We address the problem of generating novel molecules with desired interaction properties as a multi-objective optimization problem. Interaction binding models are learned from binding data using ...graph convolution networks (GCNs). Since the experimentally obtained property scores are recognised as having potentially gross errors, we adopted a robust loss for the model. Combinations of these terms, including drug likeness and synthetic accessibility, are then optimized using reinforcement learning based on a graph convolution policy approach. Some of the molecules generated, while legitimate chemically, can have excellent drug-likeness scores but appear unusual. We provide an example based on the binding potency of small molecules to dopamine transporters. We extend our method successfully to use a multi-objective reward function, in this case for generating novel molecules that bind with dopamine transporters but not with those for norepinephrine. Our method should be generally applicable to the generation in silico of molecules with desirable properties.
Wiedemann-Rautenstrauch syndrome (WRS) is a rare neonatal congenital disorder characterized by a progeroid appearance at birth. We report the ocular manifestations of WRS in a 6-year-old boy and ...compare the findings to previously reported cases. We report for the first time the findings of thin central corneas and lagophthalmos in WRS.
Dysregulation of the kynurenine pathway (KP) leads to imbalances in neuroactive metabolites associated with the pathogenesis of several neurodegenerative disorders, including Huntington's disease ...(HD). Inhibition of the enzyme kynurenine 3-monooxygenase (KMO) in the KP normalises these metabolic imbalances and ameliorates neurodegeneration and related phenotypes in several neurodegenerative disease models. KMO is thus a promising candidate drug target for these disorders, but known inhibitors are not brain permeable. Here, 19 new KMO inhibitors have been identified. One of these (
) is neuroprotective in a
HD model but is minimally brain penetrant in mice. The prodrug variant (
) crosses the blood-brain barrier, releases
in the brain, thereby lowering levels of 3-hydroxykynurenine, a toxic KP metabolite linked to neurodegeneration. Prodrug
will advance development of targeted therapies against multiple neurodegenerative and neuroinflammatory diseases in which KP likely plays a role, including HD, Alzheimer's disease, and Parkinson's disease.
Purpose: To review the epidemiology of serious ocular trauma presenting to Cairns Base Hospital, from the far north Queensland health districts.
Methods: A retrospective study of cases from January ...1995 to November 2002 inclusive. Cases were analysed with respect to demographics, cause and nature of injury, method of transport and time to and type of ophthalmic treatment, and visual outcomes.
Results: There were 226 cases identified, including 71 open‐globe and 155 closed‐globe injuries. The annual rate of injury was 3.7 per 100 000 for open‐globe and 11.8 per 100 000 in total. The Aboriginal and Torres Strait Islander population from the far north Queensland districts showed a disproportionate incidence, with 38% of the total number of injuries, despite representing only 12.3% of the population. Assault in the Aboriginal and Torres Strait Islander population resulted in 69.6% of injuries in men and 75.8% of injuries in women. Of all assaults 76.2% were alcohol‐related. The majority (71.5%) of injuries in the Caucasian population were due to accidental blunt and sharp trauma. In total, 77.4% of injuries occurred in men, with an average age of 31 years. Of all open and closed injuries in the study, a final visual acuity of 6/12 or better was achieved in 47.8% of eyes and a final visual acuity of 6/60 or less occurred in 17.7% of patients, 20.8% patients were lost to follow up. In total, 14.1% of open injuries required enucleation/evisceration.
Conclusions: The incidence of ocular trauma in far north Queensland is equal to other Australian populations. However, there is a disproportionately high incidence in the Aboriginal and Torres Strait Islander population. Alcohol‐related assault is a significant cause of visual loss in the Aboriginal and Torres Strait Islander population. Closed‐globe injuries are more common than open globe; however, the latter have poorer visual prognosis. Initial visual acuity of all injuries correlated with final visual acuity.
Importance
Indigenous communities of Far North Queensland (FNQ) have one of the highest incidences of alcohol‐related ocular trauma globally.
Background
To review the epidemiology of closed‐ and ...open‐globe trauma admitted to Cairns Hospital from FNQ health districts following the implementation of alcohol restrictions in Indigenous communities.
Design
Retrospective study of cases from January 2014 to December 2018.
Participants
A total of 142 cases identified from ICD‐10 clinical‐coding data.
Methods
Records were reviewed to determine demographics, clinical details and outcomes.
Main Outcome Measures
Annual incidence by demography and ethnicity (Indigenous vs non‐indigenous).
Results
Estimated annual incidence was 10.4/100 000 population (open‐globe: 3.6/100 000, closed‐globe: 6.8/100 000 population). Incidence rate ratio was 2.8× higher in Indigenous (22.8/100 000 population) compared to non‐indigenous populations. Injury from assault was 8.2× higher in the Indigenous population. Alcohol was involved in 76% of assaults. Paediatric injuries comprised 20.4% of the cohort, with Indigenous children over‐represented (44.8% of children). Visual acuity (VA) at presentation ranged from −0.08 logMAR to no‐perception of light (NPL), with 41.8% poorer than +1.00 logMAR. Final VA ranged from −0.18 logMAR to NPL. Mean final VA was significantly better for closed‐ than open‐globe injuries (+0.43 vs +1.01 logMAR). Ruptures had the poorest outcomes (mean +1.65 logMAR).
Conclusions and relevance
The overall incidence of severe ocular trauma in FNQ has decreased compared to that reported from 1995 to 2002. The extremely high incidence observed in the Indigenous communities of Cape York has decreased dramatically since the introduction of Alcohol Management Plans. Nevertheless, the Indigenous population still experiences significantly higher rates of severe ocular trauma, particularly from assault.
Correction
This article 1 was unintentionally published twice in this journal, by the same authors.
The following 1 should be considered the version of record and used for citation purposes: ...“Neharika Sharma and Stephen O’Hagan, The role of oral co-trimoxazole in treating Nocardia farcinica keratitis: a case report. Journal of Ophthalmic Inflammation and Infection (2016) 6:21 DOI 10.1186/s12348-016-0087-y”.
The duplicate 2: “Neharika Sharma and Stephen O’Hagan, The role of oral co-trimoxazole in treating Nocardia farcinica keratitis: a case report. Journal of Ophthalmic Inflammation and Infection (2016) 6:23 DOI 10.1186/s12348-016-0091-2” is to be ignored.
BioMed Central apologizes to the readers of the journal for not detecting the duplication during the publication process.
Conjunctival myxomas are rare, benign, connective tissue tumours that classically present as slow-growing, painless, well-circumscribed masses (Arch Ophthalmol 124:735-8, 2006; Case Rep Ophthalmol ...3:145-50, 2012). There have been 29 cases reported in the literature (Arch Ophthalmol 124:735-8, 2006; Malays J Med Sci 20(1):92-4, 2013; Case Rep Ophthalmol 3:145-50, 2012; Middle East Afr J Ophthalmol 19(3):353-3, 2012). We present a case with atypical features, and emphasize the importance of excisional biopsies for diagnosing indeterminate conjunctival lesions.
A 32 year old Korean woman presented with a 5 mm × 7 mm × 3 mm pedunculated firm cystic lesion on the inferior palpebral conjunctiva of her right lower eyelid. The lesion had rapidly enlarged over the course of a week. She gave a history of uncomplicated bilateral epiblepharon correction performed in Korea three months prior. There were no systemic features, or family history of genetic conditions. The lesion was excised under local anaesthesia and reported to be a conjunctival myxoma. The clinical and histopathological features of this lesion were consistent with previous reports on conjunctival myxoma (Arch Ophthalmol 124:735-8, 2006; Arch Ophthalmol 101:1416-20, 1983; Case Rep Ophthalmol 3:145-50, 2012; Am J Ophthalmol 102(1):80-84, 1986). The unusual features of this case were, the rapid growth of the lesion - with the previously documented mean time before presentation being 34 months (range 3 months - 24 years) (Arch Ophthalmol 124:735-8, 2006; Case Rep Ophthalmol 3:145-50, 2012); the location of the lesion in the inferior palpebral conjunctiva - 93 % of previously reported cases had occurred in the bulbar conjunctiva (Arch Ophthalmol 124:735-8, 2006; Case Rep Ophthalmol 3:145-50, 2012); and its occurrence in association with recent eyelid surgery - which has never been reported.
This case of conjunctival myxoma adds to the small number of documented cases, by demonstrating an atypical presentation. Conjunctival myxomas can occur in association with the Carney Complex, which is an autosomal dominant syndrome associated with benign tumours, spotty mucocutaneous pigmentation, and endocrine overactivity (Ophthalmic Surg Lasers Imaging 39(6):514-6, 2008). Ophthalmic manifestations of the Carney Complex have been found to precede vascular embolic events secondary to cardiac myxoma, thus early diagnosis of conjunctival myxoma can prevent potentially devastating consequences (Ophthalmic Surg Lasers Imaging 39(6):514-6, 2008). The different presentations of this rare tumour emphasise the importance of excisional biopsies in diagnosing indeterminate conjunctival lesions; and its association with cardiac myxoma, highlights the need for cardiac investigations in all patients who present with conjunctival myxoma (J Ophthalmol (1);1-5, 2014; Ophthalmic Surg Lasers Imaging 39(6):514-6, 2008).
Background
Nocardia farcinica
is one of the more recently identified species of the
Nocardia
genus.
Nocardia farcinica
keratitis is a rare occurrence, with only eight previously reported cases. ...Semi-permeable rigid contact lens use was associated with one of these reported cases. We report the first case of extended wear soft contact-lens-related
Nocardia farcinica
keratitis and recommend a new treatment regime.
Findings
A 47-year-old lady presented with a right eye keratitis after wearing her extended wear soft contact lenses for five continuous weeks. There was no history of trauma or swimming with contact lenses in. Empirical ciprofloxacin and tobramycin eye drops were not tolerated due to ocular surface irritation on application; and instead, empirical treatment was with chloramphenicol and fortified gentamicin 1.5 % eye drops. Corneal scrapings grew
Nocardia farcinica
after 3 weeks—sensitive to amikacin and co-trimoxazole. Treatment was changed to amikacin 2.5 % eye drops, resulting in partial resolution of the corneal infiltrates. Oral co-trimoxazole 160/800 mg BD was added, due to cultured drug sensitivity and its high ocular penetration, with good results and a final right eye best-corrected visual acuity of 6/5.
Conclusion
Nocardia farcinica
keratitis should be considered in the differential diagnosis of contact-lens-related keratitis. We report the first case occurring in association with extended wear soft contact lenses.
Nocardia
species can mimic fungal and
Acanthamoeba
keratitis. Treatment with oral co-trimoxazole has not been previously reported. This case demonstrates a role for co-trimoxazole in treating
Nocardia farcinica
keratitis based on cultured drug sensitivities.
Nocardia farcinica
is one of the more recently identified species of the
Nocardia
genus.
Nocardia farcinica
keratitis is a rare occurrence, with only eight previously reported cases. Semi-permeable ...rigid contact lens use was associated with one of these reported cases. We report the first case of an extended wear soft contact lens-related
Nocardia farcinica
keratitis and recommend a new treatment regime. A 47-year-old lady presented with a right eye keratitis after wearing her extended wear soft contact lenses for five continuous weeks. There was no history of trauma or swimming with contact lenses in. Empirical ciprofloxacin and tobramycin eye drops were not tolerated due to ocular surface irritation on application, and instead, empirical treatment was with chloramphenicol and fortified gentamicin 1.5 % eye drops. Corneal scrapings grew
Nocardia farcinica
after 3 weeks—sensitive to amikacin and co-trimoxazole. Treatment was changed to amikacin 2.5 % eye drops, resulting in partial resolution of the corneal infiltrates. Oral co-trimoxazole 160 mg/800 mg BD was added, due to cultured drug sensitivity and its high ocular penetration, with good results and a final right eye best-corrected visual acuity of 6/5.
Nocardia farcinica
keratitis should be considered in the differential diagnosis of contact lens-related keratitis. We report the first case occurring in association with extended wear soft contact lenses.
Nocardia
species can mimic fungal and acanthamoeba keratitis. Treatment with oral co-trimoxazole has not been previously reported. This case demonstrates the role of co-trimoxazole in treating
Nocardia farcinica
keratitis based on cultured drug sensitivities.
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