Evaluation of chemopreventive effect of Fumaria indica against N-nitrosodiethylamine and CCl4-induced hepatocellular carcinoma in Wistar rats

AbstractObjectiveTo investigation the chemopreventive potential of Fumaria indica (F. indica) extract (FIE) on N-nitrosodiethylamine and CCl4-induced hepatocarcinogenesis in Wistar rats.MethodsThe experimental animals were divided into six groups (n=6). Hepatocellular carcinoma was induced by single intraperitoneal injection of N-nitrosodiethylamine (NDEA) in normal saline at a dose of 200 mg/kg body weight followed by weekly subcutaneous injections of CCl4(3 mL/kg/week) for 6 weeks, as the promoter of carcinogenic effect. After administration of the carcinogen, 200 and 400 mg/kg of FIE were administered orally once a day throughout the study. At the end of 20 weeks, the body weight, liver weight and relative liver weight were measured. The percentage of nodule incidence and liver cancer markers such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (γ-GT), total bilirubin level (TBL), α-feto protein (AFP) and carcinoembryonic antigen were estimated along with histopathological investigation in experimental groups of rats.ResultsObtained results demonstrated that the cotreatment with FIE significantly prevented the decrease of the body weight and also increased in relative liver weight caused by NDEA. The treatment with FIE significantly reduced the nodule incidence and nodule multiplicity in the rats after NDEA administration. The levels of liver cancer markers such as AST, ALT, ALP, γ-glutamyl transferase, TBL, AFP and carcinoembryonic antigen were substantially increased by NDEA treatment. However, FIE treatment significantly reduced the liver injury and restored the entire liver cancer markers. Histological observations of liver tissues too correlated with the biochemical observations.ConclusionsThese finding powerfully supports that F. indica exert chemopreventive effect by suppressing the tumor burden and restoring the activities of hepatic cancer marker enzymes on NDEA and CCl4-induced hepatocarcinogenesis in Wistar rats

Evaluation of the Acute Phase Reactants CRP in Unstable Angina Cases

Unstable angina, a syndrome of symptoms caused by ischemia of the heart muscles, is both frightening and disabling and may herald acute myocardial infarction. The immediate precipitating events of the atherosclerotic plaque responsible for that critical degree of ischemia resulting in the syndrome of unstable angina are progression of atherosclerosis platelet aggregation, thrombosis and vasospasm. Acute phase reactants are proteins in the plasma whose levels increase during acute inflammatory states or secondary to certain types of tissue damage. A cross-sectional descriptive study was done in Safdarjung Hospital on 40 subjects and controls to establish the acute phase reactants CRP in unstable angina cases and their relationships. In our study, we found that CRP levels are increased in cases as compared to controls, thus showing a direct correlation

Randomized controlled trial of a good practice approach to treatment of childhood obesity in Malaysia: Malaysian childhood obesity treatment trial (MASCOT)

Context. Few randomized controlled trials (RCTs) of interventions for the treatment of childhood obesity have taken place outside the Western world. Aim. To test whether a good practice intervention for the treatment of childhood obesity would have a greater impact on weight status and other outcomes than a control condition in Kuala Lumpur, Malaysia. Methods. Assessor-blinded RCT of a treatment intervention in 107 obese 7- to 11-year olds. The intervention was relatively low intensity (8 hours contact over 26 weeks, group based), aiming to change child sedentary behavior, physical activity, and diet using behavior change counselling. Outcomes were measured at baseline and six months after the start of the intervention. Primary outcome was BMI z-score, other outcomes were weight change, health-related quality of life (Peds QL), objectively measured physical activity and sedentary behavior (Actigraph accelerometry over 5 days). Results. The intervention had no significant effect on BMI z score relative to control. Weight gain was reduced significantly in the intervention group compared to the control group (+1.5 kg vs. +3.5 kg, respectively, t-test p < 0.01). Changes in health-related quality of life and objectively measured physical activity and sedentary behavior favored the intervention group. Conclusions. Treatment was associated with reduced rate of weight gain, and improvements in physical activity and quality of life. More substantial benefits may require longer term and more intensive interventions which aim for more substantive lifestyle changes

Five-year safety and efficacy of leadless pacemakers in a Dutch cohort

BACKGROUND: Adequate real-world safety and efficacy of leadless pacemakers (LPs) have been demonstrated up to 3 years after implantation. Longer-term data are warranted to assess the net clinical benefit of leadless pacing.OBJECTIVE: The purpose of this study was to evaluate the long-term safety and efficacy of LP therapy in a real-world cohort.METHODS: In this retrospective cohort study, all consecutive patients with a first LP implantation from December 21, 2012, to December 13, 2016, in 6 Dutch high-volume centers were included. The primary safety endpoint was the rate of major procedure- or device-related complications (ie, requiring surgery) at 5-year follow-up. Analyses were performed with and without Nanostim battery advisory-related complications. The primary efficacy endpoint was the percentage of patients with a pacing capture threshold ≤2.0 V at implantation and without ≥1.5-V increase at the last follow-up visit.RESULTS: A total of 179 patients were included (mean age 79 ± 9 years), 93 (52%) with a Nanostim and 86 (48%) with a Micra VR LP. Mean follow-up duration was 44 ± 26 months. Forty-one major complications occurred, of which 7 were not advisory related. The 5-year major complication rate was 4% without advisory-related complications and 27% including advisory-related complications. No advisory-related major complications occurred a median 10 days (range 0-88 days) postimplantation. The pacing capture threshold was low in 163 of 167 patients (98%) and stable in 157 of 160 (98%).CONCLUSION: The long-term major complication rate without advisory-related complications was low with LPs. No complications occurred after the acute phase and no infections occurred, which may be a specific benefit of LPs. The performance was adequate with a stable pacing capture threshold.</p

Mindfulness Training Supports Quality of Life and Advance Care Planning in Adults With Metastatic Cancer and Their Caregivers: Results of a Pilot Study

Background: Emotional distress often causes patients with cancer and their family caregivers (FCGs) to avoid end-of-life discussions and advance care planning (ACP), which may undermine quality of life (QoL). Most ACP interventions fail to address emotional barriers that impede timely ACP. Aim: We assessed feasibility, acceptability, and preliminary effects of a mindfulness-based intervention to facilitate ACP for adults with advanced-stage cancer and their FCGs. Design: A single-arm pilot was conducted to assess the impact of a 6-week group mindfulness intervention on ACP behaviors (patients only), QoL, family communication, avoidant coping, distress, and other outcomes from baseline (T1) to post-intervention (T2) and 1 month later (T3). Participants: Eligible patients had advanced-stage solid malignancies, limited ACP engagement, and an FCG willing to participate. Thirteen dyads (N = 26 participants) enrolled at an academic cancer center in the United States. Results: Of eligible patients, 59.1% enrolled. Attendance (70.8% across 6 sessions) and retention (84.6% for patients; 92.3% for FCGs) through T3 were acceptable. Over 90% of completers reported high intervention satisfaction. From T1 to T3, patient engagement more than doubled in each of 3 ACP behaviors assessed. Patients reported large significant decreases in distress at T2 and T3. Family caregivers reported large significant improvements in QoL and family communication at T2 and T3. Both patients and FCGs reported notable reductions in sleep disturbance and avoidant coping at T3. Conclusions: The mindfulness intervention was feasible and acceptable and supported improvements in ACP and associated outcomes for patients and FCGs. A randomized trial of mindfulness training for ACP is warranted

Factors affecting commencement and cessation of smoking behaviour in Malaysian adults

<p>Abstract</p> <p>Background</p> <p>Tobacco consumption peak in developed countries has passed, however, it is on the increase in many developing countries. Apart from cigarettes, consumption of local hand-rolled cigarettes such as <it>bidi </it>and <it>rokok daun </it>are prevalent in specific communities. Although factors associated with smoking initiation and cessation has been investigated elsewhere, the only available data for Malaysia is on prevalence. This study aims to investigate factors associated with smoking initiation and cessation which is imperative in designing intervention programs.</p> <p>Methods</p> <p>Data were collected from 11,697 adults by trained recording clerks on sociodemographic characteristics, practice of other risk habit and details of smoking such as type, duration and frequency. Smoking commencement and cessation were analyzed using the Kaplan-Meier estimates and log-rank tests. Univariate and multivariate Cox proportional hazard regression models were used to calculate the hazard rate ratios.</p> <p>Results</p> <p>Males had a much higher prevalence of the habit (61.7%) as compared to females (5.8%). Cessation was found to be most common among the Chinese and those regularly consuming alcoholic beverages. Kaplan-Meier plot shows that although males are more likely to start smoking, females are found to be less likely to stop. History of betel quid chewing and alcohol consumption significantly increase the likelihood of commencement (p < 0.0001), while cessation was least likely among Indians, current quid chewers and kretek users (p < 0.01).</p> <p>Conclusions</p> <p>Gender, ethnicity, history of quid chewing and alcohol consumption have been found to be important factors in smoking commencement; while ethnicity, betel quid chewing and type of tobacco smoked influences cessation.</p

Designing a broad-spectrum integrative approach for cancer prevention and treatment

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered

Light regulation of metabolic pathways in fungi

Light represents a major carrier of information in nature. The molecular machineries translating its electromagnetic energy (photons) into the chemical language of cells transmit vital signals for adjustment of virtually every living organism to its habitat. Fungi react to illumination in various ways, and we found that they initiate considerable adaptations in their metabolic pathways upon growth in light or after perception of a light pulse. Alterations in response to light have predominantly been observed in carotenoid metabolism, polysaccharide and carbohydrate metabolism, fatty acid metabolism, nucleotide and nucleoside metabolism, and in regulation of production of secondary metabolites. Transcription of genes is initiated within minutes, abundance and activity of metabolic enzymes are adjusted, and subsequently, levels of metabolites are altered to cope with the harmful effects of light or to prepare for reproduction, which is dependent on light in many cases. This review aims to give an overview on metabolic pathways impacted by light and to illustrate the physiological significance of light for fungi. We provide a basis for assessment whether a given metabolic pathway might be subject to regulation by light and how these properties can be exploited for improvement of biotechnological processes