Disulfide bond reduction occurred now and then during a recombinant protein manufacturing. Their reduction often led in the loss of batches. Various prevention measures were developed. Their implementation in a manufacturing inevitably increases its operation complexity and even might impact its product qualities and process performances. It is highly desirable to apply a reduction measure only if necessary and to apply no strong measure if a moderate one works. The reduction occurrence is determined both by the reduction sensitivity of a recombinant molecule and by the reduction power of harvested cell culture fluids. The reduction power of harvested cell culture fluids varies largely and depends on cells, lysis level, growth stage, and culture conditions. The method of the quantitative risk assessment of disulfide bond reduction was reported here. The quantitative assessment is realized by comparing the reduction sensitivity of a recombinant molecule with the reduction power of its harvested cell culture fluid.

Global climate change is already contributing to the extirpation of numerous species worldwide, and sensitive species will continue to face challenges associated with rising temperatures throughout this century and beyond. It is especially important to evaluate the thermal ecology of endangered ectotherm species now so that mitigation measures can be taken as early as possible. A recent study of the thermal ecology of the federally endangered Blunt-Nosed Leopard Lizard (Gambelia sila) suggested that they face major activity restrictions due to thermal constraints in their desert habitat, but that large shade-providing shrubs act as thermal buffers to allow them to maintain surface activity without overheating. We replicated this study and also included a population of G. sila with no access to large shrubs to facilitate comparison of the thermal ecology of G. sila in shrubless and shrubbed populations. We found that G. sila without access to shrubs spent more time sheltering inside rodent burrows than lizards with access to shrubs, especially during the hot summer months. Lizards from a shrubbed population had higher midday body temperatures and therefore poorer thermoregulatory accuracy than G. sila from a shrubless population, suggesting that greater surface activity may represent a thermoregulatory tradeoff for G. sila. Lizards at both sites are currently constrained from using open, sunny microhabitats for much of the day during their short active seasons, and our projections suggest that climate change will exacerbate these restrictions and force G. sila to use rodent burrows for shelter even more than they do now, especially at sites without access to shrubs. The continued management of shrubs and of burrowing rodents at G. sila sites is therefore essential to the survival of this endangered species.

Background: Premature infants who cannot achieve full oral feeds may need a gastrostomy tube (GT) to be discharged from the neonatal intensive care unit (NICU). We previously developed a model to predict which infants born <30 weeks (w) gestational age (GA) will require a GT before discharge. Here we report the detailed respiratory variable data to describe the general respiratory course for infants in the NICU <30w GA at birth and the association between different levels of respiratory support with postmenstrual age (PMA) at the time of first oral feeding attempt (PMAff), including later need for GT for discharge. Methods: Retrospective chart review of 391 NICU admissions comprising test (2015-2016) and validation (2017-2018) cohorts. Data, including respiratory support, were collected on 204 infants, 41 GT and 163 non-GT, in the test cohort, and 187 infants, 37 GT and 150 non-GT, in the validation cohort. Results: Respiratory data were significantly different between GT and non-GT infants. Infants who required GT for discharge were on significantly higher respiratory support at 30 days of age, 32w PMA, and 36w PMA. Respiratory parameters were highly correlated with PMAff. Conclusion: Respiratory status predicts PMAff, which was the variable in our previously described model that was most predictive of failure to achieve full oral feeing. These data provide a catalyst to develop strategies for improving oral feeding outcome for infants requiring prolonged respiratory support in the NICU.

Rabbit Haemorrhagic Disease (RHD) is a significant viral disease affecting lagomorphs. The first documented cases of RHD in Singapore occurred in adult pet European rabbits in September 2020. Singapore subsequently declared the outbreak resolved in December 2020. Epidemiological investigations ruled out introductions via importation of infected rabbits and contaminated feed. The source could not be definitively determined. However, the findings suggest that the incident involved both inter- and intra-household transmission and veterinary clinic-household transmission. This incident demonstrated the importance of sustained application of biosecurity measures, epidemiological investigations, and control, including active case finding, expedient vaccine dissemination, and risk communications. It shows that Singapore, an urbanised city-state, without a significant lagomorph population, could still encounter emerging diseases such as rabbit haemorrhagic disease. Given its social impact on rabbit owners, the National Parks Board Singapore and the private veterinarians worked together to communicate and urge the adoption of biosecurity measures and assuage the concerns of rabbit owners.

Intracranial subdural hematoma following spinal anesthesia is an infrequent occurrence and has variable presentation. Due to rarity, it may often be misdiagnosed as post-dural puncture headache. In this report, we describe a case of a 25-year-old woman who presented with a headache following lower segment cesarean section after spinal anesthesia.

We recommend carrying out a detailed history and evaluation for recent or past COVID-19 infection in patients presenting with Sudden Sensorineural Hearing Loss (SSNHL) since SSNHL could be a sequelae of COVID-19 as in our case and timely diagnosis and intervention could significantly improve hearing and quality of life.

Climate change is altering the relative timing of species interactions by shifting when species appear in a community and by accelerating developmental rates. However, phenological shifts may be mediated through community contexts, such as intraspecific competition and alternative resource species, which can prolong the otherwise shortened windows of availability. Using a combination of laboratory experiments and dynamic simulations, we quantified how the effects of phenological shifts in Drosophila-parasitoid interactions differed with concurrent changes in temperature, intraspecific competition, and the presence of alternative host species. We found that community context, particularly the presence of alternative host species, supported interaction persistence across a wider range of phenological shifts than pairwise interactions. Parasitism rates declined under warming, which limited the ability of community contexts to manage mismatched interactions. These results demonstrate that ongoing declines in insect diversity may exacerbate the effects of phenological shifts in ecological communities under future global warming temperatures.

Objective: Compare the risk of recurrent adverse delivery outcome (ADO) or adverse neonatal outcome (ANO) between consecutive gestational diabetes (GDM) pregnancies. Design: Retrospective cohort Setting: Sydney, Australia Population or Sample: 424 pairs of consecutive singleton GDM pregnancies, 2003-2015 Main Outcome Measures:. ADO: instrumental delivery and emergency Caesarean. ANO: large for gestational age (LGA), small for gestational age (SGA), and composite ANO (LGA/SGA/stillbirth/neonatal death/shoulder dystocia). Methods: Using each pregnancy pair (“index” and “subsequent” pregnancy), we calculated ADO and ANO rates and determined risk factors for subsequent pregnancy outcomes (multivariate regression). Results: Subsequent pregnancies had higher rates of elective Caesarean (30.4% vs 17.0%, p<0.001) and lower rates of instrumental delivery (5% vs 13.9%, p<0.001), emergency Caesarean (7.1% vs 16.3%, p<0.001) and vaginal delivery (62.3% vs 66.3%, p=0.01). ANO rates in index and subsequent pregnancies did not differ. Index pregnancy adverse outcome was associated with a higher risk of repeat outcome: RR 3.09 (95%CI:1.30, 7.34) for instrumental delivery, RR 2.20 (95%CI:1.06, 4.61) for emergency Caesarean, RR 4.55 (95%CI:3.03, 6.82) for LGA, RR 5.01 (95%CI:2.73, 9.22) for SGA and RR 2.10 (95%CI:1.53, 2.87) for composite ANO). The greatest risk factor for subsequent LGA (RR 3.13 (95%CI:2.20, 4.47)), SGA (RR 4.71 (95%CI:2.66, 8.36)) or composite ANO (RR 2.01 (95%CI:1.46, 2.78)) was having the same outcome in the index pregnancy. Conclusions: Women with GDM and an adverse outcome are at very high risk of the same complication in their subsequent GDM pregnancy, representing a high-risk group that should be targeted for directed management over routine care.

Saprophytic fungi play vital roles in nutrient cycling and ecosystem dynamics. However, our understanding of how saprophytic fungi interact with each other to decompose organic matter is very limited. Here, we conducted field surveys of pinecone-colonizing/decomposing mushrooms, investigated the chemical compositions of decomposing pinecones, and analyzed seven new genomes of three pairs of mushrooms in the genera Auriscalpium and Strobilurus with substrate specificities. Each pair of mushrooms successively colonizes the pinecones of a different pine species: A. orientale-S. luchuensis on Pinus yunnanensis, A. vulgare-S. stephanocystis on Pinus sylvestris, and A. microsporum-S. pachcystidiatus/S. orientalis on Pinus armandii. Our analyses revealed evidence for both competition and cooperation between Auriscalpium and Strobilurus fungi during pinecone decomposition. Their successive colonization of the two fungi groups with complementary profiles of carbohydrate-active enzymes enabled efficient decomposition and utilization of pinecones. The Auriscalpium fungi are highly effective at utilizing the recalcitrant primary organic carbons such as lignin and hemicellulose in freshly fallen pinecones. The decomposition by Auriscalpium fungi enabled the successive colonization by Strobilurus fungi which can produce an arsenal of secondary metabolites such as strobilurins to inhibit other fungi and have abundant carbohydrate-active enzymes for effective utilization of the remaining organic compounds in pinecones.

Stress can be remembered by plants in a form of ‘stress memory’ that can alter future phenotypes of previously stressed plants and even phenotypes of their offspring. It was shown that DNA methylation is among the mechanisms mediating the memory. It is not known for how long the memory is kept by plants. If the memory is long lasting, it can become maladaptive in situations when parental-offspring environment differ. We investigated for how long can a parental plant “remember” that it experienced a stress and pass the memory to its clonal offspring. We grew parental plants of three genotypes of Trifolium repens for five months either in control conditions or in control conditions that were interrupted with drought pulses applied for two months in four different time-slots. We also treated half of the parental plants with 5-azacytidine (5-azaC) to test for the potential role of DNA methylation in the stress memory. Then, we transplanted parental cuttings (ramets) individually to control environment and allowed them to produce offspring ramets for two months. The drought stress experienced by parents affected phenotypes of offspring ramets. Such a memory resulted in enhanced number of offspring side branches originating from plants that experienced drought stress maximally 6 weeks before their transplantation to control environment. We did not find any transgenerational memory in offspring of plants that experienced drought stress later than 6 weeks before their transplantation. 5-azaC also reduced the effect of transgenerational memory on offspring ramets. We confirmed that drought stress can trigger transgenerational memory in T. repens that is very likely mediated by DNA methylation. Most importantly, the memory was time limited and was gradually erased. We conclude that the time limited memory on environmental stress can be adaptive as climate tends to be variable and parental-offspring environmental conditions often do not match.

Objectives. The aim of this systematic review is to assess the effects of community pharmacist-led interventions to optimize the use of antibiotics and identify which interventions are most effective. Methods. This review was conducted according to the PRISMA-P guidelines (PROSPERO: CRD42020188552). PubMed, EMBASE and the Cochrane Central Register of Controlled Trials were searched for (randomised) controlled trials. Included interventions were required to target antibiotic use, be set in the community pharmacy context and be pharmacist-led. Primary outcomes were quality of antibiotic supply and adverse effects while secondary outcomes included patient reported outcomes. Risk of bias was assessed using the ‘Cochrane suggested risk of bias criteria’ and narrative synthesis of primary outcomes conducted. Results. Seventeen studies were included covering in total 3,822 patients (mean age 45.6 years, 61.9% female). Most studies used educational interventions. Three studies reported on primary outcomes, twelve on secondary outcomes and two on both. Three studies reported improvements in quality of dispensing where interventions led to more intensive symptom assessment and a reduction of OTC or wrong choice antibiotic supply. Some interventions led to higher consumer satisfaction, effects on adherence were mixed. All studies had unclear or high risks of bias across at least one domain, with large heterogeneity between studies. Conclusions. Our review suggests some possible positive results from pharmacist-led interventions, but the role of the pharmacist needs to be expanded. This review should be interpreted as exploratory research, as more high-quality research is needed. Authors did not receive funding for the review.

Intimal sarcomas simultaneously involving the right atrium and the inferior vena cava are rare. We report an advanced cardiac intimal sarcoma in the right atrium of a 19-year-old man that was complicated by tumor-related inferior vena cava thrombosis. We initially performed partial tumor resection and vena cava thrombectomy to resolve the circulatory obstruction, because complete resection was difficult due to the invading malignancy and an unclear margin. The patient received adjuvant chemo- and radiotherapy along with anticoagulant therapy. After 3 months, the border of the residual sarcoma was clear, and the patient underwent a secondary complete sarcoma excision (including that of the right atrium) and a suprahepatic vena cava reconstruction. At the 2-year follow-up, there was no tumor recurrence. We conclude that aggressive treatment and a staged complete resection can lead to improved outcomes for advanced cardiac intimal sarcoma with poor prognosis.

Abstract Systemic infections and chronic graft rejection represent common causes of mortality and morbidity in heart transplant patients. In severe cases, cardiogenic shock (CS) may occur and require hemodynamic stabilization with temporary mechanical circulatory support (tempMCS).1 Under these devastating circumstances, treatment of sequelae of left ventricular dysfunction, such as secondary mitral regurgitation (MR) is challenging, especially when surgical repair is deemed futile. In non-transplant patients, interventional mitral valve repair strategies such as the MitraClip system (Abbott Cardiovascular, Plymouth, MN, USA) have been used to successfully treat secondary MR and allow for weaning from tempMCS.2 We report about the first patient in whom profound cardiogenic shock after heart transplantation was stabilized with tempMCS followed by interventional elimination of secondary MR.

The parasitic weed genus Striga causes huge losses to crop production in sub-Saharan Africa, estimated to be in excess of $7 billion per year, affecting subsistence farmers who frequently lack access to novel technologies proposed for control. Effective Striga management therefore requires the development of strategies utilising existing cultural and management practices. We report a multi-year, landscape-scale monitoring project for Striga asiatica in the mid-west of Madagascar, undertaken over 2019-2020 with the aims of examining cultural, climatic and edaphic factors currently driving abundance and distribution. Long-distance transects were established across the middle-west region of Madagascar, over which Striga asiatica abundance in fields was estimated. Analysis of the data highlights the importance of crop variety and legumes in driving Striga density. Moreover, the dataset revealed significant effect of precipitation seasonality, mean temperature and altitude in determining abundance. A composite management index indicated the effect of a range of cultural practices on changes in Striga abundance. The findings support the assertion that single measures are not sufficient for the effective, long-term management of Striga. Furthermore, the composite score has potential as a significant guide of ISM control beyond the geographic range of this study.

Objective: To investigate the impact of the uterine corpus inclination on pregnancy outcomes in in vitro fertilization and embryo transfer (IVF-ET). Design: Retrospective cohort study. Setting: University-based reproductive medicine center. Population: 526 patients underwent their first frozen embryo transfer (FET) cycle. Methods: All patients underwent transvaginal ultrasound examination to measure the distance from the midline of uterine cavity to the ultrasound probe, which indirectly reflect the uterine corpus inclination. The uterine corpus tends toward the horizontal position as the average distance increases. Multivariable regression analysis was used to study the effect of the uterine corpus inclination on pregnancy outcomes, even in different embryo stage cohorts as subgroup analysis. Main outcomes measures: Clinical pregnancy rate (CPR), spontaneous abortion rate, and live birth rate (LBR). Results:The patients were grouped according to the quartiles of the average distance distribution (Group 1, ≤ 1.98 cm; Group 2, 1.99-2.19 cm; Group 3, 2.20-2.50 cm; Group 4, ≥ 2.51 cm). There were statistically significant differences in the CPR and LBR between Groups 1 and 4 in the cleavage-stage ET cohort (CPR: adjusted odds ratio [OR] 0.225, 95% confidence interval [CI] 0.068-0.774; LBR: adjusted OR 0.315, 95% CI 0.100-0.996) (P < 0.05). There were no significant differences among the four groups in pregnancy outcomes in the blastocyst transfer cohort (P > 0.05). The cut-off value of 2.146 cm was calculated to predict the pregnancy outcomes in the cleavage-stage ET cohort. Conclusion:The uterine corpus inclination might be an independent risk factor for the success of cleavage-stage ET

Nutritional deficiencies such as iron, vitamin B12 and folate are recognized as etiologies for several cytopenias; although copper’s role in multiple metabolic enzymes is well-established, copper deficiency is often overlooked as a contributing entity. Frequently diagnosis is delayed, patients may undergo bone marrow investigations with findings overlapping a myelodysplastic process, which can lead to further testing and treatment considerations including hematopoietic stem cell transplant referral. We present a case of a young boy with cystic fibrosis with biliary dysplasia corrected with hepato-portoenterostomy and distal intestinal obstruction syndrome resulting in jejunal resection, with severe anemia and thrombocytopenia requiring transfusion support. Initial evaluation had been unremarkable, ongoing pancytopenia prompted bone marrow studies, which revealed vacuolated granulocytic and erythroid precursors and ring sideroblasts, suggestive of copper deficiency. Serum copper and ceruloplasmin were consistent with severe deficiency, attributed to insufficient absorption intestinal resection, chronic parenteral nutrition and prior zinc supplementation. Following enteral copper supplementation, anemia, leukopenia and thrombocytopenia significantly improved, however upon cessation, counts again worsened and has since been maintained on daily copper supplementation without further transfusion needs. Our experience exemplifies the importance of early consideration for copper deficiency in children with cytopenias, especially within context of intestinal malabsorption or inadequate nutritional intake which often occurs in children with cystic fibrosis.

Medical Management of GDM – following the evidenceMini Commentary on 21-0353.R1 - “Changing Patterns in Medication Prescription for Gestational Diabetes During a Time of Guideline Change in the USA: A Cross-sectional Study ”Aaron B. Caughey, MD, PhDDepartment of Obstetrics and Gynecology; Oregon Health & Science University; Portland, ORCorrespondence:Aaron B. Caughey, MD, PhDProfessor and ChairDepartment of Obstetrics and GynecologyOregon Health & Sciences UniversityP: 503-494-2999F: 503-494-2391E: caughey@ohsu.eduGestational diabetes mellitus (GDM) is one of the most common pregnancy complications and is associated with numerous pregnancy complications including preeclampsia, preterm birth, stillbirth, cesarean delivery, fetal macrosomia, birth injury, neonatal hypoglycemia, childhood obesity in the offspring and other short- and long-term complications.(Sweeting AN, et al. Diabetes Care. 2016;39:75-81) Many of these complications appear to be associated with hyperglycemia, so tight control of maternal plasma glucose is the primary approach to management during pregnancy. The first line approach is usually a strict carbohydrate-controlled diet and exercise, but when this fails, medical therapy is indicated.For many years, the first-line medical approach was injectable insulin. However, an oral hypoglycemic agent, glyburide, was increasingly adopted after a trial of glyburide versus insulin demonstrated no statistical difference in the outcomes, though it was underpowered to do so.(Langer O, et al. N Engl J Med 2000;343:1134-8) Another oral agent, metformin, was studied in an adequately powered randomized trial that found no differences in outcomes between pregnancies treated with metformin versus insulin.(Rowan JA, et al. N Engl J Med 2008;358:2003-15) Perhaps because glyburide was already being used, or that metformin crosses the placenta, or an odd finding of a higher rate of preterm birth in the metformin group, there was little adoption of metformin after this trial. Other trials of these medications have been conducted and a systematic review in 2015 demonstrated that a number of outcomes were worse in women randomized to glyburide whereas there are no differences in women randomized to metformin.(Balsells M, et al. BMJ 2015;350:h102) These findings led the American College of Obstetricians and Gynecologists (ACOG) to change their recommendations to encourage insulin to be first-line treatment in 2017.(ACOG. Obstet Gynecol. 2017;130:e17-e37) A follow-up recommendation from ACOG broadened to include metformin as well.(ACOG. Obstet Gynecol. 2018 Feb;131(2):e49-e64)So, how have these data and the recommendations from ACOG changed practice patterns? In a paper published in BJOG this month, the authors examined the pharmacologic approaches to management in GDM.(Venkatesh KK, et al. BJOG, 2021) In a large cohort of over 10,000 individuals with GDM requiring medical therapy, they found that from 2015 to 2018, the use of insulin increased from 26% to 44%, the use of metformin increased from 17% to 29%, and the use of glyburide decreased from 58% to 27%. These data are from either side of the 2017 ACOG recommendation, but end in the same year as the follow-up recommendation. Given how long it can take for recommendations to be adopted by clinicians, one wonders how the practice patterns may have continued to evolve in 2019 and 2020.Recalling that the 2017 ACOG recommendation was to have insulin be first line for GDM, while the trend is in the right direction, it was still less than 50% as of 2018. While it is understandable that clinicians and patients want to prescribe an oral agent, insulin remains an effective medication with great safety data. Likely this is why it is recommended as first-line treatment by many organizations and hopefully, further trends towards its primary use will be seen.

IntroductionConsistent with World Health Organization (WHO) advice [1], Public Health England (PHE) recommends that healthcare workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) should use fluid resistant surgical masks type IIR (FRSMs) as respiratory protective equipment (RPE), unless aerosol generating procedures (AGPs) are being undertaken or are likely, when a filtering face piece 3 (FFP3) respirator should be used [2]. In recent guidance, an FFP3 respirator is recommended if “an unacceptable risk of transmission remains following rigorous application of the hierarchy of control” [3]. Conversely, guidance from the Centers for Disease Control and Prevention (CDC) recommends that HCWs caring for patients with COVID-19 should use an N95 or higher level respirator [4]. WHO guidance suggests that a respirator, such as FFP3, may be used for HCWs in the absence of AGPs if availability or cost is not an issue [1].A recent systematic review undertaken for PHE concluded that: “patients with SARS-CoV-2 infection who are breathing, talking or coughing generate both respiratory droplets and aerosols, but FRSM (and where required, eye protection) are considered to provide adequate staff protection” [5]. Nevertheless, FFP3 respirators are more effective in preventing aerosol transmission than FRSMs, and observational data suggests that they may improve protection for HCWs [6]. It has therefore been suggested that respirators should be considered as a means of affording the best available protection [7], and some organisations have decided to provide FFP3 (or equivalent) respirators to HCWs caring for COVID-19 patients, despite a lack of mandate from local or national guidelines [8].Data from the HCW testing programme at Cambridge University Hospitals NHS Foundation Trust (CUHNFT) during the first wave of the UK severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic indicated a higher incidence of infection amongst HCWs caring for patients with COVID-19, compared with those who did not [9]. Subsequent studies have confirmed this observation [10, 11]. This disparity persisted at CUHNFT in December 2020, despite control measures consistent with PHE guidance and audits indicating good compliance. The CUHNFT infection control committee therefore implemented a change of RPE for staff on “red” (COVID-19) wards from FRSMs to FFP3 respirators. In this study, we analyse the incidence of SARS-CoV-2 infection in HCWs before and after this transition.

Habitat protection, by itself, is not sufficient to conserve range-restricted species with disjunct populations. Indeed, it becomes critical to characterize gene flow among the populations and factors that influence functional connectivity in order to design effective conservation programs for such species. In this study, we genotyped 314 individuals of Ivesia webberi, a United States federally threatened Great Basin Desert perennial forb using six microsatellite loci, to estimate genetic diversity and population genetic structure, as well as rates and direction of gene flow among 16 extant I. webberi populations. We assessed the effects of Euclidean distance, landscape features, and ecological dissimilarity on the genetic structure of the sampled populations, while also testing for a relationship between I. webberi genetic diversity and diversity in the vegetative communities. The results show low levels of genetic diversity overall (He = 0.200–0.441; Ho = 0.192–0.605) and high genetic differentiation among populations. Genetic diversity was structured along a geographic gradient, congruent with patterns of isolation by distance. Populations near the species’ range core have relatively high genetic diversity, supporting a central-marginal pattern, while peripheral populations have lower genetic diversity, significantly higher genetic distances, higher relatedness, and evidence of genetic bottlenecks. Genotype cluster admixture results support a predominant west to east gene flow pattern for populations near the species’ range center, as well as smaller genotype clusters with a narrow north to south distribution and little admixture, suggesting that dispersal direction and distance vary on the landscape. Pairwise genetic distance strongly correlates with actual evapotranspiration and precipitation, indicating a role for isolation by environment, which the observed phenological mismatches among the populations also support. The significant correlation between pairwise genetic distance and dissimilarity in the soil seed bank suggest that annual regeneration of the floristic communities contributes to the maintenance of genetic diversity in I. webberi.

Objective: To compare the host and biomechanical response to a fully absorbable poly-4-hydroxybutyrate (P4HB) scaffold to the response to PP mesh in an animal model of vaginal POP surgery. Design: A study employing a sheep model Setting: KU Leuven Center for Surgical Technologies Population: 14 parous female Mule sheep Methods: P4HB scaffolds were surgically implanted in the posterior vaginal wall of sheep. The comparative PP mesh data were obtained from an identical protocol. Main outcome measures: Gross necropsy, histological and biomechanical evaluation of explants, and the in vivo P4HB scaffold degradation were evaluated at 60- and 180-days post-implantation. Results: Gross necropsy revealed no implant related adverse events using P4HB scaffolds. The tensile stiffness of the P4HB explants increased at 180-days (12.498 ± 2.66 N/mm (P=0.019)) as compared to 60-days (4.585 ± 1.57 N/mm) post-implantation, while P4HB degraded gradually. P4HB scaffolds exhibited excellent tissue integration with dense connective tissue and a moderate initial host response. P4HB scaffolds induced a significantly higher M2/M1 ratio (1.70 ± 0.67 SD, score 0-4), as compared to PP mesh (0.99 ± 0.78 SEM, score 0-4) at 180-days. Conclusions: P4HB scaffold facilitated a gradual load transfer to vaginal tissue over time. The fully absorbable P4HB scaffold, in comparison to PP mesh, has a favorable host response with comparable load bearing capacity. If these results are also observed at longer follow-up, a clinical study for vaginal POP surgery may be warranted to demonstrate efficacy. Key words: Pelvic organ prolapse, vaginal surgery, Poly-4-hydroxybutyrate, degradable scaffold, host response, biomechanics.

The aim of my clinical image is to recall this rare dermatological condition and to highlight instructions to follow in treatment and proper management of the complications that can arise.

The effects of the discharge of wastewater treatment plants (WWTP) on the status of rivers have most commonly been focused on water quality. A very limited number of works have characterised the ability of treatment plants to modify flow patterns in the receiving rivers. This paper presents a methodology for the assessment of the hydrologic alteration caused by WWTP discharges, over a two-fold sequence. The first phase comprises the application of indicators derived from accessible data and informative of the capacity of treatment plants to produce significant flow alterations. The second phase, which may only be carried out when flow data in the receiving river is available, is based on the indicators of hydrologic alteration provided by the free software IAHRIS (6 indicators) and IHA (2 indicators), and on a new indicator proposed in this paper to obtain information of flow alteration at seasonal and monthly time scales. The procedure suggested in this work is applied to the Manzanares River (Central Spain), allowing the quantification of the flow alteration generated by the 12 WWTP which give service to Madrid city (3.8 million inhabitants): Large increases of annual water volumes (from 108 hm3 to 410 hm3); at a monthly scale (increase from 246% to 1516%); variability in flow decreases in wet years by up to 47% and increases in dry years by up to 380%; seasonal patterns is altered within an altered regime. Results of the analysis show: (i) the ability of the proposed methodology to characterise the modification of flow patterns due to WWTP discharges; (ii) the importance of assessing such changes when evaluating the environmental impact of treatment plants; (iii) the importance of designing preventive and mitigation measures which maintain the ecological integrity of river ecosystems in the receiving channels.

We evaluated whether evolution is faster at ecotones as niche shifts may be needed to persist under unstable environment. We mapped diet evolution along the evolutionary history of 350 sigmodontine species. Mapping was used in three new tip-based metrics of trait evolution–Transition Rates, Stasis Time, and Last Transition Time–which were spatialized at the assemblage level (aTR, aST, aTL). Assemblages were obtained by superimposing range maps on points located at core and ecotone of the 91 South American ecoregions. Using Linear Mixed Models, we tested whether ecotones have species with more changes from the ancestral diet (higher aTR), have maintained the current diet for a shorter time (lower aST) and have more recent transitions to the current diet (lower aLT) than cores. We found higher aTR, aST and aLT at ecotones than at cores. Although ecotones are more heterogeneous, both environmentally and in relation to selection pressures they exert on organisms, ecotone species change little from the ancestral diet as generalist habits are necessary toward feeding in ephemeral environments. The need to incorporate phylogenetic uncertainty in tip-based metrics was evident from large uncertainty detected. Our study integrates ecology and evolution by analyzing how fast trait evolution is across space.

Immune modulation is a key therapeutic tool for allergic diseases and asthma. It can be achieved in an antigen-specific way via allergen immunotherapy (AIT) or in endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: IgE, IL-5 and IL-4/IL-13. COVID-19 vaccine provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. It works as well through immune modulation. Thus, as there is an obvious interference between these treatment modalities recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) gathered an outstanding expert panel under its Research and Outreach Committee (ROC). This expert panel was called to evaluate the evidence and formulate recommendation on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals.