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Abstract Background In Colombia, published studies on the treatment of uncomplicated Plasmodium vivax malaria with chloroquine-primaquine are scarce. The aim of this study was to evaluate the therapeutic response to two treatment regimens at the 28-day follow-up and the occurrence of adverse events in patients with P. vivax malaria. Methods A quasi-experimental clinical trial was conducted at 3 sites in the Department of Amazonas. Patients received supervised or unsupervised anti-malarial treatment (chloroquine plus primaquine), and the primary effectiveness endpoint was the clinical and parasitological response. Safety was assessed through adverse event surveillance. Results A total of 103 patients were included: 53 in the 7-day primaquine group (Group I) and 50 in the group receiving primaquine for 14 days (Group II). Among the patients in group I, an adequate treatment response of 100% and 89.5% was found in patients who received supervised and unsupervised treatment, respectively. In Group II, adequate responses of 100% and 95% were reported for patients who received supervised and unsupervised treatment, respectively. No adverse events were detected. Conclusions The response to combined treatment with chloroquine plus primaquine continues to be adequate for treating P. vivax malaria in the Colombian Amazon region; however, a response to unsupervised treatment in the region is recommended.

Purpose:. To determine if dual-degree training [ie, completion of a National Institutes of Health (NIH)-funded MD/PhD program], among other professional development and demographic variables, predicted academic productivity (eg, K-to-R conversion, number of publications, etc.) among early-career surgeon-scientists. Methods:. We analyzed publicly available data from the National MD/PhD Program Outcomes Study and the Association of American Medical Colleges Graduate Medical Education Track database to identify trends in the number and proportion of MD/PhD graduates pursuing surgical specialties. NIH Research Portfolio Online Reporting Tool Expenditures and Results was interrogated to identify a cohort of early-career academic surgeon-scientists receiving K-awards from 2011 to 2021. Results:. The total number of MD/PhD program graduates completing Graduate Medical Education training increased each decade after the Medical Scientist Training Program was established by the National Institute of General Medical Sciences, but the proportion completing surgical specialties did not change significantly (P = 0.96) from 1965 to 2014. More recent residency match trends demonstrate an increase in both the proportion and number of MD/PhD graduates entering surgical specialties, with 21.5% entering surgical residency training in 2020. Among 476 early-career academic surgeon-scientists receiving K-awards at 70 institutions, 27% were faculty members at only 4 universities, suggesting that federally funded surgeon-scientists are concentrated at a small number of institutions. Although MD/PhD graduates represented only 2.3% of active surgical residents from 2011 to 2020, they constituted a much higher fraction of K-awardees (29%). Of 296 surgeon-scientists who completed K-awards, 35% successfully obtained an R01-equivalent award. Conclusions:. These findings emphasize the need for comprehensive career development and institutional resources to support early-career surgeon-scientists.

Validity and reliability evaluations of the Emotional Quotient Inventory: Youth Version (EQ-i: YV[S]) with children and adolescents from different countries have shown variations in the structural model proposed by Bar-On. Objective. To examine the psychometric properties of EQ-i:YV[S] with a Colombian’ sample. Method. We randomly selected a sample of 1355 children and adolescents between 8 and 14 years old (Mage = 10.80;SD = 1.41). We conducted exploratory (n1 = 416) and confirmatory (n2 = 939) factor analyses (EFA, CFA), reliability, internal consistency, and predictive validity. Results. The EFA explained 27.6% of the variance. The AFC indicated a multidimensional structure with four factors and 21 items obtained the best fit (χ 2 = 334.358; df = 183; RMSEA=0.030; CFI=.951; TLI=944; NFI=.899) with acceptable internal consistency (ω = .57,.75). EQ-i: YV[S] factors explain 18.5% of the observed variance in problem-centered coping scores. Conclusions. The psychometric fit of the inventory supports evidence of its usefulness for screening processes in clinical or educational assessment.

Acute febrile syndrome is a frequent reason for medical consultations in tropical and subtropical countries where the cause could have an infectious origin. Malaria and dengue are the primary etiologies in Colombia. As such, constant epidemiological surveillance and new diagnostic tools are required to identify the causative agents. A descriptive cross-sectional study was conducted to evaluate the circulation and differential diagnosis of six pathogens in two regions of Colombia. The results obtained via multiplex reverse transcription polymerase chain reaction combined with a microwell hybridization assay (m-RT-PCR-ELISA) were comparable to those obtained using rapid tests conducted at the time of patient enrollment. Of 155 patients evaluated, 25 (16.1%) and 16 (10.3%) were positive for malaria and dengue, respectively; no samples were positive for any of the other infectious agents tested. In most cases, m-RT-PCR-ELISA confirmed the results previously obtained through rapid testing.

The genetic diversity of Plasmodium vivax strains in South Asia isn’t well described. Here, the authors sequence P. vivax from returning UK travelers and establish South Asian isolates as subpopulation distinct from East African and South East Asian isolates.

Ticks are obligatory hematophagous ectoparasites that transmit pathogens among various vertebrates, including humans. The microbial and viral communities of ticks, including pathogenic microorganisms, are known to be highly diverse. However, the factors driving this diversity are not well understood. The tropical horse tick, Dermacentor nitens, is distributed throughout the Americas and it is recognized as a natural vector of Babesia caballi and Theileria equi, the causal agents of equine piroplasmosis. In this study, we characterized the bacterial and viral communities associated with partially fed Dermacentor nitens females collected using a passive survey on horses from field sites representing three distinct geographical areas in the country of Colombia (Bolivar, Antioquia, and Cordoba). RNA-seq and sequencing of the V3 and V4 hypervariable regions of the 16S rRNA gene were performed using the Illumina-Miseq platform (Illumina, San Diego, CA, USA). A total of 356 operational taxonomic units (OTUs) were identified, in which the presumed endosymbiont, Francisellaceae/Francisella spp., was predominantly found. Nine contigs corresponding to six different viruses were identified in three viral families: Chuviridae, Rhabdoviridae, and Flaviviridae. Differences in the relative abundance of the microbial composition among the geographical regions were found to be independent of the presence of Francisella-like endosymbiont (FLE). The most prevalent bacteria found in each region were Corynebacterium in Bolivar, Staphylococcus in Antioquia, and Pseudomonas in Cordoba. Rickettsia-like endosymbionts, mainly recognized as the etiological agent of rickettsioses in Colombia, were detected in the Cordoba samples. Metatranscriptomics revealed 13 contigs containing FLE genes, suggesting a trend of regional differences. These findings suggest regional distinctions among the ticks and their bacterial compositions.

Purpose: To identify vitreous molecular biomarkers associated with autoimmune retinopathy (AIR). Design: Case-control study. Participants: We analyzed 6 eyes from 4 patients diagnosed with AIR and 8 comparative controls diagnosed with idiopathic macular holes (IMHs) and epiretinal membranes (ERMs). Methods: Vitreous biopsies were collected from the participants and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) or multiplex enzyme-linked immunoassay (ELISA). Main Outcome Measures: Protein expression changes were evaluated by 1-way analysis of variance (significant P value < 0.05), hierarchical clustering, and pathway analysis to identify candidate protein biomarkers. Results: There were 16 significantly upregulated and 17 significantly downregulated proteins in the vitreous of 3 patients with AIR compared with controls. The most significantly upregulated proteins included lysozyme C, zinc-alpha-2-glycoprotein, complement factor D, transforming growth factor-ß (TGF-ß)–induced protein, beta-crystallin B2, and alpha-crystallin A chain. The most significantly downregulated proteins included DIP2C, retbindin, and amyloid beta precursor-like protein 2. Pathway analysis revealed that vascular endothelial growth factor (VEGF) signaling was a top represented pathway in the vitreous of patients with AIR compared with controls. In comparison with a different cohort of 3 patients with AIR analyzed by multiplex ELISA, a commonly differentially expressed protein was neuronal cell adhesion molecule (NrCAM) with P values of 0.027 in the LC-MS/MS dataset and 0.035 in the ELISA dataset. Conclusions: Protein biomarkers in the vitreous, such as NrCAM, may eventually help diagnose AIR.

Academia is often critiqued as an “ivory tower” where research, thinking, and teaching are isolated from the complexity and everyday experience of so many people. As instructors of political and other psychology courses, we strive to break down these barriers and engage with the dynamic and nuanced nature of phenomena as situated in lived social and political contexts. In this report, we unpack and detail how we strive to achieve this goal by expanding on Plous’ articulation of action teaching (2012). We first define our pedagogical focus on active engagement, critical thinking, and staying on the move between multiple perspectives. We then provide specific examples of how we enact our philosophy in activities and assessment. We end by articulating how this approach to teaching in social and political psychology can be understood as furthering not only our students’ intellectual growth as psychologists, but also their development as democratic citizens. In doing so, we argue that action teaching not only involves course activities directly engaging with social issues, but also provides students with a scaffold to actually do so in a way that is attentive to the complexity, pluralism, and dynamism of social and political issues.

The pursuit and acknowledgment of the truth of past atrocities and human rights abuses are critical processes in transitional societies. While truth commissions have become a central part of achieving these goals, there has historically been minimal attention to the role of teachers and students in this work. Critical and thoughtful teaching about the past conflict, however, may help prevent the reoccurrence of atrocities, promote acknowledgment and accountability of the past (which, in turn, fosters psychosocial healing), and support the construction of a peaceful society. In this paper, I detail a research collaboration with Colombia’s truth commission to aid its pedagogical efforts to develop effective resources and support Colombian educators’ instruction about the truth of past atrocities. I first draw on the literature to demonstrate the potential for education—and, specifically, teachers—to support the goals of truth commissions. Then, I describe the Colombian context and this specific collaboration. Finally, I end by presenting preliminary findings from surveys of teachers across Colombia and detailing future directions.

Purpose: Acanthamoeba chorioretinitis is a rare manifestation of the parasitic infection, and reported cases often result in enucleation. Surgical removal of Acanthamoeba chorioretinitis has not been previously described. We report a surgical case of Acanthamoeba chorioretinitis spread from keratitis that ultimately resulted in a disease-free outcome. Observations: A healthy 80-year-old male with a history of keratoconus requiring a penetrating keratoplasty in the fellow eye presented with a severe corneal ulcer clinically consistent with Acanthamoeba keratitis. He ultimately required a penetrating keratoplasty and improved clinically until he developed vitritis on post-operative month 1 and was diagnosed with endophthalmitis. B-scan ultrasound demonstrated vitreous opacities and a large retinal mass that reduced in size following serial intravitreal injections of antibiotics, oral antibiotics, and a limited pars plana vitrectomy. He underwent a repeat pars plana vitrectomy 6 weeks later and a retinal mass in the mid-periphery with an associated tractional retinal detachment was noted. A localized retinectomy was performed around the lesion which was excised entirely, and silicone oil was instilled. Pathology of the lesion showed acute and chronic granulomatous necrotizing inflammation with the presence of several definitive amoebic organisms and numerous cells suspicious for amoebae. The patient was maintained on oral antibiotics by the Infectious Disease Service and was disease-free 1-year post-infection. Conclusions and importance: Acanthamoeba chorioretinitis is a rare, devastating disease and often leads to enucleation. We present a surgical case showing control of the infection utilizing a surgical retinectomy. Aggressive local therapy and a multidisciplinary approach with the Infectious Disease Service may lead to a successful outcome.

Summary: Rare diseases are an emerging global health priority. Although individually rare, the prevalence of rare “orphan” diseases is high, affecting approximately 300 million people worldwide. Treatments for these conditions are often inadequate, leaving the disease to progress unabated. Here, we review the clinical features and pathophysiology of neovascular inflammatory vitreoretinopathy (NIV), a rare inflammatory retinal disease caused by mutations in the CAPN5 gene. Although the prevalence of NIV is low (1 in 1,000,000 people), the disease mimics more common causes of blindness (e.g. uveitis, retinitis pigmentosa, proliferative diabetic retinopathy, and proliferative vitreoretinopathy) at distinct clinical stages. There is no cure for NIV to date. We highlight how personalized proteomics helped identify potential stage-specific biomarkers and drug targets in liquid vitreous biopsies. The NIV vitreous proteome revealed enrichment of molecular pathways associated with common retinal pathologies and implicated superior targets for therapeutic drug repositioning. In addition, we review our pipeline for collecting, storing, and analyzing ophthalmic surgical samples. This approach can be adapted to treat a variety of rare genetic diseases.

Purpose: To profile vitreous protein expression of intermediate uveitis (IU) patients. Observations: We identified a mean of 363 ± 41 unique proteins (mean ± SD) in IU vitreous and 393 ± 69 unique proteins in control samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of liquid vitreous biopsies collected during pars plana vitrectomy. A total of 233 proteins were differentially expressed among control and IU samples, suggesting a protein signature that could distinguish the two groups. Pathway analysis identified 22 inflammatory mediators of the interleukin-12 (IL-12) signaling pathway in IU vitreous. Upstream regulator analysis identified downstream mediators of IL-23 and myeloid differentiation primary response protein (MYD88), both of which are involved in the recruitment and differentiation of myeloid cells. Taken together, our results suggest the recruitment of myeloid cells as an upstream pathway in the pathogenesis of IU. Conclusions: This study provides insights into proteins that will serve as biomarkers and therapeutic targets for IU. These biomarkers will help design future clinical trials using rational molecular therapeutics.

Background: Neurodegenerative diseases are incurable disorders caused by progressive neuronal cell death. Retinitis pigmentosa (RP) is a blinding neurodegenerative disease that results in photoreceptor death and progresses to the loss of the entire retinal network. We previously found that proteomic analysis of the adjacent vitreous served as way to indirectly biopsy the retina and identify changes in the retinal proteome. Methods: We analyzed protein expression in liquid vitreous biopsies from autosomal recessive (ar)RP patients with PDE6A mutations and arRP mice with Pde6ɑ mutations. Proteomic analysis of retina and vitreous samples identified molecular pathways affected at the onset of photoreceptor death. Based on affected molecular pathways, arRP mice were treated with a ketogenic diet or metabolites involved in fatty-acid synthesis, oxidative phosphorylation, and the tricarboxylic acid (TCA) cycle. Findings: Dietary supplementation of a single metabolite, ɑ-ketoglutarate, increased docosahexaeonic acid levels, provided neuroprotection, and enhanced visual function in arRP mice. A ketogenic diet delayed photoreceptor cell loss, while vitamin B supplementation had a limited effect. Finally, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) on ɑ-ketoglutarate-treated mice revealed restoration of metabolites that correlated with our proteomic findings: uridine, dihydrouridine, and thymidine (pyrimidine and purine metabolism), glutamine and glutamate (glutamine/glutamate conversion), and succinic and aconitic acid (TCA cycle). Interpretation: This study demonstrates that replenishing TCA cycle metabolites via oral supplementation prolongs retinal function and provides a neuroprotective effect on the photoreceptor cells and inner retinal network. Funding: NIH grants [R01EY026682, R01EY024665, R01EY025225, R01EY024698, R21AG050437, P30EY026877, 5P30EY019007, R01EY018213, F30EYE027986, T32GM007337, 5P30CA013696], NSF grant CHE-1734082. Keywords: Metabolomics, Metabolite supplementation, TCA cycle, Ketogenic diet, ɑ-ketoglutarate, Desorption electrospray ionization mass spectrometry

Abstract Background SLIT2 is a protein ligand for the Roundabout (ROBO) receptor and was found to play a major role in repulsive midline axon guidance in central nervous system development. Based on studies utilizing knockout models, it has been postulated that SLIT2 is important for preventing inappropriate axonal routing during mammalian optic chiasm development. Methods Case report. Results Here, we report a case of congenital myopia, anisometropia, and obesity in a patient with a SLIT2 point mutation. Examination of the patient’s skin biopsy revealed abnormalities in elastin and collagen fibrils that suggest an underlying connective tissue disorder. Structural modeling placed the novel mutation (p.D1407G) in the EGF-like domain 8 and was predicted to affect interactions with SLIT2 binding partners. Conclusions To the authors’ knowledge, this is the first report of a SLIT2 variant in the context of these ocular findings.

Purpose: To report a case of elevated intraocular pressure with retinal detachment. Observations: Liquid chromatography and tandem mass spectrometry was performed on the patient aqueous biopsy. Protein levels were analyzed with 1-way analysis of variance (ANOVA) and unbiased clustering. High levels of rod outer segment proteins were not detected, suggesting that this was not a case of Schwartz-Matsuo syndrome. Instead, elevated levels of Hepcidin (HEPC) and Cystatin C (CYTC; candidate biomarkers for primary open angle glaucoma) were detected, suggesting a different, unknown etiology. Conclusions and importance: Molecular diagnoses can differentiate between clinical diagnoses and point to common biomarkers or disease mechanisms.

Summary: Increased calpain activity is linked to neuroinflammation including a heritable retinal disease caused by hyper-activating mutations in the calcium-activated calpain-5 (CAPN5) protease. Although structures for classical calpains are known, the structure of CAPN5, a non-classical calpain, remains undetermined. Here we report the 2.8 Å crystal structure of the human CAPN5 protease core (CAPN5-PC). Compared to classical calpains, CAPN5-PC requires high calcium concentrations for maximal activity. Structure-based phylogenetic analysis and multiple sequence alignment reveal that CAPN5-PC contains three elongated flexible loops compared to its classical counterparts. The presence of a disease-causing mutation (c.799G>A, p.Gly267Ser) on the unique PC2L2 loop reveals a function in this region for regulating enzymatic activity. This mechanism could be transferred to distant calpains, using synthetic calpain hybrids, suggesting an evolutionary mechanism for fine-tuning calpain function by modifying flexible loops. Further, the open (inactive) conformation of CAPN5-PC provides structural insight into CAPN5-specific residues that can guide inhibitor design. : Velez et al. report the crystal structure of the calpain-5 protease core (CAPN5-PC). Sequence- and structure-based phylogenetic analysis reveals that CAPN5-PC contains three elongated loops compared to classical calpains. One loop contains a hyperactivating mutation that causes neovascular inflammatory vitreoretinopathy, revealing a function in this region for regulating proteolytic activity. Keywords: calpain, CAPN5, NIV, protease, uveitis, disease-causing mutations, structural phylogenetics, structural phylogenetics, crystal structure, synthetic biology, calcium-binding protein, enzyme kinetics

Se analizan los patrones de colaboración del sistema de investigación agropecuario en Colombia que surgen de la conformación de colegios invisibles. El análisis se hace en tres niveles: macro, referido a los patrones generales que organizan la colaboración en colegios invisibles, meso, que describe la capacidad de enlace de las distintas organizaciones en el sistema y micro, la conformación de colegios invisibles que permiten observar la diversidad temática. La combinación de los tres niveles, reflejan un sistema de investigación en proceso de consolidación, pero aún frágil. Para este estudio se consideraron las publicaciones realizadas en revistas Web of Science por autores adscritos al Programa Nacional de CTI en Ciencias Agropecuarias y aquellos relacionados con la emergencia de comunidades temáticas derivadas el acoplamiento bibliográfico. Metodológicamente se aplica un análisis multinivel de redes de co-citación y colaboración empleando coeficientes de correlación, identificando conectores del sistema y detectando las comunidades semánticas que se constituyen en colegios invisibles.

Ocular disorders originating in the retina can result in a partial or total loss of vision, making drug delivery to the retina of vital importance. However, effectively delivering drugs to the retina remains a challenge for ophthalmologists due to various anatomical and physicochemical barriers in the eye. This review introduces diverse administration routes and the accordant pharmacokinetic profiles of ocular drugs to aid in the development of safe and efficient drug delivery systems to the retina with a focus on peptidomimetics as a growing class of retinal drugs, which have great therapeutic potential and a high degree of specificity. We also discuss the pharmacokinetic profiles of small molecule drugs due to their structural similarity to small peptidomimetics. Lastly, various formulation strategies are suggested to overcome pharmacokinetic hurdles such as solubility, retention time, enzymatic degradation, tissue targeting, and membrane permeability. This knowledge can be used to help design ocular delivery platforms for peptidomimetics, not only for the treatment of various retinal diseases, but also for the selection of potential peptidomimetic drug targets.

Differences in regional protein expression within the human retina may explain molecular predisposition of specific regions to ophthalmic diseases like age-related macular degeneration, cystoid macular edema, retinitis pigmentosa, and diabetic retinopathy. To quantify protein levels in the human retina and identify patterns of differentially-expressed proteins, we collected foveomacular, juxta-macular, and peripheral retina punch biopsies from healthy donor eyes and analyzed protein content by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Protein expression was analyzed with 1-way ANOVA, gene ontology, pathway representation, and network analysis. We identified a mean of 1,974 proteins in the foveomacular retina, 1,999 in the juxta-macular retina, and 1,779 in the peripheral retina. Six hundred ninety-seven differentially-expressed proteins included those unique to and abundant in each anatomic region. Proteins with higher expression in each region include: heat-shock protein 90-alpha (HSP90AA1), and pyruvate kinase (PKM) in the foveomacular retina; vimentin (VIM) and fructose-bisphosphate aldolase C (ALDOC); and guanine nucleotide-binding protein subunit beta-1 (GNB1) and guanine nucleotide-binding protein subunit alpha-1 (GNAT1) in the peripheral retina. Pathway analysis identified downstream mediators of the integrin signaling pathway to be highly represented in the foveomacular region (P = 6.48 e-06). Metabolic pathways were differentially expressed among all retinal regions. Gene ontology analysis showed that proteins related to antioxidant activity were higher in the juxta-macular and the peripheral retina, but present in lower amounts in the foveomacular retina. Our proteomic analysis suggests that certain retinal regions are susceptible to different forms of metabolic and oxidative stress. The findings give mechanistic insight into retina function, reveal important molecular processes, and prioritize new pathways for therapeutic targeting.

This study utilized focus groups with Latinx students at a private, Midwestern university to explore the complexities inherent in the process of becoming a Hispanic-Serving Institution (HSI). The purpose of the study was: (a) to better understand Latinx students' experiences at an "emerging" HSI, and (b) to understand how students understand an institutional journey toward the HSI designation. Findings point toward the value in exploring the Latinx student experience and perspective on HSI initiatives.

[This corrects the article DOI: 10.1371/journal.pone.0169687.].

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare, pediatric, autoinflammatory disease characterized by bone pain due to sterile osteomyelitis, and is often accompanied by psoriasis or inflammatory bowel disease. There are two syndromic forms of CRMO, Majeed syndrome and DIRA, for which the genetic cause is known. However, for the majority of cases of CRMO, the genetic basis is unknown. Via whole-exome sequencing, we detected a homozygous mutation in the filamin-binding domain of FBLIM1 in an affected child with consanguineous parents. Microarray analysis of bone marrow macrophages from the CRMO murine model (cmo) determined that the Fblim1 ortholog is the most differentially expressed gene, downregulated over 20-fold in the cmo mouse. We sequenced FBLIM1 in 96 CRMO subjects and found a second proband with a novel frameshift mutation in exon 6 and a rare regulatory variant. In SaOS2 cells, overexpressing the regulatory mutation showed the flanking region acts as an enhancer, and the mutation ablates enhancer activity. Our data implicate FBLIM1 in the pathogenesis of sterile bone inflammation and our findings suggest CRMO is a disorder of chronic inflammation and imbalanced bone remodeling.

Krüppel-like factor 11 (KLF11) and the highly homologous KLF10 proteins are transcription factors originating from duplication of the Drosophila melanogaster ancestor cabut. The function of these proteins in epithelial cells has been previously characterized. In the current study, we report a functional role for KLF11 in mesenchymal cells and in mesenchymal cell dysfunction, namely, fibrosis, and subsequently perform a detailed cellular, molecular, and in vivo characterization of this phenomenon. We find that, in cultured mesenchymal cells, enhanced expression of KLF11 results in activated extracellular matrix pathways, including collagen gene silencing and matrix metalloproteinases activation without changes in tissue inhibitors of metalloproteinases. Combined, reporter and chromatin immunoprecipitation assays demonstrate that KLF11 interacts directly with the collagen 1a2 (COL1A2) promoter in mesenchymal cells to repress its activity. Mechanistically, KLF11 regulates collagen gene expression through the heterochromatin protein 1 gene-silencing pathway as mutants defective for coupling to this epigenetic modifier lose the ability to repress COL1A2. Expression studies reveal decreased levels of KLF11 during liver fibrogenesis after chemically induced injury in vivo. Congruently, KLF11(-/-) mice, which should be deficient in the hypothesized anti-fibrogenic brake imposed by this transcription factor, display an enhanced response to liver injury with increased collagen fibril deposition. Thus, KLFs expands the repertoire of transcription factors involved in the regulation of extracellular matrix proteins in mesenchymal cells and define a novel pathway that modulates the fibrogenic response during liver injury.

Objective: Unusual clinical course Background: Atrial flutter is associated with significant morbidity and mortality. Standard treatment involves rate and rhythm control medications, with ablation procedures reserved for more persistent cases. While ablation is generally successful, it carries risks, such as complete heart block, as in this case. Case Report: A 73-year-old woman presented for ablation of recurrent atypical atrial flutter. Electro-anatomic mapping demonstrated counterclockwise mitral annular flutter. An anterior ablation line was initially created from the right superior pulmonary vein to the mitral valve annulus. As the line was extended to the anterior mitral valve annulus at the 9 o'clock position, complete heart block occurred, and ablation was immediately terminated. Complete recovery of atrioventricular (AV) conduction occurred within 1 min. The catheter tip was within 1.8 cm from the His bundle, as denoted by the yellow tag on the CARTO map. A second mitral line was created anteriorly at the 11 o'clock position on the mitral valve annulus and extended to the left atrial roof line, with the termination and creation of a bi-directional mitral isthmus block. She remained in sinus rhythm after ablation, with PR prolongation and no AV block. The following day, she developed severe bradycardia due to complete heart block, with a slow ventricular escape rhythm, requiring implantation of a permanent pacemaker. Conclusions: This case underscores the importance of precise catheter positioning during anterior mitral line ablation to prevent complications, such as AV block. Anterior mitral line ablation should be performed in a more anterior location away from the septum to minimize the risk of AV block. [ABSTRACT FROM AUTHOR]

Abstract Increasing reports of chloroquine resistance (CQR) in Plasmodium vivax endemic regions have led to several countries, including Indonesia, to adopt dihydroarteminsin-piperaquine instead. However, the molecular drivers of CQR remain unclear. Using a genome-wide approach, we perform a genomic analysis of 1534 P. vivax isolates across 29 endemic countries, detailing population structure, patterns of relatedness, selection, and resistance profiling, providing insights into potential drivers of CQR. Selective sweeps in a locus proximal to pvmdr1, a putative marker for CQR, along with transcriptional regulation genes, distinguish isolates from Indonesia from those in regions where chloroquine remains highly effective. In 106 isolates from Indonesian Papua, the epicentre of CQR, we observe an increasing prevalence of novel SNPs in the candidate resistance gene pvmrp1 since the introduction of dihydroartemisinin-piperaquine. Overall, we provide novel markers for resistance surveillance, supported by evidence of regions under recent directional selection and temporal analysis in this continually evolving parasite.