Optical characterization and through-focus performance of two advanced monofocal intraocular lenses.

PURPOSE: To compare the refractive power profile, subjective depth-of-field and objective optical quality of two advanced monofocal intraocular lenses (IOLs) designed to improve intermediate vision. METHODS: This prospective study evaluated forty-six eyes of twenty-three patients, aged 54-68 years, binocularly implanted with two monofocal enhanced intraocular lenses (IOLs), the Tecnis Eyhance and the Physiol Isopure. Subjective through-focus visual acuity curves were obtained by placing trial lenses in front of the eye while wearing its best spherical-cylindrical correction for distance. Objective optical quality was defined as the area under the modulation transfer function, calculated from the wavefront maps measured with a high-resolution aberrometer. The optical design of both lenses was compared based on their refractive power profiles measured with the lenses immersed in saline solution. RESULTS: Both lenses have progressive aspherical geometries, in which the sagittal power decreases rapidly from the center to the edge of the optical zone. Mean monocular through-focus curves show a best corrected distance visual acuity of - 0.02 logMAR with both lenses. Through-focus visual acuity was marginally higher for the Eyhance, with a difference of 1 letter at the defocus position of - 0.5D and 3 letters between - 1.0D and - 2.0D. Objective assessment of optical quality revealed only a difference of about 2 points in MTF area at distance. CONCLUSION: Both IOLs use a similar approach to improve intermediate vision. The Eyhance showed marginally better subjective performance than the Isopure at the target vergences between - 1.00D and - 2.00D, although these results did not reach statistical significance and were not replicated by the objective findings.

Effects of amino acid supplementation on muscle mass, muscle performance and functional capacity in subjects undergoing total knee arthroplasty: a systematic review of randomized clinical trials.

The aim of the present study was to summarize the effectiveness of amino acid supplementation on muscle strength, muscle volume, and functional capacity in patients undergoing total knee arthroplasty. For this, in November 2022, a search was carried out in the PubMed, Cochrane Library, and EMBASE databases, identifying a total of 2182 documents, of which only 4 were included in the present review. The included studies had 148 participants (47 men and 101 women), with a minimum age of 53 and a maximum of 92 years, and supplementation times of 13 to 30 days (1 to 3 times a day). For the results, in relation to muscle performance, when comparing the control and experimental groups, greater muscle atrophy was observed in the pre- and post-moments of the control group, in relation to the experimental group. In addition, studies suggest a good tendency for muscle mass gain, and improvement in the functional capacities of patients who used supplementation. Therefore, the use of amino acids after TKA surgery reduces muscle atrophy, which preserves muscle mass and leads to better performance in tests of strength and functional capacity, when compared to the use of a placebo.

Synchrotron-based FTIR evaluation of biochemical changes in cancer and noncancer cells induced by brominated marine coelenteramine.

The mode of action toward gastric cancer cells of brominated Coelenteramine, an analogue of a metabolic product of a marine bioluminescent reaction, was investigated by synchrotron radiation-based Fourier Transform Infrared spectrocopy (FTIR). This method revealed that the anticancer activity of brominated Coelenteramine is closely connected with cellular lipids, by affecting their organization and composition. More specifically, there is an increasing extent of oxidative stress, which results in changes in membrane polarity, lipid chain packing and lipid composition. However, this effect was not observed in a noncancer cell line, helping to explain its selectivity profile. Thus, synchrotron radiation-based FTIR helped to identify the potential of this Coelenteramine analogue in targeting membrane lipids, while proving to be a powerful technique to probe the mechanism of anticancer drugs.

Discovery of the Anticancer Activity for Lung and Gastric Cancer of a Brominated Coelenteramine Analog.

Cancer is still a challenging disease to treat, both in terms of harmful side effects and therapeutic efficiency of the available treatments. Herein, to develop new therapeutic molecules, we have investigated the anticancer activity of halogenated derivatives of different components of the bioluminescent system of marine Coelenterazine: Coelenterazine (Clz) itself, Coelenteramide (Clmd), and Coelenteramine (Clm). We have found that Clz derivatives possess variable anticancer activity toward gastric and lung cancer. Interestingly, we also found that both brominated Clmd (Br-Clmd) and Clm (Br-Clm) were the most potent anticancer compounds toward these cell lines, with this being the first report of the anticancer potential of these types of molecules. Interestingly, Br-Clm possessed some safety profile towards noncancer cells. Further evaluation revealed that the latter compound induced cell death via apoptosis, with evidence for crosstalk between intrinsic and extrinsic pathways. Finally, a thorough exploration of the chemical space of the studied Br-Clm helped identify the structural features responsible for its observed anticancer activity. In conclusion, a new type of compounds with anticancer activity toward gastric and lung cancer was reported and characterized, which showed interesting properties to be considered as a starting point for future optimizations towards obtaining suitable chemotherapeutic agents.

Use of trichostatin A alters the expression of HDAC3 and KAT2 and improves in vitro development of bovine embryos cloned using less methylated mesenchymal stem cells.

The aim of this work was to investigate the methylation and hydroxymethylation status of mesenchymal stem cells (MSC) from amniotic fluid (MSC-AF), adipose tissue (MSC-AT) and fibroblasts (FIB-control) and to verify the effect of trichostatin A (TSA) on gene expression and development of cloned bovine embryos produced using these cells. Characterization of MSC from two animals (BOV1 and BOV2) was performed by flow cytometry, immunophenotyping and analysis of cellular differentiation genes expression. The cells were used in the nuclear transfer in the absence or presence of 50 nM TSA for 20 hr in embryo culture. Expression of HDAC1, HDAC3 and KAT2A genes was measured in embryos by qRT-PCR. Methylation results showed difference between animals, with MSC from BOV2 demonstrating lower methylation rate than BOV1. Meanwhile, MSC-AF were less hydroxymethylated for both animals. MSC-AF from BOV2 produced 44.92 ± 8.88% of blastocysts when embryos were exposed to TSA and similar to embryo rate of MSC-AT also treated with TSA (37.96 ± 15.80%). However, when methylation was lower in FIB compared to MSC, as found in BOV1, the use of TSA was not sufficient to increase embryo production. MSC-AF embryos expressed less HDAC3 when treated with TSA, and expression of KAT2A was higher in embryos produced with all MSC and treated with TSA than embryos produced with FIB. The use of MSC less methylated and more hydroxymethylated in combination with embryo incubation with TSA can induce lower expression of HDAC3 and higher expression of KAT2A in the embryos and consequently improve bovine embryo production.

Visualization of Urban Mobility Data from Intelligent Transportation Systems.

Intelligent Transportation Systems are an important enabler for the smart cities paradigm. Currently, such systems generate massive amounts of granular data that can be analyzed to better understand people's dynamics. To address the multivariate nature of spatiotemporal urban mobility data, researchers and practitioners have developed an extensive body of research and interactive visualization tools. Data visualization provides multiple perspectives on data and supports the analytical tasks of domain experts. This article surveys related studies to analyze which topics of urban mobility were addressed and their related phenomena, and to identify the adopted visualization techniques and sensors data types. We highlight research opportunities based on our findings.

Paralytic rabies in a goat.

BACKGROUND: Paralytic form of rabies is frequent in cattle in Latin America, but it is uncommon in goats. There are few clinical reports on furious rabies affecting goats, and the sporadic cases of rabid goats from surveillance programs worldwide lack clinical data. Furthermore, few studies reported the cerebrospinal fluid findings in rabid livestock. CASE PRESENTATION: On a farm in Midwestern Brazil, six of 47 Saanen goats died within one week. No vaccination protocols were implemented on the farm and the owner stated bat bites history on the livestock. Although rabies is endemic in Brazil, livestock vaccination is not mandatory. One 1-year-old buck was evaluated and showed non-specific clinical signs evolving within 12-h to nervous signs. Cerebrospinal fluid analysis revealed mononuclear pleocytosis, hyperproteinemia and high glucose levels. At necropsy, no gross lesions were present. Microscopically, discrete to moderate perivascular lymphoplasmacytic cuffing in gray and white matter, neuronal necrosis, neuronophagia, and mononuclear ganglioneuritis was observed in the brainstem and cervical spinal cord. Immunohistochemistry revealed strong anti-rabies virus immunostaining. Fresh central nervous system samples were positive for rabies in direct fluorescent antibody test (dFAT) and mouse intracerebral inoculation test (MIT). Exposed livestock recommendations included immediate vaccination, a strict isolation period of 90 days, and booster vaccinations during the third and eighth weeks. CONCLUSION: IHC revealed the widespread distribution of rabies virus antigen in the goat's CNS, contrasting the discrete pathological changes. In this goat, definitive diagnosis of paralytic rabies was obtained through the association of epidemiological, clinical, laboratorial, pathological findings (histology and IHC) and gold standard confirmatory tests (dFAT and MIT).

Highly efficient one-pot assembly of peptides by double chemoselective coupling.

This study describes a methodological advancement in solution-phase peptide synthesis via the development of a convenient and operational protocol to synthesize oligopeptides in a one-pot three-step cascade method, in which two peptide bonds are introduced chemoselectively. Tri- to hexapeptides were obtained in high global yields (80-95%) with virtually no epimerization as determined via HPLC. The methodology described herein represents a faster, easier and milder approach to the synthesis of peptides, and it operates at equimolar amounts. This protocol comprises the formation of secondary and tertiary amides and is compatible with Z, Boc and Fmoc N-protecting groups as well as the use of d/l and non-proteinogenic amino acids.

Novel l-prolyl-l-leucylglycinamide (PLG) tripeptidomimetics based on a 2-azanorbornane scaffold as positive allosteric modulators of the D2R.

An efficient and straightforward orthogonal methodology was successfully developed to achieve constrained l-prolyl-l-leucylglycinamide (PLG) analogues starting from two proline mimetics based on a 2-azanorbornane scaffold. A preliminary dopamine D2 receptor radiolabeled binding assay with [3H]-N-propylnorapomorphine shows that enantiopurity of PLG peptidomimetics based on 2-azanorbornane is a requirement to achieve statistically significant positive modulators of the D2 receptor. This is the first documented active peptidomimetic of PLG whose bioactivity is not correlated with the C-terminal carboxamide pharmacophore and which cannot adopt the hypothesized type II ß-turn conformation.

Partitioning the grapevine growing season in the Douro Valley of Portugal: accumulated heat better than calendar dates.

Temperature and water status profiles during the growing season are the most important factors influencing the ripening of wine grapes. To model weather influences on the quality and productivity of the vintages, it is necessary to partition the growing season into smaller growth intervals in which weather variables are evaluated. A significant part of past and ongoing research on the relationships between weather and wine quality uses calendar-defined intervals to partition the growing season. The phenology of grapevines is not determined by calendar dates but by several factors such as accumulated heat. To examine the accuracy of different approaches, this work analyzed the difference in average temperature and accumulated precipitation using growth intervals with boundaries defined by means of estimated historical phenological dates and intervals defined by means of accumulated heat or average calendar dates of the Douro Valley of Portugal. The results show that in situations where there is an absence of historical phenological dates and/or no available data that makes the estimation of those dates possible, it is more accurate to use grapevine heat requirements than calendar dates to define growth interval boundaries. Additionally, we analyzed the ability of the length of growth intervals with boundaries based on grapevine heat requirements to differentiate the best from the worst vintage years with the results showing that vintage quality is strongly related to the phenological events. Finally, we analyzed the variability of growth interval lengths in the Douro Valley during 1980-2009 with the results showing a tendency for earlier grapevine physiology.

Idiopathic intracranial hypertension and oxaliplatin: a causal association?

We report a case of a 54-year-old woman presented at the emergency service with complaints of transitory visual obscurations for four days, and headache, nausea and occasional vomiting in the last two months. She had been diagnosed of colorectal cancer one year ago and she was on treatment with oxaliplatin on a FOLFOX schedule. On ophthalmic examination, the vision was of 20/20 in both eyes and bilateral disc swelling was noted. The neurologic examination was normal. Magnetic resonance revealed no changes. A diagnostic lumbar puncture demonstrated an elevated opening pressure of 290 mm H2O with normal compounds. Due to the suspicion of ocular toxicity, oxaliplatin treatment was stopped. Treatment with oral acetazolamide was started and maintained for one month. In three weeks ocular and systemic symptoms totally disappeared and disc swelling gradually improved in the following months. Ocular toxicity has been reported as an infrequent adverse effect of oxaliplatin, but intracranial idiopathic pressure has not yet been described. Findings in this case suggest that oxaliplatin could be the cause for these symptoms. As the use of oxaliplatin is increasing as first-line treatment in colorectal cancer, we have to be alert to its potential toxicity.

[Educational technologies designed to promote cardiovascular health in adults: integrative review]. / Tecnologias educacionais desenvolvidas para promoção da saúde cardiovascular em adultos: revisão integrativa.

OBJECTIVE: Investigating the educational technologies developed for promoting cardiovascular health in adults. METHOD: Integrative review carried out in the databases of PubMed, SciELO and LILACS, with 15 articles selected. RESULTS: Over half (60%) of the studies were randomized clinical trials. The developed educational technologies were programs involving three strategies, with duration of one year, use of playful technologies with storytelling, computer programs or software for smartphones, and electronic brochure. These technologies resulted in reduction of blood pressure, weight, waist circumference, decreased hospitalizations and increased years of life. CONCLUSION: The studies with better impact on the cardiovascular health of adults were those who brought the technology in the form of program and duration of one year.

Domestic dog attacks on livestock referred to a Veterinary Teaching Hospital.

Losses and the economic impact of dog attacks (DAs) on livestock are often overlooked and include factors such as decreased production, expenses for treatment and handling, and death of injured animals. This study evaluated the epidemiological, therapeutic, and pathological findings of DAs on livestock over an 11-year survey using the records of farm animals referred to a Veterinary Teaching Hospital. Livestock attacked by dogs included 31 sheep, 11 horses, 3 cattle, 3 goats, and 2 pigs, totaling 50 animals. Anatomical locations injured by dog bites were identified as head/neck, thoracic/pelvic limbs, abdomen/flank, rump/tail, and multiple affected regions (two or more bite sites). Additionally, the severity of the injuries was classified into four degrees adapted from the classification of dog bite injuries in children. Most livestock presented Grade 1 (26%) and Grade 2 (28%) injuries, while Grade 3 and Grade 4 injuries were observed in 46% of DAs. Furthermore, 35 animals (70%) were discharged, 9 (18%) died, and 6 (12%) were humanely euthanized. DAs may represent a significant cause for referring livestock species to clinical care, severe injuries, and a considerable number of deaths. In this study, we provide information regarding DAs on livestock for the first time in Midwestern Brazil.

Utero-Cutaneous Fistula in Ruminants: Characterization of the First Cases in Ewes and Cows.

Reports on UCF in animals are still lacking in veterinary literature. Detailed clinical signs, laboratory findings, and follow-up information from the first cases of UCF in two ewes and two cows are provided. The cases occurred over a 12-year period. All ruminants presented a fistulous tract or perforated wound on the right ventral abdomen, emitting a foul-smelling secretion possibly associated with macerated fetal parts or placental remains. Laboratory findings included anemia, leukocytosis by neutrophilia, and hyperfibrinogenemia in one ewe, and hyperfibrinogenemia in one cow. Ovariohysterectomy and fistulectomy were performed in one ewe, while the other three ruminants were submitted for the removal of fetal parts and placental remains through the UCF. Two ewes died within 12-48 h, and the two Nelore cows had an uneventful recovery, achieving secondary intention healing within 30 to 35 days. As a never-reported or unnoticed disease of the reproductive tract, UCF is an unusual consequence of dead fetus retention in an end-stage pregnancy and a potentially life-threatening condition in ruminants, especially ewes. Further broad studies in large herds of cattle and small ruminant flocks must be conducted to estimate the incidence of UCF and ensure improvements in the diagnosis and knowledge of pathogenesis, aiming at prevention.

Prevalence, Incidence and Factors Associated with Diabetic Foot in People with Type 2 Diabetes: Systematic Review with Meta-Analysis.

BACKGROUND: Diabetic Foot is a severe chronic complication of diabetes and an important factor in the morbidity of diabetic people, resulting in high health costs and increased risk of death. OBJECTIVE: To analyze the incidence, prevalence, and risk factors associated with diabetic foot in people with type 2 Diabetes Mellitus. METHOD: Systematic literature review. Searches in MedLine via PubMed, LILACS, Web of Science, Scopus CINAHL, and Cochrane Library databases were performed. Inclusion of 52 studies. The R program, Metan packages, was used to calculate the meta-analysis. Given the heterogeneity of studies, the random effect was used to calculate the meta-analysis of risk factors. RESULTS: The meta-analysis showed that the prevalence of diabetic foot was 14% in a hospital setting and 5% in a community setting. The overall prevalence and incidence were 9% and 4%, respectively. Significant risk factors included time of DM (odds ratio [OR] =1.46, confidence interval [CI], 0.36-2.57, P = 0.009), smoking (OR = 1.46, CI, 1.16 -1.85, P< .001), glycated hemoglobin (OR = 0.96, CI, 0.50; 1.42, P< .001), peripheral arterial disease (OR = 3.38, CI, 2.07; 5.53, P < .001) and peripheral neuropathy (OR = 5.88, CI, 2.39-14.45, P<.001). CONCLUSION: Multidisciplinary monitoring, educational strategies, periodic foot examination for alterations, and early identification of risk factors are essential to prevent ulceration and reduce the disease burden.

Do good things really come to those who wait? An analysis of the average time of acceptance in Brazilian surgery journals.

PURPOSE: To analyze the average time between submission and acceptance of national journals in seven Brazilian surgery journals from 2017 to 2022. METHODS: It consists of a cross-sectional and observational study with a quantitative approach to analyze the acceptance time of articles approved by Brazilian journals on general surgery and its subspecialties, including Acta Cirúrgica Brasileira, Jornal Vascular Brasileiro, Arquivos Brasileiros de Cirurgia de Digestiva, Revista do Colégio Brasileiro de Cirurgiões, Journal of Coloproctology, Revista Brasileira de Cirurgia Plástica, and International Brazilian Journal of Urology. RESULTS: The journals with the lowest average waiting times were Revista do Colégio Brasileiro de Cirurgiões, Acta Cirúrgica Brasileira, and Journal of Coloproctology, respectively, and, with the lowest interquartile range there is Acta Cirúrgica Brasileira. There was no significant difference between the pre-pandemic and pandemic periods. The study designs with the highest and lowest means were, respectively, ideas and innovations - also with the highest interquartile range - and expert opinion, while with the lowest interquartile range was technical skill. CONCLUSIONS: The acceptance time for articles in Brazilian surgery journals is extremely variable. Identifying these discrepancies highlights the importance of understanding editorial processes and seeking ways to improve consistency and efficiency in reviewing articles.

Complete Thoracic Ectopia Cordis in Two Lambs.

Cardiac congenital defects related to inheritance and teratogenesis have been reported in veterinary species and humans worldwide. Among these, ectopia cordis (EC), characterized by an externalized heart through a cleft, is extremely rare in sheep. This report presents the diagnostic features of two cases of complete thoracic EC in newborn lambs. Clinical findings in the lambs, aside from the EC, were unremarkable. Both animals exhibited exteriorized hearts without pericardial coverage, delineated in the thoracic cleft by a fibrous ring of the pericardium and adjacent skin. Histologically, the epicardium was thickened by fibrous tissue in both lambs, with one animal also showing marked edema, hemorrhage, and neutrophilic inflammatory infiltration. The prognosis of EC in the lambs of this study was poor, with fatal outcomes despite attempts at surgical correction.

Exploring structural determinants of neuroprotection bias on novel glypromate conjugates with bioactive amines.

Neurodegenerative disorders of the central nervous system (CNS) such as Alzheimer's and Parkinson's diseases, afflict millions globally, posing a significant public health challenge. Despite extensive research, a critical hurdle in effectively treating neurodegenerative diseases is the lack of neuroprotective drugs that can halt or reverse the underlying disease processes. In this work, we took advantage of the neuroprotective properties of the neuropeptide glycyl-l-prolyl-l-glutamic acid (Glypromate) for the development of new peptidomimetics using l-pipecolic acid as a proline surrogate and exploring their chemical conjugation with relevant active pharmaceutical ingredients (API) via a peptide bond. Together with prolyl-based Glypromate conjugates, a total of 36 conjugates were toxicologically and biologically evaluated. In this series, the results obtained showed that a constrained ring (l-proline) at the central position of the peptide motif accounts for enhanced toxicological profiles and biological effects using undifferentiated and differentiated human neuroblastoma SH-SY5Y cells. Additionally, it was shown that biased biological responses are API-dependent. Conjugation with (R)-1-aminoindane led to a 38-43% reduction of protein aggregation induced by Aß25-35 (10 µM), denoting a 3.2-3.6-fold improvement in comparison with the parent neuropeptide, with no significative difference between functionalization at α and γ-carboxyl ends. On the other hand, the best-performing neuroprotective conjugate against the toxicity elicited by 6-hydroxydopamine (6-OHDA, 125 µM) was obtained by conjugation with memantine at the α-carboxyl end, resulting in a 2.3-fold improvement of the neuroprotection capacity in comparison with Glypromate neuropeptide. Altogether, the chemical strategy explored in this work shows that the neuroprotective capacity of Glypromate can be modified and fine-tuned, opening a new avenue for the development of biased neurotherapeutics for CNS-related disorders.

Identification of ubiquitin-specific protease 9X (USP9X) as a deubiquitinase acting on ubiquitin-peroxin 5 (PEX5) thioester conjugate.

Peroxin 5 (PEX5), the peroxisomal protein shuttling receptor, binds newly synthesized peroxisomal matrix proteins in the cytosol and promotes their translocation across the organelle membrane. During the translocation step, PEX5 itself becomes inserted into the peroxisomal docking/translocation machinery. PEX5 is then monoubiquitinated at a conserved cysteine residue and extracted back into the cytosol in an ATP-dependent manner. We have previously shown that the ubiquitin-PEX5 thioester conjugate (Ub-PEX5) released into the cytosol can be efficiently disrupted by physiological concentrations of glutathione, raising the possibility that a fraction of Ub-PEX5 is nonenzymatically deubiquitinated in vivo. However, data suggesting that Ub-PEX5 is also a target of a deubiquitinase were also obtained in that work. Here, we used an unbiased biochemical approach to identify this enzyme. Our results suggest that ubiquitin-specific protease 9X (USP9X) is by far the most active deubiquitinase acting on Ub-PEX5, both in female rat liver and HeLa cells. We also show that USP9X is an elongated monomeric protein with the capacity to hydrolyze thioester, isopeptide, and peptide bonds. The strategy described here will be useful in identifying deubiquitinases acting on other ubiquitin conjugates.