A case of Lomentospora prolificans endophthalmitis treated with the novel antifungal agent Olorofim.

PURPOSE: To report a case of endogenous Lomentospora prolificans endophthalmitis treated with the novel antifungal agent Olorofim. CASE REPORT: A 57-year-old man developed disseminated Lomentospora prolificans with right endophthalmitis on the background of immunosuppression following lung transplantation for interstitial lung disease. He was treated with early vitrectomy, intravitreal voriconazole, and systemic Olorofim, voriconazole and terbinafine. His symptoms improved and remained stable in the right eye. Eight weeks later the patient represented with Lomentopora prolificans endophthalmitis in the left eye when systemic voriconazole and terbinafine treatment were withdrawn. Despite aggressive treatment he ultimately succumbed due to vascular complications of extensive disseminated disease. CONCLUSION: We report a rare case of disseminated Lomentosporosis with panophthalmitis in an immunocompromised host with prolonged survival on systemic Olorofim, voriconazole and terbinafine in conjunction with pars plana vitrectomy and intravitreal voriconazole. Early suspicion of an opportunistic fungal infection is critical, as managing disseminated disease is often unsuccessful. Despite presumed inherent resistance, intravitreal and systemic voriconazole appeared to limit disease progression in the right eye. The potential synergistic effects of combined antifungal therapy with orotomides warrant further investigation.

Overdrive Pacing for Persistent Torsades de Pointes and Pulseless Ventricular Tachycardia.

A 53-year-old presented to the emergency department following a fall and was found to have recurrent episodes of torsades de pointes and pulseless ventricular tachycardia on cardiac monitoring. He had been abusing nimetazepam for sleep issues over the preceding one month. Despite correction of electrolytes, the arrhythmias were persistent which necessitated temporary overdrive pacing. The patient made an uneventful recovery and the temporary pacing was successfully removed with no recurrence of the malignant arrhythmias prior to discharge.

Photon Upconversion at Organic-Inorganic Interfaces.

Photon upconversion is a process that combines low-energy photons to form useful high-energy photons. There are potential applications in photovoltaics, photocatalysis, biological imaging, etc. Semiconductor quantum dots (QDs) are promising for the absorption of these low-energy photons due to the high extinction coefficient of QDs, especially in the near infrared (NIR). This allows the intriguing use of diffuse light sources such as solar irradiation. In this review, we describe the development of this organic-QD upconversion platform based on triplet-triplet annihilation, focusing on the dark exciton in QDs with triplet character. Then we introduce the underlying energy transfer steps, starting from QD triplet photosensitization, triplet exciton transport, triplet-triplet annihilation, and ending with the upconverted emission. Design principles to improve the total upconversion efficiency are presented. We end with limitations in current reports and proposed future directions. This review provides a guide for designing efficient organic-QD upconversion platforms for future applications, including overcoming the Shockley-Queisser limit for more efficient solar energy conversion, NIR-based phototherapy, and diagnostics in vivo.

Tuning the Chiral Growth of Plasmonic Bipyramids via the Wavelength and Polarization of Light.

Circularly polarized light (CPL) is a versatile tool to prepare chiral nanostructures, but the mechanism for inducing enantioselectivity is not well understood. This work shows that the energy and polarization of visible photons can initiate photodeposition at different sites on plasmonic nanocrystals. Here, CPL on achiral gold bipyramids (AuBPs) creates hot holes that oxidatively deposit PbO2 asymmetrically. We show for the first time that the location of PbO2 photodeposition and hence optical dissymmetry depends on the CPL wavelength. Specifically, 488 and 532 nm CPL induce PbO2 growth in the middle of AuBPs, whereas 660 nm CPL induces PbO2 growth at the tips. Our observations show that wavelength-dependent plasmonic field distributions are more important than surface lightning rod effects in localizing plasmon-mediated photochemistry. The largest optical dissymmetry occurs at excitation wavelengths between the transverse and longitudinal resonances of the AuBPs because higher-order modes are required to induce chiral electric fields.

Uveitis masquerade syndromes: An approach to diagnosis.

Uveitis masquerade syndromes are a diverse group of clinical entities which mimic conventional immune-mediated uveitis due to the presence of inflammatory signs but are resistant to anti-inflammatory therapy. Misdiagnosis hinders appropriate management in these conditions and may result in poor outcomes. This review discusses commonly encountered neoplastic and non-neoplastic disease processes that masquerade as intraocular inflammation with a focus on relevant clinical features and adjunctive investigations that are helpful in reaching a correct diagnosis.

Characterising the diagnosis of genetic maculopathies in a real-world private tertiary retinal practice in Australia: protocol for a retrospective clinical audit.

PURPOSE: Accurate diagnosis of macular atrophy is paramount to enable appropriate treatment when novel treatments for geographic atrophy and macular dystrophies become available. Genetic testing is useful in distinguishing between the two conditions but is not feasible for the majority of patients in real-world clinical practice. Therefore, we aimed to investigate the potential misdiagnosis of inherited macular dystrophy as age-related macular degeneration (AMD) in real-world ophthalmic practice to assist in the development of guidelines to improve diagnostic accuracy while minimizing genetic testing for targeted patients. METHODS: Retrospective review of the medical records of patients diagnosed with AMD, which included imaging, between 1995 and 2023 from a large multidisciplinary private ophthalmic practice in Australia. We will use a stepwise method to screen for probable cases of macular dystrophy, followed by a consensus review by an expert panel. The outcomes are (1) to determine the potential misdiagnosis rate of macular dystrophy as atrophic AMD by retinal specialists and general ophthalmologists; (2) to identify clinical imaging modalities that are most useful for differentiating macular dystrophy from atrophic AMD; and (3) to establish preliminary guidance for clinicians to improve the diagnosis of macular atrophy from AMD in practice, and thereby target cost-efficient genetic testing. DISCUSSION: Improving the diagnostic accuracy of both AMD and macular dystrophy, while ensuring cost-efficient genetic testing, will improve the targeted treatment of macular diseases when emerging treatments become available.

Identification and bioactivity evaluation of miliusanes from Miliusa sinensis.

Miliusanes are a class of anticancer lead molecules belonging to meroterpenoids with an 18-carbon skeleton isolated from Miliusa plants. A phytochemical study of the plant M. sinensis was carried out to discover new miliusanes with diverse structural features in order to better understand their structure-activity relationship. As a result, 20 compounds including 12 new ones (7-14 and 17-20) belonging to two sub-classes of miliusanes were isolated and identified from the twigs and leaves of this plant. Their structures, including absolute configurations, were determined by spectroscopic analyses and electronic circular dichroism. The absolute stereochemistry of miliusane structures has also been confirmed for the first time through the single crystal X-ray diffraction analysis of miliusol (1). Bioactivity evaluation showed that some of the miliusane isolates potently inhibit cell growth of several human derived cancer cell lines with IC50 values ranging from 0.52 to 23.5 µM. Compound 11 demonstrated more potent cytotoxic activity than the known miliusol (1) in stomach cancer cells though its structure contains an unconjugated 1, 4-diketone system, which added a new structure-activity feature to miliusanes. The preliminary mechanism of action studies revealed that they could be a class of dual cell migration inhibitor and senescence inducer.

A New Association Of Guillain Barre Syndrome In A Patient With Central Nervous System Melioidosis.

Burkholderia pseudomallei affecting the central nervous system has been extensively reported in the literature. However, combined central nervous system and peripheral nervous system involvement in melioidosis has never been reported. We report a 66-year-old man with diabetes mellitus who was diagnosed to have central nervous system melioidosis and developed acute flaccid quadriplegia. Nerve conduction studies and anti-ganglioside antibodies were consistent with Guillain-Barre syndrome. This case report highlights the importance to recognise the possibility of Guillain Barre syndrome complicating central nervous system melioidosis and stresses the urgency of early consideration of this complication, as early immunomodulatory therapy may hasten neurological recovery.

It Comes and Goes: Pediatric Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria (CSU) is an underrecognized and underreported condition, even more so in the pediatric population. Due to its fugacious nature, the period between the onset of symptoms and the diagnosis of CSU is often long. We discuss the case of a 10-year-old child who presented with a six-month history of recurrent, pruritic rash. Medical advice was sought on multiple occasions; however, no treatment was initiated. This resulted in the child and caretakers becoming increasingly worried. The child was subsequently diagnosed with CSU. Daily second-generation antihistamine was started, and the child responded well with marked improvement of symptoms. Our case raises a pertinent point. It is crucial for physicians to be able to recognize and treat CSU according to evidence-based guidelines, as this condition may not only negatively affect the child's quality of life, but its impact also extends to the caretakers.

Efficient photon upconversion enabled by strong coupling between silicon quantum dots and anthracene.

Hybrid structures formed between organic molecules and inorganic quantum dots can accomplish unique photophysical transformations by taking advantage of their disparate properties. The electronic coupling between these materials is typically weak, leading photoexcited charge carriers to spatially localize to the dot or to a molecule at its surface. However, we show that by converting a chemical linker that covalently binds anthracene molecules to silicon quantum dots from a carbon-carbon single bond to a double bond, we access a strong coupling regime where excited carriers spatially delocalize across both anthracene and silicon. By pushing the system to delocalize, we design a photon upconversion system with a higher efficiency (17.2%) and lower threshold intensity (0.5 W cm-2) than that of a corresponding weakly coupled system. Our results show that strong coupling between molecules and nanostructures achieved through targeted linking chemistry provides a complementary route for tailoring properties in materials for light-driven applications.

High-Level Reverse Intersystem Crossing and Molecular Rigidity Improve Spin Statistics for Triplet-Triplet Annihilation Upconversion.

The structural factors affecting triplet-triplet annihilation (TTA) at the molecular level are not well-understood. Here, our steady-state photoluminescence and transient absorption results demonstrate that the spin statistical factor, η, decreases from 0.60 to 0.46 and 0.14 going from 9,10-diphenylanthracene (DPA) to the 1,5-DPA and 2,6-DPA isomers, respectively, during photon upconversion with a platinum octaethylporphyrin sensitizer. Density functional theory (DFT) shows that η depends on the energetics of hot triplet states and molecular rigidity. The significantly high conical intersection energy between the S0 and T1 states for 9,10-DPA gives its longer triplet lifetime. Time-dependent DFT calculations show that 9,10-DPA and 1,5-DPA can undergo high-level reverse intersystem crossing from their T2 and T3 states, respectively, to the bright S1 state, increasing the limit of the spin statistical factor. Both factors ultimately serve to enhance the TTA efficiency. This work provides insight into designing molecules for efficient light-emitting and photon upconversion applications.

ACQUIRED HAEMOPHILIA A.

Acquired haemophilia A (AHA) is a rare disease believed to be caused by spontaneous inhibition of clotting Factor VIII by autoantibodies. This is in contrast to the more common congenital haemophilias which are largely due to an absolute deficiency in coagulation factors. It has a prevalence of approximately one per million per year. However, this figure may be underestimated because there are many undocumented cases due to a lack of recognition. Patients who develop this disease may present with catastrophic bleeding despite having no previous bleeding history. In this study, we report a case of acquired Haemophilia A presenting with spontaneous unprovoked bruising and discuss the approach to diagnosis and how to alert the clinician to suspect this potentially rare but devastating disease.

Gas-phase grafting for the multifunctional surface modification of silicon quantum dots.

Photon upconversion in systems incorporating inorganic quantum dots (QDs) is of great interest for applications in solar energy conversion, bioimaging, and photodynamic therapy. Achieving high up-conversion efficiency requires not only high-quality inorganic nanoparticles, but also precise control of their surface functional groups. Gas-phase surface functionalization provides a new pathway towards controlling the surface of small inorganic nanoparticles. In this contribution, we utilize a one-step low-temperature plasma technique for the synthesis and in-flight partial functionalization of silicon QDs with alkyl chains. The partially functionalized surface is then modified further with 9-vinylanthracene via thermal hydrosilylation resulting in the grafting of 9-ethylanthracene (9EA) groups. We have found that the minimum alkyl ligand density necessary for quantum dot solubility also gives the maximum upconversion quantum yield, reaching 17% for silicon QDs with Si-dodecyl chains and an average of 3 9EA molecules per particle.

Emergence and Persistent Dominance of Omicron BA.2.3.7 Variant in Community Outbreaks in Taiwan

Using high-throughput sequencing of the SARS-CoV-2 genome, we have analyzed 2405 PCR-positive swab samples from 2339 individuals and identified the Omicron BA.2.3.7 variant as a major lineage of the recent community outbreak in Taiwan. Since April 2022, a series of new waves of Omicron cases have surfaced in Taiwan and spread throughout the island. We conducted genomic surveillance with a high success rate and have submitted 1966 full-length Omicron sequences to GISAID. This has permitted identification of signature amino acid changes (ORF1a:L631F, S:K97E, N:M322I) in 1584 (80.6%) of the translated SARS-CoV-2 sequences. The newly established BA.2.3.7 lineage, which is relatively common in Asian countries, is now persistently present in Taiwan. By June 2022 this dominant strain had established a substantial existence in the sequence pool, resulting in additional mutations. The rapid spread and expansion of the Omicron BA.2.3.7 lineage in Asia has had an important socioeconomic impact on health policy.

Discovery of dearomatized isoprenylated acylphloroglucinols with colon tumor suppressive activities in mice via inhibiting NFκB-FAT1-PDCD4 signaling activation.

Dearomatized isoprenylated acylphloroglucinols (DIAPs) are specific natural products mainly distributed in the plants of genus Hypericum. In this study, guided by HPLC-UV screening, 46 DIAPs (approximately 70% of all DIAPs) including 20 new ones and an unprecedented architecture, were discovered from the roots of Hypericum henryi, which were elucidated by comprehensive spectroscopic, X-ray crystallography, and ECD methods. Compounds 1-7, 39, and 41-42 exhibited remarkable cytotoxicities (IC50 = 0.84-5.63 µM) in human colon cancer HCT116 cells, in which 2 and 6 possessed selective cytotoxicities towards colon cancer cells. The preliminary structure-activity relationships of these tested compounds were discussed. In addition, mechanistic investigations demonstrated that 2 and 6 could significantly suppress the expressions of NFκB, FAT1, and promoted novel tumor suppressor gene PDCD4 in HCT116 cells. Furthermore, in HCT116 colon xenograft-bearing mouse model, treatments with 2 and 6 reduced the growth of xenograft tumors in dose-dependent manner. Expressions of FAT1 in tumors were also decreased in mice treated with 2 and 6, suggesting their anti-tumor effects were via FAT1 signaling pathway. In conclusion, this is the first report on the mechanistic and in vivo studies of DIAP, indicating that these metabolites can be considered as a new type of anti-colon cancer lead agents for further drug development.