Profiling neuroprotective potential of trehalose in animal models of neurodegenerative diseases: a systematic review.

Trehalose, a unique nonreducing crystalline disaccharide, is a potential disease-modifying treatment for neurodegenerative diseases associated with protein misfolding and aggregation due to aging, intrinsic mutations, or autophagy dysregulation. This systematic review summarizes the effects of trehalose on its underlying mechanisms in animal models of selected neurodegenerative disorders (tau pathology, synucleinopathy, polyglutamine tract, and motor neuron diseases). All animal studies on neurodegenerative diseases treated with trehalose published in Medline (accessed via EBSCOhost) and Scopus were considered. Of the 2259 studies screened, 29 met the eligibility criteria. According to the SYstematic Review Center for Laboratory Animal Experiment (SYRCLE) risk of bias tool, we reported 22 out of 29 studies with a high risk of bias. The present findings support the purported role of trehalose in autophagic flux and protein refolding. This review identified several other lesser-known pathways, including modifying amyloid precursor protein processing, inhibition of reactive gliosis, the integrity of the blood-brain barrier, activation of growth factors, upregulation of the downstream antioxidant signaling pathway, and protection against mitochondrial defects. The absence of adverse events and improvements in the outcome parameters were observed in some studies, which supports the transition to human clinical trials. It is possible to conclude that trehalose exerts its neuroprotective effects through both direct and indirect pathways. However, heterogeneous methodologies and outcome measures across the studies rendered it impossible to derive a definitive conclusion. Translational studies on trehalose would need to clarify three important questions: 1) bioavailability with oral administration, 2) optimal time window to confer neuroprotective benefits, and 3) optimal dosage to confer neuroprotection.

Intracameral mydriatics versus topical mydriatics in pupil dilation for phacoemulsification cataract surgery.

PURPOSE: To evaluate the efficacy and safety of intracameral mydriatics (lidocaine 1.0% and phenylephrine 1.5%) versus topical mydriatics (phenylephrine 2.5% and tropicamide 1.0%) in pupil dilation for phacoemulsification surgery in Malaysians. SETTING: Department of Ophthalmology, Penang General Hospital, Georgetown Penang, Malaysia. DESIGN: Prospective comparative case series. METHOD: Patients with immature cataract were randomized to the topical mydriatic group (topical group) or intracameral mydriatic group (intracameral group). Patients with small pupils and complicated cataracts were excluded. Pupil diameter changes were measured throughout the surgery. Additional pupil dilation maneuvers and complications were recorded. RESULTS: The study comprised 112 patients. There was no difference in mean pupil dilation between the intracameral group (4.86 mm ± 0.74 [SD]) and the topical group (4.88 ± 0.91 mm) (P = .86). However, the mean pupil size before capsulorhexis in the topical group (7.23 ± 1.08 mm) was significantly larger than in the intracameral group (6.40 ± 0.80 mm) (P = .01). The pupils in the intracameral group continued to dilate during surgery (0.44 ± 0.62 mm), while those in the topical group constricted (-0.41 ± 1.04 mm) (P < .001). Three patients in the intracameral group and 6 in the topical group required additional maneuvers for pupil dilation (P = .49). Each group had 1 complication (P = 1.00). CONCLUSIONS: Intracameral mydriatic agents dilated heavily pigmented pupils for phacoemulsification cataract surgery. However, in the early stages of surgery, pupil dilation was slower than with topical agents.

The Potential of Gelam Honey in Promoting the Proliferative Phase of Corneal Reepithelialization.

OBJECTIVE: The aim of this study is to investigate the potential bene ts of Gelam honey (GH) in promoting proliferation of ex vivo cor- neal epithelial cells (CECs) and its effects on the phenotypical features. MATERIALS AND METHODS: Corneal epithelial cells were isolated from the corneas of rabbits (n = 6). The optimal dose of GH for CEC proliferation in both basal medium (BM) and cornea medium (CM) was determined via MTT (3-[4, 5-dimethyl thiazolyl-2]-2, 5-diphenyl tetrazolium bro- mide) assay. Morphology, gene and protein expressions, and cell cycle analysis of CECs were evaluated via phase contrast microscopy, real- time polymerase chain reaction, immunocytochemistry, and ow cytom- etry, respectively. RESULTS: Corneal epithelial cells cultured in 0.0015% GH-supplemented media (BM + 0.0015% GH; CM + 0.0015% GH) demonstrated optimal proliferative capacity with normal polygonal- shaped morphology. Gelam honey potentiates cytokeratin 3 (CK3) gene expression in accordance with the cytoplasmic CK3 protein expression while retaining normal cell cycle of CECs. CONCLUSION: Culture media treated with 0.0015% GH increased CEC proliferation while preserving its phenotypical features. This study demonstrated the potential devel- opment of GH-based topical treatment for super cial corneal injury.

Ophthalmic artery occlusion following neuro-embolization of the external carotid artery, a case report.

BACKGROUND: Embozene® is a new neuroembolizing microsphere used to reduce intraoperative bleeding for head and neck tumours. We report a case of iatrogenic ophthalmic artery occlusion after Embozene® embolization of the external carotid artery (ECA). CASE PRESENTATION: A 22-year-old African gentleman presented with left nasal obstruction and epistaxis for 2 years and was diagnosed with nasopharyngeal carcinoma. He subsequently underwent embolization of the maxillary branch of the left ECA using Embozene® Microspheres - 250 µm in size before endoscopic tumour excision to reduce intra-operative bleeding. He complained of sudden painless profound visual loss in the left eye (LE) two hours after embolization. Visual acuity in LE was no light perception. Fundus examination showed pale retina with no cherry red spot. Arterial narrowing and segmentation were seen in all quadrants. A diagnosis of left ophthalmic artery occlusion was made. Despite immediate management including ocular massage and lowering of intraocular pressure, the visual loss remained. Retrospective review of digital subtraction angiogram showed an anastomosis between the left ophthalmic artery and anterior deep temporal artery as a potential route for microspheres migration. CONCLUSION: Pre-operative angio-architecture understanding and diligent selection of embolic material are helpful in preventing this adverse event. The use of newer agents for embolotherapy may cause migration of embolic material from the external to the internal carotid system leading to ophthalmic artery occlusion and blindness.

Why can't I see after my heart is fixed: a case series of ocular complications after cardiac intervention.

BACKGROUND: The purpose of this study was to report case series of retinal artery occlusion (RAO) as one of the significant complication post cardiac intervention. CASE PRESENTATION: We are reporting one case of branch RAO and one case of central RAO after percutaneous coronary intervention (PCI). In case 1, a 74-year-old gentleman with pre-existing diabetes mellitus and hypertension was electively admitted for PCI for coronary artery disease (CAD) in our centre (UKMMC). Few hours after the procedure, patient complained of sudden blurring of vision in the right eye. He was found to have branch retinal artery occlusion. In case 2, a 49-year-old gentleman presented with ST segment elevation myocardial infarction (STEMI) and had an emergency PCI performed 2 h upon admission. He noticed sudden dropped of vision in his right eye immediately after the procedure. He was diagnosed to have central retinal artery occlusion. CONCLUSIONS: In conclusion, retinal artery occlusion is a possible complication post PCI. Patients need to be informed especially in high risk cases.

Undergraduate Medical Education Research in Malaysia: Time for a Change.

OBJECTIVE: Special Study Module (SSM) is a mandatory research module implemented in Universiti Kebangsaan Malaysia (UKM). The objective of this paper is to provide a brief overview on the student research activities and to find out the outcome measures in terms of publication. METHODS: It was a retrospective study done on SSM research projects at UKM. The SSM research is conducted from beginning of year-4 until 1(st) seven weeks of year-5. In year-4, students are assigned to a faculty-supervisor in small groups and spend every Thursday afternoon to plan and carry the research. Whole first seven weeks of year-5, students are placed with their supervisor continuously to collect data, do analysis, write report and present in the scientific conference. Outcomes of 5-years SSM research-projects starting from 2008/2009 to 2012/2013 academic session were analyzed. RESULTS: Total 257 projects were completed and presented in annual scientific meetings from which 57 (22.2%) articles were published in peer reviewed journals. CONCLUSION: Mandatory undergraduate student research project brings an opportunity to develop students' capacity building from conception to final report writing and thereby narrowing the gap between education and practice. Medical schools should implement research module to bring changes in research and publication culture of undergraduate medical education.

Pre-validation methods for developing a patient reported outcome instrument.

BACKGROUND: Measures that reflect patients' assessment of their health are of increasing importance as outcome measures in randomised controlled trials. The methodological approach used in the pre-validation development of new instruments (item generation, item reduction and question formatting) should be robust and transparent. The totality of the content of existing PRO instruments for a specific condition provides a valuable resource (pool of items) that can be utilised to develop new instruments. Such 'top down' approaches are common, but the explicit pre-validation methods are often poorly reported. This paper presents a systematic and generalisable 5-step pre-validation PRO instrument methodology. METHODS: The method is illustrated using the example of the Aberdeen Glaucoma Questionnaire (AGQ). The five steps are: 1) Generation of a pool of items; 2) Item de-duplication (three phases); 3) Item reduction (two phases); 4) Assessment of the remaining items' content coverage against a pre-existing theoretical framework appropriate to the objectives of the instrument and the target population (e.g. ICF); and 5) qualitative exploration of the target populations' views of the new instrument and the items it contains. RESULTS: The AGQ 'item pool' contained 725 items. Three de-duplication phases resulted in reduction of 91, 225 and 48 items respectively. The item reduction phases discarded 70 items and 208 items respectively. The draft AGQ contained 83 items with good content coverage. The qualitative exploration ('think aloud' study) resulted in removal of a further 15 items and refinement to the wording of others. The resultant draft AGQ contained 68 items. CONCLUSIONS: This study presents a novel methodology for developing a PRO instrument, based on three sources: literature reporting what is important to patient; theoretically coherent framework; and patients' experience of completing the instrument. By systematically accounting for all items dropped after the item generation phase, our method ensures that the AGQ is developed in a transparent, replicable manner and is fit for validation. We recommend this method to enhance the likelihood that new PRO instruments will be appropriate to the research context in which they are used, acceptable to research participants and likely to generate valid data.