bluuebunny/crossref_metadata_2025 huggingface dataset:
GRP78 improves the therapeutic effect of mesenchymal stem cells on hemorrhagic shock‐induced liver injury: Involvement of the NF–кB and HO‐1/Nrf‐2 pathways
Authors: Han Jiahui , Jia Di , Yao Hao , Xu Ce , Huan Zhirong , Jin Hongdou , Ge Xin
Published: December 2023

Mesenchymal stem cells (MSCs) are a popular cell source for repairing the liver. Improving the survival rate and colonization time of MSCs may significantly improve the therapeutic outcomes of MSCs. Studies showed that 78‐kDa glucose‐regulated protein (GRP78) expression improves cell viability and migration. This study aims to examine whether GRP78 overexpression improves the efficacy of rat bone marrow‐derived MSCs (rBMSCs) in HS‐induced liver damage. Bone marrow was isolated from the femurs and tibias of rats. rBMSCs were transfected with a GFP‐labeled GRP78 expression vector. Flow cytometry, transwell invasion assay, scratch assay immunoblotting, TUNEL assay, MTT assay, and ELISA were carried out. The results showed that GRP78 overexpression enhanced the migration and invasion of rBMSCs. Moreover, GRP78‐overexpressing rBMSCs relieved liver damage, repressed liver oxidative stress, and inhibited apoptosis. We found that overexpression of GRP78 in rBMSCs inhibited activation of the NLRP3 inflammasome, significantly decreased the levels of inflammatory factors, and decreased the expression of CD68. Notably, GRP78 overexpression activated the Nrf‐2/HO‐1 pathway and inhibited the NF–κB pathway. High expression of GRP78 efficiently enhanced the effect of rBMSC therapy. GRP78 may be a potential target to improve the therapeutic efficacy of BMSCs.
Knowledge and Practice Gaps in Pediatric Neurocritical Care Nursing: Lessons Learned From a Specialized Educational Boot Camp
Authors: Chang Nathan , Sperber Amelia , Casazza May , Ciraulo Leslie , Teeyagura Prathyusha , Rasmussen Lindsey
Published: December 2023

OBJECTIVES:

Pediatric neurocritical care (PNCC) is a quickly growing subspecialty within pediatric critical care medicine. Standards for care, education, and application of neuromonitoring technologies in PNCC are still being developed. We sought to identify and improve knowledge deficits in neurocritical care with an educational boot camp for nurses.

SETTING:

Quaternary children’s hospital with 36 PICU beds.

DESIGN:

Preinterventional and postinterventional study.

METHODS:

A 2-day boot camp course covering neurologic and neurosurgical topics pertinent to PNCC was provided to 46 pediatric acute and critical care nurses divided into three cohorts over 3 years. Participant characteristics were collected, and precourse and postcourse knowledge assessments were administered.

RESULTS:

Regarding participant characteristics, neither critical care registered nurse certification nor years of nursing experience were associated with better precourse baseline knowledge. Knowledge gaps spanned bedside neurologic assessments, physiologic goals in brain injury, and side effects of neurocritical care medications. In postcourse assessments, all participants showed improvement in scores, and most participants sustained improvements after 6 months. Nurses reported significant improvement in self-reported confidence in caring for the PNCC population. We also observed shorter ICU lengths of stay, decreased hospital incident reports, and decreased time to stroke imaging, although these programmatic metrics cannot be credited to nursing education alone.

CONCLUSIONS:

PNCC programs should include nursing expertise in the field. However, topics specific to PNCC may not be adequately addressed by existing general critical care nursing education and certification. A multimodal educational boot camp can be an effective method to improve nursing knowledge in PNCC. Our results demonstrate that specialty nursing education in PNCC is both innovative and feasible, with the potential to improve patient care. Further research is needed to determine the benefits of specialty education on quality of care and clinical outcomes.
Targeting beta-adrenergic receptor pathways in melanoma: how stress modulates oncogenic immunity
Authors: Switzer Benjamin , Puzanov Igor , Gandhi Shipra , Repasky Elizabeth A.
Published: December 2023

The intricate pathways of the sympathetic nervous system hold an inherently protective role in the setting of acute stress. This is achieved through dynamic immunomodulatory and neurobiological networks. However, excessive and chronic exposure to these stress-induced stimuli appears to cause physiologic dysfunction through several mechanisms that may impair psychosocial, neurologic, and immunologic health. Numerous preclinical observations have identified the beta-2 adrenergic receptor (β2-AR) subtype to possess the strongest impact on immune dysfunction in the setting of chronic stressful stimuli. This prolonged expression of β2-ARs appears to suppress immune surveillance and promote tumorigenesis within multiple cancer types. This occurs through several pathways, including (1) decreasing the frequency and function of CD8 + T-cells infiltrating the tumor microenvironment (TME) via inhibition of metabolic reprogramming during T cell activation, and (2) establishing an immunosuppressive profile within the TME including promotion of an exhausted T cell phenotype while simultaneously enhancing local and paracrine metastatic potential. The use of nonselective β-AR antagonists appears to reverse many chronic stress-induced tumorigenic pathways and may also provide an additive therapeutic benefit for various immune checkpoint modulating agents including commonly utilized immune checkpoint inhibitors. Here we review the translational and clinical observations highlighting the foundational hypotheses that chronic stress-induced β-AR signaling promotes a pro-tumoral immunophenotype and that blockade of these pathways may augment the therapeutic response of immune checkpoint inhibition within the scope of melanoma.
Effect of CYP3A4*22, CYP3A5*3 and POR*28 genetic polymorphisms on calcineurin inhibitors dose requirements in early phase renal transplant patients
Authors: Ebid Abdel-Hameed IM , Ismail Dina A. , Lotfy Neama M. , Mahmoud Mohamed A. , El-Sharkawy Magdy
Published: December 2023

Objective

This study aimed to investigate the combined effect of CYP3A5*3, CYP3A4*22, and POR*28 genetic polymorphisms on tacrolimus and cyclosporine dose requirements.

Methods

One hundred thirty renal transplant patients placed on either tacrolimus or cyclosporine were recruited, where the effect of CYP3A5*3, CYP3A4*22, and POR*28 genetic polymorphisms on their dose requirements were studied at days 14, 30, and 90 post-transplantations.

Results

The POR*28 allele frequency in the studied population was 29.61%. The tacrolimus dose-adjusted trough concentration ratio (C0/D) was significantly lower in the fast metabolizers group (CYP3A5*1/POR*28(CT/TT) carriers) than in the poor metabolizers group (CYP3A5*3/*3/CYP3A4*22 carriers) throughout the study (14, 30, and 90 days) (P = 0.001, <0.001, and 0.003, respectively). Meanwhile, there was no significant effect of this gene combination on cyclosporine C0/D.

Conclusion

Combining the CYP3A5*3, POR*28, and CYP3A4*22 genotypes can have a significant effect on early tacrolimus dose requirements determination and adjustments. However, it does not have such influence on cyclosporine dose requirements.
Development of an ARMS multiplex real-time PCR assay for the detection of HLA-B*13:01 genotype by detecting highly specific SNPs
Authors: Yao Hao , Wang Kaixuan , Lu Sihai , Cao Fang , Dai Penggao
Published: December 2023

Objectives

HLA-B*13:01 was strongly associated with Dapsone Hypersensitivity Syndrome (DHS). This study aimed to develop and validate a rapid and economical method for HLA-B*13:01 genotyping.

Methods

Two tubes multiplex real-time PCR detection system comprising amplification refractory mutation system primers and TaqMan probes was established for HLA-B*13:01 genotyping. Sequence-based typing was applied to validate the accuracy of the assay.

Results

The accuracy of the assay was 100% for HLA-B*13:01 genotyping. The detection limit of the new method was 0.025 ng DNA. The positive rate of HLA-B*13:01 in the Bouyei (20%, n = 50) populations was significantly higher than that in the Uighur population (4%, n = 100), Han (4.5%, n = 200), and Tibetan (1%, n = 100) (P < 0.05).

Conclusion

The proposed method is rapid and reliable for HLA-B*13:01 screening in a clinical setting.
Racial and ethnic differences and the role of unfavorable social determinants of health across steatotic liver disease subtypes in the United States
Authors: Ochoa-Allemant Pedro , Marrero Jorge A. , Serper Marina
Published: December 2023

Background:

The global liver community established a more precise criteria to characterize steatotic liver disease (SLD), specifically metabolic dysfunction–associated steatotic liver disease (MASLD) and metabolic dysfunction–associated and alcohol-associated liver disease (MetALD). We aimed to estimate the burden of SLD subtypes and unfavorable social determinants of health (SDOH) in US adults and whether clinical and social factors drive disparities across racial/ethnic subgroups.

Methods:

We evaluated 4263 persons aged 20 years or older from the National Health and Nutrition Examination Survey 2017–2018. We estimated the weighted age-adjusted prevalence and severity of SLD, examined the prevalence of SDOH across SLD subtypes, and performed stepwise regression analysis to evaluate associations between race/ethnicity and SLD, accounting for metabolic risks, alcohol use, and SDOH.

Results:

Hispanic adults had the highest prevalence of MASLD (22.3%), MASLD-predominant MetALD (10.3%), alcohol-associated liver disease (ALD)-predominant MetALD (5.6%), and ALD (5.4%). Hispanic adults with MASLD had the highest prevalence of high-risk metabolic dysfunction–associated steatohepatitis (18.0%) and advanced fibrosis (21.1%), whereas non-Hispanic (NH) White adults with MetALD had the highest prevalence of high-risk metabolic dysfunction–associated steatohepatitis (19.3%), advanced fibrosis (19.5%), and cirrhosis (8.1%). Adults with ALD-predominant MetALD and ALD had an increased burden of unfavorable SDOH than those with MASLD, particularly food insecurity, limited health care access, and single living. In stepwise regression, the odds of SLD in Hispanic adults decreased after adjusting for metabolic risks (OR 1.40, 95% CI, 1.06–1.84) and alcohol use (OR 1.36, 95% CI, 1.01–1.82). Differences did not persist after adjusting for cumulative SDOH and nativity status (OR 1.22, 95% CI, 0.89–1.68).

Conclusions:

We found substantial disparities in the burden of unfavorable SDOH across SLD subtypes, particularly among those with ALD-predominant MetALD and ALD. Population-based approaches targeting SDOH may mitigate racial/ethnic differences among US adults with SLD.
Long-term management and treatment of acute intermittent porphyria with recurring attacks using pharmacological prophylaxis
Authors: Kuo Hung-Chou , Ro Long-Sun , Lin Chia-Ni , Chen Hui-Yu
Published: December 2023

Background:

There is no definitive guidance on whether patients with acute intermittent porphyria (AIP) with recurrent attacks need pharmacological prophylactic treatment.

Methods:

The management strategies for patients with frequent (defined as ≥4 annualized attack rate (AAR) and less frequent attacks (<4 AAR), including treatment for acute attacks and duration of prophylaxis (weekly heme arginate 3 mg/kg body weight and/or investigational drug, givosiran), were summarized. The AAR for the following periods were presented: the first 2 years after diagnosis, before/after prophylaxis, and the most recent 2 years.

Results:

A total of 29 patients with AIP were included, 19 (34.5%) had <4 AAR and 10 (65.6%) had ≥4 AAR in the first 2 years after diagnosis. All patients experienced reduced attacks during the treatment course, 23 (79.3%) were attack-free during the most recent 2 years. Among the 9 patients who received prophylaxis (7 heme arginate; 1 givosiran, 1 heme arginate followed by givosiran), 5 (55.6%) were attack-free in the most recent 2-year period and prophylaxis was discontinued because there had been no attacks for >1 year. For patients without prophylaxis (n = 20), 18 (90.0%) were attack-free in the most recent 2-year period and 15 (75.0%) experienced attacks only in the first 2 years after diagnosis.

Conclusions:

Prophylaxis could be considered for patients with AIP with ≥4 biochemically confirmed attacks/year after routine treatment of 1–2 years, during which the severity and frequency of attacks should be closely monitored to determine the necessity of pharmacologic prophylaxis. More studies are needed to reach a consensus on the use of pharmacological prophylaxis and treatment of AIP.
Inhibition of CAF-1 histone chaperone complex triggers cytosolic DNA and dsRNA sensing pathways and induces intrinsic immunity of hepatocellular carcinoma
Authors: Chan For-Fan , Yuen Vincent Wai-Hin , Shen Jialing , Chin Don Wai-Ching , Law Cheuk-Ting , Wong Bowie Po-Yee , Chan Cerise Yuen-Ki , Cheu Jacinth Wing-Sum , Ng Irene Oi-Lin , Wong Carmen Chak-Lui , Wong Chun-Ming
Published: December 2023

Background and Aims:

Chromatin assembly factor 1 (CAF-1) is a replication-dependent epigenetic regulator that controls cell cycle progression and chromatin dynamics. In this study, we aim to investigate the immunomodulatory role and therapeutic potential of the CAF-1 complex in HCC.

Approach and Results:

CAF-1 complex knockout cell lines were established using the CRISPR/Cas9 system. The effects of CAF-1 in HCC were studied in HCC cell lines, nude mice, and immunocompetent mice. RNA-sequencing, ChIP-Seq, and assay for transposase accessible chromatin with high-throughput sequencing (ATAC-Seq) were used to explore the changes in the epigenome and transcriptome. CAF-1 complex was significantly upregulated in human and mouse HCCs and was associated with poor prognosis in patients with HCC. Knockout of CAF-1 remarkably suppressed HCC growth in both in vitro and in vivo models. Mechanistically, depletion of CAF-1 induced replicative stress and chromatin instability, which eventually led to cytoplasmic DNA leakage as micronuclei. Also, chromatin immunoprecipitation sequencing analyses revealed a massive H3.3 histone variant replacement upon CAF-1 knockout. Enrichment of euchromatic H3.3 increased chromatin accessibility and activated the expression of endogenous retrovirus elements, a phenomenon known as viral mimicry. However, cytosolic micronuclei and endogenous retroviruses are recognized as ectopic elements by the stimulator of interferon genes and dsRNA viral sensing pathways, respectively. As a result, the knockout of CAF-1 activated inflammatory response and antitumor immune surveillance and thereby significantly enhanced the anticancer effect of immune checkpoint inhibitors in HCC.

Conclusions:

Our findings suggest that CAF-1 is essential for HCC development; targeting CAF-1 may awaken the anticancer immune response and may work cooperatively with immune checkpoint inhibitor treatment in cancer therapy.
Impact of acute silent ischemic lesions on clinical outcomes of carotid revascularization
Authors: Wang Jie , Wang Tao , Yang Bin , Chen Yanfei , Gao Peng , Wang Yabin , Chen Jian , Chen Fei , Luo Jichang , Yang Renjie , Min Xiaoli , Ma Yan , Jiao Liqun
Published: December 2023

Background:

Previous literature has established an association between acute silent ischemic lesions (ASILs) and elevated susceptibility to future adverse clinical outcomes. The present study endeavors to scrutinize the prognostic significance of pre-procedural ASILs, as detected through diffusion-weighted imaging and apparent diffusion coefficient metrics, in relation to subsequent adverse events—namely, stroke, myocardial infarction, and all-cause death—following carotid revascularization in a cohort of patients with symptomatic carotid stenosis.

Materials and Methods:

Subjects were extracted from a comprehensive retrospective dataset involving symptomatic carotid stenosis cases that underwent carotid revascularization at a tertiary healthcare institution in China, spanning January 2019 to March 2022. Of the 2,663 initially screened patients (symptomatic carotid stenosis=1,600; asymptomatic carotid stenosis=1,063), a total of 1,172 individuals with symptomatic carotid stenosis were retained for subsequent analysis. Stratification was implemented based on the presence or absence of ASILs. The primary endpoint constituted a composite measure of in-hospital stroke, myocardial infarction, or all-cause death. Both carotid endarterectomy (CEA) and carotid artery stenting (CAS) treatment modalities were individually subjected to propensity score-matched analyses.

Results:

Among the 584 subjects who underwent CEA, 91 ASIL-positive and 91 ASIL-negative (NASIL) cases were propensity score-matched. Notably, the ASIL cohort demonstrated a statistically significant augmentation in the risk of primary outcomes relative to the NASIL group (10.99% vs. 1.10%; absolute risk difference, 9.89% [95% CI, 3.12%-16.66%]; RR, 10.00 [95% CI, 1.31-76.52]; P=0.01). Similarly, within the 588 CAS-treated patients, 107 ASIL-positive and 107 NASIL cases were matched, revealing a correspondingly elevated risk of primary outcomes in the ASIL group (9.35% vs. 1.87%; absolute risk difference, 7.48% [95% CI, 1.39%-13.56%]; RR, 5.00 [95% CI, 1.12-22.28]; P=0.02).

Conclusions:

ASILs portend an elevated risk for grave adverse events post-carotid revascularization, irrespective of the specific revascularization technique employed—be it CEA or CAS. Thus, ASILs may serve as a potent biomarker for procedural risk stratification in the context of carotid revascularization.
Changing patterns and surgical outcomes of small bowel obstruction in the era of minimally invasive surgery for colorectal cancer
Authors: Liang Jin-Tung , Liao Yu-Tso , Chen Tzu-Chun , Huang John , Hung Ji-Shiang
Published: December 2023

Introduction:

This study aimed to investigate whether the incidence, patterns, and surgical outcomes of small bowel obstruction (SBO) have changed in the era of minimally invasive surgery (MIS) for primary colorectal cancer (CRC).

Methods:

Consecutive patients who underwent laparotomy for SBO were divided into MIS and traditional open surgery (TOS) groups based on the previous colorectal cancer operation technique used. The MIS group was selected from 1544 consecutive patients who underwent MIS as a treatment for primary CRCs between 2014 and 2022, while the TOS group was selected from 1604 consecutive patients who underwent TOS as a treatment for primary CRCs between 2004 and 2013. The demographics, clinicopathological features, and surgical outcomes were compared between the two groups.

Results:

The SBO incidence in patients who underwent MIS for primary CRC was significantly lower than that in patients who underwent TOS (4.4%, n=68/1544 vs. 9.7%, n=156/1604, P<0.0001). Compared with the TOS group, the MIS group had significantly different (P<0.0001) SBO patterns: adhesion (48.5 vs. 91.7%), internal herniation (23.5 vs. 2.6%), external herniation (11.8 vs. 1.9%), twisted bowel limbs (4.4 vs. 0.6%), ileal volvulus with pelvic floor adhesion (5.9 vs. 1.9%), and nonspecific external compression (5.9 vs. 1.3%). A subset analysis of patients with adhesive SBO (ASBO) showed that the MIS group tended to (P<0.0001) have bands or simple adhesions (75.8%), whereas the TOS group predominantly had matted-type adhesions (59.4%). Furthermore, SBO in the MIS group had an acute (<3 months) or early (3–12 months) onset (64.7%), while that in the TOS group (P<0.0001) had an intermediate or a late onset. When the surgical outcomes of SBO were evaluated, the TOS group had significantly more (P<0.0001) blood loss and longer operation time; however, no significant difference was observed in the surgical morbidity/mortality (Clavien–Dindo classification ≧3, 11.8 vs. 14.1%, P=0.6367), hospitalization, and readmission rates between the two groups. Postoperative follow-up showed that the estimated 3-year (11.37 vs. 18.8%) and 6-year (25.54 vs. 67.4%) recurrence rates of SBO were significantly lower (P=0.016) in the MIS group than in the TOS group.

Conclusions:

The wide adoption of MIS to treat primary CRC has led to a lower incidence, altered patterns, and reduced recurrence rates of SBO. Awareness of this new trend will help develop surgical techniques to prevent incomplete restoration of anatomical defects and bowel malalignments specifically associated with MIS for CRC, as well as facilitate timely and appropriate management of SBO complications whenever they occur.
A Novel Partial Nephrectomy Technique Using Blunt Dissection, Clipping of Intrarenal Vessels, Followed by Closure Using a Fibrin Sealant and Sliding Clips
Authors: Aschwanden Fabian J. , Ditsch Dominic , von Wallenberg Fabian , Affentranger Andres , Treumann Thomas , Mattei Agostino , Fankhauser Christian D.
Published: December 2023

Purpose:

We describe a surgical technique for robotic-assisted partial nephrectomy, including 3 novel steps to facilitate resection and suturing. This approach minimizes positive surgical margins and the risk of postoperative bleeding.

Materials and Methods:

This article describes a retrospective study of a single-surgeon series, including 49 patients. The study approach includes descriptive analysis of the Intraoperative Adverse Incident Classification, analysis of postoperative complications using the Clavien-Dindo Classification, and description of pathological and oncological outcomes.

Results:

The median operative time was 221 minutes (IQR: 196-263), and the median ischemia time was 20 minutes (IQR: 12-24). Intraoperative Adverse Incident Classification Grade 1 complications occurred in 2 patients (4%). Conversion to open partial nephrectomy was necessary in 1 patient (2%). Postoperative complications were reported in 7 patients (14%). Of these, 3 patients (6%) experienced a Clavien-Dindo Classification Grade 2 complication, 2 patients (4%) experienced a Grade 3a complication, 1 patient (2%) experienced a Grade 3b complication, and 1 patient (2%) experienced a Grade 4a complication. Endovascular coiling and blood transfusion were necessary in 2 patients (4%), and 2 patients (4%) were readmitted. A positive surgical margin was reported in 1 patient (2%). Metastatic relapse occurred in 1 patient (2%) 535 days after surgery who did not have a positive surgical margin.

Conclusions:

Our novel 3 surgical steps during robotic-assisted partial nephrectomy allow an oncologically safe resection with a low risk of postoperative complications.
Microbiomes in Post–Digital Rectal Exam Urine Samples are Linked to Prostate Cancer Risk
Authors: Crawford E. David , Martin Rick , Phillips Caleb D. , Stanton Whitney N. , van Bokhoven Adrie , Lucia M. Scott , Arangua Paul B. , La Rosa Francisco G. , Grasmick Zachary , Terlecki Ryan , Meagher Margaret F. , Hirano Daisaku , Nickel J. Curtis , Werahera Priya N.
Published: December 2023

Purpose:

Bacterial species including Cutibacterium acnes (C. acnes) have been associated with different inflammatory and neoplastic conditions in prostate cancer (PCa) tissue samples, but their clinical impact is unknown. Using next-generation sequencing (NGS)–based clinical reports, we investigated the differential abundance and incidence of microbiomes in post–digital rectal exam (DRE) urine samples from patients with PCa and a matched control group at low risk of PCa.

Materials and Methods:

A total of 200 post-DRE urine samples were analyzed, 100 from patients with histopathologically confirmed PCa and 100 from men at very low risk of PCa with PSA <1.5 ng/mL as controls. Bacterial and fungal communities were characterized by NGS of 16S and internal transcribed spacer (ITS) loci, respectively, with species' relative abundances provided on physicians' clinical reports. The differential abundance and incidence of species between cancer and control groups were evaluated.

Results:

Microbes were reported in 39% and 56% of PCa and control group samples, respectively. C. acnes had a significantly higher relative abundance in patients with PCa vs controls (P < .05), and C. acnes incidence rates were also nominally higher in patients with PCa as compared with controls (12.82% and 7.27%, respectively). By contrast, Finegoldia magna (F. magna) had a significantly higher relative abundance (P < .05) and incidence rate (P < .05) in controls as compared with patients with PCa.

Conclusions:

C. acnes was among the most prevalent bacterial species in PCa urine samples. F. magna identified in the low-risk group is responsible for production of equol, a soy metabolite associated with lowering risk of PCa, suggesting a role in prostate cancer chemoprevention.
A case of truncal complex regional pain syndrome: literature review
Authors: Alhammadi Nouf A. , Alqahtani Hanan
Published: December 2023

Introduction and importance:

Complex regional pain syndrome is a rare and chronic pain disorder characterized by an abnormal level of pain disproportionate to the initiating cause, often manifesting well after the triggering event.

Case presentation:

The authors present a free past medical history 33-year-old female, employed as a nurse in an intensive care unit, presented with a 9-year history of diffuse back pain. Her symptoms initially emerged at the neck with muscle spasms and restricted neck mobility, eventually progressing along the spine. Notably, the pain became episodic and intensified over time, significantly impeding her daily activities. Analgesic (non-steroidal anti-inflammatory drugs) treatments proved ineffective, and a distinct feature emerged—a change in skin colour to dark purple spots on her back, accompanied by hyperhidrosis and extreme tenderness. Despite an exhaustive evaluation involving bloodwork, inflammatory markers, serological tests, and radiographic imaging, a definitive diagnosis remained elusive until she responded positively to Pregabilin.

Clinical discussion:

Although typically associated with extremities, this case challenges the conventional understanding of complex regional pain syndrome by showcasing its manifestation in the truncal region. The patient’s clinical history, examination findings, and diagnostic journey are detailed herein, shedding light on the complexity and diagnostic considerations associated with this condition.

Conclusion:

The case underscores the importance of a comprehensive approach and prompts a reevaluation of the existing guidelines to encompass such atypical presentations.
Examination of the traction effect in an artificial muscle-type dynamic traction orthosis using computed tomography
Authors: Nakayama Jun , Fukui Nobuyoshi , Sunagawa Kosaku , Ogawa Kazunori , Oka Hisao , Denno Kakuro
Published: December 2023

Background:

Dart-throwing motion from radial dorsiflexion to palmar flexion has recently attracted attention as a functional movement direction of the wrist joint. We developed a novel artificial muscle-type dynamic traction orthosis (DTSaM) that includes these movements. This prospective crossover controlled study aimed to compare the traction effects in the presence and absence of DTSaM using computed tomography.

Methods:

Healthy participants with no history of finger disease (6 men: 6 fingers, 4 women: 4 fingers; average age [range]: 29.4 [34–24] years) were examined. The distance and area of the joint space between the radiolunate (RL) and capitolunate (CL) joints were evaluated using 2 types of computed tomography: automatic movement and DTSaM.

Results:

Participants with DTSaM showed more dilated joint space distance on the dorsal and central sides (p < 0.05) and larger joint space areas on the dorsal side (p < 0.05) of the RL and CL joints than those without orthosis. Significant differences in the magnitude of change in each joint were observed between the RL and CL joints regarding the joint space distance on the dorsal (p = 0.021) and central (p = 0.038) sides and the joint space area on the dorsal side (p = 0.044).

Conclusions:

The movement of the CL joint is important in the dorsiflexion direction. Our results suggest that the dilated CL joint allows dorsiflexion and that combined traction and dart-throwing motion exercises may be possible for wrist joint contracture.
Single-cell Transcriptomics Reveals Activation of Macrophages in All-trans Retinoic Acid (atRA)-induced Cleft Palate
Authors: Wang Binqing , Xu Meng , Zhao Jingjing , Yin Ningbei , Wang Yongqian , Song Tao
Published: December 2023

Cleft palate is among the most common birth defects with an impact on swallowing and speaking and is difficult to diagnose with ultrasound during pregnancy. In this study, we systematically capture the cellular composition of all-trans retinoic acid (atRA)-exposed and normal embryonic gestation 16.5 days mouse palate by the single-cell RNA sequencing technique. The authors identified 14 major cell types with the largest proportion of fibroblasts. The proportion of myeloid cells in atRA-exposed palate was markedly higher than those in the normal palate tissue, especially M1-like macrophages and monocytes. The upregulated genes of the different expression genes between atRA-exposed palate and normal palate tissue were linked to the biological processes of leukocyte chemotaxis and migration. Protein TLR2, CXCR4, THBS1, MRC1, transcription factor encoding genes Cebpb, Fos, Jun, Rela, and signaling pathway IL-17 and phagosome were found to be significantly involved in these processes. Subsequently, cellular communication network analysis suggested that myeloid-centered cell interactions SELL, SELPLG, MIF, CXCL, ANNEXIN, THBS, and NECTIN were significantly more activated in atRA-exposed palate. Overall, we delineate the single-cell landscape of atRA-induced cleft palate, revealing the effects of overexposure to atRA during palate tissue development and providing insights for the diagnosis of cleft palate.
Implementing Enhanced Recovery Pathways
Authors: Yuan Christina T. , Wu JunBo , Cardell Chelsea P. , Liu Tasnuva M. , Eidman Benjamin , Hobson Deborah , Wick Elizabeth C. , Rosen Michael A.
Published: December 2023

Objective:

To explore barriers and facilitators to implementing enhanced recovery pathways, with a focus on identifying factors that distinguished hospitals achieving greater levels of implementation success.

Summary Background Data:

Despite the clinical effectiveness of enhanced recovery pathways, the implementation of these complex interventions varies widely. While there is a growing list of contextual factors that may affect implementation, little is known about which factors distinguish between higher and lower levels of implementation success.

Methods:

We conducted in-depth interviews with 168 perioperative leaders, clinicians, and staff from eight U.S. hospitals participating in the Agency for Healthcare Research and Quality Safety Program for Improving Surgical Care and Recovery. Guided by the Consolidated Framework for Implementation Research, we coded interview transcripts and conducted a thematic analysis of implementation barriers and facilitators. We also rated the perceived effect of factors on different levels of implementation success, as measured by hospitals’ adherence with nine process measures over time.

Results:

Across all hospitals, factors with a consistently positive effect on implementation included information-sharing practices and the implementation processes of planning and engaging. Consistently negative factors included the complexity of the pathway itself, hospitals’ infrastructure, and the implementation process of “executing” (particularly in altering electronic health record systems). Hospitals with the greatest improvement in process measure adherence were distinguished by clinicians’ positive knowledge and beliefs about pathways and strong leadership support from both clinicians and executives.

Conclusions:

We draw upon diverse perspectives from across the perioperative continuum of care to qualitatively describe implementation factors most strongly associated with successful implementation of enhanced recovery pathways.
Lung Transplantation for People Living With HIV: Promising Mid-term Outcomes
Authors: Ralphs Asher S. , Anderson Scott T. , Langlais Blake T. , D’Cunha Jonathan , Reck dos Santos Pedro A.
Published: December 2023

Background.

With increasing life expectancy, patients with HIV are more commonly acquiring other chronic diseases, such as end-stage lung disease, for which transplant may be the only effective solution. Until recently, HIV infection was considered a contraindication to lung transplant (LTx). As LTx in people living with HIV (PLWH) becomes more common, there remain limited data on outcomes in this population.

Methods.

Using the Organ Procurement and Transplantation Network Standard Transplant Analysis and Research file, we identified LTx recipients with HIV by either serostatus or nucleic acid testing. A control group of confirmed HIV-negative LTx recipients was propensity score matched on age, body mass index, primary diagnosis, and year of transplant. Patient characteristics, transplant parameters, survival, and postoperative outcomes were compared.

Results.

Fifty-nine LTx recipients with HIV were identified and compared with 236 HIV-negative controls. Among PLWH, cytomegalovirus status was more frequently positive (76.3% versus 58.9%, P = 0.014), and the median Lung Allocation Score at match was higher (44 versus 39, P = 0.004). PLWH were more likely to undergo dialysis postoperatively (18.6% versus 8.9%, P = 0.033), although other complication rates were similar. Fifty-three percent of LTx for PLWH occurred since 2020. One-year survival for PLWH was 91.2% versus 88.6% for controls (P = 0.620). Three-year survival for a smaller subset was also not statistically significant (HIV versus control: 82.6% versus 77.8%, respectively, P = 0.687).

Conclusions.

There was no difference in 1-y survival for LTx recipients living with HIV compared with a matched control group, supporting this group of patients as viable candidates for LTx.
The difference between induced insight by hints and induced insight by answers: an event-related potential study
Authors: Leng Haizhou , Yang Lizhu , Yang Shuang
Published: December 2023

We can solve insight problems by ourselves, by hints or by answers. This study compared the temporal features of different types of insight (spontaneous insight, induced insight by hints and induced insight by answers). Fifteen college students participated in the Chinese Remote Association Task. If they did not come up with an answer, the cue word was presented. Finally, they needed to judge whether the answer was correct or not. Participants’ brain electroencephalography–event-related potentials (ERPs) were recorded. Induced insight by hints elicited a more negative ERP deflection than spontaneous insight within 260–400 ms (N2). Induced insight by hints and induced insight by answers elicited a more negative late negative component (LNC) than spontaneous insight. Induced insight by hints elicited a more positive ERP deflection than induced insight by answers and spontaneous insight in the right frontal area. Spontaneous insight and induced insight by answers elicited a more positive ERP deflection than induced insight by hints in the right part of the central region. When solving insight problems, the N2 may be related to representation restructuring. The first LNC may be related to the breaking of mental set. The positive component of the right frontal area before pressing the button may be related to the formation of novel associations, and the positive component of the right part of the central region may be related to the intensity of the ‘Aha!’ experience.
Extraintestinal pathogenic lineages of extended-spectrum β-lactamase (ESBL)-producing E. coli are associated with prolonged ESBL gene carriage
Authors: van der Putten Boas C.L. , van Hattem Jarne M. , Penders John , Mende Daniel R. , Schultsz Constance
Published: December 2023

Objectives Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-Ec) are frequently acquired during international travel, contributing to the global spread of antimicrobial resistance. Human-adapted ESBL-Ec are predicted to exhibit increased intestinal carriage duration, resulting in a higher likelihood of onward human-to-human transmission. Yet, bacterial determinants of increased carriage duration are unknown. Previous studies analysed small traveler cohorts, with short follow-up times, or did not employ high-resolution molecular typing, and were thus unable to identify bacterial traits associated with long-term carriage after recent acquisition. We aimed to identify which ESBL-Ec lineages are associated with increased carriage duration after return from international travel.
Methods In a prospective cohort study of 2001 international travelers, we analysed 160 faecal ESBL-Ec isolates from all 38 travelers who acquired ESBL-Ec during travel and subsequently carried ESBL-Ec for at least 12 months after return, by whole-genome sequencing. For 17 travelers, we confirmed the long-term carriage of ESBL-Ec strains through single nucleotide variant typing. To identify determinants of increased carriage duration, we compared the 17 long-term carriers (≥12 months carriage) with 33 age-, sex- and destination-matched short-term carriers (<1 month carriage). Long read sequencing was employed to investigate long-term ESBL plasmid carriage.
Results We show that in healthy travelers with very low antibiotic usage, extraintestinal pathogenic lineages of E. coli (ExPEC) are significantly more likely to persist than other E. coli lineages. The long-term carriage of E. coli from ExPEC lineages is mainly driven by sequence type 131 and phylogroup D E. coli.
Conclusions Although ExPEC lineages frequently cause extra-intestinal infections such as bloodstream infections, our results indicate that ExPEC lineages are also efficient intestinal colonisers, which potentially contributes to their onward transmission.
Chemical/technical risk analysis of a new multi-directional nebulizer (MDN) and its clinical implementation for the safe administration of Pressurized Intraperitoneal Aerosol Chemotherapy (MDN-PIPAC)
Authors: Kockelmann Fabian , Göhler Daniel , Barbey Sarah , Gena Amayu Wakoya , Alsaad Hayder , Voelker Conrad , Zieren Jürgen , Ouaissi Mehdi , Giger-Pabst Urs
Published: December 2023

Background/Aim

To test the chemoresistance of a multi-directional nebulizer (MDN) and to establish and implement a perioperative clinical safety concept for its clinical use to deliver pressurised intraperitoneal aerosol chemotherapy (MDN-PIPAC).

Study design

Ex-vivo nebulization of cytostatic drugs with the MDN device to assess chemoresistance/toxicological risks. Establishment of a perioperative safety concept for the clinical administration of MDN-PIPAC by ex- and in-vivo porcine simulation studies. Unicentric case series of 30 MDN-PIPACs in 21 patients with peritoneal surface malignancies (PSM). Endpoints were intraoperative adverse events and perioperative complications (Clavien-Dindo).

Results

Toxicological studies/risk assessment confirm the safety of administering PIPAC with the MDN. The horizontal nozzles must protrude at least 7 mm beyond the most distal end of the trocar tip and lateral tilting should be prevented by fixation of the device in a single-arm holder. A total of 21 patients (male/female ratio: 2:1) with a mean age of 62 (range: 38-86) years underwent 30 consecutive MDN-PIPACs for peritoneal surface malignancies of different origin. ECOG 0 and 1 were seen in five and 16 patients, respectively. Thirteen, seven, and one patient underwent one, two, and three MDN-PIPACs, respectively. Two patients received only one cycle of MDN-PIPAC because they were considered candidates for cytoreductive surgery and heated intraperitoneal chemotherapy. There were no intraoperative technical/medical problems observed. Four patients suffered from postoperative grade I complications.

Conclusions

Compounds leached during chemotherapy nebulization with the MDN are toxicologically safe. MDN-PIPAC administrations are safe and the postoperative course is comparable to that of the conventional PIPAC nebulizer.

MINI ABSTRACT

Toxicological analyses confirm that doxorubicin, cisplatin, and oxaliplatin nebulized with the MDN do not release leachables that pose a toxicological risk to patients. Through technical risk analysis and PIPAC simulations, a safety concept for the administration of MDN-PIPAC was established. No technical/medical intraoperative adverse events were observed. The perioperative course was comparable to that of the conventional axial single-direction nebulizer (SDN) PIPAC.
Microsatellites reveal high polymorphism and high potential for use in antimalarial efficacy studies in areas with different transmission intensities in mainland Tanzania
Authors: Ishengoma Deus S. , Mandara Celine I. , Madebe Rashid A. , Warsame Marian , Ngasala Billy , Kabanywanyi Abdunoor M. , Mahende Muhidin K. , Kamugisha Erasmus , Kavishe Reginald A. , Muro Florida , Mandike Renata , Mkude Sigsbert , Chacky Frank , Njau Ritha , Martin Troy , Mohamed Ally , Bailey Jeffrey A. , Fola Abebe A.
Published: December 2023

Background

Tanzania is currently implementing therapeutic efficacy studies (TES) in areas of varying malaria transmission intensities as per the World Health Organization’s (WHO) recommendations. In TES, distinguishing reinfection from recrudescence is critical for the determination of antimalarial efficacy. Recently, the WHO recommended genotyping polymorphic coding genes (msp1, msp2, andglurp) and highly polymorphic neutral microsatellites inPlasmodium falciparumto adjust the efficacy of antimalarials in TES. This study assessed the polymorphisms of six neutral microsatellite markers and their potential use in TES, which are routinely performed in Tanzania.

Methods

P. falciparumsamples were obtained from four TES sentinel sites, Kibaha (Pwani), Mkuzi (Tanga), Mlimba (Morogoro), and Ujiji (Kigoma), between April and September 2016. Parasite genomic DNA was extracted from dried blood spots on filter papers using commercial kits. Genotyping was performed using six microsatellites (Poly-α, PfPK2, TA1, C3M69, C2M34 and 2490) by the capillary method, and the data were analyzed to determine the extent of polymorphisms and genetic diversity at the four sites.

Results

Overall, 83 (88.3%) of the 94 samples were successfully genotyped (with positive results for ≥50.0% of the markers), and >50.0% (range = 47.6-59.1%) were polyclonal, with the mean multiplicity of infection ranging from 1.68 to 1.88 among the four sites. There was high genetic diversity but limited variability among the four sites based on mean allelic richness (RS = 7.48, range= 7.27- 8.03, for an adjusted minimum sample size of 18 per site) and mean expected heterozygosity (He= 0.83, range= 0.80-0.85). Cluster analysis of haplotypes using STRUCTURE, principal component analysis, and pairwise genetic differentiation (FST) did not detect any population structure, and isolates clustered independently of geographic origin. Of the six markers, Poly-α was the most polymorphic, followed by C2M34, TA1 and C3M69, while 2490 was the least polymorphic.

Conclusion

Microsatellite genotyping revealed high polyclonality and genetic diversity but without any significant population structure. Poly-α, C2M34 and TA1 were the top polymorphic markers and could be adopted for use in TES in Tanzania.
Long-term impact of pre-natal exposure to the Ukraine famine of 1932-1933 on adult type 2 diabetes mellitus
Authors: Lumey L.H. , Li Chihua , Khalangot Mykola , Levchuk Nataliia , Wolowyna Oleh
Published: December 2023

Importance

The long-term impacts of early-life famine exposure on Type 2 Diabetes Mellitus (T2DM) have been widely documented across countries, but it remains less clear what is the critical time window and if there is a dose-response between famine intensity and risk of T2DM.

Objective

To establish the relation between prenatal famine exposure and adult Type 2 diabetes mellitus (T2DM).

Design

A national cross-sectional study.

Setting

The man-made Ukrainian Holodomor famine of 1932-1933.

Participants

A total number of 128,225 T2DM cases diagnosed at age 40 or over from the national diabetes register 2000-2008 in Ukraine. The population at risk includes 10,186,016 Soviet Ukraine births (excepting one oblast/province) between 1930-1938 classified by month and year and oblast of birth.

Exposure

Births born in January-June 1934 from oblasts that experienced extreme, severe, or significant famine in 1932-1933. Famine intensity was measured based on the excess mortality during the famine.

Main Outcomes and Measures

T2DM diagnosis was based on WHO (1999) criteria.

Results

We observed in univariate analysis a 1.8-fold increase in T2DM (OR 1.80; 95% CI 1.74-1.85) among individuals born in the first half-year of 1934 in regions with extreme, severe, or significant famine. We observed no increase among individuals born in regions with no famine. In multivariate analysis across regions and adjusting for season of birth we observed a larger than 2-fold increase (OR 2.21; 95% CI 2.00-2.45). There was a dose-response by famine intensity, with ORs increasing from 1.94 to 2.39 across regions. The pattern was similar in men and women.

Conclusions and Relevance

Births in the first half-year of 1934 were conceived at the height of the Ukraine famine in 1933. This relation for T2DM outcomes points to early gestation as a critical time window relating maternal nutrition in pregnancy to offspring health in later life. Further studies of biological mechanisms should focus on this time window for which changes in DNA methylation and later body size have also been observed.

Key Points

Question

What is the critical time window for early-life famine exposure on Type 2 Diabetes Mellitus (T2DM)? Is there any dose-response relationship between early-life famine exposure and T2DM?

Findings

We found an increased risk of T2DM (Odds Ratio 2.21; 95% CI 2.00-2.45) among individuals born during the first half-year of 1934. A clear dose-response relationship was observed using excess mortality as a measure of famine intensity.

Meaning

Early gestation is a critical time window relating maternal undernutrition in pregnancy to offspring health in later life.