The effect of mutation on an aggregation-prone protein: An in vivo, in vitro, and in silico analysis.

Aggregation of initially stably structured proteins is involved in more than 20 human amyloid diseases. Despite intense research, however, how this class of proteins assembles into amyloid fibrils remains poorly understood, principally because of the complex effects of amino acid substitutions on protein stability, solubility, and aggregation propensity. We address this question using ß2-microglobulin (ß2m) as a model system, focusing on D76N-ß2m that is involved in hereditary amyloidosis. This amino acid substitution causes the aggregation-resilient wild-type protein to become highly aggregation prone in vitro, although the mechanism by which this occurs remained elusive. Here, we identify the residues key to protecting ß2m from aggregation by coupling aggregation with antibiotic resistance in E. coli using a tripartite ß-lactamase assay (TPBLA). By performing saturation mutagenesis at three different sites (D53X-, D76X-, and D98X-ß2m) we show that residue 76 has a unique ability to drive ß2m aggregation in vivo and in vitro. Using a randomly mutated D76N-ß2m variant library, we show that all of the mutations found to improve protein behavior involve residues in a single aggregation-prone region (APR) (residues 60 to 66). Surprisingly, no correlation was found between protein stability and protein aggregation rate or yield, with several mutations in the APR decreasing aggregation without affecting stability. Together, the results demonstrate the power of the TPBLA to develop proteins that are resilient to aggregation and suggest a model for D76N-ß2m aggregation involving the formation of long-range couplings between the APR and Asn76 in a nonnative state.

A True Reverse Anomeric Effect Does Exist After All: A Hydrogen Bonding Stereocontrolling Effect in 2-Iminoaldoses.

The reverse anomeric effect is usually associated with the equatorial preference of nitrogen substituents at the anomeric center. Once postulated as another anomeric effect with explanations ranging from electrostatic interactions to delocalization effects, it is now firmly considered to be essentially steric in nature. Through an extensive research on aryl imines from 2-amino-2-deoxyaldoses, spanning nearly two decades, we realized that such substances often show an anomalous anomeric behavior that cannot easily be rationalized on the basis of purely steric grounds. The apparent preference, or stabilization, of the ß-anomer takes place to an extent that not only neutralizes but also overcomes the normal anomeric effect. Calculations indicate that there is no stereoelectronic effect opposing the anomeric effect, resulting from the repulsion between electron lone pairs on the imine nitrogen and the endocyclic oxygen. Such data and compelling structural evidence unravel why the exoanomeric effect is largely inhibited. We are now confident, as witnessed by 2-iminoaldoses, that elimination of the exo-anomeric effect in the α-anomer is due to the formation of an intramolecular hydrogen bond between the anomeric hydroxyl and the iminic nitrogen, thereby accounting for a true electronic effect. In addition, discrete solvation may help justify the observed preference for the ß-anomer.

Disorder Analysis in Infrared Spectroscopy of Acetylene Ice.

A new method to investigate disorder in ice films is proposed and applied to acetylene ice. It is based on a quantitative analysis of the infrared spectrum data, which includes: the Brendel-Bormann model for the material's dielectric function; molecular vibration modes calculated by density functional theory (DFT); a monomer-dimer model for amorphous ice; and a peak-shape analysis through Levenberg-Marquardt nonlinear regression. Acetylene ice films with different degrees of disorder were investigated with the proposed method. The results provide an estimate of the degree of disorder in the films and indicate the possibility of existence of a second amorphous phase of acetylene ice grown at temperatures of about 15 K and then annealed. This phase would be similar to the high-density amorphous phase observed for water ice. The infrared data in this work is compared with those from the literature for acetylene gas, acetylene film, and acetylene aerosol. A qualitative analysis reveals differences in the degree of disorder in each system and points to a crystallinity limit for acetylene ice film; that is, the crystalline acetylene film has a higher degree of intrinsic disorder than the crystalline acetylene aerosol.

Nurses' preferences regarding MenACWY conjugate vaccines attributes: a discrete choice experiment in Spain.

OBJECTIVES: Immunisation against preventable diseases as meningitis is crucial from a public health perspective to face challenges posed by these infections. Nurses hold a great responsibility for these programs, which highlights the importance of understanding their preferences and needs to improve the success of campaigns. This study aimed to investigate nurses' preferences regarding Meningococcus A, C, W, and Y (MenACWY) conjugate vaccines commercialised in Spain. STUDY DESIGN: A national-level discrete choice experiment (DCE) was conducted. METHODS: A literature review and a focus group informed the DCE design. Six attributes were included: pharmaceutical form, coadministration evidence, shelf-life, package contents, single-doses per package, and package volume. Conditional logit models quantified preferences and relative importance (RI). RESULTS: Thirty experienced primary care nurses participated in this study. Evidence of coadministration with other vaccines was the most important attribute (RI = 43.78%), followed by package size (RI = 22.17%), pharmaceutical form (RI = 19.07%), and package content (RI = 11.80%). There was a preference for evidence of coadministration with routine vaccines (odds ratio [OR] = 2.579, 95% confidence interval [95%CI] = 2.210-3.002), smaller volumes (OR = 1.494, 95%CI = 1.264-1.767), liquid formulations (OR = 1.283, 95%CI = 1.108-1.486) and package contents including only vial/s (OR = 1.283, 95%CI = 1.108-1.486). No statistical evidence was found for the remaining attributes. CONCLUSIONS: Evidence of coadministration with routine vaccines, easy-to-store packages, and fully liquid formulations were drivers of nurses' preferences regarding MenACWY conjugate vaccines. These findings provide valuable insights for decision-makers to optimize current campaigns.

Trends in the mortality of diabetes in Mexico from 1998 to 2022: a joinpoint regression and age-period-cohort effect analysis.

OBJECTIVE: The purpose was to analyze age-standardized trends in diabetes mortality rates (DMR) from 1998 to 2022, stratified by sex and Mexican state, and the effects attributable to age, period, and cohort by sex. STUDY DESIGN: Joinpoint regression and age-period-cohort effect analysis. METHODS: Based on the tenth revision of the International Classification of Diseases, E11, E12, E13, and E14 codes of the death certificate, a daily record of mortality was extracted from the death certificate attributable to diabetes as the main cause. From 1998 to 2022, sexes and ages (≥20 years) were used to calculate the crude mortality rates and standardized at the national and Mexican state levels. Additionally, the age-period-cohort model was used to examine age, period, and cohort effects. RESULTS: From 1998 to 2005, the age-adjusted DMR increased by 3.6% (95% confidence interval [CI]: 2.7, 4.5) for the total population, as shown by the joinpoint regression analysis at a national level; from 2017 to 2020, it increased by 7.4% (95% CI: 0.6, 14.8). The DMR with the highest increase during the study period came mainly from states in the country's southeastern region, 2.3% to 3.7% per year. The net age and period effects showed that mortality increased with advancing age and with going time, respectively; and the net cohort effect revealed that mortality increased in more recent birth cohorts, mainly in men Rate Ratio (RR) = 2.37 (95% CI: 2.29, 2.46) vs RR = 1.13 (95% CI: 1.09, 1.17). CONCLUSION: The DMR increased among older age groups. The period effect showed that mortality increased over time. Furthermore, the cohort effect showed that mortality increased in more recent birth cohorts, especially among men.

Perinatal outcome of monochorionic triamniotic triplet pregnancy: multicenter cohort study.

OBJECTIVE: Monochorionic (MC) triplet pregnancies are extremely rare and information on these pregnancies and their complications is limited. We aimed to investigate the risk of early and late pregnancy complications, perinatal outcome and the timing and methods of fetal intervention in these pregnancies. METHODS: This was a multicenter retrospective cohort study of MC triamniotic (TA) triplet pregnancies managed in 21 participating centers around the world from 2007 onwards. Data on maternal age, mode of conception, diagnosis of major fetal structural anomalies or aneuploidy, gestational age (GA) at diagnosis of anomalies, twin-to-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), twin reversed arterial perfusion (TRAP) sequence and or selective fetal growth restriction (sFGR) were retrieved from patient records. Data on antenatal interventions were collected, including data on selective fetal reduction (three to two or three to one), laser surgery and any other active fetal intervention (including amniodrainage). Data on perinatal outcome were collected, including numbers of live birth, intrauterine demise, neonatal death, perinatal death and termination of fetus or pregnancy (TOP). Neonatal data such as GA at birth, birth weight, admission to neonatal intensive care unit and neonatal morbidity were also collected. Perinatal outcomes were assessed according to whether the pregnancy was managed expectantly or underwent fetal intervention. RESULTS: Of an initial cohort of 174 MCTA triplet pregnancies, 11 underwent early TOP, three had an early miscarriage, six were lost to follow-up and one was ongoing at the time of writing. Thus, the study cohort included 153 pregnancies, of which the majority (92.8%) were managed expectantly. The incidence of pregnancy affected by one or more fetal structural abnormality was 13.7% (21/153) and that of TRAP sequence was 5.2% (8/153). The most common antenatal complication related to chorionicity was TTTS, which affected just over one quarter (27.6%; 42/152, after removing a pregnancy with TOP < 24 weeks for fetal anomalies) of the pregnancies, followed by sFGR (16.4%; 25/152), while TAPS (spontaneous or post TTTS with or without laser treatment) occurred in only 4.6% (7/152) of pregnancies. No monochorionicity-related antenatal complication was recorded in 49.3% (75/152) of pregnancies. Survival was apparently associated largely with the development of these complications: there was at least one survivor beyond the neonatal period in 85.1% (57/67) of pregnancies without antenatal complications, in 100% (25/25) of those complicated by sFGR and in 47.6% (20/42) of those complicated by TTTS. The overall rate of preterm birth prior to 28 weeks was 14.5% (18/124) and that prior to 32 weeks' gestation was 49.2% (61/124). CONCLUSION: Monochorionicity-related complications, which can impact adversely perinatal outcome, occur in almost half of MCTA triplet pregnancies, creating a challenge with regard to counseling, surveillance and management. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Mechanistic Insights into the Oxidative Degradation of Formic and Oxalic Acids with Ozone and OH Radical. A Computational Rationale.

Gas-phase and aqueous oxidations of formic and oxalic acids with ozone and OH radicals have been thoroughly examined by DFT methods. Such acids are not only important feedstocks for the iterative construction of other organic compounds but also final products generated by mineralization and advanced oxidation of higher organics. Our computational simulation unravels both common and distinctive reaction channels, albeit consistent with known H atom abstraction pathways and formation of hydropolyoxide derivatives. Notably, reactions with neutral ozone and OH radical proceed through low-energy concerted mechanisms involving asynchronous transition structures. For formic acid, carbonylic H-abstraction appears to be more favorable than the dissociative abstraction of the acid proton. Formation of long oxygen chains does not cause a significant energy penalty and highly oxygenated products are stable enough, even if subsequent decomposition releases environmentally benign side substances like O2 and H2O.

Patterns of Fourier-transform infrared estimated milk constituents in early lactation Holstein cows on a single New York State dairy.

Cows undergo immense physiological stress to produce milk during early lactation. Monitoring early lactation milk through Fourier-transform infrared (FTIR) spectroscopy might offer an understanding of which cows transition successfully. Daily patterns of milk constituents in early lactation have yet to be reported continuously, and the study objective was to initially describe these patterns for cows of varying parity groups from 3 through 10 d postpartum, piloted on a single dairy. We enrolled 1,024 Holstein cows from a commercial dairy farm in Cayuga County, New York, in an observational study, with a total of 306 parity 1 cows, 274 parity 2 cows, and 444 parity ≥3 cows. Cows were sampled once daily, Monday through Friday, via proportional milk samplers, and milk was stored at 4°C until analysis using FTIR. Estimated constituents included anhydrous lactose, true protein, and fat (g/100 g of milk); relative % (rel%) of total fatty acids (FA) and concentration (g/100 g of milk) of de novo, mixed, and preformed FA; individual fatty acids C16:0, C18:0, and C18:1 cis-9 (g/100 g of milk); milk urea nitrogen (MUN; mg/100 g of milk); and milk acetone (mACE), milk ß-hydroxybutyrate (mBHB), and milk-predicted blood nonesterified fatty acids (mpbNEFA) (all expressed in mmol/L). Differences between parity groups were assessed using repeated-measures ANOVA. Milk yield per milking differed over time between 3 and 10 DIM and averaged 8.7, 13.3, and 13.3 kg for parity 1, 2, and ≥3 cows, respectively. Parity differences were found for % anhydrous lactose, % fat, and preformed FA (g/100 g of milk). Parity differed across DIM for % true protein, de novo FA (rel% and g/100 g of milk), mixed FA (rel% and g/100 g of milk), preformed FA rel%, C16:0, C18:0, C18:1 cis-9, MUN, mACE, mBHB, and mpbNEFA. Parity 1 cows had less true protein and greater fat percentages than parity 2 and ≥3 cows (% true protein: 3.52, 3.76, 3.81; % fat: 5.55, 4.69, 4.95, for parity 1, 2, ≥3, respectively). De novo and mixed FA rel% were reduced and preformed FA rel% were increased in primiparous compared with parity 2 and ≥3 cows. The increase in preformed FA rel% in primiparous cows agreed with milk markers of energy deficit, such that mpbNEFA, mBHB, and mACE were greatest in parity 1 cows followed by parity ≥3 cows, with parity 2 cows having the lowest concentrations. When measuring milk constituents with FTIR, these results suggest it is critical to account for parity for the majority of estimated milk constituents. We acknowledge the limitation that this study was conducted on a single farm; however, if FTIR technology is to be used as a method of identifying cows maladapted to lactation, understanding variations in early lactation milk constituents is a crucial first step in the practical adoption of this technology.

Calcium dynamics and associated temporal patterns of milk constituents in early-lactation multiparous Holsteins.

At the onset of lactation, calcium (Ca) homeostasis is challenged. For the transitioning dairy cow, inadequate responses to this challenge may result in subclinical hypocalcemia at some point in the postpartum period. It has been proposed that dynamics of blood Ca and the timing of subclinical hypocalcemia allow cows to be classified into 4 Ca dynamic groups by assessing serum total Ca concentrations (tCa) at 1 and 4 days in milk (DIM). These differing dynamics are associated with different risks of adverse health events and suboptimal production. Our prospective cohort study aimed to characterize the temporal patterns of milk constituents in cows with differing Ca dynamics to investigate the potential of Fourier-transform infrared spectroscopic (FTIR) analysis of milk as a diagnostic tool for identifying cows with unfavorable Ca dynamics. We sampled the blood of 343 multiparous Holsteins on a single dairy in Cayuga County, New York, at 1 and 4 DIM and classified these cows into Ca dynamic groups using threshold concentrations of tCa (1 DIM: tCa <1.98 mmol/L; 4 DIM: tCa <2.22 mmol/L) derived from receiver operating characteristic curve analysis based on epidemiologically relevant health and production outcomes. We also collected proportional milk samples from each of these cows from 3 to 10 DIM for FTIR analysis of milk constituents. Through this analysis we estimated the milk constituent levels of anhydrous lactose (g/100 g of milk and g/milking), true protein (g/100 g of milk and g/milking), fat (g/100 g of milk and g/milking), milk urea nitrogen (mg/100 g of milk), fatty acid (FA) groups including de novo, mixed origin, and preformed FA measured in grams/100 g of milk, by relative percentage, and grams/milking, as well as energy-related metabolites including ketone bodies and milk-predicted blood nonesterified FA. Individual milk constituents were compared among groups at each time point and over the entire sample period using linear regression models. Overall, we found differences among the constituent profiles of Ca dynamic groups at approximately every time point and over the entire sample period. The 2 at-risk groups of cows did not differ from each other at more than one time point for any constituent, however prominent differences existed between the milk of normocalcemic cows and the milk of the other Ca dynamic groups with respect to FA. Over the entire sample period, lactose and protein yield (g/milking) were lower in the milk of at-risk cows than in the milk of the other Ca dynamic groups. In addition, milk yield per milking followed patterns consistent with previous Ca dynamic group research. Though our use of a single farm does limit the general applicability of these findings, our conclusions provide evidence that FTIR may be a useful method for discriminating between cows with different Ca dynamics at time points that may be relevant in the optimization of management or development of clinical intervention strategies.

Social cognition interventions for adolescents with autism spectrum disorder. A systematic review.

Early intervention during childhood in patients with Autism Spectrum Disorder (ASD) has been strongly advocated. As adolescence is reached, new, more complex social demands emerge. These demands require a therapeutic approach that has not been widely studied. The aim of this review is to examine and synthesize the existing literature on social cognition interventions in adolescence and lay the groundwork for future interventions.

Tagetes lucida Cav. essential oil and the mixture of its main compounds are antibacterial and modulate antibiotic resistance in multi-resistant pathogenic bacteria.

We evaluated an essential oil (EO) of Tagetes lucida Cav. and the mixture of its main compounds against multi-drug resistant bacteria. We found that EO and the partially reconstituted blend of its main components have antibacterial activity and inhibit antibiotic resistance (ampicillin, chloramphenicol, nalidixic acid, vancomycin and imipenem) in strains of Staphylococcus aureus ATCC 29213 and Pseudomonas aeruginosa HIM-MR01. The T. lucida EO alone or added to the antibiotics showed antimicrobial activity against S. aureus and P. aeruginosa. The EO main bioactive compounds were methyl eugenol (relative abundance in EO: 46·15%), estragole (32·93%), linalool (2·48%) and geraniol (0·33%). The mixture (PREO) of those compounds at those proportions inhibited the growth of P. aeruginosa in 45% at 683·62 µg ml-1 and that of S. aureus in 51·7% at 39·04 µg ml-1 . The PREO had higher antibacterial and modulatory activities than the original EO. In conclusion, we overcame the unpredictability of EO activity (due to their natural variability) by determining which EO components inhibited bacteria and then producing a PREO to generate a reproducible mixture with predictable antibacterial and modulation of resistance activities. Thus, the PREO, and its components, show potential as alternatives to manage multidrug-resistant pathogens.

Biologically synthesized silver nanoparticles as potent antibacterial effective against multidrug-resistant Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the most worrisome infectious bacteria due to its intrinsic and acquired resistance against several antibiotics and the recalcitrance of its infections; hence, the development of novel antimicrobials effective against multidrug-resistant P. aeruginosa is mandatory. In this work, silver nanoparticles obtained by green synthesis using a leaf extract and fungi were tested against a battery of clinical strains from cystic fibrosis, pneumonia and burnt patients, some of them with multidrug resistance. Both nanoparticles showed a potent antibacterial effect, causing severe damage to the cell wall, membrane and DNA, and inducing the production of reactive oxygen species. Moreover, the nanoparticles derived from fungi showed synergistic antibacterial effects with the antibiotics meropenem and levofloxacin for some clinical strains and both kinds of nanoparticles were nontoxic for larvae of the moth Galleria mellonella, encouraging further research for their implementation in the treatment of P. aeruginosa infections.

On the Origin of Sugar Handedness: Facts, Hypotheses and Missing Links-A Review.

By paraphrasing one of Kipling's most amazing short stories (How the Leopard Got His Spots), this article could be entitled "How Sugars Became Homochiral". Obviously, we have no answer to this still unsolved mystery, and this perspective simply brings recent models, experiments and hypotheses into the homochiral homogeneity of sugars on earth. We shall revisit the past and current understanding of sugar chirality in the context of prebiotic chemistry, with attention to recent developments and insights. Different scenarios and pathways will be discussed, from the widely known formose-type processes to less familiar ones, often viewed as unorthodox chemical routes. In particular, problems associated with the spontaneous generation of enantiomeric imbalances and the transfer of chirality will be tackled. As carbohydrates are essential components of all cellular systems, astrochemical and terrestrial observations suggest that saccharides originated from environmentally available feedstocks. Such substances would have been capable of sustaining autotrophic and heterotrophic mechanisms integrating nutrients, metabolism and the genome after compartmentalization. Recent findings likewise indicate that sugars' enantiomeric bias may have emerged by a transfer of chirality mechanisms, rather than by deracemization of sugar backbones, yet providing an evolutionary advantage that fueled the cellular machinery.

Histopathological and virological features of lung, heart and liver percutaneous tissue core biopsy in patients with COVID-19: A clinicopathological case series.

INTRODUCTION: Data on pathological changes in COVID-19 are scarce. The aim of this study was to describe the histopathological and virological findings of postmortem biopsies, and the existing clinical correlations, in people who died of COVID-19. MATERIALS AND METHODS: We performed postmortem needle core biopsies of the chest in 11 people who died of COVID-19 pneumonia. Tissue examination was done by light microscopy and real-time polymerase chain reaction (RTPCR). RESULTS: The age of the patients were between 61 to 94 years. Of the 11 postmortem chest biopsies, lung tissue was obtained in 8, myocardium tissue in 7, and liver tissue in 5. Histologically of lung, the main findings pertaining to the lung were diffuse alveolar damage in proliferative phase (n = 4, 50%), diffuse alveolar damage in exudative and proliferative phase (n = 3, 37.5%), diffuse alveolar damage in exudative (n=1; 12.5%) and acute pneumonia (n = 2, 25%). Necrotising pneumonia, acute fibrinous and organising pneumonia, and neutrophils were detected in one sample each (12.5%). Another case presented myocarditis. RT-PCR showed RNA of SARS-CoV-2 in 7 of the 8 lung samples (87.5%), 2 of the 7 myocardial tissue samples (28.6%), and 1 of the 5 liver tissue samples (20%). CONCLUSION: The postmortem examinations show diffuse alveolar damage, as well as acute or necrotising pneumonia. RT-PCR of SARS-CoV-2 was positive in most lung samples.

Squeezed-Light Enhancement and Backaction Evasion in a High Sensitivity Optically Pumped Magnetometer.

We study the effect of optical polarization squeezing on the performance of a sensitive, quantum-noise-limited optically pumped magnetometer. We use Bell-Bloom (BB) optical pumping to excite a ^{87}Rb vapor containing 8.2×10^{12} atoms/cm^{3} and Faraday rotation to detect spin precession. The sub-pT/sqrt[Hz] sensitivity is limited by spin projection noise (photon shot noise) at low (high) frequencies. Probe polarization squeezing both improves high-frequency sensitivity and increases measurement bandwidth, with no loss of sensitivity at any frequency, a direct demonstration of the evasion of measurement backaction noise. We provide a model for the quantum noise dynamics of the BB magnetometer, including spin projection noise, probe polarization noise, and measurement backaction effects. The theory shows how polarization squeezing reduces optical noise, while measurement backaction due to the accompanying ellipticity antisqueezing is shunted into the unmeasured spin component. The method is compatible with high-density and multipass techniques that reach extreme sensitivity.

Organic Sonochemistry: A Chemist's Timely Perspective on Mechanisms and Reactivity.

Sonochemistry, the use of sound waves, usually within the ultrasonic range (>20 kHz), to boost or alter chemical properties and reactivity constitutes a long-standing and sustainable technique that has, however, received less attention than other activation protocols despite affordable setups. Even if unnecessary to underline the impact of ultrasound-based strategies in a broad range of chemical and biological applications, there is considerable misunderstanding and pitfalls regarding the interpretation of cavitational effects and the actual role played by the acoustic field. In this Perspective, with an eye on mechanisms in particular, we discuss the potentiality of sonochemistry in synthetic organic chemistry through selected examples of past and recent developments. Such examples illustrate specific controlling effects and working rules. Looking back at the past while looking forward to advancing the field, some essentials of sonochemical activation will be distilled.

Doppler changes in umbilical artery, middle cerebral artery, cerebroplacental ratio and ductus venosus during open fetal microneurosurgery for intrauterine open spina bifida repair.

OBJECTIVE: To describe changes in fetal Doppler parameters during a novel technique for open fetal microneurosurgery for open spina bifida (OSB) repair. METHODS: This was a prospective study of 44 fetuses undergoing open fetal surgery for OSB repair using a novel microneurosurgery approach that is characterized by a mini-hysterotomy (diameter of 15 mm), minimal fetal manipulation and maintenance of a constant normal amniotic fluid volume throughout the procedure. Doppler velocimetry of the umbilical artery (UA), fetal middle cerebral artery (MCA) and ductus venosus (DV) was performed before the start of surgery and at prespecified timepoints during fetal surgery. UA pulsatility index (PI) > 95th percentile, DV-PI > 95th percentile, MCA-PI < 5th percentile and cerebroplacental ratio (CPR) < 5th percentile were considered abnormal. RESULTS: Median gestational age at fetal surgery was 25.2 weeks (range, 22.9-27.9 weeks). Doppler recordings were successfully obtained in all cases during all timepoints throughout the surgery. As compared with Doppler values before surgery, there was a significant increase in the proportion of fetuses with MCA-PI < 5th percentile (63.6% vs 13.6%; P < 0.001), CPR < 5th percentile (65.9% vs 15.9%; P < 0.001) and DV-PI > 95th percentile (22.7% vs 0%; P = 0.01) and a non-significant increase in the proportion of fetuses with UA-PI > 95th percentile (11.4% vs 0%; P = 0.12) during fetal surgery. None of the fetuses showed absent or reversed end-diastolic velocity in the UA or absent or reversed DV a-wave at any stage during OSB repair. All abnormal Doppler parameters returned to normal after surgery. CONCLUSIONS: During open fetal surgery for OSB repair, a small hysterotomy, reduced fetal manipulation and maintenance of a normal amniotic fluid volume seem to prevent severe fetal Doppler abnormalities. The mild Doppler changes observed during fetal surgery could be a manifestation of fetal adaptation to the stress of fetal surgery. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Long-term decline of the Amazon carbon sink.

Atmospheric carbon dioxide records indicate that the land surface has acted as a strong global carbon sink over recent decades, with a substantial fraction of this sink probably located in the tropics, particularly in the Amazon. Nevertheless, it is unclear how the terrestrial carbon sink will evolve as climate and atmospheric composition continue to change. Here we analyse the historical evolution of the biomass dynamics of the Amazon rainforest over three decades using a distributed network of 321 plots. While this analysis confirms that Amazon forests have acted as a long-term net biomass sink, we find a long-term decreasing trend of carbon accumulation. Rates of net increase in above-ground biomass declined by one-third during the past decade compared to the 1990s. This is a consequence of growth rate increases levelling off recently, while biomass mortality persistently increased throughout, leading to a shortening of carbon residence times. Potential drivers for the mortality increase include greater climate variability, and feedbacks of faster growth on mortality, resulting in shortened tree longevity. The observed decline of the Amazon sink diverges markedly from the recent increase in terrestrial carbon uptake at the global scale, and is contrary to expectations based on models.

Authentic Self and Last Resort: International Perceptions of Psychiatric Neurosurgery.

Psychiatric neurosurgery has resurfaced over the past two decades for the treatment of severe mental health disorders, with improved precision and safety over older interventions alongside the development of novel ones. Little is known, however, about current public opinions, expectations, hopes, and concerns over this evolution in neurotechnology, particularly given the controversial history of psychosurgery. To fill this knowledge gap, we conducted a study with eight focus groups in Vancouver and Montreal (Canada; n = 14), Berlin (Germany; n = 22), and Madrid (Spain; n = 12). Focus group texts were transcribed and analyzed using qualitative content analysis in the language local to each city, guided by the theoretical framework of pragmatic neuroethics. Findings indicate that participants across all cities hold concerns about the last resort nature of psychiatric neurosurgery and the potential impact on the authentic self of patients who undergo these procedures. The views captured serve to advance discussion on the appropriate timing for psychiatric neurosurgery, promote sound health policy for the allocation of this resource, and foster scientific literacy about advances for mental health internationally.

Foodborne Parasitic Diseases in the Neotropics - A Review.

Within the Universal Declaration of Human Rights, it is stated that everyone has the right to an adequate standard of living, which ensures, as well as their family, health and well-being, and food, thereby ensuring adequate nutrition. One of the major threats to overcome this is to ensure food security, which becomes particularly challenging in developing countries due to the high incidence of parasitic diseases. The World Health Organization (WHO), considers it one of the main causes of morbidity, closely linked to poverty and related to inadequate personal hygiene, consumption of raw food, lack of sanitary services, limited access to drinking water and fecal contamination in the environment. It is estimated that more than a fifth of the world's population is infected by one or several intestinal parasites, and that in many countries of Central and South America the average percentage of infected people is 45%, being Taenia solium, Echinococcus granulosus, Toxoplasma gondii, Cryptosporidium spp, Entamoeba histolytica, Trichinella spiralis, Ascaris spp, Trypanosoma cruzi and Fasciola hepatica some of the most important ones in the neotropics. One of the main reasons why these diseases are diffi cult to control is t he ignorance of their lifecycles, as well as symptoms and current epidemiology of the disease, which contributes to a late or erroneous diagnosis. The present work aims to discuss and make public the current knowledge as well as the general characteristics of these diseases to the general audience.