MYD88 L265P mutation in intraocular lymphoma: A potential diagnostic marker

Purpose:Vitreoretinal lymphoma (VRL) is the most common intraocular lymphoma (IOL). This can be either primary or secondary to the central nervous system lymphoma. The diagnosis of primary intraocular lymphoma (PIOL) currently relies on clinical diagnosis and cytological analysis of the vitreous or subretinal biopsy. Although most cases are diagnosed without much issue, the limited amount of vitreous fluid, subjectivity in cytological reporting, and special expertise in ocular pathology make the diagnosis challenging. MYD88 L265P mutation has been implicated to have diagnostic utility in PIOL. In this study, we screened consecutive vitreous biopsies for the presence of MYD88 L265P mutation to understand its diagnostic utility compared to conventional cytological analysis.Methods:Cytological analysis and MYD88 L265P mutation by PCR-based sequencing and restriction fragment length polymorphism (RFLP) were carried out on consecutive vitreous and subretinal biopsies collected from 21 patients. The diagnostic utility of the cytology and MYD88 L265P mutation analysis were compared.Results:Out of the 21 patients, 15 had clinical suspicion of having PIOL. Out of these suspected cases of PIOL, nine were confirmed on follow-up, while six were diagnosed as other intraocular pathologies. Diagnostic utility of MYD88 L265P mutation analysis revealed a sensitivity of 88.9%, specificity of 91.6%, positive and negative predictive value of 88.9% and 91.7%, respectively. Diagnostic accuracy of 90.5% was achieved with the mutation analysis that shows the superiority of MYD88 in both ruling in and ruling out PIOL. The diagnostic utility of MYD88 L265P mutation was superior to conventional cytological analysis.Conclusion:The analysis of MYD88 L265P mutation is reliable and efficient in the diagnosis of PIOL.     

Biocompatible implant mimicking cartilage: A new horizon for reconstructive facial field

Cartilage is avascular with limited to no regenerative capacity, so its loss could be a challenge for reconstructive surgery. Current treatment options for damaged cartilage are also limited. In this aspect there is a tremendous need to develop an ideal cartilage-mimicking biomaterial that could repair maxillofacial defects. Considering this fact in this study we have prepared twelve silicone-based materials (using Silicone 40, 60, and 80) reinforced with hydroxyapatite, tri-calcium phosphate, and titanium dioxide which itself has proven their efficacy in several studies and able to complement the shortcomings of using silicones. Among the mechanical properties (Young’s modulus, tensile strength, percent elongation, and hardness), hardness of Silicone-40 showed similarities with goat ear (P > .05). Silicone peaks have been detected in FTIR. Both AFM morphology and SEM images of the samples confirmed more roughed surfaces. All the materials were nonhemolytic in hemocompatibility tests, but among the twelve materials S2, S3, S5, and S6 showed the least hemolysis. For all tested bacterial strains, adherence was lower on each material than that grown on the plain industrial silicone material which was used as a positive control. S2, S3, S5, and S6 samples were selected as the best based on mechanical characterizations, surface characterizations, in vitro hemocompatibility tests and bacterial adherence activity. So, outcomes of this present study would be promising when developing ideal cartilage-mimicking biocomposites and their emerging applications to treat maxillofacial defects due to cartilage damage.     

Cooperative inhibition of NF-kappa B and Tat-induced superactivation of human immunodeficiency virus type 1 long terminal repeat.

Human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR)-regulated gene expression is stimulated independently by the cellular trans-activator NF-kappa B and the viral protein Tat. Noncytotoxic concentrations of the drug pentoxifylline (PTX) inhibited interaction of NF-kappa B with its motif and the stimulation of HIV-1 LTR-driven gene expression in Jurkat cells. Tat protein (from a cotransfected Tat-expression vector) also induced activation of HIV-1 LTR-driven gene expression. This activation was unaffected by PTX when NF-kappa B sites in the HIV-1 LTR were mutated, suggesting that this drug does not directly influence Tat function, which, however, was inhibited by the Tat-inhibitor Ro 24-7429. Transient reporter gene expression regulated by HIV-1 LTR with wild-type NF-kappa B motifs in the presence of Tat protein was 10- to 60-fold higher than in the presence of either of the trans-activators alone, demonstrating superactivation of HIV-1 LTR by the concerted action of both the trans-activators. Treatment of cells with either PTX or Ro 24-7429 inhibited this superactivation of the HIV-1 LTR. The inhibitory effect of these two drugs in combination, at concentrations that alone did not significantly influence viral promoter activity, was far more than additive. A cooperative action of PTX (NF-kappa B inhibitor) and Ro 24-7429 (Tat inhibitor) on HIV-1 LTR-regulated gene expression is suggested. Concentrations of the drugs that induced maximum inhibition of HIV-1 LTR through their cooperative action are far below cytotoxic levels. Thus, the combination of these two inhibitors could be very effective for anti-HIV therapy.     

Chronic low-level arsenic exposure reduces lung function in male population without skin lesions

Objectives

The respiratory effects of chronic low-level arsenic exposure from groundwater have been investigated in West Bengal, India.

Methods

The participants (834 non-smoking adult males) were subdivided in two groups: an arsenic-exposed group (n = 446, mean age 35.3 years) drinking arsenic-contaminated groundwater (11–50 μg/L) and a control group of 388 age-matched men drinking water containing <10 μg/L of arsenic. Arsenic in water samples was measured by atomic absorption spectroscopy. The prevalence of respiratory symptoms was documented by structured, validated questionnaire. Pulmonary function test (PFT) was assessed by portable spirometer.

Results

Compared with control, the arsenic-exposed subjects had higher prevalence of upper and lower respiratory symptoms, dyspnea, asthma, eye irritation and headache. Besides, 20.6 % of arsenic-exposed subjects had lung function deficits (predominantly restrictive and combined types) compared with 13.6 % of control (p < 0.05). A positive association was observed between arsenic concentration in drinking water and the prevalence of respiratory symptoms, while a negative association existed between arsenic level and spirometric parameters.

Conclusions

The findings suggest that even low-level arsenic exposure has deleterious respiratory effects.     

A rare image of post-CTRT iatrogenic tracheoesophageal fistula

A tracheoesophageal fistula may occur due to direct extension of tumour tissue in the trachea and oesophagus, pressure necrosis by a tracheostomy tube in apposition to a nasogastric tube, or tracheoesophageal injury due to other sorts of instrumentation. Bevacizumab is known to cause post-chemotherapy tracheoesophageal fistulae. We present barium swallow x-rays of a female with squamous cell carcinoma of the middle third of the oesophagus; she was being treated weekly with a 6-week regimen of concurrent chemoradiotherapy (CTRT). The x-rays show the formation of a tracheoesophageal fistula at the mid-oesophagus with dye traversing in both directions. It is likely that the tracheoesophageal fistula was formed by trauma due to food matter on a friable sloughed off post-CTRT oesophageal mass. In the majority of cases, these fistulae do not form during chemoradiotherapy, but manifest about six months later. However, in the case presented herein, the fistula was formed in the immediate post-radiation phase.