Comparison of performances between risk scores for predicting mortality at 30 days in patients with community acquired pneumonia.

BACKGROUND: Risk scores facilitate the assessment of mortality risk in patients with community-acquired pneumonia (CAP). Despite their utilities, there is a scarcity of evidence comparing the various RS simultaneously. This study aims to evaluate and compare multiple risk scores reported in the literature for predicting 30-day mortality in adult patients with CAP. METHODS: A retrospective cohort study on patients diagnosed with CAP was conducted across two hospitals in Colombia. The areas under receiver operating characteristic curves (ROC-curves) were calculated for the outcome of survival or death at 30 days using the scores obtained for each of the analyzed questionnaires. RESULTS: A total of 7454 potentially eligible patients were included, with 4350 in the final analysis, of whom 15.2% (662/4350) died within 30 days. The average age was 65.4 years (SD: 21.31), and 59.5% (2563/4350) were male. Chronic kidney disease was 3.7% (9.2% vs. 5.5%; p < 0.001) (OR: 1.85) higher in subjects who died compared to those who survived. Among the patients who died, 33.2% (220/662) presented septic shock compared to 7.3% (271/3688) of the patients who survived (p < 0.001). The best performances at 30 days were shown by the following scores: PSI, SMART-COP and CURB 65 scores with the areas under ROC-curves of 0.83 (95% CI: 0.8-0.85), 0.75 (95% CI: 0.66-0.83), and 0.73 (95% CI: 0.71-0.76), respectively. The RS with the lowest performance was SIRS with the area under ROC-curve of 0.53 (95% CI: 0.51-0.56). CONCLUSION: The PSI, SMART-COP and CURB 65, demonstrated the best diagnostic performances for predicting 30-day mortality in patients diagnosed with CAP. The burden of comorbidities and complications associated with CAP was higher in patients who died.

Enterovirus D68 disease burden and epidemiology in hospital-admitted influenza-like illness, Valencia region of Spain, 2014-2020 influenza seasons.

Enterovirus D68 (EV-D68) is an emerging agent for which data on the susceptible adult population is scarce. We performed a 6-year analysis of respiratory samples from influenza-like illness (ILI) admitted during 2014-2020 in 4-10 hospitals in the Valencia Region, Spain. EV-D68 was identified in 68 (3.1%) among 2210 Enterovirus (EV)/Rhinovirus (HRV) positive samples. Phylogeny of 59 VP1 sequences showed isolates from 2014 clustering in B2 (6/12), B1 (5/12), and A2/D1 (1/12) subclades; those from 2015 (n = 1) and 2016 (n = 1) in B3 and A2/D1, respectively; and isolates from 2018 in A2/D3 (42/45), and B3 (3/45). B1 and B2 viruses were mainly detected in children (80% and 67%, respectively); B3 were equally distributed between children and adults; whereas A2/D1 and A2/D3 were observed only in adults. B3 viruses showed up to 16 amino acid changes at predicted antigenic sites. In conclusion, two EV-D68 epidemics linked to ILI hospitalized cases occurred in the Valencia Region in 2014 and 2018, with three fatal outcomes and one ICU admission. A2/D3 strains from 2018 were associated with severe respiratory infection in adults. Because of the significant impact of non-polio enteroviruses in ILI and the potential neurotropism, year-round surveillance in respiratory samples should be pursued.

Fluconazole-resistant Candida parapsilosis: fast detection of the Y132F ERG11p substitution, and a proposed microsatellite genotyping scheme.

OBJECTIVES: We propose fast and accurate molecular detection of the Y132F ERG11p substitution directly on pure-cultured Candida parapsilosis isolates. We also assessed a discriminative genotyping scheme to track circulating genotypes. METHODS: A total of 223 C. parapsilosis isolates (one patient each) from 20 hospitals, located in Spain and Italy were selected. Isolates were fluconazole-resistant (n = 94; harbouring the Y132F ERG11p substitution [n = 85], the G458S substitution [n = 6], the R398I substitution [n = 2], or the wild-type ERG11 gene sequence) or fluconazole-susceptible (n = 129). Two targeted-A395T-mutation PCR formats (conventional and real-time) were engineered and optimized on fluconazole-susceptible and fluconazole-resistant pure-cultured isolates, thus skipping DNA extraction. Two genotyping schemes were compared: Scheme 1 (CP1, CP4a, CP6, and B markers), and Scheme 2 (6A, 6B, 6C, CP1, CP4a, and CP6 markers). RESULTS: The screening performed using both PCR formats showed 100% specificity (fluconazole-susceptible isolates; n = 129/129) and sensitivity (Y132F isolates; n = 85/85) values; however, results were available in 3 and 1.5 hours with the conventional and real-time PCR formats, respectively. Overall, Scheme 1 showed higher genetic diversity than Scheme 2, as shown by the number of alleles detected (n = 98; mean 23, range 13-38), the significantly higher observed and expected heterozygosity, and the probability of identity index (2.5 × 10-6). Scheme 2 markers did not provide further genotypic discrimination of Y132F fluconazole-resistant genotypes. CONCLUSION: Both proposed PCR formats allow us to speed up the accurate detection of substitution Y132F ERG11p in C. parapsilosis isolates with 100% specificity and sensitivity. In addition, we recommend CP1, CP4a, CP6, and B microsatellite markers for genotyping fluconazole-resistant isolates.

Zoledronic acid for hip fracture during initial hospitalization.

Inpatient zoledronic acid (IP-ZA) administered during the initial fracture hospitalization significantly improves the osteoporosis treatment rate. Clinical outcomes of IP-ZA after hip fracture remain uncertain. Here we report a cohort study that emulated a randomized controlled trial using real-world data and evaluated the risk of all-cause-mortality and radiologically confirmed subsequent new fractures among patients hospitalized for a hip fracture who had received IP-ZA as compared with propensity-matched controls. A total of 654 patients who had received IP-ZA and 6877 controls (for whom anti-osteoporosis treatment was indicated but no IP-ZA started during index hospitalization) were included in the study. The primary cohort comprised 652 IP-ZA patients (IP-ZA group) and 1926 matched controls (untreated group), with 71.7% female 92.1% White participants, with a mean age of 80.9 years. Cumulative all-cause mortality over the 24-month follow-up for the IP-ZA group was 12.3% and 20.7% for the untreated group (hazard ratio [HR], 0.62; 95% CI, 0.49-0.78, p < .001). A total of 585 (89.7%) patients in IP-ZA group received only a single dose of ZA during the 24 months, and the death rate of this single dose group was 13.3%, which was significantly lower than that of the untreated group (HR, 0.70; 95% CI, 0.55-0.89, p = .003). Rates of radiologically confirmed cumulative subsequent new vertebral fractures were 2.0% in the IP-ZA group and 5.4% in the untreated group (HR, 0.40; 95% CI, 0.22-0.71, p = .001). A similarly lower rate of new vertebral fractures was seen in the single dose subgroup (1.9% vs 5.4%; HR, 0.44; 95% 0.24-0.82, p = .008). IP-ZA, administered during the initial hospitalization for hip fracture, was associated with lower all-cause-mortality and risk of radiologically confirmed subsequent new vertebral fractures, and thus offers a mechanism to narrow the treatment gap in patients having sustained a hip fragility fracture.

Hip fracture is a serious complication of osteoporosis affecting approximately 300 000 Americans per year and is associated with a 20%-30% 1-year mortality rate. Most patients with hip fracture are elderly (average age, 80-81 years), with multiple underlying medical conditions and are often unable to timely attend post-hospitalization outpatient follow-up to initiate anti-osteoporosis treatment. As a result, only ~10% of post­hip fracture patients receive treatment for underlying osteoporosis. We have previously reported that zoledronic acid (ZA) administered during initial fracture hospitalization (IP-ZA) is safe and can effectively improve the osteoporosis treatment rate to 70%. The present study analyzed the clinical outcomes of 652 patients who had sustained hip fractures and were treated with IP-ZA and 1926 matched controls and revealed significantly reduced rates of all-cause mortality and vertebral compression fracture (VCF) during a 2-year follow-up period. Of note, nearly 90% of the treated patients received only a single dose of ZA (namely, IP-ZA), suggesting that, for most patients, the only opportunity to receive anti-osteoporosis treatment was during the index fracture hospitalization. Importantly, reduced mortality and VCF rates were readily seen in this single-dose group of patients. Our data suggest that IP-ZA is beneficial for osteoporotic hip fracture.

Antibody Mediated Rejection and T-cell Mediated Rejection Molecular Signatures Using Next-Generation Sequencing in Kidney Transplant Biopsies.

Recently, interest in transcriptomic assessment of kidney biopsies has been growing. This study investigates the use of NGS to identify gene expression changes and analyse the pathways involved in rejection. An Illumina bulk RNA sequencing on the polyadenylated RNA of 770 kidney biopsies was conducted. Differentially-expressed genes (DEGs) were determined for AMR and TCMR using DESeq2. Genes were segregated according to their previous descriptions in known panels (microarray or the Banff Human Organ Transplant (B-HOT) panel) to obtain NGS-specific genes. Pathway enrichment analysis was performed using the Reactome and Kyoto Encyclopaedia of Genes and Genomes (KEGG) public repositories. The differential gene expression using NGS analysis identified 6,141 and 8,478 transcripts associated with AMR and TCMR. While most of the genes identified were included in the microarray and the B-HOT panels, NGS analysis identified 603 (9.8%) and 1,186 (14%) new specific genes. Pathways analysis showed that the B-HOT panel was associated with the main immunological processes involved during AMR and TCMR. The microarrays specifically integrated metabolic functions and cell cycle progression processes. Novel NGS-specific based transcripts associated with AMR and TCMR were discovered, which might represent a novel source of targets for drug designing and repurposing.

From the Microbiome to the Electrome: Implications for the Microbiota-Gut-Brain Axis.

The gut microbiome plays a fundamental role in metabolism, as well as the immune and nervous systems. Microbial imbalance (dysbiosis) can contribute to subsequent physical and mental pathologies. As such, interest has been growing in the microbiota-gut-brain brain axis and the bioelectrical communication that could exist between bacterial and nervous cells. The aim of this study was to investigate the bioelectrical profile (electrome) of two bacterial species characteristic of the gut microbiome: a Proteobacteria Gram-negative bacillus Escherichia coli (E. coli), and a Firmicutes Gram-positive coccus Enterococcus faecalis (E. faecalis). We analyzed both bacterial strains to (i) validate the fluorescent probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol, DiBAC4(3), as a reliable reporter of the changes in membrane potential (Vmem) for both bacteria; (ii) assess the evolution of the bioelectric profile throughout the growth of both strains; (iii) investigate the effects of two neural-type stimuli on Vmem changes: the excitatory neurotransmitter glutamate (Glu) and the inhibitory neurotransmitter γ-aminobutyric acid (GABA); (iv) examine the impact of the bioelectrical changes induced by neurotransmitters on bacterial growth, viability, and cultivability using absorbance, live/dead fluorescent probes, and viable counts, respectively. Our findings reveal distinct bioelectrical profiles characteristic of each bacterial species and growth phase. Importantly, neural-type stimuli induce Vmem changes without affecting bacterial growth, viability, or cultivability, suggesting a specific bioelectrical response in bacterial cells to neurotransmitter cues. These results contribute to understanding the bacterial response to external stimuli, with potential implications for modulating bacterial bioelectricity as a novel therapeutic target.

A protocol to determine the acceptability and feasibility of a pilot intervention emergency department virtual observation unit fall prevention program.

BACKGROUND: As a third of all community dwellers aged 65+ fall each year, falls are common reasons for older adults to present to an Emergency Department (ED). Although EDs should assess patients' multifactorial fall risks to prevent future fall-related injuries, this frequently does not occur. We describe our protocol to determine the feasibility, acceptability, and safety of a pilot ED Virtual Observation Unit (VOU) Falls program. METHODS: To ensure standardized conduct and reporting, the Standard Protocol Items for Intervention Trials (SPIRIT) guidelines will be used. The VOU is a program where patients are sent home from the ED but are part of a virtual observation unit in that they can call on-call ED physicians while they are being treated for conditions such as cellulitis, congestive heart failure, or pneumonia. A paramedic conducts daily visits with the patient and facilitates a telemedicine consult with an ED physician. VOU nursing staff conduct daily assessments of patients via telemedicine. The ED VOU Falls program is one of the VOU pathways and is a multi-component fall prevention program for fall patients who present after an ED visit. The paramedic conducts a home safety evaluation, a Timed Up and Go Test (TUG). During the VOU visit, the ED physician conducts a telemedicine visit, while the paramedic is visiting the home, to review patients' fall-risk-increasing drugs and their TUG test. We will determine feasibility by calculating rates of patient enrollment refusal, and adherence to fall-risk prevention recommendations using information from 3-month follow-up telephone calls, as well as qualitative interviews with the paramedics. We will determine the acceptability of the ED VOU Falls program based on patient and provider surveys using a Likert scale. We will ask VOU nursing staff to report any safety issues encountered while the patient is in the ED VOU Falls program (e.g., tripping hazards). We will use the chi-square test or Fisher's exact test for categorical variables, Student's t-test for continuous variables, and Mann-Whitney for nonparametric data. We will review interview transcripts and generate codes. Codes will then be extracted and organized into concepts to generate an overall theme following grounded theory methods. This is a pilot study; hence, results cannot be extrapolated. However, a definite trial would be the next step in the future to determine if such a program could be implemented as part of fall prevention interventions. DISCUSSION: This study will provide insights into the feasibility and acceptability of a novel ED VOU Falls program with the aim of ultimately decreasing falls. In the future, such a program could be implemented as part of fall prevention interventions.

Environmental and Economic Viability of Using Concrete Block Wastes from a Concrete Production Plant as Recycled Coarse Aggregates.

The construction sector must incorporate the circular economy to improve sustainability and efficiency. The use of recycled aggregates (RAs) as a substitute for natural aggregates (NAs) is currently being investigated and is expected to yield considerable benefits in the future. The objective of this research is to evaluate the environmental and economic benefits of using recycled coarse aggregates (RCAs) in different 1 m3 samples of concrete, substituting the natural coarse aggregate (NCAs) with RCAs in different percentages. RCAs generally come from the treatment of construction and demolition wastes (CDWs). However, in this research, the RCAs are the concrete block wastes (CBWs) generated by a concrete production plant. Among the most notable results is that compared to concrete with no RCAs, using alternatives in which RCAs have replaced 50% of the NCAs leads to an average decrease in impact category statistics of -3.30%. In contrast to the existing literature on the subject, the process of producing RCAs generated efficiency improvements in categories such as abiotic depletion of fossil fuels (-58.72%) and global warming potential (-85.13%). This is because the transport process, a key factor in determining the viability of using RAs instead of NAs, was eliminated. In economic terms, there is a slight decrease in the financial cost of producing 1 m3 of concrete as the quantity of RCAs increases. The maximum decrease was 0.23€/m3 in the samples studied. Combining both the environmental and economic aspects resulted in a reduction factor of 0.420 g of CO2/€cent, which means fewer CO2 emissions per unit cost when using RCAs. In conclusion, these results are intended to further knowledge in the field of using RAs instead of NAs in order to help the sector achieve sustainability and find an alternative use for a particular type of business waste.

Sleep and circadian biomarkers of postoperative delirium (SLEEP-POD): protocol for a prospective and observational cohort study.

INTRODUCTION: Surgical patients over 70 experience postoperative delirium (POD) complications in up to 50% of procedures. Sleep/circadian disruption has emerged as a potential risk factor for POD in epidemiological studies. This protocol presents a single-site, prospective observational study designed to examine the relationship between sleep/circadian regulation and POD and how this association could be moderated or mediated by Alzheimer's disease (AD) pathology and genetic risk for AD. METHODS AND ANALYSIS: Study staff members will screen for eligible patients (age ≥70) seeking joint replacement or spinal surgery at Massachusetts General Hospital (MGH). At the inclusion visit, patients will be asked a series of questionnaires related to sleep and cognition, conduct a four-lead ECG recording and be fitted for an actigraphy watch to wear for 7 days before surgery. Blood samples will be collected preoperatively and postoperatively and will be used to gather information about AD variant genes (APOE-ε4) and AD-related pathology (total and phosphorylated tau). Confusion Assessment Method-Scale and Montreal Cognitive Assessment will be completed twice daily for 3 days after surgery. Seven-day actigraphy assessments and Patient-Reported Outcomes Measurement Information System questionnaires will be performed 1, 3 and 12 months after surgery. Relevant patient clinical data will be monitored and recorded throughout the study. ETHICS AND DISSEMINATION: This study is approved by the IRB at MGH, Boston, and it is registered with the US National Institutes of Health on ClinicalTrials.gov (NCT06052397). Plans for dissemination include conference presentations at a variety of scientific institutions. Results from this study are intended to be published in peer-reviewed journals. Relevant updates will be made available on ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT06052397.

A Fracture Liaison Service to Address Vitamin D Deficiency for Patients Hospitalized for Osteoporotic Fracture.

Context: Addressing vitamin D deficiency (VDD) is important for fracture secondary prevention. Objectives: To explore the function of a fracture liaison service (FLS) to address VDD. Design Setting and Patients: An observational study of patients admitted to the Massachusetts General Hospital with fractures between January 1, 2016, and October 31, 2023, cared for by the FLS. Intervention: Ergocalciferol 50 000 international units (50ku-D2) oral daily for 3 to 7 days. Main Outcomes Measures: VDD prevalence. Efficacy of inpatient daily 50ku-D2 in raising serum 25-hydroxyvitamin D (25OHD) levels. Results: Of the 2951 consecutive patients, 724 (24.53%) had VDD (defined by 25OHD ≤ 19 ng/mL). Men (252/897, or 28.09%) were more likely than women (472/2054, or 22.98%) to have VDD (P = .003). VDD was seen in 41.79% (117/280), 24.41% (332/1360), and 20.98% (275/1311) of patients of aged ≤59, 60 to 79, and ≥80 years, respectively (P < .00001). Of the 1303 patients with hip fractures, 327 (25.09%) had VDD, which was associated with a longer length of stay (8.37 ± 7.35 vs 7.23 ± 4.78 days, P = .009) and higher trend of 30-day-readmission rate (13.63% vs 18.35%, P = .037). In a cohort of 32 patients with complete data, each dose of 50ku-D2 increased serum 25OHD by 3.62 ± 2.35 ng/mL without affecting serum calcium or creatinine levels. Conclusion: VDD was seen in nearly 25% of Massachusetts General Hospital FLS patients and more prevalent in male and younger patients. VDD was associated with longer length of stay and higher 30-day-readmission risk in patients with hip fracture. Daily 50ku-D2 appeared to be a practical way to quickly replete vitamin D in the inpatient setting.

Real needle for minimal invasive procedures training using motion sensors and optical flow.

Minimally invasive percutaneous insertion procedures are widely used techniques in medicine. Their success is highly dependent on the skills of the practitioner. This paper presents a haptic simulator for training in these procedures, whose key component is a real percutaneous insertion needle with a sensory system incorporated to track its 3D location at every instant. By means of the proposed embedded vision system, the attitude (spatial orientation) and depth of insertion of a real needle are estimated. The proposal is founded on a novel depth estimation procedure based on optical flow techniques, complemented by sensory fusion techniques with the attitude calculated with data from an Inertial Measurement Unit (IMU) sensor. This procedure allows estimating the needle attitude with an accuracy of tenths of a degree and the displacement with an accuracy of millimeters. The computational algorithm runs on an embedded computer with real-time constraints for tracking the movement of a real needle. This haptic needle location data is used to reproduce the movement of a virtual needle within a simulation app. As a fundamental result, an ergonomic and realistic training simulator has been successfully constructed for healthcare professionals to acquire the mental model and motor skills necessary to practice percutaneous procedures successfully.

Ligament Injuries in Professional Male Handball Players: A 6-Year Longitudinal Study.

Handball is a sport that involves high-intensity actions throughout the game, such as sprints, jumps, landings, and high-speed, repeated throws. This, along with competitive and tactical factors, congested schedules, and the need to maintain a high level of performance throughout the season, contributes to a high injury rate. This study aimed to analyse ligament injuries in a professional handball team over six consecutive seasons. A total of 68 elite male Spanish handball players participated, with 54 time-loss injuries (i.e., injuries involving at least one day of absence) observed during this study period. Ligament injury information was recorded following the International Olympic Committee consensus statement. The overall incidence was 0.89 ligament injuries per 1000 h of exposure. Additionally, a higher incidence and burden of ligament injuries was observed during match-play compared to training. Most ligament injuries were classified as minor or moderate (i.e., 79.63% of the total), and 46.29% were reinjuries. A significantly higher incidence of ligament injuries was suffered in the lower limbs compared to the upper limbs (0.81 vs. 0.08 ligament injuries per 1000 h; p < 0.001). Specifically, the highest incidence was observed in the anterior talofibular ligament of the ankle (0.57 injuries per 1000 h of exposure), while the greatest burden was related to the anterior cruciate ligament (24.08 absence days per 1000 h of exposure). This study provides an overview of ligament injuries among professional handball players, highlighting the need to implement strategies with positive effects during competition (e.g., specific activation strategies or training programmes based on strength and balance) and to reduce injury recurrences.

Liver, renal, genitourinary and diabetic ketoacidosis risks among new users of empagliflozin versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes: Post-authorization safety study based on multinational cohorts.

AIM: To estimate risks of diabetic ketoacidosis (DKA), acute liver injury (ALI), acute kidney injury (AKI), chronic kidney disease (CKD), severe complications of urinary tract infection (UTI) and genital infection (GI) among patients with type 2 diabetes initiating empagliflozin versus those initiating a dipeptidyl peptidase-4 (DPP-4) inhibitor. MATERIALS AND METHODS: In this large multinational, observational, new-user cohort study in UK, Danish and US healthcare data sources, patients initiated empagliflozin or a DPP-4 inhibitor between August 2014 and August 2019, were aged ≥18 years, and had ≥12 months' continuous health plan enrolment. Incidence rates by exposure and incidence rate ratios, adjusted for propensity-score deciles, were calculated. RESULTS: In total, 64 599 empagliflozin initiators and 203 315 DPP-4 inhibitor initiators were included. There was an increased risk [pooled adjusted incidence rate ratios (95% confidence interval)] of DKA [2.19 (1.74-2.76)] and decreased risks of ALI [0.77 (0.50-1.19) in patients without predisposing conditions of liver disease; 0.70 (0.56-0.88) in all patients] and AKI [0.54 (0.41-0.73)]. In the UK data, there was an increased risk of GI [males: 4.04 (3.46-4.71); females: 3.24 (2.81-3.74)] and decreased risks of CKD [0.53 (0.43-0.65)] and severe complications of UTI [0.51 (0.37-0.72)]. The results were generally consistent in subgroup and sensitivity analyses. CONCLUSIONS: Compared with DDP-4 inhibitor use, empagliflozin use was associated with increased risks of DKA and GI and decreased risks of ALI, AKI, CKD and severe complications of UTI. These associations are consistent with previous studies and known class effects of sodium-glucose cotransporter 2 inhibitors, including renoprotective effects and beneficial effects on alanine aminotransferase levels.

Pseudomonas putida as a synthetic biology chassis and a metabolic engineering platform.

The soil bacterium Pseudomonas putida, especially the KT2440 strain, is increasingly being utilized as a host for biotransformations of both industrial and environmental interest. The foundations of such performance include its robust redox metabolism, ability to tolerate a wide range of physicochemical stresses, rapid growth, versatile metabolism, nonpathogenic nature, and the availability of molecular tools for advanced genetic programming. These attributes have been leveraged for hosting engineered pathways for production of valuable chemicals or degradation/valorization of environmental pollutants. This has in turn pushed the boundaries of conventional enzymology toward previously unexplored reactions in nature. Furthermore, modifications to the physical properties of the cells have been made to enhance their catalytic performance. These advancements establish P. putida as bona fide chassis for synthetic biology, on par with more traditional metabolic engineering platforms.

Trends in antifungal resistance in Candida from a multicenter study conducted in Madrid (CANDIMAD study): fluconazole-resistant C. parapsilosis spreading has gained traction in 2022.

We previously conducted a multicenter surveillance study on Candida epidemiology and antifungal resistance in Madrid (CANDIMAD study; 2019-2021), detecting an increase in fluconazole-resistant Candida parapsilosis. We here present data on isolates collected in 2022. Furthermore, we report the epidemiology and antifungal resistance trends during the entire period, including an analysis per ward of admission. Candida spp. incident isolates from blood cultures and intra-abdominal samples from patients cared for at 16 hospitals in Madrid, Spain, were tested with the EUCAST E.Def 7.3.2 method against amphotericin B, azoles, micafungin, anidulafungin, and ibrexafungerp and were molecularly characterized. In 2022, we collected 766 Candida sp. isolates (686 patients; blood cultures, 48.8%). Candida albicans was the most common species found, and Candida auris was undetected. No resistance to amphotericin B was found. Overall, resistance to echinocandins was low (0.7%), whereas fluconazole resistance was 12.0%, being higher in blood cultures (16.0%) mainly due to fluconazole-resistant C. parapsilosis clones harboring the Y132F-R398I ERG11p substitutions. Ibrexafungerp showed in vitro activity against the isolates tested. Whereas C. albicans was the dominant species in most hospital wards, we observed increasing C. parapsilosis proportions in blood. During the entire period, echinocandin resistance rates remained steadily low, while fluconazole resistance increased in blood from 6.8% (2019) to 16% (2022), mainly due to fluconazole-resistant C. parapsilosis (2.6% in 2019 to 36.6% in 2022). Up to 7 out of 16 hospitals were affected by fluconazole-resistant C. parapsilosis. In conclusion, rampant clonal spreading of C. parapsilosis fluconazole-resistant genotypes is taking place in Madrid.

Development of a thermosensitive hydrogel based on Polaxamer 407 and gellan gum with inclusion complexes (Sulfobutylated-ß-cyclodextrin-Farnesol) as a local drug delivery system.

This work proposes the development of a thermosensitive local drug release system based on Polaxamer 407, also known as Pluronic® F-127 (PF-127), Gellan Gum (GG) and the inclusion complex Sulfobutylated-ß-cyclodextrin (CD) with Farnesol (FOH). Rheological properties of the hydrogels and their degradation were studied. According to the rheological results, a solution of 20% w/v of PF-127 forms a strong gel with a gelling temperature of about 25 °C (storage modulus of 15,000 Pa). The addition of the GG increased the storage modulus (optimal concentration of 0.5 % w/v) twofold without modifying the gelling temperature. Moreover, including 0.5% w/v of GG also increased 6 times the degradation time of the hydrogel. Regarding the inclusion complex, the addition of free CD decreased the viscosity and the gel strength since polymer chains were included in CD cavity without affecting the gelling temperature. Contrarily, the inclusion complex CD-FOH did not significantly modify any property of the formulation because the FOH was hosted in the CD. Furthermore, a mathematical model was developed to adjust the degradation time. This model highlights that the addition of the GG decreases the number of released chains from the polymeric network (which coincides with an increase in the storage modulus) and that the free CD reduces the degradation rate, protecting the polymeric chains. Finally, FOH release was quantified with a specific device, that was designed and printed for this type of system, observing a sustainable drug release (similar to FOH aqueous solubility, 8 µM) dependent on polymer degradation.

Images dataset of beef meat samples with different shelf life.

Three different cuts of meat samples: inside skirt, knuckles, and sirloin were picture captioned on the first and fifth day after purchase. From each type of meat cut, ten pictures were taken at the beginning and the end of the studied shelf life, obtaining 60 different images. The images were taken under control variables in a black acrylic cabin. In addition to the original images, we proportionate another set of 60 processed images. The latter were obtained after color calibration and meat segmentation. All these images could be used for future experiments where the color in meat should be analyzed.

Bioelectrical State of Bacteria Is Linked to Growth Dynamics and Response to Neurotransmitters: Perspectives for the Investigation of the Microbiota-Brain Axis.

Inter-cellular communication is mediated by a sum of biochemical, biophysical, and bioelectrical signals. This might occur not only between cells belonging to the same tissue and/or animal species but also between cells that are, from an evolutionary point of view, far away. The possibility that bioelectrical communication takes place between bacteria and nerve cells has opened exciting perspectives in the study of the gut microbiota-brain axis. The aim of this paper is (i) to establish a reliable method for the assessment of the bioelectrical state of two bacterial strains: Bacillus subtilis (B. subtilis) and Limosilactobacillus reuteri (L. reuteri); (ii) to monitor the bacterial bioelectrical profile throughout its growth dynamics; and (iii) to evaluate the effects of two neurotransmitters (glutamate and γ-aminobutyric acid-GABA) on the bioelectrical signature of bacteria. Our results show that membrane potential (Vmem) and the proliferative capacity of the population are functionally linked in B. subtilis in each phase of the cell cycle. Remarkably, we demonstrate that bacteria respond to neural signals by changing Vmem properties. Finally, we show that Vmem changes in response to neural stimuli are present also in a microbiota-related strain L. reuteri. Our proof-of-principle data reveal a new methodological approach for the better understanding of the relation between bacteria and the brain, with a special focus on gut microbiota. Likewise, this approach will open exciting perspectives in the study of the inter-cellular mechanisms which regulate the bi-directional communication between bacteria and neurons and, ultimately, for designing gut microbiota-brain axis-targeted treatments for neuropsychiatric diseases.

Mechanical and Environmental Assessment of Lathe Waste as an Addiction to Concrete Compared to the Use of Commercial Fibres.

The use of fibres applied to concrete in order to improve its properties is widely known. Nowadays, research is not only focused on improving mechanical properties but also on the environmental implications. The aim of this research was a mechanical and environmental comparison between different types of fibres. For this purpose, commercial fibres of three materials were used: low carbon steel, modified polyolefins, and glass fibre. In order to improve the sustainability of the sector, we also analysed and compared the performance of using a waste product, such as fibres from machining operations on lathes. For the evaluation of the mechanical properties, compression and flexural tests were carried out. The results show that the use of low carbon steel fibres increases the flexural strength by 4.8%. At the environmental level, and in particular for impact categories such as the Global Warming Potential (GWP), lathe waste fibres prove to be the most suitable. For instance, compared to glass fibres, CO2 emissions are reduced by 14.39%. This is equivalent to a total of 38 kg CO2 emissions per m3 of reinforced concrete. In addition to avoiding the consumption of 482 MJ/m3 of fossil fuels, the results of the research indicate the feasibility of using waste fibres as a substitute for commercial fibres, contributing to an improved environmental balance without losing mechanical performance.

Antifungal resistance in Candida spp within the intra-abdominal cavity: study of resistance acquisition in patients with serial isolates.

OBJECTIVES: Antifungal susceptibility testing is mostly conducted on blood-cultured Candida spp isolates. Because the intra-abdominal cavity has been highlighted as a hidden echinocandin-resistant C. glabrata reservoir, we assessed whether testing sequential isolates from a given patient might increase the chances of detecting antifungal resistance. METHODS: Intra-abdominal initial and sequential isolates from the same species from patients included in the CANDIdaemia in MADrid study (January 2019 to June 2022) were studied. We assessed antifungal susceptibility to amphotericin B, azoles, anidulafungin, micafungin, and ibrexafungerp using European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology and molecularly characterized resistant isolates. RESULTS: We collected 308 isolates (C. albicans [n = 179/308; 58.1%], C. glabrata [n = 101/308; 32.8%], C. tropicalis [n = 17/308; 5.5%], and C. parapsilosis [n = 11/308; 3.6%]) from 112 patients distributed as incident (n = 125/308) and sequential (n = 183/308). Per patient resistance rates of fluconazole (13.4% [15/112] vs. 8% [9/112]); 5.4% proportions difference (95% CI, -2.7% to 13.5%, p 0.09) and echinocandins (8.9% [10/112] vs. 1.8% [2/112]); 7.1% proportions difference (95% CI; 1.2-12.9%; p 0.01) were higher when considering all available isolates than only incident isolates. Resistance was detected in 18 of 112 patients and would have been overlooked in 11 of 18 (61.1%) patients if only incident isolates had been studied. Of the patients who harboured fluconazole or echinocandin-resistant isolates, 14 of 15 and 8 of 10 had received or were receiving fluconazole or echinocandins, respectively. DISCUSSION: Testing sequential Candida isolates from intra-abdominal samples is required to detect antifungal resistance, particularly to echinocandins, in patients whose incident isolates turned out to be susceptible. Furthermore, patients with echinocandin-resistant infections had frequently used echinocandins and had common secondary resistance acquisition.