Treatment of varicose veins using the Cryo laser after foam technique.

Sclerotherapy is the treatment of choice for telangiectasias and reticular veins. The most common side effects of this procedure are hyperpigmentation and matting, which are feared owing to their aesthetic damage and difficulty of treatment. Combined treatments with laser and hypertonic glucose sclerotherapy have been described with excellent results, but limited to treatment of veins of ≤2 mm in diameter. Cryo laser after foam sclerotherapy is a procedure to treat reticular veins in the lower extremities that utilizes first foam sclerotherapy with polidocanol than immediately followed by transdermal Nd:YAG 1064 laser treatment and we can treat veins ≤5 mm. This report presents a successful case of varicose vein treatment using combined transdermal laser and sclerotherapy with foam sclerotherapy with polidocanol to treat veins >2.5 mm in diameter.

Post-mortem diagnosis of human rabies in SARS-CoV-2 coinfected patient with minimally invasive autopsy in northeastern Brazil.

INTRODUCTION: Human rabies (HR) is a lethal zoonotic disease caused by lyssaviruses with increase in the number of cases post-coronavirus disease 2019 (COVID-19) pandemic. METHODOLOGY: We report a case of human rabies in a patient from a rural area of Ceará, northeastern Brazil in 2023, who was bitten by a white-tufted-ear marmoset (Callithrix jacchus jacchus). The patient was co-infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and was diagnosed by minimally invasive autopsy (MIA). RESULTS: MIA offers many advantages related to biosafety, and speed of sample acquisition; and markedly reduces disfigurement of the body compared with complete autopsy. It is a great alternative in COVID-19 patients. CONCLUSIONS: New methods such as MIA are a promising tool for diagnosis, and have the potential to improve family cooperation and support rabies surveillance.

Unusual dark-field hyperspectral and confocal Raman microscopy features of a nanoporous gold electrode coated with porphyrazine complex.

Nanoporous gold electrodes are of great interest in electroanalytical chemistry, because of their unusual activity and large surface area. The electrochemical activity can be further improved by coating with molecular catalysts such as the tetraruthenated cobalt-tetrapyridylporphyrazines investigated in this work. The plasmonic enhancement of the scattered light at the nanoholes and borders modifies the electrode's optical characteristics, improving the transmission through the surface-enhanced Raman scattering (SERS) effect. When monitored by hyperspectral dark-field and confocal Raman microscopy, this effect allows probing of the porphyrazine species at the plasmonic nanholes, improving the understanding of the chemically modified gold electrodes.

Congenital diaphragmatic hernia treated via fetal endoscopic tracheal occlusion improves outcome in a middle-income country.

OBJECTIVES: A recent European randomized trial - Tracheal Occlusion To Accelerate Lung Growth - demonstrated that fetoscopic endoluminal tracheal occlusion (FETO) is associated with increased postnatal survival among infants with severe congenital diaphragmatic hernia (CDH). However, this differs in middle-income countries such as Brazil, where abortion is illegal and neonatal intensive care is inadequate. This study evaluated the effects of FETO on improving the survival of infants with moderate-to-severe CDH in isolated and non-isolated cases. METHODS: This retrospective cohort study selected 49 fetuses with CDH, a normal karyotype, and a lung-to-head ratio (LHR) of <1 from a single national referral center for fetal surgery in São Paulo, Brazil, between January 2016 and November 2019. FETO was performed between 26 and 29 weeks of gestation. The primary outcomes were infant survival until discharge from the neonatal intensive care unit and survival until six months of age. RESULTS: Forty-six women with singleton fetuses having severe CDH underwent prenatal intervention with FETO. Infant survival rates until discharge and at six months of age were both 38 %. The observed-to-expected LHR increased by 25 % after FETO in neonates who survived until discharge. Spontaneous intrauterine death occurred in four growth-restricted fetuses after FETO. Preterm birth in <37 weeks and preterm rupture of membranes in <34 weeks occurred in 56.5 % (26) and 26 % (12) cases, respectively. CONCLUSIONS: FETO may increase neonatal survival in fetuses with severe CDH, particularly in countries with limited neonatal intensive care.

Neurodegenerative Diseases: Unraveling the Heterogeneity of Astrocytes.

The astrocyte population, around 50% of human brain cells, plays a crucial role in maintaining the overall health and functionality of the central nervous system (CNS). Astrocytes are vital in orchestrating neuronal development by releasing synaptogenic molecules and eliminating excessive synapses. They also modulate neuronal excitability and contribute to CNS homeostasis, promoting neuronal survival by clearance of neurotransmitters, transporting metabolites, and secreting trophic factors. Astrocytes are highly heterogeneous and respond to CNS injuries and diseases through a process known as reactive astrogliosis, which can contribute to both inflammation and its resolution. Recent evidence has revealed remarkable alterations in astrocyte transcriptomes in response to several diseases, identifying at least two distinct phenotypes called A1 or neurotoxic and A2 or neuroprotective astrocytes. However, due to the vast heterogeneity of these cells, it is limited to classify them into only two phenotypes. This review explores the various physiological and pathophysiological roles, potential markers, and pathways that might be activated in different astrocytic phenotypes. Furthermore, we discuss the astrocyte heterogeneity in the main neurodegenerative diseases and identify potential therapeutic strategies. Understanding the underlying mechanisms in the differentiation and imbalance of the astrocytic population will allow the identification of specific biomarkers and timely therapeutic approaches in various neurodegenerative diseases.

Diphenyl Diselenide Attenuates Mitochondrial Damage During Initial Hypoxia and Enhances Resistance to Recurrent Hypoxia.

Hypoxia plays a significant role in the development of various cerebral diseases, many of which are associated with the potential risk of recurrence due to mitochondrial damage. Conventional drug treatments are not always effective for hypoxia-related brain diseases, necessitating the exploration of alternative compounds. In this study, we investigated the potential of diphenyl diselenide [(PhSe)2] to ameliorate locomotor impairments and mitigate brain mitochondrial dysfunction in zebrafish subjected to hypoxia. Additionally, we explored whether these improvements could confer resistance to recurrent hypoxia. Through a screening process, an appropriate dose of (PhSe)2 was determined, and animals exposed to hypoxia received a single intraperitoneal injection of 100 mg/kg of the compound or vehicle. After 1 h from the injection, evaluations were conducted on locomotor deficits, (PhSe)2 content, mitochondrial electron transport system, and mitochondrial viability in the brain. The animals were subsequently exposed to recurrent hypoxia to assess the latency time to hypoxia symptoms. The findings revealed that (PhSe)2 effectively crossed the blood-brain barrier, attenuated locomotor deficits induced by hypoxia, and improved brain mitochondrial respiration by modulating complex III. Furthermore, it enhanced mitochondrial viability in the telencephalon, contributing to greater resistance to recurrent hypoxia. These results demonstrate the beneficial effects of (PhSe)2 on both hypoxia and recurrent hypoxia, with cerebral mitochondria being a critical target of its action. Considering the involvement of brain hypoxia in numerous pathologies, (PhSe)2 should be further tested to determine its effectiveness as a potential treatment for hypoxia-related brain diseases.

Effects of substratum type and orientation on the recruitment of bryozoans in an artificial area of the Western Atlantic.

Bryozoans are commonly associated with various artificial structures in marine environments and have been responsible for several bioinvasion events worldwide. Understanding the interactions between bryozoans and artificial structures is therefore essential to prevent the establishment and spread of potential bioinvaders. This study investigated bryozoan recruitment on four different substrates (PET, nautical ropes, metal, and PVC) placed in three orientations (vertical, horizontal facing down and facing up) in an area of the Western Atlantic. In total, 15 species of bryozoans were found. The results revealed significant variations in assemblages' richness, with bryozoans showing a preference for settling on PVC (14 species found) and on the underside of horizontal substrates (15 species found), resulting in the higher representativity observed in this study. Cryptogenic (nine species) and exotic (five species) bryozoans dominated the assemblages in all treatments, indicating that the type of substrate (especially artificial) and its orientation can favor the settlement of bryozoans, particularly non-native species. Therefore, the availability of multiple types of artificial substrates in marine environments should be treated as a cause for concern.

Pyrethroid genetic resistance in the dengue vector (Aedes aegypti) in Posadas, Argentina.

Pyrethroids are extensively used to control adult populations of the arboviral vector Aedes aegypti, raising concerns regarding the increasing frequency and distribution of insecticide resistance mutations (kdr: knock-down resistance) in the voltage-gated sodium channel gene (Nav). The widespread use of pyrethroids imposes a threat to the success of mosquito control and the environment. In this study, we investigated the presence of two kdr mutations (V1016I and F1534C) in the Nav gene and their distribution across four neighborhoods in Posadas, Argentina, with different Ae. aegypti abundance and contrasting socioeconomic status (SES). Alleles at each locus were interrogated using TaqMan SNP genotyping assays in DNA extracted from adult females collected in a longitudinal study. We report the presence of both pyrethroid resistance alleles (kdr 1016I = 29.08%; kdr 1534C = 70.70%) among adult females. The frequency of combined kdr genotypes reveals that approximately 70% of local adult females have enhanced resistance to pyrethroids. Both, the proportion of resistant adult females (with at least one kdr allele in each locus) and Ae. aegypti abundance showed an uneven distribution between neighborhoods with different SES (p < 0.001). In high-SES neighborhoods, we found more mosquitoes and a higher frequency of pyrethroid resistance, possibly as a consequence of different public health interventions, social habits, and insecticide use. This is the first report of kdr mutations in Ae. Aegypti in the northeast region of Argentina. Our results focus on the need for within-population (city) distribution analyses of kdr mutations and highlight the relevance of incorporating insecticide resistance monitoring within the Integrated Vector Management initiative.

Nd:Yag laser combined with injection sclerotherapy in the treatment of reticular veins and telangiectasias (CLaCS method): A triple-blind randomized clinical trial comparing two sclerosing agents associated with same laser patterns.

BACKGROUND: Cryo-Laser & Cryo-Sclerotherapy (CLaCS) is a technique which combines thermal sclerotherapy and injection sclerotherapy. Telangiectasias and small varicosities are targeted by a transdermal laser and right after receive injection sclerotherapy. A cooling device blows -20°C air onto the skin and needle in a pre-, parallel-, and post-fashion. OBJECTIVE: Our objective was to establish if there is a difference in result and complications by varying the sclerosing agent but keeping the same ND:Yag long pulse laser parameters in the treatment of small varicosities. METHODS: Fifty five patients were enrolled prospectively and randomized to two groups; in the group 1 dextrose 75% was the sclerosing agent used in combination with the ND:Yag long pulse laser and, in the group 2, the same laser technique was used but the sclerosing agent was polidocanol 0.3% and dextrose 67%. RESULTS: The results were evaluated 30 days after the treatment by the patients and for blinded evaluators using before and after standardized photos with and without augmented reality. In the patient's perspective and in the blinded evaluation of the regular photos, no differences between the groups were found. Both groups had low rates of hyperpigmentation and bruising with no statistical difference. Patients treated with polidocanol had less pain after the treatment and a better clearance rate in the photos with augmented reality. No major complications were found. CONCLUSION: The treatment of small varicosities with CLaCS using Dextrose 75% or polidocanol 0.3% and Dextrose 67.5% is a safe and effective procedure and both sclerosing agents can be used with similar results. Possibly, in the polidocanol group more nonvisible reticular veins were cleared, but the implication of this find is not clear.

Oxidative Stress and Mitochondrial Complex I Dysfunction Correlate with Neurodegeneration in an α-Synucleinopathy Animal Model.

The α-synucleinopathies constitute a subset of neurodegenerative disorders, of which Parkinson's disease (PD) is the most common worldwide, characterized by the accumulation of misfolded α-synuclein in the cytoplasm of neurons, which spreads in a prion-like manner to anatomically interconnected brain areas. However, it is not clear how α-synucleinopathy triggers neurodegeneration. We recently developed a rat model through a single intranigral administration of the neurotoxic ß-sitosterol ß-D-glucoside (BSSG), which produces α-synucleinopathy. In this model, we aimed to evaluate the temporal pattern of levels in oxidative and nitrosative stress and mitochondrial complex I (CI) dysfunction and how these biochemical parameters are associated with neurodegeneration in different brain areas with α-synucleinopathy (Substantia nigra pars compacta, the striatum, in the hippocampus and the olfactory bulb, where α-syn aggregation spreads). Interestingly, an increase in oxidative stress and mitochondrial CI dysfunction accompanied neurodegeneration in those brain regions. Furthermore, in silico analysis suggests a high-affinity binding site for BSSG with peroxisome proliferator-activated receptors (PPAR) alpha (PPAR-α) and gamma (PPAR-γ). These findings will contribute to elucidating the pathophysiological mechanisms associated with α-synucleinopathies and lead to the identification of new early biomarkers and therapeutic targets.

Estimation of body fat in children with intellectual disability: development and cross-validation of a simple anthropometric method

Abstract Objective Population-level monitoring of body composition requires accurate, biologically-relevant, yet feasible methods for estimating percent body fat (%BF). The aim of this study was to develop and cross-validate an equation for %BF from Body Mass Index (BMI), age, and sex among children with intellectual disability (ID). This study further aimed to examine the performance of an existing BMI-based equation (Deurenberg equation) for %BF in children with ID. Method Participants were 107 children (63 boys; aged 6-15 years) with ID randomly allocated to development (n= 81) and cross-validation (n= 26) samples. Dual-Energy X-Ray Absorptiometry provided the criterion %BF. Results The model including BMI, age, and sex (0 = male; 1 = female) had a significant goodness-of-fit in determining %BF (p< 0.001; R2= 0.69; SEE =5.68%). The equation was: %BF = - 15.416 + (1.394 × BMI) + (4.538 × age) - (0.262 × age2) + (5.489 × sex). The equation was cross-validated in the separate sample based on (i) strong correlation (r = 0.82; p< 0.001) and non-significant differences between actual and predicted %BF (28.6 ± 9.6% and 30.1 ± 7.1%, respectively); (ii) mean absolute error (MAE) = 4.4%; and (iii) reasonable %BF estimations in Bland-Altman plot (mean: 1.48%; 95% CI: 12.5, -9.6). The Deurenberg equation had a large %BF underestimation (mean: -7.1%; 95% CI: 5.3, -19.5), significant difference between actual and estimated %BF (28.6 ± 9.7% and 21.5 ± 7.0%, respectively; p< 0.001), and MAE = 8.1%. Conclusions The developed equation with BMI, sex, and age provides valid %BF estimates for facilitating population-level body fat screening among children with ID.

Myrtenol Reduces Orofacial Nociception and Inflammation in Mice Through p38-MAPK and Cytokine Inhibition.

Orofacial pain is one of the commonest and most complex complaints in dentistry, greatly impairing life quality. Preclinical studies using monoterpenes have shown pharmacological potential to treat painful conditions, but the reports of the effects of myrtenol on orofacial pain and inflammation are scarce. The aim of this study was to evaluate the effect of myrtenol in experimental models of orofacial pain and inflammation. Orofacial nociceptive behavior and the immunoreactivity of the phosphorylated p38 (P-p38)-MAPK in trigeminal ganglia (TG) and spinal trigeminal subnucleus caudalis (STSC) were determined after the injection of formalin in the upper lip of male Swiss mice pretreated with myrtenol (12.5 and 25 mg/kg, i.p.) or vehicle. Orofacial inflammation was induced by the injection of carrageenan (CGN) in the masseter muscle of mice pretreated with myrtenol (25 and 50 mg/kg, i.p.) or its vehicle (0.02% Tween 80 in saline). Myeloperoxidase (MPO) activity and histopathological changes in the masseter muscle and interleukin (IL)-1ß levels in the TG and STSC were measured. The increase in face-rubbing behavior time induced by formalin and P-p38-MAPK immunostaining in trigeminal ganglia were significantly reduced by myrtenol treatment (12.5 and 25 mg/kg). Likewise, increased MPO activity and inflammatory histological scores in masseter muscle, as well as augmented levels of IL-1ß in the TG AND STSC, observed after CGN injection, were significantly decreased by myrtenol (25 and 50 mg/kg). Myrtenol has potential to treat orofacial inflammation and pain, which is partially related to IL-1ß levels in the trigeminal pathway and p38-MAPK modulation in trigeminal ganglia.

Estimation of body fat in children with intellectual disability: development and cross-validation of a simple anthropometric method.

OBJECTIVE: Population-level monitoring of body composition requires accurate, biologically-relevant, yet feasible methods for estimating percent body fat (%BF). The aim of this study was to develop and cross-validate an equation for %BF from Body Mass Index (BMI), age, and sex among children with intellectual disability (ID). This study further aimed to examine the performance of an existing BMI-based equation (Deurenberg equation) for %BF in children with ID. METHOD: Participants were 107 children (63 boys; aged 6-15 years) with ID randomly allocated to development (n = 81) and cross-validation (n = 26) samples. Dual-Energy X-Ray Absorptiometry provided the criterion %BF. RESULTS: The model including BMI, age, and sex (0 = male; 1 = female) had a significant goodness-of-fit in determining %BF (p < 0.001; R2 = 0.69; SEE =5.68%). The equation was: %BF = - 15.416 + (1.394 × BMI) + (4.538 × age) - (0.262 × age2) + (5.489 × sex). The equation was cross-validated in the separate sample based on (i) strong correlation (r = 0.82; p < 0.001) and non-significant differences between actual and predicted %BF (28.6 ± 9.6% and 30.1 ± 7.1%, respectively); (ii) mean absolute error (MAE) = 4.4%; and (iii) reasonable %BF estimations in Bland-Altman plot (mean: 1.48%; 95% CI: 12.5, -9.6). The Deurenberg equation had a large %BF underestimation (mean: -7.1%; 95% CI: 5.3, -19.5), significant difference between actual and estimated %BF (28.6 ± 9.7% and 21.5 ± 7.0%, respectively; p < 0.001), and MAE = 8.1%. CONCLUSIONS: The developed equation with BMI, sex, and age provides valid %BF estimates for facilitating population-level body fat screening among children with ID.

Phenotypic investigation of 4-nitrophenylacetyl- and 4-nitro-1H-imidazoyl-based compounds as antileishmanial agents.

Cutaneous leishmaniasis (CL) is a spectrum of clinical manifestations characterized by severe skin ulcerations that leads to social stigma. There are limited treatment options for CL, and the available drugs are becoming less efficacious due to drug resistance. More efficacious and safer antileishmanial drugs are needed. In this study, the biological effect of seven synthetically accessible nitroaromatic compounds was evaluated in vitro against amastigotes of Leishmania amazonensis, followed by in vivo evaluation using mouse models of CL. Two compounds (6 and 7) were active against amastigotes in vitro [half-maximal effective concentration (EC50): 4.57 ± 0.08 and 9.19 ± 0.68 µm, respectively], with selectivity indexes >50, and the other compounds were not selective. In vivo, compounds 6 and 7 (10 mg kg−1, twice a day for 14 days) failed to reduce skin lesion sizes and parasite loads determined by light microscopy of lesion imprints and quantitative polymerase chain reaction. Nevertheless, the in vitro leishmanicidal efficacy sustained their use as templates for nitroimidazole-based antileishmanial drug discovery programmes focusing on analogues with more suitable properties.

E.L., a modern-day Phineas Gage: Revisiting frontal lobe injury.

Background: How the prefrontal cortex (PFC) recovers its functionality following lesions remains a conundrum. Recent work has uncovered the importance of transient low-frequency oscillatory activity (LFO; < 4 Hz) for the recovery of an injured brain. We aimed to determine whether persistent cortical oscillatory dynamics contribute to brain capability to support 'normal life' following injury. Methods: In this 9-year prospective longitudinal study (08/2012-2021), we collected data from the patient E.L., a modern-day Phineas Gage, who suffered from lesions, impacting 11% of his total brain mass, to his right PFC and supplementary motor area after his skull was transfixed by an iron rod. A systematic evaluation of clinical, electrophysiologic, brain imaging, neuropsychological and behavioural testing were used to clarify the clinical significance of relationship between LFO discharge and executive dysfunctions and compare E.L.´s disorders to that attributed to Gage (1848), a landmark in the history of neurology and neuroscience. Findings: Selective recruitment of the non-injured left hemisphere during execution of unimanual right-hand movements resulted in the emergence of robust LFO, an EEG-detected marker for disconnection of brain areas, in the damaged right hemisphere. In contrast, recruitment of the damaged right hemisphere during contralateral hand movement, resulted in the co-activation of the left hemisphere and decreased right hemisphere LFO to levels of controls enabling performance, suggesting a target for neuromodulation. Similarly, transcranial magnetic stimulation (TMS), used to create a temporary virtual-lesion over E.L.'s healthy hemisphere, disrupted the modulation of contralateral LFO, disturbing behaviour and impairing executive function tasks. In contrast to Gage, reasoning, planning, working memory, social, sexual and family behaviours eluded clinical inspection by decreasing LFO in the delta frequency range during motor and executive functioning. Interpretation: Our study suggests that modulation of LFO dynamics is an important mechanism by which PFC accommodates neurological injuries, supporting the reports of Gage´s recovery, and represents an attractive target for therapeutic interventions. Funding: Fundação de Amparo Pesquisa Rio de Janeiro (FAPERJ), Universidade Federal do Rio de Janeiro (intramural), and Fiocruz/Ministery of Health (INOVA Fiocruz).

Low levels of sulfur and cobalt during the pre- and periconceptional periods affect the oocyte yield of donors and the DNA methylome of preimplantation bovine embryos.

Maternal nutrition is critical in mammalian development, influencing the epigenetic reprogramming of gametes, embryos, and fetal programming. We evaluated the effects of different levels of sulfur (S) and cobalt (Co) in the maternal diet throughout the pre- and periconceptional periods on the biochemical and reproductive parameters of the donors and the DNA methylome of the progeny in Bos indicus cattle. The low-S/Co group differed from the control with respect to homocysteine, folic acid, B12, insulin growth factor 1, and glucose. The oocyte yield was lower in heifers from the low S/Co group than that in the control heifers. Embryos from the low-S/Co group exhibited 2320 differentially methylated regions (DMRs) across the genome compared with the control embryos. We also characterized candidate DMRs linked to the DNMT1 and DNMT3B genes in the blood and sperm cells of the adult progeny. A DMR located in DNMT1 that was identified in embryos remained differentially methylated in the sperm of the progeny from the low-S/Co group. Therefore, we associated changes in specific compounds in the maternal diet with DNA methylation modifications in the progeny. Our results help to elucidate the impact of maternal nutrition on epigenetic reprogramming in livestock, opening new avenues of research to study the effect of disturbed epigenetic patterns in early life on health and fertility in adulthood. Considering that cattle are physiologically similar to humans with respect to gestational length, our study may serve as a model for studies related to the developmental origin of health and disease in humans.

CriPAV: Street-Level Crime Patterns Analysis and Visualization.

Extracting and analyzing crime patterns in big cities is a challenging spatiotemporal problem. The hardness of the problem is linked to two main factors, the sparse nature of the crime activity and its spread in large spatial areas. Sparseness hampers most time series (crime time series) comparison methods from working properly, while the handling of large urban areas tends to render the computational costs of such methods impractical. Visualizing different patterns hidden in crime time series data is another issue in this context, mainly due to the number of patterns that can show up in the time series analysis. In this article, we present a new methodology to deal with the issues above, enabling the analysis of spatiotemporal crime patterns in a street-level of detail. Our approach is made up of two main components designed to handle the spatial sparsity and spreading of crimes in large areas of the city. The first component relies on a stochastic mechanism from which one can visually analyze probable×intensive crime hotspots. Such analysis reveals important patterns that can not be observed in the typical intensity-based hotspot visualization. The second component builds upon a deep learning mechanism to embed crime time series in Cartesian space. From the embedding, one can identify spatial locations where the crime time series have similar behavior. The two components have been integrated into a web-based analytical tool called CriPAV (Crime Pattern Analysis and Visualization), which enables global as well as a street-level view of crime patterns. Developed in close collaboration with domain experts, CriPAV has been validated through a set of case studies with real crime data in São Paulo - Brazil. The provided experiments and case studies reveal the effectiveness of CriPAV in identifying patterns such as locations where crimes are not intense but highly probable to occur as well as locations that are far apart from each other but bear similar crime patterns.