bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and efficacy of a double-boosted protease inhibitor combination, saquinavir and lopinavir/ ritonavir, in pretreated children at 96 weeks
Authors:   the HIV–NAT 017 Study Team, Bunupuradah Torsak , van der Lugt Jasper , Kosalaraksa Pope , Engchanil Chulapan , Boonrak Pitch , Puthanakit Thanyawee , Mengthaisong Tawan , Mahanontharit Apicha , Lumbiganon Pagakrong , Tompkins Emily , Burger David , Ruxrungtham Kiat , Ananworanich Jintanat
Published: April 2022

Background

This study aimed to assess the long-term efficacy, safety and use of therapeutic drug monitoring (TDM) of a double-boosted protease inhibitor (PI) combination, saquinavir (SQV) and lopinavir/ritonavir (LPV/r), in Thai HIV type-1 (HIV-1)-infected children who had failed on reverse transcriptase inhibitors.

Methods

In total, 50 children from two sites in Thailand were treated with standard dosing of SQV and LPV/r. CD4+ T-cell count and percentage, viral load (VL; HIV-1 RNA), minimum plasma drug concentrations (Cmin) and drug safety laboratory evaluations were monitored. Virological failure was defined as having two consecutive VL measures >400 copies/ml after week 12. An intention-to-treat analysis was performed.

Results

Baseline data were a median age of 9.3 years (interquartile range [IQR] 7.1–11.2), VL 4.8 log10 copies/ ml (IQR 4.5–5.1) and CD4+ T-cell percentage 7% (IQR 3.0– 9.5). CDC classifications were N=4%, A=14%, B=68% and C=14% of participants. Median CD4+ T-cell percentage and CD4+ T-cell count increase were 14% (IQR 7–19) and 558 cells/mm3 (IQR 308–782), respectively (both P<0.001). Overall, 37 (74%) children achieved VL<50 copies/ml with significant differences between sites (90% versus 63%). Over 96 weeks, 10 patients had virological failure. Total cholesterol and high-density lipoprotein increased significantly over time, whereas the triglycerides and low-density lipoprotein did not. Approximately 50% of participants reported no change in body shape, and 33%, 43% and 39% reported fatter arms, face and abdomen, respectively. LPV and SQV Cmin were high and stable over time.

Conclusions

Double-boosted SQV+LPV/r was an effective and safe alternative for a second-line regimen in children. Hypercholesterolaemia needs close follow-up. On the basis of the TDM results, PI dose reduction in this population should be considered.
Self-reported alcohol consumption and its association with adherence and outcome of antiretroviral therapy in the Swiss HIV Cohort Study
Authors:   the Swiss HIV Cohort Study, Conen Anna , Fehr Jan , Glass Tracy R , Furrer Hansjakob , Weber Rainer , Vernazza Pietro , Hirschel Bernard , Cavassini Matthias , Bernasconi Enos , Bucher Heiner C , Battegay Manuel
Published: April 2022

Background

Alcohol consumption leading to morbidity and mortality affects HIV-infected individuals. Here, we aimed to study self-reported alcohol consumption and to determine its association with adherence to antiretroviral therapy (ART) and HIV surrogate markers.

Methods

Cross-sectional data on daily alcohol consumption from August 2005 to August 2007 were analysed and categorized according to the World Health Organization definition (light, moderate or severe health risk). Multivariate logistic regression models and Pearson's χ2 statistics were used to test the influence of alcohol use on endpoints.

Results

Of 6,323 individuals, 52.3% consumed alcohol less than once a week in the past 6 months. Alcohol intake was deemed light in 39.9%, moderate in 5.0% and severe in 2.8%. Higher alcohol consumption was significantly associated with older age, less education, injection drug use, being in a drug maintenance programme, psychiatric treatment, hepatitis C virus coinfection and with a longer time since diagnosis of HIV. Lower alcohol consumption was found in males, non-Caucasians, individuals currently on ART and those with more ART experience. In patients on ART ( n=4,519), missed doses and alcohol consumption were positively correlated ( P<0.001). Severe alcohol consumers, who were pretreated with ART, were more often off treatment despite having CD4+ T-cell count <200 cells/μl; however, severe alcohol consumption per se did not delay starting ART. In treated individuals, alcohol consumption was not associated with worse HIV surrogate markers.

Conclusions

Higher alcohol consumption in HIV-infected individuals was associated with several psychosocial and demographic factors, non-adherence to ART and, in pre-treated individuals, being off treatment despite low CD4+ T-cell counts.
Incidence of lipodystrophy and metabolic disorders in patients starting non-nucleoside reverse transcriptase inhibitors in Benin
Authors: Zannou Djimon Marcel , Denoeud Lise , Lacombe Karine , Amoussou-Guenou Daniel , Bashi Jules , Akakpo Jocelyn , Gougounon Alice , Akondé Alain , Adè Gabriel , Houngbé Fabien , Girard Pierre-Marie
Published: April 2022

Background

The incidence and risk factors for lipodystrophy and metabolic disorders among patients in Africa on first-line combined antiretroviral treatment (cART) mostly containing non-nucleoside reverse transcriptase inhibitors is poorly documented.

Methods

This prospective cohort study recruited 88 HIV-infected patients initiating cART between October 2004 and June 2005 in Cotonou, Benin. Patients were followed for 24 months. The main outcomes were incidence of lipodystrophy and metabolic disorders. Multivariate Cox proportional hazards regression models were used to describe factors associated with progression to lipodystrophy.

Results

After a median follow-up of 23.2 months (interquartile range 22.3–23.7), 24 (30%) patients developed lipodystrophy (lipoatrophy 9%, lipohypertrophy 24% and mixed pattern 2.5%). The incidence rate for lipodystrophy was estimated to 1.72 per person-month (95% confidence interval [CI] 1.15–2.56) occurring after a median time of 11 months on cART. Metabolic syndrome (International Diabetes Federation definition) appeared in 10 (13%) patients after a median of 15 months with an estimated incidence rate of 0.62 per person-month (95% CI 0.33–1.16). It was more common in women (19.2% versus 3.1% in men; P=0.043). Diabetes (8%) and hypercholesterolaemia (35%) were also observed. After adjustment, gender, young age (hazard ratio [HR] 0.45 [95% CI 0.22–0.90]; P=0.025), high BMI at inclusion (HR 1.53 [95% CI 1.28–1.83]; P<0.0001) and smoking (HR 28.0 [95% CI 2.5–307.4]; P=0.006) were significantly associated with lipohypertrophy.

Conclusions

Lipodystrophy and metabolic syndrome were commonly and rapidly observed in this cohort of sub-Saharan patients initiating cART.
Immunological responses during a virologically failing antiretroviral regimen are associated with in vivo synonymous mutation rates of HIV type-1 env
Authors: Mens Helene , Jørgensen Louise Bruun , Kronborg Gitte , Schønning Kristian , Benfield Thomas
Published: April 2022

Background

Little is known about the underlying causes of differences in immunological response to antiretroviral therapy during multidrug-resistant (MDR) HIV type-1 (HIV-1) infection. This study aimed to identify virological factors associated with immunological response during therapy failure.

Methods

Individuals with MDR HIV-1 receiving therapy for ≥3 months were included. CD4+ T-cell count slopes and pol and clonal env sequences were determined. Genetic analyses were performed using distance-based and maximum likelihood methods. Synonymous mutations rates of env were used to estimate viral replication.

Results

Of 1,000 patients treated between 1995 and 2003, 72 individuals fulfilled the definition for triple-class failure, but 25 were non-compliant, 21 were successfully resuppressed and 3 had died or quit therapy. Of the 23 that fulfilled study criteria, 16 had samples available for analysis. In a longitudinal mixed-effects model, plasma HIV-1 RNA only tended to predict immunological response ( P=0.06), whereas minor protease inhibitor (PI) and nucleoside reverse transcriptase (NRTI) mutations at baseline correlated significantly with CD4+ T-cell count slopes ( r=-0.56, P=0.04 and r=-0.64, P=0.008, respectively). Interestingly, synonymous mutations of env correlated inversely with CD4+ T-cell count slopes ( r=-0.60; P=0.01) and individuals with codons under positive selection had significantly better CD4+ T-cell responses than individuals without (0.42 versus -5.34; P=0.02).

Conclusions

Our results suggest that minor PI mutations and NRTI mutations present early during therapy failure are predictive of the CD4+ T-cell count slopes. Synonymous mutation rates of the env gene suggested that underlying differences in fitness could cause this association.
Virological relapse in chronic hepatitis C
Authors: Poordad F Fred , Flamm Steven L
Published: April 2022

Approximately one-third of all patients infected with hepatitis C virus (HCV) genotype 1 who complete pegylated interferon α-based therapy and have undetectable serum HCV RNA at the end of treatment will experience relapse. Although relapse is a common outcome of therapy, its pathology and strategies for optimal management are poorly understood; however, optimized ribavirin dosing is recognized as pivotal in mitigating relapse. Recent data also suggest that early viral kinetics might help identify particular patient groups, such as slow responders, who are predisposed to relapse. This review provides a comprehensive overview of the importance of relapse in patients with chronic hepatitis C, including its underlying pathobiology, potential predictors and strategies to optimize the retreatment of previous relapsers.
A review of the natural history of chronic hepatitis B in the era of transient elastography
Authors: Chan Henry Lik-Yuen , Wong Grace Lai-Hung , Wong Vincent Wai-Sun
Published: April 2022

Understanding the natural history of chronic hepatitis B is important in order to predict the prognosis, to stratify the risk of hepatocellular carcinoma and to select appropriate candidates for antiviral treatment. Liver fibrosis is the pathogenic process that leads to liver cirrhosis. The study of liver fibrosis in the past has largely been hampered by the invasive nature of a liver biopsy. Most liver biopsy series represent biased populations with more active disease. Transient elastography is a reliable and non-invasive measurement of liver fibrosis that allows the study of liver fibrosis among patients without clinical indication for liver biopsy. Large studies using transient elastography in patients with predominantly normal alanine aminotransferase levels have been reported recently. The different roles of patient age, hepatitis B virus DNA and alanine aminotransferase levels in the risk stratification for advanced liver fibrosis have been defined in hepatitis B e antigen-positive and hepatitis B e antigen-negative chronic hepatitis B patients. The relationship between metabolic syndrome and chronic hepatitis B is also explored. In this review, new insights from studies using transient elastography on the natural history of chronic hepatitis B with special focus on liver fibrosis will be summarized and discussed.
Antiviral Treatment for Chronic Hepatitis C in Illicit drug Users: A Systematic Review
Authors: Zanini Barbara , Lanzini Alberto
Published: April 2022

According to recent World Health Organization data, approximately 170–200 million people worldwide are infected with hepatitis C virus (HCV). At present, illicit drug users (IDUs) constitute the largest group of individuals infected with HCV in industrial countries. Between 50% and 90% of IDUs are estimated to be positive for anti-HCV antibodies and most of the new infections occur in IDUs. The aim of our review is to focus on tertiary prevention of HCV infection among IDUs. We review strategies to prevent HCV infection and disease progression, attitude to antiviral treatment, access to specific HCV therapy and data of efficacy and safety of antiviral treatment among IDUs.
Disulfide-mediated apoptosis of human T-lymphotrophc virus type-I (HTLV-I)-infected cells in patients with HTLV-I-associated myelopathy/ tropical spastic paraparesis
Authors: Nishiura Yoshihiro , Nakamura Tatsufumi , Fukushima Naomi , Nakamura Hideki , Ida Hiroaki , Aramaki Toshiyuki , Eguchi Katsumi
Published: April 2022

Background

This study was conducted to construct a basis for a therapeutic strategy against human T-lymphotropic virus type-I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) using a compound that contained a disulfide moiety, prosultiamine, which is a homologue of allithiamine originally synthesized by allicin and thiamine-thiol, for the targeting of HTLV-I-infected cells.

Methods

First, we analysed the apoptotic pathway in allicin or prosultiamine treatment against an HTLV-I-infected T-cell line (HCT-1), derived from an HAM/TSP patient, by flow cytometry and western blot. Second, we evaluated the effect of targeting HTLV-I-infected cells in a prosultiamine in vitro treatment and in a clinical trial in HAM/TSP patients by quantitative PCR analysis of HTLV-I proviral load.

Results

Prosultiamine, like allicin, induced caspase-dependent apoptosis against HCT-1 cells. The fact that the loss of mitochondrial membrane potential was recovered in z-VAD-fmk-pretreated HCT-1 cells with prosultiamine treatment suggested that prosultiamine can induce caspase-dependent apoptosis through the mitochondrial pathway. On the basis of data showing that prosultiamine in vitro treatment against peripheral blood CD4+ T-cells of HAM/TSP patients induced a significant decrease of HTLV-I proviral copy numbers by apoptosis of HTLV-I- infected cells, we treated six HAM/ TSP patients with intravenous administration of pro-sultiamine for 14 days. As a result of this treatment, the copy numbers of HTLV-I provirus in peripheral blood decreased to approximately 30–50% of their pretreat-ment levels with some clinical benefits in all patients.

Conclusions

Our results suggest that prosultiamine has the potential to be a new therapeutic tool that targets HTLV-I-infected cells in HAM/TSP.
Conserved domains and structure prediction of human cytomegalovirus UL27 protein
Authors: Hantz Sébastien , Couvreux Anthony , Champier Gaël , Trapes Laurène , Cotin Sébastien , Denis François , Bouaziz Serge , Alain Sophie
Published: April 2022

Background

The human cytomegalovirus (HCMV) nuclear UL27 protein (pUL27) could be involved at the stage of nuclear egress. Maribavir is a new anti-HCMV drug that targets nuclear egress through direct inhibition of the HCMV serine–threonine kinase, UL97 protein (pUL97). Because maribavir- resistance-related mutations are observed in both proteins, pUL27 is thought to interfere with pUL97 activity; however, its mechanism of action remains unclear.

Methods

As there is no available crystal structure for pUL27 or any known structures of its homologous proteins, we attempted to identify pUL27 functional domains by sequence analysis, identification of conserved domains, structure prediction and matching with previously known maribavir resistance mutations.

Results

The UL27 sequence analysis of 20 HCMV wild-type strains and 8 ganciclovir-resistant HCMV strains allowed us to describe four conserved domains, to localize the putative phosphorylation sites and to identify protein–protein interface domains, suggesting that pUL27 could interact with either pUL97 or itself.

Conclusions

Although the function of pUL27 is still unknown in the HCMV replication cycle, our approach identified target domains that appeared to be essential to the function of pUL27. This work provides a better understanding on the relative importance of each pUL27 mutation and could form the basis of later comparison analyses, when a three-dimensional structure of a pUL27 homologue will be available.
Lack of Effect on Survival of High-Dose Acyclovir and Zidovudine Compared with Zidovudine Alone for Acquired Immunodeficiency Syndrome
Authors: Collier Ann C , Schoenfeld David , Hirsch Martin , van der Horst Charles M , Davis L Gray , Stanley Ken , Corey Lawrence ,   for the AIDS Clinical Trials Group
Published: April 2022

To evaluate the effect of acyclovir on survival of adults with moderately advanced human immunodeficiency virus type 1 (HIV-1) infection, a randomized, double-blind, placebo-controlled study was conducted. A total of 334 adults with AIDS or a CD4 cell count less than 200 cells/mm3 were assigned to acyclovir 4 g per day or placebo, combined with zidovudine 500 mg per day. Characteristics of enrollees and duration of follow-up were similar in each treatment group. One-hundred and six patients died. No differences in survival were seen between treatment groups in any analyses, including intent-to-treat analyses and exploratory analyses censoring data after study therapy was discontinued, or in the subset of enrollees with CD4 cell counts less than 100 cells/mm3 or less than 50 cells/mm3. Types and time to first AIDS-defining diseases were similar in both groups. There were significantly fewer episodes of varicella-zoster virus ( P<0.0001) and herpes simplex virus ( P=0.0001) infection in patients assigned to acyclovir/zidovudine than to zidovudine alone. Both regimens had similar tolerability. These data do not support routine use of acyclovir as a treatment for HIV-1 infection.
Effect of Rimantadine on Induced Specific Serum Haemagglutination-Inhibiting Antibody and Nasal IgA Titres after Experimental Exposure of Adults to Influenza a Virus
Authors: Doyle William J , Skoner David P , Patel Asha , Hoyden Frederick G
Published: April 2022

Haemagglutination-inhibiting (HI) antibody and specific nasal IgA responses to infection with influenza A (H1N1) virus were compared between 35 rimantadine-treated subjects (100 mg, orally, twice daily from day 2 to day 10, post-challenge) and 36 placebo-treated subjects. Infection was documented in 29 (83%) and 34 (94%), viral shedding in 24 (69%) and 30 (83%), and seroconversion in 21 (60%) and 27 (75%) of the rimantadine- and placebo-treated subjects, respectively. The duration of virus shedding (1.7±1.6 days compared with 3.1±2.1 days) was significantly lower in the rimantadine-treated group. Both groups had significant increases in the HI (21 days post-challenge) and virus-specific nasal IgA antibody (7 days post-challenge) titres. Convalescent HI but not IgA antibody titre was significantly greater in the placebo group. Convalescent HI antibody titre correlated with virus shedding, suggesting that differences between treatment groups are attributable to the reduced duration of viral shedding in rimantadine-treated subjects.
Diminished HIV-1 Sensitivity to Stavudine in Patients on Prolonged Therapy Occurs Only at Low Levels and Cannot be Attributed to Any Single Amino Acid Substitution in Reverse Transcriptase
Authors: Salomon Horacio , Montaner Julio SG , Belmonte Antonietta , Wainberg Mark A
Published: April 2022

To study the extent to which phenotypic resistance to stavudine occurs under therapy, we studied 18 pairs of human immunodeficiency virus type 1 (HIV-1) isolates from patients both prior to and following 24–48 weeks of treatment with stavudine monotherapy or stavudine in combination with either didanosine or lamivudine. We also used a nested polymerase chain reaction (PCR) assay to probe for the presence of specific mutations associated in culture with stavudine resistance. The results showed that resistance to stavudine (≍3–10 fold) was observed in nine of ten cases of monotherapy, in three of four cases of therapy involving both stavudine and didanosine, and in two of four cases involving stavudine and lamivudine. Viruses from the four patients receiving stavudine plus didanosine became resistant to didanosine in only one instance while the use of lamivudine plus stavudine yielded resistance to lamivudine each time. Whereas changes in the reverse transcriptase (RT) genes of resistant isolates were frequently observed, two mutations, previously identified with stavudine resistance in tissue culture (i.e. V75T and I50T), could not be identified in the clinical samples by either direct sequencing of the RT gene or by PCR amplification. Thus, resistance to stavudine can occur, albeit at low levels, in the context of prolonged therapy with this drug but is not associated with specific mutations in HIV RT at either codons 75 or 50 in clinical samples.
Induction and Maintenance Treatment Regimens for HIV-1 Infection in Vitro
Authors: Oh Myoung-don , Merrill Debra P , Hirsch Martin S
Published: April 2022

Can aggressive anti-human immunodeficiency virus (HIV) induction regimens be simplified after sufficient virus suppression is achieved? In vitro studies were conducted to evaluate the hypothesis that aggressive induction regimens could be followed by less aggressive maintenance regimens. A clinical HIV-1 isolate and lymphoblastoid cell line (H9) were employed. Virus multiplicities were varied, as were drug inhibitory concentrations (IC90, IC99) and induction periods (1, 2 and 3 weeks) of a three-drug regimen (zidovudine plus lamivudine and indinavir), following which maintenance regimens (no drug, zidovudine alone, indinavir alone, zidovudine plus lamivudine) were employed. After 1 week inductions at IC99 concentrations, viral rebound occurred on none or one-drug maintenance regimens but not on a two-drug regimen. After 2 week inductions, viral rebound occurred with no-drug maintenance, but not with one- and two-drug regimens. After 3 week inductions, viral rebound did not occur in zero-, one-, or two-drug maintenance regimens, although HIV-1 DNA persisted in cultured cells. These studies suggest that although some induction–maintenance regimens will fail, after a sufficient period of HIV-1 suppression with a three-drug antiretroviral regimen, maintenance on fewer drugs may be feasible.
Safety and Efficacy of Once Daily Intranasal Zanamivir in Preventing Experimental Human Influenza a Infection
Authors: Calfee David P , Peng Amy W , Hussey Elizabeth K , Lobo Monica , Hayden Frederick G
Published: April 2022

Zanamivir, a potent inhibitor of influenza A and B virus neuraminidases, is protective against experimental human influenza when given intranasally twice daily. We conducted two studies to assess the pharmacokinetics and protective efficacy of a reduced frequency dosing regimen of topical zanamivir. In the first study, 36 uninfected volunteers received a single dose of zanamivir by intranasal spray (6.4 mg), intranasal drops (16 mg) or dry powder oral inhalation (10 mg). At 4 h, median nasal wash concentrations were 50-fold higher after intranasal dosing than after inhalation. Substantial levels (spray group, median 4596 ng/ml; drop group, 1239 ng/ml) were detected in nasal wash 48 h after intranasal dosing. In the double-blinded efficacy study, 47 sero-susceptible volunteers were randomized to receive either placebo or zanamivir intranasal spray (6.4 mg). Among the 43 subjects evaluated, decreases in viral shedding occurred in the group receiving one dose of zanamivir 4 h prior to inoculation, whereas no significant benefit was observed in those receiving a single dose 48 h prior to challenge. In the group given three daily doses, reductions were seen in viral shedding and infection. In the two regimens providing zanamivir 4 h prior to inoculation, significant reductions in nasal mucus weight were observed. Decreases in total symptom scores and the incidence of upper respiratory illness also occurred, but they did not reach statistical significance. The efficacy of a single dose of zanamivir given 4 h prior to inoculation supports the hypothesis that influenza virus neuraminidase is essential for initial virus spread through respiratory secretions. These findings indicate that once daily dosing of zanamivir is protective against experimental influenza A infection.
Selection and Characterization of HIV-1 Variants Resistant to the (+) and (-) Enantiomers of 2′-Deoxy-3′-Oxa-4′-Thiocytidine (Dotc)
Authors: Richard Nathalie , Quan Yudong , Salomon Horacio , Hsu Mayla , Bedard Jean , Harrigan P Richard , Rando Robert , Mansour Tarek , Bowlin Terry L , Wainberg Mark A
Published: April 2022

Human immunodeficiency virus type 1 (HIV-1) variants were selected for resistance against the (+) and (-) enantiomers of a novel nucleoside analogue, 2′-deoxy-3′-oxa-4′-thiocytidine (dOTC), using the infectious molecular clone HXB2D grown in the MT-4 line of human T cells. The variants selected with (+) dOTC were approximately 6–7-fold less sensitive than wild-type virus to this drug. Cloning and sequencing of the complete reverse transcriptase (RT) coding region of these variants identified the M184I mutation and further selection with virus containing the M184I substitution led to the appearance of an M184V mutation. In contrast, selection experiments performed with (-) dOTC yielded variants capable of growing in drug concentrations as high as 100 μM, but phenotypic analysis of these viruses revealed near wild-type 50% inhibitory concentration (IC50) values for this compound. Site-directed mutagenesis experiments in which the M184I and M184V mutations were introduced into HXB2D confirmed the importance of these mutations when viruses were grown in MT4 cells. However, wild-type IC50 values in regard to both (–) and (+) dOTC were obtained when these recombinant viruses were grown in cord blood mononuclear cells (CBMC). Clinical isolates of HIV-1 resistant to lamivudine and containing the M184V substitution also displayed low-level resistance to both (–) and (+) dOTC when grown in CBMC. Finally, cell-free RT assays were performed in the presence of either (–) dOTC triphosphate, (+) dOTC triphosphate, or the triphosphate of a racemic mixture of (+) and (–) dOTC with wild-type and mutated M184V-containing recombinant RT. The data demonstrate chain termination effects of these compounds with regard to both wild-type and mutated enzyme and that the latter was approximately twofold less sensitive than the former to these drugs.
Sensitivity and Resistance to (+)-Calanolide a of Wild-Type and Mutated Forms of HIV-1 Reverse Transcriptase
Authors: Quan Yudong , Motakis Dimitrios , Buckheit Robert , Xu Ze-Qi , Flavin Michael T , Parniak Michael A , Wainberg Mark A
Published: April 2022

We have tested both wild-type and drug-resistant mutated, recombinant human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) molecules for sensitivity to each of two non-nucleoside RT inhibitors (NNRTI), (+)-calanolide A and nevirapine, in primer extension assays. We found that RT containing either the V106A or Y181C substitutions, associated with NNRTI resistance, displayed ≍90-fold resistance to nevirapine but remained fully sensitive to (+)-calanolide A and that the Y181C mutation marginally enhanced susceptibility to the latter drug. In contrast, the Y188H substitution in RT resulted in about 30-fold resistance to (+)-calanolide A in these assays but did not result in diminished sensitivity to nevirapine. Tissue culture results indicated that the combination of (+)-calanolide A and nevirapine possessed an additive to weakly synergistic effect in blocking replication of HIV-1 in tissue culture. These results suggest that (+)-calanolide A and nevirapine might have rationale as a combination therapy for HIV disease.
Reducing Islamophobia: An assessment of psychological mechanisms that underlie anti-Islamophobia media interventions
Authors: Moore-Berg Samantha L. , Hameiri Boaz , Falk Emily , Bruneau Emile
Published: April 2022

Western countries have witnessed increased hostility towards Muslims among individuals, and structurally in the ways that the media covers stories related to Islam/Muslims and in policies that infringe on the rights of Muslim communities. In response, practitioners have created media interventions that aim to reduce Islamophobia. However, it is unclear what causal effects these interventions have on reducing Islamophobia. Here, we test the effects of 11 media interventions developed by practitioners with an intervention tournament among U.S. samples. In Study 1, we identified three videos that most effectively reduced Islamophobia both immediately after watching and 1 month later. In Studies 2–4, we examined the psychological mechanisms of these successful videos and found an indirect effect of the interventions on reduced support for anti-Muslim policies through recognition of media bias against Muslims. This research highlights that drawing attention to structural biases, including biased media coverage of Muslims, is one potential strategy for ameliorating Islamophobia.
Static effect of assembled beam bridge under statistical and stable traffic flow load
Authors: Yao Zufeng , Dan Danhui , Zhao Rui , Ma Shengqiang
Published: April 2022

The live load effect of bridge structure caused by traffic flow load is the largest in the sum of all live load effects. Study on the strain and deflection of the assembled beam bridge under the statistical stable traffic flow load can reveal the static effect and dynamic response law of the structure, and then evaluate the service performance of the structure. In this paper, the advanced bridge structure health monitoring technology is used to collect and analyze the traffic flow load parameters. First, according to the probability distribution function of each parameter in the traffic flow load model, the statistical stable traffic flow load is synthesized and the simplified bridge mechanical model is applied. Second, the variance and relative entropy are used to judge the statistical stability of the expectation, variance and probability density function of the static effect. Finally, the evolution law of the expectation, variance and probability density function of the static effect at different locations on the prefabricated beams of the whole bridge deck is analyzed when the static effect reaches the state of statistical stability.
Social value of the child in the global south: A multifaceted concept
Authors: Qamar Azher Hameed
Published: April 2022

The term “the value of the child” was coined by economists in the context of demographic transition and fertility, emphasizing economic and cultural aspects. However, the scope of the value of the child was confined to a cost-benefit analysis. The “social value of the child” is a comprehensive concept that encompasses the economic, psychological, social, and cultural value of the child. Contextual knowledge of childhood was emphasized with the emergence of the sociology of childhood, taking into account the diversity of children’s lives affected by cultural and institutional contexts across the world. This essay offers a synopsis of the social value of the child and the social construction of the value of the child in the global south. The global south represents the complex socio-cultural context of the majority world, wherein modern or global theories of childhood originating in the global north are contested. This brief article concludes that studies emphasizing the value of the children in the global south should investigate the intricate and relevant interconnections between the psychological, familial, and religious value of the child, all of which contribute to the social value of the child.
Exploring How U.S. High School Staff Support, Protect, and Affirm Sexual and Gender Minority Youth: Methods and Lessons Learned from a Qualitative Interview Study
Authors: Coulter Robert WS , Henderson Emmett R , Corey Stephanie L , Gagnon Kelly , Chugani Carla D , Egan James E , Murphy Courtney E , Plenn Eion R , Routh Nina , Roig Alyssa , Miller Elizabeth
Published: April 2022

Background. Sexual and gender minority youth (SGMY) experience health inequities compared with cisgender heterosexuals, and these inequities are heightened in areas with high structural stigma. Quantitative research shows school assets (e.g., adult support) are associated with better health for SGMY. Though some qualitative studies elucidated how school staff support SGMY, none have triangulated such strategies in a geographically and sociodemographically diverse sample of school staff and SGMY. This paper describes a multi-perspective qualitative study design and offers lessons learned from conducting such a study. Methods. Using a novel stratified sampling frame, we interviewed 60 SGMY and 29 school staff who attended/worked at high schools in U.S. states with low, medium, and high structural stigma. To ensure sociodemographic diversity, we constructed sampling quotas, and recruited SGMY using social media and staff using a multi-pronged approach. Results. The stratified sampling strategy met our goal of enrolling diverse SGMY and staff participants. SGMY participants attended schools in low ( n = 20), medium ( n = 22), and high ( n = 18) structural stigma states. We enrolled 18 cisgender girls, 18 cisgender boys, and 24 gender minority youth. Fifty-three percent of SGMY were youth of color, and 45% attended schools in rural areas. School staff participants worked at schools in low ( n = 11), medium ( n = 11), and high ( n = 7) structural stigma states. School staff participants were 55% heterosexual, 91% cisgender, and had diverse roles (e.g., teacher, principal, librarian, and nurse). Conclusions. This paper describes new methods for collecting qualitative data from diverse SGMY and school staff. Some lessons learned from this study include the importance of using trauma-informed interviewing methods, having a suicidality safety protocol, establishing a priori sampling quotas, and creating tailored social media advertisements. With these data we will explore the heterogeneity of SGMY and school staff experiences across varying structural stigma levels, yielding foundational information for future school-based interventions.
Popliteal artery pseudoaneurysms in patients affected by osteochondroma
Authors: Miri Rim , Mazzaccaro Daniela , Ziadi Jalel , Derbel Bilel , Daoud Zied , Ben Mrad Imtinene , Ben Mrad Melek , Righini Paolo , Giannetta Matteo , Nano Giovanni , Denguir Raouf
Published: April 2022

Although exostosis or osteochondroma is a common bone tumor, associated vascular complications are rare. Clinical and radiological diagnoses are sometimes challenging, and there is no codification for surgical management. We report two cases of popliteal arterial pseudoaneurysms due to osteochondroma of the distal femur. A review of the current literature about case series and case reports of patients affected by arterial pseudoaneurysm complicating osteochondroma was also performed.
Extracellular signal-regulated kinase phosphorylation enhancement and NaV1.7 sodium channel upregulation in rat dorsal root ganglia neurons contribute to resiniferatoxin-induced neuropathic pain: The efficacy and mechanism of pulsed radiofrequency therapy
Authors: Hidaka Kotaro , Maruta Toyoaki , Koshida Tomohiro , Kurogi Mio , Kage Yohko , Kouroki Satoshi , Shirasaka Tetsuro , Takeya Ryu , Tsuneyoshi Isao
Published: April 2022

Pulsed radiofrequency (PRF) therapy is one of the most common treatment options for neuropathic pain, albeit the underlying mechanism has not been hitherto elucidated. In this study, we investigated the efficacy and mechanism of PRF therapy on resiniferatoxin (RTX)-induced mechanical allodynia, which has been used as a model of postherpetic neuralgia (PHN). Adult male rats were intraperitoneally injected with a vehicle or RTX. Furthermore, PRF current was applied on a unilateral sciatic nerve in all RTX-treated rats. On both ipsilateral and contralateral sides, the paw mechanical withdrawal thresholds were examined and L4-6 dorsal root ganglia (DRG) were harvested. In the DRG of rats with RTX-induced mechanical allodynia, NaV1.7, a voltage-gated Na+ channel, was upregulated following the enhancement of extracellular signal-regulated kinase phosphorylation. Early PRF therapy, which was applied 1 week after RTX exposure, suppressed this NaV1.7 upregulation and showed an anti-allodynic effect; however, late PRF therapy, which was applied after 5 weeks of RTX exposure, failed to inhibit allodynia. Interestingly, late PRF therapy became effective after daily tramadol administration for 7 days, starting from 2 weeks after RTX exposure. Both early PRF therapy and late PRF therapy combined with early tramadol treatment suppressed NaV1.7 upregulation in the DRG of rats with RTX-induced mechanical allodynia. Therefore, NaV1.7 upregulation in DRG is related to the development of RTX-induced neuropathic pain; moreover, PRF therapy may be effective in the clinical management of patients with PHN via NaV1.7 upregulation inhibition.
How should interventions to treat hand oedema be delivered? An online Delphi Consensus Method
Authors: Miller Leanne K , Jerosch-Herold Christina , Shepstone Lee
Published: April 2022

Introduction

Hand oedema (swelling) is a common consequence of hand trauma or surgery, but there is little agreement on how interventions to treat hand oedema should be delivered in practice. The purpose of this study was to engage a group of self-identified hand therapy experts to develop consensus on how four commonly used oedema management treatments should be implemented, which could be used in clinical practice or future clinical trials.

Method

A web-based Delphi study was conducted with eight volunteer hand therapists who met the pre-defined eligibility criteria for an ‘expert’ and were members of the British Association of Hand Therapists (BAHT). An a priori level of agreement was set at 75%. Interventions requiring consensus were decided on as a result of a previous national survey of practice and consisted of compression, elevation, massage and kinesiology tape.

Results

A total of 25 items were discussed across 3 rounds. This ranged from 23 items in round 1, to three items in round 3. In round 1, consensus was reached on 7/23 (30%) items. The required 75% consensus was reached on 14 items in round 2 and 1/3 items achieved consensus in round 3. Massage was the only treatment that required a third round.

Discussion

Consensus was reached on intervention description for three of the four modalities including the materials used (what), method of application including duration and frequency (when and how much) and tailoring or modifications. Two questions relating to massage did not reach the required consensus threshold and a majority agreement was accepted. The small panel size is a limitation and may affect the credibility of the consensus reached.
Renal abscess in children: Is size an important determinant in deciding treatment options?
Authors: Jain Prashant , Prasad Ashish , Sharma Rachna , Jain Sarika
Published: April 2022

Background:

Renal abscess (RA) is rarely seen in the paediatric age group. The proposed management protocols are mainly derived from the adult series which may not be appropriate in children.

Objective:

In this retrospective analysis of cases with renal and perinephric abscesses, the objective is to correlate the clinical presentation, radiological findings and treatment options and also to propose a paediatric-specific practical management algorithm.

Study design:

This is a retrospective study of cases with renal and perinephric abscesses admitted between March 2012 and February 2020. The patients were reviewed for demographics, presentation, predisposing factors, laboratory investigations, imaging, management and outcome.

Results:

Analysis of 12 paediatric patients (13 renal units) with RA (median age 4 years) was done. Organisms were isolated in 8 of 12 (66.6%) patients with Gram-negative organisms being the commonest. On admission, all patients were started on empirical broad-spectrum antibiotics. Except for two patients who were critically ill with frank sepsis and had a tender renal lump, the rest of them were initially offered conservative management with intravenous antibiotics, and the response was reviewed after 48–72 hours. Of five units with abscess size of ⩽3 cm, two units (40%) responded to conservative management, while three units (60%) required intervention, and of eight units of size >3 cm, three units (37.5%) responded to conservative management and five units (62.5%) required intervention. None of the abscesses with perinephric collection (30.7%) responded to antibiotics and required intervention.

Conclusion:

A protocol based on the size of RA as recommended in most of the adult series may not be appropriate in the paediatric age group because of the differences in clinical presentation, predisposing factors and immune response. The clinical condition on presentation, response to antibiotic therapy and the presence of perinephric collection should be considered as an important determinant in deciding the need for intervention.

Level of evidence:

4
Effects of Perioperative Fascia Iliaca Compartment Block on Postoperative Pain and Hip Function in Elderly Patients With Hip Fracture
Authors: Hao Chao , Li Chao , Cao Ruiqi , Dai Yike , Xu Chongyang , Ma Lifeng , Guo Ai , Yu Haomiao
Published: April 2022

Purpose

Pain management is a challenging issue in elderly patients with hip fracture. Despite the accepted clinical outcomes following hip surgery, pain and prolonged recovery time are the most difficult consequences associated with the rehabilitation process. The purpose of this study was to evaluate pain relief and functional improvement associated with the Fascia Iliaca Compartment Block (FICB) during the perioperative period of elderly patients with hip fracture.

Patients and methods

This study included 120 elderly patients with hip fracture, who were admitted to our institution between January 2019 and December 2020. The participants were subsequently randomly divided into the routine analgesia (RA) and fascia iliaca compartment block (FICB) groups. Inter-group differences were compared via VAS scores at rest and during movement, Harris hip scores (HHS), presence of complications, adverse events after surgery, and length of hospital stay.

Results

The FICB group VAS scores at rest at 6 hour, 1 and 3 days, and 1 week after surgery were significantly lower than the RA group ( P < .05). Moreover, the FICB group VAS scores with movement were markedly lower at 6 hour, 1 and 3 days, as well as 1 and 2 weeks after surgery ( P < .05). The HHS of the FICB and RA groups were (53.41±8.63) and (40.02±9.61), respectively, on the seventh day after surgery, and the difference was statistically significant ( P < .05). The incidence of postoperative complications and adverse events in the FICB group were not statistically different from the RA group. The average hospital stay of the FICB group was 2.12 days shorter than the RA group, but the difference did not reach statistical significance ( P = .13).

Conclusion

FICB provides superior analgesic effect both at rest and with movement, along with rapid short-term recovery of hip function following surgery in elderly patients with hip fracture, without increasing postoperative complications or adverse events.
Implementation of a Capacity-Building Framework to Improve School Climate in an Urban School System
Authors: Solomon Bonnie J. , Stratford Brandon , Steed Heather , Sun Sarah , Temkin Deborah
Published: April 2022

Mounting evidence suggests that a positive school climate can promote learning and well-being for students and reduce bullying and other forms of violence. However, many schools lack the capacity needed to engage in comprehensive school climate improvement. As part of a broader evaluation, this study examines implementation of a capacity-building framework for school climate improvement that emphasizes shared leadership and data-informed decision making. Semi-structured interviews were conducted with points of contact at schools receiving technical assistance and those that were allowed to work through the framework on their own. Interviews were also conducted with technical assistance specialists working with schools randomly assigned to receive the intervention. Analyses explored three key research questions: 1 What factors contributed to schools’ initial decision to participate in the project? 2 What factors were associated with sustained engagement? and 3 To what extent did schools build organizational capacity through participation? Organizational readiness, including both motivation and general organizational capacity, emerged as a key facilitator of sustained engagement. In particular, the presence of a champion was facilitative despite the framework’s emphasis on shared leadership. Staff turnover and competing priorities were identified as common challenges. With technical assistance, schools that were able to invest time and effort in the framework perceived growth in their capacity for shared leadership and data literacy. However, technical assistance specialists did not feel adequately prepared to support schools in implementing the framework. Our discussion focuses on implications for evidence-based technical assistance and implementing comprehensive climate improvement efforts in urban schools.
Patient-specific comorbidities as prognostic variables for survival in myelofibrosis
Authors: Sochacki Andrew L. , Bejan Cosmin Adrian , Zhao Shilin , Patel Ameet , Kishtagari Ashwin , Spaulding Travis P. , Silver Alexander J. , Stockton Shannon S. , Pugh Kelly , Dorand R. Dixon , Bhatta Manasa , Strayer Nicholas , Zhang Siwei , Snider Christina A. , Stricker Thomas , Nazha Aziz , Bick Alexander G. , Xu Yaomin , Savona Michael R.
Published: April 2022

Treatment decisions in primary myelofibrosis (PMF) are guided by numerous prognostic systems. Patient-specific comorbidities have influence on treatment-related survival and are considered in clinical contexts but have not been routinely incorporated into current prognostic models. We hypothesized that patient-specific comorbidities would inform prognosis and could be incorporated into a quantitative score. All patients with PMF or secondary myelofibrosis with available DNA and comprehensive electronic health record (EHR) data treated at Vanderbilt University Medical Center between 1995 and 2016 were identified within Vanderbilt’s Synthetic Derivative and BioVU Biobank. We recapitulated established PMF risk scores (eg, Dynamic International Prognostic Scoring System [DIPSS], DIPSS plus, Genetics-Based Prognostic Scoring System, Mutation-Enhanced International Prognostic Scoring System 70+) and comorbidities through EHR chart extraction and next-generation sequencing on biobanked peripheral blood DNA. The impact of comorbidities was assessed via DIPSS-adjusted overall survival using Bonferroni correction. Comorbidities associated with inferior survival include renal failure/dysfunction (hazard ratio [HR], 4.3; 95% confidence interval [95% CI], 2.1-8.9; P = .0001), intracranial hemorrhage (HR, 28.7; 95% CI, 7.0-116.8; P = 2.83e-06), invasive fungal infection (HR, 41.2; 95% CI, 7.2-235.2; P = 2.90e-05), and chronic encephalopathy (HR, 15.1; 95% CI, 3.8-59.4; P = .0001). The extended DIPSS model including all 4 significant comorbidities showed a significantly higher discriminating power (C-index 0.81; 95% CI, 0.78-0.84) than the original DIPSS model (C-index 0.73; 95% CI, 0.70-0.77). In summary, we repurposed an institutional biobank to identify and risk-classify an uncommon hematologic malignancy by established (eg, DIPSS) and other clinical and pathologic factors (eg, comorbidities) in an unbiased fashion. The inclusion of comorbidities into risk evaluation may augment prognostic capability of future genetics-based scoring systems.