New horizons in treating disorders of hyperpigmentation in skin of color

Pigmentary abnormalities are among the most common reasons why patients with skin of color visit a dermatologist. Hydroquinone has been a cornerstone for the treatment of hyperpigmentation; however, concerns regarding adverse effects have prompted a search for alternative agents. Some promising topical treatments include soy, licorice, rucinol, mulberry, niacinamide, ellagic acid, resveratrol, and dioic acid. Oral agents, primarily used for the prevention of postprocedural hyperpigmentation, include procyanidins, tranexamic acid, and Polypodium leucotomos. Advances in Q-switched lasers, intense pulse light, fractional photothermolysis, and the advent of tretinoin peeling add to the clinician's armamentarium for treating hyperpigmentation.     

Binding interactions and FRET between bovine serum albumin and various phenothiazine-/anthracene-based dyes: a structure–property relationship

The present study demonstrates binding interactions and Förster resonance energy transfer (FRET) between bovine serum albumin (BSA) and a series of structurally and electronically diverse phenothiazine (PTZ) and anthracene (ANT) dyes. Upon selective excitation of tryptophan (Trp) residues of BSA, radiationless energy transfer to a dye takes place, resulting in fluorescence quenching of the former. Fluorescence quenching mechanisms, FRET parameters, possible locations, and binding constants of dyes with the BSA have been examined to deduce a structure–property relationship. The mechanism of quenching is apparently static in nature. PTZ dyes with heteroatoms and a pentyl tail (C5-PTZ) attached to them were found to have a stronger binding affinity with BSA as compared to ANT dyes. Stronger binding affinities of C5-PTZ dyes with BSA result in greater energy transfer efficiencies (E_T). A dye with a strong electron-withdrawing group present in it has shown better energy accepting capability. A FRET study with dicyanoaniline (DCA) analogs of PTZ and ANT dyes (C5-PTZDCA and ANTDCA, respectively) revealed that E_T depends on electronic and structural factors of molecules. An almost orthogonal geometry between ANT and DCA moieties (∼79°) in ANTDCA induces the greater extent of electron transfer from ANT to DCA, showing a higher E_T for this dye as compared to C5-PTZDCA in which the torsion angle is only ∼38°. Further, the observed facts have been validated by experimentally determined bandgaps (using cyclic voltammetry experiments) for all the dyes. Thus, the hydrophobic character and the presence of interactive substituents along with the electron-accepting abilities majorly control the FRET for such dyes with BSA.

The present study demonstrates binding interactions and Förster resonance energy transfer (FRET) between bovine serum albumin (BSA) and a series of structurally and electronically diverse phenothiazine (PTZ) and anthracene (ANT) dyes.     

Characteristics of a new meningococcal serogroup B vaccine,bivalent rLP2086 (MenB-FHbp; Trumenba®)

Neisseria meningitidis is a common cause of bacterial meningitis, often leading to permanent sequelae or death. N. meningitidis is classified into serogroups based on the composition of the bacterial capsular polysaccharide; the 6 major disease-causing serogroups are designated A, B, C, W, X, and Y. Four of the 6 disease-causing serogroups (A, C, Y, and W) can be effectively prevented with available quadrivalent capsular polysaccharide protein conjugate vaccines; however, capsular polysaccharide conjugate vaccines are not effective against meningococcal serogroup B (MnB). There is no vaccine available for serogroup X. The public health need for an effective serogroup B vaccine is evident, as MnB is the most common cause of meningococcal disease in the United States and is responsible for almost half of all cases in persons aged 17 to 22 years. In fact, serogroup B meningococci were responsible for the recent meningococcal disease outbreaks on college campuses. However, development of a suitable serogroup B vaccine has been challenging, as serogroup B polysaccharide-based vaccines were found to be poorly immunogenic. Vaccine development for MnB focused on identifying potential outer membrane protein targets that elicit broadly protective immune responses across strains from the vast number of proteins that exist on the bacterial surface. Human factor H binding protein (fHBP; also known as LP2086), a conserved surface-exposed bacterial lipoprotein, was identified as a promising vaccine candidate. Two recombinant protein-based serogroup B vaccines that contain fHBP have been successfully developed and licensed in the United States under an accelerated approval process: bivalent rLP2086 (MenB-FHbp; Trumenba®) and 4CMenB (MenB-4 C; Bexsero®). This review will focus on bivalent rLP2086 only, including vaccine components, mechanism of action, and potential coverage across serogroup B strains in the United States.     

Impact of magnetic resonance imaging on computed tomography-based treatment planning and acute toxicity for prostate cancer patients treated with intensity modulated radiation therapy

PurposeTo evaluate rectal and bladder dosimetric and clinical acute toxicity endpoints for prostate patients treated with intensity modulated radiation therapy (IMRT) using magnetic resonance images (MRI) registered to computed tomographic (CT) simulation images versus CT alone.Materials and MethodsThe charts of 155 consecutive prostate cancer patients at our institution from 2004 to 2008 were reviewed. A cohort of 15 IMRT treatment plans was created to compare dosimetric endpoints for CT-MRI vs CT alone. A subsequent clinical comparison involved 81 patients (CT-MRI [n = 28] vs CT alone [n = 53]). Acute genitourinary and rectal toxicity rates for the CT-MRI and CT cohorts were compared; also, univariate and multivariate regression analyses were performed using all major demographic, disease, and treatment factors as covariates.ResultsContoured prostate volumes were 43.0 vs 55.7 cm³ (P < .001, n = 15) for CT-MRI vs CT definition, with significant reductions in all bladder dose endpoints and rectal V20, V30, and V70. Grades 0, 1, and 2 toxicity rates for CT-MRI (n = 28) vs CT (n = 53) were, respectively, 25%, 25%, and 50% vs 8%, 21%, and 72% (acute genitourinary [GU], P = .024) and 39%, 29%, and 32% vs 32%, 28%, and 40% (acute rectal, P = .495). On univariate regression, only MRI use and International Prostate Symptom Scores reached significance for acute GU toxicity. On multivariate regression, age, prostate volume, and MRI use reached statistical significance for acute GU toxicity. No factor reached significance for rectal toxicity.ConclusionsThis study demonstrates a statistically significant reduction in clinical acute GU toxicity with the clinical implementation of MRI in the treatment planning process.     

Biological-effective versus conventional dose volume histograms correlated with late genitourinary and gastrointestinal toxicity after external beam radiotherapy for prostate cancer: a matched pair analysis

Background

To determine whether the dose-volume histograms (DVH's) for the rectum and bladder constructed using biological-effective dose (BED-DVH's) better correlate with late gastrointestinal (GI) and genitourinary (GU) toxicity after treatment with external beam radiotherapy for prostate cancer than conventional DVH's (C-DVH's).

Methods

The charts of 190 patients treated with external beam radiotherapy with a minimum follow-up of 2 years were reviewed. Six patients (3.2%) were found to have RTOG grade 3 GI toxicity, and similarly 6 patients (3.2%) were found to have RTOG grade 3 GU toxicity. Average late C-DVH's and BED-DVH's of the bladder and rectum were computed for these patients as well as for matched-pair control patients. For each matched pair the following measures of normalized difference in the DVH's were computed: (a) δ_AUC = (Area Under Curve [AUC] in grade 3 patient – AUC in grade 0 patient)/(AUC in grade 0 patient) and (b) δ_V60 = (Percent volume receiving = 60 Gy [V60] in grade 3 patient – V60 in grade 0 patient)/(V60 in grade 0 patient).

Results

As expected, the grade 3 curve is to the right of and above the grade 0 curve for all four sets of average DVH's – suggesting that both the C-DVH and the BED-DVH can be used for predicting late toxicity. δ_AUC was higher for the BED-DVH's than for the C-DVH's – 0.27 vs 0.23 (p = 0.036) for the rectum and 0.24 vs 0.20 (p = 0.065) for the bladder. δ_V60 was also higher for the BED-DVH's than for the C-DVH's – 2.73 vs 1.49 for the rectum (p = 0.021) and 1.64 vs 0.71 (p = 0.021) for the bladder.

Conclusions

When considering well-established dosimetric endpoints used in evaluating treatment plans, BED-DVH's for the rectum and bladder correlate better with late toxicity than C-DVH's and should be considered when attempting to minimize late GI and GU toxicity after external beam radiotherapy for prostate cancer.

     

Overlap of gastro-oesophageal reflux disease and irritable bowel syndrome: prevalence and risk factors in the general population

BACKGROUND: Gastro-oesophageal reflux disease (GERD) and irritable bowel syndrome may occur more often than expected by chance, but little community data exists and risk factors are unknown. AIM: To determine prevalence and risk factors for overlap of GERD and irritable bowel disease. METHODS: Population-based, cross-sectional survey was conducted by mailing a valid symptom questionnaire to eligible residents of Olmsted County, MN, aged 30-95 years. Irritable bowel syndrome were defined by Rome III; GERD was defined by weekly or more frequent heartburn and/or acid regurgitation. RESULTS: 2298 questionnaires returned (women 52%, 55% response). Irritable bowel syndrome and GERD occurred together more commonly than expected by chance; the prevalence of irritable bowel syndrome-GERD overlap, GERD alone and irritable bowel syndrome alone were 3%, 15% and 5% in men, and 4%, 14% and 10% in women, respectively. Predictors of irritable bowel syndrome-GERD overlap vs. irritable bowel syndrome alone, and separately, GERD alone, were insomnia (OR 1.3, 95% CI: 1.06-1.70; OR 1.5, 95% CI: 1.13-1.90, respectively) and frequent abdominal pain (OR 3.9, 2.2-6.7; OR 1.8, 1.02-3.2, respectively). An additional predictor of irritable bowel syndrome-GERD overlap vs. GERD alone was higher somatization (OR 1.7, 1.1-2.4) and for irritable bowel syndrome-GERD overlap vs. irritable bowel syndrome alone was a higher body mass index (OR 1.0, 1.003-1.07). CONCLUSIONS: Irritable bowel syndrome and GERD overlap is common in the population and does not occur by chance.