bluuebunny/crossref_metadata_2025 huggingface dataset:
Needs of patients with dementia and their caregivers in primary care: lessons learned from the Alzheimer plan of Quebec
Authors: Khanassov Vladimir , Rojas-Rozo Laura , Sourial Rosa , Yang Xin Qiang , Vedel Isabelle
Published: September 2021

Background

Persons living with dementia have various health and social care needs and expectations, some which are not fully met by health providers, including primary care clinicians. The Quebec Alzheimer plan, implemented in 2014, aimed to cover these needs, but there is no research on the effect this plan had on the needs and expectations of persons living with dementia. The objective of this study is to identify persons living with dementia and caregivers’ met and unmet needs and to describe their experience.

Methods

This is a sequential mixed methods explanatory design: Phase 1: cross-sectional study to describe the met and unmet health and social care needs of community-dwelling persons living with dementia using Camberwell Assessment of Need of the Elderly and Carers’ Assessment for Dementia tools. Phase 2: qualitative descriptive study to explore and understand the experiences of persons living with dementia and caregivers with the use of social and healthcare services, using semi-structured interviews. Data from phase 1 was analyzed with descriptive statistics, and from phase 2, with inductive thematic analysis. Results from phases 1 and 2 were compared, contrasted and interpreted together.

Results

The mean total number of needs reported by the patients was 5.03 (4.48 and 0.55 met and unmet needs, respectively). Caregivers had 0.52 met needs (3.16 unmet needs). The main needs for both were memory, physical health, eyesight/hearing/communication, medication, looking after home, money/budgeting. Three categories were mentioned by the participants: Persons living with dementia and caregiver’s attitude towards memory decline, their perception of community health services and of the family medicine practice.

Conclusions

Our study confirms the findings of other studies on the most common unmet needs of the patients and caregivers that are met partially or not at all. In addition, the participants were satisfied with access to care, and medical services in primary practices, being confident in their family. Our results indicate persons living with dementia and their caregivers need a contact person, a clear explanation of their dementia diagnosis, a care plan, written information on available services, and support for the caregivers.
Imported leishmaniasis in travelers: a 7-year retrospective from a Parisian hospital in France
Authors: Aissaoui Nesrine , Hamane Samia , Gits-Muselli Maud , Petit Antoine , Benderdouche Mazouz , Denis Blandine , Alanio Alexandre , Dellière Sarah , Bagot Martine , Bretagne Stéphane
Published: September 2021

Background

Leishmaniases are regularly seen in non-endemic areas due to the increase of international travels. They include cutaneous leishmaniases (CL) and mucocutaneous (MC) caused by different Leishmania species, and visceral leishmaniases (VL) which present with non-specific symptoms.

Methods

We reviewed all consecutive leishmaniasis cases seen between September 2012 and May 2020. The diagnostic strategy included microscopy after May-Grünwald-Giemsa staining, a diagnostic quantitative PCR (qPCR) assay, and species identification based on sequencing of the cytochrome b gene.

Results

Eighty-nine patients had a definitive leishmaniasis diagnosis. Nine patients had VL with Leishmania infantum. Eighty patients had CL. Twelve patients acquired CL after trips in Latin America (7 Leishmania guyanensis, 2 Leishmania braziliensis, 2 Leishmania mexicana, and 1 Leishmania panamensis). Species could be identified in 63 of the 68 CLs mainly after travel in North Africa (59%) with Leishmania major (65%), Leishmania tropica/killicki (24%), and L. infantum (11%), or in West Sub-Saharan Africa (32%), all due to L. major. The median day between appearance of the lesions and diagnosis was 90 [range 60–127].

Conclusions

Our diagnostic strategy allows both positive diagnoses and species identifications. Travelers in West Sub-Saharan Africa and North Africa should be better aware of the risk of contracting leishmananiasis.
Influenza in patients with respiratory failure admitted to intensive care units in Poland and the use of extracorporeal respiratory support: a survey-based multicenter study
Authors: Smiechowicz Jakub , Barteczko-Grajek Barbara , Adamik Barbara , Bojko Jozef , Gozdzik Waldemar , Lipinska-Gediga Malgorzata
Published: September 2021

Background

In Poland, little is known about the most serious cases of influenza that need admittance to the intensive care unit (ICU), as well as the use of extracorporeal respiratory support.

Methods

This was an electronic survey comprising ICUs in two administrative regions of Poland. The aim of the study was to determine the number of influenza patients with respiratory failure admitted to the ICU in the autumn–winter season of 2018/2019. Furthermore, respiratory support, outcome and other pathogens detected in the airways were investigated.

Results

Influenza infection was confirmed in 76 patients. The A(H1N1)pdm09 strain was the most common. 34 patients died (44.7%). The median age was 62 years, the median sequential organ failure assessment (SOFA) score was 11 and was higher in patients who died (12 vs. 10, p = 0.017). Mechanical ventilation was used in 75 patients and high flow nasal oxygen therapy in 1 patient. Extracorporeal membrane oxygenation (ECMO) was used in 7 patients (6 survived), and extracorporeal carbon dioxide removal (ECCO2R) in 2 (1 survived). The prone position was used in 16 patients. In addition, other pathogens were detected in the airways on admittance to the ICU.

Conclusion

A substantial number of influenza infections occurred in the autumn–winter season of 2018/2019 that required costly treatment in the intensive care units. Upon admission to the ICU, influenza patients had a high degree of organ failure as assessed by the SOFA score, and the mortality rate was 44.7%. Advanced extracorporeal respiratory techniques offer real survival opportunities to patients with severe influenza-related ARDS. The presence of coinfection should be considered in patients with influenza and respiratory failure.
Efficacy of lumbar kinetic chain training for staged rehabilitation after percutaneous endoscopic lumbar discectomy
Authors: Lyu Zhen , Bai Jinzhu , Chen Shizheng , Liu Jiesheng , Yu Wenlong
Published: September 2021

Background

Percutaneous endoscopic lumbar discectomy (PELD) is a promising minimally invasive treatment for lumbar disc herniation (LDH). Postoperative rehabilitation can improve patient outcomes. Not only rehabilitation for surgical trauma but also rehabilitation for lumbar spine and lower kinetic chain dysfunction should be performed. The aims of this study were to investigate the efficacy of a lumbar kinetic chain training for staged rehabilitation after PELD for LDH.

Methods

Fifty one LDH patients treated with PELD were studied. After surgery, patients underwent lumbar kinetic chain training for staged rehabilitation( staged group) or regular low back rehabilitation (regular group). The staged rehabilitation programme included three phases from 2 to 6, 7–12, and 13–24 weeks postoperatively, and different physical therapies were performed during these phases. The low back pain visual analogue scale (VAS), JOA score, ODI, SF-36, and cross-sectional area of the lumbar multifidus on MRI were assessed, and gait analysis was performed.

Results

Twenty five patients in staged group and twenty six patients in regular group were included. There were no significant differences in age or sex between the two groups at baseline (p > 0.05). The VAS score decreased and the JOA and SF-36 scores increased in both groups from baseline to 6 weeks (P < 0.05). In the staged group, compared with the regular group, the VAS and ODI scores were lower and the JOA and SF-36 scores were higher at 6 weeks (P < 0.05); the VAS and ODI scores were lower and the SF-36 score was higher at 12 weeks (P < 0.05); the SF-36 score was higher at 24 weeks (P < 0.05); the cross-sectional area of the lumbar multifidus showed no differences at 12 weeks (P > 0.05); and the left-right support ratio of gait was higher at 24 weeks (P < 0.05).

Conclusions

The staged rehabilitation programme for LDH after PELD promoted postoperative recovery, and the efficacy of lumbar kinetic chain training was higher than that of regular low back muscle exercise.
Hidden blood loss in adolescent idiopathic scoliosis patients undergoing posterior spinal fusion surgery: a retrospective study of 765 cases at a single centre
Authors: Wang Lipeng , Liu Jiangli , Song Xiaoxiao , Luo Muhui , Chen Yongquan
Published: September 2021

Background

In scoliosis corrective surgery, total blood loss is composed of visible blood loss, including intraoperative haemorrhage and drainage, and hidden blood loss in which blood extravasates into the tissues and accumulates in the surgical field. The purpose of this study was to investigate hidden blood loss (HBL) and its potential risk factors in adolescent idiopathic scoliosis patients undergoing posterior spinal fusion surgery and elucidate the influence of HBL on the necessity for postoperative blood transfusion.

Methods

We retrospectively studied adolescent idiopathic scoliosis patients undergoing posterior spine fusion for adolescent idiopathic scoliosis from January 2014 to December 2018 at our hospital. The patients’ demographics, blood loss-related parameters, surgeries and blood loss data were extracted. The association between patient characteristics and HBL was analyzed by Pearson or Spearman correlation analyses. Multivariate linear regression analysis was used to determine independent risk factors associated with HBL. Binary logistic regression analysis was used to analyze the influence of HBL on the necessity for postoperative blood transfusion.

Results

A total of 765 patients, of whom 128 were male and 637 were female (age range 10–18 years), were included in this study. The mean volume of HBL was 693.5 ± 473.4 ml, accounting for 53.9 % of the total blood loss. The multivariate linear regression analysis revealed that preoperative Hct (p = 0.003) and allogeneic blood transfusion (p < 0.001) were independent risk factors for HBL, while tranexamic acid (p = 0.003) was negatively correlated with HBL. Binary logistic regression analysis showed that HBL > 850 ml (P < 0.001, OR: 8.845, 95 % CI: 5.806–13.290) was an independent risk factor for the necessity for postoperative blood transfusion.

Conclusions

Substantial HBL occurred in adolescent idiopathic scoliosis patients undergoing posterior spinal fusion surgeries. Allogeneic blood transfusion and preoperative Hct were independent risk factors for HBL, while tranexamic acid was negatively related to HBL. HBL and its influencing factors should be considered when planning perioperative transfusion management. Patients with HBL greater than 850 ml should be closely monitored in cases of postoperative anaemia.

Level of evidence

Level III.
Pediatric laparoscopic partial cystectomy for the treatment of benign bladder tumors and urachal cysts
Authors: Gao Hongjie , Chen Jiawei , Li Guowei , Cui Xinhai , Sun Fengyin
Published: September 2021

Objective

To investigate the feasibility and efficacy of carrying out pediatric laparoscopic partial cystectomies (LPC) when treating benign bladder tumors and urachal cysts.

Methods

Retrospectivey analyzing 4 clinical cases involving children with bladder tumors, which were collected from October 2017 to December 2018. In these clinical cases, there were 3 male children and 1 female child, aged from 4.5 to 9.4 years old, with an average age of 6.5 years. An intraperitoneal laparoscopic partial cystectomy was performed in the treatment of 3 of these patients with benign bladder tumors and in 1 patient with an urachal cyst. The surgical procedures included a partial cystectomy and a complete intracavitary bladder suture.

Results

All 4 cases were successful and no operation was transferred to opensurgery. The operation time was 100–120 min, with an average time of 108 min. The intraoperative blood loss was 10–20 ml, with an average loss of 15 ml. 6 h after the operation, the patients still maintained a fluid diet and 1 case of hematuria had occurred, with the catheter removed 12 days after the operation. No postoperative urine leakage, intestinal adhesion or intestinal obstruction occurred, and the average postoperative hospitalization time was 14 days.

Conclusion

Laparoscopic partial cystectomy is a safe and feasible method to be used for the treatment of benign bladder tumors and urachal cysts. It presents the advantages of being minimally invasive, and having a quick recovery and short hospitalization time. It is an alternative surgical method for the treatment of pediatric benign bladder tumors.
Effect of epigallocatechin gallate on dental biofilm of Streptococcus mutans: An in vitro study
Authors: Schneider-Rayman Mor , Steinberg Doron , Sionov Ronit Vogt , Friedman Michael , Shalish Miriam
Published: September 2021

Background

Streptococcus mutans (S. mutans) plays a major role in the formation of dental caries. The aim of this study was to examine the effect of the green tea polyphenol, epigallocatechin gallate (EGCG), on biofilm formation of S. mutans.

Methods

Following exposure to increasing concentrations of EGCG, the planktonic growth was measured by optical density and the biofilm biomass was quantified by crystal violet staining. Exopolysaccharides (EPS) production was visualized by confocal scanning laser microscopy, and the bacterial DNA content was determined by quantitative polymerase chain reaction (qPCR). Gene expression of selected genes was analyzed by real time (RT)-qPCR and membrane potential was examined by flow cytometry.

Results

We observed that EGCG inhibited in a dose-dependent manner both the planktonic growth and the biofilm formation of S. mutans. Significant reduction of S. mutans biofilm formation, DNA content, and EPS production was observed at 2.2–4.4 mg/ml EGCG. EGCG reduced the expression of gtfB, gtfC and ftf genes involved in EPS production, and the nox and sodA genes involved in the protection against oxidative stress. Moreover, EGCG caused an immediate change in membrane potential.

Conclusions

EGCG, a natural polyphenol, has a significant inhibitory effect on S. mutans dental biofilm formation and EPS production, and thus might be a potential drug in preventing dental caries.
Protective and immunostimulatory effects of in-feed preparations of an anticoccidial, a probiotic, a vitamin-selenium complex, and Ferulago angulata extract in broiler chickens infected with Eimeria species
Authors: Nooreh Zahra , Taherpour Kamran , Ghasemi Hossein Ali , Akbari Gharaei Mohammad , Shirzadi Hassan
Published: September 2021

Background

Two experiments were conducted to compare the growth-promoting (experiment 1), protective, and immunostimulatory effects (experiment 2) of salinomycin, probiotic, a vitamin-selenium complex, and Ferulago angulata hydroalcoholic extract (FAE) against coccidiosis in broilers. In each experiment, 350 1-day-old broiler chickens were equally divided in 7 groups: uninfected negative control (NC); infected positive control (PC); or PC supplemented with salinomycin (Sal); probiotic (Pro); a combination of vitamin E, vitamin C, and selenium (ECSe); 200 mg/kg of FAE (FAE200); or 400 mg/kg of FAE (FAE400). All these groups (except NC) were challenged via oral gavage with oocysts of mixed Eimeria spp. on d 10 (experiment 1) or d 14 (experiment 2).

Results

In the first trial, all treatments improved growth and feed conversion compared with the PC group, where the best values were noticed in the NC and FAE400 groups throughout the entire experimental period (d 1 to 42). Further, a lower mortality rate (P < 0.05) was observed in the NC, Sal, and FAE400 groups as compared to that in the PC group. In the second trial, intestinal lesion scores and total oocyst numbers were reduced in the Sal, Pro, and FAE400 groups compared to the PC group, albeit all coccidiosis-challenged groups had higher oocyst shedding (P < 0.05) compared to NC group. Immune responses revealed that among challenged birds, those fed diets Pro, ECSE, and FAE400 had significantly higher primary total and secondary total and IgG antibody titers against sheep red blood cells, serum and cecum specific IgG levels, and serum IFN-γ concentration than the PC group.

Conclusions

Considering the results, dietary FAE, especially at high levels of inclusion in broiler diet (400 mg/kg), could beneficially influence growth performance and immune status under coccidiosis challenge, which was comparable to that of probiotic supplement.
Evaluation of bacterial hosts for conversion of lignin-derived p-coumaric acid to 4-vinylphenol
Authors: Rodriguez Alberto , Meadows Jamie A. , Sun Ning , Simmons Blake A. , Gladden John M.
Published: September 2021

Hydroxycinnamic acids such as p-coumaric acid (CA) are chemically linked to lignin in grassy biomass with fairly labile ester bonds and therefore represent a straightforward opportunity to extract and valorize lignin components. In this work, we investigated the enzymatic conversion of CA extracted from lignocellulose to 4-vinylphenol (4VP) by expressing a microbial phenolic acid decarboxylase in Corynebacterium glutamicum, Escherichia coli, and Bacillus subtilis. The performance of the recombinant strains was evaluated in response to the substrate concentration in rich medium or a lignin liquor and the addition of an organic overlay to perform a continuous product extraction in batch cultures. We found that using undecanol as an overlay enhanced the 4VP titers under high substrate concentrations, while extracting > 97% of the product from the aqueous phase. C. glutamicum showed the highest tolerance to CA and resulted in the accumulation of up to 187 g/L of 4VP from pure CA in the overlay with a 90% yield when using rich media, or 17 g/L of 4VP with a 73% yield from CA extracted from lignin. These results indicate that C. glutamicum is a suitable host for the high-level production of 4VP and that further bioprocess engineering strategies should be explored to optimize the production, extraction, and purification of 4VP from lignin with this organism.
Environmental asbestos exposure and clustering of malignant mesothelioma in community: a spatial analysis in a population-based case–control study
Authors: Airoldi C. , Magnani C. , Lazzarato F. , Mirabelli D. , Tunesi S. , Ferrante D.
Published: September 2021

Background

Neighborhood exposure to asbestos increases the risk of developing malignant mesothelioma (MM) in residents who live near asbestos mines and asbestos product plants. The area of Casale Monferrato (Northwest Italy) was impacted by several sources of asbestos environmental pollution, due to the presence of the largest Italian asbestos cement (AC) plant. In the present study, we examined the spatial variation of MM risk in an area with high levels of asbestos pollution and secondly, and we explored the pattern of clustering.

Methods

A population-based case–control study conducted between 2001 and 2006 included 200 cases and 348 controls. Demographic and occupational data along with residential information were recorded. Bivariate Kernel density estimation was used to map spatial variation in disease risk while an adjusted logistic model was applied to estimate the impact of residential distance from the AC plant. Kulldorf test and Cuzick Edward test were then performed.

Results

One hundred ninety-six cases and 322 controls were included in the analyses. The contour plot of the cases to controls ratio showed a well-defined peak of MM incidence near the AC factory, and the risk decreased monotonically in all directions when large bandwidths were used. However, considering narrower smoothing parameters, several peaks of increased risk were reported. A constant trend of decreasing OR with increasing distance was observed, with estimates of 10.9 (95% CI 5.32–22.38) and 10.48 (95%CI 4.54–24.2) for 0–5 km and 5–10 km, respectively (reference > 15 km). Finally, a significant (p < 0.0001) excess of cases near the pollution source was identified and cases are spatially clustered relative to the controls until 13 nearest neighbors.

Conclusions

In this study, we found an increasing pattern of mesothelioma risk in the area around a big AC factory and we detected secondary clusters of cases due to local exposure points, possibly associated to the use of asbestos materials.
Platelet factor 4 polyanion immune complexes: heparin induced thrombocytopenia and vaccine-induced immune thrombotic thrombocytopenia
Authors: Datta Payel , Zhang Fuming , Dordick Jonathan S. , Linhardt Robert J.
Published: September 2021

Background

This is a review article on heparin-induced thrombocytopenia, an adverse effect of heparin therapy, and vaccine-induced immune thrombotic thrombocytopenia, occurring in some patients administered certain coronavirus vaccines.

Main body/text

Immune-mediated thrombocytopenia occurs when specific antibodies bind to platelet factor 4 /heparin complexes. Platelet factor 4 is a naturally occurring chemokine, and under certain conditions, may complex with negatively charged molecules and polyanions, including heparin. The antibody-platelet factor 4/heparin complex may lead to platelet activation, accompanied by other cascading reactions, resulting in cerebral sinus thrombosis, deep vein thrombosis, lower limb arterial thrombosis, myocardial infarction, pulmonary embolism, skin necrosis, and thrombotic stroke. If untreated, heparin-induced thrombocytopenia can be life threatening. In parallel, rare incidents of spontaneous vaccine-induced immune thrombotic thrombocytopenia can also occur in some patients administered certain coronavirus vaccines. The role of platelet factor 4 in vaccine-induced thrombosis with thrombocytopenia syndrome further reinforces the importance the platelet factor 4/polyanion immune complexes and the complications that this might pose to susceptible individuals. These findings demonstrate, how auxiliary factors can complicate heparin therapy and drug development. An increasing interest in biomanufacturing heparins from non-animal sources has driven a growing interest in understanding the biology of immune-mediated heparin-induced thrombocytopenia, and therefore, the development of safe and effective biosynthetic heparins.

Short conclusion

In conclusion, these findings further reinforce the importance of the binding of platelet factor 4 with known and unknown polyanions, and the complications that these might pose to susceptible patients. In parallel, these findings also demonstrate how auxiliary factors can complicate the heparin drug development.
Awareness of obstetric fistula and associated factors among women in reproductive age group attending public hospitals in southwest Ethiopia, 2021
Authors: Rundasa Dessalegn Nigatu , Wolde Tarekegn Fekede , Ayana Kenbon Bayisa , Worke Abeya Fufa
Published: September 2021

Background

Obstetric fistula occurs in all developing countries but it is confined to the “fistula belt” across the northern half of Sub-Saharan Africa from Mauritania to Eritrea and in the developing countries of the Middle East and Asia. Ending obstetric fistula is critical to achieving Sustainable Development by 2030. So creating awareness on obstetrics fistula among women in the reproductive age group have a crucial role in reducing morbidity, mortality, and social stigma.

Objective

To assess awareness on obstetric fistula and its associated factors among reproductive-age women attending governmental hospitals in southwest Ethiopia, 2021.

Methods

An Institutional based cross-sectional study design was conducted among 413 women. The sample size was estimated by using a single population proportion formula. The collected data were coded and entered into EPI-data version 3.1 then exported to SPSS version 24 for descriptive and inferential analysis. Adjusted odds ratio (AOR) along with 95% confidence level was estimated to assess the strength of the association and variables with a p-value < 0.05 were considered to declare the statistical significance in the multivariable analysis in this study.

Results

In this study, a total of 400 clients have participated in the study. The mean ages of participants were 30.26 (SD ± 8.525) years old. Education of women who cannot read and write are 85% less likely to have good awareness than women who are above the secondary level of education [AOR = 0.162; 95% CI (0.081–0.364)]. While Women who have primary education level are 83% less likely to have good awareness than women who are above the secondary level of education [AOR = 0.170; 95% CI (0.085–0.446)]. In addition, This study shows women who have not heard about obstetric complications are 54% less likely to have awareness of obstetric fistula than those who heard about obstetric complications [AOR = 0.458; 95% CI (0.368–0.643)].

Conclusion

This study identifies that the educational level of women, history of pregnancy, distance to the nearby health institution, and awareness of obstetrics complications were the factors associated with awareness of reproductive age women on obstetrics fistula. Hence, increasing awareness on obstetric fistula plays a key role in averting this problem.
Does clozapine really affect bone mineral density? An experimental study
Authors: Aydin Bahattin Kerem , Safali Selim , Aydin Memduha , Egilmez Umran , Cebeci Hakan , Çelik Murat , Abdulrezzak Ummuhan
Published: September 2021

Purpose

The aim of this study was to investigate the effect of clozapine use on bone tissue by applying computerized tomography, dual-energy X-ray absorptiometry, and histological and biomechanical analyses in an experimental rat model.

Methods

Sixteen female Wistar Albino rats were included in this study. These animals were divided into two groups: the control group and the clozapine group. The animals in the clozapine group received 10 mg/kg clozapine, and the animals in the control group received tap water by oral gavage daily for 28 days. After sacrification, the femurs of the rats were used for radiologic, histologic, dual-energy X-ray absorptiometry, and biomechanical evaluations.

Results

Although the mean values of the clozapine group were higher in terms of histological, bone mineral density, and biomechanical evaluations, the statistical analyses were not significantly different.

Conclusion

Clozapine use did not affect bone density in the rats. Clozapine can be the preferred treatment for patients with schizophrenia to avoid osteoporosis. It will be necessary to conduct further long-term follow-up and controlled studies in animals and humans to confirm these findings.
Development and validation of a nomogram for prediction of the risk of positive hidden blood loss in the perioperative period of single-level thoracolumbar burst fracture
Authors: Wang Haosheng , Fan Tingting , Tang Zhi-Ri , Li Wenle , Liu Linjing , Lin Qiang
Published: September 2021

Background

This study aimed to develop and validate an individualized nomogram to predict the risk of positive hidden blood loss (HBL) in patients with single-level thoracolumbar burst fracture (TBF) during the perioperative period.

Methods

We conducted a retrospective investigation including 150 consecutive patients with TBL, and the corresponding patient data was extracted from March 2013 to March 2019. The independent risk factors for positive HBL were screened using univariate and multivariate logistic regression analyses. According to published literature and clinical experience, a series of variables were selected to develop a nomogram prediction model for positive HBL. The area under the receiver operating characteristic curves (AUC), C-index, calibration plot, and decision curve analysis (DCA) were used to evaluate the performance of the prediction model. Bootstrapping validation was performed to evaluate the performance of the model.

Results

Among the 150 consecutive patients, 62 patients were positive for HBL (38.0%). The multivariate logistic regression analysis showed that the six risk factors of age, length of surgical incision, duration of operation, percentage of vertebral height restoration (P1%), preoperative total cholesterol, and preoperative fibrinogen were independent risk factors of positive HBL. The C-index was 0.831 (95% CI 0.740–0.889) and 0.845 in bootstrapping validation, respectively. The calibration curve showed that the predicted probability of the model was consistent with the actual probability. Decision curve analysis (DCA) showed that the nomogram had clinical utility.

Conclusion

Overall, we explored the relationship between the positive HBL requirement and predictors. The individualized prediction model for patients with single-level TBF can accurately assess the risk of positive HBL and facilitate clinical decision making. However, external validation will be needed in the future.
The effect of preoperative hypoalbuminemia on complications after primary hip arthroplasty
Authors: Tan Yang , Jiang Lingxiao , Liu Hankun , Pan Zhengqi , Wang Hua , Chen Liaobin
Published: September 2021

Objectives

To explore the risk factors of preoperative hypoalbuminemia and its’ effects on complications in the elderly with primary hip arthroplasty.

Methods

A total of 211 elderly inpatients who underwent hip arthroplasty were collected. All patients were divided into the control group (preoperative serum albumin ≥35 g/L) and case group (preoperative serum albumin <35 g/L). The risk factors of preoperative hypoalbuminemia and the postoperative complications were analyzed.

Results

Compared to controls, hypoalbuminemia patients were older (P = 0.026), had lower BMI (P = 0.045), higher cardiac function score (P < 0.0001), higher ASA scores (P = 0.023), and longer hospital stay (P < 0.001). The intraoperative albumin loss in the case group was significantly higher than that of in control group (P < 0.001), but there was no significant difference in operation time and intraoperative blood loss between the two groups (P >0.05). Compared to controls, hypoalbuminemia patients had a higher risk for any complication (P = 0.014), such as delayed wound healing, pleural effusion, and pneumonia. The risk of postoperative complications increased by 6.9% with every 1 year old is increasing (age > 60). The risk of postoperative complications in the case group was 1.89 times higher than that in the control group.

Conclusion

Patients with older age, poor nutritional status, and more than 2 concomitant diseases are more likely to develop preoperative hypoalbuminemia. Preoperative hypoalbuminemia is related to the increased incidence of postoperative complications. Perioperative albumin loss is not only due to perioperative blood loss, but also related to vascular permeability and abnormal albumin metabolism.
Recombinant TSG-6 protein inhibits the growth of capsule fibroblasts in frozen shoulder via suppressing the TGF-β/Smad2 signal pathway
Authors: Liu Zhongfan , Pei Yongrong , Zeng Hao , Yang Yibo , Que Meng , Xiao Yuhui , Wang Jing , Weng Xiaojun
Published: September 2021

Background

The tumor necrosis factor-stimulated gene-6 (TSG-6) has been confirmed to inhibit inflammation. It is now generally accepted that local inflammatory stimulation around shoulder capsule causes proliferative fibrosis. This study aims to investigate the mechanism of recombinant TSG-6 protein inhibiting the growth of capsule fibroblasts in frozen shoulder via the TGF-β/Smad2 signal pathway.

Methods

Human frozen shoulder capsule tissue was taken for primary and passage culture, and the 3rd generation fibroblasts from pathological frozen shoulder capsule were treated with different concentrations of recombinant TSG-6 protein, or with TGF-β1 agonist SRI-011381. Immunoconfocal analysis was used to identify the isolated fibroblasts, and MTT assay, colony formation assay, and flow cytometry were used to detect the viability, proliferation, and apoptosis rate of fibroblast. The contents of fibrosis and inflammation indexes COL1A1, TNF-α, IL-6, and IL-1β in the cell supernatant were detected using ELISA and then further examined by qRT-PCR. The expression of Bax, Bcl-2, and proteins related to TGF-β/Smad2 pathway were detected by Western Blot.

Results

Compared with the blank control group, fibroblasts intervened with TSG-6 (2 μg and 5 μg) showed significantly decreased viability and proliferation ability and enhanced cell apoptosis, concurrent with the reductions in Bcl-2 expression; COL1A1, TNF-α, IL-6, and IL-1β levels; and the expression of TGF-β1 and phosphorylated Smad22, and an increase in Bax expression, while SRI-011381 treatment would reverse the effect of recombinant TSG-6 protein.

Conclusion

Recombinant TSG-6 protein inhibited the growth of primary fibroblasts from human frozen shoulder capsule by suppressing the TGF-β/Smad2 signaling pathway.
Comparison of systemic immune-inflammation index (SII), early warning score (ANDC) and prognostic nutritional index (PNI) in hospitalized patients with malignancy, and their influence on mortality from COVID-19
Authors: Bilge Muge , Akilli Isil Kibar , Karaayvaz Ekrem Bilal , Yesilova Aylia , Kart Yasar Kadriye
Published: September 2021

Introduction

We evaluated several biological indicators based on inflammation and/or nutritional status, such as systemic immune-inflammation index (SII), early warning score (ANDC) and prognostic nutritional index (PNI) in hospitalized COVID-19 patients with and without malignancies for a prognostic significance.

Methodology

This is a retrospective and observational study on 186 patients with SARS-CoV-2, who were diagnosed with COVID-19 by real-time PCR testing and hospitalized due to COVID-19 pneumonia. 75 patients had various malignancies, and the rest (111), having a similar age and comorbidity profile based on propensity score matching, had no malignancy.

Results

None of the measures as neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, monocyte to lymphocyte ratio, SII, PNI or ANDC was found to be significantly different between two groups. Odds ratio for the mortality, OR 2.39 (%95 CI 1.80–3.16) was found to be significantly higher for the malignancy group, even though the duration of hospitalization was statistically similar for both groups. PNI was found to be significantly lower for deceased patients compared with survivors in the malignancy group. Contrarily, ANDC was found to be significantly higher for deceased patients in the malignancy group.

Conclusions

PNI and ANDC have independent predictive power on determining the in-hospital death in COVID-19 malignancy cases. It is suggested that ANDC seems to be a more sensitive score than SII in COVID-19 cases with malignancies.
Arginine vasopressin in the medial amygdala causes greater post-stress recruitment of hypothalamic vasopressin neurons
Authors: Tong Wen Han , Abdulai-Saiku Samira , Vyas Ajai
Published: September 2021

Arginine vasopressin (AVP) is expressed in both hypothalamic and extra-hypothalamic neurons. The expression and role of AVP exhibit remarkable divergence between these two neuronal populations. Polysynaptic pathways enable these neuronal groups to regulate each other. AVP neurons in the paraventricular nucleus of the hypothalamus increase the production of adrenal stress hormones by stimulating the hypothalamic–pituitary–adrenal axis. Outside the hypothalamus, the medial amygdala also contains robust amounts of AVP. Contrary to the hypothalamic counterpart, the expression of extra-hypothalamic medial amygdala AVP is sexually dimorphic, in that it is preferentially transcribed in males in response to the continual presence of testosterone. Male gonadal hormones typically generate a negative feedback on the neuroendocrine stress axis. Here, we investigated whether testosterone-responsive medial amygdala AVP neurons provide negative feedback to hypothalamic AVP, thereby providing a feedback loop to suppress stress endocrine response during periods of high testosterone secretion. Contrary to our expectation, we found that AVP overexpression within the posterodorsal medial amygdala increased the recruitment of hypothalamic AVP neurons during stress, without affecting the total number of AVP neurons or the number of recently activated neurons following stress. These observations suggest that the effects of testosterone on extra-hypothalamic AVP facilitate stress responsiveness through permissive influence on the recruitment of hypothalamic AVP neurons.
The phosphorylation status of eukaryotic elongation factor-2 indicates neural activity in the brain
Authors: Yoon Sang Ho , Song Woo Seok , Oh Sung Pyo , Kim Young Sook , Kim Myoung-Hwan
Published: September 2021

Assessment of neural activity in the specific brain area is critical for understanding the circuit mechanisms underlying altered brain function and behaviors. A number of immediate early genes (IEGs) that are rapidly transcribed in neuronal cells in response to synaptic activity have been used as markers for neuronal activity. However, protein detection of IEGs requires translation, and the amount of newly synthesized gene product is usually insufficient to detect using western blotting, limiting their utility in western blot analysis of brain tissues for comparison of basal activity between control and genetically modified animals. Here, we show that the phosphorylation status of eukaryotic elongation factor-2 (eEF2) rapidly changes in response to synaptic and neural activities. Intraperitoneal injections of the GABA A receptor (GABAAR) antagonist picrotoxin and the glycine receptor antagonist brucine rapidly dephosphorylated eEF2. Conversely, potentiation of GABAARs or inhibition of AMPA receptors (AMPARs) induced rapid phosphorylation of eEF2 in both the hippocampus and forebrain of mice. Chemogenetic suppression of hippocampal principal neuron activity promoted eEF2 phosphorylation. Novel context exploration and acute restraint stress rapidly modified the phosphorylation status of hippocampal eEF2. Furthermore, the hippocampal eEF2 phosphorylation levels under basal conditions were reduced in mice exhibiting epilepsy and abnormally enhanced excitability in CA3 pyramidal neurons. Collectively, the results indicated that eEF2 phosphorylation status is sensitive to neural activity and the ratio of phosphorylated eEF2 to total eEF2 could be a molecular signature for estimating neural activity in a specific brain area.
Brain-derived neurotrophic factor produced long-term synaptic enhancement in the anterior cingulate cortex of adult mice
Authors: Miao Hui-Hui , Miao Zhuang , Pan Ji-Gang , Li Xu-Hui , Zhuo Min
Published: September 2021

Previous studies have demonstrated that brain-derived neurotrophic factor (BDNF) is one of the diffusible messengers for enhancing synaptic transmission in the hippocampus. Less information is available about the possible roles of BDNF in the anterior cingulate cortex (ACC). In the present study, we used 64-electrode array field recording system to investigate the effect of BDNF on ACC excitatory transmission. We found that BDNF enhanced synaptic responses in a dose-dependent manner in the ACC in C57/BL6 mice. The enhancement was long-lasting, and persisted for at least 3 h. In addition to the enhancement, BDNF also recruited inactive synaptic responses in the ACC. Bath application of the tropomyosin receptor kinase B (TrkB) receptor antagonist K252a blocked BDNF-induced enhancement. L-type voltage-gated calcium channels (L-VGCC), metabotropic glutamate receptors (mGluRs), but not NMDA receptors were required for BDNF-produced enhancement. Moreover, calcium-stimulated adenylyl cyclase subtype 1 (AC1) but not AC8 was essential for the enhancement. A selective AC1 inhibitor NB001 completely blocked the enhancement. Furthermore, BDNF-produced enhancement occluded theta burst stimulation (TBS) induced long-term potentiation (LTP), suggesting that they may share similar signaling mechanisms. Finally, the expression of BDNF-induced enhancement depends on postsynaptic incorporation of calcium-permeable AMPA receptors (CP-AMPARs) and protein kinase Mζ (PKMζ). Our results demonstrate that cortical BDNF may contribute to synaptic potentiation in the ACC.
Combine and conquer: manganese synergizing anti-TGF-β/PD-L1 bispecific antibody YM101 to overcome immunotherapy resistance in non-inflamed cancers
Authors: Yi Ming , Niu Mengke , Zhang Jing , Li Shiyu , Zhu Shuangli , Yan Yongxiang , Li Ning , Zhou Pengfei , Chu Qian , Wu Kongming
Published: September 2021

Background

Our previous work showed that the anti-TGF-β/PD-L1 bispecific antibody YM101 effectively overcame anti-PD-L1 resistance in immune-excluded tumor models. However, in immune-desert models, the efficacy of YM101 was limited. Bivalent manganese (Mn2+) is identified as a natural stimulator of interferon genes (STING) agonist, which might enhance cancer antigen presentation and improve the therapeutic effect of YM101.

Methods

The effect of Mn2+ on STING pathway was validated by western blotting and enzyme-linked immunosorbent assay. Dendritic cell (DC) maturation was measured by flow cytometry. The synergistic effect between Mn2+ and YM101 in vitro was determined by one-way mixed lymphocyte reaction, CFSE dilution assay, and cytokine detection. The in vivo antitumor effect of Mn2+ plus YM101 therapy was assessed in CT26, EMT-6, H22, and B16 tumor models. Flow cytometry, RNA-seq, and immunofluorescent staining were adopted to investigate the alterations in the tumor microenvironment.

Results

Mn2+ could activate STING pathway and promote the maturation of human and murine DC. The results of one-way mixed lymphocyte reaction showed that Mn2+ synergized YM101 in T cell activation. Moreover, in multiple syngeneic murine tumor models, Mn2+ plus YM101 therapy exhibited a durable antitumor effect and prolonged the survival of tumor-bearing mice. Relative to YM101 monotherapy and Mn2+ plus anti-PD-L1 therapy, Mn2+ plus YM101 treatment had a more powerful antitumor effect and a broader antitumor spectrum. Mechanistically, Mn2+ plus YM101 strategy simultaneously regulated multiple components in the antitumor immunity and drove the shift from immune-excluded or immune-desert to immune-inflamed tumors. The investigation in the TME indicated Mn2+ plus YM101 strategy activated innate and adaptive immunity, enhanced cancer antigen presentation, and upregulated the density and function of tumor-infiltrating lymphocytes. This normalized TME and reinvigorated antitumor immunity contributed to the superior antitumor effect of the combination therapy.

Conclusion

Combining Mn2+ with YM101 has a synergistic antitumor effect, effectively controlling tumor growth and prolonging the survival of tumor-bearing mice. This novel cocktail strategy has the potential to be a universal regimen for inflamed and non-inflamed tumors.
Fibrinogen-like protein 1 (FGL1): the next immune checkpoint target
Authors: Qian Wenjing , Zhao Mingfang , Wang Ruoyu , Li Heming
Published: September 2021

Immune checkpoint therapy has achieved significant efficacy by blocking inhibitory pathways to release the function of T lymphocytes. In the clinic, anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) monoclonal antibodies (mAbs) have progressed to first-line monotherapies in certain tumor types. However, the efficacy of anti-PD-1/PD-L1 mAbs is still limited due to toxic side effects and de novo or adaptive resistance. Moreover, other immune checkpoint target and biomarkers for therapeutic response prediction are still lacking; as a biomarker, the PD-L1 (CD274, B7-H1) expression level is not as accurate as required. Hence, it is necessary to seek more representative predictive molecules and potential target molecules for immune checkpoint therapy. Fibrinogen-like protein 1 (FGL1) is a proliferation- and metabolism-related protein secreted by the liver. Multiple studies have confirmed that FGL1 is a newly emerging checkpoint ligand of lymphocyte activation gene 3 (LAG3), emphasizing the potential of targeting FGL1/LAG3 as the next generation of immune checkpoint therapy. In this review, we summarize the substantial regulation mechanisms of FGL1 in physiological and pathological conditions, especially tumor epithelial to mesenchymal transition, immune escape and immune checkpoint blockade resistance, to provide insights for targeting FGL1 in cancer treatment.
circHMGCS1–016 reshapes immune environment by sponging miR-1236-3p to regulate CD73 and GAL-8 expression in intrahepatic cholangiocarcinoma
Authors: Xu Ya-Ping , Dong Ze-Ning , Wang Si-Wei , Zheng Yi-Min , Zhang Chi , Zhou Ying-Qun , Zhao Yu-Jie , Zhao Yan , Wang Feng , Peng Rui , Tang Mao-Chun , Bai Dou-sheng , Huang Xiao-Yong , Guo Chuan-Yong
Published: September 2021

Background

Accumulating evidence indicates that circRNAs may serve as essential regulators in the progression of several human cancers, but the function and mechanism of circRNAs in intrahepatic cholangiocarcinoma (ICC) are largely unknown.

Methods

RNA-seq was used to assess differentially expressed circRNAs between 4 ICC and peritumor tissues. Quantitative RT-PCR and in situ hybridization were used to determine the circHMGCS1–016 expression in ICC tissues. The function and mechanism of circHMGCS1–016 were further identified via in vivo experiments. The clinical characteristics and prognostic significance of circHMGCS1–016 were analyzed by a retrospective study. The functions of circHMGCS1–016 were assessed via modifying circRNA expression in ICC cells. Moreover, the molecular mechanisms of circHMGCS1–016 in ICC cells were explored by circRNA precipitation, miRNA immunoprecipitation, SILAC and luciferase reporter assays.

Results

We identified that compared with peritumor tissues, ICC tissues expressed hsa_circ_0008621 (circHMGCS1–016) high by RNA-seq, which was further identified by qRT-PCR and in situ hybridization. Moreover, the expression of circHMGCS1–016 was revealed to be associated with survival and recurrence of ICC patients. By regulating circHMGCS1–016 expression, we found that elevated circHMGCS1–016 promoted ICC development both in vitro and in vivo. By SILAC and circRNA-pull down, we demonstrated that circHMGCS1–016 induced ICC cell invasion and reshaped the tumor immune microenvironment via the miR-1236-3p/CD73 and GAL-8 axis. In ICC tissues, we uncovered that a high level of circHMGCS1–016 was positively associated with CD73 and GAL-8 expression and negatively related to the CD8+ T cells infiltration, which was further validated by establishing a humanized mouse tumor model. Importantly, we displayed that ICC patients with high levels of circHMGCS1–016 in tumor tissues benefited less from anti-PD1 treatment compared to those with low levels of circHMGCS1–016.

Conclusions

CircHMGCS1–016 is a forceful contributor in ICC development and immune tolerance via miR-1236-3p/CD73 and GAL-8 axis. CircHMGCS1–016 can be explored as a new potential biomarker and therapeutic target for PD1-resistant ICC.