An international delphi survey and consensus meeting to define the risk factors for ureteral stricture after endoscopic treatment for urolithiasis.

PURPOSE: Iatrogenic ureteral strictures (US) after endoscopic treatment for urolithiasis represent a significant healthcare concern. However, high-quality evidence on the risk factors associated with US is currently lacking. We aimed to develop a consensus statement addressing the definition, risk factors, and follow-up management of iatrogenic US after endoscopic treatment for urolithiasis. METHODS: Utilizing a modified Delphi method, a steering committee developed survey statements based on a systematic literature review. Then, a two-round online survey was submitted to 25 experts, offering voting options to assess agreement levels. A consensus panel meeting was held for unresolved statements. The predetermined consensus threshold was set at 70%. RESULTS: The steering committee formulated 73 statements. In the initial survey, consensus was reached on 56 (77%) statements. Following in-depth discussions and refinement of 17 (23%) statements in a consensus meeting, the second survey achieved consensus on 63 (86%) statements. This process underscored agreement on pivotal factors influencing US in endoscopic urolithiasis treatments. CONCLUSIONS: This study provides a comprehensive list of categorized risk factors for US following endoscopic urolithiasis treatments. The objectives include enhancing uniformity in research, minimizing redundancy in outcome assessments, and effectively addressing risk factors associated with US. These findings are crucial for designing future clinical trials and guiding endoscopic surgeons in mitigating the risk of US.

Ureteral stricture rate after endoscopic treatments for urolithiasis and related risk factors: systematic review and meta-analysis.

PURPOSE: We aimed to accurately determine ureteral stricture (US) rates following urolithiasis treatments and their related risk factors. METHODS: We conducted a systematic review and meta-analysis following the PRISMA guidelines using databases from inception to November 2023. Studies were deemed eligible for analysis if they included ≥ 18 years old patients with urinary lithiasis (Patients) who were subjected to endoscopic treatment (Intervention) with ureteroscopy (URS), percutaneous nephrolithotomy (PCNL), or shock wave lithotripsy (SWL) (Comparator) to assess the incidence of US (Outcome) in prospective and retrospective studies (Study design). RESULTS: A total of 43 studies were included. The pooled US rate was 1.3% post-SWL and 2.1% post-PCNL. The pooled rate of US post-URS was 1.9% but raised to 2.7% considering the last five years' studies and 4.9% if the stone was impacted. Moreover, the pooled US rate differed if follow-ups were under or over six months. Patients with proximal ureteral stone, preoperative hydronephrosis, intraoperative ureteral perforation, and impacted stones showed higher US risk post-endoscopic intervention with odds ratio of 1.6 (P = 0.05), 2.6 (P = 0.009), 7.1 (P < 0.001), and 7.47 (P = 0.003), respectively. CONCLUSIONS: The overall US rate ranges from 0.3 to 4.9%, with an increasing trend in the last few years. It is influenced by type of treatment, stone location and impaction, preoperative hydronephrosis and intraoperative perforation. Future standardized reporting and prospective and more extended follow-up studies might contribute to a better understanding of US risks related to calculi treatment.

Seguridad, consejos y límites para el uso del láser en la cirugía retrógrada intrarrenal / Laser safety, warnings, and limits in retrograde intrarenal surgery

Objetivo Analizar la información actual sobre la seguridad del láser en la cirugía retrógrada intrarrenal (CRIR), centrándonos en las dos principales tecnologías láser que utilizamos en urología, el láser de holmio:itrio-aluminio-granate (Ho:YAG) y el láser de fibra de tulio (TFL). Métodos Revisión narrativa de los artículos más relevantes publicados en las bases de datos Medline y Scopus sobre este tema. Resultados Los láseres TFL y Ho:YAG con ajustes similares (0,2 J/40 Hz) tienen un aumento de temperatura promedio por volumen similar y la tasa de calentamiento promedio aumenta proporcionalmente a la potencia del láser, especialmente cuando se utilizan frecuencias altas. Datos preclínicos recientes que comparan ambas tecnologías láser con diferentes ajustes del láser coinciden en que cuando la energía suministrada aumenta a expensas de frecuencias más altas, el daño térmico también aumenta. Las frecuencias más altas, a pesar del aumento de temperatura en el medio de irrigación, pueden causar lesiones térmicas accidentales por láser. Conclusiones El uso de ajustes de baja frecuencia y una irrigación adecuada es fundamental para evitar lesiones térmicas en la litotricia endoscópica con láser (LEL). Además, se recomienda el uso de gafas de seguridad láser en la LEL con Ho:YAG y TFL. (AU)

Objective To analyze the current information about laser safety in retrograde intrarenal surgery (RIRS), focusing on the two main laser technologies that we use in urology, the holmium:yttrium-aluminum-garnet (Ho:YAG) laser, and the thulium fiber laser (TFL). Methods Narrative overview of the most relevant articles published in Medline and Scopus databases about this subject. Results TFL and Ho:YAG laser at similar settings (0.2 J/40 Hz) have similar volume-averaged temperature increase and the average heating rate increase proportionally to laser power, especially when high frequencies are used. Recent preclinical data, comparing both laser technologies at different laser settings, agreed that when the delivered energy increases in expenses of higher frequencies, the thermal damage increases too. Higher frequencies, despite of the rise of temperature in the irrigation medium, can cause accidental thermal lasering lesions. Conclusions The use of low frequency settings and a proper irrigation is critical to avoid thermal injury in endoscopic laser lithotripsy (ELL). In addition, the use of laser safety eyeglasses is recommended in Ho:YAG and TFL ELL. (AU)

¿Cómo calcular el volumen litiásico y cuál es su aplicación quirúrgica? / How to estimate stone volume and its use in stone surgery: A comprehensive review?

Objetivo Las guías actuales para el tratamiento intervencionista sugieren el diámetro acumulativo de la litiasis (DAL) como factor decisivo en la elección del tratamiento quirúrgico óptimo (ureteroscopia [URS], litotricia extracorpórea por ondas de choque [LEOCh] y nefrolitotomía percutánea [NLPC]). El volumen litiásico (VL) se ha introducido recientemente para obtener una estimación más precisa de la carga litiásica. El objetivo de esta revisión es resumir los métodos disponibles para calcular el VL y su aplicación quirúrgica. Material y métodos En diciembre de 2022 se realizó una revisión sistemática de la literatura mediante búsquedas en las bases de datos Embase, Cochrane y Pubmed. Los artículos se consideraron elegibles si describían la medición del VL o la tasa libre de litiasis (TLL) tras diferentes modalidades de tratamiento (LEOCh, URS, NLPC) o la expulsión espontánea, basándose en la medición del VL. Dos revisores evaluaron de forma independiente la elegibilidad y la calidad de los artículos y realizaron la extracción de datos. Resultados En total se incluyeron 28 estudios. Todos los estudios utilizaron diferentes técnicas para calcular el VL. La medición automática del volumen pareció ser más precisa que la estimación del volumen. Los estudios in vitro mostraron que la medición automática del volumen se ajustaba más al volumen real de la litiasis, con una menor variabilidad interobservador. A diferencia de la NLPC y la LEOCh, en la URS se observó que el VL era un mejor predictor de mejor la TLL que el diámetro litiásico mayor o el diámetro acumulativo en litiasis >20mm. Conclusiones Calcular el VL —de forma manual o automática— es factible, y probablemente se ajuste más a la carga litiásica real. Aunque en el caso de las litiasis grandes tratadas mediante cirugía intrarrenal retrógrada el VL parece predecir mejor la TLL, la superioridad del VL en todas las cargas litiásicas y para todos los tipos de tratamiento está aún por demostrar. ... (AU)

Objective Current interventional guidelines refer to the cumulative stone diameter to choose the appropriate surgical modality (ureteroscopy (URS), extracorporeal shockwave lithotripsy (ESWL) and percutaneous nephrolithotomy (PCNL)). The stone volume (SV) has been introduced recently, to better estimate the stone burden. This review aimed to summarize the available methods to evaluate the SV and its use in urolithiasis treatment. Material and methods A comprehensive review of the literature was performed in December 2022 by searching Embase, Cochrane and Pubmed databases. Articles were considered eligible if they described SV measurement or the stone free rate after different treatment modalities (SWL, URS, PCNL) or spontaneous passage, based on SV measurement. Two reviewers independently assessed the eligibility and the quality of the articles and performed the data extraction. Results In total, 28 studies were included. All studies used different measurement techniques for stone volume. The automated volume measurement appeared to be more precise than the calculated volume. In vitro studies showed that the automated volume measurement was closer to actual stone volume, with a lower inter-observer variability. Regarding URS, stone volume was found to be more predictive of stone free rates as compared to maximum stone diameter or cumulative diameter for stones >20mm. This was not the case for PCNL and SWL. Conclusions Stone volume estimation is feasible, manually or automatically and is likely a better representation of the actual stone burden. While for larger stones treated by retrograde intrarenal surgery, stone volume appears to be a better predictor of SFR, the superiority of stone volume throughout all stone burdens and for all stone treatments, remains to be proven. Automated volume acquisition is more precise and reproducible than calculated volume. (AU)

How to estimate stone volume and its use in stone surgery: a comprehensive review.

OBJECTIVE: Current interventional guidelines refer to the cumulative stone diameter to choose the appropriate surgical modality (ureteroscopy [URS], extracorporeal shockwave lithotripsy [ESWL] and percutaneous nephrolithotomy [PCNL]). The stone volume (SV) has been introduced recently, to better estimate the stone burden. This review aimed to summarize the available methods to evaluate the SV and its use in urolithiasis treatment. MATERIAL AND METHODS: A comprehensive review of the literature was performed in December 2022 by searching Embase, Cochrane and Pubmed databases. Articles were considered eligible if they described SV measurement or the stone free rate after different treatment modalities (SWL, URS, PCNL) or spontaneous passage, based on SV measurement. Two reviewers independently assessed the eligibility and the quality of the articles and performed the data extraction. RESULTS: In total, 28 studies were included. All studies used different measurement techniques for stone volume. The automated volume measurement appeared to be more precise than the calculated volume. In vitro studies showed that the automated volume measurement was closer to actual stone volume, with a lower inter-observer variability. Regarding URS, stone volume was found to be more predictive of stone free rates as compared to maximum stone diameter or cumulative diameter for stones >20 mm. This was not the case for PCNL and SWL. CONCLUSIONS: Stone volume estimation is feasible, manually or automatically and is likely a better representation of the actual stone burden. While for larger stones treated by retrograde intrarenal surgery, stone volume appears to be a better predictor of SFR, the superiority of stone volume throughout all stone burdens and for all stone treatments, remains to be proven. Automated volume acquisition is more precise and reproducible than calculated volume.

Laser safety, warnings, and limits in retrograde intrarenal surgery.

OBJECTIVE: To analyze the current information about laser safety in retrograde intrarenal surgery (RIRS), focusing on the two main laser technologies that we use in urology, the holmium:yttrium-aluminum-garnet (Ho:YAG) laser, and the thulium fiber laser (TFL). METHODS: Narrative overview of the most relevant articles published in MEDLINE and Scopus databases about this subject. RESULTS: TFL and Ho:YAG laser at similar settings (0.2 J/40 Hz) have similar volume-averaged temperature increase and the average heating rate increase proportionally to laser power, especially when high frequencies are used. Recent preclinical data, comparing both laser technologies at different laser settings, agreed that when the delivered energy increases in expenses of higher frequencies, the thermal damage increases too. Higher frequencies, despite of the rise of temperature in the irrigation medium, can cause accidental thermal lasering lesions. CONCLUSION: The use of low frequency settings and a proper irrigation is critical to avoid thermal injury in endoscopic laser lithotripsy. In addition, the use of laser safety eyeglasses is recommended in Ho:YAG and TFL ELL.

Long-term efficacy of a new 6-session cognitive behavioral therapy for adults with attention-deficit/hyperactivity disorder: A randomized, controlled clinical trial.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that affects about 2.8 % of the adult population. Cognitive behavioral therapy (CBT) has been demonstrated to be the most effective psychological intervention for ADHD. The aim of this study was to explore the efficacy of a new 6-session CBT program in comparison with a 12-session CBT program for adults with ADHD at short- and long-term. METHODS: 81 adults with ADHD (58 % males; mean age = 41.27±9.26 years old) were randomly assigned to each treatment condition (6- or 12-session CBT). Validated instruments were used to assess ADHD symptoms, comorbidities (anxiety and depression), and functional impairments at post treatment, and at 3- and 6-month follow-up. RESULTS: A significant improvement in ADHD severity, comorbidities (anxiety and depression) and functional impairments were found in both CBT programs after treatment. Furthermore, this improvement was also reported at 3- and 6-month follow-up. CONCLUSION: The current study highlights that a 6-session CBT program is as effective as a 12-session CBT program for ADHD improvement at post treatment and follow-up. The newly developed 6-session CBT program can be used to treat a larger number of patients, reducing the financial cost.

Ablation rates with Holmium:YAG and Thulium Fiber Laser: Influence of the stone phantom homogeneity. An in vitro study.

OBJECTIVES: The lithotripsy efficiency (LE) in vitro study requires artificial or human stone samples (AS, HS). With the development of dusting lithotripsy, less ex vivo HS are available. We aimed to compare Thulium Fiber Laser (TFL) and Holmium:YAG (Ho:YAG)'s LE and define the most accurate LE parameter. METHODS: Hard and soft homogenous- and heterogenous-AS (Ho-AS, He-AS) were made to reproduce calcium-oxalate monohydrate and uric acid stones, respectively by a rapid or slow brewing of BegostonePlus (Bego) and distilled water. One hundred and fifty and 272µm-laser fibers, connected to 50W-TFL and 30W-HoYAG generators, compared three settings for TFL (FD: 0.15J/100Hz; D: 0.5J/30Hz; Fr: 1J/15Hz) and two for Ho:YAG (D-Fr). An experimental setup consisted in immerged 10mm cubic stone phantoms with a 20 seconds' lasing spiral, in contact mode, repeated four times. Stones were dried, weighted and µ-scanned (ablation weight and volume [AW and AV]). RESULTS: With He-AS, dusting AV were four- and three-fold higher with TFL compared to Ho:YAG against hard and soft (P<0.05). In fragmentation, AV were two-fold higher with TFL compared to Ho:YAG against hard (P<0.05) and soft (P<0.05). Experiments with Ho-AS were associated with non-significant differences when comparing TFL-150µm and TFL-272µm. The ablation weight-volume correlation coefficients was higher with Ho-AS than with He-AS (P<0.0001), and with hard than soft AS. If the LE can be estimated by the AW with hard AS, this approximation is not consistent for soft AS. CONCLUSION: TFL presented higher ablation rates than Ho:YAG, significant with He-AS. If the AW is acceptable and less expensive for hard Ho-AS, AV are more accurate for He-AS, which are suggested to imitate closely HS.

Methodology to geometrically age human body models to average and subject-specific anthropometrics, demonstrated using a small stature female model assessed in a side impact.

The aged population has been associated with an increased risk of injury in car-crash, creating a critical need for improved assessment of safety systems. Finite element human body models (HBMs) have been proposed, but require representative geometry of the aged population and high mesh quality. A new hybrid Morphing-CAD methodology was applied to a 26-year-old (YO) 5th percentile female model to create average 75YO and subject-specific 86YO HBMs. The method achieved accurate morphing targets while retaining high mesh quality. The three HBMs were integrated into a side sled impact test demonstrating similar kinematic response but differing rib fracture patterns.

The impact of insomnia disorder on adult attention-deficit/hyperactivity disorder severity: A six-month follow-up study.

BACKGROUND AND OBJECTIVES: The longitudinal relationship between insomnia disorder and adult attention-deficit/hyperactivity disorder (ADHD) has been scarcely investigated. This study aimed to evaluate the relationship between the remission of insomnia disorder and adult ADHD clinical severity, psychiatric and medical comorbidities, and the health-related quality of life (HRQoL) in a 6-month follow-up. METHODS: Ninety-two adult patients with ADHD and insomnia disorder (52.2% males; mean age 39.5 ± 11.0 years) were comprehensively assessed at baseline, 3 months, and 6 months of a follow-up period. The evaluation included semi-structured interviews (for ADHD and comorbidity assessment), the Pittsburgh Sleep Quality Index, Insomnia Severity Index, and Epworth Sleepiness Scale. The diagnosis of ADHD and insomnia disorder was performed according to DSM-5 criteria. At baseline and follow-up, psychoeducation/sleep hygiene and, if necessary, pharmacological were prescribed for insomnia. RESULTS: Eighty-seven patients completed the 6-month follow-up. Insomnia disorder remission was reported in 72.4% of cases and was related to a greater improvement in ADHD symptoms and severity throughout the follow-up period. Additionally, an improvement in psychiatric comorbidities and better HRQoL were associated with insomnia disorder remission. CONCLUSION: The current study highlights that the treatment of insomnia disorder in ADHD adult patients may have an important role in the outcome of ADHD therapeutic approaches by reducing their severity.

Sex, Age and Stature Affects Neck Biomechanical Responses in Frontal and Rear Impacts Assessed Using Finite Element Head and Neck Models.

The increased incidence of injury demonstrated in epidemiological data for the elderly population, and females compared to males, has not been fully understood in the context of the biomechanical response to impact. A contributing factor to these differences in injury risk could be the variation in geometry between young and aged persons and between males and females. In this study, a new methodology, coupling a CAD and a repositioning software, was developed to reposture an existing Finite element neck while retaining a high level of mesh quality. A 5th percentile female aged neck model (F0575YO) and a 50th percentile male aged neck model (M5075YO) were developed from existing young (F0526YO and M5026YO) neck models (Global Human Body Models Consortium v5.1). The aged neck models included an increased cervical lordosis and an increase in the facet joint angles, as reported in the literature. The young and the aged models were simulated in frontal (2, 8, and 15 g) and rear (3, 7, and 10 g) impacts. The responses were compared using head and relative facet joint kinematics, and nominal intervertebral disc shear strain. In general, the aged models predicted higher tissue deformations, although the head kinematics were similar for all models. In the frontal impact, only the M5075YO model predicted hard tissue failure, attributed to the combined effect of the more anteriorly located head with age, when compared to the M5026YO, and greater neck length relative to the female models. In the rear impacts, the F0575YO model predicted higher relative facet joint shear compared to the F0526YO, and higher relative facet joint rotation and nominal intervertebral disc strain compared to the M5075YO. When comparing the male models, the relative facet joint kinematics predicted by the M5026YO and M5075YO were similar. The contrast in response between the male and female models in the rear impacts was attributed to the higher lordosis and facet angle in females compared to males. Epidemiological data reported that females were more likely to sustain Whiplash Associated Disorders in rear impacts compared to males, and that injury risk increases with age, in agreement with the findings in the present study. This study demonstrated that, although the increased lordosis and facet angle did not affect the head kinematics, changes at the tissue level were considerable (e.g., 26% higher relative facet shear in the female neck compared to the male, for rear impact) and relatable to the epidemiology. Future work will investigate tissue damage and failure through the incorporation of aged material properties and muscle activation.

Importance of the cervical capsular joint cartilage geometry on head and facet joint kinematics assessed in a Finite element neck model.

Finite element human neck models (NMs) aim to predict neck response and injury at the tissue level; however, contemporary models are most often assessed using global response such as head kinematics. Additionally, many NMs are developed from subject-specific imaging with limited soft tissue resolution in small structures such as the facet joints in the neck. Such details may be critical to enable NMs to predict tissue-level response. In the present study, the capsular joint cartilage (CJC) geometry in a contemporary NM was enhanced (M50-CJC) based on literature data. The M50-CJC was validated at the segment and full neck levels and assessed using relative facet joint kinematics (FJK), capsular ligament (CL) and intervertebral disc (IVD) strains, a relative vertebral rotation assessment (IV-NIC) and head kinematics in frontal and rear impact. The validation ratings at the segment level increased from 0.60 to 0.64, with improvements for modes of deformation associated with the facet joints, while no difference was noted at the head kinematic level. The improved CJC led to increased FJK rotation (188%) and IVD strain (152.2%,) attributed to the reduced facet joint gap. Further enhancements of the capsular joint representation or a link between the FJK and CL injury risk are recommended. Enhancements at the tissue level demonstrated a large effect on the IVD strain, but were not apparent in global metrics such as head kinematics. This study demonstrated that a biofidelic and detailed geometrical representation of the CJC contributes significantly to the predicted joint response, which is critical to investigate neck injury risk at the tissue level.

Pulsed lasers and endocorporeal laser lithotripsy.

Endocorporeal laser lithotripsy (ELL) is currently the gold standard for the treatment of renal stones during retrograde intra-renal surgery (RIRS). The newly-authorised thulium fibre laser (Tm-Fibre) in now evaluated as a holmium:yttrium-aluminium-garnet (Ho:YAG) laser alternative, which is the most well-known laser source for ELL. This update aimed to present the fundamentals of pulsed lasers for EEL [technology, period, pulse characteristic (rate, duration, energy, shape), peak power, average power], and the available lithotripsy modes for both Tm-Fibre and Ho:YAG lasers.

Validation of a Football Helmet Finite Element Model and Quantification of Impact Energy Distribution.

Head injury in contact sports can be mitigated, in part, through the enhancement of protective helmets that may be enabled by detailed finite element models. However, many contemporary helmet FE models include simplified geometry and material properties and have limited verification and validation over a representative range of impact conditions. To address these limitations, a detailed numerical model of a modern football helmet was developed, integrated with two headforms and assessed for 60 impact conditions with excellent ratings (0.79-0.93). The strain energy of the helmet components was investigated for eight impact locations and three impact speeds. In general, the helmet shell had the highest strain energy followed by the compression shocks; however, the facemask and straps had the highest strain energy for impacts involving the facemask. The component strain energy was positively correlated with the Head Injury Criterion, while the strain energy was not strongly correlated with the Brain Injury Criterion due to the dependence on rotational kinematics. This study demonstrated the applicability of a detailed football helmet finite element model to investigate a range of impact conditions and to assess energy distribution as a function of impact location and severity as a means of future helmet optimization.

Coulomb Explosion Imaging for the Visualization of a Conical Intersection.

Coulomb explosion imaging is proposed as a method to directly map the presence of conical intersections encountered by a propagating wave packet in a molecular system. The case of choice is the nonadiabatic coupling between two dissociative surfaces in the methyl iodide molecule, probed by Coulomb explosion with short, intense near-infrared pulses causing multiple ionization. On-the-fly multidimensional trajectory calculations with surface hopping using perturbation theory and including spin-orbit coupling are performed to visualize the dynamics through the conical intersection and compare with experimental results. The possibilities and limitations of the technique are examined and discussed.

[The gut-brain axis in attention deficit hyperactivity disorder: the role of the microbiota]. / El eje intestino-cerebro en el trastorno por deficit de atencion/hiperactividad: papel de la microbiota.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) has a complex aetiology, mainly attributed to a number of susceptibility genes and environmental factors. Genetic association studies, however, have been inconsistent and have identified genetic variants with a moderate effect that explain a small proportion of the estimated inheritability of the disorder (< 10%). Recent studies suggest that the gut microbiota and diet play an important role in the development and symptoms of different mental disorders. Nevertheless, no clear evidence exists on the issue. This project proposes an alternative approach to identify mechanisms by which the intestinal microbial ecosystem and diet could contribute to the presence of ADHD. AIM: To identify biomarkers for ADHD by examining the gut microbiota. SUBJECTS AND METHODS: We conducted a cross-sectional study of adult patients with ADHD (n = 100) and control subjects (n = 100). Measures of ADHD evaluation and eating habits were performed in both groups. Samples of faecal material were obtained from which to extract bacterial DNA, then used to characterise the participants' gut microbiota. A meta-genomic association study was later performed to attempt to correlate the bacterial composition of the intestine with the clinical subtypes of the disorder. RESULTS AND CONCLUSIONS: Comparing the gut microbiota profiles of subjects with ADHD and controls is expected to help account for the clinical heterogeneity of the disorder and identify new mechanisms involved in its development.

TITLE: El eje intestino-cerebro en el trastorno por deficit de atencion/hiperactividad: papel de la microbiota.Introduccion. El trastorno por deficit de atencion/hiperactividad (TDAH) presenta una etiologia compleja, atribuida principalmente a multiples genes de susceptibilidad y factores ambientales. No obstante, los estudios geneticos de asociacion han sido inconsistentes, identificando variantes geneticas de efecto moderado que explican una pequeña proporcion de la heredabilidad estimada del trastorno (< 10%). Recientes estudios sugieren que la microbiota intestinal y la dieta desempeñan un papel importante en el desarrollo y los sintomas de diferentes trastornos mentales. Sin embargo, en la actualidad no existe una claridad absoluta al respecto. El presente proyecto propone un abordaje alternativo para identificar mecanismos a traves de los cuales el ecosistema microbiano intestinal y la dieta podrian contribuir a la presencia del TDAH. Objetivo. Identificar biomarcadores para el TDAH a traves del estudio de la microbiota intestinal. Sujetos y metodos. Estudio transversal de pacientes adultos con TDAH (n = 100) y de individuos control (n = 100). En ambos grupos se tomaran medidas de evaluacion de TDAH y habitos alimentarios. Se obtendran muestras fecales para la extraccion del ADN bacteriano, que permitiran caracterizar la microbiota intestinal de los participantes, para posteriormente realizar un estudio de asociacion metagenomico e intentar correlacionar la composicion bacteriana intestinal con subtipos clinicos del trastorno. Resultados y conclusiones. Se espera que la comparacion de los perfiles de microbiota intestinal entre sujetos con TDAH y controles ayude a explicar la heterogeneidad clinica del trastorno e identificar nuevos mecanismos implicados en su desarrollo.

[Treatment of attention deficit hyperactivity disorder in adults using virtual reality through a mindfulness programme]. / Tratamiento del trastorno por deficit de atencion/hiperactividad en la edad adulta a traves de la realidad virtual mediante un programa de mindfulness.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder, which presents a high comorbidity with anxiety and affective signs and symptoms. It has repercussions on the functioning of those suffering from it, who also have low therapy compliance and generate a significant cost both at a personal level and for society. Mindfulness is a psychological treatment that has proved to be effective for ADHD. Virtual reality is widely used as treatment in cases of phobias and other pathologies, with positive results. AIMS: To develop the first treatment for ADHD in adults based on virtual reality and mindfulness, while also resulting in increased treatment adherence and reduced costs. PATIENTS AND METHODS: We conducted a pilot study with 25 patients treated by means of virtual reality, in four 30-minute sessions, and 25 treated with psychostimulants. Measures will be taken pre-treatment, post-treatment and at 3 and 12 months post-treatment, to evaluate both ADHD and also depression, anxiety, functionality and quality of life. Data will be later analysed with the SPSS v. 20 statistical program. An ANOVA of independent groups will be performed to see the differences between treatments and also a test-retest to detect whether the changes will be maintained. RESULTS AND CONCLUSIONS: It is necessary to use treatments that are effective, reduce costs and increase therapy adherence. Treatment with virtual reality is an interesting alternative to the classical treatments, and is shorter and more attractive for patients.

TITLE: Tratamiento del trastorno por deficit de atencion/hiperactividad en la edad adulta a traves de la realidad virtual mediante un programa de mindfulness.Introduccion. El trastorno por deficit de atencion/hiperactividad (TDAH) es un trastorno del neurodesarrollo altamente prevalente, presenta una elevada comorbilidad con sintomatologia afectiva y ansiosa, afecta a la funcionalidad de la persona que lo padece, tienen una baja adhesion terapeutica y genera unos costes sociales y personales elevados. El mindfulness es un tratamiento psicologico que ha demostrado ser eficaz para el TDAH. La realidad virtual es un tratamiento altamente utilizado en fobias y extendido a otras patologias con resultados positivos. Objetivo. Desarrollar el primer tratamiento con realidad virtual y mindfulness para el TDAH en la edad adulta, que suponga un aumento en la adhesion terapeutica y reduzca costes. Pacientes y metodos. Estudio piloto de 25 pacientes tratados con realidad virtual, mediante cuatro sesiones de 30 minutos, y 25 mediante psicoestimulantes. Se tomaran medidas de evaluacion pretratamiento, postratamiento y postratamiento a los 3 y 12 meses, tanto de TDAH como de depresion, ansiedad, funcionalidad y calidad de vida. Se analizaran posteriormente con el programa SPSS v. 20 y se realizara un ANOVA de grupos independientes para ver las diferencias entre tratamientos y un test-retest para detectar el mantenimiento de los cambios. Resultados y conclusiones. Es necesaria la utilizacion de tratamientos que sean efectivos, supongan una reduccion en los costes y un aumento en la adhesion terapeutica. El tratamiento con realidad virtual se plantea como una alternativa a los tratamientos clasicos, que sea mas breve y atractiva para los pacientes.

IL-6 and TNF-α in unmedicated adults with ADHD: Relationship to cortisol awakening response.

There is preliminary evidence that the immune system's cytokines may have impact on ADHD in children. Nevertheless, studies exploring the possible role of pro-inflammatory cytokines in adults with ADHD are lacking. This study aimed to assess differences in serum IL-6 and TNF-α between patients and controls and their possible relationship to resting cortisol. 108 adults with ADHD (DSM-IV), 44 inattentive and 64 combined, age ranging between 18 and 55 years, and 27 healthy controls were included. Major psychiatric disorders and organic comorbidities were excluded. Serum samples for IL-6 and TNF-α and salivary samples to assess cortisol awakening response were collected on the same day. Analysis of variance was applied to study differences in IL-6 and TNF-α between groups. Pearson correlations were used to study associations between IL-6, TNF-α, and CAR. There were no significant differences in serum IL-6 or TNF-α levels between patients and controls or between combined and inattentive patients. Negative associations between IL-6 (r=-0.386, p=0.020), TNF-α (r=-0.372, p=0.023) and cortisol awakening response were found in the inattentive subtype, whereas no association was seen in the combined subtype. A negative correlation between IL-6 and cortisol was also present in the control group (r=-0.44, 0.030). The peripheral pro-inflammatory markers, IL-6 and TNF-α, do not appear to be primarily involved in ADHD in adults, although the role of other inflammatory markers cannot be ruled out. The differences regarding the association between IL-6 and TNF-α and morning cortisol response suggest possible underlying neurobiological differences between the inattentive or combined patients that merit further studies.

Pharmacogenetics of methylphenidate response and tolerability in attention-deficit/hyperactivity disorder.

Methylphenidate (MPH) is the most frequently used pharmacological treatment in children with attention-deficit/hyperactivity disorder. However, a considerable interindividual variability exists in clinical outcome, which may reflect underlying genetic influences. We analyzed 57 single-nucleotide polymorphisms in 9 dopamine-related candidate genes (TH, DBH, COMT, DAT1 and DRD1-5) as potential predictors of MPH efficacy and tolerability, and we considered prenatal and perinatal risk factors as environmental hazards that may influence treatment effects in a gene-by-environment analysis. Our results provide evidence for the contribution of DRD3 (P=0.041; odds ratio (OR)=4.00), DBH (P=0.032; OR=2.85), TH (P=5.5e-03; OR=4.34) and prenatal smoking (P=1.7e-03; OR=5.10) to the clinical efficacy of MPH, with a higher risk for treatment failure in genetically susceptible subjects whose mother smoked during pregnancy. Adverse events after MPH treatment were significantly associated with variation in DBH (P=6.4e-03; OR=0.28) and DRD2 (P=0.047; OR=3.76). This study suggests that the dopaminergic system together with prenatal smoking exposure may moderate MPH treatment effects.

Femtosecond Time-Resolved Photofragment Rotational Angular Momentum Alignment in Electronic Predissociation Dynamics.

This Letter presents an experimental and theoretical study of femtosecond time-resolved vector correlations in methyl iodide (CH3I) electronic predissociation via the second absorption B-band at 201.2 nm. The time evolution of the phenomenological anisotropy parameters ßl was determined from time-resolved photofragment angular distributions obtained by means of the femtosecond laser pump-probe technique coupled with velocity map imaging detection of vibrational ground-state CH3(ν = 0) fragments and spin-orbit excited I*(2P1/2) atoms. Theoretical interpretation of the experimental results was performed on the basis of a fitting procedure using quasiclassical theory, which elucidates vector correlations in photodissociation of symmetric top molecules. The results of the fitting are in very good agreement with the experimental data and demonstrate the important role of molecular excited-state lifetimes, parent molecule and methyl fragment rotations, and methyl fragment angular momentum alignment on the time-dependent electronic predissociation dynamics.