Search

The study of the relationship between Daylight Saving Time (DST) and road safety has yielded contrasting results, most likely in relation to the inability of crash-database approaches to unravel positive (ambient lighting-related) and negative (circadian/sleep-related) effects, and to significant geographical differences in lighting-related effects. The aim of this study was to investigate the effects of DST on driving fatigue, as measured by driving-based, physiological and subjective indicators obtained from a driving simulator experiment. Thirty-seven participants (73 % males, 23 ± 2 years) completed a series of 50-min trials in a monotonous highway environment: Trial 1 was in the week prior to the Spring DST transition, Trial 2 in the following week, and Trial 3 in the fourth week after the transition. Thirteen participants returned for Trial 4, in the week prior to the Autumn switch to civil time, and Trial 5 in the following week. Significant adverse effects of DST on vehicle lateral control and eyelid closure were documented in Trial 2 and Trial 3 compared to Trial 1, with no statistical differences between Trials 2 and 3. Further worsening in vehicle lateral control was documented in Trials 4 and 5. Eyelid closure worsened up to Trial 4, and improved in Trial 5. Participants were unaware of their worsening performance based on subjective indicators. In conclusion, DST has a detrimental impact on driving fatigue during the whole time during which it is in place. Such an impact is comparable, for example, to that associated with driving with a blood alcohol concentration of 0.5 g/L.

Introduction: Face transplantation has gained recognition, changing the clinicalsurgical scenario for restoring complex facial defects, as it attributes functional and aesthetic recovery to patients who have suffered serious accidents. At the time of writing this article, in official publications, 43 patients had already undergone facial transplantation worldwide. Face transplantation has numerous pieces of evidence that can irrefutably provide improvements to the patient. For this, preoperative care for the patient must be carefully established so that there is good surgical performance. Case Report: Male patient, 46 years old, reports that, at the age of 6, he had burns due to exposure to gasoline, with 72% of his body surface burned, showing sequelae of burns and surgical reconstructions on the face, with redundant and ptotic skin flap on the left cheek, absence of upper and lower lip and exposure of lower teeth. Conclusion: It is important to publicize this innovative procedure in different medical specialties and preoperative care through a thorough investigation, which attributes better surgical effectiveness, allowing the rescue of their facial identity, once stigmatized.

Summary: Mutations in MPV17 are a major contributor to mitochondrial DNA (mtDNA) depletion syndromes, a group of inherited genetic conditions due to mtDNA instability. To investigate the role of MPV17 in mtDNA maintenance, we generated and characterized a Drosophila melanogaster Mpv17 (dMpv17) KO model showing that the absence of dMpv17 caused profound mtDNA depletion in the fat body but not in other tissues, increased glycolytic flux and reduced lifespan in starvation. Accordingly, the expression of key genes of glycogenolysis and glycolysis was upregulated in dMpv17 KO flies. In addition, we demonstrated that dMpv17 formed a channel in planar lipid bilayers at physiological ionic conditions, and its electrophysiological hallmarks were affected by pathological mutations. Importantly, the reconstituted channel translocated uridine but not orotate across the membrane. Our results indicate that dMpv17 forms a channel involved in translocation of key metabolites and highlight the importance of dMpv17 in energy homeostasis and mitochondrial function.

Introduction: Head and neck neoplasms often affect fundamental functions, such as swallowing, speech, eating, and socializing. Evaluating their treatment should consider the physician’s opinion and the patient’s perspective. This difficulty in assessing the success of treatment led to the development of the FACE-Q Head and Neck Cancer Module, a questionnaire of patient-reported outcomes that measure the appearance, facial function, quality of life, and experience of care to head and neck neoplasms. The objective is to translation, cultural adaptation, and linguistic validation of the FACE-Q Head and Neck Cancer questionnaire for Brazilian Portuguese. Methods: The translation, cultural adaptation, and linguistic validation of the full questionnaire took place in four stages, using official guidelines from the World Health Organization and the International Society of Pharmacoeconomics and Outcomes Research. Results: A semantic, idiomatic, and conceptually equivalent Brazilian Portuguese version was achieved through a linguistically validated translation of the English FACE-Q Head and Neck Cancer module. Conclusion: The Brazilian Portuguese version presents a version equivalent to the original English instrument, which can be used as a critical patient-reported outcome assessment.

Introdução: As neoplasias de cabeça e pescoço costumam afetar funções fundamentais, como engolir, falar, comer e se socializar. A avaliação do seu tratamento deve, portanto, levar em consideração a opinião do médico e a perspectiva do paciente. Essa dificuldade em avaliar o sucesso do tratamento levou ao desenvolvimento do FACE-Q - Módulo de Câncer de Cabeça e Pescoço, um questionário de resultados relatados pelo paciente que mede a aparência, função facial, qualidade de vida e experiência de cuidado para neoplasias de cabeça e pescoço. O objetivo é a tradução, adaptação cultural e validação linguística do questionário FACE- Q Câncer de Cabeça e Pescoço para o português brasileiro. Métodos: A tradução, adaptação cultural e validação linguística do questionário completo ocorreram em quatro etapas, usando as diretrizes oficiais da Organização Mundial da Saúde e da Sociedade Internacional de Farmacoeconomia e Pesquisa de Resultados. Resultados: Uma versão em português brasileiro semântica, idiomática e conceitualmente equivalente foi obtida por meio de uma tradução validada linguisticamente do módulo FACE-Q Head and Neck Cancer em inglês. Conclusão: A versão em português brasileiro apresenta uma versão com equivalente ao instrumento original em inglês, que pode ser utilizada como avaliação crítica de resultados relatados pelo paciente.

The human circadian timing system depends on the light/dark cycle as its main cue to synchronize with the environment, and thus with solar time. However, human activities depend also on social time, i.e. the set of time conventions and restrictions dictated by society, including Daylight Saving Time (DST), which adds an hour to any degree of desynchrony between social and solar time. Here, we used Google Trends as a data source to analyze diurnal variation, if any, and the daily peak in the relative search volume of 26 Google search queries in relation to the transitions to/from DST in Italy from 2015 to 2020. Our search queries of interest fell into three categories: sleep/health-related, medication and random non sleep/health-related. After initial rhythm and phase analysis, 11 words were selected to compare the average phase of the 15 days before and after the transition to/from DST. We observed an average phase advance after the transition to DST, and a phase delay after the transition to civil time, ranging from 25 to 60 minutes. Advances or delays shorter than 60 minutes, which were primarily observed in the sleep/health-related category, may suggest that search timing for these queries is at least partially driven by the endogenous circadian rhythm. Finally, a significant trend in phase anticipation over the years was observed for virtually all words. This is most likely related to an increase in age, and thus in earlier chronotypes, amongst Google users.

Circadian clocks orchestrate a variety of physiological and behavioural functions within the 24-h day. These timekeeping systems have also been implicated in developmental and reproductive processes that span more (or less) than 24 h. Whether natural alleles of cardinal clock genes affect entire sets of life-history traits (i.e., reproductive arrest, developmental time, fecundity), thus providing a wider substrate for seasonal adaptation, remains unclear. Here we show that natural alleles of the timeless (tim) gene of Drosophila melanogaster, previously shown to modulate flies’ propensity to enter reproductive dormancy, differentially affect correlated traits such as early-life fecundity and developmental time. Homozygous flies expressing the shorter TIM isoform (encoded by the s-tim allele) not only show a lower dormancy incidence compared to those homozygous for ls-tim (which produce both the short and an N-terminal additional 23-residues longer TIM isoform), but also higher fecundity in the first 12 days of adult life. Moreover, s-tim homozygous flies develop faster than ls-tim homozygous flies at both warm (25°C) and cold (15°C) temperatures, with the gap being larger at 15°C. In summary, this phenotypic analysis shows that natural variants of tim affect a set of life-history traits associated with reproductive dormancy in Drosophila. We speculate that this provides further adaptive advantage in temperate regions (with seasonal changes) and propose that the underlying mechanisms might not be exclusively dependent on photoperiod, as previously suggested.

Summary: Circadian desynchrony and sleep deprivation related to the Spring transition to Daylight Saving Time (DST) have been associated with several unfavorable outcomes, including an increase in road traffic accidents. As previous work has mainly focused on analyzing historical crash/hospitalization data, there is virtually no literature investigating the effects of DST on specific driving performance indicators. Here, the effect of the Spring transition to DST on driving performance was investigated by means of a driving simulator experiment, in which participants completed two trials (one week distance, same time and day of the week) on exactly the same simulated route, the second trial taking place in the week after the transition to DST. Results were compared to those of a control group (who also underwent two trials, both before the DST transition), and documented significant worsening of driving performance after DST, as measured by a comprehensive set of simulator-derived indices.

Mitochondrial diseases, including those caused by defects in complex III of the respiratory chain, lack curative treatments. Here the authors report that the small molecule pyocyanin has beneficial effects in cells derived from patients with complex III-deficiency as well as in fly and zebrafish genetic models with reduced complex III activity.

Introduction: Eyelid reconstruction can be performed by primary closure, a graft of different lamellae, and local and/or regional flaps, single or combined. This reconstruction becomes more complex when the upper and lower eyelids are resected to total thickness, and the eyeball is preserved. The objective is to report the techniques used for periorbital reconstruction in bipalpebral resection cases (upper and lower) with preservation of the eyeball by the Group of Orthopalpebral Surgery of the Division of Plastic Surgery and Burns of HCFMUSP. Methods: All cases that met the inclusion criteria from 2000 to 2019 were reviewed, and epidemiological, surgical, and postoperative follow-up data were described. Results: Only two cases were submitted to total exeresis of the periorbital tissue and remained susceptible to eyeball preservation. Both were reconstructed with frontal flaps with complete occlusion of the eyeball at the first moment, followed by the release in stages, keeping the globe viable after reconstruction completion. Discussion: Similar reports are scarce in the literature, and, in these cases, surgical results were functionally acceptable but with significant aesthetic limitations. Conclusion: We suggest a new option for total reconstruction of the upper and lower eyelid (with a single pedicular flap, devoid of connective graft and in multiple stages) that protects and conserves the eyeball during the various stages of surgery. The results were functionally favorable, considering the severity of the cases.

The redox activity of cytochrome c oxidase (COX), the terminal oxidase of the mitochondrial respiratory chain (MRC), depends on the incorporation of iron and copper into its catalytic centers. Many mitochondrial proteins have specific roles for the synthesis and delivery of metal-containing cofactors during COX biogenesis. In addition, a large set of different factors possess other molecular functions as chaperones or translocators that are also necessary for the correct maturation of these complexes. Pathological variants in genes encoding structural MRC subunits and these different assembly factors produce respiratory chain deficiency and lead to mitochondrial disease. COX deficiency in Drosophila melanogaster, induced by downregulated expression of three different assembly factors and one structural subunit, resulted in decreased copper content in the mitochondria accompanied by different degrees of increase in the cytosol. The disturbances in metal homeostasis were not limited only to copper, as some changes in the levels of cytosolic and/or mitochondrial iron, manganase and, especially, zinc were observed in several of the COX-deficient groups. The altered copper and zinc handling in the COX defective models resulted in a transcriptional response decreasing the expression of copper transporters and increasing the expression of metallothioneins. We conclude that COX deficiency is generally responsible for an altered mitochondrial and cellular homeostasis of transition metals, with variations depending on the origin of COX assembly defect.

The aims of the present study were to obtain sleep quality and sleep timing information in a group of university students and to evaluate the effects of a circadian hygiene education initiative. All students of the University of Padova (approximately 64,000) were contacted by e-mail (major campaigns in October 2019 and October 2020) and directed to an ad hoc website for collection of demographics and sleep quality/timing information. Participants (n = 5,740) received one of two sets of circadian hygiene advice (“A regular life” or “Bright days and dark nights”). Every month, they were then asked how easy it had been to comply and provided with the advice again. At any even month from joining, they completed the sleep quality/timing questionnaires again. Information on academic performance was obtained post hoc, together with representative samples of lecture (n = 5,972) and examination (n = 1,800) timings, plus lecture attendances (n = 25,302). Fifty-two percent of students had poor sleep quality, and 82% showed signs of social jetlag. Those who joined in October 2020, after several months of lockdown and distance learning, had better sleep quality, less social jetlag, and later sleep habits. Over approximately a year, the “Bright days and dark nights” advice resulted in significantly earlier get-up times compared with the “A regular life” advice. Similarly, it also resulted in a trend toward earlier midsleep (i.e., the midpoint, expressed as clock time, between sleep onset and sleep offset) and toward a decrease in the latency between wake-up and get-up time, with no impact on sleep duration. Significant changes in most sleep quality and sleep timing variables (i.e., fewer night awakenings, less social jetlag, and delayed sleep timing during lock-down) were observed in both advice groups over approximately a year, mostly in association with pandemic-related events characterizing 2020. Early chronotype students had better academic performances compared with their later chronotype counterparts. In a multivariate model, sleep quality, chronotype and study subject (science and technology, health and medical, or social and humanities) were independent predictors of academic performance. Taken together, these results underlie the importance of designing circadian-friendly university timetables.

The bifid nose management in Tessier nº 0 facial cleft is controversial due to its characteristics, such as a wide bone vault, low dorsal height, excessive skin, soft tissues volume, and distant upper and lower lateral cartilages. Conservative rhinoplasty techniques, using piezoelectric instruments, can be a good option for the bifid nose treatment, as they preserve the roof and upper lateral cartilages and perform a more accurate osteotomy. We report the treatment of bifid nose in a 13-year-old boy with facial cleft No. 0, to whom was performed conservative rhinoplasty with the aid of piezoelectric material. Given the excess of skin and soft tissues, a completely external transcutaneous approach was chosen. For osteotomies, lateral fractures under direct piezo-assisted vision were performed to have better control of the bone vault narrowing. The upper lateral cartilages and the internal nasal valves were preserved and brought back to the midline with horizontal "U" sutures to obtain a projection of the cartilaginous vault. A large segment of skin and soft tissue was excised after narrowing the nasal vault. A year of follow-up shows a narrow bone pyramid, better projection, and tip definition, but persisting with a vertically short nose. Conservative rhinoplasty techniques, assisted by piezoelectrics, may be an option for bifid nose treatment, requiring long-term follow-up and a study with more cases.

Infantile hemangioma (IH) is the most common vascular tumor and the most frequent benign neoplasm in childhood, with the highest incidence in females and the white population. Almost 60% of cases occur in the head and neck, and active treatment during the proliferative phase is the most frequently indicated, due to possible functional problems and disfiguring potential. We report a case of a patient with involute infantile hemangioma of the nasal tip and upper lip, treated expectantly during childhood, submitted to residual deformity correction with rhinoplasty techniques, associated with zetaplasty and upper lip grafting with good results and patient satisfaction.

Juvenile xanthogranuloma (JXG) is the most common benign tumor of the group of non-Langerhans histiocytic proliferative diseases. Lesions; 2 cm are considered giant JXG, with reports of lesions of up to 18 cm. Oculopalpebral lesions may require surgical treatment to control symptoms. This study reports a case of an 8-year-old boy who had four eyelids and the middle third of the face affected by giant JXG. He underwent three resections, one of which was of great depth that required a full-thickness skin graft directly on the levator palpebrae superioris aponeurosis. Subsequently, three fat-grafting procedures were performed and adequate functional and aesthetic results were achieved without lesion recurrence.

O artigo busca estabelecer, a partir de fontes primárias, uma cronologia dos acontecimentos preparatórios às ações da Operação Condor (pacto criminoso das ditaduras do Cone Sul), formalizada no Chile em1975. As conexões repressivas regionais já operavam desde 1972 por meio da Confederação Anticomunista Latino americana (CAL), braço da Liga Mundial Anticomunista (WACL), demonstrando-as aqui por meio do “capítulo” brasileiro da WACL/CAL, a Sociedade de Estudos Políticos, Econômicos e Sociais (SEPES).Associou-se à WACL, atuou na fundação da CAL em 1972, e promoveu o 2º Congresso da CAL no Rio de Janeiro (1974). Apontando como as ditaduras militares regionais já planificavam, um ano antes da Condor, o intercâmbio de “subversivos”e conclui, com fontes historiográficas, que o Protótipo do Condor organizava, desde 1973, o terrorismo transnacional de Estado

Introduction: Lesions affecting the hands with significant skin loss often require flaps for early coverage, as these permit faster healing. Among the various options, the reverse posterior interosseous flap of the forearm is most commonly used for defects involving the back of the hand and wrist due to low complication rates. Normally, this flap is not used for the reconstruction of defects in the palmar region since its distal reach is insufficient. Case report: We present the case of a male patient with third-degree electrical burns on his right palm, whose reconstruction was performed on the 14th day postinjury using the reverse posterior interosseous flap of the forearm after conservative debridement. The patient presented good postoperative evolution, without long-term complications or functional sequelae. Conclusion: The reverse posterior interosseous flap of the forearm permits adequate coverage of palm injuries, preserving its functionality.

Chronobiology is not routinely taught to biology or medical students in most European countries. Here we present the results of the chronobiology practicals of a group of students of the University of Padova, with a view to highlight some interesting features of this group, and to share a potentially interesting cross-faculty teaching experience. Thirty-eight students (17 males; 22.9 ± 1.6 yrs) completed a set of self-administered electronic sleep quality [Pittsburgh Sleep Quality Index (PSQI)], chronotype and sleepiness [Epworth Sleepiness Scale (ESS)] questionnaires. They then went on to complete sleep diaries for two weeks. Sixteen also wore an actigraph, 8 wore wireless sensors for skin temperature, and 8 underwent a course of chronotherapy aimed at anticipating their sleep-wake timing. Analyses were performed as practicals, together with the students. Average PSQI score was 5.4 ± 1.9, with 15 (39%) students being poor sleepers. Average ESS score was 6.5 ± 3.3, with 3 (8%) students exhibiting excessive daytime sleepiness. Seven classified themselves as definitely/moderately morning, 25 as intermediates, 6 as moderately/definitely evening. Students went to bed/fell asleep significantly later on weekends, it took them less to fall asleep and they woke up/got up significantly later. Diary-reported sleep onset time coincided with the expected decrease in proximal skin temperature. Finally, during chronotherapy they took significantly less time to fall asleep. In conclusion, significant abnormalities in the sleep-wake patterns of a small group of university students were observed, and the students seemed to benefit from chronotherapy. We had a positive impression of our teaching experience, and the chronobiology courses obtained excellent student feedback.

Abstract Recognizing that insights into the modulation of sleep duration can emerge by exploring the functional relationships among genes, we used this strategy to explore the genome-wide association results for this trait. We detected two major signalling pathways (ion channels and the ERBB signalling family of tyrosine kinases) that could be replicated across independent GWA studies meta-analyses. To investigate the significance of these pathways for sleep modulation, we performed transcriptome analyses of short sleeping flies’ heads (knockdown for the ABCC9 gene homolog; dSur). We found significant alterations in gene-expression in the short sleeping knockdowns versus controls flies, which correspond to pathways associated with sleep duration in our human studies. Most notably, the expression of Rho and EGFR (members of the ERBB signalling pathway) genes was down- and up-regulated, respectively, consistently with the established role of these genes for sleep consolidation in Drosophila. Using a disease multifactorial interaction network, we showed that many of the genes of the pathways indicated to be relevant for sleep duration had functional evidence of their involvement with sleep regulation, circadian rhythms, insulin secretion, gluconeogenesis and lipogenesis.

Cytochrome c oxidase (COX) deficiency is the biochemical hallmark of several mitochondrial disorders, including subjects affected by mutations in apoptogenic-1 (APOPT1), recently renamed as COA8 (HGNC:20492). Loss-of-function mutations are responsible for a specific infantile or childhood-onset mitochondrial leukoencephalopathy with a chronic clinical course. Patients deficient in COA8 show specific COX deficiency with distinctive neuroimaging features, i.e., cavitating leukodystrophy. In human cells, COA8 is rapidly degraded by the ubiquitin-proteasome system, but oxidative stress stabilizes the protein, which is then involved in COX assembly, possibly by protecting the complex from oxidative damage. However, its precise function remains unknown. The CG14806 gene (dCOA8) is the Drosophila melanogaster ortholog of human COA8 encoding a highly conserved COA8 protein. We report that dCOA8 knockdown (KD) flies show locomotor defects, and other signs of neurological impairment, reduced COX enzymatic activity, and reduced lifespan under oxidative stress conditions. Our data indicate that KD of dCOA8 in Drosophila phenocopies several features of the human disease, thus being a suitable model to characterize the molecular function/s of this protein in vivo and the pathogenic mechanisms associated with its defects.

With the approach of winter, many insects switch to an alternative protective developmental program called diapause. Drosophila melanogaster females overwinter as adults by inducing a reproductive arrest that is characterized by inhibition of ovarian development at previtellogenic stages. The insulin producing cells (IPCs) are key regulators of this process, since they produce and release insulin-like peptides that act as diapause-antagonizing hormones. Here we show that in D. melanogaster two neuropeptides, Pigment Dispersing Factor (PDF) and short Neuropeptide F (sNPF) inhibit reproductive arrest, likely through modulation of the IPCs. In particular, genetic manipulations of the PDF-expressing neurons, which include the sNPF-producing small ventral Lateral Neurons (s-LNvs), modulated the levels of reproductive dormancy, suggesting the involvement of both neuropeptides. We expressed a genetically encoded cAMP sensor in the IPCs and challenged brain explants with synthetic PDF and sNPF. Bath applications of both neuropeptides increased cAMP levels in the IPCs, even more so when they were applied together, suggesting a synergistic effect. Bath application of sNPF additionally increased Ca2+ levels in the IPCs. Our results indicate that PDF and sNPF inhibit reproductive dormancy by maintaining the IPCs in an active state.

Circadian clocks control and synchronize biological rhythms of several behavioral and physiological phenomena in most, if not all, organisms. Rhythm generation relies on molecular auto-regulatory oscillations of interlocked transcriptional-translational feedback loops. Rhythmic clock-gene expression is at the base of rhythmic protein accumulation, though post-transcriptional and post-translational mechanisms have evolved to adjust and consolidate the proper pace of the clock. In Drosophila, BELLE, a conserved DEAD-box RNA helicase playing important roles in reproductive capacity, is involved in the small RNA-mediated regulation associated to the piRNA pathway. Here, we report that BELLE is implicated in the circadian rhythmicity and in the regulation of endogenous transposable elements (TEs) in both nervous system and gonads. We suggest that BELLE acts as important element in the piRNA-mediated regulation of the TEs and raise the hypothesis that this specific regulation could represent another level of post-transcriptional control adopted by the clock to ensure the proper rhythmicity.

Patients with Primary Biliary Cholangitis (PBC) exhibit delayed sleep-wake habits, disturbed night sleep and daytime sleepiness/fatigue. Such combination of symptoms is reminiscent of delayed sleep-wake phase disorder (DSPD), which benefits from morning light treatment. The aim of the present pilot study was to test the effect of morning light treatment in a group of 13 well-characterized patients with PBC [all females; (mean ± SD) 53 ± 10 years]. Six healthy individuals (4 females, 57 ± 14 years) and 7 patients with cirrhosis (1 female, 57 ± 12 years) served as controls and diseased controls, respectively. At baseline, all participants underwent an assessment of quality of life, diurnal preference, sleep quality/timing (subjective plus actigraphy), daytime sleepiness, and urinary 6-sulphatoxymelatonin (aMT6s) rhythmicity. Then they underwent a 15-day course of morning bright light treatment, immediately after getting up (light box, 10,000 lux, 45 min) whilst monitoring sleep-wake patterns and aMT6s rhythmicity. At baseline, both patients with PBC and patients with cirrhosis had significantly worse subjective sleep quality compared to controls. In patients with PBC, light treatment resulted in an improvement in subjective sleep quality and a reduction in daytime sleepiness. In addition, both their sleep onset and get-up time were significantly advanced. Finally, the robustness of aMT6s rhythmicity (i.e., strength of the cosinor fit) increased after light administration but post-hoc comparisons were not significant in any of the groups. In conclusion, a brief course of morning bright light treatment had positive effects on subjective sleep quality, daytime sleepiness, and sleep timing in patients with PBC. This unobtrusive, side-effect free, non-pharmacological treatment is worthy of further study.

RESUMO Objetivo: relatar a experiência da Divisão de Cirurgia Plástica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo no tratamento de lesões cutâneas por extravasamento acidental de drogas. Métodos: foram incluídos os pacientes com lesões por extravasamento de drogas num período de 18 meses. Os seguintes parâmetros foram avaliados retrospectivamente: idade, diagnósticos durante internação e comorbidades, níveis séricos de albumina e hemoglobina, local de internação, droga envolvida, segmento anatômico acometido, conduta terapêutica e óbito durante internação. Resultados: foram acompanhados 14 pacientes. A principal droga envolvida foi a noradrenalina (21%). Todos os pacientes foram submetidos a desbridamento da necrose tecidual. Três pacientes foram submetidos a retalhos após preparo do leito com terapia por pressão negativa, com bons resultados. Sete pacientes não tiveram tratamento definitivo de suas lesões por falta de condições clínicas. Conclusão: o tratamento definitivo por meio de retalhos se mostrou adequado para os casos de feridas por extravasamento de drogas em tecido subcutâneo, quando há exposição de estruturas nobres, em pacientes com condições clínicas favoráveis.

Light is the main environmental stimulus that synchronizes the endogenous timekeeping systems in most terrestrial organisms. Drosophila cryptochrome (dCRY) is a light-responsive flavoprotein that detects changes in light intensity and wavelength around dawn and dusk. We have previously shown that dCRY acts through Inactivation No Afterpotential D (INAD) in a light-dependent manner on the Signalplex, a multiprotein complex that includes visual-signaling molecules, suggesting a role for dCRY in fly vision. Here, we predict and demonstrate a novel Ca2+-dependent interaction between dCRY and calmodulin (CaM). Through yeast two hybrid, coimmunoprecipitation (Co-IP), nuclear magnetic resonance (NMR) and calorimetric analyses we were able to identify and characterize a CaM binding motif in the dCRY C-terminus. Similarly, we also detailed the CaM binding site of the scaffold protein INAD and demonstrated that CaM bridges dCRY and INAD to form a ternary complex in vivo. Our results suggest a process whereby a rapid dCRY light response stimulates an interaction with INAD, which can be further consolidated by a novel mechanism regulated by CaM.

Cryptochromes (CRYs) are a class of flavoproteins that sense blue light. In animals, CRYs are expressed in the eyes and in the clock neurons that control sleep/wake cycles and are implied in the generation and/or entrainment of circadian rhythmicity. Moreover, CRYs are sensing magnetic fields in insects as well as in humans. Here, we show that in the fruit fly Drosophila melanogaster CRY plays a light-independent role as “assembling” protein in the rhabdomeres of the compound eyes. CRY interacts with actin and appears to increase light sensitivity of the eyes by keeping the “signalplex” of the phototransduction cascade close to the membrane. By this way, CRY also enhances light-responses of the circadian clock.

Single microRNAs are usually associated with hundreds of putative target genes that can influence multiple phenotypic traits in Drosophila, ranging from development to behaviour. We investigated the function of Drosophila miR-210 in circadian behaviour by misexpressing it within circadian clock cells. Manipulation of miR-210 expression levels in the PDF (pigment dispersing factor) positive neurons affected the phase of locomotor activity, under both light-dark conditions and constant darkness. PER cyclical expression was not affected in clock neurons, however, when miR-210 was up-regulated, a dramatic alteration in the morphology of PDF ventral lateral neuron (LNv) arborisations was observed. The effect of miR-210 in shaping neuronal projections was confirmed in vitro, using a Drosophila neuronal cell line. A transcriptomic analysis revealed that miR-210 overexpression affects the expression of several genes belonging to pathways related to circadian processes, neuronal development, GTPases signal transduction and photoreception. Collectively, these data reveal the role of miR-210 in modulating circadian outputs in flies and guiding/remodelling PDF positive LNv arborisations and indicate that miR-210 may have pleiotropic effects on the clock, light perception and neuronal development.

Abstract We studied two monozygotic twins, born to first cousins, affected by a multisystem disease. At birth, they both presented with bilateral cryptorchidism and malformations. Since early adulthood, they developed a slowly progressive neurological syndrome, with cerebellar and pyramidal signs, cognitive impairment, and depression. Dilating cardiomyopathy is also present in both. By whole‐exome sequencing, we found a homozygous nucleotide change in XRCC4 (c.673C>T), predicted to introduce a premature stop codon (p.R225*). XRCC4 transcript levels were profoundly reduced, and the protein was undetectable in patients' skin fibroblasts. XRCC4 plays an important role in non‐homologous end joining of DNA double‐strand breaks (DSB), a system that is involved in repairing DNA damage from, for example, ionizing radiations. Gamma‐irradiated mutant cells demonstrated reduction, but not abolition, of DSB repair. In contrast with embryonic lethality of the Xrcc4 KO mouse, nonsense mutations in human XRCC4 have recently been associated with primordial dwarfism and, in our cases, with adult‐onset neurological impairment, suggesting an important role for DNA repair in the brain. Surprisingly, neither immunodeficiency nor predisposition to malignancy was reported in these patients.

Patients with liver cirrhosis can develop hyperammonemia and hepatic encephalopathy (HE), accompanied by pronounced daytime sleepiness. Previous studies with healthy volunteers show that experimental increase in blood ammonium levels increases sleepiness and slows the waking electroencephalogram. As ammonium increases adenosine levels in vitro, and adenosine is a known regulator of sleep/wake homeostasis, we hypothesized that the sleepiness-inducing effect of ammonium is mediated by adenosine. Eight adult male Wistar rats were fed with an ammonium-enriched diet for 4 weeks; eight rats on standard diet served as controls. Each animal was implanted with electroencephalography/electromyography (EEG/EMG) electrodes and a microdialysis probe. Sleep EEG recording and cerebral microdialysis were carried out at baseline and after 6 h of sleep deprivation. Adenosine and metabolite levels were measured by high-performance liquid chromatography (HPLC) and targeted LC/MS metabolomics, respectively. Baseline adenosine and metabolite levels (12 of 16 amino acids, taurine, t4-hydroxy-proline, and acetylcarnitine) were lower in hyperammonemic animals, while putrescine was higher. After sleep deprivation, hyperammonemic animals exhibited a larger increase in adenosine levels, and a number of metabolites showed a different time-course in the two groups. In both groups the recovery period was characterized by a significant decrease in wakefulness/increase in NREM and REM sleep. However, while control animals exhibited a gradual compensatory effect, hyperammonemic animals showed a significantly shorter recovery phase. In conclusion, the adenosine/metabolite/EEG response to sleep deprivation was modulated by hyperammonemia, suggesting that ammonia affects homeostatic sleep regulation and its metabolic correlates.

Drosophila CRYPTOCHROME (CRY) is a blue light sensitive protein with a key role in circadian photoreception. A main feature of CRY is that light promotes an interaction with the circadian protein TIMELESS (TIM) resulting in their ubiquitination and degradation, a mechanism that contributes to the synchronization of the circadian clock to the environment. Moreover, CRY participates in non-circadian functions such as magnetoreception, modulation of neuronal firing, phototransduction and regulation of synaptic plasticity. In the present study we used co-immunoprecipitation, yeast 2 hybrid (Y2H) and in situ proximity ligation assay (PLA) to show that CRY can physically associate with the presynaptic protein BRUCHPILOT (BRP) and that CRY-BRP complexes are located mainly in the visual system. Additionally, we present evidence that light-activated CRY may decrease BRP levels in photoreceptor termini in the distal lamina, probably targeting BRP for degradation.

Antarctic krill (Euphausia superba) is a key species in the Southern Ocean with an estimated biomass between 100 and 500 million tonnes. Changes in krill population viability would have catastrophic effect on the Antarctic ecosystem. One looming threat due to elevated levels of anthropogenic atmospheric carbon dioxide (CO2) is ocean acidification (lowering of sea water pH by CO2 dissolving into the oceans). The genetics of Antarctic krill has long been of scientific interest for both for the analysis of population structure and analysis of functional genetics. However, the genetic resources available for the species are relatively modest. We have developed the most advanced genetic database on Euphausia superba, KrillDB, which includes comprehensive data sets of former and present transcriptome projects. In particular, we have built a de novo transcriptome assembly using more than 360 million Illumina sequence reads generated from larval krill including individuals subjected to different CO2 levels. The database gives access to: 1) the full list of assembled genes and transcripts; 2) their level of similarity to transcripts and proteins from other species; 3) the predicted protein domains contained within each transcript; 4) their predicted GO terms; 5) the level of expression of each transcript in the different larval stages and CO2 treatments. All references to external entities (sequences, domains, GO terms) are equipped with a link to the appropriate source database. Moreover, the software implements a full-text search engine that makes it possible to submit free-form queries. KrillDB represents the first large-scale attempt at classifying and annotating the full krill transcriptome. For this reason, we believe it will constitute a cornerstone of future approaches devoted to physiological and molecular study of this key species in the Southern Ocean food web.

PURPOSE: To investigate the immunohistochemistry of the uterine cervix of 20 Wistar rats (Rattus norvegicus) bearing the Walker 256 tumor, treated with copaiba oil (Copaifera officinalis). METHODS: The animals were grouped into four subgroups, with five rats each: the GCT and GCopT received distilled water and topically copaiba, respectively, while the GCG and GCopG received distilled water and copaiba by gavage, respectively. The substances were administered for nine days. On the 12th day, after euthanasia, the tumor pieces were sent to the identification of T CD4+, T CD8+ and Natural Killer cells. RESULTS: It was found that the pattern of expression for specific markers of phenotypes of cells involved in tumor immune response was similar in all groups, regardless the administration way of copaiba oil (topical or gavage). CONCLUSION: Copaiba balsam, administered either topically or by gavage, did not alter the pattern of tumor immune response in rats bearing Walker 256 Tumor.

In this review, we analyse the impact of a population and evolutionary genetics approach on the study of insect behaviour. Our attention is focused on the model organism Drosophila melanogaster and several other insect species. In particular, we explore the relationship between rhythmic behaviours and the molecular evolution of clock and ion channel genes.

Diapause is an actively induced dormancy that has evolved in Metazoa to resist environmental stresses. In temperate regions, many diapausing insects overwinter at low temperatures by blocking embryonic, larval or adult development. Despite its Afro-tropical origin, Drosophila melanogaster migrated to temperate regions of Asia and Europe where females overwinter as adults by arresting gonadal development (reproductive diapause) at temperatures

PURPOSE: To verify the copaiba balsam (Copaifera officinalis) effect on Walker 256 carcinoma inoculated into vagina and uterine cervix of rats. METHODS: Eighteen female Wistar rats weighing between 180-250g were used, distributed into 2 groups (GCop, GC). On the 1st day of the experiment, 0.3 ml of Walker 256 carcinoma (2x10(6) concentration) was inoculated in both groups; on the 3rd day of the experiment, it was given 4.8 ml/kg of distilled water to the GC group, and 4.8 ml/kg of copaiba balsam to the GCop group. On the 12th day, euthanasia was performed and the tumor was grafted, being weighted and verified its volume. The data were submitted to statistical analysis with ANOVA test. RESULTS: It was observed that copaiba balsam presented a negative inhibitory potential of 70%. CONCLUSION: The copaiba balsam stimulated the tumor growth.OBJETIVO: Verificar o efeito do óleo de copaíba da espécie Copaifera officinalis no carcinoma de Walker 256 inoculado em vagina e colo de útero de ratas. MÉTODOS: Foram utilizadas 18 ratas da linhagem Wistar, pesando entre 180-250g, distribuídas em dois grupos (CCop, GC). No 1º dia de experimento, em ambos os grupos foi inoculado 0,3ml de tumor de Walker 256 na concentração de 2x10(6); no 3º dia após essa inoculação, foi iniciada a administração de água destilada na dose de 4,8 ml/kg ao GC, e copaíba na dose de 4,8 ml/kg ao GCop. No 12º dia foi realizada a eutanásia das ratas e ressecado o tumor, sendo este pesado e averiguado seu volume. Os dados obtidos foram submetidos à análise estatística pelo método ANOVA. RESULTADOS: Observou-se que o óleo de copaíba apresentou um potencial inibitório negativo de 70%. CONCLUSÃO: O óleo de copaíba estimulou o crescimento tumoral.

PURPOSE: Verify the effect of oophorectomy on the evolution of the Walker 256 tumor inoculated into the vagina and cervix of female rats. METHODS: Ten Wistar, female rats were used, distributed into two groups with 05 animals each: Tumor group (TG): Rats inoculated with Walker 256 tumor; Oophorectomy group (OG): oophorectomized rats inoculated with Walker 256 tumor. The day before the tumor vaginal inoculation, acetic acid was inoculated into the vaginas of both groups of rats; the following day, the vaginal walls were scarified with an endocervix brush, and then Walker 256 tumor was inoculated. After 12 days, the tumor was removed together with the vagina and uterine horns for macro and microscopic analyses. The data were submitted to statistical analyses. RESULTS: There was no statistical difference between the two groups; however it was observed that the behavior of tumor growth on the OG group presented greater invasion, compromising the uterine horns. CONCLUSION: The results of the study on the GO group presented a macroscopic behavior different from the TG group, however, both of them presented similar development in terms of tumor mass.OBJETIVO: Verificar o efeito da ooforectomia à inoculação do tumor de Walker 256 em vagina e colo de útero de ratas. MÉTODOS: Foram utilizadas 10 ratas Wistar, fêmeas, virgens, adultas, distribuídas em dois grupos de estudo com 05 animais cada: grupo tumor (GT): ratas inoculadas com tumor de Walker 256, e grupo Ooforectomia (GO): ratas ooforectomizadas e inoculadas com tumor de Walker 256. No dia anterior à inoculação vaginal do tumor, foram inoculados 0,3ml de ácido acético na vagina das ratas de ambos os grupos; no dia seguinte, foi realizada a escarificação da parede vaginal com uma escova de endocérvice e inoculado tumor de Walker 256. Após 12 dias, foi removido o tumor em bloco com vagina e cornos uterinos para análise macro e microscópica. Os dados foram submetidos à análise estatística. RESULTADOS: Não houve diferença estatística entre os dois grupos; no entanto, notou-se que o comportamento de crescimento do tumor no grupo GO apresentou maior invasividade em extensão, comprometendo cornos uterinos. CONCLUSÃO: Observou-se que o grupo GO apresentou comportamento macroscópico diferente ao grupo GT, no entanto, em termos totais de massa tumoral ambos apresentam desenvolvimento similar.

BACKGROUND: Polar environments are characterized by extreme seasonal changes in day length, light intensity and spectrum, the extent of sea ice during the winter, and food availability. A key species of the Southern Ocean ecosystem, the Antarctic krill (Euphausia superba) has evolved rhythmic physiological and behavioral mechanisms to adapt to daily and seasonal changes. The molecular organization of the clockwork underlying these biological rhythms is, nevertheless, still only partially understood. METHODOLOGY/PRINCIPAL FINDINGS: The genome sequence of the Antarctic krill is not yet available. A normalized cDNA library was produced and pyrosequenced in the attempt to identify large numbers of transcripts. All available E. superba sequences were then assembled to create the most complete existing oligonucleotide microarray platform with a total of 32,217 probes. Gene expression signatures of specimens collected in the Ross Sea at five different time points over a 24-hour cycle were defined, and 1,308 genes differentially expressed were identified. Of the corresponding transcripts, 609 showed a significant sinusoidal expression pattern; about 40% of these exibithed a 24-hour periodicity while the other 60% was characterized by a shorter (about 12-hour) rhythm. We assigned the differentially expressed genes to functional categories and noticed that those concerning translation, proteolysis, energy and metabolic process, redox regulation, visual transduction and stress response, which are most likely related to daily environmental changes, were significantly enriched. Two transcripts of peroxiredoxin, thought to represent the ancestral timekeeping system that evolved about 2.5 billion years ago, were also identified as were two isoforms of the EsRh1 opsin and two novel arrestin1 sequences involved in the visual transduction cascade. CONCLUSIONS: Our work represents the first characterization of the krill diurnal transcriptome under natural conditions and provides a first insight into the genetic regulation of physiological changes, which occur around the clock during an Antarctic summer day.

BACKGROUND:Intronic genes represent ~6% of the total gene complement in Drosophila melanogaster and ~85% of them encode for proteins. We recently characterized the D. melanogaster timeless2 (tim2) gene, showing its active involvement in chromosomal stability and light synchronization of the adult circadian clock. The protein coding gene named 2mit maps on the 11(th) tim2 intron in the opposite transcriptional orientation. METHODOLOGY/PRINCIPAL FINDINGS:Here we report the molecular and functional characterization of 2mit. The 2mit gene is expressed throughout Drosophila development, localizing mainly in the nervous system during embryogenesis and mostly in the mushroom bodies and ellipsoid body of the central complex in the adult brain. In silico analyses revealed that 2mit encodes a putative leucine-Rich Repeat transmembrane receptor with intrinsically disordered regions, harboring several fully conserved functional interaction motifs in the cytosolic side. Using insertional mutations, tissue-specific over-expression, and down-regulation approaches, it was found that 2mit is implicated in adult short-term memory, assessed by a courtship conditioning assay. In D. melanogaster, tim2 and 2mit do not seem to be functionally related. Bioinformatic analyses identified 2MIT orthologs in 21 Drosophilidae, 4 Lepidoptera and in Apis mellifera. In addition, the tim2-2mit host-nested gene organization was shown to be present in A. mellifera and maintained among Drosophila species. Within the Drosophilidae 2mit-hosting tim2 intron, in silico approaches detected a neuronal specific transcriptional binding site which might have contributed to preserve the specific host-nested gene association across Drosophila species. CONCLUSIONS/SIGNIFICANCE:Taken together, these results indicate that 2mit, a gene mainly expressed in the nervous system, has a role in the behavioral plasticity of the adult Drosophila. The presence of a putative 2mit regulatory enhancer within the 2mit-hosting tim2 intron could be considered an evolutionary constraint potentially involved in maintaining the tim2-2mit host-nested chromosomal architecture during the evolution of Drosophila species.

ABSTRACT Background: tissue expanders have high relevance in plastic surgery and among indications it is worth mentioning their use in the treatment of burn reconstruction. Although it shows good results, its use requires special care because some complications can interrupt the reconstruction process. The objective of this study was to report the experience of the Clinics Hospital (University of Sao Paulo) with the use of tissue expanders to treat burn sequelae, establishing the incidence of complications, and identifying risk factors for their occurrence. Methods: a retrospective, observational, and analytical study, evaluating the use of expanders in burns sequelae treatment from 2009 to 2018. Results: 245 expanders were placed in 84 patients, 215 were female, with a mean age of 19.96 years, being 40% in the trunk and 20% in the scalp, with a predominance of rectangular shape in 76.7% of cases. Complications were classified as major and minor.Complications occurred in 17.95% of cases, and extrusion and infection were the most common. There was a higher incidence of complications in expanders used in the upper and lower limbs as well as in those who did not undergo concomitant expansion (p