DNA Methylation and Demethylation Underlie the Sex Difference in Estrogen Receptor Alpha in the Arcuate Nucleus.

INTRODUCTION: Neurons expressing estrogen receptor (ER) ɑ in the arcuate (ARC) and ventromedial (VMH) nuclei of the hypothalamus sex-specifically control energy homeostasis, sexual behavior, and bone density. Females have more ERɑ neurons in the VMH and ARC than males, and the sex difference in the VMH is eliminated by neonatal treatment with testosterone or a DNA methylation inhibitor. OBJECTIVE: Here, we tested the roles of testosterone and DNA methylation/demethylation in development of ERɑ in the ARC. METHODS: ERɑ was examined at birth and weaning in mice that received vehicle or testosterone subcutaneously, and vehicle or DNA methyltransferase inhibitor intracerebroventricularly, as neonates. To examine effects of DNA demethylation on the ERɑ cell number in the ARC, mice were treated neonatally with small interfering RNAs against ten-eleven translocase enzymes. The methylation status of the ERɑ gene (Esr1) was determined in the ARC and VMH using pyrosequencing of bisulfite-converted DNA. RESULTS: A sex difference in ERɑ in the ARC, favoring females, developed between birth and weaning and was due to programming effects of testosterone. Neonatal inhibition of DNA methylation decreased ERɑ in the ARC of females, and an inhibition of demethylation increased ERɑ in the ARC of males. The promoter region of Esr1 exhibited a small sex difference in percent of total methylation in the ARC (females > males) that was opposite to that in the VMH (males > females). CONCLUSION: DNA methylation and demethylation regulate ERɑ cell number in the ARC, and methylation correlates with activation of Esr1 in this region.

Association Between Unbalanced Solutions and Acute Kidney Injury During Fluid Resuscitation in Children With Sepsis.

OBJECTIVE: To evaluate the outcomes of patients with sepsis-associated organ dysfunction and septic shock who receive fluid resuscitation with balanced and unbalanced solutions in a middle-income country. DESIGN: An observational, analytical cohort study with propensity score matching (PSM) in children admitted to a pediatric intensive care unit (PICU). Patients from one month to 17 years old who required fluid boluses due to hemodynamic instability were included. The primary outcome was the presence of acute kidney injury and the secondary outcomes were the need to begin continuous renal replacement therapy (CRRT), metabolic acidosis, PICU length of stay and mortality. MEASUREMENTS AND MAIN RESULTS: Out of the 1,074 admissions to the PICU during the study period, 99 patients had sepsis-associated organ dysfunction and septic shock. Propensity score matching was performed including each patient´s baseline characteristics. The median age was 9.9 months (IQR 4.9-22.2) with 55.5% of the patients being male. Acute kidney injury was seen less frequently in children who received a balanced solution than in those who received an unbalanced solution (20.3% vs 25.7% P = 0.006 ORa, 0.75; 95% CI, 0.65-0.87), adjusted for disease severity. In addition, the group that received balanced solutions had less need for CRRT (3.3 % vs 6.5%; P = 0.02 ORa 0.48; 95% CI, 0.36-0.64) and a shorter PICU stay (6 days IQR 4.4-20.2 vs 10.2 days IQR 4.7-26; P < 0.001) than the group with unbalanced solutions. We found no difference in the frequency of metabolic acidosis (P = 0.37), hyperchloremia (P = 0.11) and mortality (P = 0.25) between the 2 groups. CONCLUSION: In children with sepsis-associated organ dysfunction and septic shock, the use of unbalanced solutions for fluid resuscitation is associated with a higher frequency of acute kidney injury, a greater need for continuous renal support and a longer PICU stay compared to the use of balanced solutions, in a middle-income country.

Adolescent stress during, but not after, pubertal onset impairs indices of prepulse inhibition in adult rats.

Exposure to stress during adolescence is a risk factor for developing several psychiatric disorders, many of which involve prefrontal cortex (PFC) dysfunction. The human PFC and analogous rodent medial prefrontal cortex (mPFC) continue to mature functionally and anatomically during adolescence, and some of these maturational events coincide with pubertal onset. As developing brain regions are more susceptible to the negative effects of stress, this may make puberty especially vulnerable. To test this, we exposed male and female rats to isolation and restraint stress during the onset of puberty or during the post-pubertal period of adolescence. In young adulthood, both stressed groups and an unstressed control group underwent testing on a battery of tasks to assess emotional and cognitive behaviors, and the volume of the mPFC was quantified postmortem. Factor analysis revealed only subjects stressed peri-pubertally showed a long-term deficiency compared to controls in prepulse inhibition. Additionally, both sexes showed volumetric mPFC decreases following adolescent stress, and these losses were most pronounced in females. Our findings suggest that pubertal onset may be a vulnerable window wherein adolescents are most susceptible to the negative consequences of stress exposure. Furthermore, it highlights the importance of accounting for pubertal status when studying adolescents.

The genetic basis of natural antibody titers of young healthy pigs and relationships with disease resilience.

BACKGROUND: Disease resilience is the ability to maintain performance under pathogen exposure but is difficult to select for because breeding populations are raised under high health. Selection for resilience requires a trait that is heritable, easy to measure on healthy animals, and genetically correlated with resilience. Natural antibodies (NAb) are important parts of the innate immune system and are found to be heritable and associated with disease susceptibility in dairy cattle and poultry. Our objective was to investigate NAb and total IgG in blood of healthy, young pigs as potential indicator traits for disease resilience. RESULTS: Data were from Yorkshire x Landrace pigs, with IgG and IgM NAb (four antigens) and total IgG measured by ELISA in blood plasma collected ~ 1 week after weaning, prior to their exposure to a natural polymicrobial challenge. Heritability estimates were lower for IgG NAb (0.12 to 0.24, + 0.05) and for total IgG (0.19 + 0.05) than for IgM NAb (0.33 to 0.53, + 0.07) but maternal effects were larger for IgG NAb (0.41 to 0.52, + 0.03) and for total IgG (0.19 + 0.05) than for IgM NAb (0.00 to 0.10, + 0.04). Phenotypically, IgM NAb titers were moderately correlated with each other (average 0.60), as were IgG NAb titers (average 0.42), but correlations between IgM and IgG NAb titers were weak (average 0.09). Phenotypic correlations of total IgG were moderate with NAb IgG (average 0.46) but weak with NAb IgM (average 0.01). Estimates of genetic correlations among NAb showed similar patterns but with small SE, with estimates averaging 0.76 among IgG NAb, 0.63 among IgM NAb, 0.17 between IgG and IgM NAb, 0.64 between total IgG and IgG NAb, and 0.13 between total IgG and IgM NAb. Phenotypically, pigs that survived had slightly higher levels of NAb and total IgG than pigs that died. Genetically, higher levels of NAb tended to be associated with greater disease resilience based on lower mortality and fewer parenteral antibiotic treatments. Genome-wide association analyses for NAb titers identified several genomic regions, with several candidate genes for immune response. CONCLUSIONS: Levels of NAb in blood of healthy young piglets are heritable and potential genetic indicators of resilience to polymicrobial disease.

Developing and validating subjective and objective risk-assessment measures for predicting mortality after major surgery: An international prospective cohort study.

BACKGROUND: Preoperative risk prediction is important for guiding clinical decision-making and resource allocation. Clinicians frequently rely solely on their own clinical judgement for risk prediction rather than objective measures. We aimed to compare the accuracy of freely available objective surgical risk tools with subjective clinical assessment in predicting 30-day mortality. METHODS AND FINDINGS: We conducted a prospective observational study in 274 hospitals in the United Kingdom (UK), Australia, and New Zealand. For 1 week in 2017, prospective risk, surgical, and outcome data were collected on all adults aged 18 years and over undergoing surgery requiring at least a 1-night stay in hospital. Recruitment bias was avoided through an ethical waiver to patient consent; a mixture of rural, urban, district, and university hospitals participated. We compared subjective assessment with 3 previously published, open-access objective risk tools for predicting 30-day mortality: the Portsmouth-Physiology and Operative Severity Score for the enUmeration of Mortality (P-POSSUM), Surgical Risk Scale (SRS), and Surgical Outcome Risk Tool (SORT). We then developed a logistic regression model combining subjective assessment and the best objective tool and compared its performance to each constituent method alone. We included 22,631 patients in the study: 52.8% were female, median age was 62 years (interquartile range [IQR] 46 to 73 years), median postoperative length of stay was 3 days (IQR 1 to 6), and inpatient 30-day mortality was 1.4%. Clinicians used subjective assessment alone in 88.7% of cases. All methods overpredicted risk, but visual inspection of plots showed the SORT to have the best calibration. The SORT demonstrated the best discrimination of the objective tools (SORT Area Under Receiver Operating Characteristic curve [AUROC] = 0.90, 95% confidence interval [CI]: 0.88-0.92; P-POSSUM = 0.89, 95% CI 0.88-0.91; SRS = 0.85, 95% CI 0.82-0.87). Subjective assessment demonstrated good discrimination (AUROC = 0.89, 95% CI: 0.86-0.91) that was not different from the SORT (p = 0.309). Combining subjective assessment and the SORT improved discrimination (bootstrap optimism-corrected AUROC = 0.92, 95% CI: 0.90-0.94) and demonstrated continuous Net Reclassification Improvement (NRI = 0.13, 95% CI: 0.06-0.20, p < 0.001) compared with subjective assessment alone. Decision-curve analysis (DCA) confirmed the superiority of the SORT over other previously published models, and the SORT-clinical judgement model again performed best overall. Our study is limited by the low mortality rate, by the lack of blinding in the 'subjective' risk assessments, and because we only compared the performance of clinical risk scores as opposed to other prediction tools such as exercise testing or frailty assessment. CONCLUSIONS: In this study, we observed that the combination of subjective assessment with a parsimonious risk model improved perioperative risk estimation. This may be of value in helping clinicians allocate finite resources such as critical care and to support patient involvement in clinical decision-making.

Revision hip arthroplasty with a rectangular tapered cementless stem: a retrospective study of the SLR-Plus stem at a mean follow-up of 4.1 years.

PURPOSE: Demand for revision total hip arthroplasty (THA) is growing, and this type of surgery remains challenging for orthopedic surgeons. Our objectives were to assess clinical and radiographic outcomes, survivorship and complications with the SLR-Plus stem in revision THA. METHODS: We retrospectively reviewed 65 patients (66 hips) who had undergone revision THA with the SLR-Plus stem between 2008 and 2015 at two medical institutions with a minimum 2-year follow-up. The clinical outcome was assessed using the Harris hip score and the Merlé D'Aubigné score preoperatively and at final follow-up. A postoperative visual analogue scale for pain and satisfaction was also used. Radiographic subsidence and fixation, Kaplan-Meier survivorship and complications were analyzed. RESULTS: The mean follow-up was 4.1 years (SD 2.1). Aseptic loosening (57.6%) was the main indication for surgery. The mean Harris Hip Score improved from 50.4 (SD 16.5) to 83 (SD 12.7) (p < 0.001) and mean Merlé D'Aubigné score improved from 9.5 (SD 2.7) to 14.3 (SD 2.2) (p < 0.001). A total of 98.4% of stems showed radiographically stable fixation. No aseptic loosening of the stem was seen. Radiolucent lines > 1 mm were observed in 33.3% of stems. Three stems were re-revised: two due to infection and one due to instability. At 7 years, estimated stem survival was 95.5% for revision for any reason and 100% for revision for aseptic loosening. Dislocation occurred in 7.6% of hips. CONCLUSION: We have shown significant clinical improvement, 98.4% of stable fixation and 100% stem survivorship for aseptic loosening in revision THA with the SLR-Plus stem.

Anterior lens capsule strains during simulated accommodation in porcine eyes.

Experimental protocols have been developed to measure the spatial variation of the mechanical strains induced in the lens capsule during ex vivo lens stretching. The paper describes the application of these protocols to porcine lenses. The deformations and mechanical strains developed in the anterior capsule during each experiment were determined using full field digital image correlation techniques, by means of a speckle pattern applied to the lens surface. Several speckling techniques and illumination methods were assessed before a suitable combination was found. Additional data on the cross section shape of the anterior lens surface were obtained by Scheimpflug photography, to provide a means of correcting for lens curvature effects in the determination of the strains developed in the plane of the capsule. The capsule strains in porcine lenses exhibit non-linear behaviour, and hysteresis during loading and unloading. Peripheral regions experience higher magnitude strains than regions near the lens pole. The paper demonstrates the successful application of a procedure to make direct measurements of capsule strains simultaneously with ex vivo radial lens stretching. This experimental technique is applicable to future investigations on the mechanical characteristics of human lenses.

Molecular Aspects of a Robust Assay for Ferroxidase Function of Ceruloplasmin.

Ceruloplasmin (Cp) is one of the most complex multicopper oxidase enzymes and plays an essential role in the metabolism of iron in mammals. Ferrous ion supplied by the ferroportin exporter is converted by Cp to ferric ion that is accepted by plasma metallo-chaperone transferrin. Study of the enzyme at the atomic and molecular level has been hampered by the lack of a suitable ferrous substrate. We have developed the classic chromophoric complex FeIIHx(Tar)2 (H2Tar, 4-(2-thiazolylazo)resorcinol; x = 0-2; overall charge omitted) as a robust substrate for evaluation of the ferroxidase function of Cp and related enzymes. The catalysis can be followed conveniently in real time by monitoring the solution absorbance at 720 nm, a fingerprint of FeIIHx(Tar)2. The complex is oxidized to its ferric form FeIIIHx(Tar)2 via the overall reaction sequence FeIIHx(Tar)2 → FeII-Cp → FeIII-Cp → FeIIIHx(Tar)2: i.e., Fe(II) is transferred formally from FeIIHx(Tar)2 to the substrate docking/oxidation (SDO) site(s) in Cp, followed by oxidation to product Fe(III) that is trapped again by the ligand. Each Tar ligand in the above bis-complex coordinates the metal center in a meridional tridentate mode involving a pH-sensitive -OH group (pKa > 12), and this imposes rapid Fe(II) and Fe(III) transfer kinetics to facilitate the catalytic process. The formation constants of both the ferrous and ferric complexes at pH 7.0 were determined (log ß2' = 13.6 and 21.6, respectively), as well as an average dissociation constant of the SDO site(s) in Cp (log KD' = -7.2).

Validation of the Nuclear Cataract Grading System BCN 10.

PURPOSE: To evaluate a new nuclear cataract grading system which is intended as a surgical guidance system to predict lens hardness before cataract surgery. METHODS: The new BCN 10 grading system consists of frontal and cross-sectional slit-lamp images of human eye lenses, ranging from a completely transparent lens nucleus to a totally black nuclear cataract. Validation was done with 9 observers for 110 cases. Two modalities were applied, and observers were asked to use only whole digits and then half digits for grading. RESULTS: Repeatability with regard to test-retest differences showed a mean limit of agreement of 1.70 for whole digits and 1.32 for half digits. The absolute test-retest difference was close to zero for low as well high degrees of cataracts. Reliability for the entire group of 9 observers yielded an intraclass correlation coefficient which was within the same confidence interval, i.e., 0.991-0.995, for whole digits and half digits. CONCLUSIONS: BCN 10 grading repeatability was not affected by the severity of the cataract. It showed very good repeatability. Repeatability was significantly higher when the observers used half digits compared to whole digits. Reliability was found to be very good as well, independently of the use of whole or half digits.

Innervation of the medial prefrontal cortex by tyrosine hydroxylase immunoreactive fibers during adolescence in male and female rats.

Adolescence is associated with continued maturation of the cerebral cortex, particularly the medial prefrontal cortex (mPFC). We have previously documented pruning in the number of neurons, dendrites, and synapses in the rat mPFC from preadolescence to adulthood, with the period of pubertal onset being particularly important. We hypothesized that dopaminergic innervation of this region, critical for executive functions, would also be influenced by pubertal onset. Here, we measured changes in the volume of tyrosine hydroxylase (TH) immunoreactive axons in all layers of the male and female mPFC from preadolescence to adulthood (postnatal Day (P) 25, 35, 45, 60, and 90) as a marker of dopaminergic innervation. Assessing both total fiber volume and length, TH fibers were quantified by multiplying the mPFC volume by fiber density. While there were subtle layer-specific changes, TH fiber volume and length increased between P25 and P90 in both males and females. Contrary to our hypothesis, a role for pubertal onset in TH innervation of this region was not discernable. In summary, axons immunoreactive for TH increase with similar trajectories in the mPFC of male and female rats from pre-puberty to young adulthood.

Instruments for articulating the network of attention to women in situation of violence: collective construction. / Instrumentos para articulação da rede de atenção às mulheres em situação de violência: construção coletiva.

OBJECTIVE: This paper aims at identifying all the necessary information to build instruments which are designed to facilitate the professional integration of services to women in situation of violence with a view to the establishment of a network of attention. METHOD: Qualitative study, convergent, whose information has been produced from February to August 2015 by 10 group meetings, with 32 participants from the Integrated Working Group to Confront Violence in Santa Maria-RS, located at the Universidade Federal de Santa Maria. Using thematic content analysis. RESULTS: It defined the flow direction; the points to compose the network; what it would take to communicate among services: identification of wife and family, report on the situation and the continuity of care. CONCLUSIONS: There is a need for an institutional formalization of constructed devices. The articulation between the services requires communication, involvement and commitment of the professionals to ensure the continuity of care.

Health care for women in situations of violence: discoordination of network professionals.

OBJECTIVE: To learn the conceptions and actions of health professionals on the care network for women in situations of violence. METHOD: A qualitative, descriptive, exploratory study was conducted between April and July 2015 with the participation of 21 health professionals from four primary health care teams in a city of the central region of the state of Rio Grande do Sul. Data were collected by means of individual semi-structured interviews. Content analysis was used for data systematization. RESULTS: Health professionals recognized the importance of the health care network for coping with the problem of violence against women. However, their conceptions and actions were limited by the discoordination or absence of integration among professionals and services of the care network. CONCLUSION: The conceptions and actions of health professionals contribute to the discoordination among the services. It is necessary to reflect on the daily practices of care for women in situations of violence. OBJETIVO: Conhecer as concepções e ações de profissionais de saúde sobre a rede de atenção às mulheres em situação de violência. MÉTODO: Estudo qualitativo, descritivo e exploratório, realizado no período de abril a julho de 2015. Participaram 21 profissionais de saúde de quatro equipes da Atenção Primária à Saúde em um município da região central do estado do Rio Grande do Sul. A coleta de dados ocorreu mediante entrevistas semiestruturadas e individuais. Para sistematização dos dados, empregou-se a análise de conteúdo. RESULTADOS: Os profissionais de saúde reconheciam a importância da rede de atenção à saúde no enfrentamento da problemática da violência contra as mulheres. Contudo, suas concepções e ações eram limitadas pela desarticulação ou ausência de integração entre os profissionais e serviços da rede de atenção. CONCLUSÃO: As concepções e ações dos profissionais de saúde contribuem para a desarticulação entre os serviços. Faz-se necessário refletir acerca das práticas cotidianas de cuidados direcionados às mulheres em situação de violência.

Aspergillus steynii and Aspergillus westerdijkiae as potential risk of OTA contamination in food products in warm climates.

Aspergillus steynii and Aspergillus westerdijkiae are the main ochratoxin A (OTA) producing species of Aspergillus section Circumdati. Due to its recent description, few data are available about the influence of ecophysiological factors on their growth and OTA production profiles. In this work, the effect of temperature (20, 24 and 28 °C) and water activity (aw) (0.928, 0.964 and 0.995) on growth, sporulation and OTA production by these fungi was examined in CYA and media prepared from paprika, green coffee, anise, grapes, maize and barley. Growth was positively affected by the highest temperature and aw values indicating that both species might be expected in warm climates or storage conditions. However, optimal growth conditions showed differences depending on the medium. OTA production was markedly affected by substrate and showed qualitative and quantitative differences. Both species, especially A. steynii, represent a great potential risk of OTA contamination due to their high production in a variety of conditions and substrates, in particular in barley and paprika-based media. Additionally, neither growth nor sporulation did result good indicators of OTA production by A. steynii or A. westerdijkiae; therefore, specific and highly-sensitive detection methods become essential tools for control strategies to reduce OTA risk by these species.

["This conversation is professional, [...] I am a painter!": resistence at a construction site]. / "Aqui a conversa é profissional, [...] Eu sou a pintora!": resistência no canteiro de obra.

OBJECTIVE: to be familiar with the work relationships between females and their male colleagues at a construction site in the municipality of Santa Maria, RS. METHOD: Exploratory research, qualitative approach with a female worker of a construction site in August 2012. Oral history as a device for data production. Analysis of French tradition speech as an analytical device. RESULTS: Work relationship with stances of resistance, with major fights against power of male order, pointing to shifts and continuities in the test for new gender behaviors. CONCLUSIONS: The conquest of spaces in paid work is not enough to achieve balance in gender relations; public policies on gender sensitizing contribute to changes in the cultural field by understanding that equal rights and opportunities between men and women are a basic condition for achieving justice, citizenship and development.

[Care for women victims of violence: empowering nurses in the pursuit of gender equity]. / Cuidar mulheres em situação de violência: empoderamento da enfermagem em busca de equidade de gênero.

OBJECTIVES: To study the care of women victims of violence provided by nurses in emergency services and to analyse the practices that target the empowerment of women and gender equity. METHODS: A qualitative, descriptive study conducted by means of interviews with 10 nurses of an emergency and obstetrics unit of a university hospital and local emergency service of a city in southern Brazil from January to April 2013. We used thematic content analysis and defined gender as the analytical category. RESULTS: Clinical elements refer to nursing procedures and techniques. Non-clinical elements refer to conversation, listening and orientation to the women and their families. CONCLUSION: Revealing these actions is important to qualify nursing care in relation to the other health professionals and care services for women victims of violence.

Feasibility study of a SiPM-fiber detector for non-invasive measurement of arterial input function for preclinical and clinical positron emission tomography.

Pharmacokinetic positron emission tomography (PET) studies rely on the measurement of the arterial input function (AIF), which represents the time-activity curve of the radiotracer concentration in the blood plasma. Traditionally, obtaining the AIF requires invasive procedures, such as arterial catheterization, which can be challenging, time-consuming, and associated with potential risks. Therefore, the development of non-invasive techniques for AIF measurement is highly desirable. This study presents a detector for the non-invasive measurement of the AIF in PET studies. The detector is based on the combination of scintillation fibers and silicon photomultipliers (SiPMs) which leads to a very compact and rugged device. The feasibility of the detector was assessed through Monte Carlo simulations conducted on mouse tail and human wrist anatomies studying relevant parameters such as energy spectrum, detector efficiency and minimum detectable activity (MDA). The simulations involved the use of 18F and 68Ga isotopes, which exhibit significantly different positron ranges. In addition, several prototypes were built in order to study the different components of the detector including the scintillation fiber, the coating of the fiber, the SiPMs, and the operating configuration. Finally, the simulations were compared with experimental measurements conducted using a tube filled with both 18F and 68Ga to validate the obtained results. The MDA achieved for both anatomies (approximately 1000 kBq/mL for mice and 1 kBq/mL for humans) falls below the peak radiotracer concentrations typically found in PET studies, affirming the feasibility of conducting non-invasive AIF measurements with the fiber detector. The sensitivity for measurements with a tube filled with 18F (68Ga) was 1.2 (2.07) cps/(kBq/mL), while for simulations, it was 2.81 (6.23) cps/(kBq/mL). Further studies are needed to validate these results in pharmacokinetic PET studies.

Fundamental differences between quantum spin Hall edge states at zigzag and armchair terminations of honeycomb and ruby nets.

Combining an analytical and numerical approach we investigate the dispersion of the topologically protected spin-filtered edge states of the quantum spin Hall state on honeycomb and ruby nets with zigzag (ZZ) and armchair (AC) edges. We show that the Fermi velocity of the helical edge states on ZZ edges increases linearly with the strength of the spin-orbit coupling (SOC) whereas for AC edges the Fermi velocity is independent of the SOC. Also the decay length of edge states into the bulk is dramatically different for AC and ZZ edges, displaying an inverse functional dependence on the SOC.

Resolving refractive error after cataract surgery: IOL exchange, piggyback lens, or LASIK.

PURPOSE: To evaluate the efficacy, predictability, and safety of three different procedures (intraocular lens [IOL] exchange, piggyback lens implantation, and LASIK) to correct residual refractive error following cataract surgery. METHODS: A retrospective multicenter study comprised 65 eyes of 54 patients that underwent phacoemulsification, resulting in a unacceptable final refractive error. Eyes were divided into three groups: eyes that had an IOL lens exchange (17 eyes), eyes that had a piggyback lens implanted (20 eyes), and eyes that had LASIK (28 eyes). RESULTS: No differences between the IOL exchange and piggyback lens groups in the spherical equivalent, sphere, or cylinder were found (P = .072, .436, and .081, respectively). The LASIK group showed a statistically significant reduction in spherical equivalent and refractive cylinder when compared with the IOL exchange group (P < .001 and P = .001, respectively). The LASIK group showed statistically significant reduced refractive cylinder in comparison with the piggyback lens group (P = .002). The median efficacy index was 0.58 (range: 0.28 to 0.93), 0.75 (range: 0.65 to 0.92), and 0.91 (range: 0.85 to 1.14) in the IOL exchange, piggyback lens, and LASIK groups, respectively. Statistically significant differences were found between the IOL exchange and LASIK groups (P = .004) and the piggyback lens and LASIK groups (P = .003). No statistically significant differences were detected in the safety index among groups (P = .094). The predictability (±1 diopters of final spherical equivalent) was 62.5% of eyes in the IOL exchange group, 85% of eyes in the piggyback lens group, and 100% of eyes in the LASIK group. CONCLUSIONS: The three procedures were effective. The LASIK group showed the best outcomes in efficacy and predictability.

Perioperative complications and clinical outcomes of intraocular lens exchange in patients with opacified lenses.

BACKGROUND: To evaluate the perioperative complications and the outcomes of intraocular lens (IOL) exchange in patients with opacified lenses. METHODS: Retrospective multicentrical consecutive series of cases that comprised 22 eyes from 21 patients who had previous phacoemulsification with implantation of an IOL in the capsular bag and developed severe late opacification of the IOL. All patients had loss of vision and reported light disturbances. The IOLs were explanted and replaced with new IOLs. The perioperative complications were evaluated. The best spectacle-corrected visual acuity (BSCVA) before and after the surgery was compared. RESULTS: The mean time lapsed between the original cataract surgery and the IOL exchange surgery was 89.1 ± 33.6 [48-216] months. The IOL exchange was uneventful in 14 eyes (63.6 %). Anterior vitrectomy was needed in seven cases (31.8 %). Other complications included zonular dehiscence in one case (4.5 %). In most of the cases, 14 eyes (63.6 %), the IOL was implanted in the sulcus. The most explanted IOL was the Hydroview H60M (Bausch & Lomb). The mean BSCVA (LogMAR) before and after the surgery were 0.57 ± 0.69 (0.10-3) and 0.18 ± 0.22 (0.0-1.10) respectively (t paired test, p < 0.001). After the operation, 20 eyes (90.9 %) achieved a BSCVA ≤ 0.3. No eye lost 1 or more lines of corrected vision after the surgery. CONCLUSIONS: IOL exchange surgery, although associated with a high incidence of complications, restores and significantly improves the visual acuity of patients with opacified IOLs.

Feeding Neurons Integrate Metabolic and Reproductive States in Mice.

Trade-offs between metabolic and reproductive processes are important for survival, particularly in mammals that gestate their young. Puberty and reproduction, as energetically taxing life stages, are often gated by metabolic availability in animals with ovaries. How the nervous system coordinates these trade-offs is an active area of study. We identify somatostatin neurons of the tuberal nucleus (TNSST) as a node of the feeding circuit that alters feeding in a manner sensitive to metabolic and reproductive states in mice. Whereas chemogenetic activation of TNSST neurons increased food intake across sexes, selective ablation decreased food intake only in female mice during proestrus. Interestingly, this ablation effect was only apparent in animals with a low body mass. Fat transplantation and bioinformatics analysis of TNSST neuronal transcriptomes revealed white adipose as a key modulator of the effects of TNSST neurons on food intake. Together, these studies point to a mechanism whereby TNSST hypothalamic neurons modulate feeding by responding to varying levels of circulating estrogens differentially based on energy stores. This research provides insight into how neural circuits integrate reproductive and metabolic signals, and illustrates how gonadal steroid modulation of neuronal circuits can be context-dependent and gated by metabolic status.