Signs Of Malaise Research Articles

Discovery, development, and clinical proof of mechanism of LY3463251, a long-acting GDF15 receptor agonist

GDF15 and its receptor GFRAL/RET form a non-homeostatic system that regulates food intake and body weight in preclinical species. Here, we describe a GDF15 analog, LY3463251, a potent agonist at the GFRAL/RET receptor with prolonged pharmacokinetics. In rodents and obese non-human primates, LY3463251 decreased food intake and body weight with no signs of malaise or emesis. In a first-in-human study in healthy participants, single subcutaneous LY3463251 injections showed a safety and pharmacokinetic profile supporting further clinical development with dose-dependent nausea and emesis in a subset of individuals. A subsequent 12-week multiple ascending dose study in overweight and obese participants showed that LY3463251 induced significant decreases in food intake and appetite scores associated with modest body weight reduction independent of nausea and emesis (clinicaltrials.gov: NCT03764774). These observations demonstrate that agonism of the GFRAL/RET system can modulate energy balance in humans, though the decrease in body weight is surprisingly modest, suggesting challenges in leveraging the GDF15 system for clinical weight-loss applications.

Canine imaging self-assessment

Companion Animal Vol 17 June 2012 21 © 2012 Blackwell Publishing Ltd A 12-year-old male entire Shih Tzu presented with an intermittent history of bloody urethral discharge, dysuria, dyschezia and an increase in frequency of licking his prepuce. There was no pollakiuria, no gross haematuria and defecation was normal frequency and faecal consistency. He was bright and alert and no weight loss or other signs of malaise had been noticed.

Cuba's “Equity without Growth” Dilemma and the 2011 Lineamientos

AbstractCuba faces a development dilemma: it promotes equity and human capital while failing to deliver economic growth. For the government, the country's equity and human capital achievements are a source of pride, a sign that its priorities are right. This essay argues instead that this “equity without growth” dilemma is a sign of malaise. Theory and evidence suggest that high levels of equity and human capital should produce high levels of economic growth. Because growth is often weak or negative, some onerous barriers to development must be present. These barriers, it is argued, are restrictions on property and political rights. By comparing Cuba and China across two sectors, the bicycle industry and Internet access, this article shows how these restrictions have hindered growth. It also assesses how Cuba's latest economic reforms, the so-calledLineamientos, will address Cuba's development dilemma. The impact may be minimal, but perhaps more lasting than previous reforms.

Renal Cell Carcinoma: A Rare Metastasis to the Tongue – A Case Report

This paper describes the diagnosis and treatment of a patient who presented with a lesion on the left posterior scalp, who was also experiencing more generalized signs of malaise. Biopsy led to the diagnosis of renal cell carcinoma and additional lesions developed in the tongue. About 1% of all malignancies found in the oral cavity are metastatic. Metastases to the head and neck are uncommon but should always be considered among the differential diagnoses of lesions.

Mice acquire flavor preferences during shipping

Vigorous motion can cause rodents to develop flavor aversions and show other signs of malaise. We tested whether a flavor aversion could be induced by shipping mice from an animal breeder to a test site. Boxes of 12 male C57BL/6J mice were shipped ∼950 km from Bar Harbor, ME to Philadelphia, PA by truck. For some boxes, the gel provided for hydration was flavored with almond and for others it was flavored with banana. After the journey, the mice were individually housed and allowed to recover for 5 days. They then received a choice between the two flavors of gel. Contrary to expectations, mice preferred the flavor they had previously ingested during shipping. Controls given flavored gel under similar conditions but while stationary did not show a preference. These results suggest that mice find shipping or its sequelae pleasurable. If mice are travel sick this must be inconsequential relative to other components of the shipping experience.

A parvo-like virus in cultured redclaw crayfish Cherax quadricarinatus from Queensland, Australia.

In the summer of 1999/2000, an epizootic occurred in cultured juvenile redclaw crayfish Cherax quadricarinatus on one commercial crayfish farm in northern Queensland, Australia. Mortalities occurred over 4 wk, with up to 96% cumulative mortalities in 2 earthen ponds stocked with juveniles. The crayfish were weak, anorexic and lethargic. A transmission trial was conducted, using filtered, cell-free extract prepared from infected crayfish as inoculum. The disease was reproduced, with on-going mortalities occurring in inoculated crayfish over 55 d. Experimentally inoculated crayfish showed gross signs of malaise, anorexia and disorientation before dying. Two types of intranuclear inclusion bodies (INIBs) were seen in tissues of endodermal, ectodermal and mesodermal origin by light microscopy with haematoxylin and eosin (H&E) stained sections. 'Early'-stage INIBs were eosinophilic, rounded and located centrally within slightly enlarged nuclei while 'late'-stage INIBs were well-rounded and deeply basophilic. The gills, cuticular epithelium and epithelial cells of the foregut, midgut and hindgut were the most heavily infected tissues. By transmission electron microscopy, virions with an average diameter of 19.5 nm were seen within electron-dense granular inclusion bodies within enlarged nuclei of both naturally and experimentally infected crayfish. The size of the virions and cytopathology are consistent with characteristics of viruses in the Family Parvoviridae. This is the first reported case of mass mortality caused by a parvo-like virus infection in C. quadricarinatus.

Conditioning to ethanol in the fruit fly—a study using an inhibitor of ADH

To identify processes involved in the choice of ethanol by adult Drosophila, flies homozygous Adh F, reared in the absence of alcohol were placed in contact with: a) an ethanol-free medium, b) a medium containing ethanol, c) a medium supplemented with 4-methylpyrazole (4-MP, an inhibitor of the ADH pathway), d) a medium containing ethanol and 4-MP. The choice of ethanol over a medium without ethanol was evaluated by measuring the duration of extension of the proboscis of the flies in each of the media. A slight preference for the ethanol-supplemented medium was observed in the naive flies, which was enhanced by previous exposure to ethanol. Exposure to ethanol and 4-MP, however, led to an avoidance of ethanol. There was a reduction in ADH activity on treatment of the flies with 4-MP, and signs of malaise (reduced locomotor activity, loss of balance) were observed in the flies who ingested both ethanol and inhibitor. We concluded that the preference for ethanol stems from an associative learning related to ethanol utilization. Inhibition of enzymes of ADH pathway led to a conditioned aversion due to disturbance of ethanol metabolism giving rise to malaise.

MIT's Faustian Bargain: Signs of Malaise

MIT's Faustian Bargain: Signs of Malaise

MIT's Faustian Bargain: Signs of Malaise

MIT's Faustian Bargain: Signs of Malaise

MIT's Faustian Bargain: Signs of Malaise

MIT's Faustian Bargain: Signs of Malaise

Pulmonary Toxicity of Antineoplastic Drugs

Pulmonary toxicity caused by antineoplastic drugs is becoming a more frequently recognized entity, and the number of drugs known or suspected of causing this disease is steadily increasing. In general, the initial clinical appearance includes both constitutional signs of malaise and fever, as well as pulmonary complaints. Some clinical signs may suggest a particular drug as the cause. The pathological condition also is generally nonspecific, but some clues may be present histologically that help define the causal agent. This is a review of the antineoplastic drugs that are associated with pulmonary toxicity. Clinical, laboratory, and pathological data are presented as useful information for practicing physicians. Although therapeutic maneuvers are limited, these are discussed with regard to each drug.