MicroRNAs and their Modulatory Effect on the Hallmarks of Osteosarcopenia.

PURPOSE OF THE REVIEW: Osteosarcopenia is a geriatric syndrome associated with disability and mortality. This review summarizes the key microRNAs that regulate the hallmarks of sarcopenia and osteoporosis. Our objective was to identify components similarly regulated in the pathology and have therapeutic potential by influencing crucial cellular processes in both bone and skeletal muscle. RECENT FINDINGS: The simultaneous decline in bone and muscle in osteosarcopenia involves a complex crosstalk between these tissues. Recent studies have uncovered several key mechanisms underlying this condition, including the disruption of cellular signaling pathways that regulate bone remodeling and muscle function and regeneration. Accordingly, emerging evidence reveals that dysregulation of microRNAs plays a significant role in the development of each of these hallmarks of osteosarcopenia. Although the recent recognition of osteosarcopenia as a single diagnosis of bone and muscle deterioration has provided new insights into the mechanisms of these underlying age-related diseases, several knowledge gaps have emerged, and a deeper understanding of the role of common microRNAs is still required. In this study, we summarize current evidence on the roles of microRNAs in the pathogenesis of osteosarcopenia and identify potential microRNA targets for treating this condition. Among these, microRNAs-29b and -128 are upregulated in the disease and exert adverse effects by inhibiting IGF-1 and SIRT1, making them potential targets for developing inhibitors of their activity. MicroRNA-21 is closely associated with the occurrence of muscle and bone loss. Conversely, microRNA-199b is downregulated in the disease, and its reduced activity may be related to increased myostatin and GSK3ß activity, presenting it as a target for developing analogues that restore its function. Finally, microRNA-672 stands out for its ability to protect skeletal muscle and bone when expressed in the disease, highlighting its potential as a possible therapy for osteosarcopenia.

Patterns of energetic substrate modifications in response to feeding in boas, Boa constrictor (Serpentes, Boidae).

Ambush-foraging snakes that ingest large meals might undergo several months without eating when they use the internal reserves to support the energetic costs of living. Then, morphological and physiological processes might be orchestrated during the transition from fasting to the postprandial period to rapidly use the energetic stores while the metabolic rate is elevated in response to food intake. To understand the patterns of substrates deposition after feeding, we accessed the morphological and biochemical response in Boa constrictor snakes after two months of fasting and six days after feeding. We followed the plasma levels of glucose, total proteins, and total lipids, and we performed the stereological ultrastructural analysis of the liver and the proximal region of the intestine to quantify glycogen granules and lipid droplets. In the same tissues and stomach, we measured the activity of the enzyme fructose-1,6-biphosphatase (FBPase1) involved in the gluconeogenic pathway, and we measured pyruvate kinase (PK) and lactate dehydrogenase (LDH) enzymatic activities involved in the anaerobic pathway in the liver. Briefly, our results indicated an increase in boas' plasma glucose one day after meal intake compared to unfed snakes. The hepatic glycogen reserves were continuously restored within days after feeding. Also, the enzymes involved in the energetic pathways increased activity six days after feeding in the liver. These findings suggest a quick restoring pattern of energetic stores during the postprandial period.

miR-29c Increases Protein Synthesis in Skeletal Muscle Independently of AKT/mTOR.

microRNAs negatively regulate gene expression by blocking translation or increasing mRNA degradation. In skeletal muscle, these molecules play important roles in adaptive responses, and ongoing investigations are necessary to understand the fine-tune regulation of skeletal muscle mass. Herein we showed that skeletal muscle overexpression of miR-29c increased fiber size and force at 7 and 30 days after electrotransfer. At both time points, AKT/mTOR pathway components were downregulated, and, surprisingly, overall protein synthesis was strongly elevated at day 7, which normalized by day 30 after pCMVmiR-29c electrotransfer. These results indicate that miR-29c expression induces skeletal muscle hypertrophy and gain of function, which involves increased overall protein synthesis in spite of the deactivation of the AKT/mTOR pathway.

Essential oils from Cymbopogon citratus and Lippia sidoides in the anesthetic induction and transport of ornamental fish Pterophyllum scalare.

This study verified the effects of essential oils from Lippia sidoides (EOLS) and Cymbopogon citratus (EOCC) on the anesthesia of freshwater angelfish (Pterophyllum scalare) of two different sizes (juveniles I (0.82 g) and II (2.40 g)) and the transport (8 h) of juveniles II. Fish were exposed to different concentrations of EOLS and EOCC: 0, 10, 25, 50, 75, 100, 150, 200, and 250 mg L-1. Ventilatory rate (VR) and transport for 8 h with 0, 10, and 15 mg L-1 of each essential oil were evaluated in juveniles II. The major components found in EOLS and EOCC were carvacrol (44.50%) and α-citral (73.56%), respectively. The best sedation and anesthesia times for both essential oils were obtained with 10 and 25 mg L-1 and 200 and 250 mg L-1 for juveniles I and II, respectively. Fish sedated with EOLS had lower VR values than the other treatments. Blood glucose levels were higher in ornamental fish transported with 10 and 15 mg EOLS L-1 and 15 mg EOCC L-1. Hepatic glycogen values were higher in the control group. In general, fish transported with 10 mg EOLS L-1 showed fewer gill histological alterations than other transported fish. When the type of lesion was evaluated, the highest gill alterations occurred in fish transported with EOCC. In conclusion, 10 mg EOLS L-1 could be used to transport of juveniles II because although this concentration increased blood glucose levels, it decreased the VR and muscle glycogen levels and caused only mild alterations to the gills.

Dielectric-Loaded Waveguides as Advanced Platforms for Diagnostics and Application of Transparent Thin Films.

An alternative approach to classical surface plasmon resonance spectroscopy is dielectric-loaded waveguide (DLWG) spectroscopy, widely used in the past decades to investigate bio-interaction kinetics. Despite their wide application, a successful and clear approach to use the DLWGs for the one-step simultaneous determination of both the thickness and refractive index of organic thin films is absent in the literature. We propose here, for the first time, an experimental protocol based on the multimodal nature of DLWGs to be followed in order to evaluate the optical constants and thickness of transparent thin films with a unique measurement. The proposed method is general and can be applied to every class of transparent organic materials, with a resolution and accuracy which depend on the nature of the external medium (gaseous or liquid), the geometrical characteristics of the DLWG, and the values of both the thickness and dielectric constant of the thin film. From the experimental point of view, the method is demonstrated in a nitrogen environment with an accuracy of about 3%, for the special case of electroluminescent thin films of Eu3+ß-diketonate complexes, with an average thickness of about 20 nm. The high value of the refractive index measured for the thin film with the Eu(btfa)3(t-bpete) complex was confirmed by the use of a spectroscopic model based on the Judd-Ofelt theory, in which the magnetic dipole transition 5D0 → 7F1 (Eu3+) for similar films containing Eu3+ complexes is taken as a reference. The DLWGs are finally applied to control the refractive index changes of the organic thin films under UVA irradiation, with potential applications in dosimetry and monitoring light-induced transformation in organic thin films.

Feeding effects on liver mitochondrial bioenergetics of Boa constrictor (Serpentes: Boidae).

Snakes are interesting examples of taxa that can overcome energy metabolism challenges, as many species can endure long periods without feeding, and their eventual meals are of reasonably large sizes, thus exhibiting dual extreme adaptations. Consequently, metabolic rate increases considerably to attend to the energetic demand of digestion, absorption and protein synthesis. These animals should be adapted to transition from these two opposite states of energy fairly quickly, and therefore we investigated mitochondrial function plasticity in these states. Herein, we compared liver mitochondrial bioenergetics of the boid snake Boa constrictor during fasting and after meal intake. We fasted the snakes for 60 days, and then we fed a subgroup with 30% of their body size and evaluated their maximum postprandial response. We measured liver respiration rates from permeabilized tissue and isolated mitochondria. From isolated mitochondria, we also measured Ca2+ retention capacity and redox status. Mitochondrial respiration rates were maximized after feeding, reaching an approximately 60% increase from fasting levels when energized with complex I-linked substrates. Interestingly, fasting and fed snakes exhibited similar respiratory control ratios and citrate synthase activity. Furthermore, we found no differences in Ca2+ retention capacity, indicating no increase in susceptibility to mitochondrial permeability transition, and no changes in mitochondrial redox state, although fed animals exhibited increases in the release of H2O2. Thus, we conclude that liver mitochondria from B. constrictor snakes increase respiration rates during the postprandial period and quickly improve the bioenergetic capacity without compromising redox balance.

Regulation of Glucose Metabolism by MuRF1 and Treatment of Myopathy in Diabetic Mice with Small Molecules Targeting MuRF1.

The muscle-specific ubiquitin ligase MuRF1 regulates muscle catabolism during chronic wasting states, although its roles in general metabolism are less-studied. Here, we metabolically profiled MuRF1-deficient knockout mice. We also included knockout mice for MuRF2 as its closely related gene homolog. MuRF1 and MuRF2-KO (knockout) mice have elevated serum glucose, elevated triglycerides, and reduced glucose tolerance. In addition, MuRF2-KO mice have a reduced tolerance to a fat-rich diet. Western blot and enzymatic studies on MuRF1-KO skeletal muscle showed perturbed FoxO-Akt signaling, elevated Akt-Ser-473 activation, and downregulated oxidative mitochondrial metabolism, indicating potential mechanisms for MuRF1,2-dependent glucose and fat metabolism regulation. Consistent with this, the adenoviral re-expression of MuRF1 in KO mice normalized Akt-Ser-473, serum glucose, and triglycerides. Finally, we tested the MuRF1/2 inhibitors MyoMed-205 and MyoMed-946 in a mouse model for type 2 diabetes mellitus (T2DM). After 28 days of treatment, T2DM mice developed progressive muscle weakness detected by wire hang tests, but this was attenuated by the MyoMed-205 treatment. While MyoMed-205 and MyoMed-946 had no significant effects on serum glucose, they did normalize the lymphocyte-granulocyte counts in diabetic sera as indicators of the immune response. Thus, small molecules directed to MuRF1 may be useful in attenuating skeletal muscle strength loss in T2DM conditions.

Heart rate variability in the tegu lizard, Salvator merianae, its neuroanatomical basis and role in the assessment of recovery from experimental manipulation.

Using long-term, remote recordings of heart rate (fH) on fully recovered, undisturbed lizards, we identified several components of heart rate variability (HRV) associated with respiratory sinus arrhythmia (RSA): 1.) A peak in the spectral representation of HRV at the frequency range of ventilation. 2.) These cardiorespiratory interactions were shown to be dependent on the parasympathetic arm of the autonomic nervous system. 3.) Vagal preganglionic neurons are located in discrete groups located in the dorsal motor nucleus of the vagus and also, in a ventro-lateral group, homologous to the nucleus ambiguus of mammals. 4.) Myelinated nerve fibers in the cardiac vagus enabling rapid communication between the central nervous system and the heart. Furthermore, the study of the progressive recovery of fH in tegu following anesthesia and instrumentation revealed that 'resting' levels of mean fH and reestablishment of HRV occurred over different time courses. Accordingly, we suggest that, when an experiment is designed to study a physiological variable reliant on autonomic modulation at its normal, resting level, then postsurgical reestablishment of HRV should be considered as the index of full recovery, rather than mean fH.

Respiratory sinus arrhythmia is a major component of heart rate variability in undisturbed, remotely monitored rattlesnakes, Crotalus durissus.

ECG recordings were obtained using an implanted telemetry device from the South American rattlesnake, Crotalus durissus, held under stable conditions without restraining cables or interaction with researchers. Mean heart rate (fH) recovered rapidly (<24 h) from anaesthesia and operative procedures. This preceded a more gradual development of heart rate variability (HRV), with instantaneous fH increasing during each lung ventilation cycle. Atropine injection increased mean fH and abolished HRV. Complete autonomic blockade revealed a cholinergic tonus on the heart of 55% and an adrenergic tonus of 37%. Power spectral analysis of HRV identified a peak at the same frequency as ventilation. This correlation was sustained after temperature changes and it was more evident, marked by a more prominent power spectrum peak, when ventilation is less episodic. This HRV component is homologous to that observed in mammals, termed respiratory sinus arrhythmia (RSA). Evidence for instantaneous control of fH indicated rapid conduction of activity in the cardiac efferent nervous supply, as supported by the description of myelinated fibres in the cardiac vagus. Establishment of HRV 10 days after surgical intervention seems a reliable indicator of the re-establishment of control of integrative functions by the autonomic nervous system. We suggest that this criterion could be applied to other animals exposed to natural or imposed trauma, thus improving protocols involving animal handling, including veterinarian procedures.

[Benign Presentation of a Potentially Fatal Disease]. / Ateroembolismo cutâneo: relato de três casos clínicos.

Atheroembolism is a rare multisystemic disorder that is characterized by release of cholesterol crystals and particles from atheromatous plaques, which can occlude distal vessels and induce an inflammatory response. Most affected individuals are males, older than 60 years of age, with advanced atherosclerotic disease. The abdominal aorta is the most common origin of cholesterol emboli, being the peripheral arteries a rarer source. Cholesterol embolization syndrome is often associated with invasive vascular procedures, although, more rarely, it may occur spontaneously. In this paper, the authors present three cases of spontaneous atheroembolism with cutaneous manifestations and their clinical management. Being an underdiagnosed pathology, knowledge about its clinical manifestations is essential in order to allow an early diagnosis and treatment, to ensure a better prognosis for the patient.

O ateroembolismo é uma doença multissistémica rara caraterizada pela libertação de cristais de colesterol e partículas de placas ateroscleróticas, que podem ocluir vasos sanguíneos periféricos e induzir uma resposta inflamatória. A maioria dos indivíduos afetados é do sexo masculino, com idade superior a 60 anos e doença aterosclerótica avançada. A origem mais frequente de embolização de colesterol é a aorta abdominal, sendo as artérias periféricas uma fonte mais rara. A síndrome de embolização por colesterol surge frequentemente associada a procedimentos vasculares invasivos, embora, mais raramente, possa ocorrer de forma espontânea. Neste artigo os autores apresentam três casos clínicos de ateroembolismo espontâneo com envolvimento cutâneo e respetiva abordagem clínica. Sendo uma patologia subdiagnosticada, torna-se fundamental o conhecimento acerca das suas manifestações clínicas, para permitir um diagnóstico e tratamento precoces de forma a garantir um melhor prognóstico para o doente.

c-Jun integrates signals from both MEK/ERK and MKK/JNK pathways upon vaccinia virus infection.

Usurpation of the host's signalling pathways is a common strategy employed by viruses to promote their successful replication. Here we show that infection with the orthopoxvirus vaccinia virus (VACV) leads to sustained stimulation of c-Jun activity during the entire infective cycle. This stimulation is temporally regulated through MEK/ERK or MKK/JNK pathways, i.e. during the early/mid phase (1 to 6 hpi) and in the late phase (9 to 24 hpi) of the infective cycle, respectively. As a transcriptional regulator, upon infection with VACV, c-Jun is translocated from the cytoplasm to the nucleus, where it binds to the AP-1 DNA sequence found at the promoter region of its target genes. To investigate the role played by c-Jun during VACV replication cycle, we generated cell lines that stably express a c-Jun-dominant negative (DNc-Jun) mutation. Our data revealed that c-Jun is required during early infection to assist with viral DNA replication, as demonstrated by the decreased amount of viral DNA found in the DNc-Jun cells. We also demonstrated that c-Jun regulates the expression of the early growth response gene (egr-1), a gene previously shown to affect VACV replication mediated by MEK/ERK signalling. VACV-induced stimulation of the MKK/JNK/JUN pathway impacts viral dissemination, as we observed a significant reduction in both viral yield, during late stages of infection, and virus plaque size. Collectively, our data suggest that, by modulating the host's signalling pathways through a common target such as c-Jun, VACV temporally regulates its infective cycle in order to successfully replicate and subsequently spread.

[Endovascular Revascularization for Diabetic Foot Ulcer - Experience from a Dedicated Clinic]. / Revascularização Endovascular na Úlcera de Pé Diabético ­ experiência de uma Consulta Multidisciplinar.

OBJECTIVES: We aimed to assess the outcome of endovascular revascularization in Diabetic patients with Fontaine stage IV chronic ischaemia, at our Diabetic Foot Clinic. Primary outcomes were ulcer healing, major amputation and limb salvage. METHODS: Retrospective single center analysis of patients treated between January 2009 and May 2015. Time-dependent event rates were estimated by the Kaplan-Meier method. The differences between groups were evaluated with the chi-square test. A P value below 0,05 was considered statistically significant. RESULTS: There were 106 limbs (93 patients) revascularized during the study. The average age was 71 years, and PEDIS 3 or 4 infection was present in 45.3% on admission. 56.6% were treated for femoropopliteal injurie only, 17% infrapopliteal, and 26.4% for both levels. Technical success was achieved in 77.4%, and haemodynamic success in 58.3%. Ulcer healing was attained in 53.8%, with an average healing time of 8.4 months. The major amputation rate was 7.5%, with a limb salvage rate of 90.4% at 6, 12 and 24 months. Chronic pulmo- nary disease decreased the likelihood of healing (p=0,012). Restenosis was more likely to occur in patients with nephropathy (p=0,008) or insulin-treated diabetes (p=0,033). CONCLUSIONS: Dedicated multidisciplinary teams are key to successful treatment in diabetic foot disease. The good results achieved in our series arise from best medical treatment combined with timely revascularization in those ischemic.

Objetivos: Avaliar os resultados da revascularização endovascular em diabéticos com isquemia crónica grau IV de Lériche- -Fontaine, seguidos em Consulta Multidisciplinar de Pé Diabético na nossa instituição, relativamente a taxa de cicatrização, amputação major e salvamento de membro. Material e Métodos: Análise retrospetiva dos doentes tratados no período de janeiro de 2009 até maio de 2015. As taxas de eventos dependentes do tempo foram estimadas com recurso a curvas de Kaplan-Meier e as diferenças entre grupos investigadas pelo teste de qui-quadrado. Um valor de p < 0,05 foi considerado estatisticamente significativo. Resultados: No período analisado foram revascularizados 106 membros (93 doentes). A idade média foi 71 anos, sendo que 45,3% apresentavam infeção PEDIS 3 ou 4 na apresentação. Das lesões intervencionadas, 56,6% eram suprageniculares, 17% infrageniculares, e 26,4% foram intervencionados nos dois setores. Foi obtido sucesso técnico em 77,4% e sucesso hemodinâmico em 58,3%. Foi conseguido o encerramento da úlcera em 53,8%, com tempo médio de cicatrização de 8,4 meses. A taxa de amputação major foi de 7,5%, verificando-se uma taxa de salvamento de membro de 90,4% aos 6, 12 e 24 meses. A doença pulmonar crónica influenciou negativamente a probabilidade de cicatrização (p=0,012). A reestenose foi mais frequente em doentes com nefropatia (p=0,008) ou DM insulino-tratada (p=0,033). Conclusões: A existência de equipas multidisciplinares dedicadas ao Pé Diabético são fundamentais para o sucesso do tratamento. Os bons resultados obtidos resultam da melhor otimização do tratamento médico combinada com a revasculari- zação no doente isquémico, associado a um seguimento apertado e à reintervenção precoce quando clinicamente justificado.

[Deep vein thrombosis in the pediatric population - a rare entity of uncertain prognosis]. / Trombose Venosa Profunda na População Pediátrica ­ Entidade Rara de Prognóstico Incerto.

Deep vein thrombosis, whose prevalence remains unknown in the pediatric population, is an increasingly common diag- nosis in this age group. This increased incidence makes the post-thrombotic syndrome a likely long-term complication, so there is a critical need to establish high quality evidence over its suitable approach in this population. We present two cases of deep vein thrombosis in children and their management in a hospital of the northern region of Portugal, reviewing the literature on this under researched subject. In conclusion, further investigation is needed to assess the incidence, the prevalence, the predictors and the safety and efficacy of therapies for the prevention and appropriate treatment of deep vein thrombosis in children and eventual post- -thrombotic syndrome.

A trombose venosa profunda, cuja prevalência permanece desconhecida na população pediátrica, é um diagnóstico cada vez mais frequente neste grupo etário. Este aumento de incidência faz da síndrome pós-trombótica uma complicação provável a longo prazo, existindo uma necessidade crítica em estabelecer evidência de alta qualidade sobre a sua adequada abordagem nesta população. São apresentados dois casos clínicos pediátricos de trombose venosa profunda, e respetiva abordagem, num hospital da região Norte de Portugal. Em seguida, procede-se à discussão e revisão da literatura sobre o assunto. Em conclusão, são necessários estudos que avaliem a incidência, a prevalência, os fatores preditivos e a segurança e a eficácia de terapias para a prevenção e o tratamento adequados da trombose venosa profunda e da possível futura síndrome pós-trombótica associada em crianças.

Microparticles induce multifactorial resistance through oncogenic pathways independently of cancer cell type.

Multidrug resistance (MDR) is considered a multifactorial event that favors cancer cells becoming resistant to several chemotherapeutic agents. Numerous mechanisms contribute to MDR, such as P-glycoprotein (Pgp/ABCB1) activity that promotes drug efflux, overexpression of inhibitors of apoptosis proteins (IAP) that contribute to evasion of apoptosis, and oncogenic pathway activation that favors cancer cell survival. MDR molecules have been identified in membrane microparticles (MP) and can be transferred to sensitive cancer cells. By co-culturing MP derived from MDR-positive cells with recipient cells, we showed that sensitive cells accumulated Pgp, IAP proteins and mRNA. In addition, MP promoted microRNA transfer and NFκB and Yb-1 activation. Therefore, our results indicate that MP can induce a multifactorial phenotype in sensitive cancer cells.

Environmental effects on the gills and blood of Oreochromis niloticus exposed to rivers of Bahia, Brazil.

Through the integration of chemical, biochemical and morphological analyses, this study investigated the effects of multiple pollutants on environmental biomarkers, such as gill histopathological changes and hematological and biochemical parameters, in Oreochromis niloticus exposed to four sites in the Jacuipe and Subaé rivers over seven days. Sediment analyses identified Sapelba as the most contaminated site, followed by Oliveira de Campinhos, Santo Amaro and Jacuípe. Water analyses revealed aluminum, iron and manganese at all sites. Aluminum and other metal were also detected in the gills of fishes. Fish exposed to the Sapelba site exhibited significant necrosis formation, as well as higher hematological parameters and trend to increase of cortisol levels. However, filament epithelium proliferation was higher at the Oliveira de Campinhos and Santo Amaro sites, at which the lowest levels of the hematological variables were observed. Multivariate analysis grouped some gill histopathological changes together, such as epithelial detachment with edema and lamellar epithelial proliferation with the lamellar fusion of adjacent filaments, revealing relationships among them. Positive associations were identified between sediment contamination and necrosis and cortisol, while water contamination was related with filament epithelium proliferation, aneurism, lamellar fusion and several hematological parameters. Furthermore, relationships between blood parameters and gill histopathological changes demonstrated a joint physiological response that may have resulted from environmental variables such as dissolved oxygen. The results exhibited the direct influence of xenobiotics on these biomarkers but also highlighted the need to consider the complexity of environmental factors to optimize the adoption of these environmental predictive tools.

Comparing the Toxicity of Water-Soluble Fractions of Biodiesel, Diesel and 5% Biodiesel/Diesel Blend on Oreochromis niloticus Using Histological Biomarkers.

This study estimated end compared the potential toxic effects of the water-soluble fractions (WSF) of biodiesel (B100), diesel and the commercial biodiesel (B5) on Oreochromis niloticus. After a 24 h-exposition to WSF-0% (control) and WSF-serial concentrations of 4.6%, 10%, 22%, 46% and 100%, samples of gill and liver of the exposed fishes were fixed in Bouin's solution, processed, stained using hematoxylin/eosin and analyzed by light-microscopy. WSF-hydrocarbons and methanol contents, analyzed by gas chromatography, were checked against the occurrence of abnormal histopathological alterations. These were not found in the control and WSF-4.6% exposed fishes, while exposures to or above 10%-WSF resulted in histopathological alterations whose severity increased in a dose-dependent manner, being higher in fishes exposed to WSF-diesel, or WSF-B5 when compared to biodiesel. These results, which were corroborated by the chemical analyses, highlighted the histological technique as an appropriate diagnostic tool that can be used for the preservation of water bodies' quality.

[An uncommon cause of lower limb oedema - Case report]. / Causa Incomum De Edema Do Membro Inferior - Caso Clínico.

The authors report the clinical case of a 50-year-old man who was observed in the emergency department because of a one week long, painless left lower limb swelling. At presentation, a gross edema was evident and peripheral pulses were present and symmetrical. The ultrasound scan findings suggested short occlusion in the transition of the common femoral (CFV) to the external iliac veins. A venography confirmed a filling defect in the above mentioned location, with normal findings throughout proximal and distal veins. On CT scans a cyst measuring 20mm of maximal diameter was disclosed, medial to the common femoral artery, compressing the CFV and seemingly continuous to the hip joint. He underwent surgical correction through open inguinal approach that allowed to confirm a complete compression of the CFV by the cyst against the inguinal ligament. The CFV recovered its normal aspect after cyst, removal and the patient was discarded home at day 2 after surgery, with complete regression of the oedema wich is maintained one year after the event, as well as absence of local ultrasound abnormalities. The hip joint is a rare location for synovial cysts. Synovial or adventitial cysts in that area may compress de CFV. The histological tests are useless for distinguishing between the two diagnosis. The clinical presentation consists of an inguinal mass or lower limb oedema due to CFV compression. Given its location underneath the vein, these masses are often difficult to detect. Vein decompression is suggested to avoid deep vein thrombosis. When a synovial cyst is present it is possible to find a dissecting plane between the two anatomical structures. Though feasible, percutaneous cyst aspiration is linked to high recurrence rates.

[Deep Venous Thrombosis in Emergency Care: From Clinical Suspicion to Correct Diagnosis]. / Trombose Venosa Profunda dos Membros Inferiores no Serviço de Urgência: Da Suspeita Clínica ao Diagnóstico.

AIM: Retrospective analysis of suspected deep venous thrombosis (DVT) of the lower limbs admitted to an emergency unit and subsequently scanned in the vascular lab. METHODS: Clinical and demographic details of patients were retrieved from clinical files and collected in a database. The statistical software SPSS was used for statistical analysis. RESULTS: Between January 2011 and September 2013, 407 venous scans were performed for ruling out DVT. Two hundred sixty-nine (66%) patients were female. Average age was 60.1 years-old (16-93). One hundred thirty-four scans (32.9%) were positive for the diagnosis of recent DVT (simultaneous DVT and superficial thrombophlebitis in six patients of this group). In 194 exams (47.6%) there was any sign of venous thrombosis, whether recent or remote. The remaining cases showed up signs of remote DVT in 22 (5.4%) patients, and superficial thrombophlebitis in 50 (12.2%) patients. CONCLUSION: Suspected DVT was confirmed in only a third of patients, using ultrasound scan. Local implementation of guidelines for the evaluation of patients with suspected DVT may reduce the amount of unnecessary scans.

Small-molecule mediated MuRF1 Inhibition protects from Doxorubicin-induced Cardiac Atrophy and Contractile Dysfunction.

Cancer chemotherapy induces cell stress in rapidly dividing cancer cells to trigger their growth arrest and apoptosis. However, adverse effects related to cardiotoxicity underpinned by a limited regenerative potential of the heart limits clinical application: In particular, chemotherapy with doxorubicin (DOXO) causes acute heart injury that can transition to persisting cardiomyopathy (DOXO-CM). Here, we tested if MuRF1 inhibition ("MuRFi") was able to attenuate DOXO-CM. To mimic DOXO chemotherapy, we treated mice over four weeks with five DOXO injection and a cumulative dosage of 25 mg/kg. At day 28, mice had lower body and heart weights, reduced cardiac cross-sectional myofibrillar areas (CSAs), and functional ejection fractions (EFs) and fractional shortenings (FS) as indicated by echocardiography (ECHO). In contrast, mice with a 1g/kg Myomed#205 spiked diet, a previously described experimental MuRFi therapy, showed lower DOXO-CM at day 28, and also reduced acute DOXO cardiac injury at day 7 (single DOXO dose; 15 mg/kg). Underlying molecular signatures using Western blot (WB) studies showed at day 28 reduced phospho-AKT (AKTp) and phospo-4EBP1 (4EBP1p) levels following DOXO that were normalized following MuRFi treatment. Taken together, our data suggest that MuRFi treatment is suitable to attenuate DOXO-CM by preserving AKTp and 4EBP1p levels in DOXO stressed cardiomyocytes, thereby supporting de novo protein translation and cardiomyocyte survival under translational arrest stress.

Enhancing functional recovery following postpartum femoral neuropathy: early neurorehabilitation and multidisciplinary obstetric care.

Postpartum femoral neuropathy has a reported incidence of less than 1% and its total recovery time extends up to 6 months to a year. A multidisciplinary approach is vital to rule out permanent disability and to assure a correct diagnosis and earlier rehabilitation. We report a case of a 37-year-old puerperal woman with a history of intrapartum epidural analgesia, who presented post-labor unilateral lower-limb motor weakness and sensory loss, with functional compromise on independent gait. A multidisciplinary team consisting of an anesthesiologist, a physiatrist, a neurologist, and an obstetrician was then established. In the initial physiatry and neurology assessment, the patient reported pain (numerical rating scale 7/10) over the inguinal ligament, lower limb hypoesthesia, and muscle weakness. Femoral neuropathy was suspected. Magnetic resonance imaging ruled out potential complications related to the anesthetic procedure. The patient was then enrolled in a supervised rehabilitation program and, 3 weeks later, electrodiagnostic studies confirmed the initial suspicion. Two months later, the patient had regained lower-limb active range of motion and no pain nor paresthesia was reported. Our case report describes how an early multimodal rehabilitation program within a multidisciplinary framework allows for sooner neuromotor function improvement and activities of daily living independence.