Multimodal diagnostics for keratoconus and ectatic corneal diseases: a paradigm shift.

Different diagnostic approaches for ectatic corneal diseases (ECD) include screening, diagnosis confirmation, classification of the ECD type, severity staging, prognostic evaluation, and clinical follow-up. The comprehensive assessment must start with a directed clinical history. However, multimodal imaging tools, including Placido-disk topography, Scheimpflug three-dimensional (3D) tomography, corneal biomechanical evaluations, and layered (or segmental) tomography with epithelial thickness by optical coherence tomography (OCT), or digital very high-frequency ultrasound (dVHF-US) serve as fundamental complementary exams for measuring different characteristics of the cornea. Also, ocular wavefront analysis, axial length measurements, corneal specular or confocal microscopy, and genetic or molecular biology tests are relevant for clinical decisions. Artificial intelligence enhances interpretation and enables combining such a plethora of data, boosting accuracy and facilitating clinical decisions. The applications of diagnostic information for individualized treatments became relevant concerning the therapeutic refractive procedures that emerged as alternatives to keratoplasty. The first paradigm shift concerns the surgical management of patients with ECD with different techniques, such as crosslinking and intrastromal corneal ring segments. A second paradigm shift involved the quest for identifying patients at higher risk of progressive iatrogenic ectasia after elective refractive corrections on the cornea. Beyond augmenting the sensitivity to detect very mild (subclinical or fruste) forms of ECD, ectasia risk assessment evolved to characterize the inherent susceptibility for ectasia development and progression. Furthermore, ectasia risk is also related to environmental factors, including eye rubbing and the relational impact of the surgical procedure on the cornea.

Thermodynamic uncertainty relations in mesoscopic devices.

We investigate the thermodynamic uncertainty relations (TURs) in mesoscopic devices for all universal symmetry classes of Wigner-Dyson and Dirac (chiral). The observables of interest include the TUR (MS), which is defined in terms of the ratio between the mean noise and mean conductance, as well as a new TUR (R) proposed in this article, which is based on the ensemble mean of the noise-to-conductance ratio. A detailed study is made on the quantum interference corrections associated with the TURs. We also analyze the influence of orbital and sublattice/chiral degrees of freedom for the validity of the observables in these chaotic mesoscopic billiards. Our investigation is based on the concatenation between the Landauer-Büttiker theory, the Mahaux-Wendeinmüller theory, and the TURs. We simulate the universal mesoscopic chaotic quantum dots using the random-matrix theory and compare our numerical results with the pertinent experimental data. The results were obtained for a different number of channels and tunneling rates that vary from the opaque to the ideal regime and, in all cases, demonstrate a clear phenomenological distinction between the TURs. In particular, the opaque regime engenders remarkable differences between the observables, even in the semiclassical regime, which characterizes a clear violation of the central limit theorem. Furthermore, we show that the phenomenology of the quantum interference corrections is strikingly robust, surprisingly exhibiting an order of magnitude greater than the supposedly leading semiclassical term for the TUR (R).

Limits to Gauge Coupling in the Dark Sector Set by the Nonobservation of Instanton-Induced Decay of Super-Heavy Dark Matter in the Pierre Auger Observatory Data.

Instantons, which are nonperturbative solutions to Yang-Mills equations, provide a signal for the occurrence of quantum tunneling between distinct classes of vacua. They can give rise to decays of particles otherwise forbidden. Using data collected at the Pierre Auger Observatory, we search for signatures of such instanton-induced processes that would be suggestive of super-heavy particles decaying in the Galactic halo. These particles could have been produced during the post-inflationary epoch and match the relic abundance of dark matter inferred today. The nonobservation of the signatures searched for allows us to derive a bound on the reduced coupling constant of gauge interactions in the dark sector: α_{X}≲0.09, for 10^{9}≲M_{X}/GeV<10^{19}. Conversely, we obtain that, for instance, a reduced coupling constant α_{X}=0.09 excludes masses M_{X}≳3×10^{13} GeV. In the context of dark matter production from gravitational interactions alone, we illustrate how these bounds are complementary to those obtained on the Hubble rate at the end of inflation from the nonobservation of tensor modes in the cosmological microwave background.

Effects of different doses of estradiol benzoate used in a cervical relaxation protocol on the success of non-surgical embryo recovery and luteal function in superovulated ewes.

This study investigated the effectiveness of different doses of estradiol benzoate (EB) to promote cervical relaxation and their effects on luteal function and outcomes of non-surgical embryo recovery (NSER) in sheep. Multiparous (MULT) and nulliparous (NULL) crossbred Lacaune X Santa Inês ewes were superovulated and naturally bred. Seven days after progesterone withdrawal, females were randomly assigned to one of three distinct cervical relaxation protocols, consisting of i.m. treatment with 37.5 µg d-cloprostenol and different doses of EB: 0.0 mg (0.0EB group; n = 3 NULL and 14 MULT); 0.5 mg (0.5EB group; n = 4 NULL and 12 MULT) or 1.0 mg (1.0EB group, n = 6 NULL and 11 MULT) 16 h before NSER. All ewes received 50 IU of oxytocin 20 min before NSER (D17). Blood samples were collected and ultrasound exams (B-mode and color Doppler) were performed at two timepoints: immediately before d-cloprostenol and EB treatments and prior to NSER. Estrous behavior, corpora lutea count and NSER success outcomes were not affected by EB treatments nor parity (P > 0.05). Embryo recovery rate was greater for ewes in the 0.5EB group and in the NULL ewes (P < 0.05). Ovarian biometrics differed between the two evaluation timepoints in all groups (P < 0.05). Plasma estradiol increased over time, reaching a significant greater level in 1.0EB ewes compared to controls on D17 (P < 0.05), whereas progesterone concentrations decreased over time in all groups (P > 0.05). In conclusion, treatments did not affect NSER success but they did affect luteal function by altering P4 and E2 concentrations. Therefore, the NSER technique can be successfully performed in ewes with or without prior treatment with EB.

Biomechanics in Keratoconus Diagnosis.

Purpose: To prospectively review the importance of biomechanical assessment in the screening, diagnosis, prognosis, individualized planning, and clinical follow-up for ectatic corneal diseases.Methods: We demonstrate two commercially available devices to assess the corneal biomechanics in vivo, the Ocular Response Analyzer (ORA, Reichester, NY, USA) and the Corvis ST (Oculus, Wetzlar, Germany). Novel devices have been demonstrated to provide in vivo biomechanical measurements, including Brillouin optical microscopy and OCT elastography. Conclusion: The integration of biomechanical data and other data from multimodal refractive imaging using artificial intelligence demonstrated the ability to enhance accuracy in diagnosing ectatic corneal diseases.

Single dose of 300 IU hCG in the early luteal phase in superovulated ewes: Effects on corpora lutea, progesterone profile, and embryo recovery.

This study aimed to evaluate the effects of hCG treatment during the early luteal phase on ovarian function, progesterone profile, and embryo yield in superovulated ewes. Superovulated sheep were randomly assigned to receive 300 IU hCG i.m. (GhCG, n = 24) or not (GControl, n = 25) at 96 h after the removal of the progesterone (P4) device (D13). Non-surgical embryo recovery (NSER) was performed eight days after P4 withdrawal. Ultrasound evaluations were performed on D13, D14, D16, and D17. Blood samples were collected on D14, D16, and D17. Superovulation scores were recorded based on the number of corpora lutea (CL) as follows: 1 (≤ 2), 2 (3-5), 3 (6-8), and 4 (≥ 9). NSER efficiency, superovulation response, and luteal tissue area were similar in both groups (P > 0.05). Structural luteolysis tended to be higher in GControl (P = 0.07; 47.0 %) while functional luteolysis was similar in both groups (P > 0.05; 0.0 % and 5.9 %). The recovery rate was greater (P < 0.05) in GhCG (89.8 %) compared with GControl (71.0 %), with similar overall ova/embryo numbers observed for both groups (P > 0.05). GhCG showed a higher concentration of animals with a superovulatory response score of 4 (54.5 %; P < 0.05) compared with the lowest scores. Plasma progesterone on D16 was higher (P < 0.05) in GhCG ewes (11.1 ± 1.5 vs 6.9 ± 1.5 ng/mL). In conclusion, the hCG treatment improved circulating P4 and embryo recovery rate, tended to maintain luteal functionality, and thus constitutes an additional tool for improving embryo yield in superovulated ewes.

New species and new distributional records of the hygropetric water scavenger beetle genus Oocyclus Sharp (Coleoptera, Hydrophilidae) from the Brazilian Shield.

Nine new species of the water scavenger beetle genus Oocyclus Sharp, 1882 are described from the Brazilian Shield: O. ecolab sp. n., O. espinhacu sp. n., O. giganteus sp. n., O. humboldti sp. n., O. lacia sp. n., O. ovalis sp. n., O. sulcatus sp. n., O. thrixdiastematus sp. n., and O. thysanus sp. n. New locality records are provided for four species previously known from Brazil: O. rotundus Clarkson Short, 2012, O. pilosus Jordo, Clarkon Ferreira-Jr, 2018, O. xanthus Clarkson Short, 2012 and O. yubai Clarkson Short, 2012. All species are associated with rock-face seepages such as wet rocks, waterfalls, and seepages. An updated key to the Brazilian species of Oocyclus is provided.

[Assessment of the impact of pharmaceutical consultations at initiation of a treatment with emicizumab in patients with severe hemophilia A without inhibitors]. / Évaluation de l'impact de consultations pharmaceutiques à l'instauration d'un traitement par émicizumab chez les patients hémophiles A sévères sans inhibiteurs.

Since 2019, severe haemophilia A without inhibitors can be treated with emicizumab. Its action, route of administration and management justified the creation of new tools for therapeutic education sessions addressed to patients. The main objective of our work was to assess the knowledge and skills acquired by patients after therapeutic education. The various documents created were a video, a slideshow, clinical cases in form of cards, and summary sheets intended for patients. At treatment beginning, a pharmaceutical consultation was proposed to all patients. Two months later, an evaluation was carried out and a second pharmaceutical consultation aimed to consolidate the achievements of patients. Simultaneously, a clinical self-evaluation by the patients was carried out. Thirty-six patients were included in the study. Theoretical items: method of manufacture, mechanism of action and regimen, are known for more than ¾ of patients. Practical skills, such as administration modalities, management of missed doses or bleeding, are familiar for more than 8 out of 10 patients. Sixteen (44.4%) patients presented an up-to-date haemophilia card. The assessment of the knowledge and skills of patients is encouraging since most of the items are acquired. These result highlights the interest of the new tools developed for the therapeutic education sessions.

Measurement of the Fluctuations in the Number of Muons in Extensive Air Showers with the Pierre Auger Observatory.

We present the first measurement of the fluctuations in the number of muons in extensive air showers produced by ultrahigh energy cosmic rays. We find that the measured fluctuations are in good agreement with predictions from air shower simulations. This observation provides new insights into the origin of the previously reported deficit of muons in air shower simulations and constrains models of hadronic interactions at ultrahigh energies. Our measurement is compatible with the muon deficit originating from small deviations in the predictions from hadronic interaction models of particle production that accumulate as the showers develop.

Oviduct fluid during IVF moderately modulates polyspermy in in vitro-produced goat embryos during the non-breeding season.

The present study determined i) the presence of proteins (oviduct-specific glycoprotein, OVGP1; heat shock protein-70A, HSPA1A; heat shock protein-A8, HSPA8; annexin A1, ANXA1; annexin A5, ANXA5; and myosin-9, MYH9) known to be involved in early reproduction in the oviduct fluid (OF) of anestrous goats; and ii) the functional effect of during IVF on polyspermy modulation and embryonic development. In vitro-matured oocytes were co-cultured with spermatozoa (1.0, 2.0, or 4.0 x 106 cells/mL) for 18 h in SOF medium supplemented with 5 µg/mL of heparin, 4 µg/mL gentamicin, and 10% estrus sheep serum (CTRL1, CTRL2, and CTRL4 groups) or the same medium plus 10% OF (OF1, OF2, and OF4 groups) obtained from anestrus goats. The analysis of OF by western blotting confirmed the presence of the six proteins tested for. The increase in sperm concentration had no effect (P > 0.05) on the penetration rate in any group; however, monospermy rate decreased as sperm concentration was increased in both OF and CTRL. Regardless of the concentration used, when data were pooled, OF supplementation improved (P < 0.05) monospermy and tended (P = 0.057) to enhance IVF efficiency. Additionally, IVF efficiency was higher (P < 0.05) in OF1 than in OF4 [60 ± 13 vs 37 ± 5%). The development capacity was not affected (P > 0.05) by the sperm concentration and OF treatment, and the average values were cleavage (72 ± 2.6%), blastocyst (37 ± 3.0%), blastocyst in relation to the cleaved (51 ± 4.8%), hatched (62 ± 1.2%), and number of cells per blastocyst (174 ± 1.8%). In conclusion, the six proteins analyzed are present in the OF of anestrous goats, and the supplementation of this OF during IVF may modulate the polyspermy incidence and enhance IVF efficiency, especially when 1x106 sperm per mL is used.

Racial inequality in perinatal outcomes in two Brazilian birth cohorts.

This study aimed to estimate and compare racial inequality in low birth weight (LBW), preterm birth (PTB), and intrauterine growth restriction (IUGR) in two Brazilian birth cohorts. This was a cross-sectional study nested within two birth cohorts in Ribeirão Preto (RP) and São Luís (SL), whose mothers were interviewed from January to December 2010. In all, 7430 (RP) and 4995 (SL) mothers were interviewed. The maternal skin color was the exposure variable. Associations were adjusted for socioeconomic and biological covariates: maternal education, per capita family income, family economic classification, household head occupation, maternal age, parity, marital status, prenatal care, type of delivery, maternal pre-pregnancy BMI, hypertension, hypertension during pregnancy, and smoking during pregnancy collected from questionnaires applied at birth. Statistical analysis was done with the chi-squared test and logistic regression. In RP, newborns from mothers with black skin color had a higher risk of LBW and IUGR, even after adjusting for socioeconomic and biological variables (P<0.001). In SL, skin color was not a risk factor for LBW (P=0.859), PTB (P=0.220), and IUGR (P=0.062), before or after adjustment for socioeconomic and biological variables. The detection of racial inequality in these perinatal outcomes only in the RP cohort after adjustment for socioeconomic and biological factors may be reflecting the existence of racial discrimination in the RP society. In contrast, the greater miscegenation present in São Luís may be reflecting less racial discrimination of black and brown women in this city.

Birth by cesarean section and mood disorders among adolescents of a birth cohort study in northern Brazil.

The increasing number of cesarean sections worldwide has encouraged research on the long-term effects of this birth type on the offspring's mental health. The objective of this study was to investigate whether there is an association between birth by cesarean section and the development of mood disorders (depression and bipolar disorders) in adolescents. A cohort study was carried out with 1603 adolescents from 18 to 19 years old who participated in the third phase of a birth cohort study in São Luís, MA, in 2016. Information on birth type and weight, prematurity, mother's age and schooling, parity, marital status, and smoking behavior during pregnancy, were collected at birth. The study outcomes were depression, bipolar disorder, and "mood disorder" construct. A Directed Acyclic Graph (DAG) was developed to select the variables for minimal adjustment for confounding and collision bias. Associations were estimated through propensity score weighting using a two-step estimation model, and confounders for cesarean birth were used in the predictive model. There was no significant association in the relationship between birth type and depression (95%CI: -0.037 to 0.017; P=0.47), bipolar disorder (95%CI: -0.019 to 0.045; P=0.43), and mood disorder (95%CI: -0.033 to 0.042; P=0.80) in adolescents of both sexes. Birth by cesarean section was not associated with the development of mood disorders in adolescents.

Potassium reduction in food by preparation technique for the dietetic management of patients with chronic kidney disease: a review.

BACKGROUND: Chronic kidney disease patients often use food preparation techniques to reduce potassium intake. However, the most effective techniques have not yet been determined for all food groups. The present study aimed to analyse all of the available information on potassium reduction in the food and identify the best preparation techniques by comparing the trend of change in potassium level. METHODS: Nine databases were searched from 1976 to May 2020, according to the PRISMA Statement. We included all articles reporting the amount of potassium before and after the application of food preparation techniques. Data were analysed using the Wilcoxon test and statistical simulation. RESULTS: A wide variety of food and culinary processes was observed in the 65 included articles. Cooking in water, pressure cooking and cooking in a microwave oven reduced potassium levels in all food groups, particularly in cereals and derivatives, fruits and derivatives, meats and derivatives, legumes, and leafy and cruciferous vegetables. Soaking food significantly reduced the potassium content in tubers and roots and leafy and cruciferous vegetables. Steam cooking and dry heating cooking also reduced potassium, although at a level lower than the other techniques. CONCLUSIONS: The present review shows that, in general, all food preparation techniques can reduce the potassium content, although cooking in water and soaking promotes a greater reduction; however, more studies with standardised techniques and complete data are necessary.

Exogenous progestogens differentially alter gene expression of immature cumulus-oocyte complexes in sheep.

This study evaluated the role of progesterone (P4) and medroxyprogesterone acetate (MAP) on the molecular status of immature cumulus-oocyte complexes (COCs) and the implications for oocyte quality in sheep. The number of viable COCs per ewe and the rate of COCs screened for developmental competence by brilliant cresyl blue positive (BCB+) were similar (P > 0.05), respectively, across treatments (P4: 7.7 ± 0.7 and 4.7 ± 1.2; MAP: 5.7 ± 1.0 and 3.5 ± 2.3; and control: 5.7 ± 1.1 and 3.6 ± 2.4). The COCs' gene expression was altered by exogenous progestogens compared with the control group: markers of steroidogenic pathway (FSH receptor [FSHr], LH receptor [LHr], and estradiol receptor α) and of quality (zygote arrest 1, growth differentiation factor 9, and B-cell lymphoma 2) were in abundance in P4 (P < 0.05). In addition, reelin protein (RELN) was downregulated, and Bcl-2 was upregulated in MAP (P < 0.05). In the P4 vs MAP comparison, FSHr, LHr, and RELN genes were upregulated (P < 0.05) in the P4 group. In conclusion, P4 and MAP promoted dissimilar effects on transcriptome profiling of immature BCB-selected COCs, possibly due to the differences in the chemical structure of progestogens and concentrations of serum P4. Exogenous P4 impacted positively on the profile of genes related to oocyte quality.

Association between tobacco and/or alcohol consumption during pregnancy and infant development: BRISA Cohort

Fetuses exposed to alcohol and/or tobacco are at risk for perinatal adversities. However, little is currently known about the association of the separate or concomitant use of alcohol and tobacco with infant motor and cognitive development. Thus, the objective of the present study was to investigate the association between maternal consumption of alcohol and/or tobacco during pregnancy and the motor and cognitive development of children starting from the second year of life. The study included 1006 children of a cohort started during the prenatal period (22-25 weeks of pregnancy), evaluated at birth and reevaluated during the second year of life in 2011/2013. The children were divided into four groups according to the alcohol and/or tobacco consumption reported by their mothers at childbirth: no consumption (NC), separate alcohol consumption (AC), separate tobacco consumption (TC), and concomitant use of both (ACTC). The Bayley Scale of Infant and Toddler Development Third Edition screening tool was used for the assessment of motor and cognitive development. Adjusted Poisson regression models were used to determine the association between groups and delayed development. The results indicated that only the ACTC group showed a higher risk of motor delay, specifically regarding fine motor skills, compared to the NC group (RR=2.81; 95%CI: 1.65; 4.77). Separate alcohol or tobacco consumption was not associated with delayed gross motor or cognitive development. However, the concomitant use of the two substances increased the risk of delayed acquisition of fine motor skills.

Body image dissatisfaction and symptoms of depression disorder in adolescents

The objective of this study was to evaluate the effect of body image dissatisfaction on symptoms of depressive disorder in adolescents. This is a cross-sectional study that included 2,162 adolescents ages 18-19 born in São Luís, Maranhão, Brazil, which was part of the joint RPS cohort (Brazilian birth cohorts of Ribeirão Preto-SP, Pelotas-RS, and São Luís-MA). Socioeconomic characteristics, nutritional status, mental health, and body image characteristics were evaluated. Body image was assessed by Stunkard's silhouettes scale. The presence of symptoms indicative of depressive disorder was investigated through a diagnostic interview MINI (Mini International Neuropsychiatric Interview). A theoretical model was built in a Directed Acyclic Graph (DAG) in order to investigate the relationship between the variables of the study. The relationship was estimated weighting the inverse probability of selection for the variables of adjustment: sex and nutritional status. Among the dissatisfied adolescents due to overweight, 66.54% were girls, 32.85% were overweight, and 11.99% were obese (P<0.01). There was a significant association between dissatisfaction due to overweight and symptoms of depressive disorder (P=0.01), and there was no evidence of the same association with dissatisfaction due to thinness. Therefore, only dissatisfaction due to overweight was associated with the symptoms of depressive disorder in the evaluated adolescents.

Is birth weight associated with pregestational maternal BMI? BRISA Cohort, Ribeirão Preto, Brazil

Given the increase of women with excess weight or obesity and its possible effects on birth weight, the present study aimed to investigate the association between pregestational maternal body mass index (BMI) and birth weight in a birth cohort from Ribeirão Preto, SP, Brazil. This was a prospective study conducted on 1362 mother-child pairs involving singleton births. The women were evaluated using standardized questionnaires during the second trimester of pregnancy and at the time of childbirth. Information about the newborns was obtained from their medical records. The dependent variable was birth weight, categorized as low, adequate, or high. The independent variable was pregestational maternal BMI, categorized as malnutrition, adequate weight, overweight, and obesity. A multinomial regression model was used to estimate the crude and adjusted relative risk (RR) of low and high birth weight. A high frequency of pregestational excess weight (39.6%) was detected and found to be independently associated with high birth weight (RR=2.13, 95%CI: 1.19-3.80 for overweight and RR=3.34, 95%CI: 1.80-6.19 for obese pregnant women). There was no association between pregestational malnutrition and low birth weight (RR=1.70; 95%CI: 0.81-3.55). The present data showed a high rate of women with excess pregestational weight, supporting the hypothesis that pregestational BMI may contribute to high birth weight babies and indicating the need for actions aiming to prevent excessive weight in women at reproductive age.

Metabolic profile during pregnancy in BRISA birth cohorts of Ribeirão Preto and São Luís, Brazil

During pregnancy, metabolic changes that develop in women may increase the risk of diseases and conditions that may also harm the life of the growing fetus. The aim of the present study was to identify and compare the metabolic profile (MP) during pregnancy in two birth cohorts in 2010 in the cities of Ribeirão Preto (RP) and São Luís (SL), Brazil. Pregnant women (1393 in RP and 1413 in SL) were studied; information was obtained through questionnaires in addition to anthropometric, biochemical, and blood pressure measurements. Data are presented as means and proportions. To compare the characteristics of pregnant women in both cities, chi-squared and Student's t-tests were applied, with 5% significance level. Ribeirão Preto presented higher mean values than SL for pre-gestational body mass index (24.5 vs 23 kg/m2, P<0.001), systolic (108.4 vs 102.8 mmHg, P<0.001) and diastolic (65.9 vs 61.8 mmHg, P<0.001) blood pressure, total cholesterol (226.3 vs 213.7 mg/dL, P<0.001) and fractions, and glycemia (84.5 vs 80.2 mg/dL, P<0.001), except for triglycerides (P=0.135). Women from RP also showed higher rates of pre-gestational overweight and obesity compared with SL (40.1 vs 25.8%). In the present study, pregnant women in RP had a worse gestational metabolic profile than those in SL, with higher pre-gestational excess weight, indicating that nutritional transition was more advanced in the more developed city.