Apical or Septal Right Ventricular Location in Patients Receiving Defibrillation Leads: A Systematic Review and Meta-Analysis.

This study reviews the published data comparing the efficacy and safety of apical and septal right ventricle defibrillator lead positioning at 1-year follow-up. Systemic research on Medline (PubMed), ClinicalTrials.gov, and Embase was performed using the keywords "septal defibrillation," "apical defibrillation," "site defibrillation," and "defibrillation lead placement," including implantable cardioverter-defibrillator and cardiac resynchronization therapy devices. Comparisons between apical and septal position were performed regarding R-wave amplitude, pacing threshold at a pulse width of 0.5 ms, pacing and shock lead impedance, suboptimal lead performance, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter, readmissions due to heart failure and mortality rates. A total of 5 studies comprising 1438 patients were included in the analysis. Mean age was 64.5 years, 76.9% were male, with a median LVEF of 27.8%, ischemic etiology in 51.1%, and a mean follow-up period of 26.5 months. The apical lead placement was performed in 743 patients and septal lead placement in 690 patients. Comparing the 2 placement sites, no significant differences were found regarding R-wave amplitude, lead impedance, suboptimal lead performance, LVEF, left ventricular end-diastolic diameter, and mortality rate at 1-year follow-up. Pacing threshold values favored septal defibrillator lead placement (P = 0.003), as well as shock impedance (P = 0.009) and readmissions due to heart failure (P = 0.02). Among patients receiving a defibrillator lead, only pacing threshold, shock lead impedance, and readmission due to heart failure showed results favoring septal lead placement. Therefore, generally, the right ventricle lead placement does not appear to be of major importance.

Acute coronary syndrome and stress: Is there a relationship?

INTRODUCTION: Acute coronary syndrome (ACS) is the result of a complex pathophysiological process with various dynamic factors. The 10-item Perceived Stress Scale (PSS-10) is a validated instrument for estimating stress levels in clinical practice and may be useful in the assessment of ACS. METHODS: We carried out a single-center prospective study engaging patients hospitalized with ACS between March 20, 2019 and March 3, 2020. The PSS-10 was completed during the hospitalization period. The ACS group was compared to a control group (the general Portuguese population), and a subanalysis in the stress group were then performed. RESULTS: A total of 171 patients with ACS were included, of whom 36.5% presented ST-elevation myocardial infarction (STEMI), 38.1% were female and the mean PSS score was 19.5±7.1. Females in the control group scored 16.6±6.3 on the PSS-10 and control males scored 13.4±6.5. The female population with ACS scored 22.8±9.8 on the PSS-10 (p<0.001). Similarly, ACS males scored a mean of 17.4±6.4 (p<0.001). Pathological stress levels were not a predictor of major adverse cardiovascular events or severity at admission. CONCLUSIONS: ACS patients had higher perceived stress levels compared to the control group. Perceived stress level was not associated with worse prognosis in ACS patients.

A systemic review of endocardial left ventricular pacing.

BACKGROUND: Endocardial left ventricular pacing is an alternative technique used in cardiac resynchronization therapy (CRT), when placement of a left ventricular lead is not possible via the coronary sinus or in non-responders to conventional CRT. OBJECTIVES: To review the evidence regarding the efficacy and safety of endocardial left ventricular pacing. METHODS: Systematic research on Medline (PubMed), ClinicalTrials.gov and Embase with the terms "endocardial left ventricular pacing", "biventricular pacing" or "endocardial left pacing" was performed with the identification of 1038 results. Eleven studies with endocardial left ventricular pacing patients were included, independent of the technique being applied to naïve CRT patients or con non-responders to conventional CRT. The end-point of this analysis was the impact of endocardial left ventricular pacing techniques regarding New York Heart Association (NYHA) functional classification, left ventricular ejection fraction (LVEF) and QRS width, and the occurrence of complications Mean differences (MD) and confidence interval (CI) was used as a measurement of treatment. RESULTS: A total of 560 patients were included, with different techniques used (trans-atrial septal technique, trans-ventricular septal technique and transapical technique). Significant improvement was registered in NYHA class (MD 0.73, CI 0.48-0.98, p<0.00001, I2 = 87%), LVEF (MD -7.63, CI -9.93 - -5.33, p<0.00001, I2 = 69%) and QRS width (MD 29.25, CI 9.99-48.50, p<0.00001, I2 = 91%). Several complications were reported after the procedure, 11 pocket infections, 22 transient ischemic attacks, 18 ischemic strokes, 41 thromboembolic events, among other complications. The mortality rate during the follow-up was 20.54%. CONCLUSION: Left ventricular endocardial pacing is a feasible alternative to conventional CRT, with clinical, electrocardiographic and echocardiogrphic improvement. However, first data regarding this procedure was associated with significant complications rates.

Long-Term Evolution of SARS-CoV-2 in an Immunocompromised Patient with Non-Hodgkin Lymphoma.

Recent studies have shown that persistent SARS-CoV-2 infections in immunocompromised patients can trigger the accumulation of an unusual high number of mutations with potential relevance at both biological and epidemiological levels. Here, we report a case of an immunocompromised patient (non-Hodgkin lymphoma patient under immunosuppressive therapy) with a persistent SARS-CoV-2 infection (marked by intermittent positivity) over at least 6 months. Viral genome sequencing was performed at days 1, 164, and 171 to evaluate SARS-CoV-2 evolution. Among the 15 single-nucleotide polymorphisms (SNPs) (11 leading to amino acid alterations) and 3 deletions accumulated during this long-term infection, four amino acid changes (V3G, S50L, N87S, and A222V) and two deletions (18-30del and 141-144del) occurred in the virus Spike protein. Although no convalescent plasma therapy was administered, some of the detected mutations have been independently reported in other chronically infected individuals, which supports a scenario of convergent adaptive evolution. This study shows that it is of the utmost relevance to monitor the SARS-CoV-2 evolution in immunocompromised individuals, not only to identify novel potentially adaptive mutations, but also to mitigate the risk of introducing "hyper-evolved" variants in the community. IMPORTANCE Tracking the within-patient evolution of SARS-CoV-2 is key to understanding how this pandemic virus shapes its genome toward immune evasion and survival. In the present study, by monitoring a long-term COVID-19 immunocompromised patient, we observed the concurrent emergence of mutations potentially associated with immune evasion and/or enhanced transmission, mostly targeting the SARS-CoV-2 key host-interacting protein and antigen. These findings show that the frequent oscillation in the immune status in immunocompromised individuals can trigger an accelerated virus evolution, thus consolidating this study model as an accelerated pathway to better understand SARS-CoV-2 adaptive traits and anticipate the emergence of variants of concern.

Psychosocial Risks Assessment in Cryopreservation Laboratories.

BACKGROUND: Psychosocial risks are increasingly a type of risk analyzed in organizations beyond chemical, physical, and biological risks. To this type of risk, a greater attention has been given following the update of ISO 9001: 2015, more precisely the requirement 7.1.4 for the process operation environment. The update of this normative reference was intended to approximate OHSAS 18001: 2007 reference updated in 2018 with the publication of ISO 45001. Thus, the organizations are increasingly committed to achieving and demonstrating good occupational health and safety performance. METHODS: The aim of this study was to characterize the psychosocial risks in a cryopreservation laboratory and to develop a predictive model for psychosocial risk management. The methodology followed to collect the information was the inquiry by questionnaire that was applied to a sample comprising 200 employees. RESULTS: The results show that most of the respondents are aware of the psychosocial risks, identifying interpersonal relationships and emotional feelings as the main factors that lead to this type of risks. Furthermore, terms such as lack of resources, working hours, lab equipment, stress, and precariousness show strong correlation with psychosocial risks. The model presented in this study, based on artificial neural networks, exhibited good performance in the prediction of the psychosocial risks. CONCLUSION: This work presents the development of an intelligent system that allows identifying the weaknesses of the organization and contributing to the enhancement of the psychosocial risks management.

StressadaMente: Mental health promotion program for direct care workers of older people.

BACKGROUND: In the current context, associated with the increase in longevity, there is a greater need for institutionalization of old people in search of formal support. The direct care workers of institutionalized older people, who work at day care centers and residential homes, are at risk of being victims of occupational psychosocial risks. There are several psychological complaints of these workers, highlighting the need to develop a mental health promotion program aiming at job satisfaction of direct care workers, improving their provision of care at work and quality of life. AIM: The StressadaMente program is a mental health promotion program for direct care workers of institutionalized older people in day care centers and residential homes. This article aims to describe the StressadaMente program and to evaluate the level of satisfaction of the direct care workers with the program. METHODS: The program was implemented in two day centers/residential homes, enrolling 25 participants, and comprised one session per week, with 90 min per session, during 7 weeks. Sociodemographic information of direct care workers was collected. The assessment protocol comprised a satisfaction questionnaire of the program. RESULTS: In general, the program was evaluated as "very good" and "excellent" by 9.5% and 90.5% of the participants, respectively. These results may indicate that mental health promotion intervention seems to encourage new skills and changes to a better practice, prevent adverse effects of caregiving by improving the mental health of professionals.

Preparation of gentamicin sulfate eluting fiber mats by emulsion and by suspension electrospinning.

This work investigates the immobilization of the antibiotic gentamicin sulfate (GS) in electrospun fiber mats composed of poly(lactic acid) (PLA), poly(ε-caprolactone) (PCL) and the copolymer poly(lactic-co-glycolic acid) (PLGA). Since GS is highly water soluble but weakly soluble in the organic solvents commonly used in the electrospinning process, two methods of immobilization were investigated: by suspension electrospinning, in which GS particles were directly dispersed in the polymeric organic solutions, and by emulsion electrospinning, in which GS was solubilized in an aqueous phase that was then dispersed in the organic polymeric solution containing the surfactant SPAN80. Fibers with distinct diameters and morphologies were obtained for the different methods and compositions. Contrary to the fibers prepared by suspension electrospinning, emulsion electrospinning based fibers exhibited an excellent wettability, allegedly due to the effect of the surfactant SPAN80. Despite the differences between both methods the produced mats presented similar GS release profiles, with a considerable burst release in the first 8 h followed by a gradual release of the remaining drug during the next 4-6 days. Finally, all GS loaded fiber mats proved to have an antibacterial effect against the bacterial strain Staphylococcus aureus.

Click chemistry enables preclinical evaluation of targeted epigenetic therapies.

The success of new therapies hinges on our ability to understand their molecular and cellular mechanisms of action. We modified BET bromodomain inhibitors, an epigenetic-based therapy, to create functionally conserved compounds that are amenable to click chemistry and can be used as molecular probes in vitro and in vivo. We used click proteomics and click sequencing to explore the gene regulatory function of BRD4 (bromodomain containing protein 4) and the transcriptional changes induced by BET inhibitors. In our studies of mouse models of acute leukemia, we used high-resolution microscopy and flow cytometry to highlight the heterogeneity of drug activity within tumor cells located in different tissue compartments. We also demonstrate the differential distribution and effects of BET inhibitors in normal and malignant cells in vivo. This study provides a potential framework for the preclinical assessment of a wide range of drugs.

Developments in the Reactivity of 2-Methylimidazolium Salts.

Unexpected and unusual reactivity of 2-methylimidazolium salts toward aryl-N-sulfonylimines and aryl aldehydes is here reported. Upon reaction with aryl-N-sulfonylimines, the addition product, arylethyl-2-imidazolium-1-tosylamide (3), is formed with moderate to good yields, while upon reaction with aldehydes, the initial addition product (6) observed in NMR and HPLC-MS experimental analysis is postulated by us as an intermediate to the final conversion to carboxylic acids. Studies in the presence and absence of molecular oxygen allow us to conclude that the imidazolium salts is crucial for the oxidation. A detailed mechanistic study was carried out to provide insights regarding this unexpected reactivity.

Non-coding roX RNAs prevent the binding of the MSL-complex to heterochromatic regions.

Long non-coding RNAs contribute to dosage compensation in both mammals and Drosophila by inducing changes in the chromatin structure of the X-chromosome. In Drosophila melanogaster, roX1 and roX2 are long non-coding RNAs that together with proteins form the male-specific lethal (MSL) complex, which coats the entire male X-chromosome and mediates dosage compensation by increasing its transcriptional output. Studies on polytene chromosomes have demonstrated that when both roX1 and roX2 are absent, the MSL-complex becomes less abundant on the male X-chromosome and is relocated to the chromocenter and the 4th chromosome. Here we address the role of roX RNAs in MSL-complex targeting and the evolution of dosage compensation in Drosophila. We performed ChIP-seq experiments which showed that MSL-complex recruitment to high affinity sites (HAS) on the X-chromosome is independent of roX and that the HAS sequence motif is conserved in D. simulans. Additionally, a complete and enzymatically active MSL-complex is recruited to six specific genes on the 4th chromosome. Interestingly, our sequence analysis showed that in the absence of roX RNAs, the MSL-complex has an affinity for regions enriched in Hoppel transposable elements and repeats in general. We hypothesize that roX mutants reveal the ancient targeting of the MSL-complex and propose that the role of roX RNAs is to prevent the binding of the MSL-complex to heterochromatin.

Comparison of a xenogeneic and an alloplastic material used in dental implants in terms of physico-chemical characteristics and in vivo inflammatory response.

Two commercial bone grafts used in dentistry (Osteobiol Gen-Os®, a xenograft of porcine origin, and Bonelike®, a hydroxyapatite based synthetic material), in the form of granules, were characterized and evaluated in vivo regarding the intensity of the tissue inflammatory response. These biomaterials were characterized in terms of morphology, particle size distribution, porosity and pore size, specific surface area and density. The chemical composition and structure of the materials were accessed by Fourier-Transform Infrared Spectroscopy (FTIR) and X-ray Diffraction (XRD). The graft materials were implanted in the gluteus maximus muscles of Wistar rats and the inflammatory response was evaluated through histological analysis, after one week of implantation. The results showed that the two grafts have quite different characteristics in practically all the evaluated properties. While Osteobiol® exhibits a structure and composition similar to the natural bone, Bonelike® is constituted by a main crystalline phase of hydroxyapatite and two secondary phases of α- and ß-tricalcium phosphate. Osteobiol® granules, besides being larger, are irregular, and exhibit sharp-edged tips, while those of Bonelike® are approximately cylindrical, with round contours, and more uniform in size. The in vivo response evaluated from the inflammatory infiltrates revealed that although both implants did not cause severe inflammation, Bonelike® granules elicit a consistently more intense inflammatory reaction than that triggered by the granules of Osteobiol®, particularly in terms of collagen production and formation of fibrous capsule. This reaction was partly explained in terms of the characteristics evaluated for the granules of this material.

HP1a recruitment to promoters is independent of H3K9 methylation in Drosophila melanogaster.

Heterochromatin protein 1 (HP1) proteins, recognized readers of the heterochromatin mark methylation of histone H3 lysine 9 (H3K9me), are important regulators of heterochromatin-mediated gene silencing and chromosome structure. In Drosophila melanogaster three histone lysine methyl transferases (HKMTs) are associated with the methylation of H3K9: Su(var)3-9, Setdb1, and G9a. To probe the dependence of HP1a binding on H3K9me, its dependence on these three HKMTs, and the division of labor between the HKMTs, we have examined correlations between HP1a binding and H3K9me patterns in wild type and null mutants of these HKMTs. We show here that Su(var)3-9 controls H3K9me-dependent binding of HP1a in pericentromeric regions, while Setdb1 controls it in cytological region 2L:31 and (together with POF) in chromosome 4. HP1a binds to the promoters and within bodies of active genes in these three regions. More importantly, however, HP1a binding at promoters of active genes is independent of H3K9me and POF. Rather, it is associated with heterochromatin protein 2 (HP2) and open chromatin. Our results support a hypothesis in which HP1a nucleates with high affinity independently of H3K9me in promoters of active genes and then spreads via H3K9 methylation and transient looping contacts with those H3K9me target sites.

How important it is to determine the blood pressure in paediatric patients?

The prevalence of hypertension among the paediatric population is 1%-2%. The emergency physician should recognise potentially harmful blood pressure (BP) levels and ensure they are adequately treated, in order to avoid life-threatening complications. A hypertensive emergency is a severely elevated BP complicated by target organ dysfunction (cardiovascular, cerebrovascular and/or renal). Hypertensive urgency, however, is a severe elevation in BP without target organ dysfunction. This distinction is critical for the clinical approach. The authors present a case of a severe hypertension due to primary focal segmental glomerulosclerosis. In this case, the lack of BP measurement in the infant surveillance and the devaluation of an albuminuria detected in a previous routine urine examination, have culminated in a late diagnosis of a severe hypertension, with subsequent effects on target organs.

Buffering and proteolysis are induced by segmental monosomy in Drosophila melanogaster.

Variation in the number of individual chromosomes (chromosomal aneuploidy) or chromosome segments (segmental aneuploidy) is associated with developmental abnormalities and reduced fitness in all species examined; it is the leading cause of miscarriages and mental retardation and a hallmark of cancer. However, despite their documented importance in disease, the effects of aneuploidies on the transcriptome remain largely unknown. We have examined the expression effects of seven heterozygous chromosomal deficiencies, both singly and in all pairwise combinations, in Drosophila melanogaster. The results show that genes in one copy are buffered, i.e. expressed more strongly than the expected 50% of wild-type level, the buffering is general and not influenced by other monosomic regions. Furthermore, long genes are significantly more highly buffered than short genes and gene length appears to be the primary determinant of the buffering degree. For short genes the degree of buffering depends on expression level and expression pattern. Furthermore, the results show that in deficiency heterozygotes the expression of genes involved in proteolysis is enhanced and negatively correlates with the degree of buffering. Thus, enhanced proteolysis appears to be a general response to aneuploidy.

Physicochemical characterization of biomaterials commonly used in dentistry as bone substitutes--comparison with human bone.

The present work focuses on the physicochemical characterization of selected mineral-based biomaterials that are frequently used in dental applications. The selected materials are commercially available as granules from different biological origins: bovine, porcine, and coralline. Natural and calcined human bone were used for comparison purposes. Besides a classical rationalization of chemical composition and crystallinity, a major emphasis was placed on the measurement of various morphostructural properties such as particle size, porosity, density, and specific surface area. Such properties are crucial to acquiring a full interpretation of the in vivo performance. The studied samples exhibited distinct particle sizes (between 200 and 1000 microm) and shapes. Mercury intrusion revealed not only that the total sample porosity varied considerably (33% for OsteoBiol, 50% for PepGen P-15, and 60% for BioOss) but also that a significant percentage of that porosity corresponded to submicron pores. Biocoral was not analyzed by this technique as it possesses larger pores than those of the porosimeter upper limit. The density values determined for the calcined samples were close to the theoretical values of hydroxyapatite. However, the values for the collagenated samples were lower, in accordance with their lower mineral content. The specific surface areas ranged from less than 1 m(2)/g (Biocoral) up to 60 m(2)/g (BioOss). The chemical and phase composition of most of the samples, the exception being Biocoral (aragonite), were hydroxyapatite based. Nonetheless, the samples exhibited different organic material content as a consequence of the distinct heat treatments that each had received.

Microencapsulation of hemoglobin in chitosan-coated alginate microspheres prepared by emulsification/internal gelation.

Chitosan-coated alginate microspheres prepared by emulsification/internal gelation were chosen as carriers for a model protein, hemoglobin (Hb), owing to nontoxicity of the polymers and mild conditions of the method. The influence of process variables related to the emulsification step and microsphere recovering and formulation variables, such as alginate gelation and chitosan coating, on the size distribution and encapsulation efficiency was studied. The effect of microsphere coating as well its drying procedure on the Hb release profile was also evaluated. Chitosan coating was applied by either a continuous microencapsulation procedure or a 2-stage coating process. Microspheres with a mean diameter of less than 30 microm and an encapsulation efficiency above 90% were obtained. Calcium alginate cross-linking was optimized by using an acid/CaCO(3) molar ratio of 2.5, and microsphere-recovery with acetate buffer led to higher encapsulation efficiency. Hb release in gastric fluid was minimal for air-dried microspheres. Coating effect revealed a total release of 27% for 2-stage coated wet microspheres, while other formulations showed an Hb release above 50%. Lyophilized microspheres behaved similar to wet microspheres, although a higher total protein release was obtained with 2-stage coating. At pH 6.8, uncoated microspheres dissolved in less than 1 hour; however, Hb release from air-dried microspheres was incomplete. Chitosan coating decreased the release rate of Hb, but an incomplete release was obtained. The 2-stage coated microspheres showed no burst effect, whereas the 1-stage coated microspheres permitted a higher protein release.

Prevalência da leucose enzoótica bovina nos estados de Rondônia e Acre / Prevalence of bovine leukemia virus in the states of Rondonia and Acre, Brazil

Com o objetivo de se determinar a prevalência da leucose enzoótica bovina (LEB) nos estados de Rondônia e Acre, foram testados 2120 soros bovinos, 1060 de cada estado, através da técnica da imunodifusäo em gel de ágar. Encontraram-se 23% e 9,7% de positividade, nos estados de Rondônia e Acre, respectivamente. Verificou-se que a LEB está amplamente disseminada nos dois estados e que näo houve correlaçäo entre taxa de infecçäo do vírus da LEB com a finalidade de exploraçäo bovina