Prediction of atrial fibrillation in patients with severe mitral stenosis—role of atrial contribution to ventricular filling

Objective—Atrial contribution to ventricular filling was studied to assess its role in predicting the future development of atrial fibrillation (AF) in patients with severe mitral stenosis (MS) and sinus rhythm.

Design—Two hundred and eight patients with severe MS and sinus rhythm were followed up for 1 year. Baseline data were compared between group I (who developed AF at follow‐up) and group II (who maintained sinus rhythm). Left atrial size, severity of MS, velocity time integral (VTI) of mitral valve flow and VTI due to atrial systole (A‐VTI) were noted. Percentage contribution of A‐VTI to the total VTI (A‐%) was calculated. Sensitivity and specificity of A‐% to predict the onset of AF was obtained.

Results—Left atrial size, severity of MS and total VTI were similar in the two groups. Group I patients were older (31.1?±?9.1 and 18.4?±?6.5 years, respectively, p?<?0.03) with smaller A‐VTI (5.3?±?2.2 and 6.7?± 3.4?cm, respectively, p?<?0.01) and A‐% (8.9?±?1.8 and 11.2?±?2.7, respectively, p?<?0.003). A‐% of <9% (mean value of A‐VTI in group I) had high sensitivity (84%, positive predictive value 76%) and specificity (80%, negative predictive value 87%) to predict the development of AF.

Conclusion—Atrial contribution to ventricular filling is reduced in patients prone to develop AF (due to inefficient left atrial contraction, much before its dilatation). It can be used for early identification of patients likely to develop AF with high sensitivity and specificity. It is simple, easily available, cost‐effective and will guide earlier intervention and more frequent follow‐up. There is a preclinical loss in atrial pump function much before the eventual onset of AF.     

Evaluating computer-aided detection algorithms

Computer-aided detection (CAD) has been attracting extensive research interest during the last two decades. It is recognized that the full potential of CAD can only be realized by improving the performance and robustness of CAD algorithms and this requires good evaluation methodology that would permit CAD designers to optimize their algorithms. Free-response receiver operating characteristic (FROC) curves are widely used to assess CAD performance, however, evaluation rarely proceeds beyond determination of lesion localization fraction (sensitivity) at an arbitrarily selected value of nonlesion localizations (false marks) per image. This work describes a FROC curve fitting procedure that uses a recent model of visual search that serves as a framework for the free-response task. A maximum likelihood procedure for estimating the parameters of the model from free-response data and fitting CAD generated FROC curves was implemented. Procedures were implemented to estimate two figures of merit and associated statistics such as 95% confidence intervals and goodness of fit. One of the figures of merit does not require the arbitrary specification of an operating point at which to evaluate CAD performance. For comparison a related method termed initial detection and candidate analysis was also implemented that is applicable when all suspicious regions are reported. The two methods were tested on seven mammography CAD data sets and both yielded good to excellent fits. The search model approach has the advantage that it can potentially be applied to radiologist generated free-response data where not all suspicious regions are reported, only the ones that are deemed sufficiently suspicious to warrant clinical follow-up. This work represents the first practical application of the search model to an important evaluation problem in diagnostic radiology. Software based on this work is expected to benefit CAD developers working in diverse areas of medical imaging.     

Preparation and preliminary in vivo evaluation of 166Ho‐labeled microspheres for possible use in radioembolic therapy of liver cancer

Hepatocellular carcinoma (HCC) or liver cancer is an increasingly prevalent and highly morbid disease with critical significance in the Asian and African subcontinents. Among the various therapies currently used in the clinic to combat the global menace of HCC, radioembolization with suitable therapeutic isotopes is an effective targeted approach. In the Indian context, the significant cost and logistical disadvantage of imported radioembolic formulations for HCC therapy make it essential to develop more feasible indigenous alternatives—using locally available radioisotopes and microspheric carriers—that can serve the nuclear medicine community. With this aim Ho‐166 was produced with good specific activity (>13 GBq mg^?1) and purity (>99%) by reactor irradiation. Various commercially available microspheres were labeled with this therapeutic radioisotope, characterized for yield and stability of the radiolabeling, and tested for their in vivo retention and stability in Wistar rat model by viable surgery. Under the optimized reaction conditions, ¹⁶⁶Ho‐labeled microspheres were prepared with high yield (>94%‐99%) and in vitro stability (>95%) in saline and serum. Retention studies in animal model showed that ¹⁶⁶Ho‐labeled microspheres remained stable in vivo and showed excellent retention in the site of interest (~95% at 72‐hour p.i.). The study indicates good potential and warrants further investigation for application of these indigenous radiolabeled microspheres for HCC therapy. The successful application of this technology in the clinic would lead to logistically advantageous and cost‐effective indigenous alternatives to expensive imported therapeutic solutions.     

Preparation and comparative evaluation of 99mTc‐HYNIC‐cNGR and 99mTc‐HYNIC‐PEG2‐cNGR as tumor‐targeting molecular imaging probes

The tripeptide sequence asparagine‐glycine‐arginine (NGR) specifically recognizes aminopeptidase N (APN or CD13) receptors highly expressed on tumor cells and vasculature. Thus, NGR peptides can precisely deliver therapeutic and diagnostic compounds to CD13 expressing cancer sites. In this regard, 2 NGR peptide ligands, HYNIC‐c(NGR) and HYNIC‐PEG₂‐c(NGR), were synthesized, radiolabeled with ^99mTc, and evaluated in CD13‐positive human fibrosarcoma HT‐1080 tumor xenografts. The radiotracers, ^99mTc‐HYNIC‐c(NGR) and ^99mTc‐HYNIC‐PEG₂‐c(NGR), could be prepared in approximately 95% radiochemical purity and exhibited excellent in vitro and in vivo stability. The radiotracers were hydrophilic in nature with log P values being ?2.33 ± 0.05 and ?2.61 ± 0.08. The uptake of 2 radiotracers ^99mTc‐HYNIC‐c(NGR) and ^99mTc‐HYNIC‐PEG₂‐c(NGR) was similar in nude mice bearing human fibrosarcoma HT‐1080 tumor xenografts, which was significantly reduced (P < .05) during blocking studies. The 2 radiotracers being hydrophilic cleared rapidly from blood, liver, and intestine and were excreted through renal pathway. The pharmacokinetics of ^99mTc‐labeled HYNIC peptide could not be modulated through introduction of PEG₂ unit, thus posing a challenge for studies with other linkers towards enhanced tumor uptake and retention.     

Predictors of Parent Engagement Based on Child Care Providers’ Perspectives

Objective

Determine the predictors of child care providers’ parent engagement regarding child nutrition in child care centers (CCCs) and family child care homes (FCCHs).

Engaging new refugee in Australian communities at risk for chronic hepatitis B infection into care: A peer‐educator intervention

Chronic Hepatitis B (CHB) infection and subsequent liver complications are rising in prevalence in Australia due to increased migration from endemic regions. Nearly 50% of all those living with CHB in Australia are undiagnosed, leading to missed opportunities for liver cancer and cirrhosis prevention. Health literacy around CHB among refugee communities such as Afghan, Rohingyan, and Sudanese populations (all with a high prevalence of CHB) is low, partly due to a paucity of targeted health promotion programmes; despite the release of the Victorian Hepatitis B Strategy (2016–2020). We developed a peer‐education intervention in these three communities to deliver CHB focused radio programmes and community forums in their own language, following a needs assessment consisting of semistructured interviews and surveys. Effectiveness of this intervention was measured through paired comparison of disease‐knowledge assessment pre and post forum. Community forums were held between 2015 and 2016, with 25 attendees at the Rohingyan forum (68% male), 10 attendees at the Afghan forum (90% male) and 0 attendees at the Sudanese forum. Participants demonstrated a significant improvement in CHB knowledge between pre‐ and post‐forum surveys (p‐value < 0.05). A peer‐educator approach was a cost‐effective health promotion strategy in building CHB knowledge and dispelling misconceptions within the Afghan and Rohingya communities. There were significant barriers in the engagement of the South Sudanese community, which will inform future strategies for health promotion.     

Genetic polymorphisms in NQO1 and SOD2: Interactions with smoking,schistosoma infection,and bladder cancer risk in Egypt

BackgroundBladder cancer is the most prevalent form of cancer in men among Egyptians, for whom tobacco smoke exposure and Schistosoma haematobium (SH) infection are the major risk factors. We hypothesized that functional polymorphisms in NAD(P)H:quinone oxidoreductase 1 (NQO1) and superoxide dismutase 2 (SOD2), modulators of the effects of reactive oxidative species, can influence an individual's susceptibility to these carcinogenic exposures and hence the risk of bladder cancer.MethodsWe assessed the effects of potential interactions between functional polymorphisms in the NQO1 and SOD2 genes and exposure to smoking and SH infection on bladder cancer risk among 902 cases and 804 population-based controls in Egypt. We used unconditional logistic regression to estimate the odds ratios (OR) and confidence intervals (CI) 95%.ResultsWater pipe and cigarette smoking were more strongly associated with cancer risk among individuals with the TT genotype for SOD2 (OR [CI 95%] = 4.41 [1.86–10.42]) as compared with those with the CC genotype (OR [CI 95%] = 2.26 [0.97–6.74]). Conversely, the risk associated with SH infection was higher among the latter (OR [CI 95%] = 3.59 [2.21–5.84]) than among the former (OR [CI 95%] = 1.86 [1.33–2.60]). Polymorphisms in NQO1 genotype showed a similar pattern, but to a much lesser extent. The highest odds for having bladder cancer following SH infection were observed among individuals with the CC genotypes for both NQO1 and SOD2 (OR [CI 95%] = 4.41 [2.32–8.38]).ConclusionOur findings suggest that genetic polymorphisms in NQO1 and SOD2 play important roles in the etiology of bladder cancer by modulating the effects of known contributing factors such as smoking and SH infection.     

Chemopreventive potential of Apium leptophyllum (Pers.) against DMBA induced skin carcinogenesis model by modulatory influence on biochemical and antioxidant biomarkers in Swiss mice

Aim:

The study was designed to investigate the chemopreventive potential of flavonoidal fractions of Apium leptophyllum fruits (FFALF) on Swiss mice.

Materials and Methods:

Skin tumor or papilloma was developed by topical application of DMBA (25 μg in 0.1 ml acetone) on intrascapular region of mice, twice weekly for 8 weeks. The animals were divided into six groups: Group I (vehicle control); group II (FFALF control, 5 mg/kg); group III (carcinogenic control, DMBA treated initially for 8 weeks); and group IV, V and VI as pre-treated group (FFALF 5, 10 and 20 mg/kg respectively for 16 weeks along with DMBA treatment). After the 16^th week of treatment; the tumor morphology, skin histopathology, and biochemical and antioxidant biomarkers were measured and compared with carcinogenic control as well as vehicle control.

Results:

The co-administration of FFALF with DMBA-treated groups showed significant (P ≤ 0.001) prevention against skin papilloma and normalized the status of lipid peroxidation with antioxidant biomarkers in a dose-dependent manner as compared to carcinogenic control.

Conclusions:

Thus, the present study suggests that the FFALF is non-carcinogenic and has chemopreventive potential on DMBA-induced carcinogenesis in mouse, which may be due to the modulation of cutaneous lipid peroxidation or enhancement of total antioxidant capacity.KEY WORDS: Apium leptophyllum, antioxidant biomarker, chemoprevention, DMBA, skin papilloma