The engineering of insulin analogues illustrates the application of structure-based protein design to clinical medicine. Such design has traditionally been based on structures of wild-type insulin hexamers in an effort to optimize the pharmacokinetic (PK) and pharmacodynamic properties of the hormone. Rapid-acting insulin analogues (in chronological order of their clinical introduction, Humalog ^® [Eli Lilly & Co.], Novolog ^® [Novo-Nordisk], and Apidra ^® [Sanofi-Aventis]) exploit the targeted destabilization of subunit interfaces to facilitate capillary absorption. Conversely, long-acting insulin analogues exploit the stability of the insulin hexamer and its higher-order self-assembly within the subcutaneous depot to enhance basal glycemic control. Current products either operate through isoelectric precipitation (insulin glargine, the active component of Lantus ^® ; Sanofi-Aventis) or employ an albumin-binding acyl tether (insulin detemir, the active component of Levemir ^® ; Novo-Nordisk). Such molecular engineering has often encountered a trade-off between PK goals and product stability. Given the global dimensions of the diabetes pandemic and complexity of an associated cold chain of insulin distribution, we envisage that concurrent engineering of ultra-stable protein analogue formulations would benefit the developing world, especially for patients exposed to high temperatures with inconsistent access to refrigeration. We review the principal mechanisms of insulin degradation above room temperature and novel molecular approaches toward the design of ultra-stable rapid-acting and basal formulations.

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Objectives: Gastroenteritis is a leading cause of childhood morbidity and mortality in developing countries. Our aim was to determine the prevalence of bacterial, viral and parasitic aetiology of gastroenteritis in children aged < 5 years in the Najran region, south-western Saudi Arabia, to determine the contribution of these enteropathogens in childhood diarrhoeal diseases and to put forward effective preventive measures for controlling the disease in the future. Design and Setting: A descriptive study conducted at Najran Maternity and Children's Hospital and the Microbiology Department of the Najran University College of Applied Medical Sciences from October 2011 to June 2012. Patients and Methods: Stool samples were collected from 326 children aged ≤ 5 years with diarrhoea and examined for bacterial, viral and parasitic enteropathogens. Results: Seventy-two (22.1%) samples were positive for viral pathogens, including 56 (17.2%), 12 (3.7%) and 4 (1.2%) samples for rotavirus, adenovirus and astrovirus, respectively. Thirty-five (10.7%) samples were positive for bacterial pathogens, including 28 (8.6%) and 7 (2.1%) samples for Salmonella and Shigella spp. isolates, respectively. Pathogenic parasites were detected in only 4 (1.2%) samples, including 3 (0.9%) Giardia lamblia and 1 (0.3%) Entamoeba histolytica isolates. Conclusions: Rotavirus is the most common pathogen in paediatric acute gastroenteritis in the Najran region. This fact, in combination with the severity of the infections, warrants consideration of a rotavirus vaccine in the childhood immunization program in Saudi Arabia. On the basis of clinical and laboratory parameters, it appears possible to distinguish between the different causative agents of acute gastroenteritis.

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Background: Given significant regional differences globally in healthcare systems, policies, and culture, we examined rates of pharmaceutical utilization among four developed nations using antidepressant drugs as a case example. Materials and Methods: We conducted a population-based cross-sectional time series analysis of antidepressant utilization in Canada, the United States, Greece, and Ireland from January 2007 to September 2011 using data from IMS Healthcare Inc., which tracks over 80% of global prescription sales of over 1.3 million products. We studied 23 antidepressants from five drug classes, namely, 1) serotonin-specific reuptake inhibitors (SSRIs), 2) serotonin-norepinephrine reuptake inhibitors (SNRIs), 3) tricyclic antidepressants (TCAs), 4) monoamine oxidase inhibitors (MAOIs), and 5) 'other' antidepressants. We used time series analysis to examine trends in utilization patterns. Results: Overall antidepressant utilization increased steadily over time for all study regions, although regions differed considerably in the magnitude of antidepressant utilization and the rates of increase. While overall antidepressant utilization rates were similar between Canada (2,876 units per 1,000 population per month) and the United States (2,815 units per 1,000 population per month), these rates were approximately 83% higher than in Greece (1,558 units per 1,000 population per month) and approximately 50% higher than in Ireland (1,898 units per 1,000 population per month). Although the use of SSRIs, SNRIs, and other antidepressants generally increased over time, the use of TCAs and MAOIs generally decreased over time. Utilization of specific drug classes varied widely between regions, ranging from an 80% relative difference in SSRI utilization between the United States and Greece to a nearly 700% difference in the utilization of MAOIs between Canada and the United States. Conclusions: The findings of our study, using antidepressants as the case example, are consistent with previous studies demonstrating significant variation in drug utilization levels internationally. Future studies are needed to document regional variation in light of appropriateness of drug therapies to determine optimal utilization levels for maximal societal benefit.

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Research about the selection of students into health care practitioner programs, principally medical programs, and into specialty training has become a worldwide phenomenon. Set against a rapid expansion of healthcare professional students, there have been calls to make national policy considerations and provide guidance for an evidence-based selection process. This article considers the implications of the international research base underpinning current selection processes, and makes recommendations for policy makers, health educators, and institutional leaders to consider. We recommend that selection procedures into health professional education and specialty training becomes part of an international conversation that takes account of the complexities of local context, the evidence base into what works and what does not, and the efficient and effective use of resources.

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Angiolipoma is a benign variant of lipoma that is rare in the breast and may be confused clinically, radiologically and pathologically with other benign tumours. It accounts for 5 - 17% of all benign fatty tumours. Clinicians, radiologists and pathologists in particular should not forget the existence of an angiolipoma of the breast to avoid unnecessary re-aspiration of the lesion considering the smears with only adipose tissue fragments as inadequate. We report two cases of angiolipoma who presented with solitary lumps in the breast, and a clinical diagnosis of fibroadenoma was suggested in both the cases. Both were diagnosed as lipoma on cytology and, on subsequent histopathology, a diagnosis of angiolipoma was given.

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Friction in orthodontics has been blamed for many orthodontic-related problems in the literature. Much research as well as research and development by numerous companies have attempted to minimize friction in orthodontics. The aim of the present study was to critically review friction in orthodontics and present frictionless mechanics as well as differentiate between segmented arch mechanics (frictionless technique) as compared to sectional arch mechanics. Comparison of the two techniques will be presented and cases treated by either technique are presented and critically reviewed regarding treatment outcome and anchorage preservation/loss.

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Congenital epiglottic cysts are a rare cause of respiratory tract obstruction in neonates and infants with an incidence of 1.82 per 100,000 live births. The majority arise from the vallecula, aryepiglottic fold, and from the saccule of the ventricle and rarely from the epiglottis. This uncommon entity requires prompt diagnosis and treatment. Traditionally, such cysts are treated surgically via endoscopic excision or marsupialization. Recurrence occurs if excision incomplete and multiple procedures may be necessary. Some authors favour an open surgical approach for more extensive cysts. The patient presented here underwent endoscopic excision and was discharged 3 days later

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