Tuesday, 17 October 2017

Implementation of a Solution for the Remote Monitoring of Subjects Affected of Metabolic Diseases: The Metabolink Project


Diabetesrepresents one of most serious public health disease. The aim of the Metabolink project was to develop a smart solution for elderly people with diabetes and obesity, in order to promote a healthier style of life, improve diabetic control trying to reduce overall cost for the community.
It consists of an app for Smartphone linked to a system and a process of data collection based on bi dimensional barcode (qr code) and NFC-tag technologies.
Thesystem was accepted by all the patients and they learned efficaciously in a few hours to use it. Unfortunately we observed a drop-out of about 50% in the first month. Patients remaining in the study refer a slight improvement in the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and General Satisfaction Questionnaire (GSQ) and they decided to continue to use it after the end of the follow-up.

The diabetes represents one of most serious public health disease for the planet. The WHO estimated about 60 million of subjects are affected in Europe. In Italy the rough prevalence is 5.8%. The prevalence of disease in the next years will grow both as a result of the aging of the population and to the increase of the risk factors such as overweight and obesity, sedentary lifestyle and lack of proper nutrition education. Milestone studies have shown that an intensive glycemic treatment significantly reduces microvascular complications with a moderate positive long-term effect on macrovascular complications. The health care systems are called to face this disease that it has not only direct cost linked to pharmacological and complications treatment but also an indirect significant social cost. It is therefore essential for the diabetic patient to carry out a continuous and accurate monitoring of clinically relevant parameters (as blood glucose, blood pressure) and to follow a health life style in order to reduce disease complications permitting to live better maintaining independence for much more longer time. Moreover the majority of patients with diabetes is older and frequently present significant comorbidity making the integrated management of the disease more complex. 

The aim of the Metabolink project was to develop a smart solution for elderly people with diabetes and obesity, in order to promote a healthier style of life, improve diabetic control (glcaemic control, blood pressure, adherence to a specific diet and treatment) trying to reduce overall cost for the community. The approval of the study for experiments using human subjects was obtained from the local Ethics Committees on human experimentation. Written informed consent for research was obtained from each patient or from relatives/legal guardian in the case of critically disabled demented patients prior to participation in the study.

Monday, 16 October 2017

Effect of Ginseng on the Testis of Subclinical Hypothyroidism Model in Adult Male Albino Rat

Hyperstimulation of follicular cells using a goitrogen Propylthiouracil (PTU) caused Subclinical Hypothyroidism (SCH) that was associated with disturbances in adult male testicular functions. This work was carried out to study the probable relationship between follicular cells in drug-induced hypothyroidism caused by PTU and consequently its effect on testicular tissue and the possible modulating effect of ginseng. The present work was carried out on 40 adult male albino rats divided into four groups. Group I was the control group; Group II (Ginseng treated); Group III (SCH group) rats and Group IV was the treated group. Testes and thyroid glands were studied. Our results revealed the protective role of Ginseng on testis and thyroid tissue of experimentally induced hypothyroidism rat model.

Thyroid hormone plays an important role in testicular development and function. It has been established that Triiodothyronine (T3) regulates the maturation and growth of the testis, controlling Sertoli cells and Leydig cell proliferation and differentiation during testicular development in rats and other species. Subclinical Hypothyroidism (SCH) could be considered as an elevated serum thyrotropic stimulating hormone (TSH) level associated with normal Thyroxine (T4) and Triiodothyronine (T3) levels with no clinical symptoms of hypothyroidism. This thyroid dysfunction occurs in 4-20% of the adult population, the possibility of SCH progression to clinical hypothyroidism is around 7% [2]. Hypothyroidism extremely affects reproductive functions including fertility, pregnancy and postnatal development in human and rat [3]. Rat SCH model was induced mostly by administration of antithyroid drug mostly Propylthiouracil (PTU) and Methimazole (MMI). PTU is a thiouracil-derived drug which can be used to treat hyperthyroidism through lowering the amount of thyroid hormone produced by the thyroid gland [5]. PTU inhibits conversion of T4 to T3 causing hypothyroidism [6]. Ginseng is considered as an aromatic herb that is commonly used in herbal medicine. It contains saponins and high iodine content. Ginseng saponins, which are known as ginsenosides, have been studied to be responsible for its medicinal effects, specifically anticancer, antihypertensive, antidiabetic, and antistress effects. Ginseng benefits all the endocrine system, and therefore the thyroid gland. As ginseng markedly increased epididymal sperm count, motility and hyperactivation in mice. So, we studied its effect on the testis and thyroid of SCH model.

Forty adult Westar male albino rats were used in this experiment, each weighting 150-200gm. Food and water were provided ad libitum and the rats were left for 7 days for acclimatization before use in the Anatomy Department, Faculty of medicine, Menoufia University. All aspects of animal care and treatment were carried out according to the local guidelines of the ethical committee for animal research.

Friday, 13 October 2017

Small-Molecule Inhibitors of the Mcl-1 Oncoprotein

Mcl-1, an anti-apoptotic member of the Bcl-2 protein family, has emerged as an especially attractive target for the development of next generation antineoplastics owing to its direct involvement in tumor genesis as well as its role in the resistance of many cancers to current anti-cancer therapies. The efficacy of Navitoclax against a range of different cancer models that are dependent on Bcl-xL and Bcl-2, two relatives of Mcl-1, indicates that the inhibition of Mcl-1 with small-molecules might also be a viable strategy to kill cancer cells by inducing apoptosis. Herein, we provide a comprehensive review of the most potent, Mcl-1 selective small-molecule inhibitors reported in the literature to date.

The Bcl-2 (B cell lymphoma 2) family of proteins, whose anti-apoptotic members include Bcl-2, Bcl-xL, Bcl-w, A1 and Mcl-1 (myeloid cell leukemia 1), are critical regulators of apoptosis, or programmed cell death. A hallmark of cancer is the evasion of apoptosis, and many cancers are resistant to apoptosis due to overexpression of one or more of the Bcl-2 family members. ABT-263 (Navitoclax), the clinical analogue of ABT-737, is a potent, dual inhibitor of Bcl-xL and Bcl-2, and is an effective killer of cancer cells over expressing these proteins. However, Navitoclax exhibits limited activity against Mcl-1, such that cancer cells overexpressing Mcl-1 or both Bcl-xL and Mcl-1 are resistant to the drug. Over expression of the Mcl-1 protein and/or amplification of the Mcl-1 gene have been linked to a variety of human cancers, including lung, breast, pancreatic, cervical and ovarian cancers, as well as leukemia and lymphoma. Mcl-1 overexpression is directly responsible for the emerging resistance of various FDA-approved anti-cancer therapies, including vincristine, Taxol, gemcitabine and cisplatin. Importantly, down regulation of Mcl-1 by RNAi decreases tumor-igenicity in mouse xenograft models. Taken together, these observations suggest that the inhibition of Mcl-1 by small-molecules might provide an alternative strategy to kill cancer cells by inducing apoptosis. With this in mind, the focus of this mini-review is on selective small-molecule inhibitors of the Mcl-1 protein; small-molecule inhibitors of Bcl-2, Bcl-xL and dual Bcl-xL/Mcl-1 inhibitors are reviewed elsewhere.

Like the other anti-apoptotic Bcl-2 proteins, there is a hydrophobic grove on the surface of Mcl-1 that engages the BH3 “death” domains of the pro-apoptotic Bcl-2 proteins, such as Bim, Bak and Bad. The BH3 domain is an amphipathic α-helix whose hydrophobic face recognizes four hydrophobic sub-pockets, p1, p2, p3 and p4, in the BH3-binding groove on Mcl-1, while a critical Asp on the polar face of the BH3 helix binds Arg263 of Mcl-1. Figure 1A shows the crystal structure of the Bim-BH3–Mcl-1 complex, and Figure 1B is the BH3-binding groove on the surface of Mcl-1 with key binding regions and residues highlighted. Through this protein–protein interaction (PPI), Mcl-1 (and the other anti-apoptotic Bcl-2 proteins) “neutralizes” the cell-killing function of the pro-apoptotic Bcl-2 proteins. In this way, overexpression of Mcl-1 leads to the evasion of apoptosis and, hence, cancer. Small-molecules that can block this PPI through binding the hydrophobic groove on Mcl-1 are expected to counter this neutralization and allow the pro-apoptotic proteins to kill the cancer cell through restoring apoptosis. Dual Bcl-xL/ Mcl-1 inhibitors have been reported for about ten years, and these compounds are predicted and/or known to bind in some or all of these sub-pockets. Although Bcl-xL-selective inhibitors, such as ABT- 737, have been identified, there have been limited advances towards the development of Mcl-1-selective inhibitors. In the last 18 months, however, some exciting advances have been made. This mini-review reports the recent progress in the discovery of small-molecules that selectively inhibit the Mcl-1 oncoprotein.

Wednesday, 11 October 2017

Clinical Asthma Phenotypes; A Challenging but Promising Spectrum


Asthma is a common, chronic and heterogeneous syndrome, affecting people of all ages, all races and both sexes. In recent years, it has become clearly apparent that asthma management must be individualized and tailored not only to the severity of the disease but also, importantly, to the phenotypic characteristics of the patient. Researchers have tried to define asthma phenotypes based on its clinical, physiologic and cellular parameters. Interestingly, tailoring asthma therapy according to the clinical phenotype is particularly crucial since asthma diagnosis is based mainly on clinical basis. Classification methods based on clinical features included those defined by symptoms (age at onset, natural history, severity), triggers (allergic versus non-allergic, exercise, viral), and treatment response. Other clinical asthma phenotypes included cough variant asthma and obese asthma phenotype.The addition of a genetic or blood biomarker could move a phenotype towards the evolving term of “endotype”, defined as a sub grouping of disease associated with distinct functional or pathologic mechanisms. Thus, verification of clinical asthma phenotypes by correlating them with their underlying genotypes and certain airway inflammatory biomarkers is extremely pivotal.
We have previously hypothesized an approach to classify asthma phenotypes based on validated symptomatology [Shortness of Breath (SOB), cough, wheezy phenotypes] in correlation with cytokine profile and airway inflammatory biomarkers aiming to detect their impact on asthma treatment. Our study described a wide variability in the baseline characteristics of the proposed clinical phenotypes in which the SOB phenotype group were found to have significant increase of total sIgE, soluble interleukin-2 receptor serum concentration and decrease in FEV1 in comparison to both cough and wheezy groups. Other characteristics included older age (>10 years), male gender, and longer disease duration with negative family history of asthma. Whereas, cough phenotype group was found to have an eosinophilic pattern, younger age (<10 years), female gender, and shorter disease duration, with positive family history of Asthma. On the other aspect, a mixed IgE and eosinophilic pattern were noticed in the wheezy phenotype group. This wide variation in the features of each clinical asthma phenotype had its implication on treatment response where the SOB group responded to fluticasone alone, the cough group responded to montelukast alone, and the wheezy group responded to both medications.
Numerous studies suggested that genetic factors may mediate a large part of heterogeneity in response to asthma medications among asthmatics. Further, Cytokine gene polymorphisms were found to affect the serum levels of cytokines by influencing transcriptional regulation. Thus in another recent study, we explored the genetic profile of the proposed clinical asthma phenotypes, in addition to their cytokine profile and other airway biomarkers. The proposed clinical phenotypes included cough phenotype, SOB phenotype, and cough with SOB phenotype. Single nucleotide polymorphism of IL4RA 175V and IL4C-590T were studied in the different clinical phenotypes. We found that asthma as a group had AGheterozygosity genotype of IL4RA 175V, whereas, cough with SOB group showed AA and GGhomozygosity genotype. Further, cough with SOB group showed significant elevated serum levels of IL-9 among those with IL- 4RA AA and GG genotypes in comparison to the other phenotypes with similar genotypes. In addition, this group showed significant increase in serum IL-9 and peripheral eosinophilic percentage compared to cough group.

Tuesday, 10 October 2017

Annals of Yoga and Physical Therapy


Annals of Yoga and Physical Therapy is an open access, peer reviewed, scholarly journal dedicated to publish articles covering all areas of Yoga, Physical Medicine and Rehabilitation.
The journal aims to promote latest information and provide a forum for doctors, researchers, physicians, and healthcare professionals to find most recent advances in the areas of Yoga, Physical Medicine and Rehabilitation. Annals of Yoga and Physical Therapy accepts research articles, reviews, mini reviews, case reports and rapid communication covering all aspects of Yoga, Physical Medicine and Rehabilitation.
Annals of Yoga and Physical Therapy strongly supports the scientific up gradation and fortification in related scientific research community by enhancing access to peer reviewed scientific literary works. Austin Publishing Group also brings universally peer reviewed journals under one roof thereby promoting knowledge sharing, mutual promotion of multidisciplinary science.

Monday, 9 October 2017

Austin Journal of Women’s Health


Austin Journal of Women’s Health is an open access, peer reviewed, scholarly journal dedicated to publish articles in all areas of women's healthcare including gynecology, obstetrics, and breast cancer and policies.
Austin Journal of Women's Health is committed to improving the health and health care of all women throughout the lifetime and in diverse communities with focus on the prevention, diagnosis and administration of fertility.
Austin Journal of Women's Health accepts original research articles, review articles, case reports, commentaries, clinical images and rapid communication on all the aspects of Women’s Health.

Friday, 6 October 2017

Austin Journal of Vector Borne Diseases: Open Access


Austin Journal of Vector Borne Diseases: Open Access is an open access, peer reviewed, scholarly journal dedicated to publish articles in all areas of vector borne diseases including existing or new policy in the relevant areas, impact of all types of vector borne diseases and related medical research methodologies.
Vector-borne diseases are the infections transmitted by the bite of infected arthropod species, such as mosquitoes, ticks, triatomine bugs, sandflies, and blackflies. Arthropod vectors are cold-blooded (ectothermic) and thus especially sensitive to climatic factors. Or Vectors are organisms that transmit pathogens and parasites from one infected person (or animal) to another, causing serious diseases in human populations. These diseases are commonly found in tropical and sub-tropical regions and places where access to safe drinking-water and sanitation systems is problematic.
Austin Journal of vector borne diseases welcomes research manuscripts, review articles, case reports, editorials, letters to the editor, and innovations relating to all aspects of vector borne diseases.