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Neuronal hyperexcitability is a key element of many neurodegenerative disorders including the motor neuron disease Amyotrophic Lateral Sclerosis (ALS), where it occurs associated with elevated late sodium current (I NaL ). I NaL results from incomplete inactivation of voltage-gated sodium channels (VGSCs) after their opening and shapes physiological membrane excitability. However, dysfunctional increases can cause hyperexcitability-associated diseases. Here we reveal the atypical binding mechanism which explains how the neuroprotective ALS-treatment drug riluzole stabilises VGSCs in their inactivated state to cause the suppression of I NaL that leads to reversed cellular overexcitability. Riluzole accumulates in the membrane and enters VGSCs through openings to their membrane-accessible fenestrations. Riluzole binds within these fenestrations to stabilise the inactivated channel state, allowing for the selective allosteric inhibition of I NaL without the physical block of Na + conduction associated with traditional channel pore binding VGSC drugs. We further demonstrate that riluzole can reproduce these effects on a disease variant of the non-neuronal VGSC isoform Nav1.4, where pathologically increased I NaL is caused directly by mutation. Overall, we identify a model for VGSC inhibition that produces effects consistent with the inhibitory action of riluzole observed in models of ALS. Our findings will aid future drug design and supports research directed towards riluzole repurposing., (© 2024. The Author(s).)

Using generative deep learning models and reinforcement learning together can effectively generate new molecules with desired properties. By employing a multi-objective scoring function, thousands of high-scoring molecules can be generated, making this approach useful for drug discovery and material science. However, the application of these methods can be hindered by computationally expensive or time-consuming scoring procedures, particularly when a large number of function calls are required as feedback in the reinforcement learning optimization. Here, we propose the use of double-loop reinforcement learning with simplified molecular line entry system (SMILES) augmentation to improve the efficiency and speed of the optimization. By adding an inner loop that augments the generated SMILES strings to non-canonical SMILES for use in additional reinforcement learning rounds, we can both reuse the scoring calculations on the molecular level, thereby speeding up the learning process, as well as offer additional protection against mode collapse. We find that employing between 5 and 10 augmentation repetitions is optimal for the scoring functions tested and is further associated with an increased diversity in the generated compounds, improved reproducibility of the sampling runs and the generation of molecules of higher similarity to known ligands., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: Lung cancer exhibits unpredictable recurrence in low-stage tumors and variable responses to different therapeutic interventions. Predicting relapse in early-stage lung cancer can facilitate precision medicine and improve patient survivability. While existing machine learning models rely on clinical data, incorporating genomic information could enhance their efficiency. This study aims to impute and integrate specific types of genomic data with clinical data to improve the accuracy of machine learning models for predicting relapse in early-stage, non-small cell lung cancer patients., Methods: The study utilized a publicly available TCGA lung cancer cohort and imputed genetic pathway scores into the Spanish Lung Cancer Group (SLCG) data, specifically in 1348 early-stage patients. Initially, tumor recurrence was predicted without imputed pathway scores. Subsequently, the SLCG data were augmented with pathway scores imputed from TCGA. The integrative approach aimed to enhance relapse risk prediction performance., Results: The integrative approach achieved improved relapse risk prediction with the following evaluation metrics: an area under the precision-recall curve (PR-AUC) score of 0.75, an area under the ROC (ROC-AUC) score of 0.80, an F1 score of 0.61, and a Precision of 0.80. The prediction explanation model SHAP (SHapley Additive exPlanations) was employed to explain the machine learning model's predictions., Conclusion: We conclude that our explainable predictive model is a promising tool for oncologists that addresses an unmet clinical need of post-treatment patient stratification based on the relapse risk while also improving the predictive power by incorporating proxy genomic data not available for specific patients., Competing Interests: Declaration of Competing Interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Cardiac conditions are a significant cause of maternal morbidity and mortality, significantly exacerbated during the hemodynamic demands of pregnancy. Mitral stenosis in pregnancy (MSp) is rare in the USA however, it has a high risk for maternal complications., Methods: We aim to outline the burden of MSp hospitalizations nationally. A retrospective review of HCUP/NIS data from 2002-2014 was conducted., Results: There were 2014 weighted discharges for both pregnancy and mitral stenosis (MS). Patients diagnosed with MS had a more considerable mean cost per discharge than the comparison group. Pulmonary Hypertension (PH), Atrial Arrhythmias (AA), Stroke, and Heart Failure (HF) were respectively reported in 25.71%, 7.14%, 0.95%, and 19.28% of the discharges. Our study identified a low incidence of MS in the US over the 12-year period; no deaths were identified., Conclusion: Our results substantiate MSp as a risk factor for PH, AA, HF, and stroke in pregnancy. Even though the mortality is low, it is essential that clinicians be aware of this diagnosis due to higher associated morbidity and costs., Competing Interests: None., (AJCD Copyright © 2023.)

The recent manuscript entitled "Relationship between clinical features and intestinal microbiota in Chinese patients with ulcerative colitis" reported a difference in the intestinal microbiota of patients with ulcerative colitis according to the severity of the colitis. The influence of the intestinal microbiota on the development and progress of gastrointestinal disorders is well established. Besides the diversity in the microbiome, the presence of virulence factors and toxins by commensal bacteria may affect an extensive variety of cellular processes, contributing to the induction of a proinflammatory environment., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The survival of patients with lung cancer has substantially increased in the last decade by about 15%. This increase is, basically, due to targeted therapies available for advanced stages and the emergence of immunotherapy itself. This work aims to study the situation of biomarker testing in Spain., Patients and Methods: The Thoracic Tumours Registry (TTR) is an observational, prospective, registry-based study that included patients diagnosed with lung cancer and other thoracic tumours, from September 2016 to 2020. This TTR study was sponsored by the Spanish Lung Cancer Group (GECP) Foundation, an independent, scientific, multidisciplinary oncology society that coordinates more than 550 experts and 182 hospitals across the Spanish territory., Results: Nine thousand two hundred thirty-nine patients diagnosed with stage IV non-small cell lung cancer (NSCLC) between 2106 and 2020 were analysed. 7,467 (80.8%) were non-squamous and 1,772 (19.2%) were squamous. Tumour marker testing was performed in 85.0% of patients with non-squamous tumours vs 56.3% in those with squamous tumours (p-value < 0.001). The global testing of EGFR, ALK, and ROS1 was 78.9, 64.7, 35.6% respectively, in non-squamous histology. PDL1 was determined globally in the same period (46.9%), although if we focus on the last 3 years it exceeds 85%. There has been a significant increase in the last few years of all determinations and there are even close to 10% of molecular determinations that do not yet have targeted drug approval but will have it in the near future. 4,115 cases had a positive result (44.5%) for either EGFR, ALK, KRAS, BRAF, ROS1, or high PDL1., Conclusions: Despite the lack of a national project and standard protocol in Spain that regulates the determination of biomarkers, the situation is similar to other European countries. Given the growing number of different determinations and their high positivity, national strategies are urgently needed to implement next-generation sequencing (NGS) in an integrated and cost-effective way in lung cancer., (© 2022. The Author(s).)

Coronavirus disease 2019 (COVID-19) caused millions of deaths worldwide. COVID-19's clinical manifestations range from no symptoms to a severe acute respiratory syndrome, which can result in multiple organ failure, sepsis, and death. Severe COVID-19 patients develop pulmonary and extrapulmonary infections, with a hypercoagulable state. Several inflammatory or coagulatory biomarkers are currently used with predictive values for COVID-19 severity and prognosis. In this manuscript, we investigate if a combination of coagulatory and inflammatory biomarkers could provide a better biomarker with predictive value for COVID-19 patients, being able to distinguish between patients that would develop a moderate or severe COVID-19 and predict the disease outcome. We investigated 306 patients with COVID-19, confirmed by severe acute respiratory syndrome coronavirus 2 RNA detected in the nasopharyngeal swab, and retrospectively analyzed the laboratory data from the first day of hospitalization. In our cohort, biomarkers such as neutrophil count and neutrophil-to-lymphocyte ratio from the day of hospitalization could predict if the patient would need to be transferred to the intensive care unit but failed to identify the patients´ outcomes. The ratio between platelets and inflammatory markers such as creatinine, C-reactive protein, and urea levels is associated with patient outcomes. Finally, the platelet/neutrophil-to-lymphocyte ratio on the first day of hospitalization can be used with predictive value as a novel severity and lethality biomarker in COVID-19. These new biomarkers with predictive value could be used routinely to stratify the risk in COVID-19 patients since the first day of hospitalization.

Introduction: Patients with cancer may be at increased risk of more severe COVID-19 disease; however, prognostic factors are not yet clearly identified. The GRAVID study aimed to describe clinical characteristics, outcomes, and predictors of poor outcome in patients with lung cancer and COVID-19., Methods: Prospective observational study that included medical records of patients with lung cancer and PCR-confirmed COVID-19 diagnosis across 65 Spanish hospitals. The primary endpoint was all-cause mortality; secondary endpoints were hospitalization and admission to intensive care units (ICU)., Results: A total of 447 patients with a mean age of 67.1 ± 9.8 years were analysed. The majority were men (74.3 %) and current/former smokers (85.7 %). NSCLC was the most frequent type of cancer (84.5 %), mainly as adenocarcinoma (51.0 %), and stage III metastatic or unresectable disease (79.2 %). Nearly 60 % of patients were receiving anticancer treatment, mostly first-line chemotherapy. Overall, 350 (78.3 %) patients were hospitalized for a mean of 13.4 ± 11.4 days, 9 (2.0 %) were admitted to ICU and 146 (32.7 %) died. Advanced disease and the use of corticosteroids to treat COVID-19 during hospitalization were predictors of mortality. Hospitalized, non-end-of-life stage patients with lymphocytopenia and high LDH had an increased risk of death. Severity of COVID-19 correlated to higher mortality, ICU admission, and mechanical ventilation rates., Conclusions: Mortality rate was higher among patients treated with corticosteroids during hospitalization, while anticancer therapy was not associated with an increased risk of hospitalization or death. Tailored approaches are warranted to ensure effective cancer management while minimizing the risk of exposure to SARS-CoV-2., (Copyright © 2021. Published by Elsevier B.V.)

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can progress to a severe respiratory and systemic disease named coronavirus disease-2019 (COVID-19). The most common symptoms are fever and respiratory discomfort. Nevertheless, gastrointestinal infections have been reported, with symptoms such as diarrhea, nausea, vomiting, abdominal pain, and lack of appetite. Importantly, SARS-CoV-2 can remain positive in fecal samples after nasopharyngeal clearance. After gastrointestinal SARS-CoV-2 infection and other viral gastrointestinal infections, some patients may develop alterations in the gastrointestinal microbiota. In addition, some COVID-19 patients may receive antibiotics, which may also disturb gastrointestinal homeostasis. In summary, the gastrointestinal system, gut microbiome, and gut-lung axis may represent an important role in the development, severity, and treatment of COVID-19. Therefore, in this review, we explore the current pieces of evidence of COVID-19 gastrointestinal manifestations, possible implications, and interventions., Competing Interests: Conflict-of-interest statement: The authors declare having no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: AURA study reported 61% objective response rate and progression-free survival of 9.6 months with osimertinib in patients with EGFR/T790M+ non-small cell lung cancer. Due to lack of real-world data, we proposed this study to describe the experience with osimertinib in Spain., Methods: Post-authorization, non-interventional Special Use Medication Program, multicenter, retrospective study in advanced EGFR/T790M+ non-small cell lung cancer. One hundred-fifty five patients were enrolled (August 2016-December 2018) from 30 sites., Primary Objective: progression-free survival. Secondary objectives: toxicity profile, objective response rate, and use of health service resources., Results: 70% women, median age 66. 63.9% were non-smokers and 99% had adenocarcinoma. Most patients had received at least one prior treatment (97%), 91.7% had received previous EGFR-tyrosine kinase inhibitors and 2.8% osimertinib as first-line treatment. At data cutoff, median follow-up was 11.8 months. One hundred-fifty five patients were evaluable for response, 1.3% complete response, 40.6% partial response, 31% stable disease and 11.6% disease progression. Objective response rate was 42%. Median progression-free survival was 9.4 months. Of the 155 patients who received treatment, 76 (49%) did not reported any adverse event, 51% presented some adverse event, most of which were grade 1 or 2. The resource cost study indicates early use is warranted., Conclusion: This study to assess the real-world clinical impact of osimertinib showed high drug activity in pretreated advanced EGFR/T790M+ non-small cell lung cancer, with manageable adverse events., Trial Registration: Clinical trial registration number: NCT03790397 .

Biomarkers have a variety of clinical applications in multiple stages of diagnosis and therapy. Troponin T and brain natriuretic peptide are the best-known in the cardiovascular field, but experimental studies have identified new biomarkers with potential clinical value. In this article, novel biomarkers of kidney injury are investigated in the context of their relationship with atherosclerotic coronary disease. This review was carried out through a search in the PubMed database using as keywords each biomarker to be studied with the descriptor (DECS/MeSH) "Myocardial Infarction", and the keywords "coronary" and "cardiovascular", using the Boolean operator "AND". After the selection, 24 articles published between 2003 and 2017 were identified for the review. Eight biomarkers were investigated: neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor 23 (FGF23), tissue inhibitor of metalloproteinase-2 (TIMP-2), syndecan-1, interleukin-6 (IL-6), galectin-3, and the vascular cell adhesion molecules ICAM-1 and VCAM-1. Most identified articles were experimental studies, studies on human subjects having few participants. There are several promising biomarkers in the setting of coronary disease. The main evidence available in the literature suggests that elevated NGAL levels are associated with better prognosis after cardiac arrest and with comorbid kidney injury; elevated FGF23 is associated with coronary artery disease severity; TIMP-2 protects against coronary artery disease; increased expression of syndecan-1 is observed in myocardial infarction (MI) and protects against an exacerbated inflammatory response; IL-6 is associated with atherosclerotic disease and major cardiovascular outcomes; galectin-3 correlates with adverse clinical events post-MI; and elevated ICAM-1/VCAM-1 levels are associated with risk of coronary disease. Further studies are required to better investigate the role of each of these biomarkers in both stable coronary disease and acute coronary syndrome., (Copyright © 2020 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Cardiac disease is still the leading cause of non-pregnancy related maternal morbidity and mortality. Valvular disease is one of the most concerning cardiac conditions in pregnancy. Aortic stenosis (AS) is rare in young populations but deadly complications have been reported in pregnant women. This study is a retrospective review of data from the HCUP-NIS Database from 2002-2014. There were 1108 weighted discharges for both pregnancy and AS. The data contained ten or fewer unweighted discharges with AS in pregnancy that underwent a cardiac intervention: open heart surgery or percutaneous cardiac intervention. Patients who had at least one diagnosis for AS had a greater mean cost per discharge than the comparison groups. No deaths were identified in this group. We found a statistically significant increase in the billing codes for pulmonary hypertension and heart failure. Conditions commonly associated with AS such as atrial arrhythmias, ventricular arrhythmias, diastolic dysfunction, ischemic heart disease and stroke were poorly reported. Our study identified a low incidence of AS and its complications in pregnancy in the USA over our 13-year study period. Even though, the morbidity and mortality are low, it is important that clinicians be aware of this diagnosis due higher costs and risk of complications., Competing Interests: None., (AJCD Copyright © 2020.)

BACKGROUND Achromobacter xylosoxidans is a ubiquitous environmental gram-negative bacterium, very resistant to antibiotics. Endocarditis caused by these bacteria is extremely rare, with only 20 cases described in the literature to our knowledge. Mortality rates are high, and treatment usually involves a combination of antibiotics and surgery. Nosocomial infections predominate with a strong association between bacteremia and immunosuppression. CASE REPORT A 19-year-old immunocompetent male presented with endocarditis He had interatrial and interventricular communication corrected at age 11 months and aortic coarctation correction at age 10. Initial echocardiogram showed a possible interventricular patch infection, which was later ruled out. He was treated initially for endocarditis with a combination of antibiotics, but because he remained febrile after appropriate antibiotic treatment, surgery was performed. The patient had a favorable outcome after surgery and was asymptomatic on follow-up. CONCLUSIONS Endocarditis caused by A. xylosoxidans is extremely rare. To date, only 20 cases of IT have been reported in the literature, of which only two involved a native valve. Given the scarcity of cases reported, there is no consensus on the best treatment.

Background: Extra pulmonary manifestations of tuberculosis (TB) are rare in developed countries. TB is the main etiology of chronic pericarditis in developing countries, but it's epidemiology is not unknown in the United States., Methods: This retrospective study used the Healthcare Utilization Projects/Nationwide Inpatient Sample (HCUPS/NIS) database from 2002-2014 to evaluate the characteristics, risk factors, trends over time and region of tuberculous pericarditis in the United States., Results: The data during the study period consists of 100,790,900 discharges accounting for 482,872,274 weighted discharges. The data showed 744 weighted discharges with indication of both tuberculosis and pericarditis. A co-ocurrence of TB pericarditis and malignancy or chronic kidney disease was more common than in patients without TB pericarditis. The frequency of co-ocurrence of TB pericarditis and HIV infection, obesity, alcohol abuse and organ transplant was not elevated., Conclusion: TB pericarditis is rare disease in the USA and the classical risk factors for lung tuberculosis may not be associated with TB pericarditis. CKD and malignancy appear to be associated with TB pericarditis, further studies are required to determine causality., Competing Interests: None

The rhizosphere of plants contains a diversity of microorganisms, some of which play an important role in the growth and development of the host plant. In this work, the diversity of fungi and bacteria associated to the rhizosphere of Tabebuia chrysantha and T. billbergii plants was analyzed. The molecular identification was performed by sequencing the ITS and 16S rDNA for fungi and bacteria, respectively. The analysis of the rDNA sequences of the rhizosphere of T. billergii showed that for domain Eukaria, the most abundant phyla were Glomeromycota (56%) and Ascomycota (39%), and for domain Bacteria, the phylum Firmicutes (19.17%) was the most abundant followed by Actinobacteria (14.90%) and Proteobacteria (8.94%). In the rhizosphere of T. chrysantha the most abundant phylum of Eukaria was Ascomycota (98%), and for Bacteria the most representative phyla were Proteobacteria (18.61%) and Actinobacteria (11.93%). A diversity of genera and species of fungi and bacteria was observed, to be more significant in T. chrysantha than T. billbergii. The taxonomic assignment of metagenomic sequences revealed a homology associated with genomic sequences of 546 bacteria and 147 fungi in T. chrysantha and 154 bacteria and 122 fungi in T. billbergii.

An 83-year-old male who was a former smoker had pain on the left forearm accompanied with progressive swallowing in the last four to five months. Imaging studies revealed a cystic necrotic mass on the flexor digitorum superficialis muscle (biopsy: striated muscle tissue infiltrated by an adenocarcinoma). A whole-body computerized tomography (CT) scan demonstrates the presence of two lung masses that were suspicious of malignancy. Diagnosed as having stage IV lung adenocarcinoma (cT4NxM1b, IASLC TNM 8 th ), he received chemotherapy with a carboplatin/pemetrexed-based regimen and local palliative radiation for the control of arm pain.

Background: The most common microcytic and hypochromic anemias are iron deficiency anemia and thalassemia trait. Several indices to discriminate iron deficiency anemia from thalassemia trait have been proposed as simple diagnostic tools. However, some of the best discriminative indices use parameters in the formulas that are only measured in modern counters and are not always available in small laboratories. The development of an index with good diagnostic accuracy based only on parameters derived from the blood cell count obtained using simple counters would be useful in the clinical routine. Thus, the aim of this study was to develop and validate a discriminative index to differentiate iron deficiency anemia from thalassemia trait., Methods: To develop and to validate the new formula, blood count data from 106 (thalassemia trait: 23 and iron deficiency: 83) and 185 patients (thalassemia trait: 30 and iron deficiency: 155) were used, respectively. Iron deficiency, β-thalassemia trait and α-thalassemia trait were confirmed by gold standard tests (low serum ferritin for iron deficiency anemia, HbA2>3.5% for β-thalassemia trait and using molecular biology for the α-thalassemia trait)., Results: The sensitivity, specificity, efficiency, Youden's Index, area under receiver operating characteristic curve and Kappa coefficient of the new formula, called the Matos & Carvalho Index were 99.3%, 76.7%, 95.7%, 76.0, 0.95 and 0.83, respectively., Conclusion: The performance of this index was excellent with the advantage of being solely dependent on the mean corpuscular hemoglobin concentration and red blood cell count obtained from simple automatic counters and thus may be of great value in underdeveloped and developing countries., (Copyright © 2016 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.)

Objective: The aim of this study was to analyze the results of ACL (anterior cruciate ligament) reconstruction using quadruple flexor tendons as grafts, with ligament fixation in the femur using a rigid guide transverse screw and in the tibia, using a cancellous screw with a fixing washer., Methods: 173 knees (166 from males and seven from females) that had undergone surgery with ACL reconstruction using this technique between December 2002 and February 2007 were evaluated. The mean age was 30 years (from 13 to 56 years), and the mean follow-up time was 30 months (6-55 months). We divided the knees into three groups, which were assessed using the Lysholm scale: Group A with six months of follow-up; Group B with 12 months of follow-up; and Group C with 24 months of follow-up., Results: We evaluated the results, and groups A, B and C received 94, 95 and 95 points respectively on the Lysholm scale., Conclusions: The surgical technique proved to be safe and easy to perform, with good results and a low complication rate. Also, its results were maintained throughout the study period of 24 months.

The taxonomy of common dolphins (Delphinus sp.) has always been controversial, with over twenty described species since the original description of the type species of the genus (Delphinus delphis Linnaeus, 1758). Two species and four subspecies are currently accepted, but recent molecular data have challenged this view. In this study we investigated the molecular taxonomy of common dolphins through analyses of cytochrome b sequences of 297 individuals from most of their distribution. We included 37 novel sequences from the Southwestern Atlantic Ocean, a region where the short- and long-beaked morphotypes occur in sympatry, but which had not been well sampled before. Skulls of individuals from the Southwestern Atlantic were measured to test the validity of the rostral index as a diagnostic character and confirmed the presence of the two morphotypes in our genetic sample. Our genetic results show that all common dolphins in the Atlantic Ocean belong to a single species, Delphinus delphis. According to genetic data, the species Delphinus capensis is invalid. Long-beaked common dolphins from the Northeastern Pacific Ocean may constitute a different species. Our conclusions prompt the need for revision of currently accepted common dolphin species and subspecies and of Delphinus delphis distribution.

Unlabelled: Although the interference of tongue-tie with breastfeeding is a controversial subject, The use of lingual frenotomy has been widely indicated by health professionals., Objective: To observe changes in breastfeeding patterns after lingual frenotomy concerning the number of sucks, pause length between groups of sucking and mother's complaints., Material and Methods: Oral yes/no questions about breastfeeding symptoms and sucking/swallowing/breathing coordination were answered by the mothers of 109, 30 day old infants. On the same day the infants had their lingual frenulum assessed by administering a lingual frenulum protocol. After the assessment, all tongue-tied infants were referred for frenotomy; nevertheless, only 14 underwent the surgery. Of the 109 infants, 14 infants who did not have frenulum alterations were included as controls. Birth order and gender were the criteria for recruiting the control group. The tongue-tied infants underwent lingual frenotomy at 45 days of age. At the conclusion of the frenotomy, the infants were breastfed. At 75 days old, both groups--control and post-frenotomy--were reassessed. Before the reassessment the same oral yes/no questions were answered by the mothers of the 14 infants who underwent frenotomy. The mothers of the control group answered the questionnaire only at the time of the first assessment. Data were subjected to statistical analysis., Results: After frenotomy, the number of sucks increased and the pause length between sucking decreased during breastfeeding. The controls maintained the same patterns observed in the first assessment. From the questionnaire answered by the mothers of the 14 tongue-tied infants, at 30 days and 75 days, we observed that the symptoms concerning breastfeeding and sucking/swallowing/breathing coordination were improved after lingual frenotomy., Conclusions: After lingual frenotomy, changes were observed in the breastfeeding patterns of the the tongue-tied infants while the control group maintained the same patterns. Moreover, all symptoms reported by the mothers of the tongue-tied infants had improved after frenotomy.

Most Latin-American countries use subcutaneous immunotherapy (SCIT) extracts from the United States and Europe and sublingual immunotherapy (SLIT) from Europe, with the exception of Argentina, Brazil, Cuba and Mexico. The number of researches on immunotherapy (IT) in Latin America has increased extensively in the last years. Only few Latin American countries have their own guidelines on IT, and, in general, the economic resources for medical research on IT are still low in the area. A global approach for the future of IT in Latin America includes to improve standardization, quality control and the production of allergen products, to develop IT guidelines and clinical investigation by the highest number of countries, to improve the regulatory status for allergens products in the area, and to expand IT accessibility for low-income patients. In Cuba, the first registered allergen vaccines were developed and registered in 2006: a standardized (in biologic units) and freeze dried product for SCIT, with a sublingual version developed in 2009. As much as 23.000 IT treatments were applied in 2011, all provided to patients free of charge. In 2012, Cuban researchers developed an IT vaccine with adjuvant for subcutaneous route, which uses Neisseria meningitidis proteoliposome as an adjuvant, added to the purified Dermatophagoides siboney major allergens: Der s1 and Der s2. Since December 2012, this vaccine is in Phase I clinical trial, evaluating its safety, tolerability and immunogenicity in asthmatic patients sensitized to this allergen. Cuban perspectives on IT includes to work on new indications for IT, to investigate the preventive effect and cost-effectiveness for the current vaccines, to develop new products with mixed formulas of house dust mites for SLIT, to complete the phase I and II clinical study for dust mite plus adjuvant vaccine, to develop allergen vaccines for fungi allergy and to complete the Cuban guideline for allergen IT management.

An experimental protocol model for frenulum evaluation was first designed, and administered to ten infants in 2010. After obtaining the data and statistical analysis, the protocol was re-designed and administered to 100 infants. The aim of this study is to present an efficient and effective lingual frenulum protocol with scores for infants. From the experimental protocol model, a new protocol was designed. One speech-language pathologist, and specialist in orofacial myology, administered the new protocol to 100 full-term infants. All steps of the protocol were recorded and photographed. The data collected was sent to two specialists in the area, who evaluated the cases based on the recordings and photographs. The data from the three evaluations were compared. A two-part protocol was designed to evaluate the lingual frenulum in infants. The first part consists of clinical history with specific questions about family history and breastfeeding. The second part consists of clinical examination: anatomo-functional, non-nutritive and nutritive sucking evaluations. A new lingual frenulum protocol with scores for infants was designed, and has proved to be an effective tool for health professionals to assess and diagnose anatomical alterations of the lingual frenulum, and its possible interference with breastfeeding.

Purpose: To describe the changes after frenectomy concerning mobility and functions of the tongue., Methods: Participants were 53 subjects who had never undergone speech therapy or lingual frenulum surgery. A specific lingual frenulum protocol with scores was used by speech-language pathologists when there was evidence of frenulum alteration. Ten subjects had abnormal frenulum and were referred to an otolaryngologist for frenectomy. After surgery, the subjects were re-evaluated using the same protocol. Photos and videos were taken for comparison., Results: Thirty days after surgery, the subjects had the shape of the tip of the tongue and its movements improved. Lip closure and speech were also improved., Conclusion: Frenectomy is efficient to improve tongue posture, tongue mobility, oral functions, and oral communication.

Introduction: A telecardiology remote cardiology medical care system was implemented in 82 municipalities of Minas Gerais State, Brazil to support basic network services in the early diagnosis and management of cardiovascular diseases., Objective: To investigate the factors associated with the implementation of this program in the municipalities., Method: This 2006 ecological study involved 393 candidate municipalities to implement the system. The municipalities were divided into two groups: non-random intervention (n = 82) and comparative (n = 311). The social, structure, healthcare needs, and governability indexes of the two groups of municipalities were compared by descriptive and multiple regression analysis using the generalized estimation equation model., Results: After fitting for other characteristics, participation of the municipalities in the intervention was associated with a higher social responsibility index (OR: 2.44, CI: 1.50-3.96) and lower healthcare needs (OR: 2.29, CI: 1.24-4.22)., Conclusion: Greater efforts by municipality management was the key to attracting and implementing the remote cardiology intervention, even when fitted for lower healthcare needs, which suggests greater municipal political and social engagement. This translated to improved access to cardiovascular health care for Brazilian rural and remote populations in the intervention municipalities.

Background: Sensitization to three allergic mite species (Dermatophagoides pteronyssinus, Dermatophagoides siboney and Blomia tropicalis) from house dust in Cuba has been reported in different studies., Objective: To assess allergic sensitization to these mites in a north coast area of Havana city., Patients and Methods: A total of 210 allergic patients were selected, classified in two groups: from 1 to 14 years, and from 15 to 55 years. Skin Prick Test (SPT) was performed on all patients using standardized allergenic extracts VALERGEN-BT (B. tropicalis), VALERGEN-DS (D. siboney) and VALERGEN-DP (D. pteronyssinus) manufactured by BIOCEN, Cuba. The test was considered positive when the average wheal diameter was greater or equal to 3 mm., Results: Both groups showed higher sensitization to D. pteronyssinus (>78%), while for the remaining mites it was below 60%. In patients older than 14 years, the sensitization was apparently higher, although not statistically significant (p > 0.05). Nevertheless, the skin reactivity in this group was significantly greater (p < 0.05) for the three allergens. Unusually, mean wheal size in both groups was significantly superior toward B. tropicalis (p < 0.05)., Conclusions: In spite of being D. pteronyssinus the mite showing the highest sensitization, Blomia tropicalis showed to be also an important aeroallergen with more than 50% sensitization and greater skin reactivity. Therefore, in our population it would be advisable to perform SPT with the three mites extracts, simultaneously and to combine it in allergen-specific immunotherapy.

Standardized allergen vaccines have been developed and registered as biopharmaceutical products in Cuba. Three different vaccines were obtained from the most relevant allergenic mite species: Dermatophagoides pteronvssinus, Dermatophagoides siboney, and Blomia tropicalis. Immuno-analytical methods based on murine monoclonal antibodies and human IgE antibodies were developed for assessing allergenic potency, composition, and stability. Preclinical and clinical studies showed efficacy and safety in diagnostic prick-tests and subcutaneous immunotherapy in asthmatic patients. New approaches are now undertaken in order to develop new adjuvanted formulations based on liposomes or proteoliposomes from Neisseria meningitidis, and purified allergens; aiming to overcome the drawbacks of conventional immunotherapy.