bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of corrected hiPSC clones from a Cornelia de Lange Syndrome (CdLS) patient through CRISPR-Cas-based technology
Authors: Umbach Alessandro , Maule Giulia , Kheir Eyemen , Cutarelli Alessandro , Foglia Marika , Guarrera Luca , Fava Luca L. , Conti Luciano , Garattini Enrico , Terao Mineko , Cereseto Anna
Published: September 2022

Background

Cornelia de Lange syndrome (CdLS) is a rare multisystem genetic disorder which is caused by genetic defects involving the Nipped-B-like protein (NIPBL) gene in the majority of clinical cases (60–70%). Currently, there are no specific cures available for CdLS and clinical management is needed for life. Disease models are highly needed to find a cure. Among therapeutic possibilities are genome editing strategies based on CRISPR-Cas technology.

Methods

A comparative analysis was performed to test the most recent CRISPR-Cas technologies comprising base- and prime-editors which introduce modifications without DNA cleavages and compared with sequence substitution approaches through homology directed repair (HDR) induced by Cas9 nuclease activity. The HDR method that was found more efficient was applied to repair a CdLS-causing mutation in the NIPBL gene. Human-induced pluripotent stem cells (hiPSCs) derived from a CdLS patient carrying the c.5483G > A mutation in the NIPBL were modified through HDR to generate isogenic corrected clones.

Results

This study reports an efficient method to repair the NIPBL gene through HDR mediated by CRISPR-Cas and induced with a compound (NU7441) inhibiting non-homologous end joining (NHEJ) repair. This sequence repair method allowed the generation of isogenic wild-type hiPSCs clones with regular karyotype and preserved pluripotency.

Conclusions

CdLS cellular models were generated which will facilitate the investigation of the disease molecular determinants and the identification of therapeutic targets. In particular, the hiPSC-based cellular models offer the paramount advantage to study the tissue differentiation stages which are altered in the CdLS clinical development. Importantly, the hiPSCs that were generated are isogenic thus providing the most controlled experimental set up between wild-type and mutated conditions.
Multi-omics analysis of an in vitro photoaging model and protective effect of umbilical cord mesenchymal stem cell-conditioned medium
Authors: Zou Xiaocang , Zou Dayang , Li Linhao , Yu Renfeng , Li XianHuang , Du Xingyue , Guo JinPeng , Wang KeHui , Liu Wei
Published: September 2022

Background

Skin ageing caused by long-term ultraviolet (UV) irradiation is a complex biological process that involves multiple signalling pathways. Stem cell-conditioned media is believed to have anti-ageing effects on the skin. The purpose of this study was to explore the biological effects of UVB irradiation and anti-photoaging effects of human umbilical cord mesenchymal stem cell-conditioned medium (hUC-MSC-CM) on HaCaT cells using multi-omics analysis with a novel cellular photoaging model.

Methods

A cellular model of photoaging was constructed by irradiating serum-starved HaCaT cells with 20 mJ/cm2 UVB. Transcriptomics and proteomics analyses were used to explore the biological effects of UVB irradiation on photoaged HaCaT cells. Changes in cell proliferation, apoptosis, and migration, the cell cycle, and expression of senescence genes and proteins were measured to assess the protective effects of hUC-MSC-CM in the cellular photoaging model.

Results

The results of the multi-omics analysis revealed that UVB irradiation affected various biological functions of cells, including cell proliferation and the cell cycle, and induced a senescence-associated secretory phenotype. hUC-MSC-CM treatment reduced cell apoptosis, inhibited G1 phase arrest in the cell cycle, reduced the production of reactive oxygen species, and promoted cell motility. The qRT-PCR results indicated that MYC, IL-8, FGF-1, and EREG were key genes involved in the anti-photoaging effects of hUC-MSC-CM. The western blotting results demonstrated that C-FOS, C-JUN, TGFβ, p53, FGF-1, and cyclin A2 were key proteins involved in the anti-photoaging effects of hUC-MSC-CM.

Conclusion

Serum-starved HaCaT cells irradiated with 20 mJ/cm2 UVB were used to generate an innovative cellular photoaging model, and hUC-MSC-CM demonstrates potential as an anti-photoaging treatment for skin.
Time-regulated transcripts with the potential to modulate human pluripotent stem cell-derived cardiomyocyte differentiation
Authors: Muñoz Juan J. A. M. , Dariolli Rafael , da Silva Caio Mateus , Neri Elida A. , Valadão Iuri C. , Turaça Lauro Thiago , Lima Vanessa M. , de Carvalho Mariana Lombardi Peres , Velho Mariliza R. , Sobie Eric A. , Krieger Jose E.
Published: September 2022

Background

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising disease model, even though hiPSC-CMs cultured for extended periods display an undifferentiated transcriptional landscape. MiRNA–target gene interactions contribute to fine-tuning the genetic program governing cardiac maturation and may uncover critical pathways to be targeted.

Methods

We analyzed a hiPSC-CM public dataset to identify time-regulated miRNA–target gene interactions based on three logical steps of filtering. We validated this process in silico using 14 human and mouse public datasets, and further confirmed the findings by sampling seven time points over a 30-day protocol with a hiPSC-CM clone developed in our laboratory. We then added miRNA mimics from the top eight miRNAs candidates in three cell clones in two different moments of cardiac specification and maturation to assess their impact on differentiation characteristics including proliferation, sarcomere structure, contractility, and calcium handling.

Results

We uncovered 324 interactions among 29 differentially expressed genes and 51 miRNAs from 20,543 transcripts through 120 days of hiPSC-CM differentiation and selected 16 genes and 25 miRNAs based on the inverse pattern of expression (Pearson R-values < − 0.5) and consistency in different datasets. We validated 16 inverse interactions among eight genes and 12 miRNAs (Person R-values < − 0.5) during hiPSC-CMs differentiation and used miRNAs mimics to verify proliferation, structural and functional features related to maturation. We also demonstrated that miR-124 affects Ca2+ handling altering features associated with hiPSC-CMs maturation.

Conclusion

We uncovered time-regulated transcripts influencing pathways affecting cardiac differentiation/maturation axis and showed that the top-scoring miRNAs indeed affect primarily structural features highlighting their role in the hiPSC-CM maturation.
From theory to experiment: transformer-based generation enables rapid discovery of novel reactions
Authors: Wang Xinqiao , Yao Chuansheng , Zhang Yun , Yu Jiahui , Qiao Haoran , Zhang Chengyun , Wu Yejian , Bai Renren , Duan Hongliang
Published: September 2022

Deep learning methods, such as reaction prediction and retrosynthesis analysis, have demonstrated their significance in the chemical field. However, the de novo generation of novel reactions using artificial intelligence technology requires further exploration. Inspired by molecular generation, we proposed a novel task of reaction generation. Herein, Heck reactions were applied to train the transformer model, a state-of-art natural language process model, to generate 4717 reactions after sampling and processing. Then, 2253 novel Heck reactions were confirmed by organizing chemists to judge the generated reactions. More importantly, further organic synthesis experiments were performed to verify the accuracy and feasibility of representative reactions. The total process, from Heck reaction generation to experimental verification, required only 15 days, demonstrating that our model has well-learned reaction rules in-depth and can contribute to novel reaction discovery and chemical space exploration.
Multiple-site decontamination regimen decreases acquired infection incidence in mechanically ventilated COVID-19 patients
Authors: Massart Nicolas , Reizine Florian , Fillatre Pierre , Seguin Philippe , La Combe Béatrice , Frerou Aurélien , Egreteau Pierre-Yves , Hourmant Baptiste , Kergoat Pierre , Lorber Julien , Souchard Jerome , Canet Emmanuel , Rieul Guillaume , Fedun Yannick , Delbove Agathe , Camus Christophe
Published: September 2022

Background

Among strategies that aimed to prevent acquired infections (AIs), selective decontamination regimens have been poorly studied in the COVID-19 setting. We assessed the impact of a multiple-site decontamination (MSD) regimen on the incidence of bloodstream infections (BSI) and ventilator-associated pneumonia (VAP) in COVID-19 patients receiving mechanical ventilation.

Methods

We performed an ancillary analysis of a multicenter retrospective observational study in 15 ICUs in western France. In addition to standard-care (SC), 3 ICUs used MSD, a variant of selective digestive decontamination, which consists of the administration of topical antibiotics four times daily in the oropharynx and the gastric tube, chlorhexidine body wash and a 5-day nasal mupirocin course. AIs were compared between the 3 ICUs using MSD (MSD group) and the 12 ICUs using SC.

Results

During study period, 614 of 1158 COVID-19 patients admitted in our ICU were intubated for at least 48 h. Due to missing data in 153 patients, 461 patients were finally included of whom 89 received MSD. There were 34 AIs in the MSD group (2117 patient-days), as compared with 274 AIs in the SC group (8957 patient-days) (p < 0.001). MSD was independently associated with a lower risk of AI (IRR = 0.56 [0.38–0.83]; p = 0.004) (Table 2). When the same model was used for each site of infection, MSD remained independently associated with a lower risk of VAP (IRR = 0.52 [0.33–0.89]; p = 0.005) but not of BSI (IRR = 0.58, [0.25–1.34], p = 0.21). Hospital mortality was lower in the MSD group (16.9% vs 30.1%, p = 0.017).

Conclusions

In ventilated COVID-19 patients, MSD was independently associated with lower AI incidence.
Content and delivery of pre-operative interventions for patients undergoing total knee replacement: a rapid review
Authors: Anderson Anna M. , Drew Benjamin T. , Antcliff Deborah , Redmond Anthony C. , Comer Christine , Smith Toby O. , McHugh Gretl A.
Published: September 2022

Background

Total knee replacement (TKR) is a common operation typically performed for end-stage knee osteoarthritis. Patients awaiting TKR often have poor health-related quality of life. Approximately 20% of patients experience persistent pain post-TKR. Pre-operative TKR interventions could improve pre- and post-operative outcomes, but future research is required to inform their design. This review aimed to identify and synthesize recent literature on the content and delivery of pre-operative TKR interventions to help guide future research and clinical practice.

Methods

This rapid review included randomized trials of pre-operative TKR interventions (“outcomes studies”) and primary studies exploring patients’ and/or health professionals’ views of pre-operative TKR interventions (“views studies”). Medline, Embase, PsycINFO, CINAHL and the Cochrane Central Register of Controlled Trials were searched for English language studies published between January 2009 and December 2020. Eligible studies’ reference lists were screened. Studies were appraised using the Mixed Methods Appraisal Tool. The findings were narratively synthesized using a convergent segregated approach.

Results

From 3263 records identified, 52 studies were included (29 outcomes studies, 21 views studies, two outcomes/views studies). The studies’ methodological quality varied but was generally highest in qualitative studies. The outcomes studies investigated education (n=5), exercise (n=20), psychological (n=2), lifestyle (n=1), and/or other interventions (n=5). The views studies addressed education (n=20), exercise (n=3), psychological (n=1), lifestyle (n=4), and/or other interventions (n=1). Only three outcomes studies (two randomized controlled trials (RCTs) and a pilot study) compared the effectiveness of intervention components/delivery approaches. The two RCTs’ results suggest that pre-operative TKR exercise interventions are equally effective regardless of whether they include strength or strength plus balance training and whether they are hospital- or home-based. Personal tailoring and using more than one delivery format were associated with improved outcomes and/or perceived as beneficial for multiple intervention types.

Conclusions

Definitive evidence on the optimal design of pre-operative TKR interventions is lacking. Personal tailoring and employing multiple delivery formats appear to be valuable design elements. Preliminary evidence suggests that including balance training and hospital versus home delivery may not be critical design elements for pre-operative TKR exercise interventions.

Systematic review registration

PROSPERO CRD42019143248

Funder

National Institute for Health and Care Research (ICA-CDRF-2018-04-ST2-006).
Systematic review of the utility of the frailty index and frailty phenotype to predict all-cause mortality in older people
Authors: Kim Dani J. , Massa M. Sofia , Potter Caroline M. , Clarke Robert , Bennett Derrick A.
Published: September 2022

Background

Current guidelines for healthcare of community-dwelling older people advocate screening for frailty to predict adverse health outcomes, but there is no consensus on the optimum instrument to use in such settings. The objective of this systematic review of population studies was to compare the ability of the frailty index (FI) and frailty phenotype (FP) instruments to predict all-cause mortality in older people.

Methods

Studies published before 27 July 2022 were identified using Ovid MEDLINE, Embase, Scopus, Web of Science and CINAHL databases. The eligibility criteria were population-based prospective studies of community-dwelling older adults (aged 65 years or older) and evaluation of both the FI and FP for prediction of all-cause mortality. The Scottish Intercollegiate Guidelines Network’s Methodology checklist was used to assess study quality. The areas under the receiver operator characteristic curves (AUC) were compared, and the proportions of included studies that achieved acceptable discriminatory power (AUC>0.7) were calculated for each frailty instrument. The results were stratified by the use of continuous or categorical formats of each instrument. The review was reported in accordance with the PRISMA and SWiM guidelines.

Results

Among 8 studies (range: 909 to 7713 participants), both FI and FP had comparable predictive power for all-cause mortality. The AUC values ranged from 0.66 to 0.84 for FI continuous, 0.60 to 0.80 for FI categorical, 0.63 to 0.80 for FP continuous and 0.57 to 0.79 for FP categorical. The proportion of studies achieving acceptable discriminatory power were 75%, 50%, 63%, and 50%, respectively. The predictive ability of each frailty instrument was unaltered by the number of included items.

Conclusions

Despite differences in their content, both the FI and FP instruments had modest but comparable ability to predict all-cause mortality. The use of continuous rather than categorical formats in either instrument enhanced their ability to predict all-cause mortality.
Evaluation of the root system of Vetiver grass (Chrysopogon zizanioides L. Roberty) using different sampling methods
Authors: Holanda Francisco Sandro Rodrigues , Santos Luiz Diego Vidal , Pedrotti Alceu , de Araújo Filho Renisson Neponuceno , Sartor Lucas Resmini , Santos-Sobrinho Valter Rubens Alcantara , de Jesus Rayssa Juliane Souza , de Oliveira Silva Priscila Angel , Andrade Keila Maria Araújo
Published: September 2022

Background

Vetiver grass (Chrysopogon zizanioides L. Roberty) is one of the most studied and applied species in soil bioengineering techniques all over the world, but there are technical information related to its root system deserving a better comprehension provided by different methodologies’. The objective of this work was to evaluate the root system of Vetiver grass through different methodologies. The trench method evaluated 50 images in 10 × 10 cm squares in its vertical face. The volumetric ring method uses a metallic ring with a volume of 50 cm3 (diameter ≅ 4.6 cm and height ≅ 3.0 cm) to collect samples in the same trench’s vertical face. A hand auger hole method worked with soil samples and roots removed from the surface up to 0.50 m depth. The monolith method comprises a 0.50 m wide, 0.50 m long, and 1 m deep monolith. A spatial correlation between root volume and root area was observed in the kriging maps by the volumetric ring method.

Results

The root area values for both the volumetric ring method and the hand auger hole method were similar, up to 0.10 to 0.20 m. On the analyzed variables, the root area showed the best correlation coefficient among the root methods, especially those that use the limited spatial distribution by its sampling collection, such as the volumetric ring method and the hand auger hole method (r = 0.526, p < 0.05).

Conclusions

The studied methods can be separated in different groups, such as those that provide more detailed information on the behavior and distribution of the root system, like trench and monolith methods and the methods that better describe the morphological characteristics of the features, like the volumetric ring method. Both require greater spatial coverage, and therefore have greater precision.
Phytogenic feed additives alleviate pathogenic Escherichia coli-induced intestinal damage through improving barrier integrity and inhibiting inflammation in weaned pigs
Authors: Chang Se Yeon , Song Min Ho , Lee Ji Hwan , Oh Han Jin , Kim Yong Ju , An Jae Woo , Go Young Bin , Song Dong Cheol , Cho Hyun Ah. , Cho Seung Yeol , Kim Dong Jun , Kim Mi Suk , Kim Hyeun Bum , Cho Jin Ho
Published: September 2022

Background

This study was conducted to investigate the effects of each phytogenic feed additive (PFA; PFA1, bitter citrus extract; PFA2, a microencapsulated blend of thymol and carvacrol; PFA3, a mixture of bitter citrus extract, thymol, and carvacrol; PFA4, a premixture of grape seed, grape marc extract, green tea, and hops; PFA5, fenugreek seed powder) on the growth performance, nutrient digestibility, intestinal morphology, and immune response in weaned pigs infected withEscherichia coli(E. coli).

Results

A total of 63 4-week-old weaned pigs were placed in individual metabolic cages and assigned to seven treatment groups. The seven treatments were as follows: 1) NC; basal diet withoutE. colichallenge, 2) PC; basal diet withE. colichallenge, 3) T1; PC + 0.04% PFA1, 4) T2; PC + 0.01% PFA2, 5) T3; PC + 0.10% PFA3, 6) T4; PC + 0.04% PFA4, 7) T5; PC + 0.10% PFA5. The experiments lasted in 21 d, including 7 d before and 14 d after the firstE. colichallenge. In theE. colichallenge treatments, all pigs were orally inoculated by dividing a total of 10 mL ofE. coliF18 for 3 consecutive days. The PFA-added groups significantly increased (P < 0.05) average daily gain and feed efficiency and decreased (P < 0.05) the fecal score at d 0 to 14 post-inoculation (PI). Tumor necrosis factor α was significantly lower (P < 0.05) in the PFA-added groups except for T1 in d 14 PI compared to the PC treatment. The T3 had a higher (P < 0.05) immunoglobulin G and immunoglobulin A concentration compared to the PC treatment at d 7 PI. Also, T3 showed significantly higher (P < 0.05) villus height:crypt depth and claudin 1 expression in ileal mucosa, and significantly down-regulated (P < 0.05) the expression of calprotectin compared to the PC treatment.

Conclusions

Supplementation of PFA in weaned pigs challenged withE. colialleviated the negative effects ofE. coliand improved growth performance. Among them, the mixed additive of bitter citrus extract, thymol, and carvacrol showed the most effective results, improving immune response, intestinal morphology, and expression of tight junctions.
Supportive climates and science achievement in the Nordic countries: lessons learned from the 2015 PISA study
Authors: Rohatgi Anubha , Hatlevik Ove E. , Björnsson Julius K.
Published: September 2022

Teacher-student interactions are crucial in understanding the role of a supportive climate in instructional practices. The present study investigates the perceptions of 15-year-old Nordic students regarding four aspects of their science class: teacher support, fairness, feedback, and class discipline. Multilevel modelling analysis is used to examine the extent to which a perceived supportive climate can explain variation in the Nordic students’ science achievements. Overall, the main findings based on The Programme for International Student Assessment (PISA) 2015 data from Denmark, Finland, Iceland, Norway, and Sweden indicate that at the student level, perceived feedback from teachers and students perceiving their teachers as fair explains significant variations in science achievement. The study provides practical and theoretical implications about the importance of strong teacher-student relationships in comprehending the concept of a supportive climate.
Reply to “Comment on ‘Soil salinity assessment by using near-infrared channel and Vegetation Soil Salinity Index derived from Landsat 8 OLI data: a case study in the Tra Vinh Province, Mekong Delta, Vietnam’ by Kim-Anh Nguyen, Yuei-An Liou, Ha-Phuong Tran, Phi-Phung Hoang and Thanh-Hung Nguyen”
Authors: Nguyen Kim-Anh , Liou Yuei-An , Tran Ha-Phuong , Hoang Phi-Phung , Nguyen Thanh-Hung
Published: September 2022

The Vietnamese Mekong Delta has been devastatingly impacted by climate change coupled with sea level rise and natural hazards. As a result, salinity intrusion has become a pressing issue in the coastal provinces of the Mekong Delta in recent years. This environmental problem has called a great attention from the global scientists as demonstrated by the paper Nguyen et al. (Prog Earth Planet Sci 7:1, 2020. 10.1186/s40645-019-0311-0) “Soil salinity assessment by using an indicator derived from Landsat 8 OLI data: A case study in the Tra Vinh, Mekong Delta, Vietnam” (reached 27 k accesses as of July 31, 2022). Recently, Silvestri et al. (PEPS, 2022) have commented on Nguyen et al. (2020) article with three main points highlighted: (1) Within the coastal portion of the Mekong Delta, extensively ponded due to widespread shrimp farming, about 90% of Landsat 8 pixels are fully or partially covered by water so that Landsat 8 OLI spatial resolution is not suitable to distinguish between ponded and non-ponded areas; (2) The decreased near-infrared (NIR) reflectance ascribed to increased soil salinity is instead due to the presence of water in Landsat 8 mixed pixels; and (3) NIR reflectance is equally reduced independently of whether the water ponding area is salt or freshwater. We appreciate Silvestri et al. (2022) for their correspondence regarding our 2020 article (Nguyen et al. 2020) where we showed the capacity of using freely accessible Landsat 8 OLI image for the rapid soil salinity detection at the top soil layer in the agricultural land that is of valuable information for agricultural activities. We conducted field survey and collected the soil samples during the dry season at different agricultural soil types. Notably, the soil samples were collected at the same time with the satellite passing over the study area. The soil salinity derived from Landsat 8 is in line with the analysis from in situ data and consistent with the findings of previous studies. Importantly, two points are stressed in this reply: (1) The goal of our study is to utilize the freely accessible data source with rapid method of mapping soil salinity to investigate the salinity in the agricultural land, but not in the water body. Therefore, it has been a serious mistake to state that 90% of Landsat 8 pixels are fully or partially covered by water as claimed in Silvestri et al. (2022); and (2) The Tra Vinh Province has recorded the highest salinity level normally in March or April every year when the rainfall exhibits the lowest of the year, and at this time, most of the water in the river/canal is affected by saline intrusion. Thus, it is advised that Silvestri et al. (2022) should use the images acquired in March or April rather than random months.
Can neuro-oncology teaching contribute to educate medical doctors better? A reflection on the value of neuro-oncology for student teaching
Authors: Mäurer Matthias A. , Mäurer Irina , Kamp Marcel A.
Published: September 2022

Neuro-oncology, with its various conservative, surgical, and interventional disciplines, is ideally suited to teach basic knowledge, skills, and attitudes important to medical practice in general. However, training is less about teaching specific treatment protocols and more about fostering skills for interdisciplinary collaboration, development of treatment recommendations, communication skills, and an ethical stance. To adequately teach this content, new and innovative formats are needed to test and learn high levels of student interaction, communication, and collaboration.

New teaching concepts such as inverted teaching formats as well as the use of modern media technology can be helpful to improve networking between disciplines and to improve the quality of medical education.
Sardinian dietary analysis for longevity: a review of the literature
Authors: Wang Chaoyue , Murgia Marco A. , Baptista José , Marcone Massimo F.
Published: September 2022

Sardinia is one of the five Longevity Blue Zones (LBZs) in the world. Compared to other LBZs, the percentage of male centenarians in Sardinia is much higher. Due to the island’s isolation, the genetic traits of Sardinian people have shown that they are direct descendants of their Nuragic ancestors from the Neolithic era. To survive during times of food scarcity, many “famine foods” are created; acorn bread containing clay, cheese ripened in goat abomasum, and soft cheese with worms are examples of these uncommon foods. Although considered food taboo by the outside world, they are cherished as cultural heritage and local delicacy. Studies have shown that Sardinian longevity is closely related to their special famine foods. They are not only nutritious; the production of these foods resulted in low stress and increased lifespan. Moreover, local food production practices have resulted in a strong cultural bond and helped the Sardinian people to survive cultural erosion from industrialization and modernization.
The effect of Nickel hypersensitivity on the outcome of total knee arthroplasty and the value of skin patch testing: a systematic review
Authors: Peacock C. J. H. , Fu H. , Asopa V. , Clement N. D. , Kader D. , Sochart D. H.
Published: September 2022

Background

To assess the Nickel sensitizing potential of total knee arthroplasty (TKA), explore the relationship between hypersensitivity and clinical outcomes, and evaluate the utility of skin patch testing pre- and/or postoperatively.

Materials and methods

A literature search was performed through EMBASE, Medline and PubMed databases. Articles were screened independently by two investigators. The level of evidence of studies was assessed using the Oxford Centre for Evidence-Based Medicine Criteria and the quality evaluated using the Methodological Index for Non-randomized Studies and Cochrane risk-of-bias tools.

Results

Twenty studies met the eligibility criteria, reporting on 1354 knee arthroplasties. Studies included patients undergoing primary or revision TKA, pre- and/or postoperatively, and used patch testing to identify Nickel hypersensitivity. Prevalence of Nickel hypersensitivity ranged from 0% to 87.5%. One study compared the prevalence of Nickel hypersensitivity in the same patient group before and after surgery and noted newly positive patch test reactions in three patients (4.2%). Three studies reported lower prevalence of Nickel hypersensitivity in postoperative patients compared to preoperative ones. Seven studies suggested that hypersensitivity might cause adverse clinical outcomes, but six did not support any relationship. Seven studies recommended preoperative patch testing in patients with history of metal allergy, and nine concluded that testing may be valuable postoperatively.

Conclusions

Patients undergoing TKA with no prior history of metal hypersensitivity do not seem to be at an increased risk of developing Nickel hypersensitivity, and there is conflicting evidence that patients with pre-existing hypersensitivity are more likely to experience adverse outcomes. Patch testing remains the most commonly used method for diagnosing hypersensitivity, and evidence suggests preoperative testing in patients with history of metal allergy to aid prosthesis selection, and postoperatively in patients with suspected hypersensitivity once common causes of implant failure have been excluded, since revision with hypoallergenic implants may alleviate symptoms.
Lurasidone in treatment of manic episode
Authors: Sánchez-Rivero I.
Published: September 2022

Introduction

Lurasidone is an atypical antipsychotic used in the treatment of schizophrenia and bipolar depression. Both indications are approved by the FDA nowadays, whereas in Europe it is only approved for schizophrenia. Lurasidone has been barely studied for the treatment of acute mania, nonetheless it is sometimes used off-label.

Objectives

A case of a patient with a manic episode treated with lurasidone is presented, in order to provide further evidence on this topic.

Methods

The patient is a 43 year-old-woman with diagnosis of type I bipolar disorder, personality disorder and borderline intellectual functioning, resident in our Hospital’s long-stay psychiatric rehabilitation unit. She was previously under treatment with venlafaxine 75 mg/day, valproate 1500 mg/day and levomepromazine 25 mg on demand; remaining stable for months. The patient presented an episode consisting on agitation, irritability, verbiage, tachyphase, verbal aggressiveness and behavioral disturbances. Psysical restraint was needed for one day long and zuclopenthixol acetate 50 mg IM was administered twice within 5 days for the acute agitation. Venlafaxine was immediately withdrawn and lurasidone was progressively introduced up to 111 mg daily.

Results

Approximately 3 weeks after the treatment adjustment, the patient reached the psychopatological stabilty.

Conclusions

Antidepressive withdrawal and introduction of Lurasidone were effective to treat the acute manic episode in this patient. It has been previosuly suggested that lurasidone caused improvement in emergent manic symptoms in patients with bipolar depression, and in subsyndromal hypomanic symptoms in patients with mixed features of depression. However, no studies have been made yet to evaluate the efficacy of lurasidone in acute mania.

Disclosure

I received financing from Angelini Pharma, Casen Recordati, Janssen, Exeltis and Otsuka.
Lithium placental passage at delivery: an observational study
Authors: Imaz M.L. , Garcia-Esteve L. , Torra M. , Soy D. , Langohr K. , Martin-Santos R.
Published: September 2022

Introduction

Lithium is used as a first-line treatment for bipolar disorder during perinatal period. Dosing of lithium can be challenging as a result of pharmacokinetic changes in renal physiology. Frequent monitoring of lithium blood levels during pregnancy is recommended in order remain within the therapeutic window (0.5 to 1.2 mEq/L). Lower neonatal lithium blood level (<0.64 mEq/L) at time of delivery reduces the risk of lithium side effects in the neonate.

Objectives

The aim of the present study was to quantify the rate of lithium placental passage in real word.

Methods

We included a total of 68 mother-infant pairs for which a lithium measurement was performed intrapartum. Lithium serum concentrations were determined by means of an AVL 9180 electrolyte analyzer. The limit of quantification (LoQ) was 0.20 mEq/L and detection limit was 0.10 mEq/L. Pearson analyse was performer to assess the correlation between mother and umbilical cord lithium serum concentrations.

Results

The mean of umbilical cord serum concentration at delivery was 0.57 mEq/L (SD=0.26, range 0,20-1,42). The mean infant-mother lithium ratio at delivery for the 68 pairs was 1.12 (SD=0.24) across a wide range of maternal concentrations (range 0.14-1,40 mEq/L). There was a strong positive correlation between maternal and umbilical cord lithium blood levels (Peearson correlation coefficient 0.948, p<0.001).

Conclusions

Lithium demostrates complete placental passage. This finding is consistent with the results of others studies (Newport 2005; Molenaar 2021).

Disclosure

No significant relationships.
The impact of self-stigma on functioning among remitted patients with bipolar disorder
Authors: Jenhani R. , Ellouze S. , Bougacha D. , Znaidi F. , Ghachem R.
Published: September 2022

Introduction

Self-stigma is widespread in patients with bipolar disorder, with many consequences for family, social and occupational functioning, as well as treatment adherence.

Objectives

The aim of this study was to evaluate self-stigma in remitted patients with bipolar disorder and to investigate its impact upon functioning.

Methods

We conducted a cross-sectional, descriptive, and analytical study of 61 patients with bipolar disorder. Euthymia was verified using the Hamilton scale for depression and the Young scale for mania. We used the Internalized Stigma of Mental Illness (ISMI) to evaluate self-stigma, the Functioning Assessment Short Test (FAST) to assess functioning.

Results

The mean age of patients was 43.4 years. The sex ratio was 2.4. The mean score on the ISMI was 2.36. More than half of our patients (59%) were self-stigmatized. Regarding functioning, a global impairment was noted in more than two thirds of the patients (71%). Occupational functioning was the most affected area (82%). Patients with higher self-stigma scores had significantly more impaired functioning (p<10-3). To decompose the relationship between stigma and functioning into more specific spheres, we found that all scores on the different domains of functioning were associated with a significantly higher mean self-stigma score.

Conclusions

The relationship between self-stigma and functioning seems to be bidirectional. Therefore, improved social functioning could reduce self-stigma and improve self-esteem.

Disclosure

No significant relationships.
Physical health profile and associated behaviour during the COVID-19 pandemic in patients with bipolar disorder
Authors: Sperling J.D. , Dalkner N. , Berndt C. , Fleischmann E. , Ratzenhofer M. , Martini J. , Pfennig A. , Bauer M. , Reininghaus E. , Vinberg M.
Published: September 2022

Introduction

The COVID-19 pandemic has led to an increased psychological strain on public mental health and may impact behavioural, mental, and physical health, presumably with effects on patients with severe mental disorders.

Objectives

This study examines pandemic-related physical and mental health and (compensatory) behavioural changes, in patients with BD as compared to healthy control individuals.

Methods

Physical and mental health and self-reported changes in daily structure and behaviour due to pandemic were assessed using a self-constructed questionnaire and the brief symptom inventory (BSI) from outpatient clinics in Germany, Austria, and Denmark in individuals with BD and a healthy control group.

Results

The present study included 118 individuals with BD and 215 healthy controls. Individuals with BD reported statistically significant higher physical risk burden, increased weight gain, more physical comorbidities, and a decrease in physical activity and they further reported higher rate of COVID-19 testing, had more worries concerning health and experienced more anxiety but less social distancing.

Conclusions

The COVID-19 pandemic seems to have a greater impact on physical health in individuals with BD than in healthy controls. Individuals with BD appear to be having more difficulties compensating their behaviour due to the pandemic which could amplify the effect of risk factors associated with poorer physical health. This highlights the necessity for optimising and targeting the overall treatment of both mental and physical health in patients with BD during periods with far-reaching changes such as COVID-19 pandemic.

Disclosure

No significant relationships.
Lurasidone-induced mania: A case report
Authors: Fernández T. , Navarro L. , Marco O. , Tardon L. , Arbelo N. , Ilzarbe L. , Barrio P. , Pacchiarotti I.
Published: September 2022

Introduction

Lurasidone is an atypical antipsychotic agent with potential antidepressant effects through its antagonist activity at the 5-HT7 receptor. Although treatment-emergent affective switch (TEAS) induced by second-generation antipsychotics are not frequent, several cases have been reported. To our knowledge, there is no evidence of lurasidone-induced
TEAS.

Objectives

To describe a case of lurasidone-induced mania.

Methods

We describe a clinical case of a patient admitted to our psychiatric outpatient unit who developed a manic episode, presumably induced by the introduction of lurasidone. We also conduct a review of the literature on this subject.

Results

A 37-year-old man diagnosed with obsessive-compulsive disorder (OCD) and an alcohol use disorder was hospitalized due to OCD decompensation with depressive symptomatology and suicidal thoughts, and for alcohol detoxification process. Since he had a previous history of clomipramine-induced TEAS, he was started on lurasidone up to 111mg to avoid the use of antidepressants, showing a progressive improvement of depressive symptoms. Thus, the patient was discharged when alcohol detoxification process was completed. Eight days after discharge, the patient began to show manic symptoms, so he had to be readmitted. Lurasidone was discontinued and valproic acid up to 1000mg/day as mood stabilizer was added, presenting a positive remission of manic symptoms.

Conclusions

According to our experience, lurasidone may have induced an affective switch in this patient. Based on our findings, patients and psychiatrists should monitor possible lurasidone-induced mood switching. However, further research is needed in order to back-up this one case report findings.

Disclosure

No significant relationships.
Diagnostic Results of IQ-test in School-Aged Children with Fetal Alcohol Syndrome and Fetal Alcohol Spectrum of Disorders
Authors: Fadeeva E. , Nenasteva A.
Published: September 2022

Introduction

FAS and FASD are completely preventable conditions which can be reduced by methods of prevention aimed at alcohol eliminating by women during pregnancy.

Objectives

The aim of the study was to assess level of intellectual impairment in children with FAS and FASD.

Methods

All children who participated in the study had physical development retardation and various dysmorphological features of FAS or FASD. The sample included 77 children, 8.6±1.03 years of age. FAS was diagnosed in 8 children, FASD in 69 children. Assessments were carried out by pediatrician, psychiatrist and psychologist; level of intelligence was assessed using WISC test.

Results

Among children with FAS average IQ was 65.9 points (extremely low level), which corresponds to «mild mental retardation» diagnosis (F70, ICD-10). Four children with FAS had intelligence corresponding to «very low» level (IQ=70-79), three had «mild mental retardation» (IQ=50-69), and one had «moderate mental retardation» (F71, ICD-10) (IQ=35-49). Among children with FASD average IQ was higher and reached 79.5 points, corresponding to «very low» intelligence level. «Moderate mental retardation» was identified in 7.8% children with FASD; 22.1% children had «mild mental retardation», and 27.3% had «very low». In 37.7% children IQ level was within normal range: «low average» in 19.5% (IQ=80-89) and «average» in 18.2% (IQ=90-109). «Very high intelligence» (IQ=120-129) was detected in 2.6% children, «extremely high intelligence» (IQ=130 points and above) in 2.6%.

Conclusions

All children with FAS had impaired mental development. Children with FASD showed a wide range of total IQ values, from moderate degree of mental retardation to very high intelligence.

Disclosure

No significant relationships.
“Thoughts and Health”, the future prevention for adolescents today - Preventing a first depression
Authors: Wikberg C. , Augustsson P. , Sveinsdottir G. , Arnarsson E.Ö. , Craighead E. , Marteinsdottir I. , Lilja J.
Published: September 2022

Introduction

Mental illness is a growing problem among adolescents. Adolescents are sensitive and at increased risk of developing a first depression. There are knowledge gaps about the long-term effects of prevention programs against depresson for adolescents.

Objectives

A randomized controlled study among Swedish adolescents in eighth grade, who are at risk of developing depression. The study examines the long-term effects of the “Thoughts and Health” prevention program and whether it is as effective Online as In Real Life (IRL).

Methods

In a first step, about 20 junior high schools in the Västra Götaland region will be recruited and randomised into one of three groups.

The adolescents are screened for depression at school

Group 1 - Adolescents at risk of developing depression receive the course program “Thoughts and Health” Online.

Group 2 - Adolescents at risk of developing depression receive the course program “Thoughts and Health” IRL.

Group 3 - Adolescents at risk of developing depression receive the usual school health care (control group).

Psychologists decide inclusion after a diagnostic interview. OUTCOME VARIABLES

Quantitative

- development of depression is measured via self-assessment instruments and follow-up assessment, by a psychologist.

- school attendance and full grades at the end of compulsory school.

- biomarkers

Qualitative

Adolescent’s experiences and perceptions of the course program.

Results

Will create evidence for prevention programs against depression and be used to develop primary prevention for adolescents Online and IRL, which will be of great importance to public health.

Conclusions

Thoughts and Health can be a useful tool to prevent depression among adolescents

Disclosure

No significant relationships.
A good investment: longer-term cost savings of sensitive parenting in childhood
Authors: Bachmann C. , Beecham J. , O’Connor T. , Briskman J. , Scott S.
Published: September 2022

Introduction

Good quality parenting in early childhood is reliably associated with positive mental and physical health over the lifespan.

Objectives

The hypothesis that early parenting quality has significant long-term financial benefits has not been previously tested.

Methods

Design: Longitudinal study with follow-up from 2012 to 2016; UK multicentre study cohort. Participants: 174 young people drawn from 2 samples, one at moderate risk of poor outcomes and one at high risk, assessed aged 4–6 years then followed up in early adolescence (mean age 12.1 years). Measures: The primary outcome was total costs: health, social care, extra school support, out-of-home placements and family-born expenditure, determined through semistructured economic interviews. Early parenting quality was independently assessed through direct observation of parent–child interaction.

Results

Costs were lower for youths exposed to more sensitive parenting (most sensitive quartile mean £1,619, least sensitive quartile mean £21,763; p < .001). Costs were spread across personal family expenditure and education, health, social and justice services. The cost difference remained significant after controlling for several potential confounders. These included demographic variables (family poverty, parental education); exposure to child abuse; and child/young person variables including level of antisocial behaviour in both childhood and adolescence, IQ and attachment security.

Conclusions

This study is the first showing that more sensitive early parental care predicts lower costs to society many years later, independent of poverty, child and youth antisocial behaviour levels and IQ. The findings provide novel evidence for the public health impact of early caregiving quality and likely financial benefits of improving it.

Disclosure

No significant relationships.
Snapshot of a Child and Adolescent Psychiatric ER during Pandemic
Authors: Arain F. , Tohid A. , Jawad M. , Rashid A. , Korenis P. , Sanchez-Lacay J.
Published: September 2022

Introduction

The COVID-19 pandemic has disrupted numerous fundamental systems ranging from businesses to education system. The long-term consequences of the Pandemic, namely virtual learning and prolonged social isolation are coming to fruition in Child/Adolescent-Psychiatric Emergency-Rooms (CAP-ER). Discontinuity of in-person attendance of schools has poorly impacted the mental health of children and adolescents (C&A) of low-socioeconomic areas, who often rely on schools for meals, physical activity, and mental-health support. An increase in agitation, suicidal ideation, and a declining school performance has been observed in such situations.

Objectives

The primary objective of this study is to explore the increase in these symptoms as the presenting complaint in the psychiatric ER.

Methods

Between April to June 2021 a cross-sectional quality improvement (QI) study was done on children presenting to CAP-ER BronxCare-Hospital NY with psychiatric complaints. Concomitant substance use disorder was determined using CRAFT questionnaire.

Results

Our data comprised 209 patients (84 M/125 F) with 79 children and 130 adolescents. Ethnicity: 116 Hispanics (56%), 84 African Americans (40%), and 9 others. The most common presenting complaints were aggression (111, 53%), suicidal ideation/suicide attempt (50, 24%), acute exacerbation of chronic illness (7, 3.3%), accidental overdosage (5, 2.3%) and others (36, 17.4). Marijuana was the most used substance (34 patients).

Conclusions

There has been a surge in severity of presentation of psychiatric disorders among children and adolescents, aggression so far, the most prevalent. Further studies are needed to delineate the social links with this high emergent load and pandemic.

Disclosure

No significant relationships.
Health anxiety in frequently and rarely ill younger adolescents
Authors: Shishkova I. , Pervichko E.
Published: September 2022

Introduction

It is known that a high level of health anxiety is traditionally recognized as obligatory for hypochondria, which is characterized by a clear and pronounced belief of the subject in the presence of a disease or the danger of its development (A psychiatric glossary, 1975). Such patients are usually characterized by high concern about their health, but this anxiety can be represented by varying degrees of severity. At the same time, it is important to talk not only about pathological anxiety (hypochondria), but also about conditions associated with normal human anxiety about their health, also in children and adolescents.

Objectives

To study health anxiety in younger adolescents.

Methods

The sample: 101 respondents (44 rarely ill younger adolescents (mean age 10.6±0.1), 57 frequently ill younger adolescents (mean age 10.5±0.43)). We used: “Short Health Anxiety Inventory” (SHAI; Salkovskis et al., 2002), Questionnaire “Index of attitude toward health” (Deryabo, Yasvin, 1999), CPQ (Porter, Cattell, 1985).

Results

The results of multiple regression analysis for a sample of younger adolescents showed that the scale of actions to preserve and promote health and factor I (sensitivity) make up the level of severity of the general scale of health anxiety in rarely ill younger teenagers (-0.476, p=0.045; 0.628, p=0.039). Health anxiety is determined by factor O (anxiety) in frequently ill younger teenagers (0.316, p=0.029).

Conclusions

Health anxiety can be viewed as a non-pathological construct associated with personality traits and behavior and has structural differences depending on the diseases’ frequency. Research is supported by the Russian Science Foundation, project No. 21-18-00624.

Disclosure

Research is supported by the Russian Science Foundation, project No. 21-18-00624.