Publications by authors named "Buck W"

This systematic review assessed the prevalence of transmitted and acquired HIV drug resistance (HIVDR) and the associated risk factors in Mozambique. A search of the PubMed, Cochrane, B-On, and Scopus databases up to December 2023 was conducted and included 11 studies with 1118 HIV-1 pol sequences. Drug resistance mutations (DRMs) to NNRTIs were found in 13% of the drug-naive individuals and 31% of those on ART, while NRTI resistance occurred in 5% and 10%, respectively.

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Enhanced histopathology of the immune system uses a precise, compartment-specific, and semi-quantitative evaluation of lymphoid organs in toxicology studies. The assessment of lymphocyte populations in tissues is subject to sampling variability and limited distinctive cytologic features of lymphocyte subpopulations as seen with hematoxylin and eosin (H&E) staining. Although immunohistochemistry is necessary for definitive characterization of T- and B-cell compartments, routine toxicologic assessments are based solely on H&E slides.

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Mass spectrometry imaging (MSI) was used to investigate and provide insights into observed biliary pathology found in dogs and rats after administration of two different compounds. Both compounds were associated with peribiliary inflammatory infiltrates and proliferation of the bile duct epithelium. However, MSI revealed very different spatial distribution profiles for the two compounds: Compound A showed significant accumulation within the bile duct epithelium with a much higher concentration than in the parenchymal hepatocytes, while Compound T exhibited only a slight increase in the bile duct epithelium compared to parenchymal hepatocytes.

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Background: We assessed the impact of point-of-care (PoC) test-and-treat at birth on clinical outcomes and viral suppression among HIV-positive infants in Mozambique and Tanzania.

Methods: This cluster-randomized trial allocated health facilities to intervention, providing PoC-testing and antiretroviral treatment (ART) at birth and week 4-8, or control, starting these at week 4-8. The primary outcome was proportions of clinical events (mortality, morbidity, retention, virological failure, toxicity) among HIV-positive infants at month-18.

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Article Synopsis
  • Overexpression of BCL-X, an antiapoptotic protein, leads to drug resistance and disease progression in various cancers, making it an attractive target for selective inhibitors.
  • Initial selective BCL-X inhibitors were effective in preclinical models but caused serious cardiovascular toxicity in higher species, prompting the development of safer alternatives using antibody-drug conjugates.
  • The antibody-drug conjugate AM1-15 showed promise by inhibiting tumor growth without causing cardiovascular issues, though it did present other toxicities that were addressed in the modified AM1-AAA, which is now part of the first clinical trial for a selective BCL-X-targeting drug.
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Background: Bacillus Calmette-Guérin (BCG) reactions are the most common cause of immune reconstitution inflammatory syndrome (IRIS) in HIV-positive infants who initiate antiretroviral therapy (ART). There is limited evidence regarding the incidence of BCG-IRIS; however, reports from outpatient cohorts have estimated that 6-9% of infants who initiated ART developed some form of BCG-IRIS within the first 6 months. Various treatment approaches for infants with BCG-IRIS have been reported, but there is currently no widely accepted standard-of-care.

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Mid-ocean ridges (MORs) are quintessential sites of tectonic extension, at which divergence between lithospheric plates shapes abyssal hills that cover about two-thirds of the Earth's surface. Here we show that tectonic extension at the ridge axis can be partially undone by tectonic shortening across the ridge flanks. This process is evidenced by recent sequences of reverse-faulting earthquakes about 15 km off-axis at the Mid-Atlantic Ridge and Carlsberg Ridge.

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A re-examination of the original collection of described by Brotherus in 1916 indicated that this material is not homogeneous. Re-examination of the diagnosis of this species and morphological analysis supports that two separate taxa should be distinguished - Plagiotheciumnovae-seelandiaevar.novae-seelandiae and P.

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Background: Childhood acute malnutrition continues to be a serious health problem in many low-resource settings in Africa. On pediatric wards in Mozambique, missed opportunities for timely diagnosis and treatment of malnutrition may lead to poor health outcomes. To improve inpatient nutritional care, a quality improvement (QI) project was implemented that aimed to engage pediatric nurses in inpatient malnutrition diagnosis and treatment.

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Background: We evaluated dolutegravir pharmacokinetics in infants with human immunodeficiency virus (HIV) receiving dolutegravir twice daily (BID) with rifampicin-based tuberculosis (TB) treatment compared with once daily (OD) without rifampicin.

Methods: Infants with HIV aged 1-12 months, weighing ≥3 kg, and receiving dolutegravir BID with rifampicin or OD without rifampicin were eligible. Six blood samples were taken over 12 (BID) or 24 hours (OD).

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Background: MCL-1 is a prosurvival B-cell lymphoma 2 family protein that plays a critical role in tumor maintenance and survival and can act as a resistance factor to multiple anticancer therapies. Herein, we describe the generation and characterization of the highly potent and selective MCL-1 inhibitor ABBV-467 and present findings from a first-in-human trial that included patients with relapsed/refractory multiple myeloma (NCT04178902).

Methods: Binding of ABBV-467 to human MCL-1 was assessed in multiple cell lines.

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Article Synopsis
  • Optimal antituberculosis therapy is crucial for achieving good health outcomes in patients.
  • Research shows that infants with HIV receiving standard doses of first-line TB drugs have significantly lower peak plasma concentrations than adults.
  • This suggests that increasing the dosage of these TB drugs in infants may be necessary for better treatment effectiveness.
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These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents. Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.

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Repulsive guidance molecule A (RGMa) is an inhibitor of neuronal growth and survival which is upregulated in the damaged central nervous system following acute spinal cord injury (SCI), traumatic brain injury, acute ischemic stroke (AIS), and other neuropathological conditions. Neutralization of RGMa is neuroprotective and promotes neuroplasticity in several preclinical models of neurodegeneration and injury including multiple sclerosis, AIS, and SCI. Given the limitations of current treatments for AIS due to narrow time windows to intervention (TTI), and restrictive patient selection criteria, there is significant unmet need for therapeutic agents that enable tissue survival and repair following acute ischemic damage for a broader population of stroke patients.

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Intravenous (IV) administration of poorly water-soluble small molecule therapeutics can lead to precipitation during mixing with blood. This can limit characterization of pharmacological and safety endpoints in preclinical models. Most often, tests of kinetic and thermodynamic solubility are used to optimize the formulation for solubility prior to infusion in animals, but these do not capture the dynamic precipitation processes that take place during in-vivo administration.

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Article Synopsis
  • Super-boosted lopinavir/ritonavir (LPV/r) dosing strategies vary among infants with HIV due to limited access to pediatric ritonavir formulations, impacting treatment effectiveness.
  • A pharmacokinetic study involved infants aged 1-12 months in sub-Saharan Africa receiving LPV/r in conjunction with or without rifampicin-based TB treatment, assessing drug levels through blood samples.
  • Results indicated that infants on rifampicin often had subtherapeutic LPV levels, highlighting the need for alternative antiretroviral options for those with co-infection, such as dolutegravir.
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Seismically imaged axial melt lenses (AMLs) are seen almost everywhere along the axis of fast-spreading ridges but at only a few localized segment centers on slow-spreading ridges. Standard models assuming that AMLs form when melt percolating upward pools where freezing produces an impermeable cap do not explain this fundamental observation. To tackle this long-standing problem, we combine a crustal density model and a thermal model with a recent mechanical model for sill formation.

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While there is ample evidence that antiretroviral therapy (ART) can improve cognitive outcomes in older children living with HIV, encephalopathy in infants has historically been considered an advanced disease presentation with less likelihood of neurodevelopmental recovery on treatment. More recent studies suggest that timely ART can halt encephalopathic disease progression and even lead to symptom resolution. Here we present a case of an HIV-positive infant diagnosed with encephalopathy who experienced impressive and rapid improvement with a multi-disciplinary care approach that included physical and occupational therapy and ART.

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Supported by the examination of specimens from the entire range and by the analysis of type specimens and the diagnosis of individual names, morphological and genetic studies of the Plagiothecium curvifolium complex resulted in the conclusion that this taxon should be recognized as four separate taxa. In addition to P. curvifolium s.

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The utility of zebrafish is becoming more frequent due to lower costs and high similarities to humans. Zebrafish larvae are attractive subjects for drug screening and drug metabolism research. However, obtaining good quality zebrafish larvae sections for batch samples at designated planes, angles, and locations for comparison purposes is a challenging task.

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