Automated synthesis of [89Zr]ZrCl4, [89Zr]ZrDFOSquaramide-bisPh(PSMA) and [89Zr]ZrDFOSquaramide-TATE.

BACKGROUND: Automated [89Zr]Zr-radiolabeling processes have the potential to streamline the production of [89Zr]Zr-labelled PET imaging agents. Most radiolabeling protocols use [89Zr][Zr(ox)4]4- as the starting material and oxalate is removed after radiolabeling. In some instances, radiolabeling with [89Zr]ZrCl4 as starting material gives better radiochemical yields at lower reaction temperatures. In this work, a fully-automated process for production of [89Zr]ZrCl4 is reported and its use for the synthesis of [89Zr]ZrDFOSq-bisPhPSMA and [89Zr]ZrDFOSq-TATE. RESULTS: A simple automated process for the isolation of [89Zr]ZrCl4 by trapping [89Zr][Zr(ox)4]4- on a bicarbonate-activated strong anion exchange cartridge followed by elution with 0.1 M HCl in 1 M NaCl was developed. [89Zr]ZrCl4 was routinely recovered from [89Zr][Zr(ox)4]4- in > 95% yield in mildly acidic solution of 0.1 M HCl in 1 M NaCl using a fully-automated process. The [89Zr]ZrCl4 was neutralized with sodium acetate buffer (0.25 M) removing the requirement for cumbersome manual neutralization with strong base. The mixture of [89Zr]ZrCl4 was used for direct automated radiolabeling reactions to produce [89Zr]Zr-DFOSquaramide-bisPhPSMA and [89Zr]ZrDFOSquaramide-TATE in 80-90% over all RCY in > 95% RCP. CONCLUSIONS: This method for the production of [89Zr]ZrCl4 does not require removal of HCl by evaporation making this process relatively fast and efficient. The fully automated procedures for the production of [89Zr]ZrCl4 and its use in radiolabeling are well suited to support the centralized and standardized manufacture of multiple dose preparations of zirconium-89 based radiopharmaceuticals.

Comparison of dmft and behavior rating scores between children with systemic disease and healthy children at the first dental visit.

PURPOSE: To evaluate and compare oral health and behavior scores at the first dental visit and dental treatment need using general anesthesia/sedation (GA/S) of children with systemic diseases (SD) and healthy children. METHODS: Data were obtained from healthy children (n = 87) and children with SD (n = 79), aged 4 to 6 years, presenting to a hospital dental clinic for a first dental examination. The total number of decayed, missing and filled teeth (dmft), dental behavior score using Frankl Scale, and dental treatment need using GA/S were recorded. Chi-square / Fisher's exact test and Mann-Whitney U tests were used for statistical analyses. RESULTS: The patients with SD were diagnosed with cardiac disease (61%), renal disease (9%), and pediatric cancers (30%). The median dmft values of the SD group (3.00) were significantly lower than those of healthy children (5.00) (p = 0.02) and healthy children exhibited significantly more positive behavior (90.8%) than children with SD (73.4%) (p = 0.002). The number of patients needing GA/S for dental treatment did not differ significantly between the two groups (p = 0.185). There was no relationship between dental treatment need with GA/S and dental behavior scores of the patients (p = 0.05). A statistically significant relationship was found between the patients' dmft scores and the need for dental treatment using GA/S; and the cut-off value was found to be dmft > 4 for the overall comparisons. CONCLUSION: The presence of chronic disease in children appeared to affect the cooperation negatively at the first dental visit compared to healthy controls, however, it did not affect the oral health negatively. Having a negative behavior score or SD did not necessitate the use of GA/S for dental treatment.

Daughter circumcision and maternal life satisfaction: a cultural moderation effect revealed across two multicountry studies.

INTRODUCTION: The present paper assessed the relationship between maternal life satisfaction (MLS) and the intergenerational transmission of female genital cutting (FGC, female circumcision). It was hypothesised that the association would be more strongly positive in countries in which FGC is more prevalent (ie, culturally normative), suggesting a practice that is socially reinforcing within sociocultural contexts in which it is common. METHODS: Across two studies with more than 85 000 participants in 15 African and Asian countries, mothers completed surveys reporting on their own FGC experiences and those of their daughters' and on their educational history and socioeconomic status. RESULTS: The association between MLS and daughter circumcision was weak but positive for the full sample. Contrary to predictions, in countries in which FGC is uncommon, it was more positively associated with MLS, and in countries in which it is common, it was weakly or negatively associated with MLS. CONCLUSION: Results are contrary to the notion that the intergenerational transmission of FGC is a function of happiness deriving from its cultural normativity. They suggest, instead, a diversity of social motives depending on cultural context. Customised messaging to reduce the intergenerational transmission of FGC is discussed.

From progression to progress: The future of multiple sclerosis.

Significant advances have been made in the diagnosis and treatment of multiple sclerosis in recent years yet challenges remain. The current classification of MS phenotypes according to disease activity and progression, for example, does not adequately reflect the underlying pathophysiological mechanisms that may be acting in an individual with MS at different time points. Thus, there is a need for clinicians to transition to a management approach based on the underlying pathophysiological mechanisms that drive disability in MS. A Canadian expert panel convened in January 2023 to discuss priorities for clinical discovery and scientific exploration that would help advance the field. Five key areas of focus included: identifying a mechanism-based disease classification system; developing biomarkers (imaging, fluid, digital) to identify pathologic processes; implementing a data-driven approach to integrate genetic/environmental risk factors, clinical findings, imaging and biomarker data, and patient-reported outcomes to better characterize the many factors associated with disability progression; utilizing precision-based treatment strategies to target different disease processes; and potentially preventing disease through Epstein-Barr virus (EBV) vaccination, counselling about environmental risk factors (e.g. obesity, exercise, vitamin D/sun exposure, smoking) and other measures. Many of the tools needed to meet these needs are currently available. Further work is required to validate emerging biomarkers and tailor treatment strategies to the needs of individual patients. The hope is that a more complete view of the individual's pathobiology will enable clinicians to usher in an era of truly personalized medicine, in which more informed treatment decisions throughout the disease course achieve better long-term outcomes.

Development and Validation of the Combined Action Observation and Motor Imagery Ability Questionnaire.

Combined use of action observation and motor imagery (AOMI) is an increasingly popular motor-simulation intervention, which involves observing movements on video while simultaneously imagining the feeling of movement execution. Measuring and reporting participant imagery-ability characteristics are essential in motor-simulation research, but no measure of AOMI ability currently exists. Accordingly, the AOMI Ability Questionnaire (AOMI-AQ) was developed to address this gap in the literature. In Study 1, two hundred eleven participants completed the AOMI-AQ and the kinesthetic imagery subscales of the Movement Imagery Questionnaire-3 and Vividness of Motor Imagery Questionnaire-2. Following exploratory factor analysis, an 8-item AOMI-AQ was found to correlate positively with existing motor-imagery measures. In Study 2, one hundred seventy-four participants completed the AOMI-AQ for a second time after a period of 7-10 days. Results indicate a good test-retest reliability for the AOMI-AQ. The new AOMI-AQ measure provides a valid and reliable tool for researchers and practitioners wishing to assess AOMI ability.

Benefits and Limits of Phasing Alleles for Network Inference of Allopolyploid Complexes.

Accurately reconstructing the reticulate histories of polyploids remains a central challenge for understanding plant evolution. Although phylogenetic networks can provide insights into relationships among polyploid lineages, inferring networks may be hindered by the complexities of homology determination in polyploid taxa. We use simulations to show that phasing alleles from allopolyploid individuals can improve phylogenetic network inference under the multispecies coalescent by obtaining the true network with fewer loci compared to haplotype consensus sequences or sequences with heterozygous bases represented as ambiguity codes. Phased allelic data can also improve divergence time estimates for networks, which is helpful for evaluating allopolyploid speciation hypotheses and proposing mechanisms of speciation. To achieve these outcomes in empirical data, we present a novel pipeline that leverages a recently developed phasing algorithm to reliably phase alleles from polyploids. This pipeline is especially appropriate for target enrichment data, where depth of coverage is typically high enough to phase entire loci. We provide an empirical example in the North American Dryopteris fern complex that demonstrates insights from phased data as well as the challenges of network inference. We establish that our pipeline (PATÉ: Phased Alleles from Target Enrichment data) is capable of recovering a high proportion of phased loci from both diploids and polyploids. These data may improve network estimates compared to using haplotype consensus assemblies by accurately inferring the direction of gene flow, but statistical non-identifiability of phylogenetic networks poses a barrier to inferring the evolutionary history of reticulate complexes.

Immunohistochemistry as an adjunct for challenging histological patterns of borderline Brenner tumors: An illustrative study of 4 cases.

Borderline Brenner tumors (BBT) have a range of morphology that shows considerable overlap with that of malignant Brenner tumors (MBT). In particular, two histological patterns of BBT can be particularly challenging: 1) BBT with intraepithelial carcinoma (BBT-IEC) and 2) BBT with a small nested pattern (BBT-SNP). BBT-IEC is characterized by a tumor with the low-power non-infiltrative silhouette of a conventional BBT, but with increased cytological atypia and mitotic activity similar to that of MBT. Conversely, BBT-SNP is characterized by a complex proliferation of small tumor nests that closely resemble the infiltrative growth pattern of MBT, but without the obligate cytologic atypia and mitotic activity of MBT. We suggest that the combination of p16, p53 and Ki-67 may be helpful in distinguishing these 2 patterns of BBT from both conventional BBT and from MBT. While both conventional BBT and BBT-IEC show a null pattern of p16 expression, our case of BBT-IEC showed aberrant p53 overexpression, albeit with a maturation pattern similar to that described for TP53 mutant mucinous ovarian carcinoma and differentiated vulvar intraepithelial neoplasia (dVIN). Similarly, while BBT-SNP shows an infiltrative-like growth pattern similar to that of MBT, our case also showed a wild-type pattern of p53 expression and a Ki-67 proliferative index similar to areas with conventional BBT histology. In conclusion, in our small case series, we show that the use of immunohistochemistry for p53 and Ki-67 may help to distinguish challenging patterns of BBT from MBT. Further studies are needed to validate this finding in a larger case cohort.

An open pilot trial of a behavioural intervention to reduce violence by young adults with early psychosis receiving treatment in an early intervention services setting: A protocol.

AIMS: Despite the public health impact of violence among young adults with psychosis, behavioural interventions to reduce the risk of engaging in violence remain rare. For young adults with early psychosis, cognitive behavioural therapy (CBT)-based psychotherapy has efficacy in reducing impairment and improving functioning. However, no CBT-based intervention to reduce violence has been formally adapted for young adults with early psychosis. This protocol outlines the first clinical trial of a behavioural intervention to reduce violence for young adults with early psychosis. This study is set in an early intervention services (EIS) setting and seeks to adapt and pilot Psychological Intervention for Complex PTSD and Schizophrenia-Spectrum Disorder (PICASSO), a CBT-based intervention, through an iterative process utilizing mixed-methods assessments. METHODS: All research will occur at OnTrackNY, the largest EIS program in the United States. This study will consist of an open pilot trial, with four EIS clinicians delivering the intervention to one to two EIS participants per round. In this mixed-methods study, both quantitative measures (acceptability, feasibility and hypothesized mediators of target outcome collected on a weekly basis) and qualitative interviews (with EIS clinicians at weeks 4, 8 and 12) will be conducted. Transcripts will be analyzed using thematic content analysis. Two to three rounds of iterative modifications are anticipated (n = 10-16 EIS participants total). RESULTS: Recruitment began in February 2024 and is expected to continue over a 9-12-month period. CONCLUSIONS: Because violent behaviour causes interpersonal disruptions such as incarceration and increased caregiver burden, an innovative intervention to reduce violence risk could have broader health impact for this vulnerable population. Adapting the PICASSO intervention to the EIS setting will optimize its acceptability and feasibility by the intended target population.

Oxidative Stress is a shared characteristic of ME/CFS and Long COVID.

More than 65 million individuals worldwide are estimated to have Long COVID (LC), a complex multisystemic condition, wherein patients of all ages report fatigue, post-exertional malaise, and other symptoms resembling myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). With no current treatments or reliable diagnostic markers, there is an urgent need to define the molecular underpinnings of these conditions. By studying bioenergetic characteristics of peripheral blood lymphocytes in over 16 healthy controls, 15 ME/CFS, and 15 LC, we find both ME/CFS and LC donors exhibit signs of elevated oxidative stress, relative to healthy controls, especially in the memory subset. Using a combination of flow cytometry, bulk RNA-seq analysis, mass spectrometry, and systems chemistry analysis, we also observed aberrations in ROS clearance pathways including elevated glutathione levels, decreases in mitochondrial superoxide dismutase levels, and glutathione peroxidase 4 mediated lipid oxidative damage. Critically, these changes in redox pathways show striking sex-specific trends. While females diagnosed with ME/CFS exhibit higher total ROS and mitochondrial calcium levels, males with an ME/CFS diagnosis have normal ROS levels, but larger changes in lipid oxidative damage. Further analyses show that higher ROS levels correlates with hyperproliferation of T cells in females, consistent with the known role of elevated ROS levels in the initiation of proliferation. This hyperproliferation of T cells can be attenuated by metformin, suggesting this FDA-approved drug as a possible treatment, as also suggested by a recent clinical study of LC patients. Thus, we report that both ME/CFS and LC are mechanistically related and could be diagnosed with quantitative blood cell measurements. We also suggest that effective, patient tailored drugs might be discovered using standard lymphocyte stimulation assays.

Accelerated Theta Burst Transcranial Magnetic Stimulation for Refractory Depression in Autism Spectrum Disorder.

PURPOSE: Major depressive disorder (MDD) disproportionately affects those living with autism spectrum disorder (ASD) and is associated with significant impairment and treatment recidivism. METHODS: We studied the use of accelerated theta burst stimulation (ATBS) for the treatment of refractory MDD in ASD (3 treatments daily x 10 days). This prospective open-label 12-week trial included 10 subjects with a mean age of 21.5 years, randomized to receive unilateral or bilateral stimulation of the dorsolateral prefrontal cortex. RESULTS: One participant dropped out of the study due to intolerability. In both treatment arms, depressive symptoms, scored on the Hamilton Depression Rating Scale scores, diminished substantially. At 12 weeks post-treatment, full remission was sustained in 5 subjects and partial remission in 3 subjects. Treatment with ATBS, regardless of the site of stimulation, was associated with a significant, substantial, and sustained improvement in depressive symptomatology via the primary outcome measure, the Hamilton Depression Rating Scale. Additional secondary measures, including self-report depression scales, fluid cognition, and sleep quality, also showed significant improvement. No serious adverse events occurred during the study. Mild transient headaches were infrequently reported, which are expected side effects of ATBS. CONCLUSION: Overall, ATBS treatment was highly effective and well-tolerated in individuals with ASD and co-occurring MDD. The findings support the need for a larger, sham-controlled randomized controlled trial to further evaluate efficacy of ATBS in this population.

The Wisconsin silicone oil study (report #1): anatomical and functional outcomes of repair of retinal detachment with proliferative vitreoretinopathy.

BACKGROUND: Silicone oil (SO) is a long-term tamponade for repair of complex retinal pathology but has limitations including late redetachment. This study describes our experience with SO tamponade for repair of retinal detachment with proliferative vitreoretinopathy (PVR), with attention to anatomic and functional outcomes. METHODS: Retrospective consecutive case series of eyes with retinal detachment (RD) complicated by proliferative vitreoretinopathy (PVR) receiving SO tamponade at the University of Wisconsin between 2013 and 2019. Group 1 defined as primary SO placement; Group 2 had SO placed after failing prior retinal detachment repair. RESULTS: Inclusion criteria of SO placement for repair of RD with PVR was met for 117 eyes. The final reattachment rate was 84% for all eyes, with no difference between Groups 1 and 2. Vision improvement was 2.1 lines for Group 1 (p = 0.06 from baseline) and 4.6 lines for Group 2 (p < 0.0001). The mean number of silicone oil placements was 1.4. Less improvement in vision was noted with repeat SO placement, though overall functional vision of 5/200 or better was achieved in 63.2% of patients. CONCLUSIONS: SO tamponade allows long-term anatomical stabilisation and substantial vision recovery in eyes with retinal detachment complicated by PVR. Rates of anatomic and functional success have improved significantly when compared to prior studies using oil tamponade for repair of PVR.

A polygenic risk score for alcohol-associated cirrhosis among heavy drinkers with European ancestry.

BACKGROUND: Polygenic Risk Scores (PRS) based on results from genome-wide association studies offer the prospect of risk stratification for many common and complex diseases. We developed a PRS for alcohol-associated cirrhosis by comparing single-nucleotide polymorphisms among patients with alcohol-associated cirrhosis (ALC) versus drinkers who did not have evidence of liver fibrosis/cirrhosis. METHODS: Using a data-driven approach, a PRS for ALC was generated using a meta-genome-wide association study of ALC (N=4305) and an independent cohort of heavy drinkers with ALC and without significant liver disease (N=3037). It was validated in 2 additional independent cohorts from the UK Biobank with diagnosed ALC (N=467) and high-risk drinking controls (N=8981) and participants in the Indiana Biobank Liver cohort with alcohol-associated liver disease (N=121) and controls without liver disease (N=3239). RESULTS: A 20-single-nucleotide polymorphisms PRS for ALC (PRSALC) was generated that stratified risk for ALC comparing the top and bottom deciles of PRS in the 2 validation cohorts (ORs: 2.83 [95% CI: 1.82 -4.39] in UK Biobank; 4.40 [1.56 -12.44] in Indiana Biobank Liver cohort). Furthermore, PRSALC improved the prediction of ALC risk when added to the models of clinically known predictors of ALC risk. It also stratified the risk for metabolic dysfunction -associated steatotic liver disease -cirrhosis (3.94 [2.23 -6.95]) in the Indiana Biobank Liver cohort -based exploratory analysis. CONCLUSIONS: PRSALC incorporates 20 single-nucleotide polymorphisms, predicts increased risk for ALC, and improves risk stratification for ALC compared with the models that only include clinical risk factors. This new score has the potential for early detection of heavy drinking patients who are at high risk for ALC.

Characterizing Ertapenem Neurotoxicity: A Systematic Review and Experience at a Tertiary Medical Center.

Ertapenem-induced neurotoxicity has not been well characterized and is potentially underreported. We conducted a systematic review of the literature and included 11 additional cases from the University of Washington Medicine health system. A total of 125 individual patient cases were included in the data analysis. The mean age was 72 years, and 62% and 42% of patients had renal dysfunction and preexisting central nervous system (CNS) conditions, respectively. Only 15% of patients received inappropriately high ertapenem dosing based on kidney function. Patients developed neurological signs and symptoms after a median of 4 days (interquartile range, 3-9 days). The most common clinical features were seizures (70%), altered level of consciousness or delirium (27%), and hallucinations (17%). An estimated incidence in our health system was 1 in 102 courses of ertapenem. Ertapenem neurotoxicity should be suspected when a patient with renal dysfunction or predisposing CNS conditions develops neurological signs and symptoms, especially within several days after initiating the antibiotic. This study underscores the need for a large prospective study to assess the true incidence and outcomes of ertapenem neurotoxicity.

Open fractures: evidence-based best practices.

Open fracture management is a common challenge to orthopaedic trauma surgeons and a burdensome condition to the patient, health care, and entire society. Fracture-related infection (FRI) is the leading morbid complication to avoid during open fracture management because it leads to sepsis, nonunion, limb loss, and overall very poor region-specific and general functional outcomes. This review, based on a symposium presented at the 2022 OTA International Trauma Care Forum, provides a practical and evidence-based summary on key strategies to prevent FRI in open fractures, which can be grouped as optimizing host factors, antimicrobial prophylaxis, surgical site management (skin preparation, debridement, and wound irrigation), provision of skeletal stability, and soft-tissue coverage. When it is applicable, strategies are differentiated between optimal resource and resource-limited settings.

Topiramate Versus Naltrexone for Alcohol Use Disorder: A Genotype-Stratified Double-Blind Randomized Controlled Trial.

OBJECTIVE: There have been no well-controlled and well-powered comparative trials of topiramate with other pharmacotherapies for alcohol use disorder (AUD), such as naltrexone. Moreover, the literature is mixed on the effects of two polymorphisms-rs2832407 (in GRIK1) and rs1799971 (in OPRM1)-on response to topiramate and naltrexone, respectively. The authors sought to examine the comparative effectiveness of topiramate and naltrexone in improving outcomes in AUD and to examine the role of the rs2832407 and rs1799971 polymorphisms, respectively, on response to these medications. METHODS: In a 12-week, double-blind, placebo-controlled, randomized, multisite, genotype-stratified (rs2832407 and rs1799971) clinical trial comparing topiramate and naltrexone in treating AUD, 147 patients with AUD were randomly assigned to treatment with topiramate or naltrexone, stratified by genotype (rs2832407*CC and *AC/AA genotypes and rs1799971*AA and *AG/GG genotypes). The predefined primary outcome was number of heavy drinking days per week. Predefined secondary outcomes included standard drinks per drinking day per week, body mass index (BMI), craving, markers of liver injury, mood, and adverse events. RESULTS: For the number of heavy drinking days per week, there was a near-significant time-by-treatment interaction. For the number of standard drinks per drinking day per week, there was a significant time-by-treatment interaction, which favored topiramate. There were significant time-by-treatment effects, with greater reductions observed with topiramate than naltrexone for BMI, craving, and gamma-glutamyltransferase level. Withdrawal due to side effects occurred in 8% and 5% of the topiramate and naltrexone groups, respectively. Neither polymorphism showed an effect on treatment response. CONCLUSIONS: Topiramate is at least as effective and safe as the first-line medication, naltrexone, in reducing heavy alcohol consumption, and superior in reducing some clinical outcomes. Neither rs2832407 nor rs1799971 had effects on topiramate and naltrexone treatments, respectively.

Prophylactic Regenerative Peripheral Nerve Interface (RPNI) Surgery in Pediatric Lower Limb Amputation Patients.

OBJECTIVE: To evaluate the prophylactic effect of Regenerative Peripheral Nerve Interface (RPNI) surgery on pediatric post-amputation pain. SUMMARY OF BACKGROUND DATA: Chronic post-amputation pain is a debilitating and refractory sequela of limb amputation affecting up to 83% of pediatric patients with limb loss, resulting in disability and decreased quality of life. We postulate that prophylactic RPNI surgery performed during amputation may decrease the incidence of symptomatic neuroma and development of phantom limb pain, as well as limit analgesic use among pediatric patients with limb loss. METHODS: Retrospective chart review was performed on pediatric patients between the ages of 8 and 21 years who underwent major lower limb amputation with and without RPNI surgery. Documented neuroma and phantom limb pain scores as well as analgesic use was recorded. Narcotic use was converted to milligrams morphine equivalents per day (MME/day) while overall analgesic use was converted to Medication Quantification Scale version III (MQSIII) scores. Analysis was performed using Stata. RESULTS: Forty-four pediatric patients were identified; 25 RPNI patients and 19 controls. Seventy-nine percent of control patients developed chronic post-amputation pain versus 21% of RPNI patients (P<0.001). Among the patients who developed post-amputation pain, 20% of controls developed clinical neuroma pain, compared to 0% of RPNI patients (P<0.001). Additionally, RPNI patients demonstrated a significant decrease in pain score (P=0.007) and narcotic usage (P<0.01), compared to controls. Overall analgesic use did not vary significantly between groups. CONCLUSIONS: Prophylactic RPNI surgery shows promise for pediatric patients undergoing major lower limb amputation by preventing both symptomatic neuromas and possibly the development of phantom limb pain.

Genomic and phenotypic correlates of mosaic loss of chromosome Y in blood.

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer's disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole genome sequencing of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program. This approach enabled us to identify differences in mLOY frequencies across populations defined by genetic similarity, revealing a higher frequency of mLOY in the European American (EA) ancestry group compared to those of Hispanic American (HA), African American (AA), and East Asian (EAS) ancestry. Further, we identified two genes ( CFHR1 and LRP6 ) that harbor multiple rare, putatively deleterious variants associated with mLOY susceptibility, show that subsets of human hematopoietic stem cells are enriched for activity of mLOY susceptibility variants, and that certain alleles on chromosome Y are more likely to be lost than others.

Subclinical cardiovascular remodelling in HIV-infection: A multimodal case study of 2 serodiscordant, monozygotic twins.

Cardiovascular abnormalities are increasingly recognised among people newly diagnosed with HIV, but subclinical pathology may be challenging to diagnose. We present a case study of subtle cardiovascular changes in identical twins, one without HIV-infection and the other recently diagnosed with HIV (serodiscordant). We hypothesise that cardiovascular parameters would be similar between the twins, unless non-genetic (environmental) factors are at play. These differences likely represent occult pathology secondary to the effects of early HIV-infection. A 25-year-old female incidentally diagnosed with HIV, and her HIV-uninfected identical twin, living with her since birth, underwent comprehensive cardiovascular assessments. The HIV-positive twin exhibited a globular left ventricle (LV), larger LV volumes, decreased LV strain, peak atrial longitudinal strain (PALS) and higher native T1 and T2 mapping values compared to her sister. Cardiac biomarkers high sensitivity cardiac troponin T and N-terminal proBNP, as well as the novel markers of fibrosis and remodelling, galectin-3 and soluble-ST2, were higher in the HIV-infected twin. Given the twins' shared environment and genetic makeup, these differences likely stem from HIV-infection. Our study supports previous findings and suggests potential screening markers for HIV-associated cardiovascular disease, including PALS. Further research is warranted to explore PALS' utility in this context.

Essential oil composition of passiflora foetida L. (passifloraceae) flowers and chemical-biology study of the leaves extracts and isolated compound.

Passiflora foetida is a climbing herb employed in ethno-medicine for the treatment of various ailments. The essential oil from flowers of P. foetida was obtained by hydrodistillation. The ethanol extract of the leaves was dissolved in water, then partitioned with n-hexane and n-butanol to obtain the various fractions; the fractions and isolated compound were subjected to in vitro antioxidant activity. Gas chromatography-mass spectrometry afforded the identification of forty-two constituents in the floral oil, dominated by ß-caryophyllene (17.2%), cedrol (11.5%), and α-humulene (11.5%). The n-butanol fraction was the most active (70% inhibition and absorbance 0.401; 100 µg/mL) in the 2,2-diphenyl-1-picrylhydrazyl radicals and ferric reducing power assays, respectively. Chromatographic analysis facilitated the isolation of 8-C-ß-d-glucosylapigenin (vitexin) from the butanol fraction of P. foetida. Vitexin demonstrated good antioxidant activities (75% inhibition and absorbance 0.424; 100 µg/mL) compared with ascorbic acid. The volatile metabolites of P. foetida flowers are reported for the first time.