New insight into a simple high-yielding method for the production of fully folded and functional recombinant human CCL5.

Chemokines are proteins important for a range of biological processes from cell-directed migration (chemotaxis) to cell activation and differentiation. Chemokine C-C ligand 5 (CCL5) is an important pro-inflammatory chemokine attracting immune cells towards inflammatory sites through interaction with its receptors CCR1/3/5. Recombinant production of large quantities of CCL5 in Escherichia coli is challenging due to formation of inclusion bodies which necessitates refolding, often leading to low recovery of biologically active protein.

Towards a 'clicked' PSMA targeting gene delivery bioconjugate-polyplex for prostate cancer.

Prostate cancer is the most common cancer in men in the UK with over 50 000 new cases diagnosed each year and although therapeutic advances in surgery, anti-androgens, radio- and chemotherapy have increased survival rates, there still remains a need for new treatments to combat the most aggressive forms of the disease. Gene therapy offers promise as an alternative approach but is reliant on selective targeting to the cancer cell surface. Herein we describe the novel construction of a prostate specific membrane antigen (PSMA) binding bioconjugate-polyplex, based on a glutamate-urea peptide scaffold using 'click' chemistry, which we demonstrate is capable of targeted delivery of a GFP gene to PSMA overexpressing prostate cancer cells, and therefore may have potential future application as part of a prostate cancer gene delivery therapy.

Cross aldol OPAL bioconjugation outcompetes intramolecular hemiaminal cyclisation of proline adjacent N-terminal α-oxo aldehydes at acidic pH.

Novel methods to construct small molecule-protein bioconjugates are integral to the development of new biomedicines for a variety of diseases. C-C linked bioconjugates are increasingly desirable in this application due to their stability and can be accessed through cross aldol bioconjugation of reactive α-oxo aldehyde handles easily introduced at the N-terminus of proteins by periodate oxidation. We previously developed an organocatalyst-mediated protein aldol ligation (OPAL) for chemical modification of these reactive aldehydes, but the efficiency of this method was limited when a proline residue was directly adjacent to the N-terminus due to intramolecular hemiaminal formation.

Factors associated with patient perceived suboptimal dosing of in-hospital opioid agonist therapy among people who use illicit drugs in Vancouver, Canada.

Optimal dosing of opioid agonist therapy (OAT) is essential for treatment success. However, initiation and maintenance of OAT in hospital settings can be challenging given differing levels of opioid tolerance, withdrawal, and intoxication among patients. The objective of this study was to characterize the prevalence and factors associated with in-hospital patient perceived suboptimal OAT dosing among people who use illicit drugs (PWUD) in Vancouver, Canada.

A Tale of Two Bioconjugations: pH Controlled Divergent Reactivity of Protein α-oxo-Aldehydes in Competing α-oxo-Mannich and Catalyst-Free Aldol Ligations.

Site-selective chemical methods for protein bioconjugation have revolutionized the fields of cell and chemical biology through the development of novel protein/enzyme probes bearing fluorescent, spectroscopic, or even toxic cargos. Herein, we report two new methods for the bioconjugation of α-oxo aldehyde handles within proteins using small molecule aniline and/or phenol probes. The "α-oxo-Mannich" and "catalyst-free aldol" ligations both compete for the electrophilic α-oxo aldehyde, which displays pH divergent reactivity proceeding through the "Mannich" pathway at acidic pH to afford bifunctionalized bioconjugates, and the "catalyst-free aldol" pathway at neutral pH to afford monofunctionalized bioconjugates.

Migration Patterns from an Open Illicit Drug Scene and Emergency Department Visits among People Who Use Illicit Drugs in Vancouver, Canada.

Background: People who use illicit drugs (PWUD) experience various adverse health outcomes leading to increased healthcare service utilization. PWUD are also a highly mobile population which poses challenges to healthcare delivery. The objective of this study was to identify migration patterns from the Downtown Eastside (DTES), an urban illicit drug scene in Vancouver and to estimate the impact of different migration patterns on two outcomes: a) emergency department (ED) visits and b) ED visits resulting in inpatient admission among PWUD.

The impact of high-dose opioid prescription on mortality rates among people living with HIV: A retrospective cohort study.

Objectives: High-dose opioid use is associated with increased morbidity, mortality, and healthcare utilization. People living with HIV (PLHIV) are frequently prescribed these medications to manage their pain. However, little is known about the relationship between being prescribed high doses of opioids (> 90 MME/d) and mortality risk among this population.

Degradable Polymers and Nanoparticles Built from Salicylic Acid.

As more evidence emerges supporting the possibility that nonsteroidal anti-inflammatory drugs, especially aspirin (acetyl salicylic acid), might have a role in the prevention and management of certain types of cancer, there have been several attempts to fabricate salicylic acid-based polymers that can be employed in the targeted therapy of tumors. The primary disadvantage so far has been in use of nontherapeutic polymeric backbones that constitute the majority of the therapeutic particle's size. The focus of this research is the creation of a biodegradable polymer consisting only of salicylic acid, and its use as the main building block in targeted nanotherapeutics that would consequently provide both high local dose and sustained release of the active moiety.

Gene Regulatory Networks for the Haploid-to-Diploid Transition of .

The sexual cycle of the unicellular culminates in the formation of diploid zygotes that differentiate into dormant spores that eventually undergo meiosis. Mating between gametes induces rapid cell wall shedding via the enzyme g-lysin; cell fusion is followed by heterodimerization of sex-specific homeobox transcription factors, GSM1 and GSP1, and initiation of zygote-specific gene expression. To investigate the genetic underpinnings of the zygote developmental pathway, we performed comparative transcriptome analysis of both pre- and post-fertilization samples.

Segmental Surface Referencing during Intraoperative Three-dimensional Image-Guided Spine Navigation: An Early Validation with Comparison to Automated Referencing.

 Interventional human cadaver study.  Intraoperative three-dimensional (3-D)-guided navigation improves spine instrumentation accuracy. However, image acquisition may need to be repeated with segment hypermobility or distant target from reference frame (RF).

Acanthamoeba encephalitis in a patient with systemic lupus treated with rituximab.

Acanthamoeba species are free-living protozoa that can infect humans and animals. Acanthamoeba can cause serious central nervous system infections in immunocompromised hosts. Here we report a case of Acanthamoeba encephalitis in a patient with lupus nephritis, 1 month after completing a course of rituximab, an anti-CD20 chimeric antibody.

Solutions for severely angulated implants in the mandibular overdenture: a clinical report.

Results of randomized clinical trials have confirmed that implant overdentures provide patients with better outcomes than do conventional complete dentures. Several designs have been introduced for the mandibular implant-retained removable prosthesis. The most commonly used prosthesis design for the mandibular overdenture is two implants in the canine areas with a stud attachment mechanism (i.

Oxygenated diterpenes and other constituents from Moroccan Juniperus phoenicea and Juniperus thurifera var. africana.

Six new diterpenic acids isolated as their methyl ester derivatives, i.e., methyl 12-oxo-8alpha,15-dihydroxyabiet-13-en-19-oate, methyl 12-oxo-8alpha-hydroxyabiet-13-en-19-oate, methyl 15-hydroperoxy-8alpha,12alpha-epidioxiabiet-13-en-19-oate, methyl 15-hydroxy-8alpha,12alpha-epidioxiabiet-13-en-19-oate, methyl 15-hydroperoxy-8alpha,14alpha,12alpha,13alpha-diepoxiabietan-13-en-19-oate, and methyl 7alpha,12beta-dihydroxysandaracopimarate, together with two new isovalerate derivatives of p-methoxycinnamyl alcohol and linalool, were isolated from the leaves of Juniperus thurifera var.

The Saudi experience with neutron therapy in locally advanced head and neck cancers.

The neutron therapy program at King Faisal Specialist Hospital and Research Center conducted a phase II study to evaluate the toxicity and efficacy of neutrons against conventional external megavoltage irradiation in patients with locally advanced head and neck malignancy. One hundred and nineteen patients were allocated to receive either photons (46/119) or neutrons (73/119). Radiation effects were scored according to the EORTC/RTOG criteria; data was collected weekly during treatment, once a month for the first year and at 6-month intervals subsequently.

RBE variation between fast neutron beams as a function of energy. Intercomparison involving 7 neutrontherapy facilities.

In fast neutron therapy, the relative biological effectiveness (RBE) of a given beam varies to a large extent with the neutron energy spectrum. This spectrum depends primarily on the energy of the incident particles and on the nuclear reaction used for neutron production. However, it also depends on other factors which are specific to the local facility, eg, target, collimation system, etc.

Gastrointestinal lymphoma in adults: clinical features and management of 300 cases.

Background/aims: Gastrointestinal lymphoma is a rare disease. A study was conducted to assess its prevalence and clinical features in adult patients with lymphoma.

Methods: Retrospective analysis of 1352 patients with adult non-Hodgkin's lymphoma showed 300 (22%) cases with gastrointestinal involvement at initial presentation.

Obtaining pre-radiation therapy dental clearance.

Patients scheduled to receive radiation therapy that involves the mandible, maxilla or salivary glands should be referred for dental consultation, assessment and clearance before therapy begins. A form that aids the radiation oncologist and the dentist in patient referrals is presented.

Neutron therapy in Saudi Arabia: an overview and results of dose searching study in head and neck cancer.

The King Faisal Specialist Hospital and Research Centre is the only center in the Middle East that incorporates a neutron therapy facility. The neutron beam is produced by a cyclotron, which produces a beam by either a (d(15)+Be) or (p(26)+Be) reaction. The beam from the proton reaction is selected for therapy because of its superior physical characteristics.

Histiocytosis-X in Saudi children.

A retrospective analysis of 21 Saudi children with Histiocytosis-X were reviewed. 13 were males, 8 were females, with a ratio of 1.62:1.

Neutron therapy for locally advanced head and neck squamous cell carcinoma: optimum dose search.

28 patients with locally advanced primary squamous cell carcinoma of the head and neck received neutron therapy and were randomized between two dose levels: 145 cGy n gamma x twelve fractions, three fractions per week (total 17.4 Gy n gamma). 155 cGy n gamma x twelve fractions, three fractions per week (total 18.

Relative biological effectiveness (RBE) of p(26) + Be neutrons from the King Faisal Specialist Hospital and Research Centre CS-30 cyclotron measured by testis weight loss.

Testis weight loss of C3H and Swiss-Webster (SW) mice was used as endpoint to determine the relative biological effectiveness (RBE) of p(26) + Be fast neutrons with respect to Co-60 gamma irradiation. Percent weight loss versus dose curves showed two components. Comparing first component effects, the RBE was 3.

Nasopharyngeal carcinoma in Saudi Arabia: a retrospective study of 166 cases treated with curative intent.

A retrospective review was performed of the medical records of 166 adult patients with biopsy-proven carcinomas of the nasopharynx treated with curative intent at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. All patients were treated between June 1975 and December 1985 using megavoltage therapy equipment. Most patients presented with advanced nodal disease: 23 patients (13.

Epidemiology and clinical characteristics of testicular tumors in Saudi Arabia: King Faisal Specialist Hospital and Research Centre experience.

The data on 62 patients with germinal testicular tumors seen at King Faisal Specialist Hospital and Research Centre between January 1977 and June 1983 were analyzed to determine the epidemiologic and clinical characteristics of the disease in Saudi Arabia. Fifty-seven patients were Saudis. The geographic distribution of Saudi patients seemed to coincide with population concentrations.

Kaposi's sarcoma and its management by radiotherapy.

Thirteen patients with Kaposi's sarcoma were treated by radiotherapy between 1975 and 1984. Five patients were kidney transplant recipients receiving immunosuppressive drugs, while eight patients had spontaneous Kaposi's sarcoma. Eleven patients were followed up for periods from two to 63 months (mean, 27 months).