Holographic Characterization of Protein Aggregates in the Presence of Silicone Oil and Surfactants

Characterizing protein aggregates in the presence of silicone oil is a long standing challenge for the pharmaceutical industry. Silicone oil is often used as a lubricant in devices that deliver and store therapeutic protein products and has been linked to protein aggregation, which can compromise a drug’s effectiveness or cause autoimmune responses in patients. Most traditional technologies cannot quantitatively distinguish protein aggregates and silicone oil in their native formulations for sizes less than 5 μm. We use holographic video microscopy to study protein aggregation to demonstrate its capability to quantitatively distinguish protein aggregates and silicone oil in the presence of varying amounts of the surfactants SDS and polysorbate 80 in the size range of 0.5-10 μm without the need for dilution or special sample preparation. We show that SDS denatures proteins and stabilizes silicone oil. We also show that polysorbate 80 may limit protein aggregate formation if it is added to an IgG solution before introducing silicone oil.     

Blood‐based diagnostic testing for Pompe disease: Consistency between GAA enzyme activity in dried blood spots and GAA gene sequencing results

Introduction: We have identified a large consanguineous Lebanese family with 5 individuals with severe childhood‐onset recessive sensory loss associated with deafness and variable optic atrophy. Methods: Autozygosity mapping was performed in all affected individuals, followed by whole‐exome sequencing (WES) in 2 individuals. Results: WES identified a homozygous missense mutation (c.916G>A, p.G306R) in the cerebral riboflavin transporter SLC52A2, recently shown to cause Brown‐Vialetto‐Van‐Laere syndrome (BVVLS), which is considered primarily a motor neuronopathy. Our patients have a phenotype distinct from BVVLS, characterized by severe progressive sensory loss mainly affecting vibration and proprioception that evolves to include sensorineural hearing loss in childhood, variable degrees of optic atrophy, and marked upper extremity weakness and atrophy. Treatment of 3 patients with 400 mg/day riboflavin over 3 months produced definite clinical improvement. Conclusions: Mutations in SLC52A2 result in a recognizable phenotype distinct from BVVLS. Early recognition of this disorder is critical, given its potential treatability. Muscle Nerve 50 : 775–779, 2014     

Appraisal of Laparoscopic Liver Resection in the Treatment of Liver Metastasis with Special Reference to Outcome in Colorectal Malignancies

Treatment of metastatic liver disease is at the crossroads of an evolutionary transformation with more and more reports reiterating the benefits of resectional therapy in various cancers. A quest for application of laparoscopic approaches to the management of liver metastasis has arisen due to the projected benefits of less morbidity, early recovery, and equivalent oncological outcome in selected malignancies. However, the diverse and heterogenous data on indications, operative technique, and outcome evaluation make a comparative analysis of these studies difficult. This review is an appraisal of technique and outcome of minimally invasive liver resection as reported in the current literature with special reference to treatment of metastatic colorectal cancers.     

‘If I am not doing my own playing then I am not able to truly share the gift of play with children’: using poststructuralism and care ethics to examine future early childhood educators' relationships with play in adulthood

The current sociopolitical context of schooling is positioning play as incongruous with children's academic learning. As a result, teacher educators must increasingly guide future early childhood professionals to develop the skills and knowledge necessary to become effective play advocates. This includes articulating the value of play across the lifespan to a variety of stakeholders. Yet, ironically, many adult women entering the early childhood profession report that a wide range of barriers prevent them from including play in their adult lives. Two case studies highlight how early childhood graduate students use their experiences with play across the lifespan as a foundation for becoming play advocates. Nel Noddings's care ethics and feminist poststructural critiques of the construct of care inform the analysis and discussion of the findings. Implications suggest the importance of guiding early childhood professionals to acknowledge self-care as a component of care and play as an essential expression of self-care.     

Surgical management of hepatic arterioportal fistula in a neonate

Congenital arterioportal fistulae in the liver are rare malformations which can lead to portal hypertension. We report a hepatic arterioportal fistula in a neonate who presented with intestinal hypoperfusion. Computerised tomography angiography showed a fistulous communication between the left hepatic artery and portal vein with hypoperfusion of small and large bowel. A formal left hepatectomy was done followed by clinical improvement and reduction in portal venous pressures. The case and the literature pertaining to it are discussed.     

Mid Versus Late Secondary Alveolar Cleft Grafting Using Iliac Crest Corticocancellous Bone Graft

Background

Mid-secondary alveolar cleft repair performed at ages 9–12, in the mixed dentition stage, prior to eruption of the permanent canine, is generally accepted as the ideal time for residual alveolar cleft closure in cleft lip and palate cases with a cleft alveolus.

Methods

In our study, four cases of mid-secondary and five cases of late–secondary alveolar cleft grafting were carried out using iliac crest corticocancellous bone graft. Clinical defect closure and radiographic bone fill were compared.

Results

All the nine cases performed in the two different age groups showed excellent results, clinically, with complete closure of the cleft defect and achievement of continuity of the dental arches. One case was planned for a two-stage procedure owing to the large bilateral maxillary defects. Good bone fill was visualized radiographically in all nine cases.

Conclusion

Precise timing for undertaking alveolar cleft repair may not be all that crucial for a successful alveolar cleft grafting procedure.     

An evaluation of liposome-based diagnostics of pulmonary and extrapulmonary tuberculosis

ABSTRACT

Introduction: Tuberculosis (TB) is still one of the major global health threats and delayed diagnosis or misdiagnosis continues to fuel the global epidemic. The conventional diagnostic approaches have shortcomings that might hinder the process of diagnosis of the disease and ultimately affect the prognosis.

Area covered: We emphasize on the process of the synthesis of liposomes, its physicochemical properties affecting the formulation and their utilization in the field of molecular diagnostics for TB. The review also sheds a light on other nanoparticle-based molecular diagnostic approaches for TB. Despite the advent of science, we are yet to have a diagnostic tool that is simple, rapid, sensitive, and specific, and most importantly, one that enables us to demarcate patients with active tuberculosis from those with quiescent lesions, prior vaccination, or other diseases.

Expert opinion: The utility of liposomes for diagnostic purposes has been attempted so as to overcome the challenges posed by conventional diagnostic tools for TB. Through this review, we present insights into liposome formulation and selection processes, various studies that report the use of liposome-based diagnostic tools for TB, as well as the limitations associated with the same that can be improvised to make the technology more efficient.     

Persulfate-activated charcoal mixture: an efficient oxidant for the synthesis of sulfonated benzo[d][1,3]oxazines from N-(2-vinylphenyl)amides and thiols in aqueous solution

A series of 2,4-aryl-4-((arylsulfonyl)methyl)-4H-benzo[d][1,3]oxazines in good to excellent yields have directly been obtained from N-(2-vinylphenyl)amides and thiols by employing a mixture of K₂S₂O₈-activated charcoal in aqueous acetonitrile solution at 50 °C. A plausible mechanism for the reaction is reported. It reveals that the reaction follows a radical pathway and the persulfate has been the oxygen source for formation of the sulfone group in the products. It is worth mentioning that this protocol utilizes an easily accessible K₂S₂O₈-activated charcoal mixture and thiols, respectively, as an oxidant and sulfonylating precursors for the first time.

A simple method for the synthesis of 2,4-aryl-4-((arylsulfonyl)methyl)-4H-benzo[d][1,3]oxazines using an easily accessible K₂S₂O₈-activated charcoal mixture and thiols, respectively, as an oxidant and sulfonylating precursors has been described.