bluuebunny/crossref_metadata_2025 huggingface dataset:
Polymeric nanomedicines for the treatment of hepatic diseases
Authors: Luo Feixiang , Yu Ying , Li Mingqian , Chen Yuguo , Zhang Peng , Xiao Chunsheng , Lv Guoyue
Published: November 2022

The liver is an important organ in the human body and performs many functions, such as digestion, detoxification, metabolism, immune responses, and vitamin and mineral storage. Therefore, disorders of liver functions triggered by various hepatic diseases, including hepatitis B virus infection, nonalcoholic steatohepatitis, hepatic fibrosis, hepatocellular carcinoma, and transplant rejection, significantly threaten human health worldwide. Polymer-based nanomedicines, which can be easily engineered with ideal physicochemical characteristics and functions, have considerable merits, including contributions to improved therapeutic outcomes and reduced adverse effects of drugs, in the treatment of hepatic diseases compared to traditional therapeutic agents. This review describes liver anatomy and function, and liver targeting strategies, hepatic disease treatment applications and intrahepatic fates of polymeric nanomedicines. The challenges and outlooks of hepatic disease treatment with polymeric nanomedicines are also discussed.
Music festival drug checking: evaluation of an Australian pilot program
Authors: Olsen Anna , Wong Gabriel , McDonald David
Published: November 2022

Background

This paper explores the feasibility of delivering a music festival-based drug checking service in Australia, evaluating service design and stakeholder acceptability.

Methods

Questionnaire and interview data were collected from adult service users and key stakeholders. A mixed methods approach was used to analyse the data on implementation, impact and acceptability.

Results

The trial service tested 170 substances with more than 230 patrons (including individuals who attended in groups). Adult service users had an average age of 21 years. Voluntary participation in the evaluation resulted in 158 participants completing the pre-service questionnaire, most of whom also completed the post-service (147 participants). Eleven in-depth qualitative interviews were conducted with patrons in the weeks following the drug checking. Concordance between what the patron expected the drug to be and drug checking results occurred in 88 per cent (n = 139) of the sample. Evaluation results show that the experience of testing and the accompanying harm reduction brief interventions positively impacted on patrons’ self-reported drug harm reduction knowledge, trust of health providers and stated drug use intentions. The service was received positively by service users.

Conclusion

This is the first independent evaluation of a pilot drug checking service in Australia. Consideration of operational feasibility and self-reported behavioural change suggests that the program was successful, although communication about the interpretation of drug checking results could be improved. Future studies should develop strategies for follow-up and consider the applicability of behavioural change theory.
Juvenile idiopathic arthritis polygenic risk scores are associated with cardiovascular phenotypes in early adulthood: a phenome-wide association study
Authors: Clarke Sarah L. N. , Jones Hannah J. , Sharp Gemma C. , Easey Kayleigh E. , Hughes Alun D. , Ramanan Athimalaipet V. , Relton Caroline L.
Published: November 2022

Background

There is growing concern about the long-term cardiovascular health of patients with juvenile idiopathic arthritis (JIA). In this study we assessed the association between JIA polygenic risk and cardiovascular phenotypes (cardiovascular risk factors, early atherosclerosis/arteriosclerosis markers, and cardiac structure and function measures) early in life.

Methods

JIA polygenic risk scores (PRSs) were constructed for 2,815 participants from the Avon Longitudinal Study of Parents and Children, using the single nucleotide polymorphism (SNP) weights from the most recent JIA genome wide association study. The association between JIA PRSs and cardiovascular phenotypes at age 24 years was assessed using linear and logistic regression. For outcomes with strong evidence of association, further analysis was undertaken to examine how early in life (from age seven onwards) these associations manifest.

Results

The JIA PRS was associated with diastolic blood pressure (β 0.062, 95% CI 0.026 to 0.099, P = 0.001), insulin (β 0.050, 95% CI 0.011 to 0.090, P = 0.013), insulin resistance index (HOMA2_IR, β 0.054, 95% CI 0.014 to 0.095, P = 0.009), log hsCRP (β 0.053, 95% CI 0.011 to 0.095, P = 0.014), waist circumference (β 0.041, 95% CI 0.007 to 0.075, P = 0.017), fat mass index (β 0.049, 95% CI 0.016 to 0.083, P = 0.004) and body mass index (β 0.046, 95% CI 0.011 to 0.081, P = 0.010). For anthropometric measures and diastolic blood pressure, there was suggestive evidence of association with JIA PRS from age seven years. The findings were consistent across multiple sensitivity analyses.

Conclusions

Genetic liability to JIA is associated with multiple cardiovascular risk factors, supporting the hypothesis of increased cardiovascular risk in JIA. Our findings suggest that cardiovascular risk is a core feature of JIA, rather than secondary to the disease activity/treatment, and that cardiovascular risk counselling should form part of patient care.
Current perspectives on diffuse midline glioma and a different role for the immune microenvironment compared to glioblastoma
Authors: Pachocki Casper J. , Hol Elly M.
Published: November 2022

Diffuse midline glioma (DMG), formerly called diffuse intrinsic pontine glioma (DIPG), is a high-grade malignant pediatric brain tumor with a near-zero survival rate. To date, only radiation therapy provides marginal survival benefit; however, the median survival time remains less than a year. Historically, the infiltrative nature and sensitive location of the tumor rendered surgical removal and biopsies difficult and subsequently resulted in limited knowledge of the disease, as only post-mortem tissue was available. Therefore, clinical decision-making was based upon experience with the more frequent and histologically similar adult glioblastoma (GBM). Recent advances in tissue acquisition and molecular profiling revealed that DMG and GBM are distinct disease entities, with separate tissue characteristics and genetic profiles. DMG is characterized by heterogeneous tumor tissue often paired with an intact blood–brain barrier, possibly explaining its resistance to chemotherapy. Additional profiling shed a light on the origin of the disease and the influence of several mutations such as a highly recurring K27M mutation in histone H3 on its tumorigenesis. Furthermore, early evidence suggests that DMG has a unique immune microenvironment, characterized by low levels of immune cell infiltration, inflammation, and immunosuppression that may impact disease development and outcome. Within the tumor microenvironment of GBM, tumor-associated microglia/macrophages (TAMs) play a large role in tumor development. Interestingly, TAMs in DMG display distinct features and have low immune activation in comparison to other pediatric gliomas. Although TAMs have been investigated substantially in GBM over the last years, this has not been the case for DMG due to the lack of tissue for research. Bit by bit, studies are exploring the TAM–glioma crosstalk to identify what factors within the DMG microenvironment play a role in the recruitment and polarization of TAMs. Although more research into the immune microenvironment is warranted, there is evidence that targeting or stimulating TAMs and their factors provide a potential treatment option for DMG. In this review, we provide insight into the current status of DMG research, assess the knowledge of the immune microenvironment in DMG and GBM, and present recent findings and therapeutic opportunities surrounding the TAM–glioma crosstalk.
Constitutively active microglial populations limit anorexia induced by the food contaminant deoxynivalenol
Authors: Gaige Stéphanie , Barbouche Rym , Barbot Manon , Boularand Sarah , Dallaporta Michel , Abysique Anne , Troadec Jean-Denis
Published: November 2022

Microglia are involved in neuroinflammatory processes during diverse pathophysiological conditions. To date, the possible contribution of these cells to deoxynivalenol (DON)-induced brain inflammation and anorexia has not yet been evaluated. DON, one of the most abundant trichothecenes found in cereals, has been implicated in mycotoxicosis in both humans and farm animals. DON-induced toxicity is characterized by reduced food intake, weight gain, and immunological effects. We previously showed that exposure to DON induces an inflammatory response within the hypothalamus and dorsal vagal complex (DVC) which contributes to DON-induced anorexia. Here, in response to anorectic DON doses, we reported microglial activation within two circumventricular organs (CVOs), the area postrema (AP) and median eminence (ME) located in the DVC and the hypothalamus, respectively. Interestingly, this microglial activation was observed while DON-induced anorexia was ongoing (i.e., 3 and 6 h after DON administration). Next, we took advantage of pharmacological microglia deletion using PLX3397, a colony-stimulating factor 1 receptor (CSF1R)-inhibitor. Surprisingly, microglia-depleted mice exhibited an increased sensitivity to DON since non-anorectic DON doses reduced food intake in PLX3397-treated mice. Moreover, low DON doses induced c-Fos expression within feeding behavior-associated structures in PLX3397-treated mice but not in control mice. In parallel, we have highlighted heterogeneity in the phenotype of microglial cells present in and around the AP and ME of control animals. In these areas, microglial subpopulations expressed IBA1, TMEM119, CD11b and CD68 to varying degrees. In addition, a CD68 positive subpopulation showed, under resting conditions, a noticeable phagocytotic/endocytotic activity. We observed that DON strongly reduced CD68 in the hypothalamus and DVC. Finally, inactivation of constitutively active microglia by intraperitoneal administration of minocycline resulted in anorexia with a DON dose ineffective in control mice. Taken together, these results strongly suggest that various populations of microglial cells residing in and around the CVOs are maintained in a functionally active state even under physiological conditions. We propose that these microglial cell populations are attempting to protect the brain parenchyma from hazardous molecules coming from the blood. This study could contribute to a better understanding of how microglia respond to environmental contaminants.
Genetic deletion of Krüppel-like factor 11 aggravates traumatic brain injury
Authors: Zhou Chao , Sun Ping , Hamblin Milton H. , Yin Ke-Jie
Published: November 2022

Background

The long-term functional recovery of traumatic brain injury (TBI) is hampered by pathological events, such as parenchymal neuroinflammation, neuronal death, and white matter injury. Krüppel-like transcription factor 11 (KLF 11) belongs to the zinc finger family of transcription factors and actively participates in various pathophysiological processes in neurological disorders. Up to now, the role and molecular mechanisms of KLF11 in regulating the pathogenesis of brain trauma is poorly understood.

Methods

KLF11 knockout (KO) and wild-type (WT) mice were subjected to experimental TBI, and sensorimotor and cognitive functions were evaluated by rotarod, adhesive tape removal, foot fault, water maze, and passive avoidance tests. Brain tissue loss/neuronal death was examined by MAP2 and NeuN immunostaining, and Cresyl violet staining. White matter injury was assessed by Luxol fast blue staining, and also MBP/SMI32 and Caspr/Nav1.6 immunostaining. Activation of cerebral glial cells and infiltration of blood-borne immune cells were detected by GFAP, Iba-1/CD16/32, Iba-1/CD206, Ly-6B, and F4/80 immunostaining. Brian parenchymal inflammatory cytokines were measured with inflammatory array kits.

Results

Genetic deletion of KLF11 worsened brain trauma-induced sensorimotor and cognitive deficits, brain tissue loss and neuronal death, and white matter injury in mice. KLF11 genetic deficiency in mice also accelerated post-trauma astrocytic activation, promoted microglial polarization to a pro-inflammatory phenotype, and increased the infiltration of peripheral neutrophils and macrophages into the brain parenchyma. Mechanistically, loss-of-KLF11 function was found to directly increase the expression of pro-inflammatory cytokines in the brains of TBI mice.

Conclusion

KLF11 acts as a novel protective factor in TBI. KLF11 genetic deficiency in mice aggravated the neuroinflammatory responses, grey and white matter injury, and impaired long-term sensorimotor and cognitive recovery. Elucidating the functional importance of KLF11 in TBI may lead us to discover novel pharmacological targets for the development of effective therapies against brain trauma.
The neuropeptide PACAP alleviates T. gondii infection-induced neuroinflammation and neuronal impairment
Authors: Figueiredo Caio Andreeta , Düsedau Henning Peter , Steffen Johannes , Ehrentraut Stefanie , Dunay Miklos P. , Toth Gabor , Reglödi Dora , Heimesaat Markus M. , Dunay Ildiko Rita
Published: November 2022

Background

Cerebral infection with the protozoanToxoplasma gondii(T. gondii) is responsible for inflammation of the central nervous system (CNS) contributing to subtle neuronal alterations. Albeit essential for brain parasite control, continuous microglia activation and recruitment of peripheral immune cells entail distinct neuronal impairment upon infection-induced neuroinflammation. PACAP is an endogenous neuropeptide known to inhibit inflammation and promote neuronal survival. Since PACAP is actively transported into the CNS, we aimed to assess the impact of PACAP on theT. gondii-induced neuroinflammation and subsequent effects on neuronal homeostasis.

Methods

Exogenous PACAP was administered intraperitoneally in the chronic stage ofT. gondiiinfection, and brains were isolated for histopathological analysis and determination of pathogen levels. Immune cells from the brain, blood, and spleen were analyzed by flow cytometry, and the further production of inflammatory mediators was investigated by intracellular protein staining as well as expression levels by RT-qPCR. Neuronal and synaptic alterations were assessed on the transcriptional and protein level, focusing on neurotrophins, neurotrophin-receptors and signature synaptic markers.

Results

Here, we reveal that PACAP administration reduced the inflammatory foci and the number of apoptotic cells in the brain parenchyma and restrained the activation of microglia and recruitment of monocytes. The neuropeptide reduced the expression of inflammatory mediators such as IFN-γ, IL-6, iNOS, and IL-1β. Moreover, PACAP diminished IFN-γ production by recruited CD4+ T cells in the CNS. Importantly, PACAP promoted neuronal health via increased expression of the neurotrophin BDNF and reduction of p75NTR, a receptor related to neuronal cell death. In addition, PACAP administration was associated with increased expression of transporters involved in glutamatergic and GABAergic signaling that are particularly affected during cerebral toxoplasmosis.

Conclusions

Together, our findings unravel the beneficial effects of exogenous PACAP treatment upon infection-induced neuroinflammation, highlighting the potential implication of neuropeptides to promote neuronal survival and minimize synaptic prejudice.
The envelope proteins from SARS-CoV-2 and SARS-CoV potently reduce the infectivity of human immunodeficiency virus type 1 (HIV-1)
Authors: Henke Wyatt , Waisner Hope , Arachchige Sachith Polpitiya , Kalamvoki Maria , Stephens Edward
Published: November 2022

Background

Viroporins are virally encoded ion channels involved in virus assembly and release. Human immunodeficiency virus type 1 (HIV-1) and influenza A virus encode for viroporins. The human coronavirus SARS-CoV-2 encodes for at least two viroporins, a small 75 amino acid transmembrane protein known as the envelope (E) protein and a larger 275 amino acid protein known as Orf3a. Here, we compared the replication of HIV-1 in the presence of four different β-coronavirus E proteins.

Results

We observed that the SARS-CoV-2 and SARS-CoV E proteins reduced the release of infectious HIV-1 yields by approximately 100-fold while MERS-CoV or HCoV-OC43 E proteins restricted HIV-1 infectivity to a lesser extent. Mechanistically, neither reverse transcription nor mRNA synthesis was involved in the restriction. We also show that all four E proteins caused phosphorylation of eIF2-α at similar levels and that lipidation of LC3-I could not account for the differences in restriction. However, the level of caspase 3 activity in transfected cells correlated with HIV-1 restriction in cells. Finally, we show that unlike the Vpu protein of HIV-1, the four E proteins did not significantly down-regulate bone marrow stromal cell antigen 2 (BST-2).

Conclusions

The results of this study indicate that while viroporins from homologous viruses can enhance virus release, we show that a viroporin from a heterologous virus can suppress HIV-1 protein synthesis and release of infectious virus.
Characteristics of lymphocyte subset alterations in COVID-19 patients with different levels of disease severity
Authors: Dai Wei , Zhong Aifang , Qiao Qinghua , Wu Jian , Li Weiwei , Wu Qiuyue , Zhou Hongjian , Qin Shijie , Jiang Weijun , Zhang Jing , Xia Xinyi
Published: November 2022

Background

Coronavirus disease 2019 (COVID-19) is a respiratory disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which had rapidly spread all over the world and caused public health emergencies in the past two years. Although the diagnosis and treatment for COVID-19 have been well defined, the immune cell characteristics and the key lymphocytes subset alterations in COVID-19 patients have not been thoroughly investigated.

Methods

The levels of immune cells including T cells, B cells, and natural killer (NK) cells in 548 hospitalized COVID-19 patients, and 30 types of lymphocyte subsets in 125 hospitalized COVID-19 patients admitted to Wuhan Huoshenshan Hospital of China were measured using flow cytometry. The relationship between lymphocytes subsets with the cytokine interleukin-6 (IL-6) and the characteristics of lymphocyte subsets in single-cell RNA sequencing (scRNA-seq) data obtained from peripheral blood mononuclear cells (PBMCs) were also analysed in COVID-19 patients.

Results

In this study, we found that patients with critical COVID-19 infection exhibited an overall decline in lymphocytes including CD4+ T cells, CD8+ T cells, total T cells, B cells, and NK cells compared to mild and severe patients. However, the number of lymphocyte subsets, such as CD21low CD38low B cells, effector T4 cells, and PD1+ depleted T8 cells, was moderately increased in critical COVID-19 patients compared to mild cases. Notably, except for effector memory T4 cells, plasma blasts and Tregs, the number of all lymphocyte subsets was markedly decreased in COVID-19 patients with IL-6 levels over 30-fold higher than those in healthy cases. Moreover, scRNA-seq data showed obvious differences in the distribution and numbers of lymphocyte subsets between COVID-19 patients and healthy persons, and subsets-specific marker genes of lymphocyte subsets including CD4, CD19, CCR7, and IL7R, were markedly decreased in COVID-19 patients compared with those in healthy cases.

Conclusion

A comprehensive decrease in immune cell and lymphocyte subsets in critical COVID-19 patients, and peripheral lymphocyte subset alterations showed a clear association with clinical characteristics.
Right brain-to-right brain psychotherapy: recent scientific and clinical advances
Authors: Schore Allan
Published: November 2022

This article overviews my recent acceptance of a Lifetime Achievement Award from Sapienza University of Rome, in which I discussed three decades of my work on the right brain in development, psychopathogenesis, and psychotherapy. In the following, I offer current brain laterality and hemispheric asymmetry research indicating that right brain emotional and relational processes operate beneath conscious awareness not only in early human development, but over the lifespan. I discuss recent interdisciplinary studies on the central role of ultrarapid right brain-to-right brain intersubjective communications of face, voice, and gesture and the implicit regulation of emotion in nonverbal attachment dynamics. Special emphasis is on the fundamental psychobiological process of interpersonal synchrony, and on the evolutionary mechanism of attachment, the interactive regulation of biological synchrony within and between organisms. I then present some clinical applications, suggesting that effective therapeutic work with “primitive” nonverbal emotional attachment dynamics focuses not on conscious verbal insight but on the formation of an unconscious emotion-communicating and regulating bond within the therapeutic relationship. Lastly, I review recent hyperscanning research of the patient’s and therapist’s brains during a face-to-face, emotionally focused psychotherapy session that supports the right brain-to-right brain communication model. I end suggesting that the right brain is dominant in both short-term symptom-reducing and long-term growth-promoting deep psychotherapy.
Evaluation of tumor-infiltrating lymphocytes (TILs) in molecular subtypes of an Indian cohort of breast cancer patients
Authors: Vaid Pooja M. , Puntambekar Anirudha K. , Jumle Nutan S. , Banale Rituja A. , Ansari Danish , Reddy Ruhi R. , Unde Rohini R. , Namewar Namrata P. , Kelkar Devaki A. , Shashidhara L. S. , Koppiker Chaitanyanand B. , Kulkarni Madhura D.
Published: November 2022

Objectives

Evaluation of tumor-infiltrating lymphocytes (TILs) distribution in an Indian cohort of breast cancer patients for its prognostic significance.

Methods

A retrospective cohort of breast cancer patients from a single onco-surgeon’s breast cancer clinic with a uniform treatment strategy was evaluated for TILs. Tumor sections were H&E stained and scored for the spatial distribution and percent stromal TILs infiltration by a certified pathologist. The scores were analysed for association with treatment response and survival outcomes across molecular subtypes.

Results

Total 229 breast cancer tumors were evaluated. Within spatial distribution categories, intra-tumoral TILs were observed to be associated with complete pathological response and lower recurrence frequency for the entire cohort. Subtype-wise analysis of stromal TILs (sTILs) re-enforced significantly higher infiltration in TNBC compared to HER2-positive and ER-positive tumors. A favourable association of higher stromal infiltration was observed with treatment response and disease outcomes, specifically in TNBC.

Conclusion

Intra-tumoral TILs showed a higher proportion with favourable association with better patient outcomes in an Indian cohort, unlike western cohorts where both stromal and intra-tumoral TILs show similar association with prognosis. With further validation, TILs can be developed as a cost-effective surrogate marker for treatment response, especially in a low-resource setting such as India.
Treatment barriers among young adults living with a substance use disorder in Tshwane, South Africa
Authors: Nyashanu Tichaenzana , Visser Maretha
Published: November 2022

Background

Despite increasing substance use globally, substance use treatment utilisation remains low. This study sought to explore and measure substance use treatment barriers among young adults in South Africa.

Methods

The study was done in collaboration with the Community-Oriented Substance Use Programme run in Tshwane, South Africa. A mixed methods approach employing focus group discussions with key informants (n = 15), a survey with a random sample of people using substances and receiving treatment (n = 206), and individual semi-structured interviews (n = 15) was used. Descriptive statistics and thematic analysis were used to analyse data.

Results

Contextual barriers seemed more prominent than attitudinal barriers in the South African context. Fragmented services, stigma-related factors, an information gap and lack of resources and support (contextual factors), perceived lack of treatment efficacy, privacy concerns, and denial and unreadiness to give up (attitudinal factors) were treatment barriers that emerged as themes in both quantitative and qualitative data. Culture and religion/spirituality emerged as an important barrier/facilitator theme in the qualitative data.

Conclusion

Interventions need to embrace contextual factors such as culture, and more resources should be channelled towards substance use treatment. Multi-level stakeholder engagement is needed to minimise stigmatising behaviours from the community and to raise awareness of available treatment services. There is a need for strategies to integrate cultural factors, such as religion/spirituality and traditional healing, into treatment processes so that they complementarily work together with pharmacological treatments to improve health outcomes.
Chemoradiation versus surgery for superficial esophageal squamous cell carcinoma after noncurative endoscopic submucosal dissection: comparison of long-term oncologic outcomes
Authors: Suzuki Gen , Yamazaki Hideya , Aibe Norihiro , Masui Koji , Kimoto Takuya , Nagasawa Shinsuke , Watanabe Shou , Seri Shou , Asato Akito , Shiozaki Atsushi , Fujiwara Hitoshi , Konishi Hirotaka , Dohi Osamu , Ishikawa Takeshi , Elsaleh Hany , Yamada Kei
Published: November 2022

Background

Esophagectomy is the standard adjuvant treatment for superficial esophageal squamous cell carcinoma (SESCC) following noncurative endoscopic submucosal dissection (ESD). However, recent reports have also shown that ESD with adjuvant chemoradiotherapy (CRT) has promising results. This retrospective study aimed to elucidate the efficacy of CRT compared to surgery in patients with SESCC after noncurative ESD.

Methods

This study retrospectively compared the long-term outcomes of patients who received adjuvant treatment with surgery or CRT after noncurative ESD for SESCC.

Results

Data were collected from 60 patients who developed SESCC after noncurative ESD, 34 of whom received adjuvant chemoradiotherapy (CRT) and 26 underwent esophagectomy. The median follow-up periods were 46 and 56 months in the CRT and esophagectomy groups, respectively. The median patient age was significantly higher in the CRT group than in the esophagectomy group (69 vs. 65 years, p = 0.0054). CRT was completed in all patients, and the incidence of grade ≥ 3 nonhematologic adverse events was 6%. The overall and disease-free survival did not significantly differ between the two groups.

Conclusions

CRT following ESD seems a promising nonsurgical strategy for optimizing the selection of therapies for high-risk SESCC and warrant further investigation.
Clinical and radiological outcome of Mason-Johnston types III and IV radial head fractures treated by an on-table reconstruction
Authors: Kastenberger Tobias , Kaiser Peter , Spicher Anna , Stock Kerstin , Benedikt Stefan , Schmidle Gernot , Arora Rohit
Published: November 2022

Background

Only few methods treating comminuted radial head fractures have been established providing sufficient joint reconstruction, restoring radial length and enabling early joint mobilization. When an anatomical reconstruction using open reduction and internal fixation is not possible, radial head resection or primary arthroplasty is often conducted. An “Ex situ/on-table” reconstruction is widely disregarded but can be an option. The purpose of this study was to evaluate the functional and radiological outcome of comminuted radial head fractures treated with an “on-table” reconstruction and internal fixation using a low profile plate.

Methods

Fourteen patients who sustained a radial head fracture (9 Mason-Johnston type III and 5 Mason-Johnston type IV) and were treated with an “on-table” reconstruction between 2010 and 2020 were evaluated retrospectively. The patients mean age was 41.3 years (range 21–69). The clinical evaluation included active range of motion, grip strength, pain level and elbow stability. The functional outcome was assessed using the Disability of Arm, Shoulder and the Hand (DASH) score, Mayo Elbow Performance Index (MEPI), Broberg and Morrey score. The radiological examination included a.p. and lateral views of the injured elbow to evaluate nonunions, loss of reduction, joint alignment, avascular radial head necrosis, heterotopic ossifications and posttraumatic osteoarthritis.

Results

The inclusion rate was 74% with a mean follow-up of 50 months (range 16–128). The mean elbow flexion of the injured side was 126° (range110–145°) with an average extension loss of 8° (range 0–40°). Pronation was 65° (15–90°) and supination 66° (5–90°). The mean MEPI was 87 points (range 45–100). The mean DASH score was 13 points (range 1–88). According to the Broberg and Morrey functional scoring system, the average score was 92 points (range 88–100). Complete bone union was achieved in 9 cases, partial union in 4 cases and nonunion in one case. There were no signs of avascular necrosis of the radial head. Signs of post-traumatic osteoarthritis were seen in 11 cases. Five patients needed an implant removal due to a radio-ulnar impingement and one patient a revision surgery due to the nonunion and implant breakage.

Conclusions

An on-table (ex situ) reconstruction of the radial head is a reliable option with a good clinical outcome and low complication rate in the surgical treatment of comminuted radial head fractures. It can restore joint alignment and maintain radial length. The risk for avascular necrosis is neglectable, and the bone healing rate is high.
The efficacy and safety of platelet-rich plasma in the tendon-exposed wounds: a preliminary study
Authors: Deng Zhuan , Long Zhi-Sheng , Gong Fei-Peng , Chen Gang
Published: November 2022

Objective

Currently, among wounds with large skin tissue defects caused by various reasons, the treatment of refractory wounds is still a major clinical problem. This study is aimed to preliminarily assess the therapeutic potentials of platelet-rich plasma (PRP) in refractory wounds with exposed tendons, as well as corresponding efficacy and safety.

Methods

A total of 12 patients (5 males and 7 females) with refractory wounds and exposed tendons who were admitted to our hospital from June 2018 to December 2020 were included in this study. After the preparation of PRP, the included patients underwent the PRP injection after the debridement of wounds, and the efficacy and prognosis were assessed by the same group of senior surgeons.

Results

The average age of included patients was 42.7 ± 12.9 years, and the causes of injury included traffic accidents (3 cases), contusion (2 cases), burns (2 cases), diabetes complications (4 cases), and melanoma complications (1 cases). The average healing time was 23.0 ± 5.0 days, and the mean size of the wound was 3.1 × 5.1 cm2. During the whole treatment process, Vancouver Scar Scale (VSS) decreased from 7.4 ± 1.6 before PRP treatment to 3.6 ± 0.9 after treatment (P < 0.001), Manchester Scar Scale (MSS) decreased from 12.3 ± 4.5 before PRP treatment to 5.4 ± 1.2 after treatment (P < 0.001), and no redness and swelling were observed around wounds, the size and degree of wounds gradually reduced, the coverage rate of granulation tissue was acceptable, overall quality of scar was relatively good, skin sensitivity around wounds was normal, there was no local wounds secretion, and postoperative patient's satisfaction was relatively good during follow-up.

Conclusions

Our study has preliminarily indicated that PRP can promote the wounds healing, reduce the inflammation around wounds, and improve the granulation tissue and angiogenesis, thereby effectively polishing up the safety and efficacy.
Mitral annuloplasty with the interatrial groove-left atrial dome approach in a patient with Marfan syndrome
Authors: Chen Fengjie , Wang Xiang , Zhuang Xianmian , Guo Hongwei
Published: November 2022

Background

The choice of mitral valve surgical approach has always been a difficult problem in patients with small left atrium.

Case presentation

We report a case of a patient with Marfan syndrome who underwent the David operation and mitral annuloplasty. The patient had a small left atrium, so we severed the superior vena cava and opened the interatrial groove and left atrial dome. This method allows for excellent exposure of the mitral valve and subvalvular apparatus, enabling a successful operation.

Conclusion

The interatrial groove-left atrial dome approach provides an option for patients with a small left atrium undergoing mitral valve surgery.
Integrated dose–response metabolomics with therapeutic effects and adverse reactions may demystify the dosage of traditional Chinese medicine
Authors: Chen Yan-Yan , Chen Jia-Qian , Tang Yu-Ping , Shang Er-Xin , Zhao Qi , Zou Jun-Bo , Xu Ding-Qiao , Yue Shi-Jun , Yang Jie , Fu Rui-Jia , Zhou Gui-Sheng , Duan Jin-Ao
Published: November 2022

Background

Traditional Chinese medicine (TCM) has been used to treat various diseases for thousands of years. However, the uncertainty of dosage as well as the lack of systemic evaluation of pharmacology and toxicology is one major reason why TCM remains mysterious and is not accepted worldwide. Hence, we aimed to propose an integrated dose–response metabolomics strategy based on both therapeutic effects and adverse reactions to guide the TCM dosage in treatment.

Methods

The proposed methodology of integrated dose–response metabolomics includes four steps: dose design, multiple comparison of metabolic features, response calculation and dose–response curve fitting. By comparing the changes of all metabolites under different doses and calculating these changes through superposition, it is possible to characterize the global disturbance and thus describe the overall effect and toxicity of TCM induced by different doses. Rhubarb, commonly used for constipation treatment, was selected as a representative TCM.

Results

This developed strategy was successfully applied to rhubarb. The dose–response curves clearly showed the efficacy and adverse reactions of rhubarb at different doses. The rhubarb dose of 0.69 g/kg (corresponding to 7.66 g in clinic) was selected as the optimal dose because it was 90% of the effective dose and three adverse reactions were acceptable in this case.

Conclusion

An integrated dose–response metabolomics strategy reflecting both therapeutic effects and adverse reactions was established for the first time, which we believe is helpful to uncover the mysterious veil of TCM dosage. In addition, this strategy benefits the modernization and internationalization of TCM, and broadens the application of metabolomics.
“Older people tend to be invisible”: a qualitative study exploring the needs and inclusion of older Syrian refugees in the context of compounding crises in host country, Lebanon
Authors: Hachem Sarah , Ali Souad , Al-Omari Sarah , Abi Chahine Maya , Fahme Sasha Abdallah , Mehio Sibai Abla
Published: November 2022

Background

Older Syrian refugees in Lebanon are a marginalized population with under-recognized health needs. The inclusivity of this population within the humanitarian response is poorly understood. This study aims to identify the unique needs of older Syrian refugees in the context of recent concurrent crises in Lebanon, and explore the extent to which they are being met and prioritized by local and international aid agencies.

Methods

We conducted in-depth interviews with a snowball sample of 26 stakeholders from 11 organizations operating in the health, nutrition, and water, sanitation, and hygiene sectors. Data analysis followed principles of thematic analysis.

Results

Concurrent political, economic, and public health crises in host country promoted income insecurity among older refugees and increased dependency on younger relatives, leading to food insecurity, neglect, and poor health outcomes, including the sequelae of untreated non-communicable diseases. Mental illness was perceived to be exacerbated by Covid-19 related challenges, including social isolation, uncertainty about the future, and additionally due to feelings of guilt related to economic dependence and fundamental exclusion from labor force participation. Despite their vulnerability, older refugees are overlooked by the humanitarian response, which may be related to a lack of data. Pervasive medication shortages in the setting of the economic collapse, as well as inaccessible physical environments and competing interests were all identified as major barriers to care.

Conclusions

Older Syrian refugees in Lebanon experience dual vulnerability that is acutely exacerbated in the setting of concurrent crises. Sociopolitical, economic, and cultural barriers promote social exclusion and may confer an increased risk of income and food insecurity in this population, with significant implications for health. Humanitarian aid agencies operating in the context of fragmented, under-resourced health systems are currently unable to sufficiently address multi-faceted needs of this community. We recommend moving away from a donor-dependent model of aid by allocating resources toward strengthening inclusive national health systems that emphasize preventative care. We further call for age-disaggregation of routine data and normalization of data sharing among stakeholders in the academic and public health sectors in order to develop evidence-based initiatives that can meet the needs of this under-served community.
The biological activity of serum bacterial lipopolysaccharides associates with disease activity and likelihood of achieving remission in patients with rheumatoid arthritis
Authors: Parantainen J. , Barreto G. , Koivuniemi R. , Kautiainen H. , Nordström D. , Moilanen E. , Hämäläinen M. , Leirisalo-Repo M. , Nurmi K. , Eklund K. K.
Published: November 2022

Background

Dysbiotic intestinal and oral microbiota have been implicated in the pathogenesis of rheumatoid arthritis (RA), but the mechanisms how microbiota could impact disease activity have remained elusive. The aim of this study was to assess the association of the biological activity of serum lipopolysaccharides (LPS) with disease activity and likelihood of achieving remission in RA patients.

Methods

We measured Toll-like receptor (TLR) 4-stimulating activity of sera of 58 RA patients with a reporter cell line engineered to produce secreted alkaline phosphatase in response to TLR4 stimulation. Levels of LPS-binding protein, CD14, and CD163 were determined by ELISA assays.

Results

The patient serum-induced TLR4 activation (biological activity of LPS) was significantly associated with inflammatory parameters and body mass index at baseline and at 12 months and with disease activity (DAS28-CRP, p<0.001) at 12 months. Importantly, baseline LPS bioactivity correlated with disease activity (p=0.031) and, in 28 early RA patients, the likelihood of achieving remission at 12 months (p=0.009). The level of LPS bioactivity was similar at baseline and 12-month visits, suggesting that LPS bioactivity is an independent patient-related factor. Neutralization of LPS in serum by polymyxin B abrogated the TLR4 signaling, suggesting that LPS was the major contributor to TLR4 activation.

Conclusion

We describe a novel approach to study the biological activity of serum LPS and their impact in diseases. The results suggest that LPS contribute to the inflammatory burden and disease activity on patients with RA and that serum-induced TLR4 activation assays can serve as an independent prognostic factor.

Graphical Abstract

A graphical summary of the conclusions of the study.
Optic nerve sheath diameter at high altitude: standardized measures in healthy volunteers
Authors: Rodríguez Aparicio Edith Elianna , Carrizosa Gonzalez Jorge Armando , Rodriguez Lima David Rene
Published: November 2022

Background

Increases in the diameter of the optic nerve sheath (ONSD) on ultrasound are associated with high intracranial pressure (hICP). The normal value varies with altitude and the population studied. The objective of this study is to describe the normal values of the ONSD in a healthy adult population of the city of Bogotá, Colombia, at 2640 meters above sea level (masl).

Patients and methods

A prospective observational study was conducted on a total of 247 healthy individuals recruited from May 2021 to May 2022 who were subjected to the color, low power, optic disk, safety, elevated frequency, dual (CLOSED) protocol for measuring the bilateral ONSD adjusted to the eyeball transverse diameter (ETD).

Results

A total of 230 individuals were analyzed; the average ONSD of the right eye (RE) was 0.449 cm (range 0.288–0.7) and that of the left eye (LE) was 0.454 cm (range 0.285–0.698); the correlation between RE and LE was 0.93 (p < 0.005), and the correlation of the ONSD/ETD ratios for the RE and LE was lower (r2 = 0.79, p < 0.005). A total of 10.8% of the studied population had values greater than 0.55 cm.

Conclusions

The median ONSD and ONSD/ETD ratio in the city of Bogotá are similar to those described in other populations; however, approximately 10.8% of the healthy population may present higher values, which would limit the use of ONSD on its own for clinical decision-making, only repeated measurements with significant changes in the ONSD and ONSD/ETD or asymmetries between the measurements of both eyes linked to clinical findings would allow the diagnosis of hICP.
Biomimetic synthesis of iron oxide nanoparticles from Bacillus megaterium to be used in hyperthermia therapy
Authors: Hajiali Sajedeh , Daneshjou Sara , Daneshjoo Somayeh
Published: November 2022

The suitable structural characteristics of magnetic nanoparticles have resulted in their widespread use in magnetic hyperthermia therapy. Moreover, they are considered a proper and operational choice for pharmaceutical nanocarriers. Using the biomimetic method, we were able to produce iron oxide magnetic nanoparticles from the bacterial source of PTCC1250, Bacillus megaterium, for therangostic diagnosis systems and targeted drug delivery. Some of the benefits of this method include mitigated environmental and biological dangers, low toxicity, high biocompatibility, cheap and short-term mass production possibilities in each synthesis round compared to other biological sources, simple equipment required for the synthesis; and the possibility of industrial-scale production. Bacillus megaterium is a magnetotactic bacteria (MTB) that has a magnetosome organelle capable of orienting based on external magnetic fields, caused by the mineralization of magnetic nanocrystals. Utilizing this capability and adding an iron nitrate solution to the bacterial suspension, we synthesized iron oxide nanoparticles. The extent of synthesis was measured using UV–visible spectrophotometry. The morphology was evaluated using FESEM. The crystallized structure was characterized using RAMAN and XRD. The size and distribution of the nanoparticles were assessed using DLS. The surface charge of the nanoparticles was measured using zeta potential. The synthesis of iron oxide nanoparticles was confirmed using FT-IR, and the magnetic property was measured using VSM. This study is continued to identify industrial and clinical applications.
Identifying common core outcome domains from core outcome sets of musculoskeletal conditions: protocol for a systematic review
Authors: Sabet Tamer S. , Anderson David B. , Stubbs Peter W. , Buchbinder Rachelle , Terwee Caroline B. , Chiarotto Alessandro , Gagnier Joel , Verhagen Arianne P.
Published: November 2022

Background

Core outcome sets (COSs) aim to reduce outcome heterogeneity in clinical practice and research by suggesting a minimum number of agreed-upon outcomes in clinical trials. Most COSs in the musculoskeletal field are developed for specific conditions. We propose that there are likely to be common core domains within existing musculoskeletal COSs that may be used as a starting point in the development of future COSs. We aim to identify common core domains from existing COSs and to facilitate the development of new COSs for musculoskeletal conditions. As a secondary aim, we will assess the development quality of these COSs.

Methods

A systematic review including musculoskeletal COSs. We will search Core Outcome Measures in Effectiveness Trials (COMET) database, MEDLINE, EMBASE, Scopus, Cochrane Methodology Register and International Consortium for Health Outcome Measurement (ICHOM). Studies will be included if related to the development of a COS in adults with musculoskeletal conditions and for any type of intervention. Quality will be assessed using the Core Outcome Set-Standards for Development (COS-STAD) recommendations. Data extracted will include scope of the COS, health condition, interventions and outcome domains. Primary outcomes will be all core domains recommended within each COS. We define a common core outcome domain as one present in at least 67% of all COSs. All findings will be summarized and presented using descriptive statistics.

Discussion

This systematic review of COSs will describe the core domains recommended within each musculoskeletal COS. Common domains found may be used in the initial stages of development of future musculoskeletal COSs.

Systematic review registration

PROSPERO CRD42021239141
Bearing fault diagnosis method based on improved Siamese neural network with small sample
Authors: Zhao Xiaoping , Ma Mengyao , Shao Fan
Published: November 2022

Fault diagnosis of rolling bearings is very important for monitoring the health of rotating machinery. However, in actual industrial production, owing to the constraints of conditions and costs, only a small number of bearing fault samples can be obtained, which leads to an unsatisfactory effect of traditional fault diagnosis models based on data-driven methods. Therefore, this study proposes a small-sample bearing fault diagnosis method based on an improved Siamese neural network (ISNN). This method adds a classification branch to the standard Siamese network and replaces the common Euclidean distance measurement with a network measurement. The model includes three networks: a feature extraction network, a relationship measurement network, and a fault classification network. First, the fault samples were input into the same feature extraction network in pairs, and a long and short-term memory (LSTM) network and convolutional neural network (CNN) were used to map the bearing signal data to the low-dimensional feature space. Then, the extracted sample features were measured for similarity by the relationship measurement network; at the same time, the features were input into the classification network to complete the bearing fault recognition. When the number of training samples was particularly small (training set A, 10 samples), the accuracy of 1D CNN, Prototype net and Siamese net were 49.8%, 60.2% and 58.6% respectively, while the accuracy of the proposed ISNN method was 84.1%. For the 100-sample case of training set D, the accuracy of 1D CNN was improved to 93.4%, which was still higher than that of prototype and Siam network, while the accuracy of ISNN method reached 98.1%.The experimental results show that the method in this study achieved higher fault diagnosis accuracy and better generalization in the case of small samples.