A case report on usage of rituximab on complicated steroid-dependent nephrotic syndrome

Nephrotic syndrome (NS) is one of the common yet challenging childhood disease. Treating NS with immunosuppressants like corticosteroids is typically effective. However, there are significant evidences which displayed resistance patterns to the former drugs. Here in this case, a male patient came to the nephrology department with the history of steroid dependant nephrotic syndrome with complaint of its infrequent relapse. The condition was complicated since, the patient was on multiple steroids even after which there were recurrent episodes of syndrome. Considering the status, Mycophenolate mofetil was added as a supportive treatment for the management of the disease along with steroids, still the outcome was unremarkable. Hence, rituximab was ordered (four cycles). The outcome this time was appreciable, rituximab administration produced a positive result. No events were recorded during the treatment duration.

Play Preference and Pretend Play Skills between Typically Developed Children and Autism

Pretend play emerged at the age of 18 months in children. The imagination of children creates new play ideas it has incorporated into their play. But Autism children find difficulty in play. Hence, this study aimed to find the different types of pretend and preference play among autistic and typical children. The total sample of 40 is divided into 20 each group respectively. Data analyzed by using Chi-Square result in the significant difference between the pretend play and play preference X² = 42.81 (p=0.05 and p=0.01). Future study needs to examine with larger samples.© 2016. The Authors. Published for AMER ABRA by e-International Publishing House, Ltd., UK. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Peer–review under responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians) and cE-Bs (Centre for Environment-Behaviour Studies), Faculty of Architecture, Planning & Surveying, Universiti Teknologi MARA, Malaysia.Keywords: Pretend Play; Play Preferences; Autism; Typically Developed children

Results from a Phase 1 Study of Sodium Selenite in Combination with Palliative Radiation Therapy in Patients with Metastatic Cancer.

In preclinical studies, selenite had single agent activity and radiosensitized tumors in vivo. Here we report results from a Phase 1 trial in 15 patients with metastatic cancer treated with selenite (5.5 to 49.5 mg) orally as a single dose 2 hours before each radiation therapy (RT) treatment. Patients received RT regimens that were standard of care. The primary objective of the study was to assess the safety of this combination therapy. Secondary objectives included measurement of pharmacokinetics (PK) and evaluation of efficacy. Endpoints included assessment of PK, toxicity, tumor response, and pain before and after treatment. The half-life of selenite was 18.5 hours. There were no adverse events attributable to selenite until the 33 mg dose level, at which the primary toxicities were grade 1 GI side effects. One patient treated with 49.5 mg had grade 2 GI toxicity. Although this was not a DLT, it was felt that the highest acceptable dose in this patient population was 33 mg. Most patients had stabilization of disease within the RT fields, with some demonstrating objective evidence of tumor regression. Most patients had a marked improvement in pain and seven out of nine patients with prostate cancer had a decrease in PSA ranging from 11-78%. Doses up to 33 mg selenite were well tolerated in combination with RT. A randomized, well controlled study is needed at the 33 mg dose level to determine if selenite results in clinically meaningful improvements in the response to palliative RT

A Mechanistic In Vivo/Ex Vivo Pharmacokinetic-Pharmacodynamic Model of Tenofovir for HIV Prevention

Defining tissue and plasma-specific prophylactic drug concentrations is central to pre-exposure prophylaxis product development for sexual transmission of HIV-1. Pharmacokinetic (PK) data from study RMP-02/MTN-006 comparing single dose oral tenofovir disoproxil fumarate with single and multiple dose rectal tenofovir (TFV) gel administration in HIV-1 seronegative adults was used to construct a multicompartment plasma-rectal tissue population PK model for TFV and tenofovir-diphosphate (TFVdp) in plasma and rectal tissue. PK data were collected in five matrices: TFV (plasma, rectal tissue homogenate), TFVdp (peripheral blood mononuclear cells, rectal mononuclear cells (MMCs), rectal tissue homogenate). A viral growth compartment and a delayed effect compartment for p24 antigen expression measured from an ex vivo explant assay described HIV-1 infection and replication. Using a linear PK/pharmacodynamic model, MMC TFVdp levels over 9,000 fmol/million cells in the explant assay provided apparent viral replication suppression down to 1%. Parameters were estimated using NONMEM version 7.4

Association of immune-related adverse events with the outcomes of immune checkpoint inhibitors in patients with dMMR/MSI-H metastatic colorectal cancer

Background: Immune checkpoint inhibitors (ICIs) show a tremendous activity in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC), but a consistent fraction of patients does not respond. Prognostic/predictive markers are needed. Despite previous investigations in other tumor types, immune-related adverse events (irAEs) have not been well evaluated in patients with MSI-H cancers treated with ICIs. Methods: We conducted an international cohort study at tertiary cancer centers collecting clinic-pathological features from 331 patients with MSI-H mCRC treated with ICIs. Of note, the irAEs were summarized using a 'burden score' constructed in a way that the same score value could be obtained by cumulating many low-grade irAEs or few high-grade irAEs; as a result, the lower the burden the better. Clearly, the irAE burden is not a baseline information, thus it was modeled as a time-dependent variable in univariable and multivariable Cox models. Results: Among 331 patients, irAEs were reported in 144 (43.5%) patients. After a median follow-up time of 29.7 months, patients with higher burden of skin, endocrine and musculoskeletal irAEs (the latter two's effect was confirmed at multivariable analysis) had longer overall survival (OS), as opposed to gastrointestinal, pneumonitis, neurological, liver, renal and other irAEs, which showed an harmful effect. Similar results were observed for progression-free survival (PFS). Based on the results retrieved from organ-specific irAEs, 'aggregated' burden scores were developed to distinguish 'protective' (endocrine and musculoskeletal) and 'harmful' (gastrointestinal, pneumonitis, neurological, hepatic) irAEs showing prognostic effects on OS and PFS. Conclusions: Our results demonstrate that not all irAEs could exert a protective effect on oncologic outcome. An easy-to-use model for ICIs toxicity (burden score of protective and harmful irAEs) may be used as surrogate marker of response

Kinetics of nanoparticle-based DNA hybridization

This study investigated the association rate constant and equilibrium constant for the hybridization of target DNA with and without gold nanoparticles. Five experiments were conducted. Four experiments were performed using varying concentrations of DNA and the fifth was carried out using protein. The results of the protein experiment were used as a baseline with which to compare the results of the DNA experiments. All experiments utilized the Autolab SPRINGLE instrument with the accompanying Data Acquisition and Kinetic Evaluation software. The SPR binding curve corresponding to the protein experiment illustrated an increase in association across the entire 1 hour exposure time as expected. The subsequent DNA experiments tested hybridization detection for 0.1 M, 0.03 M, 0.04 M, 0.05 M, and 0.06 M concentrations of DNA at 4 hour exposure time periods. The lowest concentration of DNA for hybridization detection was 0.06 M without nanoparticles. Trials without nanoparticles yielded larger association rate constants than trials with nanoparticles. This result is in accordance with expected results since the additional weight of gold nanoparticles will slow the association rate

Controversies in Stem Cell Research

Adult stem cells, especially hematopoietic stem cells have been used to treat humans for over 20 years, but the use of embryonic stem (ES) cells has been restricted since their use involves the destruction of a human embryo. Hence, ES cell research is surrounded by ethical, moral, and religious anxieties. This IQP analyzes the controversies surrounding stem cell research, the legislations passed to regulate their use, their applications and their future in regenerative medicine

Evaluation of the Efficacy of Novel Self Disinfectant Solution in Irreversible Hydrocolloid Impression Material - An Experimental Study

Background: Irreversible hydrocolloid materials are widely used for both diagnostic and definitive impression procedures. Impressions can be disinfected by immersion or spraying in any compatible disinfectant. Disinfectants should not adversely affect the dimensional stability of the impression and physical properties of impression material and subsequent dental cast. Objective: The study aims to evaluate the efficacy of a hypochlorous disinfectant solution mixed with irreversible hydrocolloid on setting time, antibacterial efficacy, and dimensional stability. Methodology: Three groups were made with one control group and three alginate impression was made for each participants in the maxillary arch with 24-hours intervals between one another using the same brand of commercially available chromatic alginate. The working and setting time were noted. Bacterial swabs were collected using a dry sterile cotton swab in the mid palatal region. Dental casts were made using type III gypsum. Result: The working and setting time had significant differences whereas the dimension among the cast has no significant difference. Microbial growth analysis had distinct differences among the groups. Conclusion: The self disinfection method using a pioneer solution of hypochlorous HOCl (100 ppm) to mix the alginate impression material rather than the water with the same powder-liquid ratio prescribed by the manufacturer had the same dimensional stability with improved antimicrobial action