Effects of Serum, Enzyme, Thiol and Forced Degradation on the Stabilities of αO-Conotoxin GeXIVA[1,2] and GeXIVA[1,4]

Abstract

αO-conotoxin GeXIVA, which is a potent antagonist of α9α10 nicotinic acetylcholine receptor (nAChR), is of great interest as a potential analgesic for chronic neuropathic pain. It has three isomers, of which both GeXIVA[1,2] and GeXIVA[1,4] showed similar low nanomolar IC₅₀s in potent blocking rat α9α10 nAChRs. Here, we first reported stabilities of GeXIVA[1,2] and GeXIVA[1,4] in various biochemical circumstances, including human serum, enzymatic degradation and thiol, which would be the key factors to affect stabilities of the two isomers in vivo. Simultaneously, forced degradation was carried out to evaluate stabilities of the two isomers. GeXIVA[1,2] and GeXIVA[1,4] were unstable when they were incubated in serum and digestive enzymes at 37°C. Their disulfide bond frameworks were easy to be scrambled in GSH and HSA. For different stress conditions, their stabilities were impacted greatly by oxidation, temperature and alkaline conditions. The results may provide a foundation for storage conditions, structural modification and pharmaceutical preparation of GeXIVA[1,2] and GeXIVA[1,4].

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αO-conotoxin GeXIVA is of great interest as a potential analgesic for chronic neuropathic pain. The stabilities of GeXIVA were evaluated at the first time, which may provide a foundation for storage conditions, structural modification and pharmaceutical preparation of GeXIVA.

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Gender Differences in Leadership Aspirations and Job and Life Attribute Preferences among U.S. Undergraduate Students

Abstract

The purpose of the present study was to examine gender differences in constructs associated with leadership aspirations in a sample of 467 undergraduate students because these might contribute to the gender gap in leadership attainment. The results demonstrated that female participants perceived themselves as having less leadership ability than male participants, and viewed their attainment of leadership roles as less likely than male participants did, which could reflect anticipated discrimination. Female participants reported less interest than male participants in elite leadership positions (e.g., CEO, senator), and associated positive characteristics with such roles less than male participants. They were also less likely than male participants to indicate a willingness to accept a promotion that would require them to sacrifice enjoyable work. Male and female participants ranked the importance of a variety of job and life attribute preferences similarly, though female participants emphasized the importance of life attribute preferences (e.g., family, good health), whereas male participants emphasized the importance of job attribute preferences (e.g., high salary). Finally, male participants were more likely than female participants to expect and prefer that they would out-earn their future spouses. These results highlight the need for greater consideration of how young women's and men's leadership aspirations and job/life preferences contribute to the gender gap in leadership attainment.

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Number 2 Feibi Recipe Reduces PM2.5-Induced Lung Injury in Rats

Air pollution is the main cause of respiratory diseases. Fine particulates with the diameter below 2.5 μm can get into the alveoli and then enter the blood circulation through the lung tissue ventilation function and cause multiple systemic diseases especially the respiratory diseases. This study investigated the pathological mechanism of the lungs injury in rats induced by PM2.5 and the effect and mechanism of the Chinese herbal medicine number 2 Feibi Recipe (number 2 FBR) on lungs injury. In this experiment, Wistar rats were used. Lungs injury was induced by PM2.5. Number 2 FBR was used to treat the rats. The result showed that number 2 FBR could improve the lung injury in the rats. Meanwhile, it significantly reduced pathological response and inflammatory mediators including interleukin-6 (IL-6), interleukin-13 (IL-13), interleukin-17 (IL17), monocyte chemotactic protein-1 (MCP-1), and transforming growth factor-α (TNF-α) and upregulated glutathione peroxidase (GSH-Px) in the PM2.5 induced lung injury in the rats. Collectively, number 2 FBR appears to attenuate the lungs injury in rats induced by PM2.5.

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New WHO classification of pituitary adenomas (4th edition): assessment of pituitary transcription factors and the prognostic histological factors

Abstract

WHO classification of pituitary adenomas was revised in 2017. The two major and significant changes are discussed. (1) The new classification focuses on adenohypophysial-cell lineage for the designation of adenomas, and thus, assessment of pituitary transcription factors is recommended. Its appropriate use has a complementary role in obtaining an accurate diagnosis, particularly in hormone-negative adenomas. Subclassification of nonfunctioning adenomas was revised accordingly and, consequently, null cell adenomas became quite rare. (2) "Atypical adenoma", a previous category, was eliminated due to the poor reproducibility and predictive value. Assessment of tumor proliferation marker and other clinical parameters such as invasion are recommended to predict aggressiveness. "High-risk adenomas" are those with rapid growth, radiological invasion, and a high Ki-67 proliferation index, whereas some special adenoma subtypes commonly show aggressive behavior.

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Increased Micronuclei Frequency in Oral and Lingual Epithelium of Treated Diabetes Mellitus Patients

Diabetes mellitus (DM) is a metabolic disease characterized by persistent high levels of glucose in plasma. Chronic hyperglycemia is thought to increase oxidative stress and the formation of free radicals that in turn damage cells. Thus, we decided to determine the frequency of nuclear abnormalities in epithelial cells from cheek and tongue mucosa of DM patients with type 1 (DM1, treated only with insulin) and type 2 (DM2, treated with metformin) using the buccal micronucleus cytome (BMCyt) assay. Micronuclei frequency in cheek epithelial cells was higher in both DM1 ( ± ,) and DM2 ( ± ,) patients, as compared to healthy controls (0.07  ±  0.06). Similarly, micronuclei frequency in tongue epithelium was increased in DM1 (0.81  ±  0.22, ) and DM2 (0.41  ±  0.21, ) groups, in comparison to controls (0.06  ±  0.05). Besides, we found a positive correlation between micronuclei frequency and the onset time of DM2 in both cheek (ρ = 0.69, ) and tongue epithelial cells (ρ = 0.71, ), but not with onset time of DM1 or age of the patients. Considering all this, we pose that BMCyt could serve as a fast and easily accessible test to assess genotoxic damage during dental visits of DM patients, helping to monitor their disease.

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Prospective blinded surveillance screening of Swedish women with increased hereditary risk of breast cancer

Abstract

Purpose

To evaluate the sensitivity and specificity of different screening modalities in women with a family history of breast cancer.

Methods

Our blinded, prospective, comparative cohort analysis included three types of screening, mammography, ultrasound, and clinical breast examination once per year for 6 years. Eligible patients for this study were healthy women with ≥ 17% lifetime risk of breast cancer or with a mutation in BRCA1 or BRCA2.

Results

A total of 632 women were screened between 2002 and 2012 (each for 6 years). During the study, 30 women were diagnosed with breast cancer, with 10 of these diagnoses occurring between screening visits, and six of the 10 diagnosed women were gene carriers. The clinical presentation for the women diagnosed with breast cancer was followed until 2017. No consistent patterns for the diagnostic capacity of the different screening modalities were found, although mammography showed low sensitivity, whereas ultrasound showed better sensitivity in three of the six rounds. The specificity was high in mammography and improved in ultrasound over time. Most importantly, clinical breast examination provided no additional information toward the diagnosis of breast cancer.

Conclusion

Neither mammography nor ultrasound performed yearly were sensitive enough as standalone modalities, although high specificity was confirmed. Our findings indicate that high risk (> 29% life time risk) individuals and gene carriers can be screened biannually, using the same protocol as used in mutation carriers. Our results also suggest that low-risk groups (< 20%) may continue to be referred to population mammography screening program, while clinical breast examination may be omitted in all risk groups, and could be optional in gene carriers.

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Pushing the Envelope in Perihiler Cholangiocellularcarcinoma Surgery: TIPE-ALPPS

No abstract available

http://ift.tt/2Awz419