Effect of Topical Vancomycin on Surgical Site Infections in Ankle Fractures: A Randomized, Double-Blind, Controlled Trial.

Background Applying topical vancomycin has shown a decrease in the likelihood of surgical site infections (SSIs) in surgeries linked to a heightened risk of severe and resistant infections. Nevertheless, the effectiveness of this prophylactic approach has not been assessed in open ankle surgeries with internal fixation. Objective This study aimed to assess whether topical vancomycin diminishes the risk of SSI in patients with ankle fractures undergoing open reduction with internal fixation. Methods A randomized, controlled, double-blind clinical trial was carried out. Patients were divided into two groups in a 1:1 ratio. The control group received the standard prophylactic treatment with IV cephalothin 1 g, while the intervention group was administered topical vancomycin (1 g) in addition to the standard prophylactic treatment. The main outcomes were the SSI rates at 14 days, 28 days, and three months post-surgery, based on relevant clinical signs and laboratory tests. Results One hundred thirty-two patients were randomized (51.2% female), with 66 subjects included in each intervention arm. A total of 97.7% of them completed the study. Both groups were homogeneous in baseline characteristics. There were two SSIs in both the vancomycin group (3.3%) and the control group (3.5%), with no statistical differences (p = 0.945). The microorganisms isolated as causal agents were Staphylococcus aureus and Acinetobacter baumannii. By the three-month follow-up, no infections were noted in both intervention groups. Conclusion These results indicate that the topical administration of vancomycin may not represent an advantage in preventing SSI in ankle fractures requiring open reduction with internal fixation at the three-month postoperative stage.

The sunflower jacalin Helja: biological and structural insights of its antifungal activity against Candida albicans.

The limited availability of efficient treatments for Candida infections and the increased emergence of antifungal-resistant strains stimulates the search for new antifungal agents. We have previously isolated a sunflower mannose-binding lectin (Helja) with antifungal activity against Candida albicans, capable of binding mannose-bearing oligosaccharides exposed on the cell surface. This work aimed to investigate the biological and biophysical basis of Helja's binding to C. albicans cell wall mannans and its influence on the fungicidal activity of the lectin. We evaluated the interaction of Helja with the cell wall mannans extracted from the isogenic parental strain (WT) and a glycosylation-defective C. albicans with altered cell wall phosphomannosylation (mnn4∆ null mutants) and investigated its antifungal effect. Helja exhibited stronger antifungal activity on the mutant strain, showing greater inhibition of fungal growth, loss of cell viability, morphological alteration, and formation of clusters with agglutinated cells. This differential biological activity of Helja was correlated with the biophysical parameters determined by solid phase assays and isothermal titration calorimetry, which demonstrated that the lectin established stronger interactions with the cell wall mannans of the mnn4∆ null mutant than with the WT strain. In conclusion, our results provide new evidence on the nature of the Helja molecular interactions with cell wall components, i.e. phosphomannan, and its impact on the antifungal activity. This study highlights the relevance of plant lectins in the design of effective antifungal therapies.

Overcoming Barriers to Latino Participation in Alzheimer's Disease Research.

There is a critical need to increase Latino participation in research on Alzheimer's disease and related disorders (ADRD). Applying principles of community-based participatory research, we convened a community advisory board (CAB) to identify barriers and recommend strategies to increase participation of older Latinos in a longitudinal observational research study of ADRD at the Shiley-Marcos Alzheimer's Disease Research Center. Six major barriers were identified and programmatic changes to overcome them were implemented. Changes resulted in a nearly three-fold increase in the number of Latino individuals recruited, with the proportion of all newly recruited participants who were Latino increasing from 12.2% to 57.4%. Newer Latino recruits were more representative of the elderly Latino population in San Diego County than those recruited pre-CAB and remained highly agreeable to blood draw and neuroimaging, though less so to lumbar puncture and autopsy. Results demonstrate the value of CAB involvement in enhancing diversity in ADRD research.

Persistent organic pollutants and cognitive decline among middle-aged or older adults in the Hispanic Community Health Study/Study of Latinos.

Persistent organic pollutants may negatively impact cognition; however, associations between persistent organic pollutants and changes in cognition among United States Hispanic/Latino adults have not been investigated. Herein, we examined the associations between 33 persistent organic pollutants and cognitive changes among 1837 Hispanic/Latino adults. At baseline (2008-2011; Visit 1), participants provided biospecimens in which we measured levels of 5 persistent pesticides or pesticide metabolites, 4 polybrominated diphenyl ethers and 2,2',4,4',5,5'-hexabromobiphenyl, and 24 polychlorinated biphenyls. At Visit 1 and again at Visit 2 (2015-2018), a battery of neurocognitive tests was administered which included the Brief-Spanish English Verbal Learning Test, Word Fluency Test, and Digit Symbol Substitution Test. To estimate the adjusted associations between changes in cognition and each POP, we used linear regression for survey data. Each doubling in plasma levels of polychlorinated biphenyls 146, 178, 194, 199/206, and 209 was associated with steeper declines in global cognition (ßs range:-0.053 to -0.061) with stronger associations for the Brief-Spanish English Verbal Learning Test. Persistent organic pollutants, in particular polychlorinated biphenyls, were associated with declines in cognition over 7 years and may be a concern for Hispanic/Latino adults.

Strategies of Pharmacological Repositioning for the Treatment of Medically Relevant Mycoses.

Fungal infections represent a worldwide concern for public health, due to their prevalence and significant increase in cases each year. Among the most frequent mycoses are those caused by members of the genera Candida, Cryptococcus, Aspergillus, Histoplasma, Pneumocystis, Mucor, and Sporothrix, which have been treated for years with conventional antifungal drugs, such as flucytosine, azoles, polyenes, and echinocandins. However, these microorganisms have acquired the ability to evade the mechanisms of action of these drugs, thus hindering their treatment. Among the most common evasion mechanisms are alterations in sterol biosynthesis, modifications of drug transport through the cell wall and membrane, alterations of drug targets, phenotypic plasticity, horizontal gene transfer, and chromosomal aneuploidies. Taking into account these problems, some research groups have sought new therapeutic alternatives based on drug repositioning. Through repositioning, it is possible to use existing pharmacological compounds for which their mechanism of action is already established for other diseases, and thus exploit their potential antifungal activity. The advantage offered by these drugs is that they may be less prone to resistance. In this article, a comprehensive review was carried out to highlight the most relevant repositioning drugs to treat fungal infections. These include antibiotics, antivirals, anthelmintics, statins, and anti-inflammatory drugs.

Neurocognitive profiles are associated with subsequent brain integrity in a sample of Hispanics/Latinos: Findings from the SOL-INCA-MRI study (HCHS/SOL).

The Hispanic/Latino population is one of the largest and most diverse ethnoracial groups in the United States at high risk for dementia. We examined cognitive constructs and associations with subsequent hippocampal volume (HV) and white matter hyperintensity volume (WMHV). Participants were from the Hispanic Community Health Study/Study of Latinos-Magnetic Resonance Imaging Study (n = 2029). We examined confirmatory factor analysis and longitudinal invariance using neurocognitive scores at Visits 1 (2008-2011) and 2 (2014-2018) and path analyses. We obtained a longitudinally invariant two-factor episodic memory (EM) and working memory (WM) construct. Lower EM profile at both visits was associated with greater WMHV and smaller HV at Visit 2. Lower WM profile at both visits was associated with larger WMHV and smaller HV at Visit 2. Neurocognitive profiles were associated with subsequent neurodegeneration in a sample of Hispanics/Latinos. Identifying neurocognitive risk profiles may lead to early detection and intervention, and significantly impact the course of neurodegeneration. Highlights: Cognitive profiles predict brain integrity up to 10 years later.We observed two-factor latent memory constructs and longitudinal invariance.These findings were observed in a Hispanic/Latino cohort.

Intracranial Volume Is Driven by Both Genetics and Early Life Exposures: The SOL-INCA-MRI Study.

Intracranial volume (ICV) reflects maximal brain development and is associated with later-life cognitive abilities. We quantified ICV among first- and second-generation Hispanic and Latino adults from the Study of Latinos-Investigation of Cognitive Aging - MRI (SOL-INCA-MRI), estimated ICV heritability, and tested its associations with previously reported genetic variants, both individually and as a genetic risk score (GRS). We also estimated the association of ICV with early life environmental measures: nativity or age of immigration and parental education. The estimated heritability of ICV was 19% (95% CI, 0.1%-56%) in n=1781 unrelated SOL-INCA-MRI individuals. Four of 10 tested genetic variants were associated with ICV and an increase of 1 SD of the ICV-GRS was associated with an increase of 10.37 cm3 in the ICV (95% CI, 5.29-15.45). Compared to being born in the continental United States, immigrating to the United States at age 11 years or older was associated with 24 cm3 smaller ICV (95% CI, -39.97 to -8.06). Compared to both parents having less than high-school education, at least 1 parent completing high-school education was associated with 15.4 cm3 greater ICV (95% CI, 4.46-26.39). These data confirm the importance of early life health on brain development.

Admixture mapping of cognitive function in diverse Hispanic and Latino adults: Results from the Hispanic Community Health Study/Study of Latinos.

INTRODUCTION: We conducted admixture mapping and fine-mapping analyses to identify ancestry-of-origin loci influencing cognitive abilities. METHODS: We estimated the association of local ancestry intervals across the genome with five neurocognitive measures in 7140 diverse Hispanic and Latino adults (mean age 55 years). We prioritized genetic variants in associated loci and tested them for replication in four independent cohorts. RESULTS: We identified nine local ancestry-associated regions for the five neurocognitive measures. There was strong biological support for the observed associations to cognitive function at all loci and there was statistical evidence of independent replication at 4q12, 9p22.1, and 13q12.13. DISCUSSION: Our study identified multiple novel loci harboring genes implicated in cognitive functioning and dementia, and uncovered ancestry-relevant genetic variants. It adds to our understanding of the genetic architecture of cognitive function in Hispanic and Latino adults and demonstrates the power of admixture mapping to discover unique haplotypes influencing cognitive function, complementing genome-wide association studies. HIGHLIGHTS: We identified nine ancestry-of-origin chromosomal regions associated with five neurocognitive traits. In each associated region, we identified single nucleotide polymorphisms (SNPs) that explained, at least in part, the admixture signal and were tested for replication in independent samples of Black, non-Hispanic White, and Hispanic/Latino adults with the same or similar neurocognitive tests. Statistical evidence of independent replication of the prioritized SNPs was observed for three of the nine associations, at chr4q12, chr9p22.1, and chr13q12.13. At all loci, there was strong biological support for the observed associations to cognitive function and dementia, prioritizing genes such as KIT, implicated in autophagic clearance of neurotoxic proteins and on mast cell and microglial-mediated inflammation; SLC24A2, implicated in synaptic plasticity associated with learning and memory; and MTMR6, implicated in phosphoinositide lipids metabolism.

Exploring the potential of chitin and chitosan in nanobiocomposites for fungal immunological detection and antifungal action.

Chitin is a polymer of N-acetylglucosamine and an essential component of the fungal cell wall. Chitosan is the deacetylated form of chitin and is also important for maintaining the integrity of this structure. Both polysaccharides are widely distributed in nature and have been shown to have a variety of applications in biomedicine, including their potential in immune sensing and as potential antifungal agents. In addition, chitin has been reported to play an important role in the pathogen-host interaction, involving innate and adaptive immune responses. This paper will explore the role of chitin and chitosan when incorporated into nanobiocomposites to improve their efficacy in detecting fungi of medical interest and inhibiting their growth. Potential applications in diagnostic and therapeutic medicine will be discussed, highlighting their promise in the development of more sensitive and effective tools for the early diagnosis of fungal infections. This review aims to highlight the importance of the convergence of nanotechnology and biology in addressing public health challenges.

Candida tropicalis PMT2 Is a Dispensable Gene for Viability but Required for Proper Interaction with the Host.

Candidemia is an opportunistic mycosis with high morbidity and mortality rates. Even though Candida albicans is the main causative agent, other Candida species, such as Candida tropicalis, are relevant etiological agents of candidiasis and candidemia. Compared with C. albicans, there is currently limited information about C. tropicalis' biological aspects, including those related to the cell wall and the interaction with the host. Currently, it is known that its cell wall contains O-linked mannans, and the contribution of these structures to cell fitness has previously been addressed using cells subjected to chemical treatments or in mutants where O-linked mannans and other wall components are affected. Here, we generated a C. tropicalis pmt2∆ null mutant, which was affected in the first step of the O-linked mannosylation pathway. The null mutant was viable, contrasting with C. albicans where this gene is essential. The phenotypical characterization showed that O-linked mannans were required for filamentation; proper cell wall integrity and organization; biofilm formation; protein secretion; and adhesion to extracellular matrix components, in particular to fibronectin; and type I and type II collagen. When interacting with human innate immune cells, it was found that this cell wall structure is dispensable for cytokine production, but mutant cells were more phagocytosed by monocyte-derived macrophages. Furthermore, the null mutant cells showed virulence attenuation in Galleria mellonella larvae. Thus, O-linked mannans are minor components of the cell wall that are involved in different aspects of C. tropicalis' biology.

Racial Disparities in Outcomes of Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction Secondary to Spontaneous Coronary Artery Dissection.

Spontaneous coronary artery dissection (SCAD) is a rare cause of ST-segment elevation myocardial infarction (STEMI), predominantly affecting women. Because primary percutaneous coronary intervention (PPCI) is reserved for a select group of patients, vulnerable and minority patients may experience delays in appropriate management and adverse outcomes. We examined the racial differences in the outcomes for patients with SCAD who underwent PPCI for STEMI. Records of patients aged ≥18 years who underwent PPCI for SCAD-related STEMI between 2016 and 2020 were identified from the National Inpatient Sample database. Clinical, socioeconomic, and hospital characteristics were compared between non-White and White patients. Weighted multivariate analysis assessed the association of race with inpatient mortality, length of stay (LOS), and hospitalization costs. The total weighted estimate of patients with SCAD-STEMI who underwent PPCI was 4,945, constituting 25% non-White patients. Non-White patients were younger (56 vs 60.7 years, p <0.001); had a higher prevalence of diabetes, acute renal failure, and obesity; and were more likely to be uninsured and be in the lowest income group. Inpatient mortality (7.7% vs 8.4%, p = 0.74) and hospitalization costs ($34,213 vs $31,858, p = 0.27) were similar for non-White and White patients, and the adjusted analysis did not show any association between the patients' race and inpatient mortality (odds ratio 0.60, 95% confidence interval [CI] 0.32 to 1.13, p = 0.11) or hospitalization costs (ß [ß coefficient]: 215, 95% CI -4,193 to 4,623, p >0.90). Similarly, there was no association between the patients' race and LOS (incident rate ratio 1.20, 95% CI 1.00 to 1.45, p = 0.054). The weighted multivariate analysis showed that age; clinical co-morbidities such as diabetes, acute renal failure, valvular dysfunction, and obesity; low-income status; and hospitalization in the western region were associated with adverse outcomes. In conclusion, our study does not show any differences in inpatient mortality, LOS, and hospitalization costs between non-White and White patients who underwent PPCI for SCAD-related STEMI.

Eliminating malaria vectors with precision-guided sterile males.

Controlling the principal African malaria vector, the mosquito Anopheles gambiae, is considered essential to curtail malaria transmission. However, existing vector control technologies rely on insecticides, which are becoming increasingly ineffective. Sterile insect technique (SIT) is a powerful suppression approach that has successfully eradicated a number of insect pests, yet the A. gambiae toolkit lacks the requisite technologies for its implementation. SIT relies on iterative mass releases of nonbiting, nondriving, sterile males which seek out and mate with monandrous wild females. Once mated, females are permanently sterilized due to mating-induced refractoriness, which results in population suppression of the subsequent generation. However, sterilization by traditional methods renders males unfit, making the creation of precise genetic sterilization methods imperative. Here, we introduce a vector control technology termed precision-guided sterile insect technique (pgSIT), in A. gambiae for inducible, programmed male sterilization and female elimination for wide-scale use in SIT campaigns. Using a binary CRISPR strategy, we cross separate engineered Cas9 and gRNA strains to disrupt male-fertility and female-essential genes, yielding >99.5% male sterility and >99.9% female lethality in hybrid progeny. We demonstrate that these genetically sterilized males have good longevity, are able to induce sustained population suppression in cage trials, and are predicted to eliminate wild A. gambiae populations using mathematical models, making them ideal candidates for release. This work provides a valuable addition to the malaria genetic biocontrol toolkit, enabling scalable SIT-like confinable, species-specific, and safe suppression in the species.

Two protocols for the detection of oleaginous bacteria using Oil Red O.

The selection of oleaginous bacteria, potentially applicable to biotechnological approaches, is usually carried out by different expensive and time-consuming techniques. In this study, we used Oil Red O (ORO) as an useful dye for staining of neutral lipids (triacylglycerols and wax esters) on thin-layer chromatography plates. ORO could detect minimal quantities of both compounds (detection limit, 0.0025 mg of tripalmitin or 0.005 mg of cetylpalmitate). In addition, we developed a specific, rapid, and inexpensive screening methodology to detect triacylglycerol-accumulating microorganisms grown on the agar plate. This staining methodology detected 9/13 strains with a triacylglycerol content higher than 20% by cellular dry weight. ORO did not stain polyhydroxyalkanoates-producing bacteria. The four oleaginous strains not detected by this screening methodology exhibited a mucoid morphology of their colonies. Apparently, an extracellular polymeric substance produced by these strains hampered the entry of the lipophilic dye into cells. The utilization of the developed screening methodology would allow selecting of oleaginous bacteria in a simpler and faster way than techniques usually used nowadays, based on unspecific staining protocols and spectrophotometric or chromatographic methods. Furthermore, the use of ORO as a staining reagent would easily characterize the neutral lipids accumulated by microorganisms as reserve compounds. KEY POINTS: • Oil Red O staining is specific for triacylglycerols • Oil Red O staining is useful to detect oleaginous bacteria • Fast and inexpensive staining to isolate oleaginous bacteria from the environment.

Evaluation of the trade-off between water use efficiency and nutrient use efficiency in two semiarid coniferous tree species growing on an organic amended metalliferous mine tailing substrate.

We evaluated the ecophysiological responses of two semiarid coniferous tree species, Pinus halepensis and Tetraclinis articulata, growing on a nutrient-poor metalliferous mine tailings substrate to organic amendments (biochar and/or organic municipal waste). The trees were grown in mesocosms under irrigated conditions for 20 months. Then, a comprehensive characterization of soil and plant parameters (including stable isotopes) was carried out. Treatments containing municipal waste showed better soil fertility indicators (approximately 2-fold higher organic carbon and total nitrogen concentrations) and higher plant biomass (up to 5-fold higher) than unamended and only biochar treatments. Trees in most of the treatments exhibited leaf N/P ratios <14 indicating severe N limitation of plant growth. Metal uptake was below phytotoxic levels across all the treatments. Leaf δ13C values correlated positively with δ18O across treatments for both species indicating increasing water use efficiency with tighter stomatal regulation of water flux, and with T. articulata exhibiting tighter stomatal control (higher δ18O values) than P. halepensis. Trees in treatments containing only biochar did not differ in ecophysiological performance from those in the unamended treatments. In contrast, leaf stable isotopes revealed sharply increased of time-integrated photosynthetic activity (favoured by higher leaf N concentrations) combined with lower time-integrated stomatal conductance in the treatments containing municipal waste, indicating greatly enhanced water use efficiency in better nourished plants. Trade-offs between water use efficiency and nutrient (N and P) use efficiency were evident across treatments, with higher leaf nutrient concentrations associated with higher water use efficiency, at the cost of a lower nutrient use efficiency. These trade-offs were not impaired by the high metal concentrations of the tailings substrate, indicating that ecophysiological adjustments in response to changes in plant nutrient status promoted by the addition of organic amendments are critical for the adaptability of native tree species employed in the phytostabilisation of mine tailings.

Impact of the use of plaque modification techniques on coronary microcirculation using an angiography-derived index of microcirculatory resistance.

Many lesions in patients undergoing percutaneous coronary intervention (PCI) exhibit significant calcification. Several techniques have been developed to improve outcomes in this setting. However, their impact on coronary microcirculation remains unknown. The aim of this study is to evaluate the influence of plaque modification techniques on coronary microcirculation across patients with severely calcified coronary artery disease. In this multicenter retrospective study, consecutive patients undergoing PCI with either Rotablation (RA) or Shockwave-intravascular-lithotripsy (IVL) were included. Primary endpoint was the impairment of coronary microvascular resistances assessed by Δ angiography-derived index of microvascular resistance (ΔIMRangio) which was defined as the difference in IMRangio value post- and pre-PCI. Secondary endpoints included the development of peri procedural PCI complications (flow-limiting coronary dissection, slow-flow/no reflow during PCI, coronary perforation, branch occlusion, failed PCI, stroke and shock developed during PCI) and 12-month follow-up adverse events. 162 patients were included in the analysis. Almost 80% of patients were male and the left descending anterior artery was the most common treated vessel. Both RA and IVL led to an increase in ΔIMRangio (22.3 and 10.3; p = 0.038, respectively). A significantly higher rate of PCI complications was observed in patients with ΔIMRangio above the median of the cohort (21.0% vs. 6.2%; p = 0.006). PCI with RA was independently associated with higher ΔIMRangio values (OR 2.01, 95% CI: 1.01-4.03; p = 0.048). Plaque modification with IVL and RA during PCI increases microvascular resistance. Evaluating the microcirculatory status in this setting might help to predict clinical and procedural outcomes and to optimize clinical results.

Development of an application programming interface to automate downloading and processing of precision livestock data.

Advancements in technology have ushered in a new era of sensor-based measurement and management of livestock production systems. These sensor-based technologies have the ability to automatically monitor feeding, growth, and enteric emissions for individual animals across confined and extensive production systems. One challenge with sensor-based technologies is the large amount of data generated, which can be difficult to access, process, visualize, and monitor information in real time to ensure equipment is working properly and animals are utilizing it correctly. A solution to this problem is the development of application programming interfaces (APIs) to automate downloading, visualizing, and summarizing datasets generated from precision livestock technology (PLT). For this methods paper, we develop three APIs and accompanying processes for rapid data acquisition, visualization, systems tracking, and summary statistics for three technologies (SmartScale, SmartFeed, and GreenFeed) manufactured by C-Lock Inc (Rapid City, SD). Program R markdown documents and example datasets are provided to facilitate greater adoption of these techniques and to further advance PLT. The methodology presented successfully downloaded data from the cloud and generated a series of visualizations to conduct systems checks, animal usage rates, and calculate summary statistics. These tools will be essential for further adoption of precision technology. There is huge potential to further leverage APIs to incorporate a wide range of datasets such as weather data, animal locations, and sensor data to facilitate decision-making on time scales relevant to researchers and livestock managers.