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Background and Purpose: Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyradiculoneuropathy that affects nerve roots and peripheral nerves leading to motor neuropathy and flaccid paralysis. This case report describes the physical therapy examination, intervention, and outcomes for a marathon runner with GBS.Case Description: The patient was a 30-year-old male marathon runner who presented with acutely evolving motor and sensory deficits that initially stabilized and then worsened. Both GBS and chronic inflammatory demyelinating polyradiculoneuropathy were considered as diagnoses, and medical treatment included a combination of intravenous administration of immunoglobulins, plasmapheresis, and corticosteroids. During his stay in an acute inpatient rehabilitation facility, the intervention was focused on regaining functional independence and strength with care not to induce fatigue or relapse.Outcomes: After three weeks in an acute inpatient rehabilitation facility, the patient showed marked gains in Functional Independence Measure scores and muscle performance as measured by manual muscle testing. [ABSTRACT FROM AUTHOR]

STUDY DESIGN: Case report. BACKGROUND: Following total knee arthroplasty (TKA), restoration of normal quadriceps muscle function is rare. One month after surgery, quadriceps torque (force) is only 40% of preoperative values and quadriceps activation is only 82% of preoperative levels, despite initiating postoperative rehabilitation the day after surgery. Early application of neuromuscular electrical stimulation (NMES) offers a possible approach to minimize loss of quadriceps torque more effectively than traditional rehabilitation exercises alone. CASE DESCRIPTION: A 65-year-old female underwent a right, cemented TKA. Isometric quadriceps and hamstrings muscle torque were measured preoperatively and at 3, 6, and 12 weeks after TKA. Quadriceps muscle activation was measured using a doublet interpolation technique at the same time points. The patient participated in a traditional TKA rehabilitation program augmented by NMES, which was initiated 48 hours after surgery and continued twice a day for the first 3 weeks, and once daily for 3 additional weeks. OUTCOMES: Preoperatively, the involved quadriceps produced 75% of the torque of the uninvolved side and demonstrated only 72.9% activation. At 3, 6, and 12 weeks after TKA, quadriceps torque was greater than the preoperative values of the involved side by 16%, 29%, and 56%, respectively. Similarly, activation improved to 93.4%, 94.6%, and 93.5% at 3, 6, and 12 weeks after TKA. DISCUSSION: Mitigating quadriceps muscle weakness immediately after TKA using early NMES may improve functional outcomes, because quadriceps weakness has been associated with numerous functional limitations and an increased risk for falls. Despite presenting preoperatively with substantial quadriceps torque and activation deficits, the patient in this case demonstrated improvements in quadriceps function at all the times measured, all of which were superior to those reported in the literature. The patient also made substantial improvements in functional outcomes, including the Knee Injury and Osteoarthritis Outcome Score (KOOS), 6-minute walk test, timed up and go (TUG) test, stair-climbing test, and the SF-36 Physical Component Score. Appropriately controlled clinical trials will be necessary to determine whether such favorable outcomes following TKA are specifically attributable to the addition of NMES to the rehabilitation program. [ABSTRACT FROM AUTHOR]

Background: While total knee arthroplasty reduces pain and provides a functional range of motion of the knee, quadriceps weakness and reduced functional capacity typically are still present one year after surgery. The purpose of the present investigation was to determine the role of failure of voluntary muscle activation and muscle atrophy in the early loss of quadriceps strength after surgery.Methods: Twenty patients with unilateral knee osteoarthritis were tested an average of ten days before and twenty-seven days after primary total knee arthroplasty. Quadriceps strength and voluntary muscle activation were measured with use of a burst-superimposition technique in which a supramaximal burst of electrical stimulation is superimposed on a maximum voluntary isometric contraction. Maximal quadriceps cross-sectional area was assessed with use of magnetic resonance imaging.Results: Postoperatively, quadriceps strength was decreased by 62%, voluntary activation was decreased by 17%, and maximal cross-sectional area was decreased by 10% in comparison with the preoperative values; these differences were significant (p < 0.01). Collectively, failure of voluntary muscle activation and atrophy explained 85% of the loss of quadriceps strength (p < 0.001). Multiple linear regression analysis revealed that failure of voluntary activation contributed nearly twice as much as atrophy did to the loss of quadriceps strength. The severity of knee pain with muscle contraction did not change significantly compared with the preoperative level (p = 0.31). Changes in knee pain during strength-testing did not account for a significant amount of the change in voluntary activation (p = 0.14).Conclusions: Patients who are managed with total knee arthroplasty have profound impairment of quadriceps strength one month after surgery. This impairment is predominantly due to failure of voluntary muscle activation, and it is also influenced, to a lesser degree, by muscle atrophy. Knee pain with muscle contraction played a surprisingly small role in the reduction of muscle activation. [ABSTRACT FROM AUTHOR]

INTRODUCTION/ PURPOSE: The widespread occurrence of muscular atrophy during immobilization and its reversal presents an important challenge to rehabilitation medicine. We used 3D-magnetic resonance imaging (MRI) in patients with surgically-stabilized ankle mortise fractures to quantify changes in plantarflexor and dorsiflexor muscle size during immobilization and rehabilitation, as well as to evaluate changes in force generating capacity (specific torque). METHODS: Twenty-individuals participated in a 10 wk rehabilitation program after 7 wk of immobilization. MRIs were acquired at baseline, 2, and 7 wk of immobilization, and at 5 and 10 wk of rehabilitation. Isometric plantarflexor muscle strength testing was performed at 0, 5, and 10 wk of rehabilitation. RESULTS: Dorsiflexors and plantarflexors atrophied 18.9% and 24.4% respectively, the majority of which occurred during the first 2 wk of immobilization (dorsiflexors: 9.6%; plantarflexors: 14.1%). Likewise, more than 50% of hypertrophy during rehabilitation occurred within the first 5 wk of rehabilitation for both the dorsiflexors (12.9%) and plantarflexors (13.2%), when compared to the total amount of hypertrophy over 10 wk of rehabilitation (dorsiflexors: 17.6%, plantarflexors: 22.5%). There were no significant differences in hypertrophy or atrophy of the dorsiflexor or plantarflexor muscles, despite a rehabilitation emphasis on the plantarflexors. Patients had significantly lower plantarflexor specific torque (torque/CSA) than healthy, control subjects immediately after cast immobilization, which did not return to normal after 10 wk of rehabilitation (P < 0.05). CONCLUSION: Our investigation of the consequences of limb immobilization on rehabilitation outcomes in patients can be applied directly to optimizing rehabilitation programs. Although muscle hypertrophy occurred early during rehabilitation, plantarflexor muscle function (specific torque) should remain the focus of rehabilitation programs because although CSA recovered quickly, specific torque still lagged behind that of control subjects. [ABSTRACT FROM AUTHOR]

Abstract Background Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC) - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy. Methods To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC. Results The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression. Conclusion This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that thymosin-β4 may have a role in chondrosarcoma metastasis.

Background: Medication use in older adults is increasing, therefore, reducing the risk of suboptimal medicine use is imperative in achieving optimal therapeutic outcomes. Research suggests that factors such as personal beliefs and beliefs about medicines may be associated with non-adherence and inappropriate medicine use., Aim: To systematically review and identify quantitative research on the influence of beliefs about medicines and the relationship with suboptimal medicine use in older adults., Method: Searches were conducted on PubMed, EMBASE, CINAHL, and PsycINFO for quantitative studies (inception to March 2023)., Inclusion Criteria: (1) exposure: participants' beliefs (personal, cultural, and medication-related), (2) outcomes: polypharmacy, potentially inappropriate medicines use, or non-adherence, and (3) participants: community-dwelling adults 65 years or above. Study selection, data extraction and quality appraisal (Joanna Briggs Institute critical appraisal checklist) were completed independently by two investigators. Data were combined in a narrative synthesis and presented in a summary of findings table., Results: Nineteen articles were included: 15 cross-sectional and four cohort studies. Outcomes of included papers were as follows; adherence (n = 18) and potentially inappropriate medicine use (n = 1). Ten studies found stronger beliefs in the necessity of medicines and/or fewer concerns led to better adherence, with one paper contradicting these findings. Three studies did not find associations between adherence and beliefs. One study confirmed an association between unnecessary drug use and a lack of belief in a "powerful other" (e.g. doctor)., Conclusion: Further investigation is necessary to (1) ascertain the importance of necessity or concern beliefs in fostering adherence and, (2) examine the influence of beliefs on polypharmacy and inappropriate medicine use., (© 2024. The Author(s).)

Objective: This study aimed to assess the utilisation, benefits, and challenges associated with Electronic Health Records (EHR) and e-prescribing systems in Australian Community Pharmacies, focusing on their integration into daily practice and the impacts on operational efficiency, while also gathering qualitative insights from community pharmacists., Methods: A mixed-methods online survey was carried out among community pharmacists throughout Australia to assess the utilisation of EHR and e-prescribing systems, including the benefits and challenges associated with their use. Data was analysed based on pharmacists' age, gender, and practice location (metropolitan vs. regional). The chi-square test was applied to examine the relationship between these demographic factors and the utilisation and operational challenges of EHR and e-prescribing systems., Results: The survey engaged 120 Australian community pharmacists. Of the participants, 67 % reported usability and efficiency issues with EHR systems. Regarding e-prescribing, 58 % of pharmacists faced delays due to slow software performance, while 42 % encountered errors in data transmission. Despite these challenges, the benefits of e-prescribing were evident, with 79 % of respondents noting the elimination of illegible prescriptions and 40 % observing a reduction in their workload. Issues with prescription quantity discrepancies and the reprinting process were highlighted, indicating areas for improvement in workflow and system usability. The analysis revealed no significant statistical relationship between the utilisation and challenges of EHR and e-prescribing systems with the demographic variables of age, gender and location (p > 0.05), emphasising the necessity for healthcare solutions that address the needs of all pharmacists regardless of specific demographic segments., Conclusion: In Australian community pharmacies, EHR and e-prescribing may enhance patient care but come with challenges such as data completeness, technical issues, and usability concerns. Implementing successful integration relies on user-centric design, standardised practices, and robust infrastructure. While demanding for pharmacists, the digital transition improves efficiency and quality of care. Ensuring user-friendly tools is crucial for the smooth utilisation of digital health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

A tetradentate bis(amido)bis(phosphine) Fe II complex, (PNNP)Fe, is shown to activate the terminal C-H bond of aryl alkynes across its Fe-N amide bonds. (PNNP)Fe is also shown to catalytically dimerize terminal aryl alkynes to produce 1,3-enynes with Z  :  E ratios as high as 96 : 4 with yields up to 95% and loadings as low as 1 mol% at 30 °C in 2 h. A plausible metal-ligand cooperative mechanism invoking a vinylidene intermediate is proposed.

The addition of Na[BArF 24 ] (BArF 24 = tetrakis(3,5-bis(trifluoromethyl)phenyl)borate) to [Pd(PP)Cl 2 ] (PP = 1,1'-bis(phosphino)ferrocene ligands) compounds results in the loss of a chloride ligand and the formation of the dimeric species [Pd 2 (PP) 2 ( μ -Cl) 2 ][BArF 24 ] 2 . In most cases, the addition of a monodentate phosphine, PR 3 , to these dimeric species leads to cleaving of the dimer and formation of [Pd(PP)(PR 3 )Cl][BArF 24 ]. While these reactions are readily observed via a significant color change, the 31 P{ 1 H} NMR spectra offer more significant support, as the singlet for the dimer is replaced with three doublets of doublets. The reaction seems to take place for a wide range of PR 3 ligands, although there do appear to be steric limitations to the reaction. The compounds were thoroughly characterized by NMR, and X-ray crystal structures of several of the compounds were obtained. In addition, the ferrocenyl backbone of the 1,1'-bis(phosphino)ferrocene ligands provides an opportunity to examine the oxidative electrochemistry of these compounds. In general, the potential at which oxidations of these compounds occurs shows a dependence on the phosphine substituents.

Objective: To explore community pharmacy consumers' knowledge and attitudes of mental illness, support services, and community pharmacists' role in supporting people living with mental illness (PLMI)., Methods: This survey was conducted in 15 community pharmacies between June and September 2019. Participants were aged 18 years or older without prior or ongoing history of mental illness and/or with close family members with mental illness. Open-ended responses to the anonymous questionnaire were analysed using content analysis., Key Findings: Majority of the 380 participants were female (57.4%) with a mean age 52.9 years and 33.7% having completed university. Most (70.3%) believed that people with mental illness had a negative image due to poor health literacy providing possible solutions of 'awareness campaigns', 'education and training', and 'increased government funding for mental health (MH) support services'. Only 33.7% and 63.7% of participants were aware of Mental Health Week and the R U OK? Campaign, respectively. Whilst 12.4% of participants had participated in MH campaigns, only 3.4% were aware of community pharmacists-led MH educational activities. There were significant differences between adults (<65 years) and older adults (≥65 years old) with the latter reporting a more negative image for mental illness (P < 0.05) and having less exposure and engagement with MH resources (P < 0.001) and campaigns (P < 0.01)., Conclusion: Despite awareness, participants reported low engagement with MH campaigns. Additionally, older adults had lower MH literacy and exposure to resources and campaigns. This study highlighted that the community lacked awareness of what pharmacists can offer to support PLMIs., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society.)

Transition metal catalyzed alkene double bond transposition usually involves metal hydride intermediates. Despite significant advances in the design of catalysts that dictate product selectivity, control over substrate selectivity is less advanced and transition metal catalysts that selectively transpose double bonds in substrates containing multiple 1-alkene functionalities are rare. Herein, we report that the three-coordinate high spin ( S = 2) Fe(II) imido complex [Ph 2 B( t BuIm) 2 Fe═NDipp][K(18-C-6)THF 2 ] ( 1-K(18-C-6) ) catalyzes 1,3-proton transfer from 1-alkene substrates to afford 2-alkene transposition products. Mechanistic investigations involving kinetics, competition, and isotope labeling studies, supported by experimentally calibrated DFT computations, strongly support an unusual nonhydridic mechanism for alkene transposition that is enabled by the cooperative action of the iron center and basic imido ligand. As dictated by the p K a of the allylic protons, this catalyst enables the regioselective transposition of C═C double bonds in substrates containing multiple 1-alkenes. The high spin ( S = 2) state of the complex allows a wide scope of functional groups to be tolerated, including those that are typical catalyst poisons, such as amines, N -heterocycles, and phosphines. These results demonstrate a new strategy for metal-catalyzed alkene transposition with predictable substrate regioselectivity.

Despite the utility of Si-Si bonds, there are relatively few examples of Si-Si bond formation by base metals. In this work, a four-coordinate iron complex, (PNNP)Fe II , is shown to strongly activate the Si-H bonds in primary silanes across the Fe-amide bonds in a metal-ligand cooperative fashion. Upon treatment with excess silane, Si-Si dehydrogenative homocoupling is shown to occur across the Fe-N amide bond without concomitant oxidation and spin state changes at the Fe center.

A single bridging phosphinoamide ligand was shown to support a metal-metal triple bond in a Zr/Co heterobimetallic complex. The similarity of the bonding in this compound to previously synthesized Zr/Co species, and therefore the assignment of the Zr/Co triple bond, is supported by the structural parameters of the complex, the electronic structure predicted by density functional theory, and complete-active-space self-consistent-field (CASSCF) calculations. This demonstrates that metal-metal multiple bonds can be realized in heterobimetallic complexes without multiple bridging ligands to enforce the proximity of the two metals.

Introduction: Breath tests utilising 13 C-labelled substrates for the assessment of gastric emptying have been applied widely. Wagner-Nelson analysis is a pharmacokinetic model that can be utilised to generate a gastric emptying curve from the %  13 CO 2 measured in breath samples. We compared Wagner-Nelson analysis with (i) scintigraphy and (ii) conventional breath test modelling to quantify gastric emptying in type 2 diabetes., Methods: Thirteen patients (age 68.1±1.5 years, body mass index 31.0±0.9 kg/m 2 , HbA1c 6.3±0.2%) consumed a mashed potato meal comprising 65 g powdered potato, 20 g glucose, 250 ml water, an egg yolk labelled with 100 μL 13 C-octanoic acid and 20MBq 99m Tc-calcium phytate. Scintigraphic data were acquired and breath samples collected for 4 hours after the meal. Gastric emptying curves were derived based on each technique; the 50% emptying time and intragastric retention at 60 min were also calculated., Results: With Wagner-Nelson analysis, a K el =0.60 (the elimination constant) best approximated the scintigraphic gastric emptying curve. There was a relationship between the T50 calculated with scintigraphy and by both Wagner-Nelson K el =0.60 (r 2 =0.45, P<0.05) and conventional analysis (r 2 =0.44, P<0.05). There was no significant difference in the 50% gastric emptying time for scintigraphy (68.5±4.8 min) and Wagner-Nelson K el =0.60 (71.3±4.5 min), however, the 50% gastric emptying time calculated by conventional analysis was much greater at 164.7±6.0 min (P<0.001)., Conclusion: In type 2 diabetes, gastric emptying of a mashed potato meal measured using a 13 C-octanoic acid breath test analysed with Wagner-Nelson K el =0.60 closely reflects measurements obtained with scintigraphy, whereas, in absolute terms, the conventional breath test analysis does not., Competing Interests: Michael Nauck has received compensation for lectures or advisory board membership from AstraZeneca, Berlin-Chemie/Menarini, Medscape, Merck Sharp & Dohme, Novo Nordisk, Sanofi-Aventis, Takeda, and Sun Pharma; received grant support from Berlin-Chemie/Menarini, Eli Lilly and Company, Merck Sharp & Dohme, and Novo Nordisk. Tongzhi Wu has received travel support from Novartis and Sanofi and research funding from Novartis and AstraZeneca. Juris Meier has received compensation for lectures or advisory board membership from AstraZeneca, Boehringer-Ingelheim, Berlin-Chemie/Menarini, Eli Lilly, Medscape, Merck Sharp & Dohme, Novo Nordisk, Sanofi; received grant support from Novo Nordisk. Christopher Rayner has received research funding from Sanofi, Novartis, Eli Lilly, Merck Sharp & Dohme, and AstraZeneca. Michael Horowitz has participated in the advisory boards and/or symposia for Novo Nordisk, Sanofi, Novartis, Eli Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, and AstraZeneca and has received honoraria for this activity. Karen Jones has received research funding from Sanofi and AstraZeneca and drug supplies from Merck Sharp & Dohme. Laurence Trahair, Julie Stevens, Madeline Buttfield, Seva Hatzinikolas and Hung Pham have no conflicts of interest to declare., (Thieme. All rights reserved.)

Aims: The aim of this study was to evaluate the comparative effects of low-carbohydrate (LC), full-strength (FS), and low-alcohol (LA) beer on gastric emptying (GE), ethanol absorption, glycaemia and insulinaemia in health., Methods: Eight subjects (four male, four female; age: 20.4 ± 0.4 years; BMI 22.7 ± 0.4 kg/m 2 ) had concurrent measurements of GE, plasma ethanol, blood glucose and plasma insulin for 180 min on three separate occasions after ingesting 600 mL of (i) FS beer (5.0% w/v, 246 kcal, 19.2 g carbohydrate), (ii) LC beer (4.6% w/v, 180 kcal, 5.4 g carbohydrate) and (iii) LA beer (2.6% w/v, 162 kcal, 17.4 g carbohydrate) labelled with 20 MBq 99mTc-calcium phytate, in random order., Results: There was no difference in the gastric 50% emptying time (T50) (FS: 89.0 ± 13.5 min vs LC: 79.5 ± 12.9 min vs LA: 74.6 ± 12.4 min; P = .39). Plasma ethanol was less after LA than LC (P < .001) and FS (P < .001), with no difference between LC and FS (P = 1.0). There was an inverse relationship between plasma ethanol at 15 min and GE after LA (r = -0.87, P < .01) and a trend for inverse relationships after LC (r = -0.67, P = .07) and FS (r = -0.69, P = .06). The AUC 0-180 min for blood glucose was greater for LA than LC (P < .001), with no difference between LA and FS (P = .40) or LC and FS (P = 1.0)., Conclusion: In healthy young subjects, GE of FS, LC and LA beer is comparable and a determinant of the plasma ethanol response., (© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Context: Hypoglycemia is a major barrier to optimal glycemic control in insulin-treated diabetes. Recent guidelines from the American Diabetes Association have subcategorized "non-severe" hypoglycemia into level 1 (<3.9 mmol/L) and 2 (<3 mmol/L) hypoglycemia. Gastric emptying of carbohydrate is a major determinant of postprandial glycemia but its role in hypoglycemia counter-regulation remains underappreciated. "Marked" hypoglycemia (~2.6 mmol/L) accelerates gastric emptying and increases carbohydrate absorption in health and type 1 diabetes, but the impact of "mild" hypoglycemia (3.0-3.9 mmol/L) is unknown., Objective: To determine the effects of 2 levels of hypoglycemia, 2.6 mmol/L ("marked") and 3.6 mmol/L ("mild"), on gastric emptying in health., Design, Setting, and Subjects: Fourteen healthy male participants (mean age: 32.9 ± 8.3 years; body mass index: 24.5 ± 3.4 kg/m2) from the general community underwent measurement of gastric emptying of a radiolabeled solid meal (100 g beef) by scintigraphy over 120 minutes on 3 separate occasions, while blood glucose was maintained at either ~2.6 mmol/L, ~3.6 mmol/L, or ~6 mmol/L in random order from 15 minutes before until 60 minutes after meal ingestion using glucose-insulin clamp. Blood glucose was then maintained at 6 mmol/L from 60 to 120 minutes on all days., Results: Gastric emptying was accelerated during both mild (P = 0.011) and marked (P = 0.001) hypoglycemia when compared to euglycemia, and was more rapid during marked compared with mild hypoglycemia (P = 0.008). Hypoglycemia-induced gastric emptying acceleration during mild (r = 0.57, P = 0.030) and marked (r = 0.76, P = 0.0014) hypoglycemia was related to gastric emptying during euglycemia., Conclusion: In health, acceleration of gastric emptying by insulin-induced hypoglycemia is dependent on the degree of hypoglycemia and baseline rate of emptying., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Alcohol consumption is an important predictor of a variety of negative outcomes. There is an extensive literature that examines the differences in the estimated level of alcohol consumption between types of assessments (e.g., quantity-frequency [QF] questionnaires, daily diaries). However, it is typically assumed that all QF-based measures are nearly identical in their assessment of the volume of alcohol consumption in a population. Using timeline follow-back data and constructing common QF consumption measures, we examined differences among survey instruments to assess alcohol consumption and heavy drinking. Using three data sets, including clinical to community samples, we demonstrate how scale-specific item characteristics (i.e., number of response options and ranges of consumption assessed by each option) can substantially affect the estimated mean level of consumption and estimated prevalence of binge drinking. Our analyses suggest that problems can be mitigated by employing more resolved measures of quantity and frequency in consumption questionnaires.

Aims: To evaluate the effects of 8 weeks' administration of exenatide (EXE) once weekly on gastric emptying of solids and liquids (using the "gold standard" technique, scintigraphy), glucose absorption and postprandial glycaemia in healthy people., Material and Methods: A total of 32 healthy participants were randomized to receive either EXE once weekly (2 mg/wk subcutaneously; six men, 10 women, mean age 59.9 ± 0.9 years, mean body mass index [BMI] 29.6 ± 0.6 kg/m 2 ) or matching placebo (PBO; six men, 10 women, mean age 60.6 ± 1.2 years, mean BMI 29.5 ± 1.0 kg/m 2 ) for 8 weeks. Gastric emptying, nausea (visual analogue scale), and plasma glucose, insulin, C-peptide and glucagon were measured for 120 min after a solid/liquid meal, comprising 100 g ground beef (radiolabelled with 20 MBq 99m Tc-sulphur colloid) and 150 mL 10% glucose (radiolabelled with 7 MBq 67 Ga-EDTA), and containing 5 g 3-O-methyl-glucose (3-OMG) as a marker of glucose absorption, at baseline and after 8 weeks' treatment., Results: The study treatments were well tolerated. Scores for nausea were consistently low, with no difference between the EXE once weekly and PBO groups. EXE once weekly slowed gastric emptying of solids (area under the curve [AUC] 0-120min : P < 0.05) and liquids (AUC 0-120min : P = 0.01) substantially, and attenuated glucose absorption (3-OMG incremental AUC [iAUC] 0-30min : P = 0.001) and the postprandial rise in plasma glucose (iAUC 0-30min : P = 0.008). Plasma glucagon at 2 h was reduced by EXE once weekly (P = 0.001). The magnitude of the reduction in plasma glucose at t = 30 min from baseline to 8 weeks with EXE once weekly was related inversely to the 50% emptying time of the glucose drink (r = -0.55, P = 0.03)., Conclusions: In healthy participants, 8 weeks' administration of the "long-acting" glucagon-like peptide-1 receptor agonist EXE, slowed gastric emptying of solids and liquids substantially, with consequent reductions in glucose absorption and postprandial glycaemia., (© 2020 John Wiley & Sons Ltd.)

Street-based sex work is criminalized throughout much of the U.S. Diversion programs have shown mixed results. This study examined the effect a quasi-experimental intervention (prostitution diversion program, n = 149) had on prostitution rearrest compared with a waitlist control group ( n = 77) among N = 226 individuals arrested for prostitution in Baltimore. In both groups, n = 64 (28.32%) were rearrested for prostitution over 30 months. Tests of differences compared groups with a significant difference in gender only. A Cox proportional hazard model examined differences in survival time (to recidivist prostitution arrest) between individuals in the control and intervention groups at 6, 12, 18, 24, and 30 months. Results indicate that participation in the intervention did not have a significant effect on decreasing prostitution arrests over time. History of prior prostitution arrest was a significant predictor (hazard ration [HR] = 1.12, p = .02) of rearrest.Lack of program success suggests that barriers to exiting prostitution are substantial, despite availability of supportive services, and that diversion programs may not be the best intervention strategy for all sex workers. Future research should identify motivators for exiting and how to reduce exiting barriers.

Aims: To determine the effects of the dipeptidyl peptidase-4 inhibitor, sitagliptin, on gastric emptying (GE) of a high-carbohydrate meal and associated glycaemic and blood pressure (BP) responses in type 2 diabetes mellitus (T2DM)., Materials and Methods: Fourteen patients with T2DM (nine men, five women; age 67.8 ± 1.5 years; body mass index 31.2 ± 0.9 kg/m 2 ; T2DM duration: 4.2 ± 0.9 years; glycated haemoglobin: 46 ± 1.8 mmol/mol [6.4% ± 0.2%]), managed by diet and/or metformin, underwent concurrent measurements of GE, BP and plasma glucose for 240 minutes after ingestion of a radiolabelled mashed potato meal after receiving sitagliptin (100 mg) or placebo in randomized, double-blind, crossover fashion on 2 consecutive days., Results: Sitagliptin reduced postprandial plasma glucose (P < .005) without affecting GE (P = .88). The magnitude of the glucose-lowering effect (change in incremental area under the curve 0-240 min from placebo to sitagliptin) was related to GE (kcal/min) on placebo (r = 0.68, P = .008) There was a comparable fall in systolic BP (P = .80) following the meal, with no difference between the 2 days., Conclusions: In T2DM, while sitagliptin has no effect on either GE or postprandial BP, its ability to lower postprandial glucose are dependent on the basal rate of GE., (© 2019 John Wiley & Sons Ltd.)

Psychiatric diagnostic systems, such as The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), use expert consensus to determine diagnostic criteria sets and rules (DCSRs), rather than exploiting empirical techniques to arrive at optimal solutions (OS). Our project utilizes complete enumeration (i.e., generating all possible subsets of item combinations A and B with all possible thresholds, T) to evaluate all possible DCSRs given a set of relevant diagnostic data. This method yields the entire population distribution of diagnostic classifications (i.e., diagnosis of the disorder versus no diagnosis) produced by a set of dichotomous predictors (i.e., diagnostic criteria). Once unique sets are enumerated, optimization on some predefined correlate or predictor will maximally separate diagnostic groups on one or more, disorder-specific "outcome" criteria. We used this approach to illustrate how to create a common Substance Use Disorder (SUD) DCSR that is applicable to multiple substances. We demonstrate the utility of this approach with respect to alcohol use disorder and Cannabis Use Disorder (CUD) using DSM-5 criteria as input variables. The optimal SUD solution with a moderate or above severity grading included four criteria (i.e. 1) having a strong urge or craving for the substance (CR), 2) failure to fulfill major role obligations at work school or home (FF), 3) continued use of the substance despite social or interpersonal problems caused by the substance use (SI) and 4) physically hazardous use (HU)) with a diagnostic threshold of two. The derived DCSR was validated with known correlates of SUD and performed as well as DSM-5. Our findings illustrate the value of using an empirical approach to what is typically a subjective process of choosing criteria and algorithms that is prone to bias. The optimization of diagnostic criteria can reduce criteria set sizes, resulting in decreased research, clinician, and patient burden., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Much of the foundation of clinical practice, psychiatric epidemiology, and research into the etiology, course, prevention, and treatment of alcohol use disorder (AUD) rests on psychiatric diagnosis. However, existing research has failed to adequately exploit empirical techniques and existing databases to derive criteria considered optimal with respect to predicting external correlates. The current project adopts a novel approach to deriving new diagnostic criteria sets and rules for AUD. Utilizing the 2010 (N = 24,120) and 2013 (N = 23,627) National Survey on Drug Use and Health (NSDUH; Substance Abuse and Mental Health Services Administration [SAMHSA], 2011, 2014) data sets, we performed a statistical optimization procedure, using complete enumeration, on participants 21 or older who had consumed at least 1 alcoholic beverage in the past year. The goal was to maximize the distance (based on Cohen's d) between mean levels of the optimization criteria (i.e., consumption and functional impairment) in those with an AUD diagnosis versus those without. In contrast with current convention, AUD is derived transparently using a data-driven approach. The best solution included 9 criteria with a diagnostic threshold of 3, while the second-best solution comprised 5 criteria with a threshold of 2. External validation demonstrated both solutions perform similarly, suggesting it is appropriate to use either, depending on the goal of the diagnosis. Overall, statistical optimization approaches can yield highly efficient criteria sets and rules, although multiple, near equivalently performing solutions can be generated. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background: Postprandial hypotension (PPH) occurs frequently, particularly in older people and those with type 2 diabetes, and is associated with increased morbidity and mortality. The magnitude of the decrease in blood pressure (BP) induced by carbohydrate, fat, and protein appears to be comparable and results from the interaction of macronutrients with the small intestine, including an observed stimulation of mesenteric blood flow. It is not known whether artificial sweeteners, such as sucralose, which are widely used, affect BP., Objective: The aim of this study was to evaluate the effects of intraduodenal sucralose on BP and superior mesenteric artery (SMA) blood flow, compared with intraduodenal glucose and saline (control), in healthy older subjects., Design: Twelve healthy subjects (6 men, 6 women; aged 66-79 y) were studied on 3 separate occasions in a randomized, double-blind, crossover design. After an overnight fast, subjects had concurrent measurements of BP and heart rate (HR; automated device), SMA blood flow (Doppler ultrasound), and blood glucose (glucometer) during intraduodenal infusion of 1) glucose (25% wt:vol, ∼1400 mOsmol/L), 2) sucralose (4 mmol/L, ∼300 mOsmol/L), or 3) saline (0.9% wt:vol, ∼300 mOsmol/L) at a rate of 3 mL/min for 60 min followed by intraduodenal saline for a further 60 min., Results: There was a decrease in mean arterial BP (P < 0.001) during intraduodenal glucose [baseline (mean ± SEM): 91.7 ± 2.6 mm Hg compared with t = 60 min: 85.9 ± 2.8 mm Hg] but not during intraduodenal saline or intraduodenal sucralose. The HR (P < 0.0001) and SMA blood flow (P < 0.0001) also increased during intraduodenal glucose but not during intraduodenal saline or intraduodenal sucralose. As expected, blood glucose concentrations increased in response to glucose (P < 0.0001) but not saline or sucralose., Conclusions: In healthy older subjects, intraduodenal administration of the artificial sweetener sucralose was not associated with changes in BP or SMA blood flow. Further studies are therefore warranted to determine the potential role for artificial sweeteners as a therapy for PPH. This trial was registered at http://www.ANZCTR.org.au as ACTRN12617001249347.

The current article describes the adaptation of a measure of sexual orientation self-concept ambiguity (SSA) from an existing measure of general self-concept clarity. Latent "trait" scores of SSA reflect the extent to which a person's beliefs about their own sexual orientation are perceived as inconsistent, unreliable, or incongruent. Sexual minority and heterosexual women ( n = 348), ages 18 to 30, completed a cross-sectional survey. Categorical confirmatory factor analysis guided the selection of items to form a 10-item, self-report measure of SSA. In the current report, we also examine (a) reliability of the 10-item scale score, (b) measurement invariance based on respondents' sexual identity status and age group, and (c) correlations with preexisting surveys that purport to measure similar constructs and theoretical correlates. Evidence for internal reliability, measurement invariance (based on respondent sex), and convergent validity was also investigated in an independent, validation sample. The lowest SSA scores were reported by women who self-ascribed an exclusively heterosexual or exclusively lesbian/gay sexual identity, whereas those who reported a bisexual, mostly lesbian/gay, or mostly heterosexual identity, reported relatively higher SSA scores.

Aims/hypothesis: A postprandial fall in BP occurs frequently in older individuals and in patients with type 2 diabetes. The magnitude of this decrease in BP is related to the rate of gastric emptying (GE). Intravenous administration of glucagon-like peptide-1 (GLP-1) attenuates the hypotensive response to intraduodenal glucose in healthy older individuals. We sought to determine the effects of exogenous GLP-1 on BP, GE, superior mesenteric artery (SMA) flow and glycaemic response to oral ingestion of glucose in healthy older individuals and patients with type 2 diabetes., Methods: Fourteen older volunteers (six men, eight women; age 72.1 ± 1.1 years) and ten patients with type 2 diabetes (six men, four women; age 68.7 ± 3.4 years; HbA1c 6.6 ± 0.2% [48.5 ± 2.0 mmol/mol]; nine with blood glucose managed with metformin, two with a sulfonylurea and one with a dipeptidyl-peptidase 4 inhibitor) received an i.v. infusion of GLP-1 (0.9 pmol kg(-1) min(-1)) or saline (154 mmol/l NaCl) for 150 min (t = -30 min to t = 120 min) in randomised order. At t = 0 min, volunteers consumed a radiolabelled 75 g glucose drink. BP was assessed with an automated device, GE by scintigraphy and SMA flow by ultrasonography. Blood glucose and serum insulin were measured., Results: GLP-1 attenuated the fall in diastolic BP after the glucose drink in older individuals (p < 0.05) and attenuated the fall in systolic and diastolic BP in patients with type 2 diabetes (p < 0.05). GE was faster in patients with type 2 diabetes than in healthy individuals (p < 0.05). In both groups, individuals had slower GE (p < 0.001), decreased SMA flow (p < 0.05) and a lower degree of glycaemia (p < 0.001) when receiving GLP-1., Conclusions/interpretation: Intravenous GLP-1 attenuates the hypotensive response to orally administered glucose and decreases SMA flow, probably by slowing GE. GLP-1 and 'short-acting' GLP-1 agonists may be useful in the management of postprandial hypotension.

We have shown that the capacity of 25g whey preloads to slow gastric emptying and reduce postprandial glycaemia persists after 4 weeks regular exposure in patients with diet-controlled type 2 diabetes. This dietary strategy therefore appears feasible for larger clinical trials to evaluate beneficial effects on long-term glycaemic control. Registered with the Australian New Zealand Clinical Trials Registry: ACTRN12614000831684., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

A transgenic ferret model of cystic fibrosis has recently been generated. It is probable that malfunction of airway mucous glands contributes significantly to the airway pathology of this disease. The usefulness of the ferret model may therefore depend in part on how closely the airway glands of ferrets resemble those of humans. Here, we show that in the ferret trachea glands are commonest in its most ventral aspect and disappear about half way up the lateral walls; they are virtually absent from the dorsal membranous portion. Further, the aggregate volume of glands per unit mucosal surface declines progressively by about 60% between the larynx and the carina. The average frequency of glands openings for the ferret trachea as a whole is only about one-fifth that in humans (where gland openings are found at approximately the same frequency throughout the trachea). Glands in the ferret trachea are on average about one-third the size of those in the human. Therefore, the aggregate volume of tracheal glands (per unit mucosal surface area) in the ferret is only about 6% that in humans. As in other mammalian species, airway glands in the ferret disappear at an airway internal diameter of ∼1 mm, corresponding approximately in this species to airway generation 6., (Copyright © 2013 Wiley Periodicals, Inc.)

Aims/hypotheses: Glucagon-like peptide-1 (GLP-1), an important mediator of postprandial glycaemia, could potentially be stimulated by delivering small quantities of nutrient to a long length of distal gut. We aimed to determine whether enteric-coated pellets, releasing small amounts of lauric acid throughout the ileum and colon, could reduce glycaemic responses to meals in type 2 diabetes, associated with stimulation of GLP-1., Methods: Eligible patients, who had type 2 diabetes controlled by diet or metformin, were each studied on two occasions in a hospital setting. After an overnight fast, patients consumed 5 g active pellets (47% lauric acid by weight) or placebo with breakfast (T = 0 min) and lunch (T = 240 min), in a crossover design with order randomised by the hospital pharmacy and allocation concealed by numbered containers. Patients and investigators making measurements were blinded to the intervention. Blood was sampled frequently for blood glucose (the primary outcome) and hormone assays., Results: Eight patients were randomised (four to receive either intervention first), and all completed the study without adverse effects. Blood glucose was lower after breakfast (T = 0-240 min, area under the curve (AUC) 2,075 ± 368 vs 2,216 ± 163 mmol/l × min) and lunch (T = 240-480 min, AUC 1,916 ± 115 vs 2,088 ± 151 mmol/l × min) (p = 0.02 for each) after active pellets than after placebo. Plasma GLP-1 concentrations were higher after breakfast (p = 0.08) and lunch (p = 0.04) for active pellets. While there were no differences in insulin or glucose-dependent insulinotropic polypeptide concentrations, glucagon concentrations were higher after breakfast and lunch (p = 0.002 for each) for active pellets., Conclusions/interpretation: Delivering small amounts of nutrient to the ileum and colon can stimulate substantial endogenous GLP-1 release and attenuate postprandial glycaemia. This novel approach has therapeutic potential in type 2 diabetes., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12612000600842., Funding: The study was funded by Meyer Nutriceuticals.

Introduction: Gastroparesis is an important clinical disorder characterised by delayed gastric emptying in the absence of mechanical outlet obstruction. Idiopathic, diabetes and postsurgical causes represent the most common aetiologies. The condition commonly manifests as upper gastrointestinal symptoms, including nausea, vomiting, postprandial fullness, early satiety, abdominal pain and bloating., Areas Covered: This paper provides a review of the prevalence, pathophysiology and clinical features associated with gastroparesis, with a particular focus on current pharmacological management options and novel and emerging therapies. A literature search was undertaken using the search terms: gastroparesis, diabetic gastroparesis, idiopathic gastroparesis, gastric emptying, prokinetic, metoclopramide, domperidone, erythromycin, motilin, alemcinal, KC11458, mitemcinal, ghrelin, TZP-101, TZP-102, RM-131, tegaserod, prucalopride, naronapride, velusetrag, levosulpiride, itopride, botulinum toxin, gastric electrical stimulation, Enterra., Expert Opinion: Strategies for the management of gastroparesis include correction of malnutrition, dehydration and electrolyte imbalance, relief of symptoms by appropriate use of prokinetic and antiemetic agents and, in patients with gastroparesis associated with diabetes or critical illness-induced hyperglycaemia, optimisation of glycaemic control. Conventional prokinetic agents form the mainstay of treatment. While novel pharmacotherapies are in development, compelling evidence for their efficacy, particularly in symptom relief, remains to be established.