bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of young patients following mechanical thrombectomy for stroke: A systematic review and meta-analysis
Authors: Kobeissi Hassan , Liu Michael , Ghozy Sherief , Kadirvel Ramanathan , Kallmes David F
Published: August 2022

Background

Young patients experience acute ischemic stroke (AIS) at much lower rates than their older counterparts. We performed a systematic review and meta-analysis to assess the question regarding outcomes and clinical characteristics of young stroke patients who underwent mechanical thrombectomy for AIS.

Methods

Following PRISMA guidelines, a systematic review of the literature was conducted using the databases PubMed, MEDLINE, and Embase. The primary outcome of interest was 90-day modified Rankin Scale (mRS) 0–2. Secondary outcome variables included rate of successful reperfusion (TICI 2b/3), symptomatic intracerebral hemorrhage (sICH), and mortality. Using R software version 4.1.2, we calculated pooled event rates and their corresponding 95% confidence intervals (CI) for all outcomes.

Results

Our analysis included eight studies with a total of 1903 patients. Definitions of young patients included age ranges of 18–49/50 years, 18–54/55 years, and 18–64/65 years. Functional independence was achieved in 62.0% of the patients, with an overall mortality of 9.0%. Moreover, successful reperfusion was achieved in 82.0% of the patients with sICH rates of 5.7%. There was significant heterogeneity among different analyses, which could not be attributed to the differences of the definition of young patients.

Conclusions

Following mechanical thrombectomy for AIS, patients aged 18–65 years achieved relatively high rates of functional independence and successful reperfusion and low rates of mortality and sICH. Clinical Perspective In this systematic review and meta-analysis of eight studies, we examined outcomes in young stroke patients, aged 18–65 years old, following mechanical thrombectomy for acute ischemic stroke. We found that young patients achieved high rates of functional independence, high rates of successful reperfusion, and low rates of mortality and symptomatic intracerebral hemorrhage. While there have been several papers examining outcomes following mechanical thrombectomy for acute ischemic stroke in young patients, the results of these studies have yet to be pooled together in a meta-analysis. Our results indicate that young patients have good outcomes following mechanical thrombectomy. Further studies that examine these outcomes are warranted so that a higher-powered analysis can be performed to better informed clinicians regarding outcomes in this patient age-group cohort.
Real Talk: A Realist Dialogic Approach in a Realist Evaluation
Authors: Francis-Auton Emilie , Sarkies Mitchell N , Pomare Chiara , Long Janet C , Hardwick Rebecca , Nguyen Hoa Mi , Braithwaite Jeffrey
Published: August 2022

Realist evaluation is a method increasingly adopted to provide an understanding of how and why a program works, for whom, and under what circumstances. Initial program theories (IPT) are the crucial starting point of any realist evaluation, however descriptions about how they are developed in practice remain under-reported in the published literature. This article argues for the value of genuine research-group conversations using David Bohm’s concept of dialogue in realist research. We label it the realist dialogic approach. We draw out the relational qualities as well as the contextual circumstances of dialogue through our development of IPT and interview guides for a research study on the implementation and scaling of a large-system value-based program to transform complex health services. We selected the relevant middle-range theories, conducted a literature review, and drew on informal discussions with key stakeholders, to develop IPT through research-group conversations. The benefits of this approach were: 1) development of rigorous, novel, deep and well-tailored IPT, 2) detailed understanding of the complex intervention under investigation and development of rapport and networks with participants, 3) empirically grounded Context-Mechanism-Outcome (CMO) configurations, predicated on suitable abstract and contextually-contingent middle-range theories, and 4) productive research team interactions which supported the entire research process. The challenges of this approach include: 1) establishing and retaining a sense of humility across the research team, 2) contextual circumstances can hinder dialogic relationship, and 3) time and resource heavy. This paper uses middle-range theory and ethnographic insights to advance the existing practice of realist evaluations and offer transferable lessons to other scholars considering similar approaches. Moreover, we content that the use of middle-range theory to extend the methodological literature is a novel contribution to realist work.
Academic leaders: In-role perceptions and developmental approaches
Authors: Grajfoner Dasha , Rojon Céline , Eshraghian Farjam
Published: August 2022

Academic excellence is brought about by effective leadership, which may encompass the concept of distributed leadership, which signifies a collective engagement. However, leadership positions within higher education are frequently filled with scholars lacking leadership skills and experience, which can be detrimental both to their performance and well-being. To address this, we explored via interviews with academic leaders how academic leadership is defined and conceptualised and what their developmental needs are. Participants ( N = 23) came from junior, middle and senior management levels. Findings suggest that their notions of leadership as well as any developmental needs/activities perceived useful, differ according to their leadership level. Although junior leaders were more concerned with procedural elements of leading, senior leaders focused on mentoring, social expectations and knowledge of academia. These findings have important implications for a wider theoretical conceptualisation of academic leadership, which are typically focused on individual senior leaders. Further, our findings inform leadership development programmes, as universities’ dealings with academic leaders tend not to consider the differing requirements of junior, middle and senior academic leaders.
An adapted component-connection method for building SBDD encoding a dynamic fault tree
Authors: Guo Dingqing , Wang Jinkai , Lin Jian , Zhang Bing , Yong Nou , Xia Dongqin , Ge Daochuan
Published: August 2022

Dynamic fault trees (DFTs) are a commonly used tool to analyze the reliability of systems with sequential failure behaviors. A sum of disjoint product (SDP)-based analysis methods are widely accepted as efficient approaches for a DFT, such as dynamic binary decision trees (DBDTs) and sequential binary decision diagrams (SBDDs). However, for a large DFT, the process of obtaining the structure function is error-prone and very time-consuming. In contrast, SBDD built on the improved ite algorithm does not rely on the structure function but is limited to a DFT whose dynamic gates are located at the bottom. This method requires predefined variable ordering for basic events, which greatly influences the computational efficiency, and the caching operation is a problem. In this paper, an enhanced component-connection–based method is proposed to build SBDD encoding a DFT. New component-connection rules are developed to deal with dependent variables having repeated basic events, and several heuristic connection strategies are also developed to reduce the size of the final calculable terms. The proposed method is straightforward and easily implemented. To demonstrate the applications and merits of our method, several case studies are carried out, and the results show the reasonability and effectiveness.
Exploring Music Video Experiences and Their Influence on Music Perception
Authors: Dasovich-Wilson Johanna N. , Thompson Marc , Saarikallio Suvi
Published: August 2022

Streaming music videos on the internet is an increasingly popular music listening activity that has remained virtually unexplored within music psychology. Studies of the role of music in film, as well as empirical research investigating the influence of audio-visual media and memory, have shown that visual information can have a profound effect on how music is perceived and remembered. The current study aimed to create a framework for understanding music video (MV) experiences by finding out when and why individuals choose to engage with this form of media, how these experiences contribute to the perception of musical meaning and influence affective outcomes, and whether these effects carry over to subsequent listening experiences. An online questionnaire study was designed, and data were collected from 34 participants with a mean age of 22.4 years (SD  =  2.79). Abductive analysis of the qualitative data was conducted based on theories derived from topical areas of music psychology research. A framework was devised which illustrates MV listening experiences over four temporal stages: Intention, Attention, Reaction, and Retention (IARR). The IARR framework provides novel insights into MV listening experiences and outcomes by shedding light on how extra-musical information can have a long-term influence on the perception of music's meaning and affective quality.
Surgical Repair of Complete Common Atrioventricular Canal in a Conjoined Twin Following Separation
Authors: Fatuzzo Stephen H. , Greenberg Jason W. , Hirsch Russel , Iliopoulos Ilias D. , Taylor Michael D. , Morales David L.S.
Published: August 2022

Congenital heart disease (CHD) is common in conjoined twins but reports of surgical repair in this population are rare. We present the case of a conjoined twin diagnosed prenatally with a complete common atrioventricular canal defect (CAVC). Due to wound complications from twin separation, definitive repair was deferred and pulmonary arterial banding was performed initially. At 6 months, a complete CAVC repair was performed. The present case adds to the literature on successful cardiac surgical repairs in conjoined twins.
Nursing Staff Mortality During the Covid-19 Pandemic, Scoping Review
Authors: Vera-Alanis Yuliana , Aranda-Sanchez Daysi , Cano-Verdugo Guillermo , Gonzalez-Angulo Pedro , Rueda-Sanchez Cynthia Berenice , Rojas-Martinez Augusto
Published: August 2022

Introduction

In a pandemic, the risk of infection and mortality for nurses can increase substantially. This study analyzes the information reported on the mortality of nursing personnel from different countries due to COVID-19.

Methods

We performed a scoping review by searching information available in PubMed, Scielo, and Google Scholar databases using concepts related to nursing, mortality, COVID-19, etc. The studies were searched from September 1 to October 30, 2021. This review included 12 articles were selected among 73 identified for the scope search because they included nurses.

Results

Nursing personnel presented a high mortality rate after physicians and health personnel. The average age of the deceased nurses was 43 years, being higher in men than in women. Higher mortality rates were reported in services attending COVID-19, nursing homes, and psychiatric centers.

Conclusion

Contagion and deaths are attributed to lack of planning and inadequate personal protective equipment.
Tracking the Statistical Center of Global Seventh-day Adventism, from 1863 to the Present
Authors: Masfa Gabriel
Published: August 2022

The Seventh-day Adventist Church is a Christian denomination with roots in the Millerites’ experience in North America in the nineteenth century. From its inception until the 1960s, Seventh-day Adventism was concentrated in North America, with growing but scant membership in other parts of the world. Between the late 1960s and the beginning of the 1990s, however, there were dramatic and unprecedented changes in the trajectory of Seventh-day Adventism. Thousands of converts were coming from the Global South: Latin America, Africa, and Asia. This article briefly describes the movement of the statistical center of global Adventism from 1863 to the present.
Practical strategies to identify and address discordant findings in mixed methods research
Authors: Younas Ahtisham , Pedersen Maria , Inayat Shahzad
Published: August 2022

Integration of qualitative and quantitative data in mixed methods research generates confirmed, discordant, and expanded findings. Guidance is available about the methods and strategies for the meaningful integration of data. However, little has been written about strategies for managing discordant findings in mixed methods. This paper describes and illustrates practical strategies for managing and integrating discordant findings in mixed methods analyses based on researchers reflections and experiences of managing and integrating discordant findings in convergent and sequential exploratory mixed methods studies. Two strategies, namely, comprehensive case and variable analysis and sociocultural exploration are proposed. Comprehensive case analysis involves identifying discordant findings in quantitative data, identifying supportive data in qualitative data, and selecting variables for mixed analysis and interpretation. Sociocultural exploration comprises qualitative code and quantitative data matrix for themes, identification of discordant findings under each theme, and development of sociocultural profile. Identifying and addressing discordant findings in mixed methods is an essential step of rigorous mixed methods analysis. The comprehensive case and variable analysis and sociocultural exploration strategies emphasize the need to examine discordance in data at an early stage of analysis. Further use and evaluation of these strategies are warranted to expand the body of knowledge about practical methods of mixed methods data analysis.
Inlay Patellofemoral Arthroplasty: A Readily Reproducible Technique
Authors: Hevesi Mario , Berlinberg Elyse J. , Patel Harsh H. , Ramos Pablo , Forsythe Brian
Published: August 2022

Background:

Patients with recalcitrant anterior knee pain and isolated patellofemoral osteoarthritis (PFOA) may benefit from patellofemoral arthroplasty. Arthroplasty with an inlay implant may be beneficial given recreation of native biomechanics and potentially avoiding anterior overstuffing.

Indications:

Patellofemoral arthroplasty is indicated in patients with anterior knee pain from isolated PFOA in patients with neutral alignment and intact menisci and ligaments. To highlight these indications, we present a 32-year-old female with severe anterior knee pain from PFOA, not resolved by conservative measures. Preoperative imaging demonstrated full-thickness chondral loss of the lateral patellar facet and trochlea, with neutral alignment and no significant trochlear dysplasia.

Technique Description:

This technique utilized the HemiCap Wave Implant manufactured by Anika Therapeutics (Franklin, MA, USA). A standard midline approach and medial parapatellar arthrotomy is performed. The patella is everted, and the trochlea is exposed. A guide pin is placed perpendicular to the trochlear bony surface and centrally in the defect. The pin is advanced, and the surrounding area is reamed. A guide block is placed over the pin in the trochlea and over-reamed. The area is prepared and centrally drilled, then tapped. A taper post is implanted. The trochlear implant is then secured to the taper post with an impactor and mallet. On the patellar side, a guide pin is placed in the center of the patella. Consideration is given to medialization of the button to decrease Q-angle. The patella is reamed to the diameter of an appropriately sized patellar button. A trial button is used to ensure satisfactory tracking. A real patellar implant is then cemented into place. Standard closure is performed.

Results:

Overall outcomes following inlay patellofemoral arthroplasty have been positive, with up to 89% of patients engaging in sports at 2 years status post surgery and 83% survival free of total knee arthroplasty at 5 years postoperatively.

Discussion/Conclusion:

Patellofemoral arthroplasty can provide good satisfaction and high rates of return to sport in patients with symptomatic, isolated patellofemoral arthritis. The surgical technique video presented provides reproducible steps, tips, and tricks for performing this procedure.
Randomised controlled trial of first-line tyrosine-kinase inhibitor (TKI)versusintercalated TKI with chemotherapy forEGFR-mutated nonsmall cell lung cancer
Authors: Gijtenbeek Rolof G.P. , van der Noort Vincent , Aerts Joachim G.J.V. , Staal-van den Brekel Jeske A. , Smit Egbert F. , Krouwels Frans H. , Wilschut Frank A. , Hiltermann T. Jeroen N. , Timens Wim , Schuuring Ed , Janssen Joost D.J. , Goosens Martijn , van den Berg Paul M. , de Langen A. Joop , Stigt Jos A. , van den Borne Ben E.E.M. , Groen Harry J.M. , van Geffen Wouter H. , van der Wekken Anthonie J.
Published: August 2022

Introduction

Previous studies have shown interference between epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and chemotherapy in the cell cycle, thus reducing efficacy. In this randomised controlled trial we investigated whether intercalated erlotinib with chemotherapy was superior compared to erlotinib alone in untreated advanced EGFR-mutated nonsmall cell lung cancer (NSCLC).

Materials and methods

Treatment-naïve patients with an activatingEGFRmutation, ECOG performance score of 0–3 and adequate organ function were randomly assigned 1:1 to either four cycles of cisplatin-pemetrexed with intercalated erlotinib (day 2–16 out of 21 days per cycle) followed by pemetrexed and erlotinib maintenance (CPE) or erlotinib monotherapy. The primary end-point was progression-free survival (PFS). Secondary end-points were overall survival, objective response rate (ORR) and toxicity.

Results

Between April 2014 and September 2016, 22 patients were randomised equally into both arms; the study was stopped due to slow accrual. Median follow-up was 64 months. Median PFS was 8.8 months (95% CI 4.2–18.8) for CPE and 10.3 months (95% CI 7.1–15.5; hazard ratio (HR) 0.78, 95% CI 0.32–1.91) for erlotinib monotherapy; when compensating for number of days receiving erlotinib, PFS of the CPE arm was superior (HR 0.32, 95% CI 0.10–1.01; p=0.02). ORR was 64% for CPEversus55% for erlotinib monotherapy. Median overall survival was 30.9 months (95% CI 18.5–61.9 months) for CPE compared to 17.2 months (95% CI 11.5–45.5 months) for erlotinib monotherapy (HR 0.66, 95% CI 0.27–1.65 months). Patients treated with CPE had higher rates of treatment-related fatigue, anorexia, weight loss and renal toxicity.

Conclusion

Intercalating erlotinib with cisplatin-pemetrexed provides a longer PFS compared to erlotinib alone inEGFR-mutated NSCLC at the expense of more toxicity.
Underweight children are agile but lack power
Authors: Verbecque Evi , Coetzee Dané , Smits-Engelsman Bouwien
Published: August 2022

Given the knowledge gap in literature on the impact of undernutrition on muscular power and agility in school-aged children, the aim of this study was to compare physical fitness in such underweight- and normal weight children. In this cross-sectional study, 853 children were included (459 boys; mean age: 9.2 (1.8) years). The children were grouped according to their BMI-for-age-and-sex: normal weight (− 1 ≤ z-score < 2) and underweight (z-score < − 1). Within the underweight group, three thinness subgroups were composed: grade 1 (− 2 ≤ z-score < − 1), grade 2 (− 3 ≤ z-score < − 2) and grade 3 (z-score < − 3). Their agility, muscular endurance and power were assessed with the Performance and Fitness test battery (PERF-FIT). Regardless the country they lived in, the underweight children showed better agility (p = 0.012) and muscular endurance (p = 0.004) than those with normal weight. They presented with lower muscular power than the normal weight group, shown by significantly shorter overhead throwing distances (p = 0.017) and less standing long jump peak power (p < 0.001). The standing long jump peak power decreased further with increasing thinness grade (p = 0.027).

Conclusion: Underweight children are more agile, but have lower muscular power compared to their normal weight peers. Its relationship with motor competence and physical activity, necessitates attention for tackling muscular strength deficiencies in these children, enabling them to meet the basic requirements for a healthy lifestyle later in life.
Changes in retail food environments around schools over 12 years and associations with overweight and obesity among children and adolescents in Flanders, Belgium
Authors: Smets Vincent , Vandevijvere Stefanie
Published: August 2022

Background

Children are susceptible to the food environment. This research assessed changes in retail food environments near schools in Flanders between 2008 and 2020 and associations with children’s and adolescents’ weight status.

Methods

The food environment within a 500 m and 1000 m road network distance to all primary and secondary schools was mapped using spatial indicators. The commercial Locatus database, including addresses of all food retailers in Flanders, was used to calculate the density of different types of food retailers near the school perimeter, the percentage of schools with at least one food retailer of a certain type near the school perimeter and the shortest distance from the school entrance to the nearest food retailer of a certain type. A generalized linear model was used to explore associations between these indicators and the percentage of children and adolescents with overweight at the school level.

Results

Food environments near schools in Flanders were found to be unhealthy in 2020, with a significant increase in fast food restaurants and convenience stores between 2008 and 2020. The density of fast food restaurants within a 1000 m walking distance from primary and secondary schools increased from 5.3 ±0.3 to 6.3 ±0.4 and from 10.2 ±0.7 to 12.7 ±0.9 respectively between 2008 and 2020, while the density of convenience stores increased from 3.2 ±0.3 to 3.8 ±0.4 and from 6.2 ±0.6 to 7.6 ±0.8 respectively.

Food environments near schools with a higher proportion of children from a poor socio-economic background were found unhealthier, regardless of the urbanization level. A significant positive association was found between the density of fast food restaurants as well as the density of convenience stores around primary schools and the percentage of children aged < 6 years and 6–12 years with overweight. A positive, not significant association was found between the density of fast food restaurants as well as the density of convenience stores around secondary schools and the percentage of adolescents, aged 13–14 and 15–18 years with overweight.

Conclusion

Food environments around schools in Flanders became unhealthier over time and were associated with children’s weight status.
Patient handoffs among general surgery residents in Saudi Arabia: a cross-sectional study
Authors: Saleem Abdulaziz M. , Kadi Mai
Published: August 2022

Background

Communication failure is a common cause of adverse events. An essential element of communication among health care providers is patient handoff. Patient handoff is defined as a practice whereby a health care provider transfers a patient’s care information to another health care provider to ensure the patient’s safety and continuity of care. To explore this practice, we assessed patient handoffs among general surgery residents in Saudi Arabia.

Methods

A cross-sectional survey was conducted with individuals in accredited general surgery residency programs in Saudi Arabia between 2020 and 2021.

Results

Participants comprised 118 general surgery residents: 66 (57.3%) were female; 67 (72.8%) did not receive any formal training on patient handoff; and 35 (38.8%) reported that they were sometimes interrupted during the patient handoff process. The most common reason for such interruptions was medical personnel paging. Furthermore, 60 (68.1%) general surgery residents stated that these interruptions led to a decreased quality of effective communication, 39 (44.3%) believed it led to decreased quality of patient care, 63 (71.5%) believed it led to the loss of some information related to patient handoff, and 16 (18.1%) believed it led to patient harm. Finally, 31 (34.4%) general surgery residents believed that the existing handoff system at their institutions neither adequately protected the patients’ safety nor allowed for continuity of care, and 51 (68%) reported that their institution did not have a standardized protocol for the verbal patient handoff process. There was a higher proportion of patients with minor harm among residents who did not, rarely or sometimes received verbal or written hand off instructions compare to those who did so always or most of the time (67% vs. 49%, respectively).

Conclusion

The patient handoff process among general surgery residents in Saudi Arabia is subjective and is not standardized, and if not addressed, may lead to patient harm. Standardizing this process is paramount to improve patient safety.
Use of the interRAI PEDS HC in children receiving home care in Ontario, Canada
Authors: Thorburn-Winsor Emily , Doherty Megan , Jones Aaron , Vadeboncoeur Christina
Published: August 2022

Background

There is no standard assessment tool for pediatric home care recipients in Canada, limiting the availability of comparable, population-based data. The objective of this study was to describe pediatric home care recipients who were part of a pilot implementation of the interRAI Pediatric Home Care Assessment Form (PEDS-HC) among medically complex children referred to home care agencies in three regions in Ontario, Canada.

Methods

All 14 agencies providing home care to children in Ontario were invited to participate in the pilot project, and 9 participated in an education session. Three of these agencies used the PEDS-HC during the pilot implementation between February 2018 and March 2020. We used de-identified data to describe the demographics, home care needs, and diagnoses of pediatric home care recipients.

Results

The sample of 474 assessments was predominantly male (60.34%), with an average age at assessment of 12.36 years (SD 4.56). Most (78.48%) reported English as their primary language. Most children assessed had between two and eight medical diagnoses. Diagnoses reported varied: gastrointestinal, musculoskeletal, respiratory and neurological conditions were most common. The prevalence of urinary incontinence (40.1%) and bowel incontinence (70.9%) were high. Over 60% of children were rarely or only sometimes understood. A majority of children had adequate hearing (83.5%) and vision (68.6%). Extensive services were being provided in 10% of children assessed. Most children received care both at school and at home (70.89%), with 20.89% receiving home care only.

Conclusions

The PEDS-HC provides a detailed, standardised descriptive profile of medically complex children receiving home care. Expanding use of PEDS-HC would promote consistency in care planning and delivery on the patient level, enable cross-jurisdictional comparisons, and inform utilization tracking and health care funding decisions on the organization and provincial levels.
Modulation of the proteoglycan receptor PTPσ promotes white matter integrity and functional recovery after intracerebral hemorrhage stroke in mice
Authors: Yao Min , Fang Jie , Li Jiewei , Ng Anson Cho Kiu , Liu Jiaxin , Leung Gilberto Ka Kit , Song Fanglai , Zhang Jian , Chang Chunqi
Published: August 2022

Background

Intracerebral hemorrhage (ICH) is associated with high morbidity and mortality rates. However, extant investigations have mainly focused on gray matter injury within the primary injury site after ICH rather than on white matter (WM) injury in the brain and spinal cord. This focus partly accounts for the diminished therapeutic discovery. Recent evidence suggests that chondroitin sulphate proteoglycans (CSPG), which can bind to the neural transmembrane protein tyrosine phosphatase-sigma (PTPσ), may facilitate axonal regrowth and remyelination by ameliorating neuroinflammation.

Methods

A clinically relevant ICH model was established using adult C57BL/6 mice. The mice were then treated systemically with intracellular sigma peptide (ISP), which specifically targets PTPσ. Sensorimotor function was assessed by various behavioral tests and electrophysiological assessment. Western blot was used to verify the expression levels of Iba-1 and different inflammatory cytokines. The morphology of white matter tracts of brain and spinal cord was evaluated by immunofluorescence staining and transmission electron microscopy (TEM). Adeno-associated virus (AAV) 2/9 injection was used to assess the ipsilateral axonal compensation after injury. Parallel in vitro studies on the effects of CSPG interference on oligodendrocyte–DRG neuron co-culture explored the molecular mechanism through which ISP treatment promoted myelination capability.

Results

ISP, by targeting PTPσ, improved WM integrity and sensorimotor recovery via immunomodulation. In addition, ISP administration significantly decreased WM injury in the peri-hematomal region as well as cervical spinal cord, enhanced axonal myelination and facilitated neurological restoration, including electrophysiologically assessed sensorimotor functions. Parallel in vitro studies showed that inhibition of PTPσ by ISP fosters myelination by modulating the Erk/CREB signaling pathway.

Conclusions

Our findings revealed for the first time that manipulation of PTPσ signaling by ISP can promote prolonged neurological recovery by restoration of the integrity of neural circuits in the CNS through modulation of Erk/CREB signaling pathway.
Chronic maternal exposure to titanium dioxide nanoparticles alters breathing in newborn offspring
Authors: Colnot Eloïse , Cardoit Laura , Cabirol Marie-Jeanne , Roudier Lydia , Delville Marie-Helene , Fayoux Anne , Thoby-Brisson Muriel , Juvin Laurent , Morin Didier
Published: August 2022

Background

Over the last two decades, nanotechnologies and the use of nanoparticles represent one of the greatest technological advances in many fields of human activity. Particles of titanium dioxide (TiO2) are one of the nanomaterials most frequently found in everyday consumer products. But, due in particular to their extremely small size, TiO2 nanoparticles (NPs) are prone to cross biological barriers and potentially lead to adverse health effects. The presence of TiO2 NPs found in human placentae and in the infant meconium has indicated unequivocally the capacity for a materno-fetal transfer of this nanomaterial. Although chronic exposure to TiO2 NPs during pregnancy is known to induce offspring cognitive deficits associated with neurotoxicity, the impact of a gestational exposure on a vital motor function such as respiration, whose functional emergence occurs during fetal development, remains unknown.

Results

Using in vivo whole-body plethysmographic recordings from neonatal mice, we show that a chronic exposure to TiO2 NPs during pregnancy alters the respiratory activity of offspring, characterized by an abnormally elevated rate of breathing. Correspondingly, using ex vivo electrophysiological recordings performed on isolated brainstem-spinal cord preparations of newborn mice and medullary slice preparations containing specific nuclei controlling breathing frequency, we show that the spontaneously generated respiratory-related rhythm is significantly and abnormally accelerated in animals prenatally exposed to TiO2 NPs. Moreover, such a chronic prenatal exposure was found to impair the capacity of respiratory neural circuitry to effectively adjust breathing rates in response to excitatory environmental stimuli such as an increase in ambient temperature.

Conclusions

Our findings thus demonstrate that a maternal exposure to TiO2 NPs during pregnancy affects the normal development and operation of the respiratory centers in progeny.
Postoperative short-term use of the nonsteroidal anti-inflammatory drug flurbiprofen did not increase the anastomotic leakage rate in patients undergoing elective gastrointestinal surgery—a retrospective cohort study
Authors: Nie Huang , Hao Yiming , Feng Xiangying , Ma Lina , Ma Yumei , Zhang Zhen , Han Xi’an , Zhang Jian zhong , Zhang Ping , Zhao Qingchuan , Dong Hailong
Published: August 2022

Background

Flurbiprofen has been one of the most commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) in China and other Asian countries for perioperative multimodal analgesia in recent years, yet its association with anastomotic leakage in gastrointestinal anastomoses is unknown. The current study was designed to investigate whether short-term administration of flurbiprofen would increase the risk of anastomotic leakage in patients undergoing gastrointestinal surgery for cancer resection.

Methods

A total of 3653 patients (2487 (66.1%) men) undergoing elective operation for gastrointestinal cancer between 18 July 2017 and 30 Oct 2020 were included. The median age was 61 years (interquartile range 53–67 years). The exposure was the short-term postoperative use of flurbiprofen (defined as flurbiprofen treatment within the first week after surgery). The primary outcome was the frequency of clinical anastomotic leakage.

Results

Of 3653 patients with available data who were included in the final analysis, 2282 received flurbiprofen administration, and 1371 did not. Anastomotic leakage was not significantly increased among the patients receiving flurbiprofen compared with those who did not (1.62% v 1.46%; P=0.70). In-hospital mortality was comparable between the two groups (0.04% v 0.07%; P=0.72). After adjusted analysis, male sex (OR 3.51, 95% CI 1.80–6.85), ASA score of 3–4 (OR 2.69, 95% CI 1.62–4.48), and intraoperative infusion (OR 2.24, 95% CI 1.19–4.21) were identified as risk factors for anastomotic leakage.

Conclusions

Postoperative short-term use of flurbiprofen did not increase the risk of anastomotic leakage in gastrointestinal anastomoses.
Correspondence: semen parameters in men who recovered from covid-19 — a systematic review and meta-analysis
Authors: dos Santos Diogo Edele , Colonetti Tamy , Medeiros Lidia Rosi , Uggioni Maria Laura Rodrigues , Grande Antonio Jose , da Rosa Maria Inês
Published: August 2022

A recent systematic review with meta-analysis performed by Tiwari et al. (Middle East Fertil Soc J 26:44, 2021) suggested that coronavirus disease 2019 (COVID-19) affects both semen parameters and sexual hormones. However, we have observed a few inconsistencies in their systematic review methods and their synthesis of results (meta-analysis), which would have impacted their results.
A qualitative examination of barriers and facilitators of pediatric enhanced recovery protocol implementation among 18 pediatric surgery services
Authors: Davis Teaniese L. , Schäfer Willemijn L. A. , Blake Sarah C. , Close Sharron , Balbale Salva N. , Perry Joseph E. , Zarate Raul Perez , Ingram Martha , Strople Jennifer , Johnson Julie K. , Holl Jane L. , Raval Mehul V.
Published: August 2022

Background

Enhanced recovery protocols (ERPs) are an evidence-based intervention to optimize post-surgical recovery. Several studies have demonstrated that the use of an ERP for gastrointestinal surgery results in decreased length of stay, shortened time to a regular diet, and fewer administered opioids, while also trending toward lower complication and 30-day readmission rates. Yet, implementation of ERPs in pediatric surgery is lagging compared to adult surgery. The study’s purpose was to conduct a theory-guided evaluation of barriers and facilitators to ERP implementation at US hospitals with a pediatric surgery service.

Methods

We conducted semi-structured interviews at 18 hospitals with 48 participants, including pediatric surgeons, anesthesiologists, gastroenterologists, nurses, and physician assistants. Interviews were conducted online, audio-recorded, and transcribed verbatim. To identify barriers and facilitators to ERP implementation, we conducted an analysis using deductive logics based on the five Active Implementation Frameworks (AIFs).

Results

Effective practices (usable innovations) were challenged by a lack of compliance to ERP elements, and facilitators were having standardized protocols in place and organization support for implementation. Effective implementation (stages of implementation and implementation drivers) had widespread barriers to implementation across the stages from exploration to full implementation. Barriers included needing dedicated teams for ERP implementation and buy-in from hospital leadership. These items, when present, were strong facilitators of effective implementation, in addition to on-site, checklists, protected time to oversee ERP implementation, and order sets for ERP elements built into the electronic medical record. The enabling context (teams) focused on teams’ engagement in ERP implementation and how they collaborated to implement ERPs. Barriers included having surgical team members resistant to change or who were not bought into ERPs in pediatric practice. Facilitators included engaging a multi-disciplinary team and engaging patients and families early in the implementation process.

Conclusions

Barriers to ERP implementation in pediatric surgery highlighted can be addressed through providing guidelines to ERP implementation, team-based support for change management, and protocols for developing an ERP implementation team. Future steps are to apply and evaluate these strategies in a stepped-wedge, cluster randomized trial to increase the implementation of ERPs at these 18 hospitals.
Landscape of pathogenic germline variants in patients with lung cancer.
Authors: Sorscher Steven , LoPiccolo Jaclyn , Chen Elaine , Heald Brandie , Michalski Scott T. , Nielsen Sarah M. , Nussbaum Robert Luke , Martins Renato G. , Esplin Edward D.
Published: August 2022

388570

Background: Few studies have aimed to investigate the prevalence and spectrum of pathogenic germline variants (PGVs) in patients diagnosed with lung cancer. Given the growing opportunities for precision therapies based on PGVs in DNA damage-repair (DDR)/homologous recombination-repair (HRR) genes and the importance of identifying PGVs to inform future cancer screening and cascade testing, we investigated the prevalence and potential clinical implications of PGVs in individuals with lung cancer. Methods: Deidentified data were retrospectively reviewed for 7,788 individuals diagnosed with lung cancer for whom germline DNA sequencing and exon-level copy number analysis were performed between 2014-2022 at a commercial diagnostic laboratory. The diagnosis of lung cancer was based on ICD-10 codes or language on the test requisition suggesting a primary lung cancer diagnosis. Individuals with requisitions suggesting lung metastases, neuroendocrine tumors or sarcomas as the basis for testing were excluded. Number of genes tested varied per ordering clinician preference. Clinically actionable PGVs were defined as those associated with clinical management recommendations or trial eligibility per current, standard of care guidelines. Descriptive statistics were utilized. Results: The cohort was predominantly female (71.1%), White (64.5%), and most had a history of > 1 cancer (71.1%). A median of 79 genes (range 1-159) were tested. Testing identified 1,503 PGVs in 81 known cancer-risk genes in 1,161/7,788 (14.9%) patients; an additional 229 (2.9%) patients carried a single PGV in a gene associated with autosomal recessive inheritance. PGV rates stratified by self-reported ancestry: Black/African American, 11.8%; Asian or Pacific Islander, 11.8%; Hispanic, 14.5%; White, 15.4%. Among genes with >1,000 individuals tested, PGVs were most common in BRCA2 (2.8%), CHEK2 (2.1%), ATM (1.9%), TP53 (1.3%), BRCA1 (1.2%), and EGFR (1.0%). Of 1,161 individuals, 712 (61.3%) had a PGV in a DDR/HRR gene, making them potentially eligible for a clinical treatment trial, and 1,104/1,161 (95.1%) had a PGV that was potentially clinically actionable. Conclusions: From this large cohort of individuals with lung cancer, 14.9% had PGVs, nearly all of which were clinically actionable. Notably, HRR PGVs were common (64%). Currently, the U.S. Food and Drug Administration has approved and the National Comprehensive Cancer Network Guidelines endorse targeted therapies for patients with breast, pancreatic, prostate, and ovarian cancers who carry HRR PGVs. Recently, the NCCN Guidelines panel recommended germline testing be considered for all patients diagnosed with colorectal cancer. Given the profound implications for both patients and their families that result from identifying PGVs, our results suggest that all patients with lung cancer also be considered for germline genetic testing.
Factors Associated With Image-Guided Radiation Therapy Image Rejection in a Multisite Institution
Authors: Rooney Michael K. , Traube Blake , Khan Mohammed , Kumar Rachit , Walker Gary V.
Published: August 2022

PURPOSE:

Nonclinical factors and cognitive biases have been shown to significantly affect clinical decision making. In this study, we aimed to identify clinical and environmental factors that might influence the decision to approve or reject image-guided radiation therapy (IGRT) images in a large multisite institution.

METHODS:

We identified all IGRT image approval and rejection decisions recorded within an electronic imaging system from July 1, 2016, to June 30, 2018. For each decision, we tabulated the following parameters: the attending physician of the patient, the physician reviewing the image, total images reviewed by the physician that day, time of day, day of week, treatment site, and imaging modality (kilovoltage or cone beam computed tomography [CBCT]). We created a binary multivariable logistic regression model to identify factors associated with IGRT image rejection.

RESULTS:

Overall, of 51,797 total image records evaluated, 881 (1.70%) were rejected and 50,916 (98.30%) were approved. Univariable analysis revealed that images reviewed by physicians with high rejection rates (odds ratio [OR], 3.16; P < .001) and by physicians reviewing fewer IGRT images (OR, 0.99; P = .024), images from various anatomic sites (particularly skin, breast, and head and neck), and CBCT imaging compared with kilovoltage imaging (OR, 1.49; P < .001) were associated with the increased rate of rejection. On multivariable analysis, images reviewed by physicians with high rejection rates (OR, 3.28; P < .001), images from specific anatomic sites including breast ( P < .001), and CBCT imaging ( P < .001) persisted as independent predictors of image rejection.

CONCLUSION:

These data provide important insight into the clinical, cognitive, and environmental factors that might influence the routine clinical decision of IGRT image approval. Recognition of these factors may not only improve the quality of individual decisions but also identify opportunities for systems-based quality improvement in IGRT.
Meeting report – Cell dynamics: host–pathogen interface
Authors: Odendall Charlotte , Sa Pessoa Joana , Mesquita Francisco S.
Published: August 2022

Two years into the most significant infectious disease event of our generation, infections have populated every conversation and in-depth understanding of host–pathogen interactions has, perhaps, never been more important. In a successful return to in-person conferences, the host–pathogen interface was the focus of the third Cell Dynamics meeting, which took place at the glorious Wotton House in Surrey, UK. The meeting organised by Michaela Gack, Maximiliano Gutierrez, Dominique Soldati-Favre and Michael Way gathered an international group of scientists who shared their recent discoveries and views on numerous aspects, including cell-autonomous defence mechanisms, pathogen interactions with host cytoskeletal or membrane dynamics, and cellular immune regulation. More than 30 years into the beginning of cellular microbiology as a field, the meeting exhibited the unique aspect of the host–pathogen interface in uncovering the fundamentals of both pathogens and their hosts.
Σύνθεση και μελέτη βιοδραστικών ενώσεων με φασματομετρία μάζας υψηλής διακριτικής ικανότητας
Authors: Μαντζουράνη Χριστιάνα
Published: August 2022

Οι αποακετυλάσες των ιστονών (HDACs) είναι ένζυμα που καταλύουν την υδρόλυση των πλευρικών αλυσίδων ακέτυλο L-λυσίνης, μια διαδικασία που είναι απαραίτητη για την κυτταρική μεταγραφή. Σχετίζονται με παθολογικές καταστάσεις όπως ο καρκίνος και αποτελούν ελκυστικό στόχο για την ανακάλυψη αντικαρκινικών φαρμάκων. Τα υδροξαμικά οξέα και τα βενζαμίδια αποτελούν δύο ενδιαφέρουσες κατηγορίες ενώσεων που στοχεύουν τις HDACs και μάλιστα τέτοιες ενώσεις, με χαρακτηριστικό παράδειγμα το vorinostat, είναι εγκεκριμένα φάρμακα για τη θεραπεία κακοηθειών ή βρίσκονται υπό κλινικές δοκιμές. Στην παρούσα εργασία, πραγματοποιήθηκε η σύνθεση υδροξαμικών οξέων και ενός βενζαμιδίου, αναλόγων του vorinostat, που φέρουν ομάδα βενζοξαζολίου. Aκόμη, συντέθηκε ένα υδροξαμικό οξύ βασισμένο σε 4-αμινοβενζοϊκό οξύ και L-φαινυλαλανίνη και ένα βενζαμίδιο βασισμένο σε δ-L-νορλευκίνη. Στη συνέχεια, πραγματοποιήθηκε η in vitro μελέτη της βιολογικής δράσης των ενώσεων που συντέθηκαν, έναντι τριών καρκινικών σειρών (Α549, SF268, Caco-2) με τη μέθοδο ΜΤΤ. Επίσης, στις ίδιες καρκινικές σειρές, εξετάστηκαν και μια σειρά βενζαμιδικών αναλόγων καθώς και μια σειρά κορεσμένων υδρόξυ και όξο λιπαρών οξέων που είχαν συντεθεί στο εργαστήριό μας, προκειμένου να μελετηθεί η σχέση δομής-δράσης τους. Ακόμη, με χρήση ενός καινοτόμου φωτοχημικού πρωτοκόλλου σύνθεσης υδροξαμικών οξέων υποβοηθούμενου από υπεριώδες ή ορατό φως, συντέθηκε το φάρμακο bufexamac, ενώ παράλληλα, έγινε μελέτη και βελτιστοποίηση των συνθηκών της αντίδρασης, καθώς και διερεύνηση του μηχανισμού, με χρήση φασματομετρίας μάζας υψηλής διακριτικής ικανότητας (HRMS). Έχοντας μελετήσει τη βιολογική δράση των κορεσμένων υδρόξυ λιπαρών οξέων, αυτά μαζί με μια σειρά από συνήθη λιπαρά οξέα, χρησιμοποιήθηκαν ως ενώσεις αναφοράς για τον ποιοτικό και ποσοτικό τους προσδιορισμό σε δείγματα γάλακτος και γιαουρτιού με τη χρήση LC-HRMS. Τέλος, πραγματοποιήθηκε μελέτη για την παραγωγοποίηση λιπαρών οξέων μικρού μήκους, αρχικά με 4- και 3-νιτροφαινυλυδραζίνη και ακολούθησε ο σχεδιασμός και σύνθεση μιας νέας αμίνης (πρωτοταγής αμίνη βασισμένη σε 8-υδρόξυ κινολίνη) με σκοπό την αναστροφή του φορτίου τους σε προσδιορισμό φασματομετρίας μάζας.