Sex differences in brain atrophy in dementia with Lewy bodies.

INTRODUCTION: Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI). METHODS: We included 436 patients from the European-DLB consortium and the Mayo Clinic. Sex differences and sex-by-age interactions were assessed through visual atrophy rating scales (n = 327; 73 ± 8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness (n = 165; 69 ± 9 years, 72% males). RESULTS: We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex-by-age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex. DISCUSSION: We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75. HIGHLIGHTS: Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales. Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods. Sex differences in gray matter measures in DLB tended to disappear with increasing age.

The Repellent Capacity against Sitophilus zeamais (Coleoptera: Curculionidae) and In Vitro Inhibition of the Acetylcholinesterase Enzyme of 11 Essential Oils from Six Plants of the Caribbean Region of Colombia.

The repellent capacity against Sitophilus zeamais and the in vitro inhibition on AChE of 11 essential oils, isolated from six plants of the northern region of Colombia, were assessed using a modified tunnel-type device and the Ellman colorimetric method, respectively. The results were as follows: (i) the degree of repellency (DR) of the EOs against S. zeamais was 20-68% (2 h) and 28-74% (4 h); (ii) the IC50 values on AChE were 5-36 µg/mL; likewise, the %inh. on AChE (1 µg/cm3 per EO) did not show any effect in 91% of the EO tested; (iii) six EOs (Bursera graveolens-bark, B. graveolens-leaves, B. simaruba-bark, Peperomia pellucida-leaves, Piper holtonii (1b*)-leaves, and P. reticulatum-leaves) exhibited a DR (53-74%) ≥ C+ (chlorpyrifos-61%), while all EOs were less active (8-60-fold) on AChE compared to chlorpyrifos (IC50 of 0.59 µg/mL). Based on the ANOVA/linear regression and multivariate analysis of data, some differences/similarities could be established, as well as identifying the most active EOs (five: B. simaruba-bark, Pep. Pellucida-leaves, P. holtonii (1b*)-leaves, B. graveolens-bark, and B. graveolens-leaves). Finally, these EOs were constituted by spathulenol (24%)/ß-selinene (18%)/caryophyllene oxide (10%)-B. simaruba; carotol (44%)/dillapiole (21%)-Pep. pellucida; dillapiole (81% confirmed by 1H-/13C-NMR)-P. holtonii; mint furanone derivative (14%)/mint furanone (14%)-B. graveolens-bark; limonene (17%)/carvone (10%)-B. graveolens-leaves.

Development of a novel serological assay for the detection of mpox infection in vaccinated populations.

In 2022 the World Health Organization declared a Public Health Emergency for an outbreak of mpox, the zoonotic Orthopoxvirus (OPV) affecting at least 104 nonendemic locations worldwide. Serologic detection of mpox infection is problematic, however, due to considerable antigenic and serologic cross-reactivity among OPVs and smallpox-vaccinated individuals. In this report, we developed a high-throughput multiplex microsphere immunoassay using a combination of mpox-specific peptides and cross-reactive OPV proteins that results in the specific serologic detection of mpox infection with 93% sensitivity and 98% specificity. The New York State Non-Vaccinia Orthopoxvirus Microsphere Immunoassay is an important tool to detect subclinical mpox infection and understand the extent of mpox spread in the community through retrospective analysis.

Volatile Metabolites of Piper eriopodon (Miq.) C.DC. from Northern Region of Colombia and Assessment of In Vitro Bioactivities of the Leaf Essential Oil.

Piper eriopodon is one of the Piper species found in the Sierra Nevada de Santa Marta, and the species has been reported with different compositions of their essential oils (EO). In this study, the volatile fractions/essential oil (by HS-SPME/SDE/MWHD-GC-MS/1H-NMR) of different parts from the plant were characterized, and assessments of the in vitro bio-properties of the leaf EO were conducted. The results indicated the following: (i) in the volatile fractions were ß-caryophyllene (~23%)/myrcene (~20%) (inflorescences) and ß-caryophyllene (~43%)/ß-selinene (~20%) (leaves) using HS-SPME; myrcene (~31%)/ß-pinene (~23%) (inflorescences), gibbilimbol B (~60%) (fruits) and gibbilimbol B (~46%)/ß-caryophyllene (~11%) (leaves) through SDE; (ii) leaf EO contained gibbilimbol B (~72%), confirmed with 1H-NMR; (iii) the cytotoxic values (µg/mL) in erythrocytes/lymphocytes/Hep-2 were HC50: 115 ± 3 (eryth.), LC50: 71 ± 4 (lymph.) and LC50: 33 ± 2 (cell-line); (iv) the antibacterial susceptibilities (ϕ inh. zone, mm; 4-16 µg EO) were 22.5 ± 0.4-97 ± 4 (Staphylococcus aureus), 23 ± 2-77 ± 4 (Escherichia coli) and 17 ± 1-48 ± 3 (Listeria monocytogenes); (v) the TAA value was 2249 ± 130 mmol Trolox®/kg; (vi) the IC50 value was 13±1 µg/mL (AChE) with 20 ± 0-37 ± 6% repellency (2-4 h, Sitophilus zeamais). Thus, the EO of P. eriopodon leaves from northern Colombia could be a promising species for sustainable exploitation in the future due to its outstanding bioactivities.

HIV protease cleaves the antiviral m6A reader protein YTHDF3 in the viral particle.

N6-methyladenosine (m6A) is the most abundant HIV RNA modification but the interplay between the m6A reader protein YTHDF3 and HIV replication is not well understood. We found that knockout of YTHDF3 in human CD4+ T-cells increases infection supporting the role of YTHDF3 as a restriction factor. Overexpression of the YTHDF3 protein in the producer cells reduces the infectivity of the newly produced viruses. YTHDF3 proteins are incorporated into HIV particles in a nucleocapsid-dependent manner permitting the m6A reader protein to limit infection in the new target cell at the step of reverse transcription. Importantly, HIV protease cleaves the virion-incorporated full-length YTHDF3 protein, a process which is blocked by HIV protease inhibitors used to treat HIV infected patients. Mass-spectrometry confirmed the proteolytic processing of YTHDF3 in the virion. Thus, HIV protease cleaves the virion-encapsidated host m6A effector protein in addition to the viral polyproteins to ensure optimal infectivity of the mature virion.

The effect of an online exercise programme on bone health in paediatric cancer survivors (iBoneFIT): study protocol of a multi-centre randomized controlled trial.

BACKGROUND: New approaches on paediatric cancer treatment aim to maintain long-term health. As a result of radiotherapy, chemotherapy or surgery, paediatric cancer survivors tend to suffer from any chronic health condition. Endocrine dysfunction represents one of the most common issues and affects bone health. Exercise is key for bone mass accrual during growth, specifically plyometric jump training. The iBoneFIT study will investigate the effect of a 9-month online exercise programme on bone health in paediatric cancer survivors. This study will also examine the effect of the intervention on body composition, physical fitness, physical activity, calcium intake, vitamin D, blood samples quality of life and mental health. METHODS: A minimum of 116 participants aged 6 to 18 years will be randomized into an intervention (n = 58) or control group (n = 58). The intervention group will receive an online exercise programme and diet counselling on calcium and vitamin D. In addition, five behaviour change techniques and a gamification design will be implemented in order to increase the interest of this non-game programme. The control group will only receive diet counselling. Participants will be assessed on 3 occasions: 1) at baseline; 2) after the 9 months of the intervention; 3) 4 months following the intervention. The primary outcome will be determined by dual energy X-ray absorptiometry (DXA) and the hip structural analysis, trabecular bone score and 3D-DXA softwares. Secondary outcomes will include anthropometry, body composition, physical fitness, physical activity, calcium and vitamin D intake, blood samples, quality of life and mental health. DISCUSSION: Whether a simple, feasible and short in duration exercise programme can improve bone health has not been examined in paediatric cancer survivors. This article describes the design, rationale and methods of a study intended to test the effect of a rigorous online exercise programme on bone health in paediatric cancer survivors. If successful, the iBoneFIT study will contribute to decrease chronic health conditions in this population and will have a positive impact in the society. TRIAL REGISTRATION: Prospectively registered in isrctn.com: isrctn61195625 . Registered 2 April 2020.

Association of Outcomes and Socioeconomic Status in Mexican Patients Undergoing Allogeneic Stem Cell Transplantation.

The association of clinical outcomes after hematopoietic stem cell transplantation (HSCT) with the patient's socioeconomic status (SES) remains controversial, with the majority of studies reported to date performed in developed countries. Data from low- and middle-income regions where the SES varies greatly remain scarce. The objective of this study was to associate SES with outcomes after allogeneic HSCT in a referral center in Mexico. A retrospective study was performed including 124 consecutive patients. Patients were dichotomized into 2 groups based on a consensus with the Department of Social Work: low SES (level I-II) and high SES (level ≥III). Most patients were of low SES (n = 84; 68%). Age, educational attainment, employment status, and financial support were the sociodemographic characteristics that statistically differed between the 2 groups. All patients with low SES received financial support from governmental agencies or nongovernmental organizations (NGOs). Nonrelapse mortality and overall survival were similar in the 2 groups. Our study found no statistically significant differences in survival outcomes between patients of low SES and high SES. This demonstrates that our HSCT approaches are standardized and that all patients can benefit from HSCT irrespective of their financial status. It also suggests that the good outcomes in patients with low SES probably are related to the substantial governmental, NGO, and/or institutional subsidies these patients receive.

Three-dimensional structure and ligand-binding site of carp fishelectin (FEL).

Carp FEL (fishelectin or fish-egg lectin) is a 238-amino-acid lectin that can be purified from fish eggs by exploiting its selective binding to Sepharose followed by elution with N-acetylglucosamine. Its amino-acid sequence and other biochemical properties have previously been reported. The glycoprotein has four disulfide bridges and the structure of the oligosaccharides linked to Asn27 has been described. Here, the three-dimensional structures of apo carp FEL (cFEL) and of its complex with N-acetylglucosamine determined by X-ray crystallography at resolutions of 1.35 and 1.70 Å, respectively, are reported. The molecule folds as a six-bladed ß-propeller and internal short consensus amino-acid sequences have been identified in all of the blades. A calcium atom binds at the bottom of the funnel-shaped tunnel located in the centre of the propeller. Two ligand-binding sites, α and ß, are present in each of the two protomers in the dimer. The first site, α, is closer to the N-terminus of the chain and is located in the crevice between the second and the third blades, while the second site, ß, is located between the fourth and the fifth blades. The amino acids that participate in the contacts have been identified, as well as the conserved water molecules in all of the sites. Both sites can bind the two anomers, α and ß, of N-acetylglucosamine, as is clearly recognizable in the electron-density maps. The lectin presents sequence homology to members of the tachylectin family, which are known to have a function in the innate immune system of arthropods, and homologous genes are present in the genomes of other fish and amphibians. This structure is the first of a protein of this group and, given the degree of homology with other members of the family, it is expected that it will be useful to experimentally determine other crystal structures using the coordinates of cFEL as a search probe in molecular replacement.

Acremoxanthone E, a novel member of heterodimeric polyketides with a bicyclo[3.2.2]nonene ring, produced by Acremonium camptosporum W. GAMS (Clavicipitaceae) endophytic fungus.

Bioactivity-directed fractionation of the organic mycelium extract of the endophytic fungus Acremonium camptosporum W. Gams (Clavicipitaceae), isolated from the leaves of Bursera simaruba (Burseraceae), led to the isolation of six major heterodimeric polyketides, including one not previously characterized acremoxanthone derivative. In addition, the already known acremoxanthone C, acremonidins A and B, and acremoxanthones A and B were obtained. The structure of the new compound was established by extensive NMR studies, including DEPT, COSY, NOESY, HSQC, and HMBC methods. The trivial name proposed for this compound is acremoxanthone E. In addition, the structure of acremoxanthone C was unequivocally established for the first time, through X-ray crystal-structure analysis. The anti-oomycete activities of the pure compounds were tested against four economically important phytopathogenic oomycetes. Inhibitory concentration for 50% diameter growth reduction, IC50 , values for the four phytopathogens ranged from 6 to 38 µM. Also, in parallel, the cytotoxic activities against six cancer cell lines were evaluated showing IC50 values similar to those of cisplatin. To the best of our knowledge, this is the first report on three different groups of heterodimeric polyketides, linked by a bicyclo[3.2.2]nonene, such as xanthoquinodins, acremonidins, and acremoxanthones, which are isolated from an endophytic fungus. In addition, a common biosynthetic origin could be proposed.

Successes, challenges and needs regarding rural health medical education in continental Central America: a literature review and narrative synthesis.

INTRODUCTION: Central American countries, like many others, face a shortage of rural health physicians. Most medical schools in this region are located in urban areas and focus on tertiary care training rather than on community health or primary care, which are better suited for rural practice. However, many countries require young physicians to do community service in rural communities to address healthcare provider shortages. This study aimed to: (a) synthesize what is known about the current state of medical education preparing physicians for rural practice in this region, and (b) identify common needs, challenges and opportunities for improving medical education in this area. METHODS: A comprehensive literature review was conducted between December 2013 and May 2014. The stepwise, reproducible search process included English and Spanish language resources from both data-based web search engines (PubMed, Web of Science/Web of Knowledge, ERIC and Google Scholar) and the grey literature. Search criteria included MeSH terms: 'medical education', 'rural health', 'primary care', 'community medicine', 'social service', in conjunction with 'Central America', 'Latin America', 'Mexico', 'Guatemala', 'Belize', 'El Salvador', 'Nicaragua', 'Honduras', 'Costa Rica' and 'Panama'. Articles were included in the review if they (1) were published after 1984; (2) focused on medical education for rural health, primary care, community health; and (3) involved the countries of interest. A narrative synthesis of the content of resources meeting inclusion criteria was done using qualitative research methods to identify common themes pertaining to the study goals. RESULTS: The search revealed 20 resources that met inclusion criteria. Only four of the 20 were research articles; therefore, information about this subject was primarily derived from expert opinion. Thematic analysis revealed the historical existence of several innovative programs that directly address rural medicine training needs, suggesting that expertise is present in this region. However, numerous challenges limit sustainability or expansion of successful programs. Common challenges include: (a) physicians' exposure to rural medicine primarily takes place during social service commitment time, rather than during formal medical training; (b) innovative educational programs are often not sustainable due to financial and leadership challenges; (c) the majority of physician manpower is in urban areas, resulting in few rural physician role models and teachers; and (d) there is insufficient collaboration to establish clinical and educational systems to meet rural health needs. Recurring suggestions for curricular changes include: (a) making primary care training a core component of medical school education; and (b) expanding medical school curricula in cross-cultural communication and social determinants of disease. Suggestions for health system changes include: (a) improving living and working conditions for rural physicians; and (b) establishing partnerships between educational, governmental and non-governmental organizations and rural community leadership, to promote rural health training and systems. CONCLUSIONS: Expertise in rural medicine and training exists in continental Central America. However, there are numerous challenges to improving medical education to meet the needs of rural communities. Overcoming these challenges will require creative solutions, new partnerships, and evaluation and dissemination of successful educational programs. There is a great need for further research on this topic.

Drinking behavior among low-income older adults: a multimethod approach to estimating alcohol use.

BACKGROUND: Substance abuse is the fastest growing health concern for older adults. Heavy drinking among older persons is associated with an increased risk of health consequences such as diabetes, cognitive impairment, sleep issues, and depression. It is important to note, however, the prevalence estimates of alcohol use among older adults are often based on inconsistent methodology. To address these potential methodological shortcomings, this study examines drinking patterns among low-income older adults using both self-report and unobtrusive methods. METHODS: The study was conducted in a low-income residential senior center in the United States. A total of 174 participants, aged 60 years or older, completed 2 self-administered cross-sectional surveys. A bogus recycling program was implemented to assess the amount of alcohol consumed by residents. Logistic regression analysis was utilized to model predictors of drinking status and to determine predictors of 3 category Alcohol Use and Disorders Identification Test scores. Bivariate associations that predicted associations with alcohol use were included in the final multivariate model. Alcohol containers collected from recycling were converted to standard drink estimates in order to calculate the capital consumption of residents. RESULTS: About 40% of respondents reported consuming alcohol and 25% reported drinking at least once a week. On average, a total of 1,079 drinks were consumed per month. There were 3 significant predictors of drinking status: age, education, and diagnosis of diabetes. Additionally, there appears to be an increase in recycled alcohol containers coinciding with the time residents received their social security checks. CONCLUSIONS: Overall, the combination of self-report and unobtrusive measures of alcohol consumption has potential to highlight different aspects of drinking behavior with a population living in a single dwelling such as a senior center apartment complex, residential hall, and the like.

Association of Plasma Amyloid, P-Tau, GFAP, and NfL With CSF, Clinical, and Cognitive Features in Patients With Dementia With Lewy Bodies.

BACKGROUND AND OBJECTIVES: Plasma ß-amyloid-1-42/1-40 (Aß42/40), phosphorylated-tau (P-tau), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) have been widely examined in Alzheimer disease (AD), but little is known about their reflection of copathologies, clinical importance, and predictive value in dementia with Lewy bodies (DLB). We aimed to evaluate associations of these biomarkers with CSF amyloid, cognition, and core features in DLB. METHODS: This cross-sectional multicenter cohort study with prospective component included individuals with DLB, AD, and healthy controls (HCs), recruited from 2002 to 2020 with an annual follow-up of up to 5 years, from the European-Dementia With Lewy Bodies consortium. Plasma biomarkers were measured by single-molecule array (Neurology 4-Plex E kit). Amyloid status was determined by CSF Aß42 concentrations, and cognition was assessed by Mini-Mental State Examination (MMSE). Biomarker differences across groups, associations with amyloid status, and clinical core features were assessed by analysis of covariance. Associations with cognitive impairment and decline were assessed by linear regression and linear mixed-effects models. RESULTS: In our cohort consisting of 562 individuals (HC n = 89, DLB n = 342, AD n = 131; 250 women [44.5%], mean [SD] age of 71 [8] years), sex distribution did not differ between groups. Patients with DLB were significantly older, and had less years of education and worse baseline cognition than HC, but not AD. DLB participants stratified for amyloid status differed significantly in plasma Aß42/40 ratio (decreased in amyloid abnormal: ß = -0.008, 95% CI -0.016 to -0.0003, p = 0.01) and P-tau (increased in amyloid abnormal, P-tau181: ß = 0.246, 95% CI 0.011-0.481; P-tau231: ß = 0.227, 95% CI 0.035-0.419, both p < 0.05), but not in GFAP (ß = 0.068, 95% CI -0.018 to 0.153, p = 0.119), and NfL (ß = 0.004, 95% CI -0.087 to 0.096, p = 0.923) concentrations. Higher baseline GFAP, NfL, and P-tau concentrations were associated with lower MMSE scores in DLB, and GFAP and NfL were associated with a faster cognitive decline (GFAP: annual change of -2.11 MMSE points, 95% CI -2.88 to -1.35 MMSE points, p < 0.001; NfL: annual change of -2.13 MMSE points, 95% CI -2.97 to -1.29 MMSE points, p < 0.001). DLB participants with parkinsonism had higher concentrations of NfL (ß = 0.08, 95% CI 0.02-0.14, p = 0.006) than those without. DISCUSSION: Our study suggests a possible utility of plasma Aß42/40, P-tau181, and P-tau231 as a noninvasive biomarkers to assess amyloid copathology in DLB, and plasma GFAP and NfL as monitoring biomarkers for cognitive symptoms in DLB.

Bat-borne H9N2 influenza virus evades MxA restriction and exhibits efficient replication and transmission in ferrets.

Influenza A viruses (IAVs) of subtype H9N2 have reached an endemic stage in poultry farms in the Middle East and Asia. As a result, human infections with avian H9N2 viruses have been increasingly reported. In 2017, an H9N2 virus was isolated for the first time from Egyptian fruit bats (Rousettus aegyptiacus). Phylogenetic analyses revealed that bat H9N2 is descended from a common ancestor dating back centuries ago. However, the H9 and N2 sequences appear to be genetically similar to current avian IAVs, suggesting recent reassortment events. These observations raise the question of the zoonotic potential of the mammal-adapted bat H9N2. Here, we investigate the infection and transmission potential of bat H9N2 in vitro and in vivo, the ability to overcome the antiviral activity of the human MxA protein, and the presence of N2-specific cross-reactive antibodies in human sera. We show that bat H9N2 has high replication and transmission potential in ferrets, efficiently infects human lung explant cultures, and is able to evade antiviral inhibition by MxA in transgenic B6 mice. Together with its low antigenic similarity to the N2 of seasonal human strains, bat H9N2 fulfils key criteria for pre-pandemic IAVs.

Incidence, in-hospital case-fatality rates, and management practices in Puerto Ricans hospitalized with acute myocardial infarction.

OBJECTIVE: There are extremely limited data on minority populations, especially Hispanics, describing the clinical epidemiology of acute coronary disease. The aim of this study is to examine the incidence rate of acute myocardial infarction (AMI), in-hospital case-fatality rate (CFR), and management practices among residents of greater San Juan (Puerto Rico) who were hospitalized with an initial AMI. METHODS: Our trained study staff reviewed and independently validated the medical records of patients who had been hospitalized with possible AMI at any of the twelve hospitals located in greater San Juan during calendar year 2007. RESULTS: The incidence rate (# per 100,000 population) of 1,415 patients hospitalized with AMI increased with advancing age and were significantly higher for older patients for men (198) than they were for women (134). The average age of the study population was 64 years, and women comprised 45% of the study sample. Evidence-based cardiac therapies, e.g., aspirin, beta blockers, ACE inhibitors/angiotensin receptor blockers, and statins, were used with 60% of the hospitalized patients, and women were less likely than men to have received these therapies (59% vs. 65%) or to have undergone interventional cardiac procedures (47% vs. 59%) (p<0.05). The in-hospital CFR increased with advancing age and were higher for women (8.6%) than they were for men (6.0%) (p<0.05). CONCLUSION: Efforts are needed to reduce the magnitude of AMI, enhance the use of evidence-based cardiac therapies, reduce possible gender disparities, and improve the short-term prognoses of Puerto Rican patients hospitalized with an initial AMI.

Development of a Novel Serological Assay for the Detection of Mpox Infection in Vaccinated Populations.

In 2022 the World Health Organization declared a Public Health Emergency for an outbreak of mpox, the zoonotic Orthopoxvirus (OPV) affecting at least 103 non-endemic locations world-wide. Serologic detection of mpox infection is problematic, however, due to considerable antigenic and serologic cross-reactivity among OPVs and smallpox-vaccinated individuals. In this report, we developed a high-throughput multiplex microsphere immunoassay (MIA) using a combination of mpox-specific peptides and cross-reactive OPV proteins that results in the specific serologic detection of mpox infection with 93% sensitivity and 98% specificity. The New York State Non-Vaccinia Orthopoxvirus Microsphere Immunoassay is an important diagnostic tool to detect subclinical mpox infection and understand the extent of mpox spread in the community through retrospective analysis.

Mpox vaccine and infection-driven human immune signatures.

Background: Mpox (formerly known as monkeypox) outbreaks outside endemic areas peaked in July 2022, infecting > 85,000 people and raising concerns about our preparedness against this emerging viral pathogen. Licensed and approved for mpox, the JYNNEOS vaccine has fewer side effects than previous smallpox vaccines and demonstrated efficacy against mpox infection in humans. Comparing JYNNEOS vaccine- and mpox-induced immunity is imperative to evaluate JYNNEOS' immunogenicity and inform vaccine administration and design. Methods: We examined the polyclonal serum (ELISA) and single B cell (heavy chain gene and transcriptome data) antibody repertoires and T cells (AIM and ICS assays) induced by the JYNNEOS vaccine as well as mpox infection. Findings: Gene-level plasmablast and antibody responses were negligible and JYNNEOS vaccinee sera displayed minimal binding to recombinant mpox proteins and native proteins from the 2022 outbreak strain. In contrast, recent mpox infection (within 20-102 days) induced robust serum antibody responses to A29L, A35R, A33R, B18R, and A30L, and to native mpox proteins, compared to vaccinees. JYNNEOS vaccine recipients presented comparable CD4 and CD8 T cell responses against orthopox peptides to those observed after mpox infection. Interpretation: JYNNEOS immunization does not elicit a robust B cell response, and its immunogenicity may be mediated by T cells. Funding: Research reported in this publication was supported, in part, by the National Cancer Institute of the National Institutes of Health under Award Number U54CA267776, U19AI168631(VS), as well as institutional funds from the Icahn School of Medicine.

Phenotypic and genotypic characterization of Colombian clinical isolates of Sporothrix spp. / Caracterización fenotípica y genotípica de aislamientos clínicos colombianos de Sporothrix spp.

INTRODUCTION: For over a century, Sporothrix schenckii was considered the sole species responsible for sporotrichosis. In 2007, scientific community confirmed the disease could be caused by various Sporothrix species. These species differed in their virulence factors and their antifungal sensitivity. OBJECTIVE: This study aims to characterize 42 Colombian clinical isolates of Sporothrix spp. phenotypically and genotypically. MATERIAL AND METHODS: Forty-two clinical isolates were characterized using phenotypic methods. It involved various culture media to determine their growth range at different temperatures and to assess the type and distribution of pigment and colony texture. Microscopic morphology was evaluated through microcultures, as well as the conidia diameter, type of sporulation, and morphology. Additionally, the assimilation of carbohydrates was selected as a physiological trait for species identification. Genotyping of 40 isolates was performed through partial amplification of the calmodulin gene, followed by sequence analysis. RESULTS: Molecular studies enabled the identification of 32 isolates of S. schenckii and 8 isolates of S. globosa. The combination of phenotypic and genotypic methods eased these species characterizations and the recognition keys development based on parameters such as growth diameter at 25 and 30 ºC, colony texture (membranous or velvety) on potato dextrose agar, and microscopic morphology with predominance of pigmented triangular, elongated oval globose, or subglobose conidia. CONCLUSIONS: Confirmation of the phenotypic characteristics and molecular analysis is crucial for identifying Sporothrix species and determining adequate treatment. This study represents the first phenotypical and genotypical characterization of clinical isolates of Sporothrix spp. reported in Colombia.

Introducción: Por más de un siglo se creyó que Sporothrix schenckii era la única especie responsable de la esporotricosis. Sin embargo, en el 2007, se consideró que podría ser causada por diferentes especies de Sporothrix, que difieren en sus factores de virulencia y su sensibilidad a los antifúngicos. Objetivo: Caracterizar fenotípica y genotípicamente 42 aislamientos clínicos colombianos de Sporothrix spp. Materiales y métodos: Se caracterizaron 42 aislamientos clínicos mediante métodos fenotípicos. Se usaron varios medios de cultivo para determinar el rango de crecimiento a diferentes temperaturas, el tipo y la distribución del pigmento, y la textura de las colonias. Se evaluó la morfología microscópica por microcultivos mediante la determinación del diámetro, el tipo de esporulación y la morfología de las conidias. La asimilación de carbohidratos se usó como una característica fisiológica para identificar las especies. La genotipificación de los 40 aislamientos se llevó a cabo mediante la amplificación parcial del gen que codifica para la calmodulina y se confirmó por secuenciación. Resultados: Mediante estudios moleculares, se identificaron 32 aislamientos de S. schenckii y ocho de S. globosa. La combinación de métodos fenotípicos y genotípicos permitió caracterizar las especies y construir claves para su reconocimiento, con base en parámetros como el diámetro de crecimiento a 25 y 30 ºC, la textura de las colonias (membranosa, aterciopelada) en agar papa dextrosa y la morfología microscópica con predominio de conidias (triangulares pigmentadas, ovales globosas elongadas, subglobosas). Conclusiones: La caracterización fenotípica y los análisis moleculares son necesarios para identificar las especies de Sporothrix y, de esta forma, elegir el tratamiento indicado. Esta es la primera caracterización fenotípica y genotípica reportada de aislamientos clínicos colombianos de Sporothrix spp.

Mpox vaccine and infection-driven human immune signatures: an immunological analysis of an observational study.

BACKGROUND: Monkeypox virus has recently infected more than 88 000 people, raising concerns about our preparedness against this emerging viral pathogen. Licensed and approved for mpox, the JYNNEOS vaccine has fewer side-effects than previous smallpox vaccines and has shown immunogenicity against monkeypox in animal models. This study aims to elucidate human immune responses to JYNNEOS vaccination compared with mpox-induced immunity. METHODS: Peripheral blood mononuclear cells and sera were obtained from ten individuals vaccinated with one or two doses of JYNNEOS and six individuals diagnosed with monkeypox virus infection. Samples were obtained from seven individuals before vaccination to serve as a baseline. We examined the polyclonal serum (ELISA) and single B-cell (heavy chain gene and transcriptome data) antibody repertoires and T-cell responses (activation-induced marker and intracellular cytokine staining assays) induced by the JYNNEOS vaccine versus monkeypox virus infection. FINDINGS: All participants were men between the ages of 21 and 60 years, except for one woman in the group of mpox-convalescent individuals, and none had previous orthopoxvirus exposure. All mpox cases were mild. Vaccinee samples were collected 6-33 days after the first dose and 5-40 days after the second dose. Mpox-convalescent samples were collected 20-102 days after infection. In vaccine recipients, gene-level plasmablast and antibody responses were negligible and sera displayed moderate binding to recombinant orthopoxviral proteins (A29L, A35R, E8L, A30L, A27L, A33R, B18R, and L1R) and native proteins from the 2022 monkeypox outbreak strain. By contrast, recent monkeypox virus infection (within 20-102 days) induced robust serum antibody responses to monkeypox virus proteins and to native monkeypox virus proteins from a viral isolate obtained during the 2022 outbreak. JYNNEOS vaccine recipients presented robust orthopoxviral CD4+ and CD8+ T-cell responses. INTERPRETATION: Infection with monkeypox virus resulted in robust B-cell and T-cell responses, whereas immunisation with JYNNEOS elicited more robust T-cell responses. These data can help to inform vaccine design and policies for preventing mpox in humans. FUNDING: National Cancer Institute (National Institutes of Health), National Institute of Allergy and Infectious Diseases (National Institutes of Health), and Icahn School of Medicine.

Propionic acidemia in a male newborn with Noonan syndrome: a case report.

We report a case of preterm infant born with prenatal diagnosis of cystic hygroma in the neck and congenital heart defect. Physical exam showed a hypotonic infant with dysmorphic features. Noonan syndrome was diagnosed. This newborn presented with progressive encephalopathy leading to a workup for metabolic disorders. The findings of elevated glycine levels associated with ketosis prompted the diagnosis of propionic acidemia. This case demonstrates that metabolic disorders can co-exist with other genetic syndromes and a high index of suspicion is needed in order to make the diagnosis and determine available treatment options. Genetic counseling should be offered to the parents as these disorders may affect future.