bluuebunny/crossref_metadata_2025 huggingface dataset:
Asiatic acid inhibits intracellularShigella flexnerigrowth by inducing antimicrobial peptide gene expression
Authors: Maitra Priyanka , Basak Priyanka , Okamoto Keinosuke , Miyoshi Shin-ichi , Dutta Shanta , Bhattacharya Sushmita
Published: March 2023

Aims

A rapid rise in resistance to conventional antibiotics for Shigella spp. has created a problem in treating shigellosis. Hence, there is an urgent need for new and non-conventional anti-bacterial agents. The aim of this study is to show how Asiatic acid, a plant-derived compound, inhibits the intracellular growth of Shigella flexneri.

Methods and results

Shigella flexneri sensitive and resistant strains were used for checking antimicrobial activity of Asiatic acid by gentamicin protection assay. Asiatic acid inhibited the intracellular growth of all strains. Gene expression analysis showed antimicrobial peptide (AMP) up-regulation by Asiatic acid in intestinal cells. Further western blot analysis showed that ERK, p38, and JNK are activated by Asiatic acid. ELISA was performed to check IL-8, IL-6, and cathelicidin secretion. The antibacterial effect of Asiatic acid was further verified in an in vivo mouse model.

Conclusions

The reason behind the antibacterial activities of Asiatic acid is probably over-expression of antimicrobial peptide genes. Besides, direct antimicrobial activities, antimicrobial peptides also carry immunomodulatory activities. Here, Asiatic acid increased IL-6 and IL-8 secretion to induce inflammation. Overall, Asiatic acid up-regulates antimicrobial peptide gene expression and inhibits intracellular S. flexneri growth. Moreover, Asiatic acid reduced bacterial growth and recovered intestinal tissue damages in in vivo mice model.
Prevalence of Eye and Vision Disorders in the Military Health System, Fiscal Year 2018
Authors: Slepski Natalie E , Jackson Kevin M , Mitro Jessica Pope , Banaag Amanda , Madsen Cathaleen , Wittenborn John , Koehlmoos Tracey Pérez
Published: March 2023

Introduction

Eye and vision disorders are estimated to impact 7.08 million people in the United States, including 1.62 million under the age of 40. This study uses the Vision and Eye Health Surveillance System (VEHSS) case definitions to assess the burden of eye and vision disorders in a universally insured, nationally representative population.

Materials and Methods

This retrospective, cross-sectional study applied the VEHSS case definitions to TRICARE claims data collected from the Military Health System Data Repository and Defense Enrollment Eligibility Reporting System during 2018. Beneficiaries aged 0-64 years during the fiscal year 2018 were identified with inpatient and outpatient codes matching to the VEHSS diagnostic case definitions, which were organized into 17 categories of eye and vision disorders classified by the ICD-10. Beneficiaries were recorded only once per category but allowed to match to multiple categories. Analyses included descriptive statistics of patient demographics and prevalence of eye disorders.

Results

We identified 4,548,897 TRICARE Prime/Plus beneficiaries (54.86% men and 45.14% women), of whom 22.93% were diagnosed with at least one disorder in 2018. Of those with a diagnosis, the majority were men (50.13%), adults (74.91%), and of or sponsored by a senior enlisted rank (57.83%), used as socioeconomic proxy. Disorders of refraction and accommodation were most prevalent, followed by infectious and inflammatory diseases. Potentially preventable and treatable conditions, including amblyopia and strabismus, infectious and inflammatory disease, and diabetic complications, affected up to 22% of those with vision disorders.

Conclusions

This study represents the first use of VEHSS measures in a universally insured, socioeconomically diverse population. Identification of potentially treatable or preventable conditions indicates significant opportunity to mitigate the burden of eye and vision disorders in the Military Health System.
Regional anesthesia as part of enhanced recovery strategies in pediatric cardiac surgery
Authors: Yamamoto Tomohiro , Schindler Ehrenfried
Published: March 2023

Purpose of review

The purpose of this review article was to highlight the enhanced recovery protocols in pediatric cardiac surgery, including early extubation, rapid mobilization and recovery, reduction of opioid-related side effects, and length of pediatric ICU and hospital stay, resulting in decreased costs and perioperative morbidity, by introducing recent trends in perioperative anesthesia management combined with peripheral nerve blocks.

Recent findings

Efficient postoperative pain relief is essential for realizing enhanced recovery strategies, especially in pediatric patients. It has been reported that approaches to perioperative pain management using additional peripheral nerve blocks ensure early extubation and a shorter duration of ICU and hospital stay. This article provides an overview of several feasible musculofascial plane blocks to achieve fast-track anesthesia management for pediatric cardiac surgery.

Recent remarkable advances in combined ultrasound techniques have made it possible to perform various peripheral nerve blocks. The major strategy underlying fast-track anesthesia management is to achieve good analgesia while reducing perioperative opioid use. Furthermore, it is important to consider early extubation not only as a competition for time to extubation but also as the culmination of a qualitative improvement in the outcome of treatment for each patient.
The impact of air pollution and endocrine disruptors on reproduction and assisted reproduction
Authors: Seli Denis A. , Taylor Hugh S.
Published: March 2023

Purpose of review

Rapid increase in world population accompanied by global industrialization has led to an increase in deployment of natural resources, resulting in growing levels of pollution. Here, we review recent literature on the impact of environmental pollution on human reproductive health and assisted reproduction outcomes, focusing on two of the most common: air pollution and endocrine disruptors.

Recent findings

Air pollution has been associated with diminished ovarian reserve, uterine leiomyoma, decreased sperm concentration and motility. Air pollution also correlates with decreased pregnancy rates in patients undergoing infertility treatment using in-vitro fertilization (IVF). Similarly, Bisphenol A (BPA), a well studied endocrine disrupting chemical, with oestrogen-like activity, is associated with diminished ovarian reserve, and abnormal semen parameters, while clinical implications for patients undergoing infertility treatment remain to be established.

There is convincing evidence that environmental pollutants may have a negative impact on human health and reproductive potential. Air pollutions and endocrine disrupting chemicals found in water and food seem to affect male and female reproductive function. Large-scale studies are needed to determine the threshold values for health impact that may drive targeted policies.
Closed Incision Negative Pressure Therapy versus Standard of Care in Reduction of Surgical Site Complications: A Systematic Review and Meta-analysis
Authors: Cooper H. John , Singh Devinder P. , Gabriel Allen , Mantyh Christopher , Silverman Ronald , Griffin Leah
Published: March 2023

Introduction:

Closed incision negative pressure therapy (ciNPT) has been utilized to help manage closed incisions across many surgical specialties. This systematic review and meta-analysis evaluated the effect of ciNPT on postsurgical and health economic outcomes.

Methods:

A systematic literature search using PubMed, EMBASE, and QUOSA was performed for publications written in English, comparing ciNPT to standard-of-care dressings between January 2005 and August 2021. Study participant characteristics, surgical procedure, dressings used, treatment duration, postsurgical outcomes, and follow-up data were extracted. Meta-analyses were performed using random-effects models. Risk ratios summarized dichotomous outcomes. Difference in means or standardized difference in means was used to assess continuous variables reported on the same scale or outcomes reported on different scales/measurement instruments.

Results:

The literature search identified 84 studies for analysis. Significant reductions in surgical site complication (SSC), surgical site infection (SSI), superficial SSI, deep SSI, seroma, dehiscence, skin necrosis, and prolonged incisional drainage were associated with ciNPT use (P < 0.05). Reduced readmissions and reoperations were significant in favor of ciNPT (P < 0.05). Patients receiving ciNPT had a 0.9-day shorter hospital stay (P < 0.0001). Differences in postoperative pain scores and reported amounts of opioid usage were significant in favor of ciNPT use (P < 0.05). Scar evaluations demonstrated improved scarring in favor of ciNPT (P < 0.05).

Discussion:

For these meta-analyses, ciNPT use was associated with statistically significant reduction in SSCs, SSIs, seroma, dehiscence, and skin necrosis incidence. Reduced readmissions, reoperation, length of hospital stay, decreased pain scores and opioid use, and improved scarring were also observed in ciNPT patients.
First Dorsal Metacarpal Artery-pedicled Second Metacarpal Vascularized Bone Graft for Nonunion after Thumb Carpometacarpal Arthrodesis
Authors: Komura Shingo , Hirakawa Akihiro , Hirose Hitoshi , Akiyama Haruhiko
Published: March 2023

Arthrodesis is a reliable surgical procedure for treating thumb carpometacarpal osteoarthritis. However, the most frequent and problematic complication of arthrodesis is nonunion. Although postarthrodesis-related nonunion is a common complication, the indications and results of revision procedures for this pathological condition have not been well documented. A 59-year-old man underwent arthrodesis for thumb carpometacarpal osteoarthritis, which resulted in painful nonunion 7 months after the surgery. We performed revision surgery for this pathological condition, using first dorsal metacarpal artery-pedicled second metacarpal vascularized bone graft. This method resulted in successful bone union and pain relief. First dorsal metacarpal artery-pedicled second metacarpal vascularized bone grafting could be an alternative method for nonunion, which is a common complication after thumb carpometacarpal arthrodesis.
The Isabel Differential Diagnosis Generator for Orbital Diagnosis
Authors: Ing Edsel B. , Balas Michael , Nassrallah Georges , DeAngelis Dan , Nijhawan Navdeep
Published: March 2023

Purpose:

The Isabel differential diagnosis generator is one of the most widely known electronic diagnosis decision support tools. The authors prospectively evaluated the utility of Isabel for orbital disease differential diagnosis.

Methods:

The terms “proptosis,” “lid retraction,” “orbit inflammation,” “orbit tumour,” “orbit tumor, infiltrative” and “orbital tumor, well-circumscribed” were separately input into Isabel and the results were tabulated. Then the clinical details (patient age, gender, signs, symptoms, and imaging findings) of 25 orbital cases from a textbook of orbital surgery were entered into Isabel. The top 10 differential diagnoses generated by Isabel were compared with the correct diagnosis.

Results:

Isabel identified hyperthyroidism and Graves ophthalmopathy as the leading causes of lid retraction, but many common causes of proptosis and orbital tumors were not correctly elucidated. Of the textbook cases, Isabel correctly identified 4/25 (16%) of orbital cases as one of its top 10 differential diagnoses, and the median rank of the correct diagnosis was 6/10. Thirty-two percent of the output diagnoses were unlikely to cause orbital disease.

Conclusion:

Isabel is currently of limited value in the mainstream orbital differential diagnosis. The incorporation of anatomic localizations and imaging findings may help increase the accuracy of orbital diagnosis.
Ocular Surface Metrics in Blepharospasm Patients After Treatment With Botulinum Toxin Injections
Authors: Yabumoto Cristina , Osaki Midori H. , Osaki Teissy , Gameiro Gustavo R. , Campos Mauro , Osaki Tammy H.
Published: March 2023

Purpose:

The purpose of this study was to assess blepharospasm patients regarding the effect of botulinum toxin in ocular surface parameters.

Methods:

A prospective study was performed in blepharospasm patients treated with onabotulinumtoxinA. A smartphone (iPhone 6S, Apple) and custom-made software were used to record the eyelid movements for 3 minutes in a standardized manner. Optical coherence tomography of the tear meniscus was used to assess the tear meniscus area. Tear break-up time and the Ocular Surface Disease Index questionnaire were also evaluated. Patients were assessed before and 15 days after botulinum toxin injections.

Results:

Forty eyes of 20 patients were evaluated. The frequency of the spontaneous eyelid movements was significantly reduced after treatment (23.18 ± 12.85 movements/min vs. 9.29 ± 6.87 movements/min; p < 0.0001). Significant increases in the tear meniscus area (0.020 ± 0.015 mm2 vs. 0.057 ± 0.104 mm2; p = 0.01) and in break-up time (4.2 ± 1.2 seconds vs. 5.1 ± 1.3 seconds; p = 0.03) were observed 15 days after treatment. A significant reduction in the Ocular Surface Disease Index (59.05 ± 19.04 vs. 21.2 ± 19.5; p < 0.0001) was also observed.

Conclusion:

Significant changes in the tear meniscus area, break-up time, and Ocular Surface Disease Index after treatment reflect the effect of botulinum toxin on the lacrimal pump and in the improvement of dry eye symptoms. Reduction of eyelid spasms after treatment in blepharospasm patients was demonstrated using a smartphone and custom-made software. Thus, beyond relieving eyelid spasms, botulinum toxin injections were associated with subjective and objective improvement of dry eye parameters in patients with blepharospasm.
Musical Mistuning Perception and Appraisal in Cochlear Implant Recipients
Authors: Kösemihal Ebru , Yüksel Mustafa , Cesur Sidika , Çiprut Ayça
Published: March 2023

Objective

Music is a very crucial art form that can evoke emotions, and the harmonious presence of the human voice in music is an impactful part of this process. As a result, vocals have had some significant effects on contemporary music. The mechanism behind the cochlear implant (CI) recipients perceiving different aspects of music is clear; however, how well they perceive vocal tuning within music it is not well known. Hence, this study evaluated the mistuning perception of CI recipients and compared their performance with normal-hearing (NH) listeners.

Study Design, Setting, and Patients

A total of 16 CI users (7 cisgender men, 9 cisgender women) and 16 sex-matched NH controls with an average age of 30.2 (±10.9; range, 19–53) years and 23.5 (±6.1; range, 20–37) years, respectively, were enrolled in this study. We evaluated the mistuning ability using the mistuning perception test (MPT) and assessed self-perceived music perception and engagement using the music-related quality-of-life questionnaire. Test performance was measured and reported on the item-response theory metric with a z score ranging from −4 to +4.

Results

A significant difference in the MPT scores was found between NH and CI recipients, whereas a significant correlation was noted between the music-related quality-of-life questionnaire–frequency subscale and MPT scores. No significant correlations were found between age, CI age, and CI usage duration and MPT performance.

Conclusions

This study revealed that musical mistuning perception is a limitation for CI recipients, similar to previously evaluated aspects of music perception. Hence, it is important to consider this aspect in the assessment of music perception, enjoyment, and music-based auditory interventions in CI recipients, as vocals are paramount in music perception and recreation. The MPT is a convenient and accessible tool for mistuning assessment in CI and hearing-aid users.
Triglyceride-rich lipoproteins, remnant-cholesterol, and atherosclerotic cardiovascular disease
Authors: Ganda Om P.
Published: March 2023

Purpose of review

Despite indisputable role of LDL-C lowering, a considerable residual risk for atherosclerotic cardiovascular disease (ASCVD) persists. The precise mechanism(s) underlying this phenomenon remain unclear. Triglyceride-rich lipoproteins (TRL) appear to be one of the main mediators, based on the genetic and epidemiologic data. However, whether this is caused by direct effects of Triglycerides or other components of TRL remains uncertain. The cholesterol component of TRL remnants (Rem-C) has been proposed as a more pertinent mediator of the increased risk associated with high triglycerides.

Recent findings

Several long-term observational studies have shown a significant relationship between Rem-C and ASCVD events, compared with other triglyceride-related parameters. Recent trials have shown that lowering of triglyceride levels by various agents, including fibrates and omega-3 fatty acids, in statin-treated subjects, did not explain the reduction in ASCVD events. In a large clinical trial with pemafibrate, a highly selective PPAR-α agonist, in type 2 diabetes and elevated triglycerides, the reduction in triglycerides was accompanied by a significant increase in LDL-C and Apo-B levels, despite a reduction in Rem-C, and no effect on ASCVD events.

Elevated Rem-C as a risk determinant, with LDL-C at goal, requires additional studies in clinical trials. Standardization and accuracy of Rem-C assays (calculated versus direct method) is also needed.
Is human immunodeficiency virus a risk factor for the development of nonunion?—a case–control study
Authors: Graham Simon Matthew , Maqungo Sithombo , Laubscher Maritz , Ferreira Nando , Held Michael , Harrison William James , Simpson A. Hamish , MacPherson Peter , Lalloo David G.
Published: March 2023

Objective:

Human immunodeficiency virus (HIV) infection has been suggested to be associated with an increased risk of the development of nonunion after a fracture. This prospective matched case–control study in South Africa investigated common risk factors, including HIV status, that influence the development of a nonunion after a femur or tibia fracture.

Methods:

Adult participants (cases) with established nonunions of the femur or tibia shaft were recruited over a 16-month period, between December 2017 and April 2019. They were matched for (1) age; (2) sex; (3) fracture site; and (4) fracture management type, with “control” participants who progressed to fracture union within 6 months of injury. All participants were tested for HIV. Multivariable logistic regression models were constructed to investigate associations between known risk factors for the development of nonunion and impaired fracture healing.

Results:

A total of 57 cases were matched with 57 “control” participants (44/57 male, 77.2% vs. 13/57 female, 22.8%, median age 36 years). HIV status was not associated with the development of nonunion after the management of tibia and femur fractures, on both univariate (odds ratio, 0.40; confidence interval, 0.10–1.32; P = 0.151) or multivariable (odds ratio, 0.86; confidence interval, 0.18–3.73; P = 0.831) analysis. No other confounding factors were shown to have any statistically significant impact on the odds of developing nonunion in this study cohort.

Conclusion:

This study demonstrates that HIV does not seem to increase the risk of the development of nonunion and HIV-positive individuals who sustain a fracture can be managed in the same manner as those who are HIV negative.
Suicidal Behavior and Difficulty of Patients, as Perceived by Community Mental Health Nurses
Authors: van Veen Mark , Koekkoek Bauke , Kloos Margot , Braam Arjan W.
Published: March 2023

Background:

Mental health professionals who work in community mental health services play an important role in treating patients after attempted suicide or deliberate self-injury. When such behaviors are interpreted negatively, patients may be seen as difficult, which may lead to ineffective treatment and mutual misunderstanding.

Objective:

The goal of this study was to assess the association between the grading of suicidality and perceived difficulty. We hypothesized that a higher grading of suicidality is associated with increased perceived difficulty.

Methods:

We analyzed cross-sectional data from 176 patients who participated in 2 cohort studies: 92 patients in the MATCH-cohort study and 84 patients in the Interpersonal Community Psychiatric Treatment (ICPT) study. The dependent variable was perceived difficulty, as measured by the Difficult Doctor-Patient Relationship Questionnaire (DDPRQ) and the Difficulty Single-item (DSI), a single item measuring the difficulty of the patient as perceived by the professional. Grading of suicidality was considered as the independent variable. Multiple linear and logistic regression was performed.

Results:

We found a significant association between perceived difficulty (DDPRQ) and high gradings of suicidality (B: 3.96; SE: 1.44; β: 0.21; P=0.006), increasing age (B: 0.09; SE: 0.03; β: 0.22; P<0.003), sex (female) (B: 2.33; SE: 0.83; β: 0.20; P=0.006), and marital status (being unmarried) (B: 1.92; SE: 0.85; β: 0.17; P=0.025). A significant association was also found between the DSI and moderate (odds ratio: 3.04; 95% CI: 1.355-6.854; P=0.007) and high (odds ratio: 7.11; 95% CI: 1.8.43-24.435; P=0.005) gradings of suicidality.

Conclusion:

In this study, we found that perceived difficulty was significantly associated with moderate and high gradings of suicidality, increasing age, female sex, and being unmarried.
Mechanisms Linking Perfectionism and Social Anxiety: The Role of Hostility and Disqualification of Positive Social Outcomes
Authors: Barahmand Usha , Shamsina Naila , Rojas Katty , Geschwind Najae , Haruna Iya Fatima
Published: March 2023

While considerable research has focused on maladaptive perfectionism as a risk factor for social anxiety, little attention has been given to the mechanisms that mediate the effects. We integrated perfectionism with the bivalent fear of evaluation model of social anxiety to investigate 2 hypothesized mechanisms: hostile attribution bias and disqualification of positive social outcomes (DPSO). Specifically, we hypothesized that individuals with maladaptive perfectionism develop hostile attribution biases which then lead to DPSO, which in turn predisposes them to social anxiety. Participants were 242 individuals from the general population who completed measures of perfectionism, hostile attribution bias, DPSO, and social anxiety. A test of multiple mediators using bootstrapping supported the hypothesized multiple mediator models. The results suggested that maladaptive perfectionism predisposes an individual to social anxiety through hostile attribution bias and DPSO. The results further suggested that DPSO but not hostile attribution bias operates as an individual mediator in the perfectionism–social anxiety relationship. The findings from this study provide support for the bivalent fear of evaluation model of social anxiety; however, the use of a cross-sectional design limited our ability to find true cause-and-effect relationships.
Can the Publication of Case Series or Case Reports Lead to a Change in Clinical Practice?
Authors: Preskorn Sheldon H. , Armstrong Austin G.
Published: March 2023

This column provides some criteria for evaluating whether a case series or case report may warrant publication. It will emphasize the value of having biomarker data in addition to clinical data to enhance the potential validation of the report and provide ways to test the findings in randomized, controlled clinical trials (RCTs). The potential validity of the case series or report is also high if the outcome is something that would not normally be expected such as, by way of example but not limited to, sudden death or malignant hypertension in someone who had always been normotensive. Examples illustrating how case series/case reports have changed the course of clinical practice or regulatory rules governing drug approval by the US Food and Drug Administration are presented, as well as examples of how those reports have been validated by more rigorous studies including RCTs. The column also includes a discussion of situations in which case series/case reports might have an endpoint (eg, sudden death) that would not be ethical to investigate in an RCT, as well as how biomarkers have been used in such instances to avoid serious untoward outcomes for a participant while still testing the hypothesis.
Audio Care for Managing Chronic Conditions: A Rapid Review
Authors: Albritton Jordan A. , Booth Graham , Kugley Shannon , Parsons Rachael , Reddy Shivani , Coker-Schwimmer Manny , Coa Kisha I. , Chase Jo-Ana D. , Fujita Miku , Crotty Karen
Published: March 2023

  

We aimed to summarize the evidence on the effectiveness of audio care for managing chronic conditions (except diabetes) when used to replace in-person or video-based care or to supplement other usual care, and to assess differences for populations at risk for disparities.
Bictegravir/emtricitabine/tenofovir alafenamide plus doravirine in highly treatment-experienced men with multidrug-resistant HIV
Authors: Sterman Felicia L. , Lalezari Jacob P. , Kowalczyk Ula M. , Main David W. , Grant Edward M. , Caro Luzelena , Manning Cassie M. , Burke Rochelle L.
Published: March 2023

Objective:

To evaluate the safety and efficacy of switching highly treatment-experienced people with HIV (HTE PWH) from rilpivirine/emtricitabine/tenofovir alafenamide (RPV/FTC/TAF) plus dolutegravir (DTG) to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus doravirine (DOR). A pharmacokinetic (PK) analysis was conducted to assess the potential interaction between BIC and DOR.

Design and methods:

This open-label switch trial enrolled HTE PWH from a primary care private practice in the United States. Eligible participants were male, aged ≥45 years, with documented viral resistance to protease inhibitors, nucleoside reverse transcriptase inhibitors, and/or nonnucleoside reverse transcriptase inhibitors but no resistance to RPV or DOR, and no K65R or T69 insertion mutations. Virologic suppression (≤50 copies/ml) while on RPV/FTC/TAF plus DTG for ≥6 months was required prior to enrollment. The primary endpoint of the study was virologic suppression (<50 and <200 copies/ml) at 48 weeks. Secondary endpoints included safety, tolerability, changes in body mass index (BMI), and identification of PK parameters of BIC and DOR.

Results:

Twenty males [median age: 65 years (range, 46–74), median time since HIV diagnosis: 37 years (range, 12–42)] completed the study. BIC/FTC/TAF plus DOR was well tolerated with no serious or treatment-related adverse events reported and no appreciable changes in BMI from baseline to Week 48. At Week 48, 100% of participants had <50 viral copies/ml. PK parameters for BIC and DOR (n = 10) were consistent with published data.

Conclusions:

Switching from RPV/FTC/TAF plus DTG to BIC/FTC/TAF plus DOR was well tolerated and efficacious in HTE men aged ≥45 years with HIV.
Pulse wave velocity in early-treated children living with perinatal HIV infection is similar to uninfected children
Authors: Davies Claire , Vaida Florin , Otwombe Kennedy , Cotton Mark F. , Browne Sara H. , Innes Steve
Published: March 2023

Introduction:

HIV is associated with accelerated cardiovascular disease, due to HIV-associated metabolic abnormalities, antiretroviral therapy (ART), and HIV itself. Carotid-femoral pulse wave velocity (PWV) is the noninvasive gold standard measurement of arterial stiffness, and associated with incident vascular events in adults. It is unclear if arterial stiffness is accelerated in children living with perinatal HIV (CHIV) who initiate ART early in life. We compared the longitudinal trajectory of PWV in CHIV to children unexposed to HIV. A secondary comparison compared HIV exposed uninfected children (CHEU) to unexposed children.

Methods:

Four hundred and sixty-five children (141 CHIV, 160 CHEU, 164 unexposed) previously in the children with HIV early antiretroviral therapy (ART) (CHER) and P1060 trials were followed annually at Tygerberg Children's Hospital, South Africa between 2014 and 2020. CHIV initiated ART in infancy or early childhood, with excellent ART adherence and largely sustained viral suppression. The primary outcome was PWV, measured using the Vicorder system, and evaluated using linear mixed effects models.

Results:

Median (interquartile range) age at first PWV measurement was 8.64 (7.7–9.1) years, and median follow-up time 2.9 (1.6–4.0) years. Adjusted analyses showed no significant mean difference in PWV in CHIV and CHEU compared to unexposed [CHIV: 0.101 m/s, 95% confidence interval (CI) −0.012 to 0.214; CHEU: 0.068 m/s, 95% CI −0.047 to 0.183], after adjusting for gender, age, ethnicity, mean arterial pressure, resting average heart rate and family history of cardiovascular disease.

Conclusions:

Early-treated CHIV with sustained viral suppression have similar PWV to unexposed children. Excellent adherence and early ART initiation may protect against cardiovascular disease.
Postural instability in HIV infection: relation to central and peripheral nervous system markers
Authors: Sullivan Edith V. , Zahr Natalie M. , Sassoon Stephanie A. , Pohl Kilian M. , Pfefferbaum Adolf
Published: March 2023

Objectives:

Determine the independent contributions of central nervous system (CNS) and peripheral nervous system (PNS) metrics to balance instability in people with HIV (PWH) compared with people without HIV (PWoH).

Methods:

Volumetric MRI (CNS) and two-point pedal discrimination (PNS) were tested as substrates of stance instability measured with balance platform posturography.

Design:

125 PWH and 88 PWoH underwent balance testing and brain MRI.

Results:

The PWH exhibited stability deficits that were disproportionately greater with eyes closed than eyes open compared with PWoH. Further analyses revealed that greater postural imbalance measured as longer sway paths correlated with smaller cortical and cerebellar lobular brain volumes known to serve sensory integration; identified brain/sway path relations endured after accounting for contributions from physiological and disease factors as potential moderators; and multiple regression identified PNS and CNS metrics as independent predictors of postural instability in PWH that differed with the use of visual information to stabilize balance. With eyes closed, temporal volumes and two-point pedal discrimination were significant independent predictors of sway; with eyes open, occipital volume was an additional predictor of sway. These relations were selective to PWH and were not detected in PWoH.

Conclusion:

CNS and PNS factors were independent contributors to postural instability in PWH. Recognizing that myriad inputs must be detected by peripheral systems and brain networks to integrate sensory and musculoskeletal information for maintenance of postural stability, age- or disease-related degradation of either or both nervous systems may contribute to imbalance and liability for falls.
Closing the gaps in the continuum of depression care for persons with HIV: modeling the impact on viral suppression in the United States
Authors: Koenig Linda J. , Khurana Nidhi , Islam Md Hafizul , Gopalappa Chaitra , Farnham Paul G.
Published: March 2023

Objective:

Depression is prevalent among persons with HIV (PWH) and is associated with poorer adherence and lack of viral load suppression (VLS). When treated for depression, PWH are more likely to stay in HIV care and adhere to medications; however, for many PWH, depression is not adequately diagnosed or treated. We adapted Progression and Transmission of HIV (PATH 3.0), a U.S. agent-based dynamic stochastic simulation model, by incorporating a continuum of depression care and estimating the impact on VLS of an enhanced depression diagnosis and care scenario (EDC).

Methods:

We compared EDC – whereby every PWH is assessed for depression, gets treatment if diagnosed, and of those, half achieve remission – to a status quo scenario (SQ) on VLS. Based on published findings, assumptions for SQ were: 34.7% depressed, 45% diagnosed, 55.3% treated and 33% of treated achieving remission. Compared to PWH without depression, we assumed the probability of being non-virally suppressed increased by 1.57 times for PWH with depression (PWH-D), and by 0.95 times for PWH with remitted depression.

Results:

There was an average increase of 14.6% (11.5–18.5) in the proportion of PWH-D who achieved VLS in EDC compared to SQ. Among all PWH, there was a 4.7% (3.4–6.0) increase in the proportion who achieved VLS in EDC compared to SQ.

Conclusions:

Fully diagnosing and adequately treating depression would improve health and quality of life for a substantial proportion of PWH-D and result in a nearly 5% increase in expected rates of VLS in the United States, supporting national prevention goals.
Mosaic chromosomal alterations detected in men living with HIV and the relationship to non-Hodgkin lymphoma
Authors: Lin Shu-Hong , Khan Sairah M. , Zhou Weiyin , Brown Derek W. , Vergara Candelaria , Wolinsky Steven M. , Martínez-Maza Otoniel , Margolick Joseph B. , Martinson Jeremy J. , Hussain Shehnaz K. , Engels Eric A. , Machiela Mitchell J.
Published: March 2023

Objectives:

People with HIV (PWH) have an elevated risk of non-Hodgkin lymphoma (NHL) and other diseases. Studying clonal hematopoiesis (CH), the clonal expansion of mutated hematopoietic stem cells, could provide insights regarding elevated NHL risk.

Design:

Cohort analysis of participants in the Multicenter AIDS Cohort Study (N = 5979).

Methods:

Mosaic chromosomal alterations (mCAs), a type of CH, were detected from genotyping array data using MoChA. We compared CH prevalence in men with HIV (MWH) to HIV-uninfected men using logistic regression, and among MWH, assessed the associations of CH with NHL incidence and overall mortality using Poisson regression.

Results:

Comparing MWH to HIV-uninfected men, we observed no difference in the frequency of autosomal mCAs (3.9% vs. 3.6%, P-value = 0.09) or mosaic loss of the Y chromosome (mLOY) (1.4% vs. 2.9%, P-value = 0.13). Autosomal mCAs involving copy-neutral loss of heterozygosity (CN-LOH) of chromosome 14q were more common in MWH. Among MWH, mCAs were not associated with subsequent NHL incidence (autosomal mCA P-value = 0.65, mLOY P-value = 0.48). However, two MWH with diffuse large B-cell lymphoma had overlapping CN-LOH mCAs on chromosome 19 spanning U2AF2 (involved in RNA splicing), and one MWH with Burkitt lymphoma had high-frequency mCAs involving chromosome 1 gain and chromosome 17 CN-LOH (cell fractions 22.1% and 25.0%, respectively). mCAs were not associated with mortality among MWH (autosomal mCA P-value = 0.52, mLOY P-value = 0.93).

Conclusions:

We found limited evidence for a relationship between HIV infection and mCAs. Although mCAs were not significantly associated with NHL, mCAs detected in several NHL cases indicate a need for further investigation.
Cost of improved test and treat strategies in Indonesia
Authors: Hardiawan Donny , Juwita Mery N. , Vadra Jorghi , Prawiranegara Rozar , Mambea Indra Y. , Wisaksana Rudi , Handayani Miasari , Subronto Yanri W. , Kusmayanti Nur A. , Januraga Pande , Sukmaningrum Evi , Nurhayati  , Prameswari Helen D. , Sulaiman Nurjannah , Siregar Adiatma Y.M.
Published: March 2023

Objective:

To estimate and compare the cost of improved test and treat strategies in Indonesia under HIV Awal (Early) Testing and Treatment Indonesia (HATI) implementation trial in community-based and hospital-based clinics.

Design:

The cost and outcome [i.e. CD4+ cell count] and viral load (VL) at the beginning of interventions and their change overtime) analysis of Simplifying ART Initiation (SAI), Community-based Organization and community-based ART Service (CBO), Motivational Interviewing (MI), Oral Fluid-based Testing (OFT), and Short Message Service (SMS) reminder in community-based and hospital-based clinics in 2018–2019.

Method:

We estimated the total and unit costs per patient (under HATI implementation trial interventions) per year from societal perspective in various settings, including costs from patients’ perspective for SAI and MI. We also analyzed the outcome variables (i.e. CD4+ cell count and VL at the beginning of each intervention, the change in CD4+ cell count and VL over time, and adherence rate).

Result:

The unit cost per patient per year of SAI and SMS were lower at the community-based clinics, and more patients visited community-based clinics. The cost per patient visit from patient perspective for SAI and MI was mostly lower than 10% of the patients’ household monthly expenditure. Average CD4+ cell count was higher and average VL was lower at the start of interventions at the community-based clinics, while average CD4+ cell count and VL changes and adherence rate were similar between the two types of clinics.

Conclusion:

Community-based clinics hold the potential for scaling up the interventions as it costs less from societal perspective and showed better outcome improvement during the HATI implementation trial.
Incident diabetes in course of antiretroviral therapy
Authors: Taramasso Lucia , Squillace Nicola , Ricci Elena , Menzaghi Barbara , Orofino Giancarlo , Socio Giuseppe Vittorio De , Molteni Chiara , Martinelli Canio Vito , Madeddu Giordano , Vichi Francesca , Valsecchi Laura , Celesia Benedetto Maurizio , Maggi Paolo , Rusconi Stefano , Pellicanò Giovanni Francesco , Cascio Antonio , Sarchi Eleonora , Gulminetti Roberto , Falasca Katia , Di Biagio Antonio , Bonfanti Paolo
Published: March 2023

Objective:

Recent reports of excessive weight gain in people with HIV (PWH) have raised increasing concerns on the possible increase of diabetes mellitus (DM) risk in course of integrase inhibitors (INSTIs) treatment. In this study, we aimed at describing DM incidence in course of antiretroviral therapy (ART) and identifying the factors associated with new DM onset.

Design:

Observational prospective SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals) cohort.

Methods:

All people enrolled in SCOLTA between January 2003 and November 2021 were included. Multivariable Cox regression yielded adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident DM.

Results:

4366 PWH were included, 72.6% male, with mean age 45.6 years, and median CD4+460 [interquartile range (IQR) 256–710] cells/mm3cells/mm3. During the follow up, 120 incident cases of DM occurred (1.26 cases/100 person year-follow up, 95% CI 1.05–1.50).

Baseline weight, but not the amount of weight gain, resulted significantly correlated to diabetes incidence (aHR by 1 kg 1.03; 95% CI 1.01–1.04), as well as older age (aHR 1.03 by 1 year; 95% CI 1.01–1.06), being ART-experienced with detectable HIV RNA at study entry (aHR 2.27, 95% CI 1.48–3.49), having untreated high blood pressure (aHR 2.90; 95% CI 1.30–6.45) and baseline blood glucose >100 mg/dl (aHR 5.47; 95% CI 3.82–7.85). Neither the INSTI class nor individual antiretrovirals were associated with an increased risk of DM.

Conclusions:

Baseline weight, but not weight gain or the ART class, was associated with incident DM in this observational cohort.
Characteristic Muscular FDG Uptake Patterns Related to the Transportation Means Used by Patients to Visit the Hospital
Authors: Okuyama Chio , Kusano Kuninori , Ito Miki , Takase Akiko , Goda Sayaka , Kagawa Shinya
Published: March 2023

It is well-known that physiological FDG uptake in the skeletal muscles is affected by serum insulin levels and the extent to which the muscles contract before the examination. Patients are instructed to refrain from strenuous exercise, talking too much, and taking meals at least 4 hours before the administration of the tracer. Even if the patient does not intend to exercise, muscular accumulation related to specific behaviors can still be visualized in the images. In this manuscript, we present FDG PET/CT images from 4 cases reflecting the mode of transportation used by the patients to visit the hospital.
Efficacy of Prolonged-release Tacrolimus After Conversion From Immediate-release Tacrolimus in Kidney Transplantation: A Retrospective Analysis of Long-term Outcomes From the ADMIRAD Study
Authors: Kuypers Dirk , Weekers Laurent , Blogg Martin , Anaokar Swapneel , del Pilar Repetur Carola , De Meyer Vicky , Kanaan Nada
Published: March 2023

Background.

Prolonged-release tacrolimus (PRT) may offer improved outcomes after kidney transplantation compared with immediate-release tacrolimus (IRT). However, data on outcomes beyond 5-y posttransplantation are lacking.

Methods.

A retrospective, noninterventional chart review study examined long-term graft survival in adult kidney transplant participants in the Adherence Measurement in Stable Renal Transplant Patients Following Conversion From Prograf to Advagraf (ADMIRAD) clinical trial at 4 Belgian sites. Patients were randomized to receive once-daily PRT or twice-daily IRT for 6 mo, followed by treatment as per real-world clinical practice. Data were collected retrospectively from randomization day until December 31, 2018. Primary endpoints included efficacy failure, defined as a composite endpoint of graft loss, biopsy-confirmed acute rejection, and graft dysfunction. Secondary endpoints included overall patient survival and course of kidney function.

Results.

This analysis included 78.5% of patients from ADMIRAD (n = 108 PRT; n = 64 IRT). The Kaplan–Meier survival rate without efficacy failure from randomization to year 5 was 0.741 (95% confidence interval [CI]: 0.647, 0.813) for the PRT group (n = 80), and 0.667 (95% CI: 0.536, 0.768) for the IRT group (n = 42) and remained higher for PRT throughout 10 y follow-up (P = 0.041). The Kaplan–Meier estimate of overall survival from the time of last transplant was 0.981 (95% CI: 0.928, 0.995) and 0.880 (95% CI: 0.802, 0.928) at 5 and 10 y in the PRT group. Kidney function parameters and tacrolimus trough levels remained stable over the follow-up period.

Conclusions.

Patients in the ADMIRAD study who received PRT for up to 10 y had improved long-term outcomes compared with patients receiving IRT, with a consistent effect on both graft and patient survival.
Increase in prevalence of Streptococcus pneumoniae serogroup 24 in children upon introducing 13-valent pneumococcal conjugate vaccine in Japan
Authors: Ohkusu Misako , Takeshita Kenichi , Takeuchi Noriko , Ishiwada Naruhiko
Published: March 2023

After introducing the 13-valent pneumococcal conjugate vaccine (PCV13) for children, a change in the prevalence of different

Streptococcus pneumoniae

serotypes that cause invasive pneumococcal diseases (IPDs) has been observed. The prevalence of vaccine serotypes has decreased and that of non-vaccine serotypes has increased. Currently, serogroup 24 has become one of the major non-vaccine serotypes causing IPDs in children in Japan. The aim of this study was to characterize clinical and genomic features of

S. pneumoniae

serogroup 24 strains isolated from sterile body sites in Japanese children. Serotyping, multi-locus sequence typing and genomic analysis of capsular polysaccharides of 61 strains of serogroup 24 were performed from 2015 to 2021. Among the 61 strains, 36, 23 and two belonged to serotypes 24F, 24B and 24C, respectively. The 24F sequence type (ST) 2572 and 24B ST 2572 were the major serotypes and sequence types observed from 2015 to 2019. By contrast, 24F ST 162 and 24B ST 2754 were the two major serotypes and sequence types observed after 2020. Two strains of serotype 24C were detected for the first time in Japan. Sequence analysis of the abpA gene, which plays a role in the synthesis of capsular polysaccharides in

S. pneumoniae

, was performed to distinguish different strains of serogroup 24. After the introduction of PCV13 in Japan, serogroup 24 has become one of the most prevalent non-vaccine serotypes causing IPDs in children. This serogroup has not been targeted in the next-generation pneumococcal conjugate vaccines. Therefore, monitoring of

S. pneumoniae

serogroup 24 that causes IPDs in children is essential.
Microbacterium tenebrionis sp. nov. and Microbacterium allomyrinae sp. nov., isolated from larvae of Tenebrio molitor L. and Allomyrina dichotoma, respectively
Authors: Lee Soon Dong , Kim In Seop
Published: March 2023

Two Gram-positive bacterial strains, designated as YMB-B2T and BWT-G7T, were isolated from larvae of Tenebrio molitor L. and Allomyrina dichotoma, respectively, and their taxonomic positions examined by a polyphasic approach. Both of the isolates contained ornithine as the cell-wall diamino acid. The acyl type of murein was N-glycolyl. The predominant menaquinones were MK-11 and MK-12. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol and an unidentified glycolipid. Both of the isolates contained C15 : 0 anteiso and C17 : 0 anteiso as the major fatty acids. Strain YMB-B2T also had C16 : 0 iso as an additional major fatty acid. The 16S rRNA gene phylogeny showed that the novel strains formed two distinct sublines within the genus

Microbacterium

. Strain YMB-B2T was most closely related to the type strains of

Microbacterium aerolatum

(99.1 % sequence similarity) and

Microbacterium ginsengiterrae

(99.0 %), whereas strain BWT-G7T formed a tight cluster with the type strain of

Microbacterium thalassium

(98.9 %). The phylogenomic analysis based on 92 core genes supported their relationships in 16S rRNA gene phylogeny. Overall genomic relatedness indices warranted that the isolates represent two new species of the genus

Microbacterium

. Based on the results obtained here, Microbacterium tenebrionis sp. nov. (type strain YMB-B2T=KCTC 49593T=CCM 9151T) and Microbacterium allomyrinae sp. nov. (type strain BWT-G7T=KACC 22262T=NBRC 115127T) are proposed.
Ligilactobacillus ubinensis sp. nov., a novel species isolated from the wild ferment of a durian fruit (Durio zibethinus)
Authors: Heng Yu Chyuan , Menon Nandita , Chen Binbin , Loo Bryan Zong Lin , Wong Garrett Wei Jie , Lim Amber Ching Han , Silvaraju Shaktheeshwari , Kittelmann Sandra
Published: March 2023

A Gram-stain-positive, rod-shaped, non-spore-forming, catalase-negative, urease-negative, homofermentative and facultatively anaerobic strain, named WILCCON 0076T, was isolated from a wild ferment of pieces of a ‘Kampung’ durian fruit collected on the island of Ubin (Pulau Ubin), Singapore. The durian had fallen to the ground from a durian tree (Durio zibethinus), on which a group of long-tailed macaques had been observed picking and eating the fruits. Comparative analyses of 16S rRNA gene sequences indicated that WILCCON 0076T potentially represented a novel species within the genus

Ligilactobacillus

, with the most closely related type strain being

Ligilactobacillus agilis

DSM 20509T (16S rRNA gene sequence similarity of 97.2 %). Average nucleotide identity and digital DNA–DNA hybridization prediction values were only 86.0% and 18.9 %, respectively. On the basis of the results of a polyphasic approach that included phylogenomic, chemotaxonomic and morphological analyses, we propose a novel species with the name Ligilactobacillus ubinensis sp. nov. (type strain WILCCON 0076T=DSM 114293T=LMG 32698T).