The impact of pulse repetition frequency on microbubble activity and drug delivery during focused ultrasound-mediated blood-brain barrier opening.

Objective.Pulsed focused ultrasound (FUS) can deliver therapeutics to the brain by using intravenous microbubbles (MBs) to open the blood-brain barrier (BBB). MB emissions indicate treatment outcomes, like BBB opening (harmonics) and damage (broadband). Typically, a pulse repetition frequency (PRF) of 1 Hz is used, but the effect of PRF on MBs is not fully understood. We investigated the effect of PRF on MB activity and tracer delivery.Approach.The effect of PRF (0.125, 0.25, 0.5, 1, and 2 Hz) on MB activity was monitored through harmonic and wideband emissions during FUS sonications of the rat brain at 274.3 kHz. BBB opening was quantified through fluorescence imaging to estimate the concentration of Trypan Blue (TB) dye following a 75-pulse FUS exposure for PRFs of 1 and 0.25 Hz.Main results.At a fixed acoustic pressure, the percentage change in maximum harmonic amplitude compared to the control (PRF = 1 Hz) decreased with increasing PRF, with a median change of 73.8% at 0.125 Hz and -38.3% at 2 Hz. There was no difference in the pressure threshold for broadband emissions between PRFs of 0.25 and 1 Hz. PRF = 0.25 Hz, led to a 68.2% increase in the mean concentration of TB measured after FUS, with a 53.9% increase in the mean harmonic sum, compared with PRF = 1 Hz. Harmonic emissions-based control at PRF = 0.25 Hz yielded similar TB delivery, with less damage at histology, compared with 1 Hz.Significance.For a fixed number of FUS pulses, reducing the PRF was shown to increase the magnitude of harmonic emissions and TB delivery, but not the threshold for broadband emissions. While further research is necessary to understand the mechanisms involved, these results may be useful to improve clinical safety margins and sensitivity to detecting small harmonic signals from cavitating MBs.

Do High Doses of Multiple Antibiotics Loaded into Bone Cement Spacers Improve the Success Rate in Staphylococcal Periprosthetic Joint Infection When Rifampicin Cannot Be Employed?

Rifampicin is one of the mainstays in treating staphylococcal prosthetic joint infection (PJI). However, discontinuation due to intolerance, drug interactions, and adverse events is common. Two-stage revision surgery remains the gold standard, with the number of revision arthroplasties steadily increasing. This study aims to evaluate the effectiveness and safety of a novel two-stage revision protocol for staphylococcal prosthetic joint infection (PJI) utilizing bone cement spacers loaded with multiple high doses of antibiotics. Additionally, it seeks to analyze outcomes in patients ineligible for rifampicin treatment. A retrospective review of 43 cases of staphylococcal hip and knee prosthetic joint infections (PJIs) from 2012 to 2020 was conducted. In all instances, a commercial cement containing 1 g of gentamicin and 1 g of clindamycin, augmented with 4 g of vancomycin and 2 g of ceftazidime, was employed to cast a spacer manually after thorough surgical debridement. We report an eradication rate of 82%, with no significant differences observed (p = 0.673) between patients treated with (84%, n = 19) and without rifampicin (79%, n = 24). There were no disparities in positive culture rates (7%), spacer replacement (18%), or survival analysis (p = 0.514) after an average follow-up of 68 months (range 10-147) in the absence of systemic toxicity and surgical complications superimposable to those previously reported. In conclusion, two-stage revision with local high doses of ceftazidime, vancomycin, gentamicin, and clindamycin demonstrates high effectiveness in treating staphylococcal PJIs. Notably, systemic rifampicin does not influence the outcomes. This protocol, with multiple high doses of antibiotics loaded into the bone cement spacer, is presented as a viable and safe alternative for patients unsuitable for rifampicin treatment.

New RP-HPLC method for the simultaneous determination of process yield and percentage of encapsulation of Gallein in albumin nanoparticles.

A study was performed for the development and validation of a method of High Performance Liquid Chromatography (HPLC) for the identification and simultaneous quantification of Gallein and Human Serum Albumin (HSA). In addition, this work presents the development and physicochemical characterization of this new pharmaceutical formulation of HSA nanoparticles loaded with Gallein for potential use in the treatment of Alzheimer's disease. The method was developed with the purpose of determining the performance of the synthesis process of nanoparticles and the efficiency of encapsulation of the drug in the nanosystem. The HPLC mobile phase consisted of ACN:H2O:TEA:H3PO4 (50:49.8:0.1:0.1 v/v/v) pumped at a flow rate of 0.8 mL/min, isocratic mode, and the measurement were carried out at 220 nm. Chromatographic runs were performed on a C18 column (150 × 4.60 mm; 5 µm size particles). The HPLC-method was validated following the International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines and was used to simultaneously quantify the two components of the nanoformulation. Thus, the values obtained through the validated method were 43 % for drug encapsulation efficiency (% EE) and the synthesis performance (% yield) was 96 %. Moreover, the nanoformulation was characterized by DLS, the results showed that the average particle size was 217 nm, with a PDI of (0.085 ± 0.005) and a potential Z of -29.7 mV. Therefore, the developed method has proven useful in providing accurate simultaneous measurements of HSA and Gallein from albumin nanoparticles. It is advantageous since it is able to reduce the time and facilitate the determination of Gallein encapsulation efficiency and yield of albumin nanoparticles.

Evidence of the protective role of Carvacrol in a retinal degeneration animal model.

Neurodegenerative pathologies affecting the posterior segment of the eye, are characterized by being devastating and responsible for the majority of visual dysfunctions worldwide. These diseases are primarily degenerative, progressing chronically, and can inflict gradual harm to the optic nerve, retinal ganglion cells (RGC), photoreceptors, and other retinal cells. This retinal damage leads to a progressive loss of vision, marking these conditions as a significant health concern worldwide. The intravitreal administration of the phytochemical Carvacrol (CAR) is expected to demonstrate a neuroprotective and antiapoptotic effect on retinal cells, with a specific focus on RGC. This effect will be observed in a retinal degeneration model (RDM) in rabbits induced by cytotoxic and oxidative agents, namely glutamate (GLUT) and L-buthionine-S, R-sulfoximine (BSO). An in vivo study was conducted using New Zealand rabbits in which retinal damage was created to evaluate the effectiveness of CAR. The effectiveness of CAR on the functionality of retinal neuronal cells in RDM was evaluated using pupillary light reflection (PLR). Furthermore, the phytotherapeutic's influence on cell viability was determined through flow cytometry analysis. Finally, the neuroprotective and antiapoptotic capabilities of CAR were specifically scrutinized in RGC through histological studies, quantifying cell survival, and employing immunohistochemical assays to detect the apoptotic index (%) using the TUNEL technique. Our results demonstrated that CAR promoted the recovery of the pupillary contraction profile over time, maintaining the functionality of retinal cells as healthy controls. Additionally, it showed increased cell viability under oxidative and cytotoxic conditions given by GLUT-BSO agents. Finally, we found that CAR protects the survival of RGC and decreases the percentage of apoptotic cells when compared to RDM. CAR demonstrated to have positive effects on the functionality of photoreceptive nerve cells by restoring pupillary contraction. Likewise, it was shown to have neuroprotective and antiapoptotic effects when evaluated in a general and specific way on retinal nerve cells.

Process evaluation of PsyCovidApp, a digital tool for mobile devices aimed at protecting the mental health of healthcare professionals during the COVID-19 pandemic: a mixed method study.

Introduction: PsyCovidApp, a digital intervention aimed at safeguarding the mental health of healthcare workers during the COVID-19 pandemic, demonstrated in a randomized clinical trial to yield significant improvements solely among healthcare workers undergoing psychotherapy or receiving psychotropic medication. Objectives: (1) To identify contextual factors and mechanisms of action that influenced the impact of PsyCovidApp during the aforementioned trial; (2) To pinpoint enhancements for optimizing its efficacy. Materials and methods: For the first objective, a process evaluation was conducted, amalgamating quantitative techniques (surveying 216 healthcare professionals who had utilized PsyCovidApp during the trial) and qualitative methods (in-depth interviews with 16 healthcare workers). The second objective involved a panel of seven experts, utilizing the RAND-UCLA methodology. Results: The quantitative study (response rate = 40%) revealed that 22% of respondents had not fully accessed the content of PsyCovidApp. The average usage time was 22.7 min/day, being higher (p < 0.05) among consumers of psychotropic medications. Contents related to relaxation and mindfulness were most highly rated. Acceptability and usefulness scores ranged between 7.3-7.5/10 points, with higher ratings (p < 0.05) among women and older healthcare workers. The qualitative study uncovered that the primary barriers to using PsyCovidApp were workload, lack of time, and exhaustion. Its primary mechanisms of action included emotion identification, mental health regulation (e.g., insomnia, intense emotions), and learning of techniques and skills. The expert panel reached a consensus on 29 proposals to optimize PsyCovidApp. Conclusion: The knowledge derived from this study could inform the design and implementation of future similar digital tools.

[Dengue, chikungunya and the mosquito vector at the Southern limit of distribution during the 2023 epidemic, Argentina]. / Dengue, chikungunya y el mosquito vector en el límite sur de distribución durante la epidemia 2023, Argentina.

OBJECTIVES: To monitor the oviposition activity of the mosquito Aedes aegypti and of dengue and chikungunya cases in four localities of temperate Argentina, during the 2023 epidemic. METHODS: During the summer and autumn of 2023, the oviposition activity of the mosquito vector was monitored weekly using ovitraps, and the arrival of cases with dengue or chikungunya in Tandil, Olavarría, Bahía Blanca and Laprida were registered. RESULTS: Monthly variations of the percentage of positive traps were similar in the first three locations; in Laprida the mosquito was not detected. On the contrary, a significant difference was observed in the percentage of total traps that ever tested positive in each locality, being higher in Olavarría (83.3%) than in Bahía Blanca (68.6%) and Tandil (48.7%). Regarding diseases, 18 imported cases of dengue and 3 of chikungunya were registered. In addition, the first autochthonous case of dengue in the region was recorded, being the southernmost until known. CONCLUSION: It is essential to raise awareness and train the members of the health systems of the new regions exposed to Ae. aegypti for early detection of cases, and to the general population to enhance prevention actions.

OBJETIVOS: Monitorear la actividad de oviposición del mosquito Aedes aegypti y de casos de dengue y chikungunya en cuatro localidades de Argentina templada, durante la epidemia del 2023. Métodos: Durante el verano y otoño del 2023, se monitoreó semanalmente mediante ovitrampas la actividad de oviposición del mosquito vector, y se registró el arribo de casos con dengue o chikungunya a Tandil, Olavarría, Bahía Blanca y Laprida. RESULTADOS: La variación mensual del porcentaje de trampas positivas fue similar en las tres primeras localidades; en Laprida no se detectó el mosquito. Por el contrario, se observó una diferencia significativa del porcentaje de trampas que alguna vez resultó positiva en cada localidad, siendo mayor en Olavarría (83%), que en Bahía Blanca (67%) y Tandil (49%). Respecto a las enfermedades, se registraron 18 casos importados de dengue y 3 de chikungunya. Además, se registró el primer caso autóctono de dengue en la región, siendo el más austral hasta el momento. Conclusión: Es imprescindible sensibilizar y capacitar a los integrantes de los sistemas de salud de las nuevas regiones expuestas al Ae. aegypti para la detección temprana de casos, y a la población en general para potenciar las acciones de prevención.

Acetazolamide encapsulation in elastin like recombinamers using a supercritical antisolvent (SAS) process for glaucoma treatment.

Glaucoma, the second most common cause of blindness worldwide, requires the development of new and effective treatments. This study introduces a novel controlled-release system utilizing elastin-like recombinamers (ELR) and the Supercritical Antisolvent (SAS) technique with supercritical CO2. Acetazolamide (AZM), a class IV drug with limited solubility and permeability, is successfully encapsulated in an amphiphilic ELR at three different ELR:AZM ratios, yielding up to 62 %. Scanning electron microscopy (SEM) reveals spherical microparticles that disintegrate into monodisperse nanoparticles measuring approximately 42 nm under physiological conditions. The nanoparticles, as observed via Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM), do not exhibit aggregates, a fact confirmed by the zeta potential displaying a value of -33 mV over a period of 30 days. Transcorneal permeation tests demonstrate a 10 % higher permeation level compared to the control solution, which increases to 30 % after 2 h. Ocular irritation tests demonstrate no adverse effects or damage. Intraocular pressure (IOP) tests conducted on hypertensive rabbits indicate greater effectiveness for all three analyzed formulations, suggesting enhanced drug bioavailability during treatment. Consequently, the combination of recombinant biopolymers and high-pressure techniques represents a promising approach for advancing glaucoma therapy, emphasizing its potential clinical significance.

Electrification of Transit Buses in the United States Reduces Greenhouse Gas Emissions.

The transportation sector is the largest emitter of greenhouse gas emissions (GHGs) in the United States. Increased use of public transit and electrification of public transit could help reduce these emissions. The electrification of public transit systems could also reduce air pollutant emissions in densely populated areas, where air pollution disproportionally burdens vulnerable communities with high health impacts and associated social costs. We analyze the life cycle emissions of transit buses powered by electricity, diesel, gasoline, and compressed natural gas and model GHGs and air pollutants mitigated for a transition to a fully electric U.S. public transit bus fleet using transit agency-level data. The electrification of the U.S. bus fleet would reduce several conventional air pollutants and has the potential to reduce transit bus GHGs by 33-65% within the next 14 years depending on how quickly the transition is made and how quickly the electricity grid decarbonizes. A levelized cost of driving analysis shows that with falling capital costs and an increase in annual passenger-kilometers of battery electric buses, the technology could reach levelized cost parity with diesel buses when electric bus capital costs fall below about $670 000 per bus.

DiabeText, a mobile health intervention to support medication taking and healthy lifestyle in adults with type 2 diabetes: Study protocol for a randomized controlled trial.

AIM: To evaluate the effectiveness of DiabeText, a low-intensity, multifaceted, mobile health (mHealth) intervention to support medication taking and lifestyle change targeted to people with type 2 diabetes (T2D). DESIGN: Phase III, 12-months, two-arm (1:1 allocation ratio), randomized parallel-group trial. METHODS: We will recruit 740 adults with glycated hemoglobin (A1c) >8% (>64 mmol/mol) and with at least one prescription of a non-insulin antidiabetic drug. They will be allocated to a control (usual care) group or an intervention (DiabeText messaging intervention) group. The primary outcome measure will be A1c at 12 months follow-up. Secondary outcomes will include medication possession ratio and behavioral and psychological outcomes. DISCUSSION: Recent trials suggest that digital health interventions can effectively support diabetes self-management improving T2D control and reducing important T2D complications. In Spain this type of interventions is understudied. IMPACT: This trial will strengthen the evidence base of the impact of mHealth interventions to support diabetes self-management. If effective, DiabeText may offer a low-cost and highly scalable strategy to improve health at the population level in a sustainable way. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05006872; Official Title: Supporting People with Type 2 Diabetes in Effective Use of their Medicine Through a System Comprising Mobile Health Technology Integrated with Clinical Care.

Bi-coloured enhanced luminescence imaging by targeted switch on/off laser MEF coupling for synthetic biosensing of nanostructured human serum albumin.

In this communication luminescent bioconjugated human serum albumin nanostructures (HSA NPs) with tiny ultraluminescent gold core-shell silica nanoparticles (Au@SiO2-Fl) were designed with enhanced bi-coloured luminescence properties. The HSA NPs were obtained from Human Serum Albumin free (HSA free) through the desolvation method, and Au@SiO2-Fl, through modified Turkevich and Störber methods. In this manner, porous HSA Nanostructures of 150.0-200 nm and Au@SiO2-Fl 45.0 nm final diameters were obtained. Both methodologies and structures were conjugated to obtain modified Nanocomposites based on tiny gold cores of 15 nm surrounded with well spatial Nanostructured architectures of HSA (d15 Au@SiO2-Fl-HSA) that generated variable nanopatterns depending on the modified methodology of synthesis applied within colloidal dispersions. Therefore, three methodologies of non-covalent conjugation were developed. In optimal conditions, through Transmission Electronic Microscopy (TEM), well resolved multilayered nano-architectures with a size 190.0-200 nm in average with variable contrast depending of the focused nanomaterial within the nanocomposite were shown. Optimized nanoarchitecture was based on a template tiny gold core-shell surrounded by nanostructured HSA NPs (d15 Au@SiO2-Fl-HSA). In this manner, the NanoImaging generated by laser fluorescence microscopy permitted to record improved optical properties and functionalities, such as: (i) enhanced ultraluminescent d15 Au@SiO2-Fl-HSA composites in comparison to individual components based on Metal Enhanced Fluorescence (MEF); (ii) diminished photobleaching; (iii) higher dispersibility; (iv) higher resolution of single bright nano-emitters of 210.0 nm sizes; and (v) enhanced bi-coloured Bio-MEF coupling with potential non-classical light delivery towards other non-optical active biostructures for varied applications. The characterization of these nanocomposites allowed the comparison, evaluation and discussion focused on new properties generated and functionalities based on the incorporation of different types of tuneable materials. In this context, the biocompatibility, Cargo confined spaces, protein-based materials, optical transparent could be highlighted, as well as optical active materials. Thus, the potential applications of nanotechnology to both nanomedicine and nano-pharmaceutics were discussed.

Schnitzler syndrome refractory to anakinra: successful treatment with canakinumab.

Schnitzler syndrome (SchS) is a rare autoimmune and inflammatory disease mediated by interleukin-1 beta (IL-1ß). Recurrent monoclonal gammopathy and chronic urticarial rash are the symptoms required for diagnosis according to the Strasbourg criteria. The low prevalence of this syndrome (around 300 cases have been reported) and confusion with other inflammatory disorders may delay the diagnosis for up to 5 years. Although the most effective treatment for SchS is anakinra, some patients do not respond to this treatment. We report a case of SchS in a 64-year-old woman with multiple episodes of fever, severe rash, erythema, arthralgia and dyspnea. The patient was successfully treated with canakinumab after anakinra intolerance and failure of colchicine, prednisone, methotrexate and dapsone. After the first dose of canakinumab the skin wounds rapidly improved and the patient did not require any concomitant treatments. The cause of SchS is still unknown and a differential diagnosis is recommended, especially with adult-onset Still´s disease due to their similar symptoms. Canakinumab, a specific anti-IL-1ß antibody, blocks its binding to receptors, thereby preventing IL-1ß-induced gene activation and production of inflammatory mediators. Canakinumab has proven to be an effective drug in SchS, providing an alternative to anakinra.

Association Between Uropathogenic Escherichia coli Virulence Genes and Severity of Infection and Resistance to Antibiotics.

Purpose: Urinary tract infection (UTI) is the most frequent bacterial infection. Some uropathogenic Escherichia coli (UPEC) genes have been associated with disease severity and antibiotic resistance. The aim was to determine the association of nine UPEC virulence genes with UTI severity and antibiotic resistance of strains collected from adults with community-acquired UTI. Patients and Methods: A case-control study (1:3) (38 urosepsis/pyelonephritis and 114 cystitis/urethritis) was conducted. The fimH, sfa/foc, cvaC, hlyA, iroN, fyuA, ireA, iutA, and aer (the last five are siderophore genes) virulence genes were determined by PCR. The information of antibiotic susceptibility pattern of the strains was collected from medical records. This pattern was determined using an automated system for antimicrobial susceptibility testing. Multidrug-resistant (MDR) was defined as resistance to three or more antibiotic families. Results: fimH was the most frequently detected virulence gene (94.7%), and sfa/foc was the least frequently detected (9.2%); 55.3% (83/150) of the strains were MDR. The evaluated genes were not associated with UTI severity. Associations were found between the presence of hlyA and carbapenem resistance (Odds ratio [OR] = 7.58, 95% confidence interval [CI], 1.50-35.42), iutA and fluoroquinolone resistance (OR = 2.35, 95% CI, 1.15-4.84, and aer (OR = 2.8, 95% CI, 1.20-6.48) and iutA (OR = 2.95, 95% CI, 1.33-6.69) with penicillin resistance. In addition, iutA was the only gene associated with MDR (OR = 2.09, 95% CI,1.03-4.26). Conclusion: There was no association among virulence genes and UTI severity. Three of the five iron uptake genes were associated with resistance to at least one antibiotic family. Regarding the other four non-siderophore genes, only hlyA was associated with antibiotic resistance to carbapenems. It is essential to continue studying bacterial genetic characteristics that cause the generation of pathogenic and multidrug-resistant phenotypes of UPEC strains.

Development and evaluation of DiabeText, a personalized mHealth intervention to support medication adherence and lifestyle change behaviour in patients with type 2 diabetes in Spain: A mixed-methods phase II pragmatic randomized controlled clinical trial.

BACKGROUND: Despite the increasing interest in text-messaging interventions to support healthcare delivery, the available evidence about their effectiveness is still limited. OBJECTIVES: 1) to develop DiabeText, an intervention delivering automated, tailored brief text messages to support diabetes self-management; 2) to explore the potential impact of DiabeText on self-management behavior and glycaemic control, and; 3) to examine the feasibility of conducting a future phase III randomized clinical trial to evaluate the effectiveness of DiabeText. METHODS: 3-month, two-arm, randomized feasibility trial (ClinicalTrials.gov: NCT04738591) with patients with type 2 diabetes (HbA1c > 8%). Participants were allocated to the control (usual care) or DiabeText group (usual care + five text messages per week). Outcomes were: recruitment rate; follow-up rate, missing data; medication adherence; adherence to Mediterranean diet; physical activity; and HbA1c. In addition, after delivering the intervention, we conducted a qualitative study involving 14 semi-structured interviews with participants allocated to the DiabeText group, to understand their views about the intervention. RESULTS: From 444 screened people, we recruited 207 participants (recruitment rate = 47%), of which 179 completed the post-intervention interview (follow-up rate = 86%). We sent 7,355 SMS during the intervention period, of which 99% successfully reached the participants. At post-intervention, DiabeText was associated with non-statistically significant (p > 0.05) improvements in adherence to medication (OR = 2.0; 95%CI 1.0 to 4.2), Mediterranean diet (1.7; 0.9 to 3.2), and physical activity (1.7; 0.9 to 3.1). No between-group differences were observed in mean HbA1c (p = 0.670). The qualitative study indicated that participants perceived DiabeText as a helpful resource because it increased their awareness about the importance of adequate self-management and the sense of being cared for. CONCLUSIONS: DiabeText is the first system in Spain to integrate patient-generated and routinely collected clinical data to deliver tailored text messages to support diabetes self-management. More robust trials are needed to determine its effectiveness and cost-efficacy.

Assessment of burnout syndrome and associated factors among medical students during the COVID-19 pandemic.

Background: Overwhelming requirements, a high degree of work, and prolonged exposure to emotionally demanding circumstances in work and life settings can lead to burnout syndrome. The purpose of the study is to assess burnout syndrome and its associated factors among medical students during the COVID-19 pandemic. Methods: A cross-sectional, prospective, descriptive study was conducted in a Mexican medical school during the last week of the spring semester of 2021 using the Maslach Burnout Inventory-Student Survey (MBI-SS) and an associated factors survey. Results: Based on the MBI-SS definition, most students (54.2%, n = 332) had burnout symptoms and high emotional exhaustion (79.6%, n = 448), high cynicism (57.3%, n = 351), and low academic effectiveness (36.4%, n = 223). After adjusting the associated factors, a significant correlation between the school year and the presence of burnout was identified (OR 1.127, 95% CI [1.023-1.241], p<0.05). Regarding the current pandemic, the death of a family member by COVID-19 also put students at risk of developing burnout (OR 1.598*, 95% CI [1.080-2.363, p<0.05]). Limitations: The main limitation of this study was the lack of a control group (before the pandemic); therefore, the high prevalence of burnout can only be hypothesized due to the pandemic but cannot be objectively evidenced. A prospective study after the pandemic is needed to resolve this question. Conclusion: The coronavirus pandemic represents a challenge to the academic and psychological stability of students. It essential to continue assessing burnout levels in medical students and the general population to treat them in time and improve mental health.

A critical view on the current use of daptomycin in Spain: The daptomise study.

BACKGROUND: The Study on the Clinical Use of DAPTOMycin in Spain (DAPTOMISE Study) is a national surveillance program of daptomycin use. The objectives of this study are to evaluate the current variability in daptomycin consumption across the different hospitals and the adequacy of therapy, specially focused on underdosing. METHODS: All adult and pediatric patients who received, at least, one dose of daptomycin in a single week in 98 institutions in Spain were included. The adequacy of daptomycin use was evaluated with respect to the indication, dosage, adjustments after microbiology results, switching to an oral agent and length of treatment. RESULTS: A total of 615 patients received daptomycin during the study week. The prevalence use was 2.3 patients / 100,000 inhabitants per week, 12.4 patients / 1000 admissions and 9.2 Days of Therapy (DOT) / 1000 hospital stays. These rates varied between hospitals: from 0 to 13.9 patients / 100,000 inhabitants, from 0 to 76.1 patients / 1000 admissions and from 0 to 49.4 DOT / 1000 hospital stays. The most frequent infections were bacteremia (31.6 %) and skin and soft tissue infections (17.9 %). Microbiological results were available in only 65.4 % of infections. The most frequent microorganisms were Staphylococcus aureus (192 isolates, of which 87 were resistant to methicillin) and coagulase-negative staphylococci (124 isolates). A total of 136 prescriptions (22.1 %) were underdosed. Dosages < 8 mg/kg were used for 35.6 % of endovascular infections and for 26.2 % of osteoarticular infections. Overall, 57.2 % of prescriptions were not optimal in, at least, one item. Clinical cure rate was 76.1% and mortality attributable to the infection 8.1%. CONCLUSION: This is the first registry that identifies the prevalence of use of daptomycin in Spain and shows a high variability in the consumption between the different hospitals. Daptomycin underdosing was present in more than 20 % of cases.

Quantitative melanoma diagnosis using spectral phasor analysis of hyperspectral imaging from label-free slices.

Introduction: Melanoma diagnosis traditionally relies on microscopic examination of hematoxylin and eosin (H&E) slides by dermatopathologists to search for specific architectural and cytological features. Unfortunately, no single molecular marker exists to reliably differentiate melanoma from benign lesions such as nevi. This study explored the potential of autofluorescent molecules within tissues to provide molecular fingerprints indicative of degenerated melanocytes in melanoma. Methods: Using hyperspectral imaging (HSI) and spectral phasor analysis, we investigated autofluorescence patterns in melanoma compared to intradermal nevi. Using UV excitation and a commercial spectral confocal microscope, we acquired label-free HSI data from the whole-slice samples. Results: Our findings revealed distinct spectral phasor distributions between melanoma and intradermal nevi, with melanoma displaying a broader phasor phase distribution, signifying a more heterogeneous autofluorescence pattern. Notably, longer wavelengths associated with larger phases correlated with regions identified as melanoma by expert dermatopathologists using H&E staining. Quantitative analysis of phase and modulation histograms within the phasor clusters of five melanomas (with Breslow thicknesses ranging from 0.5 mm to 6 mm) and five intradermal nevi consistently highlighted differences between the two groups. We further demonstrated the potential for the discrimination of several melanocytic lesions using center-of-mass comparisons of phase and modulation variables. Remarkably, modulation versus phase center of mass comparisons revealed strong statistical significance among the groups. Additionally, we identified the molecular endogenous markers responsible for tissue autofluorescence, including collagen, elastin, NADH, FAD, and melanin. In melanoma, autofluorescence is characterized by a higher phase contribution, indicating an increase in FAD and melanin in melanocyte nests. In contrast, NADH, elastin, and collagen dominate the autofluorescence of the nevus. Discussion: This work underscores the potential of autofluorescence and HSI-phasor analysis as valuable tools for quantifying tissue molecular fingerprints, thereby supporting more effective and quantitative melanoma diagnosis.