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SARS-CoV-2 surface spike protein mediates the viral entry into the host cell and represents the primary immunological target of COVID-19 vaccines as well as post-exposure immunotherapy. Establishment of the highly immunogenic B-cell epitope profile of SARS-CoV-2 proteins in general, and that of the spike protein in particular, may contribute to the development of sensitive diagnostic tools and identification of vaccine` candidate targets. In the current study, the anti-viral antibody response in transgenic K18-hACE-2 mice was examined by implementing an immunodominant epitope mapping approach of the SARS-CoV-2 spike. Serum samples for probing an epitope array covering the entire spike protein were collected from mice following infection with the original SARS-CoV-2 strain as well as the B.1.1.7 Alpha and B.1.351 Beta genetic variants of concern. The analysis resulted in distinction of six linear epitopes common to the humoral response against all virus variants inspected at a frequency of more than 20% of the serum samples. Finally, the universality of the response was probed by cross-protective in vitro experiments using plaque-reducing neutralization tests. The data presented here has important implications for prediction of the efficacy of immune countermeasures against emerging SARS-CoV-2 variants.

To evaluate the characteristics and outcomes of women who had never delivered vaginally and underwent a trial of labor after cesarean (TOLAC) of small for gestational age (SGA) neonates, and to identify risk factors for unplanned repeat cesarean delivery. A retrospective cohort study from two tertiary medical centers. All women undergoing a TOLAC with no prior vaginal delivery, delivering a singleton SGA neonate at term between 2005 and 2020 were included. Factors associated with successful vaginal delivery were examined by a multivariable analysis. Of the 255 women who met the inclusion criteria and underwent TOLAC, 72.2% delivered vaginally. In a multivariable analysis, maternal height [adjusted odds ratio (aOR) (95% CI): 1.10 (1.02-1.19), p = 0.012] and epidural administration [aOR (95% CI): 2.78 (1.0-7.73), p = 0.050] were positively independently associated with TOLAC success, and hypertensive disorders were negatively independently associated with TOLAC success [aOR (95% CI): 0.52 (0.004-0.74), p = 0.029]. The success rate of TOLAC among women with no prior vaginal delivery, delivering a SGA neonate is relatively high. Maternal height, hypertensive disorders, and epidural administration are independent factors associated with TOLAC success. Epidural administration is a modifiable factor and should be taken in consideration during TOLAC management., (© 2021. Society for Reproductive Investigation.)

Background: Secondary organic aerosols (SOAs) formed from anthropogenic or biogenic gaseous precursors in the atmosphere substantially contribute to the ambient fine particulate matter [PM ≤ 2.5 μ m in aerodynamic diameter ( PM 2.5 )] burden, which has been associated with adverse human health effects. However, there is only limited evidence on their differential toxicological impact., Objectives: We aimed to discriminate toxicological effects of aerosols generated by atmospheric aging on combustion soot particles (SPs) of gaseous biogenic ( β -pinene ) or anthropogenic (naphthalene) precursors in two different lung cell models exposed at the air-liquid interface (ALI)., Methods: Mono- or cocultures of lung epithelial cells (A549) and endothelial cells (EA.hy926) were exposed at the ALI for 4 h to different aerosol concentrations of a photochemically aged mixture of primary combustion SP and β -pinene ( SOA β PIN -SP ) or naphthalene ( SOA NAP -SP ). The internally mixed soot/SOA particles were comprehensively characterized in terms of their physical and chemical properties. We conducted toxicity tests to determine cytotoxicity, intracellular oxidative stress, primary and secondary genotoxicity, as well as inflammatory and angiogenic effects., Results: We observed considerable toxicity-related outcomes in cells treated with either SOA type. Greater adverse effects were measured for SOA NAP -SP compared with SOA β PIN -SP in both cell models, whereas the nano-sized soot cores alone showed only minor effects. At the functional level, we found that SOA NAP -SP augmented the secretion of malondialdehyde and interleukin-8 and may have induced the activation of endothelial cells in the coculture system. This activation was confirmed by comet assay, suggesting secondary genotoxicity and greater angiogenic potential. Chemical characterization of PM revealed distinct qualitative differences in the composition of the two secondary aerosol types., Discussion: In this study using A549 and EA.hy926 cells exposed at ALI, SOA compounds had greater toxicity than primary SPs. Photochemical aging of naphthalene was associated with the formation of more oxidized, more aromatic SOAs with a higher oxidative potential and toxicity compared with β -pinene . Thus, we conclude that the influence of atmospheric chemistry on the chemical PM composition plays a crucial role for the adverse health outcome of emissions. https://doi.org/10.1289/EHP9413.

Acute myeloid leukemia (AML) is a highly aggressive disease with high relapse and mortality rates. Recent years have shown a surge in novel therapeutic development for AML, both in clinical and preclinical stages. These developments include targeted therapies based on AML-specific molecular signatures as well as more general immune modulation and vaccination studies. In this review, we will explore the evolving arena of AML therapy and suggest some intriguing connections between immune system modulation and targeted therapy. Improved understanding of the immune system involvement in various stages of the disease and the crosstalk between immune effectors, targeted therapy, and AML cells can provide a better framework for designing the next generation of AML therapies., (© 2021 Wiley-VCH GmbH.)

Somatic mutations have traditionally been associated with cancer, yet more recently, it was realized that they also appear in nontransformed cells beginning in early life. Remarkably, some of these mutations, commonly viewed as cancer driver mutations, are widely spread among cells of noncancerous tissues, sometimes affecting the majority of the tissue cells. This spreading process intensifies upon aging or exposure to extrinsic insults, such as UV irradiation, inhaling smoke, and inflammatory cues. Whereas classic driver mutations in normal cells are mostly viewed as a first step in the carcinogenesis process, here, we speculate that in certain states, they can play beneficial homeostatic roles while confronting stress and aging tissue repair., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: To report associations with visual function and quality of life (QOL) in artificial eye wearers., Methods: Multicentre, observational, cross-sectional, nationwide study, within the National Health Service England. Items were adopted from the National Eye Institute Visual Function Questionnaire, and incorporated in the National Artificial Eye Questionnaire (NAEQ). The NAEQ was completed by 951 respondents. Multiple regressions assessed associations between the QOL scores and the experiences of artificial eye wearers, their routine management, changes over time, baseline and demographic parameters., Results: Parameters predictive of a better QOL composite score included longer artificial eye wear (β = 0.18, p < 0.001), better appearance (β = 0.17, p < 0.001), better comfort (β = 0.14, p = 0.001), tumour-related anophthalmia (β = 0.13, p = 0.003), male gender (β = 0.13, p < 0.001), shorter period of adjustment to monocular vision (β = 0.12, p < 0.001) and use of soap for cleaning (β = 0.09, p = 0.046). The composite score continued to improve beyond 10 years of prosthesis wear (≤2 years mean 72.80 ± 1.65 versus >10 years mean 79.45 ± 0.70; p = 0.001). Both better prosthesis appearance (β = 0.14, p = 0.022) and improved motility (β = 0.13, p = 0.042) predicted a better dependency score. Use of lubricating ointment predicted a worse dependency score (β = 0.23, p = 0.003). Neither the frequency of removal, nor the cleaning frequency of the artificial eye correlated with QOL scales., Conclusions: Multiple factors in the artificial eye experience were found to predict visual function and QOL aspects. This study underscores the need to generate a dedicated QOL questionnaire for use in anophthalmic patients., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: The exclusion of pregnant women from initial COVID-19 messenger RNA vaccine trials raised hesitancy regarding the benefits of vaccination for pregnant women, hence little is known about vaccines' efficacy in this population., Objective: To determine the maternal-neonatal transplacental transfer of SARS-CoV-2 antibodies among vaccinated parturient women. A control group of COVID-19-recovered patients was included to compare the immunoglobulin G levels between vaccinated and recovered patients., Study Design: This is a prospective cohort study conducted in a single tertiary medical center in Israel between February and March 2021; parturient women vaccinated with the BNT162b2 messenger RNA vaccine during pregnancy were included and compared with COVID-19-recovered parturient women. SARS-CoV-2 immunoglobulin G antibodies were measured in maternal and cord sera, dried blood spot samples taken from newborns, and breast milk samples. The primary aim was to determine whether neonatal cord and dried blood spot samples were positive for SARS-CoV-2 antibodies and to evaluate the transfer ratio, defined as cord blood immunoglobulin G divided by maternal immunoglobulin G levels., Results: The study included 64 vaccinated parturient women and 11 parturient women who had COVID-19 during pregnancy. All maternal blood sera samples and 98.3% of the cord blood sera samples were positive for SARS-Cov-2 immunoglobulin G with median concentrations of 26.1 (interquartile range, 22.0-39.7) and 20.2 (interquartile range, 12.7-29.0), respectively. Similarly, 96.4% of neonatal blood spot samples and all breast milk samples were positive for SARS-CoV-2 immunoglobulin G with median concentrations of 11.0 (interquartile range, 7.2-12.8) and 4.9 (interquartile range, 3.8-6.0), respectively. There was a significant positive correlation between maternal serum levels of SARS-CoV-2 immunoglobulin G and cord blood (r=0.483; P=.0001), neonatal blood spot (r=0.515; P=.004), and breast milk levels (r=0.396; P=.005) of SARS-CoV-2 immunoglobulin G. The median placental transfer ratio of SARS-COV-2 immunoglobulin G was 0.77. Comparison of vaccinated and recovered COVID-19 patients revealed significantly higher SARS-CoV-2 immunoglobulin G levels in maternal serum and cord blood among vaccinated women (P<.0001)., Conclusion: Our study demonstrated the efficient transfer of SARS-CoV-2 immunoglobulin G across the placenta in women, vaccinated with the BNT162b2 messenger RNA vaccine during pregnancy, to their neonates, with a positive correlation between maternal serum and cord blood antibody concentrations. In addition to maternal protection against COVID-19, the vaccine may also provide neonatal humoral immunity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The multicenter randomized controlled trial Management of Myelomeningocele Study demonstrated that prenatal repair of open spina bifida by hysterotomy, compared with postnatal repair, decreases the need for ventriculoperitoneal shunting and increases the chances of independent ambulation. However, the hysterotomy approach is associated with risks that are inherent to the uterine incision. Fetal surgeons from around the world embarked on fetoscopic open spina bifida repair aiming to reduce maternal and fetal/neonatal risks while preserving the neurologic benefits of in utero surgery to the child., Objective: This study aimed to report the main obstetrical, perinatal, and neurosurgical outcomes in the first 12 months of life of children undergoing prenatal fetoscopic repair of open spina bifida included in an international registry and to compare these with the results reported in the Management of Myelomeningocele Study and in a subsequent large cohort of patients who received an open fetal surgery repair., Study Design: All known centers performing fetoscopic spina bifida repair were contacted and invited to participate in a Fetoscopic Myelomeningocele Repair Consortium and enroll their patients in a registry. Patient data entered into this fetoscopic registry were analyzed for this report. Fisher exact test was performed for comparison of categorical variables in the registry with both the Management of Myelomeningocele Study and a post-Management of Myelomeningocele Study cohort. Binary logistic regression analyses were used to assess the registry data for predictors of preterm birth at <30 weeks' gestation, preterm premature rupture of membranes, and need for postnatal cerebrospinal fluid diversion in the fetoscopic registry., Results: There were 300 patients in the fetoscopic registry, 78 in the Management of Myelomeningocele Study, and 100 in the post-Management of Myelomeningocele Study cohort. The 3 data sets showed similar anatomic levels of the spinal lesion, mean gestational age at delivery, distribution of motor function compared with upper anatomic level of the lesion in the neonates, and perinatal death. In the Management of Myelomeningocele Study (26.16±1.6 weeks) and post-Management of Myelomeningocele Study cohort (23.3 [20.2-25.6] weeks), compared with the fetoscopic registry group (23.6±1.4 weeks), the gestational age at surgery was lower (comparing fetoscopic repair group with the Management of Myelomeningocele Study; P<.01). After open fetal surgery, all patients were delivered by cesarean delivery, whereas in the fetoscopic registry approximately one-third were delivered vaginally (P<.01). At cesarean delivery, areas of dehiscence or thinning in the scar were observed in 34% of cases in the Management of Myelomeningocele Study, in 49% in the post-Management of Myelomeningocele Study cohort, and in 0% in the fetoscopic registry (P<.01 for both comparisons). At 12 months of age, there was no significant difference in the number of patients requiring treatment for hydrocephalus between those in the fetoscopic registry and the Management of Myelomeningocele Study., Conclusion: Prenatal and postnatal outcomes up to 12 months of age after prenatal fetoscopic and open fetal surgery repair of open spina bifida are similar. Fetoscopic repair allows for having a vaginal delivery and eliminates the risk of uterine scar dehiscence, therefore protecting subsequent pregnancies of unnecessary maternal and fetal risks., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Biomass burning (BB) is an important source of primary organic aerosols (POA). These POA contain a significant fraction of semivolatile organic compounds, and can release them into the gas phase during the dilution process in transport. Such evaporated compounds were termed "secondarily evaporated BB organic gases (SBB-OGs)" to distinguish them from the more studied primary emissions. SBB-OGs contribute to the formation of secondary organic aerosols (SOA) through reactions with atmospheric oxidants, and thus may influence human health and the Earth's radiation budget. In this study, tar materials collected from wood pyrolysis were taken as proxies for POA from smoldering-phase BB and were used to release SBB-OGs constantly in the lab. OH-initiated oxidation of the SBB-OGs in the absence of NO x was investigated using an oxidation flow reactor, and the chemical, optical, and toxicological properties of SOA were comprehensively characterized. Carbonyl compounds were the most abundant species in identified SOA species. Human lung epithelial cells exposed to an environmentally relevant dose of the most aged SOA did not exhibit detectable cell mortality. The oxidative potential of SOA was characterized with the dithiothreitol (DTT) assay, and its DTT consumption rate was 15.5 ± 0.5 pmol min -1 μg -1 . The SOA present comparable light scattering to BB-POA, but have lower light absorption with imaginary refractive index less than 0.01 within the wavelength range of 360-600 nm. Calculations based on Mie theory show that pure airborne SOA with atmospherically relevant sizes of 50-400 nm have a cooling effect; when acting as the coating materials, these SOA can counteract the warming effect brought by airborne black carbon aerosol., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

(1) Introduction: Most studies rely on in-hospital data to predict cardiovascular risk and do not include prehospital information that is substantially important for early decision making. The aim of the study was to define clinical parameters in the prehospital setting, which may affect clinical outcomes. (2) Methods: In this population-based study, we performed a retrospective analysis of emergency calls that were made by patients to the largest private emergency medical services (EMS) in Israel, SHL Telemedicine Ltd., who were treated on-site by the EMS team. Demographics, clinical characteristics, and clinical outcomes were analyzed. Mortality was evaluated at three time points: 1, 3, and 12 months' follow-up. The first EMS prehospital measurements of the systolic blood pressure (SBP) were recorded and analyzed. Logistic regression analyses were performed. (3) Results: A total of 64,320 emergency calls were included with a follow-up of 12 months post index EMS call. Fifty-five percent of patients were men and the mean age was 70.2 ± 13.1 years. During follow-up of 12 months, 7.6% of patients died. Age above 80 years (OR 3.34; 95% CI 3.03-3.69, p < 0.005), first EMS SBP ≤ 130 mm Hg (OR 2.61; 95% CI 2.36-2.88, p < 0.005), dyspnea at presentation (OR 2.55; 95% CI 2.29-2.83, p < 0001), and chest pain with ischemic ECG changes (OR 1.95; 95% CI 1.71-2.23, p < 0.001) were the highest predictors of 1 month mortality and remained so for mortality at 3 and 12 months. In contrast, history of hypertension and first EMS prehospital SBP ≥ 160 mm Hg were significantly associated with decreased mortality at 1, 3 and 12 months. (4) Conclusions: We identified risk predictors for all-cause mortality in a large cohort of patients during prehospital EMS calls. Age over 80 years, first EMS-documented prehospital SBP < 130 mm Hg, and dyspnea at presentation were the most profound risk predictors for short- and long-term mortality. The current study demonstrates that in prehospital EMS call settings, several parameters can be used to improve prioritization and management of high-risk patients.

The atmosphere plays an important role in transporting microorganisms on a global scale, yet the processes affecting the composition of the airborne microbiome, the aerobiome, are not fully outlined. Here we present the community compositions of bacteria and fungi obtained by DNA amplicon-sequencing of aerosol samples collected in a size-resolved manner during nine consecutive days in central Israel. The campaign captured dust events originating from the Sahara and the Arabian deserts, as well as days without dust ("clear days"). We found that the source of the aerosol was the main variable contributing to the composition of both fungal and bacterial communities. Significant differences were also observed between communities representing particles of different sizes. We show evidence for the significant transport of bacteria as cell-aggregates and/or via bacterial attachment to particles during dust events. Our findings further point to the mixing of local and transported bacterial communities, observed mostly in particles smaller than 0.6 μm in diameter, representing bacterial single cells. Fungal communities showed the highest dependence on the source of the aerosols, along with significant daily variability, and without significant mixing between sources, possibly due to their larger aerodynamic size and shorter atmospheric residence times. These results, obtained under highly varied atmospheric conditions, provide significant assurances to previously raised hypotheses and could set the course for future studies on aerobiome composition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gat, Reicher, Schechter, Alayof, Tarn, Wyld, Zimmermann and Rudich.)

The use of passively-administered neutralizing antibodies is a promising approach for the prevention and treatment of SARS-CoV-2 infection. Antibody-mediated protection may involve immune system recruitment through Fc-dependent activation of effector cells and the complement system. However, the role of Fc-mediated functions in the efficacious in-vivo neutralization of SARS-CoV-2 is not yet clear, and it is of high importance to delineate the role this process plays in antibody-mediated protection. Toward this aim, we have chosen two highly potent SARS-CoV-2 neutralizing human monoclonal antibodies, MD65 and BLN1 that target distinct domains of the spike (RBD and NTD, respectively). The Fc of these antibodies was engineered to include the triple mutation N297G/S298G/T299A that eliminates glycosylation and the binding to FcγR and to the complement system activator C1q. As expected, the virus neutralization activity ( in-vitro ) of the engineered antibodies was retained. To study the role of Fc-mediated functions, the protective activity of these antibodies was tested against lethal SARS-CoV-2 infection of K18-hACE2 transgenic mice, when treatment was initiated either before or two days post-exposure. Antibody treatment with both Fc-variants similarly rescued the mice from death reduced viral load and prevented signs of morbidity. Taken together, this work provides important insight regarding the contribution of Fc-effector functions in MD65 and BLN1 antibody-mediated protection, which should aid in the future design of effective antibody-based therapies.

The anxiety and anticipation that accompany pregnancy, labor, and delivery may be relieved by education, providing knowledge regarding the physiological process of childbirth. Intrapartum ultrasound is an available, simple, intuitive, real-time tool that enables visualization of the fetal head within the birth canal. Both the attending staff and expectant parent can assess its movements and descent in response to the pushing efforts during the active pushing phase. This review described the potential obstetrical and psychological advantages of intrapartum ultrasound in managing the active pushing phase., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Barker pioneered the idea that the epidemic of coronary heart disease in Western countries in the 20th century, which paradoxically coincided with improved standards of living and nutrition, has its origin in fetal life. Indeed, there is substantial evidence associating low birthweight because of fetal growth restriction with an increased risk of vascular disease in later adult life. These conclusions led to the second part of the Barker hypothesis, the thrifty phenotype, in which adaptation to undernutrition in fetal life leads to permanent metabolic and endocrine changes. Such changes are beneficial if the undernutrition persists after birth but may predispose the individual to obesity and impaired glucose tolerance if conditions improve. The hypothesis assumes that a poor nutrient supply during a critical period of in utero life may "program" a permanent structural or functional change in the fetus, thereby altering the distribution of cell types, gene expression, or both. The fetus, in response to placental undernutrition and to maintain sufficient vascular supply to the brain, decreases resistance to blood flow in the middle cerebral artery. Simultaneously, because of the limited blood supply to the fetus, the arterial redistribution process is accompanied by increased resistance to flow to other fetal vital organs, such as the heart, kidneys, liver, and pancreas. It may explain why individuals exposed to ischemic changes in utero develop dyslipidemia, lower nephron number, and impaired glucose tolerance, all factors contributing to metabolic syndrome later in life. Nevertheless, support for the hypotheses comes mainly from studies in rodents and retrospective epidemiologic studies. This review focused on ultrasound and Doppler studies of human fetal growth restriction in several fetal organs: the placenta, fetal circulation, brain, heart, kidneys, adrenal glands, liver, and pancreas. Support for the hypothesis was provided by animal studies involving conditions that create fetuses with growth restriction with effects on various fetal organs and by human studies that correlate impaired fetal circulation with the in utero development and function of fetal organs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To determine the rate of and risk factors for fetal and neonatal brain lesions following laser ablation for twin-to-twin transfusion syndrome (TTTS)., Methods: A retrospective cohort study of 83 women with monochorionic twin pregnancies who underwent ablation for TTTS at a single tertiary hospital. Post-laser survivors were followed-up with fetal neurosonogram every 2 weeks and fetal brain MRI at 28-32 weeks of gestation; post-natal brain imaging included neurosonogram. Cases with pre- and post-natal brain lesions were compared to those without., Results: 153 fetuses survived the immediate post-laser period and underwent brain imaging. Of these, 17 (11.11%) exhibited brain lesions on prenatal imaging studies, and 36 (32.4%) on post-natal ultrasound. Later gestational age (GA) at the time of ablation (23.0 vs. 21.4 weeks, p = 0.0244), post-laser twin-anemia-polycythemia-sequence (TAPS) (29.41% vs. 9.56%, p = 0.035) and birthweight discordancy (30% vs. 9%, p = 0.0025) were associated with prenatal brain lesions. Earlier GA at delivery (31.0 weeks vs. 32.2, p = 0.0002) and post-laser TAPS (25% vs. 9.33%, p = 0.038) were associated with post-natal brain lesions., Conclusions: Survivors of ablation for TTTS are at risk for brain lesions, which can be detected prenatally. Incorporation of neurosonogram and fetal brain MRI into the routine surveillance of such pregnancies should be considered., (© 2021 John Wiley & Sons Ltd.)

Objectives: Congenital portosystemic shunt (CPSS) in a growth-restricted fetus may lead to cardiac overload and ultimately hemodynamic imbalance. The aim of the study was to describe the application of tricuspid annular plane systolic excursion (TAPSE) for surveillance of cardiac function in growth-restricted fetuses diagnosed with CPSS., Methods: The study group consisted of 7 fetuses with growth restriction diagnosed with CPSS between 2018 and 2020. Patients were followed longitudinally every 2 weeks. Sonographic fetal-TAPSE (f-TAPSE) was performed every 2 weeks. At each visit, the following parameters were recorded: estimated fetal weight, biophysical profile, nonstress test, Doppler flow indices, and fetal cardiothoracic index. Postnatal laboratory and imaging tests were retrieved from the medical files., Results: Mean gestational age at diagnosis of CPSS was 32 + 1 weeks. Cardiomegaly was observed in all cases. All portosystemic shunts were classified as intrahepatic. Values of f-TAPSE were above the 95th percentile in 6/7 fetuses at presentation and throughout follow-up. Gestational age at delivery ranged between 36 + 5 and 38 + 5 weeks. Postnatally, spontaneous closure of the shunt was noted in 2 infants. Transient hyperammonemia was diagnosed in 2 neonates, with no signs of the characteristic complication., Conclusions: In growth-restricted fetuses diagnosed concomitantly with CPSS, f-TAPSE offers a practical sonographic tool for assessment of cardiac function and may serve as an additional clinical marker for follow-up. The appearance of cardiomegaly in growth-restricted fetuses should prompt a dedicated sonographic evaluation of the fetal portal system., (© 2021 American Institute of Ultrasound in Medicine.)

Pneumonic plague, caused by Yersinia pestis, is a rapidly progressing lethal infection. The various phases of pneumonic plague are yet to be fully understood. A well-established way to address the pathology of infectious diseases in general, and pneumonic plague in particular, is to conduct concomitant transcriptomic analysis of the bacteria and the host. The analysis of dual RNA by RNA sequencing technology is challenging, due the difficulties of extracting bacterial RNA, which is overwhelmingly outnumbered by the host RNA, especially at the critical early time points post-infection (prior to 48 h). Here, we describe a novel technique that employed the infusion of an RNA preserving reagent (RNAlater) into the lungs of the animals, through the trachea, under deep anesthesia. This method enabled the isolation of stable dual mRNA from the lungs of mice infected with Y. pestis , as early as 24 h post-infection. The RNA was used for transcriptomic analysis, which provided a comprehensive gene expression profile of both the host and the pathogen.

Objectives: To assess the prenatal growth pattern of the normal kidney contralateral to a multicystic dysplastic kidney (MCDK)., Methods: A retrospective study was conducted in a single referral center over 4 years. Cases diagnosed prenatally as MCDK and confirmed postnatally constituted the study group. For creation of nomograms, only isolated cases of MCDK were included., Results: Sixty-one fetuses had a diagnosis of an MCDK during the study period. After exclusion of cases with associated malformations, 47 fetuses remained, providing 94 measurements for creation of nomograms. The growth pattern of the normal kidney contralateral to an MCDK was linear throughout gestation (percentile = 20.01 + 1.5 gestational age; linear R 2  = 0.753; r = 0.868) and was significantly higher during the third trimester (29-38 weeks' gestation) compared to the second trimester (22-28 weeks' gestation; P < .001). A comparison of the growth pattern of the normal kidney contralateral to the MCDK to the growth pattern of a solitary kidney revealed a significant higher compensatory trend during the third trimester (P < .0001). The mean kidney lengths at 22 and 38 weeks' gestation correlated with the 52nd and 88th and with the 84th and 90th percentiles for the normal kidney contralateral to the MCDK and a solitary kidney, respectively., Conclusions: According to our study, the normal kidney contralateral to an MCDK has a unique growth pattern during intrauterine life, with dominant growth during the third trimester. The exact mechanism for this pattern, in comparison to early renal hypertrophy shown in solitary kidneys, is currently not clear. These data provide relevant information for the multidisciplinary prenatal counseling of future parents regarding the future renal outcome., (© 2020 American Institute of Ultrasound in Medicine.)

Objective: To determine maternal and neonatal outcomes among women undergoing second stage emergent cesarean delivery (ECD) versus vacuum-assisted delivery (VAD) of low birthweight neonates., Materials and Methods: A retrospective cohort study from two tertiary medical centers. We included women who underwent either ECD or VAD during the second stage of labor, and delivered neonates with a birthweight of <2500 g during 2011-2019. Characteristics and outcomes were compared between the groups. The primary outcome was the rate of a composite adverse neonatal outcome, defined as the presence of ≥1 of the following: Apgar 5 min < 7, respiratory distress syndrome, neonatal intensive care unit admission, mechanical ventilation and intrapartum fetal death., Results: The study cohort included 611 patients, of whom 46 had ECD and 565 had VAD. Baseline characteristics did not differ between the groups. The rate of Apgar score < 7 at 1 min was higher among the ECD group]10 (22%) vs. 29 (5%), OR (95% CI) 5.1 (2.3-11.3), p < 0.001[. Other neonatal and maternal outcomes were similar in both groups., Conclusions: Neonatal and maternal outcomes do not differ substantially between ECD and VAD of neonates weighing <2500 g. This information may be useful when contemplating the preferred mode of delivery in this setting., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background and Objective: Determine the ability of Lambda retinometry to predict post-cataract surgery visual acuity in vitrectomized eyes., Patients and Methods: Prospective study including 47 cataract surgery candidates with a history of pars plana vitrectomy (PPV). Lambda retinometry using a hand-held Lambda retinometer and best-corrected visual acuity (BCVA) were measured preoperatively, and BCVA was reassessed postoperatively., Results: Lambda predictions strongly correlated with postoperative BCVA (logarithm of the minimum angle of resolution [logMAR]) ( P < .001, r 2 = 0.57), especially combined with preoperative BCVA (logMAR) ( P < .001, r 2 = 0.65). In 89% of cases, postoperative BCVA was equal to or higher than the prediction. Neither cataract grades nor indications for PPV were associated with the accuracy of Lambda predictions ( P = .882 and P = .790, respectively). Underestimation of visual outcome was more common than overestimation. A Lambda prediction of ≥ 20/40 (Snellen) had a positive predictive value of 85.7% and a negative predictive value of 73.6% for the postoperative outcome., Conclusions: Lambda retinometry can reliably predict the postoperative BCVA in cataract patients who previously underwent PPV, with a tendency towards underestimation. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:535-542.] .

Aims: To compare the unique experiences related to artificial eye (AE) versus cosmetic shell (CS) wear., Methods: In this observational, cross-sectional study, the National Artificial Eye Questionnaire (NAEQ) was employed nationwide within the National Health Service England. The proportions or mean values of the aetiology of sight or eye loss, demographics, length of prosthesis wear, reported adjustment time to the prosthesis, comfort, discharge and satisfaction of appearance were compared between AE and CS respondents., Results: Overall, 951 respondents wore an AE, while 238 wore a CS. In both, trauma was the leading cause for the prosthesis (47.6% and 44.1%, respectively); however, these groups differed in the proportions of the other aetiologies (p<0.0001). AE respondents were generally older (p=0.002) and had longer overall prosthesis wear (p<0.0001) compared with CS respondents. The overall comfort score was similarly, relatively high in both AE and CS respondents (80.4±0.73 vs 81.41±1.45; p=0.51). The discharge-related patient satisfaction ranking was relatively low, in both groups, with a small trend towards worse discharge scores among AE wearers (59.41±0.76 vs 62.26±1.52, p=0.094). Self-reported length of time that has taken to adjust to wearing the prosthesis was not significantly different (p=0.17). Appearance of the eye (p=0.032) and motility of the prosthesis (p<0.0001) were ranked superior by CS respondents compared with AE., Conclusions: This study characterises unique aspects of CS versus AE in a large national cohort. The results should provide reinforcement to the gain in popularity of CS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Airborne microbial communities directly impact the health of humans, animals, plants, and receiving ecosystems. While airborne bacterial and fungal communities have been studied by both cultivation-based methods and metabarcoding surveys targeting specific molecular markers, fewer studies have used shotgun metagenomics to study the airborne mycobiome. We analyzed the diversity and relative abundance of fungi in nine airborne metagenomes collected on clear days ("background") and during dust storms in the Eastern Mediterranean. The negative correlation between the relative abundance of fungal reads and the concentrations of atmospheric particulate matter having an aerodynamic diameter smaller than 10 μm (PM10) indicate that dust storms lower the proportion of fungi in the airborne microbiome, possibly due to the lower relative abundance of fungi in the dust storm source regions and/or more effective transport of bacteria by the dust. Airborne fungal community composition was altered by the dust storms, particularly those originated from Syria, which was enriched with xerophilic fungi. We reconstructed a high-quality fungal metagenome-assembled genome (MAG) from the order Cladosporiales, which include fungi known to adapt to environmental extremes commonly faced by airborne microbes. The negative correlation between the relative abundance of Cladosporiales MAG and PM10 concentrations indicate that its origin is dominated by local sources and likely includes the indoor environments found in the city.

Sea spray aerosol (SSA) formation have a major role in the climate system, but measurements at a global-scale of this micro-scale process are highly challenging. We measured high-resolution temporal patterns of SSA number concentration over the Atlantic Ocean, Caribbean Sea, and the Pacific Ocean covering over 42,000 km. We discovered a ubiquitous 24-hour rhythm to the SSA number concentration, with concentrations increasing after sunrise, remaining higher during the day, and returning to predawn values after sunset. The presence of dominating continental aerosol transport can mask the SSA cycle. We did not find significant links between the diel cycle of SSA number concentration and diel variations of surface winds, atmospheric physical properties, radiation, pollution, nor oceanic physical properties. However, the daily mean sea surface temperature positively correlated with the magnitude of the day-to-nighttime increase in SSA concentration. Parallel diel patterns in particle sizes were also detected in near-surface waters attributed to variations in the size of particles smaller than ~1 µm. These variations may point to microbial day-to-night modulation of bubble-bursting dynamics as a possible cause of the SSA cycle., (© 2021. The Author(s).)

A wide range of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing monoclonal antibodies (mAbs) have been reported, most of which target the spike glycoprotein. Therapeutic implementation of these antibodies has been challenged by emerging SARS-CoV-2 variants harboring mutated spike versions. Consequently, re-assessment of previously identified mAbs is of high priority. Four previously selected mAbs targeting non-overlapping epitopes are now evaluated for binding potency to mutated RBD versions, reported to mediate escape from antibody neutralization. In vitro neutralization potencies of these mAbs, and two NTD-specific mAbs, are evaluated against two frequent SARS-CoV-2 variants of concern, the B.1.1.7 Alpha and the B.1.351 Beta. Furthermore, we demonstrate therapeutic potential of three selected mAbs by treatment of K18-human angiotensin-converting enzyme 2 (hACE2) transgenic mice 2 days post-infection with each virus variant. Thus, despite the accumulation of spike mutations, the highly potent MD65 and BL6 mAbs retain their ability to bind the prevalent viral mutants, effectively protecting against B.1.1.7 and B.1.351 variants., Competing Interests: Declaration of interests Patent application for the described antibodies was filed by the Israel Institute for Biological Research. None of the authors declared any additional competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Blood-contaminated fingermarks (FMs) found in violent crime scenes may directly connect the suspect to the crime by linking the FM to the suspect and the DNA from the blood to the victim. However, marks that are incomparable are considered "dead-evidence" as the link to the suspect is lost. In this study, a novel approach was attempted to uncover the trace amount of touch DNA of the suspect in such marks. We examined the effect of two enhancement methods, ninhydrin (NIN) and amido black (AB), on DNA recovery from blood-contaminated FMs. A total of 108 fingerprints were deposited in three sets of depleted blood prints, blood-contaminated FMs, and latent FMs. All FMs were developed by either NIN or AB, or left undeveloped as reference followed by the quantification of the total DNA amount. This work shows that while AB had a detrimental effect on the quantity of blood-derived DNA specifically, reducing it by half, no similar effect was observed for touch DNA in latent FMs. This reduction led to the alteration of the major-to-minor DNA profile ratio to 70:30, thus enabling to obtain two distinct DNA profiles of the suspect from the touch DNA as well as the victim's profile from the blood. From an operational perspective, the use of AB in crime scenes may have an added value to retrieve the crucial DNA profile of the suspect, thus resurrecting a "dead-evidence.", (© 2021 American Academy of Forensic Sciences.)

SARS-CoV-2 variants of interest and concern will continue to emerge for the duration of the COVID-19 pandemic. To map mutations in the receptor-binding domain (RBD) of the spike protein that affect binding to angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2, we applied in vitro evolution to affinity-mature the RBD. Multiple rounds of random mutagenic libraries of the RBD were sorted against decreasing concentrations of ACE2, resulting in the selection of higher affinity RBD binders. We found that mutations present in more transmissible viruses (S477N, E484K and N501Y) were preferentially selected in our high-throughput screen. Evolved RBD mutants include prominently the amino acid substitutions found in the RBDs of B.1.620, B.1.1.7 (Alpha), B1.351 (Beta) and P.1 (Gamma) variants. Moreover, the incidence of RBD mutations in the population as presented in the GISAID database (April 2021) is positively correlated with increased binding affinity to ACE2. Further in vitro evolution increased binding by 1,000-fold and identified mutations that may be more infectious if they evolve in the circulating viral population, for example, Q498R is epistatic to N501Y. We show that our high-affinity variant RBD-62 can be used as a drug to inhibit infection with SARS-CoV-2 and variants Alpha, Beta and Gamma in vitro. In a model of SARS-CoV-2 challenge in hamster, RBD-62 significantly reduced clinical disease when administered before or after infection. A 2.9 Å cryo-electron microscopy structure of the high-affinity complex of RBD-62 and ACE2, including all rapidly spreading mutations, provides a structural basis for future drug and vaccine development and for in silico evaluation of known antibodies., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: To determine the immunogenicity and reactogenicity of the Pfizer/BioNTech BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine among pregnant women compared with non-pregnant women, and to evaluate obstetric outcome following vaccination., Methods: This was an observational case-control study of pregnant women who were vaccinated with a two-dose regimen of the BNT162b2 vaccine during gestation between January and February 2021 (study group) and age-matched non-pregnant women who received the vaccine during the same time period (control group). Participants received a digital questionnaire 1-4 weeks after the second dose and were asked to provide information regarding demographics, medication, medical history, history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, timing of COVID-19 vaccine doses and side effects after each vaccine dose. A second digital questionnaire, regarding current pregnancy and delivery outcomes, was sent to patients in the study group after the calculated due date. All recruited women were offered a serology blood test for SARS-CoV-2 immunoglobulin G (IgG) following the second vaccination dose and SARS-CoV-2 IgG levels were compared between the two groups., Results: Of 539 pregnant women who were recruited after completion of the two-dose regimen of the vaccine, 390 returned the digital questionnaire and were included in the study group and compared to 260 age-matched non-pregnant vaccinated women. The rates of rash, fever and severe fatigue following vaccination among pregnant women were comparable to those in non-pregnant women. Myalgia, arthralgia and headache were significantly less common among pregnant women after each dose, local pain or swelling and axillary lymphadenopathy were significantly less common among pregnant women after the first and second doses, respectively, while paresthesia was significantly more common among the pregnant population after the second dose. Among pregnant women, there were no significant differences in the rates of side effects according to whether the vaccine was administered during the first, second or third trimester of pregnancy, except for local pain/swelling, which was significantly less common after the first dose when administered during the third trimester, and uterine contractions, which were significantly more common after the second dose when administered during the third trimester. The rates of obstetric complications, including uterine contractions (1.3% after the first dose and 6.4% after the second dose), vaginal bleeding (0.3% after the first dose and 1.5% after the second dose) and prelabor rupture of membranes (0% after the first dose and 0.8% after the second dose), were very low following vaccination. All serum samples in both groups were positive for SARS-CoV-2 IgG. However, pregnant women had significantly lower serum SARS-CoV-2 IgG levels compared to non-pregnant women (signal-to-cut-off ratio, 27.03 vs 34.35, respectively; P < 0.001). Among the 57 pregnant women who delivered during the study period and who completed the second questionnaire, median gestational age at delivery was 39.5 (interquartile range, 38.7-40.0) weeks, with no cases of preterm birth < 37 weeks, no cases of fetal or neonatal death and two (3.5%) cases of admission to the neonatal intensive care unit for respiratory support., Conclusions: The adverse-effect profile and short-term obstetric and neonatal outcomes among pregnant women who were vaccinated with the BNT162b2 vaccine at any stage of pregnancy do not indicate any safety concerns. The vaccine is effective in generating a humoral immune response in pregnant women, although SARS-CoV-2 IgG levels were lower than those observed in non-pregnant vaccinated women. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Purpose: To evaluate the prevalence of a spectrum of autoantibodies in adult patients with non-infectious uveitis compared to healthy controls., Methods: This is a case-control study conducted in a tertiary referral center. Serum positivity to auto-antibodies directed at membranous phospholipids (aPL), nuclear antigens, and cytoplasmic (ANCA) antigens were assessed in sera from 63 non-infectious uveitis patients, and 78 healthy controls. Uveitis patients' demographic and clinical data were collected retrospectively from their medical charts., Results: Of the spectrum of antibodies evaluated only aPL were linked with uveitis (OR 11.2, CI 1.4-92.1), as 13 (20.6%) uveitis patients were positive to at least one of the screened aPL, namely either anti-cardiolipin (aCL), anti-β2-glycoprotein (aβ2GPI), or anti-phosphatidylserine/prothrombin (aPS/PT). aCL antibodies were detected in 5/63 (7.9%) of uveitis patients and in none of controls ( p  = 0.016). Positivity to either aCL or aβ2GPI was noted in 8/63 (12.7%) of uveitis patients and in 1 (1.3%) of the controls ( p  = 0.011). Of the 13 uveitis patients positive to any of the aPL antibodies, 8 (62%) had exclusively anterior uveitis, 9 (69%) were idiopathic, and none had evidence of posterior vaso-occlusive involvement or systemic thrombotic manifestations., Conclusion: An association between aPL and uveitis among an unselected population of patients with no evidence of thrombosis or presence of the antiphospholipid syndrome was documented in this study. This link was observed, alike the general population of uveitis patients, mainly in patients with anterior eye inflammation. A possible interaction between aPL and uveitis, mediated by non-thrombotic mechanisms, requires further studies.

Adult-onset xanthogranuloma (AOX) typically affects the preseptal and anterior orbital regions. The authors report a 49-year-old man with a 6-month history of unilateral AOX, demonstrating diffuse extraconal and intraconal orbital involvement, including the lacrimal gland and extraocular muscles. There was frontal nerve enlargement, intracranial and pterygopalatine fossa involvement. Investigations excluded IgG4 disease and Erdheim-Chester disease. This case illustrates that AOX may be added to the causes of orbital nerve enlargement and may demonstrate intracranial extension., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2021 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Introduction: Maternal glycemic state is positively correlated with fetal insulin secretion. Randomized control studies have shown that treatment during pregnancy inhibits to some degree this glycemic effect. Our study aimed to assess fetal pancreas size in a population of treated mothers with gestational diabetes., Material and Methods: A cross-sectional, prospective observational study was conducted. Pregnant women at 19-36 weeks of gestation with pre-gestational diabetes receiving insulin therapy or with gestational diabetes receiving either insulin or oral hypoglycemic therapy were recruited. The fetal pancreas circumference was measured and compared to the normal reference range. The Z score of the difference between measured and normal predicted mean pancreas circumference, the regression analysis throughout pregnancy, and the correlation between estimated fetal weight centile and pancreas circumference were calculated., Results: Ninety-one women who had gestational diabetes and thirty-four women who had pre-gestational diabetes were included in the study. For both groups, fetal pancreas circumference correlated significantly with abdominal circumference, estimated fetal weight and gestational age. The mean Z score between the predicted pancreas circumference in the group of women diagnosed with gestational diabetes and the predicted pancreas circumference in a normal population peaked at around 24 weeks of gestation (1.1) and decreased gradually afterward to a value of zero at 37 weeks. The mean Z score between the predicted pancreas circumference in the group of women with pre-gestational diabetes and the predicted pancreas circumference in a normal population constantly decreased with duration of pregnancy. It was positive until the 25 th week of gestation and then presented negative values towards the term., Conclusions: The presented preliminary data suggest a possible correlation between glycemic control treatment, pancreas size, and gestational age., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2021 Termedia & Banach.)

Objective: To evaluate the effect of the coronavirus disease 2019 (COVID-19) mask-wearing on hematological laboratory components and obstetrical outcomes among women delivering during the COVID-19 pandemic., Methods: Laboratory results and obstetrical outcomes of women with singleton gestations, admitted for delivery during the COVID-19 mask-wearing period (April-June 2020) were compared with those of women delivering during the parallel period in 2019 and with a larger cohort derived from nine pre-pandemic years (March 2011-April 2020)., Results: Overall, 1838 women delivered during the COVID-19 pandemic. Compared with the pre-pandemic period, mean hemoglobin and fibrinogen levels were significantly higher during the mask-wearing period (12.15 ± 1.1 vs 11.96 ± 1.2, P < 0.001 and 472 ± 103.6 vs 448 ± 85.1 mg/dl, P < 0.001, respectively). Platelet levels were lower (200 ± 56.0 vs 206 ± 57.5 K/µl, P < 0.001). The rate of delivery at <34 weeks of gestation was lower during the mask-wearing period (1.1% vs 2%, odds ratio [OR] 0.57, 95% confidence intervals [CI] 0.37-0.88, P = 0.01), whereas cesarean delivery and postpartum hemorrhage rates were higher (26.7% vs 24.4%, OR 1.13, 95% CI 1.02-1.25, P = 0.022 and 4.1% vs 2.8%, OR 1.5, 95% CI 1.2-1.8, P = 0.001, respectively)., Conclusion: A hard-to-ventilate space created by wearing a mask during the COVID-19 era may be the underlying cause of the observed higher hemoglobin level among pregnant women, possibly affecting obstetrical outcomes., (© 2021 International Federation of Gynecology and Obstetrics.)

Objectives: To report associations with comfort and with appearance satisfaction in artificial eye wearers., Methods: Multicentre, observational, cross-sectional study, nationwide within the National Health Service England. The National Artificial Eye Questionnaire (NAEQ) was completed by 951 respondents. Multiple regressions assessed associations between the experiences of artificial eye wearers, routine management, changes over time, baseline and demographic parameters and their reported comfort, satisfaction with appearance and prosthesis motility., Results: Better comfort levels were associated with needing less lubrication (β = 0.24, p < 0.001), older age (β = 0.17, p = 0.014), less discharge (β = 0.16, p < 0.001), less frequent cleaning (β = 0.16, p = 0.043), and male gender (β = 0.06, p = 0.047). Greater satisfaction with the appearance of the artificial eye was associated with better perceived motility (β = 0.57, p < 0.001). Black ethnic origin predicted a lower satisfaction with the appearance (β = -0.17, p = 0.001). Greater satisfaction with the motility was associated with a better appearance rating (β = 0.51, p < 0.001), longer time of having an artificial eye (β = 0.13, p < 0.001), older age (β = 0.11, p = 0.042), and a shorter adjustment time (β = -0.07, p = 0.016). Of the testimonials concerning appearance aspects, the majority (21/45, 46.7%) were related to the effect on social interactions., Conclusions: The results suggest that more attention should be given to the "dry anophthalmic socket syndrome" as a key cause of discomfort. Young patients are concerned particularly about the motility of the artificial eye. Over time satisfaction with the artificial eye movement is likely to improve., (© 2020. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Personal exposure PM samples aid in determining the sources and chemical composition of real-world exposures, particularly in settings with household air pollution. However, their use in toxicological research is limited, despite uncertainty regarding health effects in these settings and evidence of differential toxicity among PM 2.5 sources and components. This study used women's PM 2.5 exposure samples collected using personal exposure monitoring in rural villages in three Chinese provinces (Beijing, Shanxi, and Sichuan) during summer and winter. Water-soluble organic carbon, ions, elements, and organic tracers ( e.g. levoglucosan and polycyclic aromatic hydrocarbons [PAHs]) were quantified in water and organic PM 2.5 extracts. Human lung epithelial cells (A549) were exposed to the extracts. Cell death, reactive oxygen species (ROS), and gene expression were measured. Biomass burning contributions were higher in Sichuan samples than in Beijing or Shanxi. Some PM characteristics (total PAHs and coal combustion source contributions) and biological effects of organic extract exposures (cell death, ROS, and cytokine gene expression) shared a common trend of higher levels and effects in winter than in summer for Shanxi and Beijing but no seasonal differences in Sichuan. Modulation of phase I/AhR-related genes (cyp1a1 and cyp1b1) and phase II/oxidative stress-related genes (HO-1, SOD1/2, NQO-1, and catalase) was either low or insignificant, without clear trends between samples. No significant cell death or ROS production was observed for water extract treatments among all sites and seasons, even at possible higher concentrations tested. These results support organic components, particularly PAHs, as essential drivers of biological effects, which is consistent with some other evidence from ambient PM 2.5 ., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Fetal urinoma is defined as an encapsulated accumulation of extravasated urine within the perirenal space or retroperitoneum. It is an uncommon finding in prenatal practice, and the vast majority of known cases are strongly associated with the existence of a urinary obstruction, such as posterior urethral valves, ureteropelvic junction obstruction, or ureterocele. We report a unique case of prenatally detected fetal bladder urinoma that occurred in the absence of an apparent obstructive uropathy, but was associated with extensive ischemic necrosis and calcifications of adjacent bladder wall, coexistent with signs of vascular supply decompensation.

Background: Ursodeoxycholic acid is commonly used to treat intrahepatic cholestasis of pregnancy, yet its largest trial detected minimal benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission). We aimed to examine whether ursodeoxycholic acid affects specific adverse perinatal outcomes., Methods: In this systematic review and individual participant data meta-analysis, we searched PubMed, Web of Science, Embase, MEDLINE, CINAHL, Global Health, MIDIRS, and Cochrane without language restrictions for relevant articles published between database inception, and Jan 1, 2020, using search terms referencing intrahepatic cholestasis of pregnancy, ursodeoxycholic acid, and perinatal outcomes. Eligible studies had 30 or more study participants and reported on at least one individual with intrahepatic cholestasis of pregnancy and bile acid concentrations of 40 μmol/L or more. We also included two unpublished cohort studies. Individual participant data were collected from the authors of selected studies. The primary outcome was the prevalence of stillbirth, for which we anticipated there would be insufficient data to achieve statistical power. Therefore, we included a composite of stillbirth and preterm birth as a main secondary outcome. A mixed-effects meta-analysis was done using multi-level modelling and adjusting for bile acid concentration, parity, and multifetal pregnancy. Individual participant data analyses were done for all studies and in different subgroups, which were produced by limiting analyses to randomised controlled trials only, singleton pregnancies only, or two-arm studies only. This study is registered with PROSPERO, CRD42019131495., Findings: The authors of the 85 studies fulfilling our inclusion criteria were contacted. Individual participant data from 6974 women in 34 studies were included in the meta-analysis, of whom 4726 (67·8%) took ursodeoxycholic acid. Stillbirth occurred in 35 (0·7%) of 5097 fetuses among women with intrahepatic cholestasis of pregnancy treated with ursodeoxycholic acid and in 12 (0·6%) of 2038 fetuses among women with intrahepatic cholestasis of pregnancy not treated with ursodeoxycholic acid (adjusted odds ratio [aOR] 1·04, 95% CI 0·35-3·07; p=0·95). Ursodeoxycholic acid treatment also had no effect on the prevalence of stillbirth when considering only randomised controlled trials (aOR 0·29, 95% CI 0·04-2·42; p=0·25). Ursodeoxycholic acid treatment had no effect on the prevalence of the composite outcome in all studies (aOR 1·28, 95% CI 0·86-1·91; p=0·22), but was associated with a reduced composite outcome when considering only randomised controlled trials (0·60, 0·39-0·91; p=0·016)., Interpretation: Ursodeoxycholic acid treatment had no significant effect on the prevalence of stillbirth in women with intrahepatic cholestasis of pregnancy, but our analysis was probably limited by the low overall event rate. However, when considering only randomised controlled trials, ursodeoxycholic acid was associated with a reduction in stillbirth in combination with preterm birth, providing evidence for the clinical benefit of antenatal ursodeoxycholic acid treatment., Funding: Tommy's, the Wellcome Trust, ICP Support, and the National Institute for Health Research., Competing Interests: Declaration of interests CO and H-UM are consultants for Mirum Pharmaceuticals. CW is a consultant for Mirum Pharmaceuticals and GlaxoSmithKline. KK is an unpaid consultant for Myriad Pharmaceuticals. WMH reports non-financial support from the Falk Foundation, during the conduct of the study, and is co-author of the Cochrane review on pharmacological interventions for treating intrahepatic cholestasis of pregnancy.(14) RMT reports grants from Tommy's and the Lauren Page Trust during the conduct of the study. All other authors declare no competing interests., (Copyright © 2021 The Authors(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To compare refractive surgery outcomes in patients with different periods without contact lenses prior laser surgery., Materials and Methods: Patients included in this study underwent myopic keratorefractive laser surgery between January 2005 and December 2014. Patients were divided into three groups based on the duration of time passed free of soft contact lens wearing prior to final preoperative evaluation and surgery (<24 h, 1-3 days or >3 days). Spectacle wearers served as a control group. Postoperative safety index, efficacy index and % of eyes within 0.5 D of the four groups were compared. A general linear model was used to compare main outcomes while adjusting for age, gender, preoperative measurements, and procedure type (LASIK vs PRK)., Results: Overall, 19,747 eyes were included. Soft contact lenses were worn by 42.3% (<24 h: 4.8%, 1-3 days: 18.5% and >3 days: 19.0%) and spectacles by 57.7% prior to surgery. In the PRK group, after adjusting for differences in baseline variables, the <24-h group had a significantly lower efficacy index than all the other groups. There were no significant differences between groups in terms of % eyes within ±0.5 D of intended correction ( p  = 0.55) or safety index (0.20). In the LASIK group, after adjusting for differences in baseline variables, there were no significant differences between groups in all primary outcomes., Conclusion: Soft contact lenses should be removed at least 24 h prior to final preoperative evaluation and refractive surgery, especially for patients undergoing PRK.

Widespread smoke from wildfires and biomass burning contributes to air pollution and the deterioration of air quality and human health. A common and major emission of biomass burning, often found in collected smoke particles, is spherical wood tar particles, also known as "tar balls". However, the toxicity of wood tar particles and the mechanisms that govern their health impacts and the impact of their complicated chemical matrix are not fully elucidated. To address these questions, we generated wood tar material from wood pyrolysis and isolated two main subfractions: water-soluble and organic-soluble fractions. The chemical characteristics as well as the cytotoxicity, oxidative damage, and DNA damage mechanisms were investigated after exposure of A549 and BEAS-2B lung epithelial cells to wood tar. Our results suggest that both wood tar subfractions reduce cell viability in exposed lung cells; however, these fractions have different modes of action that are related to their physicochemical properties. Exposure to the water-soluble wood tar fraction increased total reactive oxygen species production in the cells, decreased mitochondrial membrane potential (MMP), and induced oxidative damage and cell death, probably through apoptosis. Exposure to the organic-soluble fraction increased superoxide anion production, with a sharp decrease in MMP. DNA damage is a significant process that may explain the course of toxicity of the organic-soluble fraction. For both subfractions, exposure caused cell cycle alterations in the G2/M phase that were induced by upregulation of p21 and p16. Collectively, both subfractions of wood tar are toxic. The water-soluble fraction contains chemicals (such as phenolic compounds) that induce a strong oxidative stress response and penetrate living cells more easily. The organic-soluble fraction contained more polycyclic aromatic hydrocarbons (PAHs) and oxygenated PAHs and induced genotoxic processes, such as DNA damage.

The composition of organic aerosol has a pivotal influence on aerosol properties such as toxicity and cloud droplet formation capability, which could affect both climate and air quality. However, a comprehensive and fundamental understanding of the chemical and physical processes that occur in nanometer-sized atmospheric particles remains a challenge that severely limits the quantification and predictive capabilities of aerosol formation pathways. Here, we investigated the effects of a fundamental and hitherto unconsidered physical property of nanoparticles-the Laplace pressure. By studying the reaction of glyoxal with ammonium sulfate, both ubiquitous and important atmospheric constituents, we show that high pressure can significantly affect the chemical processes that occur in atmospheric ultrafine particles (i.e., particles < 100 nm). Using high-resolution mass spectrometry and UV-vis spectroscopy, we demonstrated that the formation of reaction products is strongly (i.e., up to a factor of 2) slowed down under high pressures typical of atmospheric nanoparticles. A size-dependent relative rate constant is determined and numerical simulations illustrate the reduction in the production of the main glyoxal reaction products. These results established that the high pressure inside nanometer-sized aerosols must be considered as a key property that significantly impacts chemical processes that govern atmospheric aerosol growth and evolution.

Objective: To report our experience with targeted scans of the fetal pancreas., Methods: Targeted scans were performed in 16 cases referred for anatomical or genetic conditions associated with structural pancreatic malformations., Results: Four fetuses were evaluated for nephromegaly and macroglossia. In three of them, the pancreas circumference was >90th percentile. Genetic testing revealed Beckwith-Wiedemann syndrome. In the fourth case, the pancreas circumference was normal; exome sequencing revealed two heterozygous ETFDH gene mutations consistent with glutaric acidemia type II. In a case referred for non-visualization of the gallbladder, the fetal pancreas was not visualized and genetic analysis revealed a mutation in the ONECUT1 gene encoding for HNF6. Targeted scan for heterotaxia revealed three cases with variable degrees of agenesis of the pancreas, one case with a normally structured right sided pancreas and one case with a normal pancreas. Cases referred following a genetic diagnosis included a case of maternal nesidioblastosis with an extremely large fetal pancreas; and five fetuses diagnosed with a TCF2 deletion all with a normal pancreas., Conclusions: Prenatal assessment of the fetal pancreas may be a significant factor in prenatal diagnosis and counselling in cases presenting with anatomical and genetic conditions reported post-natally to be associated with pancreatic structural and functional abnormalities., (© 2021 John Wiley & Sons Ltd.)

A method for the calculation of elastic constants in the NVT ensamble using molecular dynamics (MD) simulation with a realistic many-body embedded-atom-model (EAM) potential is studied in detail. It is shown that, in such NVT MD simulations, the evaluation of elastic constants is robust and accurate because it gives the elastic tensor in a single simulation which converges using a small number of time steps and particles. These results highlight the applicability of this method in (i) the calculation of local elastic constants of nonhomogeneous crystalline materials and (ii) the calibration of interatomic potentials, as a fast and accurate alternative to the common method of explicit deformation, which requires a set of consistent simulations at different conditions. The method is demonstrated for the calculation of the elastic constants of copper in the temperature range of 0-1000 K, and results agree with the target values used for the potential calibration. The various contributions to the values of the elastic constants, namely, the Born, stress fluctuation, and ideal gas terms, are studied as a function of temperature.

Key Message: Among SARS-CoV-2-infected mothers, vaginal delivery rates were high and associated with favorable outcomes with no cases of neonatal COVID-19., Purpose: To investigate the mode of delivery and its impact on immediate neonatal outcome in SARS-CoV-2-infected women., Methods: A prospective study following pregnant women diagnosed with COVID-19 who delivered between March 15th and July 4th in seven university affiliated hospitals in Israel., Results: A total of 52 women with a confirmed diagnosis of COVID-19 delivered in the participating centers during the study period. The median gestational age at the time of delivery was 38 weeks, with 16 (30.8%) cases complicated by spontaneous preterm birth. Forty-three women (82.7%) underwent a trial of labor. The remaining 9 women underwent pre-labor cesarean delivery mostly due to obstetric indications, whereas one woman with a critical COVID-19 course underwent urgent cesarean delivery due to maternal deterioration. Among those who underwent a trial of labor (n = 43), 39 (90.7%) delivered vaginally, whereas 4 (9.3%) cases resulted in cesarean delivery. Neonatal RT-PCR nasopharyngeal swabs tested negative in all cases, and none of the infants developed pneumonia. No maternal and neonatal deaths were encountered., Conclusions: In this prospective study among SARS-CoV-2-infected mothers, vaginal delivery rates were high and associated with favorable outcomes with no cases of neonatal COVID-19. Our findings underscore that delivery management among SARS-CoV-2-infected mothers should be based on obstetric indications and may potentially reduce the high rates of cesarean delivery previously reported in this setting.

Objective: Identify placental pathology-related complications, labor and neonatal outcomes in pregnancies complicated by pathological nuchal translucency (NT) with normal microarray analysis., Methods: A retrospective study in which all women with singleton pregnancy who demonstrated NT above 3 mm and a normal microarray analysis were matched to women with normal NT and a normal microarray analysis (2013-2019) in a single tertiary academic center. The following placental pathology-related parameters were measured: preeclampsia, oligohydramnios, suspected intrauterine growth restriction, abnormal Doppler studies or small for gestational age (SGA) neonates. The primary outcome was defined as a composite of complications related to placental pathology including preeclampsia and SGA neonate. Secondary outcomes were labor complications and neonatal morbidity., Results: A total of 185 women were included in the study: of them, 47 presented an abnormal NT (study group) and 138 presented normal NT (controls). Groups did not significantly differ in baseline characteristics. Regarding primary outcome, all placental-related complications frequencies were higher in the study group, with a composite rate of 17.02% versus 6.52% in controls (p = 0.042%). Secondary outcomes did not differ between groups., Conclusions: Abnormal NT measurement presented in pregnancies with normal fetal microarray analysis is associated with higher rates of placental-related complications., (© 2021 John Wiley & Sons Ltd.)

Introduction: Women with pregnancies complicated by IUGR are at increased risk for future cardiovascular disease. Nevertheless, it is unknown whether endothelial function of women with pregnancies complicated by IUGR is already impaired during pregnancy. Hence, we evaluated maternal endothelial function in pregnancies complicated by IUGR due to placental dysfunction., Methods: Prospective cohort study assessing systemic endothelial function of women with singleton pregnancies and estimated fetal weight (EFW) below 10th percentile and abnormal umbilical artery flow (n = 15). Control group included women with singleton pregnancies and normal EFW (n = 22). Endothelial function was assessed using EndoPAT™ device which evaluates the change in peripheral vascular tone in reaction to temporal ischemia, a process called reactive hyperemia. The ratio of the readings before and after ischemia is used to assess endothelial function and called reactive hyperemia index (RHI). Low RHI values indicate endothelial dysfunction., Results: The median gestational age at endoPAT examination was comparable between the IUGR and control groups (32; IQR 31,33; p = 0.18). The median RHI was significantly lower in the IUGR group compared to the control group (1.3 vs 1.5, p = 0.02). Median gestational age at delivery and mean neonatal birth weight were lower in the IUGR group compared to the control group (36.7 (35.6,37.2) vs 37.7 (35.3, 39.3), p = 0.04 and 1647 ± 414 g vs 2785 ± 587 g, p < 0.001)., Discussion: Pregnant women with IUGR due to placental dysfunction are characterized by impaired systemic endothelial function., (Copyright © 2021. Published by Elsevier Ltd.)

Background: While it is clear that first trimester congenital cytomegalovirus (CMV) infection can lead to serious neonatal and childhood adverse outcome, the extent of the effect of second and third trimester congenital CMV infection is still unclear. Our aim was to study the short- and long-term outcomes following second and third trimester infection and to evaluate the contribution of prenatal imaging in a prospective cohort., Methods: We studied pregnant women with primary CMV infection in the second and third trimesters, as diagnosed by well-dated seroconversion, and proof of vertical CMV transmission. All patients underwent serial prenatal ultrasound (US) and most of them fetal magnetic resonance imaging (MRI). Follow-up information was obtained from hospital charts and by telephone interviews with parents., Results: Primary CMV infection occurred in 135 patients, 107 and 28 with second and third trimester infection, respectively. The incidence proportion of composite outcome (hearing loss or neurodevelopmental impairment) following second trimester infection was 7% (7/100, after excluding cases that were terminated) with a 3% incidence of partial unilateral sensory neural hearing loss and a 5% incidence of minor neurodevelopmental abnormalities, including slight verbal and motor delay. Following third trimester infection, there was one case of a very mild motor delay. The incidence proportion of abnormal prenatal findings on US or MRI was not significantly correlated to hearing loss or neurodevelopmental abnormalities., Conclusions: Second trimester infection is associated with a slight risk of developing mild childhood sequelae, mostly partial unilateral hearing loss, which may develop late in childhood. Prenatal imaging failed to predict the development of childhood adverse outcome., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Neutralizing antibodies represent a valuable therapeutic approach to countermeasure the current COVID-19 pandemic. Emergence of SARS-CoV-2 variants emphasizes the notion that antibody treatments need to rely on highly neutralizing monoclonal antibodies (mAbs), targeting several distinct epitopes for circumventing therapy escape mutants. Previously, we reported efficient human therapeutic mAbs recognizing epitopes on the spike receptor-binding domain (RBD) of SARS-CoV-2. Here we report the isolation, characterization, and recombinant production of 12 neutralizing human mAbs, targeting three distinct epitopes on the spike N-terminal domain of the virus. Neutralization mechanism of these antibodies involves receptors other than the canonical hACE2 on target cells, relying both on amino acid and N -glycan epitope recognition, suggesting alternative viral cellular portals. Two selected mAbs demonstrated full protection of K18-hACE2 transgenic mice when administered at low doses and late post-exposure, demonstrating the high potential of the mAbs for therapy of SARS-CoV-2 infection., Competing Interests: Patent application for the described antibodies was filed by the Israel Institute for Biological Research. None of the authors declared any additional competing interests., (© 2021 The Author(s).)

A novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus causing coronavirus disease 2019 (COVID-19) disease, which emerged as a global pandemic. Data regarding the implications of COVID-19 disease at early gestation on fetal and obstetric outcomes is scarce. Thus, our aim was to investigate the effect of first and second trimester maternal COVID-19 disease on fetal and perinatal outcomes. This was a prospective cohort study of pregnant women with a laboratory-proven SARS-COV-2 infection contracted prior to 26 weeks gestation. Women were followed at a single tertiary medical center by serial sonographic examinations every 4-6 weeks to assess fetal well-being, growth, placental function, anatomic evaluation and signs of fetal infection. Amniocentesis was offered to assess amniotic fluid SARS-COV-2-PCR (polymerase chain reaction) and fetal brain magnetic resonance imaging (MRI) was offered at 30-32 weeks gestation. Demographic, obstetric and neonatal data were collected from history intake, medical charts or by telephone survey. Perinatal outcomes were compared between women infected at first vs. second trimester. 55 women with documented COVID-19 disease at early gestation were included and followed at our center. The mean maternal age was 29.6 ± 6.2 years and the mean gestational age at viral infection was 14.2 ± 6.7 weeks with 28 (51%) women infected at the first trimester and 27 (49%) at the second trimester. All patients but one experienced asymptomatic to mild symptoms. Of 22 patients who underwent amniocentesis, none had evidence of vertical transmission. None of the fetuses exhibited signs of central nervous system (CNS) disease, growth restriction and placental dysfunction on serial ultrasound examinations and fetal MRI. Pregnancies resulted in perinatal survival of 100% to date with mean gestational age at delivery of 38.6 ± 3.0 weeks and preterm birth <37 weeks rate of 3.4%. The mean birthweight was 3260 ± 411 g with no cases of small for gestational age infants. The obstetric and neonatal outcomes were similar among first vs. second trimester infection groups. We conclude SARS-CoV-2 infection at early gestation was not associated with vertical transmission and resulted in favorable obstetric and neonatal outcomes.

Purpose: To identify risk factors for incorrect self-identification of the treatment eye before intravitreal injections., Methods: This prospective study included consecutive patients who were asked to designate the eye for which the intravitreal injection was intended and were subsequently divided into two groups according to whether or not they identified the correct eye., Results: Overall, 349 eyes (n = 349) were included, and 8.6% (n = 30) designated the incorrect eye or did not know which eye was intended for treatment. Incorrect designation was associated with diabetic macular edema (odds ratio [OR] = 0.33 [0.15-0.75]), first injection in the intended eye or ≥1 year since previous injection (OR = 0.34 [0.14-0.87]), Arabic native tongue (OR = 0.48 [0.22-1.01]), previous injection to the fellow eye (OR = 0.26 [0.10-0.64]), and concurrent treatment of both eyes (OR = 0.35 [0.16-0.74]). Multivariate analysis showed the first injection or ≥1 year since last injection in the treatment eye (R2 = 2.24%, P = 0.004, OR = 0.20 [0.07-0.57]) and previous injection in the fellow eye (R2 = 6.55%, P < 0.001, OR = 0.20 [0.07-0.52]) as significant independent predictors of incorrect identification., Conclusion: Several factors are associated with a greater probability for incorrect patient's self-identification of the eye laterality intended for intravitreal injections. These findings may help identify patients with a higher risk of such potential errors.