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Leslie Citrome,1 Mariacristina Castelli,2 Masami Hasebe,3 Takaaki Terahara,3 Justin Faden,4 Marina Komaroff2 1Department of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, NY, USA; 2Product Development, Noven Pharmaceuticals, Inc, Jersey City, NJ, USA; 3Hisamitsu Pharmaceutical Co., Inc, Tokyo, Japan; 4Department of Psychiatry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USACorrespondence: Leslie Citrome, Department of Psychiatry and Behavioral Sciences, New York Medical College, 40 Sunshine Cottage Road, Valhalla, NY, 10595, USA, Tel +1 845-362-2081, Email nntman@gmail.comIntroduction: HP-3070, a once-daily asenapine transdermal system, is the first antipsychotic “patch” formulation FDA approved for adults with schizophrenia. Positive and Negative Syndrome Scale (PANSS) score items can be grouped into a five-factor structure to describe specific schizophrenia symptom domains. This post hoc analysis of data from a pivotal study evaluated HP-3070’s efficacy by examining these factors.Methods: In a phase 3 study, adults with an acute exacerbation of schizophrenia were randomized to six weeks of treatment with HP-3070 3.8mg/24h, 7.6mg/24h, or placebo. An analysis was performed using the five PANSS factor domains (negative symptoms, positive symptoms, disorganized thought, uncontrolled hostility/excitement, anxiety/depression). Mixed-model repeated-measures (MMRM) analysis included change from baseline (CFB) in PANSS factor score as the repeated dependent variable, with country, treatment, visit, treatment by visit interaction, and baseline PANSS score as covariates.Results: The analysis included 607 patients. Treatment with HP-3070 3.8mg/24h resulted in a statistically significant LS mean CFB (improvement) vs placebo at Weeks 4– 6 for all domains except for anxiety/depression, where a numerical difference was observed in favor of active treatments. Among the domains, the positive symptom factor demonstrated the numerically greatest LS mean (SE) difference from placebo in CFB, which for HP-3070 7.6mg/24h was − 2.0 [0.57] and for HP-3070 3.8mg/24h was − 2.3 [0.57]; P< 0.001 for both. Treatment effect size for the positive symptom factor using Cohen’s d (95% confidence intervals) was 0.39 (0.17, 0.61) for HP-3070 7.6mg/24h and 0.45 (0.20, 0.64) for HP-3070 3.8mg/24h.Discussion: Post hoc analysis using a PANSS five-factor model suggests that HP-3070 may address a broad range of symptoms in people with schizophrenia.Keywords: asenapine, transdermal, patch, schizophrenia, positive and negative syndrome scale, five-factor

This article discusses a case of pregnancy-induced enlargement of a prolactinoma, a type of tumor in the pituitary gland. The patient, a 23-year-old woman, had a history of a stable 11 mm prolactinoma that had been treated with medication. However, during her pregnancy, the tumor significantly enlarged and began to encroach upon the optic chiasm, causing persistent headaches. The patient restarted medication treatment, which stabilized the tumor size and relieved her symptoms. After delivering a healthy baby, the patient's prolactin levels were further reduced, and follow-up imaging showed a reduction in tumor size. The article emphasizes the importance of achieving tumor control before considering pregnancy and highlights the need for careful monitoring and family planning in women with prolactinomas. [Extracted from the article]

SP 123 sp I-metaiodobenzylguanidine (MIBG) scintigraphy showed a ring-like uptake in the right adrenal mass (Figure 1b), and diffusion-weighted magnetic resonance imaging (MRI) demonstrated ring-like hyperintense signals with a hypointense area in the center of the adrenal mass (Figure 1c). (b) 123I-metaiodobenzylguanidine scintigraphy (single-photon emission computed tomography/computed tomography) showing a ring-like uptake in the right adrenal mass. The abdomen's unenhanced computed tomography (CT) revealed a right adrenal mass, including a central low-density area, with a maximum dimension of 5.5 cm (Figure 1a). [Extracted from the article]

Whereas computed tomography of the brain showed no abnormality, the brain diffusion-weighted magnetic resonance imaging (MRI) revealed the hyperintense lesions in the bilateral deep cerebral white matter and the corpus callosum, which did not conform to cerebral arterial distributions (Figure 1A). Ten days after admission, a follow-up diffusion-weighted MRI showed obscured signal changes in the same areas, suggesting the resolution of the initial lesions (Figure 1B). (A) Hyperintense lesions in bilateral deep cerebral white matter (arrows) and the corpus callosum (arrowheads) at admission. [Extracted from the article]

A new Al2O3/Er3Al5O12(EAG)/ZrO2 ternary MGC (Melt Growth Composite) with a novel microstructure has been fabricated by unidirectional solidification. This ternary MGC has a microstructure consisting of continuous networks of single-crystal Al2O3, single-crystal EAG and fine cubic-ZrO2 phases without grain boundaries. The ternary MGC has also characteristic dimensions of the microstructure of around 2-4 µ m for EAG phases, around 2-4 µ m for Al2O3 phases reinforced with around 0.4-0.8 µ m cubic-ZrO2 phases. No amorphous phases are formed at interfaces between phases in the ternary MGC. The ternary MGC’s flexural strength at 1873 K is approximately 700 MPa, more than twice the 330 MPa of the Al2O3/EAG binary MGC. The fracture manner of the Al2O3/EAG/ZrO2 ternary MGC at 1873 K shows the same intergranular fracture as the Al2O3/EAG binary MGC, but is significantly different from the transgranular fracture of the sintered ceramic. [ABSTRACT FROM AUTHOR]

New Al2O3/Y3Al5O12(YAG)/ZrO2 ternary Melt Growth Composites (MGCs) with a novel microstructure have been fabricated by unidirectional solidification. These MGCs displayed superior high-temperature strength characteristics. The flexural strength increases progressively in the range 650–800 MPa with a rise in temperature from room temperature up to 1873 K. These excellent high-temperature characteristics are closely linked to such factors as: a microstructure consisting of three-dimensionally continuous and complexly entangled single-crystal Al2O3 with a hexagonal structure, single-crystal YAG with a garnet structure and fine ZrO2 with a cubic structure; characteristic dimensions of the microstructure of Al2O3/YAG/ZrO2 ternary eutectic ceramics of around 2–3 μm for YAG, around 2–3 μm for Al2O3 and around 0.4–0.8 μm for ZrO2; and the fact that no amorphous phase is formed at interfaces between any of the phases. [ABSTRACT FROM AUTHOR]

The homeodomain-leucine zipper (HD-Zip) genes encode transcription factors that are characterized by the presence of both a homeodomain and a leucine zipper motif. They belong to the homeobox gene superfamily and have been reported only from flowering plants. This article is the first report on the ferm HD-Zip genes (named Crhb1-Crhb11) isolated from the homosporous ferm Ceratopteris richardii. Phylogenetic analyses of the II Crhb genes with previously reported angiosperm HD-Zip genes show that the Crhb genes belong to three of the four different angiosperm HD-Zip subfamilies (HD-Zip I, II, and IV), indicating that these subfamilies of HD-Zip genes originated before the diversification of the ferm and seed plant lineages. The Crhb4-Crhb8 and Crhb11 genes belong to the HD-Zip I subfamily but differ from angiosperm HD-Zip I genes by the presence of a seven-amino-acid indel in the leucine zipper motif. By the northern analyses, Crhb1 and Crhb3 were expressed only in gametophyte tissue. Expression of Crhb2 and Crhb11 genes could not be detected in any tissue examined, while all other Crhb genes were expressed in most sporophytic and gametophytic tissues. Although the functions of the Crhb genes in Ceratopteris are unknown, their patterns of expression suggest that they regulate developmental or physiological processes common to both the gametophyte and the sporophyte generations of the fern. Differences in the expression of Crhb1 between male gametophytes and male-hermaphrodite mixed populations of gametophytes suggests that the Crhb1 gene is involved in gametophytic sex determination. [ABSTRACT FROM PUBLISHER]

Abstract Background Ceratopteris richardii is a useful experimental system for studying gametophyte development and sexual reproduction in plants. However, few tools for cloning mutant genes or disrupting gene function exist for this species. The feasibility of systemic gene silencing as a reverse genetics tool was examined in this study. Results Several DNA constructs targeting a Ceratopteris protoporphyrin IX magnesium chelatase (CrChlI) gene that is required for chlorophyll biosynthesis were each introduced into young gametophytes by biolistic delivery. Their transient expression in individual cells resulted in a colorless cell phenotype that affected most cells of the mature gametophyte, including the meristem and gametangia. The colorless phenotype was associated with a 7-fold decrease in the abundance of the endogenous transcript. While a construct designed to promote the transient expression of a CrChlI double stranded, potentially hairpin-forming RNA was found to be the most efficient in systemically silencing the endogenous gene, a plasmid containing the CrChlI cDNA insert alone was sufficient to induce silencing. Bombarded, colorless hermaphroditic gametophytes produced colorless embryos following self-fertilization, demonstrating that the silencing signal could be transmitted through gametogenesis and fertilization. Bombardment of young gametophytes with constructs targeting the Ceratopteris filamentous temperature sensitive (CrFtsZ) and uroporphyrin dehydrogenase (CrUrod) genes also produced the expected mutant phenotypes. Conclusion A method that induces the systemic silencing of target genes in the Ceratopteris gametophyte is described. It provides a simple, inexpensive and rapid means to test the functions of genes involved in gametophyte development, especially those involved in cellular processes common to all plants.