Ru(II) Complexes with Absorption in the Photodynamic Therapy Window: 1O2 Sensitization, DNA Binding, and Plasmid DNA Photocleavage.

Two Ru(II) complexes, [Ru(pydppn)(bim)(py)]2+ [2; pydppn = 3-(pyrid-2'-yl)-4,5,9,16-tetraaza-dibenzo[a,c]naphthacene; bim = 2,2'-bisimidazole; py = pyridine] and [Ru(pydppn)(Me4bim)(py)]2+ [3; Me4bim = 2,2'-bis(4,5-dimethylimidazole)], were synthesized and characterized, and their photophysical properties, DNA binding, and photocleavage were evaluated and compared to [Ru(pydppn)(bpy)(py)]2+ (1; bpy = 2,2'-bipyridine). Complexes 2 and 3 exhibit broad 1MLCT (metal-to-ligand charge transfer) transitions with maxima at ∼470 nm and shoulders at ∼525 and ∼600 nm that extend to ∼800 nm. These bands are red-shifted relative to those of 1, attributed to the π-donating ability of the bim and Me4bim ligands. A strong signal at 550 nm is observed in the transient absorption spectra of 1-3, previously assigned as arising from a pydppn-centered 3ππ* state, with lifetimes of ∼19 µs for 1 and 2 and ∼270 ns for 3. A number of methods were used to characterize the mode of binding of 1-3 to DNA, including absorption titrations, thermal denaturation, relative viscosity changes, and circular dichroism, all of which point to the intercalation of the pydpppn ligand between the nucleobases. The photocleavage of plasmid pUC19 DNA was observed upon the irradiation of 1-3 with visible and red light, attributed to the sensitized generation of 1O2 by the complexes. These findings indicate that the bim ligand, together with pydppn, serves to shift the absorption of Ru(II) complexes to the photodynamic therapy window, 600-900 nm, and also extend the excited state lifetimes for the efficient production of cytotoxic singlet oxygen.

Optical genome mapping identifies a novel pediatric embryonal tumor with a ZNF532::NUTM1 fusion.

The molecular characteristics of pediatric brain tumors have not only allowed for tumor subgrouping but have led to the introduction of novel treatment options for patients with specific tumor alterations. Therefore, an accurate histologic and molecular diagnosis is critical for optimized management of all pediatric patients with brain tumors, including central nervous system embryonal tumors. We present a case where optical genome mapping identified a ZNF532::NUTM1 fusion in a patient with a unique tumor best characterized histologically as a central nervous system embryonal tumor with rhabdoid features. Additional analyses including immunohistochemistry for NUT protein, methylation array, whole genome, and RNA-sequencing was done to confirm the presence of the fusion in the tumor. This is the first description of a pediatric patient with a ZNF532::NUTM1 fusion, yet the histology of this tumor is similar to that of adult cancers with ZNF::NUTM1 fusions reported in the literature. Although rare, the distinct pathology and underlying molecular characteristics of the ZNF532::NUTM1 tumor separates this from other embryonal tumors. Therefore, screening for this or similar NUTM1 rearrangements should be considered for all patients with unclassified central nervous system tumors with rhabdoid features to ensure accurate diagnosis. Ultimately, with additional cases, we may be able to better inform therapeutic management for these patients. © 2023 The Pathological Society of Great Britain and Ireland.

Stand-alone optical spinning tweezers with tunable rotation frequency.

Advances in optical trapping design principles have led to tremendous progress in manipulating nanoparticles (NPs) with diverse functionalities in different environments using bulky systems. However, efficient control and manipulation of NPs in harsh environments require a careful design of contactless optical tweezers. Here, we propose a simple design of a fibered optical probe allowing the trapping of dielectric NP as well as a transfer of the angular momentum of light to the NP inducing its mechanical rotation. A polarization conversion from linearly-polarized incident guided to circularly transmitted beam is provoked geometrically by breaking the cylindrical symmetry of a coaxial nano-aperture that is engraved at the apex of a tapered metal coated optical fiber. Numerical simulations show that this simple geometry tip allows powerful light transmission together with efficient polarization conversion. This guarantees very stable trapping of quasi spherical NPs in a non-contact regime as well as potentially very tunable and reversible rotation frequencies in both directions (up to 45 Hz in water and 5.3 MHz in air for 10 mW injected power in the fiber). This type of fiber probe opens the way to a new generation of miniaturized tools for total manipulation (trapping, sorting, spinning) of NPs.

Treatment of recurrent aphtous stomatitis: A systematic review.

BACKGROUND: Recurrent Aphtous Stomatitis (RAS) is the most common process affecting the oral mucosa. It is painful, multifactorial and generally recurrent. The aim of this systematic review is to know the last treatment approaches and their effectivity. MATERIAL AND METHODS: we compared the outcome of different kind of treatments in terms of the improvement of the lesions, reduction of the size of those lesions and the time needed for their healing. Inclusion criteria were: clinical trials, articles written in English or Spanish and published less than 5 years ago. RESULTS: we used the following keywords: "treatment", "aphtous stomatitis", "canker sores"; combined with Boolean operators AND y OR. We selected 28 articles for reading the whole text, and after applying the eligibility criteria, we selected 17 articles for our revision. Among all the treatments, we emphasize the barrier method based in compound of cellulose rubber and a calcium/sodium copolymer PVM/MA, with which the difference in the 3rd and 7th day was of -6,29 ± 0,14 points in the pain score. The treatment with insulin and chitosan gel, brought a pain suppression on the third day, with no reactivation of the pain during the whole study. The application of a film composed of polyurethane and sesame oil with chitosan, brought a reduction in the size of the lesions of 4,54 ± 2,84mm on the 6th day compared with the situation before the beginning of the treatment. The different kinds of laser, which produced a reduction in the pain score just at the beginning of the treatment up to 8,1 ± 1,6 points, and a reduction of the size of the lesions of 4,42 ± 1,02mm on the 7th day. CONCLUSIONS: Besides the classic treatments for RAS, we have to take into account other treatment modalities, above all the different kinds of laser.

Evolution of children diagnosed with attention deficit/hyperactivity disorder. Follow-up study in a Spanish simple.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a chronic condition with long-term associated risks. OBJECTIVE: To analyze the clinical status, occupation, and daily life difficulties of two cohorts of children diagnosed with ADHD (2004 and 2009) after five and 10 years. MATERIAL AND METHOD: Descriptive, longitudinal study using the WOMI database corresponding to Oviedo, Asturias, Spain. Children with ADHD detected by their primary care pediatrician were included. A voluntary follow-up telephone interview was requested. Outcome variables were current clinical and occupational status, ADHD symptoms according to SNAP-IV, and Strengths and Difficulties Questionnaire (SDQ). RESULTS: The interviewed sample consisted of 95 subjects, out of whom 71 answered the SNAP-IV and SDQ questionnaires; 60.70% of the sample did not receive treatment at the time of follow-up, 4.7% had no occupation, 25.40% still had ADHD global symptoms above the clinical cutoff point, and 66.2% had difficulties with moderate interference. CONCLUSIONS: ADHD symptoms decline as people grow up. Mental health comorbidities and academic dropout were not confirmed in the sample.

ANTECEDENTES: El trastorno de déficit de atención e hiperactividad (TDAH) constituye una condición crónica con riesgos asociados a largo plazo. OBJETIVO: Analizar el estado clínico, la ocupación y las dificultades de la vida diaria de dos cohortes de niños con diagnóstico de TDAH (2004 y 2009) después cinco y 10 años. MATERIAL Y MÉTODO: Estudio descriptivo y longitudinal de la base de datos WOMI correspondiente a Oviedo, Asturias, España. Se incluyeron niños detectados con TDAH por su pediatra de atención primaria. Se solicitó una entrevista telefónica voluntaria de seguimiento. Las variables de resultado fueron estado clínico y ocupacional al momento de la entrevista, síntomas de TDAH según SNAP-IV y Cuestionario de Fortalezas y Dificultades (SDQ). RESULTADOS: La muestra entrevistada estuvo formada por 95 sujetos, de los cuales 71 respondieron a los cuestionarios SNAP-IV y SDQ; 60.7 % de la muestra no recibía tratamiento en el momento del seguimiento, 4.7 % no tenía ninguna ocupación, 25.4 % mantenía síntomas globales de TDAH en nivel superior al punto de corte clínico y 66.2 % presentaba dificultades con interferencia moderada. CONCLUSIONES: Los síntomas del TDAH disminuyen conforme las personas crecen. Las comorbilidades de salud mental y el abandono académico no se confirmaron en la muestra.

New PCR-Based Assay for the Identification of Pectobacterium carotovorum Causing Potato Soft Rot.

Soft rot on potato tuber is a destructive disease caused by pathogenic bacterial species of the genera Pectobacterium and Dickeya. Accurate identification of the causal agent is necessary to ensure adequate disease management because different species may have distinct levels of aggressiveness and host range. One of the most important potato pathogens is Pectobacterium carotovorum, a highly heterogeneous species capable of infecting multiple hosts. The complexity of this species, until recently divided into several subspecies, has made it difficult to develop precise diagnostic tests. This study proposes a PCR assay based on the new pair of primers Pcar1F/R to facilitate the identification of potato isolates of P. carotovorum according to the most recent taxonomic description of this species. The new primers were designed on a variable segment of the 16S rRNA gene and the intergenic spacer region of available DNA sequences from classical and recently established species in the genus Pectobacterium. The results of the PCR analysis of genomic DNA from 32 Pectobacterium and Dickeya strains confirmed that the Pcar1F/R primers have sufficient nucleotide differences to discriminate between P. carotovorum and other Pectobacterium species associated with damage to potato crops, with the exception of Pectobacterium versatile, which improves the specificity of the currently available primers. The proposed assay was originally developed as a conventional PCR but was later adapted to the real-time PCR format for application in combination with the existing real-time PCR test for the potato-specific pathogen Pectobacterium parmentieri. This should be useful for the routine diagnosis of potato soft rot.

The Greatwall-Endosulfine Switch Accelerates Autophagic Flux during the Cell Divisions Leading to G1 Arrest and Entry into Quiescence in Fission Yeast.

Entry into quiescence in the fission yeast Schizosaccharomyces pombe is induced by nitrogen starvation. In the absence of nitrogen, proliferating fission yeast cells divide twice without cell growth and undergo cell cycle arrest in G1 before becoming G0 quiescent cells. Under these conditions, autophagy is induced to produce enough nitrogen for the two successive cell divisions that take place before the G1 arrest. In parallel to the induction of autophagy, the Greatwall-Endosulfine switch is activated upon nitrogen starvation to down-regulate protein phosphatase PP2A/B55 activity, which is essential for cell cycle arrest in G1 and implementation of the quiescent program. Here we show that, although inactivation of PP2A/B55 by the Greatwall-Endosulfine switch is not required to promote autophagy initiation, it increases autophagic flux at least in part by upregulating the expression of a number of autophagy-related genes.

Prepartum behavior changes in dry Holstein cows at risk of postpartum diseases.

The objective of this study was to identify changes in prepartum behavior associated with the incidence of postpartum diseases in dairy cows. Multiparous Holstein cows (n = 489) were monitored with accelerometers for 3 wk prepartum. Accelerometers measured steps, time at the feed bunk, frequency of meals, lying bouts, and lying time. Postpartum health was monitored from 0 to 30 d in milk and cases of metritis, mastitis, retained placenta, displaced abomasum (DA), ketosis, and hypocalcemia were recorded. A multivariate linear mixed model was used to assess differences in behavior between diseased and not diagnosed diseased cows. A multivariate logistic regression was used to predict the occurrence of diseases. Predictors were selected using a manual backward stepwise selection process of variables until all remaining predictors had a P < 0.10. Models were submitted to a leave-one-out cross-validation process, and sensitivity, specificity, false discovery rate, and false omission rate were calculated. On average, over the 3-wk prepartum period, cows not diagnosed diseased (n = 345) took 1,613 ± 38 steps, spent 181 ± 7.1 min at the feed bunk, had 8.3 ± 0.17 meals, had 9.8 ± 0.32 lying bouts, and spent 742 ± 11.3 min lying per day. Behavior of diseased cows (n = 144) did not differ from those not diagnosed diseased. However, differences for specific diseases were observed, being significant in the week prepartum. When considering changes in behavior for only the week before calving, cows with metritis had more lying bouts (+21%), cows with DA had fewer meals (-24%) and tended to take fewer steps (-18%), and cows with ketosis had fewer meals (-22%) and spent less time at the feed bunk (-40%). Prediction models with the best outcomes were found for DA and ketosis using data of the prepartum week only. The model for DA included time at the feed bunk. Cross-validation resulted in a 80% sensitivity, 58.1% specificity, 59.2% accuracy, 91.2% false discovery rate, and 1.7% false omission rate. The model for ketosis included time at the feed bunk and number of meals. Cross-validation resulted in 64.3% sensitivity, 59.3% specificity, 59.5% accuracy, 93.0% false discovery rate, and 2.8% false omission rate. Prepartum behavior of cows affected with metritis, DA, and ketosis was different from that of cows not diagnosed with diseases. Prediction equations were able to classify cows at high or low risk of ketosis and DA and can be used in taking management decisions, but the high false discovery rates requires further refinement.

Clinical behavior of posterior fixed partial dentures with a biologically oriented preparation technique: A 5-year randomized controlled clinical trial.

STATEMENT OF PROBLEM: Evidence of the behavior of the periodontal tissues around anterior teeth restored with the biologically oriented preparation technique (BOPT) is available. However, outcomes of this technique in posterior teeth restored with fixed partial dentures (FPDs) are lacking. PURPOSE: The purpose of this randomized controlled clinical trial was to evaluate the clinical, mechanical, and biological behavior of posterior 3-unit FPDs placed on teeth prepared with BOPT. MATERIAL AND METHODS: Forty participants received a 3-unit zirconia FPD in the posterior region of the mandible or maxilla. Twenty FPDs were placed on teeth prepared with BOPT (study group) and 20 on teeth with a horizontal chamfer finishing line (control group). Follow-up examinations were performed 1, 3, and 5 years after treatment to evaluate periodontal responses around the prepared teeth by means of the following parameters: plaque index, gingival index, probing depth, and marginal stability (MS). Mechanical behavior was also assessed, as were any complications. RESULTS: After the 5-year follow-up, 57.9% of the control group and 35% of the BOPT group presented a plaque index of 1. The gingival index was 1 in 68.4% of the control group and 30% of the BOPT group after the follow-up period. In the analysis of probing depth, 26.3% of teeth in the control group had pockets of more than 3 mm in depth, whereas the BOPT group had only 10%. Marginal stability appeared in 100% of the BOPT group, whereas only 10.5% of the control group exhibited gingival stability. Complications during the follow-up period were similar, 20% in the control group and 15% in the BOPT group. CONCLUSIONS: Posterior FPDs prepared by using BOPT had a good clinical response over a 5-year follow-up, with a low gingival index, a small increase in pocket depth, and a 100% marginal stability of the surrounding tissues. High survival rates after 5 years indicated that the technique produced predictable outcomes.

Expression of caveolin-1 in tooth germ, ameloblastoma and ameloblastic carcinoma.

BACKGROUND: The caveolin-1 protein (structural component of membrane caveolae) plays important roles in several biological functions, such as endocytosis, cell adhesion, and cell signaling. However, this protein has been associated with mechanisms of tumorigenesis in several neoplasms. The expression patterns and roles of caveolin-1 in the oral epithelium and in embryonic and odontogenic tumor tissues are still unclear. MATERIAL AND METHODS: The expression of caveolin-1 was evaluated in samples of the normal gingival epithelium (n=7), human tooth germ (TG) (n=12), ameloblastoma (AM) (n=83), and ameloblastic carcinoma (AC) (n=9) by immunohistochemistry. Additionally, AM samples were analyzed by qRT-PCR and Western blot. RESULTS: Most TG (91.7%), AM (73.5%) and AC (100%) samples showed diverse patterns of immunohistochemical positivity for caveolin-1, while only one gingival sample was positive. The transcript levels of cav-1 were significantly upregulated by 14.9-fold in AM tissue (P = 0.0014) compared to those in normal gingival epithelial tissue, as shown by qRT-PCR. Presence of caveolin-1 protein was confirmed by Western blot analysis. The caveolin-1 immunoexpression patterns throughout the stages of TG show its importance during odontogenesis. CONCLUSIONS: The overexpression of caveolin-1 in AM and AC compared to its expression in normal gingival epithelium (adult tissue) suggests a possible role of caveolin-1 in protumoral events, but due to the similar immunoexpression observed in AM and AC, caveolin-1 may not necessarily participate in the malignant transformation process. However, future studies are needed to clarify and confirm these hypotheses.

Transcriptional response of Fusarium oxysporum and Neocosmospora solani challenged with amphotericin B or posaconazole.

Some species of fusaria are well-known pathogens of humans, animals and plants. Fusarium oxysporum and Neocosmospora solani (formerly Fusarium solani) cause human infections that range from onychomycosis or keratitis to severe disseminated infections. In general, these infections are difficult to treat due to poor therapeutic responses in immunocompromised patients. Despite that, little is known about the molecular mechanisms and transcriptional changes responsible for the antifungal resistance in fusaria. To shed light on the transcriptional response to antifungals, we carried out the first reported high-throughput RNA-seq analysis for F. oxysporum and N. solani that had been exposed to amphotericin B (AMB) and posaconazole (PSC). We detected significant differences between the transcriptional profiles of the two species and we found that some oxidation-reduction, metabolic, cellular and transport processes were regulated differentially by both fungi. The same was found with several genes from the ergosterol synthesis, efflux pumps, oxidative stress response and membrane biosynthesis pathways. A significant up-regulation of the C-22 sterol desaturase (ERG5), the sterol 24-C-methyltransferase (ERG6) gene, the glutathione S-transferase (GST) gene and of several members of the major facilitator superfamily (MSF) was demonstrated in this study after treating F. oxysporum with AMB. These results offer a good overview of transcriptional changes after exposure to commonly used antifungals, highlights the genes that are related to resistance mechanisms of these fungi, which will be a valuable tool for identifying causes of failure of treatments.

Medical education from the point of view of medical students: Results from four participatory Delphi panels in Quito, Ecuador.

BACKGROUND: Medical curricula have historically been designed in a top-down approach, usually excluding students. While Delphi panels have been used as a tool for medical education curricula design, none have been conducted in Ecuador. In addition, no such approach has ever included students both as panelists and researchers. MATERIAL AND METHODS: Four Delphi panels were developed and conducted using a participatory approach that allowed medical students to take part both as expert panelists and researchers: specifically, students developed the questionnaire and conducted a qualitative synthesis. Questionnaire responses were anonymized and dispatched online to panelists. The information was organized and collected to develop the qualitative syntheses and prepare the final statements. RESULTS: Thirty-two medical students participated between February and May 2018. A total of 32 questions were developed, corresponding to five different categories. For some questions, consensus was reached; for other questions, general statements were obtained.Discussion and conclusion: Developing the questionnaire, responding to it and analyzing the answers allowed students to raise significant concerns regarding medical education topics proposing relevant policy and curricula change. Participatory Delphi panels can be an efficient tool to obtain organized feedback, improve student class involvement, and promote research skills.

Ungual warts: comparison of treatment with intralesional bleomycin and electroporation in terms of efficacy and safety.

BACKGROUND: Ungual warts are considered the most common benign nail tumour, and they are caused by the human papillomavirus. Despite the numerous treatments reported in the medical literature, ungual warts are considered frustrating, with high relapse rates and a potential risk of nail dystrophy. Bleomycin is a therapeutic option showing a good safety profile and high cure rates. OBJECTIVE: To evaluate the efficacy of electrochemotherapy using intralesional bleomycin for the treatment of ungual warts in comparison with intralesional bleomycin alone and describe the side-effects related to the use of both techniques. METHODS: This was a prospective, randomized, double-blind, controlled clinical trial. Forty-four 18- to 60-year-old female and male patients with ungual warts of only one finger were included. The patients were divided into two treatment groups: GA - intralesional bleomycin; and GB - electroporation and intralesional bleomycin. Following a single application, the patients were followed up for 180 days. RESULTS: The patients' mean age was 36 years for GA and 37 years for GB. Most patients were female (68%). Of 22 patients in GA completing the study, 11 (50%) achieved the cure, while 18 (85.7%) of 21 patients completing the study in GB showed cure. A significant association of patients with or without cure after the GA and GB treatments (P = 0.022) was observed. None of the patients in either group had systemic side-effects. Independent of the technique used, all the participants considered the adverse effects tolerable. CONCLUSION: The intralesional use of bleomycin associated with electroporation for the treatment of ungual warts (both periungual and subungual) showed a statistically superior cure when compared with intralesional bleomycin alone. Side-effects were more frequently observed in the electrochemotherapy with bleomycin group than in the bleomycin monotherapy group.

Hypocalcemia and bone mineral density changes following denosumab treatment in end-stage renal disease patients: a meta-analysis of observational studies.

The incidence of hypocalcemia and bone mineral density (BMD) changes in end-stage renal disease (ESRD) patients on denosumab remains unclear. We performed this meta-analysis to assess the incidence of denosumab-associated hypocalcemia and effects of denosumab on BMD in ESRD patients. A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through November 2017 to identify studies evaluating incidence of denosumab-associated hypocalcemia and changes in serum calcium, phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and BMD from baseline to post-treatment course of denosumab in ESRD patients. Study results were pooled and analyzed using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017081074). Six observational studies with a total of 84 ESRD patients were enrolled. The pooled estimated incidence of hypocalcemia during denosumab treatment was 42% (95% CI 29-55%, I2 = 0%). Hypocalcemia occurred approximately 7 to 20 days after the first dose and reached nadir of low calcium levels in the first 2 weeks up to 2 months. However, there were no significant changes in serum calcium or phosphate from baseline to post-treatment course (≥ 3 months after treatment) with mean differences [MDs] of 0.20 mg/dL (95% CI, - 0.30 to 0.69 mg/dL) and - 0.10 mg/dL (95% CI, - 0.70 to 0.49 mg/dL). There were significant reductions in ALP and PTH levels with standardized mean differences (SMDs) of - 0.65 (95% CI - 1.13 to - 0.16) and - 1.89 (95% CI - 3.44 to - 0.34), respectively. There were significant increases in T-scores with MDs of 0.39 (95% CI 0.10 to 0.69) and 0.79 (95% CI 0.60 to 0.98) for lumbar spine and femoral neck, respectively. Our study demonstrates the estimated incidence of denosumab-associated hypocalcemia in dialysis patients of 42%. From baseline to post-treatment course, although there are no differences in serum calcium and phosphate, our findings suggest significant reductions in ALP and PTH and a significant increase in BMD. Currently, denosumab should not be considered as the treatment of choice in ESRD patients until more safety and efficacy data are available.

C-section and the Neonatal Gut Microbiome Acquisition: Consequences for Future Health.

BACKGROUND: The human gut microbiota is assembled during infancy with an increase in diversity and stability. The correct colonization and the establishment of this microbiome are linked to the early and future health status of the individual. It is known that caesarean delivery alters this optimal microbial foundation. C-section (CS) is a common obstetrician surgery; however, it is not without risk for the mother/infant dyad. The World Health Organization recommends not exceeding 10-15% of the total deliveries; nevertheless, this rate has been increasing rapidly worldwide in the last decades. SUMMARY: This review discloses the clinical parameters for correct CS recommendation. Moreover, the major microbial changes in the infant gut microbiome acquisition as a consequence of delivery mode and medical practices surrounding it, as well as, the early and long-lasting effects for both mother and babies are discussed. In addition, some strategies for the gut microbiota restoration are analysed. The aim of this review is to show the need for the development of strategies for minimizing or limiting the impact of caesarean on the microbiome development, favouring future health.

A single nucleotide polymorphism uncovers a novel function for the transcription factor Ace2 during Candida albicans hyphal development.

Candida albicans is a major invasive fungal pathogen in humans. An important virulence factor is its ability to switch between the yeast and hyphal forms, and these filamentous forms are important in tissue penetration and invasion. A common feature for filamentous growth is the ability to inhibit cell separation after cytokinesis, although it is poorly understood how this process is regulated developmentally. In C. albicans, the formation of filaments during hyphal growth requires changes in septin ring dynamics. In this work, we studied the functional relationship between septins and the transcription factor Ace2, which controls the expression of enzymes that catalyze septum degradation. We found that alternative translation initiation produces two Ace2 isoforms. While full-length Ace2, Ace2L, influences septin dynamics in a transcription-independent manner in hyphal cells but not in yeast cells, the use of methionine-55 as the initiation codon gives rise to Ace2S, which functions as the nuclear transcription factor required for the expression of cell separation genes. Genetic evidence indicates that Ace2L influences the incorporation of the Sep7 septin to hyphal septin rings in order to avoid inappropriate activation of cell separation during filamentous growth. Interestingly, a natural single nucleotide polymorphism (SNP) present in the C. albicans WO-1 background and other C. albicans commensal and clinical isolates generates a stop codon in the ninth codon of Ace2L that mimics the phenotype of cells lacking Ace2L. Finally, we report that Ace2L and Ace2S interact with the NDR kinase Cbk1 and that impairing activity of this kinase results in a defect in septin dynamics similar to that of hyphal cells lacking Ace2L. Together, our findings identify Ace2L and the NDR kinase Cbk1 as new elements of the signaling system that modify septin ring dynamics in hyphae to allow cell-chain formation, a feature that appears to have evolved in specific C. albicans lineages.

Evaluation of Over-The-Row Harvester Damage in a Super-High-Density Olive Orchard Using On-Board Sensing Techniques.

New super-high-density (SHD) olive orchards designed for mechanical harvesting using over-the-row harvesters are becoming increasingly common around the world. Some studies regarding olive SHD harvesting have focused on the effective removal of the olive fruits; however, the energy applied to the canopy by the harvesting machine that can result in fruit damage, structural damage or extra stress on the trees has been little studied. Using conventional analyses, this study investigates the effects of different nominal speeds and beating frequencies on the removal efficiency and the potential for fruit damage, and it uses remote sensing to determine changes in the plant structures of two varieties of olive trees (‘Manzanilla Cacereña’ and ‘Manzanilla de Sevilla’) planted in SHD orchards harvested by an over-the-row harvester. ‘Manzanilla de Sevilla’ fruit was the least tolerant to damage, and for this variety, harvesting at the highest nominal speed led to the greatest percentage of fruits with cuts. Different vibration patterns were applied to the olive trees and were evaluated using triaxial accelerometers. The use of two light detection and ranging (LiDAR) sensing devices allowed us to evaluate structural changes in the studied olive trees. Before- and after-harvest measurements revealed significant differences in the LiDAR data analysis, particularly at the highest nominal speed. The results of this work show that the operating conditions of the harvester are key to minimising fruit damage and that a rapid estimate of the damage produced by an over-the-row harvester with contactless sensing could provide useful information for automatically adjusting the machine parameters in individual olive groves in the future.

Orbital malignant meningioma: a unique presentation of a rare entity.

An elderly female with progressive proptosis was found to have an aggressive retrobulbar solid orbital mass. The mass was distinct from the optic nerve sheath and intracranial meninges, and produced concave erosion of the sphenoid wing. Operative findings demonstrated an orbital mass adherent to the dura of the superior orbital fissure. The mass did not demonstrate meningeal violation, infiltrate the superior orbital fissure, or display intracranial spread. The dura remained intact after gross total resection. Histopathology revealed a malignant meningioma with papillary and focal rhabdoid morphology and bony invasion (WHO grade III). The patient received 2500cGy of stereotactic radiotherapy in addition to gross total resection. Postoperatively, the signs and symptoms of orbital mass effect resolved (proptosis, relative afferent papillary defect, and periorbital edema) and the vision improved. There was no orbital recurrence or intracranial extension. The follow-up time was limited to eight months secondary to the patient succumbing to metastatic lung adenocarcinoma, which was demonstrated to be a separate process from the orbital meningioma. We propose the etiology of this tumor to be most consistent with an orbital malignant primary extradural meningioma - the first case reported in the literature.

Comprehensive Genomic Profiling Aids in Distinguishing Metastatic Recurrence from Second Primary Cancers.

BACKGROUND: Metastatic recurrence after treatment for locoregional cancer is a major cause of morbidity and cancer-specific mortality. Distinguishing metastatic recurrence from the development of a second primary cancer has important prognostic and therapeutic value and represents a difficult clinical scenario. Advances beyond histopathological comparison are needed. We sought to interrogate the ability of comprehensive genomic profiling (CGP) to aid in distinguishing between these clinical scenarios. MATERIALS AND METHODS: We identified three prospective cases of recurrent tumors in patients previously treated for localized cancers in which histologic analyses suggested subsequent development of a distinct second primary. Paired samples from the original primary and recurrent tumor were subjected to hybrid capture next-generation sequencing-based CGP to identify base pair substitutions, insertions, deletions, copy number alterations (CNA), and chromosomal rearrangements. Genomic profiles between paired samples were compared using previously established statistical clonality assessment software to gauge relatedness beyond global CGP similarities. RESULTS: A high degree of similarity was observed among genomic profiles from morphologically distinct primary and recurrent tumors. Genomic information suggested reclassification as recurrent metastatic disease, and patients received therapy for metastatic disease based on the molecular determination. CONCLUSIONS: Our cases demonstrate an important adjunct role for CGP technologies in separating metastatic recurrence from development of a second primary cancer. Larger series are needed to confirm our observations, but comparative CGP may be considered in patients for whom distinguishing metastatic recurrence from a second primary would alter the therapeutic approach. The Oncologist 2017;22:152-157Implications for Practice: Distinguishing a metastatic recurrence from a second primary cancer can represent a difficult clinicopathologic problem but has important prognostic and therapeutic implications. Approaches to aid histologic analysis may improve clinician and pathologist confidence in this increasingly common clinical scenario. Our series provides early support for incorporating paired comprehensive genomic profiling in clinical situations in which determination of metastatic recurrence versus a distinct second primary cancer would influence patient management.

Proanthocyanidins potentiate hypothalamic leptin/STAT3 signalling and Pomc gene expression in rats with diet-induced obesity.

OBJECTIVE: Dietary obesity is usually linked with hypothalamic leptin resistance, in which the primary impact is an interference in the homeostatic control of body weight and appetite. Notably, proanthocyanidins (PACs), which are the most abundant phenolic compounds present in human diet, modulate adiposity and food intake. The aim of this study was to assess whether PACs could re-establish appropriate leptin signalling in both the hypothalamus and peripheral tissues. DESIGN: Male Wistar rats were fed either a standard chow diet (STD group, n=7) or a cafeteria diet (CD) for 13 weeks. The CD-fed rats were treated with either grape-seed PAC extract (GSPE) at 25 mg per kg of body weight per day (CD+GSPE group, n=7) or with the vehicle (CD group, n=7) for the last 21 days of the study period. Specific markers for intracellular leptin signalling, inflammation and endoplasmic reticulum stress in the hypothalamus, liver, mesenteric white adipose tissue and skeletal muscle were analysed using immunoblotting and quantitative PCR. RESULTS: GSPE treatment significantly reduced the food intake but did not reverse the hyperleptinemia and body wt gain assessed. However, the animals treated with GSPE exhibited greater hypothalamic activation of signal transducer and activator of transcription-3, which was associated with a rise in the Pomc mRNA levels compared with the CD group. In addition, this restoration of leptin responsiveness was accompanied by lower local inflammation and increased Sirt1 gene expression. The effects of the GSPE treatment in the peripheral tissues were not as evident as those in the hypothalamus, although the GSPE treatment significantly restored the mRNA levels of Socs3 and Ptp1b in the skeletal muscle. CONCLUSIONS: The use of GSPE reduces hyperphagia and improves the central and peripheral leptin resistance associated with diet-induced obesity. Our results suggest that GSPE could exert these effects partially by increasing Sirt1 expression and preventing hypothalamic inflammation.