bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in the incidence, mortality and clinical outcomes in patients with ventricular septal rupture following an ST-elevation myocardial infarction
Authors: Hiltner Emily , Sandhaus Marc , Awasthi Ashish , Hakeem Abdul , Kassotis John , Takebe Manabu , Russo Mark , Sethi Ankur
Published: June 2024

Background

Despite improvements in outcomes of ST elevation myocardial infarction (STEMI), ventricular septal rupture (VSR) remains a known complication, carrying high mortality. The contemporary incidence, mortality, and management of post-STEMI VSR remains unclear.

Methods

The National Inpatient Sample database (2009–2020) was used to study trends in admissions and outcomes of post-STEMI VSR over time. Survey estimation commands were used to determine weighted national estimates.

Results

There were 2 315 186 ± 22 888 visits for STEMI with 0.194 ± 0.01% experiencing VSR during 2009–2020 in the USA. Patients with VSR were more often older, white, female, and presented with an anterior STEMI; there was no difference in the rates of fibrinolysis. In-hospital mortality was 73.6 ± 1.8%, but only 29.2 ± 1.9 and 10 ± 1.2% received surgical repair and transcatheter repair (TCR), respectively. TCR was associated with higher and surgical repair with lower mortality. Days to surgery were longer for those who survived (5.9 ± 2.75) compared with those who died (2.44 ± 1). In a multivariable analysis, surgical repair at greater than or equal to day 4 was associated with lower in-hospital mortality (odds ratio = 0.39, 95% confidence interval: 0.17–0.88).

Conclusion

Mortality in post-STEMI VSR remains high with no improvement over time. Most patients are managed conservatively, and the frequency of surgical repair has decreased, while TCR has increased over the study period. Despite design limitations and survival bias, surgical repair at greater than or equal to 4 days was associated with a lower mortality.
Orthopaedic Nurse Navigators and Total Joint Arthroplasty Preoperative Optimization
Authors: Kebeh Martha , Dlott Chloe C. , Tung Wei Shao , Wiznia Daniel H.
Published: June 2024

Mental health and housing status have the potential to impact total joint arthroplasty (TJA) outcomes and are common TJA eligibility criteria that prevent patients from receiving surgery. Our aim was to formulate recommendations for how nurse navigators can assist patients with managing mental health and housing concerns. Through discussions with nurse navigators and a literature search across two databases, we gathered information regarding the optimization of mental health and housing status among TJA patients. We observed a lack of standardized protocols for addressing these concerns and literature supporting an increased focus on mental health and housing status, indicating the potential for greater nurse navigator involvement in developing and implementing protocols. We recommend nurse navigators use screening tools to identify mental health and housing concerns and offer the suggested resources to support patients in an effort to improve postoperative outcomes and decrease surgical risks.
Nurse-Assisted Rehabilitation Protocols Following Anterior Cruciate Ligament Reconstruction
Authors: Yu Fang , Xiao Li-En , Wang Tao , Hu Yong , Xiao Jun
Published: June 2024

Despite significant advancements in surgical instruments and operation skills, short- and long-term outcomes following anterior cruciate ligament reconstruction (ACLR) remain unsatisfactory, as many patients fail to return to their pre-injury level of sports. Inadequate ACL rehabilitation is the primary cause of poor outcomes. Nurses have become a crucial element in the rehabilitation process. Although there is no consensus regarding the optimal post-operative rehabilitation protocols, restoring muscle strength and neuromuscular control are consistently the primary goals. This literature review presents nurse-assisted rehabilitation protocols aiming at improving muscle strength and neuromuscular control. The review discusses postoperative rehabilitation, including home-based and supervised rehabilitation, open and closed kinetic chain exercises, eccentric and concentric training, blood flow restriction training, and plyometric training. Each training protocol has its benefits and drawbacks, and should be used cautiously in specific stages of rehabilitation. Neuromuscular training, such as neuromuscular electrical stimulation, neuromuscular control exercises, and vibration therapy, is considered crucial in rehabilitation.
A Quality Initiative to Prioritize Enteral Feeding in Bronchiolitis
Authors: Beam Nicholas , Long Allison , Nicholson Adam , Jary Lauren , Veele Rebecca , Kalinowski Nicole , Phad Matthew , Hadley Andrea
Published: June 2024

Introduction:

Recent studies have identified enteral feeding as a safe alternative to intravenous fluid hydration for inpatients with bronchiolitis receiving respiratory support. Specifically, it can improve vital signs, shorten time on high-flow nasal cannula, and is associated with reduced length of stay. We aimed to increase the percentage of patients receiving enteral feeding on admission with mild-to-moderate bronchiolitis, including those on high-flow nasal cannula, from 83% to 95% within 6 months.

Methods:

A multidisciplinary quality improvement team identified key drivers preventing enteral feeding as lack of standardization, perception of aspiration risk, and lack of familiarity with feeding orders. PDSA cycles focused on developing and implementing a bronchiolitis clinical practice pathway with an embedded guideline and order set as decision support to prioritize enteral feeding. Additionally, educational sessions were provided for trainees and attendings who were impacted by this pathway.

Results:

Following interventions, initiation of enteral feeding increased (83%–96%). Additionally, intravenous line placement decreased (37%–12%) with a mirrored increase in nasogastric tube placement (4%–21%). This was associated with a shorter overall length of stay and no increased transfer rate to intensive care.

Conclusions:

Using quality improvement methodology to standardize enteral feeding and hydration increased the initiation rate of enteral feeding in patients admitted with bronchiolitis. These changes were seen immediately after the implementation of the clinical pathway and sustained throughout the bronchiolitis season.
Reducing Time from Pediatric Emergency Department Arrival to Dexamethasone Administration in Wheezing Patients
Authors: Kramer Andrew W. , Erlich Jessica , Yaphockun Karen , Roderick Daniel , Farkas Kristen , Bryl Amy W. , Pade Kathryn H.
Published: June 2024

Introduction:

Asthma exacerbations are common presentations to pediatric emergency departments. Standard treatment for moderate-to-severe exacerbations includes administration of oral corticosteroids concurrently with bronchodilators. Early administration of corticosteroids has been shown to decrease emergency department length of stay (LOS) and hospitalizations. Our SMART aim was to reduce the time from arrival to oral corticosteroids (dexamethasone) administration in pediatric patients ≥2 years of age with an initial Pediatric Asthma Severity Score >6 from 60 to 30 minutes within 6 months.

Methods:

We used the model for improvement with collaboration between ED physicians, nursing, pharmacy, and respiratory therapists. Interventions included nursing education, dosage rounding in the electronic medical record, supplying triage with 1-mg tablets and a pill crusher, updates to an asthma nursing order set and pertinent chief complaints triggering nurses to document a Pediatric Asthma Severity Score in the electronic medical record and use the order set. Our primary outcome measure was the time from arrival to dexamethasone administration. Secondary outcome measures included ED LOS for discharged patients and admission rate. We used statistical process control to analyze changes in measures over time.

Results:

From October 2021 to March 2022, the average time for dexamethasone administration decreased from 59 to 38 minutes. ED LOS for discharged asthma exacerbation patients rose with overall ED LOS for all patients during the study period. There was no change in the admission rate.

Conclusions:

Using quality improvement methodology, we successfully decreased the time from ED arrival to administration of dexamethasone in asthma exacerbation patients from 59 to 38 minutes over 10 months.
Quality Improvement in Neonatal Care: Successful Adoption of the Eat, Sleep, Console Protocol in a Rural Hospital Setting
Authors: Phyu Riley , Bird Charrell , Gupta Ashish
Published: June 2024

Introduction:

The United States faces a growing burden of neonatal opioid withdrawal syndrome in rural hospitals. Traditional treatments often extend hospital stays and medication use. The Eat, Sleep, and Console (ESC) approach offers a new management strategy but is challenging in resource-limited settings. This study aimed to apply ESC in rural hospitals to reduce neonatal intensive care unit admissions, decrease length of stay (LOS) to under 7 days, and lower medication use by more than 80% within a year.

Methods:

Our quality improvement initiative at rural hospitals implemented a multimodal approach for in utero opioid-exposed infants, involving staff education, electronic medical record updates, and nonpharmacological care strategies. Data from January 2020 to December 2023 assessed treatment impact, including pharmacotherapy need and hospital stay lengths, using statistical process control for analysis.

Results:

After ESC implementation, the percentage of opioid-exposed infants receiving pharmacological treatment significantly decreased from 60.7% to 7.9%. The average LOS was reduced from 14.5 days to 5.25 days. These improvements persisted for 24 months, with no readmissions within 30 days of discharge. This approach also reduced hospital charges by over $5 million, demonstrating its clinical and financial effectiveness.

Conclusions:

The multidisciplinary approach successfully implemented ESC in a resource-limited setting, significantly reducing both the LOS and medication exposure for opioid-exposed infants while also saving significant healthcare costs. This successful model has been adopted by at least four regional rural hospitals, thus broadening the program’s impact.
Developing a Sustainable Quality Improvement Program in an Academic Center: The Experience of an Adolescent Unit
Authors: McKnight Erin R. , Ebersole Ashley , Gallup James , Haamid Fareeda W.
Published: June 2024

Introduction:

Successful quality improvement (QI) efforts use a comprehensive, institutional QI framework and professional development, but literature describing implementing QI frameworks in Adolescent Medicine practices is sparse. We aimed to implement and increase the number of formally structured QI projects (primary aim) and the number of projects achieving a centerline (CL) shift (secondary aim) in our hospital’s Adolescent Medicine Clinic.

Methods:

We used formal QI methodology to improve health outcomes by increasing the number of faculty with formalized QI education, creating interdisciplinary QI teams, and improving staff motivation. QI education was mandatory for Adolescent Medicine fellows and pediatric residents and encouraged for faculty and staff. The Divisional QI leadership team attended monthly meetings to review key driver diagrams, run and control charts, and receive intervention updates. All providers and staff received monthly updates, and the Hospital Quality and Safety Committee received biannual updates. We used run charts to share progress with primary and secondary aims.

Results:

Since Q3 2014, the Adolescent Medicine team consistently achieved the primary aim of having 5 active projects in process, with 9 projects from Q1 2018–Q4 2020. For the secondary aim, a target of 50% of active QI projects attaining a sustained centerline shift was achieved in Q2 2018 and maintained in 16 of 20 quarters since.

Conclusions:

Clinicians can use QI methodology to improve health outcomes while facilitating professional development. For this initiative to succeed, institutional leadership must provide an infrastructure prioritizing meaningful QI involvement.
Healthcare Violence and the Potential Promises and Harms of Artificial Intelligence
Authors: Kavanagh Kevin T. , Pontus Christine , Cormier Lindsay E.
Published: June 2024

Currently, the healthcare workplace is one of the most dangerous in the United States. Over a 3-month period in 2022, two nurses were assaulted every hour. Artificial intelligence (AI) has the potential to prevent workplace violence by developing unique patient insights through accessing almost instantly a patient’s medical history, past institutional encounters, and possibly even their social media posts. De-escalating dialog can then be formulated, and hot-button topics avoided. AIs can also monitor patients in waiting areas for potential confrontational behavior.

Many have concerns implementing AIs in healthcare. AIs are not expected to be 100% accurate, their performance is not compared with a computer but instead measured against humans. However, AIs are outperforming humans in many tasks. They are especially adept at taking standardized examinations, such as Board Exams, the Uniform Bar Exam, and the SAT and Graduate Record Exam. AIs are also performing diagnosis. Initial reports found that newer models have been observed to equal or outperform physicians in diagnostic accuracy and in the conveyance of empathy.

In the area of interdiction, AI robots can both navigate and monitor for confrontational and illegal behavior. A human security agent would then be notified to resolve the situation. Our military is fielding autonomous AI robots to counter potential adversaries. For many, this new arms race has grave implications because of the potential of fielding this same security technology in healthcare and other civil settings.

The healthcare delivery sector must determine the future roles of AI in relationship to human workers. AIs should only be used to support a human employee. AIs should not be the primary caregiver and a single human should not be monitoring multiple AIs simultaneously. Similar to not being copyrightable, disinformation produced by AIs should not be afforded ‘free speech’ protections. Any increase in productivity of an AI will equate with a loss of jobs. We need to ask, If all business sectors utilize AIs, will there be enough paid workers for the purchasing of services and products to keep our economy and society a float?
Computed Tomography–Derived Extracellular Volume Fraction and Splenic Size for Liver Fibrosis Staging
Authors: Kutaiba Numan , Tran Anthony , Ashraf Saad , Con Danny , Lokan Julie , Goodwin Mark , Testro Adam , Egan Gary , Lim Ruth
Published: June 2024

Objective

Extracellular volume fraction (fECV) and liver and spleen size have been correlated with liver fibrosis stages and cirrhosis. The purpose of the current study was to determine the predictive value of fECV alone and in conjunction with measurement of liver and spleen size for severity of liver fibrosis.

Methods

This was a retrospective study of 95 subjects (65 with liver biopsy and 30 controls). Spearman rank correlation coefficient was used to assess correlation between radiological markers and fibrosis stage. Receiver operating characteristic analysis was performed to assess the discriminative ability of radiological markers for significant (F2+) and advanced (F3+) fibrosis and cirrhosis (F4), by reporting the area under the curve (AUC).

Results

The cohort had a mean age of 51.4 ± 14.4 years, and 52 were female (55%). There were 36, 5, 6, 9, and 39 in fibrosis stages F0, F1, F2, F3, and F4, respectively. Spleen volume alone showed the highest correlation (r = 0.552, P < 0.001) and AUCs of 0.823, 0.807, and 0.785 for identification of significant and advanced fibrosis and cirrhosis, respectively. Adding fECV to spleen length improved AUCs (0.764, 0.745, and 0.717 to 0.812, 0.781, and 0.738, respectively) compared with splenic length alone. However, adding fECV to spleen volume did not improve the AUCs for significant or advanced fibrosis or cirrhosis.

Conclusions

Spleen size (measured in length or volume) showed better correlation with liver fibrosis stages compared with fECV. The combination of fECV and spleen length had higher accuracy compared with fECV alone or spleen length alone.
68Ga-FAPI-RGD PET/CT Detected Skull Metastasis Better Than 18F-FDG in a Patient With Radioiodine-Refractory Differentiated Thyroid Cancer
Authors: Chen Yun , Zang Jie , Wu Zenan , Miao Weibing
Published: June 2024

A 60-year-old woman underwent resection of a right humeral tumor 1 year ago, and postoperative pathology indicated metastatic papillary thyroid cancer. She had her first 131I treatment after a total thyroidectomy. Subsequent whole-body imaging after 131I administration revealed 131I-avid metastases in the left parietal bone. These metastases were observed to be larger during her second 131I treatment, conducted 6 months later. Consequently, the patient was diagnosed with radioiodine-refractory differentiated thyroid cancer. 68Ga-FAPI-RGD PET/CT demonstrated higher tracer uptake and clearer lesion boundaries compared with 18F-FDG PET/CT. This suggests that 177Lu-FAPI-RGD could potentially serve as a treatment option for radioiodine-refractory differentiated thyroid cancer.
18F-FDG PET/CT in Pediatric ALK-Positive Histiocytosis With Isolated CNS Involvement
Authors: Singh Karan , London Kevin , Ryan Jessica , Wright Dale C. , Moghimi Ali
Published: June 2024

An 11-year-old girl presented with focal impaired awareness seizures. MRI brain demonstrated a T2 hyperintense cortical lesion in the left temporal lobe with surrounding vasogenic edema. 18F-FDG PET/CT was arranged to assess metabolic activity of the cerebral lesion, to screen the whole body for other metabolically active lesions, and to assist biopsy planning. The study demonstrated intensely increased FDG uptake within the left temporal lobe lesion without evidence of hypermetabolic lesions elsewhere on the whole-body acquisition. The brain lesion was excised, and histopathology and molecular testing were consistent with ALK-positive histiocytosis.
Multifocal Burkholderia cepacia Infection in Postrenal Transplantation Fever
Authors: Sonavane Sunita Nitin , Jamale Tukaram , Bose Sreyasi , Basu Sandip
Published: June 2024

Nosocomial Burkholderia cepacia infection in the clinical setting of postrenal transplantation pyrexia of unknown origin and the role of 18F-FDG PET/CT in treatment optimization in such situation is presented in this report. The consequence of fastidious infection by nosocomial colonizing organisms like B. cepacia can be catastrophic in immunocompromised postrenal transplant individuals causing severe urinary tract infection. In the presented case, following 2 weeks of IV antibiotics, the patient didn’t show clinical response, and FDG PET scan recognized multifocal infective sites early, likely representing immune reconstitution inflammatory syndrome and timely appropriate and optimal treatment salvaged the renal graft.
Comparison of 68Ga-DOTATATE PET/CT and 123I-MIBG SPECT/CT in the Imaging of Functional Pheochromocytoma in an Adolescent Patient With Von Hippel–Lindau Syndrome
Authors: Singh Karan , Sandler Gideon , Hahn Deirdre , Chung David KV
Published: June 2024

A 17-year-old boy with Von Hippel–Lindau syndrome presented with hypertension, raised plasma catecholamines, and MRI findings of a new pancreatic tail lesion and 2 stable right adrenal lesions concerning for functional neuroendocrine tumors. A 68Ga-DOTATATE PET/CT demonstrated intense tracer avidity within the pancreatic lesion with minimal uptake in the adrenal lesions. Conversely, a 123I-MIBG SPECT/CT study demonstrated high-grade tracer uptake within the adrenal lesions, with no significant uptake appreciated in the pancreatic lesion. The adrenal lesions were resected, and pathology was consistent with pheochromocytoma. Plasma catecholamines returned to within the normal range and hypertension resolved.
The Complementary Role of 68Ga-FAPI-04 PET/CT in a Case of Neuroblastoma
Authors: Guo Linlin , Shen Guohua
Published: June 2024

As a common and highly aggressive malignancy of childhood, more than half of neuroblastomas are metastatic at the time of presentation. Herein, we reported 68Ga-FAPI-04 and 18F-FDG PET/CT findings in a 13-year-old girl with undifferentiated neuroblastoma. FAPI PET/CT showed intense uptake in the bone and bone marrow metastases. The primary lesions presented with low FAPI uptake but moderate FDG uptake. Above findings suggested the potential of FAPI PET/CT in the imaging evaluation of neuroblastoma.
18F-FAPI-42 Versus 18F-FDG PET/MRI in a Case of Primary Peripheral T-Cell Lymphoma of the Skeletal Muscles
Authors: Ran Pengcheng , Li Cheng , Lv Jieqin , Liang Xiang , Dong Aisheng
Published: June 2024

Primary skeletal muscle lymphoma is rare. We describe 18F-FAPI-42 and 18F-FDG PET/MRI findings in a case of primary peripheral T-cell lymphoma of the skeletal muscles with brain involvement. The multiple skeletal muscle tumors and one larger cerebral tumor showed intense FDG uptake and mild to moderate FAPI uptake. FDG PET was superior to FAPI PET in delineating the muscle tumors because of significantly higher FDG uptake of the muscle tumors than FAPI uptake. FAPI PET was superior to FDG PET in delineating the cerebral lesion because of a very low background FAPI activity in the brain parenchyma.
Postoperative Outcomes Among Patients Undergoing Cancer Surgery
Authors: Khan Muhammad M. M. , Munir Muhammad M. , Woldesenbet Selamawit , Khalil Mujtaba , Endo Yutaka , Katayama Erryk , Tsilimigras Diamantis , Rashid Zayed , Altaf Abdullah , Dillhoff Mary , Tsai Susan , Pawlik Timothy M.
Published: June 2024

Objective:

We sought to characterize postoperative outcomes among patients who underwent an oncologic operation relative to whether the treating surgeon was an international medical graduate (IMG) versus a United States medical graduate (USMG).

Background:

IMGs comprise approximately one quarter of the physician workforce in the United States.

Methods:

The 100% Medicare Standard Analytic Files were utilized to extract data on patients with breast, lung, hepato-pancreato-biliary (HPB), and colorectal cancer who underwent surgical resection between 2014 and 2020. Entropy balancing and multivariable regression analysis were performed to evaluate the association between postoperative outcomes among USMG and IMG surgeons.

Results:

Among 285,930 beneficiaries, 242,914 (85.0%) and 43,016 (15.0%) underwent surgery by a USMG or IMG surgeon, respectively. Overall, 129,576 (45.3%) individuals were male, and 168,848 (59.1%) patients had a Charlson Comorbidity Index score >2. Notably, IMG surgeons were more likely to care for racial/ethnic minority patients (14.7% vs 12.5%) and individuals with a high social vulnerability index (33.3% vs 32.1%) (all P<0.001). On multivariable analysis after entropy balancing, patients treated by an IMG surgeon were less likely to experience adverse postoperative outcomes, including 90-day readmission [odds ratio (OR) 0.89, 95% CI: 0.80–0.99] and index complications (OR: 0.84, 95% CI: 0.74–0.95) versus USMG surgeons (all P<0.05). Patients treated by IMG versus USMG surgeons had no difference in likelihood to achieve a textbook outcome (OR: 1.10, 95% CI: 0.99–1.21; P=0.077).

Conclusions:

Postoperative outcomes among patients treated by IMG surgeons were roughly equivalent to those of USMG surgeons. In addition, IMG surgeons were more likely to care for patients with multiple comorbidities and individuals from vulnerable communities.
MYH7 R453C induced cardiac remodelling via activating TGF-β/Smad2/3, ERK1/2 and Nox4/ROS/NF-κB signalling pathways
Authors: Wang Lingyu , Li Linquan , Zhao Dazhong , Yuan Hongming , Zhang Huanyu , Chen Jiahuan , Pang Daxin , Lu Yi , Ouyang Hongsheng
Published: June 2024

Hypertrophic cardiomyopathy (HCM) is a monogenic cardiac disorder commonly induced by sarcomere gene mutations. However, the mechanism for HCM is not well defined. Here, we generated transgenic MYH7 R453C and MYH6 R453C piglets and found both developed typical cardiac hypertrophy. Unexpectedly, we found serious fibrosis and cardiomyocyte loss in the ventricular of MYH7 R453C, not MYH6 R453C piglets, similar to HCM patients. Then, RNA-seq analysis and western blotting identified the activation of ERK1/2 and PI3K-Akt pathways in MYH7 R453C. Moreover, we observed an increased expression of fetal genes and an excess of reactive oxygen species (ROS) in MYH7 R453C piglet models, which was produced by Nox4 and subsequently induced inflammatory response. Additionally, the phosphorylation levels of Smad2/3, ERK1/2 and NF-kB p65 proteins were elevated in cardiomyocytes with the MYH7 R453C mutation. Furthermore, epigallocatechin gallate, a natural bioactive compound, could be used as a drug to reduce cell death by adjusting significant downregulation of the protein expression of Bax and upregulated Bcl-2 levels in the H9C2 models with MYH7 R453C mutation. In conclusion, our study illustrated that TGF-β/Smad2/3, ERK1/2 and Nox4/ROS pathways have synergistic effects on cardiac remodelling and inflammation in MYH7 R453C mutation.
Kinetoplastid kinetochore proteins KKT14–KKT15 are divergent Bub1/BubR1–Bub3 proteins
Authors: Ballmer Daniel , Carter William , van Hooff Jolien J. E. , Tromer Eelco C. , Ishii Midori , Ludzia Patryk , Akiyoshi Bungo
Published: June 2024

Faithful transmission of genetic material is crucial for the survival of all organisms. In many eukaryotes, a feedback control mechanism called the spindle checkpoint ensures chromosome segregation fidelity by delaying cell cycle progression until all chromosomes achieve proper attachment to the mitotic spindle. Kinetochores are the macromolecular complexes that act as the interface between chromosomes and spindle microtubules. While most eukaryotes have canonical kinetochore proteins that are widely conserved, kinetoplastids such asTrypanosoma bruceihave a seemingly unique set of kinetochore proteins including KKT1–25. It remains poorly understood how kinetoplastids regulate cell cycle progression or ensure chromosome segregation fidelity. Here, we report a crystal structure of the C-terminal domain of KKT14 fromApiculatamorpha spiralisand uncover that it is a pseudokinase. Its structure is most similar to the kinase domain of a spindle checkpoint protein Bub1. In addition, KKT14 has a putative ABBA motif that is present in Bub1 and its paralogue BubR1. We also find that the N-terminal part of KKT14 interacts with KKT15, whose WD40 repeat beta-propeller is phylogenetically closely related to a direct interactor of Bub1/BubR1 called Bub3. Our findings indicate that KKT14–KKT15 are divergent orthologues of Bub1/BubR1–Bub3, which promote accurate chromosome segregation in trypanosomes.
Beyond amyloid and tau: rethinking Alzheimer’s disease through less explored avenues
Authors: Gyimesi M. , Okolicsanyi R. K. , Haupt L. M.
Published: June 2024

Neurodegenerative diseases, particularly Alzheimer’s disease (AD), pose a significant challenge in ageing populations. Our current understanding indicates that the onset of toxic amyloid and tau protein pathologies initiates disease progression. However, existing treatments targeting these hallmark symptoms offer symptomatic relief without halting disease advancement. This review offers an alternative perspective on AD, centring on impaired adult hippocampal neurogenesis (AHN) as a potential early aetiological factor. By delving into the intricate molecular events during the initial stages of AD (Braak Stages I–III), a novel hypothesis is presented, interweaving the roles of Notch signalling and heparan sulfate proteoglycans (HSPGs) in compromised AHN. While acknowledging the significance of the amyloid and tau hypotheses, it calls for further exploration beyond these paradigms, suggesting the potential of altered HS sulfation patterns in AD initiation. Future directions propose more detailed investigations into early HS aggregation, aberrant sulfation patterns and examination of their temporal relationship with tau hyperphosphorylation. In challenging the conventional ‘triggers’ of AD and urging their reconsideration as symptoms, this review advocates an alternative approach to understanding this disease, offering new avenues of investigation into the intricacies of AD pathogenesis.
Gut microbial metabolite imidazole propionate impairs endothelial cell function and promotes the development of atherosclerosis
Authors: Nageswaran Vanasa , Carreras Alba , Reinshagen Leander , Beck Katharina R. , Steinfeldt Jakob , Ståhlman Marcus , Ramezani Rad Pegah , Lim Joseph , Strässler Elisabeth T. , Verhaar Barbara , Döring Yvonne , Weber Christian , König Maximilian , Steinhagen-Thiessen Elisabeth , Demuth Ilja , Kränkel Nicolle , Leistner David M. , Nieuwdorp Max , Knaus Petra , Ferrell Marc , Potente Michael , Hazen Stanley L. , Landmesser Ulf , Bäckhed Fredrik , Haghikia Arash
Published: June 2024

Background

The microbially generated amino acid-derived metabolite imidazole propionate (ImP) contributes to the pathogenesis of type 2 diabetes. However, the effect of ImP on endothelial cell physiology and its role in atherosclerotic coronary artery disease (CAD) is unknown. Using both human and animal model studies, we investigated the potential contributory role of ImP in the development of atherosclerosis.

Methods

Plasma levels of ImP were measured in patients undergoing elective cardiac angiography (n = 831) by means of ultra high-performance liquid chromatography coupled to tandem mass spectrometry. Odds ratios (ORs) and corresponding 95% confidence intervals for CAD were calculated based on the ImP quartiles using both univariable and multivariable logistic regression models. Atheroprone apolipoprotein E-/-(Apoe-/-) mice fed a high-fat diet were additionally treated with ImP (800 µg) or vehicle and aortic atherosclerotic lesion area was evaluated after 12 weeks. In a mouse model of carotid artery injury, the effect of ImP on vascular regeneration was examined. Using human aortic endothelial cells (HAECs) the effect of ImP on functional properties of endothelial cells were assessed. Next-generation sequencing, western blot analysis, siRNA-based gene knockdown and tamoxifen-inducible Cre-loxP experiments were performed to investigate ImP-mediated molecular mechanisms.

Results

Plasma ImP levels in subjects undergoing cardiac evaluation were associated with increased risk for prevalent CAD. In atheroproneApoe-/-mice ImP increased atherosclerotic lesion size. We found that ImP dose-dependently impaired migratory and angiogenic properties of human endothelial cells, and promoted an increased inflammatory response. Long-term exposure to ImP impaired the repair potential of the endothelium after an arterial insult. Mechanistically, ImP attenuated insulin receptor signaling by suppressing PI3K/AKT pathway leading to the sustained activation of the forkhead box protein O1 (FOXO1) transcription factor. Genetic inactivation of endothelial FOXO1 signaling in ImP-treated mice enhanced the angiogenic activity and preserved the vascular repair capacity of endothelial cells after carotid injury.

Conclusions

Our findings reveal a hitherto unknown role of the microbially produced histidine-derived metabolite ImP in endothelial dysfunction and atherosclerosis, suggesting that ImP metabolism is a potential therapeutic target in atherosclerotic cardiovascular disease.
Small extracellular vesicles from young adipose-derived stem cells ameliorate age-related changes in the heart of old mice.
Authors: Sanz-Ros Jorge , Huete-Acevedo Javier , Mas-Bargues Cristina , Romero Garcia Nekane , Dromant Mar , van Weeghel Michel van , Janssens Georges E , Borras Consuelo
Published: June 2024

Background: Aging is a process characterized by a progressive decline in physiological functions. This decline contributes to an increased risk of various age-related diseases, including conditions such as heart failure or aortic stenosis. Recent advances have highlighted the potential of stem cell therapies in mitigating the adverse effects of aging. The mechanisms underlying the therapeutic effects of these cells appear to be largely paracrine, including the exchange of different molecules via extracellular vesicles (EVs). This work aims to investigate the potential of sEVs derived from young adipose-derived stem cells (ADSC-sEVs) in restoring structural, molecular, and functional changes associated with aging in the heart. Methods: Aged C57BL/6J mice were treated intravenously with ADSC-sEVs from young mice or PBS as controls, young mice were also included to identify specific changes associated with aging. The impact of sEV treatment on cardiac function was assessed using transthoracic echocardiography and physical endurance tests. Histological and molecular analyses were conducted on heart tissue to evaluate structural changes and markers of senescence, inflammation, and oxidative stress. Additionally, a comprehensive metabolomic analysis was performed on heart tissues to identify changes in metabolic profiles associated with aging and treatment status. Results: Administration of ADSC-sEVs significantly improves several aging-associated cardiac parameters, including reductions in oxidative stress, inflammation, and cellular senescence. We also report on age-related changes reversal in myocardial structure and function, highlighted by decreased fibrosis and improved vascularization. Notably, echocardiographic assessments reveal that sEV treatments ameliorate diastolic dysfunction and left ventricle structural alterations typically associated with aging. Furthermore, the treatment shifts the heart metabolome towards a more youthful profile. Conclusions: These results denote the potential of ADSC-sEVs as a novel, non-invasive therapeutic strategy to mitigate cardiac aging-associated functional decline.
Comparing Midline and Peripherally Inserted Central Catheters – a Randomized Feasibility Trial
Authors: Burek Alina G. , Porada Kelsey , Plunk Matthew R , Bauer Sarah Corey , Liegl Melodee , Pan Amy , Flynn Kathryn E , Brousseau David C , Gedeit Reiner , Ullman Amanda J.
Published: June 2024

Objectives

The most effective use of midline catheters in children is not well understood. We aimed to test the feasibility of a trial comparing peripherally inserted central catheters (PICCs) to midline catheters in hospitalized children in need of durable vascular access.

Methods

Our study combined a single site, randomized controlled feasibility trial and a prospective observational study comparing PICCs to midline catheters. Hospitalized children ages 2-17 years old in need of non-central, medium-term vascular access (5-14 days) were enrolled for one year; enrollment goal of 30 participants/trial arm. The primary outcome was a four-measure feasibility outcome. Secondary outcomes included time-to-device removal and all-cause failure. Multi-method approaches explored patient/family experience.

Results

Between 8/2022-8/2023, only 43 of 260 screened patients met eligibility criteria due to a decrease in eligible PICCs used at our site. A total of 35 patients were enrolled: 8/10 in the trial (4 in each arm) and 27/33 in the observational study (21 midline catheters, 6 PICCs). Our trial eligibility goal was not met. The other feasibility measures were met (n=10): (1) 80% of eligible patients enrolled; (2) 100% received the assigned intervention; (3) 96% of catheter inserters found the study acceptable; (4) no missing data.

Conclusions

Due to a decrease in PICC use for non-central, medium-term vascular access needs, a trial comparing devices may not be a practical way to assess the effective use of midline catheters in hospitalized children. Next steps may include an implementation-based study evaluating an intravenous catheter selection algorithm that incorporates midline catheters.
Respiratory Viral Infection Patterns in Hospitalised Children before and after COVID-19 in Hong Kong
Authors: Sang Pun Jason Chun , Tao Kin Pong , Yam Stacy Lok , Hon Kam Lun , Sheung Chan Paul Kay , Li Albert Martin , Yi Chan Renee Wan
Published: June 2024

In the wake of Hong Kong’s zero-COVID policy, this study comprehensively analyses the epidemiological shift in respiratory viruses among hospitalized pediatric patients. The research leverages a unique natural experiment created by the policy’s stringent measures, which led to a significant reduction in virus circulation from 2020 to early 2023. The study highlights two distinct periods: pre-COVID-19 and post-mask mandate. We used pediatric hospitalization records from January 2015 to December 2019 and March 2023 to February 2024 to reveal a notable rebound in respiratory viruses. The age-stratified analysis indicated a shift in virus susceptibility. The odds ratio of having a co-infection was significantly increased in hospitalized children aged <1 to 12 years old during the post-COVID-19 mask mandate. Moreover, the adenovirus infection in younger children was more prominent, while RSV expanded its prevalence to older children aged>6 years old and raised health concerns. The study underscores the potential long-term impacts of interrupted virus exposure on children’s immune development and the need for vigilant monitoring of respiratory virus trends. It calls for further research to elucidate the causal relationships between SARS-CoV-2 exposure, subsequent respiratory virus susceptibility, and the implications for paediatric health in the post-pandemic era.

Highlights

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Children (4.37 ± 0.05 years old) hospitalized after COVID-19 and tested for respiratory viruses were significantly older than those (3.49 ± 0.03 years old) before COVID-19.

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The odds ratio of having a co-infection was significantly increased in hospitalized children aged <1 to 12 years old during the post-COVID-19 era.

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In the post-COVID-19 era, the adenovirus infection in younger children was more prominent while RSV expanded its prevalence to older children aged>6 years old
Validity and Reliability of the Executive Function Scale (UEF-1) in Cuban University Students
Authors: Díaz-Guerra Diego D. , Hernández-Lugo Marena de la C. , Ramos-Galarza Carlos , Broche-Pérez Yunier
Published: June 2024

Abstracts

Introduction

Executive functions are higher cognitive skills involved in planning, organization, decision-making, impulse control, and working memory. It is essential to have tools that allow for the accurate and reliable assessment of this construct in university students. This study aims to evaluate the validity and reliability of the Executive Functions Scale for University Students (UEF-1) in the Cuban population.

Methods

A cross-sectional study was conducted in which an online survey was administered to 1092 Cuban university students representing 14 of the country’s 16 provinces. Descriptive analyses, confirmatory factor analyses, and Pearson correlation analyses were used to assess the psychometric properties of the scale.

Results

Significant correlations were obtained between the scale factors, and the original seven-factor structure was confirmed. The scale demonstrated good internal consistency and overall reliability (α = .91, ω = .91).

Conclusions

The study provided evidence that the UEF-1 is a reliable and valid tool for assessing executive functions in Cuban university students. This measure provides a comprehensive understanding of the cognitive abilities and functioning of Cuban university students, allowing for the identification of specific areas of executive functioning that may benefit from additional support or intervention.
Attention improvement to transcranial alternating current stimulation at gamma frequency over the right frontoparietal network: a preliminary report
Authors: Lee Tien-Wen , Almeida Sergio , Tramontano Gerald
Published: June 2024

Objective

Applying transcranial alternating current stimulation (tACS) at 40 Hz to the frontal and parietal regions can improve cognitive dysfunctions. This study aimed to explore the influence of tACS at gamma frequency over right fronto-parietal (FP) region on attention.

Methods

We administered Test of Variables of Attention (TOVA; visual mode) to 44 participants with various neuropsychiatric diagnoses before and after 12 sessions of tACS treatment. Alternating currents at 2.0 mA were delivered to the electrode positions F4 and P4, following the 10-20 EEG convention, for 20 minutes in each session.

Results

We observed significant improvement across 3 indices of the TOVA, including reduction of variability in reaction time (RT;P=0.0002), increase in d-Prime (separability of targets and non-targets;P=0.0157), and decrease in commission error rate (P=0.0116). The mean RT and omission error rate largely remained unchanged.

Conclusion

Artificial injection of tACS at 40 Hz over right FP network may improve attention function, especially in the domains of consistency in performance, target/non-target discrimination, and inhibitory control.
Health Coaching 2.0: Redefining a Key Lifestyle Medicine Intervention, PrioMed Pilot Program Evaluation
Authors: Langinkoski Ari , Hämäläinen Johanna , Rapo Krista , Rinta Mikko , Aroviita Pekka , Venojärvi Mika
Published: June 2024

The world is suffering from a global epidemic of non-communicable diseases. Previous research has suggested that health coaching might be an effective way to help curb the epidemic. However, the ambiguous definition of health coaching hinders its widespread practical implementation.

We redefined the coaching process in the universal language of behavior change techniques with evidence of effectiveness, postulating this would make the process more efficient to teach and to apply and lead to results with excellent time efficiency.

This pilot study (n = 25) investigated the feasibility of such an approach. Despite the relatively short total time spent (< 4 hours per participant), the surveys conducted at baseline and six months showed significant improvements in customer-reported physical and mental health with implications of clinical significance.

These promising results pave the way for a universal definition of the coaching process, signaling a brighter future for the practice that merits further exploration.
Myocardial infarction creates a critical time window for AAV gene therapy
Authors: Chen Gonglie , Zhang Yueyang , Chen Zhan , Yang Luzi , Gao Fei , Dong Erdan , Guo Yuxuan
Published: June 2024

Recombinant adeno-associated virus (AAV) is a major gene delivery vector for cardiac gene therapy. The factors that influence AAV-based cardiac gene transfer remain incompletely understood. This study showed that myocardial infarction (MI) enhanced cardiac AAV transduction and gene expression in mice after systemic administration, peaking at the third day post MI. These additional AAV vectors enriched at the infarcted region, correlated with the pathological permeabilization of the coronary vessels. The outcome of AAV-base gene therapy for MI, viaCamk2dbase editing, was significantly improved when AAV was injected at the third day post MI. Together, our findings uncovered a critical therapeutic time window after MI that facilitated AAV-based cardiac gene transfer, which could be harnessed to boost both basic and translational cardiology.

Methods

Adult C57BL/6 mice were subjected to left anterior descending (LAD) coronary artery ligation. Permanent LAD ligation created the MI model while 30min ligation followed by reperfusion established the ischemia/reperfusion (I/R) model. 2×1011AAV vectors were injected into the mice via tail vein. The AAV vectors carried transgenes that were activated by the cardiomyocyte-specificTnnt2promoter or the constitutively active CMV promoter. AAV expressed luciferase with the hemagglutinin (HA) tag. The amount of AAV vectors were quantified by real-time quantitative PCR (RT-qPCR) analysis of genomic DNA. Transgene expression was measured by RT-qPCR at the mRNA level or HA tag immunofluorescence imaging and western blot at the protein level. Luciferase activity was measured via bioluminescence imaging.
Scaffold-enabled high-resolution cryo-EM structure determination of RNA
Authors: Haack Daniel B. , Rudolfs Boris , Jin Shouhong , Weeks Kevin M. , Toor Navtej
Published: June 2024

Cryo-EM structure determination of protein-free RNAs has remained difficult with most attempts yielding low to moderate resolution and lacking nucleotide-level detail. These difficulties are compounded for small RNAs as cryo-EM is inherently more difficult for lower molecular weight macromolecules. Here we present a strategy for fusing small RNAs to a group II intron that yields high resolution structures of the appended RNA, which we demonstrate with the 86-nucleotide thiamine pyrophosphate (TPP) riboswitch, and visualizing the riboswitch ligand binding pocket at 2.5 Å resolution. We also determined the structure of the ligand-free apo state and observe that the aptamer domain of the riboswitch undergoes a large-scale conformational change upon ligand binding, illustrating how small molecule binding to an RNA can induce large effects on gene expression. This study both sets a new standard for cryo-EM riboswitch visualization and offers a versatile strategy applicable to a broad range of small to moderate-sized RNAs, which were previously intractable for high-resolution cryo-EM studies.
NMDA receptor antagonist memantine selectively affects recurrent processing during perceptual inference
Authors: Noorman Samuel , Stein Timo , Zantvoord Jasper , Fahrenfort Johannes J. , van Gaal Simon
Published: June 2024

Perceptual inference requires the integration of visual features through recurrent processing, the dynamic exchange of information between higher and lower level cortical regions. While animal research has demonstrated a crucial role of NMDA receptors in recurrent processing, establishing a causal link between NMDA-mediated recurrent processing and human perception has remained challenging. Here, we report two pharmacological studies with randomized, double-blind, crossover designs in which we administered the NMDA antagonist memantine, while collecting human electroencephalography (EEG). We trained and tested EEG classiﬁers to reflect the processing of speciﬁc stimulus features with increasing levels of complexity, namely differences in stimulus contrast, collinearity between local line elements, and illusory surfaces of a Kanizsa triangle. In two experiments involving different participants and visual tasks, we found that memantine selectively affected decoding of the Kanizsa illusion, known to depend on recurrent processing, while leaving decoding of contrast and collinearity largely unaffected. Interestingly, the results from an attentional blink (experiment 1) and task-relevance manipulation (experiment 2) showed that memantine was only effective when the stimulus was attended and consciously accessed. These ﬁndings demonstrate that NMDA inhibition selectively affects recurrent processing, especially for attended objects, and thereby provide a crucial step toward bridging animal and human research, shedding light on the neural mechanisms underpinning perceptual inference and conscious perception.
Spontaneous emergence of alternating hippocampal theta sequences in a simple 2D adaptation model
Authors: Widloski John , Foster David J.
Published: June 2024

Spatial sequences encoded by cells in the hippocampal-entorhinal region have been observed to spontaneously alternate across the animal’s midline during navigation in the open field, but it is unknown how this occurs. We show that sinusoidal sampling patterns emerge rapidly and robustly in a simple model of the hippocampus that makes no assumptions about sequence direction. We corroborate our findings using hippocampal data from rats navigating in the open field.