Measuring the Electric Fields of Ions Captured in Crown Ethers.

Controlling reactivity with electric fields is a persistent challenge in chemistry. One approach is to tether ions at well-defined locations near a reactive center. To quantify fields arising from ions, we report crown ethers that capture metal cations as field sources and a covalently bound vibrational Stark shift probe as a field sensor. We use experiments and computations in both the gas and liquid phases to quantify the vibrational frequencies of the probe and estimate the electric fields from the captured ions. Cations, in general, blue shift the probe frequency, with effective fields estimated to vary in the range of ∼0.2-3 V/nm in the liquid phase. Comparison of the gas and liquid phase data provides insight into the effects of mutual polarization of the molecule and solvent and screening of the ion's field. These findings reveal the roles of charge, local screening, and geometry in the design of tailored electric fields.

Mid-childhood autism sibling recurrence in infants with a family history of autism.

Autism sibling recurrence in prospective infant family history studies is ~20% at 3 years but systematic follow-up to mid-childhood is rare. In population and clinical cohorts autism is not recognized in some children until school-age or later. One hundred and fifty-nine infants with an older sibling with autism underwent research diagnostic assessments at 3 years and mid-childhood (6 to 12 years (mean 9)). We report the autism sibling recurrence rate in mid-childhood and compare developmental and behavioral profiles at mid-childhood and 3 years in those with earlier versus later recognized autism, and those who had, or had not, received a community autism diagnosis. The autism recurrence rate in this sample in mid-childhood was 37.1%, 95% CI [29.9%, 44.9%] and higher in boys than girls. Around half of those diagnosed with autism in mid-childhood had not received a diagnosis at 3 years. Later, diagnosis was more common in girls than boys. While some had sub-threshold symptoms at 3, in others late diagnosis followed a largely typical early presentation. Sibling recurrence based on community clinical diagnosis was 24.5%, 95% CI [18.4%, 31.9%]. Those who also had a community diagnosis tended to be older, have lower adaptive function and higher autism and inattention symptoms. Notwithstanding limitations of a single site study, modest sample size and limits to generalisability, autism sibling recurrence in family history infants may be higher in mid-childhood than in studies reporting diagnostic outcome at 3 years. Findings have implications for families and clinical services, and for prospective family history studies.

Nutritional management after necrotizing enterocolitis and focal intestinal perforation in preterm infants.

Nutritional management of preterm infants recovering from necrotizing enterocolitis (NEC) or focal intestinal perforation (FIP) is challenging, especially in infants managed surgically. The logistics of how, when, and what to feed are unclear and current nutritional practices are primarily based on physiological principles and consensus opinion in individual units, rather than high-quality evidence. The aim of this narrative review is to summarize the literature on nutritional management after NEC or FIP in preterm infants: when to restart enteral nutrition, type of enteral nutrition to use, and how to advance nutrition. We also discuss treatment of micronutrient deficiencies, cholestasis, replacement of stoma losses, and optimal time of stoma closure. In conclusion, there are in sufficient high-quality studies available to provide evidence-based recommendations on the best nutritional practice after NEC or FIP in preterm infants. A local or national consensus based early nutrition guideline agreed upon by a multidisciplinary team including pediatric surgeons, pediatricians/neonatologists, nurses, and nutritionists is recommended. Further studies are urgently needed. IMPACT: There is no good quality evidence or nutritional standard across neonatal units treating infants after medical or surgical NEC or FIP. With this review we hope to start providing some consistency across patients and between providers treating patients with NEC and FIP. Mother's own milk is recommended when restarting enteral nutrition after NEC or FIP. In the absence of high-quality evidence, a consensus based early nutrition guideline agreed upon by a multidisciplinary team is recommended. Nutritional research projects are urgently needed in NEC and FIP patients.

Evaluating the efficacy of wearable biofeedback on the outcomes of exercise interventions in people with chronic non-specific spinal pain: protocol for a systematic review and meta-analysis.

INTRODUCTION: Wearable neuromuscular and biomechanical biofeedback technology has the potential to improve patient outcomes by facilitating exercise interventions. We will conduct a systematic review to examine whether the addition of wearable biofeedback to exercise interventions improves pain, disability and quality of life beyond exercise alone for adults with chronic non-specific spinal pain. Specific effects on clinical, physiological, psychological, exercise adherence and safety outcomes will also be examined. METHODS AND ANALYSIS: A systematic search will be conducted from inception to February 2024. Full articles in the English language will be included. MEDLINE, PubMed, CINAHL, EMBASE, Web of Science, PsycINFO, AMED, SPORTDiscus, CENTRAL databases, clinical trial registries and ProQuest (PQDT) will be used to search for eligible studies. Grey literature and conference proceedings (2022-2024) will be searched for relevant reports. Randomised controlled trials using wearable neuromuscular or kinematic biofeedback devices as an adjunct to exercise interventions for the treatment of chronic spinal pain will be included in this systematic review. The comparators will be wearable biofeedback with exercise versus exercise alone, or wearable biofeedback with exercise versus placebo and exercise. Risk of bias will be assessed using Cochrane Back Review Group criteria and the quality of evidence using Grading of Recommendations Assessment, Development and Evaluation recommendations. ETHICS AND DISSEMINATION: The systematic review will be based on published studies, and therefore, does not require ethical approval. The study results will be submitted for publication in an international, open-access, peer-reviewed journal and shared through conferences and public engagement. PROSPERO REGISTRATION NUMBER: CRD42023481393.

Characterizing and Predicting nvPM Size Distributions for Aviation Emission Inventories and Environmental Impact.

Concerns about civil aviation's air quality and environmental impacts have led to recent regulations on nonvolatile particulate matter (nvPM) mass and number emissions. Although these regulations do not mandate measuring particle size distribution (PSD), understanding PSDs is vital for assessing the environmental impacts of aviation nvPM. This study introduces a comprehensive data set detailing PSD characteristics of 42 engines across 19 turbofan types, ranging from unregulated small business jets to regulated large commercial aircraft. Emission tests were independently performed by using the European and Swiss reference nvPM sampling and measurement systems with parallel PSD measurements. The geometric mean diameter (GMD) at the engine exit strongly correlated with the nvPM number-to-mass ratio (N/M) and thrust, varying from 7 to 52 nm. The engine-exit geometric standard deviation ranged from 1.7 to 2.5 (mean of 2.05). The study proposes empirical correlations to predict GMD from N/M data of emissions-certified engines. These predictions are expected to be effective for conventional rich-burn engines and might be extended to novel combustor technologies if additional data become available. The findings support the refinement of emission models and help in assessing the aviation non-CO2 climate and air quality impacts.

MTFP1 controls mitochondrial fusion to regulate inner membrane quality control and maintain mtDNA levels.

Mitochondrial dynamics play a critical role in cell fate decisions and in controlling mtDNA levels and distribution. However, the molecular mechanisms linking mitochondrial membrane remodeling and quality control to mtDNA copy number (CN) regulation remain elusive. Here, we demonstrate that the inner mitochondrial membrane (IMM) protein mitochondrial fission process 1 (MTFP1) negatively regulates IMM fusion. Moreover, manipulation of mitochondrial fusion through the regulation of MTFP1 levels results in mtDNA CN modulation. Mechanistically, we found that MTFP1 inhibits mitochondrial fusion to isolate and exclude damaged IMM subdomains from the rest of the network. Subsequently, peripheral fission ensures their segregation into small MTFP1-enriched mitochondria (SMEM) that are targeted for degradation in an autophagic-dependent manner. Remarkably, MTFP1-dependent IMM quality control is essential for basal nucleoid recycling and therefore to maintain adequate mtDNA levels within the cell.

Self-Trephination in Cranial Excoriation Disorder.

BACKGROUND AND IMPORTANCE: Trephination is a procedure in which a small hole is made in the skull. Rare cases of self-trephination by individuals seeking medical benefit have been reported. Excoriation disorder is a compulsive skin-picking condition in which an individual self-inflicts cutaneous lesions. Left untreated, severe excoriation disorder can pose significant health risks. CLINICAL PRESENTATION: Here, we describe 5 patients who presented with self-trephination due to a severe form of compulsive cranial excoriation at 2 neighboring academic medical centers over a 4-year period. We review the clinical presentation of self-trephination in cranial excoriation disorder and associated risk factors, surgical and nonsurgical interventions, complications of the disease, treatments, and mortality. Defining clinical characteristics include repetitive self-induced destruction of the scalp and skull with entry into the intracranial compartment, frequent psychiatric comorbidities, infection or injury of the brain with consequent neurological morbidity or mortality, and frequent treatment failures because of poor adherence. CONCLUSION: Self-trephination in cranial excoriation disorder is a severe neuropsychological disorder and neurosurgical emergency that exposes the brain and is often life-threatening. Appropriate therapy requires antibiotics, surgical debridement and repair of the wound, and concomitant effective psychiatric management of the underlying compulsion, including the use of antidepressants and behavioral therapy.

Beyond the Expected: Evaluating Preoperative Predictors of a Difficult Cholecystectomy Aboard the USNS Comfort.

Mini abstract Typical preoperative markers of a difficult laparoscopic cholecystectomy did not apply during the US Naval ShipComfort Deployment in 2019. This prospective study reveals the importance of preparedness for short-term surgical missions, the impact of health care disparities on the severity of disease, and the need for deliberate and thoughtful engagement with host-nation partners.

Caesarean section for a primipara with Guillain-Barré syndrome under combined spinal epidural anaesthesia.

A primigravida in mid 30s presented to hospital at 30+2 weeks gestation, due to progressive neurological symptoms including ascending limb weakness and paraesthesia bilaterally as well as dysphagia, facial weakness and dysphasia.The patient was diagnosed with Guillain-Barré syndrome after physical examination and electromyography, which showed a patchy demyelinating sensorimotor polyneuropathy. The patient underwent a 5-day course of intravenous immunoglobulin, beginning the day after admission. Markers of severity including forced vital capacity improved thereafter until delivery.With limited evidence favouring one particular anaesthetic technique in parturients with Guillain-Barré syndrome, combined spinal epidural anaesthesia was preferred over general anaesthesia in order to avoid the potential for prolonged intubation postoperatively and to allow careful titration of neuraxial blockade. Delivery by caesarean section at 34+1 weeks due to pre-eclampsia was uncomplicated. Thereafter the patient's condition deteriorated, requiring a further 5-day course of intravenous immunoglobulin with symptoms gradually improving over a 6-month admission.

Perinatal outcomes after in-utero exposure to beta-blockers in women with heart disease: Data from the ESC EORP registry of pregnancy and cardiac disease (ROPAC).

BACKGROUND: Beta-blockers are commonly used drugs during pregnancy, especially in women with heart disease, and are regarded as relatively safe although evidence is sparse. Differences between beta-blockers are not well-studied. METHODS: In the Registry of Pregnancy And Cardiac disease (ROPAC, n = 5739), a prospective global registry of pregnancies in women with structural heart disease, perinatal outcomes (small for gestational age (SGA), birth weight, neonatal congenital heart disease (nCHD) and perinatal mortality) were compared between women with and without beta-blocker exposure, and between different beta-blockers. Multivariable regression analysis was used for the effect of beta-blockers on birth weight, SGA and nCHD (after adjustment for maternal and perinatal confounders). RESULTS: Beta-blockers were used in 875 (15.2%) ROPAC pregnancies, with metoprolol (n = 323, 37%) and bisoprolol (n = 261, 30%) being the most frequent. Women with beta-blocker exposure had more SGA infants (15.3% vs 9.3%, p < 0.001) and nCHD (4.7% vs 2.7%, p = 0.001). Perinatal mortality rates were not different (1.4% vs 1.9%, p = 0.272). The adjusted mean difference in birth weight was -177 g (-5.8%), the adjusted OR for SGA was 1.7 (95% CI 1.3-2.1) and for nCHD 2.3 (1.6-3.5). With metoprolol as reference, labetalol (0.2, 0.1-0.4) was the least likely to cause SGA, and atenolol (2.3, 1.1-4.9) the most. CONCLUSIONS: In women with heart disease an association was found between maternal beta-blocker use and perinatal outcomes. Labetalol seems to be associated with the lowest risk of developing SGA, while atenolol should be avoided.

Sex differences in social brain neural responses in autism: temporal profiles of configural face-processing within data-driven time windows.

Face-processing timing differences may underlie visual social attention differences between autistic and non-autistic people, and males and females. This study investigates the timing of the effects of neurotype and sex on face-processing, and their dependence on age. We analysed EEG data during upright and inverted photographs of faces from 492 participants from the Longitudinal European Autism Project (141 neurotypical males, 76 neurotypical females, 202 autistic males, 73 autistic females; age 6-30 years). We detected timings of sex/diagnosis effects on event-related potential amplitudes at the posterior-temporal channel P8 with Bootstrapped Cluster-based Permutation Analysis and conducted Growth Curve Analysis (GCA) to investigate the timecourse and dependence on age of neural signals. The periods of influence of neurotype and sex overlapped but differed in onset (respectively, 260 and 310 ms post-stimulus), with sex effects lasting longer. GCA revealed a smaller and later amplitude peak in autistic female children compared to non-autistic female children; this difference decreased in adolescence and was not significant in adulthood. No age-dependent neurotype difference was significant in males. These findings indicate that sex and neurotype influence longer latency face processing and implicates cognitive rather than perceptual processing. Sex may have more overarching effects than neurotype on configural face processing.

Diuretics in pregnancy: Data from the ESC Registry of Pregnancy and Cardiac disease (ROPAC).

AIMS: Data on diuretic use in pregnancy are limited and inconsistent, and consequently it remains unclear whether they can be used safely. Our study aims to evaluate the perinatal outcomes after in-utero diuretic exposure. METHODS AND RESULTS: The Registry Of Pregnancy And Cardiac disease (ROPAC) is a prospective, global registry of pregnancies in women with heart disease. Outcomes were compared between women who used diuretics during pregnancy versus those who did not. Multivariable regression analysis was used to assess the impact of diuretic use on the occurrence of congenital anomalies and foetal growth. Diuretics were used in 382 (6.7%) of the 5739 ROPAC pregnancies, most often furosemide (86%). Age >35 years (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.2-2.0), other cardiac medication use (OR 5.4, 95% CI 4.2-6.9), signs of heart failure (OR 1.7, 95% CI 1.2-2.2), estimated left ventricular ejection fraction <40% (OR 2.9, 95% CI 2.0-4.2), New York Heart Association class >II (OR 3.4, 95% CI 2.3-5.1), valvular heart disease (OR 6.3, 95% CI 4.7-8.3) and cardiomyopathy (OR 3.9, 95% CI 2.6-5.7) were associated with diuretic use during pregnancy. In multivariable analysis, diuretic use during the first trimester was not significantly associated with foetal or neonatal congenital anomalies (OR 1.3, 95% CI 0.7-2.6), and diuretic use during pregnancy was also not significantly associated with small for gestational age (OR 1.4, 95% CI 1.0-1.9). CONCLUSIONS: Our study does not conclusively establish an association between diuretic use during pregnancy and adverse foetal outcomes. Given these findings, it is essential to assess the risk-benefit ratio on an individual basis to guide clinical decisions.

Scalable Transdiagnostic Early Assessment of Mental Health (STREAM): a study protocol.

INTRODUCTION: Early childhood development forms the foundations for functioning later in life. Thus, accurate monitoring of developmental trajectories is critical. However, such monitoring often relies on time-intensive assessments which necessitate administration by skilled professionals. This difficulty is exacerbated in low-resource settings where such professionals are predominantly concentrated in urban and often private clinics, making them inaccessible to many. This geographic and economic inaccessibility contributes to a significant 'detection gap' where many children who might benefit from support remain undetected. The Scalable Transdiagnostic Early Assessment of Mental Health (STREAM) project aims to bridge this gap by developing an open-source, scalable, tablet-based platform administered by non-specialist workers to assess motor, social and cognitive developmental status. The goal is to deploy STREAM through public health initiatives, maximising opportunities for effective early interventions. METHODS AND ANALYSIS: The STREAM project will enrol and assess 4000 children aged 0-6 years from Malawi (n=2000) and India (n=2000). It integrates three established developmental assessment tools measuring motor, social and cognitive functioning using gamified tasks, observation checklists, parent-report and audio-video recordings. Domain scores for motor, social and cognitive functioning will be developed and assessed for their validity and reliability. These domain scores will then be used to construct age-adjusted developmental reference curves. ETHICS AND DISSEMINATION: Ethical approval has been obtained from local review boards at each site (India: Sangath Institutional Review Board; All India Institute of Medical Science (AIIMS) Ethics Committee; Indian Council of Medical Research-Health Ministry Screening Committee; Malawi: College of Medicine Research and Ethics Committee; Malawi Ministry of Health-Blantyre District Health Office). The study adheres to Good Clinical Practice standards and the ethical guidelines of the 6th (2008) Declaration of Helsinki. Findings from STREAM will be disseminated to participating families, healthcare professionals, policymakers, educators and researchers, at local, national and international levels through meetings, academic journals and conferences.

International Classification System for Ocular Complications of Anti-Vascular Endothelial Growth Factor Agents in Clinical Trials.

OBJECTIVE: Complications associated with intravitreal anti-vascular endothelial growth factor (VEGF) therapies are inconsistently reported in the literature, thus limiting an accurate evaluation and comparison of safety between studies. This study aimed to develop a standardized classification system for anti-VEGF ocular complications using the Delphi consensus process. DESIGN: Systematic review and Delphi consensus process. PARTICIPANTS: 25 international retinal specialists participated in the Delphi consensus survey. METHODS: A systematic literature search was conducted to identify complications of intravitreal anti-VEGF agent administration based on randomized controlled trials (RCTs) of anti-VEGF therapy. A comprehensive list of complications was derived from these studies, and this list was subjected to iterative Delphi consensus surveys involving international retinal specialists that voted on inclusion, exclusion, rephrasing, and addition of complications. As well, surveys determined specifiers for the selected complications. This iterative process helped refine the final classification system. MAIN OUTCOME MEASURES: The proportion of retinal specialists who choose to include or exclude complications associated with anti-VEGF administration. RESULTS: After screening 18,229 articles, 130 complications were initially categorized from 145 included RCTs. Participant consensus via the Delphi method resulted in the inclusion of 91 (70%) complications after three rounds. After incorporating further modifications made based on participant suggestions, such as rewording certain phrases and combining similar terms, 24 redundant complications were removed, leaving a total of 67 (52%) complications in the final list. A total of 14 (11%) complications met exclusion thresholds and were eliminated by participants across both rounds. All other remaining complications not meeting inclusion or exclusion thresholds were also excluded from the final classification system after the Delphi process terminated. In addition, 47 out of 75 (63%) proposed complication specifiers were included based on participant agreement. CONCLUSION: Using the Delphi consensus process, a comprehensive, standardized classification system consisting of 67 ocular complications and 47 unique specifiers was established for intravitreal anti-VEGF agents in clinical trials. The adoption of this system in future trials could improve consistency and quality of adverse event reporting, potentially facilitating more accurate risk-benefit analyses.

Trajectories of brain and behaviour development in the womb, at birth and through infancy.

Birth is often seen as the starting point for studying effects of the environment on human development, with much research focused on the capacities of young infants. However, recent imaging advances have revealed that the complex behaviours of the fetus and the uterine environment exert influence. Birth is now viewed as a punctuate event along a developmental pathway of increasing autonomy of the child from their mother. Here we highlight (1) increasing physiological autonomy and perceptual sensitivity in the fetus, (2) physiological and neurochemical processes associated with birth that influence future behaviour, (3) the recalibration of motor and sensory systems in the newborn to adapt to the world outside the womb and (4) the effect of the prenatal environment on later infant behaviours and brain function. Taken together, these lines of evidence move us beyond nature-nurture issues to a developmental human lifespan view beginning within the womb.

Parent-infant interaction trajectories in infants with an elevated likelihood for autism in relation to 3-year clinical outcome.

Developmental antecedents of autism may affect parent-infant interactions (PII), altering the context in which core social skills develop. While studies have identified differences in PII between infants with and without elevated likelihood (EL) for autism, samples have been small. Here, we examined whether previously reported differences are replicable. From a longitudinal study of 113 EL and 27 typical likelihood infants (TL), 6-min videotaped unstructured PII was blind rated at 8 and 14 months on eight interactional qualities. Autism outcome was assessed at 36 months. Linear mixed-effects models found higher parent sensitive responsiveness, nondirectiveness, and mutuality ratings in TL than EL infants with and without later autism. PII qualities at 8 (infant positive affect, parent directiveness) and 14 months (infant attentiveness to parent, mutuality) predicted 3-year autism. Attentiveness to parent decreased between 8 and 14 months in EL infants with later autism. This larger study supports previous findings of emerging alterations in PII in this group and extends on this by detecting earlier (8-month) predictive effects of PII for autism outcome and a more marked trajectory of decreased social attentiveness. The findings strengthen the evidence base to support the implementation of early preemptive interventions to support PII in infants with early autism signs.

Trans-activating mutations of the pseudokinase ERBB3.

Genetic changes in the ERBB family of receptor tyrosine kinases serve as oncogenic driver events and predictive biomarkers for ERBB inhibitor drugs. ERBB3 is a pseudokinase member of the family that, although lacking a fully active kinase domain, is well known for its potent signaling activity as a heterodimeric complex with ERBB2. Previous studies have identified few transforming ERBB3 mutations while the great majority of the hundreds of different somatic ERBB3 variants observed in different cancer types remain of unknown significance. Here, we describe an unbiased functional genetics screen of the transforming potential of thousands of ERBB3 mutations in parallel. The screen based on a previously described iSCREAM (in vitro screen of activating mutations) platform, and addressing ERBB3 pseudokinase signaling in a context of ERBB3/ERBB2 heterodimers, identified 18 hit mutations. Validation experiments in Ba/F3, NIH 3T3, and MCF10A cell backgrounds demonstrated the presence of both previously known and unknown transforming ERBB3 missense mutations functioning either as single variants or in cis as a pairwise combination. Drug sensitivity assays with trastuzumab, pertuzumab and neratinib indicated actionability of the transforming ERBB3 variants.

Evaluation of a Military Global Health Engagement Mission for Critical Wartime Surgical Specialty Readiness.

INTRODUCTION: Surgical volume at Military Treatment Facilities (MTFs) has been gradually decreasing for roughly the past 2 decades. The Knowledge, Skills, and Abilities (KSA) Clinical Readiness Program linked surgical volume and readiness using a tool known as the KSA metric. However, the extent to which military medical missions contribute to the readiness of critical wartime specialties has not been evaluated using this metric. METHODS: In this study, a retrospective analysis was conducted using the surgical case logs from the US Naval Ship (USNS) Comfort missions in 2018 and 2019. The comprehensive case log data were categorized by year, surgeon, procedure, and location. The analysis focused on providing detailed descriptive statistics, including percentages pertaining to the types of procedures performed during these missions. The 2018 mission was 11 weeks in duration, and supported activities in Ecuador, Peru, Colombia, and Honduras. The USNS Comfort mission in 2019 lasted 6 months (June-November 2019), and visited 12 countries in Central America, South America, and the Caribbean. RESULTS: The 2019 mission case log, spanning 6 months, was evaluated using the KSA score in order to assess readiness and compare against 6 months of MTF KSA values within the same calendar year. In 2019, the orthopedic surgeon aboard the USNS Comfort had a total KSA score of 44,006, but the 6-month USNS Comfort mission only contributed 5,364 points (12% of the annual score). The general surgery practice aboard the USNS Comfort produced lower KSA scores compared to each surgeon's respective MTF practice (Table III). Analyzing the cases logged by general surgeons also highlights minimal surgical diversity during these missions, with more than 90% of cases being hernia repairs or laparoscopic cholecystectomies (Table I). In addition, 35% of total procedures performed in 2018 and 2019 were performed laparoscopically. CONCLUSIONS: The analysis of operative data from the 2019 USNS Comfort mission, in comparison with the surgeons' work at their respective MTFs, reveals limited benefit in the ability of hospital-ship missions to bolster surgical readiness as measured by the KSA score. However, this is not a reflection on the value of Global Health Engagement (GHE) itself but a review of the way in which it is leveraged to support surgical readiness. Military surgeons participate in GHE as part of a larger strategy to strengthen relationships with partner nations, improve military medical force interoperability, and bolster partner nation medical capacity and capabilities. The KSA score offers an excellent tool to compare readiness metrics across significantly different GHE missions, and facilitates the opportunity for future prospective studies to improve case volume, diversity, and ultimately readiness.