Incobotulinum Toxin-A in Professional Musicians with Focal Task-Specific Dystonia: A Double Blind, Placebo Controlled, Cross-Over Study.

Background: Musician's focal task-specific dystonia is a complex disorder of fine motor control, with incomplete understanding of its etiology. There have been relatively few trials of botulinum toxin in upper limb task-specific dystonia, and prior studies have yielded variable results, leading to skepticism regarding the utility of this approach in elite performers. Methods: We conducted a double-blind, placebo-controlled, randomized, cross-over study of incobotulinum toxin-A in 21 professional musicians with focal upper extremity task-specific dystonia affecting performance on their instrument, using a novel paradigm of initial injections followed by booster injections at two- and four-week intervals. The primary outcome measure was the change in blinded dystonia rating of the active arm by two expert raters using a Clinical Global Impression numeric scale at week 8 compared to enrollment. Findings: 19 men and 2 women with musicians' dystonia were enrolled over a six-year period. Nineteen patients completed the study. Analysis of the primary outcome measure in comparison to baseline revealed a change in dystonia severity of P = 0.04 and an improvement in overall musical performance of P = 0.027. No clinically significant weakness was observed, and neutralizing antibodies to toxin were not found. Interpretation: Despite its small sample size, our study demonstrated a statistically significant benefit of incobotulinum toxin-A injections as a treatment for musicians' task-specific dystonia. Tailoring the use of toxin with booster injections allowed refinement of dosing strategy and outcomes, with benefits that were meaningful to patients clearly visible on videotaped evaluations. In addition to its application to musicians' dystonia, this approach may have relevance to optimize application of botulinum toxin in other forms of focal dystonia such as blepharospasm, cervical dystonia, writer's cramp, and spasmodic dysphonia.

Tissue perfusion in DIEP flaps using Indocyanine Green Fluorescence Angiography, Hyperspectral imaging, and Thermal imaging.

Flap necrosis continues to occur in skin free flap autologous breast reconstruction. Therefore, we investigated the benefits of indocyanine green angiography (ICGA) using quantitative parameters for the objective, perioperative evaluation of flap perfusion. In addition, we investigated the feasibility of hyperspectral (HSI) and thermal imaging (TI) for postoperative flap monitoring. A single-center, prospective observational study was performed on 15 patients who underwent deep inferior epigastric perforator (DIEP) flap breast reconstruction (n=21). DIEP-flap perfusion was evaluated using ICGA, HSI, and TI using a standardized imaging protocol. The ICGA perfusion curves and derived parameters, HSI extracted oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) values, and flap temperatures from TI were analyzed and correlated to the clinical outcomes. Post-hoc quantitative analysis of intraoperatively collected data of ICGA application accurately distinguished between adequately and insufficiently perfused DIEP flaps. ICG perfusion curves identified the lack of arterial inflow (n=2) and occlusion of the venous outflow (n=1). In addition, a postoperatively detected partial flap epidermolysis could have been predicted based on intraoperative quantitative ICGA data. During postoperative monitoring, HSI was used to identify impaired perfusion areas within the DIEP flap based on deoxyHb levels. The results of this study showed a limited added value of TI. Quantitative, post-hoc analysis of ICGA data produced objective and reproducible parameters that enabled the intraoperative detection of arterial and venous congested DIEP flaps. HSI appeared to be a promising technique for postoperative flap perfusion assessment. A diagnostic accuracy study is needed to investigate ICGA and HSI parameters in real-time and demonstrate their clinical benefit.

Direct RNA Sequencing of Foot-and-mouth Disease Virus Genome Using a Flongle on MinION.

Foot-and-mouth disease (FMD) is a severe and extremely contagious viral disease of cloven-hoofed domestic and wild animals, which leads to serious economic losses to the livestock industry globally. FMD is caused by the FMD virus (FMDV), a positive-strand RNA virus that belongs to the genus Aphthovirus, within the family Picornaviridae. Early detection and characterization of FMDV strains are key factors to control new outbreaks and prevent the spread of the disease. Here, we describe a direct RNA sequencing method using Oxford Nanopore Technology (ONT) Flongle flow cells on MinION Mk1C (or GridION) to characterize FMDV. This is a rapid, low cost, and easily deployed point of care (POC) method for a near real-time characterization of FMDV in endemic areas or outbreak investigation sites. Key features • Saves ~35 min of the original protocol time by omitting the reverse transcription step and lowers the costs of reagents and consumables. • Replaces the GridION flow cell from the original protocol with the Flongle, which saves ~90% on the flow cell cost. • Combines the NGS benchwork with a modified version of our African swine fever virus (ASFV) fast analysis pipeline to achieve FMDV characterization within minutes. Graphical overview Schematic of direct RNA sequencing of foot-and-mouth disease virus (FMDV) process, which takes ~50 min from extracted RNA to final loading, modified from the ONT SQK-RNA002 protocol (Version: DRS_9080_v2_revO_14Aug2019).

Elevated myocardial extracellular volume fraction is associated with the development of conduction pathway defects following transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become an established method of aortic stenosis treatment but suffers from the risk of heart block and pacemaker requirement. Risk stratification for patients who may develop heart block remains imperfect. Simultaneously, myocardial fibrosis as measured by cardiac magnetic resonance imaging (CMR) has been demonstrated as a prognostic indicator of ventricular recovery and mortality following TAVR. However, the association of CMR-based measures of myocardial fibrosis with post-TAVR conduction disturbances has not yet been explored. AIMS: We evaluated whether myocardial fibrosis, as measured by late gadolinium enhancement and extracellular volume (ECV) from CMR would be associated with new conduction abnormalities following TAVR. METHODS: One hundred seventy patients who underwent CMR within 2 months before TAVR were retrospectively reviewed. Septal late gadolinium enhancement (LGE) and ECV measurements were made as surrogates for replacement and interstitial fibrosis respectively. New conduction abnormalities were defined by the presence of transient or permanent atrioventricular block, new bundle branch blocks, and need for permanent pacemaker. Association of myocardial fibrosis and new conduction derangements were tested using receiver operator curve (ROC) and regression analysis in patients with and without pre-existing conduction issues. RESULTS: Forty-six (27.1%) patients developed post-TAVR conduction deficits. ECV was significantly higher among patients who experienced new conduction defects (26.2 ± 3.45% vs. 24.7% ± 4.15%, p value: 0.020). A greater fraction of patients that had new conduction defects had an elevated ECV of ≥26% (54.3% vs. 36.3%, p value: 0.026). ECV ≥ 26% was independently associated with the development of new conduction defects (odds ratio [OR]: 2.364, p value: 0.030). ROC analysis revealed a significant association of ECV with new conduction defects with an area under the receiver operating characteristic curve (AUC) of 0.632 (95% confidence interval: 0.555-0.705, p value: 0.005). The combination of prior right bundle branch block (RBBB) and ECV revealed a greater AUC of 0.779 (0.709-0.839, p value: <0.001) than RBBB alone (Delong p value: 0.049). No association of LGE/ECV with new conduction defects was observed among patients with pre-existing conduction disease. Among patients without baseline conduction disease, ECV was independently associated with the development of new conduction deficits (OR: 3.685, p value: 0.008). CONCLUSION: The present study explored the association of myocardial fibrosis, as measured by LGE and ECV with conduction deficits post-TAVR. Our results demonstrate an association of ECV, and thereby interstitial myocardial fibrosis, with new conduction derangement post-TAVR and introduce ECV as a potentially new risk stratification tool to identify patients at higher risk for needing post-TAVR surveillance and/or permanent pacemaker.

Chemical analysis of flotsam ambergris.

The natural product ambergris is only found rarely on beaches, as jetsam. Even more scarce, or even absent, are accounts of flotsam ambergris. Here, we report the chemical analysis of a rare, large piece (>100kg) of flotsam found in the Atlantic in 2019. About 95% of subsamples from the outside of the coprolith was soluble in dichloromethane. Of this, FTIR spectroscopy, APCI-MS and GC-MS indicated the presence of ambrein. Radiocarbon dating indicated that the sample was post 1950s in age. The 13C/12C isotope ratio (-22.5 ‰) was typical of those reported to date for whale 'body' ambergris. Metals of ambergris have hardly been reported previously. The distribution found here for the flotsam, was dominated by copper and zinc, which is similar to that of several squid species. This is also consistent with the presence of squid beaks in the coprolith. Squid are a major prey species of sperm whales.

A microbiome-directed therapeutic food for children recovering from severe acute malnutrition.

Severe acute malnutrition (SAM), defined anthropometrically as a weight-for-length z-score more than 3 standard deviations below the mean (WLZ<-3), affects 19 million children under 5-years-old worldwide. Complete anthropometric recovery after standard inventions is rare with children often left with moderate acute malnutrition (MAM; WLZ -2 to -3). Here we conduct a randomized controlled trial (RCT), involving 12-18-month-old Bangladeshi children from urban and rural sites, who after hospital-based treatment for SAM received a 3-month intervention with a microbiota-directed complementary food (MDCF-2) or a ready-to-use supplementary food (RUSF) as they transitioned to MAM. The rate of WLZ improvement was significantly greater with MDCF-2 than the more calorically-dense RUSF, as we observed in a previous RCT of Bangladeshi children with MAM without antecedent SAM. A correlated meta-analysis of aptamer-based measurements of 4,520 plasma proteins in this and the prior RCT revealed 215 proteins positively-associated with WLZ (prominently those involved in musculoskeletal and CNS development) and 44 negatively-associated proteins (related to immune activation), with a significant enrichment in levels of the positively WLZ-associated proteins in the MDCF-2 arm. Characterizing changes in 754 bacterial metagenome-assembled genomes in serially collected fecal samples disclosed the effects of acute rehabilitation for SAM on the microbiome, its transition as each child achieves a state of MAM, and how specific strains of Prevotella copri function at the intersection between MDCF-2 glycan metabolism and the rescue of growth faltering. These results provide a rationale for further testing the generalizability of the efficacy of MDCF and identify biomarkers for defining treatment responses.

antiCD49d Ab treatment ameliorates age-associated inflammatory response and mitigates CD8+ T-cell cytotoxicity after traumatic brain injury.

Patients aged 65 years and older account for an increasing proportion of patients with traumatic brain injury (TBI). Older TBI patients experience increased morbidity and mortality compared to their younger counterparts. Our prior data demonstrated that by blocking α4 integrin, anti-CD49d antibody (aCD49d Ab) abrogates CD8+ T-cell infiltration into the injured brain, improves survival, and attenuates neurocognitive deficits. Here, we aimed to uncover how aCD49d Ab treatment alters local cellular responses in the aged mouse brain. Consequently, mice incur age-associated toxic cytokine and chemokine responses long-term post-TBI. aCD49d Ab attenuates this response along with a T helper (Th)1/Th17 immunological shift and remediation of overall CD8+ T cell cytotoxicity. Furthermore, aCD49d Ab reduces CD8+ T cells exhibiting higher effector status, leading to reduced clonal expansion in aged, but not young, mouse brains with chronic TBI. Together, aCD49d Ab is a promising therapeutic strategy for treating TBI in the older people. Graphic abstract: Aged brains after TBI comprise two pools of CD8 + T cells . The aged brain has long been resided by a population of CD8 + T cells that's exhaustive and dysfunctional. Post TBI, due to BBB impairment, functional CD8 + T cells primarily migrate into the brain parenchyma. Aged, injury-associated microglia with upregulated MHC class I molecules can present neoantigens such as neuronal and/or myelin debris in the injured brains to functional CD8+ T, resulting in downstream CD8+ T cell cytotoxicity. aCD49d Ab treatment exerts its function by blocking the migration of functional effector CD8 + T cell population, leading to less cytotoxicity and resulting in improved TBI outcomes in aged mice.

Cerebral Small Vessel Disease and Infarct Growth in Acute Ischemic Stroke Treated with Intravenous Thrombolysis.

We investigated relations between cerebral small vessel disease (cSVD) markers and evolution of the ischemic tissue from ischemic core to final infarct in people with acute ischemic stroke treated with intravenous thrombolysis. Data from the Stroke Imaging Repository (STIR) and Virtual International Stroke Trials Archive (VISTA) were used. Any pre-existing lacunar infarcts and white matter hyperintensities (WMH) were assessed on magnetic resonance (MR) before thrombolytic therapy. Acute ischemic core and final infarct volume were then assessed by two independent radiologists. The relationship among baseline markers of cSVD, acute ischemic core volume, final infarct volume, infarct growth (IG = final infarct - ischemic core), and infarct growth ratio (IGR = final infarct/ischemic core) was then assessed using linear and ordinal regression adjusted for age, sex, onset-to-treatment time, and stroke severity. We included 165 patients, mean (± SD) age 69.5 (± 15.7) years, 74 (45%) males, mean (± SD) ischemic core volume 25.48 (± 42.22) ml, final infarct volume 52.06 (± 72.88) ml, IG 26.58 (± 51.02) ml, IGR 8.23 (± 38.12). Seventy (42%) patients had large vessel occlusion, 20 (12%) acute small subcortical infarct. WMHs were present in 131 (79%) and lacunar infarcts in 61 (37%) patients. Final infarct volumes were 53.8 ml and 45.2 ml (WMHs/no WMHs), p = 0.139, and 24.6 ml and 25.9 ml (lacunar infarcts/no lacunar infarcts), p = 0.842. In linear and ordinal regression analyses, presence of lacunar infarcts was associated with smaller IG (ß = - 0.17; p = 0.024; cOR = 0.52; 95%CI = 0.28-0.96, respectively) and WMHs were associated with smaller IGR (ß = - 0.30; p = 0.004; cOR = 0.27; 95%CI = 0.11-0.69, respectively). In people with acute ischemic stroke treated with intravenous thrombolysis, cSVD features were associated with smaller growth of the acute ischemic area, suggesting less salvageable tissue at time of reperfusion therapy.

Canada's approach to SARS-CoV-2 sero-surveillance: Lessons learned for routine surveillance and future pandemics.

SETTING: In Canada's federated healthcare system, 13 provincial and territorial jurisdictions have independent responsibility to collect data to inform health policies. During the COVID-19 pandemic (2020-2023), national and regional sero-surveys mostly drew upon existing infrastructure to quickly test specimens and collect data but required cross-jurisdiction coordination and communication. INTERVENTION: There were 4 national and 7 regional general population SARS-CoV-2 sero-surveys. Survey methodologies varied by participant selection approaches, assay choices, and reporting structures. We analyzed Canadian pandemic sero-surveillance initiatives to identify key learnings to inform future pandemic planning. OUTCOMES: Over a million samples were tested for SARS-CoV-2 antibodies from 2020 to 2023 but siloed in 11 distinct datasets. Most national sero-surveys had insufficient sample size to estimate regional prevalence; differences in methodology hampered cross-regional comparisons of regional sero-surveys. Only four sero-surveys included questionnaires. Sero-surveys were not directly comparable due to different assays, sampling methodologies, and time-frames. Linkage to health records occurred in three provinces only. Dried blood spots permitted sample collection in remote populations and during stay-at-home orders. IMPLICATIONS: To provide timely, high-quality information for public health decision-making, routine sero-surveillance systems must be adaptable, flexible, and scalable. National capability planning should include consortiums for assay design and validation, defined mechanisms to improve test capacity, base documents for data linkage and material transfer across jurisdictions, and mechanisms for real-time communication of data. Lessons learned will inform incorporation of a robust sero-survey program into routine surveillance with strategic sampling and capacity to adapt and scale rapidly as a part of a comprehensive national pandemic response plan.

RéSUMé: CONTEXTE: Au Canada, où le système de santé est fédéré, les 13 juridictions provinciales et territoriales ont la responsabilité individuelle de recueillir les données qui leur permettent d'élaborer leurs politiques de santé. Lors de la pandémie de COVID-19 (2020­2023), pour réaliser les enquêtes de séroprévalence à l'échelle régionale et nationale, les autorités ont principalement utilisé l'infrastructure existante pour pouvoir analyser les échantillons et recueillir des données rapidement, mais cela a également nécessité de la communication et de la coordination entre les différentes juridictions. INTERVENTION: Au Canada, il y a eu quatre enquêtes nationales et sept enquêtes régionales sur la séroprévalence du SARS-CoV-2 dans la population générale. Les méthodologies utilisées différaient selon la méthode de sélection des participants, le choix des tests d'analyses et les structures de rapports. Nous avons analysé la façon dont ces enquêtes avaient été réalisées afin d'en dégager des éléments essentiels qui permettront de planifier pour les futures pandémies. RéSULTATS: Entre 2020 et 2023, plus d'un million d'échantillons, répartis en 11 ensembles de données distincts, ont été analysés afin de rechercher la présence d'anticorps au SARS-CoV-2. Dans la plupart des enquêtes nationales, la taille de l'échantillon était insuffisante pour pouvoir estimer la prévalence à l'échelle régionale. La disparité des méthodologies utilisées a entravé la comparaison des enquêtes régionales. Seules quatre enquêtes fournissaient les données recueillies à partir des questionnaires. Il a été impossible de comparer les enquêtes entre elles en raison de la diversité des tests d'analyse utilisés, des méthodes d'échantillonnage et de la durée des enquêtes. Seules trois provinces avaient couplé leurs données avec les archives médicales. Pour réaliser les enquêtes dans les populations éloignées et lors des périodes de confinement, la méthode d'analyse sur gouttes de sang séché a été utilisée. CONCLUSION: Afin de pouvoir fournir, en temps et en heure, des données de haute qualité pour la prise de décisions en matière de santé publique, un système de sérosurveillance continuelle doit être adaptable, modulable et évolutif. En cas de pandémie, un plan national doit prévoir des consortiums pour la conception et la validation des tests d'analyse, des moyens d'amélioration de la capacité de dépistage, des documents de base pour le couplage des données, un mode de transfert du matériel entre les différentes juridictions et des moyens pour une communication en temps réel des données. Les leçons tirées de cette analyse permettront de mettre en place un solide programme d'enquêtes de séroprévalence au sein des systèmes de sérosurveillance continuelle, et que ce programme sera accompagné d'une stratégie d'échantillonnage et d'un plan d'intervention national, rapide et complet en cas de pandémie.

Sex and season influence behaviour and physiology of lake trout following angling.

Catch-and-release angling exposes fish to challenges that may result in sub-lethal effects or mortality. Lake trout (Salvelinus namaycush) undergo high rates of release because of size-based harvest regulations or voluntary angler behaviour. Here, we examine short-term impairment in lake trout angled during the summer (n = 74) and fall spawning period (n = 33) to inform best practices for angling. Immediately following capture or 0.5 h post-capture, fish underwent reflex and barotrauma assessments, and a small blood sample was collected. Fish were also fitted with an externally mounted biologger equipped with depth, temperature and tri-axial acceleration sensors, that was tethered to allow retrieval of the logger after 14 min. In the summer, reflex impairment and barotrauma at 0 and 0.5 h were significantly correlated. Loss of orientation and bloating were the most observed indicators. Larger fish and those captured at increased depth had higher barotrauma scores, while prolonged fight times decreased the barotrauma score regardless of sampling time. Plasma cortisol, lactate and glucose increased 0.5 h after capture, and extracellular and intracellular pH decreased, all signs that angling was inducing a metabolic response. However, no relationships were found between blood indices and mortality (18.9%). The time required to reach maximum depth after release was longer for fish with increased air exposure but shorter for those with longer fight times. During the fall, fish displayed no mortality or reflex impairment. Anal prolapse was the most observed indicator of barotrauma but only observed in females. Blood indices were most altered 0.5 h after capture, with increased cortisol values for fish that were female, particularly large or captured at deeper depth. Locomotor activity was highest for males and increased with depth. Together, our findings suggest that the effects of catch-and-release angling may be dependent on several factors, including sex, season and angling depth.

Incidence, Predictors, and Outcomes of Clinically Significant Post-ERCP Bleeding: a Contemporary Multi-center Study.

BACKGROUND AIMS: Clinically significant post-endoscopic retrograde cholangiopancreatography (ERCP) bleeding (CSPEB) is common. Contemporary estimates of risk are lacking. We aimed to identify risk factors for and outcomes following CSPEB. METHODS: We analyzed multi-center prospective ERCP data between 2018-2023 with 30-day follow-up. The primary outcome was CSPEB, defined as hematemesis, melena, or hematochezia resulting in: hemoglobin drop ≥20 g/L or transfusion and/or endoscopy to evaluate suspected bleeding, and/or unplanned healthcare visitation and/or prolongation of existing admission. Firth logistic regression was employed. P-values <0.05 were significant, with odds ratios (ORs) and 95% confidence intervals reported. RESULTS: CSPEB occurred following 129 (1.5%) of 8,517 ERCPs (mean onset 3.2 days), with 110 of 4,849 events (2.3%) occurring following higher-risk interventions (sphincterotomy, sphincteroplasty, pre-cut sphincterotomy, and/or needle-knife access). CSPEB patients required endoscopy and transfusion in 86.0% and 53.5% of cases, respectively, with three cases (2.3%) being fatal. P2Y12 inhibitors were held for a median of 4 days (IQR 4) prior to higher-risk ERCP. Following higher-risk interventions, P2Y12 inhibitors (OR 3.33, 1.26-7.74), warfarin (OR 8.54, 3.32-19.81), dabigatran (OR 13.40, 2.06-59.96), rivaroxaban (OR 7.42, 3.43-15.24) and apixaban (OR 4.16, 1.99-8.20) were associated with CSPEB. Significant intraprocedural bleeding post sphincterotomy (OR 2.32, 1.06-4.60), but not post sphincteroplasty, was also associated. Concomitant cardiorespiratory events occurred more frequently within 30 days following CSPEB (OR 12.71, 4.75-32.54). CONCLUSIONS: Risks of antiplatelet-related CSPEB may be underestimated by endoscopists based on observations of suboptimal holding before higher-risk ERCP. Appropriate periprocedural antithrombotic management is essential and could represent novel quality initiative targets.

Association between synovial tissue damage and pain in late-stage knee osteoarthritis: A cross-sectional study.

OBJECTIVE: To identify the presence and distribution of histopathological features of synovial inflammation and tissue damage, and to test their associations with ultrasound (US) imaging measures of synovitis and patient-reported measures of pain in knee osteoarthritis (OA). DESIGN: In the cross-sectional study of 122 patients undergoing surgery for painful late-stage (Kellgren-Lawrence Grade 3 or 4) knee OA, we compared US measures of synovitis (n = 118) and pain (Knee Injury and Osteoarthritis Outcome Score) to histopathological measures of inflammation vs. synovial tissue damage in synovial tissue biopsies. Associations of histopathological features with US measures of inflammation or pain were assessed using linear or logistic regression while controlling for covariates. RESULTS: Histopathological features of inflammation were associated with higher odds of moderate/severe US synovitis (odds ratio [OR] = 1.34 [95%CI 1.04, 1.74), whereas features of synovial tissue damage were associated with lower odds of moderate/severe US synovitis (OR = 0.77 [95%CI 0.57, 1.03]). Worse histopathological scores for synovial tissue damage were associated with more pain (-1.47 [95%CI -2.88, -0.05]), even while adjusting for synovial inflammation (-1.61 [95%CI -3.12, -0.10]). CONCLUSIONS: Synovial tissue damage is associated with pain in late-stage knee OA, independent from inflammation and radiographic damage. These novel findings suggest that preventing synovial tissue damage may be an important goal of disease-modifying OA therapy.

A seabird's eye view: visual fields of some seabirds (Laridae and Procellariidae) from tropical latitudes.

The visual field of a bird defines the amount of information that can be extracted from the environment around it, using the eyes. Previous visual field research has left large phylogenetic gaps, where tropical bird species have been comparatively understudied. Using the ophthalmoscopic technique, we measured the visual fields of seven tropical seabird species, to understand what are the primary determinants of their visual fields. The visual field topographies of the seven seabird species were relatively similar, despite the two groups of Terns (Laridae) and Shearwaters (Procellariidae) being phylogenetically distant. We propose this similarity is due to their largely similar foraging ecology. These findings support previous research that foraging ecology rather than relatedness is the key determining factor behind a bird's visual field topography. Some bird species were identified to have more limited binocular fields, such as Brown Noddies (Anous stolidus) where binocularity onsets lower down within the visual field, resulting in a larger blind area about the head.

Prospective cohort study investigating frequency and risk factors for acute pain 1 day after refractive surgery.

BACKGROUND/AIMS: To examine demographic and clinical factors associated with ocular pain 1 day after refractive surgery. METHODS: Prospective study of individuals undergoing refractive surgery. Participants rated their ocular pain on a 0-10 numerical rating scale (NRS) presurgery and 1 day after surgery. Presurgery, participants completed questionnaires on demographics, comorbidities, medications and dry eye and ocular pain symptoms; and an anaesthetised Schirmer test was performed. Acute ocular pain 1 day after surgery was defined as an NRS score of worst pain since surgery ≥3 and this group was compared with individuals with NRS scores<3. RESULTS: 251 individuals underwent refractive surgery (89% laser-assisted in situ keratomileusis, n=222; 11% PRK, n=29). Mean age was 35±8 years (range 19 to 60); 60% (n=150) self-identified as female, 80% (n=203) as White, and 36% (n=89) as Hispanic. Thirteen (5%) individuals reported ocular pain (NRS ≥3) prior to surgery and 67% (n=168) reported ocular pain 1 day after surgery (nine individuals had pain at both time points). Factors that were associated with pain 1 day after surgery included Hispanic ethnicity (adjusted relative risk (aRR) 1.42, 95% CI 1.21 to 1.68, p<0.001) and the presence of eye pain presurgery (aRR 1.10, 95% CI 1.02 to 1.18, p=0.02). CONCLUSION: A majority of individuals report moderate or greater pain within 24 hours of refractive surgery. Hispanic ethnicity and eye pain prior to surgery were associated with self-reported acute postsurgical pain.

Developing the Technology-based Parenting Young Children Check-Up Intervention for Disruptive Behavior Problems Identified in Pediatric Primary Care.

Objective: Behavioral parent training programs show clear efficacy and effectiveness in response to young children's disruptive behavior problems, but limitations in engagement and accessibility prevent many families from benefiting from these programs. The Parenting Young Children Check-up (PYCC) is a technology-based program designed to overcome these barriers and increase the reach of behavioral parent training. Developed for use in pediatric health care, the PYCC includes three components: 1) an initial check-up designed to motivate program involvement; 2) text messages to connect parents with program content and reinforce content; and 3) a parent training website involving video-based content to teach parenting skills. This report details initial steps to refine PYCC intervention components. Methods: Seventeen mothers and 17 primary care physicians participated in this mixed methods data collection across three iterations by providing feedback on early drafts of the three components of the PYCC and completing a feedback questionnaire. Results: Feedback from one iteration informed modifications that were then evaluated in subsequent iterations. Saturation of qualitative input, positive qualitative feedback, and positive quantitative ratings on the feedback questionnaire was achieved in iteration three. Conclusions: Outcomes of this investigation informed the full version of the PYCC that will subsequently be tested in a proof-of-concept trial. Implications for Impact Statement: Several barriers limit the reach of parenting skills programs that reduce child problem behavior. We gathered feedback from parents and physicians to refine a parenting program that uses technology and delivery in pediatrics to overcome barriers. Future testing of the program will further inform implementation in pediatric settings.

Patterns of Genetic Diversity and Gene Flow Associated With an Aridity Gradient in Populations of Common Mole-rats, Cryptomys hottentotus hottentotus.

Genetic adaptation is the change of a population toward a phenotype that best fits the present ecological conditions of the environment it inhabits. As environmental conditions change, allele frequencies shift, resulting in different populations of the same species possessing genetic variation and divergent phenotypes. Cooperatively breeding common mole-rats (Cryptomys hottentotus hottentotus) inhabit environments along an aridity gradient in South Africa, which provides an opportunity for local genetic adaptations to occur. Using one mitochondrial gene (cytochrome b) and 3,540 SNP loci across the whole genome, we determined the phylogenetic relationship, population structure and genetic diversity of five populations of C. h. hottentotus located along an aridity gradient. Mitochondrial data identified population-specific clades that were less distinct in the two mesic populations, potentially indicating historical or recent gene flow, or the retention of ancestral haplotypes. Arid and semi-arid populations formed a distinct cluster from the non-arid populations. Genetic diversity and gene flow were higher in arid-dwelling individuals, suggesting greater connectivity and interactions between colonies in arid regions in comparison to mesic ones. Using an Aridity Index, we determined that isolation by environment, rather than isolation by geographical distance, best explains the genetic distance between the populations. Further analyses using target loci may determine if there are differing underlying genetic adaptations among populations of C. h. hottentotus. These analyses could help unravel population differences in response to environmental factors within a subspecies of bathyergid mole-rat and determine the adaptive capacity of this small nonmigratory subterranean rodent species in response to aridification in the face of climate change.

Heterogenous expansion of polymorphonuclear myeloid-derived suppressor cells distinguishes high-risk sepsis immunophenotypes in Uganda.

BACKGROUND: Understanding of immune cell phenotypes associated with inflammatory and immunosuppressive host responses in sepsis is imprecise, particularly in low- and middle-income countries (LMICs), where the global sepsis burden is concentrated. In these settings, elucidation of immunophenotypes with prognostic importance is necessary to determine the relevance of emerging therapeutics and refine mechanistic investigations of sepsis immunopathology. METHODS: In a prospective cohort of adults hospitalized with suspected sepsis in Uganda (N = 43; median age 46 years [IQR 36-59], 24 [55.8%] living with HIV, 16 [37.2%] deceased at 60 days), we combined high-dimensional flow cytometry with unsupervised machine learning and manual gating to define peripheral immunophenotypes associated with increased risk of 60-day mortality. RESULTS: Patients who died showed heterogenous expansion of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), with increased and decreased abundance of CD16negPD-L1dim and CD16brightPD-L1bright subsets, respectively, significantly associated with mortality. While differences between CD16negPD-L1dim cell abundance and mortality risk appeared consistent throughout the course of illness, those for the CD16brightPD-L1bright subset were more pronounced early after illness onset. Independent of HIV co-infection, depletion of CD4+ T cells, dendritic cells, and CD56-CD16bright NK cells were significantly associated with mortality risk, as was expansion of immature, CD56+CD16-CD11c+ NK cells. Abundance of T cells expressing inhibitory checkpoint proteins (PD-1, CTLA-4, LAG3) was similar between patients who died versus those who survived. CONCLUSIONS: This is the first study to define high risk immunophenotypes among adults with sepsis in sub-Saharan Africa, an immunologically distinct region where biologically informed treatment strategies are needed. More broadly, our findings highlight the clinical importance and complexity of MDSC expansion during sepsis and support emerging data that suggest a host-protective role for PD-L1 myeloid checkpoints in acute critical illness.

Unilateral versus bilateral pedicle screw fixation with anterior lumbar interbody fusion: a comparison of postoperative outcomes.

PURPOSE: To determine of the impact of ALIF with minimally invasive unilateral pedicle screw fixation (UPSF) versus bilateral pedicle screw fixation (BPSF) on perioperative outcomes, radiographic outcomes, and the rates of fusion, subsidence, and adjacent segment stenosis. METHODS: All adult patients who underwent one-level ALIF with UPSF or BPSF at an academic institution between 2015 and 2022 were retrospectively identified. Postoperative outcomes including length of hospital stay (LOS), wound complications, readmissions, and revisions were determined. The rates of fusion, screw loosening, adjacent segment stenosis, and subsidence were assessed on one-year postoperative CT. Lumbar alignment including lumbar lordosis, L4-S1 lordosis, regional lordosis, pelvic tilt, pelvic incidence, and sacral slope were assessed on standing x-rays at preoperative, immediate postoperative, and final postoperative follow-up. Univariate and multivariate analysis compared outcomes across posterior fixation groups. RESULTS: A total of 60 patients were included (27 UPSF, 33 BPSF). Patients with UPSF were significantly younger (p = 0.011). Operative time was significantly greater in the BPSF group in univariate (p < 0.001) and multivariate analysis (ß=104.1, p < 0.001). Intraoperative blood loss, LOS, lordosis, pelvic parameters, fusion rate, subsidence, screw loosening, adjacent segment stenosis, and revision rate did not differ significantly between fixation groups. Though sacral slope (p = 0.037) was significantly greater in the BPSF group, fixation type was not a significant predictor on regression. CONCLUSIONS: ALIF with UPSF relative to BPSF predicted decreased operative time but was not a significant predictor of postoperative outcomes. ALIF with UPSF can be considered to increase operative efficiency without compromising construct stability.

Urinary Retention Evaluation and Catheterization Algorithm for Adult Inpatients.

Importance: Acute urinary retention (UR) is common, yet variations in diagnosis and management can lead to inappropriate catheterization and harm. Objective: To develop an algorithm for screening and management of UR among adult inpatients. Design, Setting, and Participants: In this mixed-methods study using the RAND/UCLA Appropriateness Method and qualitative interviews, an 11-member multidisciplinary expert panel of nurses and physicians from across the US used a formal multi-round process from March to May 2015 to rate 107 clinical scenarios involving diagnosis and management of adult UR in postoperative and medical inpatients. The panel ratings informed the first algorithm draft. Semistructured interviews were conducted from October 2020 to May 2021 with 33 frontline clinicians-nurses and surgeons from 5 Michigan hospitals-to gather feedback and inform algorithm refinements. Main Outcomes and Measures: Panelists categorized scenarios assessing when to use bladder scanners, catheterization at various scanned bladder volumes, and choice of catheterization modalities as appropriate, inappropriate, or uncertain. Next, qualitative methods were used to understand the perceived need, usability, and potential algorithm uses. Results: The 11-member expert panel (10 men and 1 woman) used the RAND/UCLA Appropriateness Method to develop a UR algorithm including the following: (1) bladder scanners were preferred over catheterization for UR diagnosis in symptomatic patients or starting as soon as 3 hours since last void if asymptomatic, (2) bladder scanner volumes appropriate to prompt catheterization were 300 mL or greater in symptomatic patients and 500 mL or greater in asymptomatic patients, and (3) intermittent was preferred to indwelling catheterization for managing lower bladder volumes. Interview findings were organized into 3 domains (perceived need, feedback on algorithm, and implementation suggestions). The 33 frontline clinicians (9 men and 24 women) who reviewed the algorithm reported that an evidence-based protocol (1) was needed and could be helpful to clinicians, (2) should be simple and graphically appealing to improve rapid clinician review, and (3) should be integrated within the electronic medical record and prominently displayed in hospital units to increase awareness. The draft algorithm was iteratively refined based on stakeholder feedback. Conclusions and Relevance: In this study using a systematic, multidisciplinary, evidence- and expert opinion-based approach, a UR evaluation and catheterization algorithm was developed to improve patient safety by increasing appropriate use of bladder scanners and catheterization. This algorithm addresses the need for practical guidance to manage UR among adult inpatients.