Six-minute walking distance and desaturation-distance ratio in allogeneic stem cell transplantation.

BACKGROUND: Most patients with haematological malignancies who undergo allogeneic haematopoietic stem cell transplant (HSCT) receive chemotherapy before the transplant to control the disease. Certain chemotherapy drugs can cause lung toxicity. Conversely, in patients with chronic respiratory conditions, the 6-min walking test (6MWT) and the desaturation-distance ratio (DDR) have demonstrated prognostic significance. Our objective was to determine whether the 6MWD and DDR, assessed prior to HSCT, have a prognostic impact on survival at 24 months post-HSCT. METHODS: A prospective experimental study was conducted in consecutive patients referred for allogeneic HSCT at Hospital Clinic, Barcelona, Spain. A complete functional respiratory study, including the 6MWT and DDR, was conducted prior to admission. The area under the curve (AUC) and cut-off points were calculated. Data on patients' characteristics, HSCT details, main events, with a focus on lung complications, and survival at 24 months were analysed. RESULTS: One hundred and seventy-five patients (39% women) with mean age of 48 ± 13 years old were included. Before HSCT, forced vital capacity and forced expiratory volume in the first second were 96% ± 13% predicted and 92% ± 14% predicted, respectively; corrected diffusing capacity for carbon monoxide 79% ± 15% predicted; 6MWD was 568 ± 83 m and DDR of .27 (.20-.41). The cut-off points for 6MWD and DDR were 566 m, [.58 95% CI (.51-.64)], p = .024 and .306, [.63 95% CI (.55-.70)], p = .0005, respectively. The survival rate at 24 months was 55%. CONCLUSION: Our results showed that individuals who exhibit a 6MWD shorter than 566 ms or a decline in DDR beyond .306 experienced reduced survival rates at 24 months after HSCT.

Omics biomarkers and an approach for their practical implementation to delineate health status for personalized nutrition strategies.

Personalized nutrition (PN) has gained much attention as a tool for empowerment of consumers to promote changes in dietary behavior, optimizing health status and preventing diet related diseases. Generalized implementation of PN faces different obstacles, one of the most relevant being metabolic characterization of the individual. Although omics technologies allow for assessment the dynamics of metabolism with unprecedented detail, its translatability as affordable and simple PN protocols is still difficult due to the complexity of metabolic regulation and to different technical and economical constrains. In this work, we propose a conceptual framework that considers the dysregulation of a few overarching processes, namely Carbohydrate metabolism, lipid metabolism, inflammation, oxidative stress and microbiota-derived metabolites, as the basis of the onset of several non-communicable diseases. These processes can be assessed and characterized by specific sets of proteomic, metabolomic and genetic markers that minimize operational constrains and maximize the information obtained at the individual level. Current machine learning and data analysis methodologies allow the development of algorithms to integrate omics and genetic markers. Reduction of dimensionality of variables facilitates the implementation of omics and genetic information in digital tools. This framework is exemplified by presenting the EU-Funded project PREVENTOMICS as a use case.

Effects of maternal modafinil treatment on fetal development and neonatal growth parameters - a multicenter case series of the European Network of Teratology Information Services (ENTIS).

OBJECTIVE: In recent years, safety concerns about modafinil exposure during pregnancy have emerged. In particular, increased risks for major congenital anomalies (MCA) and impaired fetal growth were reported, although study results were conflicting. Our investigation aims to examine previously reported safety signals. METHOD: Multicenter case series based on data from 18 Teratology Information Services from 12 countries. Modafinil exposed pregnancies with an estimated date of birth before August 2019 were included in this study. For prospectively ascertained pregnancies, cumulative incidences of pregnancy outcomes, rate of nonchromosomal MCA in first trimester exposed pregnancies and percentiles of neonatal/infant weight and head circumference (HC) were calculated. Potential dose-dependent effects on fetal growth were explored by linear regression models. Retrospectively ascertained cases were screened for pattern of MCA and other adverse events. RESULTS: One hundred and seventy-five prospectively ascertained cases were included, of which 173 were exposed at least during the first trimester. Cumulative incidences for live birth, spontaneous abortion and elective termination of pregnancy were 76.9% (95% CI, 68.0%-84.8%), 9.3% (95% CI, 5.0%-16.9%), and 13.9% (95% CI, 8.1%-23.1%), respectively. Nonchromosomal MCA was present in 3/150 live births, corresponding to an MCA rate of 2.0% (95%CI, 0.6%-6.1%), none were reported in pregnancy losses. Compared to reference standards, birth weight (BW) tended to be lower and neonatal HC to be smaller in exposed newborns (data available for 144 and 73 of 153 live births, respectively). In nonadjusted linear regression models, each 100 mg increase of average dosage per pregnancy day was associated with a decrease in standard deviation score (SDS) of -0.28 SDS (95% CI, -0.45 to -0.10) for BW and of -0.28 SDS (95% CI, -0.56 to 0.01) for HC. Screening of 22 retrospectively reported cases did not reveal any specific pattern of MCA or other adverse outcomes. CONCLUSION: The results do not indicate an increased risk of MCA after in utero exposure to modafinil, but a tendency toward lower BW and reduced neonatal HC. However, these findings should be regarded as preliminary. Until further studies allow for a definite conclusion, modafinil should not be used during pregnancy.

Pseudomonas fitomaticsae sp. nov., isolated at Marimurtra Botanical Garden in Blanes, Catalonia, Spain.

In the framework of the research project called fitomatics, we have isolated and characterized a bacterial plant-endophyte from the rhizomes of Iris germanica, hereafter referred to as strain FIT81T. The bacterium is Gram negative, rod-shaped with lophotrichous flagella, and catalase- and oxidase-positive. The optimal growth temperature of strain FIT81T is 28 °C, although it can grow within a temperature range of 4-32 °C. The pH growth tolerance ranges between pH 5 and 10, and it tolerates 4% (w/v) NaCl. A 16S rRNA phylogenetic analysis positioned strain FIT81T within the genus Pseudomonas, and multilocus sequence analysis revealed that Pseudomonas gozinkensis IzPS32dT, Pseudomonas glycinae MS586T, Pseudomonas allokribbensis IzPS23T, 'Pseudomonas kribbensis' 46-2 and Pseudomonas koreensis PS9-14T are the top five most closely related species, which were selected for further genome-to-genome comparisons, as well as for physiological and chemotaxonomic characterization. The genome size of strain FIT81T is 6 492 796 base-pairs long, with 60.6 mol% of G+C content. Average nucleotide identity and digital DNA-DNA hybridization analyses yielded values of 93.6 and 56.1%, respectively, when the FIT81T genome was compared to that of the closest type strain P. gozinkensis IzPS32dT. Taken together, the obtained genomic, physiologic and chemotaxonomic data indicate that strain FIT81T is different from its closest relative species, which lead us to suggest that it is a novel species to be included in the list of type strains with the name Pseudomonas fitomaticsae sp. nov. (FIT81T=CECT 30374T=DSM 112699T).

Withdrawal of hospital outpatient treatments in severe diseases due to unacceptable toxicity: A retrospective study from the register of patients and treatments.

AIM: To retrospectively analyse hospital outpatient treatment (HOT) withdrawal due to unacceptable toxicity at our hospital. Information regarding unacceptable toxicity leading to treatment withdrawal was recorded. METHODS: HOT interruptions because of unacceptable toxicity were identified from the Register of Patients and Treatments (RPT) (January 2014 to December 2017). Information regarding the demographic and clinical characteristics of patients, adverse drug reactions (ADRs) and drug treatments was retrieved from electronic health records. Causality and previous knowledge of ADRs were assessed according to the Spanish Pharmacovigilance System algorithm. Information regarding HOT risk management plans (RMPs) and their classification as inverted black triangle medicines was obtained from the European Medicines Agency (EMA). RESULTS: HOTs were withdrawn due to unacceptable toxicity in 136 (1.5%) registries corresponding to 135 (1.7%) patients. Fifty-one different HOTs (38.6% of those registered) were involved in 240 ADR/HOT pairs: 24 (47%) were additional monitoring medicines and 37 (72.5%) were EMA RMPs. The most frequent medicines involved in ADRs were lenalidomide (30, 12.5%) (mainly neutropenia, thrombocytopenia and bicytopenia), bevacizumab (19, 7.9%) (mainly venous and pulmonary thromboembolism) and sunitinib (13, 5.4%) (mainly thromboembolic events, diarrhoea and worsening of chronic renal failure). Cytopenia (40, 17.3%), diarrhoea (15, 6.5%), asthenia (9, 3.9%) and neuropathy (6, 2.6%) were the most frequent ADRs. All ADRs were severe, 10 (6 patients) had been poorly described or were unknown and only 9 (5 patients) had been reported by spontaneous notification. CONCLUSIONS: Valuable information regarding severe and unknown ADRs was obtained from the RPT. Such registers are useful tools to complement spontaneous ADR notifications.

Lactobacillus plantarum CECT 7527, 7528 and 7529: probiotic candidates to reduce cholesterol levels.

BACKGROUND: Hypercholesterolaemia plays a key role in the development and progression of coronary artery disease. There are numerous drugs available to treat this condition but they are often expensive and can have unwanted side effects. Therefore, a screening of lactic acid bacteria to select candidate probiotic strains to reduce cholesterol levels was carried out. Three Lactobacillus plantarum strains (CECT 7527, 7528 and 7529) were selected as potential probiotics to reduce cholesterol levels after conducting several in vitro tests for demonstrating the functionalities of the strains according to international guidelines. RESULTS: The three strains showed a high ability to survive under gastrointestinal tract conditions and to adhere to intestinal cells. Regarding lipid metabolism, the strains showed a great production of bile salt hydrolase, especially when combined. Moreover, the strains assimilated cholesterol directly from the medium. Part of the cholesterol present in the medium was removed via binding onto the bacterial cellular surface. Finally, the three strains, especially CECT 7529, produce large quantities of propionic and butyric acids. CONCLUSION: Combined, these characteristics suggest that these strains could be excellent candidates for reducing high blood cholesterol levels.

Effectiveness and safety of alirocumab and evolocumab for hypercholesterolemia in a population with high cardiovascular risk.

BACKGROUND AND AIMS: The criteria for the use of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) more restrictive than those approved were established in Catalonia by the Health System (CatSalut) to improve their efficiency, with different LDL-C values from which to start treatment according to risk factors. The aim of the study is to analyse adherence to these criteria and results. METHODS: A retrospective study of patients treated with PCSK9i at Vall d'Hebron University Hospital between 2016 and 2021 was performed using data from the Registry of Patients and Treatments and medical records. The degree of agreement with the CatSalut criteria, LDL-C-responders (decrease ≥30%), cardiovascular events and discontinuations were analysed. RESULTS: A total of 193 patients treated with PCSK9i were followed for a median of 27 months (IQR 23). The median age was 61 (IQR 15); 62.7% were men. Seventy percent of the patients had non-familial hypercholesterolemia. Treatment was for secondary prevention of cardiovascular disease in 82.4% of cases. The median LDL-C decreased from 139 (IQR 52) to 59 (IQR 45) mg/dL. The percentage of LDL-C reduction was 61.0% (IQR 30). In 72.5% of patients, all CatSalut criteria for starting treatment were met. The rate of responders was 85.4%. During follow-up, 19 patients (9.8%) had a cardiovascular event, and 15 (7.7%) discontinued treatment, in two cases due to toxicity. CONCLUSION: PCSK9i were used according to CatSalut criteria in three out of four cases. In this high-risk population, incidence of cardiovascular events was similar to that in clinical trials.

Implementation of a vascular access team and an intravenous therapy programme: A first-year activity analysis.

BACKGROUND: Creating Vascular Access Teams (VAT) provides an expert nursing role that contributes to the training and continuous improvement of healthcare personnel. They can offer greater clinical safety, reducing complications and costs. Peripherally inserted central catheters (PICCs) and midline catheters (ML) can be safe and cost-effective alternatives to other types of venous access (VA). The aim of the study was to analyse our centre's VAT first 12 months of activity. The primary outcome was reported complications. Secondary outcomes were cause of catheter removal, consultancy activity and economic impact of VAT implantation. METHODOLOGY: A longitudinal, descriptive study was carried out from March 2019 to March 2020. Using consecutive sampling, all VA inserted, and all consults received were included. Patients under 18 years of age were excluded. RESULTS: The VAT inserted 1257 catheters into 1056 patients (291 MLs, 966 PICCs). The mean dwell time was 14.9 days for MLs and 59.07 days for PICCs. The main reason for removing VA was end of treatment (80.7%). During VA follow-up confirmed infection was detected in 1 ML (0.3%) and nine PICCs (0.9%). Symptomatic thrombosis was reported in 2 MLs (0.7%) and 16 PICCs (1.7%). The VAT received 367 consultations, and the main reason for consultation was to resolve doubts regarding the management of VA (80.9%). The insertion of ML and PICC catheters represented annual estimated economic savings of €867,688.44€. CONCLUSIONS: Our study provides a detailed analysis of VAT's activity, its relevance to clinical safety, and to efficient resource management within our hospital. It demonstrates how VAT establishment can be a safe and efficient intervention that enhances care quality.

[How to identify physical inactivity in primary care: validation of the Catalan and Spanish versions of 2 short questionnaires]. / Cómo identificar la inactividad física en atención primaria: validación de las versiones catalana y española de 2 cuestionarios breves.

OBJECTIVE: The Brief Physical Activity Assessment Tool (BPAAT) and the General Practice Physical Activity Questionnaire (GPPAQ) are valid and reliable assessment tools to identify "inactive" patients in primary care. No similar tools exist for the Spanish population. The study aimed to evaluate the reliability and validity of the Catalan and Spanish versions (CBPAAT-CGPPAQ; CBPAAT-EGPPAQ) of such tools. DESIGN: Validation study of the linguistic and cultural adaptation of two questionnaires into Catalan/Spanish. SETTING: Centres of Primary Care. PARTICIPANTS: The load for administering the questionnaires was evaluated by 7 general practitioners and 44 patients. Construct validity and reliability was assessed in 105 patients (58 years old±20; 37% men) without any contraindication for physical activity (PA). MAIN VARIABLES: After carrying out the translation and back-translation, construct validity was assessed against the International Physical Activity Questionnaire (IPAQ short form). Reliability was assessed administering the questionnaires again within 14 to 28 days. RESULTS: The validity of the CBPAAT-EBPAAT showed a moderate percentage agreement, correctly classifying over 80% and 83% of the "inactive" cases. Reliability was also good, correctly classifying over 86% and 88% of the cases. The validity of the CGPPAQ-EGPPAQ showed a moderate percentage agreement, correctly classifying over 70% and 60% of the "inactive" cases. Reliability was good, correctly classifying over 82% and 72% of the cases. CONCLUSIONS: The CBPAAT-CGPPAQ and EBPAAT-EGPPAQ are valid instruments to identify "inactive" patients that should receive advice on PA.

Safety of Drugs Used during the First Wave of COVID-19: A Hospital-Registry-Based Study.

The emergency of the coronavirus disease 2019 (COVID-19) pandemic led to the off-label use of drugs without data on their toxicity profiles in patients with COVID-19, or on their concomitant use. Patients included in the COVID-19 Patient Registry of a tertiary hospital during the first wave were analyzed to evaluate the adverse drug reactions (ADRs) with the selected treatments. Twenty-one percent of patients (197 out of 933) had at least one ADR, with a total of 240 ADRs. Patients with ADRs were more commonly treated with multiple drugs for COVID-19 infection than patients without ADRs (p < 0.001). They were younger (median 62 years vs. 70.1 years; p < 0.001) and took less medication regularly (69.5% vs. 75.7%; p = 0.031). The most frequent ADRs were gastrointestinal (67.1%), hepatobiliary (10.8%), and cardiac disorders (3.3%). Drugs more frequently involved included lopinavir/ritonavir (82.2%), hydroxychloroquine (72.1%), and azithromycin (66.5%). Although most ADRs recovered without sequelae, fatal cases were described, even though the role of the disease could not be completely ruled out. In similar situations, efforts should be made to use the drugs in the context of clinical trials, and to limit off-label use to those drugs with a better benefit/risk profile in specific situations and for patients at high risk of poor disease prognosis.

Cork as a sustainable carbon source for nature-based solutions treating hydroponic wastewaters - Preliminary batch studies.

Reusing by-products is an important strategy to ensure the preservation of natural capital and climate change mitigation. This study aimed at evaluating the potential of cork granulates, a by-product of winery industry, as an organic carbon (OC) source for the treatment of hydroponic wastewaters. First, chemical characterization was performed and discussed. Secondly, batch studies were performed using synthetic hydroponic wastewater to understand the role of particle size (PS), pH and contact time (CT) on the release of OC. The suberin is the major compound, representing >50%. It was noticed that a variance on the content of suberin across species, within the same species and depending on the extraction part (belly, cork and back) could be expected. >60% of the sample is composed by carbon while <1% was nitrogen (high C:N ratio), indicating a low risk of releasing organic nitrogen. The statistical results suggested that the main effect of PS on the release of OC is greater than both, CT and pH. The chemical release of OC gets slower with time, being this effect greater as the PS increase. Moreover, estimations showed that using the 4 mm PS, the amount of water treated would be twice the amount if the 8 mm PS had been used. The PS seems to play an important role at design nature-based solutions (NBS) focused on denitrification. The surface response methodology indicates a significant negative interaction between CT and PS suggesting that the mathematical model could be used for further optimization studies. The reuse of organic by-products as filter media seems to be an economic and environmentally friendly alternative to enhance denitrification in NBS, while preserving natural capital. However, further real scale and long-term experiments are needed to validate cork's potential as an "internal" OC source for NBS.

RPS4Y gene family evolution in primates.

BACKGROUND: The RPS4 gene codifies for ribosomal protein S4, a very well-conserved protein present in all kingdoms. In primates, RPS4 is codified by two functional genes located on both sex chromosomes: the RPS4X and RPS4Y genes. In humans, RPS4Y is duplicated and the Y chromosome therefore carries a third functional paralog: RPS4Y2, which presents a testis-specific expression pattern. RESULTS: DNA sequence analysis of the intronic and cDNA regions of RPS4Y genes from species covering the entire primate phylogeny showed that the duplication event leading to the second Y-linked copy occurred after the divergence of New World monkeys, about 35 million years ago. Maximum likelihood analyses of the synonymous and non-synonymous substitutions revealed that positive selection was acting on RPS4Y2 gene in the human lineage, which represents the first evidence of positive selection on a ribosomal protein gene. Putative positive amino acid replacements affected the three domains of the protein: one of these changes is located in the KOW protein domain and affects the unique invariable position of this motif, and might thus have a dramatic effect on the protein function. CONCLUSION: Here, we shed new light on the evolutionary history of RPS4Y gene family, especially on that of RPS4Y2. The results point that the RPS4Y1 gene might be maintained to compensate gene dosage between sexes, while RPS4Y2 might have acquired a new function, at least in the lineage leading to humans.

Short- and long-term effectiveness of a smartphone application for improving measures of adiposity: A randomised clinical trial - EVIDENT II study.

BACKGROUND: Evidence on the efficacy of smartphone applications (apps) for reducing body weight and other measurements of adiposity sustainably is not conclusive. OBJECTIVE: To evaluate the effect of adding an app for 3 months to traditional counselling on physical activity (PA) and a heart-healthy diet for the modification of measurements of adiposity at 3 and 12 months after intervention. METHODS: This randomised clinical trial included 833 subjects. The counselling and app group (IG) had 415 subjects, while 418 were included in the counselling only group (CG). The primary outcome was adiposity measurements at 3 and 12 months after intervention. The secondary outcome was the effect of the intervention by sex. INTERVENTION: Counselling on a heart-healthy diet and PA was given to both groups. The IG also received training in the use of a smartphone app designed to promote a heart-healthy diet and PA, and this group was given access to this application for 3 months. Outcome measurements included waist circumference (WC), body mass index (BMI) and Clínica Universidad de Navarra - body adiposity estimator (CUN-BAE). RESULTS: In the IG at 12 months, the following decreased: WC -0.72 cm (95% confidence interval [CI]: -2.35 to -0.02) and CUN-BAE -0.35 (95% CI: -0.63 to -0.06). These decreases were only observed in women. After baseline adjustment, the beneficial effect was maintained in the IG compared to the CG at 12 months in terms of WC (-0.67; 95% CI: -0.29 to -0.02) and CUN-BAE (-0.57; 95% CI: -1.10 to -0.04), but only in women. CONCLUSIONS: An intervention of nutritional counselling and PA plus the smartphone app with personalised recommendations compared to CG showed beneficial results in terms of reduction of abdominal obesity and the percentage of body fat in women, but not in men.

Analyses of carnivore microsatellites and their intimate association with tRNA-derived SINEs.

BACKGROUND: The popularity of microsatellites has greatly increased in the last decade on account of their many applications. However, little is currently understood about the factors that influence their genesis and distribution among and within species genomes. In this work, we analyzed carnivore microsatellite clones from GenBank to study their association with interspersed repeats and elucidate the role of the latter in microsatellite genesis and distribution. RESULTS: We constructed a comprehensive carnivore microsatellite database comprising 1236 clones from GenBank. Thirty-three species of 11 out of 12 carnivore families were represented, although two distantly related species, the domestic dog and cat, were clearly overrepresented. Of these clones, 330 contained tRNALys-derived SINEs and 357 contained other interspersed repeats. Our rough estimates of tRNA SINE copies per haploid genome were much higher than published ones. Our results also revealed a distinct juxtaposition of AG and A-rich repeats and tRNALys-derived SINEs suggesting their coevolution. Both microsatellites arose repeatedly in two regions of the interspersed repeat. Moreover, microsatellites associated with tRNALys-derived SINEs showed the highest complexity and less potential instability. CONCLUSION: Our results suggest that tRNALys-derived SINEs are a significant source for microsatellite generation in carnivores, especially for AG and A-rich repeat motifs. These observations indicate two modes of microsatellite generation: the expansion and variation of pre-existing tandem repeats and the conversion of sequences with high cryptic simplicity into a repeat array; mechanisms which are not specific to tRNALys-derived SINEs. Microsatellite and interspersed repeat coevolution could also explain different distribution of repeat types among and within species genomes.Finally, due to their higher complexity and lower potential informative content of microsatellites associated with tRNALys-derived SINEs, we recommend avoiding their use as genetic markers.

[Physical exercise prescription]. / Prescripción de ejercicio físico.

Although being sedentary is recognized as the most prevalent cardiovascular risk factor in industrialized societies, health measures tend to concentrate on secondary and tertiary prevention methods, using pharmacological curative measures instead of favoring methods of primary prevention by means of promoting healthy lifestyles. This article hits on the essentials to promote physical exercise by our patients.

Level of adherence to an extravasation protocol over 10 years in a tertiary care hospital.

BACKGROUND: Extravasation of chemotherapy is an undesirable complication related to the administration of antineoplastic therapy. Establishing the real incidence is difficult. Because of the importance of a quick intervention after an extravasation, every hospital should have an extravasation protocol. OBJECTIVES: The purpose of this study was to determine the degree of observance of an extravasation protocol by nursing staff and to determine extravasation incidence. METHODS: This descriptive, longitudinal, retrospective study was set in a tertiary-level hospital. The researchers reviewed 117 extravasation notification forms received by the pharmacy department during a 10-year period. Nursing actuation, particularly observance of the extravasation protocol, was analyzed. FINDINGS: Protocol adherence was 89%. Twelve deviations from the protocol in the application of recommended measures were detected. An antidote was used in 41 patients, and temperature measures were applied in 14 cases. Ninety-nine patients had at least one episode of reported follow-up. No cases of necrosis or skin ulcers were described, except by one patient, who developed a delayed skin ulcer to vinorelbine. Drugs most frequently reported were etoposide, carboplatin, and paclitaxel. Nursing staff should be continuously trained in extravasation protocol because a rapid actuation can prevent skin lesions.

Pasteurella multocida exbB, exbD and tonB genes are physically linked but independently transcribed.

The exbB, exbD and tonB genes of the Pasteurella multocida animal pathogen have been cloned by complementation of an Escherichia coli tonB mutant. Despite these three genes being physically linked, RT-PCR analysis, lacZ transcriptional fusions and construction of insertional mutants have demonstrated that they do not constitute an operon, but rather are transcribed independently from each other. Furthermore, expression of these three genes is under iron control as revealed by lacZ fusions and Fur titration assay analysis. Moreover, each of these three genes is necessary for the virulence of P. multocida cells and all of them contribute equally to the infectious process of this microorganism.

The high-affinity zinc-uptake system znuACB is under control of the iron-uptake regulator (fur) gene in the animal pathogen Pasteurella multocida.

The Pasteurella multocida znuACB genes encoding a high-affinity zinc-uptake system have been identified and cloned. In contrast to what happens in Escherichia coli, znuA is not physically linked to znuCB. Through lacZ transcriptional fusions it has been demonstrated that zinc negatively regulates both znuA and znuCB operons. Nevertheless, and contrary to that determined so far for all other znuACB bacterial systems known, P. multocida znuACB genes are not under control of the zur gene, which is absent in this bacterial species, but rather are under its iron-uptake regulator (fur) gene. Furthermore, construction of defective mutants has demonstrated that P. multocida znuA and znuCB transcriptional units are required for virulence of this organism in a mouse model.