Telepsychiatry offers opportunities to provide better access to and higher quality of psychiatric care for some patients. This commentary on a case considers an analysis of clinical and ethical ...barriers to equitable telehealth for elders with mental health needs.
•Sigma 1 Receptor mediates cancer-specific apoptosis induced by combination treatment with p53 plus Rimcazole.•ROS production and ER stress are induced by combination treatment with p53 plus ...Rimcazole.•Calcium mobilization is induced by combination treatment with p53 plus Rimcazole.•p38 MAPK is activated by combination treatment with p53 plus Rimcazole.•p53 plus Rimcazole induces activation of caspase-3 and the upregulation of Bax.
Over the last years, many improvements have been made in the treatment of breast cancer; however, novel and less toxic therapies are still needed, especially for relapsing and chemo-resistant patients. Here, we analyzed the therapeutic potential of p53 and Rimcazole, a Sigma 1 Receptor antagonist. Rimcazole and p53 are being evaluated in preclinical and clinical trials, respectively. While p53 is a promising antitumor therapeutic agent, antagonists of Sigma 1 Receptor also inhibit tumor cell survival and induce apoptosis. Our current study demonstrates for the first time the synergistic effect of p53 in combination with the Sigma 1 Receptor antagonist Rimcazole. Furthermore, we show that shRNA knockdown of Sigma 1 Receptor in combination with p53, lead to a similar synergistic effect, and that this synergistic effect, in breast cancer growth suppression occurs independent of p53 status. Furthermore, this combination treatment induced ER stress, p38 MAPK activation, ROS production, and proteins involved in apoptosis (caspases-3, Bax) in breast cancer cells. Combining these therapeutic anti-cancer molecules provides an innovative approach for potentially treating human breast cancer.
Oral nitisinone has been shown to increase fur and ocular pigmentation in a mouse model of oculocutaneous albinism (OCA) due to hypomorphic mutations in tyrosinase (TYR), OCA1B. This study determines ...if nitisinone can improve ocular and/or fur pigmentation in a mouse model of OCA type 3 (OCA3), caused by mutation of the tyrosinase-related protein 1 (Tyrp1) gene.
Mice homozygous for a null allele in the Tyrp1 gene (C57BL/6J-Tyrp1 b-J/J) were treated with 8 mg/kg nitisinone or vehicle every other day by oral gavage. Changes in fur and ocular melanin pigmentation were monitored. Mature ocular melanosome number and size were quantified in pigmented ocular structures by electron microscopy.
C57BL/6J-Tyrp1 b-J/J mice carry a novel c.403T>A; 404delG mutation in Tyrp1, predicted to result in premature truncation of the TYRP1 protein. Nitisinone treatment resulted in an approximately 7-fold increase in plasma tyrosine concentrations without overt toxicity. After 1 month of treatment, no change in the color of fur or pigmented ocular structures was observed. The distribution of melanosome cross-sectional area was unchanged in ocular tissues. There was no significant difference in the number of pigmented melanosomes in the RPE/choroid of nitisinone-treated and control groups. However, there was a significant difference in the number of pigmented melanosomes in the iris.
Treatment of a mouse model of OCA3 with oral nitisinone did not have a favorable clinical effect on melanin production and minimally affected the number of pigmented melanosomes in the iris stroma. As such, treatment of OCA3 patients with nitisinone is unlikely to be therapeutic.
OBJECTIVE： Phytochemical constituents as well as antimalarial and toxicity potentials of the methanolic extract of the husk fi bre of Dwarf Red variety of Cocos nucifera were evaluated in this ...study.METHODS： The dried powdered husk fi bre was exhaustively extracted with hexane, ethyl acetate and methanol successively and the methanolic extract was screened for fl avonoids, phenolics, tannins, alkaloids, steroids, triterpenes, phlobatannins, anthraquinones and glycosides. A 4-day suppressive antimalarial test was carried out using Plasmodium berghei NK65-infected mice, to which the extract was administered at doses of 31.25, 62.5, 125, 250 and 500 mg/kg body weight（BW）. Toxicity of the extract was evaluated in rats using selected hematological parameters and organ function indices after orally administering doses of 25, 50 and 100 mg/kg BW for 14 d.RESULTS： Phytochemical analysis revealed the presence of alkaloids, tannins, phenolics, saponins, glycosides, steroids and anthraquinones in the extract. Moreover, the extract reduced parasitemia by 39.2% and 45.8% at doses of 250 and 500 mg/kg BW respectively on day 8 post-inoculation. Various hematological parameters evaluated were not significantly altered（P〉0.05） at all doses of the extract, except red blood cell count which was signifi cantly elevated（P〈0.05） at 100 mg/kg BW. The extract significantly increased（P〈0.05） urea, creatinine, cholesterol, high-density lipoprotein-cholesterol and bilirubin concentrations in the serum as well as atherogenic index, while it reduced albumin concentration significantly（P〈0.05） at higher doses compared to the controls. Alanine aminotransferase activity was reduced in the liver and heart signifi cantly（P〈0.05） but was increased in the serum signifi cantly（P〈0.05） at higher doses of the extract compared to the controls.CONCLUSION： The results suggest that methanolic extract of the Dwarf red variety has partial antimalarial activity at higher doses, but is capable of impairing normal kidney and liver function as well as predisposing subjects to cardiovascular diseases.
Abstract Poverty among widows has received little empirical attention in Africa despite women's severe vulnerability to death shock. We provided empirical evidence on widow households' transition in ...and out of poverty and factors influencing their probability of being in poverty. The Markov transition probabilities show moderate but increasing positive transitions for severely poor widows. Non‐poor widows are stayers who primarily sustain their non‐poor class. The ordered logit estimation shows that higher dependency ratio increases the chances of a widow being severely poor. Being an older widow and having literacy skills reduced the probability that a widow household will be severely poor. Household size and dependency ratio are noted to play important roles in the probability of transitions across poverty classes as shown by the estimated multinomial logit model. These findings are robust to alternative poverty measure, estimation method and different set of weights. Generally, the results echo the need for social safety nets to cushion widows' financial strains. Life insurance policy for spouses, increased sensitization of widows of their rights and adult education programmes targeted at widows could mitigate the negative impact of widowhood on women.
Levulinic acid (LA), an important chemical produced from a bio-based resource for current petrochemical operation, the details of hydrogenation to gamma (γ)-valerolactone (GVL) is reviewed. Levulinic ...acid (LA) was listed among one of the top value-added chemicals by U.S. Department of Energy and also been identified as a promising sustainable material for the synthesis of other important chemicals. It can be synthesized via a process known as hydrolysis. Its synthetic hydrolysis can be carried out employing some kinds of saccharides (e.g. glucose), the major constituent unit composed in cellulose. Its production from cellulose, the most abundant and renewable natural resource on earth is advantageous; however, recalcitrance nature that holds components together in biomass prevents the easy accessibility to the utilization of cellulose therefore as a result of this, considerable pretreatment is required. This review elucidates the details of levulinic acid (LA) synthesis starting from γ-valerolactone (GVL), its derivatives and their useful applications in various fields, most especially in the biorefinery. We concentrate on derivatives such as methyltetranhydrofuran (MTHF) as gasoline additives, ethyl levulinate as a diesel additive, succinic acid, 2-Butanol (2-BO) and 2-pentanol (2-PO) mainly synthesized from Levulinic acid (LA). Likewise, catalysts and Catalytic system for the synthesis were also reviewed. Finally, Baeyer-Villiger (BV) oxidation of levulinates into succinates was also given brief consideration in this mini review.
There are problems of project abandonment, delays, disputes among the participants in the construction projects, difference between the tender cost, and initial cost and construction cost in most ...public building projects as a result of inflation and cost overrun in Nigeria. The aim of this study is to examine the influence of inflation and cost overrun on public sector projects in Nigeria and proffer solution on ways to minimize the problems associated with these two variables impacting public sector construction projects. This research work adopted a quantitative research method. This involved design of questionnaires and also collection of secondary data. Fifty questionnaires were administered to public sector professionals and data on ten public buildings projects were collected in Lagos State. The major finding from this study is that inflation and cost overrun affect most public building projects in Lagos State.
This paper extends and contributes to the literature on tourism for transformative and inclusive growth from the corporate social responsibility (CSR) perspective. Specifically, we examine the impact ...of CSR of multinational oil companies (MOCs) on empowerment of rural women in strengthening agriculture-tourism linkages in Niger Delta region of Nigeria. A total of 800 rural women were sampled across the region. Results from the use of a logit model indicates that rural women seldom participate in the global memorandum of understandings (GMoUs) interventions in agritourism value chain projects, due to the norms and culture of the rural communities. This implies that if the tradition of the people continues to hinder direct participation of the rural women from GMoUs programmes, achieving gender equality and cultural change would be limited in the region, and rural women would remain excluded from the economic benefits of agritourism when compared with the male counterparts. The finding suggests that, GMoU interventions engaging women smallholders in the tourism value chain can be important vehicle for advancing gender empowerment and fostering social inclusion. Also, cluster development boards (CDBs) should pay close attention to which extent the participation of rural women in the GMoUs projects may be limited by traditions.
This research work asses the problems of building foundation within Sagari Estate, Akure, Southwestern Nigeria, using remotely sensed data and geophysical methods. The slope, lineament, hill, and ...contour map were generated using terrain analysis in ArcGIS 10.5 environment. Electrical Resistivity (ER) and Very Low Frequency (EM-VLF) Electromagnetic methods were used in this study. The ER method involves the use of Vertical Electrical Sounding (VES) with Schlumberger configuration. The initial geoelectric parameters obtained from the fifty three (53) VES station points interpretation (layer resistivities and thicknesses) were used to generate geoelectric maps. The variation of strata and physical strength information within the investigated area were determined from the integrated results of the three methods. Results revealed that substantial portion of the areas studied is relatively unsuitable for high rise civil engineering foundations. However, it was showed that the northern and southern parts of the investigated area were more suitable for foundations. The dominant presence of lineaments, steep slopes , fractures, streams, and thick clayey topsoil as well as weathered layers within the western, eastern, and the central portions reveals susceptibility to subsidence if adequate structural supports mitigate the effect of the persistent foundation failure are not provided.
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