A New Mathematical Theory for the Dynamics of Large Tumor Populations, a Potential Mechanism for Cancer Dormancy & Recurrence and Experimental Observation of Melanoma Progression in Zebrafish

Cancer, a family of over a hundred disease varieties, results in 600,000 deaths in the U.S. alone. Yet, improvements in imaging technology to detect disease earlier, pharmaceutical developments to shrink or eliminate tumors, and modeling of biological interactions to guide treatment have prevented millions of deaths. Cancer patients with initially similar disease can experience vastly different outcomes, including sustained recovery, refractory disease or, remarkably, recurrence years after apparently successful treatment. The current understanding of such recurrences is that they depend on the random occurrence of critical mutations. Clearly, these biological changes appear to be sufficient for recurrence, but are they necessary? In contrast, we propose a new mathematical model that predicts long-term apparent dormancy followed by recurrence can occur because of tumor population dynamics without the need for a single random event such as the occurrence of a key mutation. Understanding the mechanisms and factors that influence the likelihood and timing of recurrence can strongly impact preferred treatments. Though cancer progression is a complex interplay of many complicated biological processes such as genetic changes, chemical signals and metabolic considerations, our model examines how the dynamic interplay of just three processes can dictate disease progress. We propose a population balance model to describe how populations of a large ensemble of tumors of different sizes evolve in time due to growth (mitosis), reduction (apoptosis or immunity) and metastasis, each with a size-dependent parameter. Mathematical analysis of the model’s parameter interactions leads to insights regarding the progression of metastatic cancer, including prediction of recurrence after long-term dormancy. We successfully tested the model against literature data on human hepatocellular carcinoma and then carried out extensive experiments on a zebrafish model of melanoma to validate the model. The experimental system consists of gender-segregated immune-competent and immune-suppressed translucent, stripeless zebra­fish (casper variant) inoculated with a fluorescent GFP-expressing transgenic melanoma cell line (ZMEL). We numerically solved the model’s partial differential equations for any given initial population size distribution and used it and the data to find best-fit parameters for growth, reduction and metastasis. This novel parameter optimization detected the differences between the immune status for each gender. Because the measured fish melanoma parameters are not in a range for which we predict dormancy and recurrence within fish lifetimes, this system cannot yet verify predictions on tumor recurrence. We complemented the above experiments with mathematical analysis, including both analytical and approximate solutions to the model for select parameters. We applied the theory of birth and death processes to estimate the probability and timing of recurrence. We have also developed a Markov chain simulation model to track the progression of discrete tumors. This formulation facilitates the study of tumor merging events by allowing individual tumors to be positioned in a virtual fish body. We are exploring alternate methods of obtaining tumor growth data from different species, including CT scans of mouse lungs to infer lung metastases sizes. Ultimately, the model may offer a flexible way to predict the progression of the cancer by using noninvasive imaging data to find model parameters

Risk Factors for Hepatitis C Virus Transmission Obscure in Nigerian Patients

Aim. To determine the prevalence of anti-HCV and risk factors associated with HCV infection in Nigerians. Materials and Method. Patients attending a general outpatient clinic were administered a structured questionnaire on the risk factors for HCV infection. They were also tested for anti-HCV using a third generation enzyme-linked immunosorbent assay. Result. The seroprevalence of anti-HCV was 4.7%. Among the risk factors evaluated, none was found to be significantly associated with anti-HCV seropositivity. Conclusion. The risk factors associated with HCV infection in Nigerian patients are obscure. This warrants further studies on the epidemiology of this important cause of liver disease

Autism spectrum disorder in a community-based sample with neurodevelopmental problems in Lagos, Nigeria

Autism Spectrum Disorder (ASD) is a globally prevalent neurodevelopmental disorder for which early diagnosis and intervention is the mainstay of management. In the African continent, limited data is available regarding the non-clinic based samples. Lack of information available to caregivers and inadequate skilled manpower often limit early detection and access to the few available though under resourced services in the community. Community based screening can be an important drive to create awareness and improve information dissemination regarding services available for those living with this disorder. This is a descriptive cross-sectional study utilizing data obtained from participants of a community-based autism screening exercise. The surveillance exercise was part of the annual Orange Ribbon initiative for autism awareness and screening held in 2014. Data was obtained from 85 participants involved in the Autism Surveillance screening exercise within the Lagos community. Community public service radio announcements state wide and word of mouth were used to invite and enroll eligible participants to the screening and consultation exercise. A second stage screening and a brief sociodemographic questionnaire followed by a third stage clinical interview and evaluation using the Diagnostic and Statistical Manual of Mental Disorders - 5 Edition (DSM 5) were used. Appropriate consultation and referrals to services in the community were given. Participants had a mean age of 7.53 years (SD 4.35). Twenty-nine (34.5%) met the diagnosis of ASD. Other diagnosis included attention deficit hyperactivity disorder (ADHD), language and speech disorder, intellectual disability (8.3%) and learning disorders (9.5%). Main health concerns to caregivers were poor language development in all (100%), of which 11 (40.7%) were non-verbal; gaze avoidance was seen in 14 (48.3%) and challenging behavior in 12 (42.9%). Comorbidities included seizure disorders (3.4%) and ADHD (6.9%). Persons with autism had history of ASD behavior more often when compared to the other neurodevelopmental disorders and these findings were statistically significant. Referrals were given to caregivers to engage in services within the community. As seen in this study, community understanding of ASD is poor in such locations, in which many persons with other neurodevelopmental disorders are often presented as having autism. Caregivers in the study location are distressed by many symptoms associated with autism and their comorbid conditions. Currently there is an evident role for frequent large scale community based screening and autism awareness exercises possibly using inter-sectoral collaboration as a strategy.Yewande O. Oshodi, Andrew T. Olagunju, Motunrayo. A. Oyelohunnu, Elizabeth A. Campbell, Charles S. Umeh, Olatunji F. Aina, Wellington Oyibo, Folusho E.A. Lesi, Joseph D. Adeyem

Aflatoxin Exposure and Viral Hepatitis in the Etiology of Liver Cirrhosis in The Gambia, West Africa

BACKGROUND: Cirrhosis of the liver is thought to be a major cause of morbidity and mortality in sub-Saharan Africa, but few controlled studies on the etiology of cirrhosis have been conducted in this region. OBJECTIVES: We aimed to elucidate the association between environmental and infectious exposures and cirrhosis in The Gambia. METHODS: Ninety-seven individuals were diagnosed with cirrhosis using a validated ultrasound scoring system and were compared with 397 controls. Participants reported demographic and food frequency information. Blood samples were tested for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis C virus (HCV) antibody, HCV RNA, and the aflatoxin-associated 249(ser) TP53 mutation. RESULTS: HBsAg seropositivity was associated with a significant increase in risk of cirrhosis [odds ratio (OR) = 8.0; 95% confidence interval (CI), 4.4-14.7] as was the presence of HBeAg (OR = 10.3; 95% CI, 2.0-53.9) and HCV infection (OR = 3.3; 95% CI, 1.2-9.5). We present novel data that exposure to aflatoxin, as assessed both by high lifetime groundnut (peanut) intake and by the presence of the 249(ser) TP53 mutation in plasma, is associated with a significant increase in the risk for cirrhosis (OR = 2.8; 95% CI, 1.1-7.7 and OR = 3.8; 95% CI, 1.5-9.6, respectively). Additionally, aflatoxin and hepatitis B virus exposure appeared to interact synergistically to substantially increase the risk of cirrhosis, although this was not statistically significant. CONCLUSIONS: Our results suggest that the spectrum of morbidity associated with aflatoxin exposure could include cirrhosis

HUBUNGAN NILAI CBR LABORATORIUM DAN DCP PADA TANAH YANG DIPADATKAN PADA RUAS JALAN WORI–LIKUPANG KABUPATEN MINAHASA UTARA

ABSTRAK Cara uji Dynamic Cone Penetrometer (DCP). merupakan suatu prosedur yang cepat untuk melaksanakan evaluasi kekuatan tanah dasar dan lapis pondasi jalan dengan biaya yang relatif kecil. Tulisan ini membahas hubungan nilai CBR laboratorium dan DCP pada tanah yang dipadatkan di ruas jalan Wori–Likupang Kabupaten Minahasa Utara. Dari hasil analisa data pada lima tempat yang berbeda baik di lapangan maupun di laboratorium, diperoleh 4 titik penelitian yang memiliki nilai hampir sama yaitu pada STA 28+200, STA 28+300, STA 28+400 dan STA 29+000, sehingga penggunaan alat DCP untuk penentuan CBR tanah (CBR perkiraan awal) di lapangan di Ruas Jalan Wori-Likupang dapat dipakai sebagai suatu data perencanaan konstruksi jalan tanpa harus melakukan pengujian CBR lebih lanjut di laboratorium. Kata kunci:DCP, CBR, CBR Lapangan, CBR Laboratorium, tanah, pemadatan tanah.ABSTRACT Dynamic Cone Penetrometer (DCP) test method is a fast procedure to carry out the evaluation of subgrade strength and the foundation layer with a relatively small cost. This research examines the relationship of laboratory CBR and DCP values on compacted soil in road Wori-Likupang North Minahasa regency. From the analysis of the data at five different places both in the field and in the laboratory the results obtained 4 points of research that has almost the same value at STA 28+200, STA 28+300, STA 28+400 and STA 29+000, so the use of a DCP for the determination of CBR soil (CBR preliminary estimates) in the field at Wori-Likupang road can be used as a road construction planning data without having to perform further CBR testing in the laboratory. Keywords:DCP, CBR, CBR Field, CBR Laboratories, soil, soil compaction

Population pharmacokinetic and pharmacodynamic properties of intramuscular quinine in Tanzanian children with severe Falciparum malaria.

Although artesunate is clearly superior, parenteral quinine is still used widely for the treatment of severe malaria. A loading-dose regimen has been recommended for 30 years but is still often not used. A population pharmacokinetic study was conducted with 75 Tanzanian children aged 4 months to 8 years with severe malaria who received quinine intramuscularly; 69 patients received a loading dose of 20 mg quinine dihydrochloride (salt)/kg of body weight. Twenty-one patients had plasma quinine concentrations detectable at baseline. A zero-order absorption model with one-compartment disposition pharmacokinetics described the data adequately. Body weight was the only significant covariate and was implemented as an allometric function on clearance and volume parameters. Population pharmacokinetic parameter estimates (and percent relative standard errors [%RSE]) of elimination clearance, central volume of distribution, and duration of zero-order absorption were 0.977 liters/h (6.50%), 16.7 liters (6.39%), and 1.42 h (21.5%), respectively, for a typical patient weighing 11 kg. Quinine exposure was reduced at lower body weights after standard weight-based dosing; there was 18% less exposure over 24 h in patients weighing 5 kg than in those weighing 25 kg. Maximum plasma concentrations after the loading dose were unaffected by body weight. There was no evidence of dose-related drug toxicity with the loading dosing regimen. Intramuscular quinine is rapidly and reliably absorbed in children with severe falciparum malaria. Based on these pharmacokinetic data, a loading dose of 20 mg salt/kg is recommended, provided that no loading dose was administered within 24 h and no routine dose was administered within 12 h of admission. (This study has been registered with Current Controlled Trials under registration number ISRCTN 50258054.)

Helicobacter pylori patient isolates from South Africa and Nigeria differ in virulence factor pathogenicity profile and associated gastric disease outcome

Helicobacter pylori is a gram-negative, spiral-shaped bacterial pathogen and the causative agent for gastritis, peptic ulcer disease and classified as a WHO class I carcinogen. While the prevalence of H. pylori infections in Africa is among the highest in the world, the incidence of gastric cancer is comparably low. Little is known about other symptoms related to the H. pylori infection in Africa and the association with certain phenotypes of bacterial virulence. We established a network of study sites in Nigeria (NG) and South Africa (ZA) to gain an overview on the epidemiological situation. In total 220 isolates from 114 patients were analyzed and 118 different patient isolates examined for the presence of the virulence factors cagA, vacA, dupA, their phylogenetic origin and their resistance against the commonly used antibiotics amoxicillin, clarithromycin, metronidazole and tetracycline. We report that H. pylori isolates from Nigeria and South Africa differ significantly in their phylogenetic profiles and in their expression of virulence factors. VacA mosaicism is intensive, resulting in m1-m2 vacA chimeras and frequent s1m1 and s1m2 vacA subtypes in hpAfrica2 strains. Gastric lesions were diagnosed more frequent in Nigerian versus South African patients and H. pylori isolates that are resistant against one or multiple antibiotics occur frequently in both countries

The use of complementary and alternative medicine by women experiencing menopausal symptoms in Bologna

<p>Abstract</p> <p>Background</p> <p>The present study describes Complementary and Alternative Medicine (CAM) use amongst Italian women transitioning through menopause. Popularity and perceived effectiveness of CAM treatments, use of pharmaceutical medications, characteristics of CAM users, the extent of communication between medical practitioners and women about their use of CAM, and variables associated with CAM use were also investigated.</p> <p>Methods</p> <p>Women, aged 45-65 years attending Family Planning and Women's Health clinics or Menopause Centres in Bologna were invited to complete a voluntary, anonymous, self administered questionnaire, which was used in a previous study in Sydney. The questionnaire was translated and adapted for use amongst Italian women. Data on general demographic and health characteristics, menopause related symptoms and the use of CAM and pharmaceutical treatments during the previous 12 months were collected.</p> <p>Results</p> <p>In total, 1,203 women completed the survey, of which 1,106 were included in the final sample. Of women who had symptoms linked with menopause and/or used remedies to alleviate symptoms, 33.5% reported to have used CAM. Among these, 23.5% had consulted one or more practitioners and 24% had used at least one CAM product.</p> <p>Approximately nine out of ten respondents reported medical practitioners did not seek information about their use of CAM; while one third of CAM users did not disclose the use of CAM to their physician. Nevertheless, medical practitioners were the most popular source of information. From the multivariate analysis, variables associated with CAM use were: professional employment, time since the last natural menses, use of CAM for conditions other than menopause, and presence of some severe symptoms.</p> <p>Conclusions</p> <p>The relatively high prevalence of CAM use by women transitioning through menopause should encourage research initiatives into determining which CAM treatments are the safest and effective. The increasing and likely concomitant use of CAM with HRT and other pharmaceuticals underlines the need for the implementation of a surveillance system to report and monitor possible drug-herb adverse events. The discrepancy between women preferring to seek information about CAM from their medical doctor and the difficulties noted in communication between doctor and patient should encourage educational initiatives on CAM by health-care agencies and institutions.</p