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Abstract Introduction Critical care pharmacists improve the quality and efficiency of medication therapy whilst reducing treatment costs where they are available. UK critical care pharmacist deployment was described in 2015, highlighting a deficit in numbers, experience level, and critical care access to pharmacy services over the 7-day week. Since then, national workforce standards have been emphasised, quality indicators published, and service commissioning documents produced, reinforced by care quality assessments. Whether these initiatives have resulted in further development of the UK critical care pharmacy workforce is unknown. This evaluation provides a 2020 status update. Methods The 2015 electronic data entry tool was updated and circulated for completion by UK critical care pharmacists. The tool captured workforce data disposition as it was just prior to the COVID-19 pandemic, at critical care unit level. Main findings Data were received for 334 critical care units from 203 organisations (96% of UK critical care units). Overall, 98.2% of UK critical care units had specific clinical pharmacist time dedicated to the unit. The median weekday pharmacist input to each level 3 equivalent bed was 0.066 (0.043–0.088) whole time equivalents, a significant increase from the median position in 2015 (+ 0.021, p

Misinformation and disinformation regarding COVID-19 and vaccination against it may be contributing to vaccine hesitancy. Social media outlets have reportedly made efforts to limit false information yet untruths related to COVID-19 persist online. The purpose of this study was to describe the content on COVID-19 vaccination on TikTok, an emerging social media platform. One-hundred trending videos were identified from the hashtag #covidvaccine and were coded for content. Collectively, these videos garnered over 35 million views. The coding category with the highest number of videos was “Discouraged a Vaccine” (n = 38), followed by “Encouraged a Vaccine” (n = 36). While only 36 videos encouraged a vaccine, these videos garnered over 50% of the total cumulative views and just under 50% of the total likes; the 38 videos that discouraged a vaccine garnered 39.6% of the total cumulative views, 44.3% of likes, and 47.4% of comments. Of the 38 videos discouraging the vaccine, 25 (65.79%) showed a parody of an adverse reaction and, collectively, received 71.07% of the total views among videos in this category. Twenty-two of these 38 videos (57.89%) falsely conveyed that a vaccine was available, as they were not at the time of the study. Anti-vaccination messaging may undermine efforts to ensure widespread uptake of the various COVID-19 vaccines, particularly for young people who are more likely than other age cohorts to use TikTok.

BackgroundSocial media platforms that are based on the creation of visual media, such as TikTok, are increasingly popular with adolescents. Online social media networks provide valuable opportunities to connect with each other to share experiences and strategies for health and wellness. ObjectiveThe aim of this study was to describe the content of the hashtag #mentalhealth on TikTok. MethodsThis cross-sectional, descriptive content analysis study included 100 videos with the hashtag #mentalhealth on TikTok. All videos that included the hashtag #mentalhealth were analyzed and coded for the presence of content categories. Additionally, the comments to each video were viewed and coded for content in the following themes: offering support or validation; mentioning experience with suicide or suicidal ideation; mentioning experience with self-harm; describing an experience with hospitalization for mental health issues; describing other mental health issues; and sharing coping strategies, experiences of healing, or ways to feel better. ResultsCollectively, the 100 videos studied received 1,354,100,000 views; 266,900,000 likes; and 2,515,954 comments. On average, each video received 13,406,930.69 (SD 8,728,095.52) views; 2,657,425.74 (SD 1,449,920.45) likes; and 24,910.44 (SD 21,035.06) comments. The only content category observed in most (51/100, 51%) of the videos included in the sample was “general mental health.” The remaining content categories appeared in less than 50% of the sample. In total, 32% (32/100) of the videos sampled received more than the overall average number of likes (ie, more that 2.67 million likes). Among these 32 videos, 23 (72%) included comments offering support or validation and 20 (62%) included comments that described other mental health issues or struggles. ConclusionsWith over 1 billion cumulative views, almost half of the assessed TikTok videos included in this study reported or expressed symptoms of mental distress. Future research should focus on the potential role of intervention by health care professionals on social media.

BackgroundBlended models of therapy, which incorporate elements of both internet and face-to-face methods, have been shown to be effective, but therapists and patients have expressed concerns that fewer face-to-face therapy sessions than self-guided internet sessions may be associated with lower therapeutic alliance, lower program completion rates, and poorer outcomes. ObjectiveA multisite quasi-experimental comparison study with a noninferiority design implemented in routine clinical care was used to assess webSTAIR, a 10-module blended therapy derived from STAIR (skills training in affective and interpersonal regulation) for trauma-exposed individuals delivered with 10 weekly therapist sessions (termed Coach10) compared to 5 biweekly sessions (Coach5). It was hypothesized that Coach5 would be as good as Coach10 in a range of outcomes. MethodsA total of 202 veterans were enrolled in the study with 101 assigned to Coach5 and 101 to Coach10. Posttraumatic stress disorder (PTSD) symptoms, depression, emotion regulation, interpersonal problems, and social functioning measures were collected pre-, mid-, and posttreatment, and at a 3-month follow-up. Noninferiority analyses were conducted on symptom outcome measures. Comparisons were made of continuous and categorical measures regarding participant and therapist activities. ResultsParticipants reported moderate to severe levels of baseline PTSD, depression, or both. Significant reductions were obtained in all symptom measures posttreatment and at the 3-month follow up. Coach5 was not inferior to Coach10 in any outcome. Therapeutic alliance was at an equivalently high level across the 2 treatment conditions; completion rates and web usage were similar. Total session time was substantially less for the Coach5 therapists than the Coach10 therapists. Both programs were associated with a low, but equal number of therapist activities related to scheduling and crisis or motivational sessions. ConclusionsA blended model delivered with 5 sessions of therapist support was noninferior to 10 sessions in individuals with moderate to severe symptoms. Future studies identifying patient characteristics as moderators of outcomes with high versus low doses of therapist support will help create flexible, technology-based intervention programming.

The biological activities of dehydrocostus lactone and its analogues are suggested to be mediated by the lactone ring and α,β-methylene-γ-lactone. However, few studies exist on the structure-activity relationship of 13-amino derivatives of dehydrocostus latone. In this study new 13-amino derivatives of dehydrocostus lactone DHLC (1–4) were synthesized through Michael addition reactions, and were screened against three different breast cancer cell lines, namely hormone receptor positive breast cancer (MCF-7), triple-negative breast cancer (HCC70), and non-tumorigenic mammary epithelial (MCF-12A) cell lines. Dehydrocostus lactone (DHLC) exhibited IC50 values of 1.11 (selectivity index (SI) = 0.06), 24.70 (SI = 0.01) and 0.07 μM against HCC70, MCF-7 and MCF-12A cells, respectively. All the amino derivatives, except DHLC-3 displayed low micromolar IC50 values (ranging from 0.07–4.24 μM) against both breast cancer cell lines, with reduced toxicity towards MCF-12A non-tumorigenic mammary epithelial cells (SI values ranging from 6.00–126.86). DHLC-1 and DHLC-2 demonstrated the greatest selectivity for the MCF-7 cells (with SI of 121 and 126.86 respectively) over the MCF-12A cells. This reveals that, overall, the derivatives display greatly improved selectivity for breast cancer over non-tumorigenic mammary epithelial cells, with between 100-fold and 12 000-fold higher SI values. The improved docking scores were recorded for all the 13-amino dehydrocostus lactone derivatives for the enzymes analyzed. Compounds DHLC-4, and DHLC-3 recorded higher docking scores of -7.33 and -5.97 Kca/mol respectively, compared to the parent structure, dehydrocostus lactone (-5.34 Kca/mol) for protein kinase (PKC) theta (1XJD) and -6.22 and -5.88 Kca/mol, respectively for protein kinase iota (1RZR). The compounds further showed promising predicted adsorption, distribution, metabolisms and excretion (ADME) properties. Predicting the ADME properties of these derivatives is of importance in evaluating their drug-likeness, which could in turn be developed into potential drug candidates.

Background: The media plays as an important role in delivering information about emergent issues, such as the Eastern equine encephalitis virus (EEEV) outbreak of 2019. As such, there has been an increase in news coverage of vector-borne disease coverage due to a rise in emerging or re-emerging arboviruses. Methods: The purpose of this study was to describe the content of news clips related to the recent (2019) EEEV outbreak in the United States. Results: Only 3 of the important topics identified were mentioned in a majority of the 110 videos analyzed. These topics were, mosquito mentioned as transmitter, prevention by repellent/ pesticide, and geography. Thus, many aspects of EEEV were lacking in coverage. Conclusion: A priority for public health professionals should be to engage in discourse with news media to assure that information disseminated via news channels is not vague or misleading.

Background: Veterans have higher rates of PTSD and depression compared to the general population and experience substantial functional impairment. Impairment in social functioning has been a significant concern among Veterans, particularly rural Veterans, who have limited access to mental health care and are at risk for social isolation. Objective: A mixed-method study was implemented to evaluate the feasibility and effectiveness of webSTAIR, a web-based skills training programme, paired with home-based telehealth sessions. It was hypothesized that the programme would lead not only to reductions in PTSD and depression but also to improvements in social functioning. Method: Participants were 80 trauma-exposed Veterans enrolled in rural-serving VHA facilities with clinically elevated symptoms of either PTSD or depression. The study directed substantial outreach efforts to rural women Veterans and those who have experienced military sexual trauma (MST). Results: Significant improvements were obtained with PTSD and depression symptoms as well as in social functioning, emotion regulation, and interpersonal problems at post-treatment and 3-month follow-up. Ratings of therapeutic alliance were high as were reports of overall satisfaction in the programme. There were no differences by gender or MST status in symptom outcomes or satisfaction. Conclusions: The results support the feasibility and effectiveness of this integrated telehealth web-based skills training programme for both male and female Veterans as well as for those with and without MST. The focus on resource building and improved functioning make this programme of particular interest. Further testing is warranted.

Immune checkpoint inhibitor (ICI) therapy has revolutionized anti-cancer treatment for many late-stage cancer patients. However, ICI therapy has thus far demonstrated limited efficacy for most patients, and it remains unclear why this is so. Interleukin 10 (IL-10) is a cytokine that has been recognized as a central player in cancer biology with its ability to inhibit anti-tumor T cell responses. Recent studies suggest that IL-10 might also exert some intrinsic anti-tumor T cell responses, and clinical studies using recombinant IL-10 alone or in combination with ICI are underway. This paradoxical effect of IL-10 and its underlying mechanisms impacting ICI-modulated T cell responses remain poorly understood. In this study, using an in vitro mixed lymphocyte reaction assay, we found that treatment with ICIs such as the anti-programmed cell death receptor-1 (PD-1) mAb nivolumab elicits a strong expression of IL-10. While neutralization of IL-10 signaling with an anti-IL-10 specific mAb significantly decreases the production of IFN-γ by T cells in a cohort of donor cells, the opposite effect was observed in other donor cells. Similarly, neutralization of IL-10 signaling significantly decreases the expression of T cell activation markers Ki67 and CD25, as well as the production of Granzyme B in a cohort of donor cells, whereas the opposite effect was observed in others. Furthermore, we found that nivolumab and IL-10 differentially modulate the signal transducer and activator of transcription 3 (STAT3) and AKT serine–threonine kinase pathways. Finally, we found that nivolumab activates the mitogen-activated protein kinase (MAPK) pathway, which in turn is responsible for the observed induction of IL-10 production by nivolumab. These findings provide new insights into the mechanisms underlying anti-PD-1-modulated T cell responses by IL-10, which could lead to the discovery of novel combination treatments that target IL-10 and immune checkpoint molecules.

Abstract Objective To describe our use of intervention mapping as a systematic method to adapt an evidence-based physical activity and nutrition program to reflect the needs of rural Latinas. Methods An intervention mapping process involving six steps guided the adaptation of an evidence based physical activity and nutrition program, using a community-based participatory research approach. We partnered with a community advisory board of rural Latinas throughout the adaptation process. Results A needs assessment and logic models were used to ascertain which program was the best fit for adaptation. Once identified, we collaborated with one of the developers of the original program (StrongWomen - Healthy Hearts) during the adaptation process. First, essential theoretical methods and program elements were identified, and additional elements were added or adapted. Next, we reviewed and made changes to reflect the community and cultural context of the practical applications, intervention strategies, program curriculum, materials, and participant information. Finally, we planned for the implementation and evaluation of the adapted program, Mujeres Fuertes y Corazones Saludables, within the context of the rural community. A pilot study will be conducted with overweight, sedentary, middle-aged, Spanish-speaking Latinas. Outcome measures will assess change in weight, physical fitness, physical activity, and nutrition behavior. Conclusions The intervention mapping process was feasible and provided a systematic approach to balance fit and fidelity in the adaptation of an evidence-based program. Collaboration with community members ensured that the components of the curriculum that were adapted were culturally appropriate and relevant within the local community context.

The absence of reliable, robust, and non-invasive biomarkers for anti- Programmed cell death protein 1 (PD-1) immunotherapy is an urgent unmet medical need for the treatment of cancer patients. No predictive biomarkers have been established based on the direct assessment of T cell functions, the primary mechanism of action of anti-PD-1 therapy. In this study, we established a model system to test T cell functions modulated by Nivolumab using anti-CD3 monoclonal antibody (mAb)-stimulated peripheral blood mononuclear cells (PBMCs), and characterized T cell functions primarily based on the knowledge gained from retrospective observations of patients treated with anti-PD-1 immunotherapy. During a comprehensive cytokine profile assessment to identify potential biomarkers, we found that Nivolumab increases expression of T helper type 1 (Th1) associated cytokines such as interferon-γ (IFN-γ) and interleukin-2 (IL-2) in a subset of donors. Furthermore, Nivolumab increases production of Th2, Th9, and Th17 associated cytokines, as well as many proinflammatory cytokines such as IL-6 in a subset of donors. Conversely, Nivolumab treatment has no impact on T cell proliferation, expression of CD25, CD69, or Granzyme B, and only modestly increases in the expansion of regulatory T cells. Our results suggest that assessment of cytokine production using a simple PBMC-based T cell functional assay could be used as a potential predictive marker for anti-PD-1 immunotherapy.

Abstract Background We used a gene – based replication strategy to test the reproducibility of prior acute lung injury (ALI) candidate gene associations. Methods We phenotyped 474 patients from a prospective severe trauma cohort study for ALI. Genomic DNA from subjects’ blood was genotyped using the IBC chip, a multiplex single nucleotide polymorphism (SNP) array. Results were filtered for 25 candidate genes selected using prespecified literature search criteria and present on the IBC platform. For each gene, we grouped SNPs according to haplotype blocks and tested the joint effect of all SNPs on susceptibility to ALI using the SNP-set kernel association test. Results were compared to single SNP analysis of the candidate SNPs. Analyses were separate for genetically determined ancestry (African or European). Results We identified 4 genes in African ancestry and 2 in European ancestry trauma subjects which replicated their associations with ALI. Ours is the first replication of IL6, IL10, IRAK3, and VEGFA associations in non-European populations with ALI. Only one gene – VEGFA – demonstrated association with ALI in both ancestries, with distinct haplotype blocks in each ancestry driving the association. We also report the association between trauma-associated ALI and NFKBIA in European ancestry subjects. Conclusions Prior ALI genetic associations are reproducible and replicate in a trauma cohort. Kernel - based SNP-set analysis is a more powerful method to detect ALI association than single SNP analysis, and thus may be more useful for replication testing. Further, gene-based replication can extend candidate gene associations to diverse ethnicities.

Abstract Background Peroxiredoxin 6 (PRDX6) is involved in redox regulation of the cell and is thought to be protective against oxidant injury. Little is known about genetic variation within the PRDX6 gene and its association with acute lung injury (ALI). In this study we sequenced the PRDX6 gene to uncover common variants, and tested association with ALI following major trauma. Methods To examine the extent of variation in the PRDX6 gene, we performed direct sequencing of the 5' UTR, exons, introns and the 3' UTR in 25 African American cases and controls and 23 European American cases and controls (selected from a cohort study of major trauma), which uncovered 80 SNPs. In silico modeling was performed using Patrocles and Transcriptional Element Search System (TESS). Thirty seven novel and tagging SNPs were tested for association with ALI compared with ICU at-risk controls who did not develop ALI in a cohort study of 259 African American and 254 European American subjects that had been admitted to the ICU with major trauma. Results Resequencing of critically ill subjects demonstrated 43 novel SNPs not previously reported. Coding regions demonstrated no detectable variation, indicating conservation of the protein. Block haplotype analyses reveal that recombination rates within the gene seem low in both Caucasians and African Americans. Several novel SNPs appeared to have the potential for functional consequence using in silico modeling. Chi2 analysis of ALI incidence and genotype showed no significant association between the SNPs in this study and ALI. Haplotype analysis did not reveal any association beyond single SNP analyses. Conclusions This study revealed novel SNPs within the PRDX6 gene and its 5' and 3' flanking regions via direct sequencing. There was no association found between these SNPs and ALI, possibly due to a low sample size, which was limited to detection of relative risks of 1.93 and above. Future studies may focus on the role of PRDX6 genetic variation in other diseases, where oxidative stress is suspected.

Abstract Background Improved outcomes with expanding treatment options for patients with pulmonary arterial hypertension present the opportunity to consider additional end-points in approaching therapy, including factors that influence health-related quality of life. However, comparatively little is known about health-related quality of life and its determinants in patients with pulmonary arterial hypertension. Methods Health-related quality of life was evaluated in a cross sectional study of 155 outpatients with pulmonary arterial hypertension using generic and respiratory-disease specific measurement tools. Most patients had either World Health Organization functional Class II or III symptoms. Demographic, hemodynamic and treatment variables were assessed for association with health-related quality of life scores. Results Patients with pulmonary arterial hypertension suffered severe impairments in both physical and emotional domains of health-related quality of life. Patients with idiopathic ("primary") pulmonary arterial hypertension had the best, and those with systemic sclerosis the worst health-related quality of life. Greater six-minute walk distance correlated with better health-related quality of life scores, as did functional Class II versus Class III symptoms. Hemodynamic measurements, however, did not correlate with health-related quality of life scores. No differences in health-related quality of life were found between patients who were being treated with calcium channel antagonists, bosentan or continuously infused epoprostenol at the time of quality of life assessment. Conclusion Health-related quality of life is severely impaired in patients with pulmonary arterial hypertension and is associated with measures of functional status. Specific associations with impaired health-related quality of life suggest potential areas for targeted intervention.

Abstract Background The effects of pulmonary arterial hypertension on brain function are not understood, despite patients' frequent complaints of cognitive difficulties. Using clinical instruments normally administered during standard in-person assessment of neurocognitive function in adults, we assembled a battery of tests designed for administration over the telephone. The purpose was to improve patient participation, facilitate repeated test administration, and reduce the cost of research on the neuropsychological consequences of acute and chronic cardiorespiratory diseases. We undertook this study to validate telephone administration of the tests. Methods 23 adults with pulmonary arterial hypertension underwent neurocognitive assessment using both standard in-person and telephone test administration, and the results of the two methods compared using interclass correlations. Results For most of the tests in the battery, scores from the telephone assessment correlated strongly with those obtained by in-person administration of the same tests. Interclass correlations between 0.5 and 0.8 were observed for tests that assessed attention, memory, concentration/working memory, reasoning, and language/crystallized intelligence (p ≤ 0.05 for each). Interclass correlations for the Hayling Sentence Completion test of executive function approached significance (p = 0.09). All telephone tests were completed within one hour. Conclusion Administration of this neurocognitive test battery by telephone should facilitate assessment of neuropsychological deficits among patients with pulmonary arterial hypertension living across broad geographical areas, and may be useful for monitoring changes in neurocognitive function in response to PAH-specific therapy or disease progression.

In 2021, an 8-mg intranasal naloxone product was approved by the Food and Drug Administration; however, no studies have examined outcomes among persons who receive the 8-mg naloxone product and those who receive the usual 4-mg product. During March 2022-August 2023, New York State Department of Health (NYSDOH) supplied some New York State Police (NYSP) troops with 8-mg intranasal naloxone; other troops continued to receive 4-mg intranasal naloxone to treat suspected opioid overdose. NYSP submitted detailed reports to NYSDOH when naloxone was administered. No significant differences were observed in survival, mean number of naloxone doses administered, prevalence of most postnaloxone signs and symptoms, postnaloxone anger or combativeness, or hospital transport refusal among 4-mg and 8-mg intranasal naloxone recipients; however, persons who received the 8-mg intranasal naloxone product had 2.51 times the risk for opioid withdrawal signs and symptoms, including vomiting, than did those who received the 4-mg intranasal naloxone product (95% CI = 1.51-4.18). This initial study suggests no benefits to law enforcement administration of higher-dose naloxone were identified; more research is needed to guide public health agencies in considering whether 8-mg intranasal naloxone confers additional benefits for community organizations., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Sharon Stancliff reports institutional support from the New York State Stewardship Funding Harm Reduction. No other potential conflicts of interest were disclosed.

Background: Esophagogastric junction obstruction (EGJO) post-fundoplication (PF) is difficult to identify with currently available tests. We aimed to assess the diagnostic accuracy of EGJ opening on functional lumen imaging probe (FLIP) and dilation outcome in FLIP-detected EGJO in PF dysphagia., Methods: We prospectively collected data on PF patients referred to Esophageal Clinic over 18 months. EGJO diagnosis was made by (a) endoscopist's description of a narrow EGJ/wrap area, (b) appearance of wrap obstruction or contrast/tablet retention on esophagram, or (c) EGJ-distensibility index (DI) < 2.8 mm 2 /mmHg on real-time FLIP. In patients with EGJO and dysphagia, EGJ dilation was performed to 20 mm, 30 mm, or 35 mm in a stepwise fashion. Outcome was assessed as % dysphagia improvement during phone call or on brief esophageal dysphagia questionnaire (BEDQ) score., Results: Twenty-six patients were included, of whom 17 (65%) had a low EGJ-DI. No patients had a hiatal hernia greater than 3 cm. Dysphagia was the primary symptom in 17/26 (65%). In 85% (κ = 0.677) of cases, EGJ assessment (tight vs. open) was congruent between the combination of endoscopy (n = 26) and esophagram (n = 21) vs. EGJ-DI (n = 26) on FLIP. Follow-up data were available in 11 patients who had dilation based on a low EGJ-DI (4 with 20 mm balloon and 7 with ≥ 30 mm balloon). Overall, the mean % improvement in dysphagia was 60% (95% CI 37.7-82.3%, p = 0.0001). Nine out of 11 patients, including 6 out of 7 undergoing pneumatic dilation, had improvement ≥ 50% in dysphagia (mean % improvement 72.2%; 95% CI 56.1-88.4%, p = 0.0001)., Conclusions and Inferences: Functional lumen imaging probe is an accurate modality for evaluating for EGJ obstruction PF. FLIP may be used to select patients who may benefit from larger diameter dilation.

Many disorders of the gastrointestinal tract are common in pregnancy. Elevated levels of progesterone may lead to alterations in gastrointestinal motility which could contribute to nausea, vomiting, and/or GERD. Pregnancy-induced diarrhea may be due to elevated levels prostaglandins. This article reviews the normal physiologic and structural changes associated with pregnancy that could contribute to many of the common gastrointestinal complaints in pregnant patients. Additionally, the appropriate clinical and laboratory evaluations, other pathologic conditions that should be included in the differential, as well as the nonpharmacologic and pharmacologic therapies for each of these conditions is discussed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The implementation of regional primary percutaneous coronary intervention (PCI) programs has been critical in achieving timely intervention in patients with ST-segment elevation myocardial infarction (STEMI). However, 1 consequence has been inappropriate and false-positive cardiac catheterization laboratory (CCL) activations where either angiography is cancelled or no culprit lesion is found, respectively., Methods: We performed a retrospective cohort study of 1,391 patients referred for primary PCI to a single academic center from November 2007 to August 2013. Our purpose was to determine the incidence and characteristics of inappropriate and false-positive CCL activations by emergency departments (EDs) or emergency medical services (EMS), and the effect of a quality improvement (QI) initiative to reduce such events implemented during this period., Results: During the study period, there were 37 (2.7%) inappropriate and 206 (14.8%) false-positive CCL activations. There was no difference between the ED and EMS rates of inappropriate activation (2.1% vs 3.8%, P = .06). Among patients who proceeded to angiography, the false-positive rate for ED CCL activation was 16.9% compared to 11.5% for EMS (P = .01). Although there was no difference comparing inappropriate activation or false-positive rates before and after the QI initiative (P = .22), we observed an encouraging year-to-year trend., Conclusions: Emergency department activation of the CCL is associated with a higher false-positive rate than activation by EMS. Further QI efforts are required to improve communication between interventional cardiologists, emergency physicians, and paramedics to improve the specificity of CCL activation while taking care not to sacrifice sensitivity and rapidity of diagnosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The preparation of 7-Fc(+) -8-Fc-7,8-nido-[C2 B9 H10 ](-) (Fc(+) FcC2 B9 (-) ) demonstrates the successful incorporation of a carborane cage as an internal counteranion bridging between ferrocene and ferrocenium units. This neutral mixed-valence Fe(II) /Fe(III) complex overcomes the proximal electronic bias imposed by external counterions, a practical limitation in the use of molecular switches. A combination of UV/Vis-NIR spectroscopic and TD-DFT computational studies indicate that electron transfer within Fc(+) FcC2 B9 (-) is achieved through a bridge-mediated mechanism. This electronic framework therefore provides the possibility of an all-neutral null state, a key requirement for the implementation of quantum-dot cellular automata (QCA) molecular computing. The adhesion, ordering, and characterization of Fc(+) FcC2 B9 (-) on Au(111) has been observed by scanning tunneling microscopy., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Low-temperature scanning tunneling microscopy is used to observe self-assembled structures of ferrocenedicarboxylic acid (Fc(COOH)2) on the Au(111) surface. The surface is prepared by pulse-deposition of Fc(COOH)2 dissolved in methanol, and the solvent is evaporated before imaging. While the rows of hydrogen-bonded dimers that are common for carboxylic acid species are observed, the majority of adsorbed Fc(COOH)2 is instead found in six-molecule clusters with a well-defined and chiral geometry. The coverage and distribution of these clusters are consistent with a random sequential adsorption model, showing that solution-phase species are determinative of adsorbate distribution for this system under these reaction conditions.

Self-assembled monolayers of ferrocenecarboxylic acid (FcCOOH) contain two fundamental units, both stabilized by intermolecular hydrogen bonding: dimers and cyclic five-membered catemers. At surface coverages below a full monolayer, however, there is a significantly more varied structure that includes double-row clusters containing two to twelve FcCOOH molecules. Statistical analysis shows a distribution of cluster sizes that is sharply peaked compared to a binomial distribution. This rules out simple nucleation-and-growth mechanisms of cluster formation, and strongly suggests that clusters are formed in solution and collapse into rows when deposited on the Au(111) surface.

Background: The modest results of nonoperative modalities for the treatment of gastroparesis necessitate greater consideration of surgical therapies. However, the role of surgery is not well defined. The aim of this study is to present our experience with laparoscopic pyloroplasty as early treatment for gastroparesis., Study Design: Fifty patients with refractory gastroparesis underwent laparoscopic pyloroplasty (hand-sewn Heineke-Mikulicz configuration) from 2006 to 2013 at our institution. Preoperative and postoperative symptom data, gastric emptying scintigraphy, and technical outcomes of the procedure were reviewed. A single-factor ANOVA was performed for the comparison of continuous variables. Results are reported as mean ± SD or median absolute deviation., Results: Thirty-four of 50 (68%) patients had previous foregut procedures and/or cholecystectomy. Thirty-two of 50 (64%) patients underwent concomitant procedures (ie, paraesophageal hernia repair and gastrostomy takedown) along with the pyloroplasty. Operative time, including combined procedures, blood loss, and length of stay were 175 ± 56 minutes, 64 ± 50 mL, 2.5 ± 2.7 days, respectively. There were no conversions to open technique or intraoperative complications. There were no suture-line leaks. The readmission rate was 14%. All patients had symptom follow-up and 33 (66%) had postoperative gastric emptying scintigraphy. Postoperative symptom improvement was reported by 82% of the patients (p < 0.001). Median preoperative T1/2 was 180 ± 73 minutes and postoperative T1/2 was 60 ± 23 minutes (p < 0.001). Five patients (10%), who had normalized postoperative T1/2 times, required other gastric emptying procedures; distal gastrectomy (n = 2), duodenojejunostomy (n = 2), and gastric stimulator placement (n = 1)., Conclusions: Laparoscopic pyloroplasty is an effective early-treatment modality for selected cases of gastroparesis, with substantial improvement in objective gastric emptying times and low morbidity. The laparoscopic approach does not preclude subsequent procedures when necessary., (Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

The process of molecular self-assembly on solid surfaces is essentially one of crystallization in two dimensions, and the structures that result depend on the interplay between intermolecular forces and the interaction between adsorbates and the underlying substrate. Because a single hydrogen bond typically has an energy between 15 and 35 kilojoules per mole, hydrogen bonding can be a strong driver of molecular assembly; this is apparent from the dominant role of hydrogen bonding in nucleic-acid base pairing, as well as in the secondary structure of proteins. Carboxylic acid functional groups, which provide two hydrogen bonds, are particularly promising and reliable in creating and maintaining surface order, and self-assembled monolayers of benzoic acids produce structure that depends on the number and relative placement of carboxylic acid groups. Here we use scanning tunnelling microscopy to study self-assembled monolayers of ferrocenecarboxylic acid (FcCOOH), and find that, rather than producing dimeric or linear structures typical of carboxylic acids, FcCOOH forms highly unusual cyclic hydrogen-bonded pentamers, which combine with simultaneously formed FcCOOH dimers to form two-dimensional quasicrystallites that exhibit local five-fold symmetry and maintain translational and rotational order (without periodicity) for distances of more than 400 ångströms.

Scanning tunneling microscopy images of diferrocenylacetylene (DFA) coadsorbed with benzene on Au(111) show individual and close-packed DFA molecules, either adsorbed alongside benzene or on top of a benzene monolayer. Images acquired over a range of positive and negative tip-sample bias voltages show a shift in contrast, with the acetylene linker appearing brighter than the ferrocenes at positive sample bias (where unoccupied states primarily contribute) and the reverse contrast at negative bias. Density functional theory was used to calculate the electronic structure of the gas-phase DFA molecule, and simulated images produced through two-dimensional projections of these calculations approximate the experimental images. The symmetry of both experimental and calculated molecular features for DFA rules out a cis adsorption geometry, and comparison of experiment to simulation indicates torsion around the inter-ferrocene axis between 90° and 180° (trans); the cyclopentadienyl rings are thus angled with respect to the surface.

Potential barriers to colorectal cancer (CRC) screening include preexisting medical conditions (comorbidities), physician recommendation, psychosocial factors, and screening preparedness. This study's purpose was to investigate the impact of comorbid conditions on CRC screening among African Americans. A stage-matched randomized clinical trial was performed. Asymptomatic African Americans over age 50, with a primary care physician, and eligible for CRC screening were recruited at The Mount Sinai Hospital from 2005 to 2008. One hundred sixty-one patients were assessed for referral for, and completion of, CRC screening, comorbid conditions, "readiness to change," and number of physician visits within the observation period. Data was compared to a pretrial index to predict the likely effect of comorbid conditions on CRC screening. One hundred fifty-nine patients completed the study; 108 (68.9%) were referred for and 34 (21.2%) completed CRC screening. No demographic characteristics were associated with CRC screening completion. CRC screening referrals were similar for all patients, regardless of comorbidities or clinical visits. Comorbidities rated as having extreme influence on CRC screening showed a trend toward lower screening rates. There was a significant increase in screening rates among participants in advanced stages of readiness at enrollment. These data suggest that while comorbidities did not predict colonoscopy completion, they may play a role in concert with other factors. This is the only study to assess the effect of screening colonoscopy in an African American primary care setting. We must continue to explore interventions to narrow the disparate gap in screening and mortality rates.

Background: Adjunctive administration of the glycoprotein IIb/IIIa platelet receptor antagonist (GPA), abciximab, improves outcomes in patients undergoing rescue percutaneous coronary intervention (PCI). However, it is unknown if other GPAs provide a similar benefit in this setting., Objective: We sought to compare angiographic and clinical outcomes of patients receiving abciximab or eptifibatide as an adjunct to rescue PCI., Methods: In this prospective, nonrandomized study, consecutive patients who underwent rescue PCI and received adjunctive preprocedural GPA comprised the study population. Thrombolysis in myocardial infarction (TIMI) flow, corrected TIMI frame count (CTFC) and myocardial blush grade (MBG) were determined before and immediately after rescue PCI. Residual ST-segment elevation at 90-120 minutes and peak creatine kinase (CK) values for 48 hours after PCI were recorded. Major adverse cardiac events (MACE) including death, reinfarction and target vessel revascularization (TVR) were determined at discharge, 1 and 6 months., Results: A total of 241 patients were included in the study. 162 patients received abciximab and 79 received eptifibatide. There were no differences in baseline clinical and angiographic characteristics between groups. Post-PCI TIMI flow was similar but post-PCI CTFC was significantly lower (17 +/- 10 vs. 22 +/- 18; p = 0.01) and post-PCI MBG significantly higher (2.8 +/- 0.5 vs. 2.6 +/- 0.6; p = 0.01) in the abciximab group. Patients in the abciximab group had less ST-segment elevation (1.0 +/- 0.9 vs. 1.5 +/- 1.0 mm; p = 0.003) and lower peak CK (2,484 +/- 2,176 vs. 2,650 +/- 2,798 U/L; p = 0.001) after PCI. On multivariate analyses, abciximab administration (OR = 0.50, CI = 0.26, 0.96; p = 0.03), pre-PCI TIMI 3 flow (OR = 0.22, CI = 0.05, 0.99; p = 0.04) and female gender (OR = 0.24, CI = 0.08, 0.66; p = 0.006) were positive and cardiogenic shock (OR = 2.76, CI = 1.16, 6.58; p = 0.02) was a negative predictor of normal epicardial perfusion post PCI. Abciximab administration (OR = 0.46, CI = 0.24, 0.87; p = 0.02) and pre-PCI CTFC < 25 (OR = 0.09, CI = 0.02, 0.31, 0.0001) were positive predictors and cardiogenic shock (OR = 3.96, CI = 1.55, 10.12; p = 0.004) was a negative predictor of normal myocardial perfusion post-PCI as determined by CTFC. Abciximab administration (OR = 0.31, CI = 0.15, 0.63; p = 0.001) and pre-PCI MBG 3 (OR = 0.07, CI = 0.02, 0.23; p < 0.0001) were positive predictors of normal myocardial perfusion post-PCI as determined by MBG. In-hospital, 1- and 6-month clinical events and MACE rates did not differ between groups., Conclusions: In the setting of rescue PCI, adjunctive administration of abciximab resulted in greater improvement in angiographic and electrical estimates of myocardial perfusion and smaller infarct size compared to eptifibatide. These findings suggest that all GPA may not provide equal benefit in rescue PCI.

Findings on cranial computed tomography (CT) were correlated with autopsy findings in 58 cases with 129 lesions to determine CT reliability. When only CT scans of good quality were considered, there were no false positive cases. The number of false negative studies varied directly with lesion size: one of 42 lesions larger than 2.5 cm; four of 12 lesions between 1.5 and 2.5 cm; 12 of 15 between 0.5 and 1.5 cm; and all 21 of those smaller than 0.5 cm. Lesion size was undetermined in the remaining 18 casesbecause of the nature of the disease. While the series is small, these results suggest that the current detector threshold for CT may be in the range of 0.5-1.5 cm, although smaller lesions may be seen if there is substantial surrounding edema.