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Background: Increased rates of international travel have led to a higher demand for healthcare professionals to provide travel health services. Community-based pharmacists are capable of meeting this need., Objective: This study evaluates the impact of pharmacists providing travel health services in a community-based pharmacy on participant understanding and satisfaction of travel education and preparation., Method: A trained pharmacist met with participants to review their medical history, travel itinerary, and provide education. Indicated immunizations were administered and the participant's primary care provider was contacted if prescription medications were warranted. A questionnaire was administered before and after the travel health consultation assessing participants perceived understanding of travel health information, satisfaction, and perceived monetary value of the service. Data were collected by 5-point Likert-scale responses, with 5 equivalent to strongly agree. Wilcoxon signed-rank test and descriptive statistics were used for evaluation. Participants were included if they had international travel planned within 12 weeks of the consultation., Results: A total of 12 participants were included. Participant understanding significantly increased for all 5 survey items relating to travel health information with a p value < 0.05 for each item. The largest change was for how to find medical help during international travel (medians and IQR were 3(2-3), and 5(5-5) for pre-and post-consultation, respectively, p = 0.003). Participant satisfaction questions received a median response of 5. Participants' perceived monetary value of the service was a median of $50 (IQR $50-50)., Conclusion: Pharmacist-led travel health consultations improved participant understanding of travel health information and was of perceived value.

Objective: To examine the differences in live birth rates (LBRs), with single embryo transfer (SET), using oocytes from program generated egg donors vs. commercial egg bank donors and other factors affecting LBRs using donor oocytes., Design: Retrospective cohort study., Setting: Not applicable., Patient(s): A total of 40,485 in vitro fertilization cycles using donor oocytes reported to the Society for Assisted Reproductive Technology registry in 2016-2018., Intervention(s): None., Main Outcome Measure(s): Live birth rate and cumulative LBR for SET using donor oocytes., Result(s): Multivariate results from the first SET from 19,128 cycles, including 15,429 from program generated egg donors and 3,699 from commercial egg banks, showed, when controlling for all other variables, the following: the LBR in the first SET cycle using commercial egg banks was 53.3% compared with 55.4% using program recruited egg donors (odds ratio [OR], 0.92); a reduction in the LBR with increasing recipient age, ages 40-44 years (OR, 0.80), 45-49 years (OR, 0.77), and >49 years (OR, 0.65); a steady decline in the LBR with increases in recipient body mass index above normal; and a steady increase in the LBR in association with >16 oocytes retrieved. Double embryo transfer increased the LBR (SET, 52%, vs. double embryo transfer, 58%) but also significantly increased the multiple pregnancy LBR, with 43% twins and 0.9% triplets. Blastocyst transfer had a higher LBR than cleavage stage embryos (52.5% vs. 39.5%). Intracytoplasmic sperm injection vs. conventional insemination when using fresh oocytes from program donors had similar LBRs., Conclusion(s): When performing in vitro fertilization using donor oocytes with SET, the LBR is affected by oocyte source, recipient age, recipient body mass index, stage of embryo at transfer, and number of oocytes retrieved., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Deoxyribonucleic acid (DNA) has been hypothesized to act as a molecular wire due to the presence of an extended π-stack between base pairs, but the factors that are detrimental in the mechanism of charge transport (CT) across tunnel junctions with DNA are still unclear. Here we systematically investigate CT across dense DNA monolayers in large-area biomolecular tunnel junctions to determine when intrachain or interchain CT dominates and under which conditions the mechanism of CT becomes thermally activated. In our junctions, double-stranded DNA (dsDNA) is 30-fold more conductive than single-stranded DNA (ssDNA). The main reason for this large change in conductivity is that dsDNA forms ordered monolayers where intrachain tunneling dominates, resulting in high CT rates. By varying the temperature T and the length of the DNA fragments in the junctions, which determines the tunneling distance, we reveal a complex interplay between T , the length of DNA, and structural order on the mechanism of charge transport. Both the increase in the tunneling distance and the decrease in structural order result in a change in the mechanism of CT from coherent tunneling to incoherent tunneling (hopping). Our results highlight the importance of the interplay between structural order, tunneling distance, and temperature on the CT mechanism across DNA in molecular junctions.

Four new bis-substituted ferrocene derivatives containing either a hydroxyalkyl or methoxyalkyl group and either a thyminyl or methylthyminyl group have been synthesised and characterised by a range of spectroscopic and analytical techniques. They were included in a structure-activity-relationship (SAR) study probing anticancer activities in osteosarcoma (bone cancer) cell lines and were compared with a known lead compound, 1-(S,R p ), a nucleoside analogue that is highly toxic to cancer cells. Biological studies using the MTT assay revealed that a regioisomer of ferronucleoside 1-(S,R p ), which only differs from the lead compound in being substituted on two cyclopentadienyl rings rather than one, was over 20 times less cytotoxic. On the other hand, methylated derivatives of 1-(S,R p ) showed comparable cytotoxicities to the lead compound. Overall these studies indicate that a mechanism of action for 1-(S,R p ) cannot proceed through alcohol phosphorylation and that its geometry and size, rather than any particular functional group, are crucial factors in explaining its high anticancer activity., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A new chiral organometallic nucleoside analogue containing ruthenocene is reported, in which alkylthymine and alkylhydroxyl groups are attached in adjacent positions on one cyclopentadienyl ring. The synthetic procedures for this metallocene derivative and two control compounds are described, along with their characterisation by cyclic voltammetry and X-ray crystallography. Their biological activities in a human pancreatic cancer cell line (MIA-Pa-Ca-2) were significantly lower than those of three previously reported analogous ferrocene compounds, indicating that the choice of metallocene metal atom (Fe or Ru) plays a pivotal role in determining the anticancer properties of these nucleoside analogues, which in turn suggests a different mode of action from that of a conventional nucleoside analogue.

Gliomas are highly malignant brain tumours characterised by extensive areas of poor perfusion which subsequently leads to hypoxia and reduced survival. Therapies that address the hypoxic microenvironment are likely to significantly improve patient outcomes. Verteporfin, a benzoporphyrin-like drug, has been suggested to target the Yes-associated protein (YAP). Increased YAP expression and transcriptional activity has been proposed in other tumour types to promote malignant cell survival and thus YAP-inhibitor, verteporfin, may be predicted to impact glioma cell growth and viability. Due to the extensive hypoxic nature of gliomas, we investigated the effect of hypoxia on YAP expression and found that YAP transcription is increased under these conditions. Treatment of both primary and immortalised glioblastoma cell lines with verteporfin resulted in a significant decrease in viability but strikingly only under hypoxic conditions (1% O 2 ). We discovered that cell death occurs through a YAP-independent mechanism, predominately involving binding of free iron and likely through redox cycling, contributes to production of reactive oxygen species. This results in disruption of normal cellular processes and death in cells already under oxidative stress - such as those in hypoxia. We suggest that through repurposing verteporfin, it represents a novel means of treating highly therapy-resistant, hypoxic cells in glioma.

Background: Leg ulcers affect up to one percent of people at some time in their life. Leg ulceration is chronic in nature and ulcers may be present for months or even years without healing. After healing there is a high risk of recurrence. Treatments include wound dressings alongside the treatment of underlying medical problems such as poor blood supply, infection and poor nutrition., Objectives: To assess the effectiveness of oral zinc in healing arterial or venous leg ulcers., Search Methods: For this seventh update we searched The Cochrane Wounds Group Specialised Register (searched 02 September 2014) and The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 8). In the original version of the review a company manufacturing zinc sulphate tablets was asked for references to relevant trials., Selection Criteria: Randomised controlled trials comparing oral zinc sulphate with placebo or no treatment in people with arterial or venous leg ulcers were eligible for inclusion. There were no restrictions on date or language of publication. The main outcome measure used was complete healing of the ulcers. Trials were eligible for inclusion if they measured ulcer healing objectively by documenting time to complete healing, proportion of ulcers healed during the study, or healing rates of ulcers., Data Collection and Analysis: All data extraction and assessment of trial quality was done by both authors independently., Main Results: Six small trials (183 participants) were eligible for inclusion. Four trials considered people with venous ulcers, one trial involved people with arterial ulcers and one people with mixed aetiology ulcers. Serum zinc was measured in four trials and four trials compared oral zinc sulphate with placebo in people with venous ulcers; pooling these trials indicated no statistically significant difference between the two groups for healing (RR 1.22, 95%CI 0.88 to 1.68). Overall, there is no evidence that oral zinc increases the healing of arterial or venous leg ulcers., Authors' Conclusions: Oral zinc sulphate does not appear to aid the healing of arterial and venous leg ulcers, however all included studies were small and at unclear risk of bias (due to poor reporting).

Background: Leg ulcers affect up to one percent of people at some time in their life. Leg ulceration is chronic in nature with ulcers being present for months and in some cases years without healing, and with a high risk of recurrence. Management approaches include dressings and the treatment of underlying medical problems such as malnutrition, lack of minerals and vitamins, poor blood supply or infection., Objectives: To assess the effectiveness of oral zinc in healing arterial or venous leg ulcers., Search Methods: For this sixth update we searched The Cochrane Wounds Group Specialised Register (searched 17 May 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 5); Ovid MEDLINE (2010 to May Week 2 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations May 16, 2012); Ovid EMBASE (2010 to 2012 Week 19); and EBSCO CINAHL (2010 to May 2 2012). In the original version of the review a company manufacturing zinc sulphate tablets was asked for references to relevant trials., Selection Criteria: Randomised controlled trials comparing oral zinc sulphate with placebo or no treatment in people with arterial or venous leg ulcers were eligible for inclusion. There were no restrictions on date or language of publication. The main outcome measure used was complete healing of the ulcers. Trials were eligible for inclusion if they measured ulcer healing objectively by documenting time to complete healing, proportion of ulcers healed during the study, or healing rates of ulcers., Data Collection and Analysis: All data extraction and assessment of trial quality were done by both authors independently., Main Results: Six small trials (183 participants) were eligible for inclusion. Four trials considered people with venous ulcers, one trial arterial ulcers and one people with mixed ulcers. In four trials, serum zinc was measured at baseline or during the trial. Pooling the four trials that compared oral zinc sulphate with placebo in people with venous ulcers showed no statistically significant difference between the two group (RR 1.22, 95%CI 0.88 to 1.68). Overall, there was no evidence of a beneficial effect of treatment with zinc sulphate on the number of ulcers healed., Authors' Conclusions: Oral zinc sulphate does not appear to aid healing of arterial and venous leg ulcers, however all included studies were small and of mediocre quality.

Background and Purpose: Corticosteroids have been commonly used in medical expulsive therapy for obstructing ureteral calculi. The exact mechanism of action responsible for facilitation of stone expulsion is unknown, but it is attributed to the anti-inflammatory properties of corticosteroids. Corticosteroids inhibit the production of phospholipase A2 and cyclooxygenase-2, both of which are involved in prostaglandin synthesis. We sought to determine if hydrocortisone inhibits ureteral contractility directly by assessing its action in an isolated in vitro contractility assay., Methods: Porcine ureters were attached to force displacement transducers and suspended in organ tissue baths containing aerated Krebs buffer. Tissues were equilibrated for 1 hour, and a spontaneous contractility rate was established. After equilibration, tissues were incubated with a 10-fold concentration curve of hydrocortisone (1 nM-10 microM) for 90 minutes, and compared with indomethacin (1 microM) and dimethyl sulfoxide (DMSO) 0.1% as positive and negative controls of contraction, respectively. Contractility rates were recorded on a polygraph and analyzed for changes over exposure time during the course of the experiment., Results: Hydrocortisone inhibited ureteral contractility in a concentration dependent trend. After 90 minutes of treatment, 100 nM, 1 microM, and 10 microM all produced a statistically significant decrease in ureteral contractility rates relative to DMSO controls. The average percent decrease was 43.7% by 100 nM, 66.9% by 1 microM, and 66% by 10 microM hydrocortisone. This decrease in ureteral contractility continued to be significant at 120 minutes. In addition, 10 microM and 1 microM hydrocortisone treatment caused a similar reduction in contractility to indomethacin at 120 minutes., Conclusion: Hydrocortiosone effectively inhibits stretch-induced ureteral contractility of porcine ureter in an isolated in vitro assay.

Purpose: To compare tip temperatures of the vibrating blades of the newer-generation Harmonic Ace device and the older-generation Ultracision Harmonic Scalpel LCS-K5., Materials and Methods: Comparison of two different harmonic scalpel blades was performed by applying them to 3-mm strips of raw chicken breast at room temperature and measuring the temperature of the tip of the vibrating blade at 0.5-second intervals using a thermocouple. Following activation, the tip was allowed to passively cool to 30 degrees C each time before reactivation. Each device was tested at power settings of 3 and 5 after activation for 1 to 5 seconds. All measurements were performed 5 times., Results: Compared to the older-generation Ultracision Harmonic Scalpel LCS-K5, the newer-generation Harmonic Ace was associated with higher tip temperatures at power level 5 at all times of activation (1-5 seconds), and at power level 3 at longer times of activation (3-5 seconds). The Harmonic Ace also takes longer to reach peak temperatures and can maintain blade hyperthermia for a longer period after activation for more than 3 seconds at power levels 3 and 5., Conclusion: The newer-generation Harmonic Ace may be potentially more effective in tissue dissection, but is associated with greater increases in peak temperatures and longer blade hyperthermia periods compared to the older-generation Ultracision Harmonic Scalpel LCS-K5. The difference is greater after longer periods of activation, and this may have more potential for collateral damage, particularly to nerves and bowel.

Background: Leg ulcers affect up to 1 per cent of people at some time in their life. Management includes care of the ulcer using dressings and treatment of underlying medical problems such as malnutrition, lack of minerals, vitamins, poor blood supply or infection., Objectives: To assess the effectiveness of oral zinc in healing arterial or venous leg ulcers., Search Strategy: Searches of 19 databases, hand searching of journals and conference proceedings from 1948 onwards, and examination of bibliographies. The company manufacturing zinc sulphate tablets was asked for references to relevant trials., Selection Criteria: Randomised controlled trials comparing oral zinc sulphate with placebo or no treatment in patients with arterial or venous leg ulcers. There was no restriction on date or language. The main outcome measure used was complete healing of the ulcers. Trials were eligible for inclusion if they measured ulcer healing objectively, by time to complete healing, proportion of ulcers healed during the study, or healing rates of ulcers., Data Collection and Analysis: All data extraction and assessment of trial quality were done by both authors independently., Main Results: There were six eligible trials. All are small and serum zinc was measured at baseline or during the trial in 4 trials. Overall there is no evidence of a beneficial effect of treatment with zinc sulphate on the number of ulcers healed at the end of the trials. There is some evidence that oral zinc might have a beneficial effect on healing of venous ulcers in people with a 'low' serum zinc level at baseline., Reviewer's Conclusions: Overall, oral zinc sulphate does not appear to aid healing of leg ulcers, although it might be beneficial in those with venous leg ulcers and low serum zinc. Further research is needed to ascertain the serum zinc concentration below which treatment with zinc might be beneficial, and the dose required. [This abstract was prepared centrally]

Objective: To determine whether oral zinc sulfate is an effective treatment for promoting healing of venous or arterial leg ulcers., Data Sources: The search strategy of the Cochrane Wounds Group was used. This includes searches of electronic databases, conference proceedings, relevant bibliographies, and hand searching of journals., Study Selection: Studies were included if they were randomized controlled trials of oral zinc sulfate in the treatment of chronic venous or arterial ulcers with objective measures of healing. Six of the 10 studies initially identified were included in the review., Data Extraction: The trial method, participants, interventions, outcomes, baseline comparability, adequate reporting of withdrawals, and blinding of assessment were extracted by 2 reviewers independently., Data Synthesis: No trial showed a statistically significant benefit of zinc sulfate for healing leg ulcers. There is limited evidence to suggest that zinc might increase healing in individuals with a low serum zinc level, but more evidence is needed., Conclusions: There is no evidence of benefit from the general use of zinc sulfate in patients with chronic leg ulcers. There is a need for further research to see if oral zinc sulfate is beneficial in the treatment of patients with leg ulcers who have a low serum zinc level. If it is demonstrated to be beneficial, further trials are required to establish dose and duration of treatment.