Transcription Attenuation in Synthetic Promoters in Nonoverlapping Tandem Formation.

Closely spaced promoters are ubiquitous in prokaryotic and eukaryotic genomes. How their structure and dynamics relate remains unclear, particularly for tandem formations. To study their transcriptional interference, we engineered two pairs and one trio of synthetic promoters in nonoverlapping, tandem formation, in single-copy plasmids transformed into Escherichia coli cells. From in vivo measurements, we found that these promoters in tandem formation can have attenuated transcription rates. The attenuation strength can be widely fine-tuned by the promoters' positioning, natural regulatory mechanisms, and other factors, including the antibiotic rifampicin, which is known to hamper RNAP promoter escape. From this, and supported by in silico models, we concluded that the attenuation in these constructs emerges from premature terminations generated by collisions between RNAPs elongating from upstream promoters and RNAPs occupying downstream promoters. Moreover, we found that these collisions can cause one or both RNAPs to falloff. Finally, the broad spectrum of possible, externally regulated, attenuation strengths observed in our synthetic tandem promoters suggests that they could become useful as externally controllable regulators of future synthetic circuits.

Assessment of crAssphage as a biological variable for SARS-CoV-2 data normalization in wastewater surveillance.

AIMS: This study aimed to assess the use of cross-assembled phage (crAssphage) as an endogenous control employing a multivariate normalization analysis and its application as a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) data normalizer. METHODS AND RESULTS: A total of 188 twelve-hour composite raw sewage samples were obtained from eight wastewater treatment plants (WWTP) during a 1-year monitoring period. Employing the N1 and N2 target regions, SARS-CoV-2 RNA was detected in 94% (177) and 90% (170) of the samples, respectively, with a global median of 5 log10 genomic copies per liter (GC l-1). CrAssphage was detected in 100% of the samples, ranging from 8.29 to 10.43 log10 GC l-1, with a median of 9.46 ± 0.40 log10 GC l-1, presenting both spatial and temporal variabilities. CONCLUSIONS: Although SARS-CoV-2 data normalization employing crAssphage revealed a correlation with clinical cases occurring during the study period, crAssphage normalization by the flow per capita per day of each WWTP increased this correlation, corroborating the importance of normalizing wastewater surveillance data in disease trend monitoring.

What are the triggers for palliative care referral in burn intensive care units? Results from a qualitative study based on healthcare professionals' views, clinical experiences and practices.

BACKGROUND: Burns are a global public health problem, accounting for around 300,000 deaths annually. Burns have significant consequences for patients, families, healthcare teams and systems. Evidence suggests that the integration of palliative care in burn intensive care units improves patients' comfort, decision-making processes and family care. Research is needed on how to optimise palliative care referrals. AIM: To identify triggers for palliative care referral in critically burned patients based on professionals' views, experiences and practices. DESIGN: Qualitative study using in-depth interviews. SETTING/PARTICIPANTS: All five Burn Intensive Care Units reference centres across Portugal were invited; three participated. Inclusion criteria: Professionals with experience/working in these settings. A total of 15 professionals (12 nurses and 3 physicians) participated. Reflexive thematic analysis was performed. RESULTS: Three main triggers for palliative care referral were identified: (i) Burn severity and extension, (ii) Co-morbidities and (iii) Multiorgan failure. Other triggers were also generated: (i) Rehabilitative palliative care related to patients' suffering and changes in body image, (ii) Family suffering and/or dysfunctional and complex family processes, (iii) Long stay in the burn intensive care unit and (iv) Uncontrolled pain. CONCLUSIONS: This study identifies triggers for palliative care in burn intensive care units based on professionals' views, clinical experiences and practices. The systematisation and use of triggers could help streamline referral pathways and strengthen the integration of palliative care in burn intensive care units. Research is needed on the use of these triggers in clinical practice to enhance decision-making processes, early and high-quality integrated palliative care and proportionate patient and family centred care.

Alteration of DNA supercoiling serves as a trigger of short-term cold shock repressed genes of E. coli.

Cold shock adaptability is a key survival skill of gut bacteria of warm-blooded animals. Escherichia coli cold shock responses are controlled by a complex multi-gene, timely-ordered transcriptional program. We investigated its underlying mechanisms. Having identified short-term, cold shock repressed genes, we show that their responsiveness is unrelated to their transcription factors or global regulators, while their single-cell protein numbers' variability increases after cold shock. We hypothesized that some cold shock repressed genes could be triggered by high propensity for transcription locking due to changes in DNA supercoiling (likely due to DNA relaxation caused by an overall reduction in negative supercoiling). Concomitantly, we found that nearly half of cold shock repressed genes are also highly responsive to gyrase inhibition (albeit most genes responsive to gyrase inhibition are not cold shock responsive). Further, their response strengths to cold shock and gyrase inhibition correlate. Meanwhile, under cold shock, nucleoid density increases, and gyrases and nucleoid become more colocalized. Moreover, the cellular energy decreases, which may hinder positive supercoils resolution. Overall, we conclude that sensitivity to diminished negative supercoiling is a core feature of E. coli's short-term, cold shock transcriptional program, and could be used to regulate the temperature sensitivity of synthetic circuits.

The transcription factor network of E. coli steers global responses to shifts in RNAP concentration.

The robustness and sensitivity of gene networks to environmental changes is critical for cell survival. How gene networks produce specific, chronologically ordered responses to genome-wide perturbations, while robustly maintaining homeostasis, remains an open question. We analysed if short- and mid-term genome-wide responses to shifts in RNA polymerase (RNAP) concentration are influenced by the known topology and logic of the transcription factor network (TFN) of Escherichia coli. We found that, at the gene cohort level, the magnitude of the single-gene, mid-term transcriptional responses to changes in RNAP concentration can be explained by the absolute difference between the gene's numbers of activating and repressing input transcription factors (TFs). Interestingly, this difference is strongly positively correlated with the number of input TFs of the gene. Meanwhile, short-term responses showed only weak influence from the TFN. Our results suggest that the global topological traits of the TFN of E. coli shape which gene cohorts respond to genome-wide stresses.

The 24-h movement behaviours composition is associated with parasympathetic modulation in preschoolers.

AIM: To investigate the associations between 24-h movement behaviours and heart rate variability (HRV) in preschool children. METHODS: A total of 123 preschoolers (4.52 ± 0.25 years old; 62 girls) were assessed for physical activity (PA) and sedentary behaviour (SB) using an accelerometer (Actigraph WGT3x). Sleep duration (SD) was parent-reported. Children were laid down in a supine position for 10 min to assess HRV data. The R-R intervals recorded during the last 5 min of this period were analysed. We conducted compositional analysis in R studio, and the significance level was 95%. All ethical procedures were followed, and the study had the approval of the local ethical board. RESULTS: When considered as a composition, adjusted for age, body mass index and sex, the 24-h movement composition (PA, SB and SD) significantly predicted better parasympathetic modulation (Root mean square of the successive differences [RMSSD] [p = 0.04; r2 = 0.13]), but not high frequency (HF) (nu) (p = 0.51, r2 = 0.01), low frequency (nu) (p = 0.52, r2 = 0.02),or standard deviation (standard deviation of normal-to-normal intervals) (p = 0.55, r2 = 0.02), respectively. CONCLUSION: These results suggest the 24-h movement composition predicted the RMSSD time-domain index related to parasympathetic activity.

Multivariate statistical analysis as a tool for monitoring drinking water sources in an Atlantic Rainforest Conservation Unit.

Water quality monitoring is paramount in identifying and mitigating pollution sources, protecting aquatic ecosystems, and ensuring safe water for human and wildlife consumption. This study is aimed at evaluating the quality of drinking water sources in three communities located in a Sustainable Use Conservation Unit in the municipality of Mangaratiba, Rio de Janeiro, Brazil, employing a multivariate statistical analysis. A total of 161 water samples were collected from January to December 2022, encompassing 32 surface water and 129 tap water samples. Physicochemical parameters were determined in situ employing a Horiba U50 multiparameter probe. The samples were stored and transported at 4 °C to the laboratory for microbiological analyses concerning total coliforms and Escherichia coli using a commercial enzymatic test. All samples contained coliforms, while E. coli were detected in 87% of the samples. The multivariate analysis indicated that the microbiological water quality in sampling region R2 was influenced by rainy periods and that, in general, the water quality within R3 was the most affected by the transport of solids to the water sources. The statistical methods applied herein aided in characterizing the study areas and detecting points of attention regarding physicochemical and microbiological parameters that significantly influence the water quality of each sampling point. Representative points for each study region were identified and may be employed for future monitoring and prevention actions.

Analytical kinetic model of native tandem promoters in E. coli.

Closely spaced promoters in tandem formation are abundant in bacteria. We investigated the evolutionary conservation, biological functions, and the RNA and single-cell protein expression of genes regulated by tandem promoters in E. coli. We also studied the sequence (distance between transcription start sites 'dTSS', pause sequences, and distances from oriC) and potential influence of the input transcription factors of these promoters. From this, we propose an analytical model of gene expression based on measured expression dynamics, where RNAP-promoter occupancy times and dTSS are the key regulators of transcription interference due to TSS occlusion by RNAP at one of the promoters (when dTSS ≤ 35 bp) and RNAP occupancy of the downstream promoter (when dTSS > 35 bp). Occlusion and downstream promoter occupancy are modeled as linear functions of occupancy time, while the influence of dTSS is implemented by a continuous step function, fit to in vivo data on mean single-cell protein numbers of 30 natural genes controlled by tandem promoters. The best-fitting step is at 35 bp, matching the length of DNA occupied by RNAP in the open complex formation. This model accurately predicts the squared coefficient of variation and skewness of the natural single-cell protein numbers as a function of dTSS. Additional predictions suggest that promoters in tandem formation can cover a wide range of transcription dynamics within realistic intervals of parameter values. By accurately capturing the dynamics of these promoters, this model can be helpful to predict the dynamics of new promoters and contribute to the expansion of the repertoire of expression dynamics available to synthetic genetic constructs.

Parasacral transcutaneous electrical neural stimulation versus urotherapy in primary monosymptomatic enuresis: A prospective randomized clinical trial.

OBJECTIVE: To evaluate the clinical response of parasacral transcutaneous electrical neural stimulation (parasacral TENS) associated with urotherapy in children with primary monosymptomatic nocturnal enuresis (PMNE) compared to urotherapy alone. MATERIAL AND METHODS: This prospective controlled clinical trial enrolled 72 children over 5 years of age with PMNE. Children were randomly divided into two groups, control group (CG), treated with urotherapy and scapular stimulation, and experimental group (EG), treated with urotherapy and parasacral TENS. In both groups, 20 sessions were performed, 3 times weekly, for 20 min each, with 10 Hz frequency, 700 µS pulse width and intesity determinated by the patient threshold. The percentages of dry nights were analyzed for 14 days before treatment (T0), after the 20th session (T1), 15 (T2), 30 (T3), 60 (T4), and 90 (T5) days after the end of the sessions. Patients of both groups were followed with intervals of 2 weeks in the first month and monthly for three consecutive months. RESULTS: Twenty-eight enuretic children, 14 girls (50%) with a mean age of 9.09 ± 2.23 years completed the study. There was no difference in mean age between groups. Mean percentage of dry nights in EG at T0 was 36%, at T1 49%, at T2 54%, at T3 54%, at T4 54%, and 57% at T5; while in CG, these percentages were 28%, 39%, 37%, 35%, 36%, and 36%, respectively. CONCLUSIONS: Parasacral TENS associated with urotherapy improves the percentage of dry nights in children with PMNE, although no patient had complete resolution of symptoms in this study.

Treating asthma in patients with enuresis: repercussions on urinary symptoms.

BACKGROUND: Children presenting enuresis are more likely to be asthmatics. The association between enuresis and sleep-disordered breathing has already been demonstrated and several studies have shown at least partial improvement of two thirds or more of the cases of enuresis adenoidectomy. Studies have already described associations between enuresis and allergies but do not assess the repercussions of allergy treatment in enuretics. OBJECTIVE: This study aims to evaluated whether asthma treatment alters the course of enuresis and whether there is any predictive factor associated with this improvement. MATERIALS AND METHODS: Twenty patients (5 - 12 years old) with uncontrolled enuresis and asthma, received treatment for asthma. Children were also assessed for the presence of rhinitis and other allergies. The control of asthma was confirmed by a validated questionnaire and primary enuresis by clinical history and wet night diaries. Patients received only asthma treatment. RESULTS: At least partial improvement of enuresis was observed in 55% of the patients with an increase in 64.4% in the number of dry nights at the end of the study (p=0.01). The "presence of other allergies" and "obstruction seen in nasal endoscopy" positively influenced the improvement of urinary symptoms (OR = 3.350; CI 0.844-13.306) and (OR=1.272; CI 0.480-3.370), respectively. DISCUSSION: Until now, only patients presenting upper airway obstruction were known to benefit from the improvement of urinary symptoms when undergoing treatment for their respiratory problems. In our study, we found at least partial improvement in enuresis in 55% of our patients, with only clinical asthma treatment. CONCLUSION: Controlling asthma in children with primary enuresis resulted in a significant increase in dry nights.

What do we know about experiencing end-of-life in burn intensive care units? A scoping review.

OBJECTIVES: The aim of this article is to review and synthesize the evidence on end-of-life in burn intensive care units. METHODS: Systematic scoping review: Preferred Reporting Items for Systemic Reviews extension for Scoping Reviews was used as a reporting guideline. Searches were performed in 3 databases, with no time restriction and up to September 2021. RESULTS: A total of 16,287 documents were identified; 18 were selected for analysis and synthesis. Three key themes emerged: (i) characteristics of the end-of-life in burn intensive care units, including end-of-life decisions, decision-making processes, causes, and trajectories of death; (ii) symptom control at the end-of-life in burn intensive care units focusing on patients' comfort; and (iii) concepts, models, and designs of the care provided to burned patients at the end-of-life, mainly care approaches, provision of care, and palliative care. SIGNIFICANCE OF RESULTS: End-of-life care is a major step in the care provided to critically ill burned patients. Dying and death in burn intensive care units are often preceded by end-of-life decisions, namely forgoing treatment and do-not-attempt to resuscitate. Different dying trajectories were described, suggesting the possibility to develop further studies to identify triggers for palliative care referral. Symptom control was not described in detail. Palliative care was rarely involved in end-of-life care for these patients. This review highlights the need for early and high-quality palliative and end-of-life care in the trajectories of critically ill burned patients, leading to an improved perception of end-of-life in burn intensive care units. Further research is needed to study the best way to provide optimal end-of-life care and foster integrated palliative care in burn intensive care units.

OPTN recruitment to a Golgi-proximal compartment regulates immune signalling and cytokine secretion.

Optineurin (OPTN) is a multifunctional protein involved in autophagy and secretion, as well as nuclear factor κB (NF-κB) and IRF3 signalling, and OPTN mutations are associated with several human diseases. Here, we show that, in response to viral RNA, OPTN translocates to foci in the perinuclear region, where it negatively regulates NF-κB and IRF3 signalling pathways and downstream pro-inflammatory cytokine secretion. These OPTN foci consist of a tight cluster of small membrane vesicles, which are positive for ATG9A. Disease mutations in OPTN linked to primary open-angle glaucoma (POAG) cause aberrant foci formation in the absence of stimuli, which correlates with the ability of OPTN to inhibit signalling. By using proximity labelling proteomics, we identify the linear ubiquitin assembly complex (LUBAC), CYLD and TBK1 as part of the OPTN interactome and show that these proteins are recruited to this OPTN-positive perinuclear compartment. Our work uncovers a crucial role for OPTN in dampening NF-κB and IRF3 signalling through the sequestration of LUBAC and other positive regulators in this viral RNA-induced compartment, leading to altered pro-inflammatory cytokine secretion.

Genetic Variants of ABC and SLC Transporter Genes and Chronic Myeloid Leukaemia: Impact on Susceptibility and Prognosis.

Solute carrier (SLC) and ATP-binding cassette (ABC) transporters comprise a variety of proteins expressed on cell membranes responsible for intrusion or extrusion of substrates, respectively, including nutrients, xenobiotics, and chemotherapeutic agents. These transporters mediate the cellular disposition of tyrosine kinase inhibitors (TKIs), and their genetic variants could affect its function, potentially predisposing patients to chronic myeloid leukaemia (CML) and modulating treatment response. We explored the impact of genetic variability (single nucleotide variants-SNVs) of drug transporter genes (ABCB1, ABCG2, SLC22A1, and SLC22A5) on CML susceptibility, drug response, and BCR-ABL1 mutation status. We genotyped 10 SNVs by tetra-primers-AMRS-PCR in 198 CML patients and 404 controls, and assessed their role in CML susceptibility and prognosis. We identified five SNVs associated with CML predisposition, with some variants increasing disease risk, including TT genotype ABCB1 (rs1045642), and others showing a protective effect (GG genotype SLC22A5 rs274558). We also observed different haplotypes and genotypic profiles associated with CML predisposition. Relating to drug response impact, we found that CML patients with the CC genotype (rs2231142 ABCG2) had an increased risk of TKI resistance (six-fold). Additionally, CML patients carrying the CG genotype (rs683369 SLC22A1) presented a 4.54-fold higher risk of BCR-ABL1 mutations. Our results suggest that drug transporters' SNVs might be involved in CML susceptibility and TKI response, and predict the risk of BCR-ABL1 mutations, highlighting the impact that SNVs could have in therapeutic selection.

Monitoring Heart Rate Variability and Perceived Well-Being in Brazilian Elite Beach Volleyball Players: A Single-Tournament Pilot Study.

ABSTRACT: Nakamura, FY, Torres, VBC, da Silva, LS, Gantois, P, Andrade, AD, Ribeiro, ALB, Brasileiro-Santos, MdS, and Batista, GR. Monitoring heart rate variability and perceived well-being in Brazilian elite beach volleyball players: A single-tournament pilot study. J Strength Cond Res 36(6): 1708-1714, 2022-The aim of this study was to monitor the changes in heart rate variability (HRV) and perceptual well-being status after a beach volleyball (BV) tournament day in high-level U17 and senior players. Seventeen BV players (U17 [15-16 years]: n = 08; and senior [19-41 years]: n = 09) competing at national and/or international BV level participated in this study. Resting HRV and perceptual well-being measures were recorded across 4 moments: night 1 (prematches night), morning 1 (prematches morning), night 2 (postmatches night), and morning 2 (postmatches morning). Session rating of perceived exertion was assessed 10 minutes after each match, and accumulated match loads were used for analysis. Senior players presented higher values of natural logarithm of square root of the mean squared differences of successive RR intervals (lnRMSSD) at the 4 observation moments than U17 players (p = 0.006). Within-subjects analysis showed a larger mean difference regarding both lnRMSSD and natural logarithm SD of normal R-R intervals (lnSDNN) between night 1 vs. night 2 in U17 players (effect size = 1.11 and, 0.96, respectively) compared with senior (effect size = 0.40 and 0.32, respectively). Accumulated match loads were negatively correlated with percentage change in lnRMSSD (r = -0.54; p = 0.037). U17 players showed higher well-being variation than senior (group × time; p = 0.02). In conclusion, the lnRMSSD index was able to discriminate the U17 and senior BV players, and maintaining high vagally related HRV indices is an important response to BV training and competition.

Enuresis and upper airway obstruction: BNP and ADH hormones behavior before and after airway surgery.

INTRODUCTION: Upper airway obstruction (UAO) is a common condition in all pediatric population, with a 27% prevalence. Primary monosymptomatic nocturnal enuresis (PMNE) is a condition related to UAO in 8% to 47% of these children. The specific pathophysiological mechanism of this bond is not well understood. Some authors suggest a connection between brain natrituretic peptide (BNP) and anti-diuretic hormone (ADH) during sleep. The aim of this study was to evaluate hormone profile (ADH and BNP) and improvement in dry nights in a sample of children before and after surgical treatment of the UAO. METHODS: This is a longitudinal prospective interventionist study in children, 5 to 14 years of age, with UAO and PMNE recruited in a specialty outpatient clinic. Children presenting UAO and PMNE were evaluated with a 30-day dry night diary and blood samples were collected to evaluate ADH and BNP before and after upper airway surgery. Data were analyzed prior to surgery and 90-120 days after surgery. RESULTS: Twenty-one children with a mean age of 9.7 years were included. Mean BNP before surgery was 116.5 ± 126.5 pg/mL and 156.2 ± 112.3 pg/mL after surgery (p<0.01). Mean ADH was 5.8 ± 3.2 pg/mL and 14.6 ± 35.4 before and after surgery, respectively (p=0.26). The percentage of dry nights went from 32.3 ± 24.7 before surgery to 75.4 ± 33.4 after surgery (p˂0.01). CONCLUSION: Surgery for airway obstruction contributed to an increase in BNP without increasing ADH. A total of 85.8% of the children presented partial or complete improvement of their enuresis.

Prevalence of syphilis in female sex workers in three countryside cities of the state of Pará, Brazilian Amazon.

BACKGROUND: Syphilis is a sexually transmitted infection (STI) transmitted from person to person mainly by sexual intercourse or through vertical transmission during pregnancy. Female sex workers (FSWs) are exposed especially to syphilis infection, and besides all the efforts to control the spread of STIs, syphilis prevalence is still rising, mainly occurring in low-income countries. This study aimed to investigate the syphilis prevalence, demographic characteristics and sexual habits among FSWs in the Amazon region of Brazil. METHODS: A cross-sectional study was carried out including 184 FSWs from 3 countryside cities of the state of Pará, Amazon region of Brazil. A venereal disease research laboratory test and an indirect immunoenzyme assay to test antibodies against Treponema pallidum were used for screening syphilis infection, while sexual habits and demographic data information were collected through a semi-structured questionnaire. Data was analyzed comparing groups with/without syphilis. Poisson regression models were used to estimate the reasons of prevalence (RP). RESULTS: The overall prevalence of syphilis was 14.1% (95% CI = 9.8-17.8). FSWs had between 15 and 56 years of age, most were unmarried (65.7%), had attended less than 8 years of formal education (64.1%), had between 10 and 20 partners per week (64.1%), and reported no previous history of STIs (76.1%) and regular use of condom (52.7%). Low level of education attending up to the primary school (RP adjusted = 3.8; 95% CI = 1.4-9.2) and high frequency of anal sex during the past year (RP adjusted = 9.3; 95% CI = 3.5-28.7) were associated with a higher prevalence of syphilis. CONCLUSIONS: A high prevalence of syphilis among FSWs in the Brazilian Amazon region was identified, showing that syphilis is more likely to be transmitted in FSW working in low-income areas, which is attributed to the low level of education. Anal intercourse was found as a risk factor associated with syphilis. Health programs focused on risk populations appear as a rational way to control syphilis spread, which is a rising problem in Brazil and in other several countries.

Efficiency and Robustness of Processes Driven by Nucleoid Exclusion in Escherichia coli.

The internal spatial organization of prokaryotic organisms, including Escherichia coli, is essential for the proper functioning of processes such as cell division. One source of this organization in E. coli is the nucleoid, which causes the exclusion of macromolecules - e.g. protein aggregates and the chemotaxis network - from midcell. Similarly, following DNA replication, the nucleoid(s) assist in placing the Z-ring at midcell. These processes need to be efficient in optimal conditions and robust to suboptimal conditions. After reviewing recent findings on these topics, we make use of past data to study the efficiency of the spatial constraining of Z-rings, chemotaxis networks, and protein aggregates, as a function of the nucleoid(s) morphology. Also, we compare the robustness of these processes to nonoptimal temperatures. We show that Z-rings, Tsr clusters, and protein aggregates have temperature-dependent spatial distributions along the major cell axis that are consistent with the nucleoid(s) morphology and the volume-exclusion phenomenon. Surprisingly, the consequences of the changes in nucleoid size with temperature are most visible in the kurtosis of these spatial distributions, in that it has a statistically significant linear correlation with the mean nucleoid length and, in the case of Z-rings, with the distance between nucleoids prior to cell division. Interestingly, we also find a negative, statistically significant linear correlation between the efficiency of these processes at the optimal condition and their robustness to suboptimal conditions, suggesting a trade-off between these traits.

New Nanotechnologies for the Treatment and Repair of Skin Burns Infections.

Burn wounds are highly debilitating injuries, with significant morbidity and mortality rates worldwide. In association with the damage of the skin integrity, the risk of infection is increased, posing an obstacle to healing and potentially leading to sepsis. Another limitation against healing is associated with antibiotic resistance mainly due to the use of systemic antibiotics for the treatment of localized infections. Nanotechnology has been successful in finding strategies to incorporate antibiotics in nanoparticles for the treatment of local wounds, thereby avoiding the systemic exposure to the drug. This review focuses on the most recent advances on the use of nanoparticles in wound dressing formulations and in tissue engineering for the treatment of burn wound infections.

SCIP: a single-cell image processor toolbox.

Summary: Each cell is a phenotypically unique individual that is influenced by internal and external processes, operating in parallel. To characterize the dynamics of cellular processes one needs to observe many individual cells from multiple points of view and over time, so as to identify commonalities and variability. With this aim, we engineered a software, 'SCIP', to analyze multi-modal, multi-process, time-lapse microscopy morphological and functional images. SCIP is capable of automatic and/or manually corrected segmentation of cells and lineages, automatic alignment of different microscopy channels, as well as detect, count and characterize fluorescent spots (such as RNA tagged by MS2-GFP), nucleoids, Z rings, Min system, inclusion bodies, undefined structures, etc. The results can be exported into *mat files and all results can be jointly analyzed, to allow studying not only each feature and process individually, but also find potential relationships. While we exemplify its use on Escherichia coli, many of its functionalities are expected to be of use in analyzing other prokaryotes and eukaryotic cells as well. We expect SCIP to facilitate the finding of relationships between cellular processes, from small-scale (e.g. gene expression) to large-scale (e.g. cell division), in single cells and cell lineages. Availability and implementation: http://www.ca3-uninova.org/project_scip. Supplementary information: Supplementary data are available at Bioinformatics online.

Do patients, families, and healthcare teams benefit from the integration of palliative care in burn intensive care units? Results from a systematic review with narrative synthesis.

BACKGROUND: Burn units are intensive care facilities specialized in the treatment of patients with severe burns. As burn injuries have a major impact in physical, psychosocial, and spiritual health, palliative care can be a strengthening component of integrated care. AIM: To review and appraise the existing evidence about the integration of palliative care in burn intensive care units with respect to (1) the concept, model and design and (2) the benefits and outcomes of this integration. DESIGN: A systematic review was conducted following PRISMA guidelines. Protocol registered with PROSPERO (CRD42018111676). DATA SOURCES: Five electronic databases were searched (PubMed/NLM, Web of Science, MEDLINE/TR, Ovid, and CINAHL/EBSCO) until May 2019. A narrative synthesis of the findings was constructed. Hawker et al.'s tool was used for quality appraisal. RESULTS: A total of 299 articles were identified, of which five were included for analysis involving a total of 7353 individuals. Findings suggest that there may be benefits from integrating palliative care in burn units, specifically in terms of patients' comfort, decision-making processes, and family care. Multidisciplinary teams may experience lower levels of burden as result of integrating palliative care in burn units. CONCLUSION: This review reflects the challenging setting of burn intensive care units. Evidence from these articles suggests that the integration of palliative care in burn intensive care units improves patients' comfort, decision-making process, and family care. Further research is needed to better understand how the integration of palliative care in burn intensive care units may be fostered and to identify the outcomes of this integration.