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Background: While parent-delivered pain management has been demonstrated to effectively reduce neonatal procedural pain responses, little is known about to what extent it is utilized. Our aim was to explore the utilization of parents in neonatal pain management and investigate whether local guidelines promote parent-delivered interventions. Methods: A web-based survey was distributed to neonatal units worldwide. Results: The majority of the 303 responding neonatal intensive care units (NICUs) from 44 countries were situated in high-income countries from Europe and Central Asia. Of the responding units, 67% had local guidelines about neonatal pain management, and of these, 40% answered that parental involvement was recommended, 27% answered that the role of parents in pain management was mentioned as optional, and 32% responded that it was not mentioned in the guidelines. According to the free-text responses, parent-delivered interventions of skin-to-skin contact, breastfeeding, and parental live singing were the most frequently performed in the NICUs. Of the responding units, 65% answered that parents performed some form of pain management regularly or always. Conclusions: There appears to be some practice uptake of parent-delivered pain management to reduce neonatal pain in high-income countries. Additional incorporation of these interventions into NICU pain guidelines is needed, as well as a better understanding of the use of parent-delivered pain management in low- and middle-income countries.

Childbirth has always carried traumatic stress to the woman's body. To deliver with less perineal trauma, obstetricians have used episiotomies. Episiotomy is still a common practice despite the controversy regarding its use. Weighing the risks and benefits, the scientific literature supports its selective use. With the worldwide trend to reduce the rate of episiotomy, several techniques have been proposed to achieve that. However, further research is still needed to prove their efficacy. This review will shed light on the historical background of episiotomy, its different techniques, indications, and the future of its practice. [ABSTRACT FROM AUTHOR]

Intergroup attitudes were assessed in African-American (N = 70) and non-African-American minority (N = 80) children, evenly divided by gender, in first (M = 6.5 years old) and fourth (M = 9.6 years old) grades attending mixed-ethnicity public schools in a suburban area of a large mid-Atlantic city in the USA. Children were interviewed to test hypotheses about implicit racial biases, perceptions of similarity between peer dyads, and judgments about cross-race friendships. Implicit racial biases emerged when children evaluated ambiguous picture cards, with children viewing a White child as more likely to be a transgressor than a Black child in certain situations. There were no racial biases when evaluating potential cross-race friendship (it was judged to be feasible); nor was there any evidence of an outgroup homogeneity effect. Children who used ethnicity as a reason for judging peers to be similar, however, were less likely to judge that the cross-race dyads could be friends. The findings indicate the ways in which minority children's judgments about the majority and their perceptions of similarity between peer dyads influence their interpretations of peer interactions. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) play a critical role in resistance to immunotherapy. In this study, we identified epidermal growth factor-like 6 (Egfl6) as a regulator of myeloid cell functions. Our analyses indicated that Egfl6, via binding with β3 integrins and activation of p38 and SYK signaling, acts as a chemotactic factor for myeloid cell migration and promotes their differentiation toward an immunosuppressive state. In syngeneic mouse models of ovarian cancer (OvCa), tumor expression of Egfl6 increased the intratumoral accumulation of polymorphonuclear (PMN) MDSCs and TAMs and their expression of immunosuppressive factors, including CXCL2, IL-10, and PD-L1. Consistent with this, in an immune 'hot' tumor model, Egfl6 expression eliminated response to anti-PD-L1 therapy, while Egfl6 neutralizing antibody decreased the accumulation of tumor-infiltrating CD206+ TAMs and PMN-MDSCs and restored the efficacy of anti-PD-L1 therapy. Supporting a role in human tumors, in human OvCa tissue samples, areas of high EGFL6 expression colocalized with myeloid cell infiltration. scRNA-Seq analyses revealed a correlation between EGFL6 and immune cell expression of immunosuppressive factors. Our data provide mechanistic insights into the oncoimmunologic functions of EGFL6 in mediating tumor immune suppression and identified EGFL6 as a potential therapeutic target to enhance immunotherapy in patients with OvCa.

Background: While parent-delivered pain management has been demonstrated to effectively reduce neonatal procedural pain responses, little is known about to what extent it is utilized. Our aim was to explore the utilization of parents in neonatal pain management and investigate whether local guidelines promote parent-delivered interventions., Methods: A web-based survey was distributed to neonatal units worldwide., Results: The majority of the 303 responding neonatal intensive care units (NICUs) from 44 countries were situated in high-income countries from Europe and Central Asia. Of the responding units, 67% had local guidelines about neonatal pain management, and of these, 40% answered that parental involvement was recommended, 27% answered that the role of parents in pain management was mentioned as optional, and 32% responded that it was not mentioned in the guidelines. According to the free-text responses, parent-delivered interventions of skin-to-skin contact, breastfeeding, and parental live singing were the most frequently performed in the NICUs. Of the responding units, 65% answered that parents performed some form of pain management regularly or always., Conclusions: There appears to be some practice uptake of parent-delivered pain management to reduce neonatal pain in high-income countries. Additional incorporation of these interventions into NICU pain guidelines is needed, as well as a better understanding of the use of parent-delivered pain management in low- and middle-income countries.

Cholera is a life-threatening gastrointestinal infection caused by a toxigenic bacterium, Vibrio cholerae. After a lull of almost 30 years, a first case of cholera was detected in Lebanon in October 2022. The outbreak lasted three months, with 8007 suspected cases (671 laboratory-confirmed) and 23 deaths. In this study, we use phenotypic methods and microbial genomics to study 34 clinical and environmental Vibrio cholerae isolates collected throughout this outbreak. All isolates are identified as V. cholerae O1, serotype Ogawa strains from wave 3 of the seventh pandemic El Tor (7PET) lineage. Phylogenomic analysis unexpectedly reveals the presence of two different strains of the seventh pandemic El Tor (7PET) lineage. The dominant strain has a narrow antibiotic resistance profile and is phylogenetically related to South Asian V. cholerae isolates and derived African isolates from the AFR15 sublineage. The second strain is geographically restricted and extensively drug-resistant. It belongs to the AFR13 sublineage and clusters with V. cholerae isolates collected in Yemen. In conclusion, the 2022-2023 Lebanese cholera outbreak is caused by the simultaneous introduction of two different 7PET strains. Genomic surveillance with cross-border collaboration is therefore crucial for the identification of new introductions and routes of circulation of cholera, improving our understanding of cholera epidemiology., (© 2024. The Author(s).)

Aims: Little is known about the population pharmacokinetics (PPK) of vancomycin in neonates with perinatal asphyxia treated with therapeutic hypothermia (TH). We aimed to describe the PPK of vancomycin and propose an initial dosing regimen for the first 48 h of treatment with pharmacokinetic/pharmacodynamic target attainment., Methods: Neonates with perinatal asphyxia treated with TH were included from birth until Day 6 in a multicentre prospective cohort study. A vancomycin PPK model was constructed using nonlinear mixed-effects modelling. The model was used to evaluate published dosing guidelines with regard to pharmacokinetic/pharmacodynamic target attainment. The area under the curve/minimal inhibitory concentration ratio of 400-600 mg*h/L was used as target range., Results: Sixteen patients received vancomycin (median gestational age: 41 [range: 38-42] weeks, postnatal age: 4.4 [2.5-5.5] days, birth weight: 3.5 [2.3-4.7] kg), and 112 vancomycin plasma concentrations were available. Most samples (79%) were collected during the rewarming and normothermic phase, as vancomycin was rarely initiated during the hypothermic phase due to its nonempirical use. An allometrically scaled 1-compartment model showed the best fit. Vancomycin clearance was 0.17 L/h, lower than literature values for term neonates of 3.5 kg without perinatal asphyxia (range: 0.20-0.32 L/h). Volume of distribution was similar. Published dosing regimens led to overexposure within 24 h of treatment. A loading dose of 10 mg/kg followed by 24 mg/kg/day in 4 doses resulted in target attainment., Conclusion: Results of this study suggest that vancomycin clearance is reduced in term neonates with perinatal asphyxia treated with TH. Lower dosing regimens should be considered followed by model-informed precision dosing., (© 2024 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Model validation procedures are crucial when population pharmacokinetic (PK) models are used to develop dosing algorithms and to perform model-informed precision dosing. We have previously published a population PK model describing the PK of gentamicin in term neonates with perinatal asphyxia during controlled therapeutic hypothermia (TH), which showed altered gentamicin clearance during the hypothermic phase dependent on gestational age and weight. In this study, the predictive performance and generalizability of this model were assessed using an independent data set of neonates with perinatal asphyxia undergoing controlled TH., Methods: The external data set contained a subset of neonates included in the prospective observational multicenter PharmaCool Study. Predictive performance was assessed by visually inspecting observed-versus-predicted concentration plots and calculating bias and precision. In addition, simulation-based diagnostics, model refitting, and bootstrap analyses were performed., Results: The external data set included 323 gentamicin concentrations of 39 neonates. Both the model-building and external data set included neonates from multiple centers. The original gentamicin PK model predicted the observed gentamicin concentrations with adequate accuracy and precision during all phases of controlled TH. Model appropriateness was confirmed with prediction-corrected visual predictive checks and normalized prediction distribution error analyses. Model refitting to the merged data set (n = 86 neonates with 935 samples) showed accurate estimation of PK parameters., Conclusions: The results of this external validation study justify the generalizability of the gentamicin dosing recommendations made in the original study for neonates with perinatal asphyxia undergoing controlled TH (5 mg/kg every 36 or 24 h with gestational age 36-41 and 42 wk, respectively) and its applicability in model-informed precision dosing., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.)

Background: Primary brain rhabdomyosarcoma is a rare primary brain malignancy with few case reports. The vast majority of cases of primary brain rhabdomyosarcoma occur in pediatric patients, and immunohistochemistry can distinguish it from embryonal subtypes; however, few cases of primary brain rhabdomyosarcoma in adults have been reported in the literature., Case Presentation: We report the case of a 26-year-old White male patient who was found to have primary brain alveolar rhabdomyosarcoma after developing headaches for several months. A brain MRI revealed a mixed cystic and solid tumor along the vermis of the cerebellum. The patient underwent a gross total surgical resection, which confirmed the diagnosis of alveolar rhabdomyosarcoma. Further staging workup for another primary focus or disseminated disease yielded negative results, confirming the diagnosis of primary alveolar rhabdomyosarcoma of the brain., Conclusion: The standard of care for managing this rare type of brain tumor involves surgery with adjuvant chemoradiotherapy. Further studies should be conducted for a better diagnostic and therapeutic understanding., (© 2024. The Author(s).)

Background: A female's breasts are integrally tied to her identity and sense of femininity. Despite extensive study of breast aesthetics, there is no discrete formula for the "ideal breast" to guide the aesthetic surgeon. Racial and cultural differences heavily influence preferences in breast morphology. Artificial intelligence (AI) is ubiquitous in modern culture and may aid in further understanding ideal breast aesthetics., Objectives: This study analyzed AI-generated images of aesthetically ideal breasts, evaluated for morphologic differences based on race, and compared findings to the literature., Methods: An openly accessible AI image-generator platform was used to generate images of aesthetically ideal Caucasian, African American, and Asian breasts in 3-quarter profile and frontal views using simple text prompts. Breast measurements were obtained and compared between each racial cohort and to that of previously described ideal breast parameters., Results: Twenty-five images were analyzed per racial cohort, per pose (150 total). Caucasian breasts were observed to fit nicely into previously described ideal breast templates. However, upper-to-lower pole ratios, nipple angles, upper pole slope contours, nipple-areolar complex positions, and areolar size were observed to have statistically significant differences between racial cohorts., Conclusions: Defining the aesthetically ideal breast remains a complex and multifaceted challenge, requiring consideration of racial and cultural differences. The AI-generated breasts in this study were found to have significant differences between racial groups, support several previously described breast ideals, and provide insight into current and future ethical issues related to AI in aesthetic surgery., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Aesthetic Society.)

Introduction: Giant cell arteritis (GCA) is a systemic granulomatous vasculitis affecting the large arteries. Abnormal lymphocyte function has been noted as a pathogenic factor in GCA. Mycophenolate mofetil (MMF) inhibits inosine monophosphate dehydrogenase and is therefore a highly lymphocyte-specific immunosuppressive therapy. We aimed to assess the efficacy of MMF for inducing remission in GCA., Methods: Seven patients (5 female, 2 male) with GCA under therapy with MMF and who were treated at the outpatient clinic for rare inflammatory systemic diseases at Hannover Medical School between 2010 and 2023 were retrospectively included in the study. All patients underwent duplex sonography, 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET), magnetic resonance imaging (MRI), and/or biopsy to confirm the diagnosis. The primary endpoints were the number of recurrences, CRP levels at 3-6 and 6-12 months, and the period of remission., Results: All patients in this case series showed inflammatory activity of the arterial vessels in at least one of the imaging modalities: duplex sonography ( n  = 5), 18 F-FDG PET ( n  = 5), MRI ( n  = 6), and/or biopsy ( n  = 5). CRP levels of all patients decreased at the measurement time points 3-6 months, and 6-9 months after initiation of therapy with MMF compared with CRP levels before MMF therapy. All patients with GCA in this case series achieved disease remission., Discussion: The results of the present case series indicate that MMF is an effective therapy in controlling disease activity in GCA, which should be investigated in future randomized controlled trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pankow, Sinno, Derlin, Hiss and Wagner.)

Ceftazidime is an antibiotic commonly used to treat bacterial infections in term neonates undergoing controlled therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy after perinatal asphyxia. We aimed to describe the population pharmacokinetics (PK) of ceftazidime in asphyxiated neonates during hypothermia, rewarming, and normothermia and propose a population-based rational dosing regimen with optimal PK/pharmacodynamic (PD) target attainment. Data were collected in the PharmaCool prospective observational multicenter study. A population PK model was constructed, and the probability of target attainment (PTA) was assessed during all phases of controlled TH using targets of 100% of the time that the concentration in the blood exceeds the MIC ( T >MIC ) (for efficacy purposes and 100% T >4×MIC and 100% T >5×MIC to prevent resistance). A total of 35 patients with 338 ceftazidime concentrations were included. An allometrically scaled one-compartment model with postnatal age and body temperature as covariates on clearance was constructed. For a typical patient receiving the current dose of 100 mg/kg of body weight/day in 2 doses and assuming a worst-case MIC of 8 mg/L for Pseudomonas aeruginosa, the PTA was 99.7% for 100% T >MIC during hypothermia (33.7°C; postnatal age [PNA] of 2 days). The PTA decreased to 87.7% for 100% T >MIC during normothermia (36.7°C; PNA of 5 days). Therefore, a dosing regimen of 100 mg/kg/day in 2 doses during hypothermia and rewarming and 150 mg/kg/day in 3 doses during the following normothermic phase is advised. Higher-dosing regimens (150 mg/kg/day in 3 doses during hypothermia and 200 mg/kg/day in 4 doses during normothermia) could be considered when achievements of 100% T >4×MIC and 100% T >5×MIC are desired., Competing Interests: The authors declare no conflict of interest.

The distribution of dryland trees and their density, cover, size, mass and carbon content are not well known at sub-continental to continental scales 1-14 . This information is important for ecological protection, carbon accounting, climate mitigation and restoration efforts of dryland ecosystems 15-18 . We assessed more than 9.9 billion trees derived from more than 300,000 satellite images, covering semi-arid sub-Saharan Africa north of the Equator. We attributed wood, foliage and root carbon to every tree in the 0-1,000 mm year -1 rainfall zone by coupling field data 19 , machine learning 20-22 , satellite data and high-performance computing. Average carbon stocks of individual trees ranged from 0.54 Mg C ha -1 and 63 kg C tree -1 in the arid zone to 3.7 Mg C ha -1 and 98 kg tree -1 in the sub-humid zone. Overall, we estimated the total carbon for our study area to be 0.84 (±19.8%) Pg C. Comparisons with 14 previous TRENDY numerical simulation studies 23 for our area found that the density and carbon stocks of scattered trees have been underestimated by three models and overestimated by 11 models, respectively. This benchmarking can help understand the carbon cycle and address concerns about land degradation 24-29 . We make available a linked database of wood mass, foliage mass, root mass and carbon stock of each tree for scientists, policymakers, dryland-restoration practitioners and farmers, who can use it to estimate farmland tree carbon stocks from tablets or laptops., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

During the early years of spaceflight it was documented that astronauts were impaired and incapacitated upon return to earth. Computerized Dynamic Posturography (CDP) was devised to investigate and quantify this deficit, and eventually progressed into a clinical assessment tool. The current sprouting of virtual reality (VR) technologies has allowed for the development of an alternative approach that could be more informative. Many low-cost VR systems (including desktop gaming programs designed for rehabilitation) are now available. Continued improvements in this technology indicate a high probability that VR will become an integral component of posturography by replacing present mechanical CDP techniques. We researched the relevant literature to evaluate the strengths and weaknesses of CDP using the Equitest (Neurocom International; Clackamas USA), and the added benefits of incorporating VR to help clinicians assess the complex task of balance maintenance. VR is capable of manipulating task and environmental demands in order to assess functional postural behavior. VR is also a useful tool for clinical testing of postural disorders resulting from sensory mismatch. Although posturography is still a useful clinical tool, VR provides an inherent conflict between the visual and vestibular senses and can elevate the effectiveness of CDP for both assessment and intervention. We conclude that, when initially developed, CDP was innovative and ahead of its time. However, with the advent of VR, we have a chance to modernize CDP and enhance its value as a clinical instrument., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Keshner, Mallinson, Longridge, Sinno, Petersen and Perrin.)

Objective : The skull vibration-induced-nystagmus test (SVINT) is a noninvasive and effective screening tool for the function of the otolith and canal structures in children. It can instantaneously assess vestibular asymmetry. This study aimed to analyze the SVINT results of healthy children vs. children with hearing loss (HL) and to correlate it with sensory organization test (SOT) results as a functional balance evaluation tool. Design : This case-controlled study compared the results of SVINT to the results of the SOT of the computerized dynamic posturography (CDP) in a control group of 120 healthy normal-hearing children (i.e., NH group) vs. hearing loss (HL) group of 60 children, including 30 children with hearing aids (HAs) and 30 children with a unilateral cochlear implant (CI). The SVINT results were compared to the caloric test (CaT) and video head impulse test (vHIT) and associated with SOT scores. Results : Thirty-one children in the HL group had normal SVINT and normal SOT results. A total of 21 children in the HL group had SVINT-negative and abnormal results in the SOT (possibly due to bilateral vestibular loss (BVL)). Eight children in the HL group had positive SVINT and abnormal SOT results. However, none of the children had only positive SVINT with normal SOT findings. Moreover, 52% of children had a normal result on both the SOT and CaT, whereas 27% had abnormal results on both tests (17% bilateral weakness and 10% unilateral), and 22% had the only result of the SOT suggesting a functional abnormality. Similarly, when associating the result to vHIT, 51% had normal results on both tests, and 25% had abnormal results (13% bilateral and 12% unilateral weakness). Conclusions : SVINT findings can be correlated with SOT findings in the case of the unilateral vestibular lesion (UVL), which adds a diagnostic value in these pediatric cases but may differ in the case of the bilateral vestibular lesion (BVL). However, SVINT findings need to be cautiously interpreted in light of other test findings such as the SOT, CaT, and vHIT.

Introduction: Fluconazole is an important antifungal in the prevention and treatment of invasive Candida infections in neonates, even though its use in preterm infants is still off-label. Here, we performed a population pharmacokinetic study on fluconazole in preterm neonates in order to optimise dosing through the identified predictive patient characteristics., Methods: Fluconazole concentrations obtained from preterm infants from two studies were pooled and analysed using NONMEM V.7.3. The developed model was used to evaluate current dosing practice. A therapeutic dosing strategy aiming to reach a minimum target exposure of 400 and 200 mg×hour/L per 24 hours for fluconazole-susceptible C. albicans meningitis and other systemic infections, respectively, was developed., Results: In 41 preterm neonates with median (range) gestational age 25.3 (24.0-35.1) weeks and median postnatal age (PNA) at treatment initiation 1.4 (0.2-32.5) days, 146 plasma samples were collected. A one-compartment model described the data best, with an estimated clearance of 0.0147 L/hour for a typical infant of 0.87 kg with a serum creatinine concentration of 60 µmol/L and volume of distribution of 0.844 L. Clearance was found to increase with 16% per 100 g increase in actual body weight, and to decrease with 12% per 10 µmol/L increase in creatinine concentration once PNA was above 1 week. Dose adjustments based on serum creatinine and daily dosing are required for therapeutic target attainment., Conclusion: In preterm neonates, fluconazole clearance is best predicted by actual body weight and serum creatinine concentration. Therefore, fluconazole dosing should not only be based on body weight but also on creatinine concentration to achieve optimal exposure in all infants., Ethics Statement: The Erasmus MC ethics review board approved the protocol of the DINO Study (MEC-2014-067) and the Radboud UMC ethics review board waived the need for informed consent for cohort 2 (CMO-2021-8302). Written informed consent from parents/legal guardians was obtained prior to study initiation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

This review enumerates most of the studies on the Skull Vibration-Induced Nystagmus Test (SVINT) in the past 50 years from different research groups around the world. It is an attempt to demonstrate the evolution of this test and its increased interest around the globe. It explores clinical studies and animal studies, both permitting a better understanding of the importance of SVINT and its pathophysiology.

Background: Secondary breast reduction is complex and poses significant challenges to surgeons. Complication rates exceed those of primary reduction, commonly caused by impaired vascular supply of the nipple-areolar complex (NAC). Literature on the topic is scare and provides contradicting recommendations, especially with regard to pedicle choice in cases with unknown primary reduction technique. Aim of this study was to investigate international trends and to compare findings with literature., Methods: A large-scale web-based questionnaire on international trends in mammaplasty (mastopexy and breast reduction) was designed and distributed to over five thousand surgeons in eight geographic regions. The presented manuscript evaluated information regarding pedicle choice in secondary breast reduction and compared data to literature identified in a systematic review., Results: The survey was completed by 1431 participants. Overall, secondary procedures were performed in less than 5% or in 5 to 10% of cases. The preferred pedicle for secondary reductions differed significantly between geographic regions (p<0.001). The majority of respondents reported to use a superior or supero-medial pedicle (34.8% and 32.2%, respectively). Residual analysis revealed a strong association between the use of an inferior pedicle and procedures performed in North America., Conclusions: Secondary breast reduction is challenging and there remains international disparity with regard to pedicle choice for secondary procedures. Studies investigating outcome when the primary pedicle is unknown are scarce and provide incoherent recommendations. High-quality data is needed to provide evidence-based practice guidelines., Level of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266., (© 2021. The Author(s).)

We investigated the impact of cancer-associated mesenchymal stem cells (CA-MSCs) on ovarian tumor immunity. In patient samples, CA-MSC presence inversely correlates with the presence of intratumoral CD8 + T cells. Using an immune “hot” mouse ovarian cancer model, we found that CA-MSCs drive CD8 + T cell tumor immune exclusion and reduce response to anti–PD-L1 immune checkpoint inhibitor (ICI) via secretion of numerous chemokines (Ccl2, Cx3cl1, and Tgf-β1), which recruit immune-suppressive CD14 + Ly6C + Cx3cr1 + monocytic cells and polarize macrophages to an immune suppressive Ccr2 hi F4/80 + Cx3cr1 + CD206 + phenotype. Both monocytes and macrophages express high levels of transforming growth factor β–induced (Tgfbi) protein, which suppresses NK cell activity. Hedgehog inhibitor (HHi) therapy reversed CA-MSC effects, reducing myeloid cell presence and expression of Tgfbi, increasing intratumoral NK cell numbers, and restoring response to ICI therapy. Thus, CA-MSCs regulate antitumor immunity, and CA-MSC hedgehog signaling is an important target for cancer immunotherapy.

Introduction: Optimal neonatal nadroparin dosages to treat venous thromboembolism (VTE) are unknown., Objective: To evaluate therapeutic nadroparin dosages to reach therapeutic target ranges (TTR: 0.5-1.0 International Unit (IU)/mL) and the effectiveness and safety of nadroparin in neonatal VTE., Methods: Retrospective study including neonates with VTE on nadroparin in a tertiary center between 2007 and 2018. Two groups were distinguished: neonates before (group 1) and after (group 2) switch to higher starting dosages in 2014., Results: Sixty-one neonates (44 preterm, 17 term) with 64 VTEs were included. TTR was reached in 32/64 (50%) VTEs (group 1: 35.7%; group 2: 61.1%). Median nadroparin dosage to reach TTR was 197 (97.9-330.3) IU/kg/12 h. No therapy-related deaths occurred. Recurrent VTE developed in 6 (9.8%) neonates. Complete clot resolution was observed in 31/41 (75.6%) VTEs. TTR was reached in 58.1% VTEs with complete clot resolution. No major bleeding occurred. Non-major clinically relevant bleedings occurred in 3/64 (4.7%) VTEs, consisting of large hematomas due to the use of subcutaneous catheters., Conclusions: High nadroparin dosages are needed to reach TTR in neonates, which seem to be safe. Clot resolution may occur without reaching TTR. Subcutaneous catheters may cause important bleeding complications.

Background: The central nervous system integrates information from different sensory inputs (vestibular, visual, and somatosensory) to maintain balance. However, strategies for weighing sensory information change as maturation occurs., Purpose: The purpose of this study was to: (1) evaluate postural control development in a large sample of healthy children aged 5 to 17 years old, (2) analyze changes in sensory weighting strategies as maturation occurs, and (3) determine the extent to which anthropometric characteristics (height, weight, body mass index [BMI]) influence postural control., Sample Size: This study recruited 120 healthy children, equally distributed in gender and number, into four age groups (5-8 years, 9-11 years, 12-14 years, and 15-17 years) and compared them to a control group of 20 healthy adults (aged 20-25 years)., Research Design: The sensory organization test (SOT) was used to assess overall balance and the use of specific sensory inputs to maintain postural control. All children underwent the six SOT conditions: (1) eyes open, surround and platform stable, (2) eyes closed, surround and platform stable, (3) eyes open, sway-referenced surround, platform stable, (4) eyes open, sway-referenced platform, (5) eyes closed, sway-referenced platform, and (6) eyes open, sway-referenced surround and platform., Data Analysis: Condition-specific equilibrium scores (ES), composite equilibrium scores (CES), and sensory analysis ratios were analyzed to determine whether the performance was related to age, gender, or specific anthropometric characteristics (height, weight, and BMI)., Results: Data showed a significant age-associated improvement in ES for all 6 conditions ( p  < 0.05) and in CES ( p  = 0.001). For both genders, (1) somatosensory function was adult-like by age 5 to 8 years, (2) visual function peaked around age 12 years, and (3) vestibular function reached maturity by age 15 to 17 years ( p  < 0.05). A moderate positive correlation ( r (140) = 0.684, p  = 0.01; two-tailed) between height and CES was found and a weak positive correlation ( r (140) = 0.198, p  = 0.01) between height and somatosensory ratio was noted. Lower vestibular ratio scores were observed in children who had a higher BMI ( p  = 0.001)., Conclusion: The efficient use of individual sensory system input to maintain balance does not occur at the same age. Age and gender affect the changes in sensory weighting strategies, while height and BMI influence postural control in children. These factors need to be accounted for in child assessment., Competing Interests: None declared., (American Academy of Audiology. This article is published by Thieme.)

Summary: The American Society of Plastic Surgeons, the American Academy of Otolaryngology-Head and Neck Surgery, and the American Academy of Facial Plastic and Reconstructive Surgery commissioned the multidisciplinary Rhinoplasty Performance Measure Development Work Group to identify and draft quality measures for the care of patients undergoing both functional and aesthetic rhinoplasty. One outcome measure and three process measures were identified. The outcome looked at patient satisfaction with rhinoplasty procedures. The process measures look at motivations and expectations of the procedure, airway assessment, and nonnarcotic shared decision-making strategies for pain management. All measures in this report were approved by the American Society of Plastic Surgeons Quality and Performance Measures Work Group and Executive Committee, and the American Academy of Otolaryngology-Head and Neck Surgery Foundation, the American Academy of Facial Plastic and Reconstructive Surgery, The Rhinoplasty Society, and the American Association of Oral and Maxillofacial Surgeons. The Work Group recommends the use of these measures for quality initiatives, Continuing Medical Education, Maintenance of Certification, Qualified Clinical Data Registry reporting, and national quality reporting programs., (Copyright © 2020 by the American Society of Plastic Surgeons.)

Rationale : Aldehyde dehydrogenase (ALDH) enzymes are often upregulated in cancer cells and associated with therapeutic resistance. ALDH enzymes protect cells by metabolizing toxic aldehydes which can induce DNA double stand breaks (DSB). We recently identified a novel ALDH1A family inhibitor (ALDHi), 673A. We hypothesized that 673A, via inhibition of ALDH1A family members, could induce intracellular accumulation of genotoxic aldehydes to cause DSB and that ALDHi could synergize with inhibitors of the ATM and ATR, proteins which direct DSB repair. Methods : We used immunofluorescence to directly assess levels of the aldehyde 4-hydroxynonenal and comet assays to evaluate DSB. Western blot was used to evaluate activation of the DNA damage response pathways. Cell counts were performed in the presence of 673A and additional aldehydes or aldehyde scavengers. ALDH inhibition results were confirmed using ALDH1A3 CRISPR knockout. Synergy between 673A and ATM or ATR inhibitors was evaluated using the Chou-Talalay method and confirmed in vivo using cell line xenograft tumor studies. Results : The ALDHi 673A cellular accumulation of toxic aldehydes which induce DNA double strand breaks. This is exacerbated by addition of exogenous aldehydes such as vitamin-A (retinaldehyde) and ameliorated by aldehyde scavengers such as metformin and hydralazine. Importantly, ALDH1A3 knockout cells demonstrated increased sensitivity to ATM/ATR inhibitors. And, ALDHi synergized with inhibitors of ATM and ATR, master regulators of the DSB DNA damage response, both in vitro and in vivo. This synergy was evident in homologous recombination (HR) proficient cell lines. Conclusions : ALDHi can be used to induce DNA DSB in cancer cells and synergize with inhibitors the ATM/ATR pathway. Our data suggest a novel therapeutic approach to target HR proficient ovarian cancer cells., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Conventional upper blepharoplasty relies on skin, muscle, and fat excision to restore ideal pretarsal space-to-upper lid fold ratios. The purpose of this study was to identify presenting topographic features of upper blepharoplasty patients and their effect on cosmetic outcomes., Methods: This is a retrospective review of patients who underwent upper blepharoplasty at the authors' institution from 1997 to 2017. Preoperative and postoperative photographs were standardized using Adobe Illustrator to an iris diameter of 11.5 mm. Pretarsal and upper lid fold heights were measured at five locations. Patients were classified into three groups based on preoperative pretarsal show: none, partial, or complete. Photographs were randomized in PowerPoint and given a cosmetic score of 0 to 5 by four independent reviewers., Results: Three hundred sixteen patients were included, 42 men (13 percent) and 274 women (87 percent). Group 1 included 101 eyes (16 percent), group 2 had 159 eyes (25 percent), and group 3 had 372 eyes (59 percent). Mean cosmetic score increased from 1.75 to 2.38 postoperatively (p < 0.001), with a significantly lower improvement in scores in group 3 compared to groups 2 and 1 for both sexes (p < 0.01). For group 3, those with midpupil pretarsal heights greater than 4 mm had a significantly lower postoperative aesthetic score (1.95) compared with those less than or equal to 4 mm (2.50) (p < 0.001)., Conclusions: Many patients presenting for upper blepharoplasty have complete pretarsal show and are at risk for worse cosmetic outcomes using conventional skin excision techniques. Adjunctive procedures such as fat grafting and ptosis repair should be considered in this group., Clinical Question/level of Evidence: Risk, II.

A large proportion of dryland trees and shrubs (hereafter referred to collectively as trees) grow in isolation, without canopy closure. These non-forest trees have a crucial role in biodiversity, and provide ecosystem services such as carbon storage, food resources and shelter for humans and animals 1,2 . However, most public interest relating to trees is devoted to forests, and trees outside of forests are not well-documented 3 . Here we map the crown size of each tree more than 3 m 2 in size over a land area that spans 1.3 million km 2 in the West African Sahara, Sahel and sub-humid zone, using submetre-resolution satellite imagery and deep learning 4 . We detected over 1.8 billion individual trees (13.4 trees per hectare), with a median crown size of 12 m 2 , along a rainfall gradient from 0 to 1,000 mm per year. The canopy cover increases from 0.1% (0.7 trees per hectare) in hyper-arid areas, through 1.6% (9.9 trees per hectare) in arid and 5.6% (30.1 trees per hectare) in semi-arid zones, to 13.3% (47 trees per hectare) in sub-humid areas. Although the overall canopy cover is low, the relatively high density of isolated trees challenges prevailing narratives about dryland desertification 5-7 , and even the desert shows a surprisingly high tree density. Our assessment suggests a way to monitor trees outside of forests globally, and to explore their role in mitigating degradation, climate change and poverty.

Background: Pediatric oculomotor function can be evaluated via videonystagmography. Adult normative data for saccades and smooth pursuit tests cannot be used as a benchmark for pediatric patients because children's peripheral and central systems continue to mature throughout adolescence., Purpose: The purpose of this study was to establish normative data for saccade and smooth pursuit tests that can be used clinically in the assessment of vestibular and neurological disorders in children, and to investigate the effect of age and eye movement direction (left/right) on tests parameters., Research Design: The present study is prospective cross-sectional study., Study Sample: A total of 120 healthy children were recruited and equally distributed according to age and gender to each of the following groups: 5-8, 9-11, 12-14, and 15-17 years old. Participants had to pass a comprehensive otological and neurological assessment prior to inclusion in the study. Each subject underwent saccade and smooth pursuit testing., Data Collection and Analysis: Saccade latency, velocity and accuracy/precision, and smooth pursuit gain were analyzed across groups using a two-way repeated measure multivariate analysis of variance (MANOVA)., Results: Saccadic latency was longer in the youngest group aged 5-8 years old (305 ± 48 msec) in comparison to children aged 9-11 years old (276 ± 22 msec) ( P  = 0.017), 12-14 years old (252 ± 34 msec) ( P  = 0.001) adolescents 15-17 years (256 ± 33 msec) ( P  = 0.001). Age did not affect the results of saccadic velocity and accuracy/precision. Saccade parameters (latency, velocity, accuracy/ precision) were not affected by oculomotor direction (left vs. right). Smooth pursuit gain increased from 0.63 in children aged 5-8 years old to 0.85 in children aged 15-17 years ( P  = 0.0001). The percentage of gain asymmetry was significantly different in the youngest two groups., Conclusion: Saccade latency decreased as age increased. Smooth pursuit gains increased with increased age. Saccade velocity and accuracy/precision did not change significantly from ages 5-8 to 15-17 years of age. These data provide normative values for pediatric oculomotor evaluation and suggest that saccade and pursuit pathways may mature at different rates., Competing Interests: None declared., (American Academy of Audiology. All rights reserved.)

Background: With advancements in materials engineering, many plastic surgeons have looked to allogeneic tissue and alloplastic materials as a possible source of structure for long-lasting nipple-areola complex reconstruction. Furthermore, in light of the recent mandate from the Food and Drug Administration restricting the marketing and direct indication of acellular dermal matrices (ADMs) in breast reconstruction, we sought to highlight the overall safety and efficacy demonstrated in the existing literature surrounding all alloplastic materials in nipple-areola complex reconstruction. In this study, the authors conduct a systematic review and pooled outcomes analysis on allogenic and alloplastic implant materials utilized to achieve long-lasting nipple projection stratified by specific material used and respective outcomes., Methods: A comprehensive systematic review on allogenic and synthetic materials data utilized in nipple reconstruction was conducted utilizing Medline/PubMed database. Articles were stratified by (1) alloplastic material, as well as (2) objective and patient-reported outcomes., Results: A total of 592 nipple-areola complexes on 482 patients were featured in 15 case series. In all studies, alloplastic or allograft material was utilized to achieve and maintain nipple projection. Subjective measurements revealed a patient satisfaction rate of 93.3% or higher with the majority of patients being very satisfied with their reconstruction. The alloplastic and allograft implants analyzed had an overall complication rate of 5.3% across all materials used. The most common complication reported was flap or graft necrosis with a pooled rate of 2.5%. Overall, the Ceratite implant presented with the highest complication rate (18%) including flap/graft necrosis (13%) and extrusion of the artificial bone (5%). Other rigid implants such as the biodesign nipple reconstruction cylinder reported complications of extrusion (3.6%), projection loss requiring revision (2.5%), wound dehiscence/drainage (1.5%), flap or graft necrosis (1.0%) and excessive bleeding (0.5%). ADM implants had reported complications of both insufficient projection (0.8%) and excessive projection (1.6%), which required surgical revision. Injectable materials had minimal reported complications of pain during injection (0.8%) with Radiesse and a false-positive PET scan result (0.8%) with DermaLive., Conclusions: Allogeneic and alloplastic grafts are a reliable means of achieving satisfactory nipple projection, with a relatively low overall complication profile. The use of Ceratite (artificial bone) led to the highest complication rates. Further clinical studies are necessary to better understand the feasibility and longer-term outcomes of the use of allogeneic and synthetic augmentation grafts to improve nipple projection., Level of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Background: Although sedative premedication for endotracheal intubation is considered standard of care, less invasive surfactant administration (LISA) is often performed without sedative premedication. The aim of this study was to assess success rates, technical quality and vital parameters in LISA without sedative premedication., Methods: Prospective observational study in 86 neonates <32 weeks' gestation. LISA was performed according to a standardized protocol without use of sedative premedication. Outcome measures were success rates of LISA attempts, reasons for failure and quality of technical conditions. In 37 neonates, heart rate and oxygen saturation levels from 20 min before until 30 min after start of LISA were collected., Results: In 48% of LISAs the first attempt failed and in 34% quality of technical conditions was inadequate. The success rate was significantly correlated with quality of technical conditions and experience of the performer. Desaturations <80% occurred in 54% of patients while bradycardia <80/min did not occur., Conclusion: This study shows a relatively low success rate of the first attempt of LISA, frequent inadequacy of technical quality and frequent oxygen desaturations. These effects may be improved by the use of sedative premedication.