Effects of prolonged exposure to low dose metformin in thyroid cancer cell lines

© Ivyspring International Publisher. Background: Thyroid cancer is generally associated with an excellent prognosis, but there is significant long-term morbidity with standard treatment. Some sub-types however have a poor prognosis. Metformin, an oral anti-diabetic drug is shown to have anti-cancer effects in several types of cancer (breast, lung and ovarian cancer). The proposed mechanisms include activation of the Adenosine Mono-phosphate-activated Protein Kinase (AMPK) pathway and inhibition of the mTOR pathway (which promotes growth and proliferation). By inhibiting hepatic gluconeogenesis and increasing glucose uptake by muscles, metformin decreases blood glucose and circulating Insulin levels. Aims: Explore the effect of metformin on the growth and proliferation of thyroid cancer cell lines. Methods: The effects of metformin on thyroid cancer cell lines (FTC-133, K1E7, RO82-W-1, 8305C and TT) and normal thyroid follicular cells (Nthy-ori 3-1) were investigated using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay for cell proliferation; clonogenic assays FACS analysis for apoptosis and cell cycle, H2A.X phosphorylation (γH2AX) assay for DNA repair and scratch assay for cell migration. Results: Metformin inhibited cell proliferation and colony formation at 0.03 mM and above and inhibited cell migration at 0.3 mM. At concentrations of 0.1 mM and above metformin increased the percentage of apoptotic cells and induced cell cycle arrest in G0/G1 phase at minimum concentration of 0.3 mM. Unlike previous reports, no effect on DNA repair response was demonstrated. Conclusion: Metformin suppressed growth of all thyroid cancer cell lines, at concentrations considered to be within in the therapeutic range for diabetic patients on metformin (<0.3 mM)

Forme atypique d’une maladie de Lyme

La maladie de Lyme est une zoonose qui se manifeste essentiellement par des signes cutanés, articulaires, neurologiques et cardiaques. Elle peut exceptionnellement mimer une dermatomyosite. Nous rapportons l'observation d'une patiente âgée de 37 ans qui a présenté des myalgies et un érythroedème de la face et en péri-orbitaire. Une dermatomyosite a été fortement suspectée devant une élévation des enzymes musculaires. Elle a été traitée par une corticothérapie à forte dose. L'évolution a été marquée par l'aggravation des myalgies et l'apparition d'un déficit musculaire. Elle a été alors hospitalisée dans notre service. Les enzymes musculaires étaient élevées. L'électromyogramme était sans anomalies. Le bilan immunologique était négatif. Une enquête infectieuse a été réalisée retrouvant une sérologie de Lyme positive. Après administration d'une antibiothérapie adaptée, l'évolution était bonne avec disparition du tableau clinico-biologique de dermatomyosite. La précocité du diagnostic et l'instauration d'un traitement efficace permet d'éviter des complications graves

Difficulté diagnostique d’une tuberculose laryngée isolée chez une femme diabétique

La tuberculose laryngée isolée est rare. Elle peut mimer une tumeur maligne retardant le diagnostic et aggravant le pronostic. Le terrain diabétique favorise la survenue des infections notamment la tuberculose dans sa forme sévère. Nous rapportons l'observation d'une patiente diabétique de type 2, âgée de 51 ans, hospitalisée pour une fièvre prolongée, une dysphonie et un diabète déséquilibré. Les hémocultures étaient négatives. L'examen laryngoscopique a confirmé un aspect érythémateux et épais des deux cordes, une lésion ulcérée peu profonde de l'hémilarynx gauche et une végétation érythémateuse de 5 mm de diamètre. L'examen histologique a révélé des granulomes épithéloïodes et giganto-cellulaires avec une nécrose caséeuse évocateurs de la tuberculose. La culture sur milieu de lobstein de tissus biopsiés à partir des cordes vocales a été positive. Aucun autre foyer tuberculeux n'a été retrouvé. Le traitement par une combinaison de l'isoniazide, la rifampicine, l'éthambutol, la pyrazinamide a permis une résolution de symptôme

CCAP regulates feeding behavior via the NPF pathway in Drosophila adults

The intake of macronutrients is crucial for the fitness of any animal and is mainly regulated by peripheral signals to the brain. How the brain receives and translates these peripheral signals or how these interactions lead to changes in feeding behavior is not well-understood. We discovered that 2 crustacean cardioactive peptide (CCAP)-expressing neurons in Drosophila adults regulate feeding behavior and metabolism. Notably, loss of CCAP, or knocking down the CCAP receptor (CCAP-R) in 2 dorsal median neurons, inhibits the release of neuropeptide F (NPF), which regulates feeding behavior. Furthermore, under starvation conditions, flies normally have an increased sensitivity to sugar; however, loss of CCAP, or CCAP-R in 2 dorsal median NPF neurons, inhibited sugar sensitivity in satiated and starved flies. Separate from its regulation of NPF signaling, the CCAP peptide also regulates triglyceride levels. Additionally, genetic and optogenetic studies demonstrate that CCAP signaling is necessary and sufficient to stimulate a reflexive feeding behavior, the proboscis extension reflex (PER), elicited when external food cues are interpreted as palatable. Dopaminergic signaling was also sufficient to induce a PER. On the other hand, although necessary, NPF neurons were not able to induce a PER. These data illustrate that the CCAP peptide is a central regulator of feeding behavior and metabolism in adult flies, and that NPF neurons have an important regulatory role within this system

The Drosophila ETV5 Homologue Ets96B: Molecular Link between Obesity and Bipolar Disorder

Several reports suggest obesity and bipolar disorder (BD) share some physiological and behavioural similarities. For instance, obese individuals are more impulsive and have heightened reward responsiveness, phenotypes associated with BD, while bipolar patients become obese at a higher rate and earlier age than people without BD; however, the molecular mechanisms of such an association remain obscure. Here we demonstrate, using whole transcriptome analysis, that Drosophila Ets96B, homologue of obesity-linked gene ETV5, regulates cellular systems associated with obesity and BD. Consistent with a role in obesity and BD, loss of nervous system Ets96B during development increases triacylglyceride concentration, while inducing a heightened startle-response, as well as increasing hyperactivity and reducing sleep. Of notable interest, mouse Etv5 and Drosophila Ets96B are expressed in dopaminergic-rich regions, and loss of Ets96B specifically in dopaminergic neurons recapitulates the metabolic and behavioural phenotypes. Moreover, our data indicate Ets96B inhibits dopaminergic-specific neuroprotective systems. Additionally, we reveal that multiple SNPs in human ETV5 link to body mass index (BMI) and BD, providing further evidence for ETV5 as an important and novel molecular intermediate between obesity and BD. We identify a novel molecular link between obesity and bipolar disorder. The Drosophila ETV5 homologue Ets96B regulates the expression of cellular systems with links to obesity and behaviour, including the expression of a conserved endoplasmic reticulum molecular chaperone complex known to be neuroprotective. Finally, a connection between the obesity-linked gene ETV5 and bipolar disorder emphasizes a functional relationship between obesity and BD at the molecular level

New records of soil mites (Acari) from citrus orchards of Tunisia

An inventory of soil mites from citrus orchards was carried out in four localities situated in the regions of Mornag and Bizerte, northern Tunisia. The soil sampling was performed monthly under the canopy throughout the two years of the study (2016 and 2017). A total of 31 species of mites belonging to 20 families were identified. The acari fauna was predominantly composed of Oribatida followed by Mesostigmata mites. The most frequent and abundant Oribatida families were Oribatulidae and Phenopelopidae, while Parasitidae, Laelapidae and Pachylaelapidae were the predominant families of Mesostigmata

ХАРАКТЕРИСТИКА СКЛАДУ МІКРОФЛОРИ КИШЕЧНИКА У ХВОРИХ З ДІАРЕЄЮ ТА ПІДОЗРОЮ НА CLOSTRIDIUM DIFFICILE-ІНФЕКЦІЮ

The qualitative and quantitative composition of the microflora in the gastrointestinal tract may vary depending on various factors. However, inflammatory processes that will foster the development of such an endogenous infection as Clostridium difficile infection (CDI) may take place in the mucous membrane. The aim – to study the nature of changes in the qualitative and quantitative composition of the intestinal microflora in patients with possible CDI. Materials and Methods. The bacteriological method has been used to examine samples of biotic material (faeces) received from 73 patients with clinical manifestations of CDI. The given samples have been subjected to dysbacteriosis examination and the presence of a CDI pathogen tests. Results. The pathogen of C. difficile was isolated in 9.7 % of patients with diarrhea and possible CDI during the examination. Dysbiotic disorders of the intestinal microflora were detected in all patients without exception. The character of microflora abnormalities in both groups corresponded to grade 2 and 3 in severity. The patients with C.&nbsp;difficile showed a reduced number of representatives of normobiocenosis 10 times or more, the prevalence of coccal forms in the total number of microbes and an increase of Candida fungi in the number. It is recommended to include drugs aimed at eliminating the pathogen (metronidazole, fidaxomycin, etc.) or to carry out fecal microbiota transplantation in the schemes of correction of the intestinal microflora in patients with diarrhea in case if C. difficile is detected in their faecesКачественный и количественный состав микрофлоры кишечника в желудочно-кишечном тракте может меняться в зависимости от разных причин. При этом могут возникать воспалительные процессы в слизистой оболочке, которые будут способствовать развитию такой эндогенной инфекции, как Clostridium difficile-инфекция (CDI). Цель – изучить характер изменений качественного и количественного состава микрофлоры кишечника у пациентов с подозрением на CDI. Материал и методы. Бактериологическим методом проведено исследование образцов фекалий, отобранных от 72 пациентов с клиническими проявлениями CDI. Полученные пробы были исследованы на дисбактериоз и наличие возбудителя CDI. Результаты. При обследовании больных с диареей и подозрением на СDІ возбудитель C.&nbsp;difficile был обнаружен у 9,7 %. Дисбиотические нарушения состояния микрофлоры кишечника выявлены у всех пациентов. Характер изменений в обеих группах соответствовал 2 и 3 степеням тяжести. У пациентов с выделенной C.&nbsp;difficile выявлено уменьшение количества представителей нормобиоценоза в 10 и более раз, преобладание кокковых форм в общем количестве микробов и увеличение количества грибов рода Candida. В схемы коррекции состояния микрофлоры кишечника у больных с диареей, в фекалиях которых выделено C.&nbsp;difficile, целесообразно включать препараты, направленые на элиминацию возбудителя (метронидазол, фидаксомицин и др.) или проводить трансплантацию фекальной микробиоты.Якісний та кількісний склад мікрофлори у шлунково-кишковому тракті може змінюватись у залежності від різних чинників. При цьому в слизовій оболонці можуть виникати запальні процеси, які сприятимуть розвитку такої ендогенної інфекції, як Clostridium difficile-інфекція (CDI). Мета – вивчити характер змін якісного та кількісного складу мікрофлори кишечника у хворих з підозрою на CDI. Матеріал і методи. Бактеріологічним методом досліджено зразки біотичного матеріалу (фекалії), відібрані від 73 хворих з клінічними проявами CDI. Отримані проби підлягали дослідженню на дисбактеріоз та наявність збудника CDI. Результати. При обстеженні хворих з діареєю та підозрою на СDІ збудник C.&nbsp;difficile було виділено у 9,7&nbsp;%. Дисбіотичні порушення складу мікрофлори кишечника виявлені у всіх без винятку пацієнтів. Характер порушень мікрофлори в обох групах відповідав 2 та 3 ступеням тяжкості. У пацієнтів з наявністю C.&nbsp;difficile виявлено знижену кількість представників нормобіоценозу в 10 і більше разів, переважання кокових форм у загальній кількості мікробів та підвищення кількості грибів роду Candida. У схеми корекції стану мікрофлори кишечника хворих з діареями, у фекаліях яких виявлено C.&nbsp;difficile, доцільно включати препарати, направлені на елімінацію збудника (метронідазол, фідаксоміцин тощо) або проводити трансплантацію фекальної мікробіоти

Caregiver delivered sensory electrical stimulation for post stroke upper limb spasticity: A single blind crossover randomized feasibility study

We developed a 64 channel sensory electrical stimulator which delivers a dynamic and variable ‘Sensory Barrage’ Stimulation (SBS). Our aim was to assess the feasibility of caregivers delivering the stimulation in the community for a clinical trial comparing single channel Transcutaneous Electrical Nerve Stimulation (TENS) with SBS for post stroke upper limb spasticity. We trained caregivers of 16 participants with post stroke upper limb spasticity to sequentially administer SBS and TENS for 60 min daily for four weeks each, with a washout period of two weeks in between. Outcome measures tested were recruitment and retention rates, compliance with interventions and daily recording of Participant -reported Numerical Rating Scale (NRS). We also collected results of Action Research Arm Test (ARAT), Leeds Arm Spasticity Impact Scale (LASIS) and Modified Ashworth Scale (MAS) for spasticity. Out of 21 potential participants, 16 consented and 15 completed the protocol. Ten participants received TENS for 80% (23/28) of the intended hours. Eleven participants completed NRS for at 80% (45/56) of the study days. All participants attended all visits. The MAS reduced by at least one in five participants after SBS and in three after TENS. Minimal Clinically Important Difference (MCID) of four points increase in ARAT was seen in five participants following TENS, and in four following SBS. A MCID of 18% decrease in NRS was reported by eight participants after TENS and three after SBS. This study demonstrated the feasibility of undertaking a trial of sensory electrical stimulation for post-stroke spasticity with caregivers delivering intervention in community. The study was not powered to detect efficacy of the interventions. Trial registration number: NCT02907775.Date 20-9-2016

Evidence of superficial knowledge regarding antibiotics and their use: Results of two cross-sectional surveys in an urban informal settlement in Kenya

<div><p>We assessed knowledge and practices related to antibiotic use in Kibera, an urban informal settlement in Kenya. Surveys was employed at the beginning (entry) and again at the end (exit) of a 5-month longitudinal study of AMR. Two-hundred households were interviewed at entry, of which 149 were also interviewed at exit. The majority (>65%) of respondents in both surveys could name at least one antibiotic, with amoxicillin and cotrimoxazole jointly accounting for 85% and 77% of antibiotics mentioned during entry and exit, respectively. More than 80% of respondents felt antibiotics should not be shared or discontinued following the alleviation of symptoms. Nevertheless, 66% and 74% of respondents considered antibiotics effective for treating colds and flu in the entry and exit surveys, respectively. There was a high (87%, entry; 70% exit) level of reported antibiotic use (past 12 months) mainly for colds/flu, coughs and fever, with >80% of respondents obtaining antibiotics from health facilities and pharmacies. Less than half of respondents remembered getting information on the correct use of antibiotics, although 100% of those who did reported improved attitudes towards antibiotic use. Clinicians and community pharmacists were highly trusted information sources. Paired household responses (n = 149) generally showed improved knowledge and attitudes by the exit survey although practices were largely unchanged. Weak agreement (κ = -0.003 to 0.22) between survey responses suggest both that unintended learning had not occurred, and that participant responses were not based on established knowledge or behaviors. Targeted public education regarding antibiotics is needed to address this gap.</p></div