Evolution of the SEFH's "Proyecto 2020" in a Hospital Pharmacy Department.

OBJECTIVE: To describe the evolution of our Pharmacy Service in relation to the  objectives of Proyecto 2020 (Project 2020) of the Sociedad Española  Farmacia Hospitalaria (Spanish Society of Hospital Pharmacy), to identify weak  points, and to implement improvement actions to achieve the set  objectives. METHOD: A 10-year prospective observational study. We analysed the initial  situation of the Pharmacy Service and conducted follow-up reassessments. We  developed a questionnaire comprising the 28 goals of the five strategic focus  reas (blocks) of the project based on a 4-level quantitative classification of  these goals: level A, implementation in all areas (3 points); level B,  mplementation in some areas (2 points); level C, not implemented, but  formally discussed (1 point); or level D, not addressed (0 points). After each  assessment, we identified the goals with the lowest scores and determined  which improvement actions needed to be implemented. After each assessment,  the targets with lower score were identified and improvement  actions needed to be implemented were decided. Results: The initial assessment was conducted in 2010. The overall score was  42/84 and the highest score (7/9) related to the block scientific evidence. The  follow-up reassessments (2014, 2019) and the final one (2020) showed an  overall gradual increase in level A scores (18% vs 53%) and a  decrease in  level C (43% vs 4%) and D objectives (14% vs 4%). All blocks improved their  score, obtaining a final score of 68/84 (31% increase). A total of 18 weak  points were identified and appropriate improvement actions were implemented,  which included automation, quality management, the creation  of multidisciplinary working groups, the prevention of medication errors, the  incorporation of intelligent pumps or therapeutic drug monitoring among other  solutions. CONCLUSIONS: Projects promoted by scientific societies help to prioritize improvement actions in health organizations that contribute to  improve their quality. Follow up conducted within Project 2020 has led to  improvements in all blocks and positive impacts on the quality of  pharmaceutical practice.

OBJETIVO: Describir la evolución de nuestro Servicio de Farmacia con respecto  a los objetivos del Proyecto 2020 de la Sociedad Española de Farmacia  Hospitalaria, la identificación de puntos débiles y la implementación de  acciones de mejora dirigidas a alcanzar los objetivos planteados.Método: Estudio observacional prospectivo de 10 años de duración. Se analizó  la situación basal y se realizaron reevaluaciones de seguimiento y de  situación final. Se elaboró un cuestionario que contemplaba los 28 objetivos de  los cinco bloques del proyecto basándose en cuatro niveles según si el  objetivo estaba implantado en todas las áreas (A), implantado en algunas  áreas (B), si se había debatido formalmente pero no estaba implantado (C) o si  no se había considerado (D). Para la evaluación cuantitativa se asignaron 3  puntos a los objetivos de nivel A, 2 puntos a los de nivel B, 1 punto a los de  nivel C y 0 puntos a los de nivel D. Tras cada evaluación se identificaron los  puntos débiles (los de menor puntuación) y se decidieron acciones de mejora a  implementar. RESULTADOS: En 2010 se realizó la evaluación inicial obteniendo una  puntuación de 42/84, siendo el bloque de evidencia científica el de mayor puntuación (7/9). En las diferentes evaluaciones de seguimiento (2014,  2019) y final (2020) se observó un incremento gradual de los objetivos de  nivel A  (18% versus 53%) y una reducción de los objetivos de nivel C (43%  versus 4%) y D (14% versus 4%). Todos los bloques mejoraron, obteniendo  una puntuación global final de 68/84 (31% de incremento). Se identificaron 18  puntos débiles y se implementaron sus correspondientes acciones de  mejora, incluyendo robotización, gestión de la calidad, creación de grupos de  trabajo multidisciplinares, prevención de errores de medicación,  implementación de bombas inteligentes o la monitorización farmacocinética,  entre otras. CONCLUSIONES: La adherencia a proyectos promovidos por sociedades científicas ayudan a priorizar acciones de mejora en las  organizaciones sanitarias que contribuyen a mejorar la calidad de las mismas.  En nuestro Servicio de Farmacia, el seguimiento del Proyecto 2020 ha  conllevado una mejora en todos los bloques, lo que repercute positivamente en  la calidad de la práctica farmacéutica.

Evolución del Proyecto 2020 de la Sociedad Españolade Farmacia Hospitalaria en un Servicio de FarmaciaHospitalaria / Evolution of the SEFH’s “Proyecto 2020” in a Hospital Pharmacy Department

Objetivo: Describir la evolución de nuestro Servicio de Farmacia conrespecto a los objetivos del Proyecto 2020 de la Sociedad Española deFarmacia Hospitalaria, la identificación de puntos débiles y la implementaciónde acciones de mejora dirigidas a alcanzar los objetivos planteados.Método: Estudio observacional prospectivo de 10 años de duración.Se analizó la situación basal y se realizaron reevaluaciones de seguimientoy de situación final. Se elaboró un cuestionario que contemplabalos 28 objetivos de los cinco bloques del proyecto basándose en cuatroniveles según si el objetivo estaba implantado en todas las áreas (A),implantado en algunas áreas (B), si se había debatido formalmente pero noestaba implantado (C) o si no se había considerado (D). Para la evaluacióncuantitativa se asignaron 3 puntos a los objetivos de nivel A, 2 puntos a losde nivel B, 1 punto a los de nivel C y 0 puntos a los de nivel D. Tras cadaevaluación se identificaron los puntos débiles (los de menor puntuación) yse decidieron acciones de mejora a implementar.Resultados: En 2010 se realizó la evaluación inicial obteniendo una puntuaciónde 42/84, siendo el bloque de evidencia científica el de mayorpuntuación(7/9). En las diferentes evaluaciones de seguimiento (2014, 2019)y final (2020) se observó un incremento gradual de los objetivos de nivel A (18% versus 53%) y una reducción de los objetivos de nivel C (43% versus 4%)y D (14% versus 4%). Todos los bloques mejoraron, obteniendo una puntuaciónglobal final de 68/84 (31% de incremento). Se identificaron 18 puntosdébiles y se implementaron sus correspondientes acciones de mejora, incluyendorobotización, gestión de la calidad, creación de grupos de trabajomultidisciplinares, prevención de errores de medicación, implementación debombas inteligentes o la monitorización farmacocinética, entre otras.

Objective: To describe the evolution of our Pharmacy Service in relationto the objectives of Proyecto 2020 (Project 2020) of the SociedadEspañola Farmacia Hospitalaria (Spanish Society of Hospital Pharmacy),to identify weak points, and to implement improvement actions to achievethe set objectives.Method: A 10-year prospective observational study. We analysed theinitial situation of the Pharmacy Service and conducted follow-up reassessments.We developed a questionnaire comprising the 28 goals of thefive strategic focus areas (blocks) of the project based on a 4-level quantitativeclassification of these goals: level A, implementation in all areas(3 points); level B, implementation in some areas (2 points); level C, notimplemented, but formally discussed (1 point); or level D, not addressed(0 points). After each assessment, we identified the goals with the lowestscores and determined which improvement actions needed to be implemented.After each assessment, the targets with lower score were identifiedand improvement actions needed to be implemented were decided.Results: The initial assessment was conducted in 2010. The overall scorewas 42/84 and the highest score (7/9) related to the block scientific evidence.The follow-up reassessments (2014, 2019) and the final one (2020)showed an overall gradual increase in level A scores (18% vs 53%) and a decrease in level C (43% vs 4%) and D objectives (14% vs 4%). All blocksimproved their score, obtaining a final score of 68/84 (31% increase).A total of 18 weak points were identified and appropriate improvementactions were implemented, which included automation, quality management,the creation of multidisciplinary working groups, the prevention ofmedication errors, the incorporation of intelligent pumps or therapeutic drugmonitoring among other solutions.

Utilidad clínica de la secuenciación de nueva generación en el diagnóstico etiológico de la hipoacusia neurosensorial en una Unidad de Hipoacusia Infantil / Clinical utility of next-generation sequencing in the aetiological diagnosis of sensorineural hearing loss in a Childhood Hearing Loss Unit

INTRODUCCIÓN: La hipoacusia neurosensorial (HNS) es el déficit sensorial más prevalente en nuestro medio. La secuenciación genómica de nueva generación (NGS) permite obtener un diagnóstico etiológico en un alto porcentaje de pacientes. Nuestro estudio piloto muestra los resultados de la aplicación sistemática de la NGS en una Unidad de Hipoacusia Infantil, así como sus implicaciones en el manejo clínico de los pacientes y sus familiares. MATERIAL Y MÉTODO: Se incluyó a 27 pacientes diagnosticados de HNS entre 2014 y 2017 en los que se descartó una causa ambiental. El test genético consistió en un panel de genes analizados mediante NGS (panel OTOgenicsTM). Este panel ha sido diseñado para incluir genes asociados con hipoacusia neurosensorial o mixta, de inicio precoz o tardío, sindrómica y no sindrómica, independientemente de su patrón de herencia. RESULTADOS: Se obtuvo un diagnóstico genético en el 56% (15/27) de los pacientes (62% en el caso de las HNS bilaterales); 5/27 (19%) presentaron variantes patogénicas en el gen GJB2 y el resto variantes patogénicas o probablemente patogénicas en otros genes asociados con HNS aislada (PR2X2, TECTA y STRC), con HNS sindrómicas (CHD7, GATA3, COL4A5, MITF y SOX10) o con HNS sindrómicas y no sindrómicas (BSND, ACTG1 y CDH23). DISCUSIÓN: El diagnóstico etiológico de la HNS supone un desafío en la práctica clínica. Nuestra serie demuestra que es posible implementar el diagnóstico genético en la rutina asistencial y que esta información tiene implicaciones pronósticas y terapéuticas

INTRODUCTION: Sensorineural hearing loss (SNL) is the most prevalent sensory deficit in our environment. Next generation genomic sequencing (NGS) enables an aetiological diagnosis in a high percentage of patients. Our pilot study shows the results of the systematic application of NGS in a Childhood Hearing Loss Unit, as well as its implications for the clinical management of patients and their families. MATERIAL AND METHOD: We included 27 patients diagnosed with SNL between 2014 and 2017, in which an environmental cause was ruled out. The genetic test consisted of a panel of genes analyzed by NGS (OTOgenicsTM panel). This panel has been designed to include genes associated with sensorineural or mixed hearing loss, early onset or late, syndromic and non-syndromic, regardless of their inheritance pattern. RESULTS: A genetic diagnosis was obtained in 56% (15/27) of the patients (62% in the case of bilateral SNL). Of the patients, 5/27 (19%) presented pathogenic variants in the GJB2 gene and the rest pathogenic and / or probably pathogenic variants in other genes associated with isolated SNL (PR2X2, TECTA and STRC), with syndromic SNL (CHD7, GATA3, COL4A5, MITF and SOX10) or with syndromic and non-syndromic SNL (BSND, ACTG1 and CDH23). DISCUSSION: The aetiological diagnosis of SNL is a challenge in clinical practice. Our series demonstrates that it is possible to implement genetic diagnosis in the care routine and that this information has prognostic and therapeutic implications

Clinical utility of next-generation sequencing in the aetiological diagnosis of sensorineural hearing loss in a Childhood Hearing Loss Unit. / Utilidad clínica de la secuenciación de nueva generación en el diagnóstico etiológico de la hipoacusia neurosensorial en una Unidad de Hipoacusia Infantil.

INTRODUCTION: Sensorineural hearing loss (SNL) is the most prevalent sensory deficit in our environment. Next generation genomic sequencing (NGS) enables an aetiological diagnosis in a high percentage of patients. Our pilot study shows the results of the systematic application of NGS in a Childhood Hearing Loss Unit, as well as its implications for the clinical management of patients and their families. MATERIAL AND METHOD: We included 27 patients diagnosed with SNL between 2014 and 2017, in which an environmental cause was ruled out. The genetic test consisted of a panel of genes analyzed by NGS (OTOgenicsTM panel). This panel has been designed to include genes associated with sensorineural or mixed hearing loss, early onset or late, syndromic and non-syndromic, regardless of their inheritance pattern. RESULTS: A genetic diagnosis was obtained in 56% (15/27) of the patients (62% in the case of bilateral SNL). Of the patients, 5/27 (19%) presented pathogenic variants in the GJB2 gene and the rest pathogenic and / or probably pathogenic variants in other genes associated with isolated SNL (PR2X2, TECTA and STRC), with syndromic SNL (CHD7, GATA3, COL4A5, MITF and SOX10) or with syndromic and non-syndromic SNL (BSND, ACTG1 and CDH23). DISCUSSION: The aetiological diagnosis of SNL is a challenge in clinical practice. Our series demonstrates that it is possible to implement genetic diagnosis in the care routine and that this information has prognostic and therapeutic implications.

Perrault syndrome with neurological features in a compound heterozygote for two TWNK mutations: overlap of TWNK-related recessive disorders.

BACKGROUND: Perrault syndrome is a rare autosomal recessive disorder that is characterized by the association of sensorineural hearing impairment and ovarian dysgenesis in females, whereas males have only hearing impairment. In some cases, patients present with a diversity of neurological signs. To date, mutations in six genes are known to cause Perrault syndrome, but they do not explain all clinically-diagnosed cases. In addition, the number of reported cases and the spectra of mutations are still small to establish conclusive genotype-phenotype correlations. METHODS: Affected siblings from family SH19, who presented with features that were suggestive of Perrault syndrome, were subjected to audiological, neurological and gynecological examination. The genetic study included genotyping and haplotype analysis for microsatellite markers close to the genes involved in Perrault syndrome, whole-exome sequencing, and Sanger sequencing of the coding region of the TWNK gene. RESULTS: Three siblings from family SH19 shared similar clinical features: childhood-onset bilateral sensorineural hearing impairment, which progressed to profound deafness in the second decade of life; neurological signs (spinocerebellar ataxia, polyneuropathy), with onset in the fourth decade of life in the two females and at age 20 years in the male; gonadal dysfunction with early cessation of menses in the two females. The genetic study revealed two compound heterozygous pathogenic mutations in the TWNK gene in the three affected subjects: c.85C>T (p.Arg29*), previously reported in a case of hepatocerebral syndrome; and a novel missense mutation, c.1886C>T (p.Ser629Phe). Mutations segregated in the family according to an autosomal recessive inheritance pattern. CONCLUSIONS: Our results further illustrate the utility of genetic testing as a tool to confirm a tentative clinical diagnosis of Perrault syndrome. Studies on genotype-phenotype correlation from the hitherto reported cases indicate that patients with Perrault syndrome caused by TWNK mutations will manifest neurological signs in adulthood. Molecular and clinical characterization of novel cases of recessive disorders caused by TWNK mutations is strongly needed to get further insight into the genotype-phenotype correlations of a phenotypic continuum encompassing Perrault syndrome, infantile-onset spinocerebellar ataxia, and hepatocerebral syndrome.

Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients.

BACKGROUND: Sensorineural hearing loss (SNHL) is the most common sensory impairment. Comprehensive next-generation sequencing (NGS) has become the standard for the etiological diagnosis of early-onset SNHL. However, accurate selection of target genomic regions (gene panel/exome/genome), analytical performance and variant interpretation remain relevant difficulties for its clinical implementation. METHODS: We developed a novel NGS panel with 199 genes associated with non-syndromic and/or syndromic SNHL. We evaluated the analytical sensitivity and specificity of the panel on 1624 known single nucleotide variants (SNVs) and indels on a mixture of genomic DNA from 10 previously characterized lymphoblastoid cell lines, and analyzed 50 Spanish patients with presumed hereditary SNHL not caused by GJB2/GJB6, OTOF nor MT-RNR1 mutations. RESULTS: The analytical sensitivity of the test to detect SNVs and indels on the DNA mixture from the cell lines was > 99.5%, with a specificity > 99.9%. The diagnostic yield on the SNHL patients was 42% (21/50): 47.6% (10/21) with autosomal recessive inheritance pattern (BSND, CDH23, MYO15A, STRC [n = 2], USH2A [n = 3], RDX, SLC26A4); 38.1% (8/21) autosomal dominant (ACTG1 [n = 3; 2 de novo], CHD7, GATA3 [de novo], MITF, P2RX2, SOX10), and 14.3% (3/21) X-linked (COL4A5 [de novo], POU3F4, PRPS1). 46.9% of causative variants (15/32) were not in the databases. 28.6% of genetically diagnosed cases (6/21) had previously undetected syndromes (Barakat, Usher type 2A [n = 3] and Waardenburg [n = 2]). 19% of genetic diagnoses (4/21) were attributable to large deletions/duplications (STRC deletion [n = 2]; partial CDH23 duplication; RDX exon 2 deletion). CONCLUSIONS: In the era of precision medicine, obtaining an etiologic diagnosis of SNHL is imperative. Here, we contribute to show that, with the right methodology, NGS can be transferred to the clinical practice, boosting the yield of SNHL genetic diagnosis to 50-60% (including GJB2/GJB6 alterations), improving diagnostic/prognostic accuracy, refining genetic and reproductive counseling and revealing clinically relevant undiagnosed syndromes.

Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With ST-Segment Elevation Myocardial Infarction and Left Ventricular Dysfunction.

RATIONALE: Allogeneic cardiac stem cells (AlloCSC-01) have shown protective, immunoregulatory, and regenerative properties with a robust safety profile in large animal models of heart disease. OBJECTIVE: To investigate the safety and feasibility of early administration of AlloCSC-01 in patients with ST-segment-elevation myocardial infarction. METHODS AND RESULTS: CAREMI (Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With STEMI and Left Ventricular Dysfunction) was a phase I/II multicenter, randomized, double-blind, placebo-controlled trial in patients with ST-segment-elevation myocardial infarction, left ventricular ejection fraction ≤45%, and infarct size ≥25% of left ventricular mass by cardiac magnetic resonance, who were randomized (2:1) to receive AlloCSC-01 or placebo through the intracoronary route at days 5 to 7. The primary end point was safety and included all-cause death and major adverse cardiac events at 30 days (all-cause death, reinfarction, hospitalization because of heart failure, sustained ventricular tachycardia, ventricular fibrillation, and stroke). Secondary safety end points included major adverse cardiac events at 6 and 12 months, adverse events, and immunologic surveillance. Secondary exploratory efficacy end points were changes in infarct size (percentage of left ventricular mass) and indices of ventricular remodeling by magnetic resonance at 12 months. Forty-nine patients were included (92% male, 55±11 years), 33 randomized to AlloCSC-01 and 16 to placebo. No deaths or major adverse cardiac events were reported at 12 months. One severe adverse events in each group was considered possibly related to study treatment (allergic dermatitis and rash). AlloCSC-01 elicited low levels of donor-specific antibodies in 2 patients. No immune-related adverse events were found, and no differences between groups were observed in magnetic resonance-based efficacy parameters at 12 months. The estimated treatment effect of AlloCSC-01 on the absolute change from baseline in infarct size was -2.3% (95% confidence interval, -6.5% to 1.9%). CONCLUSIONS: AlloCSC-01 can be safely administered in ST-segment-elevation myocardial infarction patients with left ventricular dysfunction early after revascularization. Low immunogenicity and absence of immune-mediated events will facilitate adequately powered studies to demonstrate their clinical efficacy in this setting. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02439398.

Prevention of Fat Embolism in Fat Injection for Gluteal Augmentation, Anatomic Study in Fresh Cadavers.

INTRODUCTION: Liposuction is a popular surgical procedure. As in any surgery, there are risks and complications, especially when combined with fat injection. Case reports of fat embolism have described a possible explanation as the puncture and tear of gluteal vessels during the procedure, especially when a deep injection is planned. METHODS: A total of 10 dissections were performed in five fresh cadavers. Each buttocks was divided into four quadrants. We focused on the location where the gluteal vessels enter the muscle and the diameter of the vessels. Colorant at two different angles was injected (30° and 45°). We evaluated the relation of the colorant with the main vessels. RESULTS: We found two perforators per quadrant. The thickness of the gluteal muscle was 2.84 ± 1.54 cm. The area under the muscle where the superior gluteal vessels traverse the muscle was located 6.4 ± 1.54 cm from the intergluteal crease and 5.8 ± 1.13 cm from the superior border of the muscle. The inferior gluteal vessels were located 8.3 ± 1.39 cm from the intergluteal crease and 10 ± 2.24 cm from the superior border of the muscle. When we compared the fat injected at a 30° angle, the colorant stayed in the muscle. Using a 45° angle, the colorant was in contact with the superior gluteal artery and the sciatic nerve. No puncture or tear was observed in the vessels or the nerve. CONCLUSIONS: The location where the vessels come in contact with the muscle, which can be considered for fat injection, were located in quadrants 1 and 3. A 30° angle allows for an injection into the muscle without passing into deeper structures, unlike a 45° injection angle.

Rationale and Design of a Clinical Trial to Evaluate the Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With Acute Myocardial Infarction and Left Ventricular Dysfunction: The Randomized Multicenter Double-Blind Controlled CAREMI Trial (Cardiac Stem Cells in Patients With Acute Myocardial Infarction).

RATIONALE: Stem cell therapy has increased the therapeutic armamentarium in the fight against ischemic heart disease and heart failure. The administration of exogenous stem cells has been investigated in patients suffering an acute myocardial infarction, with the final aim of salvaging jeopardized myocardium and preventing left ventricular adverse remodeling and functional deterioration. However, phase I and II clinical trials with autologous and first-generation stem cells have yielded inconsistent benefits and mixed results. OBJECTIVE: In the search for new and more efficient cellular regenerative products, interesting cardioprotective, immunoregulatory, and cardioregenerative properties have been demonstrated for human cardiac stem cells. On the other hand, allogeneic cells show several advantages over autologous sources: they can be produced in large quantities, easily administered off-the-shelf early after an acute myocardial infarction, comply with stringent criteria for product homogeneity, potency, and quality control, and may exhibit a distinctive immunologic behavior. METHODS AND RESULTS: With a promising preclinical background, CAREMI (Cardiac Stem Cells in Patients With Acute Myocardial Infarction) has been designed as a double-blind, 2:1 randomized, controlled, and multicenter clinical trial that will evaluate the safety, feasibility, and efficacy of intracoronary delivery of allogeneic human cardiac stem cell in 55 patients with large acute myocardial infarction, left ventricular dysfunction, and at high risk of developing heart failure. CONCLUSIONS: This phase I/II clinical trial represents a novel experience in humans with allogeneic cardiac stem cell in a rigorously imaging-based selected group of acute myocardial infarction patients, with detailed safety immunologic assessments and magnetic resonance imaging-based efficacy end points. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02439398.

Coronary physiology assessment in the catheterization laboratory.

Physicians cannot rely solely on the angiographic appearance of epicardial coronary artery stenosis when evaluating patients with myocardial ischemia. Instead, sound knowledge of coronary vascular physiology and of the methods currently available for its characterization can improve the diagnostic and prognostic accuracy of invasive assessment of the coronary circulation, and help improve clinical decision-making. In this article we summarize the current methods available for a thorough assessment of coronary physiology.

A labor and cost effective next generation sequencing of PKHD1 in autosomal recessive polycystic kidney disease patients.

The Sanger sequencing of patients with recessive polycystic kidney disease is challenging due to the length and heterogeneous mutational spectrum of the PKHD1 gene. Next generation sequencing (NGS) might thus be of special interest to search for PKHD1 mutations. The study involved a total of 22 patients with autosomal recessive polycystic kidney disease (ARPKD) and 8 parents of non-available ARPKD patients. Five pools of 6 samples each were sequenced with the Personal Genome Machine (PGM, Ion Torrent). For each DNA pool, a total of 109 fragments that covered the entire PKHD1 coding sequence were amplified in only two tubes followed by library preparation and NGS with the PGM. To validate the technique, each pool contained the DNA of at least one patient with known mutation. The putative mutations identified in each pool were confirmed and assigned to specific individuals through Sanger sequencing. All but one of the 109 amplicons were successfully read, and we identified the two PKHD1 mutations in 11 of the ARPKD cases, one mutation in 9 patients, and no mutation in only 2 patients. Six of the 8 parents from non-available patients were mutation carriers. The reported procedure would facilitate the large scale analysis of PKHD1 with a significant reduction in cost and labor.

A unique case of a discontinuous duplication 3q26.1-3q28 resulting from a segregation error of a maternal complex chromosomal rearrangement involving an insertion and an inversion.

Until now, few cases of partial trisomy of 3q due to segregation error of parental balanced translocation and segregation of a duplicated deficient product resulting from parental pericentric inversion have been reported so far. Only five cases of chromosomal insertion malsegregation involving 3q region are available yet, thus making it relatively rare. In this case report, we are presenting a unique case of discontinuous partial trisomy of 3q26.1-q28 region which resulted from a segregation error of two insertions involving 3q26.1 to 3q27.3 and 3q28 regions with ~21Mb and ~2Mb sizes, respectively. The maternally inherited insertion was cytogenetically characterized as der(8)(8pter→8p22::3q26→3q27.3::3q28→3q28::8p22→8qter) and the patient's major clinical features involved Dandy Walker malformation, sub-aortic ventricular septal defect, upslanting palpebral fissures, clinodactyly, hirsutism, and prominent forehead. Besides, a review of the literature involving cases with similar chromosomal imbalances and cases with "3q-duplication syndrome" is also provided.

Human masseter muscle fibers from the elderly express less neonatal Myosin than those of young adults.

In contrast to limb muscles where neonatal myosin (MyHC-neo) is present only shortly after birth, adult masseter muscles contain a substantial portion of MyHC-neo, which is coexpressed with mature MyHC isoforms. Changes in the numerical and area proportion of muscle fibers containing MyHC-neo in masseter muscle with aging could be expected, based on previously reported findings that (i) developmental MyHC-containing muscle fibers exhibit lower shortening velocities compared to fibers with exclusively fast MyHC isoforms and (ii) transformation toward faster phenotype occurs in elderly compared to young masseter muscle. In this study, we detected MyHC isoforms in the anterior superficial part of the human masseter muscle in a sufficiently large sample of young, middle-aged, and elderly subjects to reveal age-related changes in the coexpression of MyHC-neo with adult MyHC isoforms. MyHC isoforms were visualized with immunoperoxidase method and the results were presented by (i) the area proportion of fibers containing particular MyHC isoforms and (ii) the numerical proportion of fiber types defined by MyHC-1, -2a, -2x, and -neonatal isoform expression from a successive transverse sections. We found a lower numerical and area proportion of fibers expressing MyHC-neo as well as a lower area proportion of fibers containing MyHC-1 in elderly than in young subjects. We conclude that the diminished expression of MyHC-neo with age could point to a lower regeneration capacity of masseter muscle in the elderly.

Four small supernumerary marker chromosomes derived from chromosomes 6, 8, 11 and 12 in a patient with minimal clinical abnormalities: a case report.

INTRODUCTION: Small supernumerary marker chromosomes are still a problem in cytogenetic diagnostic and genetic counseling. This holds especially true for the rare cases with multiple small supernumerary marker chromosomes. Most such cases are reported to be clinically severely affected due to the chromosomal imbalances induced by the presence of small supernumerary marker chromosomes. Here we report the first case of a patient having four different small supernumerary marker chromosomes which, apart from slight developmental retardation in youth and non-malignant hyperpigmentation, presented no other clinical signs. CASE PRESENTATION: Our patient was a 30-year-old Caucasian man, delivered by caesarean section because of macrosomy. At birth he presented with bilateral cryptorchidism but no other birth defects. At age of around two years he showed psychomotor delay and a bilateral convergent strabismus. Later he had slight learning difficulties, with normal social behavior and now lives an independent life as an adult. Apart from hypogenitalism, he has multiple hyperpigmented nevi all over his body, short feet with pes cavus and claw toes. At age of 30 years, cytogenetic and molecular cytogenetic analysis revealed a karyotype of 50,XY,+min(6)(:p11.1-> q11.1:),+min(8)(:p11.1->q11.1:),+min(11)(:p11.11->q11:),+min(12)(:p11.2~12->q10:), leading overall to a small partial trisomy in 12p11.1~12.1. CONCLUSIONS: Including this case, four single case reports are available in the literature with a karyotype 50,XN,+4mar. For prenatally detected multiple small supernumerary marker chromosomes in particular we learn from this case that such a cytogenetic condition may be correlated with a positive clinical outcome.

Implementation fidelity in adolescent family-based prevention programs: relationship to family engagement.

Reliability and validity of intervention studies are impossible without adequate program fidelity, as it ensures that the intervention was implemented as designed and allows for accurate conclusions about effectiveness (Bellg AJ, Borrelli B, Resnick B et al. Enhancing treatment fidelity in health behavior change studies: best practices and recommendations from the NIH behavior change consortium. Health Psychol 2004; 23: 443-51). This study examines the relation between program fidelity with family engagement (i.e. satisfaction and participation) in family-based prevention programs for adolescent alcohol, tobacco or other drug use. Families (n = 381) were those with an 11- to 12-year-old child enrolled in Kaiser Permanente in the San Francisco area. Families participated in one of two programs: Strengthening Families Program: For Parents and Youth 10-14 (SFP) (Spoth R, Redmond C, Lepper H. Alcohol initiation outcomes of universal family-focused preventive interventions: one- and two-year follow-ups of a controlled study. J Stud Alcohol Suppl 1999; 13: 103-11) or Family Matters (FM) (Bauman KE, Ennett ST. On the importance of peer influence for adolescent drug use: commonly neglected considerations. Addiction 1996; 91: 185-98). Fidelity was assessed by: (i) adherence to the program manual and (ii) quality of implementation. No relationships were found for FM, a self-directed program. For SFP, higher quality scores were related to higher parent satisfaction. Higher adherence scores were related to higher satisfaction for youth, yet surprisingly to lower satisfaction for parents. Parent sessions involve much discussion, and to obtain high adherence scores, health educators were often required to limit this to implement all program activities. Findings highlight a delivery challenge in covering all activities while allowing parents to engage in mutually supportive behavior.