bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of antioxidant and anticancer activity of crude extract and different fractions of Chlorella vulgaris axenic culture grown under various concentrations of copper ions
Authors: El-fayoumy Eman A. , Shanab Sanaa M. M. , Gaballa Hanan S. , Tantawy Mohamed A. , Shalaby Emad A.
Published: February 2021

Background

Chlorella vulgaris is a microalga potentially used for pharmaceutical, animal feed, food supplement, aquaculture and cosmetics. The current study aims to study the antioxidant and prooxidant effect of Chlorella vulgaris cultivated under various conc. of copper ions.

Methods

The axenic green microalgal culture of Chlorella vulgaris was subjected to copper stress conditions (0.00, 0.079, 0.158, 0.316 and 0.632 mg/L). The growth rate was measured at OD680 nm and by dry weight (DW). Moreover, the Antioxidant activity against DPPH and ABTS radical, pigments and phytochemical compounds of the crude extracts (methylene chloride: Methanol, 1:1) were evaluated. The promising Cu crude extract (0.316 mg/L) further fractionated into twenty-one fractions by silica gel column chromatography using hexane, chloroform and ethyl acetate as a mobile phase.

Results

The obtained results reported that nine out of these fractions exhibited more than 50% antioxidant activity and anticancer activity against Hela cancer cell lines. Based on IC50, fraction No. 7 was found to be the most effective fraction possessing a significant increase in both antioxidant and anticancer potency. Separation of active compound (s) in fraction No 7 was performed using precoated silica gel plates (TLC F254) with ethyl acetate: hexane (9:1 v/v) as mobile phase. Confirmation of active compound separation was achieved by two-dimensional TLC and visualization of the separated compound by UV lamp. The complete identification of the separated active compound was performed by UV- Vis- spectrophotometric absorption, IR, MS, H1-NMRT C13-NMR. The isolated compound ((2E,7R,11R)-3,7,11,15-Tetramethyl-2-hexadecenol) have high antioxidant activity with IC50 (10.59 μg/ml) against DPPH radical assay and comparable to the capacities of the positive controls, Butylated hydroxy toluene [BHT] (IC50 11.2 μg/ml) and Vitamin C (IC50 12.9 μg/ml). Furthermore, pure isolated compound exhibited a potent anticancer activity against Hela cell line with IC50 (4.38 μg/ml) compared to Doxorubicin (DOX) as synthetic drug (13.3 μg/ml). In addition, the interaction of the pure compound with Hela cancer cell line and gene expression were evaluated.

Conclusions

The authors recommend cultivation of Chlorella vulgaris in large scale under various stress conditions for use the crude extracts and semi purified fractions for making a pharmaco-economic value in Egypt and other countries.
A policy analysis of the national phenylketonuria screening program in Iran
Authors: Heidari Alireza , Arab Mohammad , Damari Behzad
Published: February 2021

Background

Phenylketonuria (PKU) screening is a public health measure taken to diagnose and treat the patients with PKU to prevent severe neurological disorders in them. The present study was aimed at analyzing the policies of the national PKU screening (NaPS) program in Iran.

Methods

PKU screening program policies were analyzed in compliance with the policy triangle model. Document review and 38 semi-structured interviews were used for data collection. Document review data were analyzed using content analysis, and interview data were analyzed using framework analysis.

Results

The national PKU screening (NaPS) program was a decision made at the genetics department of Ministry of Health and Medical Education (MOHME) in Iran. Many internal and external stakeholders were involved in it and valid evidence was used to formulate the policies. Despite some opposition and insufficient support, the program was implemented due to the continuous persistence of parents, interested executives, formulated valid content and a top-down approach. The main barriers included rapid substitution of managers, shortage of Phe-free milk, little awareness of patients’ families, social stigma, and inadequate co-operation of some hospital administrators.

Conclusions

The policy triangle framework contributed to explaining the different components of the PKU screening program. A successful PKU screening program requires more stability of senior managers in MOHME, enough human resources and Phe-free milk, educating patients’ families, and commitment of hospitals administrators. Meanwhile, all the stakeholders need to be involved in the program effectively.
The impact of non-pharmaceutical interventions on SARS-CoV-2 transmission across 130 countries and territories
Authors:   CMMID COVID-19 Working Group, Liu Yang , Morgenstern Christian , Kelly James , Lowe Rachel , Jit Mark
Published: February 2021

Background

Non-pharmaceutical interventions (NPIs) are used to reduce transmission of SARS coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). However, empirical evidence of the effectiveness of specific NPIs has been inconsistent. We assessed the effectiveness of NPIs around internal containment and closure, international travel restrictions, economic measures, and health system actions on SARS-CoV-2 transmission in 130 countries and territories.

Methods

We used panel (longitudinal) regression to estimate the effectiveness of 13 categories of NPIs in reducing SARS-CoV-2 transmission using data from January to June 2020. First, we examined the temporal association between NPIs using hierarchical cluster analyses. We then regressed the time-varying reproduction number (Rt) of COVID-19 against different NPIs. We examined different model specifications to account for the temporal lag between NPIs and changes inRt, levels of NPI intensity, time-varying changes in NPI effect, and variable selection criteria. Results were interpreted taking into account both the range of model specifications and temporal clustering of NPIs.

Results

There was strong evidence for an association between two NPIs (school closure, internal movement restrictions) and reducedRt. Another three NPIs (workplace closure, income support, and debt/contract relief) had strong evidence of effectiveness when ignoring their level of intensity, while two NPIs (public events cancellation, restriction on gatherings) had strong evidence of their effectiveness only when evaluating their implementation at maximum capacity (e.g. restrictions on 1000+ people gathering were not effective, restrictions on < 10 people gathering were). Evidence about the effectiveness of the remaining NPIs (stay-at-home requirements, public information campaigns, public transport closure, international travel controls, testing, contact tracing) was inconsistent and inconclusive. We found temporal clustering between many of the NPIs. Effect sizes varied depending on whether or not we included data after peak NPI intensity.

Conclusion

Understanding the impact that specific NPIs have had on SARS-CoV-2 transmission is complicated by temporal clustering, time-dependent variation in effects, and differences in NPI intensity. However, the effectiveness of school closure and internal movement restrictions appears robust across different model specifications, with some evidence that other NPIs may also be effective under particular conditions. This provides empirical evidence for the potential effectiveness of many, although not all, actions policy-makers are taking to respond to the COVID-19 pandemic.
Increasing adoption rates at animal shelters: a two-phase approach to predict length of stay and optimal shelter allocation
Authors: Bradley Janae , Rajendran Suchithra
Published: February 2021

Background

Among the 6–8 million animals that enter the rescue shelters every year, nearly 3–4 million (i.e., 50% of the incoming animals) are euthanized, and 10–25% of them are put to death specifically because of shelter overcrowding each year. The overall goal of this study is to increase the adoption rates at animal shelters. This involves predicting the length of stay of each animal at shelters considering key features such as animal type (dog, cat, etc.), age, gender, breed, animal size, and shelter location.

Results

Logistic regression, artificial neural network, gradient boosting, and the random forest algorithms were used to develop models to predict the length of stay. The performance of these models was determined using three performance metrics: precision, recall, and F1 score. The results demonstrated that the gradient boosting algorithm performed the best overall, with the highest precision, recall, and F1 score. Upon further observation of the results, it was found that age for dogs (puppy, super senior), multicolor, and large and small size were important predictor variables.

Conclusion

The findings from this study can be utilized to predict and minimize the animal length of stay in a shelter and euthanization. Future studies involve determining which shelter location will most likely lead to the adoption of that animal. The proposed two-phased tool can be used by rescue shelters to achieve the best compromise solution by making a tradeoff between the adoption speed and relocation cost.
Preexisting respiratory diseases and clinical outcomes in COVID-19: a multihospital cohort study on predominantly African American population
Authors: Lohia Prateek , Sreeram Kalyan , Nguyen Paul , Choudhary Anita , Khicher Suman , Yarandi Hossein , Kapur Shweta , Badr M. Safwan
Published: February 2021

Background

Comorbidities play a key role in severe disease outcomes in COVID-19 patients. However, the literature on preexisting respiratory diseases and COVID-19, accounting for other possible confounders, is limited. The primary objective of this study was to determine the association between preexisting respiratory diseases and severe disease outcomes among COVID-19 patients. Secondary aim was to investigate any correlation between smoking and clinical outcomes in COVID-19 patients.

Methods

 This is a multihospital retrospective cohort study on 1871 adult patients between March 10, 2020, and June 30, 2020, with laboratory confirmed COVID-19 diagnosis. The main outcomes of the study were severe disease outcomes i.e. mortality, need for mechanical ventilation, and intensive care unit (ICU) admission. During statistical analysis, possible confounders such as age, sex, race, BMI, and comorbidities including, hypertension, coronary artery disease, congestive heart failure, diabetes, any history of cancer and prior liver disease, chronic kidney disease, end-stage renal disease on dialysis, hyperlipidemia and history of prior stroke, were accounted for.

Results

 A total of 1871 patients (mean (SD) age, 64.11 (16) years; 965(51.6%) males; 1494 (79.9%) African Americans; 809 (43.2%) with ≥ 3 comorbidities) were included in the study. During their stay at the hospital, 613 patients (32.8%) died, 489 (26.1%) needed mechanical ventilation, and 592 (31.6%) required ICU admission. In fully adjusted models, patients with preexisting respiratory diseases had significantly higher mortality (adjusted Odds ratio (aOR), 1.36; 95% CI, 1.08–1.72; p = 0.01), higher rate of ICU admission (aOR, 1.34; 95% CI, 1.07–1.68; p = 0.009) and increased need for mechanical ventilation (aOR, 1.36; 95% CI, 1.07–1.72; p = 0.01). Additionally, patients with a history of smoking had significantly higher need for ICU admission (aOR, 1.25; 95% CI, 1.01–1.55; p = 0.03) in fully adjusted models.

Conclusion

 Preexisting respiratory diseases are an important predictor for mortality and severe disease outcomes, in COVID-19 patients. These results can help facilitate efficient resource allocation for critical care services.
In silico identification of novel open reading frames in Plasmodium falciparum oocyte and salivary gland sporozoites using proteogenomics framework
Authors: Gunnarsson Sophie , Prabakaran Sudhakaran
Published: February 2021

Background

Plasmodium falciparum causes the deadliest form of malaria, which remains one of the most prevalent infectious diseases. Unfortunately, the only licensed vaccine showed limited protection and resistance to anti-malarial drug is increasing, which can be largely attributed to the biological complexity of the parasite’s life cycle. The progression from one developmental stage to another in P. falciparum involves drastic changes in gene expressions, where its infectivity to human hosts varies greatly depending on the stage. Approaches to identify candidate genes that are responsible for the development of infectivity to human hosts typically involve differential gene expression analysis between stages. However, the detection may be limited to annotated proteins and open reading frames (ORFs) predicted using restrictive criteria.

Methods

The above problem is particularly relevant for P. falciparum; whose genome annotation is relatively incomplete given its clinical significance. In this work, systems proteogenomics approach was used to address this challenge, as it allows computational detection of unannotated, novel Open Reading Frames (nORFs), which are neglected by conventional analyses. Two pairs of transcriptome/proteome were obtained from a previous study where one was collected in the mosquito-infectious oocyst sporozoite stage, and the other in the salivary gland sporozoite stage with human infectivity. They were then re-analysed using the proteogenomics framework to identify nORFs in each stage.

Results

Translational products of nORFs that map to antisense, intergenic, intronic, 3′ UTR and 5′ UTR regions, as well as alternative reading frames of canonical proteins were detected. Some of these nORFs also showed differential expression between the two life cycle stages studied. Their regulatory roles were explored through further bioinformatics analyses including the expression regulation on the parent reference genes, in silico structure prediction, and gene ontology term enrichment analysis.

Conclusion

The identification of nORFs in P. falciparum sporozoites highlights the biological complexity of the parasite. Although the analyses are solely computational, these results provide a starting point for further experimental validation of the existence and functional roles of these nORFs,
Recruitment, training and supervision of nurses and nurse assistants for a task-shifting depression intervention in two RCTs in Brazil and Peru
Authors: Rocha Thais Izabel Ugeda , Aschar Suzana Crismanis de Almeida Lopes , Hidalgo-Padilla Liliana , Daley Kate , Claro Heloísa Garcia , Martins Castro Hellen Carolina , dos Santos Daniela Vera Cruz , Miranda J. Jaime , Araya Ricardo , Menezes Paulo Rossi
Published: February 2021

Background

Task-shifting and technology in psychological interventions are two solutions to increasing access to mental health intervention and overcoming the treatment gap in low and middle-income countries. The CONEMO intervention combines a smartphone app with support from non-specialized professionals, aiming to treat depression in patients with diabetes and/or hypertension. The aim of this paper is to describe the process of recruitment, training and supervision of the non-specialized professionals who participated in the CONEMO task-shifting intervention in Brazil and Peru.

Methods

We described and analyzed data related to the recruitment, training and supervision of 62 nurse assistants from the health system in Sao Paulo, Brazil, and three hired nurses in Lima, Peru. The data were collected from information provided by nurses and nurse assistants, supervisor records from supervision meetings and the CONEMO platform database.

Results

We found that task-shifting was feasible using existing resources in Sao Paulo and additional human resources in Lima. Training and supervision were found to be crucial and well received by the staff; however, time was a limitation when using existing human resources. Ensuring technological competence prior to the start of the intervention was essential. Group supervision meetings allowed non-specialized professionals to learn from each other’s experiences.

Conclusion

Carefully considering recruitment, training and supervision of non-specialized professionals is important for effective task-shifting when delivering an mHealth intervention for depression. Opportunities and challenges of working in different health systems are described, which should be considered in future implementation, either for research or real settings.

Trial registration NCT028406662 (Sao Paulo), NCT03026426 (Peru).
Effect of assist-as-needed robotic gait training on the gait pattern post stroke: a randomized controlled trial
Authors: Alingh J. F. , Fleerkotte B. M. , Groen B. E. , Rietman J. S. , Weerdesteyn V. , van Asseldonk E. H. F. , Geurts A. C. H. , Buurke J. H.
Published: February 2021

Background

Regaining gait capacity is an important rehabilitation goal post stroke. Compared to clinically available robotic gait trainers, robots with an assist-as-needed approach and multiple degrees of freedom (AANmDOF) are expected to support motor learning, and might improve the post-stroke gait pattern. However, their benefits compared to conventional gait training have not yet been shown in a randomized controlled trial (RCT). The aim of this two-center, assessor-blinded, RCT was to compare the effect of AANmDOFrobotic to conventional training on the gait pattern and functional gait tasks during post-stroke inpatient rehabilitation.

Methods

Thirty-four participants with unilateral, supratentorial stroke were enrolled (< 10 weeks post onset, Functional Ambulation Categories 3–5) and randomly assigned to six weeks of AANmDOFrobotic (combination of training in LOPES-II and conventional gait training) or conventional gait training (30 min, 3–5 times a week), focused on pre-defined training goals. Randomization and allocation to training group were carried out by an independent researcher. External mechanical work (WEXT), spatiotemporal gait parameters, gait kinematics related to pre-defined training goals, and functional gait tasks were assessed before training (T0), after training (T1), and at 4-months follow-up (T2).

Results

Two participants, one in each group, were excluded from analysis because of discontinued participation after T0, leaving 32 participants (AANmDOFrobotic n = 17; conventional n = 15) for intention-to-treat analysis. In both groups, WEXThad decreased at T1 and had become similar to baseline at T2, while gait speed had increased at both assessments. In both groups, most spatiotemporal gait parameters and functional gait tasks had improved at T1 and T2. Except for step width (T0–T1) and paretic step length (T0–T2), there were no significant group differences at T1 or T2 compared to T0. In participants with a pre-defined goal aimed at foot clearance, paretic knee flexion improved more in the AANmDOFrobotic group compared to the conventional group (T0–T2).

Conclusions

Generally, AANmDOFrobotic training was not superior to conventional training for improving gait pattern in subacute stroke survivors. Both groups improved their mechanical gait efficiency. Yet, AANmDOFrobotic training might be more effective to improve specific post-stroke gait abnormalities such as reduced knee flexion during swing.

Trial registrationRegistry number Netherlands Trial Register (www.trialregister.nl): NTR5060. Registered 13 February 2015.
Managing head and neck cancer patients during the COVID-19 pandemic: the experience of a tertiary referral center in southern Italy
Authors: Longo Francesco , Trecca Eleonora M. C. , D’Ecclesia Aurelio , Copelli Chiara , Tewfik Karim , Manfuso Alfonso , Pederneschi Nicola , Mastromatteo Annalisa , Russo Matteo Aldo , Pansini Antonio , Lacerenza Luca M. , Marano Pier Gerardo , Cassano Lazzaro
Published: February 2021

Background

The medical community has been deeply involved in fighting the Coronavirus disease 2019 (COVID-19) pandemic and, as a consequence, the care of non-COVID-19 patients has been impacted. However, the treatment of head and neck cancer patients is not deferrable, and an integrated strategy is required. The aim of the current article is to present the experience in the management of head and neck patients during the COVID-19 pandemic at the research hospital “Casa Sollievo della Sofferenza”. This review contains replicable and widely usable instructions on how to avoid delays in the diagnosis and treatment of head and neck tumors and to ensure a gradual return to elective procedures.

Main text

The Head and Neck Department of the research hospital “Casa Sollievo della Sofferenza” includes an Otolaryngology and a Maxillofacial Surgery Unit, both of which deal with the diagnosis and treatment of benign and malignant pathologies of the head and neck, as well as urgent/emergent consultations and surgical procedures that necessitate time sensitive operative management, such as cochlear implantation (CI). Given these premises and the complexity of the Department, the “COVID-19 organizing protocol” of the research hospital “Casa Sollievo della Sofferenza” was divided into two phases in accordance with the different stages of the pandemic and the priority of treatment. Special attention was given to the medical surveillance of health care workers and hospitalized patients, to the organization of the outpatient clinic and the operating setting as well as to the implementation of telehealth systems.

Conclusions

The COVID-19 pandemic is going to be a long-term situation with lasting effects on the public health and the entire society. Therefore, an efficient health care system has to adopt a double strategy: always being ready for a “new wave” of the pandemic and not forgetting non-COVID-19 patients, among whom head and neck cancer patients represent a priority. More than 1 year since the first outbreak in Wuhan, this review offers a unique and helpful perspective that incorporates awareness of the disease.
USP16 regulates castration-resistant prostate cancer cell proliferation by deubiquitinating and stablizing c-Myc
Authors: Ge Jianchao , Yu Wandong , Li Junhong , Ma Hangbin , Wang Pengyu , Zhou Yinghao , Wang Yang , Zhang Jun , Shi Guowei
Published: February 2021

Background

c-Myc, a well-established oncogene, plays an important role in the initiation and progression of various cancers, including prostate cancer. However, its mechanism in cancer cell remains largely unknown and whether there exist a deubiquitinase targeting c-Myc also remains elusive.

Methods

Bioinformatic analysis and shRNA screening methods were used to identify potential deubiquitinases that correlate with c-Myc gene signature. Cell proliferation and viability were measured by Cell-Counting-Kit 8 and colony formation assays. A mouse xenograft model of PC3 cells was established to confirm the function of USP16 in vivo. The interaction between USP16 and c-Myc protein was assessed by co-immunoprecipitation and protein co-localization assays. Immunohistochemistry staining was performed to detect the expression of USP16, Ki67, and c-Myc in xenograft tissues and clinical tumour tissues. Furthermore, the correlation between USP16 and c-Myc was confirmed by RNA sequencing.

Results

Functional analyses identified USP16, known as a deubiquitinase, was strongly correlated with the c-Myc gene signature. Depletion of USP16 was shown to significantly suppress the growth of PCa cells both in vitro and in vivo. Co-immunoprecipitation and ubiquitination assays confirmed that USP16 served as a novel deubiquitinase of c-Myc and overexpression of c-Myc significantly rescued the effects of USP16 disruption. Immunohistochemistry staining and RNA-seq tactics were further used to confirm the positive correlation between USP16 and c-Myc expression. Expression of USP16 in human PCa tissues was higher than that seen in normal prostate tissues and its high expression was found associated with poor prognosis.

Conclusions

USP16 serves as a novel deubiquitinase of c-Myc. Downregulation of USP16 markedly suppressed PCa cell growth both in vitro and in vivo. USP16 regulates PCa cell proliferation by deubiquitinating and stabilizing c-Myc, making it a potential therapeutic candidate for the treatment of PCa.
Efficacy and safety of biosimilar CT-P17 versus reference adalimumab in subjects with rheumatoid arthritis: 24-week results from a randomized study
Authors: Kay Jonathan , Jaworski Janusz , Wojciechowski Rafal , Wiland Piotr , Dudek Anna , Krogulec Marek , Jeka Slawomir , Zielinska Agnieszka , Trefler Jakub , Bartnicka-Maslowska Katarzyna , Krajewska-Wlodarczyk Magdalena , Klimiuk Piotr A. , Lee Sang Joon , Bae Yun Ju , Yang Go Eun , Yoo Jae Kyoung , Furst Daniel E. , Keystone Edward
Published: February 2021

Background

To demonstrate equivalent efficacy of the proposed high-concentration (100 mg/ml), citrate-free adalimumab biosimilar CT-P17 to European Union-approved adalimumab (EU-adalimumab) in subjects with active rheumatoid arthritis (RA).

Methods

This randomized, double-blind phase III study (ClinicalTrials.gov, NCT03789292) randomized (1:1) subjects with active RA at 52 centers to receive CT-P17 or EU-adalimumab 40 mg subcutaneously every 2 weeks until week 52. Results to week 24 are reported here. The primary endpoint was 20% improvement by American College of Rheumatology criteria (ACR20) response rate at week 24. Equivalence was concluded if the corresponding confidence intervals (CIs) for the estimate of treatment difference were within predefined equivalence margins: − 15 to 15% (95% CI; European Medicines Agency assumption); − 12 to 15% (90% CI; Food and Drug Administration assumption). Additional efficacy, pharmacokinetic, usability, safety, and immunogenicity endpoints were evaluated.

Results

648 subjects were randomized (324 CT-P17; 324 EU-adalimumab). The ACR20 response rate at week 24 was 82.7% (n = 268/324) in both groups (intention-to-treat population). The 95% CI (− 5.94 to 5.94) and 90% CI (− 4.98 to 4.98) were within predefined equivalence margins for both assumptions and equivalent efficacy was concluded. Additional endpoints and overall safety were comparable between groups. Mean trough serum concentrations of CT-P17 were slightly higher than those of EU-adalimumab. Immunogenicity was slightly lower numerically for the CT-P17 group than for the EU-adalimumab group.

Conclusions

CT-P17 and EU-adalimumab have equivalent efficacy and comparable safety and immunogenicity in subjects with active RA. Overall safety of CT-P17 is consistent with the known safety profile of reference adalimumab.

Trial registration

ClinicalTrials.gov, NCT03789292. Registered 28 December 2018—retrospectively registered.
NAMPT/SIRT2-mediated inhibition of the p53-p21 signaling pathway is indispensable for maintenance and hematopoietic differentiation of human iPS cells
Authors: Xu Yun , Nasri Masoud , Dannenmann Benjamin , Mir Perihan , Zahabi Azadeh , Welte Karl , Morishima Tatsuya , Skokowa Julia
Published: February 2021

Background

Nicotinamide phosphoribosyltransferase (NAMPT) regulates cellular functions through the protein deacetylation activity of nicotinamide adenine dinucleotide (NAD+)-dependent sirtuins (SIRTs). SIRTs regulate functions of histones and none-histone proteins. The role of NAMPT/SIRT pathway in the regulation of maintenance and differentiation of human-induced pluripotent stem (iPS) cells is not fully elucidated.

Methods

We evaluated the effects of specific inhibitors of NAMPT or SIRT2 on the pluripotency, proliferation, survival, and hematopoietic differentiation of human iPS cells. We also studied the molecular mechanism downstream of NAMPT/SIRTs in iPS cells.

Results

We demonstrated that NAMPT is indispensable for the maintenance, survival, and hematopoietic differentiation of iPS cells. We found that inhibition of NAMPT or SIRT2 in iPS cells induces p53 protein by promoting its lysine acetylation. This leads to activation of the p53 target, p21, with subsequent cell cycle arrest and induction of apoptosis in iPS cells. NAMPT and SIRT2 inhibition also affect hematopoietic differentiation of iPS cells in an embryoid body (EB)-based cell culture system.

Conclusions

Our data demonstrate the essential role of the NAMPT/SIRT2/p53/p21 signaling axis in the maintenance and hematopoietic differentiation of iPS cells.
Sympathetic stimulation increases serum lactate concentrations in patients admitted with sepsis: implications for resuscitation strategies
Authors: Jagan Nikhil , Morrow Lee E. , Walters Ryan W. , Plambeck Robert W. , Patel Tej M. , Moore Douglas R. , Malesker Mark A.
Published: February 2021

Background

Diametrically opposed positions exist regarding the deleterious effects of elevated lactate. There are data suggesting that it is a detrimental proxy for tissue hypoperfusion and anaerobic metabolism in sepsis and an alternative viewpoint is that some of the hyperlactatemia produced maybe adaptive. This study was conducted to explore the relationship between serum lactate levels, mean arterial blood pressure (MAP), and sympathetic stimulation in patients with sepsis.

Methods

Retrospective analysis of prospectively collected clinical data from four community-based hospitals and one academic medical center. 8173 adults were included. Heart rate (HR) was used as a surrogate marker of sympathetic stimulation. HR, MAP, and lactate levels were measured upon presentation.

Results

MAP and HR interacted to affect lactate levels with the highest levels observed in patients with low MAP and high HR (3.6 mmol/L) and the lowest in patients with high MAP and low HR (2.2 mmol/L). The overall mortality rate was 12.4%. Each 10 beats/min increase in HR increased the odds of death 6.0% (95% CI 2.6% to 9.4%), each 1 mmol/L increase in lactate increased the odds of death 20.8% (95% CI 17.4% to 24.2%), whereas each 10 mmHg increase in MAP reduced the odds of death 12.3% (95% CI 9.2% to 15.4%). However, HR did not moderate or mediate the association between lactate and death.

Conclusions

In septic patients, lactate production was associated with increased sympathetic activity (HR ≥ 90) and hypotension (MAP < 65 mmHg) and was a significant predictor of mortality. Because HR, lactate, and MAP were associated with mortality, our data support the present strategy of using these measurements to gauge severity of illness upon presentation. Since HR did not moderate or mediate the association between lactate and death, criticisms alleging that lactate caused by sympathetic stimulation is adaptive (i.e., less harmful) do not appear substantiated.
Correction to: Oxycodone versus other opioid analgesics after laparoscopic surgery: a meta-analysis
Authors: Li Yan , Dou Zhi , Yang Liqiang , Wang Qi , Ni Jiaxiang , Ma Jun
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Multi-omics analysis of aniline-degrading bacterium, Delftia sp. K82
Authors: Lee Sang-Yeop , Yun Sung Ho , Lee Hayoung , Seo Giwan , Kim Seung Il
Published: February 2021

Delftia sp. K82 is a soil bacterium capable of utilizing monocyclic aromatic hydrocarbons, including aniline, as its sole carbon and nitrogen source. In this study, the genome analysis of Delftia sp. K82 was completed and the genome data (6117 protein-coding genes and 62 RNA genes) were utilized for proteomic and transcriptomic analysis of Delftia sp. K82 cultured in aniline culture medium. Using these multi-omics approaches (genomics, transcriptomics, and proteomics), complete gene clusters for aniline biodegradation pathways were identified and transcriptomic or proteomic sets specifically induced in aniline culture conditions were elucidated. These data provide multi-layered information on the metabolic characteristics of Delftia sp. K82. The findings suggest that multi-omics approaches are useful analytical tools for the elucidation of the metabolic diversity of soil bacteria and for the identification of novel metabolic enzymes.
Testosterone activates glucose metabolism through AMPK and androgen signaling in cardiomyocyte hypertrophy
Authors: Troncoso Mayarling Francisca , Pavez Mario , Wilson Carlos , Lagos Daniel , Duran Javier , Ramos Sebastián , Barrientos Genaro , Silva Patricio , Llanos Paola , Basualto-Alarcón Carla , Westenbrink B. Daan , Lavandero Sergio , Estrada Manuel
Published: February 2021

Background

Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake—via AMP-activated protein kinase (AMPK)—after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR).

Methods

Cultured cardiomyocytes were stimulated with 100 nM testosterone for 24 h, and hypertrophy was verified by increased cell size and mRNA levels of β-myosin heavy chain (β-mhc). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR).

Results

Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5 weeks induced cardiac hypertrophy and upregulated β-mhc, Hk2 and Pfk2 mRNA levels.

Conclusion

These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.
Successful treatment of post chemotherapy esophageal cicatricial atresia in a pediatric patient with anaplastic large cell lymphoma through minimally invasive esophagectomy: a case report
Authors: Hozaka Yuto , Sasaki Ken , Nishikawa Takuro , Onishi Shun , Noda Masahiro , Tsuruda Yusuke , Uchikado Yasuto , Kita Yoshiaki , Arigami Takaaki , Mori Shinichiro , Maemura Kosei , Ieiri Satoshi , Kawano Yoshifumi , Natsugoe Shoji , Ohtsuka Takao
Published: February 2021

Background

Anaplastic large cell lymphoma (ALCL) is a CD30-positive T-cell lymphoma, which is a rare type of non-Hodgkin lymphoma. ALCL rarely presents in the gastrointestinal tract, and the esophageal involvement in of ALCL is extremely rare.

Case presentation

An 11-year-old boy who complained of abdominal pain and cough was diagnosed with ALK-positive ALCL on the basis of systemic lymphadenopathy findings and immunohistochemistry results of pleural effusion. Although remission was observed after chemotherapy at 5 months after diagnosis, dysphagia persisted, and esophagoscopy revealed a severe stricture in the middle thoracic esophagus. At 9 months after diagnosis, allogeneic bone marrow transplantation was performed to ensure that complete remission was maintained; however, dysphagia and saliva retention did not improve. Approximately 10 months after diagnosis, esophagoscopy revealed a blind end in the middle thoracic esophagus, similar to that in congenital esophageal atresia. Subsequently, we performed minimally invasive subtotal esophagectomy under thoracoscopy and laparoscopy and gastric conduit reconstruction via the retrosternal route more than 2 years after allogeneic bone marrow transplantation. The final pathological diagnosis was esophageal atresia with esophagitis, with no malignancy. During postoperative evaluation, the patient required swallowing training for a few months, although no major complications were noted. Oral intake was possible, and complete remission was maintained at 14 month post-surgery.

Conclusions

Oncologists must consider the possibility of acquired esophageal cicatricial atresia as a complication during chemotherapy for ALCL. If esophageal obstruction or esophageal atresia occur and if remission is maintained, esophagectomy and esophageal reconstruction are useful treatment options for maintaining oral intake.
Feasibility of the Go2Play Active Play intervention for increasing physical and social development in children with intellectual disabilities
Authors: McGarty Arlene , Jones Nathalie , Rutherford Katie , Westrop Sophie , Sutherland Lara , Jahoda Andrew , Melville Craig
Published: February 2021

Introduction

An active play is designed to increase children’s physical activity levels and fundamental movement skills through outdoor play and is well-suited to the needs of children with intellectual disabilities. However, no active play interventions have included children with intellectual disabilities. This study aims to investigate the feasibility of a school-based active play intervention for children with intellectual disabilities.

Method

Children aged 7–12 years who had intellectual disabilities and were independently ambulatory were eligible. This single-group 17-week intervention was implemented in two additional support needs schools. It consisted of a weekly 1-h active play session incorporating 30 min of structured games and 30 min of free play. Feasibility of recruitment/retention, adherence, and outcome measures were investigated. Outcome measures included school-based physical activity (ActiGraph GT3X+ accelerometer), fundamental movement skills (Test of Gross Motor Development-2), and social interactions (Playground Observation of Peer Engagement). Staff feedback was collected via open-ended questionnaire. Feasibility was investigated using descriptive statistics and questionnaire data analyzed using thematic analysis. Potential pre-post changes were investigated for school-based physical activity, fundamental movement skills, and social interactions using paired samples t tests. The progression criteria were (1) > 50% of eligible participants recruited, (2) > 50% of recruited participants retained, (3) > 50% of active play sessions spent in MVPA, and (4) > 50% of participants complete outcome measurements.

Results

All progression criteria were met. Recruitment and retention rates were 100% (n=21 participants). Intervention adherence was high, based on data from n=1 school, with 90% of participants attending all sessions. Measuring physical activity using accelerometry and fundamental movement skills using the Test of Gross Motor Development-2 were feasible. The Playground Observation of Peer Engagement tool to measure social interactions was not feasible. The only significant increase post-intervention was for social interactions during structured play (pre–post mean difference: –1.46, 95% CI −1.99, −0.93). Staff feedback was positive with the intervention well received by schools and potential benefits post-intervention identified by teachers.

Conclusion

The Go2Play Active Play intervention is feasible for children with intellectual disabilities. Future research should further investigate feasibility and implementation on a larger scale using a pilot cluster randomised controlled trial.

Trial registration

ISRCTN registry: ISRCTN10277566.
How the wisdom of crowds, and of the crowd within, are affected by expertise
Authors: Fiechter Joshua L. , Kornell Nate
Published: February 2021

We investigated the effect of expertise on the wisdom of crowds. Participants completed 60 trials of a numerical estimation task, during which they saw 50–100 asterisks and were asked to estimate how many stars they had just seen. Experiment 1 established that both inner- and outer-crowd wisdom extended to our novel task: Single responses alone were less accurate than responses aggregated across a single participant (showing inner-crowd wisdom) and responses aggregated across different participants were even more accurate (showing outer-crowd wisdom). In Experiment 2, prior to beginning the critical trials, participants did 12 practice trials with feedback, which greatly increased their accuracy. There was a benefit of outer-crowd wisdom relative to a single estimate. There was no inner-crowd wisdom effect, however; with high accuracy came highly restricted variance, and aggregating insufficiently varying responses is not beneficial. Our data suggest that experts give almost the same answer every time they are asked and so they should consult the outer crowd rather than solicit multiple estimates from themselves.
First detection of Megaselia scalaris (Loew) (Diptera: Phoridae) as a facultative endoparasitoid of Nezara viridula (L.) (Hemiptera: Pentatomidae)
Authors: El-Hawagry Magdi Shaaban Ali , Ebrahim Ayman Mohey Eldin , Nada Maha Salah Eldin
Published: February 2021

Background

The phorid flyMegaselia scalaris(Loew) (Diptera: Phoridae) is an omnivorous species, capable of exploring a large variety of environments and ecological niches. It is known as an important detritivore species with maggots feeding on a variety of food of both animal and plant origin.

Results

The present study reportsM. scalarisas an endoparasitoid attacking colonies of the southern green stink bugNezara viridula(L.) for the first time. This case of parasitism was observed inside rearing cages ofN. viridulaat  the Plant Protection Research Institute, Dokki, Egypt in August 2020. We firstly identified adult individuals ofM. scalariswhich were found moving erratically within the cages using relevant identification keys. To verify thatN. viridulaindividuals are parasitized by the same parasitoid and they are not infected with other parasitoids, some of the parasitized bugs were transferred to a separate cage at the same laboratory conditions and the developmental stages of the dipteran parasitoid were observed until the adult emergence.

Conclusion

The present investigation revealed thatM. scalariscould be included to the recorded parasitoid species ofN. viridula, and further studies should be carried out to assess the efficacy of this fly as a biocontrol agent.
Biological control of Pectobacterium carotovorum subsp. carotovorum, the causal agent of bacterial soft rot in vegetables, in vitro and in vivo tests
Authors: Abd-El-Khair Hassan , Abdel-Gaied Tarek G. , Mikhail Maurice S. , Abdel-Alim Ahmed I. , El-Nasr Hamdy I. Seif
Published: February 2021

Background

Several chemical bactericides were applied for controlling soft rot bacteria, Pectobacterium carotovorum subsp. carotovorum, which causes the destructive soft rot disease to many economically important vegetables, but because of their toxic hazards on human and environment became limit. The biocontrol was applied to control many plant pathogens. Therefore, this work is aimed to study the antagonistic activity of bacterial agents, i.e. Bacillus subtilis, Bacillus pumilus, Bacillus megaterium and Pseudomonas fluorescens, and fugal agents, i.e. Trichoderma harzianum, Trichoderma viride and Trichoderma virens, to control bacterial soft rot disease under in vitro and in vivo tests.

Results

The tested treatments could protect the potato tubers against the development of soft rot. T. viride and T. virens were highly effective in reducing soft rot symptoms on inoculated potato tuber slices, when applied at the same time or 2 h before pathogen inoculation, while B. megaterium and T. harzianum were highly effective when applied at the same time or 2 h after pathogen inoculation. In whole potato tubers technique, B.pumilus highly protected the stored potato tuber under artificially infection conditions, than P. fluorescens, T. harzianum, B. subtilis, T. viride, T. virens and B. megaterium, respectively.

Conclusion

Application of fungal agents or specify the bacterial species can play an important role in controlling bacterial soft rot disease in vegetables and increase the stored periods of potato tubers under storage conditions without any toxic effects.
Ophiocordyceps salganeicola, a parasite of social cockroaches in Japan and insights into the evolution of other closely-related Blattodea-associated lineages
Authors: Araújo João P. M. , Moriguchi Mitsuru G. , Uchiyama Shigeru , Kinjo Noriko , Matsuura Yu
Published: February 2021

The entomopathogenic genus Ophiocordyceps includes a highly diverse group of fungal species, predominantly parasitizing insects in the orders Coleoptera, Hemiptera, Hymenoptera and Lepidoptera. However, other insect orders are also parasitized by these fungi, for example the Blattodea (termites and cockroaches). Despite their ubiquity in nearly all environments insects occur, blattodeans are rarely found infected by filamentous fungi and thus, their ecology and evolutionary history remain obscure. In this study, we propose a new species of Ophiocordyceps infecting the social cockroaches Salganea esakii and S. taiwanensis, based on 16 years of collections and field observations in Japan, especially in the Ryukyu Archipelago. We found a high degree of genetic similarity between specimens from different islands, infecting these two Salganea species and that this relationship is ancient, likely not originating from a recent host jump. Furthermore, we found that Ophiocordyceps lineages infecting cockroaches evolved around the same time, at least twice, one from beetles and the other from termites. We have also investigated the evolutionary relationships between Ophiocordyceps and termites and present the phylogenetic placement of O. cf. blattae. Our analyses also show that O. sinensis could have originated from an ancestor infecting termite, instead of beetle larvae as previously proposed.
Experience with the novel unifemoral parallel sheath technique in percutaneous intervention of chronic total coronary occlusions
Authors: Reifart Joerg , Schilling Konstanze , Hamm Christian W. , Reifart Nicolaus
Published: February 2021

Background

Percutaneous interventions to address chronic coronary occlusions (CTO-PCI) often require simultaneous ipsi- and contralateral coronary injections. Although radial access is increasingly popular, bifemoral artery access is still the preferred choice of CTO operators.

The aim of this case series is to demonstrate the feasibility and safety of the unifemoral parallel sheath technique, which avoids two puncture sites, increases patient comfort, and improves procedure ergonomics.

It offers rapid second access to the femoral artery adjacent to the first sheath as well as closure by unilateral manual compression without or with 1 or 2 vascular closure devices.

Results

We retrospectively evaluated the procedure results in 90 consecutive CTO patients where an ipsilateral parallel sheath access was considered. Placement of the second sheath uneventfully failed in two because of severe femoral calcification and narrowing. In 96.6%, the first sheath was 7 F (3.4% 6F), while the second sheath was 4 F in 22.7%, 5 F in 64.7%, and 6 or 7 F in 11.4% each.

No major complications nor severe bleeding events occurred, and the mean drop of hemoglobin was low (0.6 g/dL ± 0.86).

Conclusion

In CTO-PCI requiring contralateral coronary injections or the retrograde technique, the ipsilateral parallel sheath technique might be a feasible alternative to the standard bifemoral or femoral-radial access.