In this work, we investigate the evolution of a Richtmyer-Meshkov (RM)-like instability occurring on the internal surface of particle rings impinged by divergent blast waves. Despite of the signature spike-bubble instability structure analogous to the hydrodynamic RM instability, the growth of the perturbation amplitude in granular media undergoes an exponential phase followed by a linear phase, markedly differing from the hydrodynamic RM instability, indicating a fundamentally different mechanism. The granular RM-like instability arises from the incipient transverse granular flows induced by the hydrodynamic effects upon the shock interaction. Whereas a substantial perturbation growth is initiated by the ensuing rarefaction dilation when the hydrodynamic effects are minimum. It is the interplay between the localized transverse and radial granular flows that sustains the persistent perturbation growth and drives the morphological changes of instability pattern alongside.

Environmental variability can lead to dispersal: why stay put if it is better elsewhere? Without clues about local conditions, the optimal strategy is often to disperse a set fraction of offspring. Many habitats contain environmentally differing sub-habitats. Is it adaptive for individuals to sense in which sub-habitat they find themselves, using environmental clues, and respond plastically by altering the dispersal rates? This appears to be done by some plants which produce dimorphic seeds with differential dispersal properties in response to ambient temperature. Here we develop a mathematical model to show, that in highly variable environments, not only does sensing promote plasticity of dispersal morph ratio, but individuals who can sense their sub-habitat and respond in this way have an adaptive advantage over those who cannot. With a rise in environmental variability due to climate change, our understanding of how natural populations persist and respond to changes has become crucially important.

Scimitar syndrome is rare malformation defined as partial or total anomalous pulmonary venous return of the right lung veins to the inferior vena cava just above or below the diaphragm. Severe forms of the disease are diagnosed in infancy and childhood . However, because of the mild form of the syndrome in adult patients, they remain asymptomatic and few cases are reported in the literature. We report an unusual presentation of this syndrome mimicking unstable angina in one of the two described cases.

Objective To assess adherence to anti-hypertensive medication by pregnant women and to understand the factors associated with adherence or lack thereof. Design Observational study. Setting Antenatal clinics. Population 100 pregnant women with either chronic hypertension or gestational hypertension who were being treated using at least one anti-hypertensive medication. Methods Participants were prospectively recruited through two Australian maternity hospitals over a 10-month period. A 23-item questionnaire, which incorporated a validated adherence scale, was administered to all participants. Data from clinic records were extracted as needed. Main Outcome Measures Self-reported adherence, BP control and reasons for nonadherence. Results Participants (mean age 33 [±4.9] years; mean gestation 29 (±7) weeks) had a median blood pressure (BP) of 130/80mmHg (IQR: 16/15). Sixty-five women had chronic hypertension, of whom 13 were diagnosed during the pregnancy, before 20 weeks gestation. Thirty-five women had gestational hypertension. Ninety-two per cent of participants had sub-optimal adherence. There were no significant differences in adherence scores between participants with chronic hypertension and their counterparts. The main reasons for sub-optimal adherence were: intentionally putting up with medical problems before taking any action, confusion about the medication, and making changes to the recommended medication regimen to suit lifestyle. Conclusions Nine out of 10 pregnant women using anti-hypertensives self-reported some degree of suboptimal adherence, intentionally and/or unintentionally. Health professionals, including pharmacists, general practitioners and obstetricians, have a role in promoting optimal adherence. Funding No funding received. Keywords Adherence, anti-hypertensives, pregnancy, gestational hypertension, chronic hypertension.

Hydrogel based soft materials have earned considerable interest as promising systems for biomedical filed as a consequence of their numerous properties likes softness, biodegradability, and hydrophilicity. The polysaccharide and natural polysaccharide have the numerous properties like nontoxicity, biodegradability, availability. The polysaccharide gums have outstanding benefits such as renewable, biodegradable, biocompatibility,and nontoxic. The uncontrolled release of drug and sufficient strength of hydrogels are challenges for the researcher to develop the advanced materials for the drug delivery application. An addition of inorganic nanoparticles in the hydrogels leads to improve matrix properties regarding robustness and sustain drug release profile. The rheological profile of nanocomposites hydrogels were established by carrying out amplitude sweep and frequency sweep. The release profile of prepared nanocomposites hydrogels was studied by utilizing ofloxacin as a model drug in different pH media, different content of nanoparticles and different intervals.

Introduction Tuberculosis (TB) infections and latent Mycobacterium tuberculosis (MTB) infection (LTBi) remain prevalent globally. Type 2 diabetes mellitus (DM) worsens TB outcomes but the immune mechanisms that cause this are not yet clear. We investigated a role of suppressor of cytokine signaling molecules (SOCS1 and SOC3) in regulating host cytokine responses in the diabetic host infected with MTB. Materials and Methods We studied peripheral blood cells from health endemic controls (EC), LTBi cases, diabetics with and without LTBi and TB patients. Mycobacterial antigen-stimulated cytokine secretion was determined using the Th1/Th2 11 plex cytokine assay. Antigen-induced gene expression of IFNγ, TNFα, IL6 and SOCS3 was determined by reverse-transcription PCR. Results Purified protein derivative (PPD) antigen stimulation induced higher levels of, IL-6, IL-2, TNFα and GM-CSF levels in DM-LTB as compared with EC and LTB cases. IL-13 levels were raised in DM-LTB cases as compared with DM cases. PPD-induced IFNγ and IL-6 transcripts were raised in DM-LTBi as compared with EC. TNFα mRNA levels were raised in DM-LTBi as compared with LTBi. SOCS3 mRNA levels were reduced in DM-LTBi as compared with LTBi. SOCS3 transcripts were higher in LTBi as compared with EC and TB groups. Discussion We found co-occurrence of LTBi with DM to be associated with an increased release of proinflammatory IL-6, IL-2 and TNF-α but reduced SOCS3 mRNA levels. SOCS3 protects against MTB infection therefore, reduced levels in DM-LTB may be contribute to progression from LTBi to active TB in individuals infected with MTB.

Peroxiredoxins (PRXs) are intracellular antioxidative enzymes but work as inflammatory amplifiers under the extracellular condition. To date, the function of PRXs in the pathogenesis of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is not fully understood. The aim of this study was to investigate whether PRXs play a role in the pathogenesis of MS and NMOSD. We analyzed levels of PRXs (PRX1, PRX5, and PRX6) in the CSF and serum of 16 patients with MS, 16 patients with NMOSD, and 15 patients with other neurological disorders (ONDs). We identified potential correlations between significantly elevated PRXs levels and the clinical variables in patients with MS and NMOSD. Additionally, pathological analyses of PRXs (PRX1-6) in the central nervous system were performed using the experimental autoimmune encephalomyelitis (EAE), animal model of MS. We found that serum levels of PRX5 and PRX6 in patients with MS and NMOSD were higher compared with those in patients with ONDs (p < 0.05). Furthermore, high levels of PRX5 and PRX6 were partly associated with blood–brain barrier dysfunction and disease duration in NMOSD patients. No significant elevation was found in CSF PRXs levels of MS and NMOSD. Spinal cords from EAE mice showed remarkable PRX5 staining, especially in CD45+ infiltrating cells. In conclusion, PRX5 and PRX6 may play a role in the pathogeneses of MS and NMOSD.

As Dr. Thomson eloquently notes in his valuable letter [1], underlying respiratory diseases appear to be less of a risk factor for poor outcome in COVID-19 patients than either underlying cardiovascular disease or diabetes. This intriguing finding emerged from several studies that examined underlying medical conditions in COVID-19 patients.In a single-center retrospective analysis of critically ill adults admitted to the intensive care unit of a hospital from China between late December 2019 and January 26, 2020, 22% of the non-survivors had cerebrovascular disease, 22% had diabetes, and 6% had chronic respiratory disease [2]. The analysis of data from patients with laboratory-confirmed COVID-19 from hospitals in China through January 29, 2020 found that 16.2% of those with serious disease had diabetes, 23.7% had hypertension, and 3.5% had chronic obstructive pulmonary disease [3]. A study of electronical medical records of COVID-19 patients admitted between January 16 and February 3, 2020 to a hospital from Wuhan found that hypertension and diabetes mellitus, the most common comorbidities, were present in 37.9%, 13.8%, of the patients with severe disease, respectively, but only in 3.4% of the patients with chronic obstructive pulmonary disease [4]. Finally, an analysis of all COVID-19 cases reported through February 11, 2020, extracted from the Infectious Disease Information System in China, found that case fatality rates in individuals with cardiovascular disease, chronic respiratory disease, and diabetes were 10.5%, 6.3%, and 7.3% respectively, as compared to 0.9% among patients with no comorbidities [5]. In a case series of COVID-19 patients hospitalized in Wuhan, China, ICU patients were more likely to have underlying diabetes than patients that did not receive ICU care (22.2% vs 5.9%) [6].The studies mentioned above did not stratify patients by therapies they were receiving. However, one commonality between cardiovascular disease and diabetes is that they are often treated with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type-I receptor blockers (ARBs), widely used to inhibit the formation and action of angiotensin II.ACE shares 42% amino acid identity with ACE2 [7], a membrane-bound aminopeptidase [8] extensively expressed on type II human alveolar cells [9]. The genes encoding these two proteins are thought to have emerged by duplication [10]. ACE2 is distributed on many tissues and shows highest expression levels in the heart, kidney, lung, small intestine, and testis [11]. On the apical surface of polarized respiratory epithelial cells, ACE2 is a crucial and primary receptor for the cellular entry of SARS-CoV, the virus that caused the 2002-2003 SARS outbreak [12-16]. SARS-CoV binding to ACE2 mediates entry into human or animal cells [17]. ACE2 is also the receptor for SARS-CoV-2, the etiologic agent of COVID-19 [18]. Structural analyses indicate that SARS-CoV-2 binds the ACE2 receptor with a 10-20-fold higher affinity than SARS-CoV [19, 20].The entry of SARS-CoV and SARS-CoV-2 into their target cells is mediated by the viral spike (S) glycoprotein, which is located on the outer envelope of the virion [21]. The S glycoprotein has two functional subunits, S1, which binds the cellular receptor, and S2, which contains domains required for the fusion between viral and cellular membranes [22, 23]. Viral binding and membrane fusion represent the initial and critical steps during the infection cycle of the coronavirus [24] and the first step in establishing the infection [25, 26]. Binding is followed by internalization of ACE2 and down‐regulation of its activity on the cell surface [27-29].SARS-CoV binds ACE2 through a region of the viral S1 subunit called the minimal receptor-binding domain (RBD) [17]. RBD is the most important determinant of the SARS-CoV host range, and studies about the “species jump” during the 2002-2003 SARS outbreak revealed that changes of only one or two amino acids in this region were sufficient to make the virus “jump” to a new host [26, 30, 31].ACE and ACE2 are two members of the renin angiotensin system that negatively regulate each other [32, 33] and are distinct in their substrate specificity and function [34]. ACE converts angiotensin I to angiotensin II and mediates aldosterone release, vasoconstriction, sodium retention, cell proliferation, and organ hypertrophy [35]. ACE2 cleaves a single residue from angiotensin I to form angiotensin-(1-9), and a single residue from angiotensin II to form angiotensin-(1-7). In humans, ACE2 has a 400-fold higher catalytic efficiency when it uses angiotensin II as a substrate as compared to when it uses angiotensin I [36]. ACE2 and angiotensin-(1-7), through the Mas receptors, oppose ACE and mediate vasodilation and anti-proliferative, anti-hypertrophic, cardioprotective, and reno-protective effects [8, 35, 37]. ACE2 has physiological and pathological importance [25] and its dysregulation was implicated in heart disease, hypertension, and diabetes [36, 38-40]. ACE2 is not inhibited by ACE inhibitors [32] and several studies indicate that the ACE2/Angiotensin-(1-7)/Mas axis has anti-inflammatory effects [41, 42].It was recently hypothesized that treatment with ACE inhibitors and/or ARBs may lead to ACE2 overexpression and this could increase the risk of severe COVID-19 [43], possibly by increasing the internalization of SARS-CoV-2. Several lines of evidence indicate that pharmacological manipulation of the renin-angiotensin-aldosterone pathway could affect ACE2 receptor levels. In animal studies, the selective blockade of angiotensin II synthesis or activity increased cardiac Ace2 gene expression and activity [44, 45], and treatment with ARBs increased the levels of cardiovascular ACE2 receptors [46-49]. While this link is thought-provoking as a possibility, there isn’t currently sufficient evidence to contemplate changing patients’ existing therapeutic regimens in order to minimize their risk of COVID-19 complications. The first clinical evidence exploring this link indicated that the use of ACEI and ARBs appear to improve the clinical outcome of COVID-19 patients with hypertension [50]. We will only learn about any possible associations, along with their magnitude and direction, from carefully conducted and adequately powered clinical trials.It is also important to consider that an increase in ACE2 levels does not necessarily entail a negative impact for the course of COVID-19. ACE2, by forming angiotensin-(1-7) from angiotensin II, could diminish the deleterious effects of angiotensin II and, consequently, it is also possible that ACE inhibitors or ARBs could, in fact, lower the risk of complications [51]. However, increased ACE2 and the formation of angiotensin-(1-7), by inhibiting COX-2, could exert anti-inflammatory effects [52, 53], underscoring the multitude of possible effects and the need to conduct studies to interrogate these connections. Finally, it is not known whether an increase in the expression of ACE2 would also lead to an increased shedding and increased levels of soluble ACE2, which could act as a decoy receptor and lower viral entry into cells [54]. In support of this, recombinant human ACE2 ameliorated the lung injury induced by the avian influenza H5N1 virus in mice [55]. It is also important to consider that from the relatively limited amount of human data, plasma ACE2 activity does not appear to be statistically different between individuals taking ACE inhibitors or ARBs and those not taking these medications, but these results do not reflect the levels of cellular receptors [56]. Structural analyses indicate that the binding of the SARS-CoV spike protein to ACE2 does not occlude the catalytically active site of the receptor [26, 57], and it was hypothesized that angiotensin II binding to ACE2 could induce a conformational change in the receptor, which will no longer be favorable for SARS-CoV-2 binding [54]. The mining of existing datasets, preclinical studies, and clinical trials will help shed light on these complex and sometimes conflicting scenarios.A decrease in the number of ACE2 receptors appears to be involved in acute lung injury and cardiovascular pathology [58, 59], and may be detrimental during coronavirus infection. A mouse Ace2 knockout developed severe cardiac contractility defects and increased angiotensin II levels, and the additional deletion of Ace rescued this phenotype [60]. In acute lung injury models, the loss of Ace2precipitated severe acute lung failure, and this was attenuated by the exogenous recombinant human ACE2 in both Ace2 knock-out and in wild-type mice [59]. Attenuation of the Ace2 catalytic function perturbed the pulmonary renin-angiotensin-aldosterone system and increased inflammation and vascular permeability [61], and Ace2 overexpression decreased lung inflammation in an animal model of acute lung injury [62]. In vitro and in experimental animals, SARS-CoV and the SARS-CoV spike protein downregulated ACE2 expression [12, 28]. In mice with lung injury, injection of the SARS-CoV spike protein worsened the acute lung failure and caused lung edema, increased vascular permeability, and decreased lung function, and this pathology was attenuated by blocking the renin-angiotensin-aldosterone pathway [12]. Thus, animals infected with SARS-CoV or treated with the spike protein resemble Ace2 knockout animals [12]. It is relevant that a pilot study of patients with acute respiratory distress syndrome reported the accumulation of angiotensin I and the decrease of angiotensin-(1-9), indicating decreased ACE2 activity, among non-survivors [63]. Thus, SARS-CoV and SARS-CoV-2 might contribute to severe respiratory symptomatology partly because the viruses, by binding the ACE2 receptors, also deregulate protective pathways in the lungs.Thus, either increased or decreased numbers of pulmonary ACE2 receptors may be detrimental during SARS-CoV or SARS-CoV-2 infection, most likely for distinct reasons. An increased number of ACE2 receptors may lead to a higher viral load and more severe clinical disease. Diabetes increases ACE2 expression, as shown in several experimental models, and the resulting increased viral load might explain the more severe course of COVID-19 in diabetic patients [64, 65]. Interestingly, in a rodent model of diabetes, ibuprofen inhibited the ACE/angiotensin II/angiotensin type 1 receptor axis and enhanced the ACE2/angiotensin-(1-7)/Mas receptor axis [66]. Too few functional ACE2 receptors, which decrease even more as a result of high viral loads and enhanced receptor internalization [67], might exacerbate acute lung injury, increase angiotensin II levels, and alter the balance between pro- and anti-inflammatory responses. It is relevant that in a study on twelve COVID-19 patients from China, plasma angiotensin II levels were markedly elevated as compared to healthy control individuals, and linearly associated with the viral load and with the lung injury [68]. The animal studies that documented an age-dependent decrease in ACE2 expression in the lung and the aortic might also explain, at least in part, the age-dependent increase in the risk of serious COVID-19 complications [69, 70].SARS-CoV can also bind cells through alternative receptors that include the C-type lectins DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin) and/or L-SIGN (liver/lymph node-SIGN) [14, 71-73]. It will be critical to understand the potential involvement of the same, or alternative receptors in the pathogenesis of COVID-19.It has been less clear why SARS-CoV and SARS-CoV-2 lead to severe lung disease [57], in contrast to other, previously known coronaviruses, which usually result in mild upper respiratory infections and cause pneumonia only rarely, mostly in newborn, the elderly, and immunocompromised individuals [74-77]. One of the possibilities advanced for SARS is that the burden of viral replication and the immune status of the host may both shape the severity of the infection [57, 78, 79]. The same might be true for COVID-19, and further exploring the link between viral burden, chronic medical conditions, long-term medication usage, and the severity of the infection will be critical.An important lesson from SARS and MERS is the association between the incubation period and disease severity. For any infectious disease, the incubation period varies among individuals, even for the same outbreak, and depends on the initial infective dose, the speed of pathogen replication within a host, and host defense mechanisms [80]. During the 2002-2003 SARS outbreak, a study in Hong Kong revealed that patients with shorter incubation times developed more severe disease [81]. The same was found in MERS patients from South Korea, where longer incubation times were associated with a lower risk of death [82]. Interestingly, during the SARS outbreak in Hong Kong, healthcare workers, who have a higher infecting dose, had 34% shorter median incubation times than non-healthcare workers [83]. It will be interesting to examine whether the same is true for SARS-CoV-2, and whether the incubation period is different in COVID-19 patients when they are stratified by age, coexisting morbidities, and therapies they receive for chronic diseases. While the association between the incubation period and mortality might simply indicate that the disease was confirmed earlier in patients with longer incubations, and reflect earlier treatment opportunities [82], it is also plausible that high viral loads might mediate the link between the two.Two factors decisive for the successful control of outbreaks are the ability to isolate asymptomatic individuals and the ability to trace and quarantine their contacts [84, 85]. Several studies reported asymptomatic shedding of SARS-CoV-2, indicating that asymptomatic carriers, or individuals with very mild symptoms, may sustain transmission [86-89]. For example, nearly 18% of the passengers who tested positive for SARS-CoV-2 on the Diamond Princess cruise ship were asymptomatic [88]. Another valuable finding that emerged from the COVID-19 outbreak analysis in Singapore, and has a strong impact on infection control, is that after becoming asymptomatic, some patients continued to shed the virus for up to several days. In one instance, a patient continued to have detectable respiratory shedding, as shown by PCR, for eight consecutive days after becoming asymptomatic [90]. Another study revealed that several children with COVID-19 persistently tested positive for viral RNA on fecal swabs after their nasopharyngeal cultures became negative. Even though replication-competent virus was not detected in the fecal swabs, this finding leaves open the possibility of SARS-CoV-2 fecal-oral transmission [91]. These findings illustrate the challenges in understanding SARS-CoV-2 transmission and in identifying infected individuals, tracing their contacts, and implementing preparedness plans. One of the absolute requirements, to clarify these questions and overcome these obstacles, is ensuring the prompt and large-scale testing of symptomatic individuals and of their asymptomatic contacts. This, together with the social distancing measures, are currently our only available assets in facing a pandemic that, even though it was preceded by multiple warnings in recent years, is unlike any other infectious disease that we experienced in modern history.

Large occurrence datasets provide a sizable resource for ecological analyses, but have substantial limitations. Phenological analyses in Fric et al. (2020) are flawed due to insufficient data and improper analysis. Our reanalysis of 22 univoltine species with sufficient data (from 100 original species) found substantive differences in macroscale phenological patterns.

Floral plantings are promoted to foster ecological intensification of agriculture through provisioning of ecosystem services. However, a comprehensive assessment of the effectiveness of different floral plantings, their characteristics and consequences for crop yield across global regions is lacking. Here we quantified the impacts of flower strips and hedgerows on pest control and pollination services in adjacent crops using a global dataset of 529 sites. Flower strips, but not hedgerows, enhanced pest control services in adjacent fields by 16% on average. However, effects on crop pollination and yield were more variable. Our synthesis identifies several important drivers of variability in effectiveness of plantings: pollination services declined exponentially with distance from plantings, and perennial and older flower strips with higher flowering plant diversity enhanced pollination more effectively. These findings provide promising pathways to optimize floral plantings to more effectively contribute to ecosystem service delivery and ecological intensification of agriculture in the future.

We report a case of 41-year-old woman who presented with chest tightness and shortness of breath. Transthoracic echocardiogram (TTE) showed left ventricular (LV) pseudo-aneurysm of the inferior wall with preserved LV systolic function. Coronary angiogram was normal. Surgical repair of the pseudo-aneurysm with a pericardial patch was performed, and pathological results confirmed rupture of an isolated congenital LV diverticulum.as the most likely etiology.

A poor healing split thickness graft donor site can be discouraging and problematic for surgeons. Usual management of hypergranulation and local infection consists in frequent dressings and use of nitric silver which is quite painful for patients. In this paper we examined the efficacy of a topical steroid dressing.

Specific therapies in pregnant women are discussedThe health crisis caused by the novel SARS-cov-2 (2019-nCoV) related pandemic requires urgent and necessary therapeutic response. Pregnant women are just as exposed as the general population and should not be excluded, because of their status, from discussions on effective and well tolerated candidate treatments. While in countries that have opted for national containment, daily non-emergency medical and surgical activities are suspended, obstetric services continue to operate relentlessly and are experiencing a surge in so-called ”at-risk” pregnancies. Some countries have now recommended routine screening of all pregnant women 1 but the low availability and performance of the current tests limits their use. Management of an infected pregnant women is essentially conditioned by maternal symptomatology. Women with little or no symptoms do not require routine treatment or in-patient care and simply need to be monitored for up to 15 days for evidence of respiratory deterioration. In the absence of validated specific treatment, the primary approach to therapy is mainly symptomatic and delivery is considered in the event of critical respiratory distress in order to maximize oxygenation and lung capacity2–4 . However, it has been reported that women with respiratory signs may be given antiviral treatment to improve their clinical condition 2,4To date, there is no proven effective strategy, although many teams are working tirelessly to identify an effective treatment. Four molecules are leading in this race:1) Remdesivir is a novel nucleotide analogue prodrug which incorporates into nascent viral RNA chains and results in pre-mature termination. Its effectiveness has been already demonstrated against others coronaviruses such as SARS-Cov and MERS-Cov5, and it has proven to be highly effective on in vitro 2019-nCoV infection6. Compassionate use in human were also reported 7 and phase 3 studies are currently underway.2) (Hydroxy)chloroquine has been known for years because of its effectiveness in the treatment of inflammatory diseases and against malaria. Recent studies have shown antiviral effects of chloroquine and in vitro studies concluded that it was highly effective in the control of 2019-nCoV 6,8. Elevation of endosomal pH and interference with terminal glycosylation of the cellular receptor, angiotensin-converting enzyme 2 conduct to block virus infection. (Hydroxy)chloroquine has been used in 2019-nCoV infected humans with highly controversial restuls9,10 and well-designed randomized studies should be available soon.3) Lopinavir, a viral protease inhibitor, with its pharmacological booster Ritonavir (LPV/R) are commonly used in HIV positive patients. It has already been used for SARS-Cov. Some countries such as China and India approved its use in symptomatic infected patients although a first randomized, controlled, open-label trial showed no benefit of LPV/R over standard care in patients with severe 2019-nCoV disease11.4) Ribavirin, is a guanosine analog that interferes with the replication of RNA and DNA viruses. It has been used for years in the treatment of chronic hepatitis C. Based on its direct anti‐viral activity against 2019‐nCoV in vitro and some evidence for its potential efficacity during the prior SARS-Cov and MERS-Cov outbreaks, it has been suggested as a potential candidate for the treatment of 2019-nCoV diease12. 2019-nCoV infected patients treated with Ribavirin have been reported by Chinese studies4,13but its exact benefit remains to be demonstrated in well designed randomized studies as well.To date, all four drugs are being independently tested in Phase 3 studies, mostly national, to investigate their efficacy and safety in the management of 2019-nCoV disease. Several European countries have also set up, as a result of joint efforts since mid-March, a randomized, multicentre, open-label trial to evaluate and compare the efficacy and toxicity of the first three treatments mentioned above.14With regard to the possibility of treating pregnant patients with these molecules, few data are available for Remdesivir. Only one study reports its use in six pregnant women in a randomized trial during Ebola epidemics. The authors reported no adverse effect15.Many more pharmacological studies on maternal-fetal tolerance of Hydroxy(chloroquine), Lopinavir and Ribavirin are available. The historical use of (hydroxy)chloroquine in antimalarial treatment, but also in connective tissue diseases, has resulted in a well-documented safety and tolerance profile in pregnant women16. Animal studies, undertaken during the Zika virus epidemic, have also suggested that chloroquine may also reduce the risk of viral transplacental transmission to the fetus17. The optimal dosage to be used in pregnant women will have to be specified, but it appears that there is no pharmacokinetic difference between chloroquine and its major metabolite between pregnant and non-pregnant women18. With respect to the use of protease inhibitors during pregnancy, such as Lopinavir, some teams have reported an increased risk of preterm delivery. However, a specific analysis of more than 4,000 pregnant women found a similar incidence and rate of adverse pregnancy outcomes than in controls at all three trimesters of pregnancy, including preterm birth, low birth weight and birth defects19. Significant teratogenic effects have been demonstrated in all animal species exposed to Ribavirin, it is therefore currently contraindicated in pregnant women and in their male sexual partners, although the ribavirin pregnancy registry did not bring evidence of teratogenicity in humans20.The use of antiviral therapy in infected pregnant patients should follow the same indication as in the general population, but some obstetric specificities should be emphasized.1) The main goal should be to slow down and at best stop the clinical progression of the disease, i.e to remain asymptomatic and to avoid progression to acute respiratory distress syndrome in symptomatic cases. In the latter, the obstetrician is often called on to perform an emergency delivery and thus to induce extreme prematurity. Expert consensus provided obstetric guidance, but the management of cases at between 25 and 32 weeks’ remains challenging in the absence of effective antiviral treatment1.2) The second objective would be to rapidly decrease viral load and duration of contagiousness in infected pregnant women. The majority of them are doing well, but the infection can disrupt their obstetrical calendar. Some procedures need to be performed at a specific age, such as first trimester serum markers, ultrasound examinations, chorionic villi sampling (CVS). The same applies to access to termination of pregnancy. All such procedures may indeed be delayed, either to limit contagion, to limit the burden on the health care team (due to reinforced barrier measures…) or in the particular case of CVS/amniocentesis, to limit the theoretical risk of fetal transmission.3) Finally, the third advantage could be to introduce preventive treatment in case of maternal contact with an infected person, similar to what is done for seasonal influenza and oseltamivir21.The use of immunotherapy such as Tocilizumab, plasma of recovered coronavirus patient, Interferons, were not discussed here as they are currently understudy only for critically ill COVID-19 patients. No place for these treatments in a patient who is still pregnant should be considered for the time being, since if the pregnant woman presents a very severe form, the birth will be considered as a priority.The results of the Phase 3 therapeutic studies should be available soon. However, it is unfortunate that infected pregnant women are not included in any appropriate research protocols. Consequently, in this period of pandemic, mutual exchanges of experience between all countries’ maternity hospitals must be carried out in order to ensure the best possible management of infected pregnant women.

Structural characterization of alternatively folded and partially disordered protein conformations remains challenging. Outer surface protein A (OspA) is a pivotal protein in Borrelia infection, which is the etiological agent of Lyme disease. OspA exists in equilibrium with intermediate conformations, in which the central and the C-terminal regions of the protein have lower stabilities than the N-terminal. Here, we characterize pressure- and temperature-stabilized intermediates of OspA by nuclear magnetic resonance spectroscopy combined with paramagnetic relaxation enhancement (PRE). We found that the C-terminal region of the intermediate was partially disordered; however, it retains weak specific contact with the N-terminal region, owing to a twist of the central β-sheet and increased flexibility in the polypeptide chain. The disordered C-terminal region of the pressure-stabilized intermediate was more compact than that of the temperature-stabilized form. Further, molecular dynamics simulation demonstrated that temperature-induced disordering of the β-sheet was initiated at the C-terminal region and continued through to the central region. An ensemble of simulation snapshots qualitatively described the PRE data from the intermediate and indicated that the intermediate structures of OspA may expose tick receptor-binding sites more readily than does the basic folded conformation.

Objectives: To investigate the mental status of pregnant women and to describe their obstetrical choices during the outbreak of COVID-19. Design: A cross-sectional study. Setting: Wuhan and Chongqing, two different epidemic areas. Population: A total of 1947 valid questionnaires were received. Methods: We collected information on demographic, pregnancy, and epidemic, along with their attitudes towards the epidemic, anxiety status and obstetrical choices. We described and compared the city-based distribution of all above factors, aiming to explain how anxiety and obstetrical choices existed and differed. Main Outcome Measures: To explore why differences existed, we estimated the impact of the epidemic on women’s anxiety by multivariable analysis. Results: Distribution differences could be seen between cities in employment status, household income, gestational age, fetal number, and exposure history. Women’s attitudes towards COVID-19 in Wuhan were more extreme than that in Chongqing. The anxiety rate was more than double in Wuhan (24.47%) compared to that in Chongqing (10.44%). Generally speaking, obstetrical choices were similar among the 1947 participants, but more obvious in Wuhan. Conclusions: Our study found that the outbreak aggravated prenatal anxiety, and the influence factors could be targets of mental care. Synchronously, vital obstetrical choices changed, followed by pertinent professional advice to prevent irreversible adverse pregnancy outcomes. Online platforms may play crucial roles to address patients’ needs in future PHEs. Funding: National Natural Science Foundation of China (No. 81771614 and No. 81771613), and the National Key Research and Development Program of China (No. 2016YFC1000407). Keywords: COVID-19; Pregnancy; Prenatal Anxiety; Obstetrical Choices.

A document by Zineb KHALILI. Click on the document to view its contents.

In this paper, we investigate the decay properties of the thermoelastic Timoshenko system with past history in the whole space where the thermal effects are given by Cattaneo and Fourier laws. We obtain that both systems, Timoshenko-Fourier and Timoshenko-Cattaneo, have the same rate of decay (1+t)^{-(1/4)} and the regularity-loss type property is not present in some cases. Moreover, new stability number χ is introduced, such new number controls the decay rate of the solution with respect to the regularity of the initial data. To prove our results, we use the energy method in Fourier space to build an appropriate Lyapunov functionals that give the desired results.

In this reseach work, we give a new result to guarantee the existence of homoclinic solutions for the nonperiodic fractional Hamiltonian systems -_{t}D_{∞}^{α}(_{-∞}D_{t}^{α}x(t))-L(t)x(t)+∇W(t,x(t))=0, where α∈(1/2,1], x∈H^{α}(R,R^{N}), W∈C¹(R×R^{N},R). We assume that W(t,x) do not satisfy the global Ambrosetti-Rabinowitz condition and is not necessary periodic in t. This result generalizes and improves some existing results in the literature.

This paper deals with a pseudo-parabolic equation involving variable exponents under Dirichlet boundary value condition. The authors first develop the potential well method to prove a threshold result on the existence and nonexistence of global solutions to the equations when initial energy is less than the mountain pass level $d$. By borrowing the idea from \cite{GW05,XS13} we also show some existence and nonexistence results with high energy initial data. In this case a new characterization for nonexistence of solution is given. These results extend and improve a recent result obtained by Di et al. (2017) \cite{DSP17} and Liao (2019) \cite{Liao19,LGL19}.

In this work we emphasise the use of singularity analysis in obtaining analytic solutions for equations for which standard Lie point symmetry analysis fails to make any lucid decision. We study the higher-dimensional Kadomtsev-Petviashvili, Boussinesq and Kaup-Kupershmidt Equations in a more general sense. With higher-order equations there can be a commensurate number of resonances and, when consistency for the full equation is examined, at each resonance the constant of integration is supposed to vanish from the expression so that it remains arbitrary, but if there is an instance of this not happening, the consistency can be partially established by giving the offending constant the value from the defining equation. If consistency is otherwise not compromised, the equation can be said to be partially integrable, ie, integrable on a surface of the complex space. Furthermore we propose an approach which is meant to magnify the scope of singularity analysis for equations admitting higher values for resonances or positive leading-order exponent.

Expansins have the remarkable ability to loosen plant cell walls and cellulose material without showing catalytic activity and therefore have potential applications in biomass degradation. To support the study of sequence-structure-function relationships and the search for novel expansins, the Expansin Engineering Database (ExED, https://exed.biocatnet.de) collected sequence and structure data on expansins from Bacteria, Fungi, and Viridiplantae, and expansin-like homologues such as carbohydrate binding modules, glycoside hydrolases, loosenins, swollenins, cerato-platanins, and EXPNs. Based on global sequence alignment and protein sequence network analysis, the sequences are highly diverse. However, many similarities were found between the expansin domains. Newly created profile hidden Markov models of the two expansin domains enable standard numbering schemes, comprehensive conservation analyses, and genome annotation. Conserved key amino acids in the expansin domains were identified, a refined classification of expansins and carbohydrate binding modules was proposed, and new sequence motifs facilitate the search of novel candidate genes and the engineering of expansins.

Background: Behcet’s disease (BD) is a multisystem autoimmune relapsing vasculitis with almost unknown etiology, which involves both large and small vessels. Involvement of the central nervous system (CNS) is rare condition devided in two main sub-types. First, the parenchymal type is caused by development of an immunemediated meningoencephalitis, which predominantly involves the brainstem and diencephalon region. The other type - non-parenchymal type is a consequence of thrombosis within the dural venous sinuses. Peripheral nervous system generally preserved or involved in very rare cases. Objective: To present a rare case of Neuro-Behcet Disease (NBD) and to make a thorough review on the clinical presentation, classification and neuroimaging findings. Methods: We searched the Pub Med electronic database with the keywords - Behcet Disease, Neuro-Behcet Disease and Neuroimaging. The literature search was conducted for the period from January 2000 to March 2020. Results: A total of 35 papers met the inclusion criteria and were included in the review. The review shows that NBD remains a difficult diagnosis to establish as other diseases and conditions may have similar presentation. Therefore we present the most common clinical signs and symptoms, classification, and diagnostic criteria with accent on the neuro-imaging findings. Conclusions: The diagnosis of NBD is based on the clinical presentation and the typical lesions in brain magnetic resonance imaging (MRI). The development and disappearance of lesions at MRI may correlate with the course of clinical neurologic deficits. Differential diagnosis of NBD should be considered in cerebrovascular disease, brain tumors, and demyelinating processes.

Secondary Aorto Enteric Fistula, most commonly occur after previous aortic surgery, either open or endovascular and constitute surgical emergency, requiring prompt management.Hence,is reported a case of a 63 years old male with secondary aortoenteric fistula rupture into bowel treated endovascular while mid-term results, along with a thorough literature review

AIM To describe the clinical characteristics and the care pathways of patients with multiple myeloma (MM) benefiting from hospital at home (HAH) for their parenteral anticancer treatment METHOD A retrospective scheme conducted in HAH of Assistance-Publique des Hôpitaux de Paris (APHP). All patients starting bortezomib treatment line in HAH were included in 2015. Data collection was based on CHIMIO® software and on medical records. We analyzed the patient’s characteristics, their pathways, their long-term outcomes. RESULTS Of 536 patients treated for cancer in HAH, 154 patients received bortezomib. 73,4% patients began their first line for their symptomatic MM. Mean age was 70,6 years, 27,3 % under 65 years, 53,9% of men, 27,3% living alone, a median Karnofsky Performans Status of 70. One third of elderly lived alone, 16,1% required domestic help. The median number of courses was 6 (range: 1-14), the mean duration of treatment was 6,6 m (+ 3,5) in HAH. The median time to next treatment was 17,5 (range:0-50) months. After 24 months of follow-up after the first administration in HAH, 77,9% were alive. The median overall survival was still not reached at 4 years. 58,8% -mainly the youngest- went back to HAH for the subsequent treatment. CONCLUSION Patients treated in HAH for MM - regardless of age and therapeutic goal- were mainly independent, treated from the first line in a radius close to hospital. The involvement of HAH was achieved without safety issues nor compromised long-term outcomes. This study described the real-world patterns of patients benefiting from HAH.