Pro- and anti-inflammatory cytokines mediate the progression of severe anemia in malaria-infected children: A prospective study.

BACKGROUND: Severe Plasmodium falciparum malarial anemia is still the principal cause of death in children in underdeveloped countries. An imbalance between proinflammatory and anti-inflammatory cytokines is associated with malaria progression. This study evaluated circulating levels of selected inflammatory cytokines among malaria-infected children in Ghana. METHODS: This case-control study was conducted at Tamale Teaching Hospital, Ghana. One hundred and twenty children with malaria and 60 controls, aged 12-144 months were selected from April to July, 2023 for the study. Malaria was diagnosed through microscopy, full blood count was measured using hematology analyzer, and cytokines were measured using enzyme-linked immunosorbent assay. RESULTS: Malaria-infected children had higher tumor necrosis factor alpha (TNF-α) (p < .001), interferon-gamma (IFN-É£) (p < .001), interleukin (IL)-1ß (p < .001), IL-6 (p < .001), granulocyte macrophage-colony stimulating factor (GM-CSF) (p < .001), and IL-10 (p < .001) levels than controls. Participants with high parasitemia had raised TNF-α (p < .001), IFN-É£ (p < .001), IL-1ß (p < .001), IL-6 (p < .001), GM-CSF (p < .001), and IL-10 (p < .001), but reduced IL-3 (p < .001) and TGF-ß (p < .001) than those with low parasitemia. Severe malarial anemic children had elevated TNF-α (p < .001), IFN-É£ (p < .001), IL-1ß (p < .001), IL-6 (p < .001), GM-CSF (p < .001), and IL-10 (p < .001), but lower IL-3 (p < .001) and TGF-ß (p < .001) than those with uncomplicated malaria. CONCLUSION: Parasite density was the principal predictor of the cytokine levels, as parasitemia positively associated with IL-10, GM-CSF, IL-6, IL-1ß, IFN-É£, and TNF-α, but negatively associated with IL-3 and TGF-ß. Malaria is associated with enhanced secretion of pro- and anti-inflammatory cytokines in Ghanaian children. Inflammatory cytokines may be involved in the development of severe malarial anemia in children. However, IL-3 and TGF-ß may offer protection against severe malarial anemia.

Innovative Bistable Composites for Aerospace and High-Stress Applications: Integrating Soft and Hard Materials in Experimental, Modeling, and Simulation Studies.

This study explores the development and performance of bistable materials, emphasizing their potential applications in aero-vehicles and high-stress environments. By integrating soft and hard materials within a composite structure, the research demonstrates the creation of bistable composites that exhibit remarkable flexibility and rigidity. Advanced simulations using COMSOL Multiphysics and 3D-printed prototypes reveal that these materials effectively absorb and dissipate stress, maintaining structural integrity under high-pressure conditions. Compression tests highlight the ability of bistable structures to bear significant loads, distributing stress efficiently across multiple layers. The innovative proposal of combining stiff and flexible materials within a single unit cell enhances bistable behavior, offering superior energy absorption and resilience. This work underscores the promise of bistable materials in advancing materials science, providing robust solutions for aerospace, automotive, and protective gear applications and paving the way for future research in optimizing bistable structures for diverse engineering challenges.

A heterocyclic compound inhibits viral release by inducing cell surface BST2/Tetherin/CD317/HM1.24.

The introduction of combined antiretroviral therapy (cART) has greatly improved the quality of life of human immunodeficiency virus type 1 (HIV-1)-infected individuals. Nonetheless, the ever-present desire to seek out a full remedy for HIV-1 infections makes the discovery of novel antiviral medication compelling. Owing to this, a new late-stage inhibitor, Lenacapavir/Sunlenca, an HIV multi-phase suppressor, was clinically authorized in 2022. Besides unveiling cutting-edge antivirals inhibiting late-stage proteins or processes, newer therapeutics targeting host restriction factors hold promise for the curative care of HIV-1 infections. Notwithstanding, bone marrow stromal antigen 2 (BST2)/Tetherin/CD317/HM1.24, which entraps progeny virions is an appealing HIV-1 therapeutic candidate. In this study, a novel drug screening system was established, using the Jurkat/Vpr-HiBiT T cells, to identify drugs that could obstruct HIV-1 release; the candidate compounds were selected from the Ono Pharmaceutical compound library. Jurkat T cells expressing Vpr-HiBiT were infected with NL4-3, and the amount of virus release was quantified indirectly by the amount of Vpr-HiBiT incorporated into the progeny virions. Subsequently, the candidate compounds that suppressed viral release were used to synthesize the heterocyclic compound, HT-7, which reduces HIV-1 release with less cellular toxicity. Notably, HT-7 increased cell surface BST2 coupled with HIV-1 release reduction in Jurkat cells but not Jurkat/KO-BST2 cells. Seemingly, HT-7 impeded simian immunodeficiency virus (SIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) release. Concisely, these results suggest that the reduction in viral release, following HT-7 treatment, resulted from the modulation of cell surface expression of BST2 by HT-7.

Risk factors for older people re-presenting to the emergency department with falls: A case-control analysis.

OBJECTIVE: Falls are a leading cause for ED presentations among older adults. Existing secondary falls prevention interventions have not been shown to decrease fall-related ED re-presentation, indicating a need to better understand contributing factors. Our aim was to evaluate risk factors for fall re-presentations among the older patient population presenting to the ED. METHODS: This is a single-centre case-control study. Cases were patients aged ≥65 years with two falls-related ED presentations within 6 months. Age- and sex-matched controls had a corresponding index, but no subsequent ED fall presentation. Data collected included falls risk factors and clinical features of the index presentation. Univariate and multivariate analyses were conducted to assess the relationship between potential exposures and fall re-presentation. RESULTS: A total of 300 patients (mean age 83.8 years) were studied. On univariate analysis, factors significantly associated with ED fall re-presentation included increasing multimorbidity (P < 0.0001), increasing number of medications (P < 0.0001) and residing in residential aged care facility (RACF) (odds ratio [OR] 3.06, P < 0.001). No factors remained significant on multivariate analysis. Post-hoc analyses for the RACF subgroup showed that psychotropic medication use (OR 1.65, P = 0.04) and prior fall within 12 months (OR 2.68, P < 0.001) were significantly associated with re-presentation. Initial presentation with serious musculoskeletal injury was a significant protective factor (OR 0.21, P = 0.02). CONCLUSION: The present study failed to identify factors independently associated with ED fall re-presentation, suggesting that the factors are complex and inter-related. Two high-risk populations were identified - those from RACF and those initially presenting with falls not resulting in serious injury.

Concurrent vestibular activation and postural training recalibrate somatosensory, vestibular and gaze stabilization processes.

Postural instability is a common symptom of vestibular dysfunction that impacts a person's day-to-day activities. Vestibular rehabilitation is effective in decreasing dizziness, visual symptoms and improving postural control through several mechanisms including sensory reweighting of the vestibular, visual and somatosensory systems. As part of the sensory reweighting mechanisms, vestibular activation exercises with headshaking influence vestibular-ocular reflex (VOR). However, combining challenging vestibular and postural tasks to facilitate more effective rehabilitation outcomes is under-utilized. Understanding how and why this may work is unknown. The aim of the study was to assess sensory reweighting of postural control processing and VOR after concurrent vestibular activation and weight shift training (WST) in healthy young adults. Forty-two participants (18-35years) were randomly assigned into four groups: No training/control (CTL), a novel visual feedback WST coupled with a concurrent, rhythmic active horizontal or vertical headshake activity (HHS and VHS), or the same WST with no headshake (NHS). Training was performed for five days. All groups performed baseline- and post-assessments using the video head impulse test, sensory organization test, force platform rotations and electro-oculography. Significantly decreased horizontal eye movement variability in the HHS group compared to the other groups suggests improved gaze stabilization (p = .024). Significantly decreased horizontal VOR gain (p = .040) and somatosensory downweighting (p = .050) were found in the combined headshake groups (HHS and VHS) compared to the other two groups (NHS and CTL). The training also showed a significantly faster automatic postural response (p = .003) with improved flexibility (p = .010) in the headshake groups. The concurrent training influences oculomotor function and suggests improved gaze stabilization through vestibular recalibration due to adaptation and possibly habituation. The novel protocol could be modified into progressive functional activities that would incorporate gaze stabilization exercises. The findings may have implications for future development of vestibular rehabilitation protocols.

"Nobody gave me information": Hospital experiences of Ghanaian families after maternal mortalities.

Background: Rates of maternal mortality are highest in low-resource settings. Family members are often involved in the critical periods surrounding a maternal death, including transportation to health centers and financial and emotional support during hospital admissions. Maternal death has devastating impacts on surviving family members, which are often overlooked and understudied. Objective: Our study aimed to explore the hospital experiences of family members surrounding a maternal death, and to define their access to and need for institutional and psychosocial support. Study Design: This mixed methods cross-sectional study was conducted at an urban tertiary hospital in Ghana. Maternal mortalities from June 2019 to December 2020 were identified using death certificates. Participants, defined as husbands or other heads of households in families affected by maternal mortality, were purposively recruited. An interview guide was developed using grounded theory. In-person semi-structured interviews were conducted in English or Twi to explore impacts of maternal mortality on family members, with a focus on hospital experiences. Surveys were administered on types of and needs for institutional support. Interviews were audio recorded, translated, transcribed, coded with an iteratively-developed codebook, and thematically analyzed. Survey data was descriptively analyzed. Results: Fifty-one participants included 26 husbands of the deceased woman, 5 parents, 12 siblings, and 8 second-degree relatives. Interviews revealed an overall negative hospital experience for surviving family members, who expressed substantial dissatisfaction and distress. Four themes regarding the hospital experience emerged from the interviews: 1) poor communication from healthcare workers and hospital personnel, which contributed to 2) limited understanding of the patient's clinical status, hospital course, and cause of death; 3) maternal death perceived as avoidable; and 4) maternal death perceived as unexpected and shocking. Survey data revealed that only 10% of participants were provided psychosocial support following the maternal death event, yet 93.3% of those who did not receive support desired this resource. Conclusion: The hospital experience was overall negative for family members and a lack of effective communication emerged as the root cause of this negative perception. Strategies to improve communication between healthcare providers and families are essential. In addition, there is an unmet need for formal mental health resources for families who experience a maternal death.

African Immigrant Women's Experiences of Maternity Care in the United States.

OBJECTIVE: The purpose of this study was to explore maternity care experiences of African immigrant women during the perinatal period including factors affecting access to and use of care. METHODS: We used Sandelowski's (2010) qualitative descriptive approach to examine how African immigrant women from various countries of origin and with diverse ethnic backgrounds experienced and navigated the maternity care system in the United States during pregnancy and childbirth. We conducted semi-structured interviews with 15 African immigrant women living in the Columbus, Ohio area. Participants were recruited using purposive and snowball sampling between February 2021 and May 2021. Interviews were recorded, transcribed, and analyzed using a reflexive thematic analysis approach. FINDINGS: Four major themes defined the experiences of our study participants: access to information, patient-clinician relationships, experiences of discrimination, and costs of maternity care. CLINICAL IMPLICATIONS: Findings highlight key barriers to providing quality and acceptable maternity care to African immigrant women at multiple levels. This group's unique barriers underlie the importance of incorporating their diverse experiences into maternity care models and clinical practice. Further research is needed to evaluate and improve maternity care for African immigrant women.

Assessing multilevel barriers to hydroxyurea adherence in youth with sickle cell disease using pharmacy-based refill records.

BACKGROUND: Suboptimal medication adherence is common across youth with chronic health conditions and may contribute to health disparities and adverse health outcomes, especially in underserved communities. METHODS: Using pharmacy prescription records and guided by the World Health Organization Multidimensional Adherence Model, we examined patient-, treatment-, and health system-related factors that may affect hydroxyurea adherence in 72 youth with sickle cell disease (SCD), 10-18 years who had participated in the multisite "Hydroxyurea Adherence for Personal Best in SCD" (HABIT) feasibility (6 months) and efficacy (12 months) trials. Pharmacy data were collected from the year prior to study entry through the duration of each trial. We also examined hydroxyurea dose at baseline, prescribing patterns (hydroxyurea formulation and dose prescribed), quantity of hydroxyurea dispensed, and number of daily capsules/tablets prescribed. Data were analyzed using descriptive statistics. RESULTS: On average, youth were prescribed 1095 ± 402 mg hydroxyurea per day, requiring ingestion of 3 or more capsules for 39.4% of youth. Frequently identified potential barriers were complex medication regimens in which dose of hydroxyurea differed by day of week (47.2%); receipt of an inadequate (< 30 days) supply of hydroxyurea from the pharmacy ≥ 3 times during record collection period (29.2%); and prescription of hydroxyurea suspension suggesting problems swallowing capsules (22.2%). In this sample, most youth were exclusively prescribed 500 mg capsules (62.5%), which was associated with complex medication regimens (RR 3.0, 95% CI 1.4-6.7). Potential barriers were common, occurred at all levels and are potentially modifiable with targeted interventions at the treatment- and health system-related levels.

Manganese overexposure results in ferroptosis through the HIF-1α/p53/SLC7A11 pathway in ICR mouse brain and PC12 cells.

Manganese (Mn) overexposure has been associated with the development of neurological damage reminiscent of Parkinson's disease, while the underlying mechanisms have yet to be fully characterized. This study aimed to investigate the mechanisms leading to injury in dopaminergic neurons induced by Mn and identify novel treatment approaches. In the in vivo and in vitro models, ICR mice and dopaminergic neuron-like PC12 cells were exposed to Mn, respectively. We treated them with anti-ferroptotic agents ferrostatin-1 (Fer-1), deferoxamine (DFO), HIF-1α activator dimethyloxalylglycine (DMOG) and inhibitor LW6. We also used p53-siRNA to verify the mechanism underlying Mn-induced neurotoxicity. Fe and Mn concentrations increased in ICR mice brains overexposed to Mn. Additionally, Mn-exposed mice exhibited movement impairment and encephalic pathological changes, with decreased HIF-1α, SLC7A11, and GPX4 proteins and increased p53 protein levels. Fer-1 exhibited protective effects against Mn-induced both behavioral and biochemical changes. Consistently, in vitro, Mn exposure caused ferroptosis-related changes and decreased HIF-1α levels, all ameliorated by Fer-1. Upregulation of HIF-1α by DMOG alleviated the Mn-associated ferroptosis, while LW6 exacerbated Mn-induced neurotoxicity through downregulating HIF-1α. p53 knock-down also rescued Mn-induced ferroptosis without altering HIF-1α protein expression. Mn overexposure resulted in ferroptosis in dopaminergic neurons, mediated through the HIF-1α/p53/SLC7A11 pathway.

The Utility of Prostate-Specific Membrane Antigen-11 PET in Detection and Management of Central Nervous System Neoplasms.

ABSTRACT: We present a case series of 5 patients diagnosed with schwannoma and 1 patient diagnosed with astrocytoma who underwent PSMA PET imaging for tumor detection. We retrospectively analyzed the records of 4 male and 2 female patients (mean age, 53.2 ± 13.2) who underwent PSMA PET imaging between March and September 2023. PET interpretation showed increased Ga-PSMA-11 accumulation in all patients with a mean SUV max of 3.11 ± 1.8. This series underscores PSMA PET's potential for CNS neoplasm detection.

Detecting Psychological Interventions Using Bilateral Electromyographic Wearable Sensors.

This study investigated the impact of auditory stimuli on muscular activation patterns using wearable surface electromyography (EMG) sensors. Employing four key muscles (Sternocleidomastoid Muscle (SCM), Cervical Erector Muscle (CEM), Quadricep Muscles (QMs), and Tibialis Muscle (TM)) and time domain features, we differentiated the effects of four interventions: silence, music, positive reinforcement, and negative reinforcement. The results demonstrated distinct muscle responses to the interventions, with the SCM and CEM being the most sensitive to changes and the TM being the most active and stimulus dependent. Post hoc analyses revealed significant intervention-specific activations in the CEM and TM for specific time points and intervention pairs, suggesting dynamic modulation and time-dependent integration. Multi-feature analysis identified both statistical and Hjorth features as potent discriminators, reflecting diverse adaptations in muscle recruitment, activation intensity, control, and signal dynamics. These features hold promise as potential biomarkers for monitoring muscle function in various clinical and research applications. Finally, muscle-specific Random Forest classification achieved the highest accuracy and Area Under the ROC Curve for the TM, indicating its potential for differentiating interventions with high precision. This study paves the way for personalized neuroadaptive interventions in rehabilitation, sports science, ergonomics, and healthcare by exploiting the diverse and dynamic landscape of muscle responses to auditory stimuli.

Lupus-Induced Accelerated Heart Failure in a Young African American Female: Cardiovascular and Systemic Complications of Noncompliance to Maintenance Therapy and the Social Determinants of Cardiovascular Disease.

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disorder characterized by dysregulations of the immune system with intermittent and remitting symptoms. SLE affects multiple organs and systems, including the cardiovascular system. This condition is associated with an increased risk of cardiovascular disease, particularly in younger patients. Our case report describes a patient who rapidly developed structural, functional, and electrophysiological cardiac abnormalities due to lupus-induced cardiomyopathy. The accelerating cardiac events were the result of medication noncompliance. Myocarditis and other potentially fatal cardiac complications associated with SLE have been the subject of numerous studies. This presentation appears to be the first to emphasize the rarity of lupus-induced cardiomyopathy, the importance of treatment adherence, the adverse cardiac effects of targeted therapeutic interventions, and the influence of social determinants of cardiovascular health on a patient's prognosis.

Severe Clozapine-Induced Agranulocytosis, Pharmacodynamic Synergism, and Lithium Promyelocytic Effects in Granulocyte Colony-Stimulating Factor (G-CSF) Resistance or Delayed Response: A Case Report.

Clozapine-induced agranulocytosis is documented in multiple studies, but there is limited literature on treatment-resistant agranulocytosis, the synergistic effect of multiple agranulocytosis-inducing drugs, and lithium's promyelocytic effects. This case highlights these gaps by discussing a patient with an absolute neutrophil count of zero while being treated with Depakote, Haldol, and clozapine. This case proposes more research on lithium's promyelocytic effects, especially in patients who are unresponsive or have a delayed response to discontinuing offending agents and granulocyte colony-stimulating factor (G-CSF).

Hydroxyurea Adherence for Personal Best in Sickle Cell Treatment (HABIT) efficacy trial: Community health worker support may increase hydroxyurea adherence of youth with sickle cell disease.

Despite disease-modifying effects of hydroxyurea on sickle cell disease (SCD), poor adherence among affected youth commonly impedes treatment impact. Following our prior feasibility trial, the "Hydroxyurea Adherence for Personal Best in Sickle Cell Treatment (HABIT)" multi-site randomized controlled efficacy trial aimed to increase hydroxyurea adherence for youth with SCD ages 10-18 years. Impaired adherence was identified primarily through flagging hydroxyurea-induced fetal hemoglobin (HbF) levels compared to prior highest treatment-related HbF. Eligible youth were enrolled as dyads with their primary caregivers for the 1-year trial. This novel semi-structured supportive, multidimensional dyad intervention led by community health workers (CHW), was augmented by daily tailored text message reminders, compared to standard care during a 6-month intervention phase, followed by a 6-month sustainability phase. Primary outcomes from the intervention phase were improved Month 6 HbF levels compared to enrollment and proportion of days covered (PDC) for hydroxyurea versus pre-trial year. The secondary outcome was sustainability of changes up to Month 12. The 2020-2021 peak coronavirus disease 2019 (COVID-19) pandemic disrupted enrollment and clinic-based procedures; CHW in-person visits shifted to virtual scheduled interactions. We enrolled 50 dyads, missing target enrollment. Compared to enrollment levels, both HbF level and PDC significantly - but not sustainably - improved within the intervention group (p = .03 and .01, respectively) with parallel increased mean corpuscular volume (MCV) (p = .05), but not within controls. No significant between-group differences were found at Months 6 or 12. These findings suggest that our community-based, multimodal support for youth-caregiver dyads had temporarily improved hydroxyurea usage. Durability of impact should be tested in a trial with longer duration of CHW-led and mobile health support.

Stillbirth incidence and determinants in a tertiary health facility in the Volta Region of Ghana.

BACKGROUND: Stillbirths are indicators of the quality of obstetrics care in health systems. Stillbirth rates and their associating factors vary by socio-economic and geographical settings. Published data on stillbirths and their associating factors in the Volta Region of Ghana are limited. This limits understanding of local factors that must be considered in designing appropriate interventions to mitigate the occurrence of stillbirths. This study determined the incidence of stillbirths and associated factors among deliveries at Ho Teaching Hospital (HTH) and contributes to understanding the consistent high stillbirths in the country and potentially in other low-resourced settings in sub-Saharan Africa. METHOD: This was a prospective cohort study involving pregnant women admitted for delivery at HTH between October 2019 and March 2020. Data on socio-demographic characteristics such as age and employment, obstetric factors including gestational age at delivery and delivery outcomes like birthweight were collected using a pretested structured questionnaire. The primary outcome was the incidence of stillbirths at the facility. Summary statistics were reported as frequencies, percentages and means. Logistic regression methods were used to assess for association between stillbirths and independent variables including age and birthweight. Odds ratios were reported with 95% confidence intervals and associations with p-values < 0.05 were considered statistically significant. RESULTS: A total of 687 women and their 702 newborns contributed data for analysis. The mean age (SD) was 29.3 (6.3) years and close to two-thirds had had at least one delivery previously. Overall stillbirth incidence was 31.3 per 1000 births. Of the 22 stillbirths, 17 were antepartum. Pre-eclampsia was the most common hypertensive disorder of pregnancy observed (49.3%, 33/67). Among others, less than 3 antenatal visits and low birthweight increased the odds of stillbirths in the bivariate analysis. In the final multivariate model, pregnancy and delivery at 28-34 weeks gestation [AOR 9.37(95% CI 1.18-74.53); p = 0.034] and induction of labour [AOR 11.06 (95% CI 3.10-39.42); p < 0.001] remained significantly associated with stillbirths. CONCLUSION: Stillbirth incidence was 31.3 per 1000 births with more than half being antepartum stillbirths. Pregnancy/delivery at 28-34 weeks' gestation increased the odds of a stillbirth. Improving the quality of antenatal services, ensuring adherence to evidence-based protocols, accurate and prompt diagnosis and timely interventions of medical conditions in pregnancy particularly at 28-34 weeks' gestation could reduce incidence of stillbirths.

Turkish Plants, Including Quercetin and Oenothein B, Inhibit the HIV-1 Release and Accelerate Cell Apoptosis.

The introduction of combined anti-retroviral therapy (cART) in 1996, along with a continual breakthrough in anti-human immunodeficiency virus-1 (HIV-1) drugs, has improved the life expectancies of HIV-1-infected individuals. However, the incidence of drug-resistant viruses between individuals undergoing cART and treatment-naïve individuals is a common challenge. Therefore, there is a requirement to explore potential drug targets by considering various stages of the viral life cycle. For instance, the late stage, or viral release stage, remains uninvestigated extensively in antiviral drug discovery. In this study, we prepared a natural plant library and selected candidate plant extracts that inhibited HIV-1 release based on our laboratory-established screening system. The plant extracts from Epilobium hirsutum L. and Chamerion angustifolium (L.) Holub, belonging to the family Onagraceae, decreased HIV-1 release and accelerated the apoptosis in HIV-1-infected T cells but not uninfected T cells. A flavonol glycoside quercetin with oenothein B in Onagraceae reduced HIV-1 release in HIV-1-infected T cells. Moreover, extracts from Chamerion angustifolium (L.) Holub and Senna alexandrina Mill. inhibited the infectivity of progeny viruses. Together, these results suggest that C. angustifolium (L.) Holub contains quercetin with oenothein B that synergistically blocks viral replication and kills infected cells via an apoptotic pathway. Consequently, the plant extracts from the plant library of Turkey might be suitable candidates for developing novel anti-retroviral drugs that target the late phase of the HIV-1 life cycle.

Associations of quantitative whole-body PSMA-PET metrics with PSA progression status under long-term androgen deprivation therapy in prostate cancer patients: a retrospective single-center study.

PURPOSE: To evaluate whether quantitative whole-body (WB) PSMA-PET metrics under long-term androgen deprivation therapy (ADT) and/or androgen receptor signaling inhibitors (ARSi) are associated with PSA progression. METHODS: Patients who underwent at least 2 68Ga-PSMA-11 PET/CT scans between October 2016 and April 2021 (n = 372) and started a new line of ADT ± ARSi between PET1 and PET2 were retrospectively screened for inclusion. We investigated the association between PCWG3-defined PSA progression status at PET2 and the following PSMA-PET parameters: appearance of new lesions on PET2, ≥ 20% increase in WB-PSMA tumor volume (WB-PSMA-VOL), progression of disease (PD) by RECIP 1.0, and ≥ 30% increase in WB-PSMA-SUVmean from PET1 to PET2. Spearman's rank correlation coefficients and Fisher's exact test were used to evaluate the associations. RESULTS: Thirty-five patients were included: 12/35 (34%) were treated with ADT only and 23/35 (66%) with ARSi ± ADT. The median time between PET1 and PET2 was 539 days. Changes (%) in median PSA levels, WB-PSMA-SUVmean, and WB-PSMA-VOL from PET1 to PET2 were -86%, -23%, and -86%, respectively. WB-PSMA-VOL ≥ 20%, new lesions, RECIP-PD, and WB-PSMA-SUVmean ≥ 30% were observed in 5/35 (14%), 9/35 (26%), 5/35 (14%), and 4/35 (11%) of the whole cohort, in 3/9 (33%), 7/9 (78%), 3/9 (33%), and 2/9 (22%) of patients with PSA progression at PET2, and in 2/26 (8%), 2/26 (8%), 2/26 (8%), and 2/26 (8%) of patients without PSA progression at PET2 (p = 0.058, p < 0.001, p = 0.058, p = 0.238, respectively). Changes in PSA were correlated to percent changes in WB-PSMA-VOL and WB-PSMA-SUVmean (Spearman ρ: 0.765 and 0.633, respectively; p < 0.001). CONCLUSION: Changes in PSA correlated with changes observed on PSMA-PET, although discordance between PSA and PSMA-PET changes was observed. Further research is necessary to evaluate if PSMA-PET parameters can predict progression-free survival and overall survival and serve as novel endpoints in clinical trials.

Molecular Mimicry: An Uncommon Occurrence of Vitamin B12 Deficiency Imitating Thrombotic Thrombocytopenic Purpura in an African American Male.

Thrombotic thrombocytopenic purpura (TTP) and vitamin B12 deficiency can share similar symptoms but require different treatment approaches. TTP is a blood disorder with a high mortality rate requiring immediate plasmapheresis treatment. On the other hand, vitamin B12 deficiency usually presents with anemia, low platelet counts, jaundice, and signs of disrupted red blood cell breakdown, resembling a condition called microangiopathic hemolytic anemia. Vitamin B12 deficiency can sometimes lead to or mimic pseudo-thrombotic microangiopathy (pseudo-TMA), a rare occurrence. Pseudo-TMA manifests as microangiopathic hemolytic anemia and thrombocytopenia and is characterized by schistocytes in a peripheral blood smear. Differentiating TTP cases from pseudo-TMA cases is essential and should be done promptly. The etiology, treatments, and prognosis of these two conditions differ and can be fatal if not identified and managed. We present a case that emphasizes the need for familiarity with TTP-like conditions, the use of ADAMTS13 as a diagnostic tool, prompt and accurate treatment decision-making, the complexities of therapeutic plasma exchange, and the importance of excluding an enzyme inhibitor or mutator as the cause of TTP or TTP-like cases. Lack of knowledge can lead to erroneous diagnoses, resulting in unnecessary treatments or delayed life-saving interventions.

Acute hyperthermia and hypoxia tolerance of two improved strains of nile tilapia (Oreochromis niloticus).

Tilapia production in Ghana has been hit with episodes of stress and pathogen-induced mass fish kills which have anecdotally been linked to the culture of illegally imported Genetically Improved Farmed Tilapia (GIFT) strains of Nile tilapia, Oreochromis niloticus. This study was thus set up to comprehensively assess the stress tolerance of the GIFT strain and a native strain of Nile tilapia (the Akosombo strain) following exposures to hyperthermic and hypoxic stressors. In a series of experiments, oxygen consumption (MO2), aquatic surface respiration (ASR), thermal limits and hypoxia tolerance were assessed. The effects of these stressors on haematological parameters were also assessed. The GIFT strain was less tolerant of hypoxia and performed ASR at higher O2 levels than the Akosombo strain. Under progressive hypoxia, the GIFT strain exhibited higher gill ventilations frequencies (fV) than the Akosombo strain. The thermal tolerance trial indicated that the Akosombo strain of O. niloticus has higher thermotolerance than the GIFT strain and this was reflective in the higher LT50 (45.1℃) and LTmax (48℃), compared to LT50 and LTmax of 41.5℃ and 46℃ respectively. These results imply that it is crucial to consider how the GIFT strain performs under various environmental conditions and changes during culture. Particularly, raising the GIFT strain of Nile tilapia in earthen ponds rich in phytoplankton and subject to protracted episodes of extreme hypoxia may have a detrimental physiological impact on its growth and welfare.

Biomarkers at 6 weeks' gestation in the prediction of early miscarriage in pregnancy following assisted reproductive technology.

INTRODUCTION: Miscarriage is a major concern in early pregnancy among women having conceived with assisted reproductive treatments. This study aimed to examine potential miscarriage-related biophysical and biochemical markers at 6 weeks' gestation among women with confirmed clinical pregnancy following in vitro fertilization (IVF)/embryo transfer (ET) and evaluate the performance of a model combining maternal factors, biophysical and biochemical markers at 6 weeks' gestation in the prediction of first trimester miscarriage among singleton pregnancies following IVF/ET. MATERIAL AND METHODS: A prospective cohort study was conducted in a teaching hospital between December 2017 and January 2020 including women who conceived through IVF/ET. Maternal mean arterial pressure, ultrasound markers including mean gestational sac diameter, fetal heart activity, crown rump length and mean uterine artery pulsatility index (mUTPI) and biochemical biomarkers including maternal serum soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), kisspeptin and glycodelin-A were measured at 6 weeks' gestation. Logistic regression analysis was carried out to determine significant predictors of miscarriage prior to 13 weeks' gestation and performance of screening was estimated by receiver-operating characteristics curve analysis. RESULTS: Among 169 included pregnancies, 145 (85.8%) pregnancies progressed to beyond 13 weeks' gestation and had live births whereas 24 (14.2%) pregnancies resulted in a miscarriage during the first trimester. In the miscarriage group, compared to the live birth group, maternal age, body mass index, and mean arterial pressure were significantly increased; mean gestational sac diameter, crown rump length, mUTPI, serum sFlt-1, glycodelin-A, and the rate of positive fetal heart activity were significantly decreased, while no significant differences were detected in PlGF and kisspeptin. Significant prediction for miscarriage before 13 weeks' gestation was provided by maternal age, fetal heart activity, mUTPI, and serum glycodelin-A. The combination of maternal age, ultrasound (fetal heart activity and mUTPI), and biochemical (glycodelin-A) markers achieved the highest area under the curve (AUC: 0.918, 95% CI 0.866-0.955), with estimated detection rates of 54.2% and 70.8% for miscarriage before 13 weeks' gestation, at fixed false positive rates of 5% and 10%, respectively. CONCLUSIONS: A combination of maternal age, fetal heart activity, mUTPI, and serum glycodelin-A at 6 weeks' gestation could effectively identify IVF/ET pregnancies at risk of first trimester miscarriage.