An Initial Case Series of Intensive Cognitive-Behavioral Therapy for Obsessive-Compulsive Disorder in Adolescents with Autism Spectrum Disorder.

Obsessive-compulsive disorder (OCD) is prevalent among youth with autism spectrum disorder (ASD). Cognitive-behavioral therapy (CBT) with ASD-specific modifications has support for treating OCD in this population; however, use of intensive CBT in youth with ASD and severe OCD has not been tested. The current study examined the preliminary effectiveness of an individualized intensive CBT protocol for OCD in adolescents with ASD. Nine adolescents (aged 11-17 years) completed a regimen of intensive CBT (range 24-80 daily sessions) incorporating exposure with response prevention (ERP). Treatment materials, language and techniques were modified in accordance with evidence-based findings for this population. Seven of nine participants (78%) were treatment responders, and large treatment effects (d = 1.35-2.58) were obtained on primary outcomes (e.g., obsessive-compulsive symptom severity). Preliminary findings suggest that an intensive CBT approach for OCD is effective among adolescents with ASD.

Survival of human circulating antigen-induced plasma cells is supported by plasma cell-niche cytokines and T follicular helper lymphocytes.

Human circulating Ag-induced plasma cells (PCs) contain a high proportion of cycling cells. This study reveals that these PCs spontaneously proliferate in culture during 72 h, as determined by BrdU-uptake detection. Transcriptome analysis indicates that, in comparison with tonsil and bone marrow (BM) PCs, these PCs distinctively upregulate genes involved in cell division. Blood PC proliferation occurs simultaneously with increasing apoptosis rates, and is associated with PC survival. In addition, the proliferating activity of these PCs is enhanced by the addition of cytokines present in PC survival niches. Moreover, blood Ag-induced, but not BM, PCs exhibit the expression of molecules involved in the interaction between memory B cells and T follicular helper (Tfh) cells. In fact, purified circulating and tonsil Tfh cells increased IgG secretion by blood Ag-induced, but not by BM, PCs. This effect is exerted by augmenting blood PC survival through a mechanism partly dependent on cell contact. These results strongly suggest that the proliferating capacity of circulating Ag-induced PCs contributes to their competitive migration to survival niches, either to long-living PC niches or to temporal niches present in reactive lymphoid organs and inflamed tissues, structures where Tfh cells appear to participate.

STAT-3 activation by differential cytokines is critical for human in vivo-generated plasma cell survival and Ig secretion.

Maturation and survival of plasma cells (PCs) depends on extrinsic factors provided in specialized niches. In addition, B lymphocyte differentiation into PCs requires the activation of the JAK-STAT-3 pathway. However, whether STAT-3 is needed only during the transition of B lymphocytes to PC, or it is also involved in the survival and function of PCs at different stages of maturation, has not been unequivocally clarified. This study analyzes the effect of IL-10, IL-21, and IL-6 on human in vivo-generated PCs isolated from secondary lymphoid organs, blood (circulating, recently Ag-induced PCs), and bone marrow. PCs from these different organs show specific profiles of receptors for, and responsiveness to, these cytokines required for their survival and sustained Ab secretion. However, IL-10, IL-21, and IL-6 commonly induce STAT-3 phosphorylation in the three PC subsets, and all of their effects are exerted strictly through the STAT-3 activation. The inhibition or nonactivation of this pathway in the three PC populations impairs not only the effect of STAT-3-activating cytokines, but also the action of other cytokines important at the PC level, including a proliferation-induced ligand, BAFF, insulin-like growth factor 1, vascular endothelial growth factor, and stromal cell-derived factor-1α. These results indicate that STAT-3 activation is critical for human PCs throughout their maturation.

Cutting edge: IL-21 derived from human follicular helper T cells acts as a survival factor for secondary lymphoid organ, but not for bone marrow, plasma cells.

IL-21 induces the differentiation of activated B lymphocytes into plasma cells (PC), but its direct effect on PC remains uncertain. This study analyzes the role of IL-21 on human in vivo-generated PC. IL-21R was clearly expressed on PC from the human tonsil, the lymph node, and the spleen (secondary lymphoid organs [SLO]) but barely on terminally mature bone marrow PC. IL-21 enhanced Ig secretion by isolated SLO PC but not bone marrow PC. Tonsillar T follicular helper (Tfh) lymphocytes are known to secrete IL-21. Purified Tfh cells induced a marked increase of Ig production by tonsillar PC, and this effect was impaired when endogenous IL-21 production was blocked. IL-21 provoked a rapid and transient phosphorylation of STAT3 in tonsillar PC. Tfh cells or exogenous IL-21 reduce tonsillar PC apoptosis and increases PC recovery but does not modify their nonproliferating status. These results suggest that IL-21 derived from Tfh cells acts as a survival factor for SLO PC in vivo.

Myeloma cells contain high levels of inorganic polyphosphate which is associated with nucleolar transcription.

BACKGROUND: In hematology there has recently been increasing interest in inorganic polyphosphate. This polymer accumulates in platelet granules and its functions include modulating various stages of blood coagulation, inducing angiogenesis, and provoking apoptosis of plasma cells. In this study we evaluated the characteristics of intracellular polyphosphate in myeloma cell lines, in primary myeloma cells from patients, and in other human B-cell populations from healthy donors. DESIGN AND METHODS: We have developed a novel flow cytometric method for detecting levels of polyphosphate in cell populations. We also used confocal microscopy and enzymatic analysis to study polyphosphate localization and characteristics. RESULTS: We found that myeloma plasma cells contain higher levels of intracellular polyphosphate than normal plasma cells and other B-cell populations. Localization experiments indicated that high levels of polyphosphate accumulate in the nucleolus of myeloma cells. As the principal function of the nucleolus involves transcription of ribosomal DNA genes, we found changes in the cellular distribution of polyphosphate after the inhibition of nucleolar transcription. In addition, we found that RNA polymerase I activity, responsible for transcription in the nucleolus, is also modulated by polyphosphate, in a dose-dependent manner. CONCLUSIONS: Our results show an unusually high accumulation of polyphosphate in the nucleoli of myeloma cells and a functional relationship of this polymer with nucleolar transcription.

Considerations in designing trauma-focused interventions for displaced Afghan women.

In light of the 2021 United States military withdrawal from Afghanistan, as well as the humanitarian crises of mass displacement and subsequent health system strain that have ensued, practitioners worldwide will need to develop a more nuanced understanding of the adverse life experiences that women from Afghanistan frequently endorse. As they bear a disproportionate impact of constraints within Afghan society, and as patriarchal systems affect most of their life domains, women from Afghanistan may present with high levels of baseline trauma upon resettlement, and health systems may seek to attenuate this distress; However, the nature of these traumatogenic events may shape women's receptivity to psychosocial interventions, particularly those which are at least partially rooted in Western modalities. In the absence of sufficient literature on evidence-based interventions for this population, a diversity of ethnographic and clinical literature is synthesized, including literature on interventions alleged to be compatible with Afghan norms. As it will be essential to support Afghan women's mental health following social reorganization on a massive scale, considerations arising from the interdisciplinary literature are offered so that they may inform the development of structured, trauma-focused interventions and so that the health systems with which they interface may be better prepared to serve them.

Economic evaluation of surgical treatment of obesity. / Evaluación económica del tratamiento quirúrgico de la obesidad.

INTRODUCTION: Obesity surgery is the best treatment for extreme obesity, with demonstrated long-term positive outcomes. The potential cost-savings generated by the improvement of comorbidities after surgery can justify the allocation of more resources in the surgical treatment of obesity. METHODS: This was an observational, descriptive, longitudinal and retrospective study. Eligible patients underwent Roux-en-Y gastric bypass surgery at the Hospital Universitario Central de Asturias between 2003 and 2012. The established minimum follow-up period was two years. We calculated the individualized cost per patient treated (bottom-up) as well as per Diagnosis-Related Group (DRG) codes (top-down). RESULTS: Our study included 307 patients. The average cost per hospitalization calculated by DRG codes was €6,545.90, and the average cost per patient was €10,572.20. DRG 288 represented 91% of the series, with a value of €4,631. The number of medications also decreased during this period, from 2.86 to 0.78 per medically treated patient, representing a cost reduction of €4,433 per patient with all the obesity-related comorbidities analyzed. CONCLUSIONS: Two years after Roux-en-Y gastric bypass conducted at Hospital Universitario Central de Asturias, the savings in drug costs for patients with multiple pathologies would compensate the inherent costs of the surgical treatment itself. Our results showed that DRG-related costs was insufficient to make a correct economic evaluation, so we recommend an individualized cost calculating method.

Quality of life in children and adolescents with obsessive-compulsive disorder: The Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q).

The current study examined quality of life (QOL) and its clinical correlates among 225 intensive treatment-seeking children and adolescents with obsessive-compulsive disorder (OCD) using the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q). Youth completed the PQ-LES-Q along with self-report measures assessing functional impairment, anxiety sensitivity, OCD symptoms, nonspecific anxiety, depression, and social anxiety. Parents completed measures on their child's anxiety, the presence of inattention/hyperactivity, depression, functional impairment, and frequency of family accommodation of symptoms. Contrary to expectation, child-reported OCD symptoms did not significantly predict QOL; however, lower overall QOL was strongly associated with the presence of comorbid major depressive disorder (g=3D -0.76) and slightly related to comorbid social phobia (g=3D -0.36). These results suggest that assessing and addressing comorbid conditions in the treatment of youth with OCD is an important component of intensive treatment.

Evidence in follow-up and prognosis of esophagogastric junction cancer. / Evidencia en seguimiento y pronóstico del cáncer de unión esofagogástrica.

Five-year survival of tumors of the esophagogastric junction is 50%, in the most favourable stages and with the most effective adjuvant treatments. More than 40% of patients will have recurrences within a short period, usually the first year after potentially curative surgery. Survival after this recurrence is usually less than 6 months because treatment is not very effective, be it palliative chemotherapy, radiotherapy or surgical excision of single recurrences. As the detection of asymptomatic recurrences allows for earlier and more effective treatments to be used, the type and frequency of follow-up has an influence on survival.

Laparoscopic treatment of large bowel obstruction due to a self-locating peritoneal dialysis catheter.

INTRODUCTION: Peritoneal dialysis has been used in the treatment of end-stage renal disease for a long time. The development of continuous ambulatory peritoneal dialysis (CAPD) has achieved an acceptable device of renal replacement therapy. PRESENTATION OF CASE: We report a 55 year-old patient who was initiated on CAPD in February 2016. Three months later, the Tenckhoff catheter was removed due to its malfunction, and a new self-locating peritoneal dialysis catheter was placed in the left side of the abdomen. In September 2016, the patient presented with symptoms of intestinal obstruction. A CT scan revealed a collapsed sigmoid colon with the tungsten tip of the catheter supported on the mesosigmoid as the cause of the occlusion. DISCUSSION: Herein, a rare but clinically important case of mechanical large bowel obstruction due to self-locating peritoneal dialysis catheter is presented. The weight added to the tip of the self-locating catheter for the purpose of stretching it, can be dangerous if a displacement takes place. A laparoscopic procedure was performed, resolving the obstruction by reinserting the peritoneal catheter in its right position. CONCLUSION: The weight added to the tip of self-locating catheters is a matter of concern, since intimate contact between the peritoneal catheter and the intestinal wall can result in perforation or intestinal occlusion.

VAMP2 is implicated in the secretion of antibodies by human plasma cells and can be replaced by other synaptobrevins.

The production and secretion of antibodies by human plasma cells (PCs) are two essential processes of humoral immunity. The secretion process relies on a group of proteins known as soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), which are located in the plasma membrane (t-SNAREs) and in the antibody-carrying vesicle membrane (v-SNARE), and mediate the fusion of both membranes. We have previously shown that SNAP23 and STX4 are the t-SNAREs responsible for antibody secretion. Here, using human PCs and antibody-secreting cell lines, we studied and characterized the expression and subcellular distribution of vesicle associated membrane protein (VAMP) isoforms, demonstrating that all isoforms (with the exception of VAMP1) are expressed by the referenced cells. Furthermore, the functional role in antibody secretion of each expressed VAMP isoform was tested using siRNA. Our results show that VAMP2 may be the v-SNARE involved in vesicular antibody release. To further support this conclusion, we used tetanus toxin light chain to cleave VAMP2, conducted experiments to verify co-localization of VAMP2 in antibody-carrying vesicles, and demonstrated the coimmunoprecipitation of VAMP2 with STX4 and SNAP23 and the in situ interaction of VAMP2 with STX4. Taken together, these findings implicate VAMP2 as the main VAMP isoform functionally involved in antibody secretion.

A Case Report of Intensive Exposure-Based Cognitive Behavioral Therapy for a Child With Comorbid Autism Spectrum Disorder and Obsessive-Compulsive Disorder.

Cognitive behavioral therapy (CBT) with exposure and response prevention (ERP) has proven to be an effective treatment modality for children with obsessive-compulsive disorder (OCD). Less research exists demonstrating efficacy for this treatment modality among children with comorbid diagnoses of OCD and autism spectrum disorder (ASD), and virtually, nothing has been reported examining intensive interventions for the most severe cases. As such, this article discusses the treatment of an adolescent male with severe OCD comorbid with ASD, attention deficit hyperactivity disorder (ADHD), generalized anxiety disorder (GAD), and chronic tic disorder using a cognitive behavioral approach and ERP. We conclude with recommendations for continued clinical research to understand approaches to help nonresponders to standard therapeutic approaches with this challenging population.

Intensive family exposure-based cognitive-behavioral treatment for adolescents with anorexia nervosa.

BACKGROUND: Anorexia nervosa exhibits high comorbidity rates and shared features with anxiety disorders and obsessive-compulsive disorder. Anxiety-based etiological models have proposed that fear of eating-related stimuli is the central mechanism around which avoidance of food and food-related rituals are performed. Building on this approach, exposure-based interventions have demonstrated promising results. Limited evidence in adolescents encourages the evaluation of exposure approaches in this population. METHOD: The current study presents a preliminary evaluation, in eight adolescents with anorexia nervosa, of an exposure-based CBT featuring an intensive format and parental involvement. RESULTS: significant improvements in physical and psychological outcomes were observed. CONCLUSIONS: this case series provides preliminary support for the efficacy of intensive family exposure-based CBT for treating adolescents with severe anorexia nervosa.

The transcriptional profiling of human in vivo-generated plasma cells identifies selective imbalances in monoclonal gammopathies.

Plasma cells (PC) represent the heterogeneous final stage of the B cells (BC) differentiation process. To characterize the transition of BC into PC, transcriptomes from human naïve BC were compared to those of three functionally-different subsets of human in vivo-generated PC: i) tonsil PC, mainly consisting of early PC; ii) PC released to the blood after a potent booster-immunization (mostly cycling plasmablasts); and, iii) bone marrow CD138+ PC that represent highly mature PC and include the long-lived PC compartment. This transcriptional transition involves subsets of genes related to key processes for PC maturation: the already known protein processing, apoptosis and homeostasis, and of new discovery including histones, macromolecule assembly, zinc-finger transcription factors and neuromodulation. This human PC signature is partially reproduced in vitro and is conserved in mouse. Moreover, the present study identifies genes that define PC subtypes (e.g., proliferation-associated genes for circulating PC and transcriptional-related genes for tonsil and bone marrow PC) and proposes some putative transcriptional regulators of the human PC signatures (e.g., OCT/POU, XBP1/CREB, E2F, among others). Finally, we also identified a restricted imbalance of the present PC transcriptional program in monoclonal gammopathies that correlated with PC malignancy.

Evidencia en seguimiento y pronóstico del cáncer de unión esofagogástrica / Evidence in follow-up and prognosis of esophagogastric junction cancer

La supervivencia a cinco años de los tumores de la unión esofagogástrica está en el 50% en los estadios más favorables y con los tratamientos coadyuvantes más eficaces. Más del 40% de los pacientes sufrirá recurrencias en un periodo breve, habitualmente en el primer año tras una cirugía potencialmente curativa y la supervivencia tras esa recurrencia suele ser menor de 6 meses, pues el tratamiento es poco eficaz, sea quimioterapia paliativa, radioterapia o exéresis quirúrgica de las recidivas únicas. El tipo y frecuencia del seguimiento realizado influye en la supervivencia porque la detección de recurrencias asintomáticas permite realizar tratamientos más precoces y efectivos

Five-year survival of tumors of the esophagogastric junction is 50%, in the most favourable stages and with the most effective adjuvant treatments. More than 40% of patients will have recurrences within a short period, usually the first year after potentially curative surgery. Survival after this recurrence is usually less than 6 months because treatment is not very effective, be it palliative chemotherapy, radiotherapy or surgical excision of single recurrences. As the detection of asymptomatic recurrences allows for earlier and more effective treatments to be used, the type and frequency of follow-up has an influence on survival

Intensive family exposure-based cognitive-behavioral treatment for adolescents with anorexia nervosa / Tratamiento cognitivo-conductual intensivo familiar con exposición para adolescentes con anorexia nerviosa

Background: Anorexia nervosa exhibits high comorbidity rates and shared features with anxiety disorders and obsessive-compulsive disorder. Anxiety-based etiological models have proposed that fear of eating-related stimuli is the central mechanism around which avoidance of food and food-related rituals are performed. Building on this approach, exposure-based interventions have demonstrated promising results. Limited evidence in adolescents encourages the evaluation of exposure approaches in this population. Method: The current study presents a preliminary evaluation, in eight adolescents with anorexia nervosa, of an exposure-based CBT featuring an intensive format and parental involvement. Results: significant improvements in physical and psychological outcomes were observed. Conclusions: this case series provides preliminary support for the efficacy of intensive family exposure-based CBT for treating adolescents with severe anorexia nervosa (AU)

Antecedentes: la anorexia nerviosa presenta una alta comorbilidad y características compartidas con los trastornos de ansiedad y el trastorno obsesivo-compulsivo. Los modelos etiológicos centrados en la ansiedad han propuesto que el miedo a los estímulos relacionados con la alimentación es el mecanismo principal por el cual se llevan a cabo la evitación de la comida y los rituales relacionados con la alimentación. Basándose en este enfoque las intervenciones centradas en las técnicas de exposición han demostrado resultados prometedores. La escasa evidencia en adolescentes motiva la evaluación de los enfoques basados en la exposición en esta población. Método: en el presente estudio se llevó a cabo una evaluación preliminar de la TCC con exposición en formato intensivo e inclusión familiar, en ocho adolescentes con anorexia nerviosa. Resultados: se observaron mejoras significativas en las medidas de resultado físicas y psicológicas. Conclusiones: el presente estudio de serie de casos proporciona evidencia preliminar de la eficacia de la TCC intensiva familiar con exposición para adolescentes con anorexia nerviosa severa (AU)

Differential expression of SLAMS and other modulatory molecules by human plasma cells during normal maturation.

Plasma cells (PCs) are specialized in antibody (Ab) production and they are, therefore, responsible for maintaining humoral immune responses. The human PC compartment is heterogeneous. PCs from inductive secondary lymphoid organs and from peripheral blood (PB) show less capability for prolonged survival and Ab production than bone marrow (BM) PCs, a pool consisting of fully mature cells. The HLDA9 workshop has allowed the use of labeled-monoclonal Abs (moAbs) recognizing a variety of recently identified lymphocyte modulatory surface receptors. In this study, flow cytometry analysis has been used to define the presence of these receptors on human PCs obtained from human tonsil (as an example of inductive organ), from PB and from BM. It was found that human PCs commonly expressed SLAMF1 (CD150), SLAMF2 (CD48), SLAMF3 (CD229), SLAMF6 (CD352) and SLAMF7 (CD319), but not SLAMF4 (CD244). In addition, PCs distinctively showed a low level of SLAMF5 (CD84) and a very high level of SLAMF7 expression in comparison with earlier stages of B cell maturation. All PC subsets exhibited a similar pattern of expression of SLAMF receptors suggesting a stage-dependent role for these proteins. In addition, most circulating PCs clearly expressed TNFRSF14 (CD270), BTLA (CD272), B7-1 (CD80) and B7-2 (CD86), and a substantial fraction of them were also positive for TNFRSF18 (CD357), FCRL1 (CD307a) and LAIR-1 (CD305). In contrast, tonsil and BM PCs only exhibited partial expression of TNFRSF14 and B7-2, a pattern of molecular expression similar to that detected on germinal center (GC) B cells. Present results indicate that human PCs exhibit a common pattern of SLAMF proteins, but differ in the rest of the receptors examined; this difference might be associated with their distinctive homing and functional requirements.

Evaluación económica del tratamiento quirúrgico de la obesidad / Economic evaluation of surgical treatment of obesity

INTRODUCCIÓN: La cirugía bariátrica es el mejor tratamiento de la obesidad mórbida a largo plazo. El ahorro generado por la mejoría de las comorbilidades podría justificar el empleo de más recursos sanitarios. MÉTODOS: Estudio observacional, descriptivo, longitudinal y retrospectivo, de pacientes a los que se les realizó un bypass gástrico, en el Hospital Universitario Central de Asturias entre 2003 y 2012. El seguimiento mínimo se estableció en dos años. Calculamos de manera individualizada el coste para cada uno de los pacientes intervenidos (bottom-up), así como según el grupo relacionado por el diagnóstico (GRD) (top-down). RESULTADOS: De los 307 pacientes del estudio, el coste medio del ingreso calculado por GRD fue de 6.545,9€ y el calculado por paciente de 10.572,2€. El GRD 288 representa al 91% de la serie con un valor de 4.631€. El cálculo estimativo del ahorro que supuso en nuestro entorno sanitario la disminución del número de fármacos de 2,86 a 0,78 por paciente medicado, representó 4.433€ por paciente intervenido si padecía todas las comorbilidades analizadas. CONCLUSIONES: El bypass gástrico en el Hospital Universitario Central de Asturias a los dos años de la cirugía, en pacientes con pluripatología consiguió un ahorro solo en fármacos que podría compensar los gastos inherentes al tratamiento quirúrgico. El coste por proceso mediante GRD se mostró insuficiente a la hora de hacer una correcta evaluación económica, por lo que recomendamos un método de evaluación de coste por paciente

INTRODUCTION: Obesity surgery is the best treatment for extreme obesity, with demonstrated long-term positive outcomes. The potential cost-savings generated by the improvement of comorbidities after surgery can justify the allocation of more resources in the surgical treatment of obesity. METHODS: This was an observational, descriptive, longitudinal and retrospective study. Eligible patients underwent Roux-en-Y gastric bypass surgery at the Hospital Universitario Central de Asturias between 2003 and 2012. The established minimum follow-up period was two years. We calculated the individualized cost per patient treated (bottom-up) as well as per Diagnosis-Related Group (DRG) codes (top-down). RESULTS: Our study included 307 patients. The average cost per hospitalization calculated by DRG codes was €6,545.90, and the average cost per patient was €10,572.20. DRG 288 represented 91% of the series, with a value of €4,631. The number of medications also decreased during this period, from 2.86 to 0.78 per medically treated patient, representing a cost reduction of €4,433 per patient with all the obesity-related comorbidities analyzed. CONCLUSIONS: Two years after Roux-en-Y gastric bypass conducted at Hospital Universitario Central de Asturias, the savings in drug costs for patients with multiple pathologies would compensate the inherent costs of the surgical treatment itself. Our results showed that DRG-related costs was insufficient to make a correct economic evaluation, so we recommend an individualized cost calculating method

Modulated selection of IGHV gene somatic hypermutation during systemic maturation of human plasma cells.

Systemic antigen-induced PCs are generated in inductive lymphoid tissues. Some of them are selected to travel through the circulation and finally, to home onto BM niches. BM PCs show prolonged survival and secrete high-affinity antibodies. In this study, human PCs were isolated from tonsil, blood, and BM, their IGHV3 and IGHV6 genes were sequenced, and their SHM were evaluated. The SHM analysis reveals the existence of a maturational gradient in these genes, as demonstrated by a progressive increase in the frequency of total and R mutations and total and NC aa changes following the direction: tonsil --> blood --> BM. The ratio of R to S mutations in the CDR1 and -2, but not in the FRs, increases from tonsil to blood and BM; this parameter reaches a maximum threshold when more than 10 mutations/sequence occur. Further analyses indicate that CDR1 and CDR2 SHM followed different strategies to provide appropriate amino acid changes, but both exhibited maximal resistance to incorporating drastic molecular alterations in the BM PCs. Finally, all of the findings are similar in IGHV3 and IGHV6 sequences, indicating that they reflect general rules imposed by in vivo antigen selection.