Simplifying paediatric immunization with a fully liquid DTP–HepB–Hib combination vaccine: Evidence from a comparative time-motion study in India

An observational time-motion study investigated logistic, programmatic and safety-related advantages and limits in the delivery of a fully liquid DTP–HepB–Hib combination vaccine versus a lyophilized combination vaccine requiring reconstitution. The study was conducted in 2006, observing 312 child vaccinations in a tertiary hospital setting in Kolkata, India. The time for vaccination was on average 46 s (35.12%) lower with the fully liquid vaccine (p < 0.05). In addition, the fully liquid combination was easier and potentially safer to handle and as well tolerated as the lyophilized formulation. Fully liquid combination vaccines have the potential to simplify immunization schedules, contribute to better resource management and improve efficiency of immunization programs.     

Radiological Evaluation of Cochlear Orientation and Its Implications in Cochlear Implantation

To test whether there are variations in cochlear orientation with respect to age and sex, and its relevance in cochlear implant surgery. Implant otologists rely upon the anatomic landmarks including the facial recess and round window niche and round window membrane for accessibility and placement of electrode array into scala tympani of basal turn of cochlea. Anecdotally, surgeons note variations in cochlear orientation with respect to age. Cochlear orientation studied radiologically by pre-operative CT scan of temporal bone can guide a Surgeon’s approach to cochlear implantation. To investigate the changes in cochlear orientation with respect to age and sex; and its relevance in cochlear implantation. A retrospective analytical study was performed on CT scans of temporal bones in patients (of our hospital from July 2013 to January 2015 i.e. for a period of 18 months) with no congenital or radiological abnormalities of cochlea. The basal turn angulations of cochlea varied with age and majority of change occurred during early age. The basal turn angulations of cochlea in difficult situations during cochlear implantation were correlated with the data. There is a significant variation in cochlear orientation as measured radiologically by basal turn angulations relative to midsagittal plane. The more obtuse and acute basal turn angulations have implications like difficulty in cochleostomy and electrode placement during cochlear implantation.     

Frequent Alterations of MCPH1 and ATM are Associated with Primary Breast Carcinoma: Clinical and Prognostic Implications

Background

MCPH1 is a proximal regulator of DNA damage response pathway that is involved in recruitment of phosphorylated ATM to double-stranded DNA breaks.

Methods

To understand the importance of MCPH1 and ATM in deregulation of DNA damage response pathway in breast carcinoma, we studied m-RNA expression and genetic/epigenetic alterations of these genes in primary breast carcinoma samples.

Results

Our study revealed reduced expression (mRNA/protein) and high alterations (deletion/methylation) (96 %, 121 of 126) of MCPH1 and ATM. Mutation was, however, rare in inactivation of MCPH1. In immunohistochemical analysis, reduced protein expression of MCPH1, ATM and p-ATM were concordant with their molecular alterations (P = 0.03–0.01). Alterations of MCPH1 and deletion of ATM were significantly high in estrogen/progesterone receptor–negative than estrogen/progesterone receptor–positive breast carcinoma samples compared to early or late age of onset tumors, indicating differences in pathogenesis of the molecular subtypes (P = 0.004–0.01). These genes also showed differential association with tumor stage, grade and lymph node status in different subtypes of breast carcinoma (P = 0.00001–0.01). Their coalterations showed significant association with tumor progression and prognosis (P = 0.003–0.05). Interestingly, patients with alterations of these genes or MCPH1 alone had poor outcome after treatment with DNA-interacting drugs and/or radiation (P = 0.01–0.05).

Conclusions

Inactivation of MCPH1-ATM-associated DNA damage response pathway might have an important role in the development of breast carcinoma with diagnostic, prognostic and therapeutic implications.

     

Global structure and mechanical properties of a 10-bp nucleosome positioning motif

The method of DNA cyclization kinetics reveals special properties of the TATAAACGCC sequence motif found in DNA sequences that have high affinity for core histones. Replacement of 30 bp of generic DNA by three 10-bp repeats of the motif in small cyclization constructs increases cyclization rates by two orders of magnitude. We document a 13 degrees bend in the motif and characterize the direction of curvature. The bending force constant is smaller by nearly 2-fold and there is a 35% decrease in the twist modulus, relative to generic DNA. These features are the likely source of the high affinity for bending around core histones to form nucleosomes. Our results establish a protocol for determination of the ensemble-averaged global solution structure and mechanical properties of any approximately 10-bp DNA sequence element of interest, providing information complementary to that from NMR and crystallographic structural studies.     

Intermittent outpatient ultrafiltration for the treatment of severe refractory congestive heart failure

BACKGROUND: Patients with severe congestive heart failure (CHF) become refractory to conventional medical therapy, leading to recurrent rehospitalizations. We examined the impact of intermittent outpatient ultrafiltration (UF), using either peritoneal dialysis or hemofiltration, on long-term clinical outcomes in patients with refractory CHF. METHODS AND RESULTS: We analyzed clinical and hemodynamic data in 19 consecutive patients with refractory CHF who received intermittent outpatient UF for at least 1 year between July 1998 and November 2002. The mean left ventricular ejection fraction of all 19 patients was 30.2 +/- 19.0%. All patients (100.0%) were New York Heart Association (NYHA) class IV. Only 5 patients (26.3%) received peritoneal dialysis; the remaining 14 (73.7%) received hemofiltration. There were 6 patients with a normal left ventricular ejection fraction (45%). After UF was started, the number of patients that were considered inotrope-dependent was reduced from 86.4% to 36.8% (P < .005). Compared with the year before UF was initiated, the number of CHF hospitalizations during follow-up was reduced from 2.6 to 0.3 (P < .005), and the NYHA class was improved from 4 to 3.1 (P < .005). Among all patients, 2 deaths were related to complications of UF, and cumulative 1-year survival was 63.2%. CONCLUSION: Our study suggests that UF is a safe, feasible therapy, but it needs further evaluation in carefully designed, prospective, randomized clinical trials. UF has the potential for offering another important therapeutic option for patients with severe and refractory CHF.     

Sex differences in the application of evidence-based therapies for the treatment of acute myocardial infarction: the American College of Cardiology's Guidelines Applied in Practice projects in Michigan

BACKGROUND: Studies have shown that women with acute myocardial infarction (AMI) are less likely to receive evidence-based care compared with men. The American College of Cardiology's AMI Guidelines Applied in Practice (GAP) program has been shown to increase the rates of evidence-based medicine use and reduce mortality in patients with AMI. The objective of this study was to investigate the relative benefits of the GAP program in men and women. METHODS: By using a predesign-postdesign, standard orders, and a discharge tool to improve evidence-based indicator rates and long-term mortality in patients with AMI in Michigan, this study compared the success of GAP in men vs women. Logistic regression was used to develop predictive models for death at 30 days and 1 year in men and women. RESULTS: Use of evidence-based care, including use of beta-blockers and aspirin in men and women at hospital discharge and lipid-lowering agent use in men, was higher in the post-GAP sample (P<.01 for all). Use of the discharge tool promoted by the GAP program was independently protective against death at 1 year in women (adjusted odds ratio, 0.46; 95% confidence interval, 0.27-0.79), and a trend existed for similar results in men (adjusted odds ratio, 0.62; 95% confidence interval, 0.36-1.06). However, the tool was used slightly less often with women (27.9% vs 33.96%; P=.003). CONCLUSIONS: The GAP program increased the use of evidence-based therapies in male and female patients. In addition, the GAP discharge tool may decrease mortality rates at 1 year in patients with AMI; however, the tool was used less often with women. Greater use of the GAP discharge tool in women might narrow the post-MI sex mortality gap.     

Fixation of subcondylar fractures of the mandible: a randomized clinical trial comparing one trapezoidal plate with two miniplates

Subcondylar fracture of the mandible accounts for 25–35% of all mandibular fractures. In the past, most subcondylar fractures were managed non-surgically. The traditional method of fixation for subcondylar fractures uses two miniplates; however some bench studies have reported that trapezoidal plates are superior. The aim of this study was to compare the outcomes of subcondylar fractures fixed either with two non-parallel straight miniplates or with one trapezoidal plate. A randomized clinical trial was designed and implemented. Fifty-two consecutive patients with subcondylar fractures were recruited. All patients underwent surgery via a retromandibular approach. The time taken for fixation of the plate after fracture reduction and postoperative outcomes and complications were compared between the groups. The trapezoidal plates were superior in terms of ease of adaptation and time taken for fixation (P =  0.0001). Plate fracture was observed only in the two miniplates group, in four (16%) patients. Outcomes were similar in the two groups in terms of occlusion, mouth opening, protrusion, and lateral excursion. In conclusion, both systems – two miniplates and the trapezoidal plate – provide functionally stable fixation. The outcome was significantly better for the trapezoidal plate than for two miniplates regarding the time taken for insertion and ease of adaptation, but not for other parameters.     

Two Octaves Supercontinuum Generation in Lead-Bismuth Glass Based Photonic Crystal Fiber

In this paper we report a two octave spanning supercontinuum generation in a bandwidth of 700–3000 nm in a single-mode photonic crystal fiber made of lead-bismuth-gallate glass. To our knowledge this is the broadest supercontinuum reported in heavy metal oxide glass based fibers. The fiber was fabricated using an in-house synthesized glass with optimized nonlinear, rheological and transmission properties in the range of 500–4800 nm. The photonic cladding consists of 8 rings of air holes. The fiber has a zero dispersion wavelength (ZDW) at 1460 nm. Its dispersion is determined mainly by the first ring of holes in the cladding with a relative hole size of 0.73. Relative hole size of the remaining seven rings is 0.54, which allows single mode performance of the fiber in the infrared range and reduces attenuation of the fundamental mode. The fiber is pumped into anomalous dispersion with 150 fs pulses at 1540 nm. Observed spectrum of 700–3000 nm was generated in 2 cm of fiber with pulse energy below 4 nJ. A flatness of 5 dB was observed in 950–2500 nm range.     

Alterations in candidate genes PHF2, FANCC,PTCH1 and XPA at chromosomal 9q22.3 region: Pathological significance in early- and late-onset breast carcinoma

Introduction  

Younger women with breast carcinoma (BC) exhibits more aggressive pathologic features compared to older women; young age could be an independent predictor of adverse prognosis. To find any existing differences in the molecular pathogenesis of BC in both younger and older women, alterations at chromosomal (chr.) 9q22.32-22.33 region were studied owing to its association in wide variety of tumors. Present work focuses on comparative analysis of alterations of four candidate genes; PHF2, FANCC, PTCH1 and XPA located within 4.4 Mb region of the afore-said locus in two age groups of BC, as well as the interrelation and prognostic significance of alterations of these genes.