Studies of water and electrolyte movement from oral rehydration solutions (rice- and glucose-based) across a normal and secreting gut using a dual isotope tracer technique in a rat perfusion model

Aims: To establish a model to measure bidirectional flow of water from a glucose oral rehydration solution (G-ORS) and a newly developed rice-based oral rehydration solution (R-ORS) using a dual isotope tracer technique in a rat perfusion model. To measure net water, sodium and potassium absorption from the ORS. Methods: In viva steady-state perfusion studies were carried out in normal and secreting (induced by cholera toxin) rat small intestine (n = 11 in each group). To determine bidirectional flow of water from the ORS the animals were initially labelled with tritium, and deuterium was added to the perfusion solution. Sequential perfusate and blood samples were collected after attainment of steady-state conditions and analysed for water and electrolyte content. Results: There was a significant increase in net water absorption from the R-ORS compared to the G-ORS in both the normal (P < 0.02) and secreting intestine (P < 0.05). Water efflux was significantly reduced in the R-ORS group compared to the G-ORS group in both the normal (P < 0.01) and the secreting intestine (P < 0.01). There was an increase in sodium absorption in the R-ORS group compared to the G-ORS. The G-ORS produced a significantly greater blood glucose level at 75 min compared to the R-ORS (P < 0.03) in the secreting intestine. Conclusions: This study demonstrates the improved water absorption from a rice-based ORS in both the normal and secreting intestine. Evidence that the absorption of water may be influenced by the osmolality of the ORS was also demonstrated.

Australia’s first Allied Health Prescribing Program - exploring participants' perspectives on the study program's learning objectives

BACKGROUND The Queensland University of Technology in collaboration with Queensland Health pioneered development of the Allied Health Prescribing Training Program to assist allied health professionals (AHPs) to competently prescribe medicines within their scope of practice. The study program consisted of two modules: Introduction to Clinical Therapeutics for Prescribers and Prescribing and Quality Use of Medicines. METHODS Pre- and post- surveys were developed for both modules. Key themes explored were understanding and confidence in selecting therapeutic choices for patients. For module 2 the learning objectives for safe and effective prescribing were investigated. Data were collected from participants in weeks one and thirteen of the modules via online surveys. RESULTS In the pre-module survey for the first module, participants had a limited degree of understanding and confidence regarding safe and effective use of medicines and appropriate therapeutic choices for managing patients, particularly for complex patients. This improved significantly in the post-module survey. In the pre-module survey for module 2, participants had a moderate degree of understanding and confidence regarding various prescribing learning objectives (including safe and effective prescribing, professional, legal and ethical aspects, communicating medication orders, prescribing safely in their select areas of practice, prescribing safely for complex patients in their area of practice). This increased significantly in the post-module survey. DISCUSSION This training program was implemented to develop a framework of knowledge and skills for AHPs to undertake a prescribing role. The program delivered an increase in participants’ knowledge in the key prescribing areas; and increased participants’ confidence in prescribing safely for patients and for complex patients in their select practice areas. An important aspect of this program was inclusion of prescribing–related activities under supervision of a designated medical practitioner. In conclusion, this educational program for Queensland Health AHP prescribers was successfully developed and is in the final stages of delivery.

Up close and personal with those experiencing homelessness: Pharmacist involvement in a multidisciplinary healthcare team

Introduction. The Brisbane City Council holds a biannual Homeless Connect event which brings together business and community groups on one day to provide free services to people experiencing or at risk of homelessness. Pharmacists were involved in this initiative and provided health services in a multidisciplinary healthcare environment building on the lessons of previous Homeless Connect events (Chan et al, 2015) Aims. To explore pharmacists reflections on their role in a multidisciplinary healthcare team providing services at a community outreach event for those experiencing homelessness. Methods. The pharmacists (n=2) documented the types of services provided during the Homeless Connect event. A semi-structured interview was conducted post-event to investigate barriers, facilitators and changes that would be recommended for future events. Their perceptions of their role in the multidisciplinary healthcare team were also explored. Results. Primarily, the services provided included delivery of primary healthcare, advice on accessing cost effective pharmacy services and addressing medication enquiries. The pharmacists also provided moisturiser samples and health information leaflets. Interdisciplinary referrals were primarily between the pharmacists and podiatrists; no pharmacist-medical practitioner referrals occurred. The pharmacists did believe they had a positive role in this health initiative but improvements could be implemented to improve the delivery of these services in future events. Discussion. Pharmacists can play an important role in providing services to people experiencing or at risk of homelessness and the overall experience was positive for the pharmacists. They were able to integrate into a multidisciplinary healthcare team in this setting but strategies for further collaboration were identified. The possibility of involving pharmacy students in future events was identified.

Trafficking and ethanol-induced inhibition of AMPA receptors

AMPA receptors are an important class of ionotropic glutamate receptors which participate in fast excitatory synaptic transmission in most brain areas. They have a pivotal role in adjustment of cell membrane excitability as their cell membrane expression levels is altered in brain physiology such as in learning and memory formation. AMPA receptor function and trafficking is regulated by several proteins, such as transmembrane AMPA receptor regulatory proteins (TARPs). NMDA-type glutamate receptors are important target molecules of ethanol. The role of AMPA receptors in the actions of ethanol has not been clarified as thoroughly. Furthermore, the regulation of AMPA receptor synthesis and their possible adaptation in neurons with altered inhibitory mechanisms are poorly understood. In this thesis work AMPA receptor pharmacology, trafficking and synaptic localization was studied using patch-clamp electrophysiology. Both native and recombinant AMPA receptors were studied. Hippocampal slices from transgenic Thy1alfa6 mice with altered inhibition were used to study adaptation of AMPA receptors. Ethanol was found to inhibit AMPA receptor function by increasing desensitization of the receptor, as the steady-state current was inhibited more than the peak current. Ethanol inhibition was reduced when cyclothiazide was used to block desensitization and when non-desensitizing mutant receptors were studied. Ethanol also increased the rate of desensitization, which was increased further by the coexpression of TARP-proteins. We found that the agonist binding capability is important for trafficking AMPA receptors from endoplasmic reticulum to the cell membrane. TARP rescues the surface expression of non-binding AMPA receptor mutants in HEK293 cells, but not in native neurons. Studies with Thy1alfa6 mice revealed that decreased inhibition decrease AMPA receptor mediated excitation keeping the neurotransmission in balance. Thy1alfa6 mice also had lower sensitivity to electroshock convulsions, presumably due to the decreased AMPA receptor function. The results suggest that during alcohol intoxication ethanol may inhibit AMPA receptors by increasing the rate and the extent of desensitization. TARPs appear to enhance ethanol inhibition. TARPs also participate in trafficking of AMPA receptors upon their synthesis in the cell. AMPA receptors mediate also long-term adaptation to altered neuronal excitability, which adds to their well-known role in synaptic plasticity.

Advanced practice: A survey of current perspectives of Australian pharmacists

Background An Advanced Pharmacy Practice Framework for Australia (the ‘APPF’) was published in October 2012. Further to the release of the APPF, the Advanced Pharmacy Practice Framework Steering Committee planned to develop an advanced practice recognition model for Australian pharmacists. Aim To gauge the perspectives of the pharmacy profession relating to advanced practice, via an online survey, in order to inform the design of the model. Method A survey was developed and administered to Australian pharmacists through SurveyMonkey . The survey content was based on findings from a review of national and international initiatives for recognition of advanced practice in pharmacy and other health disciplines, including medicine and nursing. Results The results of the survey showed that a high proportion of respondents considered they were already working at, or working towards achieving, an advanced level of practice. The responses relating to the assessment methods showed a clear preference for ‘submission of a professional portfolio’. A ‘written examination’ had a low level of support and in relation to an ‘oral examination by a panel’ there was a marked preference for a panel of multidisciplinary health professionals over a panel of pharmacists. Conclusion The survey outcomes will inform the development of an advanced pharmacy practice recognition model for Australian pharmacists, particularly in relation to the assessment methods. Survey outcomes also demonstrated that there is scope to further enhance the application of the APPF in the development and recognition of advanced practitioners, and to build greater awareness of the breadth of competencies encompassed by ‘advanced practice’.

Assessment of signs of foot infection in diabetes patients using photographic foot imaging and infrared thermography

Background Patients with diabetic foot disease require frequent screening to prevent complications and may be helped through telemedical home monitoring. Within this context, the goal was to determine the validity and reliability of assessing diabetic foot infection using photographic foot imaging and infrared thermography. Subjects and Methods For 38 patients with diabetes who presented with a foot infection or were admitted to the hospital with a foot-related complication, photographs of the plantar foot surface using a photographic imaging device and temperature data from six plantar regions using an infrared thermometer were obtained. A temperature difference between feet of > 2.2 °C defined a ''hotspot.'' Two independent observers assessed each foot for presence of foot infection, both live (using the Perfusion-Extent-Depth- Infection-Sensation classification) and from photographs 2 and 4 weeks later (for presence of erythema and ulcers). Agreement in diagnosis between live assessment and (the combination of ) photographic assessment and temperature recordings was calculated. Results Diagnosis of infection from photographs was specific (> 85%) but not very sensitive (< 60%). Diagnosis based on hotspots present was sensitive (> 90%) but not very specific (<25%). Diagnosis based on the combination of photographic and temperature assessments was both sensitive (> 60%) and specific (> 79%). Intra-observer agreement between photographic assessments was good (Cohen's j = 0.77 and 0.52 for both observers). Conclusions Diagnosis of foot infection in patients with diabetes seems valid and reliable using photographic imaging in combination with infrared thermography. This supports the intended use of these modalities for the home monitoring of high-risk patients with diabetes to facilitate early diagnosis of signs of foot infection.

Sitagliptin and other ‘gliptins’ - why prescribe them?

Introduction In 2008, the Federal Drug Administration (FDA) required all new glucose-lowering therapies to show cardiovascular safety, and this applies to the dipeptidyl peptidase (DPP)-4 inhibitors (‘gliptins’). At present, there is contradictory evidence on whether the gliptins increase hospitalizations for heart failure. Areas covered This is an evaluation of the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) in high risk cardiovascular subjects with type 2 diabetes [1]. TECOS demonstrated non-inferiority for sitagliptin over placebo for the primary outcome, which was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. There was no difference in the rate of hospitalization for heart failure between sitagliptin and placebo. Expert Opinion Despite the results of TECOS, debate over the effects of sitagliptin on the rates of hospitalizations for heart failure continues with some recent studies suggesting increased rates. Recently, empagliflozin (an inhibitor of sodium-glucose cotransporter 2) has been shown to reduce cardiovascular outcomes in subjects with type 2 diabetes, including the rates of hospitalization for heart failure. In our opinion, these positive findings with empagliflozin suggest that it should be prescribed in preference to the gliptins, including sitagliptin, unless any positive cardiovascular outcomes are reported for the gliptins.

Management of persistent pain in the older people

Persistent pain is a commonly experienced symptom. It affects 25% of community-dwelling older adults and up to 80% of nursing home residents, and can have a major impact on quality of life and functional capacity. Unfortunately pain in older patients is often undertreated and misunderstood. Assessment of pain type and severity is important. Most older people, even with moderately impaired cognition, are able to self-report pain. Validated assessment tools using non-verbal pain cues are available for people with more advanced cognitive impairment. Management of pain in older people can be challenging. Physiological changes may impact on pain perception and the pharmacodynamics and pharmacokinetics of medications. Older people are often more sensitive to the adverse effects of analgesic medications and are at risk of drug–drug interactions due to the presence of co-morbidities and polypharmacy. In general, analgesic medications should be commenced at low doses, titrated based on effect and tolerability, and regularly reviewed. Contemporary pain management often utilises multiple analgesics in lower doses to optimise efficacy and avoid dose-related toxicity. A bio-psycho-social approach to the management of persistent pain, utilising a multidisciplinary team and including non-drug strategies, may produce the best results. The goal of pain management is not always to eliminate pain, since this may not be attainable, but rather to enhance function and improve quality of life. This article discusses persistent non-cancer pain in older people, its assessment and management, and the risks and benefits of pharmacological treatment in this population.

Evaluation of hexane and ethyl acetate extracts of the sponge Jaspis diastra collected from Mauritius Waters on HeLa cells

Objectives Based on previous screening results, the cytotoxic effect of the hexane (JDH) and ethyl acetate extracts (JDE) of the marine sponge Jaspis diastra were evaluated on HeLa cells and the present study aimed at determining their possible mechanism of cell death. Methods Nuclear staining, membrane potential change, flow cytometry analysis of cell cycle distribution and annexin V staining were undertaken to investigate the effects of JDE and JDH. Electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance were used to characterize an isolated bioactive molecule. Key findings JDE displayed an IC50 25 times more significant than the JDH. Flow cytometry analysis revealed JDE induced apoptosis in HeLa cells accompanied by the collapse of mitochondrial membrane potential. Fractionation of JDE resulted in the isolation of the known cytotoxic cyclodepsipeptide, Jaspamide. Conclusions Taking our results together suggest that JDE can be valuable for the development of anticancer drugs, especially for cervical cancer. Further investigations are currently in progress with the aim to determine and isolate other bioactive compounds from this extract.

Spread of Salmonella enterica in the body during systemic infection: unravelling host and pathogen determinants.

Salmonella enterica causes a range of life-threatening diseases in humans and animals worldwide. Current treatments for S. enterica infections are not sufficiently effective, and there is a need to develop new vaccines and therapeutics. An understanding of how S. enterica spreads in tissues has very important implications for targeting bacteria with vaccine-induced immune responses and antimicrobial drugs. Development of new control strategies would benefit from a more sophisticated evaluation of bacterial location, spatiotemporal patterns of spread and distribution in the tissues, and sites of microbial persistence. We review here recent studies of S. enterica serovar Typhimurium (S. Typhimurium) infections in mice, an established model of systemic typhoid fever in humans, which suggest that continuous bacterial spread to new infection foci and host phagocytes is an essential trait in the virulence of S. enterica during systemic infections. We further highlight how infections within host tissues are truly heterogeneous processes despite the fact that they are caused by the expansion of a genetically homogeneous microbial population. We conclude by discussing how understanding the within-host quantitative, spatial and temporal dynamics of S. enterica infections might aid the development of novel targeted preventative measures and drug regimens.

PICES Science: the first ten years and a look to the future

Introduction [pdf, 0.17 MB] Warren S. Wooster [pdf, 0.12 MB] PICES - the first decade, and beyond Paul H. LeBlond [pdf, 0.03 MB] The Physical Oceanography and Climate Committee: The first decade D.E. Harrison and Neville Smith [pdf, 0.04 MB] Ocean observing systems and prediction - the next ten years Tsutomu Ikeda and Patricia A. Wheeler [pdf, 0.85 MB] Ocean impacts from the bottom of the food web to the top: Biological Oceanography Committee (BIO) retrospective Timothy R. Parsons [pdf, 0.2 MB] Future needs for biological oceanographic studies in the Pacific Ocean Douglas E. Hay, Richard J. Beamish, George W. Boehlert, Vladimir I. Radchenko, Qi-Sheng Tang, Tokio Wada, Daniel W. Ware and Chang-Ik Zhang [pdf, 0.2 MB] Ten years FIS in PICES: An introspective, retrospective, critical and constructive review of fishery science in PICES Richard F. Addison, John E. Stein and Alexander V. Tkalin [pdf, 0.12 MB] Marine Environmental Committee in review Robie W. Macdonald, Brian Morton, Richard F. Addison and Sophia C. Johannessen [pdf, 1.89 MB] Marine environmental contaminant issues in the North Pacific: What are the dangers and how do we identify them? R. Ian Perry, Anne B. Hollowed and Takashige Sugimoto [pdf, 0.36 MB] The PICES Climate Change and Carrying Capacity Program: Why, how, and what next? List of acronyms [pdf, 0.07 MB] (Document contains 108 pages)

Purif ication and Characterization of Jerdonitin ,a Non2hemorrhagic Metalloproteinase fromTrimeresurus jerdonii Venom

以前从菜花烙铁头蛇毒中分离纯化到J erdonitin 。与其他Ⅱ型蛇毒金属蛋白酶相比, J erdonitin 由金属蛋白酶和去整合素两个结构域组成。但没有检测到其出血和纤维蛋白原降解活性, 推测可能高压液相色谱的有机溶液影响了其酶活性。采用不含高压液相色谱柱层析的新分离手段分离得到J erdonitin 。J erdonitin 在还原和非还原SDS2PAGE 电泳中分别呈现一条表观分子量为38 和36 kDa 的条带。像其他典型的蛇毒金属蛋白酶一样, J erdonitin 优先降解人纤维蛋白原的alpha 链, 并且该活性能被EDTA 完全抑制, 而PMSF 对其没有影响。J er2 donitin 不诱导小白鼠皮下出血。

Grand Challenges for Data Sensing and Analysis

A diverse group of experts proposed the 9 grand challenges outlined in this booklet. This expert task force was assembled by the ASCE TCCIT Data Sensing and Analysis (DSA) Committee and endorsed by the TRB AFH10(1) Construction IT joint subcommittee at the request of their membership. The task force did not rank the challenges selected, nor did it endorse particular approaches to meeting them. Rather than attempt to include every important goal for data sensing and analysis, the panel chose opportunities that were both achievable and sustainable to help people and the planet thrive. The panel’s conclusions were reviewed by several subject-matter experts. The DSA is offering an opportunity to comment on the challenges by contacting the task force chair via email at becerik@usc.edu.