Detection of oncogenic mutations in paired circulating tumor DNA and circulating tumor cells in patients with hepatocellular carcinoma

Background and aimsCirculating tumor cells (CTCs) or circulating tumor DNA (ctDNA) may be used for diagnostic or prognostic purposes in patients with hepatocellular carcinoma (HCC). We aim to determine whether CTCs or ctDNA are suitable to determine oncogenic mutations in HCC patients.MethodsTwenty-six mostly advanced HCC patients were enrolled. 30 mL peripheral blood from each patient was obtained. CellSearch system was used for CTC detection. A sequencing panel covering 14 cancer-relevant genes was used to identify oncogenic mutations. TERT promoter C228T and C250T mutations were determined by droplet digital PCR.ResultsCTCs were detected in 27% (7/26) of subjects but at low numbers (median: 2 cells, range: 1–15 cells) and ctDNA in 77% (20/26) of patients. Mutations in ctDNA were identified in several genes: TERT promoter C228T (77%, 20/26), TP53 (23%, 6/26), CTNNB1 (12%, 3/26), PIK3CA (12%, 3/26) and NRAS (4%, 1/26). The TERT C228T mutation was present in all patients with one or more ctDNA mutations, or detectable CTCs. The TERT C228T and TP53 mutations detected in ctDNA were present at higher levels in matched primary HCC tumor tissue. The maximal variant allele frequency (VAF) of ctDNA was linearly correlated with largest tumor size and AFP level (Log10). CtDNA (or TERT C228T) positivity was associated with macrovascular invasion, and positivity of ctDNA (or TERT C228T) or CTCs (≥ 2) correlated with poor patient survival.ConclusionsOncogenic mutations could be detected in ctDNA from advanced HCC patients. CtDNA analysis may serve as a promising liquid biopsy to identify druggable mutations.     

Wakunza: Uses of Yuwipi Medicine Power in Contemporary Teton Dakota Culture1

Abstract

The Dakota belief in wakuⁿza or “supernatural retribution” is examined as an aspect of contemporary Sioux religion. Belief in this power is reported to be a significant mechanism in the maintenance of social control within Sioux communities on and off the reservation by insuring the chastisement of social deviants. Animistic spirits rather than individuals are attributed with possessing the power to administer justice and reprimand those committing transgressions of the Dakota moral order. Two alternative hypotheses regarding the uses of wakuⁿza are proposed.     

Towards Improving Point-of-Care Diagnosis of Non-malaria Febrile Illness: A Metabolomics Approach

IntroductionNon-malaria febrile illnesses such as bacterial bloodstream infections (BSI) are a leading cause of disease and mortality in the tropics. However, there are no reliable, simple diagnostic tests for identifying BSI or other severe non-malaria febrile illnesses. We hypothesized that different infectious agents responsible for severe febrile illness would impact on the host metabololome in different ways, and investigated the potential of plasma metabolites for diagnosis of non-malaria febrile illness.MethodologyWe conducted a comprehensive mass-spectrometry based metabolomics analysis of the plasma of 61 children with severe febrile illness from a malaria-endemic rural African setting. Metabolite features characteristic for non-malaria febrile illness, BSI, severe anemia and poor clinical outcome were identified by receiver operating curve analysis.ConclusionsThis study demonstrates the potential use of plasma metabolites to identify causality in children with severe febrile illness in malaria-endemic settings.     

The Habitat of Zygodon forsteri (Brid) Mitt. in the New Forest,Hants

Abstract

Seven species are reported here for the first time for South Georgia. Two of these were already known from Tierra del Fuego, Acrolophozia fuegiana Schust. and Marsupella sprucei (Limpr.) H. Bern., but Acrolophozia sulcata Hässel, Marsupella austrogeorgica Hässel, and Marsupella minutula Hässel are described as new. The additional two species which are described, Austrolembidium crassum Hässel and Greeneothallus gemmiparus Hässel, also required the creation of two new genera. The total number of liverwort species now known to be present on South Georgia is sixty-six.     

The Ideal Personality Form Seen in Ten Animal Tales of the Salish Flathead Indians of Montana

Abstract

The author uses a projective psychological analysis of ten Salish Flathead animal tales to try to develop information on the pre-white Salish conceptions of aggression, achievement, nature, time, the supernatural, and approved social orientations. As developed in the tales, Salish ideal psychological traits are similar to those previously found among present-day Salish and Sioux Indians.     

Explanatory Models and Mental Health Treatment: Is Vodou an Obstacle to Psychiatric Treatment in Rural Haiti?

Vodou as an explanatory framework for illness has been considered an impediment to biomedical psychiatric treatment in rural Haiti by some scholars and Haitian professionals. According to this perspective, attribution of mental illness to supernatural possession drives individuals to seek care from houngan-s (Vodou priests) and other folk practitioners, rather than physicians, psychologists, or psychiatrists. This study investigates whether explanatory models of mental illness invoking supernatural causation result in care-seeking from folk practitioners and resistance to biomedical treatment. The study comprised 31 semi-structured interviews with community leaders, traditional healers, religious leaders, and biomedical providers, 10 focus group discussions with community members, community health workers, health promoters, community leaders, and church members; and four in-depth case studies of individuals exhibiting mental illness symptoms conducted in Haiti's Central Plateau. Respondents invoked multiple explanatory models for mental illness and expressed willingness to receive treatment from both traditional and biomedical practitioners. Folk practitioners expressed a desire to collaborate with biomedical providers and often referred patients to hospitals. At the same time, respondents perceived the biomedical system as largely ineffective for treating mental health problems. Explanatory models rooted in Vodou ethnopsychology were not primary barriers to pursuing psychiatric treatment. Rather, structural factors including scarcity of treatment resources and lack of psychiatric training among health practitioners created the greatest impediments to biomedical care for mental health concerns in rural Haiti.     

IPN unit bank biology—a new type of biology curriculum

Abstract

IPN (Institut für die Pädagogik der Naturwissenschaften/Institute for Science Education) in Kiel has developed single curriculum units since 1969 showing that certain innovative aims, methods, media, and content of biology teaching are practicable in schools. These units are being published now as a flexible ‘unit bank’ which can either be adopted as a whole or the individual units, or parts thereof, fitted into existing syllabuses.     

Methodische Hinweise zur Gewinnung von Pansensaft

Abstract

erarbeitet von der RGW-Arbeitsgruppe zum Thema 9.2. ?Die Verwendung nichteiweißartiger Stickstoffsubstanzen in der Fütterung der Wiederkäuer“ anläßlich der methodischen Konferenz vom 6. bis 11. Februar 1969 in Berlin, Deutsche Demokratische Republik.

(Beteiligte Länder: Volksrepublik Bulgarien, Ungarische Volksrepublik, Deutsche Demokratische Republik, Volksrepublik Polen, Sozialistische Rumänische Republik, Union der Sozialistischen Sowjetrepubliken, Tschechoslowakische Sozialistische Republik).     

Illness Beliefs Predict Mortality in Patients with Diabetic Foot Ulcers

BackgroundPatients’ illness beliefs have been associated with glycaemic control in diabetes and survival in other conditions.ObjectiveWe examined whether illness beliefs independently predicted survival in patients with diabetes and foot ulceration.MethodsPatients (n = 169) were recruited between 2002 and 2007. Data on illness beliefs were collected at baseline. Data on survival were extracted on 1^st November 2011. Number of days survived reflected the number of days from date of recruitment to 1^st November 2011.ResultsCox regressions examined the predictors of time to death and identified ischemia and identity beliefs (beliefs regarding symptoms associated with foot ulceration) as significant predictors of time to death.ConclusionsOur data indicate that illness beliefs have a significant independent effect on survival in patients with diabetes and foot ulceration. These findings suggest that illness beliefs could improve our understanding of mortality risk in this patient group and could also be the basis for future therapeutic interventions to improve survival.     

Clinical findings for the first 1000 Gulf war veterans in the Ministry of Defence’s medical assessment programme

ObjectiveTo review the clinical findings in the first 1000 veterans seen in the Ministry of Defence’s Gulf war medical assessment programme to examine whether there was a particular illness related to service in the Gulf.DesignCase series of 1000 veterans who presented to the programme between 11 October 1993 and 24 February 1997.SubjectsGulf war veterans.Results588 (59%) veterans had more than one diagnosed condition, 387 (39%) had at least one condition for which no firm somatic or psychological diagnosis could be given, and in 90 (9%) veterans no other main diagnosis was made. Conditions characterised by fatigue were found in 239 (24%) of patients. At least 190 (19%) patients had a psychiatric condition, which in over half was due to post-traumatic stress disorder. Musculoskeletal disorders and respiratory conditions were also found to be relatively common (in 182 (18%) and 155 (16%) patients respectively).ConclusionMany Gulf war veterans had a wide variety of symptoms. This initial review shows no evidence of a single illness, psychological or physical, to explain the pattern of symptoms seen in veterans in the assessment programme. As the veterans assessed by the programme were all self selected, the prevalence of illness in Gulf war veterans cannot be determined from this study. Furthermore, it is not known whether the veterans in this study were representative of sick veterans as a group.

Key messages

• Many Gulf war veterans present with a wide variety of symptoms
• No single cause has been found to explain these symptoms
• From a clinical standpoint the variety and multiplicity of symptoms makes it unlikely that any single cause will be found to underlie Gulf war illness
• Some of the illnesses may be an example of a postwar syndrome

     

Qualitative interview study of communication between parents and children about maternal breast cancer

ObjectiveTo examine parents'' communication with their children about the diagnosis and initial treatment of breast cancer in the mother.DesignQualitative interview study within cross sectional cohort.SettingTwo breast cancer treatment centres.Participants32 women with stage I or stage II breast cancer with a total of 56 school aged children.ResultsWomen were most likely to begin talking to their children after their diagnosis had been confirmed by biopsy, but a minority waited until after surgery or said nothing at all. Family discussion did not necessarily include mention of cancer. There was considerable consistency in the reasons given for either discussing or not discussing the diagnosis. The most common reason for not communicating was avoidance of children''s questions and particularly those about death. While most mothers experienced helpful discussion with a doctor concerning their illness, few were offered help with talking to children; many would have liked help, particularly the opportunity for both parents to talk to a health professional with experience in understanding and talking to children.ConclusionsParents diagnosed with cancer or other serious illnesses should be offered help to think about whether, what, and how to tell their children and about what children can understand, especially as they may well be struggling themselves to come to terms with their illness.     

Methodische Empfehlung zur Bestimmung von einigen Stoffwechselprodukten im Pansensaft und Blut

Abstract

erarbeitet von der RGW-Arbeitsgruppe zum Thema 9.2 ?Die Verwendung nichteiweißartiger Stickstoffsubstanzen in der Fütterung der Wiederkäuer“ anläßlich der methodischen Konferenz vom 6. bis 11. Februar 1969 in Berlin, Deutsche Demokratische Republik.

(Beteiligte Länder: Volksrepublik Bulgarien, Ungarische Volksrepublik, Deutsche Demokratische Republik, Volksrepublik Polen, Sozialistische Rumänische Republik, Union der Sozialistischen Sowjetrepubliken, Tschechoslowakische Föderative Sozialistische Republik).     

Disease Etiologies in Non-Western Medical Systems

This paper argues that disease etiology is the key to cross-cultural comparison of non-Western medical systems. Two principal etiologies are identified: personalistic and naturalistic. Correlated with personalistic etiologies are the belief that all misfortune, disease included, is explained in the same way; illness, religion, and magic are inseparable; the most powerful curers have supernatural and magical powers, and their primary role is diagnostic. Correlated with naturalistic etiologies are the belief that disease causality has nothing to do with other misfortunes; religion and magic are largely unrelated to illness; the principal curers lack supernatural or magical powers, and their primary role is therapeutic . [disease, religion, and magic; ethnomedicine, medical anthropology, non-Western medical systems, shamans]     

Genetic approaches for controlling ratios of related polyketide products in fermentation processes

Simple acyl thioesters are used as precursors for both the initiation and elongation steps in polyketide biosynthetic processes. Several structurally related polyketide products are sometimes made in these processes. These analogs are typically generated by a combination of two factors: availability of structurally similar biosynthetic precursors, and biosynthetic enzymes unable to effectively discriminate between them. Often, only one polyketide product is desired from a fermentation process, requiring a method to control the ratio of these different analogs. Preferential production of one desired analog is accomplished using random mutagenesis and manipulation of fermentation conditions. A genetic enzymatic understanding of polyketide biosynthesis, as well as the pathways that provide the relevant precursors, allows for a rational and more contemporary approach for control of analogs produced in fermentation processes. This approach involves genetic manipulation of either the pathways that provide pools of the acyl CoA thioester precursors, or the function/specificity of the appropriate biosynthetic enzymes. Reviewed herein are three such examples where these approaches have been carried out successfully with polyketide biosynthetic processes. Journal of Industrial Microbiology & Biotechnology (2001) 27, 368–377. Received 01 March 2001/ Accepted in revised form 08 August 2001     

Mental Representations of Illness in Patients with Gestational Trophoblastic Disease: How Do Patients Perceive Their Condition?

BackgroundGestational Trophoblastic Disease comprises a group of benign and malignant disorders that derive from the placenta. Using Leventhal’s Common-Sense Model as a theoretical framework, this paper examines illness perception in women who have been diagnosed with this disease.MethodsThirty-one women diagnosed with Gestational Trophoblastic Disease in a hospital in Italy were asked to complete the Illness Perception Questionnaire-Revised to measure the following: illness Identity, illness opinions and causes of Gestational Trophoblastic Disease.ResultsHigh mean scores were observed in the Emotional representations and Treatment control subscales. A significant difference emerged between hydatidiform mole patients and those with gestational trophoblastic neoplasia on the Identity subscale. A significant correlation emerged between “time since diagnosis” and the Treatment control subscale.DiscussionThis study is the first to investigate illness perception in Gestational Trophoblastic Disease. From a clinical perspective the results highlight the need for multidisciplinary support programs to promote a more realistic illness perception.     

Stress Induced Hyperglycemia and the Subsequent Risk of Type 2 Diabetes in Survivors of Critical Illness

ObjectiveStress induced hyperglycemia occurs in critically ill patients who have normal glucose tolerance following resolution of their acute illness. The objective was to evaluate the association between stress induced hyperglycemia and incident diabetes in survivors of critical illness.DesignRetrospective cohort study.SettingAll adult patients surviving admission to a public hospital intensive care unit (ICU) in South Australia between 2004 and 2011.PatientsStress induced hyperglycemia was defined as a blood glucose ≥ 11.1 mmol/L (200 mg/dL) within 24 hours of ICU admission. Prevalent diabetes was identified through ICD-10 coding or prior registration with the Australian National Diabetes Service Scheme (NDSS). Incident diabetes was identified as NDSS registration beyond 30 days after hospital discharge until July 2015. The predicted risk of developing diabetes was described as sub-hazard ratios using competing risk regression. Survival was assessed using Cox proportional hazards regression.ConclusionsStress induced hyperglycemia identifies patients at subsequent risk of incident diabetes.     

Impaired Postoperative Hyperglycemic Stress Response Associated with Increased Mortality in Patients in the Cardiothoracic Surgery Intensive Care Unit

ObjectiveTo describe the association of tight glycemic control with intensive insulin therapy and clinical outcome among patients in the cardiothoracic surgery intensive care unit.MethodsAll patients who underwent cardiothoracic surgery and were admitted to the cardiothoracic surgery intensive care unit between September 13, 2007, and November 1, 2007, were enrolled. Clinical and metabolic data were prospectively collected. All patients received intensive insulin therapy using a nurse-driven dynamic protocol targeting blood glucose values of 80 to 110 mg/dL. Four stages of critical illness were defined as follows: acute critical illness (intensive care unit days 0-2), prolonged acute critical illness (intensive care unit 3 or more days), chronic critical illnesss (tracheotomy performed), and recovery (liberated from ventilator).ResultsOne hundred fourteen patients were enrolled. Seventy-three (64%) recovered during acute critical illness, 26 (23%) recovered during prolonged acute critical illness, and 15 (13%) progressed to chronic critical illness. All 6 deaths were among patients in chronic critial illness. Admission blood glucose and average blood glucose values for the first 12 hours were lower in patients who developed chronic critical illness and died and were higher in patients who developed chronic critical illness and survived (P = .007 and P = .007, respectively). Severe hypoglycemia (blood glucose < 40 mg/dL) occurred once (0.03% of all measurements). Lower initial blood glucose values, which reflect an impaired stress response immediately after surgery, were associated with increased mortality, and a significant delay in achieving tight glycemic control with intensive insulin therapy was associated with prolonged intensive care unit course, but no increase in mortality.ConclusionThe study findings suggest that acute postoperative hyperglycemia and its prompt correction with intensive insulin therapy are associated with favorable outcomes in patients in the cardiothoracic surgery intensive care unit. (Endocr Pract. 2010;16:798-804)     

Microwave-Assisted Synthesis of Acyclic C-Nucleosides from 1,2- and 1,3-Diketones

A simple, rapid and regioselective approach for the synthesis of C-acyclic nucleosides 3, 4, 6, and 9 of dihydropyrimidine, imidazole and indeno[1,2-b]pyridine-9-one derived from 1,2- and 1,3-diketones was performed. By using DMF or pyridine as solvent or bentonite clay as a support, in the presence of TMSTf, ZnCl₂, NH₄OAc, or NH₄NO₃, all the desired products were obtained within 5–25 minutes under microwave irradiation (MWI). Acid hydrolysis of 6 and 9 afforded the free acyclic C-nucleosides 7 and 10, respectively. Upon treatment with NaOMe under MWI, 3 and 14 rearranged to the C-nucleoside 4 and 16.