The first efficient intermolecular reaction of gold carbene intermediates generated via gold-catalyzed alkyne oxidation has been realized using nitriles as both the reacting partner and the reaction ...solvent, offering a generally efficient synthesis of 2,5-disubstituted oxazoles with broad substrate scope. The overall reaction is a 2 + 2 + 1 annulation of a terminal alkyne, a nitrile, and an oxygen atom from an oxidant. The reaction conditions are exceptionally mild, and a range of functional groups are easily tolerated. With complex and/or expensive nitriles, only 3 equiv could be sufficient to achieve serviceable yields in the absence of any solvent and using only 1 mol % BrettPhosAuNTf2 as the catalyst.
A general solution for the synthesis of various oxetan-3-ones is developed. This reaction uses readily available propargylic alcohols as substrates and proceeds without the exclusion of moisture or ...air (“open flask”). Notably, oxetan-3-one, a highly valuable substrate for drug discovery, can be prepared in one step from propargyl alcohol in a fairly good yield. The facile formation of the strained oxetane ring provides strong support for the intermediacy of α-oxo gold carbenes. This safe and efficient generation of gold carbenes via intermolecular alkyne oxidation offers a potentially general entry into α-oxo metal carbene chemistry without using hazardous diazo ketones.
Chiral rings made easy: Chiral azetidin‐3‐ones have been easily prepared from chiral N‐propargylsulfonamides, which in turn are readily accessible through chiral sulfinamide chemistry (see scheme). ...Using tert‐butylsulfonyl as the protecting group avoids unnecessary deprotection and reprotection steps, and allows its removal from the azetidine ring under acidic conditions.
Fungal orbital cellulitis is usually seen in immunocompromised individuals, and opportunistic pathogens are the main etiology. We herein report a case of fungal orbital cellulitis due to Aspergillus ...in a patient with no history of trauma. A 48-year-old man presented to the emergency room of our hospital with a 2-week history of periorbital swelling, conjunctival hyperemia, and chemosis of his right eye. The visual acuity of his right eye was 6/20, and the intraocular pressure was 44 mmHg. The main clinical findings were proptosis of the right ocular globe with conjunctival hyperemia and a palpable infratemporal orbital mass. Laboratory testing failed to detect the presence of a pathogenic infection, and the lesions on computed tomography images resembled those of a malignant tumor of the orbit. The diagnosis was finally confirmed by postoperative pathological examination, and the patient responded favorably to debridement combined with antifungal therapy. Histopathological examination may help to reveal the nature of this disease. Surgical removal of inflammatory lesions can serve as an important diagnostic and treatment method for fungal orbital cellulitis.
Lacrimal gland mucoepidermoid carcinoma is very rare. It has a high risk of recurrence and metastasis, however, it rarely metastasizes to the contralateral eye in clinical practice. Here, we present ...a case of a 52-year-old man with lacrimal gland mucoepidermoid carcinoma who developed multiple recurrences and metastases of another eye and other sites throughout the body after receiving surgical intervention and regular radiotherapy, which will be of ophthalmic interest and unique. Clinical features, imaging findings, histopathology, treatments, and outcomes of this very rare case are provided. A literature review of previously published cases of this disease is performed, with an emphasis on the latest diagnosis and treatment. The prognosis of tumor recurrence and metastasis is poorer, surgery with a negative margin in conjunction with adjuvant therapies is crucial for preventing local recurrence and distant metastasis and enhancing the survival rate.
Clinical whole-exome sequencing is increasingly used for diagnostic evaluation of patients with suspected genetic disorders.
To perform clinical whole-exome sequencing and report (1) the rate of ...molecular diagnosis among phenotypic groups, (2) the spectrum of genetic alterations contributing to disease, and (3) the prevalence of medically actionable incidental findings such as FBN1 mutations causing Marfan syndrome.
Observational study of 2000 consecutive patients with clinical whole-exome sequencing analyzed between June 2012 and August 2014. Whole-exome sequencing tests were performed at a clinical genetics laboratory in the United States. Results were reported by clinical molecular geneticists certified by the American Board of Medical Genetics and Genomics. Tests were ordered by the patient's physician. The patients were primarily pediatric (1756 88%; mean age, 6 years; 888 females 44%, 1101 males 55%, and 11 fetuses 1% gender unknown), demonstrating diverse clinical manifestations most often including nervous system dysfunction such as developmental delay.
Whole-exome sequencing diagnosis rate overall and by phenotypic category, mode of inheritance, spectrum of genetic events, and reporting of incidental findings.
A molecular diagnosis was reported for 504 patients (25.2%) with 58% of the diagnostic mutations not previously reported. Molecular diagnosis rates for each phenotypic category were 143/526 (27.2%; 95% CI, 23.5%-31.2%) for the neurological group, 282/1147 (24.6%; 95% CI, 22.1%-27.2%) for the neurological plus other organ systems group, 30/83 (36.1%; 95% CI, 26.1%-47.5%) for the specific neurological group, and 49/244 (20.1%; 95% CI, 15.6%-25.8%) for the nonneurological group. The Mendelian disease patterns of the 527 molecular diagnoses included 280 (53.1%) autosomal dominant, 181 (34.3%) autosomal recessive (including 5 with uniparental disomy), 65 (12.3%) X-linked, and 1 (0.2%) mitochondrial. Of 504 patients with a molecular diagnosis, 23 (4.6%) had blended phenotypes resulting from 2 single gene defects. About 30% of the positive cases harbored mutations in disease genes reported since 2011. There were 95 medically actionable incidental findings in genes unrelated to the phenotype but with immediate implications for management in 92 patients (4.6%), including 59 patients (3%) with mutations in genes recommended for reporting by the American College of Medical Genetics and Genomics.
Whole-exome sequencing provided a potential molecular diagnosis for 25% of a large cohort of patients referred for evaluation of suspected genetic conditions, including detection of rare genetic events and new mutations contributing to disease. The yield of whole-exome sequencing may offer advantages over traditional molecular diagnostic approaches in certain patients.
Neurogenesis persists in the adult brain and can be regulated by a plethora of external stimuli, such as learning, memory, exercise, environment and stress. Although newly generated neurons are able ...to migrate and preferentially incorporate into the neural network, how these cells are molecularly regulated and whether they are required for any normal brain function are unresolved questions. The adult neural stem cell pool is composed of orphan nuclear receptor TLX-positive cells. Here, using genetic approaches in mice, we demonstrate that TLX (also called NR2E1) regulates adult neural stem cell proliferation in a cell-autonomous manner by controlling a defined genetic network implicated in cell proliferation and growth. Consequently, specific removal of TLX from the adult mouse brain through inducible recombination results in a significant reduction of stem cell proliferation and a marked decrement in spatial learning. In contrast, the resulting suppression of adult neurogenesis does not affect contextual fear conditioning, locomotion or diurnal rhythmic activities, indicating a more selective contribution of newly generated neurons to specific cognitive functions.
We present an unusual case of bilateral dacryoadenitis in a middle-aged patient with adult-onset Still’s disease (AOSD). We reviewed relevant clinical studies addressing the association between ...lacrimal lesions and AOSD. A 50-year-old Chinese woman with a 4 year history of recurrent fever and rashes was admitted to the hospital. She had also developed nodules on both eyelids 10 months before admission. After undergoing resection of the left lacrimal gland, the patient received steroids and immunosuppressive therapy. The patient showed good postoperative recovery during the 20 month follow-up. In this case, the pathological examination conducted after orbital surgery helped clinicians differentiate between dacryoadenitis and other orbital lesions. In a review of the literature, dacryoadenitis occurred after the onset of AOSD, and all cases showed non-granulomatous chronic inflammation by histopathology, which indicated that the lacrimal gland may be an inflammatory target and is affected by systemic inflammation in AOSD.
This study aims to observe the accelerated aging effect of .sup.60 Co gamma (gamma) irradiation on poly (methyl methacrylate) (PMMA) under extreme conditions and determine the influence of different ...media states on aging. PMMA samples were prepared at room temperature under varying media conditions, including air and deionized water immersion. Then, the samples were irradiated with different doses (50, 250, 500, and 1000 KGy) of .sup.60 Co gamma-rays. The compositional changes of the PMMA samples exposed to the rays at different periods were determined via Fourier transform infrared spectroscopy. The light transmission of the samples was characterized through ultraviolet-visible spectrophotometry, and the surface wettability of the samples was assessed via water contact angle measurements. Surface and microscopic changes in material morphology were analyzed using optical microscopy, ImageJ software, and scanning electron microscopy. Relative molecular mass and glass transition temperature were analyzed via gel permeation chromatography and differential scanning calorimetry. Thus, a comprehensive analysis of the effect of .sup.60 Co gamma irradiation on the aging properties of PMMA was performed.
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