Association of Acute Respiratory Disease Events with Quantitative Interstitial Abnormality Progression at CT in Individuals with a History of Smoking.

Background Acute respiratory disease (ARD) events are often thought to be airway-disease related, but some may be related to quantitative interstitial abnormalities (QIAs), which are subtle parenchymal abnormalities on CT scans associated with morbidity and mortality in individuals with a smoking history. Purpose To determine whether QIA progression at CT is associated with ARD and severe ARD events in individuals with a history of smoking. Materials and Methods This secondary analysis of a prospective study included individuals with a 10 pack-years or greater smoking history recruited from multiple centers between November 2007 and July 2017. QIA progression was assessed between baseline (visit 1) and 5-year follow-up (visit 2) chest CT scans. Episodes of ARD were defined as increased cough or dyspnea lasting 48 hours and requiring antibiotics or corticosteroids, whereas severe ARD episodes were those requiring an emergency room visit or hospitalization. Episodes were recorded via questionnaires completed every 3 to 6 months. Multivariable logistic regression and zero-inflated negative binomial regression models adjusted for comorbidities (eg, emphysema, small airway disease) were used to assess the association between QIA progression and episodes between visits 1 and 2 (intercurrent) and after visit 2 (subsequent). Results A total of 3972 participants (mean age at baseline, 60.7 years ± 8.6 [SD]; 2120 [53.4%] women) were included. Annual percentage QIA progression was associated with increased odds of one or more intercurrent (odds ratio [OR] = 1.29 [95% CI: 1.06, 1.56]; P = .01) and subsequent (OR = 1.26 [95% CI: 1.05, 1.52]; P = .02) severe ARD events. Participants in the highest quartile of QIA progression (≥1.2%) had more frequent intercurrent ARD (incidence rate ratio [IRR] = 1.46 [95% CI: 1.14, 1.86]; P = .003) and severe ARD (IRR = 1.79 [95% CI: 1.18, 2.73]; P = .006) events than those in the lowest quartile (≤-1.7%). Conclusion QIA progression was independently associated with higher odds of severe ARD events during and after radiographic progression, with higher frequency of intercurrent severe events in those with faster progression. Clinical trial registration no. NCT00608764 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Little in this issue.

Detection of IgG antibodies against the receptor binding domain of the spike protein and nucleocapsid of SARS-CoV-2 at university students from Southern Mexico: a cross-sectional study.

BACKGROUND: Natural infection and vaccination against SARS-CoV-2 is associated with the development of immunity against the structural proteins of the virus. Specifically, the two most immunogenic are the S (spike) and N (nucleocapsid) proteins. Seroprevalence studies performed in university students provide information to estimate the number of infected patients (symptomatic or asymptomatic) and generate knowledge about the viral spread, vaccine efficacy, and epidemiological control. Which, the aim of this study was to evaluate IgG antibodies against the S and N proteins of SARS-CoV-2 at university students from Southern Mexico. METHODS: A total of 1418 serum samples were collected from eighteen work centers of the Autonomous University of Guerrero. Antibodies were detected by Indirect ELISA using as antigen peptides derived from the S and N proteins. RESULTS: We reported a total seroprevalence of 39.9% anti-S/N (positive to both antigens), 14.1% anti-S and 0.5% anti-N. The highest seroprevalence was reported in the work centers from Costa Grande, Acapulco and Centro. Seroprevalence was associated with age, COVID-19, contact with infected patients, and vaccination. CONCLUSION: University students could play an essential role in disseminating SARS-CoV-2. We reported a seroprevalence of 54.5% against the S and N proteins, which could be due to the high population rate and cultural resistance to safety measures against COVID-19 in the different regions of the state.

The influence of gender and temephos exposure on community participation in dengue prevention: a compartmental mathematical model.

BACKGROUND: The use of temephos, the most common intervention for the chemical control of Aedes aegypti over the last half century, has disappointing results in control of the infection. The footprint of Aedes and the diseases it carries have spread relentlessly despite massive volumes of temephos. Recent advances in community participation show this might be more effective and sustainable for the control of the dengue vector. METHODS: Using data from the Camino Verde cluster randomized controlled trial, a compartmental mathematical model examines the dynamics of dengue infection with different levels of community participation, taking account of gender of respondent and exposure to temephos. RESULTS: Simulation of dengue endemicity showed community participation affected the basic reproductive number of infected people. The greatest short-term effect, in terms of people infected with the virus, was the combination of temephos intervention and community participation. There was no evidence of a protective effect of temephos 220 days after the onset of the spread of dengue. CONCLUSIONS: Male responses about community participation did not significantly affect modelled numbers of infected people and infectious mosquitoes. Our model suggests that, in the long term, community participation alone may have the best results. Adding temephos to community participation does not improve the effect of community participation alone.

Semi-supervised Double Deep Learning Temporal Risk Prediction (SeDDLeR) with Electronic Health Records.

BACKGROUND: Risk prediction plays a crucial role in planning for prevention, monitoring, and treatment. Electronic Health Records (EHRs) offer an expansive repository of temporal medical data encompassing both risk factors and outcome indicators essential for effective risk prediction. However, challenges emerge due to the lack of readily available gold-standard outcomes and the complex effects of various risk factors. Compounding these challenges are the false positives in diagnosis codes, and formidable task of pinpointing the onset timing in annotations. OBJECTIVE: We develop a Semi-supervised Double Deep Learning Temporal Risk Prediction (SeDDLeR) algorithm based on extensive unlabeled longitudinal Electronic Health Records (EHR) data augmented by a limited set of gold standard labels on the binary status information indicating whether the clinical event of interest occurred during the follow-up period. METHODS: The SeDDLeR algorithm calculates an individualized risk of developing future clinical events over time using each patient's baseline EHR features via the following steps: (1) construction of an initial EHR-derived surrogate as a proxy for the onset status; (2) deep learning calibration of the surrogate along gold-standard onset status; and (3) semi-supervised deep learning for risk prediction combining calibrated surrogates and gold-standard onset status. To account for missing onset time and heterogeneous follow-up, we introduce temporal kernel weighting. We devise a Gated Recurrent Units (GRUs) module to capture temporal characteristics. We subsequently assess our proposed SeDDLeR method in simulation studies and apply the method to the Massachusetts General Brigham (MGB) Biobank to predict type 2 diabetes (T2D) risk. RESULTS: SeDDLeR outperforms benchmark risk prediction methods, including Semi-parametric Transformation Model (STM) and DeepHit, with consistently best accuracy across experiments. SeDDLeR achieved the best C-statistics ( 0.815, SE 0.023; vs STM +.084, SE 0.030, P-value .004; vs DeepHit +.055, SE 0.027, P-value .024) and best average time-specific AUC (0.778, SE 0.022; vs STM + 0.059, SE 0.039, P-value .067; vs DeepHit + 0.168, SE 0.032, P-value <0.001) in the MGB T2D study. CONCLUSION: SeDDLeR can train robust risk prediction models in both real-world EHR and synthetic datasets with minimal requirements of labeling event times. It holds the potential to be incorporated for future clinical trial recruitment or clinical decision-making.

Self-rated health among adolescents from vulnerable areas and their sociodemographic, lifestyle and contextual factors: A multilevel analysis.

PURPOSE: Understanding self-rated health in young people can help orient global health actions, especially in regions of social vulnerability. The present study analysed individual and contextual factors associated with self-rated health in a sample of Brazilian adolescents. DESIGN AND METHODS: Cross-sectional data from 1272 adolescents (aged 11-17; 48.5% of girls) in low human development index (HDI) neighbourhoods were analysed (HDI from 0.170 to 0.491). The outcome variable was self-rated health. Independent variables relating to individual factors (biological sex, age and economic class) and lifestyle (physical activity, alcohol, tobacco consumption and nutritional state) were measured using standardised instruments. The socio-environmental variables were measured using neighbourhood registered data where the adolescents studied. Multilevel regression was used to estimate the regression coefficients and their 95% confidence intervals (CI). RESULTS: Good self-rated health prevalence was of 72.2%. Being male (B: -0.165; CI: -0.250 to -0.081), age (B: -0.040; CI: -0.073 to -0.007), weekly duration of moderate to vigorous physical activity (B: 0.074; CI: 0.048-0.099), body mass index (B: -0.025; CI: -0.036 to -0.015), number of family healthcare teams in the neighbourhood (B: 0.019; CI: 0.006-0.033) and dengue incidence (B: -0.001; CI: -0.002; -0.000) were factors associated with self-rated health among students from vulnerable areas. CONCLUSIONS/PRACTICAL IMPLICATIONS: Approximately three in every 10 adolescents in areas of social vulnerability presented poor self-rated health. This fact was associated with biological sex and age (individual factors), physical activity levels and BMI (lifestyle) and the number of family healthcare teams in the neighbourhood (contextual).

Epigenomic regulation of human T-cell leukemia virus by chromatin-insulator CTCF.

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that causes an aggressive T-cell malignancy and a variety of inflammatory conditions. The integrated provirus includes a single binding site for the epigenomic insulator, CCCTC-binding protein (CTCF), but its function remains unclear. In the current study, a mutant virus was examined that eliminates the CTCF-binding site. The mutation did not disrupt the kinetics and levels of virus gene expression, or establishment of or reactivation from latency. However, the mutation disrupted the epigenetic barrier function, resulting in enhanced DNA CpG methylation downstream of the CTCF binding site on both strands of the integrated provirus and H3K4Me3, H3K36Me3, and H3K27Me3 chromatin modifications both up- and downstream of the site. A majority of clonal cell lines infected with wild type HTLV-1 exhibited increased plus strand gene expression with CTCF knockdown, while expression in mutant HTLV-1 clonal lines was unaffected. These findings indicate that CTCF binding regulates HTLV-1 gene expression, DNA and histone methylation in an integration site dependent fashion.

Disturbing the Spatial Organization of Biofilm Communities Affects Expression of agr-Regulated Virulence Factors in Staphylococcus aureus.

Staphylococcus aureus uses quorum sensing and nutrient availability to control the expression of agr-regulated virulence factors. Quorum sensing is mediated by autoinducing peptide (AIP), which at a high concentration reduces expression of surface attachment proteins (coa, fnbpA) and increases expression of exotoxins (lukS) and proteases (splA). Nutrient availability can be sensed through the saeS/saeR system. Low nutrients increase expression of saeR, which augments expression of coa and fnbpA, distinct from the activity of AIP. The formation of spatial structure, such as biofilms, can alter quorum sensing and nutrient acquisition. In natural environments, biofilms encounter forces that may alter their spatial structure. These forces may impact quorum sensing and/or nutrient acquisition and thus affect the expression of agr-regulated virulence factors. However, this has not been studied. We show that periodically disturbing biofilms composed of S. aureus using a physical force affected the expression of agr-regulated virulence factors. In nutrient-poor environments, disturbance increased the expression of coa, fnbpA, lukS, and splA. Disturbance in a nutrient-rich environment at low or high disturbance amplitudes moderately reduced expression of coa and fnbpA but increased expression of lukS and splA. Interestingly, at an intermediate amplitude, the overall expression of agr-regulated virulence factors was the lowest; expression of lukS and splA remained unchanged relative to an undisturbed biofilm, while expression of coa and fnbpA significantly decreased. We hypothesize that these changes are a result of disturbance-driven changes in access to AIP and nutrients. Our results may allow the identification of environments where virulence is enhanced, or reduced, owing to a disturbance. IMPORTANCE Bacteria, such as Staphylococcus aureus, integrate signals from the environment to regulate genes encoding virulence factors. These signals include those produced by quorum-sensing systems and nutrient availability. We show that disturbing the spatial organization of S. aureus populations can lead to changes in the expression of virulence factors, likely by altering the ways in which S. aureus detects these signals. Our work may allow us to identify environments that increase or reduce the expression of virulence factors in S. aureus.

Case-control study of neuropsychiatric symptoms in electronic health records following COVID-19 hospitalization in 2 academic health systems.

Neuropsychiatric symptoms may persist following acute COVID-19 illness, but the extent to which these symptoms are specific to COVID-19 has not been established. We utilized electronic health records across 6 hospitals in Massachusetts to characterize cohorts of individuals discharged following admission for COVID-19 between March 2020 and May 2021, and compared them to individuals hospitalized for other indications during this period. Natural language processing was applied to narrative clinical notes to identify neuropsychiatric symptom domains up to 150 days following hospitalization, in addition to those reflected in diagnostic codes as measured in prior studies. Among 6619 individuals hospitalized for COVID-19 drawn from a total of 42,961 hospital discharges, the most commonly-documented symptom domains between 31 and 90 days after initial positive test were fatigue (13.4%), mood and anxiety symptoms (11.2%), and impaired cognition (8.0%). In regression models adjusted for sociodemographic features and hospital course, none of these were significantly more common among COVID-19 patients; indeed, mood and anxiety symptoms were less frequent (adjusted OR 0.72 95% CI 0.64-0.92). Between 91 and 150 days after positivity, most commonly-detected symptoms were fatigue (10.9%), mood and anxiety symptoms (8.2%), and sleep disruption (6.8%), with impaired cognition in 5.8%. Frequency was again similar among non-COVID-19 post-hospital patients, with mood and anxiety symptoms less common (aOR 0.63, 95% CI 0.52-0.75). Propensity-score matched analyses yielded similar results. Overall, neuropsychiatric symptoms were common up to 150 days after initial hospitalization, but occurred at generally similar rates among individuals hospitalized for other indications during the same period. Post-acute sequelae of COVID-19 may benefit from standard if less-specific treatments developed for rehabilitation after hospitalization.

Psychosis with Methylphenidate or Amphetamine in Patients with ADHD.

BACKGROUND: The prescription use of the stimulants methylphenidate and amphetamine for the treatment of attention deficit-hyperactivity disorder (ADHD) has been increasing. In 2007, the Food and Drug Administration mandated changes to drug labels for stimulants on the basis of findings of new-onset psychosis. Whether the risk of psychosis in adolescents and young adults with ADHD differs among various stimulants has not been extensively studied. METHODS: We used data from two commercial insurance claims databases to assess patients 13 to 25 years of age who had received a diagnosis of ADHD and who started taking methylphenidate or amphetamine between January 1, 2004, and September 30, 2015. The outcome was a new diagnosis of psychosis for which an antipsychotic medication was prescribed during the first 60 days after the date of the onset of psychosis. To estimate hazard ratios for psychosis, we used propensity scores to match patients who received methylphenidate with patients who received amphetamine in each database, compared the incidence of psychosis between the two stimulant groups, and then pooled the results across the two databases. RESULTS: We assessed 337,919 adolescents and young adults who received a prescription for a stimulant for ADHD. The study population consisted of 221,846 patients with 143,286 person-years of follow up; 110,923 patients taking methylphenidate were matched with 110,923 patients taking amphetamines. There were 343 episodes of psychosis (with an episode defined as a new diagnosis code for psychosis and a prescription for an antipsychotic medication) in the matched populations (2.4 per 1000 person-years): 106 episodes (0.10%) in the methylphenidate group and 237 episodes (0.21%) in the amphetamine group (hazard ratio with amphetamine use, 1.65; 95% confidence interval, 1.31 to 2.09). CONCLUSIONS: Among adolescents and young adults with ADHD who were receiving prescription stimulants, new-onset psychosis occurred in approximately 1 in 660 patients. Amphetamine use was associated with a greater risk of psychosis than methylphenidate. (Funded by the National Institute of Mental Health and others.).

Multiview Incomplete Knowledge Graph Integration with application to cross-institutional EHR data harmonization.

OBJECTIVE: The growing availability of electronic health records (EHR) data opens opportunities for integrative analysis of multi-institutional EHR to produce generalizable knowledge. A key barrier to such integrative analyses is the lack of semantic interoperability across different institutions due to coding differences. We propose a Multiview Incomplete Knowledge Graph Integration (MIKGI) algorithm to integrate information from multiple sources with partially overlapping EHR concept codes to enable translations between healthcare systems. METHODS: The MIKGI algorithm combines knowledge graph information from (i) embeddings trained from the co-occurrence patterns of medical codes within each EHR system and (ii) semantic embeddings of the textual strings of all medical codes obtained from the Self-Aligning Pretrained BERT (SAPBERT) algorithm. Due to the heterogeneity in the coding across healthcare systems, each EHR source provides partial coverage of the available codes. MIKGI synthesizes the incomplete knowledge graphs derived from these multi-source embeddings by minimizing a spherical loss function that combines the pairwise directional similarities of embeddings computed from all available sources. MIKGI outputs harmonized semantic embedding vectors for all EHR codes, which improves the quality of the embeddings and enables direct assessment of both similarity and relatedness between any pair of codes from multiple healthcare systems. RESULTS: With EHR co-occurrence data from Veteran Affairs (VA) healthcare and Mass General Brigham (MGB), MIKGI algorithm produces high quality embeddings for a variety of downstream tasks including detecting known similar or related entity pairs and mapping VA local codes to the relevant EHR codes used at MGB. Based on the cosine similarity of the MIKGI trained embeddings, the AUC was 0.918 for detecting similar entity pairs and 0.809 for detecting related pairs. For cross-institutional medical code mapping, the top 1 and top 5 accuracy were 91.0% and 97.5% when mapping medication codes at VA to RxNorm medication codes at MGB; 59.1% and 75.8% when mapping VA local laboratory codes to LOINC hierarchy. When trained with 500 labels, the lab code mapping attained top 1 and 5 accuracy at 77.7% and 87.9%. MIKGI also attained best performance in selecting VA local lab codes for desired laboratory tests and COVID-19 related features for COVID EHR studies. Compared to existing methods, MIKGI attained the most robust performance with accuracy the highest or near the highest across all tasks. CONCLUSIONS: The proposed MIKGI algorithm can effectively integrate incomplete summary data from biomedical text and EHR data to generate harmonized embeddings for EHR codes for knowledge graph modeling and cross-institutional translation of EHR codes.

Geometric Features Associated with Middle Cerebral Artery Bifurcation Aneurysm Formation: A Matched Case-Control Study.

OBJECTIVES: The pathogenesis of intracranial aneurysms is multifactorial and includes genetic, environmental, and anatomic influences. We aimed to identify image-based morphological parameters that were associated with middle cerebral artery (MCA) bifurcation aneurysms. MATERIALS AND METHODS: We evaluated three-dimensional morphological parameters obtained from CT angiography (CTA) or digital subtraction angiography (DSA) from 317 patients with unilateral MCA bifurcation aneurysms diagnosed at the Brigham and Women's Hospital and Massachusetts General Hospital between 1990 and 2016. We chose the contralateral unaffected MCA bifurcation as the control group, in order to control for genetic and environmental risk factors. Diameters and angles of surrounding parent and daughter vessels of 634 MCAs were examined. RESULTS: Univariable and multivariable statistical analyses were performed to determine statistical significance. Sensitivity analyses with smaller (≤ 3 mm) aneurysms only and with angles excluded, were also performed. In a multivariable conditional logistic regression model we showed that smaller diameter size ratio (OR 0.0004, 95% CI 0.0001-0.15), larger daughter-daughter angles (OR 1.08, 95% CI 1.06-1.11) and larger parent-daughter angle ratios (OR 4.24, 95% CI 1.77-10.16) were significantly associated with MCA aneurysm presence after correcting for other variables. In order to account for possible changes to the vasculature by the aneurysm, a subgroup analysis of small aneurysms (≤ 3 mm) was performed and showed that the results were similar. CONCLUSIONS: Easily measurable morphological parameters of the surrounding vasculature of the MCA may provide objective metrics to assess MCA aneurysm formation risk in high-risk patients.

Reasons for long-term tunneled dialysis catheter use and associated morbidity.

OBJECTIVE: Tunneled dialysis catheters (TDCs) are generally used as a temporary means to provide hemodialysis until permanent arteriovenous (AV) access is established. However, some patients may have long-term catheter-based hemodialysis because of the lack of alternatives for other dialysis access. Our objective was to evaluate characteristics of patients with, reasons for, and mortality associated with long-term TDC use. METHODS: A retrospective single-institution analysis was performed. Long-term TDC use was defined as >180 days without more than a 7-day temporary removal time. Reasons for long-term TDC use and complications were recorded. Summary statistics were performed. Kaplan-Meier analysis compared mortality between patients with long-term TDC use and a comparison cohort who underwent AV access creation with subsequent TDC removal. RESULTS: We identified 50 patients with long-term TDC use from 2013 to 2018. The average age was 63 years, 44% were male, and 76% were African American. Previous TDC use was found in 42% of patients with subsequent removal after alternative access was established. Median TDC duration was 333 days (range, 185-2029 days). The primary reasons for long-term TDC use were failed (occluded) AV access (34%), nonmaturing AV (nonoccluded) access (32%), delayed AV access placement (14%), no AV access options (10%), patient refusal for AV access placement (6%), and medically high risk for AV access placement (4%). In 46% of patients, TDC complications including central venous stenosis (33.4%), TDC-related infections (29.6%), TDC displacement (27.8%), and thrombosis (7.9%) occurred. Overall, 47.6% required a catheter exchange during the prolonged TDC period. The majority (76.4%) had the catheter removed because of established alternative access during follow-up. The long-term TDC group, in relation to the comparator group (n = 201), had fewer male patients (44% vs 61.2%; P = .028) and higher proportion of congestive heart failure (66% vs 40.3%; P = .001). Kaplan-Meier analysis showed no significant difference in survival at 24 months for the long-term TDC group compared with the comparator group (93.6% vs 92.7%; P = .28). CONCLUSIONS: Patients with long-term TDCs experienced significant TDC-related morbidity. Whereas permanent access is preferable, some patients may require long-term TDC use because of difficulty in establishing a permanent access, limited access options, and patient preference. There was no difference in survival between the groups.

Mechanistic Investigation of the Formation of Isoindole N-Oxides in the Electron Transfer-Mediated Oxidative Cyclization of 2'-Alkynylacetophenone Oximes.

This paper describes a joint experiment-theory investigation of the formation and cyclization of 2'-alkynylacetophenone oxime radical cations using photoinduced electron transfer (PET) with DCA as the photosensitizer. Using a combination of experimental 1H and 13C nuclear magnetic resonance (NMR) spectra, high-resolution mass spectrometry, and calculated NMR chemical shifts, we identified the products to be isoindole N-oxides. The reaction was found to be stereoselective; only one of the two possible stereoisomers is formed under these conditions. A detailed computational investigation of the cyclization reaction mechanism suggests facile C-N bond formation in the radical cation leading to a 5-exo intermediate. Back-electron transfer from the DCA radical anion followed by barrierless intramolecular proton transfer leads to the final product. We argue that the final proton transfer step in the mechanism is responsible for the stereoselectivity observed in experiment. As a whole, this work provides new insights into the formation of complex heterocycles through oxime and oxime ether radical cation intermediates produced via PET. Moreover, it represents the first reported formation of isoindole N-oxides.

Rationale and design of the rigorous atrial analysis in advanced interatrial block (ARABIA) prospective study.

BACKGROUND: Advanced interatrial block (IAB) is present in 10% of subjects ≥75 years and is associated with the risk of clinical events. METHODS AND RESULTS: Prospective multicenter study that will include subjects ≥75 years without exclusion criteria (indication for anticoagulation, cardiac devices, severe valve disease, systolic dysfunction, moderate or severe cognitive impairment, poor echocardiographic window, non-sinus rhythm or partial IAB, stroke, and life expectancy <2 years). A total of 356 subjects, 178 patients with advanced IAB (exposed) and 178 matched individuals with normal P-wave (non-exposed) will be included. Electrocardiogram and advanced transthoracic echocardiography will be performed. Two substudies will include magnetic resonance imaging: cardiac (86 subjects, 43 exposed, and 43 non-exposed) and brain (86 subjects, 43 exposed, and 43 non-exposed). The follow-up will be 2 years. Our main objective is to determine the association of advanced IAB, P-wave duration, and atrial imaging parameters (I] atrial global longitudinal strain, II] maximal left atrial volume index, III] left atrial ejection fraction, IV] left atrial fibrosis - % total left atrial area V] inter- and intra-atrial asynchrony/dyssynchrony) with clinical events (atrial fibrillation, stroke, cognitive impairment, and mortality). The secondary objective is to assess the association of the P-wave duration with atrial imaging parameters and of both with cerebral microemboli in magnetic resonance imaging. CONCLUSION: Our study will provide data regarding the association of advanced IAB, P-wave duration, and atrial imaging parameters with clinical events. We will also assess the association P-wave duration-atrial imaging parameters-cerebral microemboli.

The crystal structure of ESBL TLA-1 in complex with clavulanic acid reveals a second acylation site.

ß-lactamases are the main molecules responsible for giving bacterial resistance against ß-lactam antibiotics. The study of ß-lactamases has allowed the development of antibiotics capable of inhibiting these enzymes. In this context, extended spectrum ß-lactamase (ESBL) TLA-1 has spread in Escherichia coli and Enterobacter cloacae clinical isolates during the last 30 years in Mexico. In this research, the 3D structures of ESBL TLA-1 and TLA-1 S70G mutant, both ligand-free and in complex with clavulanic acid were determined by X-ray crystallography. Four clavulanic acid molecules were found in the structure of TLA-1, two of those were intermediaries of the acylation process and were localized covalently bound to two different amino acid residues, Ser70 and Ser237. The coordinates of TLA-1 in complex with clavulanic acid shows the existence of a second acylation site, additional to Ser70, which might be extendable to several members of the subclass A ß-lactamases family. This is the first time that two serines involved in binding clavulanic acid has been reported and described to an atomic level.

Octogenarians and Nonoctogenarians Have Similar Outcomes after Upper Extremity Hemodialysis Access Creation.

BACKGROUND: Routine arteriovenous (AV) access creation in octogenarians is controversial. Our goal was to assess perioperative and long-term outcomes in octogenarians after undergoing upper extremity AV access to determine whether advanced age should influence AV access decision-making. METHODS: All AV access creations performed at a single institution from 2014-2018 were retrospectively reviewed. Patients were categorized as octogenarians and nonoctogenarians. Perioperative short-term outcomes were compared. RESULTS: Among 620 patients who underwent AV access creation, there were 40 octogenarians and 580 nonoctogenarians. Octogenarians were more likely to have private insurance, coronary artery disease, dementia, previous stroke, impaired ambulation, and less likely to be current smokers. There were no differences in outpatient status or tunneled dialysis catheter presence at creation. Access types were similar radiocephalic (12.5% vs. 14.3%), brachiocephalic (50% vs. 42.6%), brachiobasilic (12.5% vs. 26.2%), and grafts (25% vs. 13.8%). Univariable analysis demonstrated no differences in perioperative return to the operating room, hematoma, and patency loss. There were no differences in 90-day mortality (OR 0.46, 95% CI 0-2.5, P = 0.25), readmission (OR 1.36, 95% CI 0.67-2.76, P = 0.39), maturation (OR 0.97, 95% CI 0.46-2.01, P = 0.93), or reintervention (HR 0.9, 95% CI 0.64-1.25, P = 0.53). Octogenarians had lower two-year survival (82.5% vs. 91.9%, P < 0.001), but there was no difference in reintervention-free survival (55% vs. 47%, P = 0.47) or occlusion-free survival (25% vs. 24%, P = 0.62). CONCLUSIONS: Octogenarians and nonoctogenarians have similar outcomes after upper extremity dialysis access creation. Advanced age alone should not influence dialysis access creation.

Social capital is associated with lower mosquito vector indices: secondary analysis from a cluster randomised controlled trial of community mobilisation for dengue prevention in Mexico.

BACKGROUND: Control of the Aedes aegypti mosquito is central to reducing the risk of dengue, zika, chikungunya, and yellow fever. Randomised controlled trials, including the Camino Verde trial in Mexico and Nicaragua, demonstrate the convincing impact of community mobilisation interventions on vector indices. These interventions might work through building social capital but little is known about the relationship between social capital and vector indices. METHODS: A secondary analysis used data collected from 45 intervention clusters and 45 control clusters in the impact survey of the Mexican arm of the Camino Verde cluster randomised controlled trial. Factor analysis combined responses to questions about aspects of social capital to create a social capital index with four constructs, their weighted averages then combined into a single scale. We categorised households as having high or low social capital based on their score on this scale. We examined associations between social capital and larval and pupal vector indices, taking account of the effects of other variables in a multivariate analysis. We report associations as odds ratios and 95% confidence intervals. RESULTS: The four social capital constructs were involvement, participation, investment, and communication. Among the 10,112 households, those in rural communities were much more likely to have a high social capital score (OR 4.51, 95% CIca 3.26-6.26). Households in intervention sites had higher social capital, although the association was not significant at the 5% level. Households with high social capital were more likely to be negative for larvae or pupae (OR 1.38, 95% CIca 1.12-1.69) and for pupae specifically (OR 1.37, 95% CIca 1.08-1.74). There was interaction between intervention status and social capital; in multivariate analysis, a combined variable of intervention/high social capital remained associated with larvae or pupae (ORa l.56, 95% CIca 1.19-2.04) and with pupae specifically (ORa 1.65, 95% CIca 1.20-2.28). CONCLUSION: This is the first report of an association of high social capital with low vector indices. Our findings support the idea that the Camino Verde community mobilisation intervention worked partly through an interaction with social capital. Understanding such interactions may help to maximise the impact of future community mobilisation interventions.

Elevated International Normalized Ratio Is Associated With Ruptured Aneurysms.

Background and Purpose- The effects of anticoagulation therapy and elevated international normalized ratio (INR) values on the risk of aneurysmal subarachnoid hemorrhage are unknown. We aimed to investigate the association between anticoagulation therapy, elevated INR values, and rupture of intracranial aneurysms. Methods- We conducted a case-control study of 4696 patients with 6403 intracranial aneurysms, including 1198 prospective patients, diagnosed at the Massachusetts General Hospital and the Brigham and Women's Hospital between 1990 and 2016 who were on no anticoagulant therapy or on warfarin for anticoagulation. Patients were divided into ruptured and nonruptured groups. Univariable and multivariable logistic regression analyses were performed to evaluate the association of anticoagulation therapy, INR values, and presentation with a ruptured intracranial aneurysm, taking into account the interaction between anticoagulant use and INR. Inverse probability weighting using propensity scores was used to minimize differences in baseline demographics characteristics. The marginal effects of anticoagulant use on rupture risk stratified by INR values were calculated. Results- In unweighted and weighted multivariable analyses, elevated INR values were significantly associated with rupture status among patients who were not anticoagulated (unweighted odds ratio, 22.78; 95% CI, 10.85-47.81 and weighted odds ratio, 28.16; 95% CI, 12.44-63.77). In anticoagulated patients, warfarin use interacts significantly with INR when INR ≥1.2 by decreasing the effects of INR on rupture risk. Conclusions- INR elevation is associated with intracranial aneurysm rupture, but the effects may be moderated by warfarin. INR values should, therefore, be taken into consideration when counseling patients with intracranial aneurysms.

Antihyperglycemic Agents Are Inversely Associated With Intracranial Aneurysm Rupture.

BACKGROUND AND PURPOSE: Previous studies have suggested a protective effect of diabetes mellitus on aneurysmal subarachnoid hemorrhage risk. However, reports are inconsistent, and objective measures of hyperglycemia in these studies are lacking. Our aim was to investigate the association between aneurysmal subarachnoid hemorrhage and antihyperglycemic agent use and glycated hemoglobin levels. METHODS: The medical records of 4701 patients with 6411 intracranial aneurysms, including 1201 prospective patients, diagnosed at the Massachusetts General Hospital and Brigham and Women's Hospital between 1990 and 2016 were reviewed and analyzed. Patients were separated into ruptured and nonruptured groups. Univariate and multivariate logistic regression analyses were performed to determine the association between aneurysmal subarachnoid hemorrhage and antihyperglycemic agents and glycated hemoglobin levels. Propensity score weighting was used to account for selection bias. RESULTS: In both unweighted and weighted multivariate analysis, antihyperglycemic agent use was inversely and significantly associated with ruptured aneurysms (unweighted odds ratio, 0.58; 95% confidence interval, 0.39-0.87; weighted odds ratio, 0.57; 95% confidence interval, 0.34-0.96). In contrast, glycated hemoglobin levels were not significantly associated with rupture status. CONCLUSIONS: Antihyperglycemic agent use rather than hyperglycemia is associated with decreased risk of aneurysmal subarachnoid hemorrhage, suggesting a possible protective effect of glucose-lowering agents in the pathogenesis of aneurysm rupture.

Low Serum Calcium and Magnesium Levels and Rupture of Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Both low serum calcium and magnesium levels have been associated with the extent of bleeding in patients with intracerebral hemorrhage, suggesting hypocalcemia- and hypomagnesemia-induced coagulopathy as a possible underlying mechanism. We hypothesized that serum albumin-corrected total calcium and magnesium levels are associated with ruptured intracranial aneurysms. METHODS: The medical records of 4701 patients, including 1201 prospective patients, diagnosed at the Brigham and Women's Hospital and Massachusetts General Hospital between 1990 and 2016 were reviewed and analyzed. One thousand two hundred seventy-five patients had available serum calcium, magnesium, and albumin values within 1 day of diagnosis. Individuals were divided into cases with ruptured aneurysms and controls with unruptured aneurysms. Univariable and multivariable logistic regression analyses were performed to determine the association between serum albumin-corrected total calcium and magnesium levels and ruptured aneurysms. RESULTS: In multivariable analysis, both albumin-corrected calcium (odds ratio, 0.33; 95% confidence interval, 0.27-0.40) and magnesium (odds ratio, 0.40; 95% confidence interval, 0.28-0.55) were significantly and inversely associated with ruptured intracranial aneurysms. CONCLUSIONS: In this large case-control study, hypocalcemia and hypomagnesemia at diagnosis were significantly associated with ruptured aneurysms. Impaired hemostasis caused by hypocalcemia and hypomagnesemia may explain this association.