bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness and safety of aerobic exercise for rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials
Authors: Ye Hui , Weng Heng , Xu Yue , Wang Lulu , Wang Qing , Xu Guihua
Published: February 2022

Background

Rheumatoid arthritis (RA) can cause severe physical impairment and a reduced quality of life, and there is limited evidence for any effective intervention. Aerobic exercise may be beneficial for improving symptoms. Therefore, the purpose of this meta-analysis was to evaluate the effectiveness and safety of aerobic exercise for rheumatoid arthritis patients.

Methods

PubMed, The Cochrane Library, Web of Science, EMBASE, CNKI, WanFang Data and VIP databases were searched. Randomized controlled trials of the effectiveness and safety of aerobic exercise for rheumatoid arthritis were included. Risks of bias were assessed by two independent reviewers using the methods described in the RevMan 5.3, GRADEpro and the Cochrane Handbook. Meta-analyses were performed to investigate the effects of aerobic exercise on rheumatoid arthritis.

Results

A total of 13 RCTs were included, including 967 rheumatoid arthritis patients. The Meta-analysis results showed that aerobic exercise can improve functional ability [MD = − 0.25, 95% CI (− 0.38, − 0.11), P = 0.0002], relieve pain [SMD = − 0.46, 95% CI (− 0.90, − 0.01), P = 0.04], increase aerobic capacity [MD = 2.41, 95% CI (1.36, 3.45), P < 0.00001] and improve the Sit to Stand test score[MD = 1.60, 95% CI (0.07, 3.13), P = 0.04] with statistically significant differences.

Conclusion

Generally, aerobic exercise is beneficial and safe for RA patients and has a certain alleviating effect on the disease, such as functional ability improvement, pain relief and aerobic capacity increase. Limited by the quantity and quality of the included studies, future research with higher-quality studies needs to be conducted to verify the above conclusions.

Trial registration: PROPERO registration number: CRD42021242953.
A dual role of HIF1α in regulating osteogenesis–angiogenesis coupling
Authors: Shao Jingjing , Liu Shibo , Zhang Min , Chen Shujiang , Gan Shuaiqi , Chen Chenfeng , Chen Wenchuan , Li Lei , Zhu Zhimin
Published: February 2022

Objectives

The hypoxia-inducible factor 1-α (HIF1α), a key molecule in mediating bone-vessel crosstalk, has been considered a promising target for treating osteoporosis caused by gonadal hormones. However, senile osteoporosis, with accumulated senescent cells in aged bone, has a distinct pathogenesis. The study aimed at revealing the unknown role of HIF1α in aged bone, thus broadening its practical application in senile osteoporosis.

Materials and methods

Femurs and tibias were collected from untreated mice of various ages (2 months old, 10 months old, 18 months old) and treated mice (2 months old, 18 months old) underwent 4-w gavage of 2-methoxyestradiol (a kind of HIF1α inhibitor). Bone-vessel phenotypes were observed by microfil infusion, micro-CT and HE staining. Markers of senescence, osteogenesis, angiogenesis, oxidative stress and expression of HIF1α were detected by senescence β-galactosidase staining, qRT-PCR, western blot and immunostaining, respectively. Furthermore, bone mesenchymal stem cells from young mice (YBMSCs) and aged mice (ABMSCs) were transfected by knockout siRNA and overexpression plasmid of HIF1α. Senescence β-galactosidase staining, Cell Counting Kit-8, transwell assay, alkaline phosphatase staining, alizarin red-S staining and angiogenesis tests were utilized to assess the biological properties of two cell types. Then, Pifithrin-α and Nutlin-3a were adopted to intervene p53 of the two cells. Finally, H2O2on YBMSCs and NAC on ABMSCs were exploited to change their status of oxidative stress to do a deeper detection.

Results

Senescent phenotypes, impaired osteogenesis–angiogenesis coupling and increased HIF1α were observed in aged bone and ABMSCs. However, 2-methoxyestradiol improved bone-vessel metabolism of aged mice while damaged that of young mice. Mechanically, HIF1α showed opposed effects in regulating the cell migration and osteogenesis–angiogenesis coupling of YBMSCs and ABMSCs, but no remarked effect on the proliferation of either cell type. Pifithrin-α upregulated the osteogenic and angiogenic markers of HIF1α-siRNA-transfected YBMSCs, and Nutlin-3a alleviated those of HIF1α-siRNA-transfected ABMSCs. The HIF1α-p53 relationship was negative in YBMSCs and NAC-treated ABMSCs, but positive in ABMSCs and H2O2-treated YBMSCs.

Conclusion

The dual role of HIF1α in osteogenesis–angiogenesis coupling may depend on the ROS-mediated HIF1α-p53 relationship. New awareness about HIF1α will be conducive to its future application in senile osteoporosis.
Sodium nitrate has no detrimental effect on milk fatty acid profile and rumen bacterial population in water buffaloes
Authors: Xie Fang , Tang Zhenhua , Liang Xin , Wen Chongli , Li Mengwei , Guo Yanxia , Peng Kaiping , Yang Chengjian
Published: February 2022

This study evaluated the influence of dietary sodium nitrate on ruminal fermentation profiles, milk production and composition, microbial populations and diversity in water buffaloes. Twenty-four female water buffaloes were randomly divided into four groups and fed with 0, 0.11, 0.22, 044 g sodium nitrate per kg body weight diets, respectively. Results showed that the concentration of acetate, propionate, butyrate and total VFA in all sodium nitrate–adapted water buffaloes were greater than the control group (P  < 0.05). Although the milk fatty acids value at 0.11 g sodium nitrate/kg/d were slightly lower than other treatments, no significant differences were observed among different treatments (P  > 0.05). Compared to the control group, the archaea richness (ace and chao1) and diversity (Shannon index) indices were increased by nitrate supplementation (P  < 0.05). Compared with the control group, sodium nitrate did not affect bacterial abundance at the phylum and genus level, but the relative abundance of the methanogen genera was greatly changed. There was a tendency for Methanobrevibacter to decrease in the sodium nitrate group (P  = 0.091). Comparisons of archaea communities by PCoA analysis showed significant separation between the control group and nitrate treatments (P  = 0.025). It was concluded that added 0.11–0.44 g sodium nitrate/kg of body weight increased the rumen VFA production and archaeal diversity of water buffaloes but had no detrimental effect on milk yield or composition, fatty acids profile, rumen methanogen or Butyrivibrio group population related to biohydrogenation.
Identification of novel extracellular putative chitinase and hydrolase from Geomyces sp. B10I with the biodegradation activity towards polyesters
Authors: Urbanek Aneta K. , Arroyo Miguel , de la Mata Isabel , Mirończuk Aleksandra M.
Published: February 2022

Cold-adapted filamentous fungal strain Geomyces sp. B10I has been reported to decompose polyesters such as poly(e-caprolactone) (PCL), poly(butylene succinate) (PBS) and poly(butylene succinate-co-butylene adipate) (PBSA). Here, we identified the enzymes of Geomyces sp. B10I, which appear to be responsible for its biodegradation activity. We compared their amino acid sequences with sequences of well-studied fungal enzymes. Partial purification of an extracellular mixture of the two enzymes, named hydrGB10I and chitGB10I, using ammonium sulfate precipitation and ionic exchange chromatography gave 14.16-fold purity. The amino acid sequence of the proteins obtained from the MALDI-TOF analysis determined the molecular mass of 77.2 kDa and 46.5 kDa, respectively. Conserved domain homology analysis revealed that both proteins belong to the class of hydrolases; hydrGB10I belongs to the glycosyl hydrolase 81 superfamily, while chitGB10I contains the domain of the glycosyl hydrolase 18 superfamily. Phylogenetic analysis suggests a distinct nature of the hydrGB10I and chitGB10I of Geomyces sp. B10I when compared with other fungal polyester-degrading enzymes described to date.
The prevalence of urinary tract infections in type 2 diabetic patients: a systematic review and meta-analysis
Authors: Salari Nader , Karami Mohammad Mahdi , Bokaee Shadi , Chaleshgar Maryam , Shohaimi Shamarina , Akbari Hakimeh , Mohammadi Masoud
Published: February 2022

Background

Urinary tract infection is the most common infection in type 2 diabetic patients. Various studies have reported different outbreaks of urinary tract infections in type 2 diabetic patients. Therefore, the present study aimed to determine the prevalence of urinary tract infections in type 2 diabetic patients during a systematic review and meta-analysis in order to develop interventions to reduce the incidence of urinary tract infections in type 2 diabetic patients.

Methods

In this study, systematic review and meta-analysis of study data related to the prevalence of urinary tract infection in type 2 diabetic patients were conducted using keywords including type 2 diabetes, urinary tract infection, diabetes, prevalence, meta-analysis and their English equivalents in SID, MagIran, IranMedex, IranDoc, Google Scholar, Cochrane, Embase, Science Direct, Scopus, PubMed and Web of Science (WoS) databases from 1993 to 2020. In order to perform the analysis of qualified studies, the model of random-effects was used, and the inconsistency of studies with the I2 index was investigated. Data analysis was performed with Comprehensive Meta-Analysis (Version 2).

Results

Based on a total of 15 studies with a sample size of 827,948 in meta-analysis, the overall prevalence of urinary tract infection in patients with type 2 diabetes was 11.5% (95% confidence interval: 7.8–16.7%). The prevalence of urinary tract infections in diabetic Iranian patients increased with increasing number of years of research, (p < 0.05), and with increasing age of participants (p < 0.05), but however the prevalence decreased with increasing sample size (p < 0.05).

Conclusion

This study shows that urinary tract infections are highly prevalent in patients with type 2 diabetes. Therefore, due to the growing prevalence of diabetes and its complications such as urinary tract infections, the need for appropriate screening programs and health care policies is becoming more apparent.
Repurposing the drug, ivermectin, in COVID-19: toxicological points of view
Authors: Shirazi Farshad M. , Mirzaei Roya , Nakhaee Samaneh , Nejatian Amir , Ghafari Shokouh , Mehrpour Omid
Published: February 2022

The global COVID-19 pandemic has affected the world’s population by causing changes in behavior, such as social distancing, masking, restricting people’s movement, and evaluating existing medication as potential therapies. Many pre-existing medications such as tocilizumab, ivermectin, colchicine, interferon, and steroids have been evaluated for being repurposed to use for the treatment of COVID-19. None of these agents have been effective except for steroids and, to a lesser degree, tocilizumab. Ivermectin has been one of the suggested repurposed medications which exhibit an in vitro inhibitory activity on SARS-CoV-2 replication. The most recommended dose of ivermectin for the treatment of COVID-19 is 150–200 µg/kg twice daily. As ivermectin adoption for COVID-19 increased, the Food and Drug Administration (FDA) issued a warning on its use during the pandemic. However, the drug remains of interest to clinicians and has shown some promise in observational studies. This narrative reviews the toxicological profile and some potential therapeutic effects of ivermectin. Based on the current dose recommendation, ivermectin appears to be safe with minimum side effects. However, serious questions remain about the effectiveness of this drug in the treatment of patients with COVID-19.
Glucagon signaling via supraphysiologic GCGR can reduce cell viability without stimulating gluconeogenic gene expression in liver cancer cells
Authors: Godfrey Jason , Riscal Romain , Skuli Nicolas , Simon M. Celeste
Published: February 2022

Background

Deregulated glucose metabolism is a critical component of cancer growth and survival, clinically evident via FDG-PET imaging of enhanced glucose uptake in tumor nodules. Tumor cells utilize glucose in a variety of interconnected biochemical pathways to generate energy, anabolic precursors, and other metabolites necessary for growth. Glucagon-stimulated gluconeogenesis opposes glycolysis, potentially representing a pathway-specific strategy for targeting glucose metabolism in tumor cells. Here, we test the hypothesis of whether glucagon signaling can activate gluconeogenesis to reduce tumor proliferation in models of liver cancer.

Methods

The glucagon receptor, GCGR, was overexpressed in liver cancer cell lines consisting of a range of etiologies and genetic backgrounds. Glucagon signaling transduction was measured by cAMP ELISAs, western blots of phosphorylated PKA substrates, and qPCRs of relative mRNA expression of multiple gluconeogenic enzymes. Lastly, cell proliferation and apoptosis assays were performed to quantify the biological effect of glucagon/GCGR stimulation.

Results

Signaling analyses in SNU398 GCGR cells treated with glucagon revealed an increase in cAMP abundance and phosphorylation of downstream PKA substrates, including CREB. qPCR data indicated that none of the three major gluconeogenic genes, G6PC, FBP1, or PCK1, exhibit significantly higher mRNA levels in SNU398 GCGR cells when treated with glucagon; however, this could be partially increased with epigenetic inhibitors. In glucagon-treated SNU398 GCGR cells, flow cytometry analyses of apoptotic markers and growth assays reproducibly measured statistically significant reductions in cell viability. Finally, proliferation experiments employing siCREB inhibition showed no reversal of cell death in SNU398 GCGR cells treated with glucagon, indicating the effects of glucagon in this setting are independent of CREB.

Conclusions

For the first time, we report a potential tumor suppressive role for glucagon/GCGR in liver cancer. Specifically, we identified a novel cell line-specific phenotype, whereby glucagon signaling can induce apoptosis via an undetermined mechanism. Future studies should explore the potential effects of glucagon in diabetic liver cancer patients.
Experiences when implementing enhanced cognitive behavioral therapy as a standard treatment for anorexia nervosa in outpatients at a public specialized eating-disorder treatment unit
Authors: Kessler Ute , Kleppe Malin Mandelid , Rekkedal Guro Årdal , Rø Øyvind , Danielsen Yngvild
Published: February 2022

Background

Enhanced cognitive behavioral therapy (CBT-E) is a promising treatment option for outpatients with anorexia nervosa (AN). We aimed to determine the effectiveness of CBT-E as a standard treatment for adult outpatients with AN from the specialized eating-disorder unit of a public hospital with responsibilities to their catchment area.

Methods

This study had an open, longitudinal design. Thirty three (of planned 100) outpatients aged > 16 years suffering from AN were included to receive 40 sessions of CBT-E. Eating-disorder psychopathology and body mass index (BMI) were assessed before and after treatment, while comorbid psychiatric symptoms and trauma experiences were evaluated at the baseline, and therapeutic alliance was assessed after 4 weeks of treatment.

Results

A high proportion (69%) of patients dropped out of the treatment. Patient recovery was considered when they reached BMI > 18.5 and Eating Disorder Examination Questionnaire (EDE-Q) score < 2.5, and 27% of all patients recovered.

Conclusions

Patients who completed the treatment had mostly satisfactory outcomes. Considering the high dropout rate, it is necessary to improve the strategies for engaging patients in therapy. Several aspects of CBT-E as a standard treatment are discussed regarding the high dropout rate.

Trial registration ClinicalTrials.gov. Identifier: NCT02745067. Registered: April 20, 2016. https://clinicaltrials.gov/ct2/showNCT02745067
High individual repeatability of the migratory behaviour of a long-distance migratory seabird
Authors: Kürten Nathalie , Schmaljohann Heiko , Bichet Coraline , Haest Birgen , Vedder Oscar , González-Solís Jacob , Bouwhuis Sandra
Published: February 2022

Background

Understanding the evolution of migration requires knowledge of the patterns, sources, and consequences of variation in migratory behaviour, a need exacerbated by the fact that many migratory species show rapid population declines and require knowledge-based conservation measures. We therefore need detailed knowledge on the spatial and temporal distribution of individuals across their annual cycle, and quantify how the spatial and temporal components of migratory behaviour vary within and among individuals.

Methods

We tracked 138 migratory journeys undertaken by 64 adult common terns (Sterna hirundo) from a breeding colony in northwest Germany to identify the annual spatiotemporal distribution of these birds and to evaluate the individual repeatability of eleven traits describing their migratory behaviour.

Results

Birds left the breeding colony early September, then moved south along the East Atlantic Flyway. Wintering areas were reached mid-September and located at the west and south coasts of West Africa as well as the coasts of Namibia and South Africa. Birds left their wintering areas late March and reached the breeding colony mid-April. The timing, total duration and total distance of migration, as well as the location of individual wintering areas, were moderately to highly repeatable within individuals (repeatability indexes: 0.36–0.75, 0.65–0.66, 0.93–0.94, and 0.98–1.00, respectively), and repeatability estimates were not strongly affected by population-level inter-annual variation in migratory behaviour.

Conclusions

We found large between-individual variation in common tern annual spatiotemporal distribution and strong individual repeatability of several aspects of their migratory behaviour.
Categorising cheetah behaviour using tri-axial accelerometer data loggers: a comparison of model resolution and data logger performance
Authors: McGowan Natasha E. , Marks Nikki J. , Maule Aaron G. , Schmidt-Küntzel Anne , Marker Laurie L. , Scantlebury David M.
Published: February 2022

Background

Extinction is one of the greatest threats to the living world, endangering organisms globally, advancing conservation to the forefront of species research. To maximise the efficacy of conservation efforts, understanding the ecological, physiological, and behavioural requirements of vulnerable species is vital. Technological advances, particularly in remote sensing, enable researchers to continuously monitor movement and behaviours of multiple individuals simultaneously with minimal human intervention. Cheetahs, Acinonyx jubatus, constitute a “vulnerable” species for which only coarse behaviours have been elucidated. The aims of this study were to use animal-attached accelerometers to (1) determine fine-scale behaviours in cheetahs, (2) compare the performances of different devices in behaviour categorisation, and (3) provide a behavioural categorisation framework.

Methods

Two different accelerometer devices (CEFAS, frequency: 30 Hz, maximum capacity: ~ 2 g; GCDC, frequency: 50 Hz, maximum capacity: ~ 8 g) were mounted onto collars, fitted to five individual captive cheetahs. The cheetahs chased a lure around a track, during which time their behaviours were videoed. Accelerometer data were temporally aligned with corresponding video footage and labelled with one of 17 behaviours. Six separate random forest models were run (three per device type) to determine the categorisation accuracy for behaviours at a fine, medium, and coarse resolution.

Results

Fine- and medium-scale models had an overall categorisation accuracy of 83–86% and 84–88% respectively. Non-locomotory behaviours were best categorised on both loggers with GCDC outperforming CEFAS devices overall. On a coarse scale, both devices performed well when categorising activity (86.9% (CEFAS) vs. 89.3% (GCDC) accuracy) and inactivity (95.5% (CEFAS) vs. 95.0% (GCDC) accuracy). This study defined cheetah behaviour beyond three categories and accurately determined stalking behaviours by remote sensing. We also show that device specification and configuration may affect categorisation accuracy, so we recommend deploying several different loggers simultaneously on the same individual.

Conclusion

The results of this study will be useful in determining wild cheetah behaviour. The methods used here allowed broad-scale (active/inactive) as well as fine-scale (e.g. stalking) behaviours to be categorised remotely. These findings and methodological approaches will be useful in monitoring the behaviour of wild cheetahs and other species of conservation interest.
White matter damage due to vascular, tau, and TDP-43 pathologies and its relevance to cognition
Authors: Raghavan Sheelakumari , Przybelski Scott A. , Reid Robert I. , Lesnick Timothy G. , Ramanan Vijay K. , Botha Hugo , Matchett Billie J. , Murray Melissa E. , Reichard R. Ross , Knopman David S. , Graff-Radford Jonathan , Jones David T. , Lowe Val J. , Mielke Michelle M. , Machulda Mary M. , Petersen Ronald C. , Kantarci Kejal , Whitwell Jennifer L. , Josephs Keith A. , Jack Clifford R. , Vemuri Prashanthi
Published: February 2022

Multi-compartment modelling of white matter microstructure using Neurite Orientation Dispersion and Density Imaging (NODDI) can provide information on white matter health through neurite density index and free water measures. We hypothesized that cerebrovascular disease, Alzheimer’s disease, and TDP-43 proteinopathy would be associated with distinct NODDI readouts of white matter damage which would be informative for identifying the substrate for cognitive impairment. We identified two independent cohorts with multi-shell diffusion MRI, amyloid and tau PET, and cognitive assessments: specifically, a population-based cohort of 347 elderly randomly sampled from the Olmsted county, Minnesota, population and a clinical research-based cohort of 61 amyloid positive Alzheimer’s dementia participants. We observed an increase in free water and decrease in neurite density using NODDI measures in the genu of the corpus callosum associated with vascular risk factors, which we refer to as the vascular white matter component. Tau PET signal reflective of 3R/4R tau deposition was associated with worsening neurite density index in the temporal white matter where we measured parahippocampal cingulum and inferior temporal white matter bundles. Worsening temporal white matter neurite density was associated with (antemortem confirmed) FDG TDP-43 signature. Post-mortem neuropathologic data on a small subset of this sample lend support to our findings. In the community-dwelling cohort where vascular disease was more prevalent, the NODDI vascular white matter component explained variability in global cognition (partial R2of free water and neurite density = 8.3%) and MMSE performance (8.2%) which was comparable to amyloid PET (7.4% for global cognition and 6.6% for memory). In the AD dementia cohort, tau deposition was the greatest contributor to cognitive performance (9.6%), but there was also a non-trivial contribution of the temporal white matter component (8.5%) to cognitive performance. The differences observed between the two cohorts were reflective of their distinct clinical composition. White matter microstructural damage assessed using advanced diffusion models may add significant value for distinguishing the underlying substrate (whether cerebrovascular disease versus neurodegenerative disease caused by tau deposition or TDP-43 pathology) for cognitive impairment in older adults.

Graphical abstract
Defining multiple inhabitations of a cave environment using interdisciplinary archaeometry: the ‘Christmas Cave’ of the Wadi en-Nar/Nahal Qidron, West of the Dead Sea
Authors: Rasmussen Kaare Lund , van der Plicht Johannes , Degano Ilaria , Modugno Francesca , Colombini Maria Perla , de la Fuente Guillermo , Delbey Thomas , Frumkin Amos , Davidovich Uri , Porat Roi , Shamir Orit , Sukenik Naama , Doudna Greg , Taylor Joan , Popović Mladen
Published: February 2022

The present study reports a series of interdisciplinary archaeometrical analyses of objects found in the Christmas Cave, which was discovered by John Allegro and his team in 1960 on the West Bank of the Dead Sea and assumed to be inhabited only in the Chalcolithic era and by Jewish refugees of the second century CE, at the end of the Bar Kokhba Revolt. Like many other Judaean desert caves, there was an abundance of organic material, especially textiles, surviving in the dry environment. In the absence of clear stratigraphy and even a proper publication of the finds, the present study shows how archaeometry can provide important insights. We analysed food crusts on ceramics by gas chromatography with mass spectrometric detection (GC–MS), made petrographic descriptions to estimated provenance of the ceramics, produced new radiocarbon dates from organic material and thermoluminescence (TL) dates from the pottery. It appears from the data that the Christmas Cave has been briefly inhabited or visited intermittently over a very long time, starting ca. 4000 BCE (the Chalcolithic period), and extending all the way to the Medieval period, even though there is also a concentration of dates near the period of the Bar Kokhba Revolt (132–136 CE). We argue, through a detailed analysis of the radiometric and TL-datings and by the artefactual evidence, that there was likely another refuge episode connected with the First Jewish Revolt during which people fled to this cave. However, we see no material connection to Qumran and nearby caves. Overall, our study demonstrates the importance of archaeometric studies in cave environments where stratigraphy is veritably absent.
The use of osmoregulators and antioxidants to mitigate the adverse impacts of salinity stress in diploid and tetraploid potato genotypes (Solanum spp.)
Authors: Zaki Haitham E. M. , Radwan Khlode S. A.
Published: February 2022

Background

Many arid and semi-arid areas endure from extensive salinization of agricultural land. Nevertheless, it must either develop salinity-tolerant varieties or use agronomic treatments to alleviate the symptoms of stress. Although the cultivated potato, Solanum tuberosum L., is relatively salt sensitive, salinity tolerance was demonstrated in several Solanum relatives. Knowledge of genetic variation for salinity tolerance across diverse species is required for breeding of salinity-tolerant cultivars. Higher osmotic pressures associated with salinity impede plant development and cause plant death; yet, the exogenous application of cellularly recognized molecules to withstand such stress might be a key method.

Results

In vitro studies were performed to determine how much genetic variability for salinity tolerance exists in S. tuberosum (tbr), a tetraploid species and S. chacoense (chc), a diploid species in which 13 genotypes were evaluated under 100, 200 or 300 mmol L−1 NaCl and the average tested parameters were compared with the control (no stress). A further experiment was conducted to investigate the effect of exogenous application of osmoregulators and antioxidants, namely, glycine betaine (GB), proline (P) and salicylic acid (SA) at 400, 200 and 100 mg L−1, respectively, which applied solely to counteract the harmful effect of stress on potato plants. The results showed that when plants exposed to salinity, root characteristics, plantlet water content % (PWC), chlorophyll and K+ content, and callus formation all substantially reduced; however, Cl− and Na+ levels, as well as catalase and peroxidase activity, were elevated. In general, chc showed more tolerance compared to tbr with genetic diversity within and among species. Under stress, chc clones, ‘A-6’, ‘C-8’ and ‘D-2’ and tbr cultivars, ‘Diamond’ and ‘Russet Burbank’ were more tolerant and yielded the greatest salinity tolerance index. Under stress but with applied GB, SA and P, the adverse consequences of stress were relieved. GB was found to be a good treatment for enhancing all the examined traits.

Conclusion

The results indicated that there is a significant genetic variation in salt tolerance between (tbr) cultivars and (chc) clones. GB followed by SA and P could completely or partly reverse the adverse impact of salinity stress on potato plants.

Graphical Abstract
Recommendations for long-term outcomes in sepsis and septic shock: a comparison between Japanese and international guidelines
Authors: Kawai Yusuke , Nishida Osamu
Published: February 2022

The International Guidelines for Management of Sepsis and Septic Shock 2021 and the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 share a common issue on long-term outcomes of patients with sepsis and septic shock and their families; however, the focus of the clinical questions and recommendations between the two guidelines varies. Although this may be due to differences in medical resources and healthcare systems between countries and regions, the essence of providing continuous patient- and family-centered care remains unchanged, and both guidelines can be utilized to provide the best practices to improve long-term outcomes.
Metabolic imaging with FDG-PET and time to progression in patients discontinuing immune-checkpoint inhibition for metastatic melanoma
Authors: Ferdinandus Justin , Zaremba Anne , Zimmer Lisa , Umutlu Lale , Seifert Robert , Barbato Francesco , Ugurel Selma , Chorti Eleftheria , Grünwald Viktor , Herrmann Ken , Schadendorf Dirk , Fendler Wolfgang Peter , Livingstone Elisabeth
Published: February 2022

Background

The optimal duration of immune checkpoint blockade (ICB) therapy is not well established. Active residual disease is considered prohibitive for treatment discontinuation and its detection by diagnostic CT imaging is limited. Here, we set out to determine the potential added value of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) to identify patients at higher risk of relapse following discontinuation of ICB in advanced melanoma.

Methods

Metastatic melanoma patients who discontinued ICB were identified retrospectively. Eligible patients received FDG-PET and diagnostic CT within four months of ICB discontinuation. We defined morphologic response using RECIST v1.1. Complete metabolic response (CMR) was defined as uptake in tumor lesions below background, whereas any site of residual, FDG-avid disease was rated as non-CMR. The primary endpoint was time to progression (TTP) after therapy discontinuation stratified by morphologic and metabolic imaging response using Kaplan–Meier estimates and log-rank test.

Results

Thiry-eight patients were eligible for this analysis. Median follow-up was 37.3 months since ICB discontinuation. Median TTP in the overall cohort was not reached. A greater proportion of patients were rated as CMR in PET (n = 34, 89.5%) as compared to complete response (CR) in CT (n = 13, 34.2%). Median TTP was reached in patients with non-CMR (12.7 months, 95%CI 4.4-not reached) but not for patients with CMR (log-rank: p < 0.001). All patients with complete response by CT had CMR by PET. In a subset of patients excluding those with complete response by CT, TTP remained significantly different between CMR and non-CMR (log-rank: p < 0.001).

Conclusion

Additional FDG-PET at time of discontinuation of ICB therapy helps identify melanoma patients with a low risk of recurrence and favourable prognosis compared to CT imaging alone. Results may have clinical relevance especially for patients with residual tumor burden.
The Research Family Advisory Committee: the patient and family view of implementing a research-focused patient engagement strategy
Authors: Buchanan Francine , Peasgood Amy , Easton Megan , Haas Karen , Narayanan Unni
Published: February 2022

Patient engagement in research, a collaborative practice of including patients and families as active and respected partners in the research process, leads to improved quality of patient care and positively affects outcomes for patients and families. There is strong support for the benefits of patient engagement. What is less clear are the methods by which organizations can achieve authentic patient engagement in research and the ways a committee structure can support an institutional research engagement need beyond the individual investigators. In this report, we describe the mechanisms needed to support the implementation of a research-focused patient engagement strategy and lessons learned from the patient and family perspective.
Taking simulation out of its “safe container”—exploring the bidirectional impacts of psychological safety and simulation in an emergency department
Authors: Purdy Eve , Borchert Laura , El-Bitar Anthony , Isaacson Warwick , Bills Lucy , Brazil Victoria
Published: February 2022

Background

Simulation facilitators strive to ensure the psychological safety of participants during simulation events; however, we have limited understanding of how antecedent levels of psychological safety impact the simulation experience or how the simulation experience impacts real-world psychological safety.

Methods

We explored the experience of participants in an embedded, interprofessional simulation program at a large tertiary emergency department (ED) in Australia. We engaged in theoretical thematic analysis of sequential narrative surveys and semi-structured interviews using a previously derived framework of enablers of psychological safety in healthcare. We sought to understand (1) how real-world psychological safety impacts the simulation experience and (2) how the simulation experience influences real-world psychological safety.

Results

We received 74 narrative responses and conducted 19 interviews. Simulation experience was both influenced by and impacted psychological safety experienced at the individual, team, and organizational levels of ED practice. Most strikingly, simulation seemed to be an incubator of team familiarity with direct impact on real-world practice. We present a model of the bidirectional impact of psychological safety and simulation within healthcare environments.

Conclusion

Our model represents both opportunity and risk for facilitators and organizations engaging in simulation. It should inform objectives, design, delivery, debriefing, and faculty development and firmly support the situation of simulation programs within the broader cultural ethos and goals of the departments and organizations.
Endophytic ability of indigenous Bacillus thuringiensis strain VKK-BB2: new horizons for the development of novel insect pest-resistant crops
Authors: Pola Sunitha , Kesharwani Amit Kumar , Singh Jyoti , Singh Dinesh , Kalia Vinay K.
Published: February 2022

Background

Brinjal shoot and fruit borer (BSFB),Leucinodes orbonalisGuenee is the key pest of brinjal that causes a significant yield loss. Farmers spray wide range of insecticides right from vegetative stage till last harvesting stage to protect the crop from the notorious BSFB, which leads to pesticide residue and insecticide resistance problems. To overcome this, now focus has shifted to bio pesticides but their commercial application is limited due to their susceptibility to abiotic factors. To overcome these bottlenecks, a hidden ecological role played by entomopathogenic bacteria as endophytes was sought. The control of pests by establishment of potential entomopathogenic bacteria as an endophyte is an alternative method of pest management that may contribute to reduce or eliminate the use of pesticides.

Results

Present study describes the colonization of green fluorescent protein (GFP)-tagged potential nativeBacillus thuringiensisstrain VKK-BB2 (BtVKK-BB2) in brinjal plants. Seeds and seedlings of brinjal were inoculated withgfp-tagged BtVKK-BB2 cells through seed treatment, soil drenching and foliar spray. After inoculationgfp-tagged bacterium could be re-isolated from all parts of the plant. Presence of bacteria within the leaves was confirmed by amplification ofgfpandcrygene in the re-isolatedBtcolonies from brinjal leaves and shoot. Leaves taken from the BtVKK-BB2 colonized plants were able to cause mortality when fed to neonates ofLeucinodes orbonalis.

Conclusions

Establishment of nativeBtstrain as endophytes in plants, accompanied by the production of Cry proteins opens new horizons for the development of a novel pest-resistant crops which could be an alternative to Bt transgenic crops. However, inoculation of Bt through seed and foliar spray has to be further explored against larval herbivores especially internal borers to enhance its biocontrol potential through endophytic mediation which may open a novel set of strategies to control the insect pests in a sustainable way.

Graphical Abstract
Spectrum of central nervous system infections in a tertiary health care centre in Cameroon
Authors: Gams Massi Daniel , Mintyene Mintyene Marcel Roger Rodrigue , Magnerou Annick Mélanie , Eko Seraphine Mojoko , Kenmegne Caroline , Mbahe Salomon , Sounga Bandzouzi Prince Eliot , Mbatchou Ngahane Hugo Bertrand , Mapoure Njankouo Yacouba
Published: February 2022

Background

Central nervous system (CNS) infections are serious and debilitating diseases with significant mortality, and high prevalence in the context of human immunodeficiency virus (HIV) pandemic in Africa. However, their diagnosis remains challenging due to outdated technical platform. We aimed to determine the frequency of CNS infection and to describe the epidemiological, clinical and outcome of this at the Douala General Hospital (DGH), Cameroon. To carry out this study, we collected the medical records of patients hospitalized for CNS infections in the internal medicine department of DGH from January 2015 to December 2019.

Results

Among 8430 files reviewed, 336 cases of CNS infection were identified giving a frequency of CNS infection of 3.99% among which 204 files were included in the study (54.4% were male). HIV infection was found in 147 patients (72.1%) with 38.1% (n = 56) of them on regular follow-up. The most common clinical signs were fever (84.8%), headache (68.6%), meningeal syndrome (38.7%), and seizures (36.3%). Cerebral toxoplasmosis (24.5%), cryptococcal meningitis (21.1%), and acute bacterial meningitis (8.3%) were leading aetiologies. Of the 143 CSF samples, 70.6% (n = 101) were sterile. The in-hospital mortality rate was 23.5% with CNS infection of unknown cause (22.1%) be independently associated to this [OR = 2.24; 95% CI 1.04–4.80, p = 0.039].

Conclusion

Clinical presentations of CNS infections are same with classical data. HIV-related opportunistic infections are the main aetiologies. About one over four patients with CNS died. Two thirds of CSF are sterile using basic laboratory assessment giving a need to identify simple tests to increase sensibility and specificity of diagnostic tools in our setting.
Distal radial approach between theory and clinical practice.. Time to go distal!
Authors: Sanhoury Mohamed I. , Sobhy Mohamed A. , Saddaka Mohamed A. , Nassar Mohamed A. , Elwany Mostafa N.
Published: February 2022

Background

Transradial access (TRA), which has a minimal risk of problems such as radial artery occlusion (RAO), hemorrhage, spasm, and so on, is now considered the standard procedure for cardiac catheterization. The aim of the study is to present the distal transradial access (d-TRA) as a possible promising novel technique in the field of cardiac coronary interventions comparing it to the standard conventional TRA using primary and secondary endpoints, exploring its benefits and drawbacks as a new experience in Alexandria University. One hundred cases with variable indications for coronary interventions were randomized to two arms using systematic random sampling method, coronary interventions in the first one were done via d-TRA (50 patients) and in the second arm via conventional TRA group (50 patients).

Results

Technically, there were highly statistically significant differences between the two arms in favor of TRA regarding procedural success, number of punctures taken, Access time, Total procedural time, vasodilator used, and crossover to another access site; meanwhile safety profile parameters have showed statistically significant differences in favor of d-TRA regarding post-operative hematoma, AV fistula, post-operative pain and compression time, and there were no statistically significant differences regarding RAO although it occurred more in TRA group.

Conclusions

In the realm of cardiac intervention, the distal radial approach is a promising technique. When compared to TRA, we found it to be a viable and safe method for coronary angiography and interventions and it could be a real option for the interventionists in the near future, with a lower risk of radial artery blockage and no significant differences in wrist hematoma and radial artery spasm. The success rate of d-TRA is proportional to the steepness of the operator's learning curve and the quality of the examples chosen.
Implementation of a diabetes prevention program within two community sites: a qualitative assessment
Authors: Dineen Tineke E. , Bean Corliss , Jung Mary E.
Published: February 2022

Background

Despite numerous translations of diabetes prevention programs, implementation evaluations are rarely conducted. The purpose of this study was to examine the implementation process and multilevel contextual factors as an evidence-based diabetes prevention program was implemented into two local community organization sites to inform future scale-up. To build the science of implementation, context and strategies must be identified and explored to understand their impact.

Methods

The program was a brief-counseling diet and exercise modification program for individuals at risk of developing type 2 diabetes. A 1-year collaborative planning process with a local not-for-profit community organization co-developed an implementation plan to translate the program. A pragmatic epistemology guided this research. Semi-structured interviews were conducted with staff who delivered the program (n = 8), and a focus group was completed with implementation support staff (n = 5) at both community sites. Interviews were transcribed verbatim and thematically analyzed using a template approach. The consolidated framework for implementation research (CFIR) is a well-researched multilevel implementation determinant framework and was used to guide the analysis of this study. Within the template approach, salient themes were first inductively identified, then identified themes were deductively linked to CFIR constructs.

Results

Implementation strategies used were appropriate, well-received, and promoted effective implementation. The implementation plan had an impact on multiple levels as several CFIR constructs were identified from all five domains of the framework: (a) process, (b) intervention characteristics, (c) outer setting, (d) inner setting, and (e) individual characteristics. Specifically, results revealed the collaborative 1-year planning process, program components and structure, level of support, and synergy between program and context were important factors in the implementation.

Conclusion

This study offers insights into the process of implementing a community-based diabetes prevention program in two local sites. Successful implementation benefited from a fully engaged, partnered approach to planning, and subsequently executing, an implementation effort. The CFIR was a useful and thorough framework to evaluate and identify multilevel contextual factors impacting implementation. Results can be used to inform future implementation and scale-up efforts.
Quality assessment and Analytical Quality by Design-based RP-HPLC method development for quantification of Piperine in Piper nigrum L.
Authors: Parab Gaonkar Vishakha , Mannur Vinodh Kumar , Hullatti Kirankumar
Published: February 2022

Background

Piper nigrum L. is one of the widely used herbs in Ayurvedic medicine. Piperine is a major phytoconstituent that is responsible for most of the activity of the herb. Quality assessment and standardization of such phytoconstituents is the need of the hour. The present study aims at developing a Quality by design (QbD)-based RP-HPLC Method for marker-based standardization of Piper nigrum L. fruits along with its quality assessment.

Results

The quality assessment of the crude sample was carried out by evaluating pharmacognostic parameters and analysis of toxic contaminants. The analytical target profile and critical quality attributes were determined and 22 factorial design was employed for optimization of the method. By performing the experiments as per the QbD concept the optimized mobile phase was identified as Acetonitrile and Water with 0.05% Acetic acid in the ratio of 70:30, with a flow rate of 1 mL/min and UV detection at 342 nm. The retention time of Piperine was found to be 5.5 min and the amount of Piperine in crude P. nigrum fruits and its extract was found to be 3.6% w/w 5.62% w/w, respectively. The Pharmacognostic parameters showed the results within specified limits and the crude drug sample showed the absence of toxic contaminants in it thus indicating the purity of the drug.

Conclusion

The utilization of the QbD approach leads to the development of a more precise and reliable method for the quantification of phytocompounds.
Fasting salivary pepsin level as a reliable non-invasive method of screening for laryngopharyngeal reflux in Egyptian patients
Authors: Sabry Manal , Yosef Tarek Mohamed , Mahmoud Ahmed Mohammed , George Michael Tari M. A.
Published: February 2022

Background

Laryngopharyngeal reflux (LPR) is caused by the regurgitation of gastric contents above the upper esophageal sphincter. Diagnostic gold standard tests like multichannel intraluminal impedance (MII) and 24-h dual-probe pH-metry are invasive and expensive which limits their accessibility especially in resource-limited settings. Since pepsin is only produced in the stomach, detecting pepsin in the laryngopharynx would make it a specific marker for reflux.

Therefore, in this study, we measured fasting salivary pepsin in patients with symptoms suggestive of LPR. We aimed to confirm the role of fasting salivary pepsin as a non-invasive diagnostic tool of LPR, to detect a cut-off value for it in Egyptian patients and to study predictors of changes in its level.

Methods

We conducted a prospective case control study at the gastroenterology clinic in Ain Shams University Hospitals. After testing with esophageal pH-metry, 25 symptomatic patients with confirmed LPR and 25 healthy controls were enrolled in the study. Patients diagnosed with organic upper gastrointestinal disorders, autoimmune diseases, diabetes, malignancy or organ failure were excluded. Patients on PPI were advised to stop 2 weeks before testing. All patients were tested for fasting salivary pepsin levels, esophageal pH-metry, and indirect laryngoscopy in addition to routine laboratory parameters.

Results

Out of the 25 LPR patients, 16% of patients had laryngoscope abnormality in the form of mucosal hyperemia and inflammation, and the average percentage of time pH < 4 in esophageal pH-metry testing was 29.14 ± 39.5%.

Comparative study between the 2 groups revealed a significant increase in salivary pepsin in LPR group compared to control group (p < 0.001). By using ROC-curve analysis, salivary pepsin at a cut-off point > 5 ng/ml diagnosed patients with LPR, with fair (77.9%) accuracy, sensitivity = 100% and specificity = 56% (p = 0.0001) while pH-metry (% Time pH < 4) at a cut-off point > 14% diagnosed patients with LPR, with good (87%) accuracy, sensitivity = 80%, and specificity = 100% (p < 0.0001)

Conclusion

Fasting salivary pepsin level at a cut-off value of > 5 ng/ml is a reliable, non-invasive method for detection of LPR especially in resource-limited settings.