bluuebunny/crossref_metadata_2025 huggingface dataset:
Bolsonaro: A Ridiculous Caesar?
Authors: Gontijo Caio , Ramos Leonardo
Published: December 2021

In this article, we aim to set out an appropriate interpretation for the historical form that the Brazilian President Jair Bolsonaro embodies and the context that made his presidency possible. We propose a discussion on the level of ideology, although conceived from a material and historical background and integrated into a context of hegemonic dispute that presupposes ideology but which is not identical to it. We analyse the constituent elements of this ideology and its particularities, based on the Gramscian concept of ‘Caesarism’ and the notion of ‘corrosive ridicule’. Finally, we outline probable future developments for social conflict and crisis in Brazil during the coronavirus pandemic.
Discovery of a new symphytan wasp in the mid-Cretaceous Kachin amber (Hymenoptera, Syspastoxyelidae)
Authors: ZHENG YAN , KOPYLOV DMITRY S. , ZHANG QI , ZHANG HAI-GUANG , QIN MIN , CHEN JUN , ZHANG HAI-CHUN
Published: December 2021

The mid-Cretaceous Burmese amber from Kachin State of northern Myanmar provides a scanty but rather diverse fauna of sawflies. Herein Grandixyela rasnitsyni gen. et sp. nov. is described and illustrated on the basis of a well-preserved male specimen from Myanmar amber. The new fossil genus and species is characterized by wing venation and body characters, such as 15-segmented antenna with the first flagellomere distinctly shorter than the remaining, pterostigma narrow and completely sclerotized, 1-RS distinct (not dot-like), RS distal of 2r-rs gently S-shaped, ending to pterostigma beyond its apex for a short distance. A checklist and a review of known syspastoxyelid species are discussed. Additionally, our findings not only provide important morphological characters, especially the well-preserved details of the venation and genitalia, but also broaden new data on the Cretaceous diversity of symphytan wasps and further extend the records of syspastoxyelids to six genera and seven species.
The Polycytellidae viewed as Gondwanan Glosselytrodea
Authors: BÉTHOUX OLIVIER , ANDERSON JOHN M.
Published: December 2021

The material of Glosselytrodea from the Molteno Formation (Triassic, South Africa), consisting of two specimens, is herein studied. A preliminary comparative analysis is conducted based on the new material and new data on Polycytella triassica Tillyard, 1922 (Triassic, Australia), highlighting the relevance of the width of the area anterior to RA (particularly, opposite the end of ScP), an area very broad in Polycytella Tillyard, 1922, Argentinoglosselytrina Martins-Neto and Gallego, 2001 (Triassic, Argentina) and in the new material from the Molteno. An emended diagnosis of the Polycytellidae is elaborated accordingly. The material from the Molteno is assigned to Polycytella rasnitsyni gen. et sp. nov. and Moltenojurina parva gen. et sp. nov., the latter being the smallest Glosselytrodea known to date. As newly delimited, the Polycytellidae are strictly Gondwanan.
New species and records of the genus Amphichroum Kraatz, 1857 from the Himalayan Region and Tibet (Coleoptera: Staphylinidae: Omaliinae: Anthophagini)
Authors: SHAVRIN ALEXEY V.
Published: December 2021

Taxonomic and faunistic data for seven species of the genus Amphichroum Kraatz, 1857 (Omaliinae) from the Himalayan Region and Tibet are provided. All species are (re-)described and illustrated, including two new species: A. ahrensi sp. n. from India (West Bengal) and A. telnovi sp. n. from western Nepal. A new combination is proposed for A. nepalicum (Coiffait, 1982) comb. n., originally described in the genus Arpedium Erichson, 1839. The lectotype is designated for A. anthobioides Champion, 1925. Distributional distributional maps for all covered species are provided. Amphichroum monticola Cameron, 1928 is recorded from Nepal for the first time.
New species and records of the Neotropical genus Cyrnellus (Trichoptera: Polycentropodidae) and the re-establishment of C. minimus and C. marginalis
Authors: MARTÍN PAOLA A. RUEDA , GIBON FRANCOIS-MARIE , SGANGA JULIETA V.
Published: December 2021

Cyrnellus is a small genus of Polycentropodidae distributed in the Nearctic and Neotropical regions, absent from the Chilean subregion. Two new species are here described: C. boliviensis sp. nov. and C. guyanensis sp. nov. Cyrnellus minimus Banks 1913 considered as a junior synonym of Cyrnellus fraternus (Banks 1905) by Flint (1971) and C. marginalis (Banks 1930) considered as a junior synonym of Cyrnellus fraternus by Flint (1964) are revalidated at the specific level. We provide a key and illustrations for adult males and nine new country records for Bolivia.
A new sisorid catfish of the genus Pseudolaguvia (Teleostei: Sisoridae) from Nagaland, north-eastern India
Authors: PRAVEENRAJ JAYASIMHAN , VIJAYAKRISHNAN BALAJI , LIMA AKUM , GURUMAYUM SHANTABALA DEVI
Published: December 2021

Pseudolaguvia vespa, new species, is described from the Tsücha River, Mokokchung district, Nagaland, India. The new species can be distinguished from congeners in having the following combination of characters: length of dorsal-fin spine 12.3–16.8% SL, a smooth anterior edge of the dorsal-fin spine, caudal peduncle depth 9.0–10.5% SL, body depth at anus 15.6–17.7% SL, caudal fin length 20.7–24.5% SL, pectoral fin length 20.1–24.1% SL, interorbital distance 22.7–28.1% SL, thoracic adhesive apparatus extending to midway between base of last pectoral-fin ray and pelvic-fin origin, and live specimens with two irregular, chrome-yellow bands on the body.
The exact status and synonyms of three Chinese Afronurus Lestage, 1924 established by Navás in 1936 (Ephemeroptera: Heptageniidae)
Authors: YING XIAOLI , ZHOU CHANGFA
Published: December 2021

Navás named more than 20 mayfly species from China but most of them are not associated with currently known specimens. In 2021, we found three common species of Chinese Afronurus Lestage, 1924 (Heptageniidae), which genitalia and color patterns match three species described and illustrated by Navás in 1936. Therefore, three new synonyms are established: Afronurus pallescens (Navás, 1936) (=Cinygmina obliquistriata You et al., 1981, syn. nov.), Afronurus kiangsuensis (Puthz, 1971) (renamed from Ecdyonurus hyalinus Navás, 1936= Cinygmina rubromaculata You et al., 1981, syn. nov.), Afronurus costatus (Navás, 1936) (=Cinygmina yixingensis Wu & You, 1986, syn. nov.). As the type specimens for Navas’ three species are supposed to be lost, neotypes are designated for them.
A state-space approach for longitudinal outcomes: An application to neuropsychological outcomes
Authors: Chua Alicia S , Tripodis Yorghos
Published: December 2021

Longitudinal assessments are crucial in evaluating the disease state and trajectory in patients with neurodegenerative diseases. Neuropsychological outcomes measured over time often have a non-linear trajectory with autocorrelated residuals and a skewed distribution. We propose the adjusted local linear trend model, an extended state-space model in lieu of the commonly used linear mixed-effects model in modeling longitudinal neuropsychological outcomes. Our contributed model has the capability to utilize information from the stochasticity of the data while accounting for subject-specific trajectories with the inclusion of covariates and unequally spaced time intervals. The first step of model fitting involves a likelihood maximization step to estimate the unknown variances in the model before parsing these values into the Kalman filter and Kalman smoother recursive algorithms. Results from simulation studies showed that the adjusted local linear trend model is able to attain lower bias, lower standard errors, and high power, particularly in short longitudinal studies with equally spaced time intervals, as compared to the linear mixed-effects model. The adjusted local linear trend model also outperforms the linear mixed-effects model when data is missing completely at random, missing at random, and, in certain cases, even in data with missing not at random.
Mild hypobaric hypoxia influences splenic proliferation during the later phase of stress erythropoiesis
Authors: Zhang Liyuan , Patel Shailey , Soulakova Julia N , Caldwell Charles C , St. Pierre Schneider Barbara
Published: December 2021

Tissue trauma and hemorrhagic shock are common battlefield injuries that can induce hypoxia, inflammation, and/or anemia. Inflammation and hypoxia can initiate adaptive mechanisms, such as stress erythropoiesis in the spleen, to produce red blood cells and restore the oxygen supply. In a military context, mild hypobaric hypoxia—part of the environmental milieu during aeromedical evacuation or en route care—may influence adaptive mechanisms, such as stress erythropoiesis, and host defense. In the present study, healthy (control), muscle trauma, and polytrauma (muscle trauma and hemorrhagic shock) mice were exposed to normobaric normoxia or hypobaric hypoxia for ∼17.5 h to test the hypothesis that hypobaric hypoxia exposure influences splenic erythropoiesis and splenic inflammation after polytrauma. This hypothesis was partially supported. The polytrauma + hypobaric hypoxia group exhibited more splenic neutrophils, fewer total spleen cells, and fewer splenic proliferating cells than the polytrauma+normobaric normoxia group; however, no splenic erythroid cell differences were detected between the two polytrauma groups. We also compared splenic erythropoiesis and myeloid cell numbers among control, muscle trauma, and polytrauma groups. More reticulocytes at 1.7 days (40 h) post-trauma (dpt) and neutrophils at 4 dpt were produced in the muscle trauma mice than corresponding control mice. In contrast to muscle trauma, polytrauma led to a reduced red blood cell count and elevated serum erythropoietin levels at 1.7 dpt. There were more erythroid subsets and apoptotic reticulocytes in the polytrauma mice than muscle trauma mice at 4 and 8 dpt. At 14 dpt, the red blood cell count of the polytrauma + normobaric normoxia mice was 12% lower than that of the control + normobaric normoxia mice; however, no difference was observed between polytrauma + hypobaric hypoxia and control + hypobaric hypoxia mice. Our findings suggest muscle trauma alone induces stress erythropoiesis; in a polytrauma model, hypobaric hypoxia exposure may result in the dysregulation of splenic cells, requiring a treatment plan to ensure adequate immune functioning.
Galangin: A metabolite that suppresses anti-neoplastic activities through modulation of oncogenic targets
Authors: Tuli Hardeep Singh , Sak Katrin , Adhikary Shubham , Kaur Ginpreet , Aggarwal Diwakar , Kaur Jagjit , Kumar Manoj , Parashar Nidarshana Chaturvedi , Parashar Gaurav , Sharma Uttam , Jain Aklank
Published: December 2021

With the dramatic increase in cancer incidence all over the world in the last decades, studies on identifying novel efficient anti-cancer agents have been intensified. Historically, natural products have represented one of the most important sources of new lead compounds with a wide range of biological activities. In this article, the multifaceted anti-cancer action of propolis-derived flavonoid, galangin, is presented, discussing its antioxidant, anti-inflammatory, antiproliferative, pro-apoptotic, anti-angiogenic, and anti-metastatic effects in various cancer cells. In addition, co-effects with standard chemotherapeutic drugs as well as other natural compounds are also under discussion, besides highlighting modern nanotechnological advancements for overcoming the low bioavailability issue characteristic of galangin. Although further studies are needed for confirming the anti-cancer potential of galangin in vivo malignant systems, exploring this natural compound might open new perspectives in molecular oncology.
Autonomic cardiovascular response during and after a graded exercise test in concussed athletes and healthy controls
Authors: Ventura Alessandra , Romano Fausto , Bizzini Mario , Palla Antonella , Feddermann Nina
Published: December 2021

Objective

Dysfunction of the autonomic cardiovascular system after a concussion is known to cause exercise intolerance due to symptoms exacerbation. The aim of this study was to compare athletes with symptoms of a sport-related concussion and healthy controls with regard to their heart rate during a graded exercise test and their heart rate recovery during the 5 min cool-down after the graded exercise test.

Methods

Sport-related concussion patients ( N = 61; 31% female) and controls ( N = 16; 50% female) participated in a graded exercise test on a cycle ergometer followed by 5 min active cool-down. Based on the results of graded exercise tests they were divided into four groups: (1) patients who reached the symptom threshold and had to stop the graded exercise test (symptom threshold; N = 39; 33.3% female), (2) patients with symptoms who finished the graded exercise test (S; N = 16; 25% female), (3) patients without symptoms (NS; N = 6; 33.3% female), (4) controls ( N = 16; 50% female).

Main outcome measures

Heart rate, severity of headache and dizziness during graded exercise test, heart rate recovery (median (heart rate recoveries/maximal heart rate) ± median absolute deviation (MAD)) 30, 60 and 300 s after the start of cool-down.

Results

Heart rate recovery at 30 s was significantly slower in symptom (0.95 ± 0.01) compared to all other groups ( p < 0.002; symptom threshold: 0.92 ± 0.02, NS: 0.91 ± 0.02, controls: 0.93 ± 0.02). Heart rate recovery at 60 s was significantly slower in symptom (0.90 ± 0.02) compared to the symptom threshold and controls ( p < 0.041; 0.86 ± 0.03, 0.85 ± 0.04). Heart rate recovery at 300 s was significantly slower in symptom threshold (0.72 ± 0.05) compared to controls ( p = 0.003; 0.66 ± 0.02).

Conclusions

Heart rate measurements in athletes with symptoms of sport-related concussion should be continued during cool-down after the graded exercise test, as dysfunction of the autonomic cardiovascular system might manifest also during cool-down.
Pediatric tizanidine toxicity reversed with naloxone: a case report
Authors: Bader Doaa , Adam Ahmed , Shaban Mohamed , Alyahya Bader
Published: December 2021

Background

Tizanidine, an α-2 adrenoceptor agonist, is widely prescribed for the management of spasticity in adults. Case reports on pediatric tizanidine overdose are limited. Here, we report a case of pediatric tizanidine toxicity that was reversed with naloxone.

Case presentation

A 3-year-old male presented to the emergency department with lethargy, bradycardia, and bradypnea after accidental ingestion of multiple tizanidine tablets. Improvements in the level of consciousness and respiratory and heart rates were observed after two intravenous administrations of naloxone at a dose of 0.05 and 0.1 mg/kg, respectively.

Conclusions

This case report provides further evidence regarding the use of naloxone as a viable antidote for centrally acting α-2 receptor agonists and presents additional epidemiologic data on childhood tizanidine poisoning.
Molecular characterization of equine thymidine kinase 1 and preliminary evaluation of its suitability as a serum biomarker for equine lymphoma
Authors: Wang Liya , Unger Lucia , Sharif Hanan , Eriksson Staffan , Gerber Vinzenz , Rönnberg Henrik
Published: December 2021

Background

Thymidine kinase 1 (TK1) plays a key role in the synthesis of deoxythymidine triphosphate (dTTP) and is thus important for DNA replication and cell proliferation. The expression of TK1 is highest during S-phase, and it is rapidly degraded after mitosis. In cancer cells, TK1 is upregulated, resulting in leakage of excess TK1 into the blood. Consequently, serum TK1 has been used as a diagnostic and prognostic cancer biomarker, mainly in human medicine. The aims of this work were to characterize equine TK1 and to evaluate its suitability as a serum biomarker for equine lymphoma.

Results

Equine TK1 was cloned, expressed in E. coli and affinity purified. The purified recombinant horse TK1 showed broad substrate specificity, phosphorylating pyrimidine deoxyribo- and ribonucleosides and, to some extent, purine deoxynucleosides, including anticancer and antiviral nucleoside analogues. ATP was the preferred phosphate donor. Serum TK1 activity was measured in samples collected from horses with confirmed or suspected lymphoma and control horses with and without concurrent diseases. Serum TK1 activity levels were significantly higher in horses with lymphoma (p <  0.0005) and suspected lymphoma (p <  0.02) and in tumour-free groups with diverse diseases (p <  0.03) than in controls without concurrent diseases. There was a significant difference between the lymphoma group and the tumour-free group with diverse diseases (p <  0.0006). Furthermore, receiver operating characteristic analysis revealed a sensitivity of 0.86, a specificity of 0.95 and an AUC (area under the curve) of 0.92 compared to the controls without concurrent diseases, with a sensitivity of 0.97, a specificity of 0.71 and an AUC of 0.88 when compared with the tumour-free group with diverse diseases.

Conclusion

Equine TK1 showed high specific activity and broader substrate specificity than human TK1. Anticancer and antiviral thymidine analogues were efficiently phosphorylated by horse TK1, suggesting that these analogues might be good candidates for chemotherapy in horses. Serum TK1 activity was significantly higher in horses with lymphoma than in controls. ROC analysis indicated that serum TK1 could serve as a promising cancer biomarker in horses.
Eczema herpeticum subsequent to septic shock in early pregnancy: a first case report
Authors: Furuya Kiichiro , Takemoto Yuki , Kurahashi Hiroki , Hayashida Harue , Fujiwara Sho , Yamashita Saya , Chang Yangsil , Tsubouchi Hiroaki , Shikado Kayoko , Ogita Kazuhide
Published: December 2021

Background

Eczema herpeticum (EH) is a severe skin complication caused by human simplex virus (HSV) infection concomitant with immune dysfunction and dermatological conditions, mainly atopic dermatitis. We present the first case of EH subsequent to sepsis-related immunological suppression in pregnancy.

Case presentation

Septic shock developed in a 30-year-old primiparous woman at 14 weeks of pregnancy during admission for hyperemesis gravidarum. Although her life-threatening status due to sepsis improved by prompt treatment, on day 3 of treatment in the intensive care unit, blisters suddenly erupted on her face and neck and spread over her body. EH was diagnosed according to HSV type-1 antigen positivity and a past medical history of EH and atopic dermatitis. Antiviral agents were administered immediately, with positive results. Her general condition improved quickly, without central nervous system defects. This is the first report of EH following septic shock in early pregnancy. At present, we speculate that EH develops as a complication due to immunological changes in the late phase of sepsis because sepsis is mainly characterized by both an inflammatory state in the acute phase and an immunosuppressive state in the late phase. Pregnancy can also contribute to its pathogenesis, as it causes an immunosuppressive state. Mortality due to EH is relatively high; in this case, a history of EH and atopic dermatitis contributed to the initiation of prompt medical interventions for the former, with improvement in the patient’s severe condition. The combination of immunological changes in sepsis and pregnancy can cause HSV reactivation, resulting in EH recurrence.

Conclusions

In conclusion, if dermatological symptoms develop in a pregnant woman with a history of EH and/or atopic dermatitis treated for sepsis, EH should be suspected based not only on clinical features but also on immunological changes along with sepsis, and prompt medical interventions should be initiated.
Training programs to improve identification of sick newborns and care-seeking from a health facility in low- and middle-income countries: a scoping review
Authors: Fung Alastair , Hamilton Elisabeth , Du Plessis Elsabé , Askin Nicole , Avery Lisa , Crockett Maryanne
Published: December 2021

Background

Most neonatal deaths occur in low- and middle-income countries (LMICs). Limited recommendations are available on the optimal personnel and training required to improve identification of sick newborns and care-seeking from a health facility. We conducted a scoping review to map the key components required to design an effective newborn care training program for community-based health workers (CBHWs) to improve identification of sick newborns and care-seeking from a health facility in LMICs.

Methods

We searched multiple databases from 1990 to March 2020. Employing iterative scoping review methodology, we narrowed our inclusion criteria as we became more familiar with the evidence base. We initially included any manuscripts that captured the concepts of “postnatal care providers,” “neonates” and “LMICs.” We subsequently included articles that investigated the effectiveness of newborn care provision by CBHWs, defined as non-professional paid or volunteer health workers based in communities, and their training programs in improving identification of newborns with serious illness and care-seeking from a health facility in LMICs.

Results

Of 11,647 articles identified, 635 met initial inclusion criteria. Among these initial results, 35 studies met the revised inclusion criteria. Studies represented 11 different types of newborn care providers in 11 countries. The most commonly studied providers were community health workers. Key outcomes to be measured when designing a training program and intervention to increase appropriate assessment of sick newborns at a health facility include high newborn care provider and caregiver knowledge of newborn danger signs, accurate provider and caregiver identification of sick newborns and appropriate care-seeking from a health facility either through caregiver referral compliance or caregivers seeking care themselves. Key components to consider to achieve these outcomes include facilitators: sufficient duration of training, refresher training, supervision and community engagement; barriers: context-specific perceptions of newborn illness and gender roles that may deter care-seeking; and components with unclear benefit: qualifications prior to training and incentives and remuneration.

Conclusion

Evidence regarding key components and outcomes of newborn care training programs to improve CBHW identification of sick newborns and care-seeking can inform future newborn care training design in LMICs. These training components must be adapted to country-specific contexts.
Clinicopathological characteristics and survival outcomes in patients with synchronous lung metastases upon initial metastatic breast cancer diagnosis in Han population
Authors: Lin Shaoyan , Mo Hongnan , Li Yiqun , Guan Xiuwen , Chen Yimeng , Wang Zijing , Xu Binghe
Published: December 2021

Background

We investigated the clinicopathological characteristics and survival of breast cancer lung metastases (BCLM) patients at initial diagnosis of metastatic breast cancer (MBC) in the Han population.

Methods

We attained clinical data of 3155 MBC patients initially diagnosed between April 2000 and September 2019 from the China National Cancer Center and finally included 2263 MBC patients in this study, among which 809 patients presented with lung metastases at first MBC diagnosis. The risk factors for BCLM were determined using multivariate logistic regression analysis and the prognostic factors of BCLM patients were assessed by univariate and multivariate Cox regression analyses.

Results

Patients with triple-negative subtype (42.3%) harbored the highest incidence proportions of lung metastases. Age ≥ 50 years, Eastern Cooperative Oncology Group (ECOG) 2, M1, hormone receptor-negative (HR-)/human epidermal growth factor receptor 2-positive (HER2) + subtype, triple-negative subtype and disease-free survival (DFS) > 2 years were remarkably associated with higher incidence of lung metastases, while invasive lobular carcinoma (ILC) and bone metastases were significantly correlated with lower odds of lung metastases at diagnosis. The median survival of BCLM patients was 41.7 months, with triple-negative subtype experiencing the worst prognosis of 26.8 months. ECOG 2, triple-negative subtype, liver metastases, multi-metastatic sites and DFS ≤ 2 years were significantly correlated with poor survival of BCLM patients.

Conclusions

Our study provides essential information on clinicopathological features and survival outcomes of BCLM patients at initial diagnosis of MBC in China.
Population-level interventions targeting risk factors of diabetes and hypertension in South Africa: a document review
Authors: Uwimana - Nicol Jeannine , Hendricks Lynn , Young Taryn
Published: December 2021

Background

South Africa bears an increasing burden of non-communicable diseases (NCDs), particularly diabetes, cardiovascular diseases, and cancer. The objective of this study was to identify which population-level interventions, implemented at the level of governmental or political jurisdictions only, targeting risk factors of diabetes and hypertension were included in policies in South Africa. We also looked at whether these have been implemented or not.

Methods

A review of relevant reports, journal articles, and policy documents was conducted. Documentation from government reports that contains information regarding the planning, implementation and evaluation of population-level interventions targeting diabetes and hypertension were considered, and various databases were searched. The identified population-level interventions were categorized as supportive policies, supportive programs and enabling environments according to the major risk factors of NCDs i.e., tobacco use, harmful consumption of alcohol, unhealthy diet/nutrition and physical inactivity, in accordance with the WHO ‘Best buys’. A content document analysis was conducted.

Results

The source documents reviewed included Acts and laws, regulations, policy documents, strategic plans, case studies, government reports and editorials. South Africa has a plethora of policies and regulations targeting major risk factors for diabetes and hypertension implemented in line with WHO ‘Best buys’ since 1990. A total of 28 policies, legislations, strategic plans, and regulations were identified - 8 on tobacco use; 7 on harmful consumption of alcohol; 8 on unhealthy diet and 5 on physical inactivity - as well as 12 case studies, government reports and editorials. There is good progress in policy formulation in line with the ‘Best buys’. However, there are some gaps in the implementation of these policies and programs.

Conclusion

Curbing the rising burden of NCDs requires comprehensive strategies which include population-level interventions targeting risk factors for diabetes and hypertension and effective implementation with robust evaluation to identify successes and ways to overcome challenges.
Regulation of medicines advertisement in Zimbabwe: an assessment of the impact of pharmaceutical promotion on the prescribing behaviour of healthcare professionals
Authors: Semu Tafadzwa Collins , Ngara Bernard , Mudzviti Tinashe
Published: December 2021

Background

The pharmaceutical industry plays a key role in drug discovery and is considered useful regards to informing the health care workers health care workers about new medicines. Investigations concerning health care workers to industry interactions are less common. The objective of this study is to determine levels of knowledge, attitude and perception towards regulation of pharmaceutical promotion among healthcare practitioners in Zimbabwe.

Methods

A cross-sectional study was used and 330 healthcare practitioners were enrolled into the study. Data collection was done through combined face-to-face interviews and web-based online survey. The relative importance index score and used as a measure of knowledge, attitude and perception levels towards pharmaceutical promotion. Univariate and bivariate analysis was performed using STATA software package.

Results

Our study estimated that 95%, 67%, and 90% of the healthcare practitioners in Zimbabwe have a favourable (i.e. > 65%) relative importance index score of knowledge, attitudes, and perception, respectively, towards regulation of pharmaceutical promotion. Further exploration of the data indicated that the factors that had an association with the knowledge, attitude and perception levels towards regulation of pharmaceutical regulation at 5% level of significance include health care workers’ profession, gender, education level, the nature of the working institution and the number of prescriptions involved per week.

Conclusion

In conclusion, the findings of this study highlighted that in general the health care workers in Zimbabwe have higher levels of knowledge, attitude and perception towards regulation of pharmaceutical promotion, though the attitudes levels weres a  bit lower compared to other domains.
Protective effects of wogonin on lipopolysaccharide-induced inflammation and apoptosis of lung epithelial cells and its possible mechanisms
Authors: Ge Jinlin , Yang Huanhuan , Zeng Yufeng , Liu Yunjie
Published: December 2021

Background

Wogonin (5, 7-dihydroxy-8-methoxyflavone) is a natural di-hydroxyl flavonoid extracted from the root ofScutellaria baicalensisGeorgi. This paper was intended to investigate the mechanism of action of wogonin in alleviating the inflammation and apoptosis in acute lung injury (ALI).

Materials and methods

Lipopolysaccharide (LPS) was used to establish the in vitro model of ALI. After wogonin treatment, the cell viability and apoptosis of LPS-induced A549 cells were, respectively, measured by CCK-8, TUNEL assays and acridine orange/ethidium bromide dual staining, while the contents of inflammatory cytokines and oxidative stress markers were estimated by RT-qPCR, ELISA assay, western blot analysis and commercial kits. Western blot was also conducted to assess the expression of proteins involved. Subsequently, the effect of wogonin on the sirtuin 1 (SIRT1)-mediated high-mobility group box 1 protein (HMGB1) deacetylation was investigated. SIRT1 inhibitor EX527 was used to evaluate the regulatory effects of wogonin on SIRT1-mediated HMGB1 deacetylation in A549 cells under LPS stimulation.

Results

LPS induced inflammation, oxidative stress and apoptosis of A549 cells, which was abolished by wogonin. It was also found that wogonin promoted the HMGB1 deacetylation, accompanied by upregulated SIRT1 expression. However, SIRT1 inhibitor EX527 partially reversed the protective effects of wogonin on the inflammation and apoptosis of LPS-induced A549 cells.

Conclusion

Wogonin alleviated the inflammation and apoptosis in LPS-induced A549 cells by SIRT1-mediated HMGB1 deacetylation, which might represent the identification of a novel mechanism by which wogonin exerts protective effects on ALI and provide ideas for the application of wogonin to ALI treatment.
Modeling ischemic stroke in a triculture neurovascular unit on-a-chip
Authors: Wevers Nienke R. , Nair Arya Lekshmi , Fowke Tania M. , Pontier Maria , Kasi Dhanesh G. , Spijkers Xandor M. , Hallard Charlie , Rabussier Gwenaëlle , van Vught Remko , Vulto Paul , de Vries Helga E. , Lanz Henriëtte L.
Published: December 2021

Background

In ischemic stroke, the function of the cerebral vasculature is impaired. This vascular structure is formed by the so-called neurovascular unit (NVU). A better understanding of the mechanisms involved in NVU dysfunction and recovery may lead to new insights for the development of highly sought therapeutic approaches. To date, there remains an unmet need for complex human in vitro models of the NVU to study ischemic events seen in the human brain.

Methods

We here describe the development of a human NVU on-a-chip model using a platform that allows culture of 40 chips in parallel. The model comprises a perfused vessel of primary human brain endothelial cells in co-culture with induced pluripotent stem cell derived astrocytes and neurons. Ischemic stroke was mimicked using a threefold approach that combines chemical hypoxia, hypoglycemia, and halted perfusion.

Results

Immunofluorescent staining confirmed expression of endothelial adherens and tight junction proteins, as well as astrocytic and neuronal markers. In addition, the model expresses relevant brain endothelial transporters and shows spontaneous neuronal firing. The NVU on-a-chip model demonstrates tight barrier function, evidenced by retention of small molecule sodium fluorescein in its lumen. Exposure to the toxic compound staurosporine disrupted the endothelial barrier, causing reduced transepithelial electrical resistance and increased permeability to sodium fluorescein. Under stroke mimicking conditions, brain endothelial cells showed strongly reduced barrier function (35-fold higher apparent permeability) and 7.3-fold decreased mitochondrial potential. Furthermore, levels of adenosine triphosphate were significantly reduced on both the blood- and the brain side of the model (4.8-fold and 11.7-fold reduction, respectively).

Conclusions

The NVU on-a-chip model presented here can be used for fundamental studies of NVU function in stroke and other neurological diseases and for investigation of potential restorative therapies to fight neurological disorders. Due to the platform’s relatively high throughput and compatibility with automation, the model holds potential for drug compound screening.
Feasibility study of volumetric modulated arc therapy with Halcyon™ linac for total body irradiation
Authors: Uehara Takuya , Monzen Hajime , Tamura Mikoto , Inada Masahiro , Otsuka Masakazu , Doi Hiroshi , Matsumoto Kenji , Nishimura Yasumasa
Published: December 2021

Background

The use of total body irradiation (TBI) with linac-based volumetric modulated arc therapy (VMAT) has been steadily increasing. Helical tomotherapy has been applied in TBI and total marrow irradiation to reduce the dose to critical organs, especially the lungs. However, the methodology of TBI with Halcyon™ linac remains unclear. This study aimed to evaluate whether VMAT with Halcyon™ linac can be clinically used for TBI.

Methods

VMAT planning with Halcyon™ linac was conducted using a whole-body computed tomography data set. The planning target volume (PTV) included the body cropped 3 mm from the source. A dose of 12 Gy in six fractions was prescribed for 50% of the PTV. The organs at risk (OARs) included the lens, lungs, kidneys, and testes.

Results

The PTV D98%, D95%, D50%, and D2% were 8.9 (74.2%), 10.1 (84.2%), 12.6 (105%), and 14.2 Gy (118%), respectively. The homogeneity index was 0.42. For OARs, the Dmean of the lungs, kidneys, lens, and testes were 9.6, 8.5, 8.9, and 4.4 Gy, respectively. The V12Gy of the lungs and kidneys were 4.5% and 0%, respectively. The Dmax of the testes was 5.8 Gy. Contouring took 1–2 h. Dose calculation and optimization was performed for 3–4 h. Quality assurance (QA) took 2–3 h. The treatment duration was 23 min.

Conclusions

A planning study of TBI with Halcyon™ to set up VMAT-TBI, dosimetric evaluation, and pretreatment QA, was established.
Epigenetic imprinting alterations as effective diagnostic biomarkers for early-stage lung cancer and small pulmonary nodules
Authors: Zhou Jian , Cheng Tong , Li Xing , Hu Jie , Li Encheng , Ding Ming , Shen Rulong , Pineda John P. , Li Chun , Lu Shaohua , Yu Hongyu , Sun Jiayuan , Huang Wenbin , Wang Xiaonan , Si Han , Shi Panying , Liu Jing , Chang Meijia , Dou Maosen , Shi Meng , Chen Xiaofeng , Yung Rex C. , Wang Qi , Zhou Ning , Bai Chunxue
Published: December 2021

Background

Early lung cancer detection remains a clinical challenge for standard diagnostic biopsies due to insufficient tumor morphological evidence. As epigenetic alterations precede morphological changes, expression alterations of certain imprinted genes could serve as actionable diagnostic biomarkers for malignant lung lesions.

Results

Using the previously established quantitative chromogenic imprinted gene in situ hybridization (QCIGISH) method, elevated aberrant allelic expression of imprinted genes GNAS, GRB10, SNRPN and HM13 was observed in lung cancers over benign lesions and normal controls, which were pathologically confirmed among histologically stained normal, paracancerous and malignant tissue sections. Based on the differential imprinting signatures, a diagnostic grading model was built on 246 formalin-fixed and paraffin-embedded (FFPE) surgically resected lung tissue specimens, tested against 30 lung cytology and small biopsy specimens, and blindly validated in an independent cohort of 155 patients. The QCIGISH diagnostic model demonstrated 99.1% sensitivity (95% CI 97.5–100.0%) and 92.1% specificity (95% CI 83.5–100.0%) in the blinded validation set. Of particular importance, QCIGISH achieved 97.1% sensitivity (95% CI 91.6–100.0%) for carcinoma in situ to stage IB cancers with 100% sensitivity and 91.7% specificity (95% CI 76.0–100.0%) noted for pulmonary nodules with diameters ≤ 2 cm.

Conclusions

Our findings demonstrated the diagnostic value of epigenetic imprinting alterations as highly accurate translational biomarkers for a more definitive diagnosis of suspicious lung lesions.
Impact of comorbidities on risk of angioedema without urticaria in elderly patients
Authors: Bożek Andrzej , Zając Magdalena
Published: December 2021

Background

Angioedema without urticaria (AWU) is a disease found in the elderly population but is still poorly studied. The aim of this study was to investigate potential factors, especially comorbidities, that may affect the induction of angioedema without urticaria in patients over 60 years of age.

Methods

This was an observational, retrospective study of 242 patients with a diagnosis of AWU and 263 controls. The inclusion criteria were as follows: at least one episode of confirmed AWU based on the ICD-10 code (T78.3) that required treatment in the last 15 years (2004–2019); age above 60 years; detailed medical history of comorbidities; and details regarding the use of drugs at that time. Serum functional and quantitative C1 inhibitor assays were performed, and serum C4 was measured.

Comorbidities were grouped into the following panels: autoimmune, cancer, cardiac, metabolic, respiratory and allergic, liver failure and renal failure. Individual diseases were checked according to ICD code and treatment.

Results

In 1 (0.4%) patient, hereditary angioedema was confirmed. Decreased levels of C1INH were observed in 4 (1.65%) patients, dysfunction of C1INH was observed in 5 (1.76%) patients, and low levels of C4 were observed in 9 (3.71%) patients in the study group. The multiple logistic regression model revealed that patients with hyperuricemia or Hashimoto’s disease had a significantly higher chance of angioedema (OR = 3.21, 95% CI 2.92–3.66, p = 0.002; OR = 1.78 95% CI 1.37–2.21, p = 0.034, respectively).

Conclusion

The obtained results may indicate a significant influence of hyperuricemia or Hashimoto’s disease on angioedema manifestations.
First experiences with 177Lu-PSMA-617 therapy for recurrent or metastatic salivary gland cancer
Authors: Klein Nulent Thomas J. W. , van Es Robert J. J. , Willems Stefan M. , Braat Arthur. J. A. T. , Devriese Lot A. , de Bree Remco , de Keizer Bart
Published: December 2021

Background

Advanced salivary gland cancers become difficult to treat when they are technically irresectable and radiotherapy limits are exceeded. There is also an unmet need to improve palliative systemic therapy. Salivary glands depict the Prostate-Specific Membrane Antigen (PSMA) on 68Ga-PSMA-PET/CT, a transmembrane protein that is targeted for diagnosis and treatment of advanced prostate cancer. Some salivary gland carcinomas also express PSMA.

Methods

This study aimed to retrospectively evaluate the effectiveness of 177Lu-PSMA-617 therapy for recurrent or metastatic salivary gland cancers, as a last resort treatment. Patients with serious tumour-related discomfort for whom no regular option was available were selected and critically re-assessed by the tumour board. Radionuclide therapy eligibility was confirmed when tumour targeting was greater than liver SUVmax on 68Ga-PSMA-PET/CT. The protocol aimed at four cycles of 6.0–7.4 GBq 177Lu-PSMA-617 every 6–8 weeks. Clinical response was evaluated by questionnaires and radiological response by 68Ga-PSMA-PET/CT.

Results

Six patients were treated with 177Lu-PSMA: four adenoid cystic carcinomas, one adenocarcinoma NOS and one acinic cell carcinoma. In two patients, radiological response was observed, showing either stable disease or a partial response, and four patients reported immediate relief of tumour-related symptoms. Most reported side effects were grade 1–2 fatigue, nausea, bone pain and xerostomia. Four patients prematurely discontinued therapy: three due to disease progression and one due to demotivating (grade 1) side-effects.

Conclusions

Palliative 177Lu-PSMA therapy for salivary gland cancer may lead to rapid relief of tumour-associated discomfort and may even induce disease stabilization. It is safe, relatively well tolerated and can be considered when regular treatment options fail.
SIRT6 inhibition delays peripheral nerve recovery by suppressing migration, phagocytosis and M2-polarization of macrophages
Authors: Zou Ying , Zhang Jiaqi , Xu Jiawei , Fu Lanya , Xu Yizhou , Wang Xianghai , Li Zhenlin , Zhu Lixin , Sun Hao , Zheng Hui , Guo Jiasong
Published: December 2021

Background

Silent information regulator 6 (SIRT6) is a mammalian homolog of the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase sirtuin family. Prior evidences suggested that the anti-inflammatory function of SIRT6 after spinal cord and brain injury, and it plays a crucial role in macrophages polarization of adipose tissue and skin. However, the role of SIRT6 in macrophages involved peripheral nerve injury is still unknown. Given the prominent role of macrophages in peripheral nerve recovery, we aim to investigate the role of SIRT6 in the regulation of phenotypes shift and functions in macrophages after peripheral nerve injury.

Results

In the present study, we first identified a significant increase of SIRT6 expression during nerve degeneration and macrophages phagocytosis. Next, we found nerve recovery was delayed after SIRT6 silencing by injected shRNA lentivirus into the crushed sciatic nerve, which exhibited a reduced expression of myelin-related proteins (e.g., MAG and MBP), severer myoatrophy of target muscles, and inferior nerve conduction compared to the shRNA control injected mice. In vitro, we found that SIRT6 inhibition by being treated with a selective inhibitor OSS_128167 or lentivirus transfection impairs migration and phagocytosis capacity of bone marrow-derived macrophages (BMDM). In addition, SIRT6 expression was discovered to be reduced after M1 polarization, but SIRT6 was enhanced after M2 polarization in the monocyte-macrophage cell line RAW264.7 and BMDM. Moreover, SIRT6 inhibition increased M1 macrophage polarization with a concomitant decrease in M2 polarization both in RAW264.7 and BMDM via activating NF-κB and TNF-α expression, and SIRT6 activation by UBCS039 treatment could shift the macrophages from M1 to M2 phenotype.

Conclusion

Our findings indicate that SIRT6 inhibition impairs peripheral nerve repair through suppressing the migration, phagocytosis, and M2 polarization of macrophages. Therefore, SIRT6 may become a favorable therapeutic target for peripheral nerve injury.
The profile of patients with atrial fibrillation scheduled for cardioversion or catheter ablation hospitalized in a Romanian rehabilitation hospital
Authors: BLAGA Sorin Nicolae , TODOR Nicolae , ZDRENGHEA Dumitru , ROȘU Radu , CISMARU Gabriel , PUIU Mihai , GUȘETU Gabriel , POP Dana
Published: December 2021

Objectives - Structural cardiac, mainly atrial remodeling in non-valvular atrial fibrillation (NVAF) creates conditions for thromboembolic complications, despite the optimization of oral anticoagulant treatment over the past years. This study aims to provide a comparative analysis of patients with NVAF, with and without atrial thrombotic masses, in an integrated approach using clinical, electrocardiographic, anatomohemodynamic cardiac findings assessed by echocardiography, as well as an evaluation of the inflammatory status based on the usual screening blood markers. Methods – The study was based on the anonymous analysis of the medical records of 50 patients with NVAF monitored in a center of cardiology in Cluj-Napoca between March 2019 – February 2020, who received optimal oral anticoagulant treatment, all undergoing transesophageal ultrasound prior to cardioversion or ablation therapy. The statistical data processing methods were based on the “chi square” test and overall model fit logistic regression. Results – Atrial thrombotic complications were found in 7 (14%) patients with NVAF. These had, compared to patients without thrombotic masses, a mean CHA2DS2-VASc scale of 3 versus 2.76 (p=0.05), more frequently other atrial tachyarrhythmias (p<0.01), a more expressed inflammatory reaction (p=0.02), as well as a reduction of LVEF (p<0.01) and the peak left atrial appendage emptying velocity (p<0.01). Conclusions – In addition to a high CHA2DS2-VASc score, left anatomohemodynamic cardiac alteration, atrial arrhythmic complexity and background inflammatory status create conditions for high thromboembolic risk in patients with NVAF.
Keywords: non-valvular atrial fibrillation, cardiac thrombosis, left ventricular ejection fraction, inflammatory status, peak left atrial appendage velocity,
Improving functional and motor capacity through means/resources and methods specific to acvatic activities
Authors: CONDURECHE Iustina , CONFEDERAT Luminița , ROTARIU Mariana , TURNEA Marius
Published: December 2021

Introduction. Exercise programs in the aquatic environment have as their main objective the improvement and maintenance of physical capacity/ capability, these being in continuous development and diversification. Water exercise amplifies the effects of general physical exercise, by allowing a more precise control over the movement of each body segment and of the body as a whole. The aquatic environment offers a number of beneficial effects compared to ones offered by the terrestrial environment. The benefits obtained through the aquatic activities are fundamental and are reflected throughout the entire body including both motor, functional and aesthetic level.
Material and method. The objective of this study is represented by the identification of new forms of physical exercise that will increase the motor’s capacity. In order to achieve this goal, several methodological requirements were met, such as: successive engagement of the joints and muscle groups in effort (starting with the neck’s muscles, shoulders, arms, torso and legs, simultaneously with scapular-humeral joints, spine and coxo-femoral joints and legs), the gradually usage of exercises, starting with the most basic and then increasing the complexity of the exercises, the usage of the accessible exercises in the beginning of the training, executed with high amplitude and reduced speed, focusing on the correctness of the execution, the selection and the adequate/ appropriately usage of the initial positions according to the subject’s particularities and the shape/form of the exercise, the optimal control of the effort, achieved through a number of iterations, optimal execution time and breaks, the sets of general physical exercises will consist of sets of 8-12 exercises/reps, the principle of symmetry in the execution of the exercises has to be respected, the continuity of practicing a set of exercises for 6 to 8 consecutive lessons, the recommended work method is fragmented-imitative, efficiently combining the explication with the demonstration, the number of repetitions and the movement’s correction.
Results and discussions. Analyzing results obtained after the evaluation, we have noticed significant growth in the functional and motor capacities.
Conclusions. The systematization of water activities on objective criteria effectively contributes to their knowledge, while allowing them to be included in the spectrum of recreational, sporting, relaxing or therapeutic activities.
Keywords: acvatic activities, physical exercise, evaluations,