Upregulation of the microRNA cluster at the Dlk1-Dio3 locus in lung adenocarcinoma.

Mice in which lung epithelial cells can be induced to express an oncogenic Kras(G12D) develop lung adenocarcinomas in a manner analogous to humans. A myriad of genetic changes accompany lung adenocarcinomas, many of which are poorly understood. To get a comprehensive understanding of both the transcriptional and post-transcriptional changes that accompany lung adenocarcinomas, we took an omics approach in profiling both the coding genes and the non-coding small RNAs in an induced mouse model of lung adenocarcinoma. RNAseq transcriptome analysis of Kras(G12D) tumors from F1 hybrid mice revealed features specific to tumor samples. This includes the repression of a network of GTPase-related genes (Prkg1, Gnao1 and Rgs9) in tumor samples and an enrichment of Apobec1-mediated cytosine to uridine RNA editing. Furthermore, analysis of known single-nucleotide polymorphisms revealed not only a change in expression of Cd22 but also that its expression became allele specific in tumors. The most salient finding, however, came from small RNA sequencing of the tumor samples, which revealed that a cluster of ∼53 microRNAs and mRNAs at the Dlk1-Dio3 locus on mouse chromosome 12qF1 was markedly and consistently increased in tumors. Activation of this locus occurred specifically in sorted tumor-originating cancer cells. Interestingly, the 12qF1 RNAs were repressed in cultured Kras(G12D) tumor cells but reactivated when transplanted in vivo. These microRNAs have been implicated in stem cell pleuripotency and proteins targeted by these microRNAs are involved in key pathways in cancer as well as embryogenesis. Taken together, our results strongly imply that these microRNAs represent key targets in unraveling the mechanism of lung oncogenesis

A Functional Taxonomy of Tumor Suppression in Oncogenic KRAS-Driven Lung Cancer

Cancer genotyping has identified a large number of putative tumor suppressor genes. Carcinogenesis is a multistep process, but the importance and specific roles of many of these genes during tumor initiation, growth, and progression remain unknown. Here we use a multiplexed mouse model of oncogenic KRAS–driven lung cancer to quantify the impact of 48 known and putative tumor suppressor genes on diverse aspects of carcinogenesis at an unprecedented scale and resolution. We uncover many previously understudied functional tumor suppressors that constrain cancer in vivo. Inactivation of some genes substantially increased growth, whereas the inactivation of others increases tumor initiation and/or the emergence of exceptionally large tumors. These functional in vivo analyses revealed an unexpectedly complex landscape of tumor suppression that has implications for understanding cancer evolution, interpreting clinical cancer genome sequencing data, and directing approaches to limit tumor initiation and progression. SIGNIFICANCE: Our high-throughput and high-resolution analysis of tumor suppression uncovered novel genetic determinants of oncogenic KRAS–driven lung cancer initiation, overall growth, and exceptional growth. This taxonomy is consistent with changing constraints during the life history of cancer and highlights the value of quantitative in vivo genetic analyses in autochthonous cancer models

Knowledge and exposure to complementary and alternative medicine in paediatric doctors: a questionnaire survey

<p>Abstract</p> <p>Background</p> <p>Complementary and alternative medicines are increasingly used by the general population. A survey was conducted to ascertain the knowledge of Complementary and Alternative Medicines (CAMs) amongst paediatric physicians, and whether seniority increases the likelihood of its use being considered in consultations, or of families discussing it.</p> <p>Methods</p> <p>Anonymous survey of general paediatric doctors in a large inner-city district general hospital (DGH) and tertiary children's centre (TC) using a questionnaire. Statistical analysis was calculated using Minitab.</p> <p>Results</p> <p>43/49 (88%) questionnaires were returned correctly. 13 (30%, CI 17 – 46%) doctors had personally used CAMs. 24 (56%, CI 40 – 71%) of their families had used CAMs. 13 (30%, CI 17 – 46%) had received formal CAMs education. 21 (49%, CI 40 – 71%) could name a total of 5 types of CAMs. Consultants were significantly more likely to ask about CAM use than middle-grades and juniors (p < 0.05, CI 48 – 93%, 35 – 90%, 8 – 33% respectively) and have had a clinical encounter where they felt it was significant. 32 (74%, CI 59 – 86%) of the clinicians had been asked about CAMs. 33 (77%, CI 61 – 88%) of doctors had successful CAM use reported to them, and 20 (47%, CI 31 – 62%) had failure of CAMs reported to them.</p> <p>Conclusion</p> <p>CAM use is relatively common in paediatric doctors and their families. They have received little formal CAMs education. Consultants were more likely than juniors to ask about CAM use and have had a clinical encounter where it played a significant part. Around half of all doctors irrespective of grade have been asked about CAMs in a clinical encounter.</p

Development and implementation of an herbal and natural product elective in undergraduate medical education

<p>Abstract</p> <p>Background</p> <p>Medical students have consistently expressed interest in learning about alternative healing modalities, especially herbal and natural products. To fill this void in medical education at our institution, a novel elective was developed and implemented for fourth year medical students. This herbal/natural product course uses guest lecturers, classroom presentations, and active learning mechanisms that include experiential rotations, case-based learning, and team-based learning to increase student knowledge of herbal/natural product safety and efficacy.</p> <p>Methods</p> <p>Knowledge outcomes were evaluated via administration of a pre- and post-course test (paired student <it>t</it>-test). End-of-course evaluations (Likert-type questions and narrative responses) were used to assess student opinion of knowledge and skills imparted by the elective and overall course content (mean, standard deviation).</p> <p>Results</p> <p>Over three academic years, 23 students have enrolled in this elective. More than 60% of participants have been female and nearly half of the students (43%) have pursued residencies in primary care. Completion of the course significantly increased student knowledge of common herbal/natural product mechanisms, uses, adverse effects, and drug-interactions as determined by a pre- and post-course knowledge assessment (45% ± 10% versus 78% ± 6%; p < 0.0001). The course was highly rated by enrollees (overall course quality, 4.6 of 5.0 ± 0.48) who appreciated the variety of activities to which they were exposed and the open classroom discussions that resulted. While students tended to view some alternative medical systems with skepticism, they still believed it was valuable to learn what these modalities encompass.</p> <p>Conclusions</p> <p>Development and implementation of a herbal/natural product elective that engages undergraduate medical students through active learning mechanisms and critical analysis of the literature has proven effective in increasing knowledge outcomes and is deemed to be a valuable curricular addition by student participants. In the future, it will be of interest to explore mechanisms for expanding the course to reach a larger number of students within the time, financial, and logistical constraints that currently exist.</p

Reshaping maternal services in Nigeria: any need for spiritual care?

BACKGROUND:High maternal and perinatal mortalities occur from deliveries conducted in prayer houses in Nigeria. Although some regulatory efforts have been deployed to tackle this problem, less attention has been placed on the possible motivation for seeking prayer house intervention which could be hinged on the spiritual belief of patients about pregnancy and childbirth. This study therefore seeks to determine the perception of booked antenatal patients on spiritual care during pregnancy and their desire for such within hospital setting.METHOD:A total of 397 antenatal attendees from two tertiary health institutions in southwest Nigeria were sampled. A pretested questionnaire was used to obtain information on socio-demographic features of respondents, perception of spiritual care during pregnancy and childbirth; and how they desire that their spiritual needs are addressed. Responses were subsequently collated and analyzed.RESULTS:Most of the women, 301 (75.8%), believe there is a need for spiritual help during pregnancy and childbirth. About half (48.5%) were currently seeking for help in prayer/mission houses while another 8.6% still intended to. Overwhelmingly, 281 (70.8%) felt it was needful for health professionals to consider their spiritual needs. Most respondents, 257 (64.7%), desired that their clergy is allowed to pray with them while in labour and sees such collaboration as incentive that will improve hospital patronage. There was association between high family income and desire for collaboration of healthcare providers with one's clergy (OR 1.82; CI 1.03-3.21; p?=?0.04).CONCLUSION:Our women desire spiritual care during pregnancy and childbirth. Its incorporation into maternal health services will improve hospital delivery rates

Dietary Supplements and Sports Performance: Herbals

This is the fourth in a series of six articles to discuss the major classes of dietary supplements (vitamins; minerals; amino acids; herbs or botanicals; metabolites, constituents/extracts, or combinations). The major focus is on efficacy of such dietary supplements to enhance exercise or sport performance

Communication Impairments in Mice Lacking Shank1: Reduced Levels of Ultrasonic Vocalizations and Scent Marking Behavior

Autism is a neurodevelopmental disorder with a strong genetic component. Core symptoms are abnormal reciprocal social interactions, qualitative impairments in communication, and repetitive and stereotyped patterns of behavior with restricted interests. Candidate genes for autism include the SHANK gene family, as mutations in SHANK2 and SHANK3 have been detected in several autistic individuals. SHANK genes code for a family of scaffolding proteins located in the postsynaptic density of excitatory synapses. To test the hypothesis that a mutation in SHANK1 contributes to the symptoms of autism, we evaluated Shank1−/− null mutant mice for behavioral phenotypes with relevance to autism, focusing on social communication. Ultrasonic vocalizations and the deposition of scent marks appear to be two major modes of mouse communication. Our findings revealed evidence for low levels of ultrasonic vocalizations and scent marks in Shank1−/− mice as compared to wildtype Shank1+/+ littermate controls. Shank1−/− pups emitted fewer vocalizations than Shank1+/+ pups when isolated from mother and littermates. In adulthood, genotype affected scent marking behavior in the presence of female urinary pheromones. Adult Shank1−/− males deposited fewer scent marks in proximity to female urine than Shank1+/+ males. Call emission in response to female urinary pheromones also differed between genotypes. Shank1+/+ mice changed their calling pattern dependent on previous female interactions, while Shank1−/− mice were unaffected, indicating a failure of Shank1−/− males to learn from a social experience. The reduced levels of ultrasonic vocalizations and scent marking behavior in Shank1−/− mice are consistent with a phenotype relevant to social communication deficits in autism.National Institute of Mental Health (U.S.) (Intramural Research Program)Simons Foundatio

A double-blind, randomized clinical trial of dietary supplementation on cognitive and immune functioning in healthy older adults

BACKGROUND: Declining cognitive function is relatively common and increasingly prevalent. Studies have shown that different nutrients (e.g., Ginkgo biloba and vitamin E) appear to be effective at improving memory and concentration, while less is known about their effect on immunity. METHODS: This study investigated the effect of Ginkgo Synergy® plus Choline (n = 33) and OPC Synergy® plus Catalyn® (n = 31) versus placebo (n = 33) in a 6-month, randomized, double-blind trial on cognitive and immune functioning among English-speaking, non-smoking, healthy older adults. The Stroop Color and Word Test, Trail Making Test A and B, Controlled Oral Word Association, Hopkins Verbal Learning, Mini-Mental State Exam, and Digit Symbol were administered at baseline and 3 and 6 months follow-up to assess cognitive functioning. Cytokines and growth factors were measured at baseline and 6 months to assess inflammation and immune functioning. Data were analyzed with linear mixed modeling. RESULTS: No serious adverse events were noted in this study. According to time on the Trail Making Test-B, the Ginkgo Synergy® plus Choline arm showed improvement from baseline to 3 months follow-up (mean difference = 24.2; SE = 6.4; 95% CI: 8.6, 39.7; p = 0.01). On the Controlled Oral Word Association Trial-S, the scores significantly increased for the Ginkgo Synergy® plus Choline arm from baseline to 6 months follow-up (mean difference = 2.1; SE = 0.8; 95% CI: 0.2, 3.9; p < 0.05) and for the OPC Synergy® plus Catalyn® arm from baseline to 3 months follow-up (mean difference = 2.1; SE = 0.8; 95% CI: 0.2, 4.0; p < 0.05). Epidermal growth factor significantly decreased from baseline to 6 months follow-up for the Ginkgo Synergy® plus Choline arm (mean difference = 120.7; SE = 28.4; 95% CI: 62.6, 178.8; p < 0.001). CONCLUSIONS: Our study showed isolated and modest effects of a Ginkgo biloba plus choline-based formula on cognitive and immune functioning among healthy older adults with no history of significant cognitive deficits. Our trial was registered with clinicaltrials.gov (ID: NCT01672359). This study was supported by a grant from Standard Process, Inc

Complementary and alternative medicine: attitudes, knowledge and use among surgeons and anaesthesiologists in Hungary

BACKGROUND: Despite their worldwide popularity the question of using non-conventional treatments is a source of controversy among medical professionals. Although these methods may have potential benefits it presents a problem when patients use non-conventional treatments in the perioperative period without informing their attending physician about it and this may cause adverse events and complications. To prevent this, physicians need to have a profound knowledge about non-conventional treatments. METHODS: An anonymous questionnaire was distributed among surgeons and anaesthesiologists working in Hungarian university clinics and in selected city or county hospitals. Questionnaires were distributed by post, online or in person. Altogether 258 questionnaires were received from 22 clinical and hospital departments. RESULTS: Anaesthesiologists and surgeons use reflexology, Traditional Chinese Medicine, herbal medicine and manual therapy most frequently in their clinical practice. Traditional Chinese Medicine was considered to be the most scientifically sound method, while homeopathy was perceived as the least well-grounded method. Neural therapy was the least well-known method among our subjects. Among the subjects of our survey only 3.1 % of perioperative care physicians had some qualifications in non-conventional medicine, 12.4 % considered themselves to be well-informed in this topic and 48.4 % would like to study some complementary method. Women were significantly more interested in alternative treatments than men, p = 0.001427; OR: 2.2765. Anaesthesiologists would be significantly more willing to learn non-conventional methods than surgeons. 86.4 % of the participants thought that non-conventional treatments should be evaluated from the point of view of evidence. Both surgeons and anaesthesiologists accept the application of integrative medicine and they also approve of the idea of teaching these methods at universities. CONCLUSIONS: According to perioperative care physicians, non-conventional methods should be evaluated based on evidence. They also expressed a willingness to learn about those treatments that meet the criteria of evidence and apply these in their clinical practice

Global lake responses to climate change

Climate change is one of the most severe threats to global lake ecosystems. Lake surface conditions, such as ice cover, surface temperature, evaporation and water level, respond dramatically to this threat, as observed in recent decades. In this Review, we discuss physical lake variables and their responses to climate change. Decreases in winter ice cover and increases in lake surface temperature modify lake mixing regimes and accelerate lake evaporation. Where not balanced by increased mean precipitation or inflow, higher evaporation rates will favour a decrease in lake level and surface water extent. Together with increases in extreme-precipitation events, these lake responses will impact lake ecosystems, changing water quantity and quality, food provisioning, recreational opportunities and transportation. Future research opportunities, including enhanced observation of lake variables from space (particularly for small water bodies), improved in situ lake monitoring and the development of advanced modelling techniques to predict lake processes, will improve our global understanding of lake responses to a changing climate