Publisher Correction: Modular and tunable biological feedback control using a de novo protein switch.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Material assembly from collective action of shape-changing polymers.

Some animals form transient, responsive and solid-like ensembles through dynamic structural interactions. These ensembles demonstrate emergent responses such as spontaneous self-assembly, which are difficult to achieve in synthetic soft matter. Here we use shape-morphing units comprising responsive polymers to create solids that self-assemble, modulate their volume and disassemble on demand. The ensemble is composed of a responsive hydrogel, liquid crystal elastomer or semicrystalline polymer ribbons that reversibly bend or twist. The dispersions of these ribbons mechanically interlock, inducing reversible aggregation. The aggregated liquid crystal elastomer ribbons have a 12-fold increase in the yield stress compared with cooled dispersion and contract by 34% on heating. Ribbon type, concentration and shape dictate the aggregation and govern the global mechanical properties of the solid that forms. Coating liquid crystal elastomer ribbons with a liquid metal begets photoresponsive and electrically conductive aggregates, whereas seeding cells on hydrogel ribbons enables self-assembling three-dimensional scaffolds, providing a versatile platform for the design of dynamic materials.

Chemoproteomic identification of a DPP4 homolog in Bacteroides thetaiotaomicron.

Serine hydrolases have important roles in signaling and human metabolism, yet little is known about their functions in gut commensal bacteria. Using bioinformatics and chemoproteomics, we identify serine hydrolases in the gut commensal Bacteroides thetaiotaomicron that are specific to the Bacteroidetes phylum. Two are predicted homologs of the human dipeptidyl peptidase 4 (hDPP4), a key enzyme that regulates insulin signaling. Our functional studies reveal that BT4193 is a true homolog of hDPP4 that can be inhibited by FDA-approved type 2 diabetes medications targeting hDPP4, while the other is a misannotated proline-specific triaminopeptidase. We demonstrate that BT4193 is important for envelope integrity and that loss of BT4193 reduces B. thetaiotaomicron fitness during in vitro growth within a diverse community. However, neither function is dependent on BT4193 proteolytic activity, suggesting a scaffolding or signaling function for this bacterial protease.

Modular and tunable biological feedback control using a de novo protein switch.

De novo-designed proteins1-3 hold great promise as building blocks for synthetic circuits, and can complement the use of engineered variants of natural proteins4-7. One such designer protein-degronLOCKR, which is based on 'latching orthogonal cage-key proteins' (LOCKR) technology8-is a switch that degrades a protein of interest in vivo upon induction by a genetically encoded small peptide. Here we leverage the plug-and-play nature of degronLOCKR to implement feedback control of endogenous signalling pathways and synthetic gene circuits. We first generate synthetic negative and positive feedback in the yeast mating pathway by fusing degronLOCKR to endogenous signalling molecules, illustrating the ease with which this strategy can be used to rewire complex endogenous pathways. We next evaluate feedback control mediated by degronLOCKR on a synthetic gene circuit9, to quantify the feedback capabilities and operational range of the feedback control circuit. The designed nature of degronLOCKR proteins enables simple and rational modifications to tune feedback behaviour in both the synthetic circuit and the mating pathway. The ability to engineer feedback control into living cells represents an important milestone in achieving the full potential of synthetic biology10,11,12. More broadly, this work demonstrates the large and untapped potential of de novo design of proteins for generating tools that implement complex synthetic functionalities in cells for biotechnological and therapeutic applications.

De novo design of bioactive protein switches.

Allosteric regulation of protein function is widespread in biology, but is challenging for de novo protein design as it requires the explicit design of multiple states with comparable free energies. Here we explore the possibility of designing switchable protein systems de novo, through the modulation of competing inter- and intramolecular interactions. We design a static, five-helix 'cage' with a single interface that can interact either intramolecularly with a terminal 'latch' helix or intermolecularly with a peptide 'key'. Encoded on the latch are functional motifs for binding, degradation or nuclear export that function only when the key displaces the latch from the cage. We describe orthogonal cage-key systems that function in vitro, in yeast and in mammalian cells with up to 40-fold activation of function by key. The ability to design switchable protein functions that are controlled by induced conformational change is a milestone for de novo protein design, and opens up new avenues for synthetic biology and cell engineering.

Interacting pest control and pollination services in coffee systems.

Biodiversity-mediated ecosystem services (ES) support human well-being, but their values are typically estimated individually. Although ES are part of complex socioecological systems, we know surprisingly little about how multiple ES interact ecologically and economically. Interactions could be positive (synergy), negative (trade-offs), or absent (additive effects), with strong implications for management and valuation. Here, we evaluate the interactions of two ES, pollination and pest control, via a factorial field experiment in 30 Costa Rican coffee farms. We found synergistic interactions between these two critical ES to crop production. The combined positive effects of birds and bees on fruit set, fruit weight, and fruit weight uniformity were greater than their individual effects. This represents experimental evidence at realistic farm scales of positive interactions among ES in agricultural systems. These synergies suggest that assessments of individual ES may underestimate the benefits biodiversity provides to agriculture and human well-being. Using our experimental results, we demonstrate that bird pest control and bee pollination services translate directly into monetary benefits to coffee farmers. Excluding both birds and bees resulted in an average yield reduction of 24.7% (equivalent to losing US$1,066.00/ha). These findings highlight that habitat enhancements to support native biodiversity can have multiple benefits for coffee, a valuable crop that supports rural livelihoods worldwide. Accounting for potential interactions among ES is essential to quantifying their combined ecological and economic value.

Competitive fitness of asymptomatic bacteriuria E. coli strain 83972 against uropathogens in human urine.

Urinary tract infection (UTI) is one of the most common bacterial infections worldwide. The main causative agent of UTI is uropathogenic Escherichia coli (UPEC). There is an immediate need for novel prophylactic and treatment strategies against UTI because of the increasing incidence of antimicrobial resistance among uropathogens. ABU 83972, an asymptomatic bacteriuria-causing E. coli strain, prevents UTI by suppressing the colonization of UPEC. However, the nature of competition and growth repression of UPEC by ABU 83972 is unclear and is the subject of our investigation. Here, we characterized the growth kinetics of ABU 83972 and uropathogens in human urine and laboratory media. Next, we performed a series of competitive co-culture experiments where ABU 83972 and uropathogens were inoculated at a 1:1 ratio in human urine and in various media, and their relative abundance was determined. In human urine, ABU 83972 outcompeted UPEC and additional uropathogens, reaching up to 90% of the total population after 24 hours of incubation. In contrast, UPEC outcompeted ABU 83972 in LB and M9 minimal media and exhibited superior colonization than ABU 83972 in the mouse urinary bladder. Since engineered living materials (ELMs) can be used to retain an organism of interest in a particular location, we developed ABU 83972-containing ELMs that effectively outcompeted UPEC in human urine. In summary, our work establishes that ABU 83972 outcompetes UPEC in a milieu- and cell-density-dependent manner, highlighting the importance of the metabolites and nutrients found in the human urine as determinants of the competitive fitness of ABU 83972.

Three-dimensional blueprinting of molecular patterns in liquid crystalline polymers.

Exploiting the interplay of anisotropic diamagnetic susceptibility of liquid crystalline monomers and site selective photopolymerization enables the fabrication of 3D freeforms with highly refined microstructures. Utilizing chain transfer agents in the mesogenic inks presents a pathway for broadly tuning the mechanical properties of liquid crystalline polymers and their response to stimuli. In particular, the combination of 1,4-benzenedimethanethiol and tetrabromomethane is shown to enable voxelated blueprinting of molecular order, while allowing for a modulation of the crosslink density and the mechanical properties. The formulation of these monomers allows for the resolution of the voxels to approach the limits set by the coherence lengths defined by the anchoring from surfaces. These compositions demonstrate the expected thermotropic responses while allowing for their functionalization with photochromic switches to elicit photomechanical responses. Actuation strains are shown to outstrip that accomplished with prior systems that did not access chain transfer agents to modulate the structure of the macromolecular network. Test cases of this system are shown to create freeform actuators that exploit the refined director patterns during high-resolution printing. These include topological defects, hierarchically-structured light responsive grippers, and biomimetic flyers whose flight dynamics can be actively modulated via irradiation with light.

Recovery trajectories of IQ after pediatric TBI: A latent class growth modeling analysis.

OBJECTIVE: To identify latent trajectories of IQ over time after pediatric traumatic brain injury (TBI) and examine the predictive value of risk factors within and across recovery trajectories. METHOD: 206 children ages 3-7 years at injury were included: 87 TBI (23 severe, 21 moderate, 43 complicated mild) and 119 orthopedic injury (OI). We administered intelligence tests shortly after injury (1½ months), 12 months, and 6.8 years postinjury. Latent class growth modeling was used to identify latent subgroups. Separate models examined verbal and nonverbal IQ recovery trajectories following TBI versus OI. Variables included: age at injury, sex, race, socioeconomic status, injury severity, quality of the home environment, family functioning, and parenting style. RESULTS: Both the TBI and OI analyses yielded different growth models for nonverbal (k = 3) and verbal IQ (k = 3). Although all models resulted in 3 latent classes (below average, average, and aboveaverage performance); trajectory shapes, contributors to class membership, and performance within each class varied by injury group and IQ domain. TBI severity was associated with class membership for nonverbal IQ, with less severe injuries associated with higher IQ scores; however, TBI severity did not influence verbal IQ class membership. Parenting style had a more prominent effect on verbal and nonverbal IQ within the TBI than OI trajectories. CONCLUSIONS: Findings suggest TBI severity is related to recovery trajectories for nonverbal but not verbal IQ and parenting style has stronger effects on recovery in TBI than OI. Results highlight the importance of parental factors on long-term recovery after TBI.

Cutting Edge: Bispecific γδ T Cell Engager Containing Heterodimeric BTN2A1 and BTN3A1 Promotes Targeted Activation of Vγ9Vδ2+ T Cells in the Presence of Costimulation by CD28 or NKG2D.

Vγ9Vδ2+ T cell-targeted immunotherapy is of interest to harness its MHC-independent cytotoxic potential against a variety of cancers. Recent studies have identified heterodimeric butyrophilin (BTN) 2A1 and BTN3A1 as the molecular entity providing "signal 1" to the Vγ9Vδ2 TCR, but "signal 2" costimulatory requirements remain unclear. Using a tumor cell-free assay, we demonstrated that a BTN2A1/3A1 heterodimeric fusion protein activated human Vγ9Vδ2+ T cells, but only in the presence of costimulatory signal via CD28 or NK group 2 member D. Nonetheless, addition of a bispecific γδ T cell engager BTN2A1/3A1-Fc-CD19scFv alone enhanced granzyme B-mediated killing of human CD19+ lymphoma cells when cocultured with Vγ9Vδ2+ T cells, suggesting expression of costimulatory ligand(s) on tumor cells is sufficient to satisfy the "signal 2" requirement. These results highlight the parallels of signal 1 and signal 2 requirements in αß and γδ T cell activation and demonstrate the utility of heterodimeric BTNs to promote targeted activation of γδ T cells.

LIGHT (TNFSF14) Costimulation Enhances Myeloid Cell Activation and Antitumor Immunity in the Setting of PD-1/PD-L1 and TIGIT Checkpoint Blockade.

Coinhibition of TIGIT (T cell immunoreceptor with Ig and ITIM domains) and PD-1/PD-L1 (PD-1/L1) may improve response rates compared with monotherapy PD-1/L1 blockade in checkpoint naive non-small cell lung cancer with PD-L1 expression >50%. TIGIT mAbs with an effector-competent Fc can induce myeloid cell activation, and some have demonstrated effector T cell depletion, which carries a clinical liability of unknown significance. TIGIT Ab blockade translates to antitumor activity by enabling PVR signaling through CD226 (DNAM-1), which can be directly inhibited by PD-1. Furthermore, DNAM-1 is downregulated on tumor-infiltrating lymphocytes (TILs) in advanced and checkpoint inhibition-resistant cancers. Therefore, broadening clinical responses from TIGIT blockade into PD-L1low or checkpoint inhibition-resistant tumors, may be induced by immune costimulation that operates independently from PD-1/L1 inhibition. TNFSF14 (LIGHT) was identified through genomic screens, in vitro functional analysis, and immune profiling of TILs as a TNF ligand that could provide broad immune activation. Accordingly, murine and human bifunctional fusion proteins were engineered linking the extracellular domain of TIGIT to the extracellular domain of LIGHT, yielding TIGIT-Fc-LIGHT. TIGIT competitively inhibited binding to all PVR ligands. LIGHT directly activated myeloid cells through interactions with LTßR (lymphotoxin ß receptor), without the requirement for a competent Fc domain to engage Fcγ receptors. LIGHT costimulated CD8+ T and NK cells through HVEM (herpes virus entry mediator A). Importantly, HVEM was more widely expressed than DNAM-1 on T memory stem cells and TILs across a range of tumor types. Taken together, the mechanisms of TIGIT-Fc-LIGHT promoted strong antitumor activity in preclinical tumor models of primary and acquired resistance to PD-1 blockade, suggesting that immune costimulation mediated by LIGHT may broaden the clinical utility of TIGIT blockade.

Implementation of a perioperative registry in Ethiopia to enhance surgical quality improvement.

BACKGROUND: Despite a glaring need and proven efficacy, prospective surgical registries are lacking in low- and middle-income countries. The objective of this study was to design and implement a comprehensive prospective perioperative registry in a low-income country. METHODS: This study was conducted at Hawassa University Comprehensive Specialized Hospital in Hawassa, Ethiopia. Design of the registry occurred from June 2021 to May 2022 and pilot implementation from May 2022 to May 2023. All patients undergoing elective or emergent general surgery were included. Following one year, operability and fidelity of the registry were analyzed by assessing capture rate, incidence of missing data, and accuracy. RESULTS: A total of 67 variables were included in the registry including demographics, preoperative, operative, post-operative, and 30-day data. Of 440 eligible patients, 226 (51.4%) were successfully captured. Overall incidence of missing data and accuracy was 5.4% and 90.2% respectively. Post pilot modifications enhanced capture rate to 70.5% and further optimized data collection processes. CONCLUSION: The establishment of a low-cost electronic prospective perioperative registry in a low-income country represents a significant step forward in enhancing surgical care in under-resourced settings. The initial success of this registry highlights the feasibility of such endeavors when strong partnerships and local context are at the center of implementation. Continuous efforts to refine this registry are ongoing, which will ultimately lead to enhanced surgical quality, research output, and expansion to other sites.

Impact of emergency medicine clinical pharmacist practitioner-driven sepsis antibiotic interventions.

BACKGROUND: The 2021 Surviving Sepsis Campaign Guidelines recommend administration of antimicrobials within the first hour of recognition of sepsis. Over the last decade, several studies have demonstrated improved time-to-antibiotic administration and antibiotic appropriateness when a pharmacist was involved in the care of patients with sepsis. To our knowledge, no studies evaluating the appropriate use of antibiotics in sepsis driven entirely by an Emergency Medicine (EM) Clinical Pharmacist Practitioner (CPP) have been published. The purpose of this study is to evaluate the impact of an EM CPP-driven protocol on antimicrobial interventions in patients with sepsis in the emergency department (ED). METHODS: This was a retrospective comparison of patients with sepsis for whom antimicrobials were ordered in the ED without pharmacist intervention to patients whose antimicrobials were ordered by an EM CPP via a sepsis consult to pharmacy. An EM CPP reviewed individual patient profiles for pertinent historical admissions, culture data, and allergy profiles to guide antimicrobial selection for the suspected source of infection and entered orders under their scope of practice with formal documentation in the electronic medical record (EMR). The primary objective of this study was to compare the rates of appropriate empiric antibiotic utilization in septic patients admitted from the ED pre- and post-protocol implementation. Secondary endpoints included the following, broadening of ED-initiated empiric antibiotics on hospital admission, time-to-antibiotic administration, in-hospital mortality, Rapid Emergency Medicine Score (REMS) association with in-hospital mortality, and hospital length of stay. RESULTS: A total of 144 patients were included: 80 patients prescribed antibiotics without pharmacist intervention and 64 prescribed antibiotics by an EM CPP. Appropriate empiric antibiotic selection in the ED improved from 57.5% (46/80) to 86% (55/64) with EM CPP intervention (difference 28.5%; p < 0.01). Time-to-first antibiotic administration decreased by 64 min (p < 0.01). Administration of antibiotics within 60 min, broadening of antibiotics on admission, hospital length of stay, and in-hospital mortality did not significantly differ across groups. CONCLUSIONS: In this small, single-center study, an EM Clinical Pharmacist Practitioner-driven protocol for patients with sepsis in the emergency department improved the rate of appropriate empiric antimicrobial selection and time-to-antibiotic administration.

Trajectories of Daily Postconcussion Symptoms in Children.

OBJECTIVES: To identify trajectories of daily postconcussion symptoms (PCS) from the acute postinjury period to symptom resolution among concussed children and examine demographic factors and acute PCS associated with the identified symptom trajectories. SETTING AND PARTICIPANTS: Seventy-nine participants with a concussion were enrolled within 72 hours of injury and completed a daily survey that assessed PCS from enrollment until symptom resolution. DESIGN: This was a prospective cohort study among concussed children aged 11-17 years. MAIN MEASURES: Children rated their concussion symptoms daily using the Post-Concussion Symptom Scale. Symptom duration was assessed using participants' date of symptom resolution and coded as a dichotomous variable: (1) PCS duration 14 days or less or (2) PCS duration longer than 14 days. RESULTS: Of the 79 participants, most were male ( n = 53, 67%), injured during a sporting activity ( n = 67, 85%), or had PCS that persisted for more than 14 days post-injury ( n = 41, 52%). Group-based trajectory modeling yielded 4 trajectory groups: (1) low acute/resolved PCS ( n = 39, 49%), (2) moderate/persistent PCS ( n = 19, 24%), (3) high acute/persistent PCS ( n = 13, 16%), and (4) high acute/resolved PCS ( n = 8, 10%). No significant associations were found between demographic factors and the trajectory group. A higher symptom burden at injury was associated with an increased odds of being in the high acute/resolved or high acute/persistent recovery groups than being in the low acute/resolved group (odds ratio [OR] 1.39, 95% CI = 1.11-1.74; OR = 1.33, 95% CI = 1.11-1.60, respectively), as was a higher symptom severity at injury (OR = 1.09, 95% CI = 1.03-1.15; OR = 1.06, 95% CI = 1.02-1.11, respectively). CONCLUSION: Our findings may help clinicians identify concussed children on slower recovery trajectories, and implement early, individualized treatment plans that foster optimal recovery for concussed children.

Long-Term Outcomes of Pediatric Traumatic Brain Injury Following Inpatient Rehabilitation.

OBJECTIVE: Assess residual disability in youth with traumatic brain injury (TBI) treated in a pediatric inpatient rehabilitation unit and examine associations of disability with inpatient status and measures of concurrent functioning. SETTING: Large, urban, quaternary care children's hospital in the Midwestern United States. PARTICIPANTS: Forty-five youth aged 6 to 18 years treated in an inpatient rehabilitation unit for mild-complicated to severe TBI at a minimum of 12 months postdischarge (mean = 3.5 years). DESIGN: Retrospective chart review of clinical data collected from standard clinical care at admission and discharge combined with follow-up data examining current functioning at the time of study enrollment. MAIN OUTCOME MEASURES: Glasgow Outcome Scale-Extended, Pediatric Revision (GOS-E Peds), Neurology Quality of Life Measurement System Short Form (NeuroQOL) Social Interaction with Peers and Cognitive Short Forms, Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale, Strengths and Difficulties Questionnaire, and the Behavior Rating Inventory of Executive Function, 2nd Edition (BRIEF-2). RESULTS: Based on parent report at follow-up, 62% of the children had residual TBI-related disabilities on the GOS-E Peds, while 38% reported "good recovery." Children with residual disability also reported more long-term problems in overall health, social relationships, emotional regulation, behaviors, and executive functioning than those with no residual disability. Measures of functional independence and cognitive recovery at discharge were associated with these impairments. CONCLUSIONS: More than half of the children with TBI in this study had residual disability more than 1 year after inpatient rehabilitation. Findings highlight the associations between measures of functional independence and cognitive recovery during inpatient rehabilitation with later outcomes and underscore the need for continued services to support the needs of children with TBI following their inpatient rehabilitation stay.

School Readiness in Preschool-Age Children with Critical Congenital Heart Disease.

This study examined the nature, variability, and predictors of school readiness difficulties in young children with critical congenital heart disease (CCHD). We hypothesized that, compared to a community control (CC) group, children with CCHD would score less well on measures of readiness and that readiness would be associated with CCHD-related risk factors. Children (60 CCHD and 60 CC) were 4 to 5 years of age and not yet attending kindergarten. Readiness measures included tests of cognition, executive function, motor ability, and pre-academic skills. Caregivers provided child behavior ratings. Analyses examined group differences in readiness, readiness profiles, and associations of readiness with CCHD-related medical risk factors. The CCHD group had lower scores than the CC group on testing and higher caregiver ratings of problems in social communication, as well as higher rates of deficits on several of the measures. Latent class analysis provided evidence for different readiness profiles, with more children with CCHD displaying profiles characterized by weaknesses in readiness. CCHD-related medical risk factors associated with readiness problems in the CCHD group included a co-morbid genetic disorder, postnatal diagnosis of CCHD, major perioperative complication, and longer periods of hospitalizations, cardiopulmonary bypass, and aortic cross-clamp placements. Findings document multiple problems in school readiness in young children with CCHD. Deficits vary across individuals and are associated with higher medical risk. Results confirm the importance of screening for school readiness in these children and suggest areas to target in designing screening measures and providing early childhood interventions.

Ulcerative stomatitis associated with yellow bristle grass in New Zealand dairy cows.

CASE HISTORY: A line of 25 cull cows were all found to have ulcerative lesions of the tongue at post-mortem inspection in a New Zealand slaughter plant. A further 9 of 10 cows inspected at the farm of origin had similar oral lesions. There were no other clinical signs or indicators of ill-health observed at ante-mortem inspection in the abattoir or on the farm. The cows had been fed baleage for 3 weeks prior to slaughter, made from pasture in paddocks heavily contaminated with yellow bristle grass (Setaria pumila). CLINICAL FINDINGS: There was extensive and deep transverse linear ulceration in the lingual fossa immediately rostral to the torus linguae. At histological examination, full-thickness ulceration of the stratified squamous epithelium was observed with a bed of disorganised collagenous tissue and extensive mixed inflammatory infiltrate extending into the sub-epithelial connective tissue and skeletal muscle. Barbed plant fragments were embedded in both the superficial and deeper areas of inflammation. Detailed examination of the baleage also found that yellow bristle grass seedheads were present. DIAGNOSIS: Based on the presence of barbed plant material in the tongue and yellow bristle grass seeds in the baleage, a diagnosis of ulcerative stomatitis associated with yellow bristle grass was made. CLINICAL RELEVANCE: Clinicians should be aware of the potential for hay or baleage contaminated with yellow bristle grass to cause oral lesions in cattle.

Self-Assembled Microactuators Using Chiral Liquid Crystal Elastomers.

Materials that undergo reversible changes in form typically require top-down processing to program the microstructure of the material. As a result, it is difficult to program microscale, 3D shape-morphing materials that undergo non-uniaxial deformations. Here, a simple bottom-up fabrication approach to prepare bending microactuators is described. Spontaneous self-assembly of liquid crystal (LC) monomers with controlled chirality within 3D micromold results in a change in molecular orientation across thickness of the microstructure. As a result, heating induces bending in these microactuators. The concentration of chiral dopant is varied to adjust the chirality of the monomer mixture. Liquid crystal elastomer (LCE) microactuators doped with 0.05 wt% of chiral dopant produce needle-shaped actuators that bend from flat to an angle of 27.2 ± 11.3° at 180 °C. Higher concentrations of chiral dopant lead to actuators with reduced bending, and lower concentrations of chiral dopant lead to actuators with poorly controlled bending. Asymmetric molecular alignment inside 3D structure is confirmed by sectioning actuators. Arrays of microactuators that all bend in the same direction can be fabricated if symmetry of geometry of the microstructure is broken. It is envisioned that the new platform to synthesize microstructures can further be applied in soft robotics and biomedical devices.

Do Bayley-III Composite Scores at 18-22 Months Corrected Age Predict Full-Scale IQ at 6-7 Years in Children Born Extremely Preterm?

OBJECTIVE: To determine the ability of the Bayley-III cognitive and language composite scores at 18-22 months corrected age to predict WISC-IV Full Scale IQ (FSIQ) at 6-7 years in infants born extremely preterm. STUDY DESIGN: Children in this study were part of the Neuroimaging and Neurodevelopmental Outcome cohort, a secondary study to the SUPPORT trial and born 240/7-276/7 weeks gestational age. Bayley-III cognitive and language scores and WISC-IV FSIQ were compared with pairwise Pearson correlation coefficients and adjusted for medical and socioeconomic variables using linear mixed effect regression models. RESULTS: Bayley-III cognitive (r = 0.33) and language scores (r = 0.44) were mildly correlated with WISC-IV FSIQ score. Of the children with Bayley-III cognitive scores of <70, 67% also had FSIQ of <70. There was less consistency for children with Bayley-III scores in the 85-100 range; 43% had an FSIQ of <85 and 10% an FSIQ of <70. Among those with Bayley-III language scores >100, approximately 1 in 5 had an FSIQ of <85. A cut point of 92 for the cognitive composite score resulted in sensitivity (0.60), specificity (0.64). A cut point of 88 for the language composite score produced sensitivity (0.61), specificity (0.70). CONCLUSIONS: Findings indicate the Bayley-III cognitive and language scores correlate with later IQ, but may fail to predict delay or misclassify children who are not delayed at school age. The Bayley-III can be a useful tool to help identify children born extremely preterm who have below average cognitive scores and may be at the greatest risk for ongoing cognitive difficulties. TRIAL REGISTRATION: Extended Follow-up at School Age for the SUPPORT Neuroimaging and Neurodevelopmental Outcomes (NEURO) Cohort: NCT00233324.

Genotyping of dengue virus from infected tissue samples embedded in paraffin.

Dengue has become one of the vector-borne diseases that affect humans worldwide. In Latin American countries, Colombia is historically one of the most affected by epidemics of this flavivirus. The underreporting of signs and symptoms of probable cases of dengue, the lack of characterization of the serotypes of the infection, and the few detailed studies of postmortem necropsies of patients are among other conditions that have delayed progress in the knowledge of the pathogenesis of the disease. This study presents the results of fragment sequencing assays on paraffin-embedded tissue samples from fatal DENV cases during the 2010 epidemic in Colombia. We found that the predominant serotype was DENV-2, with the Asian/American genotype of lineages 1 and 2. This work is one of the few reports of the circulating genotypes of dengue during the 2010 epidemic in Colombia, one of the most lethal dates in the country's history.