Real-time elastography in differentiating metastatic from nonmetastatic liver nodules

The study was designed to evaluate the role of real-time elastography in differentiating metastatic from nonmetastatic liver nodules, which include various benign lesions, hepatocellular carcinoma (HCC) nodules and lymphoma. Out of 1000 prospective patients who underwent abdominal ultrasound (US) examination, 48 patients had liver nodules. Nodule stiffness was determined by real-time elastography (ES) using color maps and shear wave velocity (SWV) and nodules having marked stiffness or SWV of more than 2.5 m/s were diagnosed as metastatic. The final diagnosis was made on fine needle aspiration cytology. No statistically significant differences were seen on elastomaps in the stiffness of metastatic and nonmetastatic nodules (p = 0.16) while SWV showed statistically significant differences in the strain velocities of benign, metastatic and heptocellular carcinoma nodules p < 0.0001 and < 0.008, respectively. At a cutoff value of SWV 2.5 m/s, the sensitivity, specificity and false positive to detect metastatic nodules by ES were 88%, 83% and 16%, respectively. When the SWV cut off value was set at 2.0 m/s the sensitivity, specificity and false positive were 94%, 70% and 29%, respectively. The study showed that estimation of SWV by ES at a cut off value of 2.5 m/s was a better and a more useful tool in diagnosing both solid and necrotic metastatic liver nodules compared with the color stiffness maps alone. (E-mail: info@advanceddiagnostics.in)     

Adoption, acceptability, and accuracy of an online clinical trial matching website for breast cancer

Background

Less than 5% of breast cancer patients participate in clinical trials. To increase patients’ awareness and access to trials, we created BreastCancerTrials.org, a clinical trial matching website. BreastCancerTrials.org matched patients to trials based on their self-reported breast cancer history. It also provided a messaging platform through which patients could self-refer themselves to participating research sites.

Objective

To assess adoption by research sites, acceptability to patients, and patients’ accuracy in providing information to BreastCancerTrials.org.

Methods

We approached 13 research sites in Northern California to list their trials on BreastCancerTrials.org. For adoption, we examined the willingness of contacted research sites to collaborate with BreastCancerTrials.org. For acceptability, we analyzed usage statistics of visitors who completed the BreastCancerTrials.org health history questionnaire in the first 14 months after launch and surveyed users who visited the website during its first year about their experience. For accuracy, we compared the self-reported health history of 20 patients against their medical records. The health history questionnaire was divided into four sections: About Me, personal information including date of birth and sex; My Health as of Today, current status including cancer stage, menopausal status, and sites with evidence of disease; My Cancer, diagnostic information such as hormone and human epidermal growth factor receptor 2 status; and My Treatment, an itemized record of past treatment including responses to therapy.

Results

A total of 12 sites contributed 55 trials. Regarding acceptability, 733 visitors registered on the website; 428 reported their health history; and 407 matched to at least one trial. Of 375 patients who were sent a survey, 75 responded (20%); 23 of the 75 (31%) contacted a research site, 12 of the 23 (52%) were eligible for a trial, and 5 of the 12 (42%) reported enrolling. As for accuracy, 20 clinic visitors reported 1456 health history items, 1324 of which matched their clinic record (90.93%).

Conclusions

BreastCancerTrials.org was adopted by research sites. Patients found it acceptable and were able to provide accurate information for trial matching. Based on our findings, we launched an upgraded version of BreastCancerTrials.org as a national service in October 2008.     

The combined influence of knowledge, training and experience when grading contact lens complications

PURPOSE: A study was conducted to evaluate the influence of knowledge, training and experience (clinical skills set) when assessing the severity of contact lens complications. METHODS: Nine optometrists (who were in possession of a relevant clinical skills set) and nine 'non-optometrists' (subjects without the clinical skills set) were each invited to grade - to the nearest 0.1 increment - an image of each of 16 contact lens complications using Efron Grading Scales for Contact Lens Complications. This procedure was repeated 2 weeks later, yielding a total data base comprising 576 individual grading estimates. RESULTS: The mean of the test and retest grading estimates was the same for the optometrists (2.8 +/- 0.7) and the non-optometrists (2.6 +/- 0.9) (F1,15,1 = 1.3, p = 0.26); that is, non-optometrists can grade accurately. Median grading reliability for optometrists (+/-0.41) was lower than (i.e. superior to) that for non-optometrists (+/-0.67) (p = 0.001). Non-optometrists tended to display a reluctance to grade by interpolation and to less reliably grade subtle clinical signs. CONCLUSIONS: When averaged over several attempts, non-optometrists will arrive at similar estimates of severity to optometrists when grading ocular complications of contact lens wear; however, they will do so less reliably. The relative contribution of the three attributes of the clinical skills set to grading performance is presently unclear.     

Plasmodium falciparum phosphoethanolamine methyltransferase is essential for malaria transmission

Efficient transmission of Plasmodium species between humans and Anopheles mosquitoes is a major contributor to the global burden of malaria. Gametocytogenesis, the process by which parasites switch from asexual replication within human erythrocytes to produce male and female gametocytes, is a critical step in malaria transmission and Plasmodium genetic diversity. Nothing is known about the pathways that regulate gametocytogenesis and only few of the current drugs that inhibit asexual replication are also capable of inhibiting gametocyte development and blocking malaria transmission. Here we provide genetic and pharmacological evidence indicating that the pathway for synthesis of phosphatidylcholine in Plasmodium falciparum membranes from host serine is essential for parasite gametocytogenesis and malaria transmission. Parasites lacking the phosphoethanolamine N-methyltransferase enzyme, which catalyzes the limiting step in this pathway, are severely altered in gametocyte development, are incapable of producing mature-stage gametocytes, and are not transmitted to mosquitoes. Chemical screening identified 11 inhibitors of phosphoethanolamine N-methyltransferase that block parasite intraerythrocytic asexual replication and gametocyte differentiation in the low micromolar range. Kinetic studies in vitro as well as functional complementation assays and lipid metabolic analyses in vivo on the most promising inhibitor NSC-158011 further demonstrated the specificity of inhibition. These studies set the stage for further optimization of NSC-158011 for development of a class of dual activity antimalarials to block both intraerythrocytic asexual replication and gametocytogenesis.Human malaria parasites exhibit a complex life cycle consisting of asexual phases within human hepatocytes and erythrocytes, with the latter directly responsible for disease manifestations. Within red blood cells, these parasites can also undergo gametocytogenesis, a process during which they interrupt their asexual replication and differentiate to form morphologically and functionally distinct sexual-stage gametocytes (1). These sexual forms serve as precursors for male and female gametes, which develop in the mosquito where they undergo mating, meiosis and several mitotic cycles to produce sporozoites. In Plasmodium falciparum, the causative agent of the most severe form of human malaria, the progression from immature stage I to mature stage V gametocytes takes ∼10 d (2). However, the biological processes that regulate gametocytogenesis remain unknown. Thorough understanding of these processes is crucial to the development of a new generation of dual activity antimalarials that can inhibit both infection and transmission.Phosphatidylcholine (PC), the predominant phospholipid produced by malaria parasites, plays essential structural and regulatory roles in parasite development and differentiation (reviewed in ref. 3). Lipid metabolic and genetic studies in P. falciparum have demonstrated the presence of two pathways for PC biosynthesis (Fig. S1): the cytidine diphosphate (CDP)-choline pathway, which uses host choline and fatty acids as precursors, and the serine decarboxylase-phosphoethanolamine methyltransferase (SDPM) pathway, which uses host serine and fatty acids as precursors (4). The SDPM pathway involves five parasite-encoded enzymes, of which serine decarboyxlase (PfSD) and phosphoethanolamine methyltransferase (PfPMT) are absent in humans and thus are attractive targets for the development of selective and safe antimalarials (3, 4). In this pathway, serine is converted by PfSD into ethanolamine and then phosphorylated by ethanolamine kinase to form phosphoethanolamine. Phosphoethanolamine is used as a precursor by PfPMT to form phosphocholine via a three-step S-adenosyl methionine (SAM)-dependent methylation reaction (5).Here, we show that parasites lacking PfPMT are incapable of producing mature gametocytes and are not transmitted to mosquitoes. Using a PfPMT-specific enzyme-coupled assay, we screened a diverse library of small molecules and identified 11 compounds that inhibit PfPMT activity in vitro and block gametocyte development and maturation in cell culture. One compound, NSC-158011, was further validated for its inhibition of PfPMT activity and PC synthesis. NSC-158011 defines a class of chemicals that has never been used in malaria therapy and that can be further optimized to synthesize more specific, selective, and safe dual function antimalarials that inhibit both asexual replication and gametocyte development.     

Assessing the Policy Landscape for Salt Reduction in South-East Asian and Latin American Countries – An Initiative Towards Developing an Easily Accessible,Integrated, Searchable Online Repository

Background:High dietary salt intake is an avoidable cause of hypertension and associated cardiovascular diseases (CVDs). Thus, salt reduction is recommended as one of the most cost-effective interventions for CVD prevention and for achieving the World Health Organization’s (WHO) 25% reduction in premature non-communicable disease (NCD) mortality by 2025. However, current and comprehensive information about national salt reduction policies and related actions across different regions are difficult to access and impede progress and monitoring.Objectives:As an initial step to developing an online repository of salt reduction policies and related actions, and to track nation-wise progress towards the WHO’s 25 by 25 goal, we aimed to identify and assess salt reduction policies and actions in select countries from two of the top five most populous regions of the world- the South-East Asia and Latin America.Methods:We conducted a literature review to identify national and regional salt reduction policies in the selected South-East Asian and Latin American countries, from January 1990–August 2020, available in English and Spanish. We also contacted selected WHO country offices (South-East Asian region) or relevant national authorities (Latin America) to gain access to unpublished documents.Results:In both regions, we found only a few dedicated stand-alone salt reduction policies: Bhutan, Sri-Lanka and Thailand from South East Asia and Costa Rica from Latin America. Available polices were either embedded in other national health/nutritional policy documents/overall NCD policies or were unpublished and had to be accessed via personal communication.Conclusions:Salt reduction policies are limited and often embedded with other policies which may impede their implementation and utility for tracking national and international progress towards the global salt reduction target associated with the 25 by 25 goal. Developing an online repository could help countries address this gap and assist researchers/policymakers to monitor national progress towards achieving the salt reduction target.     

Intrinsic in vitro susceptibility of primary clinical isolates of Aspergillus fumigatus, Aspergillus terreus, Aspergillus nidulans, Candida albicans and Candida lusitaniae against amphotericin B

A total of 60 clinical fungal isolates from patients without prior amphotericin B treatment and three control strains were evaluated for their intrinsic susceptibility to amphotericin B (AmB) using microdilution, Etest and disc diffusion assays, on three media each, Roswell Park Memorial Institute (RPMI) 1640, Antibiotic Medium 3 (AM3) and High Resolution Medium. The fungal strains included isolates of Aspergillus fumigatus (n = 10), Aspergillus terreus (n = 12), Aspergillus nidulans (n = 9), Candida albicans (n = 6) and Candida lusitaniae (n = 23). The A. terreus strains were significantly less susceptible to AmB than the A. fumigatus strains in all nine experimental settings (P-values ranging from 0.009 to <0.00001). The A. nidulans strains were equally susceptible to AmB as the A. fumigatus strains in seven of nine experimental settings and less susceptible in two (microdilution performed on RPMI and AM3, P = 0.01 and 0.007). The C. lusitaniae strains were equally susceptible to AmB as the C. albicans strains in seven of nine experimental settings and more susceptible in two (microdilution and Etest, both performed on AM3, P = 0.01 and 0.0002). Thus, we confirmed that A. terreus is intrinsically less susceptible to AmB than A. fumigatus. In contrast, nine German clinical isolates of Aspergillus nidulans were found equally susceptible to AmB as 10 isolates of A. fumigatus. Furthermore, we found 23 German clinical isolates of C. lusitaniae from patients without prior treatment with AmB equally susceptible to AmB as C. albicans.     

Bone mineral density in Indian women with rheumatoid arthritis

Osteoporosis (OP) is being increasingly recognized in inflammatory rheumatic diseases like rheumatoid arthritis (RA). Ethnicity influences bone mineral density (BMD) and fracture risk. Due to paucity of data on this aspect of RA from Asian countries including India, we prospectively studied 84 premenopausal women with RA of at least 2 years duration and 247 healthy, age (within 5 years) and sex-matched controls. A significant difference in BMD between patients and controls was observed only at the femoral neck. As many as 22% patients with RA exhibited osteoporosis at least one site in contrast to 9% controls. Nearly 40% of patients exhibited osteopenia at all the three sites. Modified Sharp score, disease duration and DMARD naive period were found to correlate with low BMD. However, on multivariate analysis, only modified Sharp score was shown to be significantly associated with low BMD. Our study draws attention to the poor bone health in Asian Indian women with RA.     

Specificity of emotion-related effects on attentional processing in schizotypy

OBJECTIVES: In the schizophrenia spectrum, cognitive functions such as perception, language, and attention have been shown to be adversely influenced by negative affect. The present study addressed three issues of specificity and one issue of mechanism regarding affect-related attentional disruption in schizotypy: (1) Is attentional disturbance from negative affective stimuli specific to positive (PS) but not negative schizotypy (NS)? (2) Do positive affective stimuli also foster attentional disturbance? (3) Are anxiety and depression differentially related to PS and NS? (4) Whatever the degree of specificity in these relationships, does anxiety mediate the relationship between schizotypy and attentional disturbance? METHODS: Nonpatient participants (N=162) provided responses on scales of schizotypy, anxiety, and depression and performed an emotional Stroop task, judging the ink color of positive, neutral, and negative words. RESULTS: PS but not NS was associated with poorer attentional performance. This attentional disturbance was specific to negative words. PS was associated with anxiety and depression, whereas NS was associated only with depression. Finally, anxiety and depression did not fully mediate the relationship between PS and attentional interference related to negative affective stimuli. CONCLUSIONS: Findings of attentional disturbance in the presence of negative affective stimuli, particularly in positive schizotypy, have substantial theoretical implications. They provide a path by which the interplay of cognitive and affective phenomena could lead to the formation, maintenance, and exacerbation of positive symptoms, including delusions and hallucinations. Findings from this study also underscore the importance of examining the differential contribution of comorbid anxiety and depression to cognitive and affective function in the schizophrenia spectrum.