Bacterial growth in patients with low back pain and Modic changes: protocol of a multicentre, case-control biopsy study.

INTRODUCTION: Bacterial infection and Modic changes (MCs) as causes of low back pain (LBP) are debated. Results diverged between two randomised controlled trials examining the effect of amoxicillin with and without clavulanic acid versus placebo on patients with chronic LBP (cLBP) and MCs. Previous biopsy studies have been criticised with regard to methods, few patients and controls, and insufficient measures to minimise perioperative contamination. In this study, we minimise contamination risk, include a control group and optimise statistical power. The main aim is to compare bacterial growth between patients with and without MCs. METHODS AND ANALYSIS: This multicentre, case-control study examines disc and vertebral body biopsies of patients with cLBP. Cases have MCs at the level of tissue sampling, controls do not. Previously operated patients are included as a subgroup. Tissue is sampled before antibiotic prophylaxis with separate instruments. We will apply microbiological methods and histology on biopsies, and predefine criteria for significant bacterial growth, possible contamination and no growth. Microbiologists, surgeons and pathologist are blinded to allocation of case or control. Primary analysis assesses significant growth in MC1 versus controls and MC2 versus controls separately. Bacterial disc growth in previously operated patients, patients with large MCs and growth from the vertebral body in the fusion group are all considered exploratory analyses. ETHICS AND DISSEMINATION: The Regional Committees for Medical and Health Research Ethics in Norway (REC South East, reference number 2015/697) has approved the study. Study participation requires written informed consent. The study is registered at ClinicalTrials.gov (NCT03406624). Results will be disseminated in peer-reviewed journals, scientific conferences and patient fora. TRIAL REGISTRATION NUMBER: NCT03406624.

Smoking is associated with higher risk of contracting bacterial infection and pneumonia, intensive care unit admission and death.

BACKGROUND: Smoking has been associated with a higher risk of contracting pneumonia, but contradictory results have shown that smoking may or may not decrease the risk of dying in pneumonia. The aim of this study is to investigate how smoking is associated with contracting any infection and pneumonia and death. METHOD AND FINDINGS: Participants were drawn from the population-based Cohort of Swedish Men and the Swedish Mammography Cohort, which are representative of the Swedish population. Participants have answered detailed lifestyle questionnaires and have been followed in national registers, such as the Patient Register, Cause of Death register and Swedish Intensive Care Registry. The risks of contracting infection and pneumonia or dying in infection and pneumonia were assessed using Cox regression. Of 62,902 cohort participants, 25,297 contracted an infection of which 4,505 died; and 10,471 contracted pneumonia of which 2,851 died. Compared to never smokers, former smokers at baseline had hazard ratio (HR) 1.08 (95% confidence interval (CI) 1.05-1.12) of contracting and HR 1.19 (95% CI 1.11-1.28) of dying in infection and HR 1.17 (95% CI 1.12-1.23) of contracting and HR 1.16 (95% CI 1.06-1.27) of dying in pneumonia during follow-up. Compared to never smokers, current smokers at baseline had HR 1.17 (95% CI 1.13-1.21) of contracting infection and HR 1.64 (95% CI 1.52-1.77) dying in infection; HR 1.42 (95% CI 1.35-1.49) of contracting pneumonia and HR 1.70 (95% CI 1.55-1.87) of dying in pneumonia during follow-up. The risk of contracting and dying in infection and pneumonia increased in a dose-response manner with number of pack years smoked and decreased with years since smoking cessation. CONCLUSION: Smoking is associated with contracting and dying in any infection and pneumonia and the risk increases with pack years smoked, highlighting the importance of both primary prevention and smoking cessation.

Role of biomarkers in antimicrobial stewardship: physicians' perspectives.

Biomarkers are playing an increasingly important role in antimicrobial stewardship. Their applications have included use in algorithms that evaluate suspected bacterial infections or provide guidance on when to start or stop antibiotic therapy, or when therapy should be repeated over a short period (6-12 h). Diseases in which biomarkers are used as complementary tools to determine the initiation of antibiotics include sepsis, lower respiratory tract infection (LRTI), COVID-19, acute heart failure, infectious endocarditis, acute coronary syndrome, and acute pancreatitis. In addition, cut-off values of biomarkers have been used to inform the decision to discontinue antibiotics for diseases such as sepsis, LRTI, and febrile neutropenia. The biomarkers used in antimicrobial stewardship include procalcitonin (PCT), C-reactive protein (CRP), presepsin, and interleukin (IL)-1ß/IL-8. The cut-off values vary depending on the disease and study, with a range of 0.25-1.0 ng/mL for PCT and 8-50 mg/L for CRP. Biomarkers can complement clinical diagnosis, but further studies of microbiological biomarkers are needed to ensure appropriate antibiotic selection.

Changing patterns of bacterial profile and antimicrobial resistance in high-risk patients during the COVID-19 pandemic at a tertiary oncology hospital.

The widespread evolution of phenotypic resistance in clinical isolates over the years, coupled with the COVID-19 pandemic onset, has exacerbated the global challenge of antimicrobial resistance. This study aimed to explore changes in bacterial infection patterns and antimicrobial resistance during the COVID-19 pandemic. This study involved the periods before and during COVID-19: the pre-pandemic and pandemic eras. The surveillance results of bacterial isolates causing infections in cancer patients at an Egyptian tertiary oncology hospital were retrieved. The Vitek®2 or Phoenix systems were utilized for species identification and susceptibility testing. Statistical analyses were performed comparing microbiological trends before and during the pandemic. Out of 2856 bacterial isolates, Gram-negative bacteria (GNB) predominated (69.7%), and Gram-positive bacteria (GPB) comprised 30.3% of isolates. No significant change was found in GNB prevalence during the pandemic (P = 0.159). Elevated rates of Klebsiella and Pseudomonas species were demonstrated during the pandemic, as was a decrease in E. coli and Acinetobacter species (P < 0.001, 0.018, < 0.001, and 0.046, respectively) in hematological patients. In surgical patients, Enterobacteriaceae significantly increased (P = 0.012), while non-fermenters significantly decreased (P = 0.007). GPB species from either hematological or surgical wards exhibited no notable changes during the pandemic. GNB resistance increased in hematological patients to carbapenems, amikacin, and tigecycline and decreased in surgical patients to amikacin and cefoxitin (P < 0.001, 0.010, < 0.001, < 0.001, and 0.016, respectively). The study highlights notable shifts in the microbial landscape during the COVID-19 pandemic, particularly in the prevalence and resistance patterns of GNB in hematological and surgical wards.

Cascade-Targeted Nanoplatforms for Synergetic Antibiotic/ROS/NO/Immunotherapy against Intracellular Bacterial Infection.

Intracellular bacteria in dormant states can escape the immune response and tolerate high-dose antibiotic treatment, leading to severe infections. To overcome this challenge, cascade-targeted nanoplatforms that can target macrophages and intracellular bacteria, exhibiting synergetic antibiotic/reactive oxygen species (ROS)/nitric oxide (NO)/immunotherapy, were developed. These nanoplatforms were fabricated by encapsulating trehalose (Tr) and vancomycin (Van) into phosphatidylserine (PS)-coated poly[(4-allylcarbamoylphenylboric acid)-ran-(arginine-methacrylamide)-ran-(N,N'-bisacryloylcystamine)] nanoparticles (PABS), denoted as PTVP. PS on PTVP simulates a signal of "eat me" to macrophages to promote cell uptake (the first-step targeting). After the uptake, the nanoplatform in the acidic phagolysosomes could release Tr, and the exposed phenylboronic acid on the nanoplatform could target bacteria (the second-step targeting). Nanoplatforms can release Van in response to infected intracellular overexpressed glutathione (GSH) and weak acid microenvironment. l-arginine (Arg) on the nanoplatforms could be catalyzed by upregulated inducible nitric oxide synthase (iNOS) in the infected macrophages to generate nitric oxide (NO). N,N'-Bisacryloylcystamine (BAC) on nanoplatforms could deplete GSH, allow the generation of ROS in macrophages, and then upregulate proinflammatory activity, leading to the reinforced antibacterial capacity. This nanoplatform possesses macrophage and bacteria-targeting antibiotic delivery, intracellular ROS, and NO generation, and pro-inflammatory activities (immunotherapy) provides a new strategy for eradicating intracellular bacterial infections.

Comparison of bacterial species and clinical outcomes in patients with diabetic hand infection in tropical and nontropical regions.

Hand infection is a rare complication in patients with diabetes. Its clinical outcomes depend on the severity of hand infection caused by bacteria, but the difference in bacterial species in the regional disparity is unknown. The purpose of this study was to explore the influence of tropical and nontropical regions on bacterial species and clinical outcomes for diabetic hand. A systematic literature review was conducted using PubMed, EMBASE, Web of Science, and Google Scholar. Moreover, the bacterial species and clinical outcomes were analyzed with respect to multicenter wound care in China (nontropical regions). Both mixed bacteria (31.2% vs. 16.6%, p = 0.014) and fungi (7.5% vs. 0.8%, p = 0.017) in the nontropical region were significantly more prevalent than those in the tropical region. Staphylococcus and Streptococcus spp. were dominant in gram-positive bacteria, and Klebsiella, Escherichia coli, Proteus and Pseudomonas in gram-negative bacteria occupied the next majority in the two regions. The rate of surgical treatment in the patients was 31.2% in the nontropical region, which was significantly higher than the 11.4% in the tropical region (p = 0.001). Although the overall mortality was not significantly different, there was a tendency to be increased in tropical regions (6.3%) compared with nontropical regions (0.9%). However, amputation (32.9% vs. 31.3%, p = 0.762) and disability (6.3% vs. 12.2%, p = 0.138) were not significantly different between the two regions. Similar numbers of cases were reported, and the most common bacteria were similar in tropical and nontropical regions in patients with diabetic hand. There were more species of bacteria in the nontropical region, and their distribution was basically similar, except for fungi, which had differences between the two regions. The present study also showed that surgical treatment and mortality were inversely correlated because delays in debridement and surgery can deteriorate deep infections, eventually leading to amputation and even death.

The Hippo kinases control inflammatory Hippo signaling and restrict bacterial infection in phagocytes.

The Hippo kinases MST1 and MST2 initiate a highly conserved signaling cascade called the Hippo pathway that limits organ size and tumor formation in animals. Intriguingly, pathogens hijack this host pathway during infection, but the role of MST1/2 in innate immune cells against pathogens is unclear. In this report, we generated Mst1/2 knockout macrophages to investigate the regulatory activities of the Hippo kinases in immunity. Transcriptomic analyses identified differentially expressed genes (DEGs) regulated by MST1/2 that are enriched in biological pathways, such as systemic lupus erythematosus, tuberculosis, and apoptosis. Surprisingly, pharmacological inhibition of the downstream components LATS1/2 in the canonical Hippo pathway did not affect the expression of a set of immune DEGs, suggesting that MST1/2 control these genes via alternative inflammatory Hippo signaling. Moreover, MST1/2 may affect immune communication by influencing the release of cytokines, including TNFα, CXCL10, and IL-1ra. Comparative analyses of the single- and double-knockout macrophages revealed that MST1 and MST2 differentially regulate TNFα release and expression of the immune transcription factor MAF, indicating that the two homologous Hippo kinases individually play a unique role in innate immunity. Notably, both MST1 and MST2 can promote apoptotic cell death in macrophages upon stimulation. Lastly, we demonstrate that the Hippo kinases are critical factors in mammalian macrophages and single-cell amoebae to restrict infection by Legionella pneumophila, Escherichia coli, and Pseudomonas aeruginosa. Together, these results uncover non-canonical inflammatory Hippo signaling in macrophages and the evolutionarily conserved role of the Hippo kinases in the anti-microbial defense of eukaryotic hosts. IMPORTANCE: Identifying host factors involved in susceptibility to infection is fundamental for understanding host-pathogen interactions. Clinically, individuals with mutations in the MST1 gene which encodes one of the Hippo kinases experience recurrent infection. However, the impact of the Hippo kinases on innate immunity remains largely undetermined. This study uses mammalian macrophages and free-living amoebae with single- and double-knockout in the Hippo kinase genes and reveals that the Hippo kinases are the evolutionarily conserved determinants of host defense against microbes. In macrophages, the Hippo kinases MST1 and MST2 control immune activities at multiple levels, including gene expression, immune cell communication, and programmed cell death. Importantly, these activities controlled by MST1 and MST2 in macrophages are independent of the canonical Hippo cascade that is known to limit tissue growth and tumor formation. Together, these findings unveil a unique inflammatory Hippo signaling pathway that plays an essential role in innate immunity.

Potential role of Citrus bergamia flower essential oil against oral pathogens.

BACKGROUND: Oral bacterial infections are difficult to treat due to emergence of resistance against antibiotic therapy. Essential oils are considered emerging alternate therapy against bacterial infections and biofilms. We investigated Citrus bergemia flower essential oil against oral pathogens. METHODS: The essential oil was analsyed using Gas Chromatography(GC-MS), in silico investigations, antioxidant, antimicrobial, antibiofilm and antiquorum sensing assays. RESULTS: Gas Chromatography analysis confirmed presence of 17 compounds including 1,6-Octadien-3-ol,3,7-dimethyl, 48.17%), l-limonene (22.03%) and p-menth-1-ol, 8-ol (7.31%) as major components. In silico analysis showed compliance of all tested major components with Lipinski's rule, Bioavailability and antimicrobial activity using PASS (prediction of activity spectrum of substances). Molecular docking with transcriptional regulators 3QP5, 5OE3, 4B2O and 3Q3D revealed strong interaction of all tested compounds except 1,6-Octadien-3-ol,3,7-dimethyl. All tested compounds presented significant inhibition of DPPH (2,2-diphenyl-1-picrylhydrazyl) (IC50 0.65 mg/mL), H2O2 (hydrogen peroxide) (63.5%) and high FRAP (ferrous reducing antioxidant power) value (239.01 µg). In antimicrobial screening a significant activity (MIC 0.125 mg/mL) against Bacillus paramycoides and Bacillus chungangensis was observed. Likewise a strong antibiofilm (52.1 - 69.5%) and anti-QS (quorum sensing) (4-16 mm) activity was recorded in a dose dependent manner. CONCLUSION: It was therefore concluded that C. bergemia essential oil posess strong antioxidant, antimicrobial and antibiofilm activities against tested oral pathogens.

pH-Responsive Co-Assembled Peptide Hydrogel to Inhibit Drug-Resistant Bacterial Infection and Promote Wound Healing.

Drug-resistant bacterial infection and biofilm formation are the key inhibitors of wound healing, and new strategies are urgently needed to address these issues. In this study, we designed a pH-responsive co-assembled peptide hydrogel to inhibit Methicillin-resistant Staphylococcus aureus (MRSA) infection and promote wound healing. We synthesized a cationic short peptide (Nap-FFKKK) and a co-assembled hydrogel with curcumin at pH ∼ 7.8. The loaded curcumin was continuously released in a weak acid environment (pH ∼ 5.5). The lysine-rich cationic peptide inhibited biofilm formation in MRSA via electrostatic interaction with the negatively charged bacterial cell surface and, thus, provided a reinforcing antibacterial effect with curcumin. In vitro antibacterial experiments showed that the co-assembled system considerably reduced the minimum inhibitory concentration of curcumin against MRSA by 10-fold and promoted wound healing in a mouse model of MRSA-infected wounds. This study provides a simple and promising strategy to treat drug-resistant bacterial infections in wounds.

Carbon dots as a novel photosensitizer for photodynamic therapy of cancer and bacterial infectious diseases: recent advances.

Carbon dots (CDs) are novel carbon-based nanomaterials that have been used as photosensitizer-mediated photodynamic therapy (PDT) in recent years due to their good photosensitizing activity. Photosensitizers (PSs) are main components of PDT that can produce large amounts of reactive oxygen species (ROS) when stimulated by light source, which have the advantages of low drug resistance and high therapeutic efficiency. CDs can generate ROS efficiently under irradiation and therefore have been extensively studied in disease local phototherapy. In tumor therapy, CDs can be used as PSs or PS carriers to participate in PDT and play an extremely important role. In bacterial infectious diseases, CDs exhibit high bactericidal activity as CDs are effective in disrupting bacterial cell membranes leading to bacterial death upon photoactivation. We focus on recent advances in the therapy of cancer and bacteria with CDs, and also briefly summarize the mechanisms and requirements for PSs in PDT of cancer, bacteria and other diseases. We also discuss the role CDs play in combination therapy and the potential for future applications against other pathogens.

Gallium and silver-doped titanium surfaces provide enhanced osteogenesis, reduce bone resorption and prevent bacterial infection in co-culture.

Bacterial infection remains a significant problem associated with orthopaedic surgeries leading to surgical site infection (SSI). This unmet medical need can become an even greater complication when surgery is due to malignant bone tumor. In the present study, we evaluated in vitro titanium (Ti) implants subjected to gallium (Ga) and silver (Ag)-doped thermochemical treatment as strategy to prevent SSI and improve osteointegration in bone defects caused by diseases such as osteoporosis, bone tumor, or bone metastasis. Firstly, as Ga has been reported to be an osteoinductive and anti-resorptive agent, its performance in the mixture was proved by studying human mesenchymal stem cells (hMSC) and pre-osteoclasts (RAW264.7) behaviour. Then, the antibacterial potential provided by Ag was assessed by resembling "The Race for the Surface" between hMSC and Pseudomonas aeruginosa in two co-culture methods. Moreover, the presence of quorum sensing molecules in the co-culture was evaluated. The results highlighted the suitability of the mixture to induce osteodifferentiation and reduce osteoclastogenesis in vitro. Furthermore, the GaAg surface promoted strong survival rate and retained osteoinduction potential of hMSCs even after bacterial inoculation. Therefore, GaAg-modified titanium may be an ideal candidate to repair bone defects caused by excessive bone resorption, in addition to preventing SSI. STATEMENT OF SIGNIFICANCE: This article provides important insights into titanium for fractures caused by osteoporosis or bone metastases with high incidence in surgical site infection (SSI) because in this situation bacterial infection can become a major disaster. In order to solve this unmet medical need, we propose a titanium implant modified with gallium and silver to improve osteointegration, reduce bone resorption and avoid bacterial infection. For that aim, we study osteoblast and osteoclast behavior with the main novelty focused on the antibacterial evaluation. In this work, we recreate "the race for the surface" in long-term experiments and study bacterial virulence factors (quorum sensing). Therefore, we believe that our article could be of great interest, providing a great impact on future orthopedic applications.

Altered circular RNA expressions in extracellular vesicles from bronchoalveolar lavage fluids in mice after bacterial infections.

Circular RNAs (circRNAs) are a class of transcripts that often are generated by back-splicing that covalently connects the 3'end of the exon to the 5'end. CircRNAs are more resistant to nuclease and more stable than their linear counterparts. One of the well-recognized roles of circRNAs is the miRNA sponging effects that potentially lead to the regulation of downstream proteins. Despite that circRNAs have been reported to be involved in a wide range of human diseases, including cancers, cardiovascular, and neurological diseases, they have not been studied in inflammatory lung responses. Here, we analyzed the circRNA profiles detected in extracellular vesicles (EVs) obtained from the broncho-alveolar lavage fluids (BALF) in response to LPS or acid instillation in mice. Next, we validated two specific circRNAs in the BALF-EVs and BALF cells in response to endotoxin by RT-qPCR, using specific primers targeting the circular form of RNAs rather than the linear host RNAs. The expression of these selected circRNAs in the BALF inflammatory cells, alveolar macrophages (AMs), neutrophils, and lung tissue were analyzed. We further predicted the potential miRNAs that interact with these circRNAs. Our study is the first report to show that circRNAs are detectable in BALF EVs obtained from mice. The EV-cargo circRNAs are significantly altered by the noxious stimuli. The circRNAs identified using microarrays may be validated by RT-qPCR using primers specific to the circular but not the linear form. Future studies to investigate circRNA expression and function including miRNA sponging in lung inflammation potentially uncover novel strategies to develop diagnostic/therapeutic targets.

Performance of Febrile Infant Algorithms by Duration of Fever.

OBJECTIVES: To analyze the performance of commonly used blood tests in febrile infants ≤90 days of age to identify patients at low risk for invasive bacterial infection (bacterial pathogen in blood or cerebrospinal fluid) by duration of fever. METHODS: We conducted a secondary analysis of a prospective single-center registry that includes all consecutive infants ≤90 days of age with fever without a source evaluated at 1 pediatric emergency department between 2008 and 2021. We defined 3 groups based on caregiver-reported hours of fever (<2, 2-12, and ≥12) and analyzed the performance of the biomarkers and Pediatric Emergency Care Applied Research Network, American Academy of Pediatrics, and Step-by-Step clinical decision rules. RESULTS: We included 2411 infants; 76 (3.0%) were diagnosed with an invasive bacterial infection. The median duration of fever was 4 (interquartile range, 2-12) hours, with 633 (26.3%) patients with fever of <2 hours. The area under the curve was significantly lower in patients with <2 hours for absolute neutrophil count (0.562 vs 0.609 and 0.728) and C-reactive protein (0.568 vs 0.760 and 0.812), but not for procalcitonin (0.749 vs 0.780 and 0.773). Among well-appearing infants older than 21 days and negative urine dipstick with <2 hours of fever, procalcitonin ≥0.14 ng/mL showed a better sensitivity (100% with specificity 53.8%) than that of the combination of biomarkers of Step-by-Step (50.0% and 82.2%), and of the American Academy of Pediatrics and Pediatric Emergency Care Applied Research Network rules (83.3% and 58.3%), respectively. CONCLUSIONS: The performance of blood biomarkers, except for procalcitonin, in febrile young infants is lower in fever of very short duration, decreasing the accuracy of the clinical decision rules.

Perfil epidemiológico de internações por doenças infecciosas e bacterianas em menores de 5 anos, de 2017 a 2021 / Perfil epidemiológico de las hospitalizaciones por enfermedades infecciosas y bacterianas más prevalentes en niños menores de 5 años, de 2017 a 2021 / Epidemiological profile of hospitalizations for the most prevalent infectious and bacterial diseases in children under 5 years, from2017 to 2021

Introdução:A internação representa um impacto considerável na vida de qualquer pessoa, podendo tomar proporções ainda maiores quando se trata de uma criança. A impossibilidade de realizar sua rotina, como brincar e ir à escola, faz com que a internação infantil assuma um contexto marcante.Dito isso, nota-se que grande parte dessas internações é evitável, sendo denominadasde Internações por Condições Sensíveis à Atenção Primária. Dessa forma, o atendimento ambulatorial de qualidade poderia resolver a maioria das enfermidades infantis, evitando esse desfecho.Objetivo:Elaborar um perfil epidemiológico de internações por doenças infecciosas e bacterianas mais prevalentes em menores de 5 anos, de 2017 a 2021, no Brasil. Metodologia:A pesquisa em questão se trata de um estudo ecológico de série temporal,elaborado através de informações coletadas por vias secundárias.Os dados foram coletados na plataforma DataSUS e no Sistema de Informação Hospitalar. Posteriormente, os dados foram processados e armazenados no aplicativo Microsoft Excel®, onde foram tratados e selecionados de acordo com sua relevância para a pesquisa. Resultados:Constata-se que a faixa etária situadaabaixo do primeiro ano de vidaapresenta um grau de hospitalização superior ao dascrianças que vãodo primeiro ao quarto ano completo.Quanto àfrequência relativa, depreende-se que diarreia e gastroenterite de origem infecciosa presumível apresentaram o maior índice de prevalência em relação às demais patologias, com o maior número chegando a 23,8% no ano de 2017 e o menor situando-se na faixa de 13,22% em 2020. Conclusões: Apesar do avanço na Atenção Primária à Saúde e da cobertura pré-natal, a assistência ainda é deficitária, sendo necessários mais investimentos na área e o fomento de políticas públicas que abranjam essa população (AU).

Introduction: Hospitalization represents a considerable impact on the life of any person, and can even take on even greater proportions when it comes to a child. The impossibility of realizing their routine, such as playing and going to school, means that hospitalization during childhood takes ona remarkable context. That said, it is noted that mostofthese hospitalizations are avoidable,and are called Ambulatory Care Sensitive Conditions. Thus, quality ambulatory care could solve most childhood illnesses, avoiding this outcome.Objective:To elaborate an epidemiological profile of hospitalizations for the most prevalent infectious and bacterial diseases in children under 5 years of age,from 2017 to 2021,in Brazil. Methodology: The research in question is an ecological study of time series, elaborated through information collected through secondary data sources. Data were collected from the DataSUS platform and the Hospital Information System. Subsequently, data were processed and stored in Microsoft Excel® application, where they were managedand selected according to their relevance to the research. Results:It is observed that the age group below the first year of life presents a higher degree of hospitalization thanthat of children ranging from the first to the fourth year. As for the relative frequency, it can be seen that diarrhea and gastroenteritis of presumable infectious origin had the highest prevalence rate compared to other pathologies, with the highest number reaching 23.8% in 2017 and the lowest being in the range of 13.22% in 2020. Conclusions: Despite the advances in Primary Health Care and prenatal coverage, assistance is still deficient, requiring more investments in the area and the promotion of public policies that cover this population (AU).

Introducción: La hospitalización representa un impacto considerable en la vida de cualquier persona, quepuede adquirir proporciones aún mayores cuando se trata de un niño. La imposibilidadde realizar su rutina, como jugar e ir al colegio, hace que la hospitalización infantiltengaun contexto notable. Dicho esto, cabe señalar que una gran parte de estas hospitalizaciones son evitables, denominándose Hospitalizaciones por Condiciones Sensibles a la Atención Ambulatoria. Así pues, una atención ambulatoria de calidad podría resolver la mayoría de las enfermedades infantiles, evitando este desenlace. Objetivo: Elaborar un perfil epidemiológico de las hospitalizaciones por enfermedades infecciosas y bacterianas más prevalentes en niños menores de 5 años, de 2017 a 2021, en Brasil. Metodología: La investigación en cuestión es un estudio ecológico de series temporales, elaborado a partir de información recogida por vías secundarias. Los datos se recogieron de la plataforma DataSUS y del Sistema de Información Hospitalaria. Posteriormente, los datos se procesaron y almacenaron en la aplicación Microsoft Excel®, donde se trataron y seleccionaron en función de su relevancia para la investigación. Resultados: Se observa que el grupo de edad inferior al primer año de vida presenta un mayor grado de hospitalización que los niños del primero al cuarto año completo. En cuanto a la frecuencia relativa, se puede inferirque la diarreay lagastroenteritis presumible origen infeccioso tuvieron la tasa de prevalencia más alta en relación con las demáspatologías, siendola cifra más alto el 23,8% en 2017 y lamás bajael rango del 13,22% en el 2020. Conclusiones: A pesar de los avances en la Atención Primariade Salud y en la cobertura prenatal, la asistencia aún es deficiente, por lo que se requieren mayoresinversiones en el área y la promoción de políticas públicas que cubran a esta población (AU).

Resilient anatomy and local plasticity of naive and stress haematopoiesis.

The bone marrow adjusts blood cell production to meet physiological demands in response to insults. The spatial organization of normal and stress responses are unknown owing to the lack of methods to visualize most steps of blood production. Here we develop strategies to image multipotent haematopoiesis, erythropoiesis and lymphopoiesis in mice. We combine these with imaging of myelopoiesis1 to define the anatomy of normal and stress haematopoiesis. In the steady state, across the skeleton, single stem cells and multipotent progenitors distribute through the marrow enriched near megakaryocytes. Lineage-committed progenitors are recruited to blood vessels, where they contribute to lineage-specific microanatomical structures composed of progenitors and immature cells, which function as the production sites for each major blood lineage. This overall anatomy is resilient to insults, as it was maintained after haemorrhage, systemic bacterial infection and granulocyte colony-stimulating factor (G-CSF) treatment, and during ageing. Production sites enable haematopoietic plasticity as they differentially and selectively modulate their numbers and output in response to insults. We found that stress responses are variable across the skeleton: the tibia and the sternum respond in opposite ways to G-CSF, and the skull does not increase erythropoiesis after haemorrhage. Our studies enable in situ analyses of haematopoiesis, define the anatomy of normal and stress responses, identify discrete microanatomical production sites that confer plasticity to haematopoiesis, and uncover unprecedented heterogeneity of stress responses across the skeleton.

Protocol for the diagnostic performance of C reactive protein, procalcitonin and interleukin-6 for serious bacterial infections among children ≤36 months old presenting with fever without source: a systematic review and meta-analysis.

INTRODUCTION: The management of fever without source in children ≤36 months old remains a diagnostic challenge as the underlying aetiologies can vary from self-limiting viral infections to serious bacterial infections (SBIs). Biomarkers such as C reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) have varying thresholds in the prediction of SBIs due to differences in SBI definitions, SBI prevalence, patient characteristics and timing of presentation. This protocol describes a systematic review and meta-analysis that aims to determine the thresholds at which CRP, PCT and IL-6 can perform optimally in distinguishing the presence of SBIs in children ≤36 months old, as well as to determine their performances in early detection of bacterial infections within 48 hours of fever onset. METHODS AND ANALYSIS: We will systematically search electronic databases including MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane CENTRAL, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and Science Citation Index from 1 July 2023 to 31 July 2023. We will include studies that report the diagnostic accuracy of CRP, PCT and IL-6 in detecting SBIs in children aged ≤36 months presenting with fever without apparent source. Randomised controlled trials (RCTs) and non-randomised studies including non-RCTs and controlled before-and-after studies will be included. A meta-analysis will be performed and diagnostic performances of these biomarkers will be reported. ETHICS AND DISSEMINATION: The results of this study will provide guidance on clinical decision-making in young children presenting with fever without source. Ethics approval will not be required for this study. The authors aim to publish the findings in a peer-reviewed journal as well as present at international conferences. PROSPERO REGISTRATION NUMBER: CRD42023439093.

Evaluation of novel compounds as anti-bacterial or anti-virulence agents.

Antimicrobial resistance is a global threat, leading to an alarming increase in the prevalence of bacterial infections that can no longer be treated with available antibiotics. The World Health Organization estimates that by 2050 up to 10 million deaths per year could be associated with antimicrobial resistance, which would equal the annual number of cancer deaths worldwide. To overcome this emerging crisis, novel anti-bacterial compounds are urgently needed. There are two possible approaches in the fight against bacterial infections: a) targeting structures within bacterial cells, similar to existing antibiotics; and/or b) targeting virulence factors rather than bacterial growth. Here, for the first time, we provide a comprehensive overview of the key steps in the evaluation of potential new anti-bacterial and/or anti-virulence compounds. The methods described in this review include: a) in silico methods for the evaluation of novel compounds; b) anti-bacterial assays (MIC, MBC, Time-kill); b) anti-virulence assays (anti-biofilm, anti-quorum sensing, anti-adhesion); and c) evaluation of safety aspects (cytotoxicity assay and Ames test). Overall, we provide a detailed description of the methods that are an essential tool for chemists, computational chemists, microbiologists, and toxicologists in the evaluation of potential novel antimicrobial compounds. These methods are cost-effective and have high predictive value. They are widely used in preclinical studies to identify new molecular candidates, for further investigation in animal and human trials.

Anti-Interleukin-23 Autoantibodies in Adult-Onset Immunodeficiency.

BACKGROUND: Autoantibodies against interleukin-12 (anti-interleukin-12) are often identified in patients with thymoma, but opportunistic infections develop in only some of these patients. Interleukin-12 (with subunits p40 and p35) shares a common subunit with interleukin-23 (subunits p40 and p19). In a patient with disseminated Burkholderia gladioli infection, the identification of both anti-interleukin-23 and anti-interleukin-12 prompted further investigation. METHODS: Among the patients (most of whom had thymoma) who were known to have anti-interleukin-12, we screened for autoantibodies against interleukin-23 (anti-interleukin-23). To validate the potential role of anti-interleukin-23 with respect to opportunistic infection, we tested a second cohort of patients with thymoma as well as patients without either thymoma or known anti-interleukin-12 who had unusual infections. RESULTS: Among 30 patients with anti-interleukin-12 who had severe mycobacterial, bacterial, or fungal infections, 15 (50%) also had autoantibodies that neutralized interleukin-23. The potency of such neutralization was correlated with the severity of these infections. The neutralizing activity of anti-interleukin-12 alone was not associated with infection. In the validation cohort of 91 patients with thymoma, the presence of anti-interleukin-23 was associated with infection status in 74 patients (81%). Overall, neutralizing anti-interleukin-23 was detected in 30 of 116 patients (26%) with thymoma and in 30 of 36 patients (83%) with disseminated, cerebral, or pulmonary infections. Anti-interleukin-23 was present in 6 of 32 patients (19%) with severe intracellular infections and in 2 of 16 patients (12%) with unusual intracranial infections, including Cladophialophora bantiana and Mycobacterium avium complex. CONCLUSIONS: Among patients with a variety of mycobacterial, bacterial, or fungal infections, the presence of neutralizing anti-interleukin-23 was associated with severe, persistent opportunistic infections. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

In Vitro Antibacterial Activity of Ozonated Olive Oil against Bacteria of Various Antimicrobial Resistance Profiles Isolated from Wounds of Companion Animals.

Frequent colonization and bacterial infection of skin wounds in small animals prevent or impair their healing. However, the broadly applied antimicrobial therapy of wounds is not always necessary and promotes the spread of bacterial resistance. Thus, alternatives to antimicrobial therapy, including preventive measures in the form of wound dressings with antibiotic properties, should be searched for. The aim of this study was to develop a new, efficient, cost-effective and non-toxic formulation with antimicrobial properties to serve as an alternative to antibiotic administration in wound-healing stimulation in companion animals. Nano/microencapsulated ozonated olive oil in a hyaluronan matrix was developed, with ozone concentration high enough to prevent bacterial growth. The presence and size of nano- and microcapsules were determined with scanning electron microscopy (SEM). Antibacterial activity of developed formulations was examined in vitro on 101 Gram-positive and Gram-negative bacteria isolated from the wounds of companion animals. The highest ozone concentration in the developed formulations inhibited the growth of 40.59% bacteria. Species and genus-specific differences in reactions were observed. Enterococcus spp. proved the least susceptible while non-pathogenic Gram-positive bacteria were the most susceptible to the examined formulations. Changes in the bacterial morphology and cell structure of Psychrobacter sanguinis suspension mixed with Ca-stabilized formulations with nano/microencapsulated ozonized olive oil were revealed during SEM observations. The combination of compounds that promote wound healing (hyaluronic acid, olive oil, ozone and calcium) with the antibacterial activity of the developed formula makes it a promising bionanocomposite for use as a topical dressing.