Underlying and proximate drivers of biodiversity changes in Mesoamerican biosphere reserves.

Protected areas are of paramount relevance to conserving wildlife and ecosystem contributions to people. Yet, their conservation success is increasingly threatened by human activities including habitat loss, climate change, pollution, and species overexploitation. Thus, understanding the underlying and proximate drivers of anthropogenic threats is urgently needed to improve protected areas' effectiveness, especially in the biodiversity-rich tropics. We addressed this issue by analyzing expert-provided data on long-term biodiversity change (last three decades) over 14 biosphere reserves from the Mesoamerican Biodiversity Hotspot. Using multivariate analyses and structural equation modeling, we tested the influence of major socioeconomic drivers (demographic, economic, and political factors), spatial indicators of human activities (agriculture expansion and road extension), and forest landscape modifications (forest loss and isolation) as drivers of biodiversity change. We uncovered a significant proliferation of disturbance-tolerant guilds and the loss or decline of disturbance-sensitive guilds within reserves causing a "winner and loser" species replacement over time. Guild change was directly related to forest spatial changes promoted by the expansion of agriculture and roads within reserves. High human population density and low nonfarming occupation were identified as the main underlying drivers of biodiversity change. Our findings suggest that to mitigate anthropogenic threats to biodiversity within biosphere reserves, fostering human population well-being via sustainable, nonfarming livelihood opportunities around reserves is imperative.

Specification of the endocrine primordia controlling insect moulting and metamorphosis by the JAK/STAT signalling pathway.

The corpora allata and the prothoracic glands control moulting and metamorphosis in insects. These endocrine glands are specified in the maxillary and labial segments at positions homologous to those forming the trachea in more posterior segments. Glands and trachea can be homeotically transformed into each other suggesting that all three evolved from a metamerically repeated organ that diverged to form glands in the head and respiratory organs in the trunk. While much is known about tracheal specification, there is limited information about corpora allata and prothorathic gland specification. Here we show that the expression of a key regulator of early gland development, the snail gene, is controlled by the Dfd and Scr Hox genes and by the Hedgehog and Wnt signalling pathways that induce localised transcription of upd, the ligand of the JAK/STAT signalling pathway, which lies at the heart of gland specification. Our results show that the same upstream regulators are required for the early gland and tracheal primordia specification, reinforcing the hypothesis that they originated from a segmentally repeated organ present in an ancient arthropod.

Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis (ReSTORE): a multicentre, double-blind, double-dummy, randomised phase 3 trial.

BACKGROUND: Rezafungin is a next-generation, once-a-week echinocandin in development for the treatment of candidaemia and invasive candidiasis and for the prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis spp after blood and marrow transplantation. We aimed to compare the efficacy and safety of intravenous rezafungin versus intravenous caspofungin in patients with candidaemia and invasive candidiasis. METHODS: ReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial done at 66 tertiary care centres in 15 countries. Adults (≥18 years) with systemic signs and mycological confirmation of candidaemia or invasive candidiasis were eligible for inclusion and randomly assigned (1:1) to receive intravenous rezafungin once a week (400 mg in week 1, followed by 200 mg weekly, for a total of two to four doses) or intravenous caspofungin (70 mg loading dose on day 1, followed by 50 mg daily) for no more than 4 weeks. The primary endpoints were global cure (consisting of clinical cure, radiological cure, and mycological eradication) at day 14 for the European Medical Agency (EMA) and 30-day all-cause mortality for the US Food and Drug Administration (FDA), both with a target non-inferiority margin of 20%, assessed in the modified intention-to-treat population (all patients who received one or more doses of study drug and had documented Candida infection based on a culture from blood or another normally sterile site obtained within 96 h before randomisation). Safety was evaluated by the incidence and type of adverse events and deaths in the safety population, defined as all patients who received any amount of study drug. The trial is registered with ClinicalTrials.gov, NCT03667690, and is complete. FINDINGS: Between Oct 12, 2018, and Aug 29, 2021, 222 patients were screened for inclusion, and 199 patients (118 [59%] men; 81 [41%] women; mean age 61 years [SD 15·2]) were randomly assigned (100 [50%] patients to the rezafungin group and 99 [50%] patients to the caspofungin group). 55 (59%) of 93 patients in the rezafungin group and 57 (61%) of 94 patients in the caspofungin group had a global cure at day 14 (weighted treatment difference -1·1% [95% CI -14·9 to 12·7]; EMA primary endpoint). 22 (24%) of 93 patients in the rezafungin group and 20 (21%) of 94 patients in the caspofungin group died or had an unknown survival status at day 30 (treatment difference 2·4% [95% CI -9·7 to 14·4]; FDA primary endpoint). In the safety analysis, 89 (91%) of 98 patients in the rezafungin group and 83 (85%) of 98 patients in the caspofungin group had at least one treatment-emergent adverse event. The most common treatment-emergent adverse events that occurred in at least 5% of patients in either group were pyrexia, hypokalaemia, pneumonia, septic shock, and anaemia. 55 (56%) patients in the rezafungin group and 52 (53%) patients in the caspofungin group had serious adverse events. INTERPRETATION: Our data show that rezafungin was non-inferior to caspofungin for the primary endpoints of day-14 global cure (EMA) and 30-day all-cause mortality (FDA). Efficacy in the initial days of treatment warrants evaluation. There were no concerning trends in treatment-emergent or serious adverse events. These phase 3 results show the efficacy and safety of rezafungin and support its ongoing development. FUNDING: Cidara Therapeutics and Mundipharma.

Community-acquired pneumonia: a US perspective on the guideline gap.

Community-acquired pneumonia continues to be one of the most common causes of morbidity and mortality due to infectious disease. The aetiologies, clinical presentations, diagnostic modalities and therapeutic options are changing and outpacing the creation of management guidelines. This educational article summarizes a roundtable activity sponsored by an unrestricted educational grant by Paratek that included US experts discussing these changes and identifying gaps in the current guidelines.

Sphenomandibular ligament and degenerating Meckel's cartilage revisited: Sequential variations with temporal bone deformity for ligament attachment in near-term human fetuses.

BACKGROUND: The sphenomandibular ligament (SML) is considered to originate from Meckel's cartilage (MC). However, no study has examined how the os goniale contributes to SML development. METHODS: Semiserial histological sections of heads from 18 near-term fetuses at 27-40 weeks of gestation were examined. OBSERVATIONS: The os goniale and the anterior process of the malleus (AP) provided a long, bar-like membranous bone complex that passed through the petrotympanic and tympanosquamosal fissures. Notably, the AP-goniale complex is sometimes elongated inferiorly to join the SML (n = 4 specimens). Along the complex in the bone fissures, a degenerating MC was often present (n = 12). With (n = 6) or without (n = 3) the MC remnant, the tympanic bone (TYB) protruded inferomedially near the tympanosquamosal fissure, and it sometimes continued to a cartilaginous SML (n = 3). The temporal bone squamosa or petrosa provided a similar bony process approaching the SML. The middle meningeal artery often ran between the sphenoid and petrosa. CONCLUSIONS: Most of the specimens (n = 15) exhibited a sequential change from a cartilaginous SML as a continuation of the MC remnant to the ligament after the disappearance of the cartilage. The degenerating MC appeared to cause transformation from the AP-goniale complex and/or TYB to "another ligament" that replaced the usual SML at the upper part. Near the MC remnant, a similar transformation was also suggested on the squamosa or petrosa. The sphenoid spine appeared to originate often from the sphenoid ala major but sometimes from the TYB.

The vomeronasal system of the wolf (Canis lupus signatus): The singularities of a wild canid.

Wolves, akin to their fellow canids, extensively employ chemical signals for various aspects of communication, including territory maintenance, reproductive synchronisation and social hierarchy signalling. Pheromone-mediated chemical communication operates unconsciously among individuals, serving as an innate sensory modality that regulates both their physiology and behaviour. Despite its crucial role in the life of the wolf, there is a lacuna in comprehensive research on the neuroanatomical and physiological underpinnings of chemical communication within this species. This study investigates the vomeronasal system (VNS) of the Iberian wolf, simultaneously probing potential alterations brought about by dog domestication. Our findings demonstrate the presence of a fully functional VNS, vital for pheromone-mediated communication, in the Iberian wolf. While macroscopic similarities between the VNS of the wolf and the domestic dog are discernible, notable microscopic differences emerge. These distinctions include the presence of neuronal clusters associated with the sensory epithelium of the vomeronasal organ (VNO) and a heightened degree of differentiation of the accessory olfactory bulb (AOB). Immunohistochemical analyses reveal the expression of the two primary families of vomeronasal receptors (V1R and V2R) within the VNO. However, only the V1R family is expressed in the AOB. These findings not only yield profound insights into the VNS of the wolf but also hint at how domestication might have altered neural configurations that underpin species-specific behaviours. This understanding holds implications for the development of innovative strategies, such as the application of semiochemicals for wolf population management, aligning with contemporary conservation goals.

Topological Fano-resonance with type-II and type-III corner states.

Topological corner states have been used to develop topologically robust Fano-resonant systems immune to structural perturbations while preserving the ultra-sensitive profiles under external factors. In this work, we have extended the possibility of obtaining Fano-resonant systems by introducing type-II and type-III corner states with a large modal surface to this class of resonance. Through photonic lattices with low symmetry, such as C2, it is easy to obtain type-II and type-III corner states due to the tailoring of long-range interactions. Subsequently, one can combine topological cavities of type-II and type-III corner modes with topological waveguides obtained from a first-order topological insulating phase. Our results may pave the way to generate devices suitable for creating non-classical light applicable in quantum computing and ultra-sensitive sensors employing large-area topological states.

KRAS-mutant non-small cell lung cancer (NSCLC) therapy based on tepotinib and omeprazole combination.

BACKGROUND: KRAS-mutant non-small cell lung cancer (NSCLC) shows a relatively low response rate to chemotherapy, immunotherapy and KRAS-G12C selective inhibitors, leading to short median progression-free survival, and overall survival. The MET receptor tyrosine kinase (c-MET), the cognate receptor of hepatocyte growth factor (HGF), was reported to be overexpressed in KRAS-mutant lung cancer cells leading to tumor-growth in anchorage-independent conditions. METHODS: Cell viability assay and synergy analysis were carried out in native, sotorasib and trametinib-resistant KRAS-mutant NSCLC cell lines. Colony formation assays and Western blot analysis were also performed. RNA isolation from tumors of KRAS-mutant NSCLC patients was performed and KRAS and MET mRNA expression was determined by real-time RT-qPCR. In vivo studies were conducted in NSCLC (NCI-H358) cell-derived tumor xenograft model. RESULTS: Our research has shown promising activity of omeprazole, a V-ATPase-driven proton pump inhibitor with potential anti-cancer properties, in combination with the MET inhibitor tepotinib in KRAS-mutant G12C and non-G12C NSCLC cell lines, as well as in G12C inhibitor (AMG510, sotorasib) and MEK inhibitor (trametinib)-resistant cell lines. Moreover, in a xenograft mouse model, combination of omeprazole plus tepotinib caused tumor growth regression. We observed that the combination of these two drugs downregulates phosphorylation of the glycolytic enzyme enolase 1 (ENO1) and the low-density lipoprotein receptor-related protein (LRP) 5/6 in the H358 KRAS G12C cell line, but not in the H358 sotorasib resistant, indicating that the effect of the combination could be independent of ENO1. In addition, we examined the probability of recurrence-free survival and overall survival in 40 early lung adenocarcinoma patients with KRAS G12C mutation stratified by KRAS and MET mRNA levels. Significant differences were observed in recurrence-free survival according to high levels of KRAS mRNA expression. Hazard ratio (HR) of recurrence-free survival was 7.291 (p = 0.014) for high levels of KRAS mRNA expression and 3.742 (p = 0.052) for high MET mRNA expression. CONCLUSIONS: We posit that the combination of the V-ATPase inhibitor omeprazole plus tepotinib warrants further assessment in KRAS-mutant G12C and non G12C cell lines, including those resistant to the covalent KRAS G12C inhibitors.

Efficacy of biofilm disrupters against Candida auris and other Candida species in monomicrobial and polymicrobial biofilms.

Candida species are now considered global threats by the CDC and WHO. Candida auris specifically is on the critical pathogen threat list along with Candida albicans. In addition, it is not uncommon to find Candida spp. in a mixed culture with bacterial organisms, especially Staphylococcus aureus producing polymicrobial infections. To eradicate these organisms from the environment and from patient surfaces, surface agents such as chlorhexidine (CHD) and Puracyn are used. Biofilm disrupters (BDs) are novel agents with a broad spectrum of antimicrobial activity and have been used in the management of chronic wounds and to sterilise environmental surfaces for the past several years. The goal of this study was to evaluate BDs (BlastX, Torrent, NSSD) and CHD against Candida spp. and S. aureus using zone of inhibition assays, biofilm and time-kill assays. All BDs and CHD inhibited C. auris growth effectively in a concentration-dependent manner. Additionally, CHD and the BDs showed excellent antimicrobial activity within polymicrobial biofilms. A comparative analysis of the BDs and CHD against C. auris and C. albicans using biofilm kill-curves showed at least 99.999% killing. All three BDs and CHD have excellent activity against different Candida species, including C. auris. However, one isolate of C. auris in a polymicrobial biofilm assay showed resistance/tolerance to CHD, but not to the BDs. The fungicidal activity of these novel agents will be valuable in eradicating surface colonisation of Candida spp, especially C. auris from colonised environmental surfaces and from wounds in colonised patients.

Comparative Analysis of Meteorological versus In Situ Variables in Ship Thermal Simulations.

Thermal simulations have become increasingly popular in assessing energy efficiency and predicting thermal behaviors in various structures. Calibration of these simulations is essential for accurate predictions. A crucial aspect of this calibration involves investigating the influence of meteorological variables. This study aims to explore the impact of meteorological variables on thermal simulations, particularly focusing on ships. Using TRNSYS (TRaNsient System Simulation) software (v17), renowned for its capability to model complex energy systems within buildings, the significance of incorporating meteorological data into thermal simulations was analyzed. The investigation centered on a patrol vessel stationed in a port in Galicia, northwest Spain. To ensure accuracy, we not only utilized the vessel's dimensions but also conducted in situ temperature measurements onboard. Furthermore, a dedicated weather station was installed to capture real-time meteorological data. Data from multiple sources, including Meteonorm and MeteoGalicia, were collected for comparative analysis. By juxtaposing simulations based on meteorological variables against those relying solely on in situ measurements, we sought to discern the relative merits of each approach in enhancing the fidelity of thermal simulations.

Growth of the brachial nerve plexus with reference to topographical relation of the medianus nerve ansa with the thoracic wall and shoulder: a histologic study using human embryos and fetuses.

BACKGROUND: There is currently no information on positional changes in the brachial nerve plexus during prenatal growth. The subclavian-axillary artery passing through the medianus nerve ansa is considered a good landmark for evaluating the height of the plexus. MATERIALS AND METHODS: We used histologic sections from 9 embryos and 17 fetuses (approximately 6-15 weeks of gestational age) to identify the height of the ansa by referring to the level of the rib and the glenohumeral joint. RESULTS: The nerve ansa was usually (23 plexuses) observed at the level of the first and/or second ribs. However, it was sometimes observed above the first rib, at a distance equal to or more than an intercostal width (7 plexuses). In the latter group, the ansa was usually located below the glenohumeral joint. Thus, the joint was located higher than the first rib, although the upper extremities were in the anatomic position for all specimens. The left-right difference in the height of the plexus corresponded to or was less than the width of the first intercostal space. Despite the synchronized growth between the thorax and shoulder girdle, the brachial plexus showed a considerable variation in comparative height; the range corresponded to twice of an intercostal width. Whether the nerve plexus is located high or low is determined at an early developmental stage and is maintained during the later growth stages. CONCLUSION: The high-positioned plexus might cause nerve injury at delivery, followed by a glenohumeral joint deformity because of the fragility without fixation in the thorax.

Growth of muscles and nerves in the upper eyelid: a morphometrical and immunohistochemical study using term human fetuses.

BACKGROUND: There is no information about muscle growth in eyelids with infrequent blinking in fetuses. METHODS: To examine the muscle and nerve morphology, we morphometrically and immunohistochemically examined sagittal sections of unilateral upper eyelids obtained from 21 term fetuses (approximately 30-42 weeks of gestation) and, for the comparison, those from 10 midterm fetuses (12-15 weeks). RESULTS: The approximation margin of the upper eyelid always corresponded to the entire free margin in midterm fetuses, whereas it was often (18/21) restricted in the posterior part in term fetuses. Thus, in the latter, the thickness at the approximation site to the lower lid often ranged from 0.8 to 1.6 mm and corresponded to 18-56% of the nearly maximum thickness of the lid. In the lower part of the upper eyelid, a layer of the orbicularis oculi muscles often (14/21) provided posterior flexion at 90-120° to extend posteriorly. Nerve fibers running along the mediolateral axis were rich along the approximation surface at term, but they might not be reported in the upper eyelid of adults. CONCLUSION: Being different from adult morphologies, the term eyelid was much thicker than the approximation surface and it carried a flexed muscle layer and transversely-running nerve. The infrequent blinking in fetuses seemed to provide a specific condition for the muscle-nerve growth. Plastic and pediatric surgeons should pay attention to a fact that infants' upper eyelid was unlikely to be a mini-version of the adult morphology.

Mentalis nerve branches supplying the lower lip revisited: a study of human fetuses and donated elderly cadavers.

PURPOSE: Little information is known about the mentalis nerve course from the lower lip approximation margin (free margin) to the upper lip. Likewise, no difference in nerve distribution has been observed between the cutaneous and mucosal parts of the lip. Therefore, this study reexamined mentalis nerve morphology. METHODS: For macroscopic observations, three fresh cadavers were dissected (one male and two females; aged 78-93). We also evaluated histological sections obtained from five donated elderly cadavers (two males and three females, aged 82-96 years) and 15 human fetuses (11-40 weeks or crown-rump length 80-372 mm). Immunohistochemical analysis for S100 protein and tyrosine hydroxylase was performed. RESULTS: In both fetuses and adult cadavers, one to three nerve branches ran upward in the submucosal tissue from the mental foramen. Near the free margin of the lip, some branches passed through the orbicularis oris muscle layer toward the lip skin, whereas others followed a reversed J-shaped course along the free margin. Nerve twigs ran in parallel beneath the mucosa, whereas wavy nerve twigs attached to the basal lamina of the lip epidermis. The difference in nerve endings abruptly occurred at the skin-mucosal junction. Tyrosine hydroxylase-positive sympathetic nerve twigs surrounded arteries and formed a branch composed of S100-negative unmyelinated fibers. CONCLUSION: The lower lip skin was innervated by a perforating branch passing through the orbicularis oris muscle, that was different from the lip mucosa. A sudden change in the nerve ending configuration at the mucocutaneous junction seemed to develop postnatally.

Genome-wide association analysis of heifer livability and early first calving in Holstein cattle.

BACKGROUND: The survival and fertility of heifers are critical factors for the success of dairy farms. The mortality of heifers poses a significant challenge to the management and profitability of the dairy industry. In dairy farming, achieving early first calving of heifers is also essential for optimal productivity and sustainability. Recently, Council on Dairy Cattle Breeding (CDCB) and USDA have developed new evaluations of heifer health and fertility traits. However, the genetic basis of these traits has yet to be thoroughly studied. RESULTS: Leveraging the extensive U.S dairy genomic database maintained at CDCB, we conducted large-scale GWAS analyses of two heifer traits, livability and early first calving. Despite the large sample size, we found no major QTL for heifer livability. However, we identified a major QTL in the bovine MHC region associated with early first calving. Our GO analysis based on nearby genes detected 91 significant GO terms with a large proportion related to the immune system. This QTL in the MHC region was also confirmed in the analysis of 27 K bull with imputed sequence variants. Since these traits have few major QTL, we evaluated the genome-wide distribution of GWAS signals across different functional genomics categories. For heifer livability, we observed significant enrichment in promotor and enhancer-related regions. For early calving, we found more associations in active TSS, active Elements, and Insulator. We also identified significant enrichment of CDS and conserved variants in the GWAS results of both traits. By linking GWAS results and transcriptome data from the CattleGTEx project via TWAS, we detected four and 23 significant gene-trait association pairs for heifer livability and early calving, respectively. Interestingly, we discovered six genes for early calving in the Bovine MHC region, including two genes in lymph node tissue and one gene each in blood, adipose, hypothalamus, and leukocyte. CONCLUSION: Our large-scale GWAS analyses of two heifer traits identified a major QTL in the bovine MHC region for early first calving. Additional functional enrichment and TWAS analyses confirmed the MHC QTL with relevant biological evidence. Our results revealed the complex genetic basis of heifer health and fertility traits and indicated a potential connection between the immune system and reproduction in cattle.

Clinical Efficacy and Safety of a Novel Antifungal, Fosmanogepix, in Patients with Candidemia Caused by Candida auris: Results from a Phase 2 Trial.

Fosmanogepix (FMGX), a novel antifungal available in intravenous (IV) and oral formulations, has broad-spectrum activity against pathogenic yeasts and molds, including fungi resistant to standard of care antifungals. This multicenter, open-label, single-arm study evaluated FMGX safety and efficacy for treatment of candidemia and/or invasive candidiasis caused by Candida auris. Eligible participants were ≥18 years, with established candidemia and/or invasive candidiasis caused by C. auris, (cultured within 120 h [for candidemia] or 168 h [for invasive candidiasis without candidemia] with accompanying clinical signs) and limited treatment options. Participants were treated with FMGX (≤42 days; loading dose: 1000 mg IV twice daily [Day 1], followed by 600 mg IV once daily [QD]). Switching to oral FMGX 800 mg QD was permitted from Day 4. Primary endpoint was treatment success (survival and clearance of C. auris from blood/tissue cultures without additional antifungals) at the end of the study treatment (EOST), assessed by an independent data review committee (DRC). Day 30 survival was a secondary endpoint. In vitro susceptibility of Candida isolates was assessed. Nine participants with candidemia (male:6, female:3; 21 to 76 years) in intensive care units in South Africa were enrolled; all received IV FMGX only. DRC-assessed treatment success at EOST and Day 30 survival were 89% (8/9). No treatment related adverse events or study drug discontinuations were reported. FMGX demonstrated potent in vitro activity against all C. auris isolates (MIC range: 0.008 to 0.015 µg/mL [CLSI]; 0.004-0.03 µg/mL [EUCAST]), with the lowest MICs compared to other antifungals tested. Thus, the results showed that FMGX was safe, well-tolerated, and efficacious in participants with candidemia caused by C. auris.

Clinical safety and efficacy of novel antifungal, fosmanogepix, for the treatment of candidaemia: results from a Phase 2 trial.

BACKGROUND: Fosmanogepix is a first-in-class antifungal targeting the fungal enzyme Gwt1, with broad-spectrum activity against yeasts and moulds, including multidrug-resistant fungi, formulated for intravenous (IV) and oral administration. METHODS: This global, multicenter, non-comparative study evaluated the safety and efficacy of fosmanogepix for first-line treatment of candidaemia in non-neutropenic adults. Participants with candidaemia, defined as a positive blood culture for Candida spp. within 96 h prior to study entry, with ≤2 days of prior systemic antifungals, were eligible. Participants received fosmanogepix for 14 days: 1000 mg IV twice daily on Day 1, followed by maintenance 600 mg IV once daily, and optional switch to 700 mg orally once daily from Day 4. Eligible participants who received at least one dose of fosmanogepix and had confirmed diagnosis of candidaemia (<96 h of treatment start) composed the modified intent-to-treat (mITT) population. Primary efficacy endpoint was treatment success at the end of study treatment (EOST) as determined by the Data Review Committee. Success was defined as clearance of Candida from blood cultures with no additional antifungal treatment and survival at the EOST. RESULTS: Treatment success was 80% (16/20, mITT; EOST) and Day 30 survival was 85% (17/20; 3 deaths unrelated to fosmanogepix). Ten of 21 (48%) were switched to oral fosmanogepix. Fosmanogepix was well tolerated with no treatment-related serious adverse events/discontinuations. Fosmanogepix had potent in vitro activity against baseline isolates of Candida spp. (MICrange: CLSI, 0.002-0.03 mg/L). CONCLUSIONS: Results from this single-arm Phase 2 trial suggest that fosmanogepix may be a safe, well-tolerated, and efficacious treatment for non-neutropenic patients with candidaemia, including those with renal impairment.

Nasal capsule ossification: A histological study using human foetuses to find an association between the foetus and adult morphologies of the nasal wall.

Recent molecular biology studies have revealed the process of nasal capsule determination. We aimed to create a fate map showing the association between the adult and embryonic components of the nasal wall and nasal capsule derivatives. We examined paraffin-embedded histological sections between 15 mid-term (9-16 weeks) and 12 near-term (27-40 weeks) foetuses. Until 15 weeks, membranous ossification occurred 'along' the capsular cartilage, contributing to the formation of the vomer, maxilla and bony nasal septum as well as the nasal, frontal and lacrimal bones. After 15 weeks, a wide lateral part of the capsule became thin and fragmented, and degenerative cartilage was observed near the lacrimal bone, in the three conchae, and at the inferolateral end of the capsule sandwiched between the maxilla and palatine bone. The disappearing cartilages appeared to be replaced by nearby membranous bones. This type of membranous ossification did not appear to use the capsular cartilage as a 'mould', although the perichondrium may have a role in inducing ossification. Calcified cartilage indicated endochondral ossification in the inferior concha until 15 weeks and, later, at the bases of three conchae and around the future sphenoid sinus (i.e. the concha sphenoidalis). The capsular cartilage extended antero-superiorly over the frontal bone and inserted into the nasal bone. At 40 weeks, the capsular cartilage remained in the cribriform plate and at the inferolateral end along the palatine bone. Consequently, less guidance from the nasal capsule seemed to provide great individual variation in the shape of the wide anterolateral wall of the nasal cavity.

Multiresonant plasmon excitation in slit antennas on metallic and hyperbolic metamaterials.

A comparative study of the optical properties of random and ordered arrays of metallic and hyperbolic slit antennas is presented. The metallic slits are fabricated on Au layers, whereas the hyperbolic ones are fabricated on Au/MgO multilayers. The random arrays show, for both types of antennas, similar slit plasmon resonances whose positions depend on the internal structure of the supporting layer. On the other hand, the spectra of the ordered arrays of the hyperbolic slits present additional resonances related to the excitation of Bloch plasmon polaritons in the hyperbolic layer. By varying the slit length and periodicity, an analysis of the interaction between slit localized resonance and Bloch plasmon polaritons is also presented.

Soluble factors in COVID-19 mRNA vaccine-induced myocarditis causes cardiomyoblast hypertrophy and cell injury: a case report.

BACKGROUND: Inflammation affecting the heart and surrounding tissues is a clinical condition recently reported following COVID-19 mRNA vaccination. Assessing trends of these events related to immunization will improve vaccine safety surveillance and best practices for forthcoming vaccine campaigns. However, the causality is unknown, and the mechanisms associated with cardiac myocarditis are not understood. CASE PRESENTATION: After the first dose, we reported an mRNA vaccine-induced perimyocarditis in a young patient with a history of recurrent myocardial inflammation episodes and progressive loss of cardiac performance. We tested this possible inflammatory cytokine-mediated cardiotoxicity after vaccination in the acute phase (ten days), and we found a significant elevation of MCP-1, IL-18, and IL-8 inflammatory mediators. Still, these cytokines decreased considerably at the recovery phase (42 days later). We used the cardiomyoblasts cell line to test the effect of serum on cell viability, observing that serum from the acute phase reduced the cell viability to 75%. We did not detect this toxicity in cells when we tested serum from the patient in the recovery phase. We also tested serum-induced hypertrophy, a phenomenon in myocarditis and heart failure. We found that acute phase-serum has hypertrophy effects, increasing 25% of the treated cardiac cells' surface and significantly increasing B-type natriuretic peptide. However, we did not observe the hypertrophic effect in the recovery phase or sera from healthy controls. CONCLUSION: Our results opened the possibility of the inflammatory cytokines or serum soluble mediators as key factors for vaccine-associated myocarditis. In this regard, identifying anti-inflammatory molecules that reduce inflammatory cytokines could help avoid vaccine-induced myocardial inflammation.

Confirmation of the presence of Rickettsia felis infecting Ornithodoros puertoricensis in Mexico.

Soft ticks are neglected competent vectors of a wide range of pathogenic microorganisms, among which bacteria of the genera Rickettsia and Borrelia stand out. In Mexico, previous studies have shown the presence of a member of the Ornithodoros talaje complex in the Virginia opossum (Didelphis virginiana Didelphimorphia: Didelphidae Kerr) from southeastern Mexico. However, its specific identification has not been achieved. Two D. virginiana were treated in a private clinic during the period of April-May 2022. Tick larvae were manually removed, DNA extraction was performed, and some genes from various bacterial and parasitic pathogens were amplified and sequenced. A total of 96 larvae were recovered, which were morphologically identified as Ornithodoros puertoricensis (Ixodida: Argasidae Fox); the 16 S sequences showed a similarity of 96.79%-99.51% with sequences of O. puertoricensis from Panama and Colombia. The presence of Rickettsia felis (Rickettsiales: Rickettsiaceae Bouyer et al.) was detected in 15 specimens from one host. The soft tick O. puertoricensis is recorded for the first time as an ectoparasite of the Virginia opossum in America and represents the second report for this soft tick in Mexico since 1963. This represents the most northern record of this tick species in its geographic distribution and brings a new soft tick-Rickettsia association.