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Ghana Medical Journal Mar 2024To assess the adherence, adverse drug reactions (ADR), and virologic outcomes of dolutegravir-based antiretroviral therapy.
OBJECTIVE
To assess the adherence, adverse drug reactions (ADR), and virologic outcomes of dolutegravir-based antiretroviral therapy.
DESIGN
This was a retrospective chart review.
SETTING
A tertiary health facility-based study in Abakaliki, Nigeria.
PARTICIPANTS
Five hundred and fifteen (515) adult patients on dolutegravir were selected using a Random Number Generator. Demographic and clinical data were extracted from patients' case notes and analysed with IBM-SPSS version-25.
MAIN OUTCOME MEASURES
Adherence to dolutegravir, ADRs, virologic outcome, and change in Body Mass Index (BMI) were estimated.
RESULTS
The mean age of the patients was 45.5±10.8 years; 68.2% of them were females; 97.1% of them had good self-reported adherence. The majority (82.9%) of them reported no ADRs and among those (17.1%) that did, headache (9.7%), body-itching (3.1%), and skin rash (2.7%) dominated. Most achieved viral suppression (94.4%) and did not have detectable viral particles (57.4%). There was a significant increase in the BMI of the patients with a mean weight increase of 0.9kg, a mean BMI increase of 0.3 kg/m, and a 2.6% increase in the prevalence of overweight and obesity.
CONCLUSIONS
Patients on dolutegravir reported low ADRs, good self-reported adherence, and a high viral suppression rate. However, dolutegravir is associated with weight gain. We recommend widespread use and more population-wide studies to elucidate the dolutegravir-associated weight gain.
FUNDING
None declared.
Topics: Humans; Oxazines; Pyridones; Heterocyclic Compounds, 3-Ring; Female; Piperazines; Male; Middle Aged; Retrospective Studies; HIV Infections; Adult; Nigeria; Tertiary Care Centers; Medication Adherence; HIV Integrase Inhibitors; Body Mass Index; Viral Load; Treatment Outcome
PubMed: 38957273
DOI: 10.4314/gmj.v58i1.14 -
Ophthalmic Genetics Jul 2024BCL6 co-repressor () gene variants are involved in oculofaciocardiodental (OFCD) syndrome, acute myeloid leukaemia, renal tumours, and photoreceptor degenerative...
BACKGROUND
BCL6 co-repressor () gene variants are involved in oculofaciocardiodental (OFCD) syndrome, acute myeloid leukaemia, renal tumours, and photoreceptor degenerative diseases. Here, we describe a British family with a pathogenic heterozygous variant in the gene causing congenital nuclear cataract.
METHODS
Whole-exome sequencing was conducted on an individual affected by X-linked dominant congenital cataract in a three-generation family to establish the underlying genetic basis. Bioinformatics analysis confirmed the variants with damaging pathogenicity scores.
RESULTS
A novel likely pathogenic frameshift variant NM_001123385.1: c.3621del; p.Lys1207AsnfsTer31, was identified and found to co-segregate with the disease in this family.
CONCLUSIONS
This is apparently the first report of a variant in causing X-linked dominant congenital cataract which is potentially isolated or presenting with a remarkably mild systemic phenotype. Our findings extend the genetic basis for congenital cataract and add to the phenotypic spectrum of variants.
PubMed: 38957147
DOI: 10.1080/13816810.2024.2373248 -
Analytical Chemistry Jul 2024It is well-known that the bacterial microenvironment imposes restrictions on the growth and behavior of bacteria. The localized monitoring of microenvironmental factors...
It is well-known that the bacterial microenvironment imposes restrictions on the growth and behavior of bacteria. The localized monitoring of microenvironmental factors is appreciated when consulting bacterial adaptation and behavior in the presence of chemical or mechanical stimuli. Herein, we developed a novel liquid crystal (LC) biosensor in a microsphere configuration for real-time 3D monitoring of the bacteria microenvironment, which was implemented by a microfluidic chip. As a proof of concept, a LC gel (LC-Gel) microsphere biosensor was prepared and employed in the localized pH changes of bacteria by observing the configuration change of LC under polarized optical microscopy. Briefly, the microsphere biosensor was constructed in core-shell configuration, wherein the core contained LCE7 (a nematic LC) doped with 4-pentylbiphenyl-4'-carboxylic acid (PBA), and the shell encapsulated the bacteria. The protonation of carboxyl functional groups of the PBA induced a change in charge density on the surface of LCE7 and the orientation of E7 molecules, resulting in the transitions of the LC nucleus from axial to bipolar. The developed LC-Gel microspheres pH sensor exhibited its dominant performance on localized pH real-time sensing with a resolution of 0.1. An intriguing observation from the prepared pH biosensor was that the diverse bacteria impelled distinct acidifying or alkalizing effects. Overall, the facile LC-Gel microsphere biosensor not only provides a versatile tool for label-free, localized pH monitoring but also opens avenues for investigating the effects of chemical and mechanical stimuli on cellular metabolism within bacterial microenvironments.
PubMed: 38957093
DOI: 10.1021/acs.analchem.4c02040 -
Ophthalmic Genetics Jul 2024This case report explores the relationship between genetics and phenotypic variability in autosomal dominant vitreoretinochoroidopathy (ADVIRC). The study focuses on a...
BACKGROUND
This case report explores the relationship between genetics and phenotypic variability in autosomal dominant vitreoretinochoroidopathy (ADVIRC). The study focuses on a case presenting a novel mutation in the gene and its phenotype in the case's relatives, shedding light on the structural and functional intricacies underlying this rare ophthalmologic disorder.
CASE PRESENTATION
A 33-year-old female presented for consultation with a history of bilateral retinal damage accompanied by a complaint of decreased visual acuity, progressive visual field deficit, and night blindness over the past year. Ophthalmic examination revealed a distinctive phenotype, including fibrillar vitreous, pigmented cells, and atrophic hyperpigmented retina in the periphery which was suggestive of a diagnosis of ADVIRC. Genetic testing revealed a heterozygous c.1101-1 G>T variant in , a novel splice site mutation. Functional analysis confirmed its impact on pre-mRNA splicing, resulting in an in-frame deletion (p(Ser367_Asn579del)). Family investigation revealed varying degrees of ophthalmologic impairment in the patient's mother and half-sister, both carrying the same mutation.
CONCLUSIONS
This case report provides the first clinical description of the c.1101-1 G>T mutation in the gene associated with ADVIRC. The presence of intrafamilial variability, as evidenced by the differing clinical features observed in the index case and her half-sister, suggests the potential involvement of mechanisms influencing phenotype expression.: ADVIRC : autosomal dominant vitreoretinochoroidopathy; RNA : ribonucleic acid; RPE : retinal pigment epithelium.
PubMed: 38957071
DOI: 10.1080/13816810.2024.2368797 -
Phytochemical Analysis : PCA Jul 2024Sophora flavescens Aiton (Fabaceae), a ubiquitous plant species in Asia, contains a wide range of pharmacologically active compounds, such as flavonoids, with potential...
Quaternity method for integrated screening, separation, extraction optimization, and bioactivity evaluation of acetylcholinesterase inhibitors from Sophora flavescens Aiton.
INTRODUCTION
Sophora flavescens Aiton (Fabaceae), a ubiquitous plant species in Asia, contains a wide range of pharmacologically active compounds, such as flavonoids, with potential anti-Alzheimer's disease (anti-AD) effects.
OBJECTIVES
The objective of the study is to develop a quaternity method for the screening, isolation, extraction optimization, and activity evaluation of acetylcholinesterase (AChE)-inhibiting compounds from S. flavescens to realize high-throughput screening of active substances in traditional Chinese medicine and to provide experimental data for the development of anti-AD drugs.
METHODS
With AChE as the target molecule, affinity ultrafiltration and liquid chromatography-mass spectrometry were applied to screen for potential inhibitors of the enzyme in S. flavescens. Orthogonal array experiments combined with the multi-objective Non-Dominated Sorting Genetic Algorithm III was used for the first time to optimize the process for extracting the active substances. Enzyme inhibition kinetics and molecular docking studies were performed to verify the potential anti-AD effects of the active compounds.
RESULTS
Five AChE-inhibiting compounds were identified: kushenol I, kurarinone, sophoraflavanone G, isokurarinone, and kushenol E. These were successfully separated at purities of 72.88%, 98.55%, 96.86%, 96.74%, and 95.84%, respectively, using the n-hexane/ethyl acetate/methanol/water (4.0/5.0/4.0/5.0, v/v/v/v), n-hexane/ethyl acetate/methanol/water (5.0/5.0/6.0/4.0, v/v/v/v), and n-hexane/ethyl acetate/methanol/water (4.9/5.1/5.7/4.3, v/v/v/v) mobile phase systems. Enzyme inhibition kinetics revealed that kushenol E had the best inhibitory effect.
CONCLUSION
This study elucidates the mechanism of action of five active AChE inhibitors in S. flavescens and provides a theoretical basis for the screening and development of anti-AD and other therapeutic drugs.
PubMed: 38957046
DOI: 10.1002/pca.3415 -
Korean Circulation Journal Jun 2024The recent developments in chronic thromboembolic pulmonary hypertension (CTEPH) are emphasizing the multidisciplinary team. We report on the changes in clinical...
BACKGROUND AND OBJECTIVES
The recent developments in chronic thromboembolic pulmonary hypertension (CTEPH) are emphasizing the multidisciplinary team. We report on the changes in clinical practice following the development of a multidisciplinary team, based on our 7 years of experience.
METHODS
Multidisciplinary team was established in 2015 offering both balloon pulmonary angioplasty (BPA) and pulmonary endarterectomy (PEA) with technical upgrades by internal and external expertise. For operable cases, PEA was recommended as the primary treatment modality, followed by pulmonary angiography and right heart catheterization after 6 months to evaluate treatment effect and identify patients requiring further BPA. For patients with inoperable anatomy or high surgical risk, BPA was recommended as the initial treatment modality. Patient data and clinical outcomes were closely monitored.
RESULTS
The number of CTEPH treatments rapidly increased and postoperative survival improved after team development. Before the team, 38 patients were treated by PEA for 18 years; however, 125 patients were treated by PEA or BPA after the team for 7 years. The number of PEA performed was 64 and that of BPA 342 sessions. World Health Organization functional class I or II was achieved in 93% of patients. The patients treated with PEA was younger, male dominant, higher pulmonary artery pressure, and smaller cardiac index, than BPA-only patients. In-hospital death after PEA was only 1 case and none after BPA.
CONCLUSIONS
The balanced development of BPA and PEA through a multidisciplinary team approach proved synergistic in increasing the number of actively treated CTEPH patients and improving clinical outcomes.
PubMed: 38956937
DOI: 10.4070/kcj.2024.0021 -
HGG Advances Jul 2024Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed, essential enzymes that complete the first step of protein translation: ligation of amino acids to cognate...
Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed, essential enzymes that complete the first step of protein translation: ligation of amino acids to cognate tRNAs. Genes encoding ARSs have been implicated in myriad dominant and recessive phenotypes, the latter often affecting multiple tissues but with frequent involvement of the central and peripheral nervous systems, liver, and lungs. Threonyl-tRNA synthetase (TARS1) encodes the enzyme that ligates threonine to tRNA in the cytoplasm. To date, TARS1 variants have been implicated in a recessive brittle hair phenotype. To better understand TARS1-related recessive phenotypes, we engineered three TARS1 missense variants at conserved residues and studied these variants in S. cerevisiae and C. elegans models. This revealed two loss-of-function variants, including one hypomorphic allele (R433H). We next used R433H to study the effects of partial loss of TARS1 function in a compound heterozygous mouse model (R432H/null). This model presents with phenotypes reminiscent of patients with TARS1 variants and with distinct lung and skin defects. This study expands the potential clinical heterogeneity of TARS1-related recessive disease, which should guide future clinical and genetic evaluations of patient populations.
PubMed: 38956874
DOI: 10.1016/j.xhgg.2024.100324 -
Ophthalmic Genetics Jul 2024Fleck corneal dystrophy (FCD) is a rare autosomal dominant disease that affects exclusively the corneal stroma. The disease is caused by heterozygous variants in...
BACKGROUND
Fleck corneal dystrophy (FCD) is a rare autosomal dominant disease that affects exclusively the corneal stroma. The disease is caused by heterozygous variants in PIKFYVE, a gene encoding a lipid kinase involved in multiple cellular pathways, primarily participating in membrane dynamics and signaling. This report describes a familial case of FCD caused by a complete deletion of the PIKFYVE gene.
MATERIAL AND METHODS
A clinical ophthalmic examination was performed on the proband and family members. Genetic testing included next-generation sequencing (multigene panel), and chromosomal microarray analysis. A quantitative PCR assay was designed in order to segregate the deletion.
RESULTS
A 19-year-old male, with no family or personal history of ocular disease, presented for evaluation due to an acute illness consisting of burning, foreign body sensation, and red eye. Slit lamp biomicroscopy revealed bilateral small pterygia and scattered bilateral white opacities in the corneal stroma, a very similar corneal phenotype was found in the 47-year-old father, who was asymptomatic. NGS detected a heterozygous deletion of the entire PIKFYVE coding sequence. CMA in DNA from the propositus indicated a 543 kb deletion in 2q33.3q34 spanning the entire PIKFYVE gene. The deletion was confirmed in the father.
CONCLUSIONS
We add to the molecular spectrum of FCD by describing a familial case of a whole PIKFYVE gene deletion in affected subjects. Our findings support that normal expression of PIKFYVE is necessary for corneal keratocytes homeostasis and normal corneal appearance. We conclude that PIKFYVE haploinsufficiency is the molecular mechanism underlying this familial case of FCD.
PubMed: 38956867
DOI: 10.1080/13816810.2024.2365737 -
The Journal of Contemporary Dental... Apr 2024To elucidate the factors that determine the success of direct pulp capping (DPC) in permanent teeth with pulp exposure due to dental caries.
AIM
To elucidate the factors that determine the success of direct pulp capping (DPC) in permanent teeth with pulp exposure due to dental caries.
MATERIALS AND METHODS
A comprehensive electronic search from 1980 to 2023 across PubMed, Scopus, and ISI Web databases was conducted using specific keywords and MeSH terms in Q1 or Q2 journals. Only prospective/retrospective clinical studies in English on 15 or more human permanent teeth with carious pulpal exposure treated with DPC agents-mineral trioxide aggregate (MTA), Biodentine, or calcium hydroxide with a rubber dam and minimum 1-year follow-up, were considered. The factors retrieved and analyzed were based on study design, patient age, sample size, type of cavity, exposure size and location, pulp diagnosis, solutions to achieve hemostasis, hemostasis time, capping material, restoration type, follow-up period, methods of evaluation, and overall success.
REVIEW RESULTS
Out of 680 articles, only 16 articles were selected for the present systematic review on application of the selection criteria. A wide age range of patients from 6 to 88 years were considered among these studies with sample sizes ranging from 15 to 245 teeth with reversible pulpitis being the predominant diagnosis of the cases. Mineral trioxide aggregate as a capping material was evaluated in 4 studies as a lone agent, while compared with other capping agents such as biodentine or calcium hydroxide in 7 studies. The follow-up period ranged from 9 days to nearly 80 months. While both clinical and radiographic evaluation was carried out in all studies, cold testing dominated the clinical tests while IOPR was the common radiograph considered. Mineral trioxide aggregate success rate was higher and similar to biodentine than calcium hydroxide.
CONCLUSION
Direct pulp capping has a high and predictable success rate in permanent teeth with carious exposure to reversible and irreversible pulpitis. Currently, mineral trioxide aggregate and biodentine have better long-term results in DPC than calcium hydroxide, hence, they should be used as an alternative to calcium hydroxide. Definitive restoration within a short period improves long-term prognosis.
CLINICAL SIGNIFICANCE
The significance of this review lies in its provision of evidence-based information on the effectiveness of DPC and the factors that influence its success. By considering these factors, clinicians can optimize treatment outcomes and improve the long-term prognosis of the treated teeth. This systematic review serves as a valuable resource for clinicians and researchers in the field of endodontics. How to cite this article: Gomez-Sosa JF, Granone-Ricella M, Rosciano-Alvarez M, . Determining Factors in the Success of Direct Pulp Capping: A Systematic Review. J Contemp Dent Pract 2024;25(4):392-401.
Topics: Humans; Dental Pulp Capping; Dental Caries; Calcium Compounds; Silicates; Calcium Hydroxide; Pulp Capping and Pulpectomy Agents; Oxides; Aluminum Compounds; Drug Combinations; Treatment Outcome; Dental Pulp Exposure
PubMed: 38956856
DOI: 10.5005/jp-journals-10024-3673 -
Morphology of the scaphotrapeziotrapezoid joint: A multi-domain statistical shape modeling approach.Journal of Orthopaedic Research :... Jul 2024The scaphotrapeziotrapezoid (STT) joint is involved in load transmission between the wrist and thumb. A quantitative description of baseline STT joint morphometrics is...
The scaphotrapeziotrapezoid (STT) joint is involved in load transmission between the wrist and thumb. A quantitative description of baseline STT joint morphometrics is needed to capture the variation of normal anatomy as well as to guide staging of osteoarthritis. Statistical shape modeling (SSM) techniques quantify variations in three-dimensional shapes and relative positions. The objectives of this study are to describe the morphology of the STT joint using a multi-domain SSM. We asked: (1) What are the dominant modes of variation that impact bone and articulation morphology at the STT joint, and (2) what are the morphometrics of SSM-generated STT joints? Thirty adult participants were recruited to a computed tomography study of normal wrist imaging and biomechanics. Segmentations of the carpus were converted to three-dimensional triangular surface meshes. A multi-domain, particle-based entropy system SSM was used to quantify variation in carpal bone shape and position as well as articulation morphology. Articular surface areas and interosseous proximity distributions were calculated between mesh vertex pairs on adjacent bones within distance (2.0 mm) and surface-normal angular (35°) thresholds. In the SSM, the first five modes of variation captured 76.2% of shape variation and contributed to factors such as bone scale, articular geometries, and carpal tilt. Median interosseous proximities-a proxy for joint space-were 1.39 mm (scaphotrapezium), 1.42 mm (scaphotrapezoid), and 0.61 mm (trapeziotrapezoid). This study quantifies morphological and articular variations at the STT joint, presenting a range of normative anatomy. The range of estimated interosseous proximities may guide interpretation of imaging-derived STT joint space.
PubMed: 38956833
DOI: 10.1002/jor.25918