Background: Oxidative stress is fundamental in initiating pathophysiological mechanisms leading to premature hemolysis resulting in iron overload in patients with beta thalassemia. Peroxiredoxin 2 (Prdx2) is one of the crucial cytoprotective and antioxidant systems that play a key role against oxidation. Our aim was to investigate serum Prdx2 levels in children with beta-thalassemia and to explore its possible relations with iron overload. Methods: The patients were divided into two groups: beta thalassemia major (BTM) group (n=40) and beta thalassemia intermedia (BTI) group (n=20). To compare serum Prdx2 and iron status parameters levels, a control group (n=20) was include in the study. Serum Prdx2 levels were determined by enzyme linked immunosorbent assay technique. Serum levels of iron and ferritin were measured using automated chemistry analyzer and electrochemiluminescence immunoassay respectively. Results: Serum Prdx2 concentrations in thalassemia major patients were significantly lower than those in thalassemia intermedia patients (P= 0.026); and Prdx2 concentrations in thalassemia intermedia patients were significantly lower than those in control group (P<0.001). In both thalassemia major and intermedia groups, serum Prdx2 concentration was positively correlated with serum iron (r = 0.558, P=0.002; r = 0.718, P=0.004, respectively) and ferritin levels (r = 0.422, P=0.007; r = 0.550, P=0.012, respectively). Conclusions: Our results demonstrate the positive association between Prdx2 and iron overload in thalassaemia patients. These findings may suggest unconventional therapeutic approach to control consequences of iron overload through modification of Prx2 activity.

Introduction: Litigation against the National Health Service (NHS) in England is rising, costing £2.4 billion in 2018/19. The aim of this study was to determine the incidence and characteristics of otolaryngology clinical negligence claims in England. Methods: A retrospective review was undertaken of all clinical negligence claims in England held by NHS Resolution relating to otolaryngology between April 2013 and April 2018. Analysis was performed using information for cause, patient injury and claim cost. Where claim information was adequately detailed, the authors categorised claims by subspecialty, diagnosis and operation. Results: A total of 727 claims were identified with an estimated potential cost of £108 million. From these, 463 were closed claims. Including open claim reserves, the mean cost of a claim was £148,923. Head and neck surgery was the subspecialty with the highest number of claims (n=313, 43%) and highest cost (£51.5 million) followed by otology (n=171, £24.5 million) and rhinology (n=171, £13.6 million). Over half of claims were associated with an operation (n=429, 59%) where mastoid surgery (n=46) and endoscopic sinus surgery (n=46) were equally associated with the greatest number of claims. The most frequent reasons for litigation included failure or delay to diagnose (n=178, 25%) failure or delay to treat (n=136, 19%), intra-operative complications (n=130, 18%) and failure of the consent process (n=107, 15%). Discussion: Clinical negligence claims in otolaryngology are related to several different components of patient management and is not limited to post-operative complications. This study highlights the importance of robust pathways in outpatient diagnostics and the consenting process, especially in the high-risk speciality of head and neck surgery, in order to deliver better patient care and reduce the impact of litigation.

Objectives: Clinical studies have shown low toxicity and a favorable safety profile for sirolimus in vascular anomalies. Here, we describe severe adverse events (SAEs) observed during “off-label use”. Methods: We performed a retrospective, multicenter chart review for SAEs during “off-label” sirolimus therapy for vascular anomalies and analyzed these cases by a pre-designed workflow. Results: We identified 17 SAEs in 14 patients diagnosed with generalized lymphatic anomaly (n=4), Gorham-Stout disease (n=2), central conducting lymphatic anomaly (n=1), lymphatic malformation (n=4), tufted angioma (n=1), kaposiform hemangioendothelioma (n=1), and venous malformation in a CLOVES syndrome (n=1). Three patients presented two SAEs. The age at initiation of sirolimus therapy was under the age of 2 years (5x), 2 to 6 years (5x) and older than 12 years (4x). SAEs occurred during the first 3 months of sirolimus therapy (7x), between 3 and 12 months (7x) and after one year of therapy (3x). The most frequent SAE was viral pneumonia (8x) resulting in death due to a metapneumovirus infection in a 3 months old and generalized adenovirus infection in a 28 months old child. Sirolimus blood level at the time of SAEs ranged between 2.7 and 21 ng/L. Five patients were on antibiotic prophylaxis during sirolimus therapy. Conclusions: Most SAEs are observed in the first year of sirolimus therapy; however, SAEs can also occur after a longer treatment period. SAEs are potentially life threatening, especially in early infancy. Presence risk factors, i.e. underlying vascular anomaly or immune status, may contribute to the risk of SAEs.

Post-fire managers throughout the world use predictive models to estimate potential erosion risks to aid in evaluating downstream impacts of increased runoff and erosion, and to target critical areas within a fire for applying mitigation practices. Erosion prediction can be complicated by forest road networks. Using GIS technology and a soil erosion model, this study evaluated the effect of roads on erosion and sediment yield following a wildfire, and whether the predictive models were providing reasonable results. The GeoWEPP model was used to simulate onsite erosion and offsite sediment delivery before and after fire disturbance. A 2-m resolution DEM was used as the terrain layer. Erosion rates in excess of 4 Mg ha-1 yr-1 were predicted mainly from the moderate and high severity burn areas. Roads influenced both flow path and sub-catchment delineations, affecting the spatial distribution of sediment detachment and transport. Through that influence, roads tended to reduce estimated erosion on slopes below the roads, but road fillslopes and steep channels were areas of significant increases in erosion risks. Measured deposition amounts along roads and in sediment basins were similar to predicted amounts. The results confirm that road prisms, culverts and road ditches greatly influence sedimentation processes after wildfire, and they present opportunities to detain eroded sediments before they reach downstream water bodies.

Background Type B influenza virus circulates every year with lower activity than that of influenza A virus in China. During 2017 to 2018 winter season, a sharp surge of influenza activity dominated by type B/Yamagata lineage virus caused unprecedented medical burden in Beijing. The research aimed to understand the underlying mechanism for this circulation and be prepared for epidemics in the future. Methods Sera samples collected from the patients in 2016-2017 and 2017-2018 flu seasons were tested for profiling hemagglutinin inhibition (HI) antibodies against both prevailing Victoria and Yamagata lineages of type B influenza viruses. Results It showed that the positivity of HI antibodies against both lineages of the virus in 2017-2018 winter was higher than that in 2016-2017, while no difference of the positivity of HI antibodies was observed between the two winter seasons. Meanwhile, significant elevated geometric mean titer (GMT) against both lineages of influenza B viruses was found in the specimens collected during 2017-2018 flu season than that from 2016-2017, suggesting the viruses might undergo antigenic changes. These results also suggested that lower GMT against both type B variants in 2016-2017 might serve as an immunological niche for the dominating of B/Yamagata virus in China during 2017-2018 winter season. Conclusions Our findings have implication that vaccines including both lineages of influenza B virus in formula might be a better preparation against influenza B epidemics.

Follicular T helper (Tfh) and regulatory (Tfreg) cells are distinct subsets of CD4+T lymphocytes, regulating humoral immune responses in the germinal center. Dysregulated Tfh and Tfreg cells are believed to associate with autoimmunity. Here, we evaluated the frequencies of circulating CXCR5+PD-1+ Tfh (cTfh) and CXCR5+PD-1+FoxP3+CD25+ Tfreg (cTfreg) cells, and their corresponding cytokines from the peripheral blood mononuclear cells of 20 patients with relapsing-remitting multiple sclerosis (MS) and 12 age- and sex-matched healthy controls (HC). Subsets of cTfh cells by Th1 and Th17 related surface markers (CXCR3 and CCR6) were also evaluated. We found the frequency of cTfh cells was significantly higher in MS patients compared to HC (p=0.002). Conversely, cTfreg cells were downregulated in MS patients (p<0.0001). IL-21 producing cTfh cells were significantly increased in MS patients (p=0.003), while IL-10 secreting cTfreg cells were decreased in MS compared to HC (p=0.02). Among cTfh cells, cTfh17.1 cells were major subtypes that were significantly increased in MS compared to HC (p=0.002) and the frequency of IL-21 secreting cells were highest. These results suggest that an imbalanced distribution of cTfh and cTfreg exist in MS, which contributes to reciprocally altered IL-21 and IL-10 production.

In the effort to improve treatment effectiveness in glioblastoma, this short note reviewed collected data on the pathophysiology of glioblastoma with particular reference to intersections with the pharmacology of perphenazine. That study identified five areas of potentially beneficial intersection. Data showed seemingly 5 independent perphenazine attributes of benefit to glioblastoma treatment - i) blocking dopamine receptor 2, ii) reducing centrifugal migration of subventricular zone cells by blocking dopamine receptor 3, iii) blocking serotonin receptor 7, iv) activation of protein phosphatase 2, and v) nausea reduction. Perphenazine is fully compatible with current chemoirradiation protocols and with the commonly used ancillary medicines used in clinical practice during the course of glioblastoma. All these attributes argue for a trial of perphenazine’s addition to current standard treatment with temozolomide and irradiation. The subventricular zone seeds the brain with mutated cells that become recurrent glioblastoma after centrifugal migration. The current paper shows how perphenazine might reduce that contribution. Perphenazine is an old, generic, cheap, phenothiazine antipsychotic drug that has been in continuous clinical use worldwide since the 1950’s. Clinical experience and research data over these decades have shown perphenazine to be well-tolerated in psychiatric populations, in normals, and in non-psychiatric, medically ill populations for whom perphenazine is used to reduce nausea. For now (Summer, 2020) the nature of glioblastoma requires a polypharmacy approach until/unless a core feature and means to address it can be identified in the future. Conclusions: Perphenazine possesses a remarkable constellation of attributes that recommend its use in GB treatment.

Clinicians, patients, administrators and researchers have become increasingly frustrated by the lack of indication (i.e. problem) information included in prescriptions, despite the obvious benefit this would provide to patients and other healthcare providers [1]. Medication indications are not routinely documented by prescribers, both in inpatient and outpatient settings.[2, 3] Calls have been made to introduce a sixth ‘right’ into the medication management process, whereby the right patient is given the right drug and dose at the right time via the right route for the right indication [4]. Indications-based prescribing has recently gained traction as a potential way forward to facilitate indication documentation [4, 5]. Indications-based prescribing, not currently supported by most electronic prescribing systems (EPSs), describes the scenario where prescribers initially select an indication, not a medication, and the EPS presents the user with suggested medications for addressing the problem. There are clear advantages with this approach, including those associated with guided prescribing (e.g. more appropriate drug selections) and with indication documentation (e.g. improved communication between providers), prompting work to begin on developing EPS functionality in the US to support indications-based prescribing. In a recent usability evaluation of a prototype of this functionality, indications-based prescribing was more efficient to use, resulted in fewer medication errors and in higher usability scores than the traditional EPS functionality [6].

The hydrological processes in Upper Choctawhatchee River Watershed were modeled using the Soil and Water Assessment Tool (SWAT) to investigate the impacts of climate and land use change. We integrated land use projection based in the Shared Socioeconomic Pathways with future climate data to study the combined effects on Hydrological response of the watershed. Future rainfall and temperature, for two time periods, were obtained using General Climate Models to provide SWAT with the climatic forcing in order to project water balance variables. The simulation was carried out under two radiative forcing pathways of RCP4.5 and RCP6.0. Model calibration metrics of NSE, R2, and p-factor were 0.88, 0.89, and 0.68, respectively. Results revealed increases as high as 2.55 ℃ and 2.4 ℃ for average annual minimum and maximum temperature, respectively, especially during Summer and Winter. Average annual precipitation was estimated to increase up to 11% under both emission scenarios; however, under severe emissions of RCP6.0, it was projected for two decades earlier. Land use change focused on urbanization dominated the climate changes. Impacts on water balance variables differed seasonally. Results showed surface runoff experienced major changes under both emission scenarios in some months up to 5 times increase. Among the water balance variables, ET as the least dominant pathways for water loss, showed the modest changes with the largest decrease during Fall and Summer. Projection indicated more frequent extreme behavior regarding water balance during midcentury. Discharge was estimated to increase through the year and the highest changes were projected during Summer and Fall with 186.3% increase in November under RCP6.0. Relying on rainfall for farming along with reduced agricultural landuse (11.8%) and increased urban area (47%) and population growth, would likely make the water use efficiency critical. The model demonstrated satisfactory performance, capturing the hydrologic parameters. It thus can be used for further modelling of water quality to determine the sustainable conservation practices, extreme weather events such as hurricane and tropical storms.

Hydrogen peroxide (H2O2), as clean oxidant, has long suffered from low efficiency and selectivity for the oxidation of olefins. In the present paper, the redox important ferrate anion (FeO42-) has been anchored into a silanol-decorated polyoxometalates (POM) to form single–site supported Fe-POM catalyst. And possible reaction mechanism for the epoxidation of propylene with hydrogen peroxide (H2O2) catalyzed by the Fe-POM catalyst have been investigated based on density functional theory with M06L functional. The study of molecular geometry, electronic structure, and bonding feature shows that the Fe-POM complex can be viewed as a high-valent Fe-oxo (Fe=O) species. The propylene molecule was activated by the Fe-POM catalyst via an effective electron transfer from propylene to the Fe-POM catalyst to form a cation propylene radical. Due to the high reactivity of radical species, the calculated activation energy barrier is only 4.50 kcal mol-1 for epoxidation of propylene to epoxypropane catalyzed by the Fe-POM catalyst. Subsequently, the calculated free energy profiles show that H2O2 was decomposed into a H2O molecule and a surface O species over the Fe-POM catalyst, and the remaining O atom attaches to the exposed the Fe center, resulting in the replenishing of Fe-POM catalyst via a two-state reaction pathway. The calculated activation energy barrier for this process is 23.42 kcal mol–1, and thus decomposition of H2O2 is the rate-determining step for the whole reaction. The Fe center serves as an electron acceptor, accepting electrons from the binding propylene molecule to form radical species in the first half of the reaction, and acts as the role of electron donor in the rest reaction steps to eliminate the radical feature, reduce the reactivity, and stop the reaction at the stage of the desired epoxypropane product.

The mechanisms of rhodium-catalyzed coupling reaction of ketoxime and 1,3-enynes were investigated by employing the density functional theory (DFT) calculations. Different 1,3-enynes would lead to different annulation products. Reaction A undergoes five sequential steps (C-H activation, 1,3-enyne migratory insertion, 1,4-Rh migration, cyclization, and deprotonation) to lead to [4 + 1] annulation product. Whereas, due to the electronic effect, the process generating [4 + 2] product in reaction A is restricted. In contrast, the electron-withdrawing group of N(Me)2 group in 1,3-enyne would bring about the [4 + 2] annulation product in reaction B. Our calculated results indicate that no [4 + 1] annulation product could be obtained in reaction C, in agreement with the experimental observation that the cis-allyl hydrogen in 1,3-enyne is crucial for the [4 + 1] annulation reaction.

Gene therapy medicinal products have the potential to provide curative treatment to many diseases with current limited therapeutic options. As advanced therapy medicinal products (ATMPs), these therapies undergo a centralised, single European Union authorisation by the European Medicines Agency, but the risks, and potential harm to the environment and population at large are weighted in each application, and different interpretations at national level exist. A streamlined procedure is now in place to facilitate a consistent approach for the assessment of the environmental risks of medicines containing genetically modified organisms. This article provides an overview of basic requirements across the EU, an overview of the new streamlined process and discusses available guidance for developers. All these initiatives are aimed to remove hurdles for ATMP developers and facilitate faster access to patients.

Reactivity of thymine peroxy radical in DNA and its fate under hypoxia or oxygen-less conditions are studied at the M06-2X/6-31+G(d,p) level. The spaciously most accessible H2’ can be abstracted by C6-peroxy radical in an intranucleotidyl manner with the estimated barriers of 18.8 ~ 21.1 kcal/mol. The calculations show that C6-peroxy radical has a highly more reactivity towards C(sp3)-H abstraction reactions than its relative C6-yl, which is a counter-intuitive case. The formed hydroperoxide with the C6-OaObH2’ constituent can fast transfer ObH2’ group to C2’ radical in an intranucleotidyl manner with a low barrier (ca. 13.2 kcal/mol) and very strong heat release. The results show that the formed hydroperoxide product is unstable so that it could be quickly transformed into other species and thus is very hard to be experimentally observed. Afterwards, H2’ can be again abstracted by C6-oxyl radical to result in formation of thymine glycol which is the main products. The parallel C5-C6 bond scission reaction leads to formation of the precursor for 5-hydroxy-5-methylhydantion. The two competitive reactions have very low barriers. Based on our present calculations, the new radical reaction paths to formation of the DNA oxidation products are suggested under hypoxia or oxygen-less conditions, which is different from the previously suggested paths under high oxygen concentration surroundings.

Background: The relationship between socioeconomic status (SES) and the prognosis of HF with reduced (HFrEF) vs. preserved (HFpEF) ejection fraction remains unsettled. Objective: To analyze the relationship between SES and the prognosis of patients with incident HFrEF and HFpEF. Methods: Prospective study over 15 years (2003-2017) on 9658 patients diagnosed with HF. Main outcomes were mortality and hospitalizations for HF. The independent relationship between SES and the prognosis, stratifying patients for cardiovascular co-morbidity after propensity score-matching was analyzed. Results: After matching 7116 patients, during a median follow-up of 8.11 years, 5616 patients died (78.9%) and 5549 patients were hospitalized (78.0%). High income level was associated with a lower all-cause mortality (RR for HF patients [95% CI]: 0.86 [0.80-0.92], RR for HFrEF: 0.88 [0.82-0.95] and RR for HFpEF: 0.82 [0.75-0.90], P <0.001 in all cases), and cardiovascular mortality (RR for HF: 0.84 [0.76-0.92], RR for HFrEF: 0.87 [0.81-0.93] and RR for HFpEF: 0.88 [0.77-0.88], P <0.001 in all cases), less hospitalizations (RR for HF: 0.70 [0.65-0.78], RR for HFrEF: 0.78 [0.68-0.88] and RR for HFpEF: 0.61 [0.55-0.68], P <0.001 in all cases), and less 30-day readmissions (RR for HF: 0.67 [0.59-0.75], RR for HFrEF: 0.71 [0.63-0.79] and RR for HFpEF: 0.61 [0.55-0.69], P <0.001 in all cases), after adjustment for comorbidities, and other potential confounders. Analyses of recurrent hospitalizations gave larger SES benefits than time-to-first-event analyses. Conclusions: In this propensity-matched study, a high net annual household income is associated with an improved prognosis of patients with incident HFrEF and HFpEF.

Background: We retrospectively analyzed the data of children with non-malignant diseases who have received a haploidentical hematopoietic stem cell transplant (haplo-HSCT). A total of 31 haplo-HSCT were performed in 26 pediatric patients using ex vivo T cell-depleted (TCD) graft platforms or post-transplantation cyclophosphamide (PT-Cy) from January 2001 to December 2016 in 7 Spanish centres. Procedure: A total of five cases were unmanipulated PT-Cy haplo-HSCT, sixteen received highly purified CD34+ cells, ten were ex vivo TCD graft manipulated either with CD3+CD19+ depletion (n= 1), TCΡαβ+CD19+ selection (n= 7) or naive CD45RA+ T cells depletion (n=2). Peripheral blood stem cells were the only source in patients following TCD haplo-HSCT, and bone marrow was the source for one PT-Cy haplo-HSCT. The most common indications for transplant were primary immune deficiency disorders (PIDs) 18, severe aplastic anemia (SAA) 4, osteopetrosis 2 and thalassemia 2. Results: The 1-year cumulative incidence of graft failure was 27.4 %. The 1-year III-IV acute graft versus host disease (aGvHD) and 1-year chronic graft versus host disease (cGvHD) were 34.6% and 16.7% respectively. Besides, the 2-year overall survival (OS) and the 2-year GvHD-free and relapse-free survival (GRFS) were 44.9% for PIDS and 37.6% for the other NMDs. The TRM at day 100 was 30.8%. Conclusions : These results are discouraged and need to be improved to offer a guaranteed treatment for these patients. Improvements will come if procedures are centralized in centres of expertise. The decision between T-cell depletion platforms will depend on the patients’ underlying diseases, comorbidities, and conditioning regimens.

The biological reduction of ferrous ethylenediaminetetraacetic acid (EDTA-FeII-NO and EDTA-FeIII) is an important process in integrated electrobiofilm reduction method, and this method has been regarded as a promising alternative for removing NOx from industrial boiler flue gas. EDTA-FeII-NO and EDTA-FeIII are crucial substrates that should be biologically reduced at a high rate. However, they would inhibit one another’s reduction processes when they are present together, which might limited the further promotion of this integrated method. In this study, an integrated electrobiofilm reduction system with high reduction rate of EDTA-FeII- NO and EDTA-FeIII was established. The microbial communities in electrobiofilms were mainly studied to analyze their changes during the reduction of these two substrates under different conditions. It presents a better performance of substrates- resistance shock loading and high microbial diversities compared with the conventional chemical absorption-biological reduction system. High-throughput sequencing analysis showed that the changes in concentrations of EDTA-FeII-NO and EDTA-FeIII significantly impacted the genera of the microbial community. Alicycliphilus, Enterobacteriaceae and Raoultella were found to be the dominant genera (>25%, respectively) involved in EDTA-FeII-NO reduction. As an EDTA-FeIII reducing bacteria, Chryseobacterium can endure shock loading of substrates. Ochrobactrum can reduce nitrate using electrons and exhibited better stability under shock loading. Furthermore, higher microbial diversity and stable reactor operation could be achieved when the concentrations of EDTA-FeII-NO and EDTA-FeIII approached the same value.

The mountains of southern China are an excellent system for investigating the processes driving the geographic distribution of biodiversity and radiation of plant populations in response to Pleistocene climate fluctuations. How the key mountain ranges in southern China have affected the evolution of narrowly distributed species is less studied than more widespread species. Here we focused on Cercis chuniana, a woody species endemic to the southern mountain ranges in subtropical China, to elucidate its population dynamics. We used genotyping by sequencing (GBS) to investigate the spatial pattern of genetic variation among 11 populations. Bayesian time estimation revealed that population divergence occurred in the middle Pleistocene, when populations in the Nanling Mts. separated from those to the east. Geographical isolation was detected between the populations located in adjacent mountain ranges, thought to function as geographical barriers due to their complex physiography. As inferred by ecological niche modeling and coalescent simulations, secondary contact occurred during the warm Lushan-Tali interglacial period in China, with intensified East Asia summer monsoon and continuous habitat available for occupation. Complex physiography plus long-term stable ecological conditions across glacial cycles facilitated the demographic expansion in the Nanling Mts., from which contemporary migration began. Our work shows that population genomic approaches are effective in detecting the population dynamics of narrowly distributed species. This study advances our understanding how glacial cycles have affected the evolutionary history of plant species in southern China montane ecosystems.

Objective: Cancer Antigen 125 (CA125), the biomarker in common clinical use for ovarian cancer, is limited by low sensitivity for early disease and high false positives. The aim of this study was to evaluate several candidate biomarkers, alone or in combination, compared to CA125. Design: A prospective observational cohort study Setting: St. James’s Hospital (SJH), a tertiary referral centre for gynaecological malignancy in Dublin, Ireland. Population: 274 patients undergoing surgery for symptomatic pelvic masses between 2012 and 2018. Methods: Preoperative Human Epididymis Protein 4 (HE4), the Risk of Ovarian Malignancy Algorithm, the Risk of Malignancy Index I and II, D-dimer, and fibrinogen were assessed. Logistic regression models were fitted for each biomarker alone and in combination. AUCs and pAUCs in the 90-100% specificity range were determined. Main Outcome measures: The accuracy of biomaker(s) in the prediction of malignant/borderline versus benign tumour status compared to CA125. Results: 89 pre- and 185 post-menopausal women were included. In premenopausal women, no biomarker(s) outperformed CA125 (AUC 0.73; 95% CI 0.63-0.84). In postmenopausal women, HE4 had a pAUC of 0.71 (95% CI 0.64-0.79) compared with 0.57 (95% CI 0.51-0.69) for CA125 (p = 0.009). HE4 + D-dimer had an improved pAUC of 0.74 (95% CI 0.68-0.81, p < 0.001). Conclusion: A novel biomarker panel of HE4 + D-dimer outperformed CA125 alone as a high specificity biomarker in postmenopausal women and could aid in the preoperative triaging of symptomatic pelvic masses.

Objectives: To estimate the incidence of breast cancer diagnosed during pregnancy in the UK, to describe its management and short-term outcomes for mothers and babies. Design: A population-based descriptive study using the UK Obstetric Surveillance System (UKOSS). Setting: All UK consultant-led maternity units. Participants: All cases of breast cancer diagnosed first during pregnancy, between 1st October 2015 and 30th September 2017, with 84 confirmed cases analysed. Women with breast cancer diagnosed before pregnancy or with a recurrence were excluded. Method: Prospective case identification through monthly UKOSS mailings. Main outcome measures: Incidence of breast cancer arising for the first time in pregnancy, maternal mortality, severe maternal morbidity, perinatal mortality and severe neonatal morbidity. Results: The incidence found was 5.4/100,000 maternities (95% CI 4.37, 6.70). Nine women (11%) had an IVF pregnancy. During pregnancy, 30 women (36%) underwent surgery and 37 women (44%) received chemotherapy. Three women had major maternal morbidity during pregnancy. Two women died and there were two perinatal deaths. Conclusions: The incidence of breast cancer arising in pregnancy in the UK is similar to that reported in other countries. The higher proportion of IVF pregnancies among these women diagnosed with breast cancer during pregnancy needs further investigation. With caveats, the management followed that outside pregnancy, but there was considerable variation in practice. Although the short-term outcome was in general good for mothers and babies, a larger prospective study is required. It is often possible to avoid exposing the baby to iatrogenic prematurity.

Background and Purpose L-DOPA induced dyskinesia is a debilitating side effect of treating Parkinson’s disease with L-DOPA. There is a need to discover a treatment that has the same benefits as L-DOPA treatment without the associated side effects. Here, we demonstrate the anti-dyskinetic potential of doxycycline and the analog compound COL-3 (without antimicrobial activity) in hemiparkinsonian rats presenting L-DOPA-induced dyskinesia. Experimental Approach Wistar adult male rats received a unilateral medial forebrain bundle injection of 6-hydroxydopamine and were then orally administered L-DOPA once a day for 14 days. This resulted in dyskinetic-like behavior. Key Results A single injection of doxycycline (intraperitoneal) or COL-3 (intracerebroventricular) together with L-DOPA attenuated the dyskinesia. Co-treatment with doxycycline from the first day of L-DOPA suppressed the onset of dyskinesia. The improved motor responses to L-DOPA remained intact in the presence of doxycycline or COL-3, indicating the preservation of the L-DOPA benefits. Doxycycline treatment was associated with decreased expression of FosB, cyclooxygenase-2, astrocytes, and microglia, which had previously been found to be elevated in the basal ganglia of rats exhibiting dyskinesia. In addition, metalloproteinase-2/-9 activity, metalloproteinase-3 expression, and production of reactive oxygen species in the basal ganglia of dyskinetic rats showed a significant positive correlation with the intensity of dyskinesia, which was decreased with the doxycycline treatment. Conclusion and Implications Given the long-established and safe use of doxycycline and the similar effect of COL-3 (without antimicrobial activity), this study indicates that both drugs should undergo testing for their ability to reduce signs of dyskinesia induced by L-DOPA in patients with Parkinson’s disease.

Until recently, ibuprofen has been avoided in all COVID-19 protocols world-wide. The author has been trying since March, 2020 to publish a paper that disputes this unfortunate incident and he finally managed since May 2020 to publish two manuscripts that not only prove non-steroidal anti-inflammatory drugs not harmful for COVID-19, rather they were shown to possess a potential to cure the disease based on a unique new theory suggested to explain COVID-19 pathogenesis and he suggested NSAIDs to be added to unique protocol he suggested using nitazoxanide/azithromycin to manage early cases of COVID-19. In this manuscript, considered the fourth related to the subject, the author represents the first clinical results of using NSAIDs/Nitazoxanide/Azithromycin protocol, used partly or fully, that includes relatively cheap FDA approved drugs used in seventeen Egyptian patients, whether confirmed or suspected, including children, adults and two pregnant ladies whom have been mostly symptoms-free in five days. The manuscripts also presents a road-map to illustrate how to deal efficiently with early cases of COVID-19 according to the author’s clinical experience.

Introduction COVID-19 has presented an unprecedented situation to the medical world. With the high infectivity rate, the search for ideal prognostic tests is on. Neutrophil lymphocyte ratio (NLR) has been used as a prognostic marker in several infectious, inflammatory and malignant conditions. We aim to assess the utility of NLR as a prognostic marker in COVID-19. Materials and methods: 142 confirmed COVID-19 patients were included in the study. A detailed clinical Performa was filled. Complete blood count and coagulation parameters were done in each patient. Based on the clinical criteria, the patients were classified as asymptomatic (100) and symptomatic (42). The symptomatic patients were subjected to CT chest examination and were assigned a CT severity index. Using clinical presentation, organ dysfunction, oxygen requirement and CT severity index the patients were classified as mild and severe COVID-19 groups. NLR, coagulation parameters and CT severity index were compared. Results: 46.4 % of males and 17.8 % of females had neutrophilia. 37(38.1 %) males had 14 (31.1 %) females had lymphopenia. NLR was between 1-3.5 in 83 (58.45%) cases and 59 cases (41.5%) had NLR >3.5.Of these 59 cases, 50 had a deranged FDP/D-dimer levels. The Receiver Operating Characteristics (ROC) curve analysis was carried out to indicate the sensivity and specifity of NLR and its respective optimal cut-off value for predicting severity in COVID. NLR >3.5 helped in predicting severity of COVID with a sensitivity of 60% and specificity of 70%. Conclusion: High NLR (>3.5) indicates a severe form of disease. ’What is already known about this topic? Covid 19 is an emerging pandemic and researchers are trying to find the various diagnostic and prognostic parameters. What does this article add? This article tries to assess a new prognostic marker for covid 19

COVID-19-related anxiety and post-traumatic stress symptoms (PTSS) or disorder (PTSD) are likely to be a significant long-term issue emerging from the current pandemic. We hypothesise that cannabidiol (CBD), a chemical isolated from Cannabis Sativa with reported anxiolytic properties, could be a therapeutic option for the treatment of COVID-19-related anxiety disorders. In the global over-the-counter CBD market, anxiety, stress, depression and sleep disorders are consistently the top reasons people use CBD. In small randomised, controlled clinical trials, CBD reduces anxiety in healthy volunteers, patients with social anxiety disorder, those at clinical high risk of psychosis, in patients with Parkinson’s disease, and in individuals with heroin use disorder. Case reports and series support these findings, extending to patients with anxiety and sleep disorders, Crohn’s disease, depression and in PTSD. Preclinical studies reveal the molecular targets of CBD in these indications as the cannabinoid receptors type 1 and 2 (CB1 and CB2) receptors (mainly in fear memory processing), serotonin 5HT1a receptors (mainly in anxiolysis) and peroxisome proliferator-activated receptor gamma (PPARγ) (mainly in the underpinning anti-inflammatory/anti-oxidant effects). Observational and preclinical data also support CBD’s therapeutic value in improving sleep (increased sleep duration/quality and reduction in nightmares) and depression, often comorbid with anxiety. Together these features of CBD to reduce anxiety and depression, and improve sleep disturbances, could be an attractive novel therapeutic option in relieving COVID-related post-traumatic stress symptoms.

Background/purpose: The antiviral activity of quaternary ammonium salt type surfactant has been reported, however, part of those surfactant has enhancement effect of the skin permeability of matters. In this study, the effect of those surfactant on skin barrier function has been evaluated.Methods: The Transmission Index method, which is a relative value of a substance's skin permeation rate was applied for evaluation of surfactant. The skin injury was evaluated by microscopic observation.Results: Some cationic and amphoteric quaternary ammonium salt type surfactants significantly enhanced the skin permeability of the substance. However, unlike sodium laurate, there was no skin tissue damage.Conclusion: The quaternary ammonium salt type surfactant has no skin tissue damage and may be used as a safe disinfectant. However, on the skin which surface-treated by surfactant, the permeation of substances through the skin is increased, which may allow the percutaneous penetration of viruses and other substances. Therefore, be careful when using it.KeywordsSkin barrier function, Skin permeability, Skin injury, Ionic type of surfactant