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OBJECTIVES Students often express uncertainty regarding changing their answers on multiple choice tests despite multiple studies quantitatively showing the benefits of changing answers. METHODS Data was collected from 86 first-year podiatric medical students over one semester for the course of Biochemistry, as shown in electronic testing data collected via ExamSoft's® Snapshot Viewer. Quantitative analysis was performed comparing frequency of changing answers and whether students changed their answers from incorrect-to-correct, correct-to-incorrect, or incorrect-to-incorrect. A correlation analysis was performed to assess the relationship between the frequency of each type of answer change and class rank. Independent-sample t -tests were used to assess differences in the pattern of changing answers amongst the top and bottom performing students in the class. RESULTS The correlation between total changes made from correct-to-incorrect per total answer changes and class rank yielded a positive correlation of r = 0.218 ( P = .048). There was also a positive correlation of r = 0.502 ( P

Background: The Autoimmune Bullous Disease Quality of Life (ABQOL) and the Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaires, which are specific for autoimmune blistering diseases (AIBDs), were developed in Australia. Aims and Objectives: The aim of this study was to validate the Turkish version of the ABQOL and TABQOL questionnaires and to assess the reliability of them in the Turkish population. Materials and Methods: The Turkish versions of the ABQOL and TABQOL questionnaires were produced by forward-backward translation of the original English version. The patients were requested to complete ABQOL and TABQOL questionnaires on day 0 and after 7 days for a 2nd time sent by post. Furthermore, patients also completed other health-related quality of life scales on day 0. Results: A total of 68 patients with AIBDs were recruited. A subset of 20 (29.4%) patients completed the day 7 questionnaire. Both the Turkish versions of the ABQOL and TABQOL questionnaires had a high internal consistency (0.86 and 0.88, respectively) and test-retest reliability (0.87 and 0.87, respectively). The correlation between ABQOL and TABQOL scores was moderate (Pearson's R = 0.609). Conclusion: We have shown that the Turkish versions of ABQOL and TABQOL questionnaires are valid and reliable instruments. They can be used to measure treatment burden in Turkish AIBD patients. [ABSTRACT FROM AUTHOR]

Background: High rates of reoperation following breast‐conserving surgery (BCS) for positive margins are associated with costs to healthcare providers. The aim was to assess the quality of evidence on reported re‐excision costs and compare the direct patient‐level costs between patients undergoing successful BCS versus reoperations after BCS. Methods: The study used data from women who had BCS with or without reoperation at a single institution between April 2015 and March 2016. A systematic review of health economic analysis in BCS was conducted and scored using the Quality of Health Economic Studies (QHES) instrument. Financial data were retrieved using the Patient‐Level Information and Costing Systems (PLICS) for patients. Exchange rates used were: US $1 = £0·75, £1 = €1·14 and US $1 = €0·85. Results: The median QHES score was 47 (i.q.r. 32·5–79). Only two of nine studies scored in the upper QHES quartile (score at least 75). Costs of initial lumpectomy and reoperation were in the range US $1234–11786 and $655–9136 respectively. Over a 12‐month interval, 153 patients had definitive BCS and 59 patients underwent reoperation. The median cost of reoperations after BCS (59 patients) was £4511 (range 1752–18 019), representing an additional £2136 per patient compared with BCS without reoperation (P < 0·001). Conclusion: The systematic review demonstrated variation in methodological approach to cost estimates and a paucity of high‐quality cost estimate studies for reoperations. Extrapolating local PLICS data to a national level suggests that getting BCS right first time could result in substantial savings. Reoperations expensive [ABSTRACT FROM AUTHOR]

The article offers information on the effectiveness of using actual size computed tomography (CT) scan images, using mobile device, in designing customized laryngoplasty implant in Great Britain. The topics discussed include the diverse surgical management of unilateral vocal fold immobility (UVFI) like arythenoid adduction, open medialisation, and injection, the reformatting of images of CT scans using the software the Picture Archiving System, and ways on how surgeries are carried out.

BUB1 (budding uninhibited by benzimidazoles-1) is required for efficient TGF-β signaling, through its role in stabilizing the TGFBR1 and TGFBR2 complex. Here we demonstrate that TGFBR2 phosphorylates BUB1 at Serine-318, which is conserved in primates. S318 phosphorylation abrogates the interaction of BUB1 with TGFBR1 and SMAD2. Using BUB1 truncation domains (1–241, 241–482 and 482–723), we demonstrate that multiple contact points exist between BUB1 and TGF-β signaling components and that these interactions are independent of the BUB1 tetratricopeptide repeat (TPR) domain. Moreover, substitutions in the middle domain (241–482) encompassing S318 reveals that efficient interaction with TGFBR2 occurs only in its dephosphorylated state (241–482 S318A). In contrast, the phospho-mimicking mutant (241–482 S318D) exhibits efficient binding with SMAD2 and its over-expression results in a decrease in TGFBR1-TGFBR2 and TGFBR1-SMAD2 interactions. These findings suggest that TGFBR2 mediated BUB1 phosphorylation at S318 may serve as a switch for the dissociation of the SMAD2-TGFBR complex, and therefore represents a regulatory event for TGF-β signaling. Finally, we provide evidence that the BUB1-TGF-β signaling axis may mediate aggressive phenotypes in a variety of cancers. Keywords: BUB1 (budding uninhibited by benzimidazoles-1), kinase, TGFb (transforming growth factor-beta), SMAD2, SMAD3, TGFBR1, TGFBR2, signaling, phosphorylation, regulation

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Humans infected with West Nile virus (WNV) may clinically present with symptoms that are suggestive of neurological infection. Nearly all treatments of WNV disease have been effective in animal models only if administered before or soon after viral challenge. Here, we evaluated whether a potent neutralizing anti-WNV humanized monoclonal antibody (MAb), hE16, could improve the course of disease in a hamster model when administered after the virus had infected neurons in the brain. Five days after viral injection, WNV was detected in the brains of hamsters by cytopathic assay, quantitative reverse-transcription polymerase chain reaction, and immunohistochemical staining of WNV envelope in neurons. Notably, 80%–90% of the hamsters treated 5 days after viral injection by intraperitoneal injection with hE16 survived the disease, compared with 37% of the placebo-treated hamsters (P ≤ .001). The hamsters that received hE16 directly in the brain also exhibited markedly improved survival rates, compared with those in the placebo-treated hamsters. In prospective experiments, hamsters with high levels of infectious WNV in their cerebrospinal fluid were also protected by hE16 when administered 5 days after viral injection. These experiments suggest that humanized MAbs with potent neutralizing activity are a possible treatment for human patients after WNV has infected neurons in the central nervous system. [ABSTRACT FROM AUTHOR]

MRI phase imaging in multiple sclerosis (MS) patients and in autopsy tissue have demonstrated the presence of iron depositions in white matter lesions. The accumulation of iron in some but not all lesions suggests a specific, potentially disease-relevant process, however; its pathophysiological significance remains unknown. Here, we explore the role of lesional iron in multiple sclerosis using multiple approaches: immunohistochemical examination of autoptic MS tissue, an in vitro model of iron-uptake in human cultured macrophages and ultra-highfield phase imaging of highly active and of secondary progressive MS patients. Using Perls' stain and immunohistochemistry, iron was detected in MS tissue sections predominantly in non-phagocytosing macrophages/microglia at the edge of established, demyelinated lesions. Moreover, iron-containing macrophages but not myelin-laden macrophages expressed markers of proinflammatory (M1) polarization. Similarly, in human macrophage cultures, iron was preferentially taken up by non-phagocytosing, M1-polarized macrophages and induced M1 (super) polarization. Iron uptake was minimal in myelin-laden macrophages and active myelin phagocytosis led to depletion of intracellular iron. Finally, we demonstrated in MS patients using GRE phase imaging with ultra-highfield MRI that phase hypointense lesions were significantly more prevalent in patients with active relapsing than with secondary progressive MS. Taken together, our data provide a basis to interpret iron-sensitive GRE phase imaging in MS patients: iron is present in non-phagocytosing, M1-polarized microglia/macrophages at the rim of chronic active white matter demyelinating lesions. Phase imaging may therefore visualize specific, chronic proinflammatory activity in established MS lesions and thus provide important clinical information on disease status and treatment efficacy in MS patients.

Introduction: There has been a resurgence in nicotine inhalation in adolescents due to the popularity and availability of Electronic Nicotine Delivery Systems (ENDS). Almost five times as many US high-school seniors inhale nicotine vapor daily compared with those who smoke tobacco. This study was conducted to determine the impact of repeated adolescent vapor inhalation of nicotine on behavior in adulthood., Methods: Male and female Sprague-Dawley rats were exposed to 30-minute sessions of ENDS vapor inhalation, twice daily, from post-natal day (PND) 31-40. Conditions included vapor from the propylene glycol (PG) vehicle or nicotine (30 mg/mL in the PG). Animals were assessed for effects of nicotine on open field (PND 74-105) and wheel activity (PND 126-180) and for volitional exposure to nicotine vapor (PND 285-395). Plasma nicotine and cotinine were assessed in separate groups of male and female Wistar and Sprague-Dawley rats after a single nicotine inhalation session., Results: Group mean plasma nicotine ranged from 39 to 59 ng/mL post-session with minimal strain differences detected. Adolescent nicotine exposure enhanced sensitivity to the locomotor stimulating effects of nicotine (0.1-0.8 mg/kg, s.c.) in an open field in female rats, but didn't change the effects of nicotine on wheel activity. Female rats exposed to nicotine (30 mg/mL) vapor as adolescents responded more vigorously than PG-exposed females to nicotine vapor in a fixed ratio 5 challenge., Conclusions: Repeated adolescent nicotine vapor inhalation leads to enhanced liability for volitional exposure to nicotine vapor in adulthood in female rats, but minimal change in spontaneous locomotor behavior., Implications: These results show that adolescent vaping of nicotine can lead to lasting sensitization to the effects of nicotine in adulthood, including volitional responding for nicotine vapor. Demonstration of this in a controlled animal model establishes causality in a manner not possible from longitudinal evidence in human populations. These findings further highlight the importance of decreasing adolescent nicotine exposure to e-cigarettes to reduce consumption in adulthood., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rationale: Use of electronic drug delivery systems (EDDS, "e-cigarettes") to ingest nicotine and Δ 9 -tetrahydrocannabinol (THC) has surged in adolescents in the USA; five times as many high-school seniors vape nicotine daily using tobacco. At the same time, 19.5% of seniors use cannabis at least monthly, with 12% using EDDS to deliver it., Objectives: This study was conducted to examine the impact of repeated adolescent vapor inhalation of nicotine and THC in rats., Methods: Female Sprague-Dawley rats were exposed to 30-min sessions of vapor inhalation, twice daily, from post-natal day (PND) 31 to PND 40. Conditions included vapor from the propylene glycol (PG) vehicle, nicotine (60 mg/mL in the PG), THC (100 mg/mL in the PG), or the combination of nicotine (60 mg/mL) and THC (100 mg/mL). Rats were assessed on wheel activity, heroin anti-nociception and nicotine and heroin vapor volitional exposure during adulthood., Results: Nicotine-exposed rats exhibited few differences as adults, but were less sensitive to anti-nociceptive effects of heroin (1 mg/kg, s.c.). THC- and THC + nicotine-exposed rats were less spontaneously active, and obtained fewer nicotine vapor deliveries as adults. In contrast, THC-exposed rats obtained volitional heroin vapor at rates indistinguishable from the non-THC-exposed groups. Repeated THC exposure also caused tolerance to temperature-disrupting effects of THC (5 mg/kg, i.p.)., Conclusions: These studies further confirm that the effects of repeated vapor exposure to THC in adolescence last into early to middle adulthood, including decreased volitional consumption of nicotine. Effects of repeated nicotine in adolescence were comparatively minor., (© 2024. The Author(s).)

Competing Interests: None declared

Objective: To evaluate the impact of axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) on upper limb (UL) morbidity in breast cancer patients., Background: Axillary de-escalation is motivated by a desire to reduce harm of ALND. Understanding the impact of axillary surgery and disparities in operative procedures on postoperative arm morbidity would better direct resources to the point of need and cement the need for de-escalation strategies., Methods: Embase, MEDLINE, CINAHL, and PsychINFO were searched from 1990 until March 2020. Included studies were randomized-controlled and observational studies focusing on UL morbidities, in breast surgery patients. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The prevalence of UL morbidity comparing SLNB and ALND at <12 months, 12 to 24 months, and beyond 24 months were analyzed., Results: Sixty-seven studies were included. All studies reported a higher rate of lymphedema and pain after ALND compared with SLNB. The difference in lymphedema and pain prevalence between SLNB and ALND was 13.7% (95% confidence interval: 10.5-16.8, P <0.005) and 24.2% (95% confidence interval: 12.1-36.3, P <0.005), respectively. Pooled estimates for prevalence of reduced strength and range of motion after SLNB and ALND were 15.2% versus 30.9% and 17.1% versus 29.8%, respectively. Type of axillary surgery, greater body mass index, and radiotherapy were some of the predictors for UL morbidities., Conclusions: Prevalence of lymphedema after ALND was higher than previously estimated. ALND patients experienced greater rates of lymphedema, pain, reduced strength, and range of motion compared with SLNB. The findings support the continued drive to de-escalate axillary surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Following therapeutic mammoplasty (TM), the contralateral breast may require a later balancing procedure to optimize shape and symmetry. The alternative is to offer patients simultaneous TM with immediate contralateral symmetrization via a dual-surgeon approach, with the goal of reducing costs and minimizing the number of subsequent hospital appointments in an era of COVID-19 surges. The aim of this cost-consequence analysis is to characterize the cost-benefit of immediate bilateral symmetrization dual-operator mammoplasty versus staged unilateral single operator for breast cancer surgery., Method: A prospective single-centre observational study was conducted at an academic teaching centre for breast cancer surgery in the UK. Pseudonymized data for clinicopathological variables and procedural care information, including the type of initial breast-conserving surgery and subsequent reoperation(s), were extracted from the electronic patient record. Financial data were retrieved using the Patient-Level Information and Costing Systems., Results: Between April 2014 and March 2020, 232 women received either immediate bilateral (n = 44), staged unilateral (n = 57) for breast cancer, or unilateral mammoplasty alone (n = 131). The median (interquartile range (i.q.r.)) additional cost of unilateral mammoplasty with staged versus immediate bilateral mammoplasty was €5500 (€4330 to €6570) per patient (P < 0.001), which represents a total supplementary financial burden of €313 462 to the study institution. There was no significant difference between groups in age, Charlson comorbidity index, operating minutes, time to adjuvant radiotherapy in months, or duration of hospital stay., Conclusion: Synchronous dual-surgeon immediate bilateral TM can deliver safe immediate symmetrization and is financially beneficial, without delay to receipt of adjuvant therapy, or additional postoperative morbidity., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd.)

Rationale: Opioids are effective medications, but they have several key limitations including the development of tolerance, establishment of dependence, diversion for non-medical use, and the development of addiction. Therefore, any drugs which act in an additive or synergistic fashion with opioids to address medical applications have the potential to reduce opioid-related harms., Objectives: To determine if heroin and Δ 9 -tetrahydrocannabinol (THC) interact in an additive or independent manner to alter nociception, body temperature, and spontaneous locomotor activity when inhaled or injected., Methods: Groups of female and male rats, implanted with radiotelemetry transmitters, were exposed to vapor generated from heroin (50 mg/mL in propylene glycol vehicle; PG), THC (50 mg/mL), or the combination for assessment of effects on temperature and activity. Thermal nociception was assessed with a warm water tail-withdrawal assay., Results: Heroin inhalation increased temperature and activity whereas THC inhalation decreased temperature and activity in both female and male Sprague-Dawley rats. Effects of combined inhalation were in opposition, and additional experiments found the same outcome for the injection of heroin (0.5 mg/kg, s.c.) and THC (10 mg/kg, i.p.) alone and in combination. In contrast, the co-administration of heroin and THC by either inhalation or injection produced additive effects on thermal nociception in both male and female Sprague-Dawley and Wistar rats., Conclusions: This study shows that additive effects of THC with an opioid on a medical endpoint such as analgesia may not generalize to other behavioral or physiological effects, which may be a positive outcome for unwanted side effects., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Male rats escalate intravenous self-administration of entactogen psychostimulants, 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxymethamphetamine (MDMA) under extended access conditions, as with typical psychostimulants. Here, we investigated whether female rats escalate self-administration of methylone, 3,4-methylenedioxypentedrone (pentylone), and MDMA and then studied consequences of MDMA and pentylone self-administration on GABA A receptor and kappa opioid receptor (KOR) signaling in the central nucleus of the amygdala (CeA), a brain area critically dysregulated by extended access self-administration of alcohol or cocaine. Adult female Wistar rats were trained to self-administer methylone, pentylone, MDMA (0.5 mg/kg/infusion), or saline-vehicle using a fixed-ratio 1 response contingency in 6-h sessions (long-access: LgA) followed by progressive ratio (PR) dose-response testing. The effects of pentylone-LgA, MDMA-LgA and saline on basal GABAergic transmission (miniature post-synaptic inhibitory currents, mIPSCs) and the modulatory role of KOR at CeA GABAergic synapses were determined in acute brain slices using whole-cell patch-clamp. Methylone-LgA and pentylone-LgA rats similarly escalated their drug intake (both obtained more infusions compared to MDMA-LgA rats), however, pentylone-LgA rats reached higher breakpoints in PR tests. At the cellular level, baseline CeA GABA transmission was markedly elevated in pentylone-LgA and MDMA-LgA rats compared to saline-vehicle. Specifically, pentylone-LgA was associated with increased CeA mIPSC frequency (GABA release) and amplitude (post-synaptic GABAA receptor function), while mIPSC amplitudes (but not frequency) was larger in MDMA-LgA rats compared to saline rats. In addition, pentylone-LgA and MDMA-LgA profoundly disrupted CeA KOR signaling such as both KOR agonism (1 mM U50488) and KOR antagonism (200 nM nor-binaltorphimine) decreased mIPSC frequency suggesting recruitment of non-canonical KOR signaling pathways. This study confirms escalated self-administration of entactogen psychostimulants under LgA conditions in female rats which is accompanied by increased CeA GABAergic inhibition and altered KOR signaling. Collectively, our study suggests that CeA GABA and KOR mechanisms play a critical role in entactogen self-administration like those observed with escalation of alcohol or cocaine self-administration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Khom, Nguyen, Vandewater, Grant, Roberto and Taffe.)

Background: Therapeutic mammaplasty (TM) is an oncological procedure which combines tumour resection with breast reduction and mastopexy techniques. Previous systematic reviews have demonstrated the oncological safety of TM but reporting of critically important outcomes, such as quality of life, aesthetic and functional outcomes, are limited, piecemeal or inconsistent. This systematic review aimed to identify all outcomes reported in clinical studies of TM to facilitate development of a core outcome set., Methods: Medline, EMBASE, CINAHL and Web of Science were searched from inception to 5 August 2020. Included studies reported clinical outcomes following TM for adult women. Two authors screened articles independently for eligibility. Data were extracted regarding the outcome definition and classification type (for example, oncological, quality of life, etc.), time of outcome reporting and measurement tools., Results: Of 5709 de-duplicated records, 148 were included in the narrative synthesis. The majority of studies (n = 102, 68.9 per cent) reported measures of survival and/or recurrence; approximately three-quarters (n = 75, 73.5 per cent) had less than 5 years follow-up. Aesthetic outcome was reported in half of studies (n = 75, 50.7 per cent) using mainly subjective, non-validated measurement tools. The time point at which aesthetic assessment was conducted was highly variable, and only defined in 48 (64.0 per cent) studies and none included a preoperative baseline for comparison. Few studies reported quality of life (n = 30, 20.3 per cent), functional outcomes (n = 5, 3.4 per cent) or resource use (n = 28, 18.9 per cent)., Conclusion: Given the oncological equivalence of TM and mastectomy, treatment decisions are often driven by aesthetic and functional outcomes, which are infrequently and inconsistently reported with non-validated measurement tools., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

The α-pyrrolidino-phenone cathinone stimulants first came to widespread attention because of bizarre behavior consequent to the use of α-pyrrolidinopentiophenone (α-PVP, "flakka") reported in popular press. As with other designer drugs, diversification of cathinones has been driven by desirable subjective effects, but also by attempts to stay ahead of legal controls of specific molecules. The α-pyrrolidinohexiophenone (α-PHP) and α-pyrrolidinopropiophenone (α-PPP) compounds have been relatively under-investigated relative to α-PVP and provide a key opportunity to also investigate structure-activity relationships, i.e., how the extension of the alpha carbon chain may affect potency or efficacy. Female rats were used to contrast the effects of α-PHP and α-PPP with those of α-PVP in altering wheel activity and effects on spontaneous locomotion, temperature and intracranial self-stimulation reward. The α-PPP, α-PHP and α-PVP compounds (5, 10 mg/kg, i.p.) suppressed wheel activity. Inhalation of α-PHP or α-PVP also suppressed wheel activity, but for an abbreviated duration compared with the injection route. Spontaneous activity was increased, and brain reward thresholds decreased, in a dose-dependent manner by all three compounds; only small decrements in body temperature were observed. These data show that all three of the α-pyrrolidino-phenone cathinones exhibit significant stimulant-like activity in female rats. Differences were minor and abuse liability is therefore likely to be equivalent for all three α-pyrrolidino-phenones., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: The extra medical use of, and addiction to, prescription opioid analgesics is a growing health problem. To characterize how prescription opioid abuse develops, this study investigated the affective consequences of escalating prescription opioid use using intracranial self-stimulation (ICSS) reward and oxycodone intravenous self-administration (IVSA) models., Experimental Approach: Male Wistar rats were given access to oxycodone IVSA (0.15 mg·kg -1 per infusion, i.v.) in short-access (ShA; 1 h) or long-access (LgA; 12 h) sessions for five sessions per week followed by intermittent 60-h discontinuations from drug access, a novel explicit test of the negative reinforcement hypothesis. Separate groups were first trained in the ICSS procedure and then in oxycodone IVSA in 11-h LgA sessions., Key Results: Rats given LgA to oxycodone escalated their responding more than ShA rats, with further significant increases observed following each 60-h discontinuation. Presession brain reward thresholds increased with sequential daily LgA IVSA sessions, consistent with a growing negative affective state consequent to successive daily intoxication/abstinence cycles. A 1-h oxycodone IVSA interval was sufficient to normalize these elevated reward thresholds, as was, paradoxically, a 60-h weekend abstinence. The increase in ICSS thresholds was attenuated in a group treated with the long-acting κ-opioid antagonist norbinaltorphimine prior to IVSA training., Conclusion and Implications: Changes in brain reward function during escalation of oxycodone self-administration are driven by an interplay between κ-opioid receptor-mediated negative affective state associated with escalated oxycodone intake and dynamic restoration of brain reward status during longer periods of abstinence., (© 2021 The British Pharmacological Society.)

The ideal choice of vascular access in patients requiring haemodialysis is an arteriovenous fistula. However, an important often under-reported complication encountered at follow-up is symptoms of tingling or numbness in the hand. This may represent carpal tunnel syndrome, impairment of the median nerve as it traverses through the carpal tunnel at the wrist by focal compression of this nerve. Contributory factors in the presence of an arteriovenous fistula may include venous hypertension and varying steal syndrome phenomena provoking micro-ischaemia. Studies that investigated the evolution of carpal tunnel syndrome in haemodialysis patients with an arteriovenous fistula revealed that the frequency of carpal tunnel syndrome associated with an arteriovenous fistula on haemodialysis ranged from 10.4% to 42.6%. An association between duration of haemodialysis with arteriovenous fistula and carpal tunnel syndrome development was also observed. Surgical release of carpal tunnel provided complete relief of paraesthesia in all treated patients in the examined, demonstrating an alleviation of symptoms and improved function of hand and quality of life in patients with an arteriovenous fistula. However, the aetiology and risk factors for development of carpal tunnel syndrome remain unclear and further studies should attempt to elucidate the pathophysiology of this occurrence in the presence of arteriovenous fistulas.

The use of Δ 9 -tetrahydrocannabinol (THC) by inhalation using e-cigarette technology grows increasingly popular for medical and recreational purposes. This has led to development of e-cigarette based techniques to study the delivery of THC by inhalation in laboratory rodents. Inhaled THC reliably produces hypothermic and antinociceptive effects in rats, similar to effects of parenteral injection of THC. This study was conducted to determine the extent to which the hypothermic response depends on interactions with the CB 1 receptor, using pharmacological antagonist (SR141716, AM-251) approaches. Groups of rats were implanted with radiotelemetry devices capable of reporting activity and body temperature, which were assessed after THC inhalation or injection. SR141716 (4 mg/kg, i.p.) blocked or attenuated antinociceptive effects of acute THC inhalation in male and female rats. SR141716 was unable to block the initial hypothermia caused by THC inhalation, but temperature was restored to normal more quickly. Alterations in antagonist pre-treatment time, dose and the use of a rat strain with less sensitivity to THC-induced hypothermia did not change this pattern. Pre-treatment with SR141716 (4 mg/kg, i.p.) blocked hypothermia induced by i.v. THC and reversed hypothermia when administered 45 or 90 min after THC (i.p.). SR141716 and AM-251 (4 mg/kg, i.p.) sped recovery from, but did not block, hypothermia caused by vapor THC in female rats made tolerant by prior repeated THC vapor inhalation. The CB 2 antagonist AM-630, had no effect. These results suggest that hypothermia consequent to THC inhalation is induced by other mechanisms in addition to CB 1 receptor activation., Competing Interests: Declaration of Competing Interest SAV has consulted for LJARI., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Growing nonmedical use of prescription opioids is a global problem, motivating research on ways to reduce use and combat addiction. Medical cannabis ("medical marijuana") legalization has been associated epidemiologically with reduced opioid harms and cannabinoids have been shown to modulate effects of opioids in animal models. This study was conducted to determine if Δ 9 -tetrahydrocannabinol (THC) enhances the behavioral effects of oxycodone. Male rats were trained to intravenously self-administer (IVSA) oxycodone (0.15 mg/kg/infusion) during 1 h, 4 h or 8 h sessions. Following acquisition rats were exposed to THC by vapor inhalation (1 h and 8 h groups) or injection (0-10 mg/kg, i.p.; all groups) prior to IVSA sessions. Fewer oxycodone infusions were obtained by rats following vaporized or injected THC compared with vehicle treatment prior to the session. Follow-up studies demonstrated parallel dose-dependent effects of THC, i.p., on self-administration of different per-infusion doses of oxycodone and a preserved loading dose early in the session. These patterns are inconsistent with behavioral suppression. Additional groups of male and female Wistar rats were assessed for nociception following inhalation of vaporized THC (50 mg/mL), oxycodone (100 mg/mL) or the combination. Tail withdrawal latency was increased more by the THC/oxycodone combination compared to either drug alone. Similar additive antinociceptive effects were produced by injection of THC (5.0 mg/kg, i.p.) and oxycodone (2.0 mg/kg, s.c.). Together these data demonstrate additive effects of THC and oxycodone and suggest the potential use of THC to enhance therapeutic efficacy, and to reduce the abuse, of opioids., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Early aortic stenting in chronic type B aortic dissection (TBAD) may lead to long-term benefit, although the optimal treatment strategy is hotly debated. A robust comparison to outcomes seen in medically managed patients is challenging as the rate of antihypertensive medication adherence is unknown. The aims of this study were therefore to identify the rate of antihypertensive medication adherence and predictors of adherence in TBAD., Methods: This was a cross-sectional mixed methods study of patients with TBAD. Medication adherence was assessed by the eight-item Morisky Medication Adherence Scale together with an assessment of demographic, behavioral, and psychological variables and disease-specific knowledge., Results: There were 47 patients (mean age, 59 years; 81% male) who were recruited from a tertiary vascular unit. The mean total number of medications taken was 5.8 (2-14), and the mean number of antihypertensive medications was 1.9 (1-6). Of the 47 patients, 20 (43%) reported high levels of medication adherence, 17 (36%) reported moderate adherence, and 10 (21%) reported low adherence. Previous aortic surgery was associated with higher levels of adherence (β = 0.332; P = .03), as was taking a greater number of medications (β = 0.332; P = .026), perceived benefit from treatment (β = 0.486; P < .001), good memory (β = 0.579; P < .001), and low fears of side effects (β = 0.272; P < .014)., Conclusions: Medical management remains the mainstay of treatment in uncomplicated TBAD; however, the majority of patients are poorly adherent to their antihypertensive medications. The merits of thoracic endovascular aortic repair in TBAD are argued, and poor adherence is an important factor in the debate; one cannot robustly compare two strategies when half of a treatment group may not be receiving the stated intervention. To develop an evidence-based treatment strategy for TBAD, we must take into account the direct and indirect effects of medical therapy and thoracic endovascular aortic repair. Further work to improve medication adherence and to understand its impact on disease progression is vital to inform the debate and to deliver the best outcomes for patients., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)