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Background/aim Hundreds of air pollution and COVID-19 papers have been published in a short time varying widely in quality. The Greater London Authority commissioned a comprehensive overview of the most credible evidence for the links between air pollution and COVID-19 and other lung infections. Methods Building on the Brunekreef et al (2021) review, a literature search was performed from November 2020 – May 2021, classifying the evidence by exposure, the potential mechanism and the health outcome. Studies on hospital admissions for lower respiratory infections were reviewed from 2011 Results Long-term exposure increased the risk of hospitalization in people already infected with COVID-19 in two good-quality cohort studies with individual data, perhaps due to respiratory and cardiovascular disease from air pollution increasing vulnerability to COVID-19 adverse outcomes. Mortality results were conflicting. Inconsistent results were found for long-term exposure and COVID-19 cases in ecological studies. Studies on short-term exposure were unclear and hard to evaluate. Several studies demonstrated that inhaled pollutant increased expression of the ACE2 receptor and other host susceptibility genes in both alveolar epithelial cells and macrophages. Susceptibility to infection by SARS-CoV-2 can be inferred from these results but only one study used SARS-CoV-2 directly. Several studies from 2011-2021 showed a link between air pollution and hospital admissions for lung infections although the studies were spread across different age groups and disease definitions. Particulate matter does not appear to play any important part in transporting COVID-19 in the environment, as had been suggested by some earlier studies. Conclusions The publication of cohort studies with individual data in this time period is an important step forward. Results are suggestive for long-term exposure and hospital admissions for COVID-19 and some toxicological effects are plausible but further research will be necessary to strengthen these emerging findings. Keywords Air pollution, COVID-19, lower respiratory infections.

Background: It is known that on days with high temperatures higher mortality is observed and there is a minimum mortality temperature (MMT) point which is higher in places with warmer climate. This indicates some population adaptation to local climate but information on how quickly this adaptation will occur under climate change is lacking. Methods: To investigate this, we associated daily mortality data with temperature during the warm period in 2004–2013 for London inhabitants born in five climatic zones (UK, Tropical, Sub-tropical, Boreal and Mixed). We fitted Poisson regression with distributed-lag non-linear models for each climatic zone group separately to estimate group-specific exposure-response associations and MMTs. We report relative risks of death comparing the 95th percentile (21 °C) and maximum (25 °C) of the temperature distribution in London with the zone-specific minimum mortality temperature. Results: No heat-related mortality was observed for people born in countries with Sub-tropical and Mixed climates. We observed an increase of 26%, 35% and 39% in the risk of death at 25 °C compared to the MMT in people born in the UK (marine climate), Tropical and Boreal climate respectively. The temperatures with the lowest mortality in these groups ranged from 15.9 to 17.7 °C. Discussion: Our findings imply that people born in different climatic zones do not adapt fully to their new environment within their lifetime. This implies that populations may not adapt readily to climate change and will suffer increased effects from heat. In the presence of climate change, policy makers should be aware of a delayed process of adaptation. © 2020

Mononuclear phagocytes such as monocytes, tissue-specific macrophages, and dendritic cells are primary actors in both innate and adaptive immunity. These professional phagocytes can be parasitized by intracellular bacteria, turning them from housekeepers to hiding places and favoring chronic and/or disseminated infection. One of the most infamous is the bacteria that cause tuberculosis (TB), which is the most pandemic and one of the deadliest diseases, with one-third of the world’s population infected and an average of 1.8 million deaths/year worldwide. Here we demonstrate the effective targeting and intracellular delivery of antibiotics to infected macrophages both in vitro and in vivo, using pH-sensitive nanoscopic polymersomes made of PMPC–PDPA block copolymer. Polymersomes showed the ability to significantly enhance the efficacy of the antibiotics killing Mycobacterium bovis, Mycobacterium tuberculosis, and another established intracellular pathogen, Staphylococcus aureus. Moreover, they demonstrated to easily access TB-like granuloma tissues—one of the harshest environments to penetrate—in zebrafish models. We thus successfully exploited this targeting for the effective eradication of several intracellular bacteria, including M. tuberculosis, the etiological agent of human TB.

Background: The use of proxy exposure estimates for PM2.5 and NO2 in air pollution studies instead of personal exposures, introduces measurement error, which can produce biased epidemiological effect estimates. Most studies consider total personal exposure as the gold standard. However, when studying the effects of ambient air pollution, personal exposure from outdoor sources is the exposure of interest. Objectives: We assessed the magnitude and variability of exposure measurement error by conducting a systematic review of the differences between personal exposures from outdoor sources and the corresponding measurements for ambient concentrations in order to increase understanding of the measurement error structures of the pollutants. Data sources and eligibility criteria: We reviewed the literature (ISI Web of Science, Medline, 2000–2016) for English language studies (in any age group in any location (NO2) or Europe and North America (PM2.5)) that reported repeated measurements over time both for personal and ambient PM2.5 or NO2 concentrations. Only a few studies reported personal exposure from outdoor sources. We also collected data for infiltration factors and time-activity patterns of the individuals in order to estimate personal exposures from outdoor sources in every study. Study appraisal and synthesis methods: Studies using modelled rather than monitored exposures were excluded. Type of personal exposure monitor was assessed. Random effects meta-analysis was conducted to quantify exposure error as the mean difference between “true” and proxy measures. Results: Thirty-two papers for PM2.5 and 24 for NO2 were identified. Outdoor sources were found to contribute 44% (range: 33–55%) of total personal exposure to PM2.5 and 74% (range: 57–88%) to NO2. Overall estimates of personal exposure (24-hour averages) from outdoor sources were 9.3 μg/m3 and 12.0 ppb for PM2.5 and NO2 respectively, while the corresponding difference between these exposures and the ambient concentrations (i.e. the measurement error) was 5.72 μg/m3 and 7.17 ppb. Our findings indicated also higher error variability for NO2 than PM2.5. Large heterogeneity was observed which was not explained sufficiently by geographical location or age group of the study sample. Limitations, conclusions and implications of key findings: Relying only on information available in published studies led to some limitations: the contribution of outdoor sources to total personal exposure for NO2 had to be inferred, individual variation in exposure misclassification was unavailable and instrument error could not be addressed. The larger magnitude and variability of errors for NO2 compared with PM2.5 has implications for biases in the health effect estimates of multi-pollutant epidemiological models. Results suggest that further research is needed regarding personal exposure studies and measurement error bias in epidemiological models. © 2020 The Authors

The initial adaptive transcriptional response to nitrogen (N) starvation in Escherichia coli involves large-scale alterations to the transcriptome mediated by the transcriptional activator, NtrC. One of these NtrC-activated genes is yeaG, which encodes a conserved bacterial kinase. Although it is known that YeaG is required for optimal survival under sustained N starvation, the molecular basis by which YeaG benefits N starved E. coli remains elusive. By combining transcriptomics with targeted metabolomics analyses, we demonstrate that the methionine biosynthesis pathway becomes transcriptionally dysregulated in ΔyeaG bacteria experiencing sustained N starvation. It appears the ability of MetJ, the master transcriptional repressor of methionine biosynthesis genes, to effectively repress transcription of genes under its control is compromised in ΔyeaG bacteria under sustained N starvation, resulting in transcriptional derepression of MetJ-regulated genes. Although the aberrant biosynthesis does not appear to be a contributing factor for the compromised viability of ΔyeaG bacteria experiencing sustained N starvation, this study identifies YeaG as a novel regulatory factor in E. coli affecting the transcription of methionine biosynthesis genes under sustained N starvation.

Previous time series or panel studies of asthmatics have reported respiratory health effects following short-Term exposure to ozone (O3). We followed 186 children aged 10 years old in Athens and Thessaloniki, Greece for 5 weeks during the academic year 2013-2014 and recorded daily their respiratory symptoms, absenteeism and peak expiratory flow (PEF). We applied mixed models controlling for various possible confounders to investigate the daily associations between O3 exposure - derived from weekly personal and fixed school site measurements calibrated using daily values of the fixed monitoring site nearest to the child's school location -And PEF, presence of any symptom, cough and stuffy nose, as well as absenteeism. We tested the robustness of our findings to varying modeling assumptions and confounders and investigated effect modification patterns by medication use, time spent outdoors and prevalence of asthma. A 10 μg/m3 increase in O3 personal exposure was associated with increased odds of any symptom (odds ratio (OR): 1.19, 95% confidence interval (CI): 0.98, 1.44), largely attributed to the increase in the odds of stuffy nose (OR: 1.23, 95% CI: 1.00, 1.51). PEF and absenteeism were not related to O3 exposure. Our results were robust to several sensitivity analyses. Effects were modified by medication use as presence of symptoms but also decreases in PEF were mainly reported among non-users, while our effect estimates were not driven by the asthmatic subgroup of children. Our findings indicate that short-Term O3 exposure may be associated with respiratory symptoms extending previously reported results for asthmatics to the general population. © 2017 Nature America, Inc., part of Springer Nature. All rights reserved.

New chemotherapeutic agents with novel mechanisms of action are in urgent need to combat the tuberculosis pandemic. A library of 12 C8-linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD)-heterocyclic polyamide conjugates (1-12) was evaluated for anti-tubercular activity and DNA sequence selectivity. The PBD conjugates were screened against slow-growing Mycobacterium bovis Bacillus Calmette-Guérin and M. tuberculosis H37Rv, and fast-growing Escherichia coli, Pseudomonas putida and Rhodococcus sp. RHA1 bacteria. DNase I footprinting and DNA thermal denaturation experiments were used to determine the molecules' DNA recognition properties. The PBD conjugates were highly selective for the mycobacterial strains and exhibited significant growth inhibitory activity against the pathogenic M. tuberculosis H37Rv, with compound 4 showing MIC values (MIC=0.08 mg l-1) similar to those of rifampin and isoniazid. DNase I footprinting results showed that the PBD conjugates with three heterocyclic moieties had enhanced sequence selectivity and produced larger footprints, with distinct cleavage patterns compared with the two-heterocyclic chain PBD conjugates. DNA melting experiments indicated a covalent binding of the PBD conjugates to two AT-rich DNA-duplexes containing either a central GGATCC or GTATAC sequence, and showed that the polyamide chains affect the interactions of the molecules with DNA. The PBD-C8 conjugates tested in this study have a remarkable anti-mycobacterial activity and can be further developed as DNA-targeted anti-tubercular drugs.

Novel pyrroles have been designed, synthesized, and evaluated against mycobacterial strains. The pyrroles have originally been designed as hybrids of the antitubercular drugs BM212 (1) and SQ109 (2), which showed common chemical features with very similar topological distribution. A perfect superposition of the structures of 1 and 2 revealed by computational studies suggested the introduction of bulky substituents at the terminal portion of the pyrrole C3 side chain and the removal of the C5 aryl moiety. Five compounds showed high activity toward Mycobacterium tuberculosis, while 9b and 9c were highly active also against multidrug-resistant clinical isolates. Compound 9c showed low eukaryotic cell toxicity, turning out to be an excellent lead candidate for preclinical trials. In addition, four compounds showed potent inhibition (comparable to that of verapamil) toward the whole-cell drug efflux pump activity of mycobacteria, thus turning out to be promising multidrug-resistance-reversing agents.

Introduction: As part of the primary investigation, polytrauma patients arriving at our emergency department are examined in accordance with the Advanced Trauma Life Support (ATLS) rules, using the new Lodox Statscan (LS) digital low-radiation imaging device. The aim of this study was to establish whether entrance and effective radiation doses using LS in children were comparable to those of paediatric Computed Radiography (CR) and to evaluate the duration of scanning for both techniques in young polytrauma patients. Methods: 19 consecutive polytrauma patients aged

Objectives \ud \ud (S)-Leucoxine, isolated from the Colombian Lauraceae tree Rhodostemonodaphne crenaticupula Madriñan, was found to inhibit the growth of Mycobacterium tuberculosis H37Rv. A biomimetic approach for the chemical synthesis of a wide array of 1-substituted tetrahydroisoquinolines was undertaken with the aim of elucidating a common pharmacophore for these compounds with novel mode(s) of anti-TB action.\ud \ud Methods \ud \ud Biomimetic Pictet–Spengler or Bischler–Napieralski synthetic routes were employed followed by an evaluation of the biological activity of the synthesized compounds.\ud \ud Results \ud \ud In this work, the synthesized tetrahydroisoquinolines were found to inhibit the growth of M. tuberculosis H37Rv and affect its whole-cell phenotype as well as the activity of the ATP-dependent MurE ligase, a key enzyme involved in the early stage of cell wall peptidoglycan biosynthesis.\ud \ud Conclusions \ud \ud As the correlation between the MIC and the half-inhibitory enzymatic concentration was not particularly strong, there is a credible possibility that these compounds have pleiotropic mechanism(s) of action in M. tuberculosis.

Aim: Posterior cervical spine fixation has undergone tremendous advancement in recent years. The purpose of this study is to present our experience with the Roy-Camille instrumentation for posterior cervical stabilization after injury in a long-term follow-up. Patients and methods: From 1985 to 1995, 76 patients with a lower cervical spine traumatic lesion were treated in a single institution by posterior plate stabilization using the Roy-Camille plates (R-C plates). Fifty-four men and 22 women with a mean age of 43.2 years were involved. In 59 patients the injuries were due to a road traffic accident, in 14 cases the fall from a high was responsible, while in two cases the injuries were due to sport activities. There were four bilateral dislocations, nine unilateral dislocations, 56 fracture dislocations, five fracture separations of a lateral mass and two burst fractures. Neurological lesions were present in 65 patients (9 ASIA A, 16 ASIA B, 22 ASIA C, 18 ASIA D and 11 ASIA E). All patients had minimum follow-up of 7 years. Fifty-nine patients were followed up for a mean period of 21 years (14-27 years). Results: Stability was obtained in all but two cases. Reoperation was done in two cases: in one for the correction of the lost reduction and in a second for the reinsertion of a screw irritating a nerve root. No case in the ASIA A group showed neurological improvement, a fact observed in the other groups. Conclusions: The R-C plates were used in the last quarter of the last century. This technique showed good short-time results, and we have shown good results in a long-term follow-up as well. The literature referred to this technique was favorable, as far as the biomechanical behavior and also clinical application concern. The question about this plating system abundance still remains unanswered. © 2013 Springer-Verlag France.

Distal locking of intramedullary nails (IMNs) is a difficult part of intramedullary nailing (IMN) that could be time-consuming and expose the surgeon, the surgery personnel and the patient to a considerable amount of radiation as fluoroscopy is usually guiding the procedure. Utilization of electromagnetic fields for that purpose offers an attractive alternative. The SURESHOT™ Distal Targeting System (Smith & Nephew, Inc., Memphis, TN, USA) is a novel commercially available radiation-free aiming system that utilizes computerized electromagnetic field tracking technology for the distal locking of IMNs. In order to evaluate the efficacy of the system we conducted the present study. Nineteen patients (six females-thirteen males, mean age 39.5 years, range 17-85 years) with closed diaphyseal fracture of the femur (eight patients) or the tibia (eleven patients) were treated with IMN using the SURESHOT™ Distal Targeting System for the distal interlocking. All targeting attempts were successful at first try and followed by correct positioning of the screws. Mean time for distal locking of tibial IMNs (two screws) was 219 sec (range 200-250 sec). Mean time for distal locking of femoral IMNs (two screws) was 249 (range 220-330 sec). In the current study the SURESHOT™ Distal Targeting System proved to be accurate, fast and easy to learn. © 2012 Elsevier Ltd.

Purpose. The rectofemoral fistula represents a devastating complication of colorectal surgery. Its early diagnosis and treatment are critical to obtain a good patient outcome. Case Presentation. A 75-year-old Caucasian female patient presented with high fever, ileus, low back pain, sciatic nerve palsy, and infection of the right knee. After numerous surgical debridements and antibiotic therapies, a rectofemoral fistula was diagnosed. Conclusion. Increased doctors' alertness is mandatory for the early identification and surgical treatment of patients suffering from a rectofemoral fistula before the stage of diffuse infection has significantly decreases their postoperative morbidity and mortality.