Clinical Impact of 3- versus 5-Minute Delay and 30- versus 60-Second Intervals on Unattended Automated Office Blood Pressure Measurements.

BACKGROUND: Guidelines advise automated office blood pressure (AOBP) with an initial 5-minute delay and multiple measurements at least 60 seconds apart. Recent studies suggest that AOBP may be accurate with shorter delays or intervals, but evidence in clinical settings is limited. METHODS: Patients referred to one hypertension (HTN) center underwent 24-hour ambulatory blood pressure monitoring (ABPM) and one of four non-randomized, unattended AOBP protocols: a 3- or 5-minute delay with a 30 or 60-second interval, i.e., 3 min/30 sec/30 sec, 3/60/60, 5/30/30 and 5/60/60 protocols. HTN was defined as systolic blood pressure ≥140 or diastolic blood pressure ≥90 mmHg. RESULTS: We compared differences in mean blood pressure and HTN classification between average AOBP and awake-time ABPM by t-tests and Fisher's exact test. Among 212 participants (mean 58.9 years, 61% women, 25% Black), there was substantial overlap in the probability distributions of awake-time ABPM and each of the three AOBP measures. Systolic blood pressure means were similar between the 5/60/60 and 3/30/30 protocols and 5/30/30 and 3/60/60 protocols. The 5/30/30 was associated with a higher proportion of systolic HTN, while the 3/60/60 protocol was associated with a higher proportion of diastolic HTN. There were no significant differences in systolic or diastolic HTN between 5/60/60 and 3/30/30 protocols with respect to awake-time ABPM. CONCLUSIONS: In this quality improvement study, the shortest AOBP protocol did not differ significantly from the longest protocol. The time savings of shorter protocols may improve AOBP adoption in clinical practice without meaningfully compromising accuracy.

Two-step or one-step - are all methods for neonatal incubator decontamination equal?

Healthcare-associated pathogens, including Staphylococcus capitis, can contaminate incubator surfaces and are of significant concern in neonatal intensive care units (NICUs). Effective incubator decontamination is essential for infection prevention and control, with submersion decontamination often recommended. This may not always be achievable, with wipe decontamination seen as an alternative. Here we compare the ability of a two-step (submersion in enzymatic detergent followed by wiping with hypochlorite-based wipes) with a one-step (wiping with quaternary ammonium compound-impregnated wipes) decontamination procedure to remove microbial surrogate markers from neonatal incubator surfaces. Three cauliflower-mosaic-virus-derived microbial surrogate markers were inoculated on to the fan, a mattress seam and the external arm port door clips of two Giraffe™ Omnibed™ Carestation™ incubators. Incubators were decontaminated either by the one-step or the two-step decontamination process. Swab samples were collected from 28 sites on each incubator and surrounding environment, with marker presence determined by qPCR. Following two-step decontamination, three of 28 (11%) sample sites were positive for any marker, compared with 12 of 28 (43%) after one-step decontamination. Markers were transferred to several incubator surfaces and recovered from the originally inoculated sites following one-step decontamination, with the marker inoculated on door clips having the greatest transfer. Markers inoculated on to the mattress persisted through both decontamination strategies. In conclusion, microbial surrogate markers were not completely removed from incubator surfaces by one-step decontamination alone. Two-step decontamination was the most effective method and removed markers from submergible surfaces, but not from the mattress. These findings indicate that micro-organisms can persist after incubator terminal decontamination, particularly on mattresses and when a two-step decontamination process is not used. This highlights the importance of effective decontamination practices to mitigate micro-organism persistence on incubator surfaces.

A microbiological survey approach to understanding the virulence factors of Pseudomonas species in healthcare sinks.

BACKGROUND: Hospital water is involved in both the prevention and spread of healthcare-associated infections (HCAIs). Handwashing is key to reducing the transmission of pathogens, yet numerous outbreaks have been found to be caused by organisms within sinks, taps and showers. Pseudomonas aeruginosa and increasingly non-aeruginosa Pseudomonas cause waterborne HCAI, however, little is known about the virulence potential of Pseudomonas species found within hospital environments. METHODS: Swabs were taken from 62 sinks within two newly opened wards at Great Ormond Street Hospital, samples were taken before and after the wards opened to understand the impact of patient occupancy on sink micro-organisms. Culturable bacteria were identified by MALDI-TOF and virulence factors assessed through phenotypic methods. RESULTS: A total of 106 bacterial isolates were recovered including 24 Pseudomonas isolates. Of these 25% were identified as P. oleovorans, 21% P. aeruginosa, 17% P. composti, 13% P. alicalipha, 8% P. monteilii, 4% P. putida, 4% P. stutzeri and 8% could only be identified to genus level by MALDI-TOF. Differences were seen in both the number of Pseudomonas isolates and virulence production between the two wards, overall 25% of the Pseudomonas isolates produced pigment, 58% were capable of haemolysis, 87.5% were able to swim, 83.3% were capable of twitching motility, 33.3% produced alkaline protease and 8.3% produced gelatinase. CONCLUSIONS: Results suggest that patients may be back-contaminating sinks with colonizing organisms which has ongoing implications for infection prevention and control. Additionally, this work highlights the ability of non-aeruginosa Pseudomonas to produce virulence factors traditionally associated with P. aeruginosa.

Trends in viable microbial bioburden on surfaces within a paediatric bone marrow transplant unit.

BACKGROUND: Despite their role being historically overlooked, environmental surfaces have been shown to play a key role in the transmission of pathogens causative of healthcare-associated infection. To guide infection prevention and control (IPC) interventions and inform clinical risk assessments, more needs to be known about microbial surface bioburdens. AIM: To identify the trends in culturable bacterial contamination across communal touch sites over time in a hospital setting. METHODS: Swab samples were collected over nine weeks from 22 communal touch sites in a paediatric bone marrow transplant unit. Samples were cultured on Columbia blood agar and aerobic colony counts (ACC) per 100 cm2 were established for each site. Individual colony morphologies were grouped and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or 16s rDNA sequencing. FINDINGS: Highest mean counts were observed for sites associated with ward management activity and computer devices (3.29 and 2.97 ACC/100 cm2 respectively). A nurses' station keyboard had high mean ACC/100 cm2 counts (10.67) and diversity, while laundry controls had high mean ACC/100 cm2 counts (4.70) and low diversity. Micrococcus luteus was identified in all sampling groups. Clinical staff usage sites were contaminated with similar proportions of skin and environmental flora (52.19-46.59% respectively), but sites associated with parental activities were predominantly contaminated by environmental microflora (86.53%). CONCLUSION: The trends observed suggest patterns in microbial loading based on site activities, surface types and user groups. Improved understanding of environmental surface contamination could help support results interpretation and IPC interventions, improving patient safety.

Prediction of tumor-reactive T cell receptors from scRNA-seq data for personalized T cell therapy.

The identification of patient-derived, tumor-reactive T cell receptors (TCRs) as a basis for personalized transgenic T cell therapies remains a time- and cost-intensive endeavor. Current approaches to identify tumor-reactive TCRs analyze tumor mutations to predict T cell activating (neo)antigens and use these to either enrich tumor infiltrating lymphocyte (TIL) cultures or validate individual TCRs for transgenic autologous therapies. Here we combined high-throughput TCR cloning and reactivity validation to train predicTCR, a machine learning classifier that identifies individual tumor-reactive TILs in an antigen-agnostic manner based on single-TIL RNA sequencing. PredicTCR identifies tumor-reactive TCRs in TILs from diverse cancers better than previous gene set enrichment-based approaches, increasing specificity and sensitivity (geometric mean) from 0.38 to 0.74. By predicting tumor-reactive TCRs in a matter of days, TCR clonotypes can be prioritized to accelerate the manufacture of personalized T cell therapies.

Compositionality in visual perception.

Quilty-Dunn et al.'s wide-ranging defense of the Language of Thought Hypothesis (LoTH) argues that vision traffics in abstract, structured representational formats. We agree: Vision, like language, is compositional - just as words compose into phrases, many visual representations contain discrete constituents that combine in systematic ways. Here, we amass evidence extending this proposal, and explore its implications for how vision interfaces with the rest of the mind.

The Newport Quinsy Simulator.

BACKGROUND: The junior otolaryngologist is responsible for recognition and drainage of the peritonsillar abscess. Although other simulators have been proposed, there is still a need for an accessible, educationally useful, low-cost peritonsillar abscess simulator to build skills and confidence in the novice. METHODS: The peritonsillar abscess simulator was constructed from basic disposable healthcare equipment and a party balloon. Evaluation of this Newport Quinsy Simulator was performed by expert and novice clinicians, who provided feedback in the form of Likert scales and free-text qualitative responses. RESULTS: Overall, 24 clinicians evaluated the simulator. All felt the simulator was useful for the novice otolaryngologist, and represented the key anatomy and motor skills needed to drain a peritonsillar abscess. Qualitative evaluation highlighted the educational usefulness of the simulator as a peritonsillar abscess training device. CONCLUSION: The Newport Quinsy Simulator is affordable, accessible, easy to use and educationally valuable to the novice otolaryngologist.

Problems and Mysteries of the Many Languages of Thought.

"What is the structure of thought?" is as central a question as any in cognitive science. A classic answer to this question has appealed to a Language of Thought (LoT). We point to emerging research from disparate branches of the field that supports the LoT hypothesis, but also uncovers diversity in LoTs across cognitive systems, stages of development, and species. Our letter formulates open research questions for cognitive science concerning the varieties of rules and representations that underwrite various LoT-based systems and how these variations can help researchers taxonomize cognitive systems.

Right coronary artery to left ventricle coronary cameral fistula in a cat.

A six-month-old female intact domestic shorthair cat was presented for evaluation of a loud heart murmur. Transthoracic echocardiography revealed dilation of the left ventricle secondary to an abnormal vessel shunting blood into the left ventricular outflow tract at a high velocity during diastole. Multidetector computed tomography angiography revealed a coronary cameral fistula that originated at the right coronary artery, encircled the heart, and then terminated into the left ventricular outflow tract. This case report documents the first known case of a coronary cameral fistula in a cat. Multimodal imaging was an essential aspect to diagnosing the congenital lesion in this case.

Do water and soil nutrient scarcities differentially impact the performance of diploid and tetraploid Solidago gigantea (Giant Goldenrod, Asteraceae)?

Plants require water and nutrients for survival, although the effects of their availabilities on plant fitness differ amongst species. Genome size variation, within and across species, is suspected to influence plant water and nutrient requirements, but little is known about how variations in these resources concurrently affect plant fitness based on genome size. We examined how genome size variation between autopolyploid cytotypes influences plant morphological and physiological traits, and whether cytotype-specific trait responses differ based on water and/or nutrient availability. Diploid and autotetraploid Solidago gigantea (Giant Goldenrod) were grown in a greenhouse under four soil water:N+P treatments (L:L, L:H, H:L, H:H), and stomata characteristics (size, density), growth (above- and belowground biomass, R/S), and physiological (Anet , E, WUE) responses were measured. Resource availabilities and cytotype identity influenced some plant responses but their effects were independent of each other. Plants grown in high-water and nutrient treatments were larger, plants grown in low-water or high-nutrient treatments had higher WUE but lower E, and Anet and E rates decreased as plants aged. Autotetraploids also had larger and fewer stomata, higher biomass and larger Anet than diploids. Nutrient and water availability could influence intra- and interspecific competitive outcomes. Although S. gigantea cytotypes were not differentially affected by resource treatments, genome size may influence cytogeographic range patterning and population establishment likelihood. For instance, the larger size of autotetraploid S. gigantea might render them more competitive for resources and niche space than diploids.

Biophotonic tools for probing extracellular matrix mechanics.

The complex, hierarchical and heterogeneous biomechanics of the extracellular matrix (ECM) are central to the health of multicellular organisms. Characterising the distribution, dynamics and above all else origins of ECM biomechanics are challenges that have captivated researchers for decades. Recently, a suite of biophotonics techniques have emerged as powerful new tools to investigate ECM biomechanics. In this mini-review, we discuss how the non-destructive, sub-micron resolution imaging capabilities of Raman spectroscopy and nonlinear microscopy are being used to interrogate the biomechanics of thick, living tissues. These high speed, label-free techniques are implemented during mechanical testing, providing unprecedented insight into the compositional and structural response of the ECM to changes in the mechanical environment.

Thymic B Cells as a New Player in the Type 1 Diabetes Response.

Type 1 diabetes (T1d) results from a sustained autoreactive T and B cell response towards insulin-producing ß cells in the islets of Langerhans. The autoreactive nature of the condition has led to many investigations addressing the genetic or cellular changes in primary lymphoid tissues that impairs central tolerance- a key process in the deletion of autoreactive T and B cells during their development. For T cells, these studies have largely focused on medullary thymic epithelial cells (mTECs) critical for the effective negative selection of autoreactive T cells in the thymus. Recently, a new cellular player that impacts positively or negatively on the deletion of autoreactive T cells during their development has come to light, thymic B cells. Normally a small population within the thymus of mouse and man, thymic B cells expand in T1d as well as other autoimmune conditions, reside in thymic ectopic germinal centres and secrete autoantibodies that bind selective mTECs precipitating mTEC death. In this review we will discuss the ontogeny, characteristics and functionality of thymic B cells in healthy and autoimmune settings. Furthermore, we explore how in silico approaches may help decipher the complex cellular interplay of thymic B cells with other cells within the thymic microenvironment leading to new avenues for therapeutic intervention.

Risk of torsion in superior rectus transposition surgery augmented with posterior scleral fixation sutures.

It has been reported that superior rectus transposition combined with medial rectus recession can provide as good results as transposition of both vertical rectus muscles, with no adverse effects on torsion or postoperative vertical misalignment. Further augmentation of transposition surgery can be achieved through the use of posterior fixation sutures, myopexy and botulinum toxin into the medial rectus. We report a patient with complete bilateral traumatic sixth cranial nerve palsies who underwent sequential superior rectus transposition surgery combined with medial rectus recession. The surgery was augmented with a myopexy (posterior suture joining superior and lateral recti with no scleral fixation) in the first eye and with a posterior fixation suture (with scleral fixation) in the second eye. After the second procedure, despite a significant improvement in horizontal alignment, the patient developed 15 degrees of incyclotorsion which was attributed to the scleral fixation suture. The patient underwent removal of the scleral suture and 3 months postoperatively had a significant reduction in incyclotorsion to 8 degrees; however this continued to be a barrier to fusion. Vertical rectus transposition of superior and inferior recti augmented with posterior scleral fixation sutures is one type of conventional surgery for complete lateral rectus palsy. In more recent times, it has become common to transpose the superior rectus alone along with recession of the contracted medial rectus. This procedure can also be augmented with a posterior fixation suture which may or may not be attached to the sclera. Whilst this surgery has gained popularity it is not without risk as demonstrated by our case in which transposition of the superior rectus was associated with postoperative incyclotorsion. In this case a possible explanation may be the use of a the posterior scleral fixation suture as it did not occur when no scleral fixation was used. Furthermore, removal of the posterior scleral fixation suture did reduce the torsion significantly although it did not eliminate it.

Evaluation of DISORDER: Retrospective Image Motion Correction for Volumetric Brain MRI in a Pediatric Setting.

BACKGROUND AND PURPOSE: Head motion causes image degradation in brain MR imaging examinations, negatively impacting image quality, especially in pediatric populations. Here, we used a retrospective motion correction technique in children and assessed image quality improvement for 3D MR imaging acquisitions. MATERIALS AND METHODS: We prospectively acquired brain MR imaging at 3T using 3D sequences, T1-weighted MPRAGE, T2-weighted TSE, and FLAIR in 32 unsedated children, including 7 with epilepsy (age range, 2-18 years). We implemented a novel motion correction technique through a modification of k-space data acquisition: Distributed and Incoherent Sample Orders for Reconstruction Deblurring by using Encoding Redundancy (DISORDER). For each participant and technique, we obtained 3 reconstructions as acquired (Aq), after DISORDER motion correction (Di), and Di with additional outlier rejection (DiOut). We analyzed 288 images quantitatively, measuring 2 objective no-reference image quality metrics: gradient entropy (GE) and MPRAGE white matter (WM) homogeneity. As a qualitative metric, we presented blinded and randomized images to 2 expert neuroradiologists who scored them for clinical readability. RESULTS: Both image quality metrics improved after motion correction for all modalities, and improvement correlated with the amount of intrascan motion. Neuroradiologists also considered the motion corrected images as of higher quality (Wilcoxon z = -3.164 for MPRAGE; z = -2.066 for TSE; z = -2.645 for FLAIR; all P < .05). CONCLUSIONS: Retrospective image motion correction with DISORDER increased image quality both from an objective and qualitative perspective. In 75% of sessions, at least 1 sequence was improved by this approach, indicating the benefit of this technique in unsedated children for both clinical and research environments.

Caregiver self-efficacy to talk about sex predicts conversations about HIV transmission risk with perinatally infected young people in Zimbabwe.

Given advances in care and treatment for HIV, perinatally infected young people are surviving into adolescence. These young people are making decisions about engaging in sexual relationships and it is critical to ensure they have the information they need to engage responsibly in sexual activity, particularly in an era where adherence to treatment could make their virus undetectable. The main objective of this analysis was to examine whether an HIV-positive young person's knowledge about forward transmission is associated with caregiver self-efficacy to talk about sex and general caregiver communication. Using data from a 12-month prospective cohort of caregivers of HIV-positive children aged 9-15 on ART and pre-ART in rural Zimbabwe, we found that caregiver self-efficacy to talk about sex predicted whether conversations about HIV transmission would occur between caregiver and the young person. However, by the end of 12-months, nearly two-thirds of caregivers of HIV-positive teenagers in our sample had still not explained how their adolescents could spread the virus to others despite these caregivers saying their adolescent should know this information at baseline. We discuss the implications for designing sexual and reproductive health (SRH) programs among populations of young people perinatally infected with HIV to ensure that this breakthrough generation receives the SRH support they need.

Synergistic Antibacterial Effects of Metallic Nanoparticle Combinations.

Metallic nanoparticles have unique antimicrobial properties that make them suitable for use within medical and pharmaceutical devices to prevent the spread of infection in healthcare. The use of nanoparticles in healthcare is on the increase with silver being used in many devices. However, not all metallic nanoparticles can target and kill all disease-causing bacteria. To overcome this, a combination of several different metallic nanoparticles were used in this study to compare effects of multiple metallic nanoparticles when in combination than when used singly, as single elemental nanoparticles (SENPs), against two common hospital acquired pathogens (Staphylococcus aureus and Pseudomonas. aeruginosa). Flow cytometry LIVE/DEAD assay was used to determine rates of cell death within a bacterial population when exposed to the nanoparticles. Results were analysed using linear models to compare effectiveness of three different metallic nanoparticles, tungsten carbide (WC), silver (Ag) and copper (Cu), in combination and separately. Results show that when the nanoparticles are placed in combination (NPCs), antimicrobial effects significantly increase than when compared with SENPs (P < 0.01). This study demonstrates that certain metallic nanoparticles can be used in combination to improve the antimicrobial efficiency in destroying morphologically distinct pathogens within the healthcare and pharmaceutical industry.

Precision Health: Bringing Oral Health into the Context of Overall Health.

Unprecedented advances in genomics, data science, and biotechnology have ushered in a new era of health care in which interventions are increasingly tailored to individual patients. Precision-based approaches extend to oral health, which is essential to overall health. Harnessing the full potential of precision oral health will depend on research to more fully understand the factors that underlie health and contribute to disease-including the human genome, microbiome, epigenome, proteome, and others.