bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of advanced imaging with cardiac computed tomography and MRI in atrial and ventricular ablation
Authors: Morris Michael F. , Carlson Chelsea , Bhagat Abhishek
Published: July 2022

Purpose of review

Increasing evidence supports the use of advanced imaging with cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) in the work-up of patients with arrythmias being considered for ablation.

Recent findings

Advances in imaging technology and postprocessing are facilitating the use of advanced imaging before, during and after ablation in patients with both atrial and ventricular arrhythmias.

In atrial arrythmias, quantitative assessment of left atrial wall thickness on CCT and quantification of late gadolinium enhancement (LGE) on CMR identify patients more likely to develop recurrent atrial arrythmias following ablation. In addition, in patients with recurrent arrythmia post ablation, LGE CMR can potentially identify targets for repeat ablation.

In ventricular arrythmias, qualitative assessment of LGE can aide in determining the optimal ablation approach and predicts likelihood of ventricular arrythmias inducibility. Quantitative assessment of LGE can identify conduction channels that can be targeted for ablation. On CCT, quantitative assessment of left ventricular wall thickness can demonstrate myocardial ridges associated with re-entrant circuits for ablation.

This review focuses on the utility of CCT and CMR in identifying key anatomical components and arrhythmogenic substrate contributing to both atrial and ventricular arrhythmias in patients being considered for ablation. Advanced imaging has the potential to improve procedural outcomes, decrease complications and shorten procedural time.
Is myocardial strain an early marker of systolic dysfunction in obstructive sleep apnoea? Findings from a meta-analysis of echocardiographic studies
Authors: Tadic Marijana , Gherbesi Elisa , Faggiano Andrea , Sala Carla , Carugo Stefano , Cuspidi Cesare
Published: July 2022

Aim:

We investigated the association between obstructive sleep apnoea (OSA) and subclinical systolic dysfunction through a meta-analysis of echocardiographic studies that provided data on left ventricular (LV) mechanics as assessed by global longitudinal strain (GLS).

Design:

The PubMed, OVID-MEDLINE, and Cochrane library databases were systematically analyzed to search English-language articles published from inception to 31 December 2021. Studies were detected by using the following terms: ‘obstructive sleep apnea’, ‘sleep quality’, ‘sleep disordered breathing’, ‘cardiac damage’, ‘left ventricular hypertrophy’, ‘systolic dysfunction’, ‘global longitudinal strain’, ‘left ventricular mechanics’, ‘echocardiography’ and ‘speckle tracking echocardiography’.

Results:

The meta-analysis included 889 patients with OSA and 364 non-OSA controls from 12 studies. Compared with controls, GLS was significantly reduced in the pooled OSA group (SMD −1.24 ± 0.17, CI: −1.58 to −0.90, P < 0.0001), as well as in the normotensive OSA subgroup (SMD: −1.17 ± 0.12 CI:−1.40 to −0.95, P < 0.0001). Similar findings were obtained in sub-analyses performed separately in mild, moderate and severe OSA. This was not the case for LV ejection fraction (LVEF) (i.e. comparisons between controls vs. mild OSA, mild vs. moderate OSA, moderate vs. severe OSA).

Conclusion:

GLS is impaired in patients with OSA (independently from hypertension), worsening progressively from mild to moderate and severe forms, thus allowing to identify subclinical alterations of the systolic function not captured by LVEF. Therefore, myocardial strain assessment should be implemented systematically in the OSA setting to timely detect systolic dysfunction.
Ultrasound Cyclo Plasty in Glaucoma: 2-Year Outcomes
Authors: Almobarak Faisal A. , Alrubean Ahmed , Alsarhani Waleed K. , Aljenaidel Abdullah , Osman Essam A.
Published: July 2022

Précis:

UCP offers reasonable IOP control and reduction of the antiglaucoma medication burden.

Purpose:

The purpose of this study is to evaluate the 2-year outcomes of Ultrasound Cyclo Plasty (UCP) in uncontrolled glaucoma.

Materials and Methods:

A retrospective cohort study included patients with uncontrolled primary or secondary glaucoma who underwent UCP at King Abdul Aziz University Hospital, Riyadh, Saudi Arabia, between 2016 and 2021. The main outcome measures were intraocular pressure (IOP), number of antiglaucoma medications, and presence of vision-threatening complications. The surgical outcome of each eye was classified as complete success, qualified success, or failure based on the main outcome measures.

Results:

One hundred and eighty-two eyes of 158 patients were included in the study. The mean follow-up period was 29.71 months (±18.1). The IOP and the number of antiglaucoma medications decreased significantly from a mean of 23.46 mm Hg (±6.3) and 3.33 (±0.9) to 17.33 (±7.1) and 2.14 (±1.4), and 16.24 (±6.3) and 1.90 (±1.5) on the 12th and 24 months, respectively. The overall success rates were 78.0% (143/182) and 85.6% (95/111), and the failure rates were 21.4% (39/182) and 14.4% (16/111) on the 12th and 24th months, respectively. The most common complications were cataract development/progression and anterior chamber reaction.

Conclusions:

UCP offers reasonable IOP control and reduction of the antiglaucoma medication burden.
Effects of Smoking on Optic Nerve Head Microvasculature Density in Glaucoma
Authors: Eslani Medi , Nishida Takashi , Weinreb Robert N. , Baxter Sally , Mahmoudinezhad Golnoush , Kamalipour Alireza , Yarmohammadi Adeleh , Zangwill Linda M. , Moghimi Sasan
Published: July 2022

Précis:

Decreased superficial whole image capillary density was observed in open angle glaucoma (OAG) patients with high smoking intensity.

Purpose:

To investigate the effects of smoking on optic nerve head capillary density measured by optical coherence tomography angiography in patients with OAG.

Methods:

In this retrospective cross-sectional study, perimetric and preperimetric glaucoma patients enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) with optical coherence tomography angiography follow-up were included. Univariable and multivariable linear mixed analysis were performed to determine the effects of different variables on the superficial whole image capillary density.

Results:

A total of 432 eyes of 271 glaucoma patients comprising 63 preperimetric (106 eyes) and 208 perimetric OAG (326 eyes) were included. A history of tobacco consumption was reported in 105 (38.8%). Among smokers, mean (95% confidence interval) smoking intensity was 12.8 (10.2, 15.5) pack-years. After adjusting for age, glaucoma severity and other confounders, each 10 pack-year increase in smoking intensity (95% confidence interval) was associated with −0.54 (−1.06, −0.02) % lower whole image capillary density (P=0.041).

Conclusions:

Smoking intensity is associated with reduced optic nerve vessel density in glaucoma.
The Group A Streptococcus Interleukin-8 Protease SpyCEP Promotes Bacterial Intracellular Survival by Evasion of Autophagy
Authors: Bergmann René , Gulotta Giuseppe , Andreoni Federica , Sumitomo Tomoko , Kawabata Shigetada , Zinkernagel Annelies S. , Chhatwal Gursharan S. , Nizet Victor , Rohde Manfred , Uchiyama Satoshi
Published: July 2022

Autophagy serves an innate immune function in defending the host against invading bacteria, including group A Streptococcus (GAS). Autophagy is regulated by numerous host proteins, including the endogenous negative regulator calpain, a cytosolic protease. Globally disseminated serotype M1T1 GAS strains associated with high invasive disease potential express numerous virulence factors and resist autophagic clearance. Upon in vitro infection of human epithelial cell lines with representative wild-type GAS M1T1 strain 5448 (M1.5448), we observed increased calpain activation linked to a specific GAS virulence factor, the interleukin-8 protease SpyCEP. Calpain activation inhibited autophagy and decreased capture of cytosolic GAS in autophagosomes. In contrast, the serotype M6 GAS strain JRS4 (M6.JRS4), which is highly susceptible to host autophagy-mediated killing, expresses low levels of SpyCEP and does not activate calpain. Overexpression of SpyCEP in M6.JRS4 stimulated calpain activation, inhibited autophagy, and significantly decreased bacterial capture in autophagosomes. These paired loss- and gain-of-function studies reveal a novel role for the bacterial protease SpyCEP in enabling GAS M1 evasion of autophagy and host innate immune clearance.
Violence Is a Public Health and Healthcare Issue
Authors:   International Association of Forensic Nurses
Published: July 2022

Violence is a global issue that destroys the quality of life in communities and societies. Violence includes intentional and unintentional injury found in individuals who seek health care after acts of family violence, intimate partner violence, child abuse, elder abuse, sexual assault, trafficking, youth-on-youth violence, gang warfare, terror, war, disaster, and violence in schools, workplaces and prisons. The nature of violence is evolving. Death as a result of crime victimization now exceeds that of armed conflict. It is the position of the International Association of Forensic Nurses that forensic nurses are uniquely positioned to improve health outcomes that result from violence, including early identification of patients at risk of victimization or perpetration.
Liver-Intestinal Involvement in Graft Versus Host Disease in Pediatric Hematopoietic Stem Cell Transplantation Patients: Ten Years of Experience in 2 Centers of Latin America
Authors: Sepúlveda Andrea , Tagliaferro Gustavo , Arancibia Gabriel , Barriga Francisco , Busoni Verónica , Orsi Marina
Published: July 2022

Objectives:

To describe the behavior and characteristics of children with diagnosis of graft versus host disease (GVHD) with liver-intestinal involvement.

Methods:

Retrospective cohort study of pediatric patients with history of hematopoietic stem cell transplantation for diagnosis of GVHD with gastrointestinal (GI) or liver involvement, from 2 pediatric centers.

Results:

Between 2007 and 2017, 57 pediatric patients presented with liver or intestinal GVHD; 74% with GI GVHD, 11% with liver GVHD, and 15% with liver-intestinal involvement. Diarrhea (96%) and abdominal pain (55%) were the most frequent symptoms. Endoscopies were performed in 88%, and 35% required a second procedure to confirm diagnosis. Normal-appearing mucosa was observed in 17% of upper GI endoscopies and in 29% of colonoscopies. Endoscopic pathological findings were observed mainly in colon (62%). There was greater severity on colonoscopic classification in those with liver-intestinal compromise than in those with GI compromise only. Overall mortality was 26%.

Conclusion:

GI and liver GVHD diagnosis may present serious complications. GI involvement tends to manifest early, so it is appropriate to suspect it in the first days after transplantation, unlike liver involvement, which occurs late when other organs are involved. We did not observe a direct relationship between endoscopic and histological classification. Both GI and liver involvement in GVHD could predict greater target organ involvement.
An Almost Herbst’s Triad: Finger Clubbing and Iron Deficiency Anemia Associated With Severe Gastroesophageal Reflux
Authors: Blagec Paola , Šalamon Janečić Mia , Hojsak Iva
Published: July 2022

Digital clubbing is most commonly caused by pulmonary or cardiac disease, and only rarely it is a manifestation of a gastroenterological disorder. We report a pediatric patient in whom severe gastroesophageal reflux disease caused anemia and digital clubbing, partial clinical presentation of the Herbst triad.
Adoptive Cellular Therapy for Pediatric Solid Tumors: Beyond Chimeric Antigen Receptor-T Cell Therapy
Authors: Hensel Jonathan , Metts Jonathan , Gupta Ajay , Ladle Brian H. , Pilon-Thomas Shari , Mullinax John
Published: July 2022

Children and adolescents with high-risk (metastatic and relapsed) solid tumors have poor outcomes despite intensive multimodal therapy, and there is a pressing need for novel therapeutic strategies. Adoptive cellular therapy (ACT) has demonstrated activity in multiple adult cancer types, and opportunity exists to expand the use of this therapy in children. Employment of immunotherapy in the pediatric population has realized only modest overall clinical trial results, with success thus far restricted mainly to antibody-based therapies and chimeric antigen receptor T-cell therapies for lymphoid malignancy. As we improve our understanding of the orchestrated cellular and molecular mechanisms involved in ACT, this will provide biologic insight and improved ACT strategies for pediatric malignancies. This review focuses on ACT strategies outside of chimeric antigen receptor T-cell therapy, including completed and ongoing clinical trials, and highlights promising preclinical data in tumor-infiltrating lymphocytes that enhance the clinical efficacy of ACT for high-risk pediatric solid tumors.
Neoantigen-Specific T Cells in Adoptive Cell Therapy
Authors: Tran Eric
Published: July 2022

The holy grail of cancer therapeutics is the destruction of cancer cells while avoiding harm to normal cells. Cancer is unique from normal tissues because of the presence of somatic mutations that accumulate during tumorigenesis. Some nonsynonymous mutations can give rise to mutated peptide antigens (hereafter referred to as neoantigens) that can be specifically recognized by T cells. Thus, the immunological targeting of neoantigens represents a safe and promising strategy to treat patients with cancer. This article reviews the clinical application of adoptive cell therapy targeting neoantigens in patients with epithelial cancers.
γδ T Cell–Based Adoptive Cell Therapies Against Solid Epithelial Tumors
Authors: Bustos Xiomar , Snedal Sebastian , Tordesillas Leticia , Pelle Eleonora , Abate-Daga Daniel
Published: July 2022

Conventionally, adoptive cell therapies have been developed and optimized using αβ T cells. However, the understudied and less abundant γδ T cells offer unique advantages to the immunotherapy field especially for therapies against solid tumors. Recently, γδ T-cell potential against a broad spectrum of malignant cells has been demonstrated in the preclinical setting. In the clinic, γδ T-cell–based immunotherapies have proven to be safe; however, their efficacy needs improvement. Considering the growing body of literature reflecting the increasing interest in γδ T cells, we sought to capture the current topics of discussion in the field, pertaining to their use in adoptive immunotherapy. We aimed to compile information about γδ T-cell enhancement in terms of expansion, phenotype, and inhibitory receptors, in addition to the latest advances in preclinical and clinical research using γδ T cells specifically against solid epithelial tumors.
Current State of Cell Therapies for Breast Cancer
Authors: Gautam Namrata , Elleson Kelly M. , Ramamoorthi Ganesan , Czerniecki Brian J.
Published: July 2022

Metastatic breast cancer (BC) is an aggressive form of cancer and is an absolute challenge to treat. This review discusses the standard treatments available for metastatic BC. It further highlights the rationale for targeting oncodrivers, tumor-associated antigens, and neoantigens in BC. Explaining the significance of immune response in successful immunotherapeutic studies, it draws attention towards how adoptive cell therapy can be a useful immunotherapeutic tool. We focus on adoptive cell therapy in BC covering tumor-infiltrating lymphocyte therapy, engineered T cell receptor therapy, chimeric antigen receptor therapy, dendritic cell therapy and natural killer cell therapy. In this work, we aim to provide an overview of clinical data regarding the use of cellular immunotherapies in BC. Eventually, we conclude by proposing future adoptive cell therapy approaches, which can be used to cure BC.
Preclinical In Vitro and In Vivo Models for Adoptive Cell Therapy of Cancer
Authors: Kaushik Garima , Venkatesha Shivaprasad , Verma Bhavna , Vishwakarma Bandana , Zhang Ai-Hong , Wesa Amy
Published: July 2022

Adoptive cellular therapies are making major strides in the treatment of cancer, both for hematologic and solid tumors. These cellular products include chimeric antigen receptor T cells and T-cell receptor–modified T cells, tumor-infiltrating lymphocytes, marrow-infiltrating T cells, natural killer cells as well as macrophage-based therapeutics. Advancement in genomics, computational biology, immunology, and cell therapy manufacturing has facilitated advancement of adoptive T cell therapies into the clinic, whereas clinical efficacy has driven Food and Drug Administration approvals. The growth of adoptive cellular therapy has, in turn, led to innovation in the preclinical models available, from ex vivo cell-based models to in vivo xenograft models of treatment. This review focuses on the development and application of in vitro models and in vivo models (cell line xenograft, humanized mice, and patient-derived xenograft models) that directly evaluate these human cellular products.
Natural Killer Cell Recognition and Control of Epithelial Cancers
Authors: de Souza Fernandez Pereira Marcelo , Carr David R. , Gatti-Mays Margaret E. , Olsen Mallery R. , Setty Bhuvana A. , Shahwan Kathryn T. , Lee Dean A.
Published: July 2022

Natural killer (NK) cells possess an innate ability to recognize cancer and are key mediators of cytotoxic efficacy for anticancer antibodies. Recent advances in the ability to generate, qualify, and safely infuse NK cells have led to a wide variety of clinical trials in oncology. Although their efficacy is best established for liquid cancers, their potential application in solid cancers has received increased attention. Here, we provide general background across a disparate group of exemplary solid tumors for which there is evidence for an NK cell role, discuss NK cell recognition motifs specific to each and murine and human studies of each that are supportive of NK cell adoptive immunotherapy, and end with special considerations relevant to the solid tumor microenvironment.
The Split Hypoglossal Nerve and Cross-Face Nerve Graft for Dual Innervation of the Functional Muscle Transfer in Facial Reanimation
Authors: Amer Tarek A. , ElSharkawy Omar A.
Published: July 2022

Facial paralysis is a disabling deformity. The affected individual is seriously affected both esthetically and functionally. Free functional muscle transfer is currently the corner stone in the management of long-standing facial nerve paralysis. Several nerve options are available to supply the free muscle transfer. These nerves can be used alone or in combination. The aim of this work is to study the possibility and results of dually innervating the free functioning muscle transfer. The dual innervation is done using the split hypoglossal nerve and cross-face nerve graft (CFNG) both sutured in an end-to-end manner to the nerve to gracilis. Twenty-nine patients with unilateral long-standing facial nerve paralysis (more than 1 y) were treated using free gracilis muscle transfer dually supplied by the split hypoglossal nerve and CFNG, both sutured in an end-to-end manner. The gained excursion after the free gracilis transfer was 9 to 29 mm (mean: 17.24 mm). A statistically significant increase (P-value=0.0001) in the distance from where the midline crosses the lower vermilion border to commissure occurred from preoperative (mean: 16.55 mm) to postoperative setting (mean: 33.79 mm). Spontaneity was achieved in 26 patients (89.6%). In conclusion, dual innervation of the free muscle transfer using both the split hypoglossal nerve and CFNG (both sutured in an end-to-end manner to the nerve to gracilis) is a good possible option to treat long-standing cases of facial nerve paralysis. It yields adequate muscle excursion with acceptable spontaneity.
Accuracy of Detecting Obstructive Sleep Apnea Using Ambulatory Sleep Studies in Patients With Syndromic Craniosynostosis
Authors: Yang Sumin , de Goederen Robbin , Bredero-Boelhouwer Hansje , Joosten Koen F.M. , Mathijssen Irene M.J.
Published: July 2022

Study Objectives:

Obstructive sleep apnea (OSA) is seen in up to two-third of the patients with syndromic craniosynostosis. Gold standard to diagnose OSA is the hospital-based polysomnography, although alternatively ambulatory home sleep apnea devices are available. Aim of this study was to assess (1) accuracy of ambulatory sleep studies, (2) clinical decision making following sleep studies, and (3) course of OSA during long-term follow-up.

Materials and Methods:

A retrospective cohort study was performed in children with syndromic craniosynostosis, of whom polysomnographies and home sleep apnea device recordings were collected. Measurements of apnea-hypopnea index, respiratory event index, total sleep/recording time, heart rate, oxygen saturation, and oxygen desaturation index were derived from the sleep studies. Primary clinical care subsequent to the sleep studies was determined using electronic patient files.

Results:

In total, 123 patients were included, with 149 polysomnographies and 108 ambulatory studies. Performing an ambulatory study was associated with increased age at time of measurement (OR=1.1, 95% CI=1.02 to 1.17, P=0.01). No significant difference was found between the 2 types of sleep studies regarding sleep study parameters. Subsequent to sleep studies, patients with no-mild OSA had expectant care whereas patients with moderate-severe OSA underwent OSA-related treatment. OSA was most prevalent up to the age of 5 years, but also noticeable after the age of 10 years in patients with the Crouzon syndrome.

Conclusions:

Ambulatory sleep studies are reliable for diagnosing OSA in older children and can be used to determine clinical decision-making. Hence, we recommend implementing ambulatory sleep studies in a protocolized management.
Gastric Bypass Resolves Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Low-BMI Patients
Authors: Billeter Adrian T. , Scheurlen Katharina M. , Israel Barbara , Straub Beate K. , Schirmacher Peter , Kopf Stefan , Nawroth Peter P. , Müller-Stich Beat P.
Published: July 2022

Objective:

Metabolic dysfunction-associated fatty liver disease (MAFLD) reflects the multifactorial pathogenesis of fatty liver disease in metabolically sick patients. The effects of metabolic surgery on MAFLD have not been investigated. This study assesses the impact of Roux-en-Y gastric bypass (RYGB) on MAFLD in a prototypical cohort outside the guidelines for obesity surgery.

Methods:

Twenty patients were enrolled in this prospective, single-arm trial investigating the effects of RYGB on advanced metabolic disease (DRKS00004605). Inclusion criteria were an insulin-dependent type 2 diabetes, body mass index of 25 to 35 kg/m2, glucagon-stimulated C-peptide of >1.5 ng/mL, glycated hemoglobin >7%, and age 18 to 70 years. A RYGB with intraoperative liver biopsies and follow-up liver biopsies 3 years later was performed. Steatohepatitis was assessed by expert liver pathologists. Data were analyzed using the Wilcoxon rank sum test and a P value <0.05 was defined as significant.

Results:

MAFLD completely resolved in all patients 3 years after RYGB while fibrosis improved as well. Fifty-five percent were off insulin therapy with a significant reduction in glycated hemoglobin (8.45±0.27% to 7.09±0.26%, P=0.0014). RYGB reduced systemic and hepatic nitrotyrosine levels likely through upregulation of NRF1 and its dependent antioxidative and mitochondrial genes. In addition, central metabolic regulators such as SIRT1 and FOXO1 were upregulated while de novo lipogenesis was reduced and β-oxidation was improved in line with an improvement of insulin resistance. Lastly, gastrointestinal hormones and adipokines secretion were changed favorably.

Conclusions:

RYGB is a promising therapy for MAFLD even in low-body mass index patients with insulin-treated type 2 diabetes with complete histologic resolution. RYGB restores the oxidative balance, adipose tissue function, and gastrointestinal hormones.
Identification of an EMT-related Gene Signature Predicting Recurrence in Stage II/III Colorectal Cancer
Authors: Ren Haoyu , Bösch Florian , Pretzsch Elise , Jacob Sven , Westphalen C. Benedikt , Walter Holch Julian , Werner Jens , Angele Martin K.
Published: July 2022

Objective:

To identify a prognostic significant gene signature for predicting colorectal cancer (CRC) recurrence.

Background:

Traditional prognostic risk assessment in stage II/III CRC patients remains controversial. Epithelial-mesenchymal transition is thought to be closely related to the malignant progression of tumors. Thus, it is promising to establish a prognostic model based on epithelial-mesenchymal transition–related gene (ERG) signature.

Materials and Methods:

We retrospectively analyzed transcriptome profiles and clinical information of 1780 stage II/III CRC patients from 15 public datasets. Coefficient variant analysis was used to select reference genes for normalizing gene expression levels. Univariate, LASSO, and multivariate Cox regression analyses were combined to develop the ERG signature predicting disease-free survival (DFS). The patients were divided into high-risk and low-risk based on the ERG signature recurrence risk score. The survival analysis was performed in different CRC cohorts.

Results:

The proposed ERG signature contained 7 cancer-related ERGs and 3 reference genes. The ERG signature recurrence risk score was prognostically relevant in all cohorts (P<0.05) and proved as an independent prognostic factor in the training cohort. In the pooled cohort, high-risk CRC patients exhibited worse DFS (P<0.0001) and overall survival (P=0.0058) than low-risk patients. The predictive performance of the ERG signature was superior to Oncotype DX colon cancer. An integrated decision tree and nomogram were developed to improve prognosis evaluation.

Conclusions:

The identified ERG signature is a promising and powerful biomarker predicting recurrence in CRC patients. Moreover, the presented ERG signature might help to stratify patients according to their tumor biology and contribute to personalized treatment.
Machine learning and murine models explain failures of clinical sepsis trials
Authors: Stolarski Allan E. , Kim Jiyoun , Rop Kevin , Wee Katherine , Zhang Qiuyang , Remick Daniel G.
Published: July 2022

BACKGROUND

Multiple clinical trials failed to demonstrate the efficacy of hydrocortisone, ascorbic acid, and thiamine (HAT) in sepsis. These trials were dominated by patients with pulmonary sepsis and have not accounted for differences in the inflammatory responses across varying etiologies of injury/illness. Hydrocortisone, ascorbic acid, and thiamine have previously revealed tremendous benefits in animal peritonitis sepsis models (cecal ligation and puncture [CLP]) in contradiction to the various clinical trials. The impact of HAT remains unclear in pulmonary sepsis. Our objective was to investigate the impact of HAT in pneumonia, consistent with the predominate etiology in the discordant clinical trials. We hypothesized that, in a pulmonary sepsis model, HAT would act synergistically to reduce end-organ dysfunction by the altering the inflammatory response, in a unique manner compared with CLP.

METHODS

Using Pseudomonas aeruginosa pneumonia, a pulmonary sepsis model (pneumonia [PNA]) was compared directly to previously investigated intra-abdominal sepsis models. Machine learning applied to early vital signs stratified animals into those predicted to die (pDie) versus predicted to live (pLive). Animals were then randomized to receive antibiotics and fluids (vehicle [VEH]) vs. HAT). Vitals, cytokines, vitamin C, and markers of liver and kidney function were assessed in the blood, bronchoalveolar lavage, and organ homogenates.

RESULTS

PNA was induced in 119 outbred wild-type Institute of Cancer Research mice (predicted mortality approximately 50%) similar to CLP. In PNA, interleukin 1 receptor antagonist in 72-hour bronchoalveolar lavage was lower with HAT (2.36 ng/mL) compared with VEH (4.88 ng/mL; p = 0.04). The remaining inflammatory cytokines and markers of liver/renal function showed no significant difference with HAT in PNA. PNA vitamin C levels were 0.62 mg/dL (pDie HAT), lower than vitamin C levels after CLP (1.195 mg/dL). Unlike CLP, PNA mice did not develop acute kidney injury (blood urea nitrogen: pDie, 33.5 mg/dL vs. pLive, 27.6 mg/dL; p = 0.17). Furthermore, following PNA, HAT did not significantly reduce microscopic renal oxidative stress (mean gray area: pDie, 16.64 vs. pLive, 6.88; p = 0.93). Unlike CLP where HAT demonstrated a survival benefit, HAT had no impact on survival in PNA.

CONCLUSION

Hydrocortisone, ascorbic acid, and thiamine therapy has minimal benefits in pneumonia. The inflammatory response induced by pulmonary sepsis is unique compared with the response during intra-abdominal sepsis. Consequently, different etiologies of sepsis respond differently to HAT therapy.
Altered voxel-wise degree centrality associated with patients with comitant exotropia
Authors: Tonga Yan , Huangb Xin
Published: July 2022

Objective of the study is to investigate the altered intrinsic functional hubs in patients with comitant exotropia (CE) using the voxel-wise degree centrality (DC) analysis method. A total of 28 CE patients and 28 healthy controls (HCs) similarly matched in sex, age, and education level were recruited in this study. All subjects underwent a resting-state functional MRI scan, the voxel-wise DC method was applied to evaluate brain network hubs alterations in CE patients. Then, the DC maps between two groups were chosen to be classification features to distinguish patients with CE from HCs based on the support vector machine (SVM) model. The algorithm performance was evaluated by a permutation test. Compared with HCs, CE patients exhibited significant enhanced DC value in the left cerebelum 8 and the right cerebelum 3; and remarkably decreased DC value in the right precentral gyrus, right anterior cingulated, and paracingulate gyri (two-tailed, voxel level: P < 0.01; GRF correction, cluster level: P < 0.05). However, no relationship was found between the observed average DC of the different brain regions and the clinical features (P > 0.05). In addition, the SVM model showed an accuracy of 83.93% to clarify CE patients from HCs using the DC maps as a classification feature. CE patients displayed altered functional network hubs in multiple brain areas associated with cognition and motor control, and the DC variability could classify patients from HCs with high accuracy. These findings may assist to understand the neuropathological mechanism for the disease.
The effect of electroacupuncture on the expression of Sirt1 and STAT3 in hippocampus and amygdala of vascular dementia rats
Authors: Zhao Jian , Li Wenqiang , Wang Yue , Jiang Yuanhe , Ding Chunyan , Li Huaibin , Ding Jian , Wang Lin
Published: July 2022

Objective

Inflammation has long been considered a key factor in learning and memory impairment in patients with vascular dementia (VaD). Studies have confirmed that electroacupuncture can improve the learning and memory impairment of patients with VaD by reducing inflammation, but the specific mechanism of this effect is still unclear. The aim of this study was to explore the underlying mechanism of electroacupuncture in the treatment of VaD.

Methods

The vascular dementia animal model was established by bilateral occlusion of common carotid arteries, and electroacupuncture treatment was given at Baihui (DU20) and Zusanli (ST36). The morris water maze (MWM) was used to test the spatial learning and memory ability of rats in each group. To evaluate the expression of Sirtuin1 (Sirt1), Signal transducer and activator of transcription 3 (STAT3) and inflammatory cytokine (IL-17) in the hippocampus and amygdala, immunohistochemistry and western blot were performed.

Results:

The MWM test and Nissl staining results show that electroacupuncture can significantly improve the learning and memory impairment of VaD rats, and can repair damaged neurons. Immunohistochemistry and western blot results showed that electroacupuncture could enhance the expression of sirt1 in VaD rats, on the contrary, the expression of STAT3 and IL-17 was reduced due to electroacupuncture.

Conclusions

The result suggests that electroacupuncture can suppress inflammation through the Sirt1/STAT3 pathway and improve spatial learning and memory in VaD rats.
A large Australian longitudinal cohort registry demonstrates sustained safety and efficacy of oral medicinal cannabis for at least two years
Authors: Vickery Alistair W , Roth Sebastian , Ernenwein Tracie , Kennedy Jessica , Washer Patrizia
Published: July 2022

Introduction

Oral medicinal cannabis (MC) has been increasingly prescribed for a wide range of clinical conditions since 2016. Despite an exponential rise in prescriptions and publications, high quality clinical efficacy and safety studies are lacking. The outcomes of a large Australian clinical electronic registry cohort are presented.

Methods

A prospective cannabis-naïve patient cohort prescribed oral MC participated in an ongoing longitudinal registry at a network of specialised clinics. Patient MC dose, safety and validated outcome data were collected regularly over two years and analysed.

Results

3,961 patients (mean age 56.07 years [SD 19.08], 51.0% female) with multimorbidity (mean diagnoses 5.14 [SD 4.08]). and polypharmacy (mean 6.26 medications [SD 4.61]). Clinical indications were for: chronic pain (71.9%), psychiatric (15.4%), neurological (2.1%), and other diagnoses (10.7%). Median total oral daily dose was 10mg for Δ9-tetrahydrocannabinol (THC) and 22.5mg for cannabidiol (CBD). A stable dose was observed for over two years. Treatment related adverse events (37.3%) were mild (dry mouth 79.9%), dose-related (sedation/dizziness, 68.2%) with fewer than 2% (n=23) experiencing severe and only two serious adverse events.

Highly significant improvements across all outcomes were sustained for over two years, including: clinical global impression (CGI-E, +39%: CGI-I, +52%; p<0.001), pain interference and severity (BPI, 26.1% and 22.2%; p<0.001), mental health (DASS-21, depression 24.5%, anxiety 25.5%, stress 27.7%; p<0.001), insomnia (ISI, 35.0%; p<0.001), and health status (RAND SF36: physical function, 34.4%: emotional well-being, 37.3%; p<0.001). Mean number of concomitant medications did not significantly change over 2 years.

Conclusions

Oral MC was demonstrated to be safe and well-tolerated for a sustained period in a large complex cohort of cannabis-naïve, multimorbid patients with polypharmacy. There was highly significant improvement across all clinical outcomes over two years. Results are subject to limitations of real world data for causation and generalisability. Future high quality randomised controlled trials are awaited.
Clinical practice competencies for standard critical care nursing: Consensus statement based on a systematic review and Delphi survey
Authors: Sakuramoto Hideaki , Kuribara Tomoki , Ouchi Akira , Haruna Junpei , Unoki Takeshi ,   the AdHoc Committee of Intensive Care Registered Nurse,   Japanese Society of Intensive Care Medicine
Published: July 2022

Clinical practice competencies in standard critical care nursing (SCCN) are necessary to improve the quality of care and patient outcomes. Competency enables definition and provides a framework for the evaluation of actual knowledge, skills, and abilities. However, a clear development process and scientifically validated competencies have not yet been developed in Japan. Thus, this study aimed to develop a consensus-based set of SCCN competencies to cover a framework for critical care nursing education, training, and evaluation. A consensus-based set of SCCN competencies was developed in four stages: (1) development of an initial set of SCCN competencies derived from a systematic review; (2) focus group interviews via video conference to supplement and content expert validation based on initial competencies made from a systematic review; (3) a three-round web-based Delphi survey of health professionals to prioritize and gain consensus on the most essential SCCN competencies; and (4) external validation, feedback, and endorsement from critical care experts. A systematic review of 23 studies and reports identified 685 unique competencies. Of the 239 participants representing a range of health professionals (physicians, nurses, and physical therapists) who registered, 218 (91.2% of registered professionals), 209 (98.9% of round 1 participants), and 201 (96.2% of round two participants) participants responded in round one, round two, and round three of the Delphi survey, respectively. The withdrawal rates between enrollment and each round were less than 10%. After three rounds of the Delphi survey and external validation by experts, the final set of competencies was classified into 6 domains, 26 subdomains, 99 elements, and 525 performance indicators. In summary, a consensus-based, contemporary set of SCCN competencies was identified to cover a framework for critical care nursing education, training, and evaluation.

Trial registration

None
A differential effect of visual cortex tDCS on reading of English and Chinese in patients with central vision loss
Authors: Silva A.E. , Lyu A. , Leat S.J. , Khan S. , Labreche T. , Chan J.C.H. , Li Q. , Woo G.C. , Woo S. , Cheong A.M.Y , Thompson B.
Published: July 2022

We report that visual cortex a-tDCS influences reading performance in individuals with macular degeneration differently depending on the writing system employed. This finding will help to guide the international development of vision rehabilitation programs for macular degeneration that may utilize non-invasive brain stimulation.
MODEL FAMILY CENTERED CARE IN CHILDREN WITH DIABETES MELITUS : A PHILOSOPHICAL PERSPECTIVE
Authors: Maimuna Siti
Published: July 2022

Introduction

Diabetes mellitus is the most widespread chronic non-infectious disease, with an increase in the frequency in childhood that could be the epidemic of the 21st century. This literature aims to study the philosophy of family center care interventions to improve the quality of life of children with diabetes melitus viewed from three philosophical perspectives, namely ontology, epistemology, and axiology.

Method

A literature search was performed on five databases, namely SCOPUS, ProQuest, PubMed, ScienceDirect, SAGEPub, and Google Scholar. Population limitations and diagnoses in this literature of children with diabetes melitus. This research is a quantitative study focusing on publications between 2017-2022.

Result

Family centered care can improve the quality of life of children with diabetes. Children with diabetes successfully manage their disease is possible because parents have understood and received ongoing training and in this case, children with connections to the diabetes care team (family) and medical team play an important role in the management of children’s diabetes. Training and strengthening education helps families to control disease. Teaching children and their families to improve knowledge and control diabetes and metabolic diseases.

Conclusion

Family centered care for children with diabetes requires family knowledge about care, training skills, building strong motivation for children with diabetes so that complications do not occur.
Lowered quality of life in Long COVID is strongly predicted by affective symptoms and chronic fatigue syndrome which are associated with inflammatory processes during the acute infectious phase and consequent neuroimmunotoxic pathways
Authors: Maes Michael , Al-Rubaye Haneen Tahseen , Almulla Abbas F. , Al-Hadrawi Dhurgham Shihab , Stoyanova Kristina , Kubera Marta , Al-Hakeim Hussein Kadhem
Published: July 2022

The physio-affective phenome of Long COVID-19 is predicted by a) immune- inflammatory biomarkers of the acute infectious phase, including peak body temperature (PBT) and oxygen saturation (SpO2), and b) the subsequent activation of immune and oxidative stress pathways during Long COVID. The purpose of this study was to delineate the effects of PBT and SpO2 during acute infection, as well as increased neurotoxicity on the physical, psychological, social and environmental domains of health-related quality of life (HR-QoL) in people with Long COVID. We recruited 86 participants with Long COVID and 39 normal controls, assessed the WHO-QoL-BREF (World Health Organization Quality of Life Instrument-Abridged Version) and the physio-affective phenome of Long Covid (comprising depression, anxiety and fibromyalgia-fatigue rating scales) and measured PBT and SpO2 during acute infection, and neurotoxicity (NT, comprising serum interleukin (IL)-1β, IL-18 and caspase-1, advanced oxidation protein products and myeloperoxidase, calcium and insulin resistance) in Long COVID. We found that 70.3% of the variance in HR-QoL was explained by the regression on the physio-affective phenome, lowered calcium and increased NT, whilst 61.5% of the variance in the physio-affective phenome was explained by calcium, NT, increased PBT, lowered SpO2, female sex and vaccination with Astra-Zeneca and Pfizer. The effects of PBT and SpO2 on lowered HR-QoL were mediated by increased NT and lowered calcium yielding increased severity of the physio-affective phenome which largely affects HR- QoL. In conclusion, lowered HR-Qol in Long COVID is largely predicted by the severity of neuro-immune and neuro-oxidative pathways during acute and Long COVID.
Material deprivation is associated with neural resilience for late-life depression
Authors: Zhang Wei , Bijsterbosch Janine D.
Published: July 2022

Late-life depression (LLD) is a major source of global morbidity and mortality, influenced by multiple risk factors. Yet, a major challenge is to quantify the degree of resilience or vulnerability to LLD at the individual level, which could offer neurobiological insight and ultimately inform future interventions and treatment. Here, applying a non-parametric regression model to the UK Biobank data (N=1,988), we quantified brain-based resilience and vulnerability to LLD and tested whether risk factors could explain individual differences in the estimated magnitude of such neural resilience and vulnerability. Our results show that social isolation was positively associated with the median magnitude of neural vulnerability whereas material deprivation was negatively associated with the greatest neural resilience (top 10 percentile). These results together highlight the importance of social interaction and access to sufficient resources and services in diminishing neural vulnerability and promoting neural resilience to LLD, respectively. Our findings therefore provide insights into preventive strategies for LLD, and thus are of importance for policy makers as well as the broader society.
A generalizable connectome-based marker of in-scan sustained attention in neurodiverse youth
Authors: Horien Corey , Greene Abigail S. , Shen Xilin , Fortes Diogo , Brennan-Wydra Emma , Banarjee Chitra , Foster Rachel , Donthireddy Veda , Butler Maureen , Powell Kelly , Vernetti Angelina , Mandino Francesca , O’Connor David , Lake Evelyn M. R. , McPartland James C. , Volkmar Fred R. , Chun Marvin , Chawarska Katarzyna , Rosenberg Monica D. , Scheinost Dustin , Constable R. Todd
Published: July 2022

Difficulty with attention is an important symptom in many conditions in psychiatry, including neurodiverse conditions such as autism. There is a need to better understand the neurobiological correlates of attention and leverage these findings for individuals in healthcare settings. Nevertheless, it remains unclear if it is possible to build robust dimensional predictive models of attention in neurodiverse populations. Here, we use five datasets to identify and validate functional connectome-based markers of attention. In dataset one, we use connectome-based predictive modelling and observe successful prediction of performance on an in-scan sustained attention task in a neurodiverse sample of youth. The predictions are not driven by confounds, such as head motion. In dataset two, we find the attention network model defined in dataset one generalizes to predict in-scan attention in a separate sample of neurotypical participants performing the same attention task. In datasets three to five, we use connectome-based identification and longitudinal scans to probe the stability of the attention network across months to years in individual participants. Our results help elucidate the brain correlates of attention in neurodiverse youth and support the further development of predictive dimensional models of other clinically-relevant phenotypes.
“Intellect”, a Mobile Health Application based on cognitive-behavioral therapy principles, improves Anxiety and Worry: A Randomized Controlled Trial with an Active Control and a 2-Week Follow-Up
Authors: Kosasih Feodora Roxanne , Sing Yee Vanessa Tan , Yang Toh Sean Han , Suendermann Oliver
Published: July 2022

Digital self-guided mobile health (mHealth) applications are cost-effective, accessible, and well-suited to improve mental health at scale. This randomized controlled trial (RCT) evaluated the effectiveness of a recently developed mHealth programme based on cognitive-behavioral therapy (CBT) principles in improving worry. We also examined psychological mindedness (PM) as a mediator by which app engagement is thought to improve outcomes. The intervention group completed a 2-week “Anxiety and Worry” programme with daily CBT-informed activities, while the active waitlist-control completed a matched 2-week mHealth programme on procrastination. Participants filled out the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire (PHQ-9), and Psychological Mindedness Scale (PMS) at baseline, post-intervention and 2-week follow-up. App engagement was measured at post-intervention only. Both groups showed significant improvements on anxiety and depression scores from baseline to post-intervention, but no group differences were observed. From post-intervention to follow-up, only the intervention group showed further improvements for anxiety levels. Higher engagement with the mHealth app reported lower anxiety at post-intervention, and this relationship was fully mediated by psychological mindedness. This study provides evidence that (a) engaging in a CBT mHealth App can effectively reduce anxiety and worry, and (b) Psychological mindedness is a potential pathway by which engaging with a mHealthapp improves worry. While overall effect sizes were small, at the population level, these can make significant contributions to public mental health.

Author Summary

Increasing burden of anxiety amongst young adults has made widely accessible mobile health applications a promising tool in improving anxiety levels at scale. We conducted a randomized controlled trial (N=309) to examine the effectiveness of a brief, publicly available mobile health application (Intellect’s “Anxiety and Worry” programme) in reducing anxiety and worry levels among young adults. Participants who received the intervention showed significant reduction in anxiety and depression levels, however, effects did not significantly differ from active control. At post-intervention, only the intervention group continued to experience improvements in anxiety level. We also found that higher app engagement with the mHealth app predicted better anxiety and depression outcomes, and this relationship was fully mediated by psychological mindedness. Future work would benefit from inclusion of waitlist control, a larger sample size, and identification of alternative mediators.