bluuebunny/crossref_metadata_2025 huggingface dataset:
Resistance profiles after different periods of exposure to a first-line antiretroviral regimen in a Cameroonian cohort of HIV type-1-infected patients
Authors: Soria Alessandro , Porten Klaudia , Fampou-Toundji Jean-Calvin , Galli Laura , Mougnutou Rose , Buard Vincent , Kfutwah Anfumbom , Vessière Aurelia , Rousset Dominique , Teck Roger , Calmy Alexandra , Ciaff Laura , Lazzarin Adriano , Gianotti Nicola
Published: April 2022

Background

The lack of HIV type-1 (HIV-1) viral load (VL) monitoring in resource-limited settings might favour the accumulation of resistance mutations and thus hamper second-line treatment efficacy. We investigated the factors associated with resistance after the initiation of antiretroviral therapy (ART) in the absence of virological monitoring.

Methods

Cross-sectional VL sampling of HIV-1-infected patients receiving first-line ART (nevirapine or efavirenz plus stavudine or zidovudine plus lamivudine) was carried out; those with a detectable VL were genotyped.

Results

Of the 573 patients undergoing VL sampling, 84 were genotyped. The mean number of nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) mutations increased with the duration of ART exposure ( P=0.02). Multivariable analysis showed that patients with a CD4+ T-cell count ≤50 cells/ mm3 at ART initiation (baseline) had a higher mean number of both NRTI and non-NRTI (NNRTI) mutations than those with a baseline CD4+ T-cell count >50 cells/mm3 (2.10 versus 0.56; P<0.0001; and 1.65 versus 0.76; P=0.005, respectively). A baseline CD4+ T-cell count ≤50 cells/mm3 predicted ≥1 NRTI mutation (adjusted odds ratio [AOR] 7.49, 95% confidence interval [CI] 2.20-32.14), ≥1 NNRTI mutation (AOR 4.25, 95% CI 1.36-15.48), ≥1 thymidine analogue mutation (AOR 8.45, 95% CI 2.16-40.16) and resistance to didanosine (AOR 6.36, 95% CI 1.49-32.29) and etravirine (AOR 4.72, 95% CI 1.53-15.70).

Conclusions

Without VL monitoring, the risk of drug resistance increases with the duration of ART and is associated with lower CD4+ T-cell counts at ART initiation. These data might help define strategies to preserve second-line treatment options in resource-limited settings.
HIV Type-1 Transmission Dynamics in Recent Seroconverters: Relationship with Transmission of drug Resistance and Viral Diversity
Authors: Recordon-Pinson Patricia , Anies Guerric , Bruyand Mathias , Neau Didier , Morlat Philippe , Pellegrin Jean-Luc , Groppi Alexis , Thiébaut Rodolphe , Dabis François , Fleury Hervé , Masquelier Bernard ,   the ANRS CO3 Aquitaine Cohort
Published: April 2022

Background

HIV type-1 (HIV-1) has been shown to be frequently transmitted by acutely infected patients. We investigated the relationship between the dynamics of HIV-1 transmission within recently infected patients, the HIV-1 variability and the transmission of antiretroviral drug resistance.

Methods

We included patients infected between 1996 and 2006, with a plasma sample obtained <18 months after seroconversion and prior to antiretroviral therapy initiation. Reverse transcriptase (RT) and protease sequences were determined by direct population sequencing from plasma samples. Genotypic resistance was interpreted with the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales 2006 algorithm and International AIDS Society–USA list. Phylogenetic analysis (neighbour-joining and maximum likelihood methods) of RT sequences was used to determine the HIV-1 subtype and the interrelationship between sequences.

Results

Genotypic resistance was detected in 37/263 (14.1%) patients. Patients were infected by HIV-1 clade B in 222 (84%) cases and with non-B subtypes in 41 (16%). A total of 80 (30.4%) RT sequences were segregated in 24 clusters with bootstrap values >98% for 22 clusters. The frequency of grouping in clusters was higher within B sequences compared with non-B sequences (35.1% versus 4.9%; P<2.10-4). Drug-resistant isolates were retrieved in only 3 clusters, but the prevalence of resistance in clustering viruses (10/80, 12.5%) was not different than in isolated sequences.

Conclusions

The segregation into clusters suggested frequent forward transmission events in patients infected with HIV-1 subtype B, including the possibility of transmission of drug-resistant isolates. These findings warrant increasing prevention efforts and serological screening in the at-risk populations.
Adefovir dipivoxil resistance patterns in patients with lamivudine-resistant chronic hepatitis B
Authors: Santantonio Teresa , Fasano Massimo , Durantel Sandra , Barraud Luc , Heichen Manuela , Guastadisegni Angela , Pastore Giuseppe , Zoulim Fabien
Published: April 2022

Background

Lamivudine (3TC)-resistant chronic hepatitis B patients demonstrated a higher rate of adefovir dipivoxil (ADV) resistance compared with nucleoside-naive patients. This study describes ADV mutation patterns in 3TC-resistant patients treated with ADV+3TC or ADV monotherapy, investigating whether mutations selected during 3TC therapy predispose to ADV resistance. Risk factors for ADV resistance were also evaluated.

Methods

A total of 60 3TC-experienced patients were treated with (or switched to) ADV monotherapy (30 patients) or ADV+3TC combination therapy (30 patients), and followed for at least 12 months. In all patients the hepatitis B virus reverse transcriptase (RT) region was amplified and directly sequenced before initiating ADV. The RT sequence was reevaluated for virological breakthrough patients and phenotypic analysis was performed for several patients.

Results

In total, 14 (23%) patients showed virological breakthrough (10/30 on ADV monotherapy and 4/30 on ADV+3TC). ADV resistance mutations (rtA181V/T and rtN236T) were detected alone or in combination for 11/14 patients, whereas novel substitutions were present in 3 patients. Before ADV treatment, apart from 3TC resistance signature mutations, additional changes were found, including the rtA181T mutation, which was already present in 2/14 ADV-resistant patients.

Conclusions

Although most patients showed virological breakthrough because of the well known rtA181V/T and rtN236T substitutions, more complex patterns were also found. ADV monotherapy, dose reduction and suboptimal virological response after 48 weeks of therapy were significantly associated with ADV resistance.
Meta-Analysis of Antiretroviral Effects on HIV-1 RNA, CD4 Cell Count and Progression to AIDS or Death
Authors: Hill Andrew M , DeMasi Ralph , Dawson Debra
Published: April 2022

There is uncertainty as to how the effects of antiretroviral treatments on human immunodeficiency virus type 1 (HIV-1) RNA levels and CD4 cell counts can predict reductions in clinical progression to AIDS or death. A meta-analysis was conducted for 27 pairwise comparisons of antiretroviral treatments in 15 randomized trials of antiretroviral treatments. For each trial, three measures of treatment effect were used: (i) 16 week change from baseline in HIV-1 RNA; (ii) 16 week change from baseline in CD4 cell count; and (iii) rate of clinical progression. Treatments which caused greater increases in CD4 cell count and greater reductions in HIV-1 RNA were more effective at reducing the rate of clinical progression ( P<0.05 for each comparison). However, there was variability in the consistency of this correlation between different trials and treatments. The results support the use of both CD4 count and HIV-1 RNA levels as the primary markers of the efficacy of antiretroviral treatment.
Quantitative p24 Antigenaemia for Monitoring Response to Antiretroviral Therapy in HIV-1 Group O-Infected Patients
Authors: Machuca Ana , Gutiérrez Maite , Mur Antonio , Soriano Vincent
Published: April 2022

Failure to recognize infection caused by human immunodeficiency virus type 1 (HIV-1) group 0 variants has been described using both serological and genetic techniques. Moreover, the monitoring of response to antiretroviral therapy is difficult in persons carrying this infection since most currently available tests for quantifying viral load are not reliable for group 0 viruses. Considering the low level of divergence between the p24 proteins of group M and 0 viruses, we have examined whether the quantification of circulating p24 antigenaemia might be used as a surrogate marker of response to therapy in three subjects with HIV-1 group 0 infection treated with antiretroviral drugs. In summary, all three patients showed a significant decline in circulating plasma p24 antigenaemia, although only one achieved undetectable levels. The decline in p24 antigenaemia was parallel to an increase in the CD4 count and was associated with an improvement in clinical status.
Kinetics of Productive and Latent HIV Infection in Lymphatic Tissue and Peripheral Blood during Triple-Drug Combination Therapy with or without Additional Interleukin-2
Authors: Stellbrink Hans-Jürgen , Hufert Frank T , Tenner-Racz Klara , Lauer Johannes , Schneider Claus , Albrecht Helmut , Racz Paul , van Lunzen Jan
Published: April 2022

Objective

To study decay rates of productively and latently infected cells in peripheral blood and lymph nodes during triple antiretroviral therapy and the possible impact of interleukin-2 (IL-2) on viral kinetics. Methods: In this non-randomized study, nine antiretro-viral-naive HIV-positive patients received either saquinavir hard gel capsules 2400 mg three times daily (group I; four patients) or saquinavir soft gel capsules 1200 mg three times daily and IL-2 (group II), in both cases together with two nucleoside analogues. Plasma viraemia and lymphocyte subsets were analysed. Axillary lymph nodes were excised before and after 12 weeks of therapy. Lymph node sections were examined by in situ hybridization for HIV RNA, and productively infected cells were counted. Infection rates of FACS-sorted CD3, CD4 lymph node and peripheral blood mononuclear cells were determined by nested DNA PCR.

Results

Baseline plasma HIV RNA levels ranged from <25 to >1x106 copies/ml and remained undetectable throughout the study in one patient in group I. Plasma viraemia became undetectable after 3 months in four patients (three in group I). Productively infected cells were markedly reduced in the follow-up lymph node specimens. HIV DNA-positive CD4 T cells were reduced in lymphoid tissue and peripheral blood in all six evaluable patients. There were no significant differences between the groups in the clearance rates of plasma virus and of HIV DNA-positive cells.

Conclusions

Combined antiretroviral therapy rapidly suppressed active HIV replication in plasma and lymphoid tissue. Latently infected cells were cleared at a slower rate. Viral clearance did not appear to be markedly affected by additional IL-2 therapy.
Evaluation of Mixtures of Wild-Type HIV-1 and HIV-1 with Resistance Point Mutations against Reverse Transcriptase Inhibitors
Authors: Villahermosa María Luisa , Contreras Gerardo , Pérez-Alvarez Lucía , Bru Francisco , Medrano Leandro , Delgado Elena , Colomo Concha , Thomson Miguel , Nájera Rafael
Published: April 2022

The presence of resistance-related mutations in 185 serial proviral DNA samples from 108 HIV-infected patients was monitored using the line probe assay (LiPA). The proportions of wild-type and mutant virus in each sample were determined. Subsequent samples from the same patient were analysed.

Resistance mutations were detected in 58 of 108 patients studied (53.7%), 53 of 73 (72.6%) treated with antivirals and 5 of 35 (14.2%) untreated. The mutations were against zidovudine (51), lamivudine (1), zidovudine and lamivudine (4), zidovudine and zalcitabine (1) and zidovudine and didanosine (1). Among the 58 patients with resistant virus, 168 related mutations were observed: 161 to zidovudine (90 in codon 70, 25 in codon 41 and 46 in codon 215), 5 to lamivudine (codon 184), 1 to zalcitabine (codon 69) and 1 to didanosine (codon 74). Mixtures of wild-type and resistant mutants were detected in 76 of 90 (84.4%) mutated at codon 70, 28 of 46 (60.8%) mutated at codon 215 and in 21 of 25 (84%) mutated at codon 41. The mutations at codon 184 were mixtures of wild-type and resistant in 4 of 5 samples. The agreement between LiPA and sequencing was 96.5%. LiPA was more sensitive for the detection of mutants that were present at low frequency. The analysis of sequential samples from the same patient allowed evaluation of the dynamics of appearance of the resistant mutants.
Quality of Life Outcomes of Saquinavir, Zalcitabine and Combination Saquinavir plus Zalcitabine Therapy for Adults with Advanced HIV Infection with CD4 Counts between 50 and 300 Cells/mm3
Authors: Revicki Dennis A , Swartz Cassandra , Wu Albert W , Haubrich Richard , Collier Ann C
Published: April 2022

Background

Benefits in patient health-related quality of life (HRQL) have not yet been demonstrated for combination antiretroviral therapy with protease inhibitors and nucleoside analogues. This double-blind study evaluated zalcitabine or saquinavir monotherapy and combination saquinavir plus zalcitabine therapy on HRQL of human immunodeficiency virus (HIV)-infected adults.

Methods

940 HIV-infected patients (CD4 counts 50–300 cells/mm3) who had discontinued zidovudine therapy (for intolerance or treatment failure) were randomized to one of three regimens: zalcitabine 0.75 mg every 8 h; saquinavir 600 mg every 8 h; or combination zalcitabine 0.75 mg plus saquinavir 600 mg every 8 hours. HRQL was measured at baseline, 24 and 48 weeks using the Medical Outcome Study HIV Health Survey (MOS-HIV). The primary endpoints were the physical and mental health summary scores (PHS; MHS) of the MOS-HIV as well as a global visual analogue scale (VAS) score.

Results

After 24 weeks, the zalcitabine-treated patients demonstrated significantly greater decreases in PHS scores (-4.4±0.6; saquinavir: -1.3±0.6; zalcitabine plus saquinavir: -1.7±0.6; P<0.0001) and MHS scores (-2.2±0.5; saquinavir: -1.0±0.5; zalcitabine plus saquinavir: -0.5±0.5; P=0.032) compared to saquinavir and zalcitabine plus saquinavir treated patients. No differences were observed on the VAS ( P=0.172). Nine of 10 MOS-HIV subscales demonstrated results consistent with the primary endpoints. After 48 weeks, a statistically significant difference between the saquinavir-treated groups and the zalcitabine monotherapy group was observed for PHS scores (zalcitabine: -5.8±0.6; saquinavir: -4.1±0.6; zalcitabine plus saquinavir: -3.5±0.6; P=0.014).

Conclusions

Saquinavir monotherapy and combination saquinavir plus zalcitabine demonstrated a benefit in HRQL relative to zalcitabine monotherapy in patients with prior zidovudine therapy. The HRQL findings are concordant with improved survival and reduced clinical progression of HIV infection found in this study.
Presence of Genotypic Resistance in Nucleoside Analogue-Treated HIV-1-Infected Patients with Undetectable Viral Load
Authors: Rubio Amalia , Gómez-Cano María , Puig Teresa , Leal Manuel , Pérez-Olmeda Mayte , Ruiz Lidia , Clotet Bonaventura , Rey Concepción , Zamora Laura , Xaus Nuria , Soriano Vicenç
Published: April 2022

Patients harbouring drug-resistant viruses usually suffer a rise in serum viraemia after a variable period of time. We have investigated the relationship between the appearance of resistant genotypes and the viral load of each patient after treatment. Our objective was to assess the association between human immunodeficiency virus (HIV) RNA plasma levels and the number of drug resistance-associated point mutations after treatment. A total of 150 patients from three reference centres in Spain (Madrid, Barcelona and Seville) from a previous study (Erase Study) were included. Patients had at that time undergone antiretroviral treatment with nucleoside analogues for at least 1 year (zidovudine/didanosine; zidovudine/zalcitabine; zidovudine/zalcitabine/lamivudine; zidovudine/didanosine/lamivudine). In this study, plasma viraemia in these patients was quantified and a line probe assay was used to determine the genotype of the virus. Viral load was significantly higher in patients harbouring virus with more than three mutations than in those individuals who harboured wild-type strains ( P<0.05). Surprisingly, when patients with viral load <500 copies/ml (13/150) were analysed, only two carried wild-type strains, whereas three had virus with more than three point mutations. The viral load of six samples was assayed using an ultrasensitive test (detection limit <20 copies/ml). Of the three samples where viral load was <20 copies/ml, one patient harboured wild-type virus, whereas two carried mutant virus strains. These results suggest that even in patients with undetectable viral loads by conventional methods, viral replication may continue and mutations develop. Therefore, standard values of plasma viraemia for measuring the effectiveness of the treatment should be reconsidered when patients are on antiviral regimens of just two or three nucleoside analogues.
Safety and Efficacy of the Neuraminidase Inhibitor Zanamivir in Treating Influenza Virus Infection in Adults: Results from Japan
Authors: Matsumoto Keizo , Ogawa Nobuya , Nerome Kuniaki , Numazaki Yoshio , Kawakami Yoshikazu , Shirato Kunio , Arakawa Masaaki , Kudoh Shoji , Shimokata Kaoru , Nakajima Shigenori , Yamakido Michio , Kashiwagi Seizaburo , Nagatake Tsuyoshi ,   the GG167 Group, Kawakami Y , Miyamoto H , Inoue H , Shirato K , Miura Y , Watanabe A , Nakai Y , Ishii M , Sakamoto M , Kudoh S , Abe S , Yamaguchi T , Arakawa M , Sega H , Shimatsu Y , Yoshimine F , Shimokata K , Masuda T , Yamamoto M , Iwata M , Nakajima S , Ito M , Takeda T , Ohsawa N , Kato M , Yamakido M , Takahashi J , Miyazawa T , Soejima R , Sasaki T , Nagatake T , Masaki H , Kashiwagi S , Ueno K , Hayashida K , Ando M , Ikegami A
Published: April 2022

The study was carried out to evaluate the therapeutic effects of zanamivir, a highly selective, potent and specific inhibitor of influenza A and B virus neuraminidases, in adult patients with acute influenzalike illness. Patients who presented within 36 h of the onset of influenza-like symptoms were randomly assigned to receive one of three treatments, twice daily, for 5 days: 10 mg zanamivir powder for inhalation (zanamivir inhalation group), 10 mg zanamivir powder for inhalation plus 6.4 mg zanamivir nasal spray (zanamivir inhalation plus intranasal group) or placebo (placebo group). The primary end point was the time to alleviation of the three major symptoms (fever, headache and myalgia). The secondary end point was the time to alleviation of five influenza symptoms (fever, headache, myalgia, cough and sore throat). One hundred and sixteen patients with influenza-like illness were recruited to the study. No differences were observed between the two groups of patients who received zanamivir (inhalation group or inhalation plus intranasal group). Patients who received zanamivir recovered significantly faster (median 3 days to recovery) than the patients in the placebo group (median 4 days to recovery; P<0.01). Topically administered zanamivir was well tolerated. This study confirms that in adults, topically administered zanamivir is well tolerated and is effective in reducing the time to alleviation of influenza symptoms.
Evolution of Genotypic Resistance to Nucleoside Analogues in Patients Receiving Protease Inhibitor-Containing Regimens
Authors: Pèrez-Olmeda M , Rubio A , Puig T , Gômez-Cano M , Ruiz L , Leal M , Clotet B , Soriano V
Published: April 2022

The prevalence of genotypic resistance to nucleoside analogues (NA) was examined using a line probe assay (LiPA, Innogenetics, Spain) and a point mutation assay to test for codon 151 polymorphism in plasma from 34 individuals who had been exposed to NA for longer than 1 year. The testing was repeated in the same population after 6 months of being on a new potent protease inhibitor (PI)-containing antiretroviral combination. Only nine (47%) of the 19 patients initially carrying the codon 41 mutation restored zidovudine wild-type (WT) virus population. Similarly, eight (33%) out of 24 carrying the codon 215 mutation restored the wild-type variant. Two subjects carrying codon 74 didanosine mutation reverted to wild-type genotype, as well as two (18%) out of 11 harbouring the codon 184 lamivudine-resistant variant. To conclude, the extent to which drug recycling might be of benefit in subjects showing a restoration of genotypic sensitivity to former drugs needs to be explored.
Adherence in Clinical Trials and in Clinical Practice
Authors: Walsh John C
Published: April 2022

The degree of patient adherence is increasingly recognized to be a key factor in the success of highly active antiretroviral therapy (HAART). HAART regimens are also among the most complex ever prescribed and low adherence is directly related to treatment complexity. Physicians prescribing HAART need to make adherence a priority both in clinical practice and in the design and interpretation of clinical trials if HAART really is to succeed in the long term.
More than perfect: Cosmetic surgery and ageing single women in contemporary China
Authors: Chow Yiu Fai
Published: April 2022

In this article, I want to connect my inquiry into cosmetic surgery not only to a general category of women, but to its intersections with ageing, singlehood and China. Facilitating dialogues between cultural studies, feminist studies and ageing studies, I argue for the need to be less normative, but more inquisitive, for the need to heed specificities, to hear what the women themselves have to say. Departing from the dominant feminist and neoliberal critique against beautification practices in general and cosmetic surgery in particular, I argue for alternative ways to connect with, and the concomitant refusal to flatten, women’s experience. In other words, I am less interested in how they are used by the beauty industries, but how they use beautification practices – under their specific circumstances. I draw from intersectional perspectives to re-examine the dominant critique against beauty work through this group of single, ageing, Chinese women. What motivates them to agree to acid filling, Botox injection, facial manipulation and other bodily interventions? How do they choose what to do? What factors are involved? How does the surgery impact on their personal and professional life? To answer these questions, I recruited 12 women, born between 1970 and 1989, who have undergone a diversity of interventions. Far from the type or stereotype of women who desire perfection, they articulate their experiences using four repertoires: to demonstrate they are more thoughtful, knowledgeable and mature; to underline their single sisterhood; to distance themselves from the perfectionist longing; and to experience themselves better as single women.
Co-production and the issue of urban up-scaling and governance change in the global south: The case of Uganda
Authors: Siame Gilbert , Watson Vanessa
Published: April 2022

Co-production has emerged as a prominent strategy for producing urban spaces, delivering urban services and improving governance in poor but rapidly growing cities of the South. In the field of planning, it has been put forward as a more appropriate approach to what has generally been termed ‘public participation’: a term with its roots in the concept of collaborative planning emerging largely from experience in advanced economies of the West. Co-production has been used in several specific cases to build state-society alliances for community change and socio-spatial transformation. This paper argues that the transformative potential of the co-production approach lies in its ability to drive change at local, city-wide and trans-local scales. We argue that the capacity and ability to institutionalise and scale-up co-production activities depend on the ability of state and society locating and securing their ‘locus standi’ through political alignment, conflict resolution, political negotiations and collaboration. The paper contributes to literature in co-production and planning by analysing how the state and society use multiple tactics to achieve both collaboration and resistance as means of creating and sustaining a governance middle ground.
Long-term friction performance monitoring of sliding layer in China railway track system Ⅱ slab track on bridge superstructure
Authors: Li Shunlong , Wang Dedao , Lin Chao , Wang Senrong
Published: April 2022

The sliding layer is an important component of the China Railway Track System (CRTS) Ⅱ slab track on bridges, and its friction performance has a significant influence on the intensity of track–bridge interaction (TBI). However, the friction performance deterioration of this sliding layer under actual repeated abrasion and harsh environmental conditions is difficult to grasp since structural health monitoring implementation into in-service high-speed railway tracks is extremely hard to be permitted and only limited valuable monitoring datasets are available at present. In this study, the friction performance degradation of the sliding layer was therefore investigated using long-term monitoring data from a multi-span simply supported box girder bridge. First, the friction-induced strain in the base plate was decoupled using the monitored strain at the fixing point and mid-span based on mechanical properties of TBI. Then, structural health monitoring and finite element analysis both indicated an approximately linear relationship between the decoupled friction-induced strain and the temperature of the investigated bridge under certain circumstances. Furthermore, the correspondence between the slope of this linear relationship and the friction coefficient was modelled. Finally, the friction coefficients of the sliding layers on target spans were identified using 4 years of monitoring data and the established correspondence model to analyse the statistical characteristics and degradation performance of the layers. This investigation of the friction performance degradation of the sliding layer in the CRTS II slab track system provides guidance for future maintenance and replacement decision making.
Low-Dose Gamma Radiation Modulates Liver and Testis Tissues Response to Acute Whole Body Irradiation
Authors: Abdel-Aziz Nahed , Haroun Riham A.-H. , Mohamed Hebatallah E.
Published: April 2022

Aim

This work aims to investigate whether the pre-exposure to low dose/low dose rate (40 mGy, 2.2 mGy/hour) γ-radiation as a priming dose can produce a protective effect against the subsequent high one (4 Gy, .425 Gy/minute).

Methods

Rats were divided into Group I (control), Group II (L); exposed to 40 mGy, Group III (H); exposed to 4 Gy, and Group IV (L+H); exposed to 40 mGy 24 hours before the exposure to 4Gy. The molecular and biochemical changes related to oxidative stress, DNA damage, apoptosis, and mitochondrial activity in the liver and testis were studied 4 hours after irradiation.

Results

Exposure to 40 mGy before 4 Gy induced a significant increase in the levels of Nrf2, Nrf2 mRNA, TAC, and mitochondrial complexes I & II accompanied by a significant decrease in the levels of LPO, 8-OHdG, DNA fragmentation, TNF-α, caspase-3, and caspase-3 mRNA compared with H group.

Conclusion

Exposure to low-dose γ-radiation before a high dose provides protective mechanisms that allow the body to survive better after exposure to a subsequent high one via reducing the oxidative stress, DNA damage, and apoptosis-induced early after irradiation. However, further studies are required to identify the long-term effects of this low dose.
Reflexive Integration of Research Elements in Mixed-Method Research
Authors: Olaghere Ajima
Published: April 2022

This article highlights “reflexive integration” as a methodological tool that can facilitate the explicit integration of quantitative or qualitative elements in mixed-methods research. Reflexive integration of research elements (RIRE) is advocated as a mechanism that can be used in any mixed-method study to enhance depth of inquiry and transparency of the steps involved in mixed-method research. An illustrative example is presented to show the step-by-step process of reflexive integration at various stages of a mixed-method study.
Contemporary management and time to revascularization in upper extremity arterial injury
Authors: Chipman Amanda M , Ottochian Marcus , Ricaurte Daniel , Gunter Grahya , DuBose Joseph J , Stonko David P , Feliciano David V , Scalea Thomas M , Morrison Jonathan
Published: April 2022

Introduction

Upper extremity arterial injury is associated with significant morbidity and mortality for trauma patients, but there is a paucity of data to guide the clinician in the management of these injuries. The goals of this review were to characterize the demographics, presentation, clinical management, and outcomes, and to evaluate how time to intervention associates with outcomes in trauma patients with upper extremity vascular injuries.

Methods

The National Trauma Data Bank (NTDB) Research Data Set for the years 2007–2016 was queried in order to identify adult patients (age ≥ 18) with an upper extremity arterial injury. Patients with brachiocephalic, subclavian, axillary, or brachial artery injury using the 1998 and 2005 versions of the Abbreviated Injury Scale were included. Patients with non-survivable injuries to the brain, traumatic amputation, or other major arterial injuries to the torso or lower extremities were excluded.

Results

The data from 7908 patients with upper extremity arterial injuries was reviewed. Of those, 5407 (68.4%) underwent repair of the injured artery. The median Injury Severity Score (ISS) was 10 (IQR = 7–18), and 7.7% of patients had a severe ISS (≥ 25). Median time to repair was 120 min (IQR = 60–240 min). Management was open repair in 52.3%, endovascular repair in 7.3%, and combined open and endovascular repairs in 8.8%; amputation occurred in 1.8% and non-operative management was used in 31.6% of patients. Blunt mechanism of injury, crush injury, concomitant fractures/dislocations, and nerve injuries were associated with amputation, whereas simultaneous venous injury was not. There was a significant decrease in the rate of amputation when patients undergoing surgical revascularization did so within 90 min of injury (P = 0.007).

Conclusion

Injuries to arteries of the upper extremity are managed with open repair, endovascular repair, and, rarely, amputation. Expeditious transport to the operating room for revascularization is the key for limb salvage.
Multilateralism and public support for drone strikes
Authors: Lushenko Paul , Raman Shyam , Kreps Sarah
Published: April 2022

The use of armed drones has emerged as a principal counterterrorism tool for western militaries, especially France and the United States. While France submits its strikes to the United Nations for approval, the United States typically does not. Does this difference matter for public support and perceptions of legitimacy? To better understand these dynamics, we fielded original survey experiments across nationally representative samples in France and the United States totaling in over 1800 respondents. Our results reflect that international approval is associated with both higher public support and greater perceived legitimacy for a strike. Further, we find that respondents emphasize international law as the basis for support and legitimacy, suggesting a cross-national belief in multilateralism for normative rather than strictly instrumental reasons. These relationships are moderated by the identity of the country conducting a hypothetical strike, implying both an “othering” effect and the emergence of distinct models of strikes across countries that deserve more study amid the ongoing proliferation of armed drones.

Video Abstract: https://www.youtube.com/watch?v=YevyaKThae0
Extent of Community Stakeholders’ Involvement and Outcomes in Communal Water Supply Systems in Malawi
Authors: Mwakilama Shawo G.
Published: April 2022

It is argued that community participation in development interventions result in positive outcomes and sustainability, unlike where it is absent. This article assesses the extent of community involvement in communal water interventions in Malawi. This came against a backdrop of witnessing high failure rate, that is, about 30%. The study, therefore, sought to assess the extent of community stakeholders’ involvement, and whether this can explain the outcomes in these interventions. A mixed methods approach was followed, and primary data was collected through a survey and key informant interviews. Key documents were also reviewed. The study findings show that the very idea to bring a communal water point into the community is largely exogenous, and that there are significant levels of exclusion of community-based stakeholders in first three phases of water projects, with the exception of maintenance phase as it is essentially fate accompli. When functional and non-functional water points are compared in areas where there is evidence of community involvement, the former shows significant degrees of community involvement unlike the latter. This is one key aspect explaining positive outcomes and sustainability. All this, arguably, entails serious shortcomings in water sector in Malawi, demonstrated by failure of policy and enforcement of standards.
Editing TINF2 as a potential therapeutic approach to restore telomere length in dyskeratosis congenita
Authors: Choo Seunga , Lorbeer Franziska K. , Regalado Samuel G. , Short Sarah B. , Wu Shannon , Rieser Gabrielle , Bertuch Alison A. , Hockemeyer Dirk
Published: April 2022

Mutations in the TINF2 gene, encoding the shelterin protein TIN2, cause telomere shortening and the inherited bone marrow (BM) failure syndrome dyskeratosis congenita (DC). A lack of suitable model systems limits the mechanistic understanding of telomere shortening in the stem cells and thus hinders the development of treatment options for BM failure. Here, we endogenously introduced TIN2-DC mutations in human embryonic stem cells (hESCs) and human hematopoietic stem and progenitor cells (HSPCs) to dissect the disease mechanism and identify a gene-editing strategy that rescued the disease phenotypes. The hESCs with the T284R disease mutation exhibited the short telomere phenotype observed in DC patients. Yet, telomeres in mutant hESCs did not trigger DNA damage responses at telomeres or show exacerbated telomere shortening when differentiated into telomerase-negative cells. Disruption of the mutant TINF2 allele by introducing a frameshift mutation in exon 2 restored telomere length in stem cells and the replicative potential of differentiated cells. Similarly, we introduced TIN2-DC disease variants in human HSPCs to assess the changes in telomere length and proliferative capacity. Lastly, we showed that editing at exon 2 of TINF2 that restored telomere length in hESCs could be generated in TINF2-DC patient HSPCs. Our study demonstrates a simple genetic intervention that rescues the TIN2-DC disease phenotype in stem cells and provides a versatile platform to assess the efficacy of potential therapeutic approaches in vivo.
Microwave complex permittivity and anisotropy of conifer wood chips vs moisture content: experiments and modeling
Authors: Rönnow D. , Ottosson P. , Andersson D.
Published: April 2022

The complex microwave permittivity—including anisotropy- of wood chips of softwood has been measured for different moisture contents in the band 0.75 to 2.5 GHz using an ultra-wide band radio transmission technique. The real and imaginary parts increase monotonically with moisture content. The wood chips are oriented by gravity, which gives anisotropic permittivity. The anisotropy ratio of the real part increases from 1.1 to 1.6 with moisture content from 0 to 120%. The anisotropy ratio of the imaginary part is around 2.5 at all moisture contents. Effective medium models were used to model the permittivity. The Bruggeman, and two versions of the Maxwell Garnett model gave good results at low moisture content (below the fiber saturation point). Above the fiber saturation point only the Bruggeman model gave results in agreement with experiments. The difference in model performance suggests that the free water does not follow the wood chips geometry.
Antimicrobial resistance of Escherichia coli, Enterobacter spp., Klebsiella pneumoniae and Enterococcus spp. isolated from the feces of giant panda
Authors: Wang Xin , Zhang Yi , Li Caiwu , Li Guo , Wu Daifu , Li Ti , Qu Yuanyuan , Deng Wenwen , He Yongguo , Penttinen Petri , Zhang Hemin , Huang Yan , Zhao Ke , Zou Likou
Published: April 2022

Background

Escherichia coli, Enterobacter spp., Klebsiella pneumoniae and Enterococcus spp., common gut bacteria in giant pandas, include opportunistic pathogens. The giant panda is an endangered species, classified as vulnerable by the World Wildlife Foundation. Continuous monitoring for the emergence of antimicrobial resistance (AMR) among bacterial isolates from giant pandas is vital not only for their protection but also for public health.

Results

A total of 166 E. coli, 68 Enterobacter spp., 116 K. pneumoniae and 117 Enterococcus spp. isolates were collected from fecal samples of 166 giant pandas. In the antimicrobial susceptibility tests, 144 E. coli isolates, 66 Enterobacter spp. isolates, 110 K. pneumoniae isolates and 43 Enterococcus spp. isolates were resistant to at least one antimicrobial. The resistant isolates carried antimicrobial resistance genes (ARGs), including sul3, blaTEM, blaSHV and tetA. The differences in the prevalence of the bla types implied that the genetic basis for β-lactam resistance among the E. coli, Enterobacter spp. and K. pneumoniae isolates was different. The strain K. pneumoniae K85 that was resistant to sixteen antimicrobials was selected for whole genome sequencing. The genome contained Col440I, IncFIBK and IncFIIK plasmids and altogether 258 ARGs were predicted in the genome; 179 of the predicted ARGs were efflux pump genes. The genetic environment of the β-lactamase genes blaCTX-M-3 and blaTEM-1 in the K. pneumoniae K85 genome was relatively similar to those in other sequenced K. pneumoniae genomes. In comparing the giant panda age groups, the differences in the resistance rates among E. coli, K. pneumoniae and Enterobacter spp. isolates suggested that the infections in giant pandas of different age should be treated differently.

Conclusions

Antimicrobial resistance was prevalent in the bacterial isolates from the giant pandas, implying that the gut bacteria may pose serious health risks for captive giant pandas. The resistance genes in the genome of K. pneumoniae K85 were associated with insertion sequences and integron-integrase genes, implying a potential for the further spread of the antimicrobial resistance.
Changes in objectively measured lifestyle factors during the COVID-19 pandemic in community-dwelling older adults
Authors: Ataka Takuya , Kimura Noriyuki , Eguchi Atsuko , Matsubara Etsuro
Published: April 2022

Background

In this manuscript, we investigate whether objectively measured lifestyle factors, including walking steps, sedentary time, amount of unforced physical activity, level of slight and energetic physical activity, conversation time, and sleep parameters, were altered before and during the COVID-19 pandemic among community-dwelling older adults.

Methods

Data were obtained from a prospective cohort study conducted from 2015 to 2019 and a subsequent dementia prevention study undertaken in September 2020. Community-dwelling adults aged ≥ 65 years wore wearable sensors before and during the pandemic.

Results

A total of 56 adults were enrolled in this study. The mean age was 74.2 ± 3.9 years, and 58.9% (n = 33) of the participants were female. Moderate and vigorous physical activity time significantly decreased, and sedentary time significantly increased during the pandemic.

Conclusions

This is the first study to demonstrate differences in objectively assessed lifestyle factors before and during the COVID-19 pandemic among community-dwelling older adults. The findings show that the pandemic has adversely affected physical activity among older adults living on their own in Japan.
Comparing prevalence of chronic kidney disease and its risk factors between population-based surveys in Russia and Norway
Authors: Cook Sarah , Solbu Marit D. , Eggen Anne Elise , Iakunchykova Olena , Averina Maria , Hopstock Laila A. , Kholmatova Kamila , Kudryavtsev Alexander V. , Leon David A. , Malyutina Sofia , Ryabikov Andrew , Williamson Elizabeth , Nitsch Dorothea
Published: April 2022

Background

Little data exists on the prevalence of chronic kidney disease (CKD) in the Russian population. We aimed to estimate the prevalence of CKD in a population-based study in Russia, compare with a similar study in Norway, and investigate whether differences in risk factors explained between-study differences in CKD.

Methods

We compared age- and sex-standardised prevalence of reduced eGFR (< 60 ml/min/1.73m2 CKD-EPI creatinine equation), albuminuria and or a composite indicator of CKD (one measure of either reduced eGFR or albuminuria) between participants aged 40–69 in the population-based Know Your Heart (KYH) study, Russia (2015–2018 N = 4607) and the seventh Tromsø Study (Tromsø7), Norway (2015–2016 N = 17,646). We assessed the contribution of established CKD risk factors (low education, diabetes, hypertension, antihypertensive use, smoking, obesity) to between-study differences using logistic regression.

Results

Prevalence of reduced eGFR or albuminuria was 6.5% (95% Confidence Interval (CI) 5.4, 7.7) in KYH and 4.6% (95% CI 4.0, 5.2) in Tromsø7 standardised for sex and age. Odds of both clinical outcomes were higher in KYH than Tromsø7 (reduced eGFR OR 2.06 95% CI 1.67, 2.54; albuminuria OR 1.54 95% CI 1.16, 2.03) adjusted for sex and age. Risk factor adjustment explained the observed between-study difference in albuminuria (OR 0.92 95% CI 0.68, 1.25) but only partially reduced eGFR (OR 1.42 95% CI 1.11, 1.82). The strongest explanatory factors for the between-study difference was higher use of antihypertensives (Russian sample) for reduced eGFR and mean diastolic blood pressure for albuminuria.

Conclusions

We found evidence of a higher burden of CKD within the sample from the population in Arkhangelsk and Novosibirsk compared to Tromsø, partly explained by between-study population differences in established risk factors. In particular hypertension defined by medication use was an important factor associated with the higher CKD prevalence in the Russian sample.
A stepwise data interpretation process for renal amyloidosis typing by LMD-MS
Authors: Ke Ming , Li Xin , Wang Lin , Yue Shuling , Zhao Beibei
Published: April 2022

Backgrounds

Systemic amyloidosis is classified according to the deposited amyloid fibril protein (AFP), which determines its best therapeutic scheme. The most common type of AFP found are immunoglobulin light chains. The laser microdissection combined with mass spectrometry (LMD-MS) technique is a promising approach for precise typing of amyloidosis, however, the major difficulty in interpreting the MS data is how to accurately identify the precipitated AFP from background.

Objectives

The objective of the present study is to establish a complete data interpretation procedure for LMD-MS based amyloidosis typing.

Methods

Formalin-fixed paraffin-embedded specimens from patients with renal amyloidosis and non-amyloid nephropathies (including diabetic nephropathy, fibrillary glomerulonephritis, IgA nephropathy, lupus nephritis, membranous nephropathy, and normal tissue adjacent to tumors) were analyzed by LMD-MS. Forty-two specimens were used to train the data interpretation procedure, which was validated by another 50 validation specimens. Area under receiver operating curve (AUROC) analysis of amyloid accompanying proteins (AAPs, including apolipoprotein A-IV, apolipoprotein E and serum amyloid P-component) for discriminating amyloidosis from non-amyloid nephropathies was performed.

Results

A stepwise data interpretation procedure that includes or excludes the types of amyloidosis group by group was established. The involvement of AFPs other than immunoglobulin was determined by P-score, as well as immunoglobulin light chain by variable of λ-κ, and immunoglobulin heavy chain by H-score. This achieved a total of 88% accuracy in 50 validation specimens. The AAPs showed significantly different expression levels between amyloidosis specimens and non-amyloid nephropathies. Each of the single AAP had a AUROC value more than 0.9 for diagnosis of amyloidosis from non-amyloid control, and the averaged level of the three AAPs showed the highest AUROC (0.966), which might be an alternative indicator for amyloidosis diagnosis.

Conclusions

The proteomic data interpretation procedure for LMD-MS based amyloidosis typing was established successfully that has a high practicability in clinical application.
SNCA correlates with immune infiltration and serves as a prognostic biomarker in lung adenocarcinoma
Authors: Zhang Xiuao , Wu Zhengcun , Ma Kaili
Published: April 2022

Background

The SNCA gene is a critical gene in Parkinson’s disease (PD) pathology. Accumulating evidence indicates that SNCA is involved in tumorigenesis; however, the role of SNCA in lung adenocarcinoma (LUAD) remains unclear. This study aimed to explore the potential value of SNCA as a prognostic and diagnostic molecular marker in LUAD.

Methods

In this study, we explored the expression pattern, prognostic value, and promoter methylation status of SNCA in LUAD based on Oncomine, UALCAN, and Kaplan–Meier Plotter. Then, using TIMER, we investigated the correlation between SNCA expression and immune infiltration. And cBioPortal were used to analysis the correlation between SNCA expression and immune checkpoint. The transcriptome data of A549 cells overexpressing SNCA were used to further study the potential immune role of SNCA in LUAD. The effect of SNCA on proliferation of A549 cells were evaluated by CCK-8, EdU and colony formation. Finally, LUAD cell lines treated with 5-aza-dC were used to explore the correlation between increased promoter methylation and downregulated mRNA expression of SNCA.

Results

In general, the expression level of SNCA in LUAD tissue was lower than that in normal tissue, and high expression of SNCA was related to better prognosis.

There were significant positive correlations between SNCA expression and immune infiltrations, including CD8+ T cells, macrophages, neutrophils, dendritic cells, B cells, and CD4+ T cells, and immune checkpoints, suggesting that immune infiltration was one of the reasons for the influence of SNCA on prognosis in LUAD. The transcriptome data of A549 cells overexpressing SNCA were further used to screen the relevant immune-related genes regulated by SNCA. Enrichment analysis confirmed that SNCA participates in the PI3K-AKT signaling pathway and other key tumor signaling pathways and regulates the expression of MAPK3, SRC, PLCG1, and SHC1. Cellular proliferation assay showed that SNCA could inhabit the growth of A549 cells via inhibiting activity of PI3K/AKT/ mTOR pathway. Finally, analysis of the methylation level of SNCA promoter showed that the promoter methylation negatively correlated with mRNA level. The expression of SNCA in LUAD cell lines was significantly upregulated by treatment with 5-aza-dC.

Conclusion

High methylation of SNCA promoter in LUAD is one of the reasons for the downregulation of SNCA mRNA level. Given that SNCA could inhibit the proliferation of A549 cells and correlates with immune infiltrates, it may serve as a prognostic biomarker in LUAD.