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Abstract Background Overlapping microdeletions of chromosome 3q26-3q28 have been reported in eight individuals. The common phenotype observed in these individuals include intrauterine growth restriction, short stature, microcephaly, feeding difficulties, facial dysmorphisms, limb abnormalities and developmental delay. The most striking clinical features shared among all reported cases is prenatal and postnatal growth restriction and neurodevelopmental abnormalities. Case presentation We identified two additional individuals with overlapping deletions and shared clinical features by high-resolution SNP oligonucleotide microarray, and refined the smallest region of overlap (SRO) to a 1.2 Mb genomic location in chromosome 3q27.1 by reviewing and comparing all published cases. We evaluated the SRO using ACMG/ClinGen current recommendations for classifying copy number variants (CNVs), and discussed the contribution of the genes deleted in the SRO to the abnormal phenotype observed in these individuals. Conclusions This study provides further evidence supporting the existence of a novel 3q27.1 microdeletion syndrome and suggests that haploinsufficiency of potential candidate genes, DVL3, AP2M1, and PARL in the SRO in 3q27.1 is responsible for the phenotype.

Abstract Mammalian captive dietary specialists like folivores are prone to gastrointestinal distress and primate dietary specialists suffer the greatest gut microbiome diversity losses in captivity compared to the wild. Marmosets represent another group of dietary specialists, exudivores that eat plant exudates, but whose microbiome remains relatively less studied. The common occurrence of gastrointestinal distress in captive marmosets prompted us to study the Callithrix gut microbiome composition and predictive function through bacterial 16S ribosomal RNA V4 region sequencing. We sampled 59 wild and captive Callithrix across four species and their hybrids. Host environment had a stronger effect on the gut microbiome than host taxon. Wild Callithrix gut microbiomes were enriched for Bifidobacterium, which process host-indigestible carbohydrates. Captive marmoset guts were enriched for Enterobacteriaceae, a family containing pathogenic bacteria. While gut microbiome function was similar across marmosets, Enterobacteriaceae seem to carry out most functional activities in captive host guts. More diverse bacterial taxa seem to perform gut functions in wild marmosets, with Bifidobacterium being important for carbohydrate metabolism. Captive marmosets showed gut microbiome composition aspects seen in human gastrointestinal diseases. Thus, captivity may perturb the exudivore gut microbiome, which raises implications for captive exudivore welfare and calls for husbandry modifications.

In a first approximation to the use of hyperspectral DESIS data to ocean colour applications in inland waters, we present here a comparison of the DESIS vs. MSI spectra from two reservoirs located in the province of Valencia. Benagerber and Tous are two small, oligo-mesotrophic reservoirs in need of constant water quality monitoring. These preliminary results have shown us the advantages and limitations of DESIS imagery for these types of dark and small lakes, but also pointed out the need for a specific over water atmospheric correction, as well as further understanding of the band combinations that can lead to accurate water quality parameter estimations.

The development of energy storage devices with better performance relies on the use of innovative materials and electrolytes, aiming to reduce the carbon footprint through the screening of low toxicity electrolytes and solvent-free electrode design protocols. The application of nanostructured carbon materials with high specific surface area, to prepare composite electrodes, is being considered as a promising starting point towards improving the power and energy efficiency of energy storage devices. Non-aqueous electrolytes synthesized using greener approaches with lower environmental impact make deep eutectic solvents (DES) promising alternatives for electrochemical energy storage and conversion applications. Accordingly, this work proposes a systematic study on the effect of the composition of DES containing a diol and an amide as HBD (hydrogen bond donor: 1,2-propylene glycol and urea), on the electrochemical performance of graphene and graphite composite electrodes/DES electrolyte interface. Glassy carbon (GC) was selected as the bare electrode material substrate to prepare the composite formulations since it provides an electrochemically reproducible surface. Gravimetric capacitance was measured for commercial graphene and commercial graphite/GC composite electrodes in contact with choline chloride, complexed with 1,2-propylene glycol, and urea as the HBD in 1:2 molar ratio. The electrochemical stability was followed by assessing the charge/discharge curves at 1, 2, and 4 A g−1. For comparison purposes, a parallel study was performed using commercial graphite. A four-fold increase in gravimetric capacitance was obtained when replacing commercial graphite (1.70 F g−1) by commercial graphene (6.19 F g−1) in contact with 1,2-propylene glycol-based DES. When using urea based DES no significant change in gravimetric capacitance was observed when commercial graphite is replaced by commercial graphene.

Historic monuments and construction capture the knowledge of civilizations of the past and are a source of pride for people of the present. Over the centuries, these buildings have been at risk from natural and man-made causes. The Alhambra, a UNESCO World Heritage Site in Granada, Spain, is one of such places. This paper aims to evaluate the structural performance of the Torre de la Vela, a tower in the Alhambra, under blast loads. The loads were based on historical records of barrels of gunpowder and were modeled as simplified pressure profiles using existing empirical equations. The effect of impulsive loading on the material properties was accounted for using dynamic increase factors, determined experimentally by previous authors. The model was created using finite element methods (FEM) and the problem was solved using explicit dynamic analysis available in Abaqus/Explicit. Using the failure volume damage index, a blast load applied outside and inside of the building would create a low damage level, which should be treated with caution given the occurrence of localized damage. The removal of elements exceeding a given damage threshold led to more visible damage patterns than the Concrete Tension Damage option in Abaqus.

Carbon nanotubes (CNTs) are receiving special attention due to their remarkable thermal, electrical, and mechanical properties. The present work reports an innovative synthesis procedure to decorate MWCNTs with silver nanoparticles (Ag-NPs) via pulsed reverse deposition technique using a deep eutectic solvent (DES) based on choline chloride and glycerol as an electrolyte at room temperature, not requiring any previous surface modification of MWCNTs.MWCNTs decorated with Ag-NPs disclose a significant enhancement of their electrochemical performance as demonstrated by the increase of electrode stability and specific capacitance. Electrochemical characterization of the composite material was performed using cyclic voltammetry and charge/discharge curves, achieving a specific capacitance up to 28.50 F. g−1, against 4.70 F. g−1 for the commercial MWCNTs in a three-electrode system. Retention of the specific capacitance up to 99% for the Ag-MWCNTs composites compared with a value of 78% for electrodes modified with commercial MWCNTs.The Ag-MWCNTs composites were characterized through SEM/EDX analysis, ultrahigh-resolution STEM, in which the Z – Contrast image was collected, and Raman analysis to prove the successful attachment of the Ag-NPs to the MWCNTs surface. AFM was performed to evaluate the conductivity of the composites.

Abstract Background Test anxiety is a crucial factor in determining academic outcomes, and it may lead to poor cognitive performance, academic underachievement, and psychological distress, interfering specifically with their ability to think and perform during tests. The main objective of this study was to explore the applicability and psychometric properties of a Portuguese version of the Reactions to Tests scale (RTT) in a sample of medical students. Method A sample of 672 medical students completed the RTT. The sample was randomly split in half to allow for independent Exploratory Factor Analysis (EFA) and to test the best fit model—Confirmatory Factor Analysis (CFA). CFA was used to test both the first-order factor structure (four subscales) and second-order factor structure, in which the four subscales relate to a general factor, Test Anxiety. The internal consistency of the RTT was assessed through Cronbach’s alpha, Composite reliability (CR) and Average Variance Extracted (AVE) for the total scale and each of the four subscales. Convergent validity was evaluated through the correlation between RTT and the State-Trait Anxiety Inventory (STAI-Y).To explore the comparability of measured attributes across subgroups of respondents, measurement invariance was also studied. Results Results from exploratory and confirmatory factor analyses showed acceptable fits for the Portuguese RTT version. Concerning internal consistency, results indicate that RTT was found to be reliable to measure test anxiety in this sample. Convergent validity of the RTT with both state and trait anxiety STAI-Y’s subscales was also shown. Moreover, multigroup analyses showed metric invariance across gender and curriculum phase. Conclusion Our results suggest that the RTT scale is a valid and reliable instrument for the measurement of test anxiety among Portuguese Medical Students.

Abstract Continuous development, improvement and innovation of ballistic material systems with superior energy absorption performance has been the subject of numerous works nowadays. Some research has been carried out with the objective of replacing traditional metallic and ceramic materials and composites with high-performance polymeric composites. Due to their excellent properties, multi-scale polymer composites have been used in the most varied segments of the industry, being recently researched in applications such as ballistic materials. This work promotes the combination of high-strength three-dimensional woven aramid fiber fabrics with vinyl ester resin to produce a panel through the compression molding process. The resin was reinforced with graphene nanoplatelets (0.1, 0.2 and 0.3% wt). The impact, tensile and flexural strength were evaluated, along with dynamic-mechanical analysis by DMA and by Hopkinson split bar test, indicating a trend of better performance for the composite containing 0.1% of graphene nanoplatelets.

BackgroundIncreased wave reflections assessed by pulse wave analysis (PWA) was proposed as one of the potential culprits of hypertension seen in women with pregnancy-associated hypertension (PAH). However, this statement has never been confirmed with “Wave Separation Analysis” (WSA), a more sophisticated mathematical approach that analyzes the amplitude and interaction between forward and backward aortic pressure waveform components.ObjectiveTo characterize potential changes in pressure wave components of PAH compared to healthy non-pregnant (NP) women and women with normal pregnancies (HP) by using WSA and compared these findings with PWA-derived indexes; secondarily, to evaluate differences in WSA-derived indexes between subgroups of PAH (i.e., preeclampsia [PE] and gestational hypertension [GH]).MethodsUsing radial and carotid applanation tonometry, we quantified in HP (n = 10), PAH (n = 16), and NP (n = 401): (i) PWA-derived indexes; (ii) WSA-derived indexes: forward (Pf) and backward (Pb) waveform components, backward component arrival time (PbAT), reflection magnitude (RM = Pb/Pf) and index [RIx = Pb/(Pf + Pb)].ResultsWhile PAH was associated with a higher Pf compared to HP and NP, Pb and PbAT were similar between the groups. Both GH and PE showed a higher Pf compared to HP, but only PE had a trend of presenting with higher Pb and lower PbAT compared to the other groups. Finally, PAH showed a trend of having lower RM and RIx compared to NP and HP, with no differences between GH and PE.ConclusionPAH was associated with higher Pf, but not higher Pb, compared to NP and HP, although PE also demonstrated a trend of higher Pb.

Oropharyngeal squamous cell cancer (OPC) accounts for 3% of all cancers and greater than 1.5% of all cancer deaths in the United States, with marked treatment-associated morbidity in survivors. More than 80% of OPC is caused by HPV16. Tumors induced by HPV have been linked to impaired immune functions, with most studies focused on the local tumor microenvironment. Fewer studies have characterized the effects of these tumors on systemic responses in OPC, especially innate responses that drive subsequent adaptive responses, potentially creating feed-back loops favorable to the tumor. Here we report that elevated plasma levels of PGE2 are expressed in half of patients with OPC secondary to overexpression of COX-2 by peripheral blood monocytes, and this expression is driven by IL-1α secreted by the tumors. Monocytes from patients are much more sensitive to the stimulation than monocytes from controls, suggesting the possibility of enhanced immune-modulating feed-back loops. Furthermore, control monocytes pre-exposed to PGE2 overexpress COX-2 in response to IL-1α, simulating responses made by monocytes from some OPC patients. Disrupting the PGE2/IL-1α feed-back loop can have potential impact on targeted medical therapies.

Resumen: Introducción y objetivos: Las metástasis espinales pueden ocurrir en el 5-30% de los pacientes con cáncer, provocando dolor, deformidad y/o déficit neurológico. Las complicaciones postoperatorias son un motivo de preocupación y las complicaciones relacionadas con la herida (CRH) pueden retrasar el inicio del tratamiento adyuvante. El objetivo de este estudio fue analizar la incidencia de CRH en pacientes con metástasis espinales sometidos a tratamiento quirúrgico y evaluar los posibles factores de riesgo relacionados con estas complicaciones. Materiales y métodos: Se analizaron pacientes operados por metástasis espinales entre 2011 y 2021. Se analizaron características demográficas, tumor primario, estado general y neurológico, score de Tokuhashi, tipo de tratamiento quirúrgico, duración de la cirugía, albúmina sérica y hemoglobina preoperatorias, tratamiento adyuvante pre- y postoperatorio. Se evaluó la incidencia y los factores de riesgo de la CRH (infección del sitio quirúrgico, hematoma y/o dehiscencia) a los 90 días. Los pacientes se clasificaron en dos grupos según la ausencia/presencia de CRH. Resultados: Se analizaron 198 pacientes (121 hombres y 77 mujeres) con una edad promedio de 65 años (rango 54-73 años). Se observaron CRH en 44 pacientes (22%). En el análisis multivariado, los predictores significativos para el desarrollo de CRH fueron un score de Tokuhashi bajo (OR = 7,89; IC del 95% = 1,37-45,35; p = 0,021), cáncer de próstata como tumor primario (OR = 6,73; IC del 95% = 1,14-39,65; p = 0,035) y albúmina sérica preoperatoria ≤ 3,5 g/dL (OR = 2,31; IC del 95% = 1,02-5,22; p = 0,044). No hubo diferencias entre los grupos en la supervivencia a los 90 días (p = 0,714). Conclusiones: En nuestra serie, la incidencia de CRH fue del 22%, los principales factores de riesgo para su aparición fueron el score de Tokuhashi bajo, la albúmina sérica preoperatoria más baja y el cáncer de próstata. Finalmente, la tasa de supervivencia a corto plazo no se vio afectada por la ocurrencia de CRH. Abstract: Introduction and objectives: Spinal metastases (SM) account for 5-30% of patients with cancer, causing pain, deformity and/or neurological deficit. Postoperative complications are a concerning subject and wound-related complications (WRC) may delay adjuvant treatment. The objective of this study was to analyze the incidence of WRC in patients with SM that underwent surgical treatment as well as possible risk factors related to the occurrence of complications. Materials and methods: Patients with SM operated between 2011 and 2021 were analyzed. Demographics characteristics, primary tumor, general and neurological status, Tokuhashi score, type of surgical treatment, surgical length, preoperative serum albumin and hemoglobin, pre and postoperative adjuvant treatment were analyzed. The incidence and risk factors of WRC –surgical site infection, hematoma, and/or dehiscence– at 90 days was evaluated. Patients were classified in two groups according to the absence/presence of WRC. Results: 198 patients (121 males and 77 females) with an average age of 65 years (range 54-73 years) were analyzed. WRC were observed in 44 patients (22%). On multivariable analysis, significant predictors for developing WRC were low Tokuhashi score (OR = 7.89, 95% CI = 1.37–45.35, p = .021), prostate cancer as primary tumor (6.73, 1.14–39.65, p = .035), and preoperative serum albumin level ≤3.5 g/dL (2.31, 1.02–5.22, p = .044). There was no difference between groups on 90 days survival rate (p = .714). Conclusions: In our series, the incidence of WRC was 22%, main risk factors for complications were low Tokuhashi score, lower preoperative serum albumin, and prostate cancer. Finally, short-term survival rate was not affected by the occurrence of WRC.

Guava is a world-renowned fruit of climacteric nature. It is characterized as a perishable fruit and has a short post-harvest shelf life when stored at room temperature. The objective of this work is to study the effects of coatings on the physiology and shelf life of 'Pedro Sato' guavas harvested early. For this, the effect of edible coatings based on hydroxypropyl methylcellulose (HPMC) and beeswax (BW) applied to guavas harvested green and stored for eight days at 22 °C was evaluated. Guavas were coated with HPMC+10% BW; HPMC+20% BW; HPMC+40% BW and Control-uncoated. The coatings reduced the respiration rate, inhibited ethylene synthesis and slowed the ripening process. The main benefits were the reduction in mass loss, maintenance of green color and firmness retention. The treatment with HPMC+20% BW presented the best results in maintaining the quality of the fruits, reducing the activity of the PG enzyme and delaying the ripening of 'Pedro Sato' guavas without promoting the activity of the ADH enzyme and consequently the fermentation of the fruits. fruits. The fruits treated with HPMC+20% CA showed a gain in shelf life of at least six days and despite being harvested green, no disorder affected the ripening process and its quality.

Abstract Scientists have repeatedly argued that transformative, multiscale global scenarios are needed as tools in the quest to halt the decline of biodiversity and achieve sustainability goals. As a first step towards achieving this, the researchers who participated in the scenarios and models expert group of the Intergovernmental Science‐Policy Platform on Biodiversity and Ecosystem Services (IPBES) entered into an iterative, participatory process that led to the development of the Nature Futures Framework (NFF). The NFF is a heuristic tool that captures diverse, positive relationships of humans with nature in the form of a triangle. It can be used both as a boundary object for continuously opening up more plural perspectives in the creation of desirable nature scenarios and as an actionable framework for developing consistent nature scenarios across multiple scales. Here we describe the methods employed to develop the NFF and how it fits into a longer term process to create transformative, multiscale scenarios for nature. We argue that the contribution of the NFF is twofold: (a) its ability to hold a plurality of perspectives on what is desirable, which enables the development of joint goals and visions and recognizes the possible convergence and synergies of measures to achieve these visions and (b), its multiscale functionality for elaborating scenarios and models that can inform decision‐making at relevant levels, making it applicable across specific places and perspectives on nature. If humanity is to achieve its goal of a more sustainable and prosperous future rooted in a flourishing nature, it is critical to open up a space for more plural perspectives of human–nature relationships. As the global community sets out to develop new goals for biodiversity, the NFF can be used as a navigation tool helping to make diverse, desirable futures possible. A free Plain Language Summary can be found within the Supporting Information of this article.

Abstract Background First-line treatment for prolactinomas is a medical treatment with dopamine agonists (DAs), which effectively control hyperprolactinaemia in most patients, although post-withdrawal remission rates are approximately 34%. Therefore, many patients require prolonged DA treatment, while side effects negatively impact health-related quality of life (HRQoL). Endoscopic transsphenoidal resection is reserved for patients with severe side effects, or with DA-resistant prolactinoma. Surgery has a good safety profile and high probability of remission and may thus deserve a more prominent place in prolactinoma treatment. The hypothesis for this study is that early or upfront surgical resection is superior to DA treatment both in terms of HRQoL and remission rate in patients with a non-invasive prolactinoma of limited size. Methods We present a combined randomised clinical trial and observational cohort study design, which comprises three unblinded randomised controlled trials (RCTs; PRolaCT-1, PRolaCT-2, PRolaCT-3), and an observational study arm (PRolaCT-O) that compare neurosurgical counselling, and potential subsequent endoscopic transsphenoidal adenoma resection, with current standard care. Patients with a non-invasive prolactinoma (< 25 mm) will be eligible for one of three RCTs based on the duration of pre-treatment with DAs: PRolaCT-1: newly diagnosed, treatment-naïve patients; PRolaCT-2: patients with limited duration of DA treatment (4–6 months); and PRolaCT-3: patients with persisting prolactinoma after DA treatment for > 2 years. PRolaCT-O will include patients who decline randomisation, due to e.g. a clear treatment preference. Primary outcomes are disease remission after 36 months and HRQoL after 12 months. Discussion Early or upfront surgical resection for patients with a limited-sized prolactinoma may be a reasonable alternative to the current standard practice of DA treatment, which we will investigate in three RCTs and an observational cohort study. Within the three RCTs, patients will be randomised between neurosurgical counselling and standard care. The observational study arm will recruit patients who refuse randomisation and have a pronounced treatment preference. PRolaCT will collect randomised and observational data, which may facilitate a more individually tailored practice of evidence-based medicine. Trial registration US National Library of Medicine registry (ClinicalTrials.gov) NCT04107480 . Registered on 27 September 2019, registered retrospectively (by 2 months).

Abstract Citizen science platforms are quickly accumulating hundreds of millions of biodiversity observations around the world annually. Quantifying and correcting for the biases in citizen science datasets remains an important first step before these data are used to address ecological questions and monitor biodiversity. One source of potential bias among datasets is the difference between those citizen science programs that have unstructured protocols and those that have semi-structured or structured protocols for submitting observations. To quantify biases in an unstructured citizen science platform, we contrasted bird observations from the unstructured iNaturalist platform with that from a semi-structured citizen science platform—eBird—for the continental United States. We tested whether four traits of species (body size, commonness, flock size, and color) predicted if a species was under- or over-represented in the unstructured dataset compared with the semi-structured dataset. We found strong evidence that large-bodied birds were over-represented in the unstructured citizen science dataset; moderate evidence that common species were over-represented in the unstructured dataset; strong evidence that species in large groups were over-represented; and no evidence that colorful species were over-represented in unstructured citizen science data. Our results suggest that biases exist in unstructured citizen science data when compared with semi-structured data, likely as a result of the detectability of a species and the inherent recording process. Importantly, in programs like iNaturalist the detectability process is two-fold—first, an individual organism needs to be detected, and second, it needs to be photographed, which is likely easier for many large-bodied species. Our results indicate that caution is warranted when using unstructured citizen science data in ecological modelling, and highlight body size as a fundamental trait that can be used as a covariate for modelling opportunistic species occurrence records, representing the detectability or identifiability in unstructured citizen science datasets. Future research in this space should continue to focus on quantifying and documenting biases in citizen science data, and expand our research by including structured citizen science data to understand how biases differ among unstructured, semi-structured, and structured citizen science platforms.

Abstract Background Maspin (SERPINB5) is a potential tumor suppressor gene with pleiotropic biological activities, including regulation of cell proliferation, death, adhesion, migration and gene expression. Several studies indicate that nuclear localization is essential for maspin tumor suppression activity. We have previously shown that the EGFR activation leads to maspin nuclear localization in MCF-10A cells. The present study investigated which EGFR downstream signaling molecules are involved in maspin nuclear localization and explored a possible role of cell–cell contact in this process. Methods MCF-10A cells were treated with pharmacological inhibitors against EGFR downstream pathways followed by EGF treatment. Maspin subcellular localization was determined by immunofluorescence. Proteomic and interactome analyses were conducted to identify maspin-binding proteins in EGF-treated cells only. To investigate the role of cell–cell contact these cells were either treated with chelating agents or plated on different cell densities. Maspin and E-cadherin subcellular localization was determined by immunofluorescence. Results We found that PI3K-Akt and JAK2-STAT3, but not MAP kinase pathway, regulate EGF-induced maspin nuclear accumulation in MCF-10A cells. We observed that maspin is predominantly nuclear in sparse cell culture, but it is redistributed to the cytoplasm in confluent cells even in the presence of EGF. Proteomic and interactome results suggest a role of maspin on post-transcriptional and translation regulation, protein folding and cell–cell adhesion. Conclusions Maspin nuclear accumulation is determined by an interplay between EGFR (via PI3K-Akt and JAK2-STAT3 pathways) and cell–cell contact. Video Abstract

The design and synthesis of artificial receptors based on molecular imprinting (MI) technology for the development of a new MIP-based biosensor for detection of the stress biomarker α-amylase in human saliva in point-of-care (PoC) applications is described in this work. The portable electrochemical devices for monitoring α-amylase consists of cost-effective and disposable gold screen-printed electrodes (AuSPEs). To build the electrochemical device, the template biomolecule was firstly immobilized directly over the working area of the gold chip previously activated with a self-assembled monolayer (SAM) of cysteamine (CA). Then, pyrrole (Py) monomer was selected as building block of a polymeric network prepared by CV electropolymerization. After the electropolymerization process, the enzyme was removed from the polymer film in order to build the specific recognition sites for the target enzyme. The MIP biosensor showed a very wide linear concentration range (between 3.0 × 10−4 to 0.60 mg mL−1 in buffer solution and between 3.0 × 10−4 to 3.0 × 10−2 mg mL−1 in human saliva) and low detection levels were achieved (LOD < 3.0 × 10−4 mg mL−1) using square wave voltammetry (SWV) as the electroanalytical technique.

Rare diseases are complex health entities with low prevalence (by the European definition less than 1 in 2000 people); some are so rare that only a few patients suffer from the condition in a whole region. In Europe, it is estimated that more than 7000 distinct rare diseases affect 6–8% of the population. Thus, only specially constructed and nationally endorsed combined efforts could address the challenges regarding that type of special health care management. During the past years, with the active involvement of clinical scientists as well as that of patients’ advocates, the European Commission (EC) has recognized the unmet long-term needs of patients with rare diseases. The EC adopted the 2011/24/EU directive on cross-border health care and launched large-scope programs aiming at standardized care and improvement in research and education (1).

Objective: To describe a case of acute invasive fungal sinusitis (AIFS), unique in its presentation with limited superficial invasion, underlying a fungal crust, in a patient on antifungal prophylaxis. To present accompanying images and pathology results that capture the very early stages of fungal invasion and depict the ongoing battle between fungal organisms and the immune system. Methods: Case report with literature review. Results: We present the case of a 74-year-old immunocompromised male on prophylactic voriconazole who was admitted with neutropenic fever and was found to have superficially invasive fungal sinusitis. Pathology from the initial surgical debridement showed superficial invasion of the middle turbinate mucosa, but no angioinvasion. Biopsies from a second surgical debridement were negative for fungal organisms, but fungal cultures were positive. The patient was treated with amphotericin B and posaconazole and discharged with plans for likely lifelong posaconazole. Conclusion: This case augments the existing AIFS literature in that the histopathology uniquely demonstrates limited superficial invasion, underlying a fungal crust, likely portraying the early stages of AIFS. Additionally, this case highlights new and ongoing clinical questions surrounding AIFS prevention and diagnosis, particularly in immunocompromised patients.

Partial tetrasomy of distal 13q has a reported association with a variable phenotype including microphthalmia, ear abnormalities, hypotelorism, facial dysmorphisms, urogenital defects, pigmentation and skin defects, and severe learning difficulties. A wide range of mosaicism has been reported, which may, to some extent, account for the variable spectrum of observed phenotypes. We report here a pregnancy conceived using intrauterine insemination in a 32-year-old female with a history of infertility. Non-invasive prenatal screening (NIPS) was performed in the first trimester which reported an increased risk for trisomy 13. Follow-up cytogenetic workup using chorionic villus sampling (CVS) and amniotic fluid samples showed a mosaic karyotype with a small supernumerary marker chromosome (sSMC). Chromosomal microarray analysis (CMA) identified a mosaic 31.34 Mb terminal gain on chr13q31.1q34 showing the likely origin of the sSMC to distal chromosome 13q. Follow-up metaphase FISH testing suggested an inverted duplication rearrangement involving 13q31q34 in the marker chromosome and the presence of a neocentromere. At 21 months of age, the proband has a history of gross motor delay, hypotonia, left microphthalmia, strabismus, congenital anomaly of the right optic nerve, hemangiomas, and a tethered spinal cord. Postnatal chromosome analyses in buccal, peripheral blood, and spinal cord ligament tissues were consistent with the previous amniocentesis and CVS findings, and the degree of mosaicism varied from 25 to 80%. It is often challenging to pinpoint the chromosomal identity of sSMCs using banding cytogenetics. A combination of low-pass genome sequencing of cell-free DNA, chromosomal microarray, and FISH enabled the identification of the precise chromosomal rearrangement in this patient. This study adds to the growing list of clinically identified neocentric marker chromosomes and is the first described instance of partial tetrasomy 13q31q34 identified in a mosaic state prenatally. Since NIPS is now being routinely performed along with invasive testing for advanced maternal age, an increased prenatal detection rate for mosaic sSMCs in otherwise normal pregnancies is expected. Future studies investigating how neocentromeres mediate gene expression changes could help identify potential epigenetic targets as treatment options to rescue or reverse the phenotypes seen in patients with congenital neocentromeres.

The homeostasis of eukaryotic cells is inseverable of that of the endoplasmic reticulum (ER). The main function of this organelle is the synthesis and folding of a significant portion of cellular proteins, while it is also the major calcium reservoir of the cell. Upon unresolved ER stress, a set of stress response signaling pathways that are collectively labeled as the unfolded protein response (UPR) is activated. Prolonged or intense activation of this molecular machinery may be deleterious. It is known that compromised ER homeostasis, and consequent UPR activation, characterizes the pathogenesis of neurodegenerative diseases. In an effort to discover new small molecules capable of countering ER stress, we subjected a panel of over 100 natural molecules to a battery of assays designed to evaluate several hallmarks of ER stress. The protective potential of these compounds against ER stress was evaluated at the levels of calcium homeostasis, key gene and protein expression, and levels of protein aggregation in fibroblasts. The most promising compounds were subsequently tested in neuronal cells. This framework resulted in the identification of several bioactive molecules capable of countering ER stress and deleterious events associated to it. Delphinidin stands out as the most promising candidate against neurodegeneration. This compound significantly inhibited the expression of UPR biomarkers, and displayed a strong potential to inhibit protein aggregation in the two aforementioned cell models. Our results indicate that natural products may be a valuable resource in the development of an effective therapeutic strategy against ER stress-related diseases.