First gaining worldwide attention in February 2020, COVID-19 has infected 500,000, and taken the lives of 21,000 as of the 27th March 20201. In response to the rapidly escalating global crisis, most countries have employed drastic measures such as travel bans and nationwide lockdowns in an urgent attempt to slow down viral spread so as not to overwhelm limited healthcare resources. “Social distancing” is the catchphrase of the day. Singapore saw her first imported case on the 23rdJanuary 20202 and felt déjà vu , having experienced the Severe Acute Respiratory Syndrome [SARS] outbreak in 2003.Singapore’s response to SARS demonstrated two key priorities: sustainability of patient care and protection of healthcare professionals [HCPs]. While manpower was reorganised into teams segregated by time, place and expertise, many important hospital functions such as medical education and intermediate exam preparation for specialist trainees [STs] were ignored3 4. The only training was “on-the-job,” focusing on essential care. Both specialist and general training for junior doctors was neglected despite their frontline role. The situation with COVID-19 is no different, and globally we are already witnessing a negative impact on education and training5. While understandable, work-arounds do exist. In Singapore, we have been preparing for this6and our unit made it an early priority to continue medical education while balancing increased service needs and the requirement to avoid congregation. With the COVID-19 pandemic expected to last until the end of 2020 and possibly beyond, we share our strategies.To safeguard HCPs and ensure continuity of services in the inevitable event that HCPs contract COVID-19, hospitals nationwide have implemented team segregation. In our department, different teams work shifts to cover five geographically distinct service areas- outpatient services [two teams], emergency department [four teams], labour ward [four teams], sonography unit [two teams] and inpatient services [two teams]. The greatly increased manpower needs, non-standard working hours, the need to avoid congregation and depletion of staff through illness initially stopped our morning didactic sessions. However, within two weeks, we started using videoconferencing methods for synchronous distance teaching. While the use of videoconferencing in medical education is not new7 8, it has found revived utility in these times. The lead and assistant program directors created a timetable with topics blueprinted to the Royal College of Obstetricians and Gynaecologists membership examination [MRCOG] syllabus incorporating Green Top Guidelines, NICE guidelines, TOG articles and other RCOG documents such as consent advice, good practice, scientific impact papers, audits and key publications. This timetable was divided amongst the STs who committed to 1-2 sessions each per month. They were encouraged to select topics which represented personal knowledge gaps. The format comprises a 30-minute presentation with assessment of learning through Q&A, EMQs or SBA. These sessions are facilitated by senior faculty with our programme coordinators tracking education hours and attendance by verifying on-screen presence. We hold sessions at 0730hrs as it constitutes a quieter period prior to hand over and when most STs are awake. Those who are commuting, off work, or on quarantine / stay home notice still find it easy to participate.Zoom® [Zoom Video Communications Inc., San Jose, California, USA] has several features which have greatly assisted our mission. The most significant is its stability over a wide variety of platforms [i.e. smart phones and computers] running different operating systems over local 4G networks. Presenters found the “Share Screen” function very user friendly to allow voice-over teaching with their presentation slides. A pre-determined, recurrent meeting code is fixed for the morning session. Zoom® also allows recordings of the session which are stored on a hospital-based intranet server together with the presentation slides and the source guideline or article. This serves as a form of asynchronous teaching for those who missed the session or wish to revise.Comical usage of virtual backgrounds and participation of some our STs’ very young children at home brought in humour and gave a sense of solidarity at a time of isolation. Senior STs revealed themselves as natural peer trainers regarding exam technique. Interestingly, some of our junior STs felt that this style of teaching was more interactive than our typical Departmental didactic sessions. One remarked, “Zoom® meetings are more fun and meaningful because they are directed at what is really important for us to know and it is easy to ask questions fearlessly.” This is a positive consequence as many cultures fear “losing face” by asking questions in an audience of senior faculty. The end of the meeting also allows for any “on the ground” operational issues to be raised while serving as a conduit to pass on information from department leaders.A vital aspect of Singapore’s response to COVID-19 was to cut all non-time-sensitive surgical cases in order to boost surge critical care capacity and redistribute manpower and resources. In our unit, there is an 80-90% reduction in operating for benign gynaecology cases with only obstetric and gynaecologic oncology cases proceeding. Due to manpower constraints, all surgeries and on-table consultations are being undertaken by consultants with house officer assistance. As a result, STs’ gynaecological operative training has been greatly reduced. To partly address this, we started Zoom®-based surgical sharing sessions by experienced faculty, taping segments of current surgical cases or using archived videos to train on anatomy, surgical principles and pre- and post-operative care. A session on the management of ovarian cysts in pregnancy coincided with three recent cases and was particularly well received. Although videoconferencing has a role in surgical training9, it is very clear that it will not entirely remedy case-log deficiencies and the loss of hands-on experience. Simulators housed within the Department are available for individual use and we plan to incorporate these into “live” sessions.The MRCOG examinations, which are used to certify competence for progression within Singapore’s obstetrics and gynaecology specialist training programme, have been postponed10. To keep our exam candidates’ preparedness honed while waiting for the next exam window, we have also continued in-house Zoom® OSCE practice sessions. Prior to this pandemic, our STs were supported to take up RCOG Associate status in order to facilitate access to the RCOG’s excellent e-learning11 12 portal. We strongly recommend it as a staple for asynchronous learning as it is a repository for a wide array of modules pertaining to core knowledge, case discussions, technical skills and professionalism. Many Colleges globally have similar material, and these should be explored.This pandemic will undoubtedly affect the training and psychosocial wellbeing of STs who constitute a major component of the frontline staff. Disruption to training affects confidence and exam cancellations instil fear for the future as key purchases and family plans are put on hold. However, while this pandemic is expected to last until the end of the year, women’s health issues will continue to exist. It is important for the global community of obstetricians and gynaecologists to start seeing how to ensure continuity of training in this new environment. We offer a few simple suggestions on how to achieve this despite dyssynchronous rosters, home stay notices, anxiety, exhaustion and illness. Anecdotally, our STs report have found solidarity in a time of isolation through these morning sessions and it probably contributes to their ability to cope. The pandemic of today is daunting. We need to support our STs because to do so is to invest into the future of women’s health.

Abstract: Objective: The objective of this paper was to evaluate the outcome of transabdominal amnioinfusion in pregnant patients with oligohydramnios. Method: This is a prospective observational study involving 80 cases of oligohydramnios treated with transabdominal ultrasound, in the period between 2011 and 2016. The patients were treated in two centers; however, all the procedures were performed by the same operator. Results: The mean gestational age at the first treatment was 24 weeks. Some patients received more than one amnioinfusion. The mean interval between the first infusion and delivery was 31 days. Perinatal and neonatal mortalities were 45% and 35%, respectively. There were 5 cases of chorioamnioitis and in majority of the cases, the final diagnosis was made after amnioinfusion. Conclusion: The procedure has been proven to be very safe. The result showed a high perinatal mortality which was not surprising, as these pregnancies were complicated by a major fetal malformation. Significantly, this study showed that the diagnosis accuracy of the concomitant congenital fetal malformation was significantly improved. The diagnosis accuracy had a major impact on the management of patients, especially the mode of delivery.

A 26 years old lady presented to us with primary amenorrhoea. On examination and investigation she was found to have MRKH syndrome with Situs inversus totalis. Likewise what we do for these syndromic patients, we did sigmoid vaginoplasty. This is one of the uncommon anatomical variants we encountered in our series of cases. Our literature search did not reveal such patient undergoing sigmoid vaginoplasty and so is this case presented for publication.

Lung ultrasound (LU) has rapidly become a tool for assessment of patients stricken by the novel coronavirus 2019 (COVID-19). Over the past two and a half months (January, February and first half of March 2020) we have used this modality for identification of lung involvement along with pulmonary severity in patients with suspected or documented COVID-19 infection. Use of LU has helped us in clinical decision making and reduced the use of both chest x-rays and computed tomography (CT).

Orleans Parish in Louisiana is in the midst of an exponentially increasing number of patient admissions with COVID-19 and respiratory symptoms. Patients have been described having CT findings most consistent with an Early stage (< 7 days from symptoms onset) or an Advanced stage (8-14 days from symptoms onset).We describe and illustrate those Early and Advanced stage CT findings from patients with documented COVID-19 who have been admitted to University Medical Center in New Orleans, Louisiana.

A 57-year-old man was diagnosed with acute aortic dissection (AAD), but had marked infiltration shadows in his right lung. Intraoperative findings showed that large subadventitial hematomas had spread from the ascending aorta to the right pulmonary artery, which may have caused the infiltration of the lung. Subadventitial hematoma must be considered in rare cases of AAD with pulmonary infiltration.

The occurrence of mycobacterial infections in different hosts and their implication as obligate or opportunistic pathogens remain mainly unclear. In addition to the well-known pathogenic members of the Mycobacterium tuberculosis - complex (MTBC), over 180 nontuberculous mycobacteria (NTM) species have been described. Although the large majority of the NTM are assumed to be non-pathogenic to most individuals, an increasing trend in NTM infections has been observed over the last decades. The reasons of such augmentation are probably more than one: improved laboratory diagnostics, an increasing number of immunocompromised patients and individuals with lung damage are some of the possible aspects. Mandibular lymph nodes of 176 hunted wild boars from the pre-Alpine region of Canton Ticino, Switzerland, were collected. Following gross inspection, each lymph node was subjected to culture and to an IS6110 based real-time PCR specific for MTBC members. Histology was performed of a selection of lymph nodes presenting gross visible lesions. Moreover, accuracy of matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry species identification was compared with sequence analysis of a combination of housekeeping genes. Mycobacteria of the MTBC were detected in five out of 176 wild boars (2.8%; CI95% 1.2 - 6.5) and were all confirmed to be Mycobacterium microti by molecular methods. In addition, based on the examined lymph nodes, NTM were detected in 57.4% (CI95% 50.0 – 64.5) of the wild boars originating from the study area. The 111 isolates belonged to 24 known species and three potentially undescribed Mycobacterium species. M. avium subsp. hominissuis thereby predominated (22.5%) and was found in lymph nodes with and without macroscopic changes. Overall, the present findings show that, with the exception of undescribed Mycobacterium species where identification was not possible (3.6%; 4/111), MALDI-TOF had a high concordance rate (90.1%; 100/111 isolates) to the sequence based reference method.

Intensive agriculture needs new sustainable tools for weed management. Allelopathy offered a valid alternative. Sesquiterpene lactones (STLs) are the most important cultivated cardoon (Cynara cardunculus L. var. altilis DC.) allelochemicals involved in weed toxicity. The present study aims to investigate the effect of field light stress (by 60% of plant shading) on the qualitative and quantitative composition of STLs in cultivated cardoon leaf extracts harvested in January and April. The phytotoxicity of leaf extracts was evaluated on the wheat coleoptile elongation, seed germination, root and shoot length of the weeds Amaranthus retroflexus L. and Portulaca oleracea L. Light stress significantly increased the concentrations of total and single STLs, and this increase was more marked if combined with harvest time (+338, 102 and 94 of cynaratriol, desacylcynaropicrin and 11,13-dihydro-deacylcynaropicrin, respectively) in April. The concentration of STLs and the phytotoxic activity were correlated (light stressed extracts belonging from April reduced by 91, 86 and 93% the wheat coleoptile elongation and the root and shoot length of A. retroflexus, respectively, at 800 ppm). Therefore, the induction of light stress could be used to increase the concentrations of STLs in cultivated cardoon leaves for industrial applications and to improve their phytotoxic potential.

Background: The corona virus disease 2019 (COVID-19) outbreak originating in Wuhan, Hubei province, China, coincided with chunyun, the period of mass migration for the annual Spring Festival. To contain its spread, China adopted unprecedented nationwide interventions on January 23 2020. These policies included large-scale quarantine, strict controls on travel and extensive monitoring of suspected cases. However, it is unknown whether these policies have had an impact on the epidemic. We sought to show how these control measures impacted the containment of the epidemic. Methods: Web of Science database was searched on February 26, 2020 for Corona virus (COVID-19) publications published between 1997 to 2020. It was performed on the same day in order to avoid the possible bias came from update on the database because the metrics are changing over time. All publication types were considered; however publications as errata were excluded. Analysis parameters include year of publication, publication type, patterns of international collaboration, research institutions, journals, impact factor, h-index, language, and times cited. Results: A total of 12612Corona virus (COVID-19) research publications were published across the world. The Corona virus (COVID-19) associated publications were originated from 25 countries/territories, indicating the international spread of Corona virus (COVID-19) research. The USA was the largest contributor, with 4524 articles published over 32 years, followed by Peoples R China(2667 articles). The total number of citations for these publications has already achieved 8,015, with an average of 9.01 citations per each publication. The h-index for Corona virus (COVID-19) -associated publications was 48. The USA also have the highest h-index (32), followed by KSA (26) and UK (22). Netherland produced the greatest proportion of publications with international research collaboration (72.7 %) followed by the UK (71 %) and Germany (69.1 %) out of the total number of publications for each country.

Previously, our lab developed high molecular weight (MW) tense (T) state glutaraldehyde polymerized bovine hemoglobins (PolybHbs) that exhibited reduced vasoactivity in several small animal models. In this work, we prepared PolybHb in the T- and relaxed (R) quaternary state with ultrahigh MW (> 500 kDa) with varying cross-link densities and investigated the effect of MW on key biophysical properties (i.e., O2 affinity, cooperativity coefficient, hydrodynamic diameter, polydispersity, polymer composition, viscosity, gaseous ligand-binding kinetics, autoxidation, and haptoglobin-binding kinetics). To further optimize current PolybHb synthesis and purification protocols, we performed a comprehensive meta-data analysis to evaluate correlations between procedural parameters (i.e. cross-linker:bovine Hb (bHb) molar ratio, gas/liquid exchange time, temperature during dithionite addition, and number of diafiltration cycles) and the biophysical properties of both T-state and R-state PolybHbs. Our results showed that, the duration of the fast-step autoxidation phase of R-state PolybHb increased with decreasing glutaraldehyde:bHb molar ratio. Additionally, T-state PolybHb exhibited significantly higher biomolecular rate constants for binding to haptoglobin and unimoleular O2 offloading rate constants compared to R-state PolybHb. The methemoglobin (metHb) level in the final product was insensitive to the molar ratio of glutaraldehyde to bHb for all PolybHb. During tangential flow filtration processing of the final product, 14 diafiltration cycles was found to yield the lowest metHb level.

Microwave assisted hydrodistillation (MAHD) and conventional hydrodistillation techniques were compared in the extraction of essential oils from Amomum subulatum seeds. The time required for MAHD method (70 min) is lesser than that for HD method (4 hr). There is a slight increase in the yield of extracted oil in MAHD method (3.35%) compared to HD (3%). GC-MS results show that MAHD extracted essential oil was wealthier in oxygenated compounds. 1, 8-Cineole was found to be a major compound in case of both the essential oil, followed by α-pinene. In MAHD the percentage of the major oxygenated monoterpene (1, 8- cineol) slightly increases from 88% to 89% as compared to hydrodistillation. Contrarily to this, the percentage of monoterpene hydrocarbon were decreased in MAHD than HD extracted oil. MAHD and HD extracted oils show good antibacterial activities against gram-negative and gram-positive bacteria. MAHD extracted oil shows better antibacterial activity than HD extracted against both gram positive and gram-negative bacteria. 2, 2-diphenyl-1-picrylhydrazyl (DPPH•) radical scavenging antioxidant activities show that MAHD extract has better inhibition percentage than HD extract, and the IC50 value of MAHD was less than HD extracted oil.

COVID-19 pandemic disease spread by SARS-COV-2 single-strand structure RNA virus belongs to the 7th generation of the coronavirus family. Following an unusual replication mechanism, its extreme ease of transmissibility has put many counties under lockdown. With a cure for the infection uncertain in the near future, the pressure currently lies in the current healthcare infrastructure, policies, government activities, and behaviour of the people to contain the virus. This research seeks to understand the spreading patterns of the COVID-19 virus through exponential growth modelling and identifies countries that have showed an initial sign of containment until 26th March 2020. Post identification of countries that have shown an initial sign of containment, predictive supervised machine learning models were built with infrastructure, environment, policies, and infection related independent variables. For the purpose, COVID-19 infection data across 42 countries were used. Logistic regression results shows a positive significant relationship of healthcare infrastructure and lockdown policies on the sign of early containment in countries. Machine learning models based on logistic regression, decision tree, random forest, and support vector machines were developed and are seen to have accuracies between 76.2% to 92.9% to predict early sign of infection containment. Other policies and activities taken by countries to contain the infection are also discussed.

Background: Cladribine (CdA), an oral prodrug approved for the treatment of relapsing multiple sclerosis, selectively depletes lymphocytes. CdA passes the blood-brain barrier suggesting a potential effect on CNS resident cells. Objective: We examined, if CdA modifies the phenotype and function of naïve and activated primary mouse microglia, when applied in different concentrations including 0.1-1 µM that putatively overlaps human CSF concentrations. Methods: Primary microglia cultures without stimulation or in the presence of proinflammatory lipopolysaccharide (LPS) or anti-inflammatory IL-4 were co-treated with different concentrations of CdA for 24 hours. Viability was assessed by MTT assay. Phagocytotic ability and morphology were examined by flow cytometry, and random migration by IncuCyte Zoom and TrackMate. Change in gene expression was examined by qPCR, and protein secretion by Meso Scale Discovery. Results: LPS and IL-4 upregulated deoxycytidine kinase (DCK) expression. Only activated microglia were affected by CdA, and this was unrelated to viability. CdA 0.1-1 µM significantly reduced granularity, phagocytotic ability and random migration of activated microglia. CdA 10 µM increased the IL-4-induced gene expression of Arg1 and LPS-induced expression of IL-1beta, TNF, iNOS, and Arg1, but protein secretion remained unaffected. CdA 10 µM potentiated the increased expression of anti-inflammatory TNFR2 but not TNFR1 induced by LPS. Conclusion: Microglia acquire a less activated phenotype when treated with 0.1–1 µM CdA that putatively overlaps human CSF concentrations. This may be related to the upregulated gene expression of DCK upon activation and suggests a potential alternative mechanism of CdA with direct effect on CNS resident cells.

The average lifespan of HIV-infected subjects remains shorter compared to uninfected individuals. Immunosenescence may be responsible for this difference despite effective antiretroviral therapy (ART) with successful viral suppression. Here, we evaluated the effects of HIV and ART exposure on T cell aging in male homosexual HIV subjects. CD4+ T cell activation (HLA-DR+) and senescence (CD57+) markers were analyzed by flow cytometry, and telomere length was quantified by real-time PCR. Specifically, we observed an increase in activation and senescence markers on total CD4+ T cell populations in HIV-infected subjects. We also observed a reduction in senescence markers on terminally differentiated memory T(TemRA) cells and activation markers on central memory T(TCM), effector memory T(TEM), and TemRA cells in ART-treated HIV subjects. Furthermore, we also observed an extension of telomere length in memory CD4+ T cells, rather than naive CD4+ T cells, after viral control by ART. Our results indicate that HIV-infected patients exhibit a premature T cell aging phenotype with accelerated immune senescence. Partial recovery of immune senescence and differentiation aberrances is achieved in CD4+ T cells in HIV patients on ART. Overall, these results suggest that HIV infection, rather than ART exposure, influences the T cell aging process.

In-crop soil waterlogging caused by extreme rainfall events, high ground water tables, excessive irrigation and lateral ground water flow inhibit potential grain yields. However, the extent to which yield is influenced by the timing and duration of waterlogging relative to crop phenology is unknown. To investigate this, we conducted various waterlogging treatments on a range of modern barley genotypes varying in their waterlogging tolerance, with tolerance conferred through aerenchyma formation under oxygen deficit conditions. Results showed that yield was reduced by 35% in W1 (waterlogging at Zadoks stage (ZS) 12.5 for one month) to 52% in WL3 (waterlogging at ZS 15 for two months) due to fewer spikes/m2 and kernels/spike. Two weeks waterlogging at ear emergency stage had the greatest impact on yield (70% reduction) due to its effect on spikelet fertility and grain filling. Phenology was delayed 1-8 ZS at the end of waterlogging treatments, with the waterlogging-susceptible cultivar Franklin showing the greatest delays, and waterlogging tolerant genotypes capable of AF (Macquarie+, TAMF169) having the least delays (0-4 ZS). Genotypes with the AF QTL (Macquarie+) showed a slight and nonsignificant yield reduction compared with unwaterlogged controls and mitigated around 23% yield loss under early phenological waterlogging stress.

Coronaviruses are a large group of viruses which are found in avian and mammalian species. It has been reported that, the identification and characterization of a novel coronavirus (2019-nCoV) which caused a pandemic of acute respiratory syndrome in humans in Wuhan, China. By 26 January 2020 it has caused 2,050 laboratory-confirmed infections with 56 fatal cases. Furthermore, it was found that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus.The new coronavirus SARS-CoV-2 binds with human respiratory cells in order to hijack them to produce more viruses. The new virus attaches to a receptor on respiratory cells called angiotensin-converting ACE2. The most abundant protein in coronavirus is the nucleocapsid protein.

Respiratory infections in general and rhinovirus (RV) infection specifically are the main reason for asthma exacerbation in children. Here we found increased level of Programmed cell death protein 1 ligand (PD-L1) mRNA in total blood cells isolated from pre-school children with virus-induced asthma, with lower FEV1% and with high serum levels of the C-Reactive-Protein (CRP). These data indicate that, in the presence of infection in the airways of preschool children, worse asthma is associated with induced PD-L1 mRNA expression. Further, the activation of regulatory elements that induce IFNβ, a cytokine that is involved in immunity of infections, was found to be associated with better lung function in asthmatic children. Finally, IFN-beta released by peripheral blood Mononuclear cells (PBMC) was found associated with an induced expression of PD-L1mRNA in control but no asthmatic children. These data suggest that improving peripheral blood IFN type I expression in PBMCs in pediatric asthma could improve disease exacerbation because suppressing PDL1 expression in blood cells.

Carbon dioxide has attracted considerable attention owing to its physics and abundant polymorphs. Despite decades of extensive experiments and theoretical simulations, the structure and properties of carbon dioxide under extreme pressures and temperatures are yet to be properly understood. Particularly, the intermediate phase IV of solid carbon dioxide, which separates the molecular phases at low pressures from the non-molecular phases at high pressures, has not been fully investigated, and its structure remains controversial. Here, based on the second-order Møller−Plesset perturbation (MP2) theory and the embedded fragment method, we study the crystal structure, equation of state, and Raman spectra of solid carbon dioxide phase IV at high pressures and temperatures. We demonstrate that the solid carbon dioxide phase IV is a molecular structure that remains in a molecular state rather than the bent state shown in other literatures, which is consistent with the experimental work by Datchi et al. and denies the observed results by Park et al. The proposed work is of great significance in determining the structure of the high-pressure phases of carbon dioxide and further exploring the new phase of molecular crystals.

The ab initio molecular dynamics simulations are performed to study the atomic structures of Co92-xBxTa8 (x = 30, 32.5, 35, 37.5, at.%) glassy alloys. The result shows that the local packing of B-centered clusters is more efficient than that for Co- and Ta-centered clusters. It is also found that B-centered clusters are the primary structure-forming clusters. The Kasper polyhedra with a Voronoi index of <0 3 6 0> and <0 2 8 0> are dominant in B-centered clusters. Specially, the <0 3 6 0> clusters can form a robust network structure, which plays a key role in mechanical properties. Such a network structure has a higher activation barrier for structural rearrangement and a better resist to plastic flow. Thus, the increase in the fraction of <0 3 6 0> with B content would result in an increase in yield strength as well as a sharp decrease in compression plasticity.

Rationale, aims and objectives :Over the past decades, thrombophilia testing in patients with venous thrombo-embolism (VTE) has increased tremendously. However, the role of inherited thrombophilia (IT) in prediction the risk of recurrence remains controversial. Consequently, it is still unclear whether thrombophilia testing influences decisions regarding duration of anticoagulation in clinical practices. The aim of this study was to evaluate the impact if IT on VTE treatment decisions and on predicting the risk of recurrence. Methods : A retrospective longitudinal study (January 2011-Decembre 2016) including 190 patients with confirmed VTE referred from internal medicine department for inherited thrombophilia screening was carried out. Results : The mean age patients was 40.2 years and the sex ratio (M/F) was 0.78. IT was confirmed in 27.5% of patients. A long term anticoagulation was decided in 51.6% of patients with IT. There was no significant difference in the duration of anticoagulation between patients with or without IT. VTE recurrence was recorded in 26 (13.7 %) patients. The 24 years cumulative incidence of recurrence was 9% in patients with IT and 14% in those without. IT was not associated with increased risk of recurrence after treatment withdrawal (Hazard ratio=1.31 IC(0.47-3.63); p=0.6). Conclusion : In clinical practice, IT did not influence anticoagulation duration and was not associated with a higher VTE risk of recurrence. It seems to be less relevant for decision making than presumed.

Background and purpose. The purpose of this study was to evaluate the effects of CBD on the behavioural and gene expression changes induced by a new animal model of spontaneous cocaine withdrawal. Experimental approach. Six hours after cessation of progressive increase of cocaine administration for 12 days (15 mg·kg-1·day-1 to 60 mg·kg-1·day-1, i.p.), spontaneous cocaine withdrawal was evaluated in male mice. The effects of CBD (10, 20 and 40 mg·kg-1, i.p.) were evaluated on cocaine withdrawal-induced alterations in motor activity, somatic signs and anxiety-like behaviour. Furthermore, gene expression changes in dopamine transporter (DAT) and tyrosine hydroxylase (TH) in the ventral tegmental area, and in cannabinoid receptors 1 (CNR1) and 2 (CNR2) in the nucleus accumbens were analysed by real-time PCR. Key results. Mice exposed to the spontaneous cocaine withdrawal model showed increased motor activity, somatic withdrawal signs and high anxiety-like behaviour. Interestingly, the administration of CBD normalized motor and somatic signs disturbances and induced an anxiolytic effect. Moreover, the administration of CBD blocked the increase of DAT and TH gene expression in mice exposed to the cocaine withdrawal. In addition, the administration of CBD modulated the cocaine withdrawal-induced decrease of CNR1 and induced an additional up-regulation of CNR2 gene expression. Conclusions and implications. These results show behavioural and gene expression alterations in mice exposed to a new model of spontaneous cocaine withdrawal. Interestingly, CBD alleviates cocaine withdrawal-induced behavioural and gene expression alterations suggesting potential for the management of cocaine withdrawal.

BACKGROUND AND PURPOSE In this study, we compared the different effect of Dimethyl-2-ketoglutarate (DMKG) on energy metabolism, autophagy, and apoptosis between parental and doxorubicin-resistant liver cancer cell lines. EXPERIMENTAL APPROACH In the energy metabolism section, cell viability, adenosine triphosphate (ATP) level, doxorubicin (DOX) content, energy metabolism phenotype, and enzymes expression were measured. In the autophagy part, autophagy vesicles were observed, enzymes expression and cell viability were detected. Apoptosis rate and expression of enzymes were detected in the apoptosis part. KEY RESULTS DMKG can directly act on ATP synthase and prolyl hydroxylase, affecting the cellular oxidative phosphorylation and glycolysis levels, respectively, in both SMMC-7721 and SMMC-7721/DOX cells. However, its practical effects depend on the function of the mitochondrial malate-aspartate shuttle. Furthermore, ATP-reduced cell autophagy had partial anti-apoptotic effects in SMMC-7721 cells, which is an important reason for the weak inhibition of cell viability observed at low doses of DMKG. In contrast, DMKG showed no significant effect on autophagy but a high cell death rate in SMMC-7721/DOX cells. Induced high expression levels of p-AMPK, p-mTOR, and Bcl-2 could inhibit DMKG-induced apoptosis in SMMC-7721 cells. However, activation of Caspase-3 was the most important molecular effect that was observed in relation to the DMKG-induced apoptosis in SMMC-7721/DOX cells. CONCLUSIONS AND IMPLICATIONS These results suggest that inhibition of energy metabolism can reduce the effects of autophagy in DOX resistant cells, which could improve the therapeutic outcomes and reverse the resistance to chemotherapeutic drugs. This article provides a new idea and method for reversing tumor resistance.

Background and purposes Preeclampsia(PE) is associated with abnormal function of various factors in placentas. 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is abundantly expressed in placenta and controls the local availability of glucocorticoids. We aimed to elucidate the role of 11β-HSD2 in the pathogenesis of PE. Experimental approach Pregnant rats were administrated with 11β-HSD2 inhibitor carbenoxolone (CBX) subcutaneously or by placenta-targeted delivery system. The blood pressure, renal and placental morphology, placental blood flow and circulatory levels of fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF) were subsequently examined. Cultured human trophoblasts were used to investigate the role of 11β-HSD2 in migration and invasion function and sFlt1 release in vitro. Key results Subcutaneous administration and placenta-targeted delivery of CBX resulted in the hallmark of PE-like features including hypertension, proteinuria, renal damages, elevated circulatory sFlt1 level and increased sFlt1/ PlGF in pregnant rats. These animals displayed reduced trophoblast invasion in uterus, impaired spiral artery remodeling and reduced placental blood flow. In vitro study showed that 11β-HSD2 dysfunction inhibited migration and invasion of the extravillous trophoblasts and promoted sFlt1 release in syncytiotrophoblasts. Mechanically, sFlt1 release induced by 11β-HSD2 dysfunction is mediated by enhancement of a disintegrin and metalloprotease (ADAM)17 transcription in placenta.

Background and purpose: Amphetamine use disorder is a serious health concern, but surprisingly little is known about the vulnerability to the moderate and compulsive use of this psychostimulant and its underlying mechanisms. Previous research showed that inherited serotonin transporter (SERT) down-regulation increases the motor response to cocaine, as well as moderate and compulsive intake of this psychostimulant. Here we sought to investigate whether these findings generalize to amphetamine and the underlying mechanisms in the nucleus accumbens. Experimental Approach: In serotonin transporter knockout (SERT−/−) and wild-type control (SERT+/+) rats we assessed the locomotor response to acute amphetamine (AMPH) and intravenous AMPH self-administration under short access (ShA: 1 hr daily sessions) and long access (LgA: 6 hr daily sessions) conditions. 24 hrs after AMPH self-administration we analysed the expression of glutamate system components in the nucleus accumbens shell and core. Key results: We found that SERT−/− animals displayed an increased AMPH-induced locomotor response and increased AMPH self-administration under LgA, but not ShA conditions. Further, we observed changes in the vesicular and glial glutamate transporters, NMDA and AMPA receptor subunits and their respective postsynaptic scaffolding proteins as function of serotonin transporter genotype, AMPH exposure (baseline, ShA and LgA) and nucleus accumbens sub region. Conclusion and implications: We demonstrate that SERT gene deletion increases the psychomotor and reinforcing effects of AMPH, and that the latter is potentially mediated, at least in part, by homeostatic changes in the glutamatergic synapse of the nucleus accumbens shell and/or core.