bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge and perceptions about Dolutegravir and Dolutegravir counselling: a qualitative study among women living with HIV
Authors: Chapola John C. , Lee Fan , Bula Agatha , Rosenberg Nora E. , Tseka Jennifer , Chagomerana Maganizo , Hosseinipour Mina C. , Tang Jennifer Hui-Yu
Published: September 2023

Introduction

In 2018, the Malawi Ministry of Health adopted the recommendation to switch first-line antiretroviral therapy (ART) from an efavirenz (EFV)-based to a dolutegravir (DTG)-based regimen. Little is known about patients’ experience during this transition. We conducted a qualitative study to explore DTG-related counselling challenges among providers of HIV care and factors influencing regimen switching or non-switching among women living with HIV in Lilongwe, Malawi.

Methods

Between February-July 2020, we recruited participants who took part in DTG counselling on reasons to switch, side effects, and benefits from two government health facilities providing HIV care: Area 18 health centre and Bwaila district hospital in Lilongwe, Malawi. We purposively sampled and interviewed 8 women living with HIV who remained on an EFV-based regimen after counselling, 10 women who switched to a DTG-based regimen, and 10 HIV care providers who provided counselling about ART switching. In-depth interviews were used to explore patient’s perceptions of DTG, factors affecting the decision to switch, and both patient and provider experience with counselling. Interview data was coded for themes using inductive and deductive codes. Interviews were conducted until thematic saturation was achieved. Data matrices were used for analysis and thematic extraction.

Results

Most women in both groups were well versed on DTG’s potential side effects and felt well counselled on the benefits of switching, such as quicker viral load suppression. Many women associated DTG with birth defects and expressed concern. However, the primary reason for not switching was concern with how the new medication would be tolerated, especially when they were satisfied with their current regimen. Almost all providers expressed difficulty providing DTG counselling. Primary reasons included feeling inadequately trained and/or not having resources to use during counselling, such as diagrams or brochures.

Conclusion

DTG counselling was well accepted by women; however, some felt that their concerns were not fully addressed. Providers reflected this sentiment in that they did not feel adequately trained or well-equipped to provide adequate counselling. Training on counselling for new ART regimens should be intensified and utilize patient-centered educational materials to address the concerns raised by both patients and health care providers.
Mitigating underreported error in food frequency questionnaire data using a supervised machine learning method and error adjustment algorithm
Authors: Popoola Anjolaoluwa Ayomide , Frediani Jennifer Koren , Hartman Terryl Johnson , Paynabar Kamran
Published: September 2023

Background

Food frequency questionnaires (FFQs) are one of the most useful tools for studying and understanding diet-disease relationships. However, because FFQs are self-reported data, they are susceptible to response bias, social desirability bias, and misclassification. Currently, several methods have been created to combat these issues by modelling the measurement error in diet-disease relationships.

Method

In this paper, a novel machine learning method is proposed to adjust for measurement error found in misreported data by using a random forest (RF) classifier to label the responses in the FFQ based on the input dataset and creating an algorithm that adjusts the measurement error. We demonstrate this method by addressing underreporting in selected FFQ responses.

Result

According to the results, we have high model accuracies ranging from 78% to 92% in participant collected data and 88% in simulated data.

Conclusion

This shows that our proposed method of using a RF classifier and an error adjustment algorithm is efficient to correct most of the underreported entries in the FFQ dataset and could be used independent of diet-disease models. This could help nutrition researchers and other experts to use dietary data estimated by FFQs with less measurement error and create models from the data with minimal noise.
Design and evaluation of an educational mobile program for liver transplant patients
Authors: Langarizadeh Mostafa , Moghbeli Fateme , Ahmadi Shamim , Langarizadeh Mohammad Hossein , Sayadi Mohammadjavad , Sarpourian Fatemeh , Fatemi Aghda Seyed Ali
Published: September 2023

Background

Liver transplantation, the last treatment for advanced liver failure, necessitates patient education due to its wide range of complications and subsequent disabilities. The present study was development-applied research and aimed to design a mobile-based educational program to provide liver transplant patients with critical health information.

Methods

In the first phase of the study, the crucial educational components were collected from the literature and organized in the form of a questionnaire using library studies and available global guidelines. The validity and reliability of this researcher-made questionnaire were confirmed by a panel of experts (n = 15), including gastroenterologists and liver specialists working in the Motahari liver clinic and AbuAli Sina Hospital in Shiraz. The application was designed followed by analyzing the data gathered from the first phase. To evaluate the mobile phone program’s usability, to evaluate the application, 30 liver transplant patients were randomly selected.

Results

Most educational components covered in the questionnaire were deemed necessary by experts in the first phase. As a result, the educational contents were classified under 10 categories. The application had a good level of usability since the participants’ satisfaction score was 8.1 (out of 9 points).

Conclusions

Due to the increase in liver transplantation and the use of mobile phones, applications increase the patient’s role in their health, and their awareness. It also leads to a better interaction and follow-up of the patient, the treatment staff of the medical centers.
Assessment of magnitude and associated factors of attitude towards time management among health professionals working in public hospitals of Dessie City, Northeast Ethiopia
Authors: Yimer Ali , Ahmed Mohammed , Zewdie Amare , Fenta Sefineh
Published: September 2023

Background

Good attitude towards to time management is the backbone to bring a change at individual and organizational levels in different sectors across the globe. But it has been ignored by different institutions, particularly in low and middle-income countries including Ethiopia. However, this can be alleviated if there are punctual, committed, and accessible health professionals that could translate the national aspirations and the desire of the community into reality. This study aims to determine the magnitude and associated factors of attitude towards time management among health professionals working in public hospitals of Dessie City, Northeast Ethiopia,

Methods

Institution-based cross-sectional study was conducted from March 24 –April 24, 2021 among 409 health professionals using a stratified sampling technique, Frequency and percentage were used to describe the study population. Multivariable logistic regression analysis was used to identify independent predictors. A p-value of < 0.05 with 95% CI were used to declare statistically significant associations.

Results

The overall good time management attitude among sample was 67%(95%CI:66.77–67.22%). Satisfaction with organizational policy and strategy (AOR: 2.69, 95%CI: 1.42–5.09), satisfaction with supervisor support (AOR: 2.12, 95% CI: 1.19–3.77), and managers’ good attitude towards time management (AOR: 2.00, 95%CI: 1.23–3.25) were significantly associated with good attitude towards time management among health professionals.

Conclusion

The attitude towards time management in public hospitals of Dessie City was low. Satisfaction with organizational policies and strategies, satisfaction with supervisor support, and managers’ good attitude towards time management were delineated factors. This low attitude towards time management could affect the practice and it compromise the health service coverage and quality unless timely and appropriate interventions should be taken. Strengthening strategies aimed at maximizing job satisfaction and emphasizing an attitude towards time might have a substantial contribution.
Cost-effective production of alginate oligosaccharides from Laminaria japonica roots by Pseudoalteromonas agarivorans A3
Authors: Sun Xiao-Hui , Chen Xiu-Lan , Wang Xiao-Fei , Zhang Xin-Ru , Sun Xiao-Meng , Sun Mei-Ling , Zhang Xi-Ying , Zhang Yu-Zhong , Zhang Yu-Qiang , Xu Fei
Published: September 2023

Background

Alginate oligosaccharides (AOs) are the degradation products of alginate, a natural polysaccharide abundant in brown algae. AOs generated by enzymatic hydrolysis have diverse bioactivities and show broad application potentials. AOs production via enzymolysis is now generally with sodium alginate as the raw material, which is chemically extracted from brown algae. In contrast, AOs production by direct degradation of brown algae is more advantageous on account of its cost reduction and is more eco-friendly. However, there have been only a few attempts reported in AOs production from direct degradation of brown algae.

Results

In this study, an efficient Laminaria japonica-decomposing strain Pseudoalteromonas agarivorans A3 was screened. Based on the secretome and mass spectrum analyses, strain A3 showed the potential as a cell factory for AOs production by secreting alginate lyases to directly degrade L. japonica. By using the L. japonica roots, which are normally discarded in the food industry, as the raw material for both fermentation and enzymatic hydrolysis, AOs were produced by the fermentation broth supernatant of strain A3 after optimization of the alginate lyase production and hydrolysis parameters. The generated AOs mainly ranged from dimers to tetramers, among which trimers and tetramers were predominant. The degradation efficiency of the roots reached 54.58%, the AOs production was 33.11%, and the AOs purity was 85.03%.

Conclusion

An efficient, cost-effective and green process for AOs production directly from the underutilized L. japonica roots by using strain A3 was set up, which differed from the reported processes in terms of the substrate and strain used for fermentation and the AOs composition. This study provides a promising platform for scalable production of AOs, which may have application potentials in industry and agriculture.
Natural diversity of lactococci in γ-aminobutyric acid (GABA) production and genetic and phenotypic determinants
Authors: Laroute Valérie , Aubry Nathalie , Audonnet Marjorie , Mercier-Bonin Muriel , Daveran-Mingot Marie-Line , Cocaign-Bousquet Muriel
Published: September 2023

Background

γ-aminobutyric acid (GABA) is a bioactive compound produced by lactic acid bacteria (LAB). The diversity of GABA production in the Lactococcus genus is poorly understood. Genotypic and phenotypic approaches were therefore combined in this study to shed light on this diversity. A comparative genomic study was performed on the GAD-system genes (gadR, gadC and gadB) involved in GABA production in 36 lactococci including L. lactis and L. cremoris species. In addition, 132 Lactococcus strains were screened for GABA production in culture medium supplemented with 34 mM L-glutamic acid with or without NaCl (0.3 M).

Results

Comparative analysis of the nucleotide sequence alignments revealed the same genetic organization of the GAD system in all strains except one, which has an insertion sequence element (IS981) into the PgadCB promoter. This analysis also highlighted several deletions including a 3-bp deletion specific to the cremoris species located in the PgadR promoter, and a second 39-bp deletion specific to L. cremoris strains with a cremoris phenotype. Phenotypic analysis revealed that GABA production varied widely, but it was higher in L. lactis species than in L. cremoris, with an exceptional GABA production of up to 14 and 24 mM in two L. lactis strains. Moreover, adding chloride increased GABA production in some L. cremoris and L. lactis strains by a factor of up to 16 and GAD activity correlated well with GABA production.

Conclusions

This genomic analysis unambiguously characterized the cremoris phenotype of L. cremoris species and modified GadB and GadR proteins explain why the corresponding strains do not produce GABA. Finally, we found that glutamate decarboxylase activity revealing GadB protein amount, varied widely between the strains and correlated well with GABA production both with and without chloride. As this protein level is associated to gene expression, the regulation of GAD gene expression was identified as a major contributor to this diversity.
Dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of HIV-infected Ugandan adults
Authors: Mulindwa Frank , Castelnuovo Barbara , Brusselaers Nele , Nabwana Martin , Bollinger Robert , Buzibye Allan , Agnes Odongpiny Eva Laker , Kiguba Ronald , Schwarz Jean-Marc
Published: September 2023

Background

The Uganda Ministry of Health issued restrictive guidelines on the use of dolutegravir (DTG) in persons stratified to have a heightened risk of diabetes mellitus. This followed multiple reports of persons with HIV (PWH) presenting with accelerated hyperglycemia after a few weeks to months of exposure to DTG. Having demonstrated a low incidence of diabetes mellitus and improving blood glucose trajectories in a cohort of ART naïve Ugandan PWH on DTG, we sought to determine whether the observed improvement in blood glucose did not mask background compensated insulin resistance.

Methods

In this analysis, 63 patients underwent serial oral glucose tolerance tests over 48 weeks. Using fasting serum insulin and glucose, we calculated insulin resistance and pancreatic beta cell function by homeostatic modelling (HOMA IR and HOMA%β respectively). Absolute mean changes between baseline and post-baseline blood glucose, pancreatic beta cell function and insulin resistance were computed by subtracting each post-baseline value from the baseline value and compared using student t-test. Multiple linear regression models were used to determine the factors associated with changes in pancreatic beta cell function and insulin resistance.

Results

Of the 63 participants, 37 (58%) were female. Median age was 31 (IQR: 28–37). Despite a trend towards an initial increase in both HOMA IR and HOMA%β at 12 weeks followed by a decline through 36 weeks to 48 weeks, the HOMA IR and HOMA%β at 48 weeks were not significantly different from baseline i.e. (difference in mean HOMA IR from baseline: 0.14, 95%CI: -0.46, 0.733, p = 0.648) and (difference in mean HOMA %β from baseline: 6.7, 95%CI: -13.4, 26.8, p = 0.506) respectively.

Conclusion

We demonstrated insignificant changes in both insulin resistance and pancreatic beta cell function in clinically stable young adult Ugandan PWH on dolutegravir for 48 weeks. We add to the body of evidence demonstrating glucose metabolic safety of dolutegravir in ART naïve patients. Ugandan guidelines should reconsider restricting DTG initiation in ART naive adults at high risk for diabetes.
The capacity to consent to treatment is altered in suicidal patients
Authors: Olié Emilie , Catanzaro Thomas , Malestroit Manon , Guija Julio A. , Giner Lucas , Courtet Philippe
Published: September 2023

Background

Many patients with depression refuse treatment. Moreover, suicide attempters often display low perceived need of treatment and impaired decision-making. These observations raise questions about the capacity to treatment consent in depressed suicide attempters (SA).

Methods

In patients with current depressive episode (N = 33 SAs and N = 27 non-SAs), consent capacity was evaluated with the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), insight with the Beck Cognitive Insight Scale, and depression severity with the Beck Depression Inventory (BDI).

Results

The median BDI score in the whole sample (N = 60) was 21 [10;36], and was higher in SAs than non-SAs (27 [11;36] vs. 15 [10:33], p < 0.001). Consent capacity was impaired in 30% (appreciation), 53% (reasoning) and 60% (understanding) of all patients. MacCAT-T sub-scores were lower in SAs than non-SAs (understanding: 4.4 [2.35;5.8] vs. 5.3 [3.13;6]); appreciation: 3 [1;4] vs. 4 [2;4]); reasoning (4 [1;7] vs. 7 [3;8]), and ability to express a choice: 1 [0;2] vs. 2 [0;2]; all p < 0.001). In multivariate analyses, suicide attempt history and depression severity (but not insight) were negatively associated with MacCAT-T sub-scores.

Conclusion

More research is needed on the capacity to consent to treatment of patients with depression, particularly suicidal individuals, to make informed choices about their treatment.

Trial registration The Montpellier University Hospital Institutional Review Board approved the study (No. 202100714).
2023 WSES guidelines for the prevention, detection, and management of iatrogenic urinary tract injuries (IUTIs) during emergency digestive surgery
Authors: de’Angelis Nicola , Schena Carlo Alberto , Marchegiani Francesco , Reitano Elisa , De Simone Belinda , Wong Geoffrey Yuet Mun , Martínez-Pérez Aleix , Abu-Zidan Fikri M. , Agnoletti Vanni , Aisoni Filippo , Ammendola Michele , Ansaloni Luca , Bala Miklosh , Biffl Walter , Ceccarelli Graziano , Ceresoli Marco , Chiara Osvaldo , Chiarugi Massimo , Cimbanassi Stefania , Coccolini Federico , Coimbra Raul , Di Saverio Salomone , Diana Michele , Dioguardi Burgio Marco , Fraga Gustavo , Gavriilidis Paschalis , Gurrado Angela , Inchingolo Riccardo , Ingels Alexandre , Ivatury Rao , Kashuk Jeffry L. , Khan Jim , Kirkpatrick Andrew W. , Kim Fernando J. , Kluger Yoram , Lakkis Zaher , Leppäniemi Ari , Maier Ronald V. , Memeo Riccardo , Moore Ernest E. , Ordoñez Carlos A. , Peitzman Andrew B. , Pellino Gianluca , Picetti Edoardo , Pikoulis Manos , Pisano Michele , Podda Mauro , Romeo Oreste , Rosa Fausto , Tan Edward , Ten Broek Richard P. , Testini Mario , Tian Wei Cheng Brian Anthony , Weber Dieter , Sacco Emilio , Sartelli Massimo , Tonsi Alfredo , Dal Moro Fabrizio , Catena Fausto
Published: September 2023

Iatrogenic urinary tract injury (IUTI) is a severe complication of emergency digestive surgery. It can lead to increased postoperative morbidity and mortality and have a long-term impact on the quality of life. The reported incidence of IUTIs varies greatly among the studies, ranging from 0.3 to 1.5%. Given the high volume of emergency digestive surgery performed worldwide, there is a need for well-defined and effective strategies to prevent and manage IUTIs. Currently, there is a lack of consensus regarding the prevention, detection, and management of IUTIs in the emergency setting. The present guidelines, promoted by the World Society of Emergency Surgery (WSES), were developed following a systematic review of the literature and an international expert panel discussion. The primary aim of these WSES guidelines is to provide evidence-based recommendations to support clinicians and surgeons in the prevention, detection, and management of IUTIs during emergency digestive surgery. The following key aspects were considered: (1) effectiveness of preventive interventions for IUTIs during emergency digestive surgery; (2) intra-operative detection of IUTIs and appropriate management strategies; (3) postoperative detection of IUTIs and appropriate management strategies and timing; and (4) effectiveness of antibiotic therapy (including type and duration) in case of IUTIs.
Risk factors associated with prolonged intensive care unit stay following surgery for total anomalous pulmonary venous connection: a retrospective study
Authors: Huang Jinjin , Tang Jian , Fan Yong , Wang Dongpi , Ye Lifen
Published: September 2023

Background

Prolonged intensive care unit (ICU) stays consume medical resources and increase medical costs. This study identified risk factors associated with prolonged postoperative intensive care unit (ICU) stay in children with total anomalous pulmonary venous connection (TAPVC).

Methods

The medical records of 85 patients who underwent surgical repair of TAPVC were retrospectively analyzed. The patients were divided into prolonged-stay and standard-stay groups. The prolonged stay group included all patients who exceeded the 75th percentile of the ICU stay duration, and the standard stay group included all remaining patients. The effects of patient variables on ICU stay duration were investigated using univariate and logistic regression analyses.

Results

Patient median age was 41 (18–103) days, and median weight was 3.80 (3.30–5.35) kg.Postoperative duration of ICU stay was 11–68 days in the prolonged stay group (n = 23) and 2–10 days in the standard stay group (n = 62). Lower preoperative pulse oximetry saturation (SpO2), higher intraoperative plasma lactate levels, and prolonged postoperative mechanical ventilation were independent risk factors for prolonged ICU stay. Preoperative SpO2 < 88.5%, highest plasma lactate value > 4.15 mmol/L, and postoperative mechanical ventilation duration was longer than 53.5 h, were associated with increased risk of prolonged ICU stay. Young age, low body weight, subcardiac type, need for vasoactive drug support, emergency surgery, long anesthesia time, low SpO2 after anesthesia induction, long cardiopulmonary bypass (CPB) and aortic clamp times, high lactate level, low temperature, large volume of ultrafiltration during CPB, large amounts of chest drainage, large red blood cells (RBCs) and plasma transfusion, and postoperative cardiac dysfunction may be associated with prolonged ICU stay.

Conclusions

Lower preoperative SpO2, higher intraoperative plasma lactate levels, and prolonged postoperative mechanical ventilation were independent risk factors for prolonged ICU stay in children with TAPVC. When SpO2 was lower than 88.5%, the highest plasma lactate value was more than 4.15 mmol/L, and the postoperative mechanical ventilator duration was longer than 53.5 h, the risk of prolonged ICU stay increased. Improved clinical management, including early diagnosis and timely surgical intervention to reduce hypoxia time and protect intraoperative cardiac function, may reduce ICU stay time.
Concordance of a decision algorithm and multidisciplinary team meetings for patients with liver cancer—a study protocol for a randomized controlled trial
Authors: Ng Sharlyn S. T. , Oehring Robert , Ramasetti Nikitha , Roller Roland , Thomas Philippe , Chen Yuxuan , Moosburner Simon , Winter Axel , Maurer Max-Magnus , Auer Timo A. , Kamali Can , Pratschke Johann , Benzing Christian , Krenzien Felix
Published: September 2023

Introduction

Multidisciplinary team meetings (MDMs), also known as tumor conferences, are a cornerstone of cancer treatments. However, barriers such as incomplete patient information or logistical challenges can postpone tumor board decisions and delay patient treatment, potentially affecting clinical outcomes. Therapeutic Assistance and Decision algorithms for hepatobiliary tumor Boards (ADBoard) aims to reduce this delay by providing automated data extraction and high-quality, evidence-based treatment recommendations.

Methods and analysis

With the help of natural language processing, relevant patient information will be automatically extracted from electronic medical records and used to complete a classic tumor conference protocol. A machine learning model is trained on retrospective MDM data and clinical guidelines to recommend treatment options for patients in our inclusion criteria. Study participants will be randomized to either MDM with ADBoard (Arm A: MDM-AB) or conventional MDM (Arm B: MDM-C). The concordance of recommendations of both groups will be compared using interrater reliability. We hypothesize that the therapy recommendations of ADBoard would be in high agreement with those of the MDM-C, with a Cohen’s kappa value of ≥ 0.75. Furthermore, our secondary hypotheses state that the completeness of patient information presented in MDM is higher when using ADBoard than without, and the explainability of tumor board protocols in MDM-AB is higher compared to MDM-C as measured by the System Causability Scale.

Discussion

The implementation of ADBoard aims to improve the quality and completeness of the data required for MDM decision-making and to propose therapeutic recommendations that consider current medical evidence and guidelines in a transparent and reproducible manner.

Ethics and dissemination

The project was approved by the Ethics Committee of the Charité – Universitätsmedizin Berlin.

Registration details

The study was registered on ClinicalTrials.gov (trial identifying number: NCT05681949; https://clinicaltrials.gov/study/NCT05681949) on 12 January 2023.
Sustainable production of photosynthetic isobutanol and 3-methyl-1-butanol in the cyanobacterium Synechocystis sp. PCC 6803
Authors: Xie Hao , Kjellström Jarl , Lindblad Peter
Published: September 2023

Background

Cyanobacteria are emerging as green cell factories for sustainable biofuel and chemical production, due to their photosynthetic ability to use solar energy, carbon dioxide and water in a direct process. The model cyanobacterial strain Synechocystis sp. PCC 6803 has been engineered for the isobutanol and 3-methyl-1-butanol production by introducing a synthetic 2-keto acid pathway. However, the achieved productions still remained low. In the present study, diverse metabolic engineering strategies were implemented in Synechocystis sp. PCC 6803 for further enhanced photosynthetic isobutanol and 3-methyl-1-butanol production.

Results

Long-term cultivation was performed on two selected strains resulting in maximum cumulative isobutanol and 3-methyl-1-butanol titers of 1247 mg L−1 and 389 mg L−1, on day 58 and day 48, respectively. Novel Synechocystis strain integrated with a native 2-keto acid pathway was generated and showed a production of 98 mg isobutanol L−1 in short-term screening experiments. Enhanced isobutanol and 3-methyl-1-butanol production was observed when increasing the kivdS286T copy number from three to four. Isobutanol and 3-methyl-1-butanol production was effectively improved when overexpressing selected genes of the central carbon metabolism. Identified genes are potential metabolic engineering targets to further enhance productivity of pyruvate-derived bioproducts in cyanobacteria.

Conclusions

Enhanced isobutanol and 3-methyl-1-butanol production was successfully achieved in Synechocystis sp. PCC 6803 strains through diverse metabolic engineering strategies. The maximum cumulative isobutanol and 3-methyl-1-butanol titers, 1247 mg L−1 and 389 mg L−1, respectively, represent the current highest value reported. The significantly enhanced isobutanol and 3-methyl-1-butanol production in this study further pave the way for an industrial application of photosynthetic cyanobacteria-based biofuel and chemical synthesis from CO2.
Healing effects of autologous platelet gel and growth factors on cutaneous leishmaniasis wounds in addition to antimony; a self-controlled clinical trial with randomized lesion assignment
Authors: Shadmand Enayatollah , Solhjoo Kavous , Taghipour Ali , Tayer Akbar Hashemi , Sadeghi Fatemeh , Meshkin Ahmad
Published: September 2023

Objective

Autologous platelet gel (APG) is used in most surgeries to treat a variety of tissue defects because of its healing factors composition. This randomized parallel clinical trial was conducted to investigate the healing effects of APG on cutaneous leishmaniasis (CL) wounds. Eighteen male patients with CL wounds were recruited and followed for two months. The patients had more than one cutaneous wound, one of which was examined as the control and the other one as the intervention wound. APG was applied to the intervention wounds once a week, up to eight times. The primary endpoint was wound healing which defined as complete epithelialization and tissue granulation. Other clinical evaluation criteria were assessment of the wound size, and histopathology analyses.

Results

Of 18 patients, 15 patients completed the trial (83.3%, mean age 28 years). The use of APG on the wounds was associated with complete and faster healing in 66% of the wounds and partial healing in 34% of the wounds. During the study, none of the control wounds were completely healed. The wound area in the intervention cases showed a statistically significant decrease throughout the study (P < 0.01) compared with controls. Following treatment of CL lesions with APG, the inflammatory process in the epidermis and dermis were decreased significantly (P < 0.01) compared with controls.

Conclusion

Our preliminary results confirm the clinical healing improvement described in the literature for APG-GF treatment of chronic non-leishmania wounds via immunomodulation.

Trial registration: IRCT, IRCT20190212042694N1. Registered 20 February 2019, https://en.irct.ir/trial/37522
Introduce a novel post-biotic against Pseudomonas aeruginosa biofilm formation using Escherchia coli Nissle1917 outer membrane vesicles
Authors: Alaei Maryam , Aghakhani Fatemeh , Falsafi Sarvenaz , Mazaheri Hoora , Behrouzi Ava
Published: September 2023

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that can cause acute infections as well as chronic ones in humans. The expression of algD and PpyR genes involved in biofilm formation in clinical isolates of P. aeruginosa in the presence of Escherichia coli Nissle1917 outer membranes vesicles (EcN OMVs) was evaluated. All isolates were tested for biofilm formation. qPCR and disk diffusion were used to identify the expression of algD and PpyR genes, and antimicrobial resistance, respectively. EcN OMVs caused a more significant loss of algD and PpyR expression, compared with the control group. EcN OMVs contain a variety of biomolecules that are capable of influencing the biofilm formation genes. EcN OMVs treatment reduced P. aeruginosa biofilm formation significantly, which emphasizes their positive role in inhibiting biofilm formation. As a result, EcN OMVs can be used as new therapeutic strategies for inhibiting P. aeruginosa biofilm formation.
Habitual glucosamine use, APOE genotypes, and risk of incident cause-specific dementia in the older population
Authors: Zhou Chun , Zhang Yanjun , Yang Sisi , Ye Ziliang , Wu Qimeng , Liu Mengyi , He Panpan , Zhang Yuanyuan , Qin Xianhui
Published: September 2023

Background

The relationship of glucosamine use with incident dementia in the older population remains uncertain. We aimed to evaluate the longitudinal association between habitual glucosamine supplement and the risk of cause-specific dementia and examine the possible effect modifiers on this association.

Methods

The study included 214,945 participants over the age of 60 who had available information on glucosamine use and did not have dementia at baseline in the UK Biobank. The APOE genotypes were determined by a combination variant of rs429358 and rs7412. The primary outcome was incident vascular dementia, incident Alzheimer’s disease, and incident frontotemporal dementia, respectively.

Results

Over a median follow-up duration of 12 years, 1039, 1774, and 122 participants developed vascular dementia, Alzheimer’s disease, and frontotemporal dementia, respectively. Overall, habitual glucosamine use was significantly associated with a lower risk of incident vascular dementia (adjusted HR, 0.82; 95%CI, 0.70–0.96), but not significantly associated with incident Alzheimer’s disease (adjusted HR, 1.02; 95%CI, 0.92–1.14) and incident frontotemporal dementia (adjusted HR, 0.95; 95%CI, 0.63–1.43). Moreover, the inverse association between habitual glucosamine use and incident vascular dementia was more pronounced in participants with concomitant supplement of calcium (P-interaction = 0.011), and those without concomitant supplement of zinc (P-interaction = 0.018). However, APOE ε4 dosage and baseline cognitive function did not significantly modify the relationships of glucosamine use with incident vascular dementia or Alzheimer’s disease (All P-interactions > 0.05).

Conclusions

Regardless of APOE genotypes and baseline cognitive function, habitual glucosamine use was significantly inversely associated with incident vascular dementia in the older population.
Validity of fractional exhaled nitric oxide and small airway lung function measured by IOS in the diagnosis of cough variant asthma in preschool children with chronic cough
Authors: Hu Ying , Zheng Shouyan , Chen Zhiqiang , Yu Dan , Lai Tianxia , Chen Yao , Liao Wei
Published: September 2023

Background

To investigate the role of combined impulse oscillometry (IOS) and fractional exhaled nitric oxide (FeNO) in the diagnosis of cough variant asthma (CVA) in preschool children.

Methods

A total of 197 preschool-aged children with chronic cough were selected from the paediatric outpatient clinic. Allergy histories were collected for all children along with IOS and FeNO. Paediatric respiratory specialists divided the children into a CVA group (n = 90) and a noncough variant asthma (nCVA) group (n = 107) according to the diagnostic criteria for CVA After diagnostic treatment, the correlation between the FeNO and IOS values and the diagnosis in the two groups was analysed, and the area under the curve (AUC) of each index was calculated.

Results

(1) X5 was significantly different between the CVA group and the nCVA group (− 4.22 vs. − 3.64, p < 0.001), as was the FeNO value (29.07 vs. 16.64, p < 0.001). (2) Receiver operating characteristic (ROC) analysis showed that the AUCs of FeNO alone and X5 alone were 0.779 and 0.657, respectively, while the AUC of FeNO (cut-off value of 18 ppb) plus X5 (cut-off value of -4.15 cmH2O/(l/s)) reached 0.809.

Conclusions

Children with CVA may have small airway dysfunction at an early stage. For preschool children with chronic cough, the combination of FeNO and X5 can better identify those with CVA.

Trial registration number: This trial was registered with and approved by the Chinese Clinical Trial Registry, with registration number ChiCTRcRRC-17011738, and was reviewed and approved by the Ethics Committee of Southwest Hospital.
Phosphorylation at tyrosine 317 and 508 are crucial for PIK3CA/p110α to promote CRC tumorigenesis
Authors: Wang Ting , Sun Longci , Chen Chengkun , Zhang Yingchao , He Baoyu , Zhang Yanhua , Wang Zhenghe , Xue Hanbing , Hao Yujun
Published: September 2023

Background

PI3K/AKT signaling pathway plays important role in tumorigenesis of human cancer. Protein phosphorylation is crucial for signaling transduction of this pathway. PIK3CA, encoding the catalytic subunit p110α of PI3K complex, is one of the most frequently mutated oncogenes in human cancers. However, phosphorylation sites of PIK3CA/p110α and their underlying mechanism in tumorigenesis are largely unknown.

Methods

Tyrosine phosphorylation sites of PIK3CA/p110α are identified with Mass-Spectrum. Crispr/CAS9 strategy is applied to generate Y317F and Y508F mutant knock-in cell clones. The growth and metastasis abilities of cells are evaluated in vitro and in vivo. Phospho-proteomics analysis and Western blots are used to demonstrate downstream signaling pathways of PIK3CA/p110α tyrosine phosphorylation. In vitro kinase assay is applied to identify the kinase of PIK3CA/p110α tyrosine phosphorylation.

Results

Tyrosine phosphorylation of PIK3CA/p110α is stimulated by growth factors such as EGF, HGF and PDGF. Two tyrosine residues, Y317 and Y508, are identified on PIK3CA/p110α. Either Y317 or Y508 phosphorylation is essential for tumorigenesis of CRC. Mutation at Y317 of p110α reduces the proliferation, migration, and invasion of cancer cells through Src-MLC2 pathway, while mutation at Y508 of p110α impairs AKT signaling. Moreover, Src interacts with and phosphorylates p110α.

Conclusions

PIK3CA/p110α phosphorylation at Y317 and Y508 play important role in tumorigenesis of colorectal cancer through two independent pathways.
Severe anaemia secondary to a perforated gastric ulcer in a male alpaca
Authors: Wagener Matthias Gerhard , Punsmann Teresa Maria , Kleinschmidt Sven , Surholt Ralf , Neubert Saskia , Marahrens Hannah , Großmann Thekla , Ganter Martin
Published: September 2023

Background

Anaemia is a common condition in alpacas and attributable to a variety of causes. Severe anaemia with a packed cell volume (PCV) less than 10% is frequently diagnosed, usually due to blood loss resulting from haemonchosis. Many South American camelids (SACs) also suffer from gastric ulcers, which are often associated with anaemia in other species. However, in alpacas and llamas, gastric ulcers usually do not lead to anaemia due to blood loss according to the current literature. There are no detailed clinical and laboratory data on this condition in the scientific literature so far.

Case presentation

We report on the case of a nine-year-old male alpaca that was presented to the clinic with suspected forestomach acidosis. The animal showed clinical signs of colic, hypothermia, tachypnea, tachycardia, pale mucous membranes, and died shortly after admission to the clinic. Laboratory diagnosis revealed a markedly decreased haematocrit (0.13 l/l), leucopaenia with band neutrophils, azotaemia, hypocalcaemia, hyperphosphataemia and vitamin D deficiency. Post-mortem examination revealed multiple ulcers in the first and third compartment with perforation of one ulcer in the first compartment, resulting in intraluminal blood loss and purulent peritonitis.

Conclusions

To the authors’ knowledge, this is the first detailed description of clinical and laboratory data of severe anaemia due to a perforated gastric ulcer in a SAC. Although the current literature suggests that severe blood loss due to gastric ulcers does not occur in SACs, this condition should be considered as a possible differential diagnosis in anaemic animals. Clinical indicators can be colic and pale mucous membranes.
Impaired autophagy contributes to the aggravated deterioration of osteoarthritis articular cartilage by peroxisome proliferator-activated receptor α deficiency, associated with decreased ERK and Akt activation
Authors: Zhou Yang , Li Li , Chen Xiaolei , Zhao Qiubo , Qu Ning , Zhang Bing , Jin Xin , Xia Chun
Published: September 2023

Background

Although the chondroprotection of peroxisome proliferator-activated receptor α (PPARα) activation against osteoarthritis (OA) has been revealed, the regulatory mechanism of PPARα deficiency to aggravate osteoarthritic cartilage deterioration remains unclear. Here, we aimed to investigate whether and how autophagy is involved in OA pathological progression.

Methods

Model of experimental OA was established using destabilization of the medial meniscus in PPARα-KO 129S4/SvJae male mice, followed by histopathological detection of articular cartilage and immunohistochemistry detection of extracellular matrix (ECM) or autophagy-related signal molecules. Meanwhile, human OA chondrocytes obtained from total knee replacement surgery patients with OA were cultured with the pretreatment of IL-1β, followed with the treatment of PPARα agonist WY14643 and the detection of related signal molecules.

Results

PPARα deficiency aggravated cartilage damage with decreased LC3B level in combination with an increase in P62 level, accompanied with reduced p-Akt and p-ERK levels in PPARα-KO mouse model of experimental OA. On the contrary, PPARα activation by WY14643 promoted ECM synthesis in IL-1β-treated human OA chondrocytes, accompanied with increased LC3B-II/I ratio and Beclin 1 level and decreased P62 and Bcl2 levels. Meanwhile, it was observed that activated ERK and Akt by PPARα activation contributed to the enhancement of autophagy and ECM synthesis in human OA chondrocytes.

Conclusions

Impaired autophagy contributed to the aggravated deterioration of osteoarthritis articular cartilage by PPARα deficiency associated with the suppression of ERK and Akt, with an implication that triggering PPARα activation ought to be a potential promising therapeutic target for OA therapy.
Neddylation inhibitor MLN4924 sensitizes head and neck squamous carcinoma cells to (S)-10-hydroxycamptothecin
Authors: Gu Shanshan , Lin Chen , Li Yanguo , Wei Zhengyu , cao Bing , Shen Zhisen , Deng Hongxia
Published: September 2023

Head and neck squamous carcinoma (HNSCC) is the seventh most common cancer worldwide. Targeted therapeutic drugs for HNSCC are still being explored. Among them, (S)-10-hydroxycamptothecin (10-HCPT), a specific inhibitor of TOP1, functions by DNA double-strand breaks that can inhibit DNA replication and trigger apoptotic cell death subsequently. Previous studies have reported that MLN4924 exerts potent anti-tumor effects by inhibiting cullin–RING ligases and causing substrate accumulation in a variety of cancers. Here, we show that MLN4924 effectively causes dose-dependent accumulation of topoisomerase I (TOP1) and blocks TOP1 ubiquitination. Importantly, neddylation inhibition with MLN4924 acts synergistically with 10-HCPT to suppress cell growth, migration and apoptosis in HNSCC cells. Mechanistically, transcriptome sequencing shows that the cytotoxic effects of the combination of MLN4924 and 10-HCPT may involve activation of the NFKB1 pathway. Taken together, our results suggest that combined treatment with MLN4924 and 10-HCPT may be an effective strategy in HNSCC.
Development of nomograms to predict recurrence after conversion hepatectomy for hepatocellular carcinoma previously treated with transarterial interventional therapy
Authors: Deng Min , Zhao Rongce , Guan Renguo , Li Shaohua , Zuo Zhijun , Lin Wenping , Wei Wei , Guo Rongping
Published: September 2023

Background

Lack of opportunity for radical surgery and postoperative tumor recurrence are challenges for surgeons and hepatocellular carcinoma (HCC) patients. This study aimed to develop nomograms to predict recurrence risk and recurrence-free survival (RFS) probability after conversion hepatectomy for patients previously receiving transarterial interventional therapy.

Methods

In total, 261 HCC patients who underwent conversion liver resection and previously received transarterial interventional therapy were retrospectively enrolled. Nomograms to predict recurrence risk and RFS were developed, with discriminative ability and calibration evaluated by C-statistics, calibration plots, and the Area under the Receiver Operator Characteristic (AUROC) curves.

Results

Univariate/multivariable logistic regression and Cox regression analyses were used to identify predictive factors for recurrence risk and RFS, respectively. The following factors were selected as predictive of recurrence: age, tumor number, microvascular invasion (MVI) grade, preoperative alpha‐fetoprotein (AFP), preoperative carbohydrate antigen 19-9 (CA19-9), and Eastern Cooperative Oncology Group performance score (ECOG PS). Similarly, age, tumor number, postoperative AFP, postoperative protein induced by vitamin K absence or antagonist-II (PIVKA-II), and ECOG PS were incorporated for the prediction of RFS. The discriminative ability and calibration of the nomograms revealed good predictive ability. Calibration plots showed good agreement between the nomogram predictions of recurrence and RFS and the actual observations.

Conclusions

A pair of reliable nomograms was developed to predict recurrence and RFS in HCC patients after conversion resection who previously received transarterial interventional therapy. These predictive models can be used as guidance for clinicians to help with treatment strategies.
Validity of distal radius fracture diagnoses in the Swedish National Patient Register
Authors: Südow Hanna , Sjödin Linda , Mellstrand Navarro Cecilia
Published: September 2023

Distal radius fractures are one of the most common fractures in adults. More research is needed to establish evidence-based clinical practice guidelines to generate cost-effective and fair fracture treatment. The Swedish National Patient Register is a principal source for population-based epidemiologic studies in Sweden. The validity of some–but not all–diagnoses in the register is high. Little is known regarding the validity of registration of distal radius fractures.

A dataset of cases registered with diagnosis of distal radius fracture (S52.5) or distal radius and ulna fracture (S52.6) were collected from the Swedish National Inpatient and Outpatient Registers. Six cohorts, each containing 240 simple random samples, were constructed. Radiographic reports and medical records were reviewed to confirm or reject the diagnosis as well as, in relevant cases, the surgical intervention. Positive predictive values (PPV) were calculated.

The PPV for distal radius fracture in the register ranges between 92 and 100%, lower if coded as S52.6 and higher if there was an adherent code of surgical intervention. Codes for surgical intervention reached a PPV of 95–100%.

In conclusion, the validity of the codes for diagnosis and the surgical treatment of distal radius fracture is high in the Swedish National Patient Register. According to our results, the register may be used as a reliable data source for population-based research of distal radius fractures.
Association between diastolic blood pressure during the first 24 h and 28-day mortality in patients with septic shock: a retrospective observational study
Authors: Gao Zhiwei , Li Cong , Chen Hui , Chen Dongyu , Ma ShaoLei , Xie Jianfeng , Wu Changde , Liu Ling , Yang Yi
Published: September 2023

Background

Although the mean arterial pressure (MAP) target of 65 mmHg was achieved, diastolic blood pressure (DBP) was still low in some septic shock patients. The effects of DBP on the prognosis and optimal target for patients with septic shock are unclear. We sought to investigate the relationship between DBP and 28-day mortality in septic shock patients.

Methods

In this retrospective observational study, we obtained data from the Chinese Database in Intensive Care (CDIC). We included patients with an admission diagnosis of septic shock and shock was controlled. DBP was measured every 1 h, and the mean DBP during the first 24 h (mDBP24h) was recorded. The primary outcome was 28-day mortality. Multivariable logistic regression determined the relationship between mDBP24h and 28-day mortality.

Results

In total, 1251 patients were finally included. The 28-day mortality of included septic shock patients was 28.3%. The mDBP24h, not mSBP24h, was higher among 28-day survivors compared with non-survivors. 28-day mortality was inversely associated with mDBP24h (unadjusted OR 0.814 per 10 mmHg higher mDBP24h, P = 0.003), with a stepwise increase in 28-day mortality at lower mDBP24h. The 28-day mortality of patients with mDBP24h < 59 mmHg had an absolute risk reduction of 9.4% (P = 0.001). And mDBP24h < 59 mmHg was the remaining high risk factor inversely associated with 28-day mortality after multivariable adjustment (adjusted OR 1.915, 95% CI 1.037–3.536, P = 0.038), while mMAP24h and mSBP24h were not.

Conclusion

In patients with septic shock after initial resuscitation, we observed an inverse association between mDBP24h and 28-day mortality. The poor outcomes in patients with mDBP24h < 59 mmHg provide indirect evidence supporting a further DBP goal of 59 mmHg for patients with septic shock after MAP of 65 mmHg was achieved.