bluuebunny/crossref_metadata_2025 huggingface dataset:
Door to balloon time in primary percutaneous coronary intervention in ST elevation myocardial infarction: every minute counts
Authors: Marcusohn Erez , Reiner Benaim Anat , Ronen Shay , Kerner Arthur , Beyar Rafael , Almog Ronit
Published: July 2022

Objectives

This study examines relationships between door to balloon (D2B) time and subsequent admissions due to heart failure (HF), acute coronary syndrome (ACS), and mortality for up to 1 year.

Background

Current guidelines set 90-min for D2B time for primary percutaneous coronary intervention (PPCI) as a goal, which has been shown to reduce mortality and adverse events.

Methods

Using the MDclone ADAMS system integrated with our electronic medical records, we conducted retrospective analysis of all patients admitted due to ST-elevation myocardial infarction from home, without any history of HF or coronary disease, and who underwent PPCI during 2013–2019. Data on D2B time, baseline clinical and demographic characteristics, and outcomes of HF, ACS and mortality were collected. Adjusted HR for each of the outcomes was calculated by multivariate Cox model.

Results

A total of 826 patients were included in the final analysis. D2B had no significant effect on incidence of heart failure admissions for up to 1-year follow-up. D2B had a significant effect on mortality at 180 days, showing a 30% increase for each 30-min increase (HR 1.308; CI, 1.046–1.635) as for ACS at 90 days (HR 1.307; 1.025–1.638). The 30-min D2B cutoff showed a significant increase in ACS recurrence throughout the follow-up period at 90 days (HR 2.871, 1.239–6.648), 180 days (HR 2.607, 1.255–5.413), and 1 year (HR 1.886, 1.073–3.317).

Conclusions

Patients with shorter D2B times had significantly reduced mortality and recurrence of ACS, with no effect on heart failure admission incidence.
Bulking agents in gastrointestinal endoscopy: present applications and future advances
Authors: Steinway Steven N. , Singh Anmol , Akshintala Venkata S.
Published: July 2022

Purpose of the review

Bulking agents are inert materials injected into an organ to affect the physical properties of the organ for a therapeutic purpose. Various agents have been developed to aid in the treatment of diseases like gastroesophageal reflux disease (GERD), fecal incontinence, obesity, malignancy, hemostasis, and tissue dissection. Here, we review the state of the art in bulking agents in gastrointestinal endoscopy, past failures, current limitations, and where we see the field heading in the future.

Recent findings

Though bulking agents have been trialed for various different gastrointestinal diseases, there are currently limited uses in gastrointestinal endoscopy. Though various agents have been trialed for GERD, numerous complications and adverse events have limited its current use. However, for the treatment of fecal incontinence endoscopic bulking agent therapy is a reasonable option. Though in early stages of exploration, bulking agent therapy for enteric protection from radiotherapy may be a promising tool to improve treatment of pancreatic cancer. Bulking agents for tissue dissection have substantially improved lifting agents and complex polyp removal. Bulking agent therapy has not really been explored for endoscopic bariatric therapy or hemostasis but may be a fruitful area for exploration in the future.

Bulking agent therapy has been trialed for various gastrointestinal diseases with mixed success. There is currently a therapeutic roll in the endoscopic management of fecal incontinence and tissue dissection. A future role in the treatment of GERD, obesity, malignancy, and hemostasis seem feasible.
The Impact of COVID-19 on Family Caregivers of Individuals With End-Stage Heart Failure
Authors: Cross Lisa A. , Koren Ainat , Dowling Jacqueline S. , Gonzales Joseph E.
Published: July 2022

Before the COVID-19 pandemic, family caregivers were providing a tremendous amount of care for family members with heart failure with the prevalence of caregiver reliance in heart failure expected to increase in the United States. Social distancing and other restrictions during the COVID-19 pandemic may have added further challenges to caregiving routines. The purpose of this study was to examine the family caregiver perception of the effect of COVID-19 on caregiving routines. To determine caregiver perception of COVID-19's impact, 1 Likert question and 1 open-ended response were asked. Braun and Clark's method guided open-ended response thematic analysis. The 113 replies to the open-response question yielded themes such as social isolation, added fear, anxiety, or worry, changed appointments, wearing masks, and living status change. Social isolation (41.6%) was the most common theme; the most significant theme was living status change (P = .003), and family caregivers reported that the pandemic affected their routines either negatively or somewhat negatively (62.1%). Family caregivers are affected during times of crisis. Research and policies that recognize the residual effects of COVID-19 on caregiving practices and support care transitions for family caregivers in the heart failure population are needed.
Parents' Needs and Their Perceived Obstacles With Team Members in Perinatal Palliative Care
Authors: Yasar Beril Nisa , Terzioglu Fusun
Published: July 2022

Advances in prenatal diagnosis have made medical, psychological, and ethical issues regarding the diagnosis of fetal anomalies a crucial topic of research. This study identified the needs of parents of unborn babies with fetal anomalies and their views regarding the services of interdisciplinary team members in charge of assisting them. The sample consisted of 30 parents and 40 team members from a women's health education and research hospital. Data were collected through face-to-face interviews and were qualitatively analyzed using the phenomenological method of interpretation. The results showed that parents' physical, psychological, social, and spiritual needs during pregnancy, childbirth, and postpartum were not fully met after their unborn babies were diagnosed with fetal anomalies. The results also showed that team members needed a structured program, legal regulations, and training to provide holistic care.
The Relevance of Airway Resistance in Children Requiring Mechanical Ventilatory Support
Authors: Bruno Francisco , Andreolio Cinara , Garcia Pedro Celiny R. , Piva Jefferson
Published: July 2022

Objectives:

To describe pulmonary resistance in children undergoing invasive mechanical ventilation (MV) for different causes.

Design:

A cross-sectional study.

Setting:

Two PICUs in the South region of Brazil.

Patients:

Children 1 month to 15 years old undergoing MV for more than 24 hours were included. We recorded ventilator variables and measured pulmonary mechanics (inspiratory and expiratory resistance, auto positive end-expiratory pressure [PEEP], and dynamic and static compliance) in the first 48 hours of MV.

Interventions:

Measurements of the respiratory mechanics variables during neuromuscular blockade.

Measurements and Main Results:

A total of 113 children were included, 5 months (median [interquartile range (IQR) [2.0–21.5 mo]) old, and median (IQR) weight 6.5 kg (4.5–11.0 kg), with 60% male. Median (IQR) peak inspiratory pressure (PIP) was 30 cm H2O (26–35 cm H2O), and median (IQR) PEEP was 5 cm H2O (5–7 cm H2O). The median (IQR) duration of MV was 7 days (5–9 d), and mortality was nine of 113 (8%). The median (IQR) inspiratory and expiratory resistances were 94.0 cm H2O/L/s (52.5–155.5 cm H2O/L/s) and 117 cm H2O/L/s (71–162 cm H2O/L/s), with negative association with weight and age (Spearman –0.850). When we assess weight, in smaller children (< 10 kg) had increased pulmonary resistance, with mean values over 100 mH2O/L/s, which were higher than larger children (p < 0.001).

Conclusions:

Increased pulmonary resistance is prevalent in the pediatric population undergoing invasive MV. Especially in children less than 1 year old, this variable should be considered when defining a ventilatory strategy.
Updated Diagnosis Grouping System for Pediatric Emergency Department Visits
Authors: Fant Colleen , Marin Jennifer R. , Ramgopal Sriram , Simon Norma-Jean E. , Richards Rachel , Olsen Cody S. , Alessandrini Evaline A. , Alpern Elizabeth R. ,   for the PECARN Registry Study Group
Published: July 2022

Objectives

This study aims to update the Diagnosis Grouping System (DGS) for International Classification of Disease, Tenth Revision (ICD-10) codes for ongoing use. The DGS was developed in 2010 using ICD-9 codes with 21 major groups and 27 subgroups to facilitate research on pediatric patients presenting to emergency departments and required updated classification for more recent ICD codes.

Methods

All emergency department discharges available in the Pediatric Emergency Care Applied Research Network (PECARN) database for 2016 were included to identify ICD-10 codes. These codes were then mapped onto the DGS codes originally derived from ICD-9. We used ICD-10 codes from the PECARN database from 2017 to 2019 to confirm validity.

Results

The DGS was updated with ICD-10 codes based on 2016 PECARN data, and this updated DGS was successfully applied to 6,853,479 (97.3%) of all codes from 2017 to 2019.

Discussion

Using ICD-10 codes from the PECARN Registry, the DGS was updated to reflect ICD-10 codes to facilitate ongoing research.
Rehabilitation interventions for improving balance in Parkinson’s disease: a narrative review
Authors: Lena Francesco , Modugno Nicola , Greco Giulio , Torre Monica , Cesarano Simone , Santilli Marco , Abdullahi Auwal , Giovannico Giuseppe , Etoom Mohammad
Published: July 2022

Introduction

Postural instability (PI) is one of the latest clinical manifestations of Parkinson's disease (PD). Due to the limited therapeutic effect of pharmacological therapies, a favorable consideration has now become towards rehabilitation interventions. Thus, this study aimed to synthesize literature evidence to summarize the effects of rehabilitation interventions for improving balance in PD.

Materials and methods

We conducted a narrative review of randomized-controlled clinical trials (RCTs) comparing the effects of interventions, control interventions, and no interventions on balance-related outcomes. A comprehensive search using the MEDLINE database was conducted from January 2000 to September 2021. This review included the following causes of balance-related impairments: inability to control body weight in the base of support, impaired attention and focus on balance, postural deformities, proprioceptive deficiency, sensory-motor integration, and coordination disorders, including visual and auditory-motor coordination.

Results

20 RCTs were included in the review. Various balance-related outcomes were included. The included studies focused on the effectiveness of different rehabilitation interventions, including physical therapy, virtual reality and telerehabilitation, treadmill training, hydrotherapy, action observation training, balance and cues-training interventions, and cognitive rehabilitation.

Conclusions

The results suggest that most of the included rehabilitation interventions have promising therapeutic effects in improving balance in PD.
Current State of Cell Therapies for Genitourinary Malignancies
Authors: Alkhouli Mohammed A. , Bazargan Sarah , Pilon-Thomas Shari , Poch Michael , Chahoud Jad
Published: July 2022

Genitourinary (GU) cancers have greatly benefited from immunotherapy treatments, such as immune checkpoint inhibitors. However, the durable clinical response rate for these agents remains relatively low, calling for more innovative immunotherapy approaches. Adoptive cell therapy has shown a significant advancement in the treatment of cancer in recent years and represents a great potential for the treatment of GU cancers. This review summarizes the current advancements in cellular therapy strategies for the treatment of renal cell carcinoma, bladder cancer, and prostate and penile cancers. Further, current and past clinical trials of adoptive cell therapy in GU tumors are reviewed. Finally, a perspective on the future of cell therapy in GU tumors is discussed.
Surgical Considerations for Tumor Tissue Procurement to Obtain Tumor-Infiltrating Lymphocytes for Adoptive Cell Therapy
Authors: Mullinax John E. , Egger Michael E. , McCarter Martin , Monk Bradley J. , Toloza Eric M. , Brousseau Susan , Jagasia Madan , Sarnaik Amod
Published: July 2022

Adoptive cell therapy with tumor-infiltrating lymphocytes (TILs), an investigational cellular therapy, has demonstrated antitumor efficacy in patients with advanced solid tumors, including melanoma. Tumor-infiltrating lymphocyte cell therapy involves surgical resection of a patient's tumor, ex vivo TIL expansion under conditions that overcome immunosuppressive responses elicited by the tumor and the tumor microenvironment, administration of a lymphodepleting regimen, and infusion of the final TIL cell therapy product back into the patient followed by interleukin 2 administration to support T-cell activity. The surgeon plays a central role in patient identification and tumor selection—steps that are critical for successful outcomes of TIL cell therapy. Commercialization of TIL cell therapy and its broader access to patients will require education and collaboration among surgeons, oncologists, and cellular therapists. This review highlights the unique role that surgeons will play in the implementation of TIL cell therapy and serves as a contemporary report of best practices for patient selection and tumor resection methods.
Current State of Cell Therapies for Gastrointestinal Cancers
Authors: Kooragayala Keshav , Lou Johanna , Hong Young Ki
Published: July 2022

Adoptive cell therapies include multiple cell-based therapies to harness the immune system's power to mount a robust anticancer effect. Early successes in solid tumors with checkpoint inhibition have increased the research and development of immunotherapy. The utilization of cell-based therapy for gastrointestinal malignancies is still in its infancy because of challenges of antigen specificity and access to the tumor microenvironment. In this review, we discuss the current state of adoptive cell therapies in terms of challenges and early successes in preclinical and clinical studies.
Patient Discomfort After Rhinoplasty With and Without Osteotomy Under Conscious Sedation
Authors: Kim Jung Soo , Heo Sung Jae
Published: July 2022

Objective:

Many rhinoplasty techniques, including dorsum augmentation and tip surgery, could be performed under conscious sedation rather than general anesthesia. However, as osteotomy is an invasive procedure, it is burdensome for surgeons to perform osteotomy under conscious sedation. As patient ratings of pain and satisfaction when osteotomy is performed under conscious sedation are unknown, this study aimed to determine discomfort of osteotomy performed under conscious sedation.

Methods:

Patients who underwent rhinoplasty with conscious sedation were prospectively included in the study. The patients were classified into an osteotomy and a nonosteotomy group. Questionnaires with a visual analog scale ranging from 0 to 10 were utilized to assess patient pain and satisfaction. Patients were also asked whether they would choose conscious sedation for future rhinoplasty operations. To evaluate adverse events, cardiopulmonary vital signs and nausea or vomiting were assessed.

Results:

Forty-five patients with a mean age of 32.7 years were included in the study. The mean patients’ visual analog scale scores for pain and satisfaction were 3.3±2.0 and 7.2±1.9, respectively. Most of the patients [42, (93%)] stated that they would choose conscious sedation again if they had further operations in the future. No significant adverse effects occurred, and there were no significant differences in patients’ ratings of pain and satisfaction between osteotomy and nonosteotomy groups when conscious sedation was used.

Conclusion:

Patients’ ratings of pain and satisfaction, and a lack of significant adverse effects, indicated that rhinoplasty can be performed under conscious sedation, even with osteotomy.
Furlow Palatoplasty and Tonsillectomy for Treating Patients With Submucous Cleft Palate and Tonsillar Hypertrophy: A One-Stage Procedure
Authors: Abdel-Aziz Mosaad , Abdel-Fattah Gamal , Abdel-Aziz Nada M. , Sabry Omar , Elsherbeeny Motaz
Published: July 2022

Background:

Children with cleft palate are more liable to have obstructive sleep apnea than children with normal palate due to narrow airways. Tonsillar hypertrophy is a common cause of pediatric obstructive sleep apnea; hence, it is not surprising to be encountered during cleft palate repair. The aim of this study was to evaluate the feasibility of tonsillectomy and Furlow palatoplasty performed as a 1-stage operation in patients presenting with submucous cleft palate (SMCP) and tonsillar hypertrophy.

Materials and Methods:

Eleven pediatric patients with SMCP and hypertrophied tonsils were included in this case series study. Furlow palatoplasty and tonsillectomy were performed for the patients in 1 sitting. The evaluation of velopharyngeal function was done preoperatively and postoperatively via auditory-perceptual-assessment, nasometry, and flexible nasopharyngoscopy. In addition, the Epworth sleepiness scale for children/adolescents was administered to the parents to assess daytime sleepiness of their children.

Results:

The speech improved postoperatively. Auditory-perceptual-assessment showed significant reductions in hypernasal speech, nasal air escape, and weak pressure consonants. In addition, nasometry revealed significantly decreased nasalance scores for nasal and oral sentences. A postoperative increased velar movement was observed with a significant improvement in velopharyngeal closure. The preoperative Epworth sleepiness scale for children/adolescents assessment revealed excessive daytime sleepiness in 8 patients, with significant improvement of scores postoperatively.

Conclusions:

Removal of hypertrophied tonsils during the repair of SMCP with Furlow palatoplasty did not negatively affect speech outcome or velar movement postoperatively. It is logical to perform both procedures simultaneously in 1 sitting to avoid postoperative sleep-related breathing disorder, which may necessitate a second stage operation.
Maxillofacial Fractures in the Province of Terni (Umbria, Italy) in the Last 11 Years: Impact of COVID-19 Pandemic
Authors: Spallaccia Fabrizio , Vellone Valentino , Colangeli Walter , De Tomaso Silvia
Published: July 2022

The main purpose of this retrospective study is to analyze the main causes and the main anatomical structures involved in maxillofacial traumas in the province of Terni, Umbria. From January 2009 to July 2021, 603 patients were admitted with a maxillofacial trauma diagnosis and underwent surgery at “Santa Maria Hospital” in Terni, Italy. The collected data included sex, age, nationality, cause of trauma, type of fractures, comorbidities, clinical signs, symptoms, date of admission, and date of discharge from the hospital. Causes were divided into 5 categories: road traffic accidents, accidental falls, physical assault, sport accidents, and occupational injuries. Men were more involved than women, with a male:female ratio of 325:1. The mean age of the population was 41.7 years. The main cause of trauma were road traffic accidents (36%), followed by accidental falls (27%), an increasing phenomenon during the current SARS-CoV-2 global pandemic. The orbital floor was the most fractured anatomical site, followed by zygoma and nasal bones.
A Combination Method of Costal Cartilage Injection Techniques for Augmentation Rhinoplasty
Authors: Gu Tianyi , Li Xin , Yang Xiaoning , Yu Lu , Ma Jiguang
Published: July 2022

Background:

The multiple toothpick-shaped costal cartilage (MTCC) injection technique was introduced as an improvement based on the free diced costal cartilage (FDCC) injection technique for augmentation rhinoplasty. However, radix irregularities may occur when using the MTCC technique. Considering that the FDCC grafts are easier to shape at the nasal radix, we adopted a combination method of the 2 techniques to achieve natural and smooth contour.

Methods:

Four patients accepted this method for augmentation rhinoplasty. Through a unilateral marginal incision, the costal cartilage grafts were injected for nasal augmentation at the subperiosteal plane. The FDCC grafts and the MTCC grafts were used for nasal radix and dorsum augmentation, respectively. Nasal contour was adjusted by external shaping. The follow-up ranged from 24 to 43 months.

Results:

All patients were satisfied with the surgical outcome. There were no major complications occurred during the follow-up. One patient underwent rasping revision due to her own beauty-appreciation changes.

Conclusions:

The combination method can take advantages of the FDCC and MTCC injection techniques. It can effectively lower the incidence of contour irregularities and graft displacement. Meanwhile, it is easy to perform without special procedure, and is time-saving and cartilage-saving.
Immediate Ear Lobule Reconstruction After Melanoma Resection
Authors: Bushong Elizabeth E. , Komorowska-Timek Ewa
Published: July 2022

Ear Lobule Reconstruction

Cancer removal from aesthetically vulnerable areas of the face strikes a delicate balance between oncologically appropriate excision and preservation of a unique structure. A 72-year-old male presented with melanoma of the right earlobe requiring complete excision. Partial or complete absence of an ear causes a deformity and is difficult to conceal. Thus, lobule reconstruction postmelanoma excision eliminates deformity and aids in psychological recovery. In this case report, we describe our novel technique of a 2-stage lobule reconstruction immediately after melanoma resection using a direct template of the excised lobule. This template allowed us to sculpt its identical size and shape using harvested contralateral conchal cartilage graft. After the cartilage was banked in a subcutaneous pocket for 8.5 weeks, the second stage liberated the reconstructed lobule. This immediate 2-stage technique eliminated a period of soft tissue contracture and presented a rare surgical opportunity to recreate a structure using its direct template.

Level of Evidence:

Level IV—case report.
Surgical Stress Evaluation of Left Lateral Sectionectomy Based on Skeletal Muscle Catabolism
Authors: Kawasaki Yota , Yamasaki Yoichi , Hozaka Yuto , Oi Hideyuki , Sonoda Tomohiro , Fukuda Kosuke , Idichi Tetsuya , Kurahara Hiroshi , Mataki Yuko , Ueno Shinichi , Ohtsuka Takao
Published: July 2022

Background:

By examining skeletal muscle catabolism, we aimed to investigate whether laparoscopic left lateral sectionectomy (LLS) is less invasive compared with the open approach.

Methods:

The psoas muscle index (PMI) was measured using computed tomography images before and after surgery. We assessed the relationship between the perioperative PMI reduction rate and the estimation of physiologic ability and surgical stress (E-PASS) score and then compared the PMI reduction rates associated with different approaches.

Results:

Of the 31 patients, 13 and 18 underwent the open and laparoscopic approaches, respectively. A strong correlation was observed between the PMI reduction rates and surgical stress scores (SSS) (r=0.561, P<0.01). The laparoscopic approach was associated with a significantly lower PMI reduction rate (P<0.01) and SSS (P<0.01) than the open approach.

Conclusion:

Laparoscopic LLS should be less invasive than the open approach from the perspective of not only perioperative outcomes but also skeletal muscle catabolism.
The Critical View of Safety in Laparoscopic Cholecystectomy: User Trends Among Residents and Consultants
Authors: Terho Petra , Sallinen Ville , Lampela Hanna , Harju Jukka , Koskenvuo Laura , Mentula Panu
Published: July 2022

Background:

The Critical View of Safety (CVS) aims at preventing bile duct injuries (BDIs) in laparoscopic cholecystectomy (LCC). This study investigated CVS utilization among surgeons.

Methods:

Photos from LCCs were scored for satisfactory CVS. Rates of satisfactory CVS, BDIs, and postoperative complications among residents and consultants were compared. A lecture on CVS was given halfway through the study.

Results:

The study comprised 1532 patients. Residents had higher rates of satisfactory CVS in elective LCCs compared with consultants (34.9% vs. 23.0%, P<0.001), but not in emergency LCCs (18.4% vs. 15.0%, P=0.252). No significant differences in BDIs or postoperative complications emerged between residents and consultants. After the lecture, elective LCCs were photographed more frequently (80.3% vs. 74.0%, P=0.032), but rates of satisfactory CVS, BDIs, and postoperative complications remained unchanged.

Conclusions:

Utilization of CVS can be affected by a single lecture but affecting rates of satisfactory CVS may require stronger interventions.
In-vitro differentiation of human embryonic stem cells into spinal cord neural stem cells
Authors: Chen Xueying , Zhao Tianyi , Ke Naiyu , Qian Yutong , Wang Wanrong , Liu Lihua , Liu Chao
Published: July 2022

In-vitro differentiation of human embryonic stem cells into spinal cord neural stem cells (NSCs) can help researchers better understand the cellular processes associated with spinal cord development and regeneration, and provide therapeutic strategies for spinal cord disorders. However, effective and consistent methods for the generation of human spinal cord NSCs are rare. Objective of the study is to establish methods for the in-vitro induction and long-term maintenance of human spinal cord NSCs. H9 cells were treated with neural induction medium for 10 days under single-cell seeding condition, followed by treatment with neural maintenance medium and replacement with NSC medium after five passages. The identity of the generated cells was determined by immunofluorescence, immunoblotting, and cleavage under targets and tagmentation (CUT&Tag) assays. After the neural induction, OCT4, an embryonic stem cell marker, was significantly reduced, whereas NESTIN and PAX6, two NSC markers, were clearly increased. After the neural maintenance, most of the H9-derived cells consistently expressed NESTIN and PAX6 together with SOX1 and HOXC9, two spinal cord markers. The Homer known motif enrichment results of the CUT&Tag assay confirmed the expression of HOXC9 in the H9-derived spinal cord NSCs, which can be maintained for more than 40 days under an in vitro culture system. This study sheds new light on effective induction and maintenance of human spinal cord NSCs.
Blast-related traumatic brain injury is mediated by the kynurenine pathway
Authors: Zhang Yu , Wang Lei , Ren Wenjie
Published: July 2022

Objectives

The overactivation of the kynurenine pathway, the major metabolic pathway of tryptophan, induced by inflammation and oxidative stress, might bring about excessive neurotoxic metabolites. This study aimed to investigate whether kynurenine pathway is overactivated in blast-related traumatic brain injury (bTBI) and whether inhibitors of kynureninase and kynurenine-3-monooxygenase (KMO), important enzymes in kynurenine pathway, could alleviate bTBI in rats.

Methods

A shock tube was used to establish the bTBI animal models. Pathological changes in the hippocampus were observed using Nissl, propidium iodide and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining. Immunohistochemistry was used to evaluate the expression levels of kynureninase and KMO. After the establishment of bTBI rat models, they were treated with KMO inhibitor (Ro 61-8048) and kynureninase inhibitor (benserazide hydrochloride), and the animals’ behavioral performance was assessed using an elevated plus maze (EPM).

Results

After blast exposure, the number of neurons decreased, whereas the expression of kynureninase and KMO increased in the CA1 area of the rat hippocampus. In vitro, KMO inhibitor (Ro) and kynureninase inhibitor (benserazide hydrochloride) intervention could reduce the proportion of TUNEL-positive neurons in the hippocampus. In vivo, after Ro treatment, the behavior of the bTBI rats was significantly improved, and more neurons survived in the hippocampus CA1 region; however, following benserazide hydrochloride treatment, the behavior of bTBI rats was not significantly improved, and neuron survival could not be improved in the hippocampal CA1 region.

Conclusion

The expression levels of KMO and kynureninase were increased in the hippocampus of the bTBI rats, suggesting that these factors might mediate the bTBI damage. Furthermore, the KMO inhibitor showed a significant protective effect on bTBI.
EEG coherence as a marker of Alzheimer’s disease
Authors: Radinskaia Dina , Radinski Crystal
Published: July 2022

Background

Progressive deterioration of synaptic plasticity and synaptic connectivity between neurons is a neurophysiological hallmark of brain ageing and has been linked to the severity of dementia. We hypothesized that if synaptic disconnection as the neuropathology of Alzheimer’s disease (AD) is responsible for the failure of the brain to integrate various regions into effective networks, then electroencephalographic evidence of the disruption of functional connectivity might be used to diagnose Alzheimer’s dementia. We proposed that changes in EEG coherence, a measure of functional interaction between the brain collaborating areas, can be detected in a clinical setting and serve as a marker of neuronal disconnection. Improving the accuracy and reducing the time needed to diagnose AD could allow timely interventions, treatments, and care cost reduction.

Methods

This study examined group differences in EEG coherence within global cortical networks at rest and during executive challenges among patients with AD, individuals with mild cognitive impairment, and healthy controls.

Results

Decreased EEG coherence has been discovered in cross-hemisphere frontal, temporal, parietal and occipital pairs in the AD group at rest and when challenged with tasks requiring comprehension, analysis, perceptual-motor response, and executive functioning. The most notable changes were detected in F3-F4 Beta with the visual-spatial task challenge, P7-P8 Beta during the writing task, T7-T8 Gamma during a task requiring speech understanding and O1-O2 Alpha during orientation in space task.

Conclusions

The study identified several potential EEG biomarkers of AD. More research is needed to identify sensitivity and specificity of the markers.
Antibiotic choice for Group B Streptococcus prophylaxis in mothers with documented penicillin allergies and associated newborn outcomes
Authors: Snider Josephine B. , Mithal Leena B. , Kwah Jason H. , Rhodes Nathaniel J. , Son Moeun
Published: July 2022

Objective

To evaluate intrapartum Group B Streptococcus (GBS) prophylaxis in women with documented penicillin allergy compared to women without penicillin allergy, and to investigate associated differences in neonatal outcomes.

Study Design

This retrospective cohort study included GBS positive pregnant women who had a vaginal delivery or cesarean section after trial of labor at >35 weeks of gestation at a high-volume urban hospital (2005-2018). Management of women who reported penicillin allergy was compared to women without a reported penicillin allergy. Maternal outcome was type of antibiotic administered for GBS prophylaxis (beta-lactam antibiotic prophylaxis defined as administration of penicillin, ampicillin, or cefazolin; alternative antibiotic prophylaxis defined as vancomycin or clindamycin). Neonatal outcomes included number of blood draws, antibiotic administration, neonatal intensive care unit (NICU) admission, and length of stay. Univariate analyses were performed.

Results

Of the 11,334 mother-neonate pairs meeting eligibility criteria, 1170 (10.3%) women had a documented penicillin allergy, and of these women 51 (4.4%) had a co-existing cephalosporin allergy. Among women with a reported penicillin allergy (n=1170), 49 (4.2%) received penicillin or ampicillin, 259 (22.1%) received cefazolin, 449 (38.4%) received clindamycin and 413 (35.3%) received vancomycin. Women with documented penicillin allergy were significantly more likely to receive alternative GBS prophylaxis compared to women without penicillin allergy (73.7% vs. 0.2%, p<0.01). Neonates of women who received alternative GBS prophylaxis had more lab draws compared to neonates of women who received beta-lactam antibiotic agents (20.8% vs. 17.3%, p<0.01).

Conclusion

Pregnant women with documented penicillin allergy received alternative antibiotics for GBS prophylaxis at a significantly higher frequency than women without a penicillin allergy. This was associated with an increased frequency of blood draws among neonates of mothers with penicillin allergy.
SARS-CoV-2 BA.5 vaccine breakthrough risk and severity compared with BA.2: a case-case and cohort study using Electronic Health Records in Portugal
Authors: Kislaya Irina , Casaca Pedro , Borges Vítor , Sousa Carlos , Ferreira Bibiana I. , Fernandes Eugénia , Dias Carlos Matias , Duarte Sílvia , Almeida José Pedro , Grenho Inês , Coelho Luís , Ferreira Rita , Ferreira Patrícia Pita , Isidro Joana , Pinto Miguel , Menezes Luís , Sobral Daniel , Nunes Alexandra , Santos Daniela , Gonçalves António Maia , Vieira Luís , Gomes João Paulo , Leite Pedro Pinto , Nunes Baltazar , Machado Ausenda , Peralta-Santos André
Published: July 2022

Background

In a context of multiple Omicron lineages circulation, it is relevant to clarify the effect of vaccination and previous infections on the risk of infection and severe post-infection outcomes.

Methods

Using electronic health records and SARS-CoV-2 laboratory surveillance data, we conducted a case-case and a cohort study covering the period of Omicron BA.2/BA.5 lineage replacement in Portugal, to compare vaccine effectiveness of complete primary and booster dose against infection, COVID-19 hospitalization, and mortality. Variant classification was performed through whole-genome sequencing (WGS) or Spike Gene Target Failure (SGTF).

Findings

Between April 25 and June 10, 2022, within a total of 27702 collected samples, 55.5% were classified as BA.2 and the remaining as BA.5. We observed no evidence of reduced vaccine effectiveness for the primary complete vaccination (OR=1.07, CI95%:0.93-1.23) or booster dose vaccination (OR=0.96, CI95%:0.84-1.09) against BA.5 infection compared with BA.2. The protection against reinfection was inferior in BA.5 cases when compared with BA.2 (OR=1.44; CI95%:1.30-1.60). Among those infected with BA.5, booster vaccination was associated with 77% and 88% of reduction in risk of COVID-19 hospitalization and death, respectively, while higher risk reduction was found for BA.2 cases, with 93% and 94%, respectively.

Interpretation

This study shows that the SARS-CoV-2 Omicron BA.5 lineage is associated with higher odds of reinfection compared with Omicron BA.2, regardless of the vaccination status.

Although less effective compared with BA.2, COVID-19 booster vaccination still offers substantial protection against severe outcomes following BA.5 infection.
Leveraging large-scale genetics of PTSD and cardiovascular disease demonstrates robust shared risk and improves risk prediction accuracy
Authors: Seligowski Antonia V. , Misganaw Burook , Duffy Lucie A. , Ressler Kerry J. , Guffanti Guia
Published: July 2022

Individuals with posttraumatic stress disorder (PTSD) are significantly more likely to be diagnosed with cardiovascular disease (CVD; e.g., myocardial infarction, stroke). The evidence for this link is so compelling that the National Institutes of Health convened a working group to determine gaps in the current literature, including the need for large-scale genomic studies to identify shared genetic risk. The current study used a large healthcare biobank dataset ofN= 36,412 individuals, combined with GWAS summary statistics from publicly available, large-scale PTSD and CVD studies. We found significant genetic correlations between PTSD and CVD (rG=0.24, S.E.= 0.05982,p=5.09E-05), and Mendelian randomization analyses indicated a potential causal link from PTSD to hypertension (β=0.20, S.E.= 0.04,p=5.97e-6), but not the reverse. PTSD summary statistics significantly predicted PTSD diagnostic status (R2=0.27%,p=5.31E-08), and this was significantly improved by incorporating summary statistics from CVD and major depressive disorder (R2=1.30%,p=2.16E-32). Further, pathway enrichment analyses indicated that genetic variants involved in shared PTSD-CVD risk included those involved in postsynaptic structure (p=0.00001), synapse organization (p=0.0001), and interleukin-7 (IL-7) mediated signaling pathways (p=0.0002). While additional research is needed to determine the clinical utility of these findings, these data further support the biological shared risk for stress-related disorders of mental health and cardiovascular illness.
Health impacts of COVID-19 disruptions to primary cervical screening by time since last screen: A model-based analysis for current and future disruptions
Authors: Burger Emily A. , de Kok Inge M.C.M. , O’Mahony James F , Rebolj Matejka , Jansen Erik E.L. , de Bondt Daniel D. , Killen James , Hanley Sharon J. , Castanon Alejandra , Kim Jane J. , Canfell Karen , Smith Megan A. , Regan Mary Caroline
Published: July 2022

Background

We evaluated how temporary disruptions to primary cervical cancer (CC) screening services may differentially impact women due to heterogeneity in their screening history and test modality.

Methods

We used three CC models to project the short- and long-term health impacts assuming an underlying primary screening frequency (i.e., 1, 3, 5, or 10 yearly) under three alternative COVID-19-related screening disruption scenarios (i.e., 1-, 2- or 5-year delay) versus no delay, in the context of both cytology-based and HPV-based screening.

Results

Models projected a relative increase in symptomatically-detected cancer cases during a 1-year delay period that was 38% higher (Policy1-Cervix), 80% higher (Harvard) and 170% higher (MISCAN-Cervix) for under-screened women whose last cytology screen was 5 years prior to the disruption period compared with guidelines-compliant women (i.e., last screen three years prior to disruption). Over a woman’s lifetime, temporary COVID-19-related delays had less impact on lifetime risk of developing CC than screening frequency and test modality; however, CC risks increased disproportionately the longer time had elapsed since a woman’s last screen at the time of the disruption. Excess risks for a given delay period were generally lower for HPV-based screeners than for cytology-based screeners

Conclusions

Our independent models predicted that the main drivers of CC risk were screening frequency and screening modality, and the overall impact of disruptions from the pandemic on CC outcomes may be small. However, screening disruptions disproportionately affect under-screened women, underpinning the importance of reaching such women as a critical area of focus, regardless of temporary disruptions.

Funding

This study was supported by funding from the National Cancer Institute (U01CA199334). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Megan A Smith receives salary support from the National Health and Medical Research Council, Australia (APP1159491) and Cancer Institute NSW (ECF181561). Matejka Rebolj is funded by Cancer Research UK (reference: C8162/A27047). James O’Mahony is funded by Ireland’s Health Research Board (EIA2017054). Karen Canfell receives salary support from the National Health and Medical Research Council, Australia (APP1194679). Emily A. Burger receives salary support from the Norwegian Cancer Society.
Integrated Machine Learning Approaches Highlight the Heterogeneity of Human Myeloid-Derived Suppressor Cells in Acute Sepsis
Authors: Bonavia Anthony S. , Samuelsen Abigail , Halstead E. Scott
Published: July 2022

Highly heterogeneous cell populations require multiple flow cytometric markers for appropriate phenotypic characterization. This exponentially increases the complexity of 2D scatter plot analysis and exacerbates human errors due to variations in manual gating of flow data. We describe a workflow involving the stepwise integration of several, newly available machine learning tools for the analysis of myeloid-derived suppressor cells (MDSCs) in septic and non-septic critical illness. Unsupervised clustering of flow cytometric data showed good correlation with, but significantly different numbers of, MDSCs as compared with the cell numbers obtained by manual gating. However, both quantification methods revealed a significant difference between numbers of PMN-MDSC at day 1 in healthy volunteers and critically ill patients having septic or non-septic illness. Numbers of PMN-MDSC obtained by machine learning positively correlated with 30 days hospital readmission following critical illness, whereas manual gating of this cell population distinguished between septic and non-septic critical illness. Neither gating strategy found a correlation between number of MDSCs and 30-day mortality or hospital length of stay.
A genome-wide association study of mammographic texture variation
Authors: Liu Yuxi , Chen Hongjie , Heine John , Lindstroem Sara , Turman Constance , Warner Erica T. , Winham Stacey J. , Vachon Celine M. , Tamimi Rulla M. , Kraft Peter , Jiang Xia
Published: July 2022

Background

Breast parenchymal texture features, including gray scale variation (V), capture the patterns of texture variation on a mammogram and are associated with breast cancer risk, independent of mammographic density (MD). However, our knowledge on the genetic basis of these texture features is limited.

Methods

We conducted a genome-wide association study of V in 7,040 European-ancestry women. Four V assessments representing different amounts of breast edge erosion and image resolutions were generated from digitized film mammograms. We used linear regression to test the single-nucleotide polymorphism (SNP)-phenotype associations adjusting for age, body mass index (BMI), MD phenotypes, and the top four genetic principal components. Multivariate phenotype association tests combining all four V assessments were performed. We further calculated genetic correlations and performed SNP-set tests of V with MD, breast cancer risk, and other breast cancer risk factors.

Results

We identified three genome-wide significant loci associated with V: rs138141444 (6q24.1) inECT2L, rs79670367 (8q24.22) inLINC01591, and rs113174754 (12q22) nearPGAM1P5. 6q24.1 and 8q24.22 have not previously been associated with MD phenotypes or breast cancer risk, whilst 12q22 is a known locus for both MD and breast cancer risk. Among known MD and breast cancer risk SNPs, we identified four variants that were associated with V at the Bonferroni-corrected thresholds accounting for the number of SNPs tested: rs335189 (5q23.2) inPRDM6, rs13256025 (8p21.2) inEBF2, rs11836164 (12p12.1) nearSSPN, and rs17817449 (16q12.2) inFTO. We observed significant genetic correlations between V and mammographic dense area (rg= 0.79,P= 5.91 × 10−5), percent density (rg= 0.73,P= 1.00 × 10−4), and adult BMI (rg= -0.36,P= 3.88 × 10−7). Additional significant relationships were observed for nondense area (z = -4.14,P= 3.42 × 10−5), estrogen receptor-positive breast cancer (z = 3.41,P= 6.41 × 10−4), and childhood body fatness (z = -4.91,P= 9.05 × 10−7) from the SNP-set tests.

Conclusions

These findings provide new insights into the genetic basis of mammographic texture variation and their associations with MD, breast cancer risk, and other breast cancer risk factors.
Determination of significant immunological timescales from mRNA-LNP-based vaccines in humans
Authors: Moyles Iain R. , Korosec Chapin S. , Heffernan Jane M.
Published: July 2022

A compartment model for an in-host liquid nanoparticle delivered mRNA vaccine is presented. Through non-dimensionalisation, five timescales are identified that dictate the lifetime of the vaccine in-host: decay of interferon gamma, antibody priming, autocatalytic growth, antibody peak and decay, and interleukin cessation. Through asymptotic analysis we are able to obtain semi-analytical solutions in each of the time regimes which allows us to predict maximal concentrations and better understand parameter dependence in the model. We compare our model to 22 data sets for the BNT162b2 and mRNA-1273 mRNA vaccines demonstrating good agreement. Using our analysis, we estimate the values for each of the five timescales in each data set and predict maximal concentrations of plasma B-cells, antibody, and interleukin. Through our comparison, we do not observe any discernible differences between vaccine candidates and sex. However, we do identify an age dependence, specifically that vaccine activation takes longer and that peak antibody occurs sooner in patients aged 55 and greater.
Glutamine synthetase mRNA releases sRNA from its 3’UTR to regulate carbon/nitrogen metabolic balance
Authors: Miyakoshi Masatoshi , Morita Teppei , Kobayashi Asaki , Berger Anna , Takahashi Hiroki , Gotoh Yasuhiro , Hayashi Tetsuya , Tanaka Kan
Published: July 2022

Glutamine synthetase is the key enzyme of nitrogen assimilation, which is encoded in the first cistron ofglnALGoperon and is induced under nitrogen limiting conditions through transcriptional activation by NtrBC inSalmonellaandE. coli. 2-oxoglutarate serves as the carbon skeleton of glutamate and glutamine, but how 2-oxoglutarate fluctuation is controlled in response to nitrogen availability remained unknown. We show that theglnAmRNA produces an Hfq-dependent GlnZ sRNA from its 3’ sUTR through RNase E-mediated cleavage. Through a base-pairing mechanism, GlnZ primarily regulatessucA, encoding the E1o component of 2-oxoglutarate dehydrogenase. In the cells grown on glutamine as the nitrogen source, the endogenous GlnZ represses the expression of SucA to redirect the carbon flow from the TCA cycle to the nitrogen assimilation pathway. This study also clarifies that the release of GlnZ sRNA from theglnAmRNA by RNase E is essential for the post-transcriptional regulation ofsucA, and thus the mRNA coordinates the two independent functions to balance the supply and demand of the fundamental metabolites.
Early pre-neural serotonin modulates balance of late monoamines and behavioral patterns in fish model system
Authors: Ivashkin Evgeny , Spulber Stefan , Zinovyev Andrei , Yoshitake Takashi , Yoshitake Shimako , Kharchenko Olga , Khabarova Marina Yu. , Theofilopoulos Spyridon , Kehr Jan , Arenas Ernest , Ceccatelli Sandra , Voronezhskaya Elena E. , Adameyko Igor
Published: July 2022

The presence of serotonergic system during early pre-neural development is enigmatic and conserved amongst all studied invertebrate and vertebrate animals. We took advantage of zebrafish model system to address what is the role of early serotonin before first neurons form. Unexpectedly, we experimentally revealed the existence of delayed developmental neurogenic and behavioral effects resulting from the manipulations of pre-neural (zygote, blastula and gastrula) serotonergic system. In particular, the delayed effects included differences in the synthesis of serotonin in early serotonergic neurons in the central nervous system as well as in behavioral alterations after habituation in zebrafish larvae. These effects appeared as highly specific and did not coincide with any major abnormalities. The same manipulations of the serotonergic system at neural developmental stages did not show such effects, which confirms that early effects of serotonergic system manipulation are not based on retained serotonin in embryonic cells. Accordingly, gene expression analysis demonstrated specific changes only in response to the elevation of early pre-neural serotonin, which included the delayed and pre-mature onsets of different gene expression programs. Taken together, our results introduce a novel function of early pre-neural serotonergic system in a vertebrate embryo – tuning and fine control of specific mechanisms at later neural developmental stages that result in a mild variation of a behavioral adaptive spectrum.