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Objective. To understand the impact of alternate warm and cold therapy (AWCT) on uricemia, sleep, pain, functional ability, and quality of life in gout patients. Methods. A quasiexperimental, nonequivalent control group, pre and posttest design was adopted among 120 gout patients. The data were collected on demographics, comorbidities, pain level, joint swelling/joint tenderness, patient global assessment of response to treatment (PGART), health-related quality of life (HRQoL) with SF-36, sleep quality by Pittsburgh Sleep Quality Index (PSQI), and serum uric acid and assessed. Descriptive and inferential statistics were used to analyze the data. Results. Patients had mean age of 58 and 61 years, mean number of comorbidities was 1.8 and 1.4, as well as presence of arthritic comorbidities except gout was 1.1 and 0.8 among study and control group participants, respectively. Pain ( p < 0.001 ), PGART ( p = − 0.01 ), HRQoL, sleep quality, and level of SUA (mg/dl) improved significantly ( p < 0.01 ) among the study group over study periods. It affirms that the AWCT is effective in reducing pain, functional disability, and SUA, as well as improving the sleep quality and HRQoL of the gout patients. There was a reduced incidence of gout flares ( p < 0.001 ), and taking additional medicines for pain ( p < 0.01 ) was statistically significant among study participants. Except social functioning, other domains of health were significantly ( p < 0.05 ) affected by the comorbidities like hypertension, diabetes, heart disease, renal disease, and asthma/chronic obstructive pulmonary disease. Conclusions. Gout is independently associated with higher medical and arthritic comorbidity, and AWCT can be better and cost-effective alternative therapy for gout patients. In addition, it may lead to improved cardiac function, hypertension, and renal insufficiency.

Osteoporosis is a skeletal disease that is both systemic and silent characterized by an unbalanced activity of bone remodeling leading to bone loss. Rising evidences demonstrate that thyroid stimulating hormone (TSH) has an important role in the regulation on the metabolism of bone. However, TSH regulation on human osteoblast essential transcriptional factors has not been identified. Current study examined the role of TSH on human osteoblastic Runx2 expression and their functional genes by in vitro and in slico analysis. Human osteoblast like (HOS and SaoS-2) cells were cultured with DMEM and treated with hTSH at the concentration of 0.01 ng/mL and 10 ng/mL. After treatment, osteoblastic Runx2 and IGF-1R beta expression were studied using RT-PCR and western blot analysis. TSH treatment induced osteoblastic essential transcriptional factor, Runx2 in HOS and SaOS2 cells on 48 h duration and elevated the expression of IGF-IR β gene and Protein in SaoS-2 cells. TSH also promotes Runx2 responsive genes such as ALP, Collagen and osteocalcin in SaOS2 cells on day 2 to day 14 of 10 ng/mL of treatment and favors’ matrix mineralization matrix in these cells. In addition, TSH facilitated human osteoblastic cells to mineralize their matrix confirmed by day 21 of alizarin red calcium staining. In silico study was performed to check CREB and ELK1 interaction with Runx2. Results of in silico analysis showed that TSH mediated signalling molecules such as CREB and ELK1 showed interaction with Runx2 which involve in osteobalstic gene expression and differentiation. Present findings confirm that TSH promotes Runx2 expression, osteoblastic responsive genes and bone matrix formation.

The investigation is to increase the cytotoxicity of soluble curcumin (SC) by loading it onto pectin and skimmed milk powder (SMP) dual layered solid lipid nanoparticles (DL-SLN). The DL-SLN exhibited significantly higher encapsulation efficiency (83.94 ± 6.16), better stability (90 days), and sustained the drug release in different gastro intestional (GI) environments upto 72 h. Molecular docking revealed that the Vander Waals (57420.669 Kcal-mol-1) and electrostatic (-197.533) bonds were involved in the DL-SLN complex formation. The in vivo toxicity of DL-SLN was performed by the zebrafish model, the cell cycle arrest at G2/M phase (64.34 %) by flow cytometry, and western blot investigation was recognized molecular level cell death using SW480 cells. Pharmacokinetic (PK) evaluation (Cmax-5.78 ± 3.26 μg/mL; Tmax-24 h) and organ distribution studies confirmed that the co-functionalized pectin based SLN could efficiently improve the oral bioavailability (up to 72 h) of curcumin (CMN) on colon-targeted release.

Interferon regulatory factor 1 (IRF-1) plays a vital role in cell proliferation and cell differentiation by acting as a tumor suppressor gene and its role is linked to various types of cancers, including leukemia and pre-leukemia myelodysplasia. Mutations in the coding region of the IRF-1 are likely to influence the IRF-1 and its DNA binding affinity. The molecular mechanism of the DNA recognition with the IRF-1 protein upon mutations is still unknown. In this study, we have elucidated the structural and functional behavior of the wild-type and mutant (K75E and E222K) IRF-1 proteins and their corresponding molecular mechanisms with DNA recognition at the molecular level, using molecular dynamics simulations. Furthermore, we also applied the docking approach to examine the binding between the IRF-1 protein and DNA upon mutations. This study evidently explains that, due to mutations, the IRF-1 structure loses its stability and becomes more flexible than the wild-type protein. This structural loss might affect IRF-1-DNA interaction and lead to the inhibition of cancer suppression. Identifying the effects of IRF-1 at the molecular level will be beneficial for designing drugs for IRF-1 associated cancers. These drugs should be designed so that they can help reactivate the IRF-1 function, by increasing the transcriptional activity, to treat leukemia.

Background Despite progress in recent years, Afghanistan is lagging behind in realizing the full potential of immunization. The country is still endemic for polio transmission and measles outbreaks continue to occur. In spite of significant reductions over the past decade, the mortality rate of children under 5 years of age continues to remain high at 91 per 1000 live births. Methods The study was a descriptive community-based cross sectional household survey. The survey aimed to estimate the levels of immunization coverage at national and province levels. Specific objectives are to: establish valid baseline information to monitor progress of the immunization program; identify reasons why children are not immunized; and make recommendations to enhance access and quality of immunization services in Afghanistan. The survey was carried out in all 34 provinces of the country, with a sample of 6125 mothers of children aged 12–23 months. Results Nationally, 51% of children participating in the survey received all doses of each antigen irrespective of the recommended date of immunization or recommended interval between doses. About 31% of children were found to be partially vaccinated. Reasons for partial vaccination included: place to vaccinate child too far (23%), not aware of the need of vaccination (17%), no faith in vaccination (16%), mother was too busy (15%), and fear of side effects (11%). Conclusion The innovative mechanism of contracting out delivery of primary health care services in Afghanistan, including immunization, to non-governmental organizations is showing some positive results in quickly increasing coverage of essential interventions, including routine immunization. Much ground still needs to be covered with proper planning and management of resources in order to improve the immunization coverage in Afghanistan and increase survival and health status of its children.