bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional rather than global brain age mediates cognitive function in cerebral small vessel disease
Authors: Lee Pei-Lin , Kuo Chen-Yuan , Wang Pei-Ning , Chen Liang-Kung , Lin Ching-Po , Chou Kun-Hsien , Chung Chih-Ping
Published: September 2022

The factors and mechanisms underlying the heterogeneous cognitive outcomes of cerebral small vessel disease are largely unknown. Brain biological age can be estimated by machine learning algorithms that use large brain MRI data sets to integrate and compute neuroimaging-derived age-related features. Predicted and chronological ages difference (brain-age gap) reflects advanced or delayed brain aging in an individual. The present study firstly reports the brain aging status of cerebral small vessel disease. In addition, we investigated whether global or certain regional brain age could mediate the cognitive functions in cerebral small vessel disease. Global and regional (400 cortical, 14 subcortical and 28 cerebellum regions of interest) brain-age prediction models were constructed using grey matter features from MRI of 1482 healthy individuals (age: 18–92 years). Predicted and chronological ages differences were obtained and then applied to non-stroke, non-demented individuals, aged ≥50 years, from another community-dwelling population (I-Lan Longitudinal Aging Study cohort). Among the 734 participants from the I-Lan Longitudinal Aging Study cohort, 124 were classified into the cerebral small vessel disease group. The cerebral small vessel disease group demonstrated significantly poorer performances in global cognitive, verbal memory and executive functions than that of non-cerebral small vessel disease group. Global brain-age gap was significantly higher in the cerebral small vessel disease (3.71 ± 7.60 years) than that in non-cerebral small vessel disease (−0.43 ± 9.47 years) group (P = 0.003, η2 = 0.012). There were 82 cerebral cortical, 3 subcortical and 4 cerebellar regions showing significantly different brain-age gap between the cerebral small vessel disease and non-cerebral small vessel disease groups. Global brain-age gap failed to mediate the relationship between cerebral small vessel disease and any of the cognitive domains. In 89 regions with increased brain-age gap in the cerebral small vessel disease group, seven regional brain-age gaps were able to show significant mediation effects in cerebral small vessel disease-related cognitive impairment (we set the statistical significance P < 0.05 uncorrected in 89 mediation models). Of these, the left thalamus and left hippocampus brain-age gap explained poorer global cognitive performance in cerebral small vessel disease. We demonstrated the interconnections between cerebral small vessel disease and brain age. Strategic brain aging, i.e. advanced brain aging in critical regions, may be involved in the pathophysiology of cerebral small vessel disease-related cognitive impairment. Regional rather than global brain-age gap could potentially serve as a biomarker for predicting heterogeneous cognitive outcomes in patients with cerebral small vessel disease.
Psychometric properties of the Brazilian version of the European Health Literacy Survey Questionnaire short form
Authors: Mialhe Fábio Luiz , Sampaio Helena Alves De Carvalho , Moraes Katarinne Lima , Brasil Virgínia Visconde , Rebustini Flávio
Published: September 2022

The aim of this study was to analyze the psychometric properties of the Portuguese Brazilian version of the instrument for measuring health literacy European Health Literacy Survey Questionnaire short form (HLS-EU-Q16). The study sample consisted of 783 Brazilian adults with a mean age of 38.6 years. The data were analyzed through an extensive and robust process of testing the properties with the combination of exploratory factor analysis (EFA), confirmatory factor analysis (CFA) and item response theory (IRT) techniques, aiming to search for strong validation evidence in the internal structure and stability step for other sub-samples. The instrument’s reliability was tested using Cronbach’s alpha and McDonald’s Omega. The analyses indicated the existence of only one dimension and good reliability values. The model tested with cross-validation indicated satisfactory, adequate, consistent and stable levels for EFA, IRT via item discrimination and CFA, both for primary indicators as factor loadings, communalities, item discrimination as well as for the model adequacy indicators. It is concluded that the Brazilian Portuguese version of the HLS-EU-Q16 proved to be a one-dimensional, consistent, accurate and stable model for measuring health literacy in Brazilian adults.
Shifting baselines and deciding on the desirable form of multispecies maximum sustainable yield
Authors: Fulton E A , Sainsbury K , Noranarttragoon P , Leadbitter D , Staples D J , Porobic J , Ye Y , Phoonsawat R , Kulanujaree N
Published: September 2022

Multispecies, multigear fisheries occur in most ecosystems in the world, but are typical in tropical ecosystems and especially in emerging economies. However, much of fishery science has been developed from a single-species perspective. Management schemes based on single-species reference points often ignore the trophic link among species and the technical interaction between gears, essentially disconnecting management objectives from the context of an ecosystem—or socioecological system—where fisheries operate. Using the Gulf of Thailand fishery as an example, we demonstrate how aggregate production models can be used to estimate system-level fishery reference points for multispecies fisheries. Our results show that the multispecies maximum sustainable yield changes with ecosystem state—the systemic productivity level due to species composition and ecological (trophic/habitat, etc.) structure—under various development levels of fishing and varies with management objectives such as biodiversity, system resilience, total catch, total value, and employment. Aggregate approaches are a tractable way of estimating sustainable ecosystem-scale extraction for multispecies fisheries, avoiding the dilemma of facing conflicting advice derived from single-species methods and providing a practical, operational step toward ecosystem-based management. However, these methods are sensitive to the ecosystem states over time and decision makers need to make informed decisions on which state they want to maintain (or recover) and thus which system-level reference points to use. Consequently, management of multispecies fisheries must be clear on their system-level fisheries policy objectives.
Infinite-order accuracy limit of finite difference formulas in the complex plane
Authors: Fornberg Bengt
Published: September 2022

It was recently found that finite difference (FD) formulas become remarkably accurate when approximating derivatives of analytic functions $f(z)$ in the complex $z=x+\text{i}y$ plane. On unit-spaced grids in the $x,y$-plane, the FD weights decrease to zero with the distance to the stencil center at a rate similar to that of a Gaussian, typically falling below the level of double precision accuracy $\mathcal{O}(10^{-16})$ already about four node spacings away from the center point. We follow up on these observations here by analyzing and illustrating the features of such FD stencils in their infinite-order accurate limit (for traditional FD approximations known as their pseudospectral limit).
Weight change with integrase strand transfer inhibitors among virally suppressed Thai people living with HIV
Authors: Han Win Min , Kerr Stephen J , Avihingsanon Anchalee , Boettiger David C
Published: September 2022

Background

We compared weight changes in virally suppressed people living with HIV (PLWH) switching to integrase strand transfer inhibitors (INSTIs) with those remaining on an INSTI or non-INSTI regimen.

Methods

PLWH aged ≥18 years with weight measurements available at baseline between 2001 and 2020 were included. Viral suppression was defined as having had a viral load <400 copies/mL for 6 months. Baseline was defined as the time of switching from a non-INSTI to an INSTI regimen whilst virally suppressed (switch group) or the time that viral suppression was achieved (remain groups). Generalized estimating equations adjusted for age, sex and baseline weight were used to model weight changes 6, 12, 18 and 24 months after baseline.

Results

A total of 1673 PLWH contributed 1952 episodes of viral suppression—143 (7.3%) episodes were among PLWH who had switched from a non-INSTI to an INSTI, 102 (5.2%) episodes were among PLWH who remained on an INSTI and 1707 (87.4%) episodes were among PLWH who remained on a non-INSTI. PLWH in the switch group had significantly greater weight gain than those in the remain groups at 6, 12 and 18 months after achieving viral suppression. By 24 months, weight change on all regimens started to converge. Tenofovir alafenamide use was not significantly associated with weight gain in adjusted models.

Conclusions

Our findings suggest that the mechanisms of weight gain due to INSTI use go beyond their superior efficacy over other antiretrovirals in controlling HIV or the effect of the ‘return-to-health’ phenomenon. Further research is needed to understand the mechanisms of such weight gain.
In vitro antibacterial activity of OPS-2071 against Gram-positive and Gram-negative enteropathogenic bacteria
Authors: Oka Daisuke , Changkwanyeun Ruchirada , Yamaguchi Tomoyuki , Nakajima Chie , Suzuki Yasuhiko , Matsumoto Makoto
Published: September 2022

Background

Enteric infections are a major public health issue in developing countries. Antimicrobial resistance is also a problem for enteric infection. OPS-2071 is a novel quinolone antibiotic with low oral absorption and potent antibacterial activity against Clostridioides difficile.

Objectives

This study was conducted to confirm the antimicrobial activity of OPS-2071 against major enteropathogenic bacteria and to evaluate the risk of emergence of drug resistance.

Methods

The antibacterial activity was evaluated by the agar dilution method. The inhibitory activity against DNA gyrase and topoisomerase IV was determined by supercoiling assay and decatenation assay, respectively. The mutant prevention concentration and frequency of spontaneous resistance were determined by inoculation on drug-containing agar.

Results

Compared with the reference drugs, the antibacterial activity of OPS-2071 was more potent against Gram-positive bacteria and Campylobacter jejuni, including quinolone-resistant strains. Against other Gram-negative bacteria, OPS-2071 was comparable to existing quinolones. The inhibitory activities against DNA gyrase with quinolone-resistant mutations closely correlated with the antibacterial activity. Spontaneous resistance to OPS-2071 was not observed in Staphylococcus aureus and Escherichia coli and was lower than that of existing quinolones and higher than that of azithromycin in C. jejuni. The mutant prevention concentration of OPS-2071 was lower than that of tested compounds in S. aureus and C. jejuni and slightly higher than that of existing quinolones in E. coli.

Conclusions

The broad and potent in vitro antibacterial activity and lower risk of drug resistance suggested that OPS-2071 may be useful for enteric infections caused by major pathogens including quinolone-resistant Campylobacter.
The nutritive value of soybean meal from different sources for sows during mid- and late gestation
Authors: Wang Ke , Zou Xiangyang , Guo Lei , Huang Long , Wang Ya , Yang Pu , Huang Liansu , Ma Xiangyuan , Zhuo Yong , Che Lianqiang , Xu Shengyu , Hua Lun , Li Jian , Feng Bin , Wu Fali , Fang Zhengfeng , Zhao Xilun , Jiang Xuemei , Lin Yan , Wu De
Published: September 2022

A precise understanding of the nutritive value of soybean meal (SBM) for pregnant sow is required for accurate feeding. Hence, we evaluated the nutritive value of 11 SBM samples from different sources for sows during mid and late gestation. In total, 24 mid-gestating sows (parity three; 230.3 ± 12.0 kg on day 37 of gestation) and 24 late-gestating sows (parity three; 238.8 ± 20.9 kg on day 72 of gestation) were assigned to a replicated 12 × 3 Youden square design with 12 diets and 3 periods. The 12 diets included a corn-based diet and 11 diets containing 25.50% SBMs from different sources. After 5-d adaptation, urine and feces were collected for 5 d. Although the chemical characteristics of SBM varied between samples, no differences were observed in digestible energy (DE), metabolizable energy (ME), apparent total tract digestibility (ATTD) of dry matter, gross energy, crude fiber, and neutral detergent fiber values in SBMs fed to both animal groups. However, de-hulled SBM 4 from Brazil displayed greater ATTD for nitrogen (N) in late-gestating sows (P < 0.05); animals displayed significantly (P < 0.01) greater ME, ME:DE ratio, and N net utilization values when compared with mid-gestating sows. The chemical composition of SBMs can be used to predict DE and ME values. In conclusion, ME, ME:DE ratio, and N net utilization SBM values for late-gestating sows were greater than in mid-gestating sows. Therefore, we should consider differences in ME values for SBMs when formulating diets for sows in mid and late gestation periods.
Opinions on the Assessment of Breast Density Among Members of the Society of Breast Imaging
Authors: Zhang Zi , Conant Emily F , Zuckerman Samantha
Published: September 2022

Objective

Dense breast decreases the sensitivity and specificity of mammography and is associated with an increased risk of breast cancer. We conducted a survey to assess the opinions of Society of Breast Imaging (SBI) members regarding density assessment.

Methods

An online survey was sent to SBI members twice in September 2020. The survey included active members who were practicing radiologists, residents, and fellows. Mammograms from three patients were presented for density assessment based on routine clinical practice and BI-RADS fourth and fifth editions. Dense breasts were defined as heterogeneously or extremely dense. Frequencies were calculated for each survey response. Pearson’s correlation coefficient was used to evaluate the correlation of density assessments by different definitions.

Results

The survey response rate was 12.4% (357/2875). For density assessments, the Pearson correlation coefficients between routine clinical practice and BI-RADS fourth edition were 0.05, 0.43, and 0.12 for patients 1, 2, and 3, respectively; these increased to 0.65, 0.65, and 0.66 between routine clinical practice and BI-RADS fifth edition for patients 1, 2, and 3, respectively. For future density grading, 79.0% (282/357) of respondents thought it should reflect both potential for masking and overall dense tissue for risk assessment. Additionally, 47.1% (168/357) of respondents thought quantitative methods were of use.

Conclusion

Density assessment varied based on routine clinical practice and BI-RADS fourth and fifth editions. Most breast radiologists agreed that density assessment should capture both masking and overall density. Moreover, almost half of respondents believed computer or artificial intelligence–assisted quantitative methods may help refine density assessment.
Coaching: A Strategy for Breast Radiologists’ Professional Development
Authors: Gatto Rex P , Berg Wendie A , Mainiero Martha B
Published: September 2022

The continually increasing demands placed on physicians have led to high levels of burnout, and breast radiologists are no exception. Professional coaching is a means to guide and support the radiologist through a process of positive thinking, stress reduction, goal setting, mental growth, work-life balance, and behavioral change. Professional coaching may be effective in preparation for leadership roles or in response to workplace issues or conflict. The radiologist, with the help of a coach, establishes goals, expands perception and mindset, and collaboratively may find ways to resolve issues by taking new and different approaches. This article discusses why radiologists should seek out a certified coach and what a coach can offer radiologists during these trying times, as well as outlining the coaching process. Coaching has proven useful in addressing professional growth, workplace issues, and physician burnout. At the conclusion of the article, the readers will be able to discern whether coaching can support a better quality of life for them.
The influence of biofertilizers on leaf economics spectrum traits in a herbaceous crop
Authors: Martin Adam R , Mariani Rachel O , Dörr de Quadros Patricia , Fulthorpe Roberta R
Published: September 2022

Microbial inoculations or ‘biofertilizers’ represent novel contributions to sustainable agriculture. While belowground mechanisms surrounding how biofertilizers enhance crop production are well described, their role in aboveground trait expression remains less well explored. We quantified infraspecific variation in leaf economics spectrum (LES) traits in response to 10 biofertilizer treatments in basil (Ocimum basiclicum) cultivated under hydroponic conditions. Multiple physiological (i.e. maximum photosynthesis rates (A), dark respiration (R), and leaf-level light compensation points) and morphological (i.e. leaf mass per area (LMA) and leaf thickness) traits varied significantly across microbial treatments. Following treatments, basil plants differentiated from one another along an infraspecific LES, with certain plants expressing more resource-acquiring LES trait values (i.e. high A, R, leaf N, and low LMA), versus others that expressed the opposite suite of resource-conserving LES trait values. Infraspecific trait covariation largely matched LES patterns observed among plants globally. Bivariate and multivariate trait analyses further revealed that certain treatments—namely those including closely related Bacillus and Brevibacillus species strains—increased leaf resource capture traits such as A and leaf N. Biofertilizers influence plant performance through a role in moderating infraspecific leaf trait variation, thereby suggesting aboveground leaf traits may be used to diagnose optimal biofertilizer formulations in basil and other crops.
Formin protein DRT1 affects gross morphology and chloroplast relocation in rice
Authors: Zhang Yanli , Dong Guojun , Wu Limin , Wang Xuewen , Chen Fei , Xiong Erhui , Xiong Guosheng , Zhou Yihua , Kong Zhaosheng , Fu Ying , Zeng Dali , Ma Dianrong , Qian Qian , Yu Yanchun
Published: September 2022

Plant height and tiller number are two major factors determining plant architecture and yield. However, in rice (Oryza sativa), the regulatory mechanism of plant architecture remains to be elucidated. Here, we reported a recessive rice mutant presenting dwarf and reduced tillering phenotypes (drt1). Map-based cloning revealed that the phenotypes are caused by a single point mutation in DRT1, which encodes the Class I formin protein O. sativa formin homolog 13 (OsFH13), binds with F-actin, and promotes actin polymerization for microfilament organization. DRT1 protein localized on the plasma membrane (PM) and chloroplast (CP) outer envelope. DRT1 interacted with rice phototropin 2 (OsPHOT2), and the interaction was interrupted in drt1. Upon blue light stimulus, PM localized DRT1 and OsPHOT2 were translocated onto the CP membrane. Moreover, deficiency of DRT1 reduced OsPHOT2 internalization and OsPHOT2-mediated CP relocation. Our study suggests that rice formin protein DRT1/OsFH13 is necessary for plant morphology and CP relocation by modulating the actin-associated cytoskeleton network.
On the parameter combinations that matter and on those that do not: data-driven studies of parameter (non)identifiability
Authors: Evangelou Nikolaos , Wichrowski Noah J , Kevrekidis George A , Dietrich Felix , Kooshkbaghi Mahdi , McFann Sarah , Kevrekidis Ioannis G
Published: September 2022

We present a data-driven approach to characterizing nonidentifiability of a model’s parameters and illustrate it through dynamic as well as steady kinetic models. By employing Diffusion Maps and their extensions, we discover the minimal combinations of parameters required to characterize the output behavior of a chemical system: a set of effective parameters for the model. Furthermore, we introduce and use a Conformal Autoencoder Neural Network technique, as well as a kernel-based Jointly Smooth Function technique, to disentangle the redundant parameter combinations that do not affect the output behavior from the ones that do. We discuss the interpretability of our data-driven effective parameters, and demonstrate the utility of the approach both for behavior prediction and parameter estimation. In the latter task, it becomes important to describe level sets in parameter space that are consistent with a particular output behavior. We validate our approach on a model of multisite phosphorylation, where a reduced set of effective parameters (nonlinear combinations of the physical ones) has previously been established analytically.
From Market Making to Matchmaking: Does Bank Regulation Harm Market Liquidity?
Authors: Saar Gideon , Sun Jian , Yang Ron , Zhu Haoxiang
Published: September 2022

Postcrisis bank regulations raised market-making costs for bank-affiliated dealers. We show that this can, somewhat surprisingly, improve overall investor welfare and reduce average transaction costs despite the increased cost of immediacy. Bank dealers in OTC markets optimize between two parallel trading mechanisms: market making and matchmaking. Bank regulations that increase market-making costs change the market structure by intensifying competitive pressure from nonbank dealers and incentivizing bank dealers to shift their business activities toward matchmaking. Thus, postcrisis bank regulations have the (unintended) benefit of replacing costly bank balance sheets with a more efficient form of financial intermediation.
Assessment of Patient-Reported Outcomes in Patients with Anal Squamous Cell Cancer Undergoing Combined Modality Therapy
Authors: Taylor James P. , Wei Iris H. , Smith J. Joshua , Tin Amy L. , Aiken Nate , Vickers Andrew J. , Romesser Paul B. , Crane Christopher H. , Widmar Maria , Nash Garrett M. , Weiser Martin R. , Paty Philip B. , Garcia-Aguilar Julio , Pappou Emmanouil
Published: September 2022

BACKGROUND:

There is limited knowledge on long-term bowel, sexual, and urinary function after combined modality therapy for anal squamous cell cancer.

OBJECTIVE:

To evaluate long-term changes in bowel, sexual, and urinary function in patients treated with combined modality.

DESIGN:

This was a retrospective study of prospectively collected patient reported outcome surveys.

SETTING:

Single institution.

PATIENTS:

There were 143 patients with stage I-III anal cancer who were treated with chemoradiation and had completed the survey.

MAIN OUTCOME MEASURES:

Patient-reported outcomes reflecting bowel, sexual, and urinary function.

RESULTS:

Thirty-nine percent of patients had major low anterior resection syndrome scores at baseline. Major low anterior resection syndrome scores remained stable (38%; 95% CI 31%, 46%) with no change over time (OR 0.95, 95% CI 0.74, 1.21, p = 0.7). Higher rates of major low anterior resection syndrome scores were observed for patients who had major low anterior resection syndrome scores at baseline (OR 20.7; 95% CI 4.70, 91.3, p < 0.001) and for females (OR 2.14; 95% CI 1.01, 4.56; p = 0.047). On 5-point scales, we saw a non-significant increased level of sexual arousal during sexual activity after therapy for women (β for 1 year = 0.15; 95% CI -0.01, 0.32; p = 0.072) and non-significant decreased confidence in getting and keeping an erection after therapy for men (β for 1 year = -0.33; 95% CI -0.66, 0.00; p = 0.053).

LIMITATIONS:

This is a single-institution study. Only patients who answered the questionnaire were included in the study.

CONCLUSIONS:

A significant proportion of patients have major low anterior resection syndrome scores at baseline and after successful treatment for anal cancer. Having major low anterior resection syndrome scores at baseline was the biggest predictor of having major low anterior resection syndrome scores after treatment. Bowel, sexual, and urinary function did not improve over time up to 2 years after end of treatment. Physicians should counsel their patients prior to treatment that baseline poor bowel function is a risk factor for post treatment bowel dysfunction. See Video Abstract at http://links.lww.com/DCR/C29.
Damage to the Temporal Branch of the Facial Nerve From Mohs Micrographic Surgery
Authors: Axibal Eileen L. , Fisher Marlie H. , Miller Misha D. , Brown Mariah R.
Published: September 2022

BACKGROUND

The temporal branch of the facial nerve is at risk of damage during Mohs micrographic surgery (MMS). This complication leads to motor deficit in the ipsilateral upper face with resultant functional and cosmetic impairment.

OBJECTIVE

To identify patient, tumor, and surgical risk factors associated with temporal nerve damage.

MATERIALS AND METHODS

A single-institution, retrospective review of MMS cases involving anatomic sites within the temporal nerve danger zone was performed. Risk factors were compared between cases with and without nerve damage.

RESULTS

Of 616 cases within the danger zone, 28 (4.5%) had postoperative nerve dysfunction. Variables significantly associated with dysfunction included patient immunosuppression, tumor size, aggressive tumor histology, recurrent tumors, high degree of subclinical spread, and greater average number of Mohs stages. Preoperative tumor size and postoperative defect size of ≥3 cm resulted in a ×37 and ×40 increased odds of nerve damage, respectively. Sex, age, and basal versus squamous cell carcinoma were not significantly associated with temporal nerve damage. No patients with a postoperative defect size measuring <2 cm had nerve damage.

CONCLUSION

The overall risk of damage to the temporal nerve during MMS is low, but there are certain risk factors that warrant increased counseling about this potential complication.
Expression of Key Steroidogenic Enzymes in Human Placenta and Associated Adverse Pregnancy Outcomes
Authors: Cao Jiasong , Wang Yixin , Wang Shuqi , Shen Yongmei , Li Wen , Wei Zhuo , Li Shanshan , Lin Qimei , Chang Ying
Published: September 2022

Steroid hormones, including progestagens, estrogens, androgens, corticosteroids, and their precursor cholesterol, perform essential functions in the successful establishment and maintenance of pregnancy and normal fetal development. As the core endocrine organ at the prenatal stage, the human placenta is involved in the biosynthesis, metabolism, and delivery of steroid hormones. Steroidogenic pathways are tightly regulated by placenta-intrinsic cytochrome P450 and hydroxysteroid dehydrogenase. However, the relationship between placental steroidogenic enzyme expression and adverse pregnancy outcomes is controversial. In this review, we summarize the possible upstream regulatory mechanisms of placental steroidogenic enzymes in physiologic and pathophysiologic states. We also describe the human placental barrier model and examine the potential of single-cell sequencing for evaluating the primary functions and cellular origin of steroidogenic enzymes. Finally, we examine the existing evidence for the association between placental steroidogenic enzyme dysregulation and adverse pregnancy outcomes.
Viability of Fat Cells in Frozen Fat Tissue in Relation to Thawing Technique
Authors: Lashin Riham , Abu Zahra Fatma A. , Elshahat Ahmed , Elgazzar Khaled
Published: September 2022

Background:

Damage of frozen fat, which will be used for retransplantation, is inevitable. Reuse of frozen fat requires a thawing process. No standardized method has yet been established for thawing frozen fat.

Methods:

Microscopic analysis of count and viability of frozen fat of 21 patients. Two fat samples from each patient were harvested and frozen at –20°C in a common commercial refrigerator for different freezing durations. Thawing of fat samples was done. There was one (3 mL) sample for each thawing technique; technique A included natural thawing at 25°C for 15 minutes, while rapid thawing at 37°C for 10 minutes in a water bath was included in technique B. Survival rates of adipocytes were assessed with trypan blue staining. Culturing of adipose-derived stem cells to assess their ability to divide was done. Relating survival rate of frozen fat to patients’ age and to duration of freezing was done. Results were statistically analyzed.

Results:

The count of viable adipocytes is higher in technique A. Adipose-derived stem cells of frozen fat do not have the ability to divide in culture media. Viable adipocytes were higher in younger ages and in shorter freezing duration.

Conclusion:

Natural thawing is better in maintaining frozen adipocyte viability. Younger patients will benefit from frozen fat more than older ones. Duration of freezing should not exceed 7 months.
Back to Basics: Lifestyle Interventions for Adolescent Depression
Authors: Benheim Talia S. , Dalal Michelle , Holcomb Juliana M. , Dutta Anamika , Hosker Daniel , Jellinek Michael S. , Murphy J. Michael
Published: September 2022

Learning objectives

After completing this activity, practitioners will be better able to:

• Discuss and better understand the recently adopted screening standards for adolescents with depression and the potential advantages of using “lifestyle medicine”

• Set up a process for providing effective interventions for the increased number of patients with adolescent depression

• Design or update their toolbox of treatment options for adolescents with depression based on the new literature and increased demand

Recently adopted quality standards recommend that pediatricians screen adolescents for depression and that they document follow-up plans for those who screen positive. As a result of these new recommendations, pediatricians and other pediatric providers, as well as psychiatrists and other mental health professionals, may face an increasing number of referrals and a growing need for effective interventions for adolescent depression. Given the widely acknowledged scarcity of traditional mental health resources, the current study reviewed the rapidly expanding array of evidence-based, but nontraditional, interventions applicable to outpatient pediatric and mental health care settings. Many of these interventions come from a lifestyle medicine framework. Lifestyle medicine interventions are congruent with the cultures of pediatrics and outpatient psychiatry, and offer additional evidence-based tools for providers managing adolescent depression. These interventions can be implemented individually or within group or community settings, and may be used in conjunction with more common interventions such as psychotherapy or psychotropic medications.
Management of Extensive Central Nervous System Cladophialophora bantiana Infection in a 9-Year-Old Child
Authors: Boguniewicz Juri , Demmler-Harrison Gail J. , Lotze Timothy E. , Jarjour Imad T. , Whitehead William E. , Frontiero Jessica , Dutta Ankhi , Fogarty Thomas , Hunter Jill V. , Ogunbona Oluwaseun B. , Pareek Aishwarya V. , Cameron Lindsay H.
Published: September 2022

Background:

Pediatric central nervous system (CNS) phaeohyphomycosis is a rare invasive fungal infection associated with high mortality.

Methods:

We describe a child with progressive neurologic symptoms whose ultimate diagnosis was Cladophialophora bantiana-associated CNS phaeohyphomycosis. We discuss her clinical presentation, medical and surgical management and review the current literature.

Results:

A 9-year-old female presented with acute onset of headaches, ophthalmoplegia and ataxia. Initial infectious work-up was negative, including serial fungal cerebrospinal fluid cultures. Over 2 months, she experienced progressive cognitive and motor declines, and imaging revealed worsening meningitis, ventriculitis and cerebritis. Ultimately, Cladophialophora was detected by plasma metagenomic next-generation sequencing (mNGS). Fourth ventricle fluid sampling confirmed the diagnosis of C. bantiana infection. Given the extent of her disease, complete surgical resection was not feasible. She required multiple surgical debridement procedures and prolonged antifungal therapy, including the instillation of intraventricular amphotericin B. With aggressive surgical and medical management, despite her continued neurologic deficits, she remains alive 3 years after her initial diagnosis. To our knowledge, this is one of a few published pediatric cases of CNS phaeohyphomycosis and the first with the causative pathogen identified by plasma mNGS.

Conclusion:

CNS phaeohyphomycosis is a serious, life-threatening infection. The preferred management includes a combination of surgical resection and antifungal therapy. In cases complicated by refractory ventriculitis, intraventricular antifungal therapy can be considered as adjuvant therapy. Direct sampling of the CNS for pathogen identification and susceptibility testing is the gold standard for diagnosis; however, the use of plasma mNGS may expedite the diagnosis.
Incidence of Early and Late Onset Neonatal Sepsis in Suriname: A National Tertiary Hospital Birth-cohort Study
Authors: Juliana Amadu E. , Holband Natanael , Lissone Neirude P. A. , Zonneveld Rens , Evers Niels , Plötz Frans B. , Achten Niek B.
Published: September 2022

Background:

Early onset neonatal sepsis (EONS) and late onset neonatal sepsis (LONS) are important causes of neonatal mortality and morbidity. A pressing need for reliable and detailed data of low- and middle-income countries exists. This study aimed to describe the incidence and outcome of neonatal sepsis in the only tertiary hospital of Suriname, a middle-income country in South America.

Methods:

Infants born at the Academic Hospital of Paramaribo from May 2017 through December 2018 were prospectively included at birth. Perinatal data, duration of antibiotic treatment, blood culture results and mortality data were gathered. Neonatal sepsis was defined as positive blood culture with a pathogenic microorganism within the first 28 days of life.

Results:

Of the 2190 infants included, 483 (22%) were admitted to neonatal (intensive) care. The incidence of EONS was 2.1 (95% CI: 0.9–5) per 1000 live births, with no deaths. Antibiotics for suspected EONS were administrated to 189 (8.6%) infants, of whom 155 (82%) were born prematurely. The incidence of LONS cases was 145 (95% CI: 114–176) per 1000 admissions. Gramnegative bacteria accounted for 70% (48 out of 70) of causative organisms. Seventeen deaths were directly caused by sepsis (35 per 1000 admissions).

Conclusions:

Findings from this tertiary center birth cohort study in a middle-income setting indicate EONS incidence and outcomes comparable to high-income settings, whereas LONS is a more prevalent and significant challenge with a predominance of gram-negative bacteria, and high mortality.
Outpatient Antibiotic Prescribing for 357,390 Children With Otitis Media
Authors: Csonka Péter , Palmu Sauli , Heikkilä Paula , Huhtala Heini , Korppi Matti
Published: September 2022

Aim:

This study aimed to evaluate antibiotic prescriptions for children with otitis media (OM) in a large nationwide network of private clinics between 2014 and 2020. Special focus was paid to amoxicillin and amoxicillin-clavulanic acid prescriptions, which the national guidelines recommend for first-line drugs. We also focused on macrolides, which are commonly prescribed for respiratory tract infections in children but are not appropriate for OM cases.

Methods:

The data were obtained from the electronic health records of about 250,000 annual visits in <18 years old children. The collected variables were all diagnoses, age, visit year, doctor’s specialty, and prescribed antibiotics. Children with OM and upper respiratory tract infections were included, but those with lower respiratory tract infections were excluded.

Results:

The number of children with OM was 357,390 (55.2% boys). Antibiotics were prescribed in 44.8% of cases, with the lowest proportion (44.1%) being in <2 years old children. The overall prescription rate decreased from 48.3% in 2014 to 41.4% in 2020. The rates were 19.3% and 18.1% for amoxicillin and 12.6% and 13.2% for amoxicillin-clavulanic acid, respectively. Macrolide prescriptions were reduced from 7.5% to 3.5%. Pediatricians prescribed antibiotics for 38.8%, general practitioners for 54.0% and ear, nose and throat physicians for 39.8% of children with OM.

Conclusion:

The selection of antibiotics for OM, when prescribed, was according to the recommendations (amoxicillin or amoxicillin-clavulanic acid) in 80.1% of pediatricians, 67.0% of general practitioners and 55.1% of ear, nose and throat physicians.
Frequency of Bacteremia and Urinary Tract Infection in Pediatric Renal Transplant Recipients
Authors: Cruz Andrea T. , Tanverdi Melisa S. , Swartz Sarah J. , Dayan Peter S. , Combs Veronica A. , Lubell Tamar R.
Published: September 2022

Background:

Our primary goal was to determine the frequency of bacteremia and urinary tract infections (UTI) in pediatric renal transplant recipients presenting with suspected infection within 2 years of transplant and to identify clinical and laboratory factors associated with bacteremia.

Methods:

We conducted a retrospective cross-sectional study for all pediatric (<18 years old) renal transplant recipients seen at 3 large children’s hospitals from 2011 to 2018 for suspected infection within 2 years of transplant date, defined as pyrexia (>38°C) or a blood culture being ordered. Patients with primary immunodeficiencies, nontransplant immunosuppression, intestinal failure, and patients who had moved out of the local area were excluded. The primary outcome was bacteremia or UTI; secondary outcomes included pneumonia, bacterial or fungal meningitis, respiratory viral infections, and antibiotic resistance. The unit of analysis was the visit.

Results:

One hundred fifteen children had 267 visits for infection evaluation within 2 years of transplant. Bacteremia (with or without UTI) was diagnosed in 9/213 (4.2%) and UTIs in 63/189 (33.3%). Tachycardia and hypotension were present in 66.7% and 0% of visits with documented bacteremia, respectively. White blood cell (12,700 cells/mm3 vs. 10,900 cells/mm3; P = 0.43) and absolute neutrophil count (10,700 vs. 8200 cells/mm3; P = 0.24) were no different in bacteremic and nonbacteremic patients. The absolute band count was higher in children with bacteremia (1900 vs. 600 cells/mm3; P = 0.02). Among Gram-negative pathogens, antibiotic resistance was seen to 3rd (14.5%) and 4th (3.6%) generation cephalosporins, 12.7% to semisynthetic penicillins, and 3.6% to carbapenems.

Conclusions:

Bacteremia or UTIs were diagnosed in one-quarter of all pediatric renal transplant recipients presenting with suspected infection within 2 years of transplant. Evaluations were highly variable, with one-third of visits not having urine cultures obtained. No single demographic, clinical or laboratory variable accurately identified patients with bacteremia, although combinations of findings may identify a high-risk population.
Multisystem Inflammatory Syndrome in Children in Western Countries? Decreasing Incidence as the Pandemic Progresses?: An Observational Multicenter International Cross-sectional Study
Authors: Buonsenso Danilo , Perramon Aida , Català Martí , Torres Juan P. , Camacho-Moreno Germán , Rojas-Solano Mariela , Ulloa-Gutierrez Rolando , Camacho-Badilla Kattia , Pérez-Corrales Cristian , Cotugno Nicola , Yamazaki-Nakashimada Marco A. , Estripeaut Dora , Buddingh Emilie Pauline , von Asmuth Erik , van Rossum Annemarie M.C. ,   COPP-consortium, Soler-Palacin Pere , Rivière Jacques G. , Prats Clara , Pino Rosa , Paredes-Carmona Fernando , Visa-Reñé Núria , García-Salido Alberto , Martínez-Mejias Abel ,   COPEDI-CAT Research Group, Soriano-Arandes Antoni
Published: September 2022

Background:

SARS-CoV-2 variations as well as immune protection after previous infections and/or vaccination may have altered the incidence of multisystemic inflammatory syndrome in children (MIS-C). We aimed to report an international time-series analysis of the incidence of MIS-C to determine if there was a shift in the regions or countries included into the study.

Methods:

This is a multicenter, international, cross-sectional study. We collected the MIS-C incidence from the participant regions and countries for the period July 2020 to November 2021. We assessed the ratio between MIS-C cases and COVID-19 pediatric cases in children <18 years diagnosed 4 weeks earlier (average time for the temporal association observed in this disease) for the study period. We performed a binomial regression analysis for 8 participating sites [Bogotá (Colombia), Chile, Costa Rica, Lazio (Italy), Mexico DF, Panama, The Netherlands and Catalonia (Spain)].

Results:

We included 904 cases of MIS-C, among a reference population of 17,906,432 children. We estimated a global significant decrease trend ratio in MIS-C cases/COVID-19 diagnosed cases in the previous month (P < 0.001). When analyzing separately each of the sites, Chile and The Netherlands maintained a significant decrease trend (P < 0.001), but this ratio was not statistically significant for the rest of sites.

Conclusions:

To our knowledge, this is the first international study describing a global reduction in the trend of the MIS-C incidence during the pandemic. COVID-19 vaccination and other factors possibly linked to the virus itself and/or community transmission may have played a role in preventing new MIS-C cases.
Visual outcomes and complications of combined vs sequential cataract surgery and pars plana vitrectomy: multicenter database study
Authors: Elhusseiny Abdelrahman M. , Soliman Mohamed K. , Shakarchi Ahmed F. , Fouad Yousef A. , Yang Yit C. , Sallam Ahmed B.
Published: September 2022

Purpose:

To compare the visual outcomes and rates of intraoperative complications in eyes that underwent combined cataract extraction (CE) and pars plana vitrectomy (combined group) with those that underwent sequential surgery (sequential group).

Setting:

Multicenter study.

Design:

Retrospective chart review.

Methods:

CE data set pooled from 8 UK sites between 2000 and 2015. The main outcome measures were the mean postoperative visual acuity (VA) and the rate of intraoperative complications in both groups.

Results:

2236 eyes in the combined group and 2270 eyes in the sequential group were included in this study. Mean preoperative VA was 1.0 logMAR in both groups. The mean logMAR postoperative VA was worse in the combined group than in the sequential group (P < .0001) at all timepoints, however, the differences in visual improvement between both groups decreased with longer follow-up time: 1.0 ± 0.7 vs 0.6 ± 0.6, 0.7 ± 0.6 vs 0.4 ± 0.5, and 0.7 ± 0.6 vs 0.5 ± 0.5 at 0 to 4 weeks, 4 to 12 weeks, and 12 to 24 weeks, respectively. Proportions of eyes that gained >3 logMAR units were 49% in the combined group and 66.2% in the sequential group (P < .0001). Logistic regression analysis showed that sequential surgery (odds ratio, 2.1) was a predictor for reaching 20/40 vision by 6 months. In the combined group, there was a statistically significantly higher rate of posterior capsular rupture.

Conclusions:

Postoperative visual gain was less in the combined group with a higher rate of posterior capsular rupture as compared with sequential phacovitrectomy. However, small differences in visual improvements between both groups by 6 months were observed.
Diet and the microbiota–gut–brain-axis: a primer for clinical nutrition
Authors: Ribeiro Gabriela , Ferri Aimone , Clarke Gerard , Cryan John F.
Published: September 2022

Purpose of review

Diet is an essential modulator of the microbiota–gut–brain communication in health and disease. Consequently, diet-induced microbiome states can impact brain health and behaviour. The integration of microbiome into clinical nutrition perspectives of brain health is sparse. This review will thus focus on emerging evidence of microbiome-targeted dietary approaches with the potential to improve brain disorders.

Recent findings

Research in this field is evolving toward randomized controlled trials using dietary interventions with the potential to modulate pathways of the microbiota–gut–brain-axis. Although most studies included small cohorts, the beneficial effects of Mediterranean-like diets on symptoms of depression or fermented foods on the immune function of healthy individuals shed light on how this research line can grow. With a clinical nutrition lens, we highlight several methodological limitations and knowledge gaps, including the quality of dietary intake information, the design of dietary interventions, and missing behavioural outcomes.

Findings in diet–microbiome–brain studies can have groundbreaking implications in clinical nutrition practice and research. Modulating brain processes through diet via the gut microbiota raises numerous possibilities. Novel dietary interventions targeting the microbiota–gut–brain-axis can offer various options to prevent and treat health problems such as mental disorders. Furthermore, knowledge in this field will improve current nutritional guidelines for disease prevention.
Sleep in the intensive care unit
Authors: Lee Eugenia Y. , Wilcox M. Elizabeth
Published: September 2022

Purpose of review

Sleep is particularly important for critically ill patients. Here, we review the latest evidence on how sleep and circadian disruption in the intensive care unit (ICU) affects physiology and clinical outcomes, as well as the most recent advances in sleep and circadian rhythm promoting interventions including therapeutics.

Recent findings

On a molecular level, clock genes dysrhythmia and altered immunity are clearly linked, particularly in sepsis. Melatonin may also be associated with insulin sensitivity in ICU patients. Clinically, changes in sleep architecture are associated with delirium, and sleep-promoting interventions in the form of multifaceted care bundles may reduce its incidence. Regarding medications, one recent randomized controlled trial (RCT) on melatonin showed no difference in sleep quality or incidence of delirium.

Further investigation is needed to establish the clinical relevance of sleep and circadian disruption in the ICU. For interventions, standardized protocols of sleep promotion bundles require validation by larger multicenter trials. Administratively, such protocols should be individualized to both organizational and independent patient needs. Incorporating pharmacotherapy such as melatonin and nocturnal dexmedetomidine requires further evaluation in large RCTs.
Modifying organs with gene therapy and gene modulation in the age of machine perfusion
Authors: Pavan-Guimaraes Juliana , Martins Paulo N.
Published: September 2022

Purpose of review

This review aims to highlight current advances in gene therapy methods, describing advances in CRISPR–Cas9 gene editing and RNA interference in relevance to liver transplantation, and machine perfusion.

Recent findings

In order to minimize rejection, increase the donor pool of available organs, and minimize the effects of ischemia–reperfusion injury, gene therapy and gene modification strategies are, thus, required in the context of liver transplantation.

Gene therapy has been used successfully in a diverse array of diseases, and, more recently, this technique has gained interest in the field of organ transplantation. Biological and logistical challenges reduce the rate of successful procedures, increasing the waiting list even more. We explore the exciting future implications of customized gene therapy in livers using machine perfusion, including its potential to create a future in which organs destined for transplant are individualized to maximize both graft and recipient longevity.