomised, double-blind, parallel, placebo-controlled, non-inferiority Phase II study in The Gambia, children 6-35 months with IDA (7≤Hb < 11 g/dL and ferritin<30 μg/L) were randomly assigned (1:1:1) to receive either IHAT, ferrous sulphate (FeSO 4 ) or placebo daily for 3 months (85 days). The daily iron dose was 12.5 mg Fe equivalent for FeSO 4 and the estimated dose with comparable iron-bioavailability for IHAT (20 mg Fe). The primary efficacy endpoint was the composite of haemoglobin response at day 85 and correction of iron deficiency. The non-inferiority margin was 0.1 absolute difference in response probability. The primary safety endpoint was moderate-severe diarrhoea analysed as incidence density and prevalence over the 3 months intervention. Secondary endpoints reported herein include hospitalisation, acute respiratory infection, malaria, treatment failures, iron handling markers, inflammatory markers, longitudinal prevalence of diarrhoea and incidence density of bloody diarrhoea. Main analyses were per-protocol (PP) and intention-to-treat (ITT) analyses. This trial is registered with clinicaltrials.gov (NCT02941081)., Findings: Between Nov 2017 and Nov 2018, 642 children were randomised into the study (214 per group) and included in the ITT analysis, the PP population included 582 children. A total of 50/177 (28.2%) children in the IHAT group achieved the primary efficacy endpoint, as compared with 42/190 (22.1%) in the FeSO 4 group (OR 1.39, 80% CI 1.01-1.91, PP population) and with 2/186 (1.1%) in the placebo group. Diarrhoea prevalence was similar between groups, with 40/189 (21.2%) children in the IHAT group developing at least one episode of moderate-severe diarrhoea over the 85 days intervention, compared with 47/198 (23.7%) in the FeSO 4 group (OR 1.18, 80% CI 0.86-1.62) and 40/195 (20.5%) in the placebo group (OR 0.96, 80% CI 0.7-1.33, PP population). Incidence density of moderate-severe diarrhoea was 2.66 in the IHAT group and 3.42 in the FeSO 4 group (RR 0.76, 80% CI 0.59-0.99, CC-ITT population).There were 143/211 (67.8%) children with adverse events (AEs) in the IHAT group, 146/212 (68.9%) in the FeSO 4 group and 143/214 (66.8%) in the placebo group. There were overall 213 diarrhoea-related AEs; 35 (28.5%) cases reported in the IHAT group compared with 51 (41.5%) cases in the FeSO 4 group and 37 (30.1%) cases in the placebo group., Interpretation: In this first Phase II study conducted in young children with IDA, IHAT showed sufficient non-inferiority compared to standard-of-care FeSO 4 , in terms of ID correction and haemoglobin response, to warrant a definitive Phase III trial. In addition, IHAT had lower incidence of moderate-severe diarrhoea than FeSO 4 , with no increased adverse events in comparison with placebo., Funding: The Bill & Melinda Gates Foundation (OPP1140952)., Competing Interests: D.I.A.P., N.F. and J.J.P. are inventors of the IHAT iron supplementation technology, for which they could receive future awards to inventors through the MRC Awards to Inventor scheme. They are also scientific advisors to Nemysis Ltd, who now hold the license for IHAT. They have received honoraria or consultancy fees from some or all of: Vifor Pharma UK, Shield Therapeutics, Entia Ltd, Danone Nutricia, UN Food and Agriculture Organisation (FAO) and Nemysis Ltd, for work concerning iron in health. D.I.A.P. has since moved to full employment in the iron and health industry with Vifor Pharma UK but all work pertaining to this publication was conducted whilst at the University of Cambridge and MRC Unit The Gambia at LSHTM. Nemysis Ltd paid consulting fees to J.W.’s Institution. Notwithstanding, the authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2023 The Authors.)

In a study of antibiotic resistance in Staphylococcus aureus, specific cell wall mutants were previously generated for the peptidoglycan biosynthesis gene murF , by the insertion of an integrative plasmid. A collection of 30 independent mutants was obtained, and all harbored a variable number of copies of the inserted plasmid, arranged in tandem in the chromosome. Of the 30 mutants, only 3, F9, F20 and F26, with a lower number of plasmid copies, showed an altered peptidoglycan structure, lower resistance to β-lactams and a different loss-of-function mutation in rho gene, that encodes a transcription termination factor. The rho mutations were found to correlate with the level of oxacillin resistance, since genetic complementation with rho gene reestablished the resistance and cell wall parental profile in F9, F20 and F26 strains. Furthermore, complementation with rho resulted in the amplification of the number of plasmid tandem repeats, suggesting that Rho enabled events of recombination that favored a rearrangement in the chromosome in the region of the impaired murF gene. Although the full mechanism of reversion of the cell wall damage was not fully elucidated, we showed that Rho is involved in the recombination process that mediates the tandem amplification of exogeneous DNA fragments inserted into the chromosome. IMPORTANCE The cell wall of bacteria, namely, peptidoglycan, is the target of several antibiotic classes such as β-lactams. Staphylococcus aureus is well known for its capacity to adapt to antibiotic stress and develop resistance strategies, namely, to β-lactams. In this context, the construction of cell wall mutants provides useful models to study the development of such resistance mechanisms. Here, we characterized a collection of independent mutants, impaired in the same peptidoglycan biosynthetic step, obtained through the insertion of a plasmid in the coding region of murF gene. S. aureus demonstrated the capacity to overcome the cell wall damage by amplifying the copy number of the inserted plasmid, through an undescribed mechanism that involves the Rho transcription termination factor.

Extracellular vesicles (EVs) are emerging as powerful players in cell-to-cell communication both in healthy and diseased brain. In Parkinson's disease (PD)-characterized by selective dopaminergic neuron death in ventral midbrain (VMB) and degeneration of their terminals in striatum (STR)-astrocytes exert dual harmful/protective functions, with mechanisms not fully elucidated. Here, this study shows that astrocytes from the VMB-, STR-, and VMB/STR-depleted brains release a population of small EVs  in a region-specific manner. Interestingly, VMB-astrocytes secreted the highest rate of EVs, which is further exclusively increased in response to CCL3, a chemokine that promotes robust dopaminergic neuroprotection in different PD models. The neuroprotective potential of nigrostriatal astrocyte-EVs is investigated in differentiated versus undifferentiated SH-SY5Y cells exposed to oxidative stress and mitochondrial toxicity. EVs from both VMB- and STR-astrocytes counteract H 2 O 2 -induced caspase-3 activation specifically in differentiated cells, with EVs from CCL3-treated astrocytes showing a higher protective effect. High resolution respirometry further reveals that nigrostriatal astrocyte-EVs rescue neuronal mitochondrial complex I function impaired by the neurotoxin MPP + . Notably, only EVs from VMB-astrocyte fully restore ATP production, again specifically in differentiated SH-SY5Y. These results highlight a regional diversity in the nigrostriatal system for the secretion and activities of astrocyte-EVs, with neuroprotective implications for PD., (© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

BACKGROUND: Accurate diagnosis of TB infection (TBI) is challenging due to the lack of a gold standard. Tuberculin skin test (TST) and interferon-gamma release assay (IGRA) are currently useful in TBI diagnosis, but both have several limitations. This study aims to evaluate inter-operator variability in TST measurements and determine its impact on TBI diagnosis and treatment. METHODS: This was a retrospective analysis of patients screened for TBI using at least TST at a public outpatient clinic specialised in TB from January 2019 to August 2021. TST readings performed by five experienced nurses were compared. RESULTS: A total of 671 screenings were analysed. TST positivity rate ( P < 0.001) and mean TST measurements obtained by our nurses were significantly different ( P < 0.001). Concordance of TST and IGRA results was of 83.4% in the overall population (κ = 0.479). However, TST/IGRA agreement was significantly different among nurses ( P = 0.003). CONCLUSION: Our analysis of TST measurements by experienced nurses shows significant differences in TST positivity rate, mean measured values and overall concordance with IGRA. This led to significant different outcomes in TBI diagnosis and subsequent treatment. TST measurement differences could potentially be more pronounced if we considered untrained operators or those with occasional reading experience.

Aromatic compounds are an important class of chemicals with different industrial applications. They are usually produced by chemical synthesis from petroleum-derived feedstocks, such as toluene, xylene and benzene. However, we are now facing threats from the excessive use of fossil fuels causing environmental problems such as global warming. Furthermore, fossil resources are not infinite, and will ultimately be depleted. To cope with these problems, the sustainable production of aromatic chemicals from renewable non-food biomass is urgent. With this in mind, the search for alternative methodologies to produce aromatic compounds using low-cost and environmentally friendly processes is becoming more and more important. Microorganisms are able to produce aromatic and aromatic-derivative compounds from sugar-based carbon sources. Metabolic engineering strategies as well as bioprocess optimization enable the development of microbial cell factories capable of efficiently producing aromatic compounds. This review presents current breakthroughs in microbial production of specialty aromatic and aromatic-derivative products, providing an overview on the general strategies and methodologies applied to build microbial cell factories for the production of these compounds. We present and describe some of the current challenges and gaps that must be overcome in order to render the biotechnological production of specialty aromatic and aromatic-derivative attractive and economically feasible at industrial scale., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)