Osteoblastic Cell Behavior and Gene Expression Related to Bone Metabolism on Different Titanium Surfaces.

The surface topography of titanium dental implants has a great influence on osseointegration. In this work, we try to determine the osteoblastic behavior and gene expression of cells with different titanium surfaces and relate them to the physicochemical properties of the surface. For this purpose, we have used commercial titanium discs of grade 3: as-received corresponds to machined titanium without any surface treatment (MA), chemically acid etched (AE), treated via sand blasting with Al2O3 particles (SB) and a sand-blasting treatment with acid etching (SB+AE). The surfaces have been observed using scanning electron microscopy (SEM) and the roughness, wettability and surface energy with dispersive and polar components have been characterized. Osteoblastic cultures were performed with SaOS-2 osteoblastic cells determining cell viability as well as alkaline phosphatase levels for 3 and 21 days, and osteoblastic gene expression was determined. The roughness values of the MA discs was 0.02 µm, which increases to 0.3 µm with acid attack and becomes the maximum for the sand-blasted samples, reaching values of 1.2 µm for SB and SB+AE. The hydrophilic behavior of the MA and AE samples with contact angles of 63° and 65° is superior to that of the rougher samples, being 75° for SB and 82° for SB+AE. In all cases, they show good hydrophilicity. GB and GB+AE surfaces present a higher polar component in the surface energy values, 11.96 and 13.18 mJ/m2, respectively, than AE and MA, 6.64 and 9.79 mJ/m2, respectively. The osteoblastic cell viability values at three days do not show statistically significant differences between the four surfaces. However, the viability of the SB and SB+AE surfaces at 21 days is much higher than that of the AE and MA samples. From the alkaline phosphatase studies, higher values were observed for those treated with sand blasting with and without acid etching compared to the other two surfaces, indicating a greater activity in osteoblastic differentiation. In all cases except in the Osterix (Ostx) -osteoblast-specific transcription factor-a decrease in gene expression is observed in relation to the MA samples (control). The most important increase was observed for the SB+AE condition. A decrease in the gene expression of Osteoprotegerine (OPG), Runt-related transcription factor 2 (Runx2), Receptor Activator of NF-κB Ligand (RANKL) and Alkaline Phosphatase (Alp) genes was observed in the AE surface.

Effects of a multidisciplinary approach on the effectiveness of antiviral treatment for chronic hepatitis C.

UNLABELLED:  Background. Despite the introduction of direct antiviral agents, pegylated interferon remains the mainstay of treatment for chronic hepatitis C. However, pegylated interferon is associated with a high rate of severe adverse events and decreased quality of life. Specific interventions can improve adherence and effectiveness. We aimed to determine whether implementing a multidisciplinary approach improved outcomes in the treatment of chronic hepatitis C. MATERIAL AND METHODS: We analyzed consecutive patients treated with pegylated interferon plus ribavirin between August 2001 and December 2011. We compared patients treated before and after the implementation of a multidisciplinary approach in 2007. We compared the baseline demographic and clinical characteristics and laboratory findings between groups, and used bivariate logistic regression models to detect factors involved in attaining a sustained virological response, calculating the odds ratios with their respective 95% confidence intervals. To evaluate the effect of the multidisciplinary team, we fitted a multivariate logistic regression model to compare the sustained virological response after adjusting for unbalanced variables and predictive factors. RESULTS: We included 514 patients [228 (44.4%) in the pre-intervention cohort]. Age, viral genotype, previous treatment, aspartate transaminase, ferritin, and triglyceride were prognostic factors of sustained virological response. After adjusting for prognostic factors, sustained virological response was higher in the multidisciplinary cohort (58 vs. 48%, p = 0.038). Despite higher psychiatric comorbidity and age in the multidisciplinary cohort, we observed a trend toward a lower rate of treatment abandonment in this group (2.2 vs. 4.9%, p = 0.107). CONCLUSION: Multidisciplinary management of chronic hepatitis C improves outcomes.

An Exploratory Analysis on the 2D:4D Digit Ratio and Its Relationship with Social Responsiveness in Adults with Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a genetic disorder produced by a lack of expression of paternally derived genes in the 15q11-13 region. Research has generally focused on its genetic and behavioral expression, but only a few studies have examined epigenetic influences. Prenatal testosterone or the maternal testosterone-to-estradiol ratio (MaTtEr) has been suggested to play an important role in the development of the 'social brain' during pregnancy. Some studies propose the 2D:4D digit ratio of the hand as an indirect MaTtEr measure. The relationship between social performance and MaTtEr has been studied in other neurodevelopmental conditions such as Autism Spectrum Disorder (ASD), but to our best knowledge, it has never been studied in PWS. Therefore, our study aims to clarify the possible existence of a relationship between social performance-as measured using the Social Responsiveness Scale (SRS)-and MaTtEr levels using the 2D:4D ratio. We found that, as a group, PWS individuals have shorter index and ring fingers than the control group, but no significant difference in the 2D:4D ratios. The 2D:4D ratio showed a correlation only with Restricted Interests and Repetitive Behavior Subscale, where a positive correlation only for male individuals with PWS was found. Considering only PWS with previous GH treatment during childhood/adolescence (PWS-GH), index and ring fingers did not show differences in length with the control group, but the 2D:4D ratio was significantly higher in the right or dominant hand compared to controls.

Recommendations for the Implementation of the Self-Administration of Alpha-1 Antitrypsin.

Purpose: Administration of exogenous alpha-1 antitrypsin (AAT) is the only specific therapy for the management of pulmonary morbidity in patients with AAT deficiency. It requires weekly or biweekly intravenous infusions, which may impact patient independence and quality of life. Self-administration of AAT therapy is an alternative to reduce the burden for patients who require AAT therapy. We presented herein experts' recommendations for the implementation of a program for the self-administration of AAT. Methods: This project was conducted using a modified nominal group technique and was undertaken in two online meetings involving the participation of 25 experts: specialists in pulmonology (n=17), nurses (n=5) and hospital pharmacists (n=3). Results: The following issues were discussed, and several recommendations were agreed upon on the following topics: a) patient profile and clinical evaluation, establishing selection criteria that should include clinical as well as social criteria; b) role of health care professionals, suggested roles for specialists in pulmonology, nurses, and hospital pharmacists; c) training by the nurse, including recommendations before initiating the training and the content of the training sessions; and d) logistic issues and follow-up, adherence, and patient support. Conclusion: We expect this proposal to increase awareness of this therapeutic alternative and facilitate the implementation of self-administration programs, thus contributing to optimizing the patient experience with AAT therapy. Further research on the outcomes of these programs, especially from the patient perspective, will also help to improve their design and implementation.

Toxicity of cultured bullseye puffer fish Sphoeroides annulatus.

The toxin content in various life cycle stages of tank-cultivated bullseye puffer (Sphoeroides annulatus) were analyzed by mouse bioassay and ESI-MS spectrometry analysis. The presence of toxin content was determined in extracts of sperm, eggs, embryo, larvae, post-larvae, juvenile, pre-adult, and adult fish, as well as in food items used during the cultivation of the species. Our findings show that only the muscle of juveniles, the viscera of pre-adults, and muscle, liver, and gonad of adult specimens were slightly toxic (<1 mouse unit). Thus, cultivated S. annulatus, as occurs with other cultivated puffer fish species, does not represent a food safety risk to consumers. This is the first report of toxin analysis covering the complete life stages of a puffer fish under controlled conditions.

Impact of the COVID-19 Pandemic on the Incidence of Suicidal Behaviors: A Retrospective Analysis of Integrated Electronic Health Records in a Population of 7.5 Million.

The COVID-19 pandemic has caused remarkable psychological overwhelming and an increase in stressors that may trigger suicidal behaviors. However, its impact on the rate of suicidal behaviors has been poorly reported. We conducted a population-based retrospective analysis of all suicidal behaviors attended in healthcare centers of Catalonia (northeast Spain; 7.5 million inhabitants) between January 2017 and June 2022 (secondary use of data routinely reported to central suicide and diagnosis registries). We retrieved data from this period, including an assessment of suicide risk and individuals' socioeconomic as well as clinical characteristics. Data were summarized yearly and for the periods before and after the onset of the COVID-19 pandemic in Spain in March 2020. The analysis included 26,458 episodes of suicidal behavior (21,920 individuals); of these, 16,414 (62.0%) were suicide attempts. The monthly moving average ranged between 300 and 400 episodes until July 2020, and progressively increased to over 600 episodes monthly. In the postpandemic period, suicidal ideation increased at the expense of suicidal attempts. Cases showed a lower suicide risk; the percentage of females and younger individuals increased, whereas the prevalence of classical risk factors, such as living alone, lacking a family network, and a history of psychiatric diagnosis, decreased. In summary, suicidal behaviors have increased during the COVID-19 pandemic, with more episodes of suicidal ideation without attempts in addition to younger and lower risk profiles.

Social Responsiveness and Psychosocial Functioning in Adults with Prader-Willi Syndrome.

Although various studies have investigated symptoms of autism spectrum disorder (ASD) in Prader−Willi syndrome (PWS), little is known about the consequences of these symptoms, especially in psychosocial function. We aimed to explore ASD symptoms in adults with PWS with special attention to psychosocial functionality. This cross-sectional study included 26 adults (15 women) with PWS who attended a reference unit for rare diseases. Participants' primary caregivers completed the Social Responsiveness Scale (SRS), and clinicians assessed multidimensional functioning with the Personal and Social Performance Scale (PSP). Impaired social responsiveness was identified in 20 (76.9%) participants, and manifest to marked difficulties in social functioning were identified in 13 (50%). Participants with impaired social responsiveness (SRS ≥ 60) had significantly worse scores in functionality measured with the PSP (U = 12.5; p = 0.009) and with three of the four PSP main areas. Moreover, scores for the Social Cognition domain of the SRS correlated positively with the Socially useful activities (p < 0.05) and Personal and social relationships (p < 0.01) main areas of the PSP. These results suggest that difficulties in social skills should be assessed in all psychosocial evaluations of patients with PWS.

Correction: Impact of treatment with direct-acting antivirals on anxiety and depression in chronic hepatitis C.

[This corrects the article DOI: 10.1371/journal.pone.0208112.].

Impact of treatment with direct-acting antivirals on anxiety and depression in chronic hepatitis C.

BACKGROUND AND AIM: Treatment of hepatitis C with direct-acting antiviral agents (DAA) has few side effects. Although pivotal studies suggested that DAA were safe in patients with psychiatric diseases who could not be treated with previous antiviral therapies, their effects on anxiety and depression have not yet been analysed in clinical practice. The aim of our study was to analyse anxiety and depression in the setting of DAA treatment in a clinical practice series. METHODS: All patients starting DAA treatment between November 1, 2014 and October 31, 2015 were eligible. Patients completed the Hospital Anxiety and Depression scale at different times during treatment. The results were plotted on line graphs and evaluated using a linear regression model with repeated measures. RESULTS: One hundred and forty-five patients were included (11% with major psychiatric disorders; 32% on psychiatric treatment). Sustained virologic response (SVR) was achieved in 97.3% of cases. Anxiety and depression measures did not differ between time points. No differences between patients on psychiatric treatment or with advanced fibrosis or cirrhosis were found at any time point analysed. CONCLUSION: DAA treatment had no impact on anxiety or depression during or after chronic hepatitis C infection treatment, even in high-risk patients with major psychiatric disorders.

Telephone Management Program for Patients Discharged From an Emergency Department After a Suicide Attempt: A 5-Year Follow-Up Study in a Spanish Population.

AIM: In a previous controlled study, the authors reported on the significant beneficial effects of a telephone intervention program for prevention of suicide attempts by patients for up to 1 year. This study reports the 5-year follow-up data. Outcomes were number of recurrences and time to recurrence. METHOD: The intervention was carried out on patients discharged from the emergency room (ER) following attempted suicide (Sabadell). It consisted of a systematic, 1-year telephone follow-up program: after 1 week, and thereafter at 1-, 3-, 6-, 9-, and 12-month intervals to assess the risk of suicide and encourage adherence to treatment. The population in the control group (Terrassa) received treatment as usual after discharge, without additional telephone contact. RESULTS: The effect of reattempt prevention observed in the first year was not maintained over the long term. CONCLUSION: A telephone management program for patients discharged from an ER after attempted suicide could be considered a useful strategy in delaying further suicide attempts and reducing the rate of reattempts in the first year. However, results showed that the beneficial effects were not maintained at the 5-year follow-up.

Thymic carcinoid tumours.

Carcinoid tumours of the thymus are rare. The case of a 57-year-old asymptomatic man with a carcinoid tumour of the thymus, who showed a widened mediastinum by chest x-ray, is presented. Fine needle aspiration suggested the diagnosis, which was confirmed by biopsy.

Effectiveness of a telephone management programme for patients discharged from an emergency department after a suicide attempt: controlled study in a Spanish population.

OBJECTIVE: To determine the effectiveness over one year of a specific telephone management programme on patients discharged from an emergency department (ED) after a suicide attempt. We hypothesized that the programme will reduce the percentage of patients re-attempting suicide and delay the time between attempts. DESIGN: A multicentre, case-control, population-based study. The effect of the 1-year intervention on the main outcome measures was evaluated with respect to a 1-year baseline period and a control group. SETTING: Two hospitals with distinct catchment areas in Catalonia (Spain). PARTICIPANTS: A total of 991 patients discharged from the ED of either hospital after a suicide attempt during the baseline year and the intervention year. INTERVENTION: The intervention was carried out on patients discharged from the ED for attempted suicide (Sabadell). It consisted of a systematic, one-year telephone follow-up programme: after 1 week, thereafter at 1, 3, 6, 9 and 12-month intervals, to assess the risk of suicide and increasing adherence to treatment. The population in the control group (Terrassa) received treatment as usual after discharge, without additional telephone management. MAIN OUTCOME MEASURES: Time elapsed between initial suicide attempt and subsequent one, and changes in the annual rate of patients who reattempted suicide in the year of the intervention and the preceding one. RESULTS: The telephone management programme delayed suicide reattempts in the intervention group compared to the baseline year (mean time in days to first reattempt, year 2008=346.47, sd=4.65; mean time in days to first reattempt, year 2007=316.46, sd=7.18; P<0.0005; χ²=12.1, df=1) and compared to the control population during the same period (mean time in days to first reattempt, treatment period=346.47, sd=4.65; mean time in days to first reattempt, pre-treatment period=300.36, sd=10.67; P<0.0005; χ²=16.8, df=1). The intervention reduced the rate of patients who reattempted suicide in the experimental population compared to the previous year (Intervention 6% (16/296) v Baseline 14% (39/285) difference 8%, 95% confidence interval 2% to 12%) and to the control population (Intervention 6% (16/296) v Control 14% (31/218) difference 8%, -13% to -2%) LIMITATIONS: One of the main obstacles was the difficulty to contact all patients within the established deadlines. Another limitation of our study was that patients under the age of 18 underwent an intensive intervention in the day hospital, although their number was very small (13/319 in 2008) and did not significantly influence the results. But the main limitation of our study was that it was performed within the EAAD project. This project includes a comprehensive multilevel intervention practically in the same experimental area and aimed at an early diagnosis and treatment of depression, which is the main psychiatric disorder associated with suicide. Moreover, longer-term studies should be encouraged to determine whether such interventions really reduce suicide CONCLUSION: A telephone management programme for patients discharged from an ED after a suicide attempted would be a useful strategy in delaying further suicide attempts and in reducing the rate of reattempts, which is known as the highest risk factor for suicide completion.

Lymphocutaneous nocardiosis and cutaneous pheohyphomycosis in a liver transplant recipient.

BACKGROUND: Infections are the leading cause of morbidity and mortality in transplanted patients. The increasing number of immunocompromised patients has not only augmented infections by specific pathogens, but also by opportunistic microbial agents. METHODS: A mixed cutaneous infection caused by Nocardia brasiliensis and Exophiala jeanselmei is reported in a liver transplant patient. RESULTS: The cutaneous lesions were painful nodules which drained purulent material. They were located on the right lower limb, with lymphadenopathies in the groin. CONCLUSIONS: The patient was treated with itraconazole (600 mg/day) plus trimethoprim (1600 mg/day)-sulfamethoxazole (320 mg/day) for 8 weeks, with complete remission of the lesions.

Xantomas eruptivos como primera expresión de dislipidemias y diabetes en un paciente con pancreatitis aguda / Eruptive xanthomas as first expression of dislipidemia and diabetes on a patient with acute pancreatitis

El xantomas eruptivos constituyen una entidad poco frecuente. Son una expresión clínica de trastornos severos del metabolismo lipídico, primario o secundario. En ocasiones se resentan asociados a condiciones que amenazan la vida del paciente. Clínicamete se manifiestan como pápulas amarillento-anaranjadas, de aparición súblita, asintomáticas. El estudio histopatológico evidencia macrófagos espumosos dérmicos. Si bien suelen ser autorresolutivos, el tratamiento de las alteraciones metabólicas y subyacentes acelera su desaparición y disminuye las complicaciones asociadas, como pancreatitis aguda y ateroesclerosis. Se presenta el caso clínico de un paciente con pancratitis aguda grave, que 15 días previos había comenzado con una erupción papular, que ante ojos avezados, podría haber alertado de la condición metabólica bajo la que se encontraba...

Reacción adversa mucocutánea por imatinib / Adverse cutaneous reaction secondary to imatinib

El imatinib es el paradigma de los fármacos inhibidores de las tirosina quinasas. Se utiliza de primera línea como tratamiento de leucemia mieloide crónica y tumores sólidos del estroma gastrointestinal. Las reacciones adversas cutáneas son los efectos adversos no hematológicos más frecuentes. Se ha descrito un amplio rango de presentación, son dosis dependientes y se sugiere que se producen por efecto directo del fármaco. Presentamos el caso de una mujer de 61 años que tuvo un rash maculopapular secundario...

Eritema multiforme ampollar asociado a infección por herpes simple virus / bullous erythema multiforme associated with herpes simplex virus infection

El eritema multiforme (EM) es una reacción aguda de la piel que agrupa un amplio espectro de lesiones cutáneas con diferentes grados de severidad clínica. Su evolución es por lo general benigna, recurrente y de remisión espontánea. Presentamos un caso de EM ampollar secundario a infección por virus herpes simple, una variedad poco frecuente, que puede ser difícil de diferenciar de otras patologías ampollares, llevando a diagnósticos erróneos y tardíos...

Steatosis Hepática en Niños y Adolecentes obesos: Asociación con adiposidad, lípidos, insulina y enzimas hepática

Objetivos: Estudiar la frecuencia de presentación de esteatosis hepática (EH) en un grupo de niños y adolescentes obesos y su asociación con medidas antropométricas, niveles de lípidos sanguíneos, resistencia a la insulina y aminotransferasas. Métodos: Se incluyeron 22 niños y adolescentes obesos (IMC>pc97) entre 6 y 13 años de edad, con promedio de 9,28 ± 1,9 años, 59% de sexo masculino y 41% femenino. Se tomaron tensión arterial y medidas antropométricas, incluyendo cintura, y se calcularon índice de masa corporal (IMC), área grasa y área muscular. Se hicieron determinaciones sanguíneas de glicemia e insulina en ayunas y post-prandial, lípidos y aminotransferasas. Con estos datos se calculó el índice de resistencia insulínica, HOMA-IR. Se realizó ecografía hepática con transductores entre 3 y 5 MHz para determinar la presencia de EH de acuerdo a la presencia de ecogenicidad, atenuación del sonido y visualización de vasos y diafragma.Resultados: El 45% (10/22) de los participantes presentó EH, 6 de sexo femenino y 4 de masculino, diferencia que no llegó a ser significativa. En el 14% la EH fue leve, en el 27% moderada y en el 4% severa. Se observó asociación significativa de la presencia de EH con elevación de la aspartato aminotransferasa (AST; p=0,029) y de la alanina aminotransferasa (ALT; p=0,003). No fue significativa la asociación con resistencia a la insulina y alteraciones lipídicas. Los niños con EH presentaron valores significativamente más altos de IMC (p<0,005), cintura (p<0,005), área grasa (p<0,05), insulina post-prandial (p<0,05), AST (p<0,0001), ALT (p<0,0001) y fosfatasas alcalinas (p<0,0001) que aquellos sin EH. En el análisis de regresión logística, con la presencia de EH como variable dependiente, se encontró que el IMC fue la variable antropométrica explicativa más significante (p=0,018; IC 95%: 1,12-3,52), y la AST la variable bioquímica explicativa más significante (p=0,032; IC 95%; 1,02-1,63).Conclusiones: La EH es una complicación frecuente de la obesidad en niños y adolescentes, y se asocia con los indicadores de adiposidad, principalmente el IMC, así como con los niveles de aminotransferasas.

Objectives: To study the frequency of hepatic steatosis (HS) in a group of obese children and adolescents and its association with anthropometric measurements, blood lipid levels, insulin resistance and aminotransferase. Methods: Twenty-two obese children (BMI> PC97) between 6 and 13 years old, (9.28 ± 1.9 years), 59% male and 41% female were included. Blood pressure and anthropometric measurements, including waist, were taken, and body mass index (BMI), fat and muscle area were calcaulated. Determinations of blood glucose and insulin in fasting and post-prandial, lipids and aminotransferases were made. With these data insulin resistance index, HOMA-IR was calculated. A liver ultrasound with transducers between 3 and 5 MHz was performed to study the presence of HS, according to the echogenicity, sound attenuation and visualization of vessels and diaphragm.Results: Forty-five percent (45%) of participants presented HS, 6 female and 4 male, a difference that did not become significant. In 14% the HS was mild, 27% moderate and 4% severe. Significant association was ob-served between the presence of HS and the elevated levels of aspartate aminotransferase (AST, P = 0.029) and alanine aminotransferase (ALT, P = 0.003). There was not a significant association with insulin resistance and lipid abnormalities. Those children with HS showed significantly higher values of BMI (p <0.005), waist (p <0.005), fat area (p <0.05), postprandial insulin (p <0.05), AST (p < 0.0001), ALT (p <0.0001) and alkaline phosphatase (p <0.0001) than those without HS. The logistic regression analysis, with the presence of HS as the dependent variable, showed that BMI was the most significant explanatory anthropometric variable (p=0.018, CI 95%: 1,12-3,52), and AST the most significant explanatory biochemistry variable (p = 0.032, CI 95%, 1,02-1,63).Conclusion: Hepatic steatosis is a common complication of obesity in children and adolescents, and it is associated with indicators of adiposity, mainly BMI, and with aminotransferase levels.

Cutaneous necrosis by calcific uremic arteriolopathy.

BACKGROUND: Calcific uremic arteriolopathy is a rare and serious disorder characterized by systemic medial calcification of the arteries and tissue ischemia. Most often it is found in patients with chronic renal failure on dialysis and in renal transplant recipients with secondary hyperparathyroidism. METHODS: We report six patients with end-stage renal disease [five on hemodialysis (one with a nonfunctioning renal graft) and one on peritoneal dialysis] who developed painful livedo reticularis and skin necrosis of the limbs. All had secondary hyperparathyroidism and elevated calcium-phosphorus product. Our patients presented with the following clinical features: white race (six patients), hypoalbuminemia (three patients), diabetes (one patient), and obesity (four patients). RESULTS: Subtotal parathyroidectomy was performed in three cases. Despite this procedure, two patients died; one patient survived and his lesions healed. One patient was treated with aggressive wound care and hemodialysis (with low dialysate calcium concentration and Renagel phosphorus binders) and one patient received only local wound care, both with improvement of their lesions. In one case, no therapy was performed because the patient died immediately after diagnosis. CONCLUSIONS: The three patients who survived (Cases 4, 5 and 6) had distal lesions, normal serum albumin, and an early diagnosis. There was a relationship between the outcome of the patients and these factors, rather than the type of treatment received.

Enfermedad de morbihan / Morbihan´s disease

La enfermedad de Morbihan (morbus Morbihan) es una entidad poco frecuente, que se caracteriza por la aparición recurrente, a nivel del tercio medio y superior del rostro, de eritema y edema, que conducen a una induración desfigurante. Actualmente se plantea que la urticaria de contacto inmunológica desempeña un rol crucial en la patogenia. Presentamos un paciente de 65 años con enfermedad de Morbihan de 2 años de evolución.

Morbihan’ s disease (morbus Morbihan) is an infrecuent entity, characterized by the appearance of relapsing erithema and edema on the center and upper aspect of the face, leading to disfi guring induration.Nowadays, immunologic contact urticaria plays a crucial role in the pa-togenesis. We present a 65 year-old patient with Morbihan’ s disease, with its onset 2 years ago.