bluuebunny/crossref_metadata_2025 huggingface dataset:
The Hepatitis C Virus NS3 Proteinase: Structure and Function of a Zinc-Containing Serine Proteinase
Authors: De Francesco Raffaele , Pessi Antonello , Steinkühler Christian
Published: April 2022

The hepatitis C virus (HCV) NS3 protein contains a serine proteinase domain implicated in the maturation of the viral polyprotein. NS3 forms a stable heterodimer with NS4A, a viral memebrane protein that acts as an activator of the IMS3 proteinase. The three-dimensional structure of the NS3 proteinase complexed with an NS4A-derived peptide has been determined. The NS3 proteinase adopts a chymotrypsin-like fold. A β-strand contributed by NS4A is clamped between two β-strands within the N terminus of NS3. Consistent with the requirement for extraordinarily long peptide substrates (P6-P4’), the structure of the NS3 proteinase reveals a very long, solvent-exposed substrate-binding site. The primary specificity pocket of the enzyme is shallow and closed at its bottm by Phe-154, explaining the preference of the NS3 proteinase for cysteine residues in the substrate P, position. Another important feature of the NS3 proteinase is the presence of a tetrahedral zinc-binding site formed by residues Cys-97, Cys-99, Cys-145 and His-149. The zinc-binding site has a role in maintaining the structural stability and guiding the folding of the NS3 serine proteinase domain. Inhibition of the NS3 proteinase activity is regarded as a promising strategy to control the disease caused by HCV. Remarkably, the NS3 proteinase is susceptible to inhibition by the N-terminal cleavage products of substrate peptides corresponding to the NS4A/NS4B, NS4B/NS5A and NS5A/NS5B cleavage sites. The Ki values of the inhibitory products are lower than the Km values of the respective substrates and follow the order NS4A<NS5A<NS4B. Starting from the observation that the NS3 proteinase undergoes product inhibition, very potent, active site-directed inhibitors have been generated using a combinatorial peptide chemistry approach.
Interferon-α Therapy Exerts Selective Pressure on Hepatitis C Virus Quasispecies Equilibrium
Authors: Mizokami Masashi , Ohno Tomoyoshi , Ohba Ken-ichi , Davis Gary L , Suzuki Kaoru , Orito Etsuro , Lau Johnson YN
Published: April 2022

Two patients with chronic hepatitis C virus (HCV) genotype 2b infection were studied. They responded biochemically to interferon (IFN) but had early virological and later biochemical relapse. The HCV quasispecies equilibrium in these patients was studied by a combination of cloning, sequencing and construction of phylogenetic trees. Another patient with chronic HCV genotype 2b infection was followed every 6 months for 30 months (including one episode of biochemical exacerbation) to serve as the control. Quasispecies equilibrium drifted during IFN therapy but moved back in the direction of the original equilibrium during biochemical relapse. In the control patient, there was no significant drifting throughout the follow-up period. These data suggest that IFN therapy exerts selective pressure on HCV quasispecies equilibrium.
In vitro Selection and Characterization of HIV-1 with Reduced Susceptibility to PMPA
Authors: Wainberg Mark A , Miller Michael D , Quan Yudong , Salomon Horacio , Mulato Andrew S , Lamy Patrick D , Margot Nicolas A , Anton Kristin E , Cherrington Julie M
Published: April 2022

9-(2-phosphonomethoxypropyl)adenine (PMPA) has demonstrated remarkable anti-simian immunodeficiency virus (SIV) activity in macaque models of SIV infection and transmission prevention. Recently, PMPA and its oral prodrug, bis-POC PMPA, have also shown potent anti-human immunodeficiency virus type 1 (HIV-1) activity in Phase I clinical studies. In vitro experiments were performed to address the resistance properties of PMPA. After eight passages in increasing concentrations of PMPA, HIV-1IIIB was able to grow in the presence of 2 μM PMPA, fivefold above the IC50 of PMPA for wild-type parental virus. Sequence analysis of the reverse transcriptase (RT) genes from four of 15 RT clones demonstrated the presence of a K65R substitution in RT and recombinant HIV expressing the K65R RT mutation showed a threefold to fourfold increase in IC50 value for PMPA as compared to wild-type. Additional experiments demonstrated that viruses expressing other nucleoside-associated RT resistance mutations all showed wild-type or <threefold reduced susceptibility to PMPA in vitro. Interestingly, lamivudine-resistant viruses expressing the M184V RT mutation showed wild-type to slightly increased susceptibility to PMPA in vitro and addition of the M184V mutation to HIV with the K65R mutation resulted in reversion to wild-type susceptibility for PMPA. In agreement with the cell culture findings, Escherichia coli-expressed K65R RT showed fivefold reduced susceptibility to PMPA diphosphate, the active moiety of PMPA. Furthermore, in combination experiments, PMPA with hydroxyurea showed synergistic inhibition of HIV replication in vitro. The potent anti-retroviral activity and favourable resistance profile of PMPA and bis-POC PMPA are being further investigated in ongoing clinical trials.
A Combination of Nucleoside Analogues and a Protease Inhibitor Reduces HIV-1 RNA Levels in Semen: Implications for Sexual Transmission of HIV Infection
Authors: Liuzzi Giuseppina , Chirianni Antonio , Bagnarelli Patrizia , Clementi Massimo , Piazza Marcello
Published: April 2022

Direct contact with semen is the major route of sexual acquisition of human immunodeficiency virus (HIV) in homosexual and heterosexual partners of seropositive men. In this study, we show that concentrations of HIV-1 RNA molecules in plasma and semen of seropositive patients are related to the duration and type of anti-retroviral agents used in treatment. In patients treated with zidovudine alone, 1, 3 and 6 months after the start of therapy, the mean HIV-1 load in plasma was reduced by 0.57, 0.38 and 0.21 log10 and in semen by 0.66, 0.50 and 0.15 log10, respectively. In patients treated with zidovudine plus didanosine at months 1, 3 and 6, the mean decrease in plasma HIV-1 RNA was 1.40, 1.25 and 1.12 log10 and in semen 1.10, 1.41 and 1.32 log10, respectively. In patients treated with a combination of a protease inhibitor and two nucleoside analogues the mean log10 decrease was 1.77, 1.83, 1.71 and 2.38 log10 in plasma and 1.17, 1.74, 2.19 and 3.02 log10 in semen at 1, 2, 3 and 4 months, respectively. Treatment with a combination of a protease inhibitor and two nucleoside analogues caused a dramatic decrease in cell-free HIV-1 RNA in semen, which is a reliable measure of viral load. These findings could have implications for the sexual transmission of HIV-1.
Kinetics of β-Chemokine Levels during Anti-HIV Therapy
Authors: Aleman Soo , Pehrson PehrOlov , Sönnerborg Anders
Published: April 2022

Chemokines are pro-inflammatory cytokines that inhibit human immunodeficiency virus type 1 (HIV-1) replication in vitro. We studied the kinetics of the β-chemokines, macrophage inhibitory protein (MIP)-1α, MIP-1β, RANTES, and monocyte chemotactic protein (MCP)-1 in plasma during 12 months of antiretroviral therapy in 26 HIV-1-infected patients and in 11 untreated subjects. Eleven patients with moderate immunodeficiency had HIV-1 RNA levels <50 copies/ml after 1 year, whereas 12 out of 15 patients with severe immunodeficiency had detectable virus. At baseline, MCP-1 levels correlated positively with HIV-1 RNA and DNA levels and inversely with CD4 cell counts. A reverse pattern was seen for the MIP-1β levels. No correlation was seen between MIP-1α or RANTES and any of the parameters. Also, there was a dichotomy between the different β-chemokines in response to therapy. Decreases of MCP-1 and RANTES levels were found, but no durable changes of MIP-1α and MIP-1β. The MCP-1 levels rebounded back to baseline after 1 year in the patients who responded virologically, which could possibly reflect an increased immune activation. The biological consequences of the changes in β-chemokines levels during antiretroviral treatment are still unknown and deserve further studies.
Patients Failing Saquinavir Therapy Require an Early Change to Indinavir before HIV-1 Viral Load Reaches High Levels
Authors: Dronda Fernando , Pérez-Elías María J , Antela Antonio , Casado José L , Martí-Belda Paloma , Cobo Javier
Published: April 2022

Sequential use of antiretroviral therapy with protease inhibitors (PI) is frequently prescribed owing to failure or intolerance of the first selected agent. Controversial data exist about the virological and immunological outcome of patients in whom a change to a second PI regimen is needed. A prospective study of 113 HIV-positive patients (male, 84%; mean age 36 years; previous AIDS-defining event, 35%; previous antiretroviral therapy with nucleoside analogues, 94%) who started a saquinavir-containing regimen between March 1996 and March 1997 and had to change to indinavir ( n=79) owing to intolerance, failure or medical criteria was performed. At the time of the switch, median CD4 cell count was 221 cells/mm3 and the HIV RNA level was 3.98 log10 copies/ml. The rate of viral suppression (HIV RNA levels below 200 copies/ml) was 40% at 3 months and 28% at month 6 after indinavir was instituted. In a logistic regression analysis, only the baseline viral load [relative risk (RR), 2.85; 95% confidence interval (CI), 1.31–6.05; P=0.007] was statistically associated with the lack of viral suppresion on indinavir. Although there are not sufficient data about the best therapeutic option if a change in PI-containing regimens therapy is considered, this study supports the recommendation of an early change of the PI-containing regimens, before the HIV-1 viral load reaches high levels.
Efficiency of Drug Resistance Genotypic Tests in Specimens with Low HIV Viral Load
Authors: Gómez-Cano M , Rubio A , Ruiz L , Pérez-Olmeda M , Leal M , Clotet B , Soriano V
Published: April 2022

The early recognition of resistance to antiretroviral agents could allow a rapid switch in therapy and therefore avoid the accumulation of mutations and reduce the risk of cross-resistance. However, the efficiency of genotypic tests in specimens with low viral load (VL) is severely compromised since human immunodeficiency virus (HIV) RNA in these samples often goes unrecognized. The frequency of results provided by a line probe assay (LiPA, Murex), a commercially available drug resistance test and a home-made point mutation assay (PMA) for recognizing the codon 151 multidrug-resistance mutation was examined in 664 plasma samples stratified with respect to VL values. Overall, 421 (63%) samples could be interpreted by both LiPA and PMA. The sensitivity decreased as plasma VL lowered: 89% for samples with VL >10000 HIV RNA copies/ml, 77% for those with VL between 500 and 10000 HIV RNA copies/ml and 37% for specimens with VL <500 HIV RNA copies/ml. A good agreement existed comparing the sensitivity of the home-made PMA and LiPA. Although the former tends to produce more results, the difference did not achieve statistical significance. Our results support that new, more sensitive, HIV RNA extraction methods need to be implemented for the rapid recognition of drug-resistant mutants in patients experiencing an early rebound in plasma viraemia.
Lipid Evaluation in HIV-1-Positive Patients Treated with Protease Inhibitors
Authors: Schmidt Hartmut H-J , Behrens Georg , Genschel Janine , Stoll Matthias , Dejam André , Haas Regina , Manns Michael P , Schmidt Reinhold E
Published: April 2022

There is accumulating evidence that human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) can induce hyperlipidaemia. To evaluate the frequency and type of hyperlipidaemia in PI-treated patients, 98 outpatients were prospectively analysed for their lipoprotein characteristics at the Medizinische Hochschule in Hannover, Germany. Fifty-seven percent of the patients studied presented with hyperlipidaemia. Both hypertrigylceridaemia (type IV and V hyperlipoproteinaemia, 33%) and hypercholesterolaemia (type IIa hyperlipoproteinaemia, 6%) were detectable. The remaining 18% had a type IIb hyperlipoproteinaemia. Increased lipid levels were highly statistically significant compared to a control group of PI-naive HIV-1-infected patients [low-density lipoprotein (LDL) 146 mg/dl (range, 53–274 mg/dl) versus 105 mg/dl (range, 22–188 mg/dl; P=0.0006); very-low-density lipoprotein (VLDL) 35.5 mg/dl (5–253 mg/dl) versus 18 mg/dl (range, 3–94 mg/dl; P=0.0002)]. All PIs used (saquinavir, indinavir, nelfinavir and ritonavir) were associated with this variable form of hyperlipidaemia according to the Fredrickson classification. There was no significant correlation of any determined lipid value with the duration of treatment. A higher frequency of the apolipoprotein E2 allele and E4 allele was observed in the hyperlipidaemic subjects. Patients with excessive hypertriglyceridaemia showed a reduced lipoprotein lipase activity. Lipodystrophy was observed especially in hyperlipidaemic patients and to a lesser extent in normolipidaemic subjects. The frequency of hyperlipidaemic risk factors was surprisingly high in the group studied, which in turn may explain the proposed increased risk of atherogenesis in HIV-1 PI-treated patients. Therefore, PI-treated subjects should also be evaluated for their lipoprotein pattern, which may require antihyperlipidaemic interventions.
Comparison of Once and Twice Daily Dosing of Didanosine in Combination with Stavudine for the Treatment of HIV-1 Infection
Authors: Monno Laura , Cargnel Antonietta , Soranzo Maria Luisa , Chirianni Antonio , Ferraro Teresa , Di Stefano Mariantonietta , Angarano Gioacchino ,   the AI 454-146 Team
Published: April 2022

Objective

To compare the antiviral activity, safety and tolerability of didanosine dosed once and twice daily when administered in combination with stavudine dosed twice daily in human immunodeficiency virus type 1 (HIV-1)-infected individuals with little or no previous exposure to antiretroviral drugs.

Design

Comparative, multicentre, randomized, open-label, short-term study.

Patients and Methods

Eighty-four HIV-1-infected adults with qualifying baseline CD4 cell counts of 200 to 500 cells/mm3 were included in the study. Of these, 43 patients received once daily didanosine plus twice daily stavudine (group A) and 41 subjects received twice daily didanosine plus twice daily stavudine (group B). The primary efficacy analysis used was the time-averaged difference (TAD) between treatment regimens of variations in plasma HIV-1 RNA levels from baseline over the first 12 weeks of therapy. Plasma HIV-1 RNA levels, CD4 cell counts and adverse events were monitored. Results: At week 12, median HIV-1 RNA variations were –1.18 log10 copies/ml in group A and –0.88 log10 copies/ml in group B. For patients who were followed up to week 24, median variations of HIV-1 RNA levels from baseline were –1.21 log10 copies/ml in group A and –0.78 log10 copies/ml in group B. The TAD between the two treatment groups for variations from baseline plasma HIV-1 RNA levels over the first 12 weeks was 0.10 log10 copies/ml (95% confidence interval, –0.19 to 0.40), indicating equivalence.

Conclusion

Once daily didanosine plus twice daily stavudine and twice daily didanosine plus twice daily stavudine are equally effective in reducing plasma HIV-1 RNA levels and increasing CD4 cell counts. Both regimens are safe and well tolerated.
Pharmacology of Antiretroviral Drugs
Authors: Hoetdmans Richard MW
Published: April 2022

In this paper, an overview of the pharmacokinetics of currently available antiretroviral drugs is provided. Included in this article are the agents zidovudine, stavudine, zalcitabine, lamivudine, didanosine, abacavir, nevirapine, delavirdine, efavirenz, saquinavir, indinavir, ritonavir and nelfinavir. Key pharmacokinetic parameters, drug penetration in body compartments and drug interactions are discussed for each agent.
Primary HIV Infection
Authors: Perrin Luc
Published: April 2022

Acute human immunodeficiency virus (HIV) infection, referred to as primary HIV infection (PHI), is associated in the majority of patients with an acute retroviral syndrome presenting similarities with infectious mononucleosis and an exponential rise in viral titres. Symptoms rapidly amend and viraemia levels decline spontaneously to reach a set point at 6 months. The intensity of the acute retroviral syndrome and viraemia levels at set point are predictive of HIV disease progression. There are a number of arguments favouring initiation of treatment at the time of PHI (homogeneity of viral populations, preservation of the immune system, prevention of virus spreading) but these arguments should be weighted against parameters more difficult to evaluate such as long-term drug-associated toxicities and adherence. In clinical practice, adherence is closely linked to the patient's commitment, which is the key parameter for treatment decision.
When they want to take away what is “ours”: Collective ownership threat and negative reactions towards refugees
Authors: Bagci Sabahat Cigdem , Verkuyten Maykel , Canpolat Esra
Published: April 2022

People can display negative reactions towards those who challenge their sense of psychological ownership. We tested whether natives would show negativity towards refugees upon perceiving collective ownership threat (COT)—the fear of losing control over a territory that is perceived to be “ours”—in the context of mass immigration (Syrian refugees in Turkey; total N = 1,598). Correlational Studies 1 and 2 demonstrated COT to be associated with intolerance and negative reactions towards refugees through negative intergroup emotions (anger specifically). Preregistered experimental studies demonstrated that while there was no causal effect of COT in neighborhoods with relatively high refugee concentration (Study 3a), COT decreased outgroup tolerance and increased defensive reactions towards Syrian refugees via outgroup anger among a more general community sample (Study 3b). The wider intergroup implications of the fear of losing one’s sense of territorial ownership are discussed.
Perceived Muslim population growth triggers divergent perceptions and reactions from Republicans and Democrats
Authors: Bai Hui
Published: April 2022

The Muslim population is rapidly growing worldwide. Five experiments show that Republicans and Democrats respond to this demographic change with divergent reactions in three domains: perception of threats, celebratory reactions, and emotional responses. In terms of threat perceptions, Republicans tend to perceive Muslim population growth as a threat to Christians and the U.S. society in terms of American culture, legal norms, and peace. Furthermore, Republicans are less likely to have celebratory reactions to Muslim population growth (a theoretically novel reaction). They experience less hope and pride, along with more anxiety and anger. The divergent responses from partisans are partially explained by their ideological orientation and media exposure, but they are not explained by any racial mechanisms or the partisans’ religious identity. Together, these studies reveal that political leaning can be an antecedent to reactions to the demographic change in many complex ways beyond the dominant group’s concern for their status.
Social background concealment among first-generation students: The role of social belonging and academic achievement concerns
Authors: Veldman Jenny , Meeussen Loes , van Laar Colette
Published: April 2022

Although higher education has become more accessible to people from lower socioeconomic backgrounds, the transition to university is more difficult for first- compared to continuing-generation students. Previous research showed that social identity processes are key to understand differences between first- and continuing-generation students’ experiences at university. In the present paper, we argue that social background identity concealment may occur as a coping process among first-generation students. A longitudinal study among 829 first-year university students showed that first-generation students indeed concealed their social background at university more than continuing-generation students. This was especially the case when they had experienced concerns about their social belonging at university, indicating that identity concealment resulted from concerns to fit in at university. Finally, social background concealment was related to a decrease in well-being, suggesting that concealment is a costly social identity management strategy. Instead, universities should put in efforts to increase first-generation students’ sense of belonging.
The analysis on the seismic behavior of L-shaped prefabricated special-shaped CFST with rectangular multi-cell columns
Authors: Wang Lai , Cui Wenbin , Liu Su , Chen Huirong , Chen Haitao
Published: April 2022

In this paper, a prefabricated special-shaped concrete-filled steel tube (CFST) with rectangular multi-cell column has been subjected to low cyclic reversed loading experiment and finite element (FE) parameter analysis. A total of three full-scale L-shaped specimens were tested under constant axial compression load and transverse cyclic load. The main variable in the experiment was the direction of loading. The results show that the failure mode of the special-shaped column specimen is compression-bending failure. Within 300 mm of the bottom of the column, the steel tube bulges or even cracks, the concrete powder fells and fails to exit the work. Among them, the L-135° specimen has the highest peak bearing capacity while the L-0° specimen has better ductility. The main variables of FE parametric analysis are axial compression ratio, concrete grade, steel tube thickness and loading angle. The analysis results show that the lower axial compression ratio and higher concrete grade are conducive to the improvement of bearing capacity. As the thickness of the steel tube increases, the peak bearing capacity and displacement of the specimen increases but the ductility decreases. The special-shaped column model has better seismic behavior when loaded along various loading angles. The peak bearing capacity of the special-shaped column specimen loaded at 135° is consistent with the test results and compared with the L-45° specimen, its bearing capacity is increased by up to 62.04%, which has better comprehensive seismic behavior.
Advances in intelligent long-term vibration-based structural health-monitoring systems for bridges
Authors: Desjardins Serge , Lau David
Published: April 2022

The true realization of the benefits of vibration based structural health monitoring (VBSHM) in real-world applications is acquired through long-term continuous monitoring so that one can attain a detailed grasp of the behavior of the monitored structure. The challenges in long-term continuous VBSHM include: the large volume of accumulated monitoring data; the effective extraction of engineering information amid the influences of noise and uncertainties embedded in the monitoring data; maintaining continuity and consistency in the long-term monitoring data considering that the system and instrumentation may change due to sensor failure or renewal due to advances in sensing technologies. To meet these challenges, this paper presents recent research that has resulted in the development of a framework and specialized signal processing and data analytic tools for long-term continuous VBSHM suitable for real-world monitoring applications of structures in the field. These include efficient tools for large scale intelligent data processing and analysis, management of monitoring database and extracted information relevant to the structural health of the monitored structure. The novel Automated In-Line Full Space Identification (AI-FSI) method is presented to address the needs and challenges associated with long-term continuous VBSHM, such as the automation of all data processing and analysis operations including modal parameter estimations and mode tracking, and the need of minimizing the measurement and computational uncertainties and variability in the operational modal analysis results. A smart self-diagnostic system for the monitoring of the health of the data collection sensors and monitoring system has also been developed that will allow the consistent use of the monitoring data of different sensor configurations and era in the monitoring project. Examples on the efficiency of analyzing the monitoring data collected over 20 years from the Confederation Bridge monitoring project in Atlantic Canada by using the developed novel framework and data analytic tools are presented.
Characteristics of indoor human-induced particle resuspension under different ventilation conditions
Authors: Sun Zenan , Zheng Shuihua , Fu Yueyao , Chai Min
Published: April 2022

This study performed a series of experiments to study the characteristics of human-induced particle resuspension under different ventilation conditions. Four modes of supplied airspeed were evaluated: no wind, low wind (2.742 m/s), medium wind (3.849 m/s) and high wind (4.422 m/s). Results show that the steady-state particle concentration can be approximated as a linear function of the airspeed. Human walking and ventilation conditions can have a significant and coupling role in particle behaviours. In particular, human walking provides initial energy for resuspension by disturbing the local fields, and thus increases the resuspension, especially for large particles of 5–10 μm in size. The wind has two competitive effects, that is, supplying energy to keep particles suspended and pushing the particles downward, and the latter becomes dominant when the airspeed was too high. Consequently, intermediate airspeeds can intensify the effect of human walking, and introduce higher peaks of particle concentration in the human-walking stages. As for the particle number density, similar conclusions can be drawn that the effect of ventilation conditions is more pronounced on small particles less than 1 μm while that of human walking is on large particles. This work lays a foundation for revealing the particle resuspension mechanism.
Conditional citizenship in the UK: Polish migrants’ experiences of diversity
Authors: Mogilnicka Magda
Published: April 2022

This paper explores Polish experiences of lived diversities in the UK through the lens of their precarious socio-economic status and ambivalent racial identity. Using the concept of conditional citizenship, the article explores how being only tentatively accepted in British society affects Polish migrants’ understandings of British diversity. Drawing on qualitative data from a study of Polish migrants’ lived diversities, this paper exposes the repertoires of actions that individuals apply in different social contexts in the process of learning to live with diversity. It advances the academic debate on everyday multiculturalism through an exploration of the relationship between conditional citizenship and lived diversities and contributes to an understanding of migrants’ racism by contextualising it within national hierarchies of belonging.
Personal and complex: The needs and experiences related to technology use for people living with dementia
Authors: Liddle Jacki , Worthy Peter , Frost Dennis , Taylor Eileen , Taylor Dubhglas , Beleno Ron , Angus Daniel , Wiles Janet , Angwin Anthony ,   The Florence Project Living Experience Expert Reference Group
Published: April 2022

Background

With increasing focus on living well with dementia, technology has been identified as having potential benefits for safety, independence and wellbeing. Despite a large growth in specialised technology development, there has been limited uptake. There is a need to understand the current use and needs related to technology for people living with dementia and their care partners (informal carers).

Methods

As part of a participatory design study, a qualitative inquiry into technology experiences and needs was undertaken within an interpretive description approach. A cross-disciplinary team including living experience experts (people living with dementia, unpaid care partners) was involved. Semi-structured interviews, including sharing technology locations and supports, were conducted, audio-recorded and transcribed. Key aspects of the technology use experience were constructed.

Findings

Thirteen people living with dementia and 21 care partners participated in the study. Two core aspects of technology use were identified: Lots of moving parts: the complex context, and A technology cycle: the use and non-use. The findings indicated that the context involved an individual configuration of multiple factors including the user, their technology identity, their supporters, the technology and the environment. The experience is underpinned by shifting foundations created by constantly changing technologies and user characteristics. The cycle of use and non-use identified the processes required to maintain technology engagement.

Conclusion

The use of technology for people living with dementia is complex and personal. Future technology development, policies and practices need to consider this complexity and the effort required to keep using technology to realise the benefits.
Racial bias toward children in the early childhood education setting
Authors: Blackson Emma A , Gerdes Marsha , Segan Ellie , Anokam Crystal , Johnson Tiffani J
Published: April 2022

Racial disparities in the education setting are well-documented, including suspensions and expulsion for Black children beginning in pre-school. Racial bias has been hypothesized as a factor contributing to these disparities. However, little is known about the racial attitudes that childcare educators and staff have toward children. To describe levels of implicit and explicit racial bias toward children among early childhood educators, we measured implicit pro-White/anti-Black racial bias of teachers and staff from three urban childcare centers using the Child Race Implicit Association Test (IAT). Explicit bias was measured using a racial preference scale. Of the 48 participants in this sample, 56% were White, 29% Black, and 10% Hispanic. Although 21% ( n = 10) of participants had no racial bias on the Child Race IAT, most had implicit pro-White bias ranging from weak to strong ( n = 29%and 60%). The remaining participants had implicit pro-Black bias ranging from weak to strong ( n = 9%and 19%). In contrast, 95% of participants reported no having no explicit racial preferences toward White or Black children. Additionally, we asked participants about perceptions, knowledge, and beliefs about sources of early childhood disparities. Knowledge of bias can be used in developing strategies to mitigate bias and reduce disparities in childcare settings.
Percutaneous mechanical thrombectomy in the management of early acute superior mesenteric artery embolism
Authors: Yu Zuanbiao , Wang Shuyuan , Lang Dehai , Yin Xiaoliang , Lin Zuodong , Hu Songjie , Wang Di , Xu Qiyang , Hu Jiangnan
Published: April 2022

Purpose

This study was performed to summarize our experience in the management of early-stage acute superior mesenteric artery embolism (ASMAE) by percutaneous mechanical thrombectomy (PMT).

Methods

The clinical data of 12 patients with early-stage ASMAE treated by PMT in our institution from November 2019 to September 2021 were retrospectively analyzed. The patients had no obvious evidence of bowel infarction as shown by peritoneal puncture and computed tomography angiography. Thrombectomy of the superior mesenteric artery was performed using a 6F AngioJet catheter.

Results

The emboli were completely removed in 10 (83.3%) patients. Six patients were treated only by the AngioJet device. The other six patients underwent combined treatment with a 6F multipurpose drainage catheter after PMT, including one patient who underwent simultaneous stent implantation. Two patients showed no significant improvement in their symptoms after the operation; one was found to have intestinal necrosis and underwent resection by exploratory laparotomy, and the other died of septic shock 3 days after PMT (further intervention had been discontinued because of complications with multiple underlying diseases). No other PMT-related complications occurred. Only one patient was found to have a pseudoaneurysm of the superior mesenteric artery 1 week after PMT and underwent resection by exploratory laparotomy. The 11 surviving patients were smoothly discharged from the hospital after their symptoms were relieved. At a mean follow-up of 13.2 months, computed tomography angiography showed smooth patency of the superior mesenteric artery. No patients developed serious symptoms during follow-up.

Conclusions

PMT by the AngioJet device is a minimally invasive, safe, and effective technique to remove ASMAE. Early application of PMT can avoid acute intestinal necrosis. Combining the AngioJet device with a 6F multipurpose drainage catheter might be more helpful to remove residual emboli.
Virtual reality and augmented reality as strategies for teaching social skills to individuals with intellectual disability: A systematic review
Authors: Montoya-Rodríguez María M. , de Souza Franco Vanessa , Tomás Llerena Clementina , Molina Cobos Francisco J. , Pizzarossa Sofía , García Ana C. , Martínez-Valderrey Vanesa
Published: April 2022

Virtual reality (VR) and augmented reality (AR) programs have proliferated significantly in recent years and they are finding their way into different educational and therapeutic purposes. This systematic review aims at analyzing the virtual reality and augmented reality programs designed to promote the development of social skills in individuals with intellectual disability. Searches were carried out in the Scopus, Science Direct, Springer and Web of Science databases in the period from 2005 to 2020. A total of six articles met the inclusion criteria. A descriptive data analysis was performed. The results show that the clinical profile of the individuals who participated in the interventions is diverse. It can be concluded that there is some scientific evidence that points to the usefulness of VR and AR in the development of intervention programs to improve the social skills of individuals diagnosed with developmental deficits. However, it is necessary to acknowledge methodological limitations such as the lack of control groups, follow-up measures and of generalization of the results.
Pre-Operative Medications as a Predictor for Post-Operative Complications Following Geriatric Hip Fracture Surgery
Authors: McDonald Christopher L. , Cohen Brian H. , Medina Pérez Giancarlo , Modest Jacob M. , Kuris Eren O. , Born Christopher
Published: April 2022

Background

Fragility hip fractures are a common orthopedic injury seen in Emergency Departments, with variable outcomes that can range from average to devastating. Currently, few reliable metrics to predict which patients will suffer post-operative complications exist. The aim of this study was to determine if the number and type of pre-operative medications can help predict post-operative complications.

Methods

A prospectively collected database of hip fracture patients was retrospectively reviewed. Patients with isolated greater trochanteric fractures, periprosthetic fractures, or re-fractures were excluded. Pre-operative baseline characteristics as well as number and type of post-operative complications were reviewed. Any complication within 6 months of surgery and complications that could be directly attributable to the surgical procedure within 2 years of surgery were examined. Major complications (return to the operating room, deep infection, pulmonary, cardiac, and hematologic) and minor medical complications were assessed. A multivariate regression model was performed to identify independent risk factors.

Results

Three-hundred ninety-one patients were included. A majority were aged 80–90 and female, and lived at home prior to presentation. Overall, 33.7% of patients suffered a complication within a 2-year follow-up period. Mortality rates were 5.4%, 10.0%, and 14.9% over 30 days, 1 year, and 2 years, respectively. After assessing this relationship while controlling for age, sex, injury type, pre-operative residence, ambulatory status, ASA score, and CCI score, the relationship remained significant for both an increased number of complications ( P = .048) and a higher likelihood of having a complication ( P = .008). Cardiovascular ( P = .003), pulmonary ( P = .001), gout ( P = .002), or diabetes ( P = .042) medications were associated with a higher likelihood for experiencing a complication.

Conclusions

Our study suggests that there is a strong and linear relationship between the number and type of pre-operative medications taken and risk of post-operative complications. This exists for up to 8 medications, at which point further increase does not contribute to an increased risk of complication. This relationship exists even after controlling for confounding variables and can be used by surgeons to better counsel patients and families regarding their specific risk for suffering perioperative complications.
Using whole-genome sequencing to characterize clinically significant blood groups among healthy older Australians
Authors: Jadhao Sudhir , Davison Candice , Roulis Eileen V. , Lee Simon , Lacaze Paul , Riaz Moeen , McNeil John J. , Thomas David M. , Pecheniuk Natalie M. , Hyland Catherine A. , Flower Robert L. , Nagaraj Shivashankar H.
Published: April 2022

There have been no comprehensive studies of a full range of blood group polymorphisms within the Australian population. This problem is compounded by the absence of any databases carrying genomic information on chronically transfused patients and low frequency blood group antigens in Australia. Here, we use RBCeq, a web server–based blood group genotyping software, to identify unique blood group variants among Australians and compare the variation detected vs global data. Whole-genome sequencing data were analyzed for 2796 healthy older Australians from the Medical Genome Reference Bank and compared with data from 1000 Genomes phase 3 (1KGP3) databases comprising 661 African, 347 American, 503 European, 504 East Asian, and 489 South Asian participants. There were 661 rare variants detected in this Australian sample population, including 9 variants that had clinical associations. Notably, we identified 80 variants that were computationally predicted to be novel and deleterious. No clinically significant rare or novel variants were found associated with the genetically complex ABO blood group system. For the Rh blood group system, 2 novel and 15 rare variants were found. Our detailed blood group profiling results provide a starting point for the creation of an Australian blood group variant database.
Identification of sentinel plant species for evaluating phytotoxicity of veterinary antibiotics in Mediterranean Europe
Authors: García Rosa M. , Martínez-Fernández Jesús , Rodríguez Antonio , de la Torre Ana
Published: April 2022

Background

Antibiotics used to treat livestock species enter agricultural fields when they are excreted by grazing animals or are present in manure that is added to fields as fertiliser. In the European Union, the potential effects of such antibiotics on terrestrial plants must be evaluated following the standardised OECD 208 method, which specifies the crop and wild species that should serve as “sentinels” for assessing antibiotic exposure. The present study aimed to compare this approved list of sentinel species against crop and wild plant species actually present in agricultural and pasture lands in Mediterranean Europe in order to identify the most appropriate sentinel plants for the region. The study focused on Spain as a region representative of Mediterranean Europe. Georeferenced layers for wild plant species and cultivated areas (crops), livestock density and land cover were combined, and then selection criteria were applied, leading to the identification of sentinel crop and wild species for crop land and pasture scenarios.

Results

In the crop land scenario, the sentinel crop species were barley (Hordeum vulgare L.), wheat (Triticum spp.), corn (Zea mays L), sunflower (Helianthus annuus L.), dried pea (Pisum sativum L.), alfalfa (Medicago sativa L.), vetch (Vicia sativa L.), oilseed rape (Brassica napus L.) and sugar beet (Saccharum officinarum L.), all of them listed in the OECD 208 method with the exception of alfalfa; the sentinel wild species were Papaver rhoeas L., Galium aparine L. and Chenopodium album L. In the pasture scenario, sentinel wild species were Bromus tectorum L., Agrostis capillaris  L., Trifolium pratense L., Lotus corniculatus L. and Galium aparine L. The following common weed species in field boundaries or in pasture lands also emerged as potential sentinel species for risk assessment, even though they are not listed in the OECD 208 method: Sonchus oleraceus L., Avena sterilis L., Dactylis glomerata L., Hordeum murinum L. and Lolium rigidum Gaudin.

Conclusions

The sentinel species identified in this study may be useful in risk assessment procedures covering the Mediterranean Europe. The method developed for this study could be applied to identify sentinel species for other representative agroclimatic regions in Europe (such as Atlantic and Continental).
Intermittent fasting induces chronic changes in the hepatic gene expression of Red Jungle Fowl (Gallus gallus)
Authors: Lindholm Caroline , Batakis Petros , Altimiras Jordi , Lees John
Published: April 2022

Background

Intermittent fasting (IF), the implementation of fasting periods of at least 12 consecutive hours on a daily to weekly basis, has received a lot of attention in recent years for imparting the life-prolonging and health-promoting effects of caloric restriction with no or only moderate actual restriction of caloric intake. IF is also widely practiced in the rearing of broiler breeders, the parent stock of meat-type chickens, who require strict feed restriction regimens to prevent the serious health problems associated with their intense appetites. Although intermittent fasting has been extensively used in this context to reduce feed competition and its resulting stress, the potential of IF in chickens as an alternative and complementary model to rodents has received less investigation. In both mammals and birds, the liver is a key component of the metabolic response to IF, responding to variations in energy balance. Here we use a microarray analysis to examine the liver transcriptomics of wild-type Red Jungle Fowl chickens fed either ad libitum, chronically restricted to around 70% of ad libitum daily or intermittently fasted (IF) on a 2:1 (2 days fed, 1 day fasted) schedule without actual caloric restriction. As red junglefowl are ancestral to domestic chicken breeds, these data serve as a baseline to which existing and future transcriptomic results from farmed birds such as broiler breeders can be compared.

Results

We find large effects of feeding regimen on liver transcriptomics, with most of the affected genes relating to energy metabolism. A cluster analysis shows that IF is associated with large and reciprocal changes in genes related to lipid and carbohydrate metabolism, but also chronic changes in genes related to amino acid metabolism (generally down-regulated) and cell cycle progression (generally up-regulated). The overall transcription pattern appears to be one of promoting high proliferative plasticity in response to fluctuations in available energy substrates. A small number of inflammation-related genes also show chronically changed expression profiles, as does one circadian rhythm gene.

Conclusions

The increase in proliferative potential suggested by the gene expression changes reported here indicates that birds and mammals respond similarly to intermittent fasting practices. Our findings therefore suggest that the health benefits of periodic caloric restriction are ubiquitous and not restricted to mammals alone. Whether a common fundamental mechanism, for example involving leptin, underpins these benefits remains to be elucidated.
Blood pressure profile of primary school children in Eastern Cape province, South Africa: prevalence and risk factors
Authors: Gomwe Howard , Seekoe Eunice , Lyoka Philemon , Marange Chioneso Show
Published: April 2022

Background

The problem of cardiovascular diseases and lack of adequate information about the blood pressure profiles among children in South Africa has enormous consequences for public health and the general well-being of communities.

Aim

The aim of this study is to determine the blood pressure profiles and associated risk factors of primary school children in South Africa.

Methods

A cross sectional study was conducted among 876 children aged 9 to 14 years from 18 randomly selected schools in the Eastern Cape province of South Africa. Standardised blood pressure measuring instruments were used and an average of three readings was considered. Blood pressure status was classified according to the percentiles of systolic blood pressure (SBP).

Results

The overall prevalence of hypertension was 5.2% and pre-hypertension was 18.5% while normal blood pressure was 76.3%. The multilevel binary logistic regression’s crude and adjusted analysis revealed that increase in age was significantly associated with elevated BP in children ([crude OR = 1.17 [1.05 – 1.29] and [adjusted OR = 1.12 [1.01 – 1.25]). In addition, increase in BMI was significantly associated with elevated BP in children ([crude OR = 1.08 [1.04 – 1.12] and [adjusted OR = 1.06 [1.02 – 1.11]). There was no statistically significant association between elevated BP and gender for both the univariate and multivariate models. There was also no statistical significant risk for elevated BP associated with place of residence.

Conclusions

In this sampled population the established proportion of primary school children with elevated BP is of great concern. In addition, older children and those with high BMI (that is, overweight/obesity) were associated with elevated BP. Interventions towards promoting healthy lifestyles among school learners is a necessity if we are to prevent cardiovascular diseases.