ANNaMo: Coarse-grained modeling for folding and assembly of RNA and DNA systems.

The folding of RNA and DNA strands plays crucial roles in biological systems and bionanotechnology. However, studying these processes with high-resolution numerical models is beyond current computational capabilities due to the timescales and system sizes involved. In this article, we present a new coarse-grained model for investigating the folding dynamics of nucleic acids. Our model represents three nucleotides with a patchy particle and is parameterized using well-established nearest-neighbor models. Thanks to the reduction of degrees of freedom and to a bond-swapping mechanism, our model allows for simulations at timescales and length scales that are currently inaccessible to more detailed models. To validate the performance of our model, we conducted extensive simulations of various systems: We examined the thermodynamics of DNA hairpins, capturing their stability and structural transitions, the folding of an MMTV pseudoknot, which is a complex RNA structure involved in viral replication, and also explored the folding of an RNA tile containing a k-type pseudoknot. Finally, we evaluated the performance of the new model in reproducing the melting temperatures of oligomers and the dependence on the toehold length of the displacement rate in toehold-mediated displacement processes, a key reaction used in molecular computing. All in all, the successful reproduction of experimental data and favorable comparisons with existing coarse-grained models validate the effectiveness of the new model.

[History and challenges of clinical simulation in the learning of procedural skills by nursing students]. / El rol de la simulación en el aprendizaje de habilidades procedimentales en estudiantes de enfermería: historia y desafíos.

Procedural skills are essential in the nursing profession and should be acquired during undergraduate training according to new regulations. Clinical simulation is a good alternative to teach such skills. During COVID pandemic, face-to-face learning activities were reduced to a minimum amount, thus hampering the use of clinical simulations. Since simulations should adapt to the new scenario, their virtual implementation appears as an alternative. The latter should become an important teaching tool while restrictions in mobility last. We herein review the evolution of clinical simulation as a teaching tool and to determine its future challenges.

Which is the best communication strategy, based on anti-tobacco ads, to impress teenagers? A multicenter cross-sectional study.

BACKGROUND: Well-planned mass-media campaigns can increase health literacy and raise awareness about the consequences of tobacco use. This study aims to evaluate the emotions and opinions of adolescents about several anti-tobacco spots delivered by the mass media over the world. STUDY DESIGN: Cross-sectional study. METHODS: The study was conducted in Italy in 2016-2017 among students aged 13-17 years. Students expressed their emotions and opinions about seven anti-tobacco spots from all over the world on different topics and styles. RESULTS: 499 students attended. The video "Sponge" was found to be the most impressive (30.2%) and what they would have chosen if they had been responsible for campaign launched by the Minister of Health (40.5%). The "Icons" spot ranged second, with 19.2% and 17.4%, respectively. CONCLUSIONS: In summary, this study showed that the communication strategies most effective, according to the students interviewed, are those that give clear messages with a scientific profile or that discover the false stereotypes, as in the video "Icons". However, further research is needed to investigate the effectiveness of TV campaigns against smoking, in terms of habits and knowledge in young people.

Cardiac Kir2.1 and NaV1.5 Channels Traffic Together to the Sarcolemma to Control Excitability.

RATIONALE: In cardiomyocytes, NaV1.5 and Kir2.1 channels interact dynamically as part of membrane bound macromolecular complexes. OBJECTIVE: The objective of this study was to test whether NaV1.5 and Kir2.1 preassemble during early forward trafficking and travel together to common membrane microdomains. METHODS AND RESULTS: In patch-clamp experiments, coexpression of trafficking-deficient mutants Kir2.1Δ314-315 or Kir2.1R44A/R46A with wild-type (WT) NaV1.5WT in heterologous cells reduced inward sodium current compared with NaV1.5WT alone or coexpressed with Kir2.1WT. In cell surface biotinylation experiments, expression of Kir2.1Δ314-315 reduced NaV1.5 channel surface expression. Glycosylation analysis suggested that NaV1.5WT and Kir2.1WT channels associate early in their biosynthetic pathway, and fluorescence recovery after photobleaching experiments demonstrated that coexpression with Kir2.1 increased cytoplasmic mobility of NaV1.5WT, and vice versa, whereas coexpression with Kir2.1Δ314-315 reduced mobility of both channels. Viral gene transfer of Kir2.1Δ314-315 in adult rat ventricular myocytes and human induced pluripotent stem cell-derived cardiomyocytes reduced inward rectifier potassium current and inward sodium current, maximum diastolic potential and action potential depolarization rate, and increased action potential duration. On immunostaining, the AP1 (adaptor protein complex 1) colocalized with NaV1.5WT and Kir2.1WT within areas corresponding to t-tubules and intercalated discs. Like Kir2.1WT, NaV1.5WT coimmunoprecipitated with AP1. Site-directed mutagenesis revealed that NaV1.5WT channels interact with AP1 through the NaV1.5Y1810 residue, suggesting that, like for Kir2.1WT, AP1 can mark NaV1.5 channels for incorporation into clathrin-coated vesicles at the trans-Golgi. Silencing the AP1 ϒ-adaptin subunit in human induced pluripotent stem cell-derived cardiomyocytes reduced inward rectifier potassium current, inward sodium current, and maximum diastolic potential and impaired rate-dependent action potential duration adaptation. CONCLUSIONS: The NaV1.5-Kir2.1 macromolecular complex pre-assembles early in the forward trafficking pathway. Therefore, disruption of Kir2.1 trafficking in cardiomyocytes affects trafficking of NaV1.5, which may have important implications in the mechanisms of arrhythmias in inheritable cardiac diseases.

[Monitoring of COVID-19 patients by telemedicine with telemonitoring]. / Telemedicina con telemonitorización en el seguimiento de pacientes con COVID-19.

AIM: To asses if telemedicine with telemonitoring is a clinically useful and secure tool in the tracking of patients with COVID-19. METHODS: A prospective observational study of patients with COVID-19 diagnosis by positive PCR considered high-risk tracked with telemedicine and telemonitoring was conducted in the sanitary area of Lugo between March 17th and April 17th, 2020. Two groups of patients were included: Outpatient Tracing from the beginning and after discharge. Every patient sent a daily clinical questionnaire with temperature and oxygen saturation 3 times a day. Proactive monitoring was done by getting in touch with every patient at least 11 a day. RESULTS: 313 patients (52.4% female) with a total average age of 60.9 (DE 15.9) years were included. Additionally, 2 patients refused to join the program. Since the beginning, 224 were traced outpatient and 89 after being discharged. Among the first category, 38 (16.90%) were referred to Emergency department on 43 occasions; 18 were hospitalized (8.03%), and 2 deceased. Neither deaths nor a matter of vital emergency occurred at home. When including patients after admissions monitoring was done in 304 cases. One patient re-entered (0.32%) to the hospital, and another one left the program (0.32%). The average time of monitoring was 11.64 (SD 3.58) days, and 224 (73.68%) patients were discharged during the 30 days of study. CONCLUSIONS: Our study suggests that telemedicine with home telemonitoring, used proactively, allows for monitoring high-risk patients with COVID-19 in a clinically useful and secure way.

Repair of transperineal recto-urethral fistula using a fibrin sealant haemostatic patch.

AIM: Recto-urethral fistula (RUF) is a rare complication of radical prostatectomy. We report a transperineal approach using a fibrin sealant haemostatic patch. METHOD: Five consecutive patients who developed RUF following radical prostatectomy had a direct transperineal repair with a haemostatic patch (TachoSil®) and were assessed at a median follow-up of 35.5 (21-45) months. RESULTS: There were no early postoperative complications. The average length of hospital stay was 5 (4-7) days. One patient developed recurrence 4 weeks after removal of the urethral catheter. Following healing in four patients the stoma was reversed at a median interval of 3 months, and 9.5 (7-10) months following the prostatic surgery. In the four patients with successful closure there was no case of recurrence or anorectal or urinary dysfunction at a median follow-up of 35.5 (21-45) months. CONCLUSION: Direct transperineal repair of RUF reinforced with a fibrin haemostatic patch of TachoSil is safe and effective.

Observational study of the effectiveness of spinal cord injury rehabilitation using the Spinal Cord Injury-Ability Realization Measurement Index.

STUDY DESIGN: Retrospective observational study. OBJECTIVES: The objective of this study was to determine the rehabilitation potential and the extent to which it is realized in a cohort of spinal cord injury patients using the Spinal Cord Injury-Ability Realization Measurement Index (SCI-ARMI) and to study the clinical factors that influence this realization. SETTING: Two spinal units in Italy. METHODS: Consecutive patients were assessed at the end of an in-patient rehabilitation program using the Spinal Cord Independence Measure and the International Standards for Neurological Classification of Spinal Cord Injury. On the basis of these data and of the age and gender of the patients, we calculated the SCI-ARMI score. Regression analyses were performed to study the relationship between clinical factors and the extent to which rehabilitation potential is realized. RESULTS: We examined the data for 306 patients. Most patients were discharged without having reached their rehabilitation potential, with an SCI-ARMI score <80%. SCI-ARMI scores at discharge were positively influenced by etiology and the lesion level and correlated negatively with lesion severity and the presence of complications during rehabilitation. CONCLUSION: The SCI-ARMI is an effective tool that can be used to measure the achievement of rehabilitation potential in SCI patients and to identify groups of patients who are at risk of not meeting their rehabilitative potential.

Green tea and glycine aid in the recovery of tendinitis of the Achilles tendon of rats.

PURPOSE: Green tea (GT) is widely used due to its anti-inflammatory properties. Previous studies have shown beneficial effects of a glycine diet on the remodeling process in inflamed tendons. Tendinitis is commonly observed in athletes and is of concern to surgeons due to the slowness of the recovery process. Our hypothesis is that GT + a glycine diet may improve tendinitis. AIM OF THE STUDY: To analyze the effect of GT and/or glycine in the diet on tendinitis. MATERIALS AND METHODS: Wistar rats were divided into seven groups (G): control group (C); G1 and G4, tendinitis; G2 and G5, tendinitis supplied with GT; and G3 and G6, tendinitis supplied with GT and a glycine diet for 7 or 21 days, respectively. We performed zymography for metalloproteinase, biochemical, morphological and biomechanics tests. RESULTS: G2, G3 and G5 showed high levels of hydroxyproline in relation to G1, while G4 showed high levels of glycosaminoglycans. High activity of metalloproteinase-2 was detected in G3. The organization of collagen bundles was better in G2 and G3. G5 showed similar birefringence measurements compared with C. G5 withstood a larger load compared with G4. CONCLUSIONS: The presence of metalloproteinase-2 indicates that a tissue is undergoing a remodeling process. High birefringence suggests a better organization of collagen bundles. After 21 days, G5 sustained a high load before rupture, unlike G4. The results suggest that GT + a glycine diet has beneficial effects that aid in the recovery process of the tendon after tendinitis.

Human papillomavirus and cancerous diseases of the head and neck: a systematic review and meta-analysis.

The increasing incidence of head and neck cancer (HNSCC) highlights the need to better understand the role of human papillomavirus (HPV) in the development of these cancers. The aims of this study were to conduct a systematic review and a meta-analysis concerning observational studies on the association between HPV infection and HNSCC and to quantify this association, thereby obtaining a reliable estimation of the risk of HPV infection in the development of head and neck cancer. Literature searches were performed using PubMed and Scopus databases. StatsDirect 2.7.8 program was used for the analysis. We found 15 case-control studies, 63 prevalence studies, and no cohort studies. The pooled odds ratio (OR) for all the included case-control studies resulted in a value of 1.63 (95% CI 1.27-2.09; P < 0.0001). The highest pooled OR resulted from the analysis of all the studies that examined HPV 16 genotype in association oral cavity (OR 5.36; 95% CI 1.4-20). The strong evidence of association between HPV infection and HNSCC highlights the importance of the introduction of specific tests in the cancer prevention practices to evaluate the presence of the virus, especially in the oral cavity, and the possibility of an extension of the vaccine anti-HPV in the male population too.

Long-term evaluation of bulking agents for the treatment of fecal incontinence: clinical outcomes and ultrasound evidence.

BACKGROUND: The injection of bulking agents into the anal canal has been reported to help patients with fecal incontinence. Although it has been advocated as a safe and effective option, substantial data concerning long-term efficacy are still lacking, and the resorption process of the implants has not yet been carefully studied. The aim of our study was to investigate the long-term outcomes of bulking agents for the treatment of fecal incontinence and the behavior of implanted materials in the anorectum. METHODS: At a median follow-up of 7 years, 19 patients with idiopathic fecal incontinence who had received bulking agent implants were evaluated. Clinical, manometric and ultrasound assessments were carried out. RESULTS: The clinical improvements that were achieved in the short term were not maintained over time. For each patient, the number of implants that could no longer be identified on ultrasound was significantly correlated with poorer clinical long-term outcomes. On average, only 14% of the originally injected volume was still detectable. CONCLUSIONS: In the long term, perianally injected bulking agents seem to lose effectiveness. The ultrasound assessment suggests that the process of resorption is almost complete, and the implants are no longer effective in treating incontinence.

Fetoscopic laser coagulation for twin-twin transfusion syndrome before 17 weeks' gestation: laser data, complications and neonatal outcome.

OBJECTIVE: To compare laser data, complications and neonatal outcome in pregnancies that undergo 'early' (≤ 17 weeks' gestation) fetoscopic laser ablation of placental vascular anastomoses for twin-twin transfusion syndrome (TTTS) with those from 'conventional' cases treated after 17 weeks. METHODS: This was a cohort study of data collected prospectively between January 2004 and December 2012. We included monochorionic diamniotic twin pregnancies complicated by TTTS and treated by fetoscopic laser coagulation. Pregnancies were grouped according to laser treatment ≤ 17 gestational weeks or > 17 weeks and obstetric and neonatal outcomes were compared between groups. RESULTS: A total of 178 pregnancies with TTTS underwent laser therapy: 40 at or before 17 weeks and 138 after 17 weeks. There was no statistically significant difference between these two groups with respect to the rate of preterm prelabor rupture of membranes (PPROM), gestational age at PPROM and rate of PPROM occurring in the 7 days following fetoscopic laser coagulation. In the early group, the interval between performing fetoscopic laser coagulation and the time of delivery was significantly longer (104 days vs 74 days, P=0.0002) and the delivery rate within 7 days of laser treatment was significantly lower (2.5% vs 15.9%, P=0.026). There was no significant difference between the two groups with regard to the rates of pregnancy without live birth (15.4% vs 15.4%, P=0.993), with one live birth (84.6% vs 84.6%, P=0.993) and with two live births (64.1% vs 58.1%, P=0.500). CONCLUSION: In the event of early TTTS, fetoscopic laser coagulation is technically feasible before 17 gestational weeks and obstetric and neonatal outcomes are comparable with those in cases of laser treatment performed after 17 weeks.

Predictive value of cardiovascular parameters in twin-to-twin transfusion syndrome.

OBJECTIVE: To evaluate the prognostic value of the Children's Hospital Of Philadelphia (CHOP) cardiovascular score and the modified myocardial performance index (MPI), in determining the risk of recipient fetal loss in twin-to-twin transfusion syndrome (TTTS). METHODS: This cohort study was based on data collected prospectively from 105 pregnancies complicated by TTTS (Quintero stages I-IV) and treated with laser photocoagulation between May 2008 and February 2013. Fetuses underwent detailed anatomical and Doppler ultrasonography with cardiac assessment as part of routine care. CHOP score and right MPI were calculated and cut-offs selected using receiver-operating characteristics curve analysis. These were compared according to loss of recipient fetus, using univariate and multivariate logistic regression. The correlation between CHOP score, MPI and Quintero stage was determined and we investigated differences in MPI before and after laser coagulation in a cohort of 90 recipient fetuses. RESULTS: Rates of recipient fetal loss were significantly higher when the CHOP score was ≥ 3 (39.5% vs 12.9%, P = 0.002) and when MPI z-score was > 1.645 (34.5% vs 10.6%, P = 0.004). After adjustment for Quintero stage, the risk of recipient fetal loss remained significantly higher when the CHOP score was ≥ 3 (odds ratio, 3.09; 95% CI, 1.035-9.21). There was a positive correlation between CHOP score, MPI and Quintero stage. MPI was significantly lower after compared with before laser coagulation. CONCLUSION: CHOP score and MPI are predictors of recipient fetal loss in TTTS and may be used to supplement Quintero's classification.

Immunotherapy reduces CD40L expression and modifies cytokine production in the CD4 cells of pollen allergy patients.

BACKGROUND: Allergen-specific immunotherapy (SIT) is the only intervention for IgE-mediated respiratory disorders. OBJECTIVE: The aim of the study was to investigate the immunological modifications induced by SIT in patients allergic to olive and/or grass pollen by attempting to establish an association between these modifications and clinical improvements. METHODS: We studied 29 patients who were allergic to olive and/or grass pollen. Patients were randomized to 2 groups: an active treatment group, comprising 19 allergic patients who received SIT, and a control group, formed by 10 allergic patients who received pharmacological treatment for their allergic symptoms but not immunotherapy. We used flow cytometry to analyze intracellular expression of the cytokines IL-4, IFN-gamma, IL-10, and TGF-beta1 in CD4+ T cells, as well as expression of Foxp3, the costimulatory CTLA-4 molecule, and the non-costimulatory CD40L molecule. To assess clinical changes, patients recorded their medication consumption, symptoms, and the limitation of daily activities using diary cards and quality of life questionnaires. RESULTS: Six months after initiation of SIT, we recorded a reduction in cell surface CD40L expression in the CD4+ T-cell population and a shift in the cytokine production profile (decrease in IL-4-producing CD4+ T cells and increase in IFN-gamma, IL-10, and TGF-beta1). These changes persisted after 12 months. Simultaneously, a clinical improvement was observed. CONCLUSIONS: SIT-induced clinical improvement is the result of immunological modifications such as a reduction in CD40L expression on CD4 cells and alteration in the cytokine production profile.

Laparoscopic management of left paraduodenal hernia. Case report and review of literature.

We report a rare case of left paraduodenal hernia in patient with symptoms of abdominal subobstruction treated successful with laparoscopic management in urgent situation that have reduced the length of stay and postoperative pain. Internal hernia is only 1% of the causes of abdominal obstruction and the left paraduodenal hernia about 50% of them; it is a congenital defect that derive from malrotation and abnormal mesenteric adhesion. The modern imaging techniques help for the correct diagnosis despite difficult identification of the pathology for the various clinical presentation. The treatment of choice is the surgical intervention; the laparoscopic approach is rarely described in literature but it can reduce the morbidity, postoperative pain and the length of hospital stay.

Antifungal activity of Annona crassiflora Mart. dichloromethane fraction against strains of C. albicans.

Products derived from medicinal plants with antimicrobial activity are considered a promising alternative in the treatment of fungal infections. In this perspective, this study proposed to evaluate the antifungal activity of the dichloromethane fraction of Annona crassiflora Mart. against C. albicans strains. Tests were carried out to determine Minimum Inhibitory Concentration (MIC), Minimum Fungicide Concentration (MFC), microbial growth kinetics, fungal cell wall and membrane mechanisms of action, antifungal biofilm activity, and cytotoxic effects on human erythrocytes. The extract presented MIC and MFC values that ranged from 256 µg/mL to 1,024 µg/mL, with fungicidal activity in the microbial growth kinetics assay. The mechanism of action did not occur through damage to the cell wall or via binding to ergosterol in the membrane, though the fraction presents activity against biofilm and is not cytotoxic in human erythrocytes. The dichloromethane fraction of Annona crassiflora Mart. presented antifungal activity and reduced biofilm growth, without toxicity against human erythrocytes; however, further studies are needed to define its mechanism of action.

Human immunodeficiency virus-associated depression: contributions of immuno-inflammatory, monoaminergic, neurodegenerative, and neurotrophic pathways.

In the era of greatly improved pharmacological treatment of HIV infection through highly active antiretroviral therapy (HAART), HIV patients experience reduced viral loads, reduced opportunistic infections, increased CD4+ T cell count, and greater life expectancy. Although life expectancy is increased, patients often develop neurological disturbances that may persist for long periods, seriously jeopardizing quality of life and adherence to the medication protocols of HAART. For these reasons, HIV-associated neurological disorders have gained importance in both clinical and basic investigations of HIV infection. Depression is the most prevalent neuropsychiatric disorder among people living with HIV. In this review, we discuss how HIV can predispose infected individuals to depression by several interrelated mechanisms. These include inducing chronic elevation of cytokines through activation of microglia and astrocytes; decreasing monoaminergic function; inducing neurotoxicity, especially in dopaminergic neurons; and reducing brain-derived neurotrophic factor. These viral pathways interact with psychosocial factors to create the depressive state. HIV depression has a great impact on quality of life and implementation of antiretroviral therapy, and thus, recognition of these modes of action is significant for understanding HIV neuropathology and for selecting modalities for pharmacologic treatment.