bluuebunny/crossref_metadata_2025 huggingface dataset:
From personal responsibility to an eco-socialist state: Political economy, popular discourses and the climate crisis
Authors: Flanagan Erin , Raphael Dennis
Published: December 2022

The adverse effects of climate change are already apparent with action required to forestall a full blown climate catastrophe. Despite findings that social democratic welfare states – Denmark, Finland, Norway and Sweden – more proactively respond to climate change through environmental policies that complement public policies promoting economic and social security, even these eco-social welfare state environmental policies are unlikely to avert a climate catastrophe. To avert a catastrophe will require gaining public control over energy policy and countering the power and influence of fossil-extracting industries. In theory, this could be accomplished through existing policy instruments. In reality, it may require establishment of a post-capitalist eco-socialist state, the outlines of which remain uncertain even among leading eco-socialist scholars. To effect either of these paths will require public awareness and support for such action. To that end, we identify public discourses of climate change which reflect these two ways forward as well as four other means of responding to climate change: (1) individual responsibility; (2) local action; (3) technocratic solution; (4) public policy advocacy; (5) balancing power in society; and (6) establishing a post-capitalist society. Despite the latter two discourses being the most likely to support effective action, they are the most marginalized.
Nurses Barriers to Evidence-Based Practice in Palliative Care: A Systematic Review
Authors: Dakka Falah Jamal
Published: December 2022

Background

Research shows low evidence-based practice (EBP) uptake among palliative care nurses, a global concern because the demand for palliative care services is rising, raising the urgent need to improve healthcare quality. Promoting EBP uptake in palliative care can improve healthcare quality. This systematic review investigated nurses’ barriers to EBP implementation in palliative care.

Methods

PubMed, MEDLINE, CINHAL, and Google Scholar were used to identify seven articles. Articles were included for review if they were published within the past 10 years (English only) and investigated barriers to EBP implementation in palliative care.

Results

Four barriers were identified: (a) time and resource constraints, (b) lack of readiness for organizational change, (c) negative attitudes toward palliative care, and (d) process-specific difficulties.

Conclusion

This systematic review's findings can inform policy changes to improve the uptake of EBP in palliative care.
Worsening premature death burden gap from systemic sclerosis in men and black persons: A US nationwide population-based study
Authors: Singh Ram Raj , Singh Devanshu R , Yen Eric Y
Published: December 2022

Objective:

Male sex and black race incur poor prognosis in systemic sclerosis (SSc). There is no nationwide population-based assessment of premature SSc death burden by sex and race.

Methods:

This is a population-based study comprising all recorded SSc deaths across the United States. We constructed histograms depicting the number of SSc deaths for each age by sex and race, and calculated the cumulative percent death at each age and the median age of death. We determined the odds ratios for the risk of premature death from SSc by sex and race. We then calculated the percent of total SSc deaths for different age groups by sex and race from 1970 to 2015. We performed chi-square test with Yates’s correction and quantified the odds ratio (OR) with 95% confidence interval (CI).

Results:

The median age of SSc death was 63 years in males versus 68 years in females, and 57 years in blacks versus 70 years in whites. The odds for SSc death before 65 years age was 1.8 (95% CI, 1.6–2.0) for males compared with females and 5.1 (95% CI, 4.4–6.0) for blacks compared with whites. The higher odds for premature death in males than in females was similar for both races. Differences in the proportions of premature deaths from 1970 to 2015 increased between males and females (−5% to 17%) and between blacks and whites (14% to 36%).

Conclusion:

Males and black persons die of SSc at younger ages. The worsening premature death burden gap between the two sexes and races over the last five decades is troublesome.
Glenoid Prosthesis Design Considerations in Anatomic Total Shoulder Arthroplasty
Authors: Liu Charles , Shi Lewis , Amirouche Farid
Published: December 2022

Total shoulder arthroplasty is an increasingly popular option for the treatment of glenohumeral arthritis. Historically, the effectiveness of the procedure has largely been determined by the long-term stability of the glenoid component. Glenoid component loosening can lead to clinically concerning complications including pain with movement, loss of function, and accumulation of debris which may require surgery to revise. In response, there has been a push to optimize the design of the glenoid prosthesis. Traditional contemporary glenoid components use pegs for fixation and are made entirely of polyethylene. Variations on the standard implant include keeled, metal-backed, hybrid, augmented, and inlay designs. There is a wealth of biomechanical and clinical studies that report on the effectiveness of these different designs. The purpose of this review is to summarize existing literature regarding glenoid component design and identify key areas for future research. Knowledge of the rationale underlying glenoid design will help surgeons select the best component for their patients and optimize outcomes following TSA.
Muttalip green clay and its ultraviolet and infrared absorption and reflection
Authors: Kuru Mutlu Hülya
Published: December 2022

The search for sufficiently high-quality clays for use in the tile industry represents a significant challenge. This study aimed to prepare Muttalip green clay tiles with flexural strengths adhering to the TS EN 1304:2016 standard. Muttalip green clay was subjected to sieving, vacuum pressed, dried and then baked to obtain galette tiles. The tiles were analysed subsequently using optical techniques, including X-ray diffraction, X-ray fluorescence spectrometry and field-emission scanning electron microscopy. The influence of various firing temperatures (900, 950 and 1000°C) on the flexural strength of the tiles was also investigated. The tiles obtained at 950°C exhibited a maximum flexural strength of 153.91 kg cm–2. Fourier-transform infrared spectroscopy revealed that the tiles reflect ultraviolet A radiation and absorb infrared radiation. Muttalip green clay is a suitable material for preparing tiles for roofing applications.
Novel investigational approaches for high-risk genetic subsets of AML: TP53, KMT2A, FLT3
Authors: Sahasrabudhe Kieran D. , Mims Alice S.
Published: December 2022

The treatment landscape in acute myeloid leukemia (AML) is rapidly evolving, with multiple new therapies approved in recent years. However, the prognosis for patients with high-risk genetic subsets of AML remains poor, and the development of more effective treatment options for these patients is ongoing. Three of these high-risk AML patient subsets include TP53-mutated AML, FLT3-internal tandem duplication (ITD)-mutated AML, and AML harboring rearrangements affecting the KMT2A locus (KMT2A-r AML). The prognosis for TP53-mutated AML remains poor with both intensive and targeted regimens, including those incorporating the BCL-2 inhibitor, venetoclax. Allogeneic hematopoietic stem cell transplantation is the only potentially curative therapy for these patients, but posttransplant relapse rates remain high. Patients with FLT3-ITD-mutated AML continue to have suboptimal outcomes with standard therapies and experience high rates of relapse following transplant. KMT2A-r AML is also associated with poor outcomes with current treatment approaches, and effective standards of care are lacking for patients with relapsed/refractory disease. This article discusses current treatment approaches, along with the investigational agents being explored for the treatment of these 3 AML subsets, focusing primarily on agents that are further along in development.
Treatment of CML in pregnancy
Authors: Robertson Harry F. , Apperley Jane F.
Published: December 2022

Since the introduction of tyrosine kinase inhibitors (TKIs) at the beginning of the millennium, the outlook for patients with chronic myeloid leukemia (CML) has improved remarkably. As such, the question of life expectancy and survival has become less problematic while quality of life and family planning have become more so. While TKIs are the cornerstone of CML management, their teratogenicity renders them contraindicated during pregnancy. In recent years, patients who satisfy standardized criteria can stop TKI therapy altogether, and indeed, in eligible patients who wish to become pregnant, these objectives overlap. However, not all patients satisfy these criteria. Some pregnancies are unplanned, and a number of patients are pregnant when diagnosed with CML. In these patients the way forward is less clear, and there remains a paucity of good evidence available to guide treatment. In this article, we summarize the relevant literature and provide a framework for clinicians faced with the challenge of managing CML and pregnancy.
Ph+ ALL in 2022: is there an optimal approach?
Authors: Wieduwilt Matthew J.
Published: December 2022

Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) carried a very poor prognosis prior to the advent of tyrosine kinase inhibitors (TKIs) that block the activity of the BCR-ABL1 oncoprotein. With improvements in TKI efficacy and allogeneic hematopoietic cell transplantation (HCT), survival has improved over the past 3 decades, and the role of chemotherapy and allogeneic HCT is now changing. Better risk stratification, the application of the third-generation TKI ponatinib, and the use of immunotherapy with the CD19-CD3 bifunctional T-cell engaging antibody blinatumomab in place of chemotherapy has made therapy for Ph+ ALL more tolerable and arguably more efficacious, especially for older patients who comprise most patients with Ph+ ALL.
Novel therapies and combinations in CLL refractory to BTK inhibitors and venetoclax
Authors: Scarfò Lydia
Published: December 2022

Patients with chronic lymphocytic leukemia (CLL) refractory to covalent BTK and BCL2 inhibitors have a new unmet clinical need. Standard treatment options are able to obtain only limited and short-lasting disease control associated with reduced overall survival, and thus these patients have become ideal candidates for enrollment in clinical trials. Favorable results have been obtained with the use of noncovalent BTK inhibitors (roughly 70% overall response rate regardless of the actual resistance or intolerance to previous covalent BTK inhibitors) and anti-CD19 chimeric antigen receptor (CAR) T-cell therapy (with complete responses in up to 45% of cases and an undetectable measurable residual disease rate of 65% in the bone marrow). These 2 approaches should be considered valid options in this setting, although not yet approved. For young fit patients achieving remissions with salvage treatments, the option of allogeneic stem cell transplantation should be discussed as the outcome appears to be unaffected by number and type of previous targeted agents. Novel treatment strategies interfering with different mechanisms of CLL cell survival and proliferation are warranted, including small molecules with novel targets (eg, CDK9, MCL1, ERK inhibitors), CAR T cells targeting different antigens, CAR natural killer cells, or bispecific antibodies.
High or low? Assessing disease risk in multiple myeloma
Authors: Schmidt Timothy Martin
Published: December 2022

Based upon the development of highly effective therapies such as immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies that target plasma cell biology, a dramatic improvement in overall survival has been observed for most patients with multiple myeloma (MM) over the past 2 decades. Although it is now commonplace for many patients with myeloma to live in excess of 10 years after diagnosis, unfortunately a large subset of patients continues to experience an aggressive disease course marked by substantial morbidity and early mortality. Many clinical biomarkers and staging systems in use today can help with prognostication, but accurate risk assessment can be difficult due to the presence of many different biomarkers with variable prognostic value. Furthermore, with the implementation of novel therapies and unprecedented rates of deep and durable responses, it is becoming apparent that risk assessment is best envisioned as a dynamic process that requires ongoing reevaluation. As risk and response-adapted approaches are becoming more commonplace, it is essential that clinicians understand the biological and prognostic implications of clinical, genomic, and response-based biomarkers in order to promote management strategies that will help improve both survival and quality of life for patients across the risk spectrum.
Risk stratifying MDS in the time of precision medicine
Authors: Cazzola Mario
Published: December 2022

Myelodysplastic syndromes (MDS) are myeloid neoplasms characterized by morphologic dysplasia, persistent cytopenia, and a variable risk of evolution to acute myeloid leukemia (AML). Risk stratification is crucial in a patient-centered approach to the treatment of MDS. Based on hematologic parameters and cytogenetic abnormalities, the Revised International Prognostic Scoring System is currently used for this purpose. In the past years, the use of massively parallel DNA sequencing has clarified the genetic basis of MDS and has enabled development of novel diagnostic and prognostic approaches. When conventional cytogenetics is combined with gene sequencing, more than 90% of patients are found to carry a somatic genetic lesion. In addition, a portion of patients has germline variants that predispose them to myeloid neoplasms. The recently developed International Consensus Classification of MDS includes new entities that are molecularly defined—namely, SF3B1-mutant and TP53-mutant MDS. The International Working Group for Prognosis in MDS has just developed the International Prognostic Scoring System–Molecular (IPSS-M) for MDS, which considers hematologic parameters, cytogenetic abnormalities, and somatic gene mutations. The IPSS-M score is personalized and can be obtained using a web-based calculator that returns not only the individual score but also the expected leukemia-free survival, overall survival, and risk of AML transformation. Providing an efficient risk stratification of patients with MDS, the IPSS-M represents a valuable tool for individual risk assessment and treatment decisions.
Targeting inflammation in lower-risk MDS
Authors: Gonzalez-Lugo Jesus D. , Verma Amit
Published: December 2022

The myelodysplastic syndromes (MDS) are a heterogeneous group of malignant hematopoietic stem cell disorders characterized by ineffective growth and differentiation of hematopoietic progenitors leading to peripheral blood cytopenias, dysplasia, and a variable risk of transformation to acute myelogenous leukemia. As most patients present with lower-risk disease, understanding the pathogenesis of ineffective hematopoiesis is important for developing therapies that will increase blood counts in patients with MDS. Various inflammatory cytokines are elevated in MDS and contribute to dysplastic differentiation. Inflammatory pathways mediated by interleukin (IL) 1b, IL-6, IL-1RAP, IL-8, and others lead to growth of aberrant MDS stem and progenitors while inhibiting healthy hematopoiesis. Spliceosome mutations can lead to missplicing of genes such as IRAK4, CASP8, and MAP3K, which lead to activation of proinflammatory nuclear factor κB–driven pathways. Therapeutically, targeting of ligands of the transforming growth factor β (TGF-β) pathway has led to approval of luspatercept in transfusion-dependent patients with MDS. Presently, various clinical trials are evaluating inhibitors of cytokines and their receptors in low-risk MDS. Taken together, an inflammatory microenvironment can support the pathogenesis of clonal hematopoiesis and low-risk MDS, and clinical trials are evaluating anti-inflammatory strategies in these diseases.
Updates in infant acute lymphoblastic leukemia and the potential for targeted therapy
Authors: Kotecha Rishi S.
Published: December 2022

Outcomes for infants diagnosed under 1 year of age with KMT2A-rearranged acute lymphoblastic leukemia (ALL) have remained stagnant over the past 20 years. Successive treatment protocols have previously focused on intensification of conventional chemotherapy, but increased treatment-related toxicity and chemoresistance have led to a plateau in survival. We have now entered an era of immunotherapy with integration of agents, such as blinatumomab or chimeric antigen receptor T-cell therapy, into the standard chemotherapy backbone, showing significant promise for improving the dismal outcomes for this disease. There remains much optimism for the future as a wealth of preclinical studies have identified additional novel targeted agents, such as venetoclax or menin inhibitors, ready for incorporation into treatment, providing further ammunition to combat this aggressive disease. In contrast, infants with KMT2A-germline ALL have demonstrated excellent survival outcomes with current therapy, but there remains a high burden of treatment-related morbidity. Greater understanding of the underlying blast genetics for infants with KMT2A-germline ALL and incorporation of immunotherapeutic approaches may enable a reduction in the intensity of chemotherapy while maintaining the excellent outcomes.
Management of marginal zone lymphomas
Authors: Merli Michele , Arcaini Luca
Published: December 2022

Marginal zone lymphomas (MZLs) represent about 7% of B-cell non-Hodgkin lymphomas and include 3 different subtypes—namely, extranodal (EMZL), nodal, and splenic (SMZL). The initial assessment requires specific diagnostic and staging procedures depending on organ-related peculiarities. In particular, although positron emission tomography/computed tomography was not initially recommended, recent data have reassessed its role in the routine staging of MZL, especially when only localized treatment is planned or there is a suspicion of histologic transformation. Recent findings have improved the risk stratification of MZL patients, highlighting the association of early progression after frontline therapy with worse overall survival. A significant fraction of MZL cases may be related to specific bacterial (ie, Helicobacter pylori in gastric EMZL) or viral infections (hepatis C virus), and in the earlier phases of disease, a variable percentage of patients may respond to anti-infective therapy. Involved-site radiotherapy has a central role in the management of localized EMZL not amenable to or not responding to anti-infective therapy. Although rituximab-based treatments (bendamustine- rituximab in advanced EMZL or rituximab monotherapy in SMZL) have demonstrated favorable results, the current therapeutic scenario is predicted to rapidly change as emerging novel agents, especially Bruton's tyrosine kinase inhibitors, have demonstrated promising efficacy and safety profiles, leading to their approval in the relapsed setting. Moreover, a large variety of novel agents (phosphatidylinositol 3-kinase inhibitors, chimeric antigen receptor T-cells, bispecific antibodies) are being tested in MZL patients with encouraging preliminary results.
Long-term health outcomes following curative therapies for sickle cell disease
Authors: Chakravarthy Rohini , Friedman Debra L.
Published: December 2022

Treatment options for patients with sickle cell disease (SCD) continue to rapidly expand and evolve. The goal of therapies such as an allogeneic hematopoietic stem cell transplant (HSCT), gene therapy, and gene editing is to cure rather than control SCD. The benefits of these therapies must be accompanied by minimizing long-term adverse health outcomes from SCD and its treatment. SCD can have adverse effects on a variety of organ systems, including the heart, lung, kidney, and reproductive system, leading to high disease burden, morbidity, and premature mortality in both pediatric and adult patients. While curative therapies are being increasingly used, there remains a paucity of data on the long-term health outcomes associated with these treatments in children and adults with SCD. There are data available regarding the effects of HSCT performed largely for malignant diseases, from which data on SCD outcomes may be extrapolated. However, given the significant differences between these 2 populations of patients who undergo HSCT, such extrapolation is imprecise at best. Furthermore, there are currently no published data on long-term health outcomes following gene therapy for SCD due to current short follow-up times. We summarize the limited data reported on health outcomes following HSCT for SCD and emphasize the need for more research within this area.
Thrombopoietin receptor agonists for chemotherapy-induced thrombocytopenia: a new solution for an old problem
Authors: Al-Samkari Hanny
Published: December 2022

Chemotherapy-induced thrombocytopenia (CIT) is common, resulting in increased bleeding risk and chemotherapy delays, dose reduction, and treatment discontinuation, which can negatively affect oncologic outcomes. The only agent approved by the US Food and Drug Administration to manage CIT (oprelvekin) was voluntarily withdrawn from the market by the manufacturer, leaving few options for patients. Therefore, patients experiencing CIT present a significant clinical challenge in daily practice. The availability of thrombopoietin receptor agonists has led to formal clinical trials describing efficacy in CIT as well as a rather extensive body of published observational data from off-label use in this setting but no formal regulatory indications for CIT to date. The accumulated data, however, have affected National Comprehensive Cancer Network guidelines, which now recommend consideration of TPO-RA clinical trials as well as off-label use of romiplostim. This review article details the evidence to date for the management of CIT with thrombopoietin receptor agonists (TPO-RAs), discussing the efficacy data, the specific circumstances when treatment is warranted (and when it is generally unnecessary), and safety considerations. Specific recommendations regarding patient selection, initiation, dosing, titration, and discontinuation for TPO-RA therapy in CIT are given, based on published data and expert opinion where evidence is lacking.
Evidence-based management of pregnant women with sickle cell disease in high-income countries
Authors: Oteng-Ntim Eugene , Shangaris Panicos
Published: December 2022

Globally, patients living with sickle cell disease are now surviving to reproductive age, with life expectancy approaching 50 years in most countries. Thus, reproductive options are now essential for patients living with the condition. However, it can be associated with maternal, delivery, and fetal complications. Outcomes may vary depending on the level of expertise and resources. In this piece we provide an optional guideline for managing sickle cell disease in pregnancy. The therapeutic option of serial exchange prophylactic transfusion has been offered in the context of a clinical trial (TAPS2).
Epidemiology and treatment of priapism in sickle cell disease
Authors: Idris Ibrahim M. , Burnett Arthur L. , DeBaun Michael R.
Published: December 2022

Ischemic priapism is a common but underrecognized morbidity affecting about 33% of adult men with sickle cell disease (SCD). The onset of priapism occurs in the prepubertal period and tends to be recurrent with increasing age. Significantly, priapism is associated with an unrecognized high burden of mental duress and sexual dysfunctions. The diagnosis of priapism is clinical. Many episodes of priapism will resolve spontaneously, but when an episode lasts longer than 4 hours, the episode is considered a urologic emergency requiring quick intervention with either corporal aspiration or shunt surgery. Only 3 randomized clinical trials (stilbesterol, ephedrine or etilefrine, and sildenafil) have been conducted for secondary priapism prevention in SCD. All 3 trials were limited with small sample sizes, selection biases, and inconclusive results after completion. The current molecular understanding of the pathobiology of priapism suggests a relative nitric oxide (NO) deficiency secondary to chronic hemolysis in SCD and associated phosphodiesterase type 5 dysregulation. We posit an increase in NO levels will restore the normal homeostatic relationship between voluntary erection and detumescence. Currently, 2 randomized phase 2 trials (1 double-blind, placebo-controlled trial and 1 open-label, single-arm intervention) are being conducted for secondary priapism prevention in men at high risk for recurrent priapism (NCT03938454 and NCT05142254). We review the epidemiology and pathobiology of priapism, along with mechanistic therapeutic approaches for secondary prevention of priapism in SCD.
Thrombosis and anticoagulation: clinical issues of special importance to hematologists who practice in Asia
Authors: Boonyawat Kochawan , Angchaisuksiri Pantep
Published: December 2022

There are clinical issues of special importance and practice variation in the management of venous thromboembolism (VTE) and in the use of anticoagulants among hematologists who practice in Asia. In Asian-inherited thrombophilia, coagulation is disturbed due to loss-of-function mutations of protein S and protein C causing protein S and protein C deficiencies, whereas the gain-of-function factor V Leiden and prothrombin G20210A mutations are almost absent. Thrombophilia screening is not recommended in patients with VTE patients who have major provoking factors. However, it can be considered in unprovoked young patients with VTE who have a strong family history of VTE. Cancer is the most important acquired risk factor for VTE in Asians. Limited cancer screening at the initial presentation of unprovoked VTE is appropriate, especially in the elderly. Direct oral anticoagulants have been shown to have similar efficacy and reduce risk of major bleeding, including intracranial hemorrhage and bleeding requiring hospitalization, compared with warfarin. Most clinical trials evaluating therapies for treatment and prevention of VTE have included small numbers of Asian patients. Despite this lack of evidence, direct oral anticoagulants have been increasingly used in Asia for cancer-associated thrombosis. Individualized assessment of thrombotic and bleeding risks should be used for all hospitalized Asian patients when deciding on pharmacologic thromboprophylaxis. More research is needed to understand the factors that contribute to risks of VTE and anticoagulant-associated bleeding in Asian patients as these may differ from Western populations.
Anticoagulant therapy for women: implications for menstruation, pregnancy, and lactation
Authors: DeLoughery Emma , Bannow Bethany Samuelson
Published: December 2022

Estrogen exposure, in the setting of pregnancy, the postpartum state, combined hormonal contraceptives (CHCs), or hormone therapy use, has been clearly associated with increased rates of venous thromboembolism (VTE). Although recurrence rates are low in these settings, up to 70% of anticoagulated menstruating individuals experience abnormal or heavy menstrual bleeding (HMB), which commonly results in iron deficiency with or without anemia. Patients taking rivaroxaban appear to experience higher rates of HMB compared with those on apixaban, dabigatran, or warfarin. HMB can often be diagnosed in a single visit with a good menstrual history assessing for factors with a known association with increased or heavy bleeding, such as changing pads or tampons more often than every 2 hours, clots larger than a quarter, and iron deficiency (ferritin <50  ng/mL). HMB can be managed with hormonal therapies, including those associated with VTE risk, such as CHCs and depot-medroxyprogesterone acetate (DMPA). In many cases, continuing CHCs or DMPA while a patient is therapeutically anticoagulated is reasonable, so long as the therapy is discontinued before anticoagulation is stopped. Modification of the anticoagulation regimen, such as decreasing to a prophylactic dose in the acute treatment period, is not currently recommended. For patients who are currently pregnant, low-molecular-weight heparin (LMWH) is still standard of care during pregnancy; routine monitoring of anti–factor Xa levels is not currently recommended. Warfarin or LMWH may be considered in the postpartum setting, but direct-acting oral anticoagulants are currently not recommended for lactating patients.
Newly diagnosed multiple myeloma: making sense of the menu
Authors: Costello Caitlin L.
Published: December 2022

The development of new drugs and subsequent novel combinations for the treatment of newly diagnosed multiple myeloma (NDMM) has resulted in a plethora of treatment options that can make the choice of initial induction therapy a challenge. A greater understanding of both patient- and disease-specific factors can provide a personalized approach to help design a treatment course. Historically, the choice of an induction regimen has been tethered to an initial impression of transplant eligibility at the time of diagnosis. As more effective and better-tolerated induction regimens have emerged, there has been increasing overlap in the induction strategies used for all patients with NDMM, which increasingly provide the ultimate goal of deep and durable remissions. The current treatment options and strategies for the management of NDMM are evaluated using the best available data to provide a rationale for these decisions.
Impacts of COVID-19 restrictions on level of physical activity and health in home-dwelling older adults in Norway
Authors: Nygård Arnhild J. , Taraldsen Kristin , Granbo Randi , Selbæk Geir , Helbostad Jorunn L.
Published: December 2022

Background

The spread of the coronavirus in spring 2020 led to a lockdown of physical activity (PA) offers. The aim of this study was to investigate how PA, as well as general and mental health, in community-dwelling older adults were affected by the COVID-19 restrictions in Norway.

Methods

Invitation to participate in the study was sent via Facebook and the Norwegian Pensioners’ Association. Inclusion criteria were being ≥ 65 years old and living at home. Participants completed a questionnaire either digitally or on paper in June–August 2020. The questionnaire included questions on PA, general health, and mental health both before (13th of March) and during lockdown.

Results

We included 565 participants (mean age 74 ± 5.3 years, 60.4% female); almost 60% had a university degree, 84% reported performing PA more than once per week, and 20% reported a fall in the previous 12 months. The Wilcoxon signed-rank test indicated that the corona lockdown significantly reduced activity level (Z = -4.918, p < 0.001), general health (Z = -6,910, p < 0.001) and mental health (Z = -12.114, p < 0.001). Those who were less active during lockdown had higher odds of experiencing worse health than those who maintained their activity level, odds ratio: 9.36 (95% CI = 4.71–18.58, p < 0.001) for general health and 2.41 (95% CI = 1.52–3.83, p < 0.001) for mental health. Those who attended organized exercise offers before lockdown had higher odds of being less active during lockdown compared to those who did not exercise in an organized setting, odds ratio: 3.21 (95% CI = 2.17–5.76, p < 0.001).

Conclusions

In a relatively highly educated and active group of older participants, COVID-19 restrictions still negatively affected level of activity as well as general and mental health. These short-term decreases in activity level and health suggest that preventive actions and increased focus on measures to support older adults in maintaining an active lifestyle are needed.
Ultrasmall Fe3O4 and Gd2O3 hybrid nanoparticles for T1-weighted MR imaging of cancer
Authors: Sarikhani Abolfazl , Alamzadeh Zahra , Beik Jaber , Irajirad Rasoul , Mirrahimi Mehri , Pirhajati Mahabadi Vahid , Kamrava S. Kamran , Ghaznavi Habib , Khoei Samideh
Published: December 2022

Gadolinium-based contrast agents (GdCAs) have been the most frequently used T1-weighted magnetic resonance imaging (MRI) contrast agents for decades. However, they have serious disadvantages such as low longitudinal relaxivity value (r1) and high dose associated-nephrotoxicity that restrict their wide applications. These emphasize the need for an ideal stable and biocompatible T1-weighted CA with high contrast enhancement performance. Here, we propose a wet-chemical synthesis technique to form a nanocomposite consisting of ultrasmall iron oxide nanoparticles (US-IO) and Gd2O3 hybrid nanoparticles stabilized with dextran (FG-HNPs) for T1-weighted MR imaging. Relaxometry study showed that FG-HNPs have a high r1 value (42.28 mM−1S−1) and low relaxivity ratio (r2/r1: 1.416) at 3.0T. In vivo MRI contrast enhancement factor (ΔSNR) for FG-HNPs (257.025 ± 17.4%) was found to be 1.99-fold higher than US-IO (129.102 ± 15%) and 3.35-fold higher than Dotarem (76.71 ± 14.2%) as routinely used T1-weighted CA. The cytotoxicity assay and histological examination confirmed the biocompatibility of FG-HNPs. The biodistribution study, transmission electron microscopy (TEM) and Prussian blue (PB) staining of tumor tissue proved the effective tumor localization of FG-HNPs. Therefore, FG-HNPs can be suggested as a promising CA for T1-weighted MRI of tumors by virtue of their remarkable relaxivities and high biocompatibility.
Insights into metabolic and pharmacological profiling of Aspergillus ficuum through bioinformatics and experimental techniques
Authors: Shah Zafar Ali , Khan Khalid , Rashid Haroon Ur , Shah Tanzeel , Jaremko Mariusz , Iqbal Zafar
Published: December 2022

Background

Recently, numerous novel bioactive fungal metabolites have been identified that possess broad therapeutic activities including anti-inflammatory, antibiotic, antioxidant, and antitumor. The fungal mycochemicals as well as extracts have increased the interest of the scientific community in drug discovery research through a combination approach such as, molecular metabolic, pharmacological and computational techniques. Therefore, the natural fungus Aspergillus ficuum (A. ficuum) (FCBP-DNA-1266) was selected for metabolic and pharmacological profiling in this study.

Results

The metabolic profile of A. ficuum was explored for the first time and revealed the presence of bioactive compounds such as choline sulfate, noruron, hydroxyvittatine, aurasperone D, cetrimonium, kurilensoside, heneicosane, nonadecane and eicosane. Similarly, a pharmacological screen of A. ficuum was performed for the first time in in vivo and in vitro models. Interestingly, both the ethyl acetate and n-hexane fractions of A. ficuum were found to be more active against Bacillus subtilis among five tested bacteria with their zone of inhibition (ZOI) values of 21.00 mm ±1.00 and 23.00 mm ±1.00, at a concentration of 150 μgmL-1 respectively. Similarly, a significant decrease (P<0.001) and (P<0.01) in paw edema was observed in A. ficuum-treated animals at doses of 50 and 150 mgkg-1, respectively, reflecting its potent anti-inflammatory effect. Furthermore, the docking results supported the antibacterial and anti-inflammatory effects of A. ficuum. In addition, the crude extract demonstrated no acute toxicity and the highest percent radical scavenging was recorded for both n-hexane and ethyl acetate extracts.

Conclusion

The metabolic profile of A. ficuum indicated the presence of biological relevant compounds. A. ficuum extract exhibited potent antibacterial and anti-inflammatory effects supported by docking results. Furthermore, A. ficuum extract demonstrated the highest percentage of radical scavenging activity along with no acute toxicity.
Increased protein phosphatase 5 expression in inflammation-induced left ventricular dysfunction in rats
Authors: Manilall Ashmeetha , Mokotedi Lebogang , Gunter Sulè , Le Roux Regina , Fourie Serena , Flanagan Colleen A. , Millen Aletta M. E.
Published: December 2022

Background

Titin phosphorylation contributes to left ventricular (LV) diastolic dysfunction. The independent effects of inflammation on the molecular pathways that regulate titin phosphorylation are unclear.

Methods

We investigated the effects of collagen-induced inflammation and subsequent tumor necrosis factor-α (TNF-α) inhibition on mRNA expression of genes involved in regulating titin phosphorylation in 70 Sprague-Dawley rats. LV diastolic function was assessed with echocardiography. Circulating inflammatory markers were quantified by enzyme-linked immunosorbent assay and relative LV gene expression was assessed by Taqman® polymerase chain reaction. Differences in normally distributed variables between the groups were determined by two-way analysis of variance (ANOVA), followed by Tukey post-hoc tests. For non-normally distributed variables, group differences were determined by Kruskal–Wallis tests.

Results

Collagen inoculation increased LV relative mRNA expression of vascular cell adhesion molecule 1 (VCAM1), pentraxin 3 (PTX3), and inducible nitric oxide synthase (iNOS) compared to controls, indicating local microvascular inflammation. Collagen inoculation decreased soluble guanylate cyclase alpha-2 (sGCα2) and soluble guanylate cyclase beta-2 (sGCβ2) expression, suggesting downregulation of nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) signaling. Inhibiting TNF-α prevented collagen-induced changes in VCAM1, iNOS, sGCα2 and sGCβ2 expression. Collagen inoculation increased protein phosphatase 5 (PP5) expression. Like LV diastolic dysfunction, increased PP5 expression was not prevented by TNF-α inhibition.

Conclusion

Inflammation-induced LV diastolic dysfunction may be mediated by a TNF-α-independent increase in PP5 expression and dephosphorylation of the N2-Bus stretch element of titin, rather than by TNF-α-induced downregulation of NO-sGC-cGMP pathway-dependent titin phosphorylation. The steady rise in number of patients with inflammation-induced diastolic dysfunction, coupled with low success rates of current therapies warrants a better understanding of the systemic signals and molecular pathways responsible for decreased titin phosphorylation in development of LV diastolic dysfunction. The therapeutic potential of inhibiting PP5 upregulation in LV diastolic dysfunction requires investigation.
Comparison of clinical outcomes of single-incision versus multi-port laparoscopic surgery for descending colon cancer: a propensity score-matched analysis
Authors: Tei Mitsuyoshi , Suzuki Yozo , Sueda Toshinori , Iwamoto Kazuya , Naito Atsushi , Nomura Masatoshi , Yoshikawa Yukihiro , Ohtsuka Masahisa , Imasato Mitsunobu , Mizushima Tsunekazu , Akamatsu Hiroki
Published: December 2022

Background

The clinical impact of single-incision laparoscopic surgery (SILS) for descending colon cancer (DCC) is unclear. The aim of this study was to evaluate the clinical outcomes of SILS for DCC compared with multi-port laparoscopic surgery (MPLS).

Methods

We retrospectively analyzed 137 consecutive patients with stage I–III DCC who underwent SILS or MPLS at two high-volume multidisciplinary tertiary hospitals between April 2008 and December 2018, using propensity score-matched analysis.

Results

After propensity score-matching, we enrolled 88 patients (n = 44 in each group). SILS was successful in 97.7% of the matched cohort. Compared with the MPLS group, the SILS group showed significantly less blood loss and a greater number of harvested lymph nodes. Morbidity rates were similar between groups. Recurrence pattern did not differ between groups. No significant differences were found between groups in terms of 3-year disease-free and overall survivals.

Conclusion

SILS appears safe and feasible and can provide satisfactory oncological outcomes for patients with DCC.
Does a short luteal phase correlate with an increased risk of miscarriage? A cohort study
Authors: Duane Marguerite , Schliep Karen , Porucznik Christina A. , Najmabadi Shahpar , Stanford Joseph B.
Published: December 2022

Background

Miscarriage is defined as spontaneous loss of pregnancy prior to 20 weeks gestation. With an estimated risk of 15% of clinically confirmed pregnancies ending in miscarriage, it is the most common adverse event in pregnancy. Woman’s age is the primary risk factor for miscarriage, while medical conditions, including hormonal abnormalities, are also associated. Progesterone is essential for maintaining pregnancy. A short luteal phase may reflect inadequate levels of progesterone production, but it is unclear whether a short luteal phase correlates with an increase in the risk of miscarriage.

Methods

Using a cohort study design, we conducted a secondary data analysis from four cohorts of couples who used a standardized protocol to track biomarkers of the female cycles. A short luteal phase was defined as less than 10 days, with < 11, < 9, and < 8 days as alternate definitions in sensitivity analyses. We included women who experienced a pregnancy with a known outcome, identified the length of the luteal phase in up to 3 cycles prior to conception and assessed the relationship with miscarriage using a modified Poisson regression analysis, adjusting for demographic characteristics, smoking, alcohol use and previous pregnancy history.

Results

In our sample of 252 women; the overall miscarriage rate was 18.7%. The adjusted incident risk ratio of miscarriage in women who had at least one short luteal phase < 10 days, compared to those who had none, was 1.01 (95% CI: 0.57, 1.80) Similar null risk was found when assessing alternative lengths of short luteal phase. Women who had short luteal phases < 10 days in all 3 cycles prior to the conception cycle had an incident risk ratio of 2.14 (95% CI: 0.7, 6.55).

Conclusions

Our study found that a short luteal phase in the three cycles prior to conception was not associated with higher rates of miscarriage in an international cohort of women tracking their cycles, but our sample size was limited. Further research to determine if short luteal phases or luteal phase deficiency is associated with early pregnancy losses among preconception cohorts with daily tracking of cycle parameters, in addition to progesterone and human chorionic gonadotropin levels, is warranted. Additionally, future studies should include women with recurrent short luteal phases as a more likely risk factor than isolated short luteal phases.
The influence of social class and institutional relationships on the experiences of vaccine-hesitant mothers: a qualitative study
Authors: Glassman Lindsay W. , Szymczak Julia E.
Published: December 2022

Background

Vaccine hesitancy is a growing problem in the United States. However, our understanding of the mechanisms by which socioeconomic status (SES) shapes the experience of vaccine hesitancy and decision-making is incomplete.

Aim

The aim of this study was to understand how social class influences the experiences and perspectives of vaccine-hesitant mothers.

Methods

We conducted semistructured interviews with middle- and working-class vaccine-hesitant mothers. Participants were identified through neighborhood parenthood groups in the Philadelphia area, as well as in-person and online groups whose members express concerns about vaccines. Interviews were audio recorded and inductively analyzed.

Results

Interviews were conducted with 37 vaccine-hesitant mothers, who described their vaccine decision-making through the lens of interactions with three institutional stakeholders: 1) pediatric clinicians; 2) school administrators; and 3) emergency room staff. In discussing these interactions, middle- and working-class mothers invoked distinct levels of authority in relation to these institutions. Specifically, working-class mothers expressed concerns that medical or school professionals could act as reporters for state intervention, including Child Protective Services, while middle-class mothers did not. These interactions highlighted the ways middle- and working-class mothers in our study felt differently empowered and constrained in their vaccine choices, and ultimately influenced their perceptions of available actions.

Conclusions

Our findings indicate that experiences of vaccine hesitancy may be influenced by mothers’ social class via their relationships to institutional authorities. These findings have implications for how clinicians communicate with parents from different social backgrounds to best build trust and facilitate vaccine uptake.
Preventative practices and effects of the COVID-19 pandemic on caregivers of children with pediatric pulmonary hypertension
Authors: Nelson Erik J. , Cook Ella , Pierce Megan , Nelson Samara , Seelos Ashley Bangerter , Stickle Heather , Brown Rebecca , Johansen Michael
Published: December 2022

Background

Pulmonary hypertension (PH) is a serious and life-threatening disease characterized by elevated mean arterial pressure and pulmonary vascular resistance. COVID-19 may exacerbate PH, as evidenced by higher mortality rates among those with PH. The objective of this study was to understand the unique burdens that the COVID-19 pandemic has placed upon families of children living with PH.

Methods

Participants were recruited online through the “Families of children with pulmonary hypertension” Facebook group and asked to complete a survey about their experiences during the COVID-19 pandemic.

Results

A total of 139 parents/caregivers of children living with PH completed the online survey. Almost all (85.6%) of parents/caregivers had received the COVID-19 vaccine, though only 59.7% reported a willingness to vaccinate their child with PH against COVID-19. Over 75% of parents/caregivers felt that they practiced preventative measures (e.g., wearing a facemask, social distancing, and avoiding gatherings) more than those in the community where they live. They also reported several hardships related to caring for their child with PH during the pandemic such as financial duress, loss of work, and affording treatment costs.

Conclusions

These findings indicate that parents/caregivers of children at higher risk for COVID-19 complications may be more willing to act on clinical recommendations themselves as proxy for protecting those at high risk. The economic, emotional and social impacts of COVID-19 are significantly greater for high-risk individuals.