The Raf kinase inhibitory protein (RKIP) has been demonstrated to modulate different intracellular signaling pathways in cancers. Studies have shown that RKIP is frequently downregulated in cancers; therefore, attempts have been made to upregulate the expression of RKIP using natural and synthetic agents for the treatment of human malignancies. Moreover, various regulators such as specific proteins and microRNAs (miRNAs) that are involved in the regulation of RKIP expression have also been identified. RKIP mechanistically modulates the apoptotic regulators of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling. Because of its critical role in human cancers, RKIP has drawn much research attention, and our understanding is expanding rapidly. Here, we summarize some of the biological complexities of RKIP regulation. However, we restrict our discussion to selected tumors by focusing on TRAIL, miRNAs and natural agents. Emerging evidence suggests a role for natural agents in RKIP regulation in cancer cells; therefore, naturally occurring agents may serve as cancer-targeting agents for cancer treatment. Although the literature suggests some advancement in our knowledge of RKIP biology, it is incomplete with regard to its preclinical and clinical efficacy; thus, further research is warranted. Furthermore, the mechanism by which chemotherapeutic drugs and novel compounds modulate RKIP and how nanotechnologically delivered RKIP can be therapeutically exploited remain to be determined.
Apoptosis ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; MicroRNAs/genetics ; Neoplasms/genetics/*metabolism ; Phosphatidylethanolamine Binding Protein/genetics/*metabolism ; Protein Interaction Maps ; *Signal Transduction ; TNF-Related Apoptosis-Inducing Ligand/genetics/metabolism

The long agonistic protocol for controlled ovarian hyperstimulation (COH) is effective and used most often, thus is considered the gold standard. Therefore any new regimen has to be compared in its results with those obtained with the long protocol. This report compares the efficacy of GnRH agonist and antagonist in a retrospective study of IVF/ICSI carried out in a tertiary teaching hospital from 2003 to 2006. Only the first COH cycle followed by IVF-ICSI from 200 couples (agonist = 120 and antagonist = 80) were analysed. The end points studied included the number of oocytes recovered, number of mature (MII) oocytes, fertilization, cleavage, morphology based embryo quality, pregnancy rate, quantity and cost of gonadotrophin. The average age of female subjects was 35.1 +/- 4.7 years with 50% being 35 years and above. Major infertility factors were tubal blockage, male factor and endometriosis altogether comprising 68%. GnRH agonist and antagonist cycle parameters were comparable except lesser amount of gonadotrophin was used with lower resultant costs (both p < 0.0005) in antagonistic regime. Antagonist regime produce somewhat more good quality embryos (p = 0.065), an insignificant difference. A clinical pregnancy rate per embryo transfer of 16.3% in agonist and 20.6% in antagonist regime was achieved respectively. In conclusion, GnRH antagonist protocol produced a COH response, embryonic development and pregnancy rates on par to GnRH agonist regime. Moreover GnRH antagonist protocol required a shorter stimulation period plus fewer complications. Hence GnRH antagonist regime provided means for a friendlier, convenient and cost effective protocol for patients.
Gonadorelin ; Protocols documentation ; Pregnancy ; Encounter due to In vitro fertilization ; Sperm Injections, Intracytoplasmic

The aim of this work was to study radiation and the effects of temperature on conductivity properties of polyvinyl alcohol (PVA)-based potassium hydroxide (KOH) and propylene carbonate (PC), where the ionic conduction preferentially occurs in the amorphous phase by free radicals ions through gamma-irradiation. Alkaline composite polymer electrolyte (ACPE) consisting of PVA, KOH and PC of different concentration ratios were prepared by solvent-casting technique. The ACPE were irradiated with different doses from 5 kGy up to 200 kGy. The conductivity properties of the electrolyte films were measured at different frequencies in the range 20 Hz to 1 MHz using LCR meter. The results showed that the conductivity properties were dependent on the radiation dose, temperature and the concentration of the polymer blends.
Radiation ; asparaginase/prednisone/vincristine ; Personal Computers ; Temperature ; Concentration

OBJECTIVES: This study compared the amount of apically extruded bacteria during the glide-path preparation by using multi-file and single-file glide-path establishing nickel-titanium (NiTi) rotary systems. MATERIALS AND METHODS: Sixty mandibular first molar teeth were used to prepare the test apparatus. They were decoronated, blocked into glass vials, sterilized in ethylene oxide gas, infected with a pure culture of Enterococcus faecalis, randomly assigned to 5 experimental groups, and then prepared using manual stainless-steel files (group KF) and glide-path establishing NiTi rotary files (group PF with PathFiles, group GF with G-Files, group PG with ProGlider, and group OG with One G). At the end of canal preparation, 0.01 mL NaCl solution was taken from the experimental vials. The suspension was plated on brain heart infusion agar and colonies of bacteria were counted, and the results were given as number of colony-forming units (CFU). RESULTS: The manual instrumentation technique tested in group KF extruded the highest number of bacteria compared to the other 4 groups (p < 0.05). The 4 groups using rotary glide-path establishing instruments extruded similar amounts of bacteria. CONCLUSIONS: All glide-path establishment instrument systems tested caused a measurable apical extrusion of bacteria. The manual glide-path preparation showed the highest number of bacteria extruded compared to the other NiTi glide-path establishing instruments.
Agar ; Bacteria* ; Brain ; Enterococcus faecalis ; Ethylene Oxide ; Glass ; Heart ; In Vitro Techniques* ; Molar ; Stem Cells ; Tooth

Objective: Human exposure to multiple xenobiotics, over various developmental windows, results in adverse health effects arising from these concomitant exposures. Humans are widely exposed to bisphenol A, and acetaminophen is the most commonly used over-the-counter drug worldwide. Bisphenol A is a well-recognized male reproductive toxicant, and increasing evidence suggests that acetaminophen is also detrimental to the male reproductive system. The recent recognition of male reproductive system dysfunction in conditions of suboptimal reproductive outcomes makes it crucial to investigate the contributions of toxicant exposures to infertility and sub-fertility. We aimed to identify toxicity in the male reproductive system at the mitochondrial level in response to co-exposure to bisphenol A and acetaminophen, and we investigated whether melatonin ameliorated this toxicity. Methods: Male Wistar rats were divided into six groups (n=10 each): a control group and groups that received melatonin, bisphenol A, acetaminophen, bisphenol A and acetaminophen, and bisphenol A and acetaminophen with melatonin treatment. Results: Significantly higher lipid peroxidation was observed in the testicular mitochondria and sperm in the treatment groups than in the control group. Levels of glutathione and the activities of catalase, glutathione peroxidase, glutathione reductase, and manganese superoxide dismutase decreased significantly in response to the toxicant treatments. Likewise, the toxicant treatments significantly decreased the sperm count and motility, while significantly increasing sperm mortality. Melatonin mitigated the adverse effects of bisphenol A and acetaminophen. Conclusion Co-exposure to bisphenol A and acetaminophen elevated oxidative stress in the testicular mitochondria, and this effect was alleviated by melatonin.

Introduction: First permanent molars (FPMs) erupt early and their anatomy and location leave them susceptible to dental caries. This study aimed to retrospectively determine the prevalence, severity and pattern of dental caries of FPMs and investigate their relationship if any with demographics and medical health status of the partcipants. Methods: This was a retrospective cross-sectional study. A sample of the digital case notes and radiographs of children aged 5 to 12 years who attended the only postgraduate dental hospital in Dubai were accessed. The recorded data included the children’s demographic variables and the carious status of each FPM as recorded in the notes on the initial assessment. Descriptive and statistical analyses were conducted (P<0.05). Results: A total of 2984 FPMs were obtained from the digital records of 774 children. Their mean age was 8.07 (±2.23) years and only those that met the inclusion criteria were included in the study. The prevalence of dental caries and mean Decayed Missing Filled Surfaces of FPMs, were 42% and 0.3 (±0.04), respectively. The most prevalent decayed surface was the occlusal (29.2%), followed by mesial, buccal, palatal/ lingual, distal surfaces (24.2 %; 6.6 %; 3.1 %; 2.3 %) respectively. Children with medical problems and/or special needs had a significantly higher level of caries in the buccal surfaces (12.3%) (P=0.042). Conclusion: Caries of FPMs in a sample of Dubai children studied was prevalent, especially in those with special healthcare needs, thus indicating a necessity for targeted prevention and treatment focused on these keystone teeth.

Introduction: Ankle arthrodesis using the Ilizarov technique provides high union rate with the added benefits of early weight-bearing, and the unique advantage of its ability to promote regeneration of soft tissue around the bone, including skin, muscle and neuro-vascular structures, and its versatility to allow correction of the position of the foot by adjusting the frame post-operatively as needed. We describe our experience with this technique and the functional outcomes in our patients. Materials and Methods: This retrospective study was conducted in 20 ankle fusion cases using the Ilizarov method between the years 2007 and 2017. We defined success in treatment by loss of preoperative symptoms and radiological union on plain radiographs of the ankle. Results: Fusion was achieved in all patients (100%). Immediate post-operative ambulation was with full weight bearing (FWB) in 16 (83%) of the participants and non-weight bearing (NWB) in 3 patients (17%). Postprocedure 11 patients (67%) of the participants who were full weight bearing required some form of support for walking for 2-3 weeks. Post-operatively three patients had pin tract infection requiring intravenous antibiotics. Radiological union took range of 6-12 weeks, mean union time was 8 weeks. Only one patient required bone grafting due to bone loss. Average follow-up period was 10-45 months. Conclusion: The Ilizarov technique has a high union rate and leads to general favourable clinical outcome and may be considered for any ankle arthrodesis but is especially useful in complex cases such as for revisions, soft-tissue compromise, infection and in patients with risk for non-union. Early weight bearing is an extra benefit.

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.