bluuebunny/crossref_metadata_2025 huggingface dataset:
Tocilizumab promotes repair of spinal cord injury by facilitating the restoration of tight junctions between vascular endothelial cells
Authors: Luo Yang , Yao Fei , Shi Yi , Zhu Zhenyu , Xiao Zhaoming , You Xingyu , Liu Yanchang , Yu Shuisheng , Tian Dasheng , Cheng Li , Zheng Meige , Jing Juehua
Published: January 2023

Background

Our previous study demonstrated that M1 macrophages could impair tight junctions (TJs) between vascular endothelial cells by secreting interleukin-6 (IL-6) after spinal cord injury (SCI). Tocilizumab, as a humanized IL-6 receptor (IL-6R) monoclonal antibody approved for the clinic, has been applied in the treatment of neurological diseases in recent years, but the treatment effect of Tocilizumab on the TJs restoration of the blood-spinal cord barrier (BSCB) after SCI remains unclear. This study aimed to explore the effect of Tocilizumab on the restoration of TJs between vascular endothelial cells and axon regeneration after SCI.

Methods

In this study, the mouse complete spinal cord crush injury model was used, and Tocilizumab was continuously injected intrathecally until the day of sample collection. A PBS injection in the same location was included as a control. At 14 days postinjury (dpi) and 28 dpi, spinal cord tissue sections were examined via tissue immunofluorescence. The Basso Mouse Scale (BMS) scores and footprint analysis were used to verify the effect of Tocilizumab on the recovery of motor function in mice after SCI.

Results

We demonstrated that depletion of macrophages has no effect on axon regeneration and motor functional recovery after SCI, but mice subjected to Tocilizumab showed a significant increase in axon regeneration and a better recovery in motor function during the chronic phase after SCI. Moreover, our study demonstrated that at 14 and 28 dpi, the expression of claudin-5 (CLDN5) and zonula occludens-1 (ZO-1) between vascular endothelial cells was significantly increased and the leakage of BSCB was significantly reduced in the injured core after daily intrathecal injection of Tocilizumab. Notably, the infiltration of CD68+ macrophages/microglia and the formation of fibrotic scar were decreased in the injured core after Tocilizumab treatment. Tocilizumab treatment could effectively reduce the IL-6 expression in macrophages in the injured core.

Conclusion

The application of Tocilizumab to antagonize IL-6R can effectively reduce the expression of IL-6 in macrophages and facilitate TJs restoration of the BSCB, which is beneficial for axon regeneration and motor functional recovery after SCI. Hence, Tocilizumab treatment is a potential therapeutic strategy for SCI.
Apicobasal transferrin receptor localization and trafficking in brain capillary endothelial cells
Authors: Nielsen Simone S. E. , Holst Mikkel R. , Langthaler Kristine , Christensen Sarah Christine , Bruun Elisabeth Helena , Brodin Birger , Nielsen Morten S.
Published: January 2023

The detailed mechanisms by which the transferrin receptor (TfR) and associated ligands traffic across brain capillary endothelial cells (BECs) of the CNS-protective blood–brain barrier constitute an important knowledge gap within maintenance and regulation of brain iron homeostasis. This knowledge gap also presents a major obstacle in research aiming to develop strategies for efficient receptor-mediated drug delivery to the brain. While TfR-mediated trafficking from blood to brain have been widely studied, investigation of TfR-mediated trafficking from brain to blood has been limited. In this study we investigated TfR distribution on the apical and basal plasma membranes of BECs using expansion microscopy, enabling sufficient resolution to separate the cellular plasma membranes of these morphological flat cells, and verifying both apical and basal TfR membrane domain localization. Using immunofluorescence-based transcellular transport studies, we delineated endosomal sorting of TfR endocytosed from the apical and basal membrane, respectively, as well as bi-directional TfR transcellular transport capability. The findings indicate different intracellular sorting mechanisms of TfR, depending on the apicobasal trafficking direction across the BBB, with the highest transcytosis capacity in the brain-to-blood direction. These results are of high importance for the current understanding of brain iron homeostasis. Also, the high level of TfR trafficking from the basal to apical membrane of BECs potentially explains the low transcytosis which are observed for the TfR-targeted therapeutics to the brain parenchyma.
Early management of isolated severe traumatic brain injury patients in a hospital without neurosurgical capabilities: a consensus and clinical recommendations of the World Society of Emergency Surgery (WSES)
Authors: Picetti Edoardo , Catena Fausto , Abu-Zidan Fikri , Ansaloni Luca , Armonda Rocco A. , Bala Miklosh , Balogh Zsolt J. , Bertuccio Alessandro , Biffl Walt L. , Bouzat Pierre , Buki Andras , Cerasti Davide , Chesnut Randall M. , Citerio Giuseppe , Coccolini Federico , Coimbra Raul , Coniglio Carlo , Fainardi Enrico , Gupta Deepak , Gurney Jennifer M. , Hawryluk Gregory W. J. , Helbok Raimund , Hutchinson Peter J. A. , Iaccarino Corrado , Kolias Angelos , Maier Ronald W. , Martin Matthew J. , Meyfroidt Geert , Okonkwo David O. , Rasulo Frank , Rizoli Sandro , Rubiano Andres , Sahuquillo Juan , Sams Valerie G. , Servadei Franco , Sharma Deepak , Shutter Lori , Stahel Philip F. , Taccone Fabio S. , Udy Andrew , Zoerle Tommaso , Agnoletti Vanni , Bravi Francesca , De Simone Belinda , Kluger Yoram , Martino Costanza , Moore Ernest E. , Sartelli Massimo , Weber Dieter , Robba Chiara
Published: January 2023

Background

Severe traumatic brain-injured (TBI) patients should be primarily admitted to a hub trauma center (hospital with neurosurgical capabilities) to allow immediate delivery of appropriate care in a specialized environment. Sometimes, severe TBI patients are admitted to a spoke hospital (hospital without neurosurgical capabilities), and scarce data are available regarding the optimal management of severe isolated TBI patients who do not have immediate access to neurosurgical care.

Methods

A multidisciplinary consensus panel composed of 41 physicians selected for their established clinical and scientific expertise in the acute management of TBI patients with different specializations (anesthesia/intensive care, neurocritical care, acute care surgery, neurosurgery and neuroradiology) was established. The consensus was endorsed by the World Society of Emergency Surgery, and a modified Delphi approach was adopted.

Results

A total of 28 statements were proposed and discussed. Consensus was reached on 22 strong recommendations and 3 weak recommendations. In three cases, where consensus was not reached, no recommendation was provided.

Conclusions

This consensus provides practical recommendations to support clinician’s decision making in the management of isolated severe TBI patients in centers without neurosurgical capabilities and during transfer to a hub center.
Hypertonic saline infusion does not improve the chance of primary fascial closure after damage control laparotomy: a randomized controlled trial
Authors: García Alberto F. , Manzano-Nunez Ramiro , Carrillo Diana Cristina , Chica-Yanten Julian , Naranjo María Paula , Sánchez Álvaro I. , Mejía Jorge Humberto , Ospina-Tascón Gustavo Adolfo , Ordoñez Carlos A. , Bayona Juan Gabriel , Puyana Juan Carlos
Published: January 2023

Background

Previous observational studies showed higher rates of abdominal wall closure with the use of hypertonic saline in trauma patients with abdominal injuries. However, no randomized controlled trials have been performed on this matter. This double-blind randomized clinical trial assessed the effect of 3% hypertonic saline (HS) solution on primary fascial closure and the timing of abdominal wall closure among patients who underwent damage control laparotomy for bleeding control.

Methods

Double-blind randomized clinical trial. Patients with abdominal injuries requiring damage control laparotomy (DCL) were randomly allocated to receive a 72-h infusion (rate: 50 mL/h) of 3% HS or 0.9 N isotonic saline (NS) after the index DCL. The primary endpoint was the proportion of patients with abdominal wall closure in the first seven days after the index DCL.

Results

The study was suspended in the first interim analysis because of futility. A total of 52 patients were included. Of these, 27 and 25 were randomly allocated to NS and HS, respectively. There were no significant differences in the rates of abdominal wall closure between groups (HS: 19 [79.2%] vs. NS: 17 [70.8%]; p = 0.71). In contrast, significantly higher hypernatremia rates were observed in the HS group (HS: 11 [44%] vs. NS: 1 [3.7%]; p < 0.001).

Conclusion

This double-blind randomized clinical trial showed no benefit of HS solution in primary fascial closure rates. Patients randomized to HS had higher sodium concentrations after the first day and were more likely to present hypernatremia. We do not recommend using HS in patients undergoing damage control laparotomy.

Trial registration The trial protocol was registered in clinicaltrials.gov (identifier: NCT02542241).
The incidence and risk factors for femoral head necrosis after femoral neck fracture in pediatric patients: a systematic review and meta-analysis
Authors: Xin Pengfei , Li Ziqi , Pei Shaoqiang , Shi Qi , Xiao Lianbo
Published: January 2023

Background

The incidence of avascular necrosis (AVN) after pediatric femoral neck fracture (PFNF) in the literature varies widely, and the risk factors associated with AVN after PFNF are controversial. Therefore, this study aimed to accurately investigate the incidence of AVN after PFNF and systematically evaluate and meta-classify their risk factors.

Methods

A comprehensive search was performed of PubMed, Web of Science, and Embase. The pooled rate and 95% confidence interval (CI) were used to assess the incidence of AVN after PFNF, and pooled odds ratio (OR) were calculated to measure the effect sizes. In addition, we performed subgroup, stratified, and publication bias analyses.

Results

A total of 30 articles were included in our meta-analysis, with 303 AVN cases among 1185 patients. The pooled incidence of AVN after PFNF was 22% (95% CI 18%, 27%). Subgroup analyses indicated Delbet type I–IV fracture incidences with AVN of 45%, 32%, 17%, and 12%, respectively. The incidence of AVN after PFNF in Asia was 19%, lower than in Africa at 36%, Europe at 26%, and North America at 23%. In addition, the larger sample size group and the earlier published literature group showed a higher incidence of necrosis. Stratified analyses showed that patient age and Delbet fracture classification were both important factors affecting AVN after PFNF (OR = 1.61, p = 0.02 and OR = 3.02, p < 0.001, respectively), while the time to treatment was not (OR = 0.9, p = 0.71).

Conclusion

The pooled incidence of AVN after PFNF was ~ 22%; furthermore, the available evidence demonstrates that patient age and Delbet type of fracture were important influencing factors of AVN after PFNF.
ATAC-seq and RNA-seq analysis unravel the mechanism of sex differentiation and infertility in sex reversal chicken
Authors: Zhang Xiuan , Li Jianbo , Wang Xiqiong , Jie Yuchen , Sun Congjiao , Zheng Jiangxia , Li Junying , Yang Ning , Chen Sirui
Published: January 2023

Background

Sex determination and differentiation are complex and delicate processes. In female chickens, the process of sex differentiation is sensitive and prone to be affected by the administration of aromatase inhibitors, which result in chicken sex reversal and infertility. However, the molecular mechanisms underlying sex differentiation and infertility in chicken sex reversal remain unclear. Therefore, we established a sex-reversed chicken flock by injecting an aromatase inhibitor, fadrozole, and constructed relatively high-resolution profiles of the gene expression and chromatin accessibility of embryonic gonads.

Results

We revealed that fadrozole affected the transcriptional activities of several genes, such as DMRT1, SOX9, FOXL2, and CYP19A1, related to sex determination and differentiation, and the expression of a set of gonadal development-related genes, such as FGFR3 and TOX3, by regulating nearby open chromatin regions in sex-reversed chicken embryos. After sexual maturity, the sex-reversed chickens were confirmed to be infertile, and the possible causes of this infertility were further investigated. We found that the structure of the gonads and sperm were greatly deformed, and we identified several promising genes related to spermatogenesis and infertility, such as SPEF2, DNAI1, and TACR3, through RNA-seq.

Conclusions

This study provides clear insights into the exploration of potential molecular basis underlying sex differentiation and infertility in sex-reversed chickens and lays a foundation for further research into the sex development of birds.
Electric field stimulation boosts neuronal differentiation of neural stem cells for spinal cord injury treatment via PI3K/Akt/GSK-3β/β-catenin activation
Authors: Liu Qian , Telezhkin Vsevolod , Jiang Wenkai , Gu Yu , Wang Yan , Hong Wei , Tian Weiming , Yarova Polina , Zhang Gaofeng , Lee Simon Ming-yuen , Zhang Peng , Zhao Min , Allen Nicholas D. , Hirsch Emilio , Penninger Josef , Song Bing
Published: January 2023

Background

Neural stem cells (NSCs) are considered as candidates for cell replacement therapy in many neurological disorders. However, the propensity for their differentiation to proceed more glial rather than neuronal phenotypes in pathological conditions limits positive outcomes of reparative transplantation. Exogenous physical stimulation to favor the neuronal differentiation of NSCs without extra chemical side effect could alleviate the problem, providing a safe and highly efficient cell therapy to accelerate neurological recovery following neuronal injuries.

Results

With 7-day physiological electric field (EF) stimulation at 100 mV/mm, we recorded the boosted neuronal differentiation of NSCs, comparing to the non-EF treated cells with 2.3-fold higher MAP2 positive cell ratio, 1.6-fold longer neuronal process and 2.4-fold higher cells ratio with neuronal spontaneous action potential. While with the classical medium induction, the neuronal spontaneous potential may only achieve after 21-day induction. Deficiency of either PI3Kγ or β-catenin abolished the above improvement, demonstrating the requirement of the PI3K/Akt/GSK-3β/β-catenin cascade activation in the physiological EF stimulation boosted neuronal differentiation of NSCs. When transplanted into the spinal cord injury (SCI) modelled mice, these EF pre-stimulated NSCs were recorded to develop twofold higher proportion of neurons, comparing to the non-EF treated NSCs. Along with the boosted neuronal differentiation following transplantation, we also recorded the improved neurogenesis in the impacted spinal cord and the significantly benefitted hind limp motor function repair of the SCI mice.

Conclusions

In conclusion, we demonstrated physiological EF stimulation as an efficient method to boost the neuronal differentiation of NSCs via the PI3K/Akt/GSK-3β/β-catenin activation. Pre-treatment with the EF stimulation induction before NSCs transplantation would notably improve the therapeutic outcome for neurogenesis and neurofunction recovery of SCI.
The burden of disease of fatal and non-fatal burn injuries for the full spectrum of care in the Netherlands
Authors: Spronk Inge , van Baar Margriet E. , Verheij Robert A. , Panneman Martien J. , Dokter Jan , Polinder Suzanne , Haagsma Juanita A.
Published: January 2023

Background

A comprehensive overview of the burden of disease of burns for the full spectrum of care is not available. Therefore, we estimated the burden of disease of burns for the full spectrum in the Netherlands in 2018, and explored whether the burden of disease changed over the past 5 years (2014-2018).

Methods

Data were collected at four levels: general practice, emergency department, hospital, and mortality data. For each level, years lived with disability (YLD), years of life lost (YLL), and disability-adjusted life-years (DALY) were estimated using a tailored methodology.

Results

Burns resulted in a total of 9278 DALYs in the Netherlands in 2018, comprising of 7385 YLDs (80%) and 1892 YLLs (20%). Burn patients who visited the general practice contributed most DALYs (64%), followed by deceased burn patients (20%), burn patients admitted to hospital (14%) and those treated at the emergency department (2%). The burden of disease was comparable in both sexes (4734 DALYs (51%) for females; 4544 DALYs (49%) for males), though the distribution of DALYs by level of care varied; females contributed more DALYs at the general practice level, and males at all other levels of care. Among children boys 0-4 years had the highest burden of disease (784 DALYs (9%)), and among adults, females 18-34 years old (1319 DALYs (14.2%)) had the highest burden of disease. Between 2014 and 2018 there was a marginal increase of 0.8% in the number of DALYs.

Conclusions

Burns cause a substantial burden of disease, with burns requiring care at the general practice level contributing most DALYs. Information on burden of burns by the full level of care as well as by subgroup is important for the development of tailored burn prevention strategies, and the updated figures are recommended to be used for priority setting and resource allocation.
p85S6K sustains synaptic GluA1 to ameliorate cognitive deficits in Alzheimer’s disease
Authors: Li Jia-Bing , Hu Xiao-Yu , Chen Mu-Wen , Xiong Cai-Hong , Zhao Na , Ge Yan-Hui , Wang Hao , Gao Xiao-Ling , Xu Nan-Jie , Zhao Lan-Xue , Yu Zhi-Hua , Chen Hong-Zhuan , Qiu Yu
Published: January 2023

Background

Ribosomal protein S6 kinase 1 (S6K1) is a serine–threonine kinase that has two main isoforms: p70S6K (70-kDa isoform) and p85S6K (85-kDa isoform). p70S6K, with its upstream mammalian target of rapamycin (mTOR), has been shown to be involved in learning and memory and participate in the pathophysiology of Alzheimer’s disease (AD). However, the function of p85S6K has long been neglected due to its high similarity to p70S6k. The role of p85S6K in learning and memory is still largely unknown.

Methods

We fractionated the postsynaptic densities to illustrate the differential distribution of p85S6K and p70S6K. Coimmunoprecipitation was performed to unveil interactions between p85S6K and the GluA1 subunit of AMPA receptor. The roles of p85S6K in synaptic targeting of GluA1 and learning and memory were evaluated by specific knockdown or overexpression of p85S6K followed by a broad range of methodologies including immunofluorescence, Western blot, in situ proximity ligation assay, morphological staining and behavioral examination. Further, the expression level of p85S6K was measured in brains from AD patients and AD model mice.

Results

p85S6K, but not p70S6K, was enriched in the postsynaptic densities. Moreover, knockdown of p85S6K resulted in defective spatial and recognition memory. In addition, p85S6K could interact with the GluA1 subunit of AMPA receptor through synapse-associated protein 97 and A-kinase anchoring protein 79/150. Mechanistic studies demonstrated that p85S6K could directly phosphorylate GluA1 at Ser845 and increase the amount of GluA1 in synapses, thus sustaining synaptic function and spine densities. Moreover, p85S6K was found to be specifically decreased in the synaptosomal compartment in the brains of AD patients and AD mice. Overexpression of p85S6K ameliorated the synaptic deficits and cognitive impairment in transgenic AD model mice.

Conclusions

These results strongly imply a significant role for p85S6K in maintaining synaptic and cognitive function by interacting with GluA1. The findings provide an insight into the rational targeting of p85S6K as a therapeutic potential for AD.
Challenges to joint planning, monitoring, and evaluation for nutrition-sensitive agriculture in Ethiopia: an exploratory qualitative study
Authors: Bezabih Afework Mulugeta , Kahsay Znabu Hadush , Kahsay Amaha , Bekele Abate , Seid Omer , Asfaw Selemawit , Gebrearegay Freweeini , Tadesse Kidane , Bazzano Alessandra N. , Jogo Wellington , Covic Namukolo , Busse Heidi
Published: January 2023

Background

Nutrition-sensitive agriculture is an effective multi-sectoral approach to address the underlying causes of malnutrition. However, successful implementation requires the involvement of different sectors to jointly plan, monitor, and evaluate key activities, which is often challenged by contextual barriers. Previous studies in Ethiopia have not adequately explored these contextual barriers. Hence, the current study aimed to qualitatively explore the challenges to joint planning, monitoring, and evaluation for nutrition-sensitive agriculture among sectors in Ethiopia.

Methods

A qualitative exploratory study was conducted in Tigray and Southern Nations, Nationalities, and Peoples (SNNP) of Ethiopia regional states in 2017. Ninety-four key informants were purposively selected from government agencies primarily in health and agriculture, from local (kebele) to national levels, and ranging from academic organizations, research institutions, and implementing partners. Researchers developed a semi-structured guide and conducted key informant interviews which were audiotaped, transcribed verbatim in local language, and translated to English. All transcriptions were imported into ATLAS.ti Version 7.5 software for coding and analysis. The data analysis followed an inductive approach. Transcriptions were coded line by line; then similar codes were grouped into categories. Subsequently, non-repetitive themes were identified from the categories using thematic analysis methodology.

Results

The following themes were identified as challenges that hinder joint planning, monitoring, and evaluation to link nutrition to agriculture: (1) limited capacity, (2) workload in home sector (agriculture or nutrition), (3) lack of attention to nutrition interventions, (4) inadequate supportive supervision, (5) problematic reporting system, and (6) weak technical coordinating committees.

Conclusions and recommendations

Gaps in human and technical resources, limited attention from different sectors, and absence of routine monitoring data hindered joint planning, monitoring, and evaluation activities for nutrition-sensitive agriculture in Ethiopia. Short-term and long-term training for experts and intensification of supportive supervision may address gaps in capacity. Future studies should address whether routine monitoring and surveillance in nutrition-sensitive multi-sectoral activities provides long-term improvement in outcomes.
Differential effects of mutations of POPDC proteins on heteromeric interaction and membrane trafficking
Authors: Swan Alexander H. , Schindler Roland F. R. , Savarese Marco , Mayer Isabelle , Rinné Susanne , Bleser Felix , Schänzer Anne , Hahn Andreas , Sabatelli Mario , Perna Francesco , Chapman Kathryn , Pfuhl Mark , Spivey Alan C. , Decher Niels , Udd Bjarne , Tasca Giorgio , Brand Thomas
Published: January 2023

The Popeye domain containing (POPDC) genes encode sarcolemma-localized cAMP effector proteins. Mutations in blood vessel epicardial substance (BVES) also known as POPDC1 and POPDC2 have been associated with limb-girdle muscular dystrophy and cardiac arrhythmia. Muscle biopsies of affected patients display impaired membrane trafficking of both POPDC isoforms. Biopsy material of patients carrying mutations in BVES were immunostained with POPDC antibodies. The interaction of POPDC proteins was investigated by co-precipitation, proximity ligation, bioluminescence resonance energy transfer and bimolecular fluorescence complementation. Site-directed mutagenesis was utilised to map the domains involved in protein–protein interaction. Patients carrying a novel homozygous variant, BVES (c.547G > T, p.V183F) displayed only a skeletal muscle pathology and a mild impairment of membrane trafficking of both POPDC isoforms. In contrast, variants such as BVES p.Q153X or POPDC2 p.W188X were associated with a greater impairment of membrane trafficking. Co-transfection analysis in HEK293 cells revealed that POPDC proteins interact with each other through a helix-helix interface located at the C-terminus of the Popeye domain. Site-directed mutagenesis of an array of ultra-conserved hydrophobic residues demonstrated that some of them are required for membrane trafficking of the POPDC1–POPDC2 complex. Mutations in POPDC proteins that cause an impairment in membrane localization affect POPDC complex formation while mutations which leave protein–protein interaction intact likely affect some other essential function of POPDC proteins.
Population pharmacokinetics and limited sampling strategy for therapeutic drug monitoring of mycophenolate mofetil in Japanese patients with lupus nephritis
Authors: Mizaki Tomoko , Nobata Hironobu , Banno Shogo , Yamaguchi Makoto , Kinashi Hiroshi , Iwagaitsu Shiho , Ishimoto Takuji , Kuru Yukiko , Ohnishi Masafumi , Sako Ken-ichi , Ito Yasuhiko
Published: January 2023

Background

Mycophenolate mofetil (MMF), a prodrug of the immunosuppressive agent mycophenolic acid (MPA), is difficult to administer because of the pharmacokinetic complexity of MPA. Although dosage adjustment according to the 12-h area under the concentration–time curve (AUC0-12) is thought to be desirable, multiple blood samplings for AUC calculation may pose a clinical challenge. A limited sampling strategy (LSS) would provide a solution; however, little is known about MPA pharmacokinetics in lupus nephritis patients, especially in those with Asian backgrounds, or few, if any, LSSs are reported for them.

Methods

Thirty-four adult Japanese patients receiving MMF for lupus nephritis were examined retrospectively. MPA pharmacokinetics were investigated, and a PPK model was developed using Phoenix® NLME™ software. Single and double blood sampling strategies from Bayesian estimation using the PPK model and from multiple linear regression were compared. Tolerability was also evaluated.

Results

In the pharmacokinetic analysis, renal function and serum albumin had significant effects on dose-normalized AUC0-12; and serum albumin, concomitant proton pump inhibitor (PPI) and iron/magnesium oxide did on dose-normalized maximum concentration. As a PPK model, a two-compartment model was developed with a transit absorption model and first-order elimination, in which creatinine clearance and serum albumin were covariates for MPA clearance. The double sampling strategy at 1 and 4 h by multiple linear regression showed the best agreement with the observed AUC0-12 (r2 = 0.885). Of the single sampling strategies, the one at 6 h by Bayesian estimation performed best (r2 = 0.769). The tolerability evaluation showed that correlations were suggested for gastrointestinal involvement.

Conclusions

The present study developed the first PPK model of MPA for Japanese lupus nephritis patients. As for LSSs, a double sampling strategy at 1 and 4 h by multiple linear regression would work best; when only a single blood sampling is allowed, a strategy at 6 h by Bayesian estimation using the PPK model developed in this study would be best. The LSSs good enough for clinical use may facilitate safer, more effective, and individualized therapy.
Transient loss of consciousness immediately after total pancreatectomy for pancreatic metastases from renal cell carcinoma: a case report
Authors: Masuda Yasutaka , Kiritani Sho , Arita Junichi , Ichida Akihiko , Kawaguchi Yoshikuni , Akamatsu Nobuhisa , Kaneko Junichi , Hasegawa Kiyoshi
Published: January 2023

Background

Total pancreatectomy (TP) is often selected for treatment of various pancreatic diseases. However, the resultant lack of autoregulation of glycometabolism necessitates careful postoperative management.

Case presentation

A 77-year-old man who had undergone right nephrectomy for renal cell carcinoma 11 years previously presented with multiple histologically diagnosed pancreatic metastases. The patient had no notable comorbidities, including diabetes. Because no extrapancreatic organ metastasis was identified, he underwent TP as a curative treatment. He awoke from anesthesia and was extubated without any problems in the operating room. However, 15 min after entering the intensive care unit, he suddenly lost consciousness and became apneic, resulting in reintubation. Blood gas analysis revealed an increased glucose concentration (302 mg/dL) and mixed acid–base disorder (pH of 7.21) due to insulin insufficiency and fentanyl administration. After induction of continuous intravenous insulin infusion and termination of fentanyl, the glucose concentration and pH gradually improved. He regained clear consciousness and spontaneous ventilation and was extubated the next day with no difficulties or complications.

Conclusion

This case highlights the importance of active monitoring of the glycemic state and pH after TP because of the possibility of deterioration due to TP itself as well as the lingering effects of anesthesia.
Exercise Mode in Heart Failure: A Systematic Review and Meta-Analysis
Authors: Edwards Jamie , Shanmugam Nesan , Ray Robin , Jouhra Fadi , Mancio Jennifer , Wiles Jonathan , Marciniak Anna , Sharma Rajan , O’Driscoll Jamie
Published: January 2023

Background

Optimising exercise prescription in heart failure (HF) with a preserved (HFpEF) or reduced (HFrEF) ejection fraction is clinically important. As such, the aim of this meta-analysis was to compare traditional moderate intensity training (MIT) against combined aerobic and resistance training (CT) and high-intensity interval training (HIIT) for improving aerobic capacity (VO2), as well as other clinically relevant parameters.

Methods

A comprehensive systematic search was performed to identify randomised controlled trials published between 1990 and May 2021. Research trials reporting the effects of MIT against CT or HIIT on peak VO2 in HFpEF or HFrEF were considered. Left-ventricular ejection fraction (LVEF) and various markers of diastolic function were also analysed.

Results

Seventeen studies were included in the final analysis, 4 of which compared MIT against CT and 13 compared MIT against HIIT. There were no significant differences between MIT and CT for peak VO2 (weighted mean difference [WMD]: 0.521 ml min−1 kg−1, [95% CI] =  − 0.7 to 1.8, Pfixed = 0.412) or LVEF (WMD: − 1.129%, [95% CI] =  − 3.8 to 1.5, Pfixed = 0.408). However, HIIT was significantly more effective than MIT at improving peak VO2 (WMD: 1.62 ml min−1 kg−1, [95% CI] = 0.6–2.6, Prandom = 0.002) and LVEF (WMD: 3.24%, [95% CI] = 1.7–4.8, Prandom < 0.001) in HF patients. When dichotomized by HF phenotype, HIIT remained significantly more effective than MIT in all analyses except for peak VO2 in HFpEF.

Conclusions

HIIT is significantly more effective than MIT for improving peak VO2 and LVEF in HF patients. With the exception of peak VO2 in HFpEF, these findings remain consistent in both phenotypes. Separately, there is no difference in peak VO2 and LVEF change following MIT or CT, suggesting that the addition of resistance exercise does not inhibit aerobic adaptations in HF.

Graphical Abstract
Effect of Moringa oleifera leaves powder in diets of lactating buffaloes
Authors: El-Badawi Alaa-Eldin Y. , Hassan Ayman A. , Khalel Mohamed S. , Yacout Mohamed H. M. , El Naggar Soad
Published: January 2023

Background

Egyptian water buffalo as a dairy animal is adapted to the environmental conditions in Egypt and most of it is with small farmers, therefore, it was necessary to pay attention to improve its nutrition, increase its milk production, and improve its components by adding some feedstuffs of high nutritional value as Moringa oleifera which is a rapidly growing plant that is planted in tropical and subtropical area, in addition its leaves have high nutritive value, and it contains anti-oxidative and bioactive compounds, low anti-nutrient content and high amount of magnesium, which has positive effects on milk yield.

Results

The results revealed that, daily milk or 4% FCM yields was significantly (P < 0.05) highest for diet supplemented by 50 g Moringa olifera leaves powder (MOLP, R2) compared with the other groups. By increasing MOLP supplementation level there was a significant (P < 0.05) decrease in daily milk yield than control. Milk contents of protein, fat and total solids were significantly (P < 0.05) increased, but lactose or solid not fat contents were significantly (P < 0.05) decreased than control with increasing MOLP level. The highest values of dietary nutrients digestibility and nutritive values (TDN and DCP%) were recorded with R2 and the lowest were recorded for R4. Blood serum total protein, albumin and globulin contents were significantly (P < 0.05) higher with feeding MOLP supplemented diets than control particularly for R2 and R3. While, there were significant (P < 0.05) decrease in urea, glucose and cholesterol but creatinine, AST and ALT were gradually increased with increasing MOLP level. Rations supplemented with MOLP was associated with obvious increase (P < 0.05) of antioxidant enzymes (GR, GPx, Cat and SOD) and decrease free radicals and the effect was more pronounced with increasing the supplementation level.

Conclusions

These results indicated that 50 g Moringa olifera leaves powder supplementation to the diets of milking buffaloes improved milk yield, milk composition, nutrients digestibility, nutritive value and total antioxidant capacity.
Re-evaluating benzodiazepines for anxiety disorders – déjà-vu all over again?
Authors: Anderson Ian M.
Published: January 2023

Benzodiazepines have attracted controversy from shortly after their introduction. They have been subject to periodic calls for their use to be re-evaluated on the basis that their risks have been overstated and their benefits underappreciated. Claims made in recent editorials from the International Task Force on Benzodiazepines in support of their wider use are critiqued in this issue. I examine here whether there is a case to change the conclusions of previous reconsiderations of the question.
Hypoparathyroidism, Sensorineural Deafness, and Renal Disease Syndrome Presenting With Febrile Seizures and Hypocalcemia
Authors: Gandolfi Anne , Ratnasamy Kevin , Minutti Carla
Published: January 2023

HDR syndrome is a rare genetic disorder caused by mutations in the GATA3 gene and characterized by hypoparathyroidism, sensorineural deafness, and renal disease. Here, we report case of a 9-month-old male with history of hydronephrosis and sensorineural deafness who presented with febrile seizures. He was found to have hypocalcemia and inappropriately normal parathyroid hormone. His neurologic and infectious workup were negative. Genetic testing revealed a nonsense mutation in the GATA3 gene, consistent with HDR syndrome. Hypocalcemia was responsive to calcium carbonate and calcitriol treatment. This case highlights hypocalcemia caused by hypoparathyroidism as a potential etiology of seizures. When hypoparathyroidism is detected with either hearing loss or renal disease, HDR syndrome should be considered, and other features of the syndrome should be investigated.
Epidemiology of Enterococcus, Staphylococcus aureus, Klebsiella, Acinetobacter, Pseudomonas, and Enterobacter Species Transmission in the Pediatric Anesthesia Work Area Environment With and Without Practitioner Use of a Personalized Body-Worn Alcohol Dispenser
Authors: Fernandez Patrick G. , Dexter Franklin , Brown Jeremiah , Whitney Gina , Koff Matthew D. , Cao Scott , Loftus Randy W.
Published: January 2023

BACKGROUND:

Personalized body-worn alcohol dispensers may serve as an important tool for perioperative infection control, but the impact of these devices on the epidemiology of transmission of high-risk Enterococcus, Staphylococcus aureus, Klebsiella, Acinetobacter, Pseudomonas, and Enterobacter (ESKAPE) pathogens is unknown. We aimed to characterize the epidemiology of ESKAPE transmission in the pediatric anesthesia work area environment with and without a personalized body-worn alcohol dispenser.

METHODS:

This controlled before and after study included 40 pediatric patients enrolled over a 1-year study period. Two groups of operating room cases were compared: (1) operating room cases caring for patients with usual care (December 17, 2019, to August 25, 2020), and (2) operating room cases caring for patients with usual care plus the addition of a personalized, body-worn alcohol hand rub dispenser (September 30, 2020, to December 16, 2020). Operating rooms were randomly selected for observation of ESKAPE transmission in both groups. Device use was tracked via wireless technology and recorded in hourly hand decontamination events.

RESULTS:

Anesthesia providers used the alcohol dispenser 3.3 ± 2.1 times per hour. A total of 57 ESKAPE transmission events (29 treatment and 28 control) were identified. The personalized body-worn alcohol dispenser impacted ESKAPE transmission by increasing the contribution of provider hand contamination at case start (21/29 device versus 10/28 usual care; relative risk, [RR] 2.03; 99.17% confidence interval [CI], 1.025–5.27; P = .0066) and decreasing the contribution of environmental contamination at case end (3/29 device versus 12/28 usual care; RR, 0.24; 99.17% CI, 0.022–0.947; P = .0059). ESKAPE pathogen contamination involved 20% (8/40) of patient intravascular devices. There were 85% (34/40) of preoperative patient skin surfaces contaminated with ≥1 (1.78 ± 0.19 [standard deviation {SD}]) ESKAPE pathogens.

CONCLUSIONS:

A personalized body-worn alcohol dispenser can impact the epidemiology of ESKAPE transmission in the pediatric anesthesia work area environment. Improved preoperative patient decolonization and vascular care are indicated to address ESKAPE pathogens among pediatric anesthesia work area reservoirs.
Archive as Offering
Authors: Sanders Johnson Grace L.
Published: January 2023

This essay tells the story of Estrea Jean Gilles, a nineteen-year-old girl who was killed by Marines during the US occupation of Haiti (1915–34). With the crash described as an “unavoidable” accident and the documents cataloged under “miscellaneous,” Estrea’s archived life guides this study of transnational practices of anti-Black violence and accounts for the possibilities of Black women’s futures beyond their record of disappearance. Naming the layered applications, quotidian quality, and refusals of physical, psychological, and archival violence during the US occupation, this essay ultimately considers experimental historical practices as an opportunity to intervene in the presumed teleology of Black women’s lives through the practice of archival offering.
Understanding and modeling nerve–cancer interactions
Authors: Le Thanh T. , Oudin Madeleine J.
Published: January 2023

The peripheral nervous system plays an important role in cancer progression. Studies in multiple cancer types have shown that higher intratumoral nerve density is associated with poor outcomes. Peripheral nerves have been shown to directly regulate tumor cell properties, such as growth and metastasis, as well as affect the local environment by modulating angiogenesis and the immune system. In this Review, we discuss the identity of nerves in organs in the periphery where solid tumors grow, the known mechanisms by which nerve density increases in tumors, and the effects these nerves have on cancer progression. We also discuss the strengths and weaknesses of current in vitro and in vivo models used to study nerve–cancer interactions. Increased understanding of the mechanisms by which nerves impact tumor progression and the development of new approaches to study nerve–cancer interactions will facilitate the discovery of novel treatment strategies to treat cancer by targeting nerves.
MADAM: A temporary seismological survey experiment in Aetolia-Akarnanian region (Western Greece)
Authors: Lefils Valentine , Rigo Alexis , Sokos Efthimios
Published: January 2023

The Aetolia-Akarnanian region, in Western Greece, is considered to be part of a micro-plate in formation, named the Ionian Island-Akarnanian Block (IAB), in the larger-scale Central Mediterranean tectonic context. The IAB accommodates the deformations between the surrounding tectonic structures that are the Corinth Gulf, the Hellenic subduction, the Kefalonia Transform Fault and the Apulian collision. This work presents the first results of a dense temporary seismic survey in the Aetolia-Akarnanian region (from the Amvrakikos Gulf to the Patras Gulf). Our local dense network has been designed in order to avoid gaps and to allow the recording of a major part of the Akarnania seismicity. With a semi-automatic events detection and picking program, we detected more than 15000 events from October 2015 to December 2018. With this important data set we constrained a 1D local velocity model. The comparison with the previous published models shows a possible significant velocity variation inside the region and especially at the Trichonis lake graben. Thanks to our data set and our velocity model, we precisely located 12723 seismic events with magnitude 0 < ML < 4.6, and a magnitude of completeness Mc = 1.0, that represents actually the most important catalogue for the Aetolia-Akarnania. Seismicity highlights specific seismic structures as clusters and a seismic plane below the West of Corinth Gulf that are briefly discussed.
Κίνητρα και εμπόδια για μείωση πλαστικού μιας χρήσης στο Πανεπιστήμιο προς έναν αειφορικό μετασχηματισμό του
Authors: Ηλιοπούλου Ιφιγένεια
Published: January 2023

Σκοπός της παρούσας μελέτης είναι η διερεύνηση των απόψεων μελών του Πανεπιστημίου Θεσσαλίας σχετικά με δράσεις μείωσης του πλαστικού μιας χρήσης και πιο συγκεκριμένα σχετικά με τη χρήση του ψύκτη αντί για την αγορά πλαστικών μπουκαλιών νερού και τη χρήση επαναχρησιμοποιούμενων ποτηριών αντί για ποτήρια μιας χρήσης. Πραγματοποιήθηκε ποσοτική έρευνα και χρησιμοποιήθηκε το ερωτηματολόγιο για τη συλλογή δεδομένων. Το δείγμα αποτελείται από 1027 άτομα, μέλη της πανεπιστημιούπολης. Τα αποτελέσματα δείχνουν ότι το 62,7% του δείγματος δήλωσε την πρόθεσή του να χρησιμοποιήσει τον ψύκτη αντί να αγοράζει εμφιαλωμένο νερό έχοντας ως ισχυρό κίνητρο την αίσθηση της προσωπικής συμβολής στην προστασία του περιβάλλοντος και ως βασικό εμπόδιο την αμφιβολία για ασφαλή χρήση του ψύκτη. Το 61,6% του δείγματος θα έφερνε ποτήρι από το σπίτι για το ρόφημά του αντί να το αγόραζε σε ένα πλαστικό ποτήρι μιας χρήσης. Το κύριο εμπόδιο φάνηκε ότι ήταν η δυσκολία να κουβαλούν ένα ποτήρι από το σπίτι, ενώ το μεγαλύτερο κίνητρό τους ήταν να υπάρχει στην αγορά ένα εύκολο στη μεταφορά ποτήρι. Τέλος, υπάρχουν κάποιες προτάσεις με βάση τα αποτελέσματα της έρευνας.
Novel Helicobacter pylori-associated hemolysis Hp0499 and Hp1490 and its association with severity of gastritis
Authors: Widiana Sang Ketut , Sugihartono Titong , Doohan Dalla , Waskito Langgeng Agung , Fauzia Kartika Afrida , Rezkitha Yudith Annisa Ayu , Prakosa Adi Wasis , Alfaray Ricky Indra , Safitri Camilia Metadea Aji , Amalia Rizki , Yamaoka Yoshio , Miftahussurur Muhammad
Published: January 2023

Background: Gastritis is an inflammation of the stomach lining often caused by Helicobacter pylori infection. Among three H. pylori genes coding for hemolytic toxins, the clinical outcome of hp0499 and hp1490 is unclear. We conducted molecular and histological analyses to evaluate the correlation between these genes and gastritis severity.

Methods: We analyzed the hp0499 and hp1490 variants of 116 Indonesian samples using next generation sequencing and validated them using polymerase chain reaction (PCR). The updated Sydney system was used to grade gastritis through histological analyses. We then calculated the influence of hp0499 and hp1490 on the gastritis severity, using multivariate analysis and cagA and vacA as major H. pylori virulence factors.

Results: Two variants of each gene were identified and named hp0499-1 and -2, and hp1490-1 and -2. We noted that hp0499 expression was significantly correlated with corporal atrophy (p = 0.037). H. pylori hp1490 significantly correlated with antral acute and chronic inflammation as well as corporal density (p = 0.025, p = 0.07, p = 0.010, respectively). After adjusting for age and sex, we found that vacA s1m1 was an independent risk factor for acute antral inflammation (p = 0.032). hp1490 and vacA s1m1 were independent risk factors for chronic antral inflammation (p = 0.030 and p = 0.031, respectively).

Conclusions: We identified the variants hp0499-1 and -2 and hp1490-1 and -2 and demonstrated that hp0499 plays a significant role in the severity of corporal atrophy. Moreover, hp1490 was characterized as an independent risk factor for chronic inflammation in the antral region. Therefore, hp0499 and hp1490 are new potential targets for therapeutics.
Epigallocatechin-3-gallate chitosan nanoparticles in an extender improve the antioxidant capacity and post-thawed quality of Kacang goat semen
Authors: Mustofa Imam , Susilowati Suherni , Suprayogi Tri Wahyu , Akintunde Adeyinka Oye , Oktanella Yudit , Purwanto Djoko Agus
Published: January 2023

Background and Aim: The Kacang goat (Capra hircus) is an indigenous livestock species in Indonesia that is at risk of extinction due to cross-breeding. Artificial insemination (AI) techniques are expected to increase the population of these goats. This study aimed to determine the addition of epigallocatechin-3-gallate chitosan nanoparticles (EGCG CNPs) to skim milk–egg yolk (SM–EY) extender to obtain the best possible quality of post-thawed Kacang buck semen for AI.

Materials and Methods:  Fresh Kacang buck semen was diluted in SM–EY without or with the addition of 0.5, 1.0, 1.5, or 2.0 µg of EGCG CNPs/mL extender. Extended semen was packaged in French mini straws, frooze, and stored in liquid nitrogen at −196℃ for 24 hours. Six replicates from each treatment group were thawed for catalase, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, malondialdehyde (MDA), sperm intact plasma membrane (IPM), viability and motility analyses.

Results: Post-thawed semen that was previously frozen without EGCG CNPs in the extender (control group) exhibited the lowest levels of catalase, DPPH, sperm viability, sperm motility, IPM, and the highest levels of MDA. However, the addition of EGCG CNPs at doses of 1.5 µg/mL extender increased post-thawed catalase, DPPH, sperm IPM, viability, and sperm motility and decreased MDA levels (p < 0.05) than those of control group.

Conclusion: This study was the first in which EGCG CNPs were used in SM–EY extender, and the addition of only 1.0 µg/mL of EGCG CNPs in this extender increased the antioxidant capacity and post-thawed quality of Kacang buck semen.
Od walki publicystycznej do magazynu informacyjnego. Lewicowe dziennikarstwo filmowe Heleny Lemańskiej
Authors: Kosma Cieśliński Marek
Published: January 2023

Tematem artykułu jest publicystyka polityczna Heleny Lemańskiej, w latach 1949–1967 redaktorki naczelnej Polskiej Kroniki Filmowej. Tekst ma na celu wskazanie zależności pomiędzy lewicowym światopoglądem dziennikarki a uprawianą przez nią formą filmowej propagandy i jej ewolucją: od narzędzia politycznej indoktrynacji do filmowego zwierciadła, w którym odbijała się rzeczywistość społeczna Polski lat „małej stabilizacji”.