bluuebunny/crossref_metadata_2025 huggingface dataset:
Transplanting cells from old but not young donors causes physical dysfunction in older recipients
Authors: Wang Binsheng , Liu Zukai , Chen Vicky P. , Wang Lichao , Inman Christina L. , Zhou Yueying , Guo Chun , Tchkonia Tamar , Rowe David W. , Kuchel George A. , Robson Paul , Kirkland James L. , Xu Ming
Published: January 2020

Adipose‐derived mesenchymal stem cell (ADSC)‐based regenerative therapies have shown potential for use in many chronic diseases. Aging diminishes stem cell regenerative potential, yet it is unknown whether stem cells from aged donors cause adverse effects in recipients. ADSCs can be obtained using minimally invasive approaches and possess low immunogenicity. Nevertheless, we found that transplanting ADSCs from old donors, but not those from young donors, induces physical dysfunction in older recipient mice. Using single‐cell transcriptomic analysis, we identified a naturally occurring senescent cell‐like population in ADSCs primarily from old donors that resembles in vitro‐generated senescent cells with regard to a number of key pathways. Our study reveals a previously unrecognized health concern due to ADSCs from old donors and lays the foundation for a new avenue of research to devise interventions to reduce harmful effects of ADSCs from old donors.
Digital depression: a new disease of the millennium?
Authors: Ghaemi S. N.
Published: January 2020

Objective

In the past decade, since the innovation of the smartphone, there has been an increase in depression, anxiety, and suicidality among teenagers and young adults. The objective of this article was to review the current evidence for these associations and to provide initial clinical guidance.

Methods

A narrative review of the available literature on digital technology, social media, and psychiatric outcomes in adolescents.

Results

Psychiatric outcomes have worsened in adolescents in the past decade, correlating with the invention of the smartphone and the rise of social media. Depressive symptoms among American teenagers rose rapidly around 2012 and now are reported in 22% of adolescents, which is at least double the rate in adults. Suicide rates have risen, especially among teenage girls in the United States, in whom there has been a doubling of completed suicide in the past decade. A causal relationship between social media use and these harmful psychiatric outcomes is supported by emerging randomized data showing reduced depressive symptoms associated with a decrease in social media use in college students.

Conclusions

Social media and digital technology correlate with harmful psychiatric outcomes in adolescents and young adults. Clinical recommendations should include limitations in social media use.
Simvastatin alleviated diabetes mellitus‐induced erectile dysfunction in rats by enhancing AMPK pathway‐induced autophagy
Authors: Ding Fan , Shan Changyu , Li Hongwei , Zhang Yuping , Guo Chunling , Zhou Zhansong , Zheng Ji , Shen Wenhao , Dai Qiang , Ouyang Qin , Wu Xiaojun
Published: January 2020

Background

Diabetes mellitus‐induced erectile dysfunction is a common diabetic complication, and new therapeutics and the pathogenesis of diabetes mellitus‐induced erectile dysfunction need to be investigated.

Objectives

The aim was to investigate the pathogenesis of diabetes mellitus‐induced erectile dysfunction and the pharmacological mechanism of simvastatin treatment in diabetes mellitus‐induced erectile dysfunction model rats.

Materials and methods

A total of 86 male Sprague Dawley rats aged 8 weeks old were used in this study. The rats were divided into three groups: control (normal), diabetes mellitus‐induced erectile dysfunction (streptozotocin‐injected), and diabetes mellitus‐induced erectile dysfunction + simvastatin (sim). Each group was subdivided into two subgroups for in vitro and in vivo analyses. A bioinformatics method was used to detect differences in gene expression in the corpus cavernosum between normal and diabetes mellitus‐induced erectile dysfunction rats. Erectile function was measured by a cavernous nerve electrostimulation test. Corpus cavernosum fibrosis was assessed by Masson staining and Western blotting. Immunofluorescence and Western blotting were performed to explore the differential expression of autophagy‐related genes and the AMPK‐SKP2‐CARM1 pathway genes in rat cavernous smooth muscle cells and the corpus cavernosum. The autophagosomes of the corpus cavernosum tissue were observed by transmission electron microscopy.

Results

Autophagy‐related genes and pathways (the AMPK and FoxO pathway) were identified by bioinformatics analysis and confirmed at the protein level. Simvastatin, an AMPK agonist, was used to treat diabetes mellitus‐induced erectile dysfunction rats for 8 weeks, demonstrating that erectile function was improved for 80.5% (P < .05) of rats. Corpus cavernosum fibrosis was alleviated (P < .05), and autophagy was further enhanced (P < .05); these results might be partially caused by AMPK‐SKP2‐CARM1 pathway activation (P < .05).

Discussion and conclusion

Simvastatin could enhance protective autophagy by activating the AMPK‐SKP2‐CARM1 pathway to improve erectile function in diabetes mellitus‐induced erectile dysfunction rats.
The physician's gender influences the results of the diagnostic workup for erectile dysfunction
Authors: Rastrelli Giulia , Cipriani Sarah , Craparo Andrea , De Vincentis Sara , Granata Antonio R. M. , Spaggiari Giorgia , Simoni Manuela , Maggi Mario , Santi Daniele
Published: January 2020

Background

Despite the well‐known influence of psychological and situational factors on erectile dysfunction, the influence of the physician's gender on the andrological workup has never been investigated so far.

Objectives

To investigate physician's gender influence on the erectile dysfunction diagnostic workup.

Materials and methods

Cross‐sectional study with retrospective data collection. We evaluate a consecutive series of erectile dysfunction patients: 95 at the University of Modena and Reggio Emilia (UNIMORE) and 1808 at the University of Florence (UNIFI). In the UNIMORE cohort (Cohort 1), intracavernousal injection test was performed in case of suspected vascular pathogenic component. In the UNIFI cohort (Cohort 2), patients were evaluated by structured interview on erectile dysfunction and ANDROTEST. Both cohorts were divided into two groups according to the gender of the physician who performed the intracavernousal injection test or the structured interview.

Results

In Cohort 1, patients who had the intracavernousal injection test performed by a female physician had a significantly higher probability of obtaining a better intracavernousal injection test response. In Cohort 2, patients interviewed by female physician more frequently reported to have a conflictual couple relationship and a reduced frequency of climax in their partners. However, they reported less difficulties in achieving and maintaining erection, higher frequency of autoeroticism, lower occurrence of erectile dysfunction during masturbation and lower impairment in morning erections.

Conclusions

Physician's gender affects the results obtained during the erectile dysfunction diagnostic workup. Men interviewed by a female physician describe a less severe erectile dysfunction probably as attempt to defend their own virility. On the other hand, the presence of a male physician during intracavernousal injection test is associated to a worse response suggesting a possible unconscious competition.
Identification of malignant early repolarization pattern by late QRS activity in high‐resolution magnetocardiography
Authors: Iwakami Naotsugu , Aiba Takeshi , Kamakura Shiro , Takaki Hiroshi , Furukawa Toshiaki A. , Sato Tosiya , Sun Wenxu , Shishido Toshiaki , Nishimura Kunihiro , Yamada‐Inoue Yuko , Nagase Satoshi , Shimizu Wataru , Yasuda Satoshi , Sugimachi Masaru , Kusano Kengo
Published: January 2020

Background

The early repolarization pattern (ERP) in electrocardiography (ECG) has been considered as a risk for ventricular fibrillation (VF), but effective methods for identification of malignant ERP are still required. We investigated whether high spatiotemporal resolution 64‐channel magnetocardiography (MCG) would enable distinction between benign and malignant ERPs.

Methods

Among all 2,636 subjects who received MCG in our facility, we identified 116 subjects (43 ± 18 years old, 54% male) with inferior and/or lateral ERP in ECG and without structural heart disease, including 13 survivors of VF (ERP‐VF(+)) and 103 with no history of VF (ERP‐VF(−)). We measured the following MCG parameters in a time‐domain waveform of relative current magnitude: (a) QRS duration (MCG‐QRSD), (b) root‐mean‐square of the last 40 ms (MCG‐RMS40), and (c) low amplitude (<10% of maximal) signal duration (MCG‐LAS).

Results

Compared to ERP‐VF(−), ERP‐VF(+) subjects presented a significantly longer MCG‐QRS (108 ± 24 vs. 91 ± 23 ms, p = .02) and lower MCG‐RMS40 (0.10 ± 0.08 vs. 0.25 ± 0.20, p = .01) but no difference in MCG‐LAS (38 ± 22 vs. 29 ± 23 ms, p = .17). MCG‐QRSD and MCG‐RMS40 showed significantly larger area under the ROC curve compared to J‐peak amplitude in ECG (0.72 and 0.71 vs. 0.50; p = .04 and 0.03). The sensitivity, specificity, and odds ratio for identifying VF(+) based on MCG‐QRSD ≥ 100 ms and MCG‐RMS40 ≤ 0.24 were 69%, 74%, and 6.33 (95% CI, 1.80–22.3), and 92%, 48%, and 10.9 (95% CI, 1.37–86.8), respectively.

Conclusion

Magnetocardiography is an effective tool to distinguish malignant and benign ERPs.
Short‐term surgical complications after radical hysterectomy—A nationwide cohort study
Authors: Wenzel Hans H. B. , Kruitwagen Roy F. P. M. , Nijman Hans W. , Bekkers Ruud L. M. , van Gorp Toon , de Kroon Cornelis D. , van Lonkhuijzen Luc R. C. W. , Massuger Leon F. A. G. , Smolders Ramon G. V. , van Trommel Nienke E. , Yigit Refika , Zweemer Ronald P. , van der Aa Maaike A.
Published: January 2020

Introduction

Centralization has, among other aspects, been argued to have an impact on quality of care in terms of surgical morbidity. Next, monitoring quality of care is essential in identifying areas of improvement. This nationwide cohort study was conducted to determine the rate of short‐term surgical complications and to evaluate its possible predictors in women with early‐stage cervical cancer.

Material and methods

Women diagnosed with early‐stage cervical cancer, 2009 FIGO stages IB1 and IIA1, between 2015 and 2017 who underwent radical hysterectomy with pelvic lymphadenectomy in 1 of the 9 specialized medical centers in the Netherlands, were identified from the Netherlands Cancer Registry. Women were excluded if primary treatment consisted of hysterectomy without parametrial dissection or radical trachelectomy. Women in whom radical hysterectomy was aborted during the procedure, were also excluded. Occurrence of intraoperative and postoperative complications and type of complications, developing within 30 days after surgery, were prospectively registered. Multivariable logistic regression analysis was used to identify predictors of surgical complications.

Results

A total of 472 women were selected, of whom 166 (35%) developed surgical complications within 30 days after radical hysterectomy. The most frequent complications were urinary retention with catheterization in 73 women (15%) and excessive perioperative blood loss >1000 mL in 50 women (11%). Open surgery (odds ratio [OR] 3.42; 95% CI 1.73‐6.76), chronic pulmonary disease (OR 3.14; 95% CI 1.45‐6.79), vascular disease (OR 1.90; 95% CI 1.07‐3.38), and medical center (OR 2.83; 95% CI 1.18‐6.77) emerged as independent predictors of the occurrence of complications. Body mass index (OR 0.94; 95% CI 0.89‐1.00) was found as a negative predictor of urinary retention. Open surgery (OR 36.65; 95% CI 7.10‐189.12) and body mass index (OR 1.15; 95% CI 1.08‐1.22) were found to be independent predictors of excessive perioperative blood loss.

Conclusions

Short‐term surgical complications developed in 35% of the women after radical hysterectomy for early‐stage cervical cancer in the Netherlands, a nation with centralized surgical care. Comorbidities predict surgical complications, and open surgery is associated with excessive perioperative blood loss.
"It's probably nothing, but…" Couples' experiences of pregnancy following an uncertain prenatal genetic result
Authors: Lou Stina , Lomborg Kirsten , Lewis Celine , Riedijk Sam , Petersen Olav Bjørn , Vogel Ida
Published: January 2020

Introduction

A common concern regarding the introduction of chromosomal microarray in prenatal testing is the concomitant identification of an uncertain copy number variant (CNV) where significance and clinical implication for the unborn child can be difficult or impossible to predict. Following the identification of an uncertain CNV, prospective parents may decide to continue the pregnancy. The aim of this study was to explore how prospective parents manage uncertainty and experience pregnancy in light of an uncertain CNV result.

Material and methods

Qualitative interviews with 16 women and 10 partners who had received a prenatally diagnosed, uncertain CNV. Participants were recruited from the Aarhus University Hospital, Denmark and most were interviewed in their homes 1‐14 weeks after birth. Data were analyzed using thematic analysis.

Results

Following the CNV diagnosis, some couples focused on the severe syndromes ruled out by the result, whereas others were more concerned with the new potential risks, for example, learning disabilities. Most couples did not remember the actual diagnosis, but all described a number of attention points generated by the CNV result. During pregnancy, the couples used various strategies to limit worry and enjoy their pregnancy, such as limiting information seeking, reducing talk of the CNV, and deferring thoughts of potential consequences. Furthermore, ultrasound was considered a valuable resource for reducing worry as it provided reassurance about the development of the baby. Inherited CNVs caused relief on one hand, but also feelings of responsibility for the child's potential challenges. After birth, worry decreased considerably, but all couples paid some extra attention to the child's development, while also being alert to the risk of wrongfully interpreting the child's development in terms of the CNV. Eleven couples expressed satisfaction with knowing about the child's CNV, whereas five couples would rather not have known.

Conclusions

The results indicate that health professionals should be mindful of terminology, remember to point out what has been ruled out by the CNV result, and discuss potential coping strategies with the couple. Furthermore, these couples may have a higher need for ultrasound during pregnancy to help reduce worry. More research is needed on the families' long‐term coping.
Venoarterial extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock—A six‐year service evaluation
Authors: Charlesworth Michael , Garcia Miguel , Head Laura , Barker Julian M. , Ashworth Alan D. , Barnard James B. , Feddy Lee , Venkateswaran Rajamiyer V.
Published: January 2020

Only a small number of English hospitals provide postcardiotomy venoarterial extracorporeal membrane oxygenation (VA‐ECMO) and there are doubts about its efficacy and safety. The aim of this service evaluation was to determine local survival rates and report on patient demographics. This was a retrospective service evaluation of prospectively recorded routine clinical data from a tertiary cardiothoracic center in the United Kingdom offering services including cardiac and thoracic surgery, heart and lung transplantation, venovenous extracorporeal membrane oxygenation (VV‐ECMO) for respiratory failure, and all types of mechanical circulatory support. In six years, 39 patients were supported with VA‐ECMO for refractory postcardiotomy cardiogenic shock (PCCS). We analyzed survival data and looked for associations between survival rates and patient characteristics. The intervention was venoarterial‐ECMO in patients with PCCS either following weaning from cardiopulmonary bypass or following a trial of inotropes and intra‐aortic balloon counterpulsation on the intensive care unit. 30‐day, hospital discharge, 1‐year and 2‐year survivals were 51.3%, 41%, 37.5%, and 38.5%, respectively. The median (IQR [range]) duration of support was 6 (4‐9 [1‐35]) days. Nonsurvival was associated with advanced age, shorter intensive care length of stay, and the requirement for postoperative hemofiltration. Reasonable survival rates can be achieved in selected patients who may have been expected to have a worse mortality without VA‐ECMO. We suggest postoperative VA‐ECMO should be available to all patients undergoing cardiac surgery be it in their own center or through an established pathway to a specialist center.
Recommendations on neonatal light environment from the French Neonatal Society
Authors: Zores‐Koenig Claire , Kuhn Pierre , Caeymaex Laurence ,   the Group of Reflection and  Evaluation of the Environment of Newborns study group of the French Neonatology Society
Published: January 2020

Aim

Hospital light may affect neonatal neurosensory development and the well‐being of parents and caregivers. We aimed to issue practical recommendations regarding the optimal light environment for neonatal units.

Methods

A systematic evaluation was performed using PubMed to identify relevant papers published in English or French up to July 2018, and the different grades of evidence were evaluated.

Results

We identified 89 studies and one meta‐analysis and examined 31 eligible studies. The major results were that natural or artificial light should not exceed 1000 lux and that all changes in light level should be gradual. Light protection should be used for infants of <32 weeks of postmenstrual age and but must be individualised to each infant. Infants should not be exposed to continuous high light levels regardless of their term and postnatal age. Cycled light before discharge seemed to be safe and beneficial. For medical caregivers’ well‐being, higher light levels and access to natural light are recommended. Special attention should be given to protecting neonatal patients from high light levels that may be necessary when performing specific care procedures.

Conclusion

Consideration of general principles and practical applications can improve the neonatal light environment for newborn infants, parents and caregivers.
IL33 rs1342326 gene variation is associated with allergic rhinitis at school age after infant bronchiolitis
Authors: Korppi Matti , Teräsjärvi Johanna , Lauhkonen Eero , Huhtala Heini , Nuolivirta Kirsi , He Qiushui
Published: January 2020

Aim

Interleukin (IL)‐33, encoded by the IL33 gene, is associated with allergy and asthma. We evaluated IL33 rs1342326 polymorphism in relation to asthma, asthma medication and allergic rhinitis after infant bronchiolitis.

Methods

IL33 rs1342326 polymorphism was studied in children, who were hospitalised for bronchiolitis at age younger than 6 months and who were prospectively followed until 5‐7 years (N = 141) and 11‐13 years (N = 125) of ages.

Results

The presence of the wild AA vs variant AC or CC genotypes of the IL33 rs1342326 showed no significant associations with previous or current asthma at the mean ages of 6.4 or 11.7 years. However, 22.5% of children with the variant genotype used inhaled corticosteroids at the 5‐7 years of visit (adjusted OR: 2.94, 95% CI: 1.04‐8.33 vs those 8.9% with the wild genotype). The variant IL33 rs1342326 genotype was associated with allergic rhinitis at 6.4 years (adjusted OR: 2.17, 95% CI: 1.01‐4.76) and 11.7 years (3.23, 1.18‐9.09) of ages.

Conclusion

The frequent use of asthma control medication in 6.4‐year‐old children with IL33 rs1342326 polymorphism suggests that this variation may increase susceptibility to severe asthma at preschool age. The IL33 rs1342326 variant genotype was associated with a 3‐fold risk of allergic rhinitis at school age.
Children with home mechanical ventilation—Parents' health‐related quality of life, family functioning and sleep
Authors: Israelsson‐Skogsberg Åsa , Persson Carina , Markström Agneta , Hedén Lena
Published: January 2020

Aim

Children requiring home mechanical ventilation (HMV) have grown in number and complexity. Parents of children with HMV are often responsible for the advanced homecare. This study explored the health‐related quality of life (HRQoL), family functioning and sleep in parents of children with HMV. A secondary aim was to explore the impact on HRQoL, family functioning and sleep of selected potential determinants.

Methods

Questionnaires were completed by 45 mothers and 40 fathers, to 55 children receiving HMV. Parents were identified via respiratory clinics in the Swedish national quality register for oxygen and home respiratory treatment and invited to participate between December 2016 and December 2018.

Results

There were no differences between mothers and fathers overall HRQoL or family functioning reports, although differences within the physical (P < .043) and cognitive (P < .009) functioning dimensions were found. One of four parents reported moderate or severe insomnia. The variability in HRQoL and family functioning was predicted by HMV mode and sleep quality to an extent of 45% and 21%, respectively.

Conclusion

Sleep quality and the child's HMV mode predicted parental HRQoL and family functioning. The results underscore the importance of evaluating parents' sleep and of being aware that invasive ventilation influences parental HRQoL and family functioning.
A triple‐chamber parenteral nutrition solution was associated with improved protein intake in very low birthweight infants
Authors: Immeli Lotta , Mäkelä Pauliina M. , Leskinen Markus , Rinta‐Koski Olli‐Pekka , Sund Reijo , Andersson Sture , Luukkainen Päivi
Published: January 2020

Aim

We evaluated the nutrient intakes of very low birthweight (VLBW) infants weighing less than 1500 g and tested the hypothesis that using a triple‐chamber parenteral nutrition (PN) solution, containing lipids, glucose and amino acids, would improve protein intake.

Methods

This retrospective cohort study comprised 953 VLBW infants born in 2005‐2013 at a gestational age of less than 32 + 0/7 weeks and admitted to the neonatal care unit at Helsinki Children's Hospital, Finland. The infants were divided into four groups according their birth year and PN regime. Nutrient intakes were obtained from computerised medication administration records.

Results

In 2012‐2013, when a triple‐chamber PN solution was used, infants were more likely to reach the target parenteral protein intake of 3.5 g/kg/d, and reach it 3‐7 days earlier, compared with infants who received individual PN or standard two‐in‐one PN solutions in 2005‐2011. In addition, infants in the triple‐chamber group had the highest median energy intake (90 kcal/kg/d) during the first week. They also had higher median protein intakes in weeks one, two and three (3.1, 3.4 and 3.7 g/kg/d) than infants born in 2005‐2011 (P < .05).

Conclusion

Using a triple‐chamber PN solution was associated with improved protein intake, and the protein target was more likely to be achieved.
Chest computed tomography for staging renal tumours: validation and simplification of a risk prediction model from a large contemporary retrospective cohort
Authors: Voss James , Drake Tamsin , Matthews Hannah , Jenkins James , Tang Stanley , Doherty Joshua , Chan Keith , Dawe Harriet , Thomas Tittu , Kearley Samantha , Manners James , Carter Charles , Al‐Buheissi Salah , Klatte Tobias
Published: January 2020

Objectives

To externally validate a nomogram recently proposed by Larcher et al. (BJU Int. 2017; 120: 490) and to develop a simplified model with comparable accuracy to guide on the need for staging chest computed tomography (CT) for patients with new renal masses.

Patients and Methods

We analysed the data of 1082 consecutive patients with unilateral enhancing renal masses referred to urology multidisciplinary team meetings at two centres between 2011 and 2017. All patients underwent a staging chest CT at diagnosis. We fitted multivariable logistic regression models and tested the Larcher model performance using area under the receiver‐operating curve (AUC), calibration and decision curve analysis.

Results

Forty‐two patients (3.9%) had a positive chest CT. The Larcher nomogram had an AUC of 83.8% (95% confidence interval [CI] 77.1–90.6), but was only moderately well calibrated (calibration‐in‐the‐large = −0.61, slope = 0.82). Specifically, the nomogram overestimated the risk of positive chest CT, and the magnitude of miscalibration increased with increasing predicted risks. Using a stepwise backward approach, a new model was developed including tumour size, nodal stage and systemic symptoms. Compared with the Larcher model, the new model had a similar AUC (82.7% [95% CI 75.5–90.0]), but improved calibration and clinical net benefit. The predicted risk of positive chest CT was <1% in the low‐risk group and 1.9–79.9% in the high‐risk group.

Conclusion

The Larcher nomogram is an accurate prediction tool that was moderately well calibrated with our dataset. However, our simplified model has similar accuracy and uses more objective variables available from referral, so may be easier to incorporate into clinical practice. The low‐risk group from our model (tumour size ≤4 cm and no systemic symptoms) had a risk of positive chest CT <1%, suggesting these patients may forego chest CT.
Prostate cancer in kidney transplant recipients – a nationwide register study
Authors: Bratt Ola , Drevin Linda , Prütz Karl‐Göran , Carlsson Stefan , Wennberg Lars , Stattin Pär
Published: January 2020

Objective

To investigate whether post‐transplantation immunosuppression negatively affects prostate cancer outcomes in male kidney transplant recipients.

Patients and Methods

We used the Swedish Renal Register and the National Prostate Cancer Register to identify all kidney transplantation recipients diagnosed with prostate cancer in Sweden 1998–2016. After linking these registers with Prostate Cancer Database Sweden (PCBaSe), a case‐control study was designed to compare time period and risk category‐specific probabilities of a prostate cancer diagnosis amongst kidney transplantation recipients versus the male general population. The registers did not include information about the specific immunosuppression agent used in all transplantation recipients. Data from PCBaSe were used to compare prostate cancer characteristics at diagnosis and survival for patients with prostate cancer with versus without a kidney transplant. Propensity score matching, Cox regression analysis and Fisher's exact test were used and 95% confidence intervals (CIs) calculated.

Results

Almost half of the 133 kidney transplantation recipients were transplanted before the mid‐1990s, when PSA testing became common. The transplant recipients were not more likely than age‐matched control men to be diagnosed with any (odds ratio [OR] 0.84, 95% CI 0.70–0.99) or high‐risk or metastatic prostate cancer (OR 0.84, 95% CI 0.62–1.13). None of the ORs for the different categories of prostate cancer increased with time since transplantation. Cancer characteristics at the time of diagnosis and cancer‐specific survival were similar amongst transplant recipients and the control group of 665 men diagnosed with prostate cancer without a kidney transplant.

Conclusions

This Swedish nationwide, register‐based study gave no indication that immunosuppression after kidney transplantation increases the risk of prostate cancer or adversely affects prostate cancer outcomes. The study suggests that men with untreated low‐grade prostate cancer can be accepted for transplantation.
Synthetic lethal therapy based on targeting the vulnerability of SWI/SNF chromatin remodeling complex‐deficient cancers
Authors: Sasaki Mariko , Ogiwara Hideaki
Published: January 2020

The SWI/SNF chromatin remodeling complex is composed of approximately 15 subunits, and approximately 20% of all cancers carry mutations in the genes encoding these subunits. Most of the genetic alterations in these genes are loss‐of‐function mutations. The identification of vulnerability based on synthetic lethality in cancers with SWI/SNF chromatin remodeling complex deficiency contributes to precision medicine. The SWI/SNF chromatin remodeling complex is involved in transcription, DNA repair, DNA replication, and chromosomal segregation. Cancers with deficiency in the SWI/SNF chromatin remodeling complex show increased vulnerability derived from the loss of these functions. Synthetic lethal targets have been identified based on vulnerabilities in the functions of the SWI/SNF chromatin remodeling complex. In this review article, we propose a precision medicine strategy using chemotherapeutic methods, such as molecular targeted therapy and immunotherapy, based on harnessing synthetic lethality in cancers with deficiency in the SWI/SNF chromatin remodeling complex.
Empirical Evidence Supporting Neural Contributions to Episodic Memory Development in Early Childhood: Implications for Childhood Amnesia
Authors: Riggins Tracy , Canada Kelsey L. , Botdorf Morgan
Published: January 2020

Memories for events that happen early in life are fragile—they are forgotten more quickly than expected based on typical adult rates of forgetting. Although numerous factors contribute to this phenomenon, data show that one major source of change is the protracted development of neural structures related to memory. Recent empirical studies in early childhood reveal that the development of specific subdivisions of the hippocampus (i.e., the dentate gyrus) is related directly to variations in memory. Yet, the hippocampus is only one region within a larger network supporting memory. Data from young children have also shown that activation of cortical regions during memory tasks and the functional connectivity between the hippocampus and cortex relate to memory during this period. Taken together, these results suggest that protracted neural development of the hippocampus, cortex, and connections between these regions contribute to the fragility of memories early in life and may ultimately contribute to childhood amnesia.
The Empirical Child? A Framework for Investigating the Development of Scientific Habits of Mind
Authors: Butler Lucas P.
Published: January 2020

We live in the information age. Broad access to vast troves of information can benefit society considerably, providing conduits for inquiry by individuals of all ages, enabling the spread of important information to previously isolated populations, and facilitating social connections across the globe. However, inundated with information from an ever‐expanding array of sources, we also live in the misinformation age. Thus, it is of paramount importance to raise the next generation to approach the world through an empirical, evaluative lens, and to work to foster the development of habits of mind that will guide how children engage with the world. In this article, I present a new theoretical framework for investigating children’s engagement in and understanding of three key steps in the empirical process: (a) asking questions and forming a hypothesis, (b) collecting and analyzing data, and (c) communicating evidence. I discuss young children’s capacities for engaging in each step as well as the obstacles they may encounter in doing so, and suggest approaches for researchers working toward this pressing societal goal.
Statistical Language Learning in Infancy
Authors: Saffran Jenny R.
Published: January 2020

Research suggests that infants use statistical regularities in linguistic input to identify and learn a range of linguistic structures, from the sounds of language (e.g., native‐language speech sounds, word boundaries in continuous speech) to aspects of grammatical structure (e.g., lexical categories like nouns and verbs, basic aspects of syntax). In this article, I review the literature on statistical language learning in infants and raise questions about why infants are sensitive to statistical regularities. In doing so, I consider the relationship among statistical learning, prediction, and reducing uncertainty in infancy.
Children’s Emerging Understanding of Death
Authors: Menendez David , Hernandez Iseli G. , Rosengren Karl S.
Published: January 2020

Children’s understanding of death has been a topic of interest to researchers investigating the development of children’s thinking and clinicians focusing on how children cope with the death of a loved one. Traditionally, researchers in cognitive development have studied death from a biological perspective. Current research suggests that exploring religious and spiritual conceptualizations might enrich our understanding of how children come to think about death. In this article, we review different methodological approaches that suggest that children form their understanding of death by engaging in conversations with and asking questions of family members, consuming cultural products, and participating in cultural rituals. We provide examples of how children combine different belief systems to form their understanding of death. We conclude by discussing recent research on how death‐related socialization might be related to coping and bereavement after the death of a loved one.
Reintroduction failure after negative food challenges in adults is common and mainly due to atypical symptoms
Authors: Versluis Astrid , Knulst André C. , van Erp Francine C. , Blankestijn Mark A. , Meijer Yolanda , Le Thuy‐My , van Os‐Medendorp Harmieke
Published: January 2020

Background

Reintroduction of a food after negative food challenge (FC) faces many obstacles. There are no studies available about this subject in adults.

Objective

To investigate the frequency, reasons and risk factors of reintroduction failure in adults.

Methods

In this prospective study, adult patients received standardized follow‐up care after negative FCs including a reintroduction scheme and supportive telephone consultations. Data were collected by telephone interview (2 weeks after FC) and questionnaires (at baseline and 6 months after FC(s)): food habits questionnaire, State‐Trait Anxiety Inventory, Food Allergy Quality of Life Questionnaire‐Adult Form and Food Allergy Independent Measure. Frequency and reasons of reintroduction failure were analysed using descriptive statistics and risk factors with univariate analyses.

Results

Eighty patients were included with, in total, 113 negative FCs. Reintroduction failed on short‐term (2 weeks after FC) in 20% (95% CI: 13%‐28%). Common reasons were symptoms upon ingestion during the reintroduction scheme (50%) and no need to eat the food (23%). On the long‐term (5‐12 months after FC(s)), reintroduction failure increased to 40% (95% CI: 28%‐53%). Common reasons were atypical symptoms after eating the food (59%) and fear for an allergic reaction (24%). Five risk factors for long‐term reintroduction failure were found: if culprit food was not one of the 13 EU regulated allergens, reintroduction failure at short‐term, atypical symptoms during FC, a lower quality of life and a higher state anxiety.

Conclusions and clinical relevance

Reintroduction failure after negative FCs in adults is common, increases over time, and is primarily due to atypical symptoms. This stresses the need for more patient‐tailored care before and after negative food challenges.
Emergent laparoscopic sigmoid resection for perforated diverticulitis: can it be safely performed by residents?
Authors: Dreifuss N. H. , Schlottmann F. , Bun M. E. , Rotholtz N. A.
Published: January 2020

Aim

Outcomes after resident involvement in emergent colectomies have rarely been studied. The aim of this study was to analyse the outcomes of laparoscopic sigmoidectomy for Hinchey III diverticulitis performed by residents.

Method

This study was a retrospective analysis of patients undergoing laparoscopic sigmoidectomy for diverticulitis. The sample was divided into two groups: patients operated on by a supervised resident (SR) or a senior surgeon (SS). Supervising surgeons and SSs could be general surgeons (GSs) or colorectal surgeons (CSs). A SR was considered the first surgeon if he/she completed at least three of five defined steps of the procedure. The primary end‐points included length of hospital stay (LOS), morbidity and 30‐day mortality. A sub‐analysis of patients operated on by a SR assisted by either a CS or GS was performed.

Results

Supervised residents and SSs operated on 59 and 42 patients, respectively. The presence of a CS was more frequent in the SS group (SR 41% vs SS 81%, P < 0.001). LOS (SR 9.4 days vs SS 6.4 days, P = 0.04) was higher in the SR group. Overall morbidity (SR 39% vs SS 43%, P = 0.69) and 30‐day mortality (SR 5% vs SS 5%, P = 0.94) were also comparable among the groups. Procedures performed by SRs and supervised by a CS were associated with lower morbidity (GS 48% vs CS 25%, P = 0.06) and mortality (GS 8% vs CS 0%, P = 0.26).

Conclusion

Laparoscopic sigmoidectomy for Hinchey III diverticulitis has comparable outcomes when performed by a supervised SR or a SS. Procedures performed by residents assisted by a CS seem to have better outcomes than those assisted by a GS.
The role of gamut, intuition and engagement in colour management in a design context
Authors: Henry Phil , Westland Stephen
Published: January 2020

Colour management is ubiquitous in the digital world. However, despite the many advances in colour management over the last couple of decades, it remains an imperfect process. In the art and design community there is often a level of dissatisfaction and deep cynicism about colour management that can lead to lac of engagement with the process. This research explores colour management in a design context though three issues: the gamut issue, the intuitive issue and the engagement issue; each relates to areas where colour management could better connect with tacit design knowhow. The work focusses on the selection of colour in a digital context since for many users this is the first touch point that they have with colour management. Psychophysical studies have been carried out in both laboratory and design‐studio settings. It is shown that users can better predict the results from subtractive colour mixing than from additive colour mixing. The performance of various types of colour picker are explored and consequences for the design of user interfaces are discussed.
Immunohistochemistry utilization in the diagnosis of melanoma
Authors: Dinehart Matthew S. , Dinehart Scott M. , Sukpraprut‐Braaten Suporn , High Whitney A.
Published: January 2020

Background

The use of immunohistochemical (IHC) stains in dermatopathology is commonplace; however, little is known regarding utilization trends in melanoma diagnosis. Current Medicare local coverage determinations (LCDs) state that most pigmented lesions, including melanoma, can be diagnosed using H&E alone.

Methods

Histopathology reports for all biopsy‐proven melanomas excised between January 1, 2017 and June 30, 2018, at a single dermatology clinic, were identified with the following parameters abstracted: laboratory/dermatopathologist rendering the diagnosis, whether IHC was performed, type/number of stains utilized, presence/depth of invasion, and melanoma subtype. The association of characteristics with IHC utilization was evaluated using χ2 test for categorical variables.

Results

Three hundred and fifty six eligible melanomas were identified. IHC was employed in 228 (64%) of the diagnoses. Invasive melanoma was diagnosed in 199 cases (55.9%) while 157 (44.1%) were identified as melanoma in situ (MIS). Of the 228 that utilized IHC, 117 were performed on invasive melanoma (58.8%) and 111 were performed on MIS (70.7%).

Conclusion

Our findings suggest a higher IHC usage for the diagnosis of melanoma than previously reported. Existing LCDs regarding IHC utilization in melanoma do not reflect the current state of practice. Further investigation regarding IHC utilization and the development of appropriate‐use criteria for melanoma IHC is necessary.
Investigating the histopathological findings and immunolocalization of rickettsialpox infection in skin biopsies: A case series and review of the literature
Authors: Vyas Nikki S. , Shieh Wun‐Ju , Phelps Robert G.
Published: January 2020

Background

Recognition of rickettsialpox infection on skin biopsy can be challenging. The histopathology is non‐specific and inconsistently described. We assess classic histopathologic features in confirmed cases and review the literature.

Methods

We searched for cases of “rickettsialpox” diagnosed between 2006 and 2018 with positive immunostaining for Spotted Fever Group Rickettsia species. Original slides were evaluated for vacuolar alterations, granulomatous inflammation, vasculitis, necrosis, fibrin thrombi, microvesiculation, papillary dermal edema, and extravasated red blood cells. All biopsies were stained for CD3, CD20, CD68, and myeloperoxidase.

Results

Six biopsy specimens were compiled, three of which were sampled from vesiculopapules, one from a maculopapule, and two from eschars. Vacuolar alterations and vasculitis were present in all specimens (6/6; 100%). Granulomatous inflammation was present in five specimens (5/6; 83.3%). Fibrin thrombi and red blood cells were seen in 3/6 (50%) of specimens. The eschars showed necrosis of the epidermis and superficial dermis (2/6, 33.3%). Only one specimen showed intraepidermal vesiculation and papillary dermal edema (1/6; 16.7%). All six specimens showed perivascular infiltration with CD3+ T‐cells, and low amounts of CD20+ B‐cells and neutrophils. Five of the six specimens (83.3%) showed significant levels of CD68+ histiocytes.

Conclusion

The histopathology of rickettsialpox infection is septic lymphocytic and granulomatous vasculitis.
Seasonal variations in incidence and maternal–fetal outcomes of gestational diabetes
Authors: Meek C. L. , Devoy B. , Simmons D. , Patient C. J. , Aiken A. R. , Murphy H. R. , Aiken C. E.
Published: January 2020

Aims

To determine whether the neonatal and delivery outcomes of gestational diabetes vary seasonally in the context of a relatively cool temperate climate.

Methods

A retrospect cohort of 23 735 women consecutively delivering singleton, live‐born term infants in a single tertiary obstetrics centre in the UK (2004–2008) was identified. A total of 985 (4.1%) met the diagnostic criteria for gestational diabetes. Additive dynamic regression models, adjusted for maternal age, BMI, parity and ethnicity, were used to compare gestational diabetes incidence and outcomes over annual cycles. Outcomes included: random plasma glucose at booking; gestational diabetes diagnosis; birth weight centile; and delivery mode.

Results

The incidence of gestational diabetes varied by 30% from peak incidence (October births) to lowest incidence (March births; P=0.031). Ambient temperature at time of testing (28 weeks) was strongly positively associated with diagnosis (P<0.001). Significant seasonal variation was evident in birth weight in gestational diabetes‐affected pregnancies (average 54th centile June to September; average 60th centile December to March; P=0.027). Emergency Caesarean rates also showed significant seasonal variation of up to 50% (P=0.038), which was closely temporally correlated with increased birth weights.

Conclusions

There is substantial seasonal variation in gestational diabetes incidence and maternal–fetal outcomes, even in a relatively cool temperate climate. The highest average birth weight and greatest risk of emergency Caesarean delivery occurs in women delivering during the spring months. Recognizing seasonal variation in neonatal and delivery outcomes provides new opportunity for individualizing approaches to managing gestational diabetes.
A prominent brachiocephalic vein masquerading as an aortic dissection flap on transthoracic echocardiogram: A case for multimodality imaging
Authors: Gajjar Kushani , Biederman Robert
Published: January 2020

A 30‐year‐old female patient with past medical history of supraventricular tachycardia presented with shortness of breath and underwent a transthoracic echocardiogram (TTE). The TTE noted a concerning partially mobile linear echo density, with positive Doppler color flow across it along the aortic arch, which was concerning for a dissection flap. The patient accordingly underwent a cardiac MRI which revealed that the anomaly seen on echocardiogram was in the setting of a prominent left brachiocephalic (innominate) vein and without evidence of aortic dissection. While this is a relatively common phenomenon, there is no literature on prominent brachiocephalic vein masquerading as an aortic dissection flap on TTE.
Observational study of left ventricular global longitudinal strain in ST‐segment elevation myocardial infarction patients with extended pharmaco‐invasive strategy: A six months follow‐up study
Authors: Manjunath Satvic C. , Doddaiah Balaraju , Ananthakrishna Rajiv , Sastry Sridhar Lakshmana , Patil Vikram S. , Devegowda Lachikrathman , Veervhadraiah Sumangala B. , bhat Prabhavathi , Nanjappa Manjunath Cholenahally
Published: January 2020

Aims and Objectives

To evaluate left ventricular (LV) function by assessment of LV global longitudinal strain (GLS) in ST‐segment elevation myocardial infarction (STEMI) patients who underwent delayed fibrinolysis and coronary intervention (extended pharmaco‐invasive strategy), since LV function is one of the determinants of both immediate and long‐term outcomes.

Methods

Prospective study of consecutive STEMI patients who underwent extended pharmaco‐invasive strategy. The LV function was estimated using LV GLS at baseline and at 6 months.

Results

The study included eighty‐seven STEMI patients who received delayed pharmaco‐invasive therapy and coronary intervention. The primary aim of the study was to evaluate a change in LV function by assessment of GLS at 6 months as compared to baseline. Prior to PCI, LV ejection fraction was 48.08 ± 6.23% and GLS was −11.11 ± 2.99%. Procedural success was achieved in all patients. LV ejection fraction after 6 months of follow‐up increased to 53.12 ± 5.61% and the GLS improved to −13.03 ± 3.06% In comparison to baseline, there was a significant improvement in both LV ejection fraction and GLS at 6 months of follow‐up (P < .001).The cardiac mortality was 1.1% at 6 months.

Conclusion

There is a significant improvement of LV function as assessed by GLS and ejection fraction at short‐term follow‐up. In a stable cohort of STEMI patients, extended pharmaco‐invasive strategy is also a reasonable option if PCI cannot be performed within the first 24 hours, due to logistic and infrastructural constraints.
Diagnosis of double‐chambered left ventricle by echocardiogram and cardiac magnetic resonance imaging: A rare case in an adult
Authors: Li Tianjing , Han Jiancheng , Li Yu , Gao Shuang , Hao Xiuxiu , He Yihua
Published: January 2020

Double‐chambered left ventricle (DCLV) is a very rare malformation which is congenital. In most cases, the left ventricle (LV) is divided into two parallel chambers by a septum or aberrant muscular structure, with fewer superior–inferior arrangement. Here, we present the case of an asymptomatic 25‐year‐old man who was diagnosed with superior–inferior arrangement DCLV on transthoracic echocardiography and cardiac magnetic resonance (CMR). DCLV generally does not cause serious outcomes. Owing to absence of any symptoms, no treatment was provided, and the patient was regularly followed up.