Pontificia Universidad Católica de Chile

Background Carbapenem-resistant Enterobacterales (CRE) are a major public health threat, largely due to the presence of carbapenemases, which are globally disseminated in mobile genetic elements. The emergence of CRE carrying multiple carbapenemases has been reported in several countries, particularly after the COVID-19 pandemic. In this study, we report the emergence of dual-producing CRE (DP-CRE) in Chile and provide a phenotipic and genomic characterization using whole-genome sequencing (WGS). Methods We evaluated the presence of carbapenemase in a total of 1367 CRE isolates recovered from invasive infections in 11 healthcare centers since 2018. Among them, 9 DP-CRE were detected and included in this report. Antimicrobial susceptibility was tested by broth microdilution and disk diffusion methods (CLSI, 2023), while blaKPC, blaVIM, blaIMP and blaNDM genes were detected by PCR. WGS was carried out using short and long reads (Illumina and Oxford Nanopore) and hybrid assemblies were performed. Results All 9 DP-CRE identified were recovered between November 2021 and June 2022 from 3 healthcare centers of a single city. In terms of species, 6 were identified as E. coli, one isolate of K. pneumoniae, one K. oxytoca and one C. freundii. All DP-CRE identified carried the combination of blaKPC and blaNDM. Genomic analyses confirmed all but one isolate carried blaKPC-2 and blaNDM-7. The remaining genome belonged to a K. pneumoniae that harboured blaKPC-3 and blaNDM-7. All 9 isolates exhibited resistance to all β-lactams, including carbapenems, aztreonam (ATM), cephalosporins and β-lactam/β-lactamase inhibators. Cefiderocol (FDC) was the only compound active against all the isolates. Also, all the DP-CRE became susceptible to ATM when combined with ceftazidime/avibactam (CZA). Hybrid assemblies revealed that blaKPC and blaNDM were harboured on independent plasmids (∼58,900 bp and ∼41,100 bp, respectively) as shown in Figure 1. Conclusion To the best of our knowledge, this is the first report of the emergence of DP-CRE in Chile after COVID-19 pandemic. Our results highlight the relevance of active surveillance of multidrug-resistance pathogens. FDC and CZA/ATM were the only compounds that remained active in vitro against these pathogens. Disclosures All Authors: No reported disclosures

Background Carbapenem resistance (CR) in Klebsiella pneumoniae is most frequently mediated by the production of carbapenemases. However, non-carbapenemase-producing K. pneumoniae (non-CP-Kpn) have been well documented. Overexpression of narrow β-lactamases can play an important role in the development of CR in the absence of carbapenemases. Here, we investigated the role of avibactam, a potent β-lactamase inhibitor, in preventing the in vitro development of CR in a non-CP-Kpn. Methods We used SCL-1, a non-CP-Kpn strain recovered from the bloodstream of a patient that developed CR in vivo during treatment with imipenem (IMI). SCL-1 was exposed to serial passages of increasing concentrations of IMI alone [0.25-16 μg/mL] or in combination with avibactam (IMI-AVI) during 8 days. In the case of IMI-AVI, the concentration of AVI was fixed at 4 μg/mL. Evolution assays were performed in triplicate and considered 3 independent evolutionary lines (ELs). MICs at each time-point were measured to IMI and IMI-AVI by broth microdilution as per CLSI. Growth curves of SCL-1 and evolved strains were performed to assess fitness. The expression levels of narrow spectrum β-lactamases blaOXA-1,blaOXA-10, and of the ESBL blaCTX-M-15 were measured by RT-qPCR. Results In vitro exposure to IMI led to CR, with the MICs increasing from 0.5 μg/mL to 8 μg/mL in all 3 ELs. In contrast, all ELs exposed to IMI-AVI remained fully susceptible to IMI after 8 days, with a final MIC of 1 μg/mL. In addition, the MIC to IMI of the evolved, IMI-resistant strains, in the presence of AVI (4 μg/mL) dropped from 8 to 1 μg/mL. Growth curves revealed that IMI-resistant strains evolved in IMI alone exhibited a growth defect as compared to both SCL-1 and the susceptible strains evolved in IMI-AVI. Finally, compared to the SCL-1, the expression level of blaOXA-1 was significantly increased (p< 0.05) in all evolved isolates that developed IMI resistance (MIC=8 μg/mL). No significant changes were observed in the expression of blaOXA-10 and blaCTX-M-15 (Figure 1).Figure 1.RT-qPCR analysis of β-lactamase gene transcript levels for SCL-1 and evolutive lines (A and B). Data shown are individual data points with mean±SD superimposed. Conclusion Our findings suggest that the addition of AVI can prevent the in vitro development of IMI resistance in non-CP-Kpn. Our results have important implications for the clinical use of AVI as a strategy to combat CR in non-CP-Kpn infections. Disclosures All Authors: No reported disclosures

Type 2 Diabetes Mellitus (T2DM) is a globally escalating health issue, with its complications significantly reducing life expectancy and imposing considerable economic and social burdens. Particularly in Chile, prevalence soars to 25–30% among individuals aged 65 and over from mid to low socioeconomic backgrounds. However, only 34% of T2DM patients achieve a target glycated hemoglobin (HbA1c) level of less than 7%. Our proposed project aims to address this challenge by developing and validating an Artificial Intelligence (AI)-integrated, cloud-based mobile health (mHealth) platform designed to enhance T2DM management. This platform facilitates lifestyle modifications and medication adherence, reducing treatment burden, while fostering patient education and self-management. It leverages biometric sensors in smartphones and wearable devices to generate metabolic control indicators to improve glycemic control beyond HbA1c and utilizes AI image processing techniques for early detection of feet ulcers. The mHealth concept, bolstered by increasing mobile connectivity, integrates patients and health providers into digital platforms, thereby creating a collaborative care model. Evidence has shown that multidimensional strategies have superior outcomes to unidimensional approaches, emphasizing the importance of incorporating various determinants into T2DM management. This novel AI-integrated cloud-based mHealth platform has the potential to revolutionize T2DM care by providing comprehensive, personalized, and efficient management solutions that not only address medical needs but also empower patients. By integrating cutting-edge AI and mHealth technology, our project is set to transform the landscape of T2DM management and improve the quality of life for millions of patients.

Estudios de Psicología ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/redp20 Kindergarten children's math anxiety and its relationship with mathematical performance (Ansiedad matemática en niños y niñas de kínder y su relación con el rendimiento matemático)

Natural fiber is a viable and possible option when looking for a material with high specific strength and high specific modulus that is lightweight, affordable, biodegradable, recyclable, and eco-friendly to reinforce polymer composites. There are many methods in which natural fibres can be incorporated into composite materials. The purpose of this research was to evaluate the physico-chemical, structural, thermal, and mechanical properties of Acacia pennata fibres (APFs). Scanning electron microscopy was used to determine the AP fibers' diameter and surface shape. The crystallinity index (64.47%) was discovered by XRD. The irregular arrangement and rough surface are seen in SEM photos. The findings demonstrated that fiber has high levels of cellulose (55.4%), hemicellulose (13.3%), and low levels of lignin (17.75%), which were determined through chemical analysis and validated by Fourier Transform Infrared Spectroscopy (FTIR). By using FTIR, the functional groups of the isolated AP fibers were examined, and TG analysis was used to look into the thermal degrading behaviour of the fibers treated with potassium permanganate (KMnO4) Due to their low density (520 kg/m³) and high cellulose content (55.4%), they have excellent bonding qualities. Additionally, tensile tests were used for mechanical characterisation to assess their tensile strength (685 MPa) and elongation.

Background This study aims to analyze the mid- to long-term results of the latissimus dorsi tendon for the treatment of massive posterosuperior irreparable rotator cuff tears as reported in high-quality publications and to determine its efficacy and safety. Methods A systematic review was performed according to the PRISMA guidelines. PubMed, Scopus, and EMBASE databases were searched until December 2022 to identify studies with a minimum 4-year follow-up. Clinical and radiographic outcomes, complications, and revision surgery data were collected. The publications included were analyzed quantitatively using the DerSimonian Laird random-effects model to estimate the change in outcomes from the preoperative to the postoperative condition. The proportion of complications and revisions were pooled using the Freeman-Tukey double arcsine transformation. Results Of the 618 publications identified through database search, 11 articles were considered eligible. A total of 421 patients (432 shoulders) were included in this analysis. Their mean age was 59.5 ± 4 years. Of these, 277 patients had mid-term follow-up (4 to 9 years), and 144 had long-term follow-up (more than 9 years). Postoperative improvements were considered significant for the following outcome parameters: Constant-Murley Score (0-100 scale), with a mean difference (MD) = 28 points (95% CI 21, 36; I2= 89%; P<.001); visual analog scale, with a standardized MD = 2.5 (95%CI 1.7, 3.3; P<.001; I2= 89%; P<.001); forward flexion, with a MD = 43° (95% CI 21°, 65°; I2=95% P<.001); abduction, with a MD = 38° (95% CI 20°, 56°; I2=85%; P < .01), and external rotation, with a MD = 8° (95% CI 1°, 16°; I2=87%; P= .005). The overall reported mean complication rate was 13% (95% CI 9%, 19%; I2=0%), while the reported mean revision rate was 6% (95% CI: 3%, 9%; I2=0%). Conclusions Our pooled estimated results seem to indicate that latissimus dorsi tendon transfer significantly improves patient-reported outcomes, pain relief, range of motion, and strength, with modest rates of complications and revision surgery at mid- to long-term follow-up. In well-selected patients, latissimus dorsi tendon transfer may provide favorable outcomes for irreparable posterosuperior cuff tears.

This systematic review and meta-analysis aimed to (1) determine the proportion of patients who underwent anterior shoulder instability surgery and did not return to sports for psychological reasons and (2) estimate differences in psychological readiness scores between patients who did and did not return to sports. The EBSCOhost/SPORTDiscus, PubMed/Medline, Scopus, EMBASE and Cochrane Library databases were searched for relevant studies. The data synthesis included the proportion of patients who did not return to sports for psychological reasons and the mean differences in the psychological readiness of athletes who returned and those who did not return to sports. Non-binomial data were analysed using the inverse-variance approach and expressed as the mean difference with 95% confidence intervals. The search yielded 700 records, of which 13 (1093 patients) were included. Fourteen psychological factors were identified as potential causes for not returning to sports. The rates of return to sports at any level or to the preinjury level were 79.3% and 61.9%, respectively. A total of 55.9% of the patients cited psychological factors as the primary reason for not returning to sports. The pooled estimate showed that patients who returned to sports had a significantly higher Shoulder Instability-Return to Sport After Injury score (P < 0.00001) than those who did not, with a mean difference of 30.24 (95% CI 24.95–35.53; I2 = 0%; n.s.). Psychological factors have a substantial impact on the rate of return to sports after anterior shoulder instability surgery. Patients who returned to sports had significantly higher psychological readiness than those who did not return to sports. Based on these results, healthcare professionals should include psychological and functional measurements when assessing athletes’ readiness to return to sports. Level IV.

The adverse impacts of the COVID-19 pandemic on scientific work and outputs have been a growing global concern after significant and varied effects have been reported in the United States and Europe. Looking to gain insight into the impact of the pandemic in Latin America, we designed and administered an anonymous online survey to researchers based in Chile or Colombia. The survey was implemented in July-August 2020, as the continent was declared the epicentre of COVID-19, and total lockdowns were enacted in both countries. We aimed to understand the overall impact of this situation on research time, exploring unequal effects by discipline and individual characteristics. Results based on 3257 responses indicate that, after accounting by discipline, individual-level differences related to gender and care responsibilities explain the more significant gaps. Specifically, we find that being a woman is linked to higher reductions of time devoted to research, followed by a parenthood penalty for those with children under 12 at home. We also tested a possible relationship between time devoted to research and personal beliefs about gender roles. We found that women who support traditional gender roles and have children reduced their research time more than any other group. Also, men who support progressive views are more impacted than their conservative peers. We conclude that given the heterogeneous impact of the pandemic on researchers, universities and research centres should target specific populations when creating policies aiming to mitigate its effects.

In hepatorenal syndrome-acute kidney injury (HRS-AKI), accurate and early diagnosis is crucial. HRS is a severe condition seen in advanced cirrhosis, requiring prompt recognition and proper management to enhance patient outcomes. Diagnosis of HRS-AKI relies on serum creatinine elevations, similar to other AKI cases in cirrhosis. However, distinguishing HRS-AKI from other renal impairments in these patients can be challenging. Biomarkers and clinical criteria aid in diagnosis and guide treatment. The management of HRS-AKI initially involves improving the haemodynamic profile using albumin and vasoconstrictors like terlipressin, a synthetic vasopressin analogue. Despite some reports linking terlipressin to increased adverse events compared with norepinephrine, it remains the preferred choice in HRS-AKI and acute-on-chronic liver failure due to its faster, stronger response and improved survival. Additional therapies like midodrine (alpha-1 adrenergic agonist), octreotide (somatostatin analogue) and transjugular intrahepatic portosystemic shunt are proposed as adjuvant treatments for HRS-AKI, aiming to improve vasoconstriction and renal blood flow. However, these adjunctive therapies cannot replace the definitive treatment for HRS-AKI—liver transplantation (LT). In cases unresponsive to medical management, LT is the only option to restore liver function and improve renal outcomes. Current evidence favours combined liver and kidney transplantation (CLKT) in certain situations. This review aims to evaluate the present evidence and recommendations on AKI in patients with cirrhosis, the pathophysiology of HRS-AKI, different treatments and indications for LT and CLKT. Understanding the complexities of managing HRS-AKI is crucial for optimising patient care and achieving better outcomes in this challenging clinical setting.

Purpose of Review Alpha-gal (α-gal) syndrome (AGS) represents a paradigm shift in food allergy since the allergen (α-gal), unlike most protein allergens, is an oligosaccharide found in mammalian meat and because of the delayed onset of allergic symptoms (3 to 6 h after consumption). Given the variability and non-specificity of the symptoms, in addition to the lack of highly sensitive diagnostic tests, its diagnosis and management can be challenging. The aim of this review is to provide an overview of the current status of AGS, with a special focus on the new therapeutic strategies. Recent Findings The association of AGS with tick bites is increasingly well documented and the pathogenic mechanism would be given by the induction of immunoglobulin E (IgE) against α-gal present in tick saliva. Treatment is based on avoiding mammalian meat consumption and in some cases also mammalian-derived products. In recent years, a few studies of oral desensitization against α-gal have been published with promising results. Summary Advances in the knowledge of the mechanisms underlying AGS have contributed to a better understanding of this syndrome, which has clinical features that often make it difficult to diagnose and treat. Future treatment strategies may involve combining anti-IgE therapy with oral desensitization to improve management outcomes.

Sperm production represents a costly reproductive investment by males. High reproductive competition within the female reproductive tract may select for higher sperm counts or quality resulting in selection for larger testes size. In species where females mate multiply or have more offspring per litter (litter size), or more litters per year (litter rate), male reproductive competition may select for larger relative testes size (i.e., scaled by body mass). Given that different mating systems vary in the alternative forms of reproductive investment available to males, sperm production levels may vary with social system. Here, we examined the relationship between testes size and mating systems, litter size, and litter rate while considering male lifespan and investment in paternal care in 224 terrestrial mammalian species in 15 orders. Relative testes size was larger in species where females mated with multiple males. Furthermore, in species with multiple mating females, species with higher litter rates had larger testes compared to species with fewer litters per year. In contrast, in monogamous species, species that had multiple litters per year had smaller relative testes sizes compared to species with fewer litters per year. Neither longevity nor paternal care influenced testes size. Our results elucidate the effect of female reproductive strategies on relative testes size is nuanced and varies between mating systems. Our findings suggest that the interplay between male reproductive investment and female reproductive investment may be different within similar social mating systems.

Topology optimization is a technique to solve the material distribution problem. However, to consider manufacturing constraints within this technique can be challenging. A type of manufacturing constraint that has not been thoroughly addressed is the ability to optimally select among a set of design subdomains. Examples of situations that may require such constraint in their design process are: the design and optimal location of a bridge pier, and the design and location of an outrigger system for a high-rise building, to name a few. This paper presents a novel formulation to address the simultaneous optimal subdomain selection and topology design problem which is based on the well-known SIMP formulation. The proposed method optimally selects the design subdomains in (2D and 3D) structures, and topology optimizes these with the remainder of the design domain which does not belong to any subdomain.

Background We investigated the association between changes in retinal thickness and cognition in people with MS (PwMS), exploring the predictive value of optical coherence tomography (OCT) markers of neuroaxonal damage for global cognitive decline at different periods of disease. Method We quantified the peripapillary retinal nerve fibre (pRFNL) and ganglion cell-inner plexiform (GCIPL) layers thicknesses of 207 PwMS and performed neuropsychological evaluations. The cohort was divided based on disease duration (≤5 years or >5 years). We studied associations between changes in OCT and cognition over time, and assessed the risk of cognitive decline of a pRFNL≤88 µm or GCIPL≤77 µm and its predictive value. Results Changes in pRFNL and GCIPL thickness over 3.2 years were associated with evolution of cognitive scores, in the entire cohort and in patients with more than 5 years of disease (p<0.01). Changes in cognition were related to less use of disease-modifying drugs, but not OCT metrics in PwMS within 5 years of onset. A pRFNL≤88 µm was associated with earlier cognitive disability (3.7 vs 9.9 years) and higher risk of cognitive deterioration (HR=1.64, p=0.022). A GCIPL≤77 µm was not associated with a higher risk of cognitive decline, but a trend was observed at ≤91.5 µm in PwMS with longer disease (HR=1.81, p=0.061). Conclusions The progressive retinal thinning is related to cognitive decline, indicating that cognitive dysfunction is a late manifestation of accumulated neuroaxonal damage. Quantifying the pRFNL aids in identifying individuals at risk of cognitive dysfunction.

Berries are highly regarded as flavorful and healthy fruits that may prevent or delay some chronic diseases attributed to oxidative stress and inflammation. Berries are low in calories and harbor diverse bioactive phytochemicals, antioxidants, dietary fibers, and vitamins. This review delves into the main characteristics of fresh berries and berry products as foods and the technologies associated with their production. The main effects of processing operations and related variables on bioactive components and antioxidants are described. This review critically discusses why some health claims based on in vitro antioxidant data and clinical studies and intervention trials are difficult to assess. The review suggests that the beneficial health effects of berries are derived from a multifactorial combination of complex mixtures of abundant phenolic components, antioxidants, and their metabolites acting synergistically or additively with other nutrients like fibers and vitamins and possibly by modulating the gut microbiota. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 15 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Paediatric trigger finger is rare compared to adult trigger finger or paediatric trigger thumb, and the aetiology is unclear. Proposed causes include local trauma, anatomical anomalies and systemic conditions. The aim of the present study was to detail the anatomical causes of surgically treated paediatric trigger fingers and provide an operative algorithm based on the anatomical findings. A total of 76 trigger fingers in 38 patients were identified retrospectively at our institution between 1975 and 2022. In total, 41 fingers in 26 patients had anatomical variations. A nodular thickening on the tendon, similar to Notta’s nodule in trigger thumbs, was the most common anatomical cause. Abnormal decussation of the flexor digitorum superficialis tendon was the second most common variation. The recurrence rate was significantly lower after resection of one slip of the flexor digitorum superficialis tendon compared to other surgical techniques in these patients. We recommend that surgeons assess for possible anatomical variation during surgery for the trigger finger. Level of evidence: IV

The COVID-19 pandemic has led to the introduction of unprecedented safety measures, one of them being physical distancing recommendations. Here, we assessed whether the pandemic has led to long-term effects on two important physical distancing aspects, namely interpersonal distance preferences and interpersonal touch behaviors. We analyzed nearly 14,000 individual cases from two large, cross-cultural surveys – the first conducted 2 years prior to the pandemic and the second during a relatively stable period of a decreased infection rate in May-June 2021. Preferred interpersonal distances increased by 54% globally during the COVID-19 pandemic. This increase was observable across all types of relationships, all countries, and was more pronounced in individuals with higher self-reported vulnerability to diseases. Unexpectedly, participants reported a higher incidence of interpersonal touch behaviors during than before the pandemic. We discuss our results in the context of prosocial and self-protection motivations that potentially promote different social behaviors.

Background SARS-CoV-2 infection had specific characteristics in the pediatric population described in previous studies. These clinical features included specific COVID-19 presentation, antibiotic usage, and predictors of disease severity. In addition to patient related factors, external influences could affect COVID-19 outcomes. The features of children with COVID-19 of five Latin American countries were described. Study participants were members of the Prevencionistas e Infectólogos para Cáncer Pediátrico en América Latina (PRINCIPAL) Network of the Global Infectious Diseases Program at St Jude Children's Research Hospital. This study aims to analyze the differences between patients with non-severe and severe disease when the circulation of the Delta variant was predominant, and few children had received SARS-CoV-2 vaccines. Methods This is a retrospective, observational, multinational study that included children with a confirmed diagnosis of COVID-19 between January 2021 and January 2022. Epidemiological, clinical, and treatment characteristics are described and compared between patients with severe and non-severe disease. Frequencies and percentages are presented as well as median and interquartile ranges (IQR). Comparisons were made using the chi-squared test for proportions and the Wilcoxon test for nonparametric quantitative variables. Results 745 patients were included. Patients had a median age of 51 (13-139) months, 194 (26%) had comorbidities, and 701 (94%) presented with symptomatic disease. Fever was present in 524 (74.8%) patients, respiratory symptoms in 550 (78.5%), followed by gastrointestinal manifestations in 218 (31.1%). X-ray findings were abnormal in 175/362 patients, with interstitial infiltrates being the most common finding, 123 (70.7%). Almost a third of patients (29%) received an antibiotic; ceftriaxone was most frequently prescribed in 123/216 cases. Of 745 patients, 526 (70.8%) were hospitalized, of which 165 (31.4%) required PICU admission. Patients presenting with severe disease and requiring PICU admission we more likely to have a comorbidity, 128 (22%) vs. 66 (40%), p<0.001. Mucocutaneous findings or adenitis were more frequently described in severe cases, 19 (11.5) vs. 18 (5.0%), p=0.007. Regarding laboratory results, low lymphocytes 2445 vs. 1676 (p<0.001) and low platelets 294,000 vs. 250,000 (p=0.0002) were most common in patients with severe disease. The proportion of patients with lymphocytopenia was also higher in those with severe disease, 39% vs. 52% p= 0.010. Not surprisingly, antibiotic usage (broad and narrow spectrum) was higher in patients admitted to the PICU (32 vs. 16.5%) p=0.001, despite no significant difference in the frequency of bacterial coinfection (5.56% vs. 9.7% p=0.081) when compared to patients with non-severe disease. Specific treatment strategies were more frequent in PICU patients (39.1% vs. 72.1%) p<0.001, and steroids were the most frequently used drug, 35.2% vs. 70.7% (p<0.001). Table 1. Conclusions Regardless of the variant, COVID-19 is an important cause of hospitalization in children. Fever, respiratory and gastrointestinal symptoms are the most frequent manifestations in children. Despite the low frequency of bacterial coinfection, a high proportion of antibiotic usage is described. Compared to recent publications, mucocutaneous involvement, lower lymphocyte and platelet counts, and higher inflammatory markers were more frequently found in admissions to the PICU. Currently, with higher vaccine coverage and more comprehensive knowledge of the disease, optimization of pediatric COVID-19 management is expected, especially concerning antibiotic use. It is essential to continue multicenter surveillance of the behavior of COVID-19 in the pediatric population.

Plant–plant positive interactions are key drivers of community structure. Yet, the underlying molecular mechanisms of facilitation processes remain unexplored. We investigated the ‘nursing’ effect of Maihueniopsis camachoi , a cactus that thrives in the Atacama Desert between c . 2800 and 3800 m above sea level. We hypothesised that an important protective factor is thermal amelioration of less cold‐tolerant species with a corresponding impact on molecular phenotypes. To test this hypothesis, we compared plant cover and temperatures within the cactus foliage with open areas and modelled the effect of temperatures on plant distribution. We combined eco‐metabolomics and machine learning to test the molecular consequences of this association. Multiple species benefited from the interaction with M. camachoi . A conspicuous example was the extended distribution of Atriplex imbricata to colder elevations in association with M. camachoi (400 m higher as compared to plants in open areas). Metabolomics identified 93 biochemical markers predicting the interaction status of A. imbricata with 79% accuracy, independently of year. These findings place M. camachoi as a key species in Atacama plant communities, driving local biodiversity with an impact on molecular phenotypes of nursed species. Our results support the stress‐gradient hypothesis and provide pioneer insights into the metabolic consequences of facilitation.