Reflecting and Adapting to an Academic Workplace Before and After the Lockdown in Greek-Speaking Cyprus

Higher education institutions (HEIs) are required to constantly adapt and respond to the needs of society, both economic and social, including the current pandemic situation. The traditional representation of university as an educational side is being challenged leading to the inclusion of the practitioner side, emphasising on the need for business education. In this context, the present study examines how academics reflect and adapt to an HEI and enhance their workplace literacy and work-related practices inside and outside the foreign language classroom. The participants were 36 academics of all ranks involving part- and full-timers working in a private English-speaking HEI. The findings indicate that participants could need more support with the subject area that is English, and an extended access to the shared repertoire of their communities, which may strengthen their connections with other academics and reduce high job demands, resulting in better adaptation to new workplaces.

Self-Administration of Entactogen Psychostimulants Dysregulates Gamma-Aminobutyric Acid (GABA) and Kappa Opioid Receptor Signaling in the Central Nucleus of the Amygdala of Female Wistar Rats

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 GABAA 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.

Comparison of Methamphetamine and MDMA Extended Access Self-administration: Acquisition, Maintenance, and Response Patterns

<p>Rationale. 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine are two amphetamine derivatives with contrasting pharmacological profiles. Therefore, self- administration profiles might be expected to reflect these differences. Objectives. This study compared the latency and proportion to acquire self-administration, maintenance of self-administration, and within-session response patterns. Methods. Rats were given extended access (8-hour daily sessions) to either methamphetamine, MDMA or vehicle self-administration over a period of 10 consecutive days. A criterion based on the performance of the vehicle control group was used to determine acquisition of reliable MDMA and methamphetamine self-administration. In conjunction, for MDMA self-administration the infusion dose was halved for each rat that achieved a total of 85mg/kg for the remaining sessions. Temporal patterns of responding were assessed using hourly data of the first day of self-administration, the day following acquisition, and the final day of self-administration. Results. A greater proportion of rats in the methamphetamine group acquired self- administration and self-administration was acquired with a shorter latency compared to the MDMA group. Responding maintained by methamphetamine on day one was high. By the third day a pattern developed that was maintained throughout testing. The greatest proportion of responding occurring within the first hour of each daily test session. A progressive escalation of intake was also observed within the methamphetamine group. Responding maintained by MDMA was low on the first day, but by day 5 responding had increased with most of the responding within the session occurring during the first three hours. On day 10 the greatest amount of responding occurred during the first hour. No escalation of intake as a function of test day was observed for MDMA self-administration.</p>

Comparison of Methamphetamine and MDMA Extended Access Self-administration: Acquisition, Maintenance, and Response Patterns

<p>Rationale. 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine are two amphetamine derivatives with contrasting pharmacological profiles. Therefore, self- administration profiles might be expected to reflect these differences. Objectives. This study compared the latency and proportion to acquire self-administration, maintenance of self-administration, and within-session response patterns. Methods. Rats were given extended access (8-hour daily sessions) to either methamphetamine, MDMA or vehicle self-administration over a period of 10 consecutive days. A criterion based on the performance of the vehicle control group was used to determine acquisition of reliable MDMA and methamphetamine self-administration. In conjunction, for MDMA self-administration the infusion dose was halved for each rat that achieved a total of 85mg/kg for the remaining sessions. Temporal patterns of responding were assessed using hourly data of the first day of self-administration, the day following acquisition, and the final day of self-administration. Results. A greater proportion of rats in the methamphetamine group acquired self- administration and self-administration was acquired with a shorter latency compared to the MDMA group. Responding maintained by methamphetamine on day one was high. By the third day a pattern developed that was maintained throughout testing. The greatest proportion of responding occurring within the first hour of each daily test session. A progressive escalation of intake was also observed within the methamphetamine group. Responding maintained by MDMA was low on the first day, but by day 5 responding had increased with most of the responding within the session occurring during the first three hours. On day 10 the greatest amount of responding occurred during the first hour. No escalation of intake as a function of test day was observed for MDMA self-administration.</p>

Physicians’ Opinion Regarding Extended Access to Hormonal Contraception in Switzerland

(1) Background: Access to hormonal contraceptives (HC) strongly differs between countries and varies from over the counter (OTC) to prescription-only availability. This study aimed to identify opinions among physicians in Switzerland regarding extended access to HC. (2) Methods: Web-based survey among physicians (gynecologists, general practitioners, and pediatricians) in Switzerland. (3) Results: Hundred sixty-three physicians, mainly gynecologists, participated in this survey and 147 (90%) were included for analysis. A total of 68% (n = 100) answered that prescription-only status could be extended under certain conditions but physicians were concerned about patients’ safety (97%, n = 142). Moreover, there was concern about insufficient patient education on HC (93%, n = 136) and that women may forego preventive examinations (80%, n = 118). Participants did not support OTC availability (93%, n = 136). Pharmacists prescribing (including initiation of HC) revealed controversial results, but a combined access model (initial prescription from physician and follow-up prescriptions by pharmacists) found acceptance in 70% (n = 103). (4) Conclusions: Participating physicians stated that prescription-only status for HC could be lifted under certain conditions but also some concerns, e.g., patients’ safety or neglection of preventive examinations, were raised. Future research should focus on specific conditions in which extended access to HC could be agreed on.

CTNI-02. NERATINIB FOR TREATMENT OF LEPTOMENINGEAL METASTASES FROM HER2-POSITIVE BREAST CANCER IN EXTENDED ACCESS PROGRAM: PRELIMINARY RESULTS

INTRODUCTION The aim of the study was to evaluate the activity of neratinib in LM from HER2-positive BC after the failure of multiple lines of treatment. PATIENTS AND METHODS Inclusion criteria were as follows: age ≥ 18 years; histological diagnosis of primary HER2-positive BC; newly-diagnosed LM (LANO criteria); KPS ≥ 60; coexistence of BM that have or not received radiotherapy; life expectancy ≥ 3 months; previous drugs, including capecitabine, trastuzumab, T-DM1, pertuzumab, and hormone therapy, were allowed, with the exclusion of lapatinib or other investigational agents. Neratinib was administered 240 mg daily continuously. Primary endpoint was the OS. Secondary endpoints were progression-free survival (PFS), neurological benefit, radiological response rate, and tolerability. RESULTS Nine patients with LM have been enrolled with a median age of 44 years, and a median KPS of 80. Median time since LM onset from the diagnosis of primary BC was 42 months, and patients underwent a median number of adjuvant treatments before LM of 3. Three patients developed LM alone, and other 6 had LM associated with multiple BM. Six-months and 1-year OS were 66.7% and 22.3%, respectively, with a median OS of 8 months (95%CI 3-13*). Median PFS was 3.5 months (95%CI 2-6) after the start of treatment. A neurological improvement was reported in 2/9 patients (22.2%), while in other 4/9 patients (44.5%) was achieved a neurological stabilization lasting for a median time of 5 months (95%CI 2-19). The best radiological response was a stable disease in 5/9 patients (55.6%), while no complete or partial were achieved according to LANO criteria. A CSF clearance was observed in 1 patient only (11.1%). Grade III-IV adverse events were not reported, and 2 patients only (22.2%) had mild diarrhea correlated with neratinib. CONCLUSIONS Neratinib might be a safe and effective treatment in LM from heavily pretreated HER2-positive BC.

Investigating the impact of distance on the use of primary care extended hours

IntroductionPoor access to general practice services has been attributed to increasing pressure on the health system more widely and low satisfaction among patients. Recent initiatives in England have sought to expand access by the provision of appointments in the evening and at weekends. Services are provided using a hub model. NHS national targets mandate extended opening hours as a mechanism for increasing access to primary care, based on the assumption that unmet need is caused by a lack of appointments at the right time. However, research has shown that other factors affect access to healthcare and it may not simply be appointment availability that limits an individual's ability to access general practice services. ObjectivesTo determine whether distance and deprivation impact on the uptake of extended hours GP services that use a hub practice model. MethodsWe linked a dataset (N = 25,408) concerning extended access appointments covering 158 general practice surgeries in four Clinical Commissioning Groups (CCGs) to the General Practice Patient Survey (GPPS) survey, deprivation statistics and primary care registration data. We used negative binomial regression to estimate associations between distance and deprivation on the uptake of extended hours GP services in the Greater Manchester City Region. Distance was defined as a straight line between the extended hours provider location and the patient's home practice, the English Indices of Multiple Deprivation were used to determine area deprivation based upon the home practice, and familiarity was defined as whether the patient's home practice provided an extended hours service. ResultsThe number of uses of the extended hours service at a GP practice level was associated with distance. After allowing for distance, the number of uses of the service for hub practices was higher than for non-hub practices. Deprivation was not associated with rates of use. ConclusionThe results indicate geographic inequity in the extended hours service. There may be many patients with unmet need for whom the extension of hours via a hub and spoke model does not address barriers to access. Findings may help to inform the choice of hub practices when designing an extended access service. Providers should consider initiatives to improve access for those patients located in practices furthest away from hub practices. This is particularly of importance in the context of closing health inequality gaps.

Self-Administration of entactogen psychostimulants dysregulates GABA and Kappa Opioid Receptor signaling in the central nucleus of the amygdala of female Wistar rats

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 GABAA 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-hour 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 postsynaptic 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 (postsynaptic 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 (1mM U50488) and KOR antagonism (200nM 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.

Caveolin-1 Expression in the Dorsal Striatum Drives Methamphetamine Addiction-Like Behavior

Dopamine D1 receptor (D1R) function is regulated by membrane/lipid raft-resident protein caveolin-1 (Cav1). We examined whether altered expression of Cav1 in the dorsal striatum would affect self-administration of methamphetamine, an indirect agonist at the D1Rs. A lentiviral construct expressing Cav1 (LV-Cav1) or containing a short hairpin RNA against Cav1 (LV-shCav1) was used to overexpress or knock down Cav1 expression respectively, in the dorsal striatum. Under a fixed-ratio schedule, LV-Cav1 enhanced and LV-shCav1 reduced responding for methamphetamine in an extended access paradigm compared to LV-GFP controls. LV-Cav1 and LV-shCav1 also produced an upward and downward shift in a dose–response paradigm, generating a drug vulnerable/resistant phenotype. LV-Cav1 and LV-shCav1 did not alter responding for sucrose. Under a progressive-ratio schedule, LV-shCav1 generally reduced positive-reinforcing effects of methamphetamine and sucrose as seen by reduced breakpoints. Western blotting confirmed enhanced Cav1 expression in LV-Cav1 rats and reduced Cav1 expression in LV-shCav1 rats. Electrophysiological findings in LV-GFP rats demonstrated an absence of high-frequency stimulation (HFS)-induced long-term potentiation (LTP) in the dorsal striatum after extended access methamphetamine self-administration, indicating methamphetamine-induced occlusion of plasticity. LV-Cav1 prevented methamphetamine-induced plasticity via increasing phosphorylation of calcium calmodulin kinase II, suggesting a mechanism for addiction vulnerability. LV-shCav1 produced a marked deficit in the ability of HFS to produce LTP and, therefore, extended access methamphetamine was unable to alter striatal plasticity, indicating a mechanism for resistance to addiction-like behavior. Our results demonstrate that Cav1 expression and knockdown driven striatal plasticity assist with modulating addiction to drug and nondrug rewards, and inspire new strategies to reduce psychostimulant addiction.