Instituto de Cardiología y Cirugía Cardiovascular

<P>Abstract copyright UK Data Service and data collection copyright owner.</P>The introduction of the National Childcare Strategy in 1998 marked a radical shift in government policy and for the first time put childcare provision firmly on the political map. Since then a wide range of childcare initiatives and funding streams have been introduced, and hence there is a need for regular data to aid the evaluation of recent policy interventions in these areas. The <i>Childcare and Early Years Provision</i> survey series is divided into two survey strands: the Parents’ Survey and the Providers’ Survey. <br> <br> The Parents’ Survey provides data on parents’ take-up, views and experiences of childcare. Families in England are randomly selected from the Child Benefit Records and all parents had children aged 0-14 years. They are asked about their use and experiences of childcare for all children in the family and to give more detailed information about childcare for a particular child (selected at random where there is more than one child in the family). The current Parents' Survey series replaces two previous surveys: the <i>Survey of Parents of Three and Four-Year-Old Children and Their Use of Early Years Services</i> (conducted between 1997 and 2002) and <i>Parents' Demand for Childcare,&nbsp;</i>conducted in 1999 and 2001 (see SNs 4380 and 4970 respectively).<br> <br> The Providers' Survey monitors the characteristics and development of childcare and early years providers and the workforce in England. Information was collected on the number and characteristics of providers, the characteristics of the children enrolled, workforce composition, qualifications and training, recruitment and retention, and business operation. The 2016 survey underwent an extensive redesign, which means findings are not comparable with previous surveys.<br><br>The 2020 survey was cancelled due to the COVID-19 pandemic<br> <br> Further information is available on the GOV.UK&nbsp;<a href="https://www.gov.uk/government/collections/statistics-childcare-and-early-years" title="Childcare and Early Years Statistics" target="_blank">Childcare and Early Years Statistics</a> webpage.<br><br><div><span style="font-style: italic;">Special licence data</span></div><div>Additional, more detailed variables from the Providers' Survey in 2018, 2019 and 2021 are available under Special Licence (SL). The SL data have more restrictive access conditions than those made available under the standard End User Licence (EUL) agreement. Prospective users of the SL version will need to complete an extra application form and demonstrate to the data owners exactly why they need access to the additional variables in order to get permission to use that version. Users are advised to consult the EUL version first and the list of variables available under each study before applying.</div><div><br></div>

Introduction: The research landscape was enriched with new forms of inquiry that deviated from the positivist and neopositivist paradigms. For these idealists and subjective currents, I just think science can explain reality. Objective: To argue the use of qualitative research as scientific and complementary method of quantitative research. Methods: A review of texts in which qualitative research and its possible applications in health is defined was performed. Results: The study provides quantitative information derived from the relationships between variables, however, multivariate methods applied are insufficient to provide all the information on the phenomena being studied. Meanwhile, qualitative research allows the researcher to participate in the observation of the object of study. Both methods have their advantages and their weaknesses. Conclusions: The investigator must be careful when designing research and choose the method that provides more reliability to the study conducted. The combination of both methods seems to be the most acceptable option and reduce the possibility of bias.

Background: Despite the epidemic of cardiovascular disease and the benefits of cardiac rehabilitation (CR), availability is known to be insufficient, although this is not quantified. This study ascertained CR availability, volumes and its drivers, and density. Methods: A survey was administered to CR programs globally. Cardiac associations and local champions facilitated program identification. Factors associated with volumes were assessed using generalized linear mixed models, and compared by World Health Organization region. Density (i.e. annual ischemic heart disease [IHD] incidence estimate from Global Burden of Disease study divided by national CR capacity) was computed. Findings: CR was available in 111/203 (54.7%) countries; data were collected in 93 (83.8% country response; N = 1082 surveys, 32.1% program response rate). Availability by region ranged from 80.7% of countries in Europe, to 17.0% in Africa (p b .001). There were 5753 programs globally that could serve 1,655,083 patients/year, despite an estimated 20,279,651 incident IHD cases globally/year. Volume was significantly greater where patients were systematically referred (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.35-1.38) and programs offered alternative models (OR = 1.05, 95%CI = 1.04-1.06), and significantly lower with private (OR = .92, 95%CI = .91-.93) or public (OR = .83, 95%CI = .82-84) funding compared to hybrid sources. Median capacity (i.e., number of patients a program could serve annually) was 246/program (Q25-Q75 = 150-390). The absolute density was one CR spot per 11 IHD cases in countries with CR, and 12 globally. Interpretation: CR is available in only half of countries globally. Where offered, capacity is grossly insufficient, such that most patients will not derive the benefits associated with participation.

Lower extremity ulceration is one of the serious and long-term diabetic complications rendering a significant social burden in terms of amputation and quality-of-life reduction. Diabetic patients experience a substantial wound-healing deficit. These lesions are featured by an exaggerated and prolonged inflammatory reaction with a significant impairment in local bacterial invasion control. Experimental and clinical evidences document the deleterious consequences of the wound's pro-inflammatory phenotype for the repair process. From a biochemical standpoint, hyperinflammation favours wound matrix degradation, thus, amplifying a pre-existing granulation tissue productive cells' invasiveness and recruitment deficit. Tumour necrosis factor perpetuates homing of inflammatory cells, triggers pro-apoptotic genes and impairs reepithelialisation. Advanced glycation end-products act in concert with inflammatory mediators and commit fibroblasts and vascular cells to apoptosis, contributing to granulation tissue demise. Therapeutic approaches aimed to downregulate hyperinflammation and/or attenuate glucolipotoxicity may assist in diabetic wound healing by dismantling downstream effectors. These medical interventions are demanded to reduce amputations in an expanding diabetic population.

BACKGROUND: Cardiac rehabilitation (CR) is a clinically-effective but complex model of care. The purpose of this study was to characterize the nature of CR programs around the world, in relation to guideline recommendations, and compare this by World Health Organization (WHO) region. METHODS: In this cross-sectional study, a piloted survey was administered online to CR programs globally. Cardiac associations and local champions facilitated program identification. Quality (benchmark of ≥ 75% of programs in a given country meeting each of 20 indicators) was ranked. Results were compared by WHO region using generalized linear mixed models. FINDINGS: 111/203 (54.7%) countries in the world offer CR; data were collected in 93 (83.8%; N = 1082 surveys, 32.1% program response rate). The most commonly-accepted indications were: myocardial infarction (n = 832, 97.4%), percutaneous coronary intervention (n = 820, 96.1%; 0.10), and coronary artery bypass surgery (n = 817, 95.8%). Most programs were led by physicians (n = 680; 69.1%). The most common CR providers (mean = 5.9 ± 2.8/program) were: nurses (n = 816, 88.1%; low in Africa, p < 0.001), dietitians (n = 739, 80.2%), and physiotherapists (n = 733, 79.3%). The most commonly-offered core components (mean = 8.7 ± 1.9 program) were: initial assessment (n = 939, 98.8%; most commonly for hypertension, tobacco, and physical inactivity), risk factor management (n = 928, 98.2%), patient education (n = 895, 96.9%), and exercise (n = 898, 94.3%; lower in Western Pacific, p < 0.01). All regions met ≥ 16/20 quality indicators, but quality was < 75% for tobacco cessation and return-to-work counseling (lower in Americas, p = < 0.05). INTERPRETATION: This first-ever survey of CR around the globe suggests CR quality is high. However, there is significant regional variation, which could impact patient outcomes.

BACKGROUND: the coronavirus disease 2019 (COVID-19) is characterized by poor outcomes and mortality, particularly in older patients. METHODS: post hoc analysis of the international, multicentre, 'real-world' HOPE COVID-19 registry. All patients aged ≥65 years hospitalised for COVID-19 were selected. Epidemiological, clinical, analytical and outcome data were obtained. A comparative study between two age subgroups, 65-74 and ≥75 years, was performed. The primary endpoint was all cause in-hospital mortality. RESULTS: about, 1,520 patients aged ≥65 years (60.3% male, median age of 76 [IQR 71-83] years) were included. Comorbidities such as hypertension (69.2%), dyslipidaemia (48.6%), cardiovascular diseases (any chronic heart disease in 38.4% and cerebrovascular disease in 12.5%), and chronic lung disease (25.3%) were prevalent, and 49.6% were on ACEI/ARBs. Patients aged 75 years and older suffered more in-hospital complications (respiratory failure, heart failure, renal failure, sepsis) and a significantly higher mortality (18.4 vs. 48.2%, P < 0.001), but fewer admissions to intensive care units (11.2 vs. 4.8%). In the overall cohort, multivariable analysis demonstrated age ≥75 (OR 3.54), chronic kidney disease (OR 3.36), dementia (OR 8.06), peripheral oxygen saturation at admission <92% (OR 5.85), severe lymphopenia (<500/mm3) (OR 3.36) and qSOFA (Quick Sequential Organ Failure Assessment Score) >1 (OR 8.31) to be independent predictors of mortality. CONCLUSION: patients aged ≥65 years hospitalised for COVID-19 had high rates of in-hospital complications and mortality, especially among patients 75 years or older. Age ≥75 years, dementia, peripheral oxygen saturation <92%, severe lymphopenia and qSOFA scale >1 were independent predictors of mortality in this population.

Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP > or =140 mm Hg, <180 mm Hg, diastolic BP <110 mm Hg) were randomly assigned (age 59+/-9 years, 77% previously treated for hypertension). Results from 457 patients (intention-to-treat analysis) were available. After a 4-week placebo period, patients with albuminuria >20 and <500 microg/min were randomly assigned to a combination of 2 mg perindopril/0.625 mg indapamide or to 10 mg daily enalapril. After week 12, doses were adjusted on the basis of BP to a maximum of 8 mg perindopril/2.5 mg indapamide or 40 mg enalapril. The main outcome measures were overnight AER and supine BP. Both treatments reduced BP. Perindopril/indapamide treatment resulted in a statistically significant higher fall in both BP (-3.0 [95% CI -5.6, -0.4], P=0.012; systolic BP -1.5 [95% CI -3.0, -0.1] diastolic BP P=0.019) and AER -42% (95% CI -50%, -33%) versus -27% (95% CI -37%, -16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.

Calcium channels of the P/Q subtype mediate transmitter release at the neuromuscular junction and at many central synapses, such as the calyx of Held. Transgenic mice in which alpha1A channels are ablated provide a powerful tool with which to test compensatory mechanisms at the synapse and to explore mechanisms of presynaptic regulation associated with expression of P/Q channels. Using the calyx of Held preparation from the knock-out (KO) mice, we show here that N-type channels functionally compensate for the absence of P/Q subunits at the calyx and evoke giant synaptic currents [approximately two-thirds of the magnitude of wild-type (WT) responses]. However, although evoked paired-pulse facilitation is prominent in WT, this facilitation is greatly diminished in the KO. In addition, direct recording of presynaptic calcium currents revealed that the major functional difference was the absence of calcium-dependent facilitation at the calyx in the P/Q KO animals. We conclude that one physiological function of P/Q channels is to provide additional facilitatory drive, so contributing to maintenance of transmission as vesicles are depleted during high throughput synaptic transmission.

SNCA (α-synuclein) misfolding and aggregation is strongly associated with both idiopathic and familial forms of Parkinson disease (PD). Evidence suggests that SNCA has an impact on cell clearance routes and protein quality control systems such as the ubiquitin-proteasome system (UPS) and autophagy. Recent advances in the key role of the autosomal recessive PARK2/PARKIN and PINK1 genes in mitophagy, highlighted this process as a prominent new pathogenic mechanism. Nevertheless, the role of autophagy/mitophagy in the pathogenesis of sporadic and autosomal dominant familial forms of PD is still enigmatic. The yeast Saccharomyces cerevisiae is a powerful "empty room" model that has been exploited to clarify different molecular aspects associated with SNCA toxicity, which combines the advantage of being an established system for aging research. The contribution of autophagy/mitophagy for the toxicity induced by the heterologous expression of the human wild-type SNCA gene and the clinical A53T mutant during yeast chronological life span (CLS) was explored. A reduced CLS together with an increase of autophagy and mitophagy activities were observed in cells expressing both forms of SNCA. Impairment of mitophagy by deletion of ATG11 or ATG32 resulted in a CLS extension, further implicating mitophagy in the SNCA toxicity. Deletion of SIR2, essential for SNCA toxicity, abolished autophagy and mitophagy, thereby rescuing cells. These data show that Sir2 functions as a regulator of autophagy, like its mammalian homolog, SIRT1, but also of mitophagy. Our work highlights that increased mitophagy activity, mediated by the regulation of ATG32 by Sir2, is an important phenomenon linked to SNCA-induced toxicity during aging.

AIMS: To describe the characteristics and assess the 1-year outcomes of hospitalized (HHF) and chronic (CHF) heart failure patients with chronic obstructive pulmonary disease (COPD) enrolled in a large European registry between May 2011 and April 2013. METHODS AND RESULTS: Overall, 1334/6920 (19.3%) HHF patients and 1322/9409 (14.1%) CHF patients were diagnosed with COPD. In both groups, patients with COPD were older, more frequently men, had a worse clinical presentation and a higher prevalence of co-morbidities. In HHF, the increase in the use of heart failure (HF) medications at hospital discharge was greater in non-COPD than in COPD for angiotensin-converting enzyme inhibitors (+13.7% vs. +7.2%), beta-blockers (+20.6% vs. +11.8%) and mineralocorticoid receptor antagonists (+20.9% vs. +17.3%), thus widening the gap in HF treatment already existing between the two groups at admission. In CHF patients, there was a similar increase in the use of these medications after enrollment visit in the two groups, leaving a significant difference of 8.2% for beta-blockers in favour of non-COPD patients (89.8% vs. 81.6%, P < 0.001). At 1-year follow-up, the hazard ratios for COPD in multivariable analysis confirmed its independent association with hospitalizations both in HHF [all-cause: 1.16 (1.04-1.29), for HF: 1.22 (1.05-1.42)] and CHF patients [all-cause: 1.26 (1.13-1.41), for HF: 1.37 (1.17-1.60)]. The association between COPD and all-cause mortality was not confirmed in both groups after adjustments. CONCLUSIONS: COPD frequently coexists in HHF and CHF, worsens the clinical course of the disease, and significantly impacts its therapeutic management and prognosis. The matter should deserve greater attention from the cardiology community.

OBJECTIVES: Lesions affecting the lateral recess of the sphenoid sinus are rarely discussed in the literature as a separate entity. This region is difficult to visualize and manipulate through the transnasal routes, especially when extensive pneumatization is present. External approaches to this area involve extensive surgery and are associated with significant morbidity. The objectives of this study are to present our experience with the endoscopic transpterygopalatine fossa approach as a method for exposing and manipulating lesions of the lateral recess of the sphenoid and to illustrate the detailed surgical steps of the procedure. STUDY DESIGN: Retrospective review. METHODS: Clinical charts of patients who had lesions originating from or extending into the lateral recess of the sphenoid sinus and who were treated at our institutions from September 1995 to June 2002 were retrospectively reviewed. All these patients were managed by the endoscopic transpterygopalatine fossa approach. RESULTS: Twelve patients (7 males and 5 females) were included in the study. Lesions included seven cerebrospinal fluid (CSF) leaks and five tumors. One patient with squamous cell carcinoma (SCC) of the sphenoid died of his disease. All CSF leaks were successfully repaired, and benign tumors were removed with good local control through the follow-up period. CONCLUSION: The endoscopic transpterygopalatine fossa approach is an excellent approach for dealing with lesions of the sphenoid lateral recess.

Heterogeneous nuclear ribonucleoprotein (hnRNP) K is a nucleocytoplasmic shuttling protein that is a key player in the p53-triggered DNA damage response, acting as a cofactor for p53 in response to DNA damage. hnRNP K is a substrate of the ubiquitin E3 ligase MDM2 and, upon DNA damage, is de-ubiquitylated. In sharp contrast with the role and consequences of the other post-translational modifications, nothing is known about the role of SUMO conjugation to hnRNP K in p53 transcriptional co-activation. In the present work, we show that hnRNP K is modified by SUMO in lysine 422 within its KH3 domain, and sumoylation is regulated by the E3 ligase Pc2/CBX4. Most interestingly, DNA damage stimulates hnRNP K sumoylation through Pc2 E3 activity, and this modification is required for p53 transcriptional activation. Abrogation of hnRNP K sumoylation leads to an aberrant regulation of the p53 target gene p21. Our findings link the DNA damage-induced Pc2 activation to the p53 transcriptional co-activation through hnRNP K sumoylation. Heterogeneous nuclear ribonucleoprotein (hnRNP) K is a nucleocytoplasmic shuttling protein that is a key player in the p53-triggered DNA damage response, acting as a cofactor for p53 in response to DNA damage. hnRNP K is a substrate of the ubiquitin E3 ligase MDM2 and, upon DNA damage, is de-ubiquitylated. In sharp contrast with the role and consequences of the other post-translational modifications, nothing is known about the role of SUMO conjugation to hnRNP K in p53 transcriptional co-activation. In the present work, we show that hnRNP K is modified by SUMO in lysine 422 within its KH3 domain, and sumoylation is regulated by the E3 ligase Pc2/CBX4. Most interestingly, DNA damage stimulates hnRNP K sumoylation through Pc2 E3 activity, and this modification is required for p53 transcriptional activation. Abrogation of hnRNP K sumoylation leads to an aberrant regulation of the p53 target gene p21. Our findings link the DNA damage-induced Pc2 activation to the p53 transcriptional co-activation through hnRNP K sumoylation.

Abstract Rationale The role of and needs for extracorporeal membrane oxygenation (ECMO) at a population level during the coronavirus disease (COVID-19) pandemic have not been completely established. Objectives To identify the cumulative incidence of ECMO use in the first pandemic wave and to describe the Nationwide Chilean cohort of ECMO-supported patients with COVID-19. Methods We conducted a population-based study from March 3 to August 31, 2020, using linked data from national agencies. The cumulative incidence of ECMO use and mortality risk of ECMO-supported patients were calculated and age standardized. In addition, a retrospective cohort analysis was performed. Outcomes were 90-day mortality after ECMO initiation, ECMO-associated complications, and hospital length of stay. Cox regression models were used to explore risk factors for mortality in a time-to-event analysis. Measurements and Main Results Ninety-four patients with COVID-19 were supported with ECMO (0.42 per population of 100,000, 14.89 per 100,000 positive cases, and 1.2% of intubated patients with COVID-19); 85 were included in the cohort analysis, and the median age was 48 (interquartile range [IQR], 41–55) years, 83.5% were men, and 42.4% had obesity. The median number of pre-ECMO intubation days was 4 (IQR, 2–7), the median PaO2/Fi O2 ratio was 86.8 (IQR, 64–99) mm Hg, 91.8% of patients were prone positioned, and 14 patients had refractory respiratory acidosis. Main complications were infections (70.6%), bleeding (38.8%), and thromboembolism (22.4%); 52 patients were discharged home, and 33 died. The hospital length of stay was a median of 50 (IQR, 24–69) days. Lower respiratory system compliance and higher driving pressure before ECMO initiation were associated with increased mortality. A duration of pre-ECMO intubation ≥10 days was not associated with mortality. Conclusions Documenting nationwide ECMO needs may help in planning ECMO provision for future COVID-19 pandemic waves. The 90-day mortality of the Chilean cohort of ECMO-supported patients with COVID-19 (38.8%) is comparable to that of previous reports.

A low threshold, voltage-gated calcium current is reported in most cardiac tissues but rarely in ventricular cells. This article reports some recently described characteristics and discusses their possible pathophysiologic implications. It also reviews the alterations induced in this current by a variety of chemical agents including several neuromediators in cardiac and other tissues.

Several investigators have demonstrated that streptozotocin (STZ) diabetes induces changes in the autonomic control of the cardiovascular system. Changes in cardiovascular function may be related to peripheral neuropathy. The aim of the present study was to analyze changes in heart rate (HR) and arterial pressure (AP) as well as baroreflex and chemoreflex sensitivity in STZ-induced diabetic male Wistar rats (STZ, 50 mg/kg, i.v., 15 days). Intra-arterial blood pressure signals were obtained for control and diabetic rats (N = 9, each group). Data were processed in a data acquisition system (CODAS, 1 kHz). Baroreflex sensitivity was evaluated by measuring heart rate changes induced by arterial pressure variation produced by phenylephrine and sodium nitroprusside injection. Increasing doses of potassium cyanide (KCN) were used to evaluate bradycardic and pressor responses evoked by chemoreflex activation. STZ induced hyperglycemia (447 +/- 49 vs 126 +/- 3 mg/dl), and a reduction in AP (99 +/- 3 vs 118 +/- 2 mmHg), resting HR (296 +/- 11 vs 355 +/- 16 bpm) and plasma insulin levels (16 +/- 1 vs 57 +/- 11 microU/ml). We also observed that the reflex bradycardia (-16.8 +/- 0.1 vs -12.5 +/- 0.1 bpm/mmHg, in the diabetic group) and tachycardia (-3.68 +/- 0.5 vs -1.75 +/- 0.3 bpm/mmHg, in the diabetic group) produced by vasopressor and depressor agents were impaired in the diabetic group. Bradycardia evoked by chemoreflex activation was attenuated in diabetic rats (control: -17 +/- 1, -86 +/- 19, -185 +/- 18, -208 +/- 17 vs diabetic: -7 +/- 1, -23 +/- 5, -95 +/- 13, -140 +/- 13 bpm), as also was the pressor response (control: 6 +/- 1, 30 +/- 7, 54 +/- 4, 59 +/- 5 vs diabetic: 6 +/- 1, 8 +/- 2, 33 +/- 4, 42 +/- 5 mmHg). In conclusion, the cardiovascular response evoked by baroreflex and chemoreflex activation are impaired in diabetic rats. The alterations of cardiovascular responses may be secondary to the autonomic dysfunction of cardiovascular control.

The phytochemical profile of a hydroalcoholic extract of Citrus aurantium var. amara L. peel, used as herbal medicine, was characterized by HPLC-PDA-MS. Two di-C-glycosyl flavones (vincenin II and diosmetin 6,8-di-C-glucoside), a series of flavones (luteolin 7-O-neohesperidoside, rhoifolin, and neodiosmin), and flavanone (neoeriocitrin, naringin, and neohesperidin) 7-O-neohesperidosides and two methoxyflavones (nobiletin and tangeretin), commonly present in Citrus, were identified. Furthermore, brutieridin and melitidin, two 3-hydroxy-3-methylglutaryl flavanone glycosides, were also characterized along with rhoifolin 4'-glucoside and three coumarins (8,3'-β-D-glucopyranosyloxy-2'-hydroxy-3'-methylbutyl-7-methoxycoumarin, merazin hydrate, and isomerazin). A preparative isolation procedure followed by NMR spectroscopy confirmed the proposed structures of the major flavonoids and identified the coumarins. The phenolic content was found to be 14.8 mg mL(-1), and naringin and neohesperidin were the compounds present in the highest concentration (3.6 and 2.6 mg mL(-1)). The extract of C. aurantium peel inhibited significantly (p < 0.05) both histamine- and dextran-induced edema in rats in a concentration-dependent manner (IC(50) = 119.6 and 118.3 mg kg(-1), respectively), providing evidence for the therapeutic use of C. aurantium var. amara peel.

Rac1b is an alternatively spliced isoform of the small GTPase Rac1 that includes the 57-nucleotide exon 3b. Rac1b was originally identified through its over-expression in breast and colorectal cancer cells, and has subsequently been implicated as a key player in a number of different oncogenic signaling pathways, including tumorigenic transformation of mammary epithelial cells exposed to matrix metalloproteinase-3 (MMP-3). Although many of the cellular consequences of Rac1b activity have been recently described, the molecular mechanism by which MMP-3 treatment leads to Rac1b induction has not been defined. Here we use proteomic methods to identify heterogeneous nuclear ribonucleoprotein (hnRNP) A1 as a factor involved in Rac1 splicing regulation. We find that hnRNP A1 binds to Rac1 exon 3b in mouse mammary epithelial cells, repressing its inclusion into mature mRNA. We also find that exposure of cells to MMP-3 leads to release of hnRNP A1 from exon 3b and the consequent generation of Rac1b. Finally, we analyze normal breast tissue and breast cancer biopsies, and identify an inverse correlation between expression of hnRNP A1 and Rac1b, suggesting the existence of this regulatory axis in vivo. These results provide new insights on how extracellular signals regulate alternative splicing, contributing to cellular transformation and development of breast cancer.

PURPOSE OF REVIEW: The most effective strategy for reducing acute myocardial ischemic injury is timely and effective reperfusion. However, myocardial reperfusion can induce further cardiomyocyte death (reperfusion injury). Interventions that protect the heart from ischemia/reperfusion injury, reducing infarct size, can involve remote ischemic preconditioning and postconditioning. These interventions have a promising potential clinical application, and have been the focus of recent research. In this review, we provide an update of remote ischemic preconditioning and postconditioning mechanisms. RECENT FINDINGS: Remote ischemic preconditioning cardioprotection can occur via a humoral pathway and/or a neural pathway. These two pathways have been described as mechanistically different, but it has been suggested that they could be interdependent. However, remote ischemic postconditioning mainly involves the humoral pathway. In this review, we will discuss the different pathways and mechanisms involved in remote ischemic preconditioning and postconditioning. SUMMARY: Remote ischemic preconditioning and postconditioning is possible to perform in a clinical setting by intermittent ischemia of an upper or lower limb. Furthermore, clinical trials using this procedure in the context of predictable ischemia-reperfusion have produced promising results, and other studies to define the potential clinical use of these strategies are ongoing.

Size discrepancy in microvascular anastomosis is a common issue in free flap transfer. The sudden change of caliber may cause turbulence to the blood flow and predisposes to platelet aggregation. Discrepancies in the cut end diameters have been managed by many geometrical methods in order to reduce the risk to thrombosis. In this paper, we pretended to summarize the techniques described and published about the management of size discrepancies in microvascular anastomosis, from the simple mechanical expansion with the jeweler's forceps to the sophisticated hardware such as devices or laser. Advantages and disadvantages are analyzed for many geometrical designs of anastomosis. We may conclude there is not an ideal technique to manage every size discrepancy, rather to question for the best method with the less complications, we should search for the best procedure to fit a specific case. A small caliber discrepancy may be well managed only with mechanical expansion. In traumatic or ischemic leg reconstruction, an end to side anastomosis will offer the continuity of the blood flow to both the vessel and the flap. In head and neck reconstruction, when a great discrepancy may be anticipated and the upstream donor vessel is smaller than the recipient one, a sleeve anastomosis can be performed. In the clinical set of a gap between the vessel ends, a graft must be used. Other geometrical designs (fish mouth or oblique cut), devices, glues or adhesives and laser helped anastomosis should be considered according the surgeon experience.

FATTY acid oxidation in tissues has been studied by measuring the oxygen uptake or the reaction products (acetoacetic and fl-hydroxybutyric acids). The quantitative importance of s-oxidation cannot be ascertained in this way, as a fraction of the acids might undergo some other type of oxidation, such as the c-oxidation of Verkade & van der Lee [1934].