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.

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.

Aureochromes maintain polyunsaturated fatty acid content in Nannochloropsis oceanica.

Nannochloropsis oceanica, like other stramenopile microalgae, is rich in long-chain polyunsaturated fatty acids (LC-PUFAs) such as eicosapentaenoic acid (EPA). We observed that fatty acid desaturases (FADs) involved in LC-PUFA biosynthesis were among the strongest blue light-induced genes in N. oceanica CCMP1779. Blue light was also necessary for maintaining LC-PUFA levels in CCMP1779 cells, and growth under red light led to a reduction in EPA content. Aureochromes are stramenopile-specific proteins that contain a light-oxygen-voltage (LOV)-sensing domain that associates with a flavin mononucleotide and is able to sense blue light. These proteins also contain a basic leucine zipper DNA-binding motif and can act as blue light-regulated transcription factors by associating with an E-box like motif, which we found enriched in the promoters of blue light-induced genes. We demonstrated that, in vitro, two CCMP1779 aureochromes were able to absorb blue light. Moreover, the loss or reduction of the expression of any of the three aureochrome genes led to a decrease in the blue light-specific induction of several FADs in CCMP1779. EPA content was also significantly reduced in NoAUREO2 and NoAUREO4 mutants. Taken together, our results indicate that aureochromes mediate blue light-dependent regulation of LC-PUFA content in N. oceanica CCMP1779 cells.

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.

Combining Wire Localization of Clipped Nodes with Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Node-Positive Breast Cancer: Preliminary Results from a Prospective Study.

BACKGROUND: The ideal technique for lymph node staging for patients with pathologically confirmed node-positive breast cancer at diagnosis and neoadjuvant chemotherapy (NAC) is unclear. OBJECTIVE: The aim of this study was to analyze the feasibility of wire/clip localization and sentinel lymph node biopsy (SLNB) for the axillary staging of these patients. METHODS: We conducted a prospective study in which lymph node staging was performed using wire localization of positive lymph nodes and an SLNB with dual tracer. All patients who presented no metastatic involvement of the sentinel lymph node (SLN) or clip/wire-marked lymph node were spared an axillary lymph node dissection (ALND). The multidisciplinary committee agreed on axillary treatment for patients with lymph node involvement. RESULTS: Forty-two patients met the inclusion criteria. We identified and extirpated the clip/wire-marked node in all patients (100%), with SLNB performed successfully in 95.3% of patients. The SLN and wire-marked node matched in 80% of patients; 73.8% of patients did not undergo ALND. DISCUSSION AND CONCLUSIONS: Several studies have evaluated the efficacy of various procedures for lymph node marking for women with prechemotherapy lymph node involvement. Most of the studies reported high identification rates (> 94.8%), with false negative rates of < 7%. Similarly, our study allows us to conclude that combined axillary marking (clip and SLNB) in patients with metastatic lymph node at diagnosis and NAC offers a high identification rate (100%) and a high correlation between the wire-marked lymph node and the SLN (80%). This procedure has enabled the suppression of ALND for a significant number of patients (73%).

Whole genome sequencing and de novo assembly of Staphylococcus pseudintermedius: a pangenome approach to unravelling pathogenesis of canine pyoderma.

BACKGROUND: Staphylococcus pseudintermedius is the main aetiological agent of canine pyoderma. Whole genome sequencing is the most comprehensive way of obtaining relevant genomic information about micro-organisms. HYPOTHESIS/OBJECTIVES: Oxford Nanopore technology enables quality sequencing and de novo assembly of the whole genome of S. pseudintermedius. Whole genome analysis of S. pseudintermedius may help to better understand the pathogenesis of canine pyodermas. METHODS AND MATERIALS: Twenty-two strains of S. pseudintermedius isolated from the skin of five healthy dogs and 33 strains isolated from skin of 33 dogs with pyoderma were analysed. DNA was extracted and sequenced using Oxford Nanopore MinION, a new technology that delivers longer reads in a hand-held device. The pangenome was analysed and visualised with Anvi'o 6.1. RESULTS: Nanopore technology allowed the sequencing and de novo assembly of the genomes of 55 S. pseudintermedius strains isolated from healthy dogs and from dogs with pyoderma. The average genome size of S. pseudintermedius was 2.62 Mbp, with 48% being core genome. Pyoderma isolates contained a higher number of antimicrobial resistance genes, yet the total number of virulence factors genes did not change between isolates from healthy dogs and from dogs with pyoderma. Genomes of meticillin-resistant S. pseudintermedius (MRSP) strains were larger than those of meticillin-susceptible (MSSP) strains (2.80 Mbp versus 2.59 Mbp), as a consequence of a greater presence of antimicrobial resistance genes, phages and prophages. CONCLUSIONS AND CLINICAL IMPORTANCE: This technique allows much more precise and easier characterisation of canine S. pseudintermedius populations and may lead to a better understanding of the pathogenesis of canine pyodermas.

Neuroprotective effect of melatonin loaded in ethylcellulose nanoparticles applied topically in a retinal degeneration model in rabbits.

We are reporting for the first time the synthesis and application of an innovative nanometric system for the controlled topic release of melatonin in the retina. The ethylcellulose nanocapsules were characterized by diverse physicochemical techniques (scanning electron microscopy, zeta potential, hydrodynamic diameters) and an in vitro release study was done. A complete ex vivo and in vivo trans-corneal permeation and an irritation study were carried out with the new formulations in albino rabbits, to which a retinal degenerative model was induced. The results obtained demonstrate that the in vitro release of melatonin (1 mg/mL and 2 mg/mL) transported by nanocapsules is slower when compared to a solution of melatonin. Greater penetration of melatonin through the cornea was demonstrated by ex vivo and in vivo tests. This can be attributable to an enhanced neuroprotective effect of melatonin on retinal ganglion cells when it is included in ethylcellulose nanocapsules compared to a solution of melatonin. These outstanding findings add promising new perspectives to current knowledge about administrations using nano-technological tools in the treatment of neurodegenerative diseases at the ocular level.

Identification of Antimalarial Compounds That Require CLAG3 for Their Uptake by Plasmodium falciparum-Infected Erythrocytes.

During the intraerythrocytic asexual cycle malaria parasites acquire nutrients and other solutes through a broad selectivity channel localized at the membrane of the infected erythrocyte termed the plasmodial surface anion channel (PSAC). The protein product of the Plasmodium falciparum clonally variant clag3.1 and clag3.2 genes determines PSAC activity. Switches in the expression of clag3 genes, which are regulated by epigenetic mechanisms, are associated with changes in PSAC-dependent permeability that can result in resistance to compounds toxic for the parasite, such as blasticidin S. Here, we investigated whether other antimalarial drugs require CLAG3 to reach their intracellular target and consequently are prone to parasite resistance by epigenetic mechanisms. We found that the bis-thiazolium salts T3 (also known as albitiazolium) and T16 require the product of clag3 genes to enter infected erythrocytes. P. falciparum populations can develop resistance to these compounds via the selection of parasites with dramatically reduced expression of both genes. However, other compounds previously demonstrated or predicted to enter infected erythrocytes through transport pathways absent from noninfected erythrocytes, such as fosmidomycin, doxycycline, azithromycin, lumefantrine, or pentamidine, do not require expression of clag3 genes for their antimalarial activity. This suggests that they use alternative CLAG3-independent routes to access parasites. Our results demonstrate that P. falciparum can develop resistance to diverse antimalarial compounds by epigenetic changes in the expression of clag3 genes. This is of concern for drug development efforts because drug resistance by epigenetic mechanisms can arise quickly, even during the course of a single infection.

Carbon-substrate utilization profiles by Cladorrhinum (Ascomycota).

Fungi from the genus Cladorrhinum (Ascomycota) are promising agents in the biocontrol of phytopathogens, in the promotion of plant growth, and in the production of enzymes with technological application. We analyzed comparatively the ability of 5 native strains of Cladorrhinum samala and Cladorrhinum bulbillosum with reference strains belonging to the same genus. We used 95 individual carbon sources available in microplates from the Biolog® FF system. Although most of the strains mainly used soluble carbohydrates, the metabolic profile was highly dependent upon each isolate and it revealed intraspecific physiological variability in Cladorrhinum species.

Expression of the Plasmodium falciparum Clonally Variant clag3 Genes in Human Infections.

Background: Many genes of the malaria parasite Plasmodium falciparum show clonally variant expression regulated at the epigenetic level. These genes participate in fundamental host-parasite interactions and contribute to adaptive processes. However, little is known about their expression patterns during human infections. A peculiar case of clonally variant genes are the 2 nearly identical clag3 genes, clag3.1 and clag3.2, which mediate nutrient uptake and are linked to resistance to some toxic compounds. Methods: We developed a procedure to characterize the expression of clag3 genes in naturally infected patients and in experimentally infected human volunteers. Results: We provide the first description of clag3 expression during human infections, which revealed mutually exclusive expression and identified the gene predominantly expressed. Adaptation to culture conditions or selection with a toxic compound resulted in isolate-dependent changes in clag3 expression. We also found that clag3 expression patterns were reset during transmission stages. Conclusions: Different environment conditions select for parasites with different clag3 expression patterns, implying functional differences between the proteins encoded. The epigenetic memory is likely erased before parasites start infection of a new human host. Altogether, our findings support the idea that clonally variant genes facilitate the adaptation of parasite populations to changing conditions through bet-hedging strategies.

Deciphering the principles that govern mutually exclusive expression of Plasmodium falciparum clag3 genes.

The product of the Plasmodium falciparum genes clag3.1 and clag3.2 plays a fundamental role in malaria parasite biology by determining solute transport into infected erythrocytes. Expression of the two clag3 genes is mutually exclusive, such that a single parasite expresses only one of the two genes at a time. Here we investigated the properties and mechanisms of clag3 mutual exclusion using transgenic parasite lines with extra copies of clag3 promoters located either in stable episomes or integrated in the parasite genome. We found that the additional clag3 promoters in these transgenic lines are silenced by default, but under strong selective pressure parasites with more than one clag3 promoter simultaneously active are observed, demonstrating that clag3 mutual exclusion is strongly favored but it is not strict. We show that silencing of clag3 genes is associated with the repressive histone mark H3K9me3 even in parasites with unusual clag3 expression patterns, and we provide direct evidence for heterochromatin spreading in P. falciparum. We also found that expression of a neighbor ncRNA correlates with clag3.1 expression. Altogether, our results reveal a scenario where fitness costs and non-deterministic molecular processes that favor mutual exclusion shape the expression patterns of this important gene family.

Seasonal Variation in Vitamin D in Association with Age, Inflammatory Cytokines, Anthropometric Parameters, and Lifestyle Factors in Older Adults.

Vitamin D deficiency is present even in sunny regions. Ageing decreases pre-vitamin D production in the skin and is associated with altered cytokine profile. We performed a multivariate analysis considering lifestyle factors, anthropometric, and inflammatory markers according to seasonal variation in Mexican healthy older adults. The same cohort was followed during 12 months. Vitamin D deficiency/insufficiency was found in 91.3% of the subjects despite living in appropriate latitude (25°40'0″N). 25(OH)D levels remained below <30 ng/mL through all seasons. Vitamin D deficiency did not correlate to sun exposure or dietary intake. Gender was the strongest associated factor, explaining a variance of 20%. Waist circumference (WC) greater than 88 cm was a risk factor for vitamin D deficiency. Age (>74 years) combined with WC (>88 cm) and BMI (>32.7) showed a high probability (90%) of vitamin D deficiency. Remarkably, an increase in one centimeter in WC decreased 25(OH)D by 0.176 ng/mL, while an increase in one point BMI decreased 25(OH)D by 0.534 ng/mL. A cutoff point of 74 years of age determined probability of vitamin D hipovitaminosis. Vitamin D deficiency was correlated with TNF-α serum levels, possibly increasing the susceptibility of older adults to a proinflammatory state and its related diseases.

Epigenetic switches in clag3 genes mediate blasticidin S resistance in malaria parasites.

Malaria parasites induce changes in the permeability of the infected erythrocyte membrane to numerous solutes, including toxic compounds. In Plasmodium falciparum, this is mainly mediated by PSAC, a broad-selectivity channel that requires the product of parasite clag3 genes for its activity. The two paralogous clag3 genes, clag3.1 and clag3.2, can be silenced by epigenetic mechanisms and show mutually exclusive expression. Here we show that resistance to the antibiotic blasticidin S (BSD) is associated with switches in the expression of these genes that result in altered solute uptake. Low concentrations of the drug selected parasites that switched from clag3.2 to clag3.1 expression, implying that expression of one or the other clag3 gene confers different transport efficiency to PSAC for some solutes. Selection with higher BSD concentrations resulted in simultaneous silencing of both clag3 genes, which severely compromises PSAC formation as demonstrated by blocked uptake of other PSAC substrates. Changes in the expression of clag3 genes were not accompanied by large genetic rearrangements or mutations at the clag3 loci or elsewhere in the genome. These results demonstrate that malaria parasites can become resistant to toxic compounds such as drugs by epigenetic switches in the expression of genes necessary for the formation of solute channels.

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.

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.

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.

[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.

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.

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.

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.