Herein, we present a neonatal case of coarctation of the aorta, with aortic arch thrombus confirmed by echocardiography. We performed thrombus removal and aortic arch repair emergently. This critical condition necessitates quick preoperative evaluation with echocardiography. Moreover, postoperative evaluation using computed tomography is reasonable to assess an aortic arch configuration, and exclude the remnant thrombus.

Aorto-Pulmonary Mismatch (APM) in Transposition of the Great Arteries (TGA) may be accountable for dilatation of neoaortic root and regurgitation of neoaortic valve as late complications of ASO. The manuscript from Arcieri et al. highlights an important aspect about ASO technique: should we approach APM during ASO and what would be the best strategy to do so? Techniques to approach APM at the time of ASO have been published sporadically and are very rarely employed by surgeons. Reconstruction of the neoaorta is generally achieved by trimming of the suture line between pulmonary root (neoaortic root) and ascending aorta resulting in an abnormal dilated and bulky neoaortic root already at the time of ASO. Reduction of the pulmonary root dimension by ressection of a fragment of the pulmonary artery wall possibly results in a more homogenous neoaorta with consequent better hemodynamics. We believe that approaching APM during ASO will have a compelling positive impact in the late survival of the patients with complex TGA.

Antidepressants are not safe during pregnancy and in women of child bearing age.Alain Braillon (1), Susan Bewley(2), Aubrey Blumsohn(3), Florian Naudet (4) Jean-Louis Montastruc(5), Joel R Lexchin(6)(1) Previously senior consultant, Amiens, France braillon.alain@gmail.com(2) Department of Women & Children’s Health, King’s College London, London, UK(3) Previously Senior Lecturer in Medicine, University of Sheffield, Sheffield, UK(4) University of Rennes 1, Rennes, France Clinical Investigation Center (INSERM 1414) and Adult Psychiatry Department, Rennes University Hospital, Rennes, France(5) Medical and Clinical Pharmacology, University Hospital-Faculty of Medicine, Toulouse, France(6) School of Health Policy and Management Faculty of Health, York University, Toronto, Ontario, CanadaCorrespondanceAlain Braillon, 27 rue Voiture, 80000 Amiens, France. braillon.alain@gmail.com757 w + 9 ref. (Limit 800 words + 10 references)Keywords: risk minimization measures; drug safety; serotonin reuptake inhibitors; teratogenicity; developmental disorders; post-partum hemorrhage; EBMNo fundingCoI: Alain Braillon, JL and SB are among industry independent experts on Jeanne Lenzer’s list (https://jeannelenzer.com/list-independent-experts). SB chairs Healthwatch, a charity promoting science and integrity in healthcare (https://www.healthwatch-uk.org/) and her interests are declared at https://www.whopaysthisdoctor.org/doctor/58/active. JL received payments for writing a brief in an action for side effects of a drug for Michael F. Smith, Lawyer and a second brief on the role of promotion in generating prescriptions for Goodmans LLP in 2017-2020. He is a member of the Foundation Board of Health Action International. He receives royalties from University of Toronto Press and James Lorimer & Co. Ltd. for books he has written.Cabaillot and colleagues’ pharmaco-epidemiological study of antidepressants use during pregnancy in France raises a number of questions about the validity of their conclusions.(1)Firstly, what is their basis for making the claim that “[selective serotonin-norepinephrine reuptake inhibitors] appear to be safe in pregnant women”?(1) This claim ignores significant evidence to the contrary:a) the odds ratio for maternal use of serotonin reuptake inhibitor antidepressants (SRIs) (we use SRI to refer to both serotonin-norepinephrine reuptake inhibitors and so-called ‘selective’ serotonin reuptake inhibitors as selectivity is restricted to the experimental setting) during the first trimester of pregnancy and the presence of congenital heart defects is 1.57 (95% CI 1.25–1.97) for paroxetine, 1.36 (95% CI 1.08–1.72) for fluoxetine and 1.29 (95% CI 1.14–1.45) for sertraline.(2) Further, observational studies reported developmental disorders that are in line with experimental studies and with human infant MRI studies: SRIs exposure has an association with changes in brain structure, white matter microstructure, brain connectivity, and cerebral metabolism, particularly in brain regions critical to emotional processing;(3)b) previous warnings about SRIs’ harms in core clinical journals were overlooked;(4,5)c) post-partum hemorrhage, a serious SRI complication acknowledged by Cabaillot and colleagues, is a very serious issue; with cardiovascular conditions it is the most common underlying causes of pregnancy-related death.(6)Secondly, Cabaillot et al misrepresent the references that they cite in their statement that “[selective serotonin-norepinephrine reuptake inhibitors] are recommended by the National Agency for Health and Medicines (ANSM) and the 2018 International Cochrane Review International Publications ”?(1)a) the link for the recommendation (ref. 19 in Cabaillot et al) does not work and the summary of product characteristics for fluoxetine warns “Overall, the data suggest that the risk of cardiovascular malformation in children after maternal exposure to fluoxetine is approximately 2/100 … Fluoxetine should not be used during pregnancy unless the clinical condition of the patient requires treatment with fluoxetine and justifies the potential risk to the fetus”.(7)b) the Cochrane Review (ref. 20 in Cabaillot et al) is about postnatal depression, not pregnancy. It concluded: “Due to the limitations of the current evidence base, such as the low statistical power of the included studies, it is not possible to draw any clear conclusions about the effectiveness of antidepressants for the prevention of postnatal depression.”Thirdly, Cabaillot and colleagues should provide data (malformations, deprescription) according to the various classes of antidepressants and their princeps. The risk of malformations varies among antidepressant classes and within classes, e.g., it is highest for SRIs containing paroxetine.(2)Fourthly, the widespread prescribing of antidepressants in France may be the result of France’s universal healthcare scheme consistently refusing to reimburse effective psychotherapy. In contrast is the 2008 Improving Access to Psychological Therapies strategy in England that provides free and direct access to psychotherapy without barriers.(8)Overplaying benefits and downplaying harms are not serving the patient’s interests. All prescribers must be warned that antidepressants have not been shown to be risk free during pregnancy, either for the woman or her fetus. Quantitative explanation of the degree of risk expressed in easily understood terms such as number needed to harm must be provided, not binary assertions of apparent “safety” based on a value judgment only women should make. The well documented harms of SRIs during pregnancy contrast with purported benefits _a limited effectiveness of SRIs in the general population and no controlled trials during pregnancy. Available SRI vs placebo trials are short-term (6-8 weeks) and although the decreases in depression scores are statistically significant, their clinical relevance is doubtful.(9) In contrast, many patients with depression respond to judicious ‘watchful waiting’ and psychotherapies successfully treat most episodes of even persistent depression. These interventions are evidence-based in real-life settings: their benefits persist over the long term (improving self-esteem, agency, and social functioning and, they are safe.(9) Evidence based psychosocial interventions must be the preferred initial option in treating depression, especially in women of child bearing age as many pregnancies are unintended.(4)Regulatory agencies must implement and monitor a series of risk minimization measures for SRIs as for other teratogens: a) an assessment of each woman’s potential to become pregnant; b) shared decision making about the risks of antidepressant treatment in general and specifically during pregnancy, and an explanation about the need for effective contraception throughout treatment; c) informed pregnancy testing before and during treatment as needed; d) a ‘risk acknowledgement form’, in which the woman and prescriber confirm that appropriate counselling has been given and understood. Finally, prescription of antidepressants during pregnancy should be recorded in specific registries to closely monitor clinical outcomes.References1. Cabaillot A, Bourset A, Mulliez A et al. Trajectories of antidepressant drugs during pregnancy: A cohort study from a community-based sample. Br J Clin Pharmacol. 2021;87(3):965-987.doi: 10.1111/bcp.14449.2. De Vries C, Gadzhanova S, Sykes MJ, Ward M, Roughead E. A Systematic Review and Meta-Analysis Considering the Risk for Congenital Heart Defects of Antidepressant Classes and Individual Antidepressants. Drug Saf. 2020;44(3):291-312.doi: 10.1007/s40264-020-01027-x3. Lugo-Candelas C, Cha J, Hong S, et al. Associations Between Brain Structure and Connectivity in Infants and Exposure to Selective Serotonin Reuptake Inhibitors During Pregnancy. JAMA Pediatr. 2018; 172(6):525-533. doi: 10.1001/jamapediatrics.2017.5227.4. Braillon A, Bewley S. Prescribing in pregnancy shows the weaknesses in pharmacovigilance. BMJ. 2018;361:k2334. doi: 10.1136/bmj.k2334.5. Braillon A, Bewley S. The easy misuse of antidepressants during pregnancy is depressing. Br J Clin Pharmacol. 2018;84(10):2445-2446. doi: 10.1111/bcp.13713.6. Davis NL, MPH, Smoots AN, Goodman, DA. Pregnancy-Related Deaths: Data from 14 U.S. Maternal Mortality Review Committees, 2008-2017. Maternal Mortality Review Data-Brief. 2019. Available at https://www.cdc.gov/reproductivehealth/maternal-mortality/erase-mm/MMR-Data-Brief_2019-h.pdf Accessed 27 May 2020.7. French National Agency for Health and Medicines (ANSM). Fluoxetine: Summary of Product Characteristics. 3 April 2016. Available at http://agence-prd.ansm.sante.fr/php/ecodex/rcp/R0278605.htm Accessed 27 May 2021.8. Thornicroft G. Improving access to psychological therapies in England. Lancet. 2018;391(10121):636-637. doi: 10.1016/S0140-6736(17)32158-X.9. Braillon A, Lexchin J, Noble JH, Menkes D, M’sahli L, Fierlbeck K, Blumsohn A, Naudet F. Challenging the promotion of antidepressants for nonsevere depression. Acta Psychiatr Scand. 2019;139(3):294-295. doi: 10.1111/acps.13010.

The Klein Krames equation (KKE) stands for the probability distribution function (PDF) that describes the diffusion of particles subjected an external force. It is shown that 2 A. A. Alderremy, H. I. Abdel-Gawad, Khaled M. Saad, Shaban Aly the conformable fractional derivative (CFD) KKE can be reduced to the classical one's by using similarity transformations. Here, the objective of this work is to find the exact solutions of CFD-KKE.. To this issue, an approach is presented. It is based on transforming the KKE to a system of first order PDEs. The solutions are found by implementing extended unified method. It is found that, the integrability condition is that the external force is constant. The numerical results of the solutions are calculated and the are shown graphically. 2020 Mathematics Subject Classification: 34A08; 35A22; 41A30; 65N22.

Urogenital Atrophy – a silent epidemic 1Paula Briggs1,2, Gayathri Delanerolle3, Rachel Burton2, Jian Qing Shi4,5, Haitham Hamoda6, Dharani K. Hapangama1,2Affiliations:1Liverpool Women’s Hospital NHS Foundation Trust, Liverpool, UK2Department of Women’s & Children’s Health, Institute of Life Course and Medical Sciences, University of Liverpool, UK3University of Oxford, UK4The Alan Turing Institute, UK5Southern University of Science and Technology, China6King’s College Hospital, London UK, Chairman of the British Menopause SocietyCorresponding author: Paula Briggs, Email: paula.briggs@lwh.nhs.ukUrogenital atrophy describes the multiple changes in urogenital tissues, most commonly due to hypoestrogenism associated with the menopause and ageing. It results in an alteration of the appearance and function of the vulva, vagina, urethra and bladder. The mucosal epithelium becomes thinner and is prone to inflammation and trauma and the collagen fibres in the dermal layer hyalinise and fuse, which in association with fragmentation of elastin fibres, reduces tissue elasticity. These changes can collectively result in pain and bleeding, most notably in association with sexual activity. Most menopausal women are affected by these changes in tissue quality to some degree, and therefore there is a need for better communication and education for women, their partners and their health care providers, to reduce any potential negative effect on sexual function and quality of life2,3. Similarly, to optimise clinical outcomes and maximise patient benefit, fit for purpose diagnostic standards should be developed4.There are two key research surveys that demonstrate valuable information that could aid in advancing current clinical practices, namely The European REVIVE Survey5 and VIVA-LATAM6. The REVIVE survey was conducted in four European countries including Germany, Spain, Italy and the UK (3768 postmenopausal women between the ages of 45-75 participated), while the VIVA-LATAM survey was conducted in Latin American countries including Argentina, Brazil, Chile, Colombia and Mexico (2509 women aged 55-65 participated). Both surveys were designed to establish awareness of the effect of lack of estrogen on urogenital tissue quality. Symptoms were frequent and treatment, particularly local hormone therapy was more likely in women who have had a discussion with a health care professional (HCP). Women wanted advice, but it was offered proactively only in a small proportion of cases. The conclusion of both surveys confirms that urogenital atrophy is an under-recognised, under-diagnosed and under-treated chronic condition and they highlight that there is a need for a public awareness and education campaign. Women surveyed in REVIVE felt most concerned about loss of sexual intimacy and youth. This was echoed by the findings in another survey CLOSER7, a quantitative internet survey, including 8200 individuals from nine different countries, with participation of 500 men and 500 women from the UK. The results of this study highlighted the adverse emotional and physical impact of urogenital atrophy on postmenopausal women and their partners, with vaginal dryness and dyspareunia associated with loss of arousal and desire. The conclusion focussed on the potential benefit of more open communication with affected women, to improve access to treatment and for healthcare providers to initiate the discussion. Another study, the AGATA8 study, involved 913 Italian women and following clinical assessment in women with symptoms, prevalence of urogenital atrophy was estimated to range between 65-84%. Authors concluded that urogenital atrophy is a common condition, which is underdiagnosed and therefore undertreated. However, a follow up study by the same group, undertaken in a subset of already diagnosed women, demonstrated lack of consistency in the management of the condition from a clinician perspective and lack of compliance from a patient’s perspective9. This further reinforces the need for education of both the clinicians and women and the requirement of support including a validated objective method of assessment to assist in diagnosis.The impact of urogenital atrophy on sexual function is determined by a number of factors including a reduction in blood flow to the vulva & vagina with a decrease in vaginal secretions and an adverse effect on neuronal function both of which can alter sensation and sexual pleasure. Some authors have reported nerve density and size to be influenced by dehydroepiandrosterone (DHEA) and androgens, thus explaining the beneficial effects demonstrated with such therapy on postmenopausal sexual function. Sexual intimacy remains an important aspect of relationships for older women and enquiry about symptoms of urogenital atrophy should be routinely included in all consultations about menopause. This would help to remove a major barrier restricting access to treatment for affected women, who find the subject difficult to broach. Other hurdles to accessing treatment include limited research, the cost of treatment and patient fear of treatment options10.Reported prevalence rates for urogenital atrophy vary even more widely than the figure quoted for the AGATA study, with 10% - 84%7 of women going through menopause affected by urogenital atrophy associated symptoms to some degree. Many women accept symptoms as a normal part of aging and thus, may not seek medical help20. It is difficult to predict which women will develop urogenital atrophy, with some women unaffected possibly due to genetically determined tissue quality and also possibly due to production of DHEA from the adrenal glands. However, in general the number of women affected increases year on year from menopause onwards due to the progressive effect of estrogen deficiency.The Stages of Reproductive Ageing Workshop (STRAW)11suggested that symptoms of urogenital atrophy are likely to present between three and six years after last menstruation, although this can occur at an earlier time. Some affected women may not associate their symptoms with the menopause, if there is a long period between the cessation of menstruation and the appearance of symptoms. For this reason, it is particularly important that clinicians providing health care to menopausal women proactively ask about common symptoms of urogenital atrophy including vaginal dryness, itching, burning, pain during sexual intercourse and urinary problems.

Background: The novel coronavirus ( SARS CoV 19) is responsible for the pandemic infection after starting in 2019 in Wuhan city /China, several small studies were done since then to determine the effects of smoking on the severity, outcome & mortality of patients with COVID-19 but the results were inconclusive, this study aims to assess the impact of active smoking on severity and outcome in patients with COVID-19 infection in Mosul city/Iraq. Methods: A prospective cohort study was conducted on 160 patients ( 80 patients were active smokers & 80 non-smoker patients) who have been diagnosed with COVID-19 infection by using real-time PCR, the study was done at Ibn-Sina teaching hospital in Mosul city/Iraq from May 2020 until December 2020. A detailed history was taken from the patients, full clinical examination & blood tests were done. The following parameters were recorded & compared between the 2 groups: severity of symptoms, inflammatory markers, D dimer, liver function test (LFT), oxygen use, hospitalization & outcome. Results: the symptoms of COVID-19 were more severe in the non smokers group (34.4%) compared to the smokers (25%) & it was statistically significant (p-value = 0.016), the inflammatory markers were also higher in the non-smokers (31.9%) compared to the smokers (20.0%) ( p-value = 0.011) , D dimer & LFT were also higher in the non-smoker group ( p-value = 0.01 & 0.008 respectively). There was no statistical difference regarding oxygen use, hospitalization, ICU admission, mortality, or post-recovery complications. Conclusion: severe symptomatic COVID-19 infection was more common in the non-smoker group, the inflammatory markers, D-dimer & LFT were higher in the non-smokers compared to the smokers. No statistical difference was found regarding O2 use, hospitalization, ICU admission, mortality & residual complications.

Objective: To estimate the effect of oestrogen-only and combined hormone replacement therapy (HRT) on the hazards of overall and age-specific all-cause mortality in healthy women aged 46 to 65 at first prescription. Design: Matched cohort study.  Setting: Electronic primary care records from The Health Improvement Network (THIN) database, UK (1984−2017). Population: 105,199 HRT users (cases) and 224,643 non-users (controls) matched on age and general practice. Methods: Weibull-Double-Cox regression models adjusted for age at first treatment, birth cohort, type 2 diabetes, hypertension and hypertension treatment, coronary heart disease, oophorectomy/hysterectomy, body mass index, smoking, and deprivation status. Main outcome measures: All-cause mortality. Results: A total of 21,751 women died over an average of 13.5 years follow-up per participant, of whom 6,329 were users and 15,422 non-users. The adjusted hazard ratio (HR) of overall all-cause mortality in combined HRT users was 0.91 (95%CI 0.88−0.94), and in oestrogen-only users was 0.99 (0.93−1.07), compared to non-users. Age-specific adjusted HRs for participants aged 46-50, 51-55, 56-60, and 61-65 years at first treatment were 0.98 (0.92−1.04), 0.87 (0.82−0.92), 0.88 (0.82−0.93), and 0.92 (0.85−0.98), for combined HRT users compared to non-users, and 1.01 (0.84−1.21), 1.03 (0.89−1.18), 0.98 (0.86−1.12), and 0.93 (0.81−1.07) for oestrogen-only users, respectively. Conclusions: Combined HRT was associated with a 9% lower risk of all-cause mortality and oestrogen-only formulation was not associated with any significant changes.  Funding: IFoA. Keywords: Hormone replacement therapy, menopause, mortality, primary care records, THIN. Tweetable abstract: Oestrogen-only HRT is not associated with all-cause mortality and combined HRT reduces the risks.

Backgraound: Transfix and Tightrope are widely used devices for femoral graft fixation in arthroscopic anterior cruciate ligament (ACL) reconstruction. The purpose of the study is to reveal differences between Transfix and Tightrope fixation technique by evaluating clinical results of cases. Materials and Methods: 87 patients who underwent arthroscopic ACL reconstruction for ACL rupture between January 2013 and June 2017 by the same senior surgeon and in whom the fixation methods evaluated in this study had been employed were retrospectively reviewed. Transfix was used in 45 (52%) patients and ACL Tightrope was used in 42 (48%) patients. In the first group (Transfix) mean age was 26,3± 5.8 (18-45) second group (Tightrope) mean age was 26,7± 6.1 (17-46). Patients in both groups were retrospectively screened for anamnesis and physical examination records in the hospital registry system. In addition, IKDC(International Knee Documentation Committee) and Lysholm scores were calculated in the preoperative and postoperative follow-up period, and all findings were evaluated over a mean period of 42.5 ± 7.4 (24-54) months. Results: Clinical evaluation and stability tests indicated that statistically no significant difference found between two groups. For the first group preoperative Lysholm scores was 47,3 and postoperatively 93 and second group scores were respectivly 47,6 and 94 (P<0.05). IKDC scoring system for first group preoperatively there were 13 poor, 26 good and 6 fair knees ; postoperatively 2 fair, 27 good and 16 excellent .In the second group preoperatively 11 poor, 25 fair and 6 good knees and postoperatively 2 fair, 26 good and 14 excellent knees evaluated. Conclucions: In ACL reconstruction for fixation femoral graft, Transfix and Tightrope are frequently used implants. Therefore, both femoral fixation implants can be safely used in arthroscopic ACL reconstruction based on the experience and preference of the surgeon, provided that they are properly applied.

Background The same dosing schedule, 1000 SQ-U times three, with one-month intervals, have been evaluated in most trials of intralymphatic immunotherapy (ILIT) for the treatment of allergic rhinitis (AR). The present studies evaluated if a dose escalation in ILIT can enhance the clinical and immunological effects, without compromising safety. Methods Two randomized double-blind placebo-controlled trials of ILIT for grass pollen induced AR were performed. The first included 29 patients that had recently ended 3 years of SCIT and the second contained 39 not previously vaccinated patients. An up-dosage of 1000-3000-10 000 (5000 + 5000 with 30 minutes apart) SQ-U with one month in between was evaluated. Results Doses up to 10 000 SQ-U was safe after recent SCIT. The combined symptom-medication scores (CSMS) were reduced by 31% and the grass specific IgG4 levels in blood were doubled. In ILIT de novo, the two first patients that received active treatment developed serious adverse reactions at 5000 SQ-U. A modified up-dosing schedule; 1000-3000-3000 SQ-U appeared to be safe but failed to improve the CSMS. Flow cytometry analyses showed increased activation of lymph node derived dendritic but not T-cells. Quality of life and nasal provocation response did not improve in any study. Conclusion ILIT in high doses after SCIT appears to further reduce grass pollen induced seasonal symptoms and may be considered as an add-on treatment for patients that do not reach full symptom control after SCIT. Up-dosing schedules de novo with three monthly injections that exceeds 3 000 SQ-U should be avoided.

In general, it is accepted that gap formation significantly affects the placement of scatter-hoarded seeds by small rodents, but the effects of different forest gap sizes on the seed-eating and scatter-hoarding behaviors of small rodents remain unclear. Thus, we examined the effects of a closed canopy forest, forest edge, and gaps with different sizes on the spatial dispersal of Quercus variabilis acorns and cache placement by small rodents using coded plastic tags in the Taihang Mountains, China. The seeds were removed rapidly and there were significant differences in the seed-eating and caching strategies between the stand types. We found that Q. variabilis acorns were usually eaten after being removed from the closed canopy forest and forest edges. By contrast, the Q. variabilis acorns in the forest gap stands were more likely to be scatter hoarded. The dispersal distances of Q. variabilis acorns were significantly longer in the forest gap plots compared with the closed canopy and forest edge plots. However, the proportions of scatter-hoarded seeds did not increase significantly as the gap size increased. In small-scale oak reforestation projects or research, creating small gaps to promote rodent-mediated seed dispersal may effectively accelerate forest recovery and successional processes.

ABSTRACT Objective: Studies have shown that neutrophil / lymphocyte ratio (NLR), platelet / lymphocyte ratio (PLR) and mean platelet volume (MPV) can be used in CSU to evaluate inflammation marker and response to treatment. In our study, we aimed to compare the NLR, PLR and MPV values in the control group and pre-treatment patient groups, and to investigate the changes with antihistamine treatment and omalizumab treatment in the CSU patient group and control group. Materials and Methods: 146 patients who applied to Manisa Celal Bayar University Dermatology and Venereal Diseases outpatient clinic, with a diagnosis of chronic spontaneous urticaria, using antihistamine or omalizumab were included in the study. Results: The neutrophil and NLR values of the antihistamine and omalizumab treatment group with CSU diagnosis were found to be significantly higher than the pre-treatment control group, but there was no significant difference between each other. Platelet count was found higher and MPV value was found lower in omalizumab group compare to control group. In the omalizumab group, a significant decrease in neutrophil count and platelet count was measured at 3rd months. Conclusion: Neutrophil count, platelet count, NLR values were higher and MPV values were found to be low compared to the control group, these values can be used to measure disease activity. After the treatment, a significant decrease in neutrophil count and platelet count was detected in the omalizumab group. In addition to its anti-IgE effect, omalizumab can show its anti-inflammatory effect by reducing the neutrophil count and platelet count to be within the normal range.

Plasmablastic lymphoma with aberrant expression of CD3 and CD4Jiong Yan1, Ali Sakhdari11 Department of Laboratory Medicine and Pathobiology, University Health Network, Toronto, CanadaRunning title: T cell antigen expression in PBLCorresponding author:Ali Sakhdari, MD, MScToronto General HospitalDept. of Laboratory Hematology200 Elizabeth Street, 11E-453Toronto, ONM5G 2C4Tel: 001 - 416 340-4800, x 5201E-mail: asakhdari@gmail.com; ali.sakhdari@uhn.caKey words: Plasmablastic lymphoma, T cell antigen

Early treatment of polycythemia vera with ultra-low-dose interferon-α 2a is well tolerated and results in complete hematologic and major molecular remission and a strong reduction of all symptoms, especially pruritus and fatigue.

Disentangling the relative role of environmental filtering and dispersal limitation in driving metacommunity structure across mountainous regions remains challenging, as the way we quantify spatial connectivity in topographically and environmentally heterogeneous landscapes can influence our perception of which process predominates. More empirical datasets are required to account for taxon- and context-dependency but relevant research is often compromised by coarse taxonomic resolution. We here employed haplotype-level community DNA metabarcoding, enabled by stringent filtering of Amplicon Sequence Variants (ASVs), to characterize metacommunity structure of soil microarthropod assemblages across a mosaic of five forest habitats on the Troodos mountain range in Cyprus. We found similar β diversity patterns at ASV and species (OTU, Operational Taxonomic Unit) levels, which pointed to a primary role of habitat filtering resulting in the existence of largely distinct metacommunities linked to different forest types. Within-habitat turnover was correlated to topoclimatic heterogeneity, again emphasizing the role of environmental filtering. However, when integrating landscape matrix information for the highly fragmented Golden Oak habitat, we also detected a major role of dispersal limitation imposed by patch connectivity, indicating that stochastic and niche-based processes synergistically govern community assembly. Alpha diversity patterns varied between ASV and OTU levels, with OTU richness decreasing with elevation and ASV richness following a longitudinal gradient, potentially reflecting a decline of genetic diversity eastwards due to historical pressures. Our study demonstrates the utility of haplotype-level community metabarcoding for characterising metacommunity structure of complex assemblages and improving our understanding of biodiversity dynamics across mountainous landscapes worldwide.

Background: Some of atrial fibrillation (AF) drivers are found in lesser late-gadolinium enhancement (LGE) areas, as well as heterogenous ones. The atrial wall thickness (AWT) has been reported to be important as a possible AF substrate. However, the AWT and degree of LGEs as an AF substrate has not been fully validated in humans. Objective: The purpose of this study was to evaluate the impact of the AWT in lesser LGE areas on AF drivers. Methods: A total of 287 segments in 15 persistent AF patients were assessed. AF drivers were defined as non-passively activated areas (NPAs), where rotational activation was frequently observed, and were detected by the novel real-time phase mapping (ExTRa Mapping). Lesser LGE areas were defined as areas with a volume ratio of the enhancement voxel of <10%. The AWT was defined as the minimum distance from the manually determined endocardium to the epicardial border on the LGE-MRI. Results: NPAs were found in 20 (18.0%) of 131 lesser LGE areas where the AWT was significantly thicker than that in the passively activated areas (PAs) (2.46±0.26 vs. 2.20±0.25 mm, p<0.001). However, NPAs were found in 61 (21.3%) of 287 LGE areas where the AWT was similar to that of the PAs (2.24±0.24 vs. 2.22±0.25 mm, p=0.58). An ROC curve analysis yielded an optimal cutoff value of 2.24 mm for predicting the presence of an NPA in lesser LGE areas. Conclusion: The location of AF drivers in lesser LGE areas might be more accurately identified by evaluating the AWT.

Objective To explore the impact of the COVID-19 pandemic on pain and fatigue symptoms and their interactions with the impact on mental health in people with endometriosis. Design Global cross-sectional survey. Setting Online survey. Sample A total of 4717 adults with a surgical or radiological diagnosis of endometriosis. Methods An online global study collected data in 5 languages between 11th May to 8th June 2020. The survey included questions on current-status and changes of endometriosis-symptoms, mental health, demographics, and the impact of the COVID-19 pandemic on the respondents’ lives. Main Outcome Measures Self-reported changes to endometriosis-associated symptoms (pelvic pain, tiredness/fatigue, bleeding) and to mental health during the early stages of the COVID-19 pandemic. Results Respondents reported a marked worsening of their endometriosis symptoms (endo-associated pain (39.3%; 95% CI [37.7, 40.5]), tiredness/fatigue (49.9%; 95% CI [48.4, 51.2]) and bleeding (39.6%; 95% CI [38.2, 41])) and mental health (38.6%; 95% CI [37.2, 39.9]). Those with a pre-existing mental health diagnosis (38.8%) were more negatively impacted. The worsening of pain and TF were significantly correlated with worsening of mental health (p<0.001) and these relationships were found to be weakly mediated by pain catastrophising scores (pain: effect size: 0.071, LLCI= 0.060, ULCI= 0.082, TF: effect size: 0.050, LLCI= 0.040, ULCI= 0.060). Conclusions This study demonstrates that stressful experiences impact the physical and mental health of people with endometriosis. The findings highlight the need to consider psychological approaches in the holistic management of people with endometriosis.

Objective: To determine the sexual outcomes and motherhood plans of the Mayer Rokitansky Küster Hauser (MRKH) Syndrome patients operated with Uncu Modified Remnant-Supported Laparoscopic Double-Layer Peritoneal Pull-Down Vaginoplasty operation Design: Cohort Study Setting: Tertiary University Hospital Patients: Women with MRKH syndrome Methods: This study involves the patients with MRKH syndrome who underwent Uncu Modified Remnant-Supported Laparoscopic Double-Layer Peritoneal Pull-Down Vaginoplasty Operation between the years 2008-2020. The first step of the study is about our surgical technique outcomes. The second step consists of long-term results for sexual functioning which was assessed by female sexual function index (FSFI) survey and motherhood plans by another survey. Main Outcome Measure: FSFI and Motherhood Survey Results Results Total 42 patients with MRKH syndrome underwent vaginoplasty operation. At least one year after surgery all patients was physically examined. The mean vaginal length was 8.4 + 1.9 cm. The mean FSFI score was 31.5 + 3.9 (min:24-max:36) Thirty-six of the patients answered a survey about motherhood. Thirty-one of the patients (86%) had a desire for motherhood. Most of the patients (21/31 – 68%) choose uterine transplantation as a first option. Three of the patients (9.6%) choose mater option and seven patients (22.5%) wants to be a mother by adoption. Conclusion: Uncu Modified Remnant-Supported Laparoscopic Double-Layer Peritoneal Pull-Down Vaginoplasty Operation is a satisfactory option for patients with MRKH syndrome with high FSFI scores and low complication rates. But creating only a neovagina is not enough for these patients, because of nearly 70% motherhood desire by uterine transplantation.

Objective and design: Our prospective observational study is the first study that evaluates the LUS findings of cardiopulmonary interactions in acutely ill children with elevated pro-BNP levels,with the aim of establishing the specific LUS pattern in this category of patients without primary lung diseases.Methodology:We prospectively analyzed epidemiological, clinical, laboratory, instrumental and lung ultrasound parameters in acutely ill children aged 1 month to 18 years admitted to the Department of Pediatrics between March 2020 to August 2020.Among the acutely ill patients evaluated, only patients with pro-BNP> 300 pg / ml and who underwent LUS before the start of any treatment were included. They were stratified into three sub-categories based on the diagnosis A) cardiac disease, B) systemic inflammatory disease / sepsis without functional and / or organic alterations of the myocardium and C) systemic inflammatory disease / sepsis and cardiac disease, and were classified into two groups based on the level of pro-BNP.We also enrolled patients belonging to two other categories (patients with primary infectious lung disease and completely healthy patients) analyzing their epidemiological, clinical, laboratory, instrumental parameters and lung ultrasound findings and comparing them with those of acutely ill children.Results and Conclusion: We found that LUS findings in these acutely ill children are different from the ultrasound pattern of other categories of children and in particular 1) children with acute lower respiratory tract infections and 2) healthy infants.The finding in a child of a sonographic interstitial syndrome with multiple, bright, long, separate and non-confluent B-lines / long vertical artefacts deriving from a normal and regular pleural line, in the absence of subpleural consolidations, is strongly predictive of cardiogenic pulmonary edema or pulmonary congestion in the course of systemic inflammatory disease / sepsis.

Warning signals are often characterized by highly contrasting, distinctive and memorable colors. Both chromatic (hue) and achromatic (brightness) contrast contribute to signal efficacy, making longwave colored signals (red and yellow) that generate both chromatic and achromatic contrast common. Shortwave colors (blue and ultraviolet) do not contribute to luminance perception, yet are also common in warning signals. The presence of UV aposematic signals is paradoxical as UV perception is not universal, and evidence for its utility is at best mixed. We used visual modeling to quantify how UV affects signal contrast in aposematic butterflies and frogs. We found that UV only appreciably affected visual contrast in the butterflies. As the butterflies, but not the frogs, have UV-sensitive vision these results support the notion that UV reflectance is associated with intraspecific communication, but appears to be non-functional in frogs. Consequently, we should be careful when assigning a selection-based benefit from UV reflectance.

Attualmente, il trattamento e smaltimento dei fanghi di depurazione prodotti dai processi a fanghi attivi comportano costi elevati per gli impianti di trattamento di acque reflue. La necessità di ridurre gli oneri coinvolti in questi processi con alternative sostenibili ha condotto alla ricerca di tecnologie innovative per il pretrattamento dei fanghi. Questo articolo analizza alcune delle opzioni che possono essere implementate. Principalmente si concentra negli effetti dell’utilizzo di trattamenti ad ultrasuoni per migliorare la digestione anaerobica dei fanghi attivi, con conseguente significativa riduzione della produzione di fanghi e un aumento della generazione di biogas come una fonte di energia rinnovabile, il quale può essere utilizzato non solo per compensare i costi intervenenti nel pretrattamento del fango ma anche per le terze parti. Sebbene studi più approfonditi siano necessari, i benefici economici ed ambientali son evidenti.

This review presents state-of-the-art knowledge and identifies knowledge gaps for future research in the area of exercise-associated modifications of infection susceptibility. Regular moderate-intensity exercise is believed to have beneficial effects on immune health through lowering inflammation intensity and reducing susceptibility to respiratory infections. Infection-promoting consequences are attributed to strenuous exercise as performed by professional athletes. In about half of the athletes presenting respiratory symptoms, no causative pathogen can be identified. Acute bouts of exercise enhance release of proinflammatory mediators thus probably leading to appearance of infection-like respiratory symptoms. Studies assessing influence of regularly repeated exercise on immune response and systemic inflammation are far less numerous than those regarding acute exercise effects. This identifies another knowledge gap requiring further assessment both in recreational and in professional athletes Additionally, ambient and environmental conditions modify systemic inflammatory response and infection susceptibility in particular in outdoor athletes. Both acute and chronic regular exercise influence humoral and cellular immune response mechanisms resulting in decreased specific and non-specific response in competitive athletes. Most promising areas of further research in exercise immunology include: detailed immunological characterization of infection-prone and infection-resistant athletes; efficacy of nutritional and pharmaceutical interventions as countermeasures to infections’ symptoms; and influence of various exercise loads on susceptibility to infections with respiratory viruses, including SARS-CoV-2. Establishing uniform definition of “elite athlete’ shall hopefully allow for comparable and straightforward interpretation of data coming from different studies and settings.

Pathogenic variants of the nuclear receptor subfamily 2 group F member 1 gene (NR2F1) are responsible for Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS), an autosomal dominant disorder characterized by optic atrophy associated with developmental delay and intellectual disability, but with a clinical presentation which appears to be multifaceted. We created the first public locus-specific database (LSDB) dedicated to NR2F1. All variants and clinical cases reported in the literature, as well as new unpublished cases, were integrated into the database using standard nomenclature to describe both molecular and phenotypic anomalies. We subsequently pursued a comprehensive approach based on computed representation and analysis suggesting a refinement of the BBSOAS clinical description with respect to neurological features and the inclusion of musculoskeletal hypotonia and intestinal signs with feeding difficulties. This database is fully accessible for both clinician and molecular biologists and should prove useful in further refining the clinical synopsis of NR2F1 as new data is recorded.

The outcomes of surgery for Acute Stanford type A aortic dissection (ATAAD) have significantly improved in recent decades due to advances in surgical techniques and, surgical adhesives such as BioGlue. However, this convenient material can sometimes cause complications such as thrombotic embolism and pseudoaneurysm. Here, we present the case of a 61-year-old male with ATAAD who successfully underwent total arch replacement. Five days after the surgery, he collapsed due to right hemiplegia. We immediately performed cerebral thrombectomy and removed the thrombotic embolus caused by BioGlue, which was used to obliterate the false lumen of the dissected aorta during ATAAD repair.

An international robin round was carried out to validate a method for the quantification of 2-monochloropropane-1,3-diol (2-MCPD), 3-monochloropropane-1,2-diol (3-MCPD) and 2,3-epoxy-1-propanol (Glycidol) being present as fatty acid esters in plant-based food emulsifiers. The evaluated method was a modification of the American Oil Chemist´s Society (AOCS) Official Method Cd29b-13. Briefly, this method consists from parallel analysis of two sample aliquots that are spiked with different sets of internal standards. Mild alkaline interesterification overnight in the freezer releases the core analytes. Reaction stop and glycidol conversion into monobromopropanediol (MBPD) is realised by addition of acidified sodium bromide solution. Subsequently, matrix removal and analyte extraction are achieved by two liquid/liquid (l/l) extraction steps. After derivatisation with phenylboronic acid (PBA) the final extracts are analysed by gas chromatography-mass spectrometry (GC-MS). Quantification is carried out by internal one-point-calibration. 6 laboratories from 4 European countries participated in the trial and reported 8 data sets for 10 test materials (mono- and diacylglycerides as well as polyglycerol polyricinoleates) that were analysed as blind duplicates, giving a total of 20 samples. Result outliers were eliminated according to accepted standards. At 2-MCPD levels above 0.02 mg/kg, 3-MCPD levels above 0.06 mg/kg and glycidol levels above 0.22 mg/kg repeatability (RSDr) ranged from 1.5 % to 24.9 %, reproducibility (RSDR) ranged from 7.8 % to 29.0 % and HORRATR-values ranged from 0.5 to 1.7. The tested method showed to be suitable for the determination of 2-MCPD, 3-MCPD and glycidol in food emulsifiers consisting from mono- and diacylglycerides as well as polyglycerol polyricinoleates.