Blood pressure response during exercise testing in individuals with and without hypertension: The value of the recovery phase.

BACKGROUND: Hypertension and exercise testing are essential for cardiovascular risk assessment. However, an exact description of blood pressure (BP) in patients with a hypertensive response during exercise (HRE), especially in the recovery phase is lacking. Herein, we aimed to analyse BP and heart rate during exercise testing and recovery in patients with an HRE. METHODS: 800 patients aged 17-90 with an HRE during a standardized bicycle ergometry test were recruited. The BP behaviour during exercise testing was correlated with clinical data. Furthermore, data were analysed according to the presence of pre-existent hypertension. RESULTS: Of the 800 patients included in this study 497 (62%) were previously diagnosed with hypertension. Analysis of covariance showed a significantly faster systolic (ß [95% CI] 8.0 [4.9-11.1]) and diastolic (2.4 [0.4-4.4]) BP recovery 3 min after maximal exercise in patients without hypertension in univariable models. These results remained robust in fully adjusted models taking into account age, sex, body mass index, cardiovascular disease, and antihypertensive treatment for systolic (5.3 [1.2-9.4]) and diastolic BP (4.5 [1.9-7.0]). Furthermore, patients with hypertension displayed higher systolic BP during maximal exercise in univariable (3.8 [0.1-7.5]) and fully adjusted (5.5 [1.1-10.0]) models. There was no difference in maximum diastolic BP between groups. CONCLUSION: In this large cohort study, patients without hypertension showed a faster systolic and diastolic BP recovery and lower maximal systolic BP compared to patients with hypertension. Overall, this study provides new insights into cardiovascular health during recovery phase.

Evaluating nutrition in advanced ovarian cancer: which biomarker works best?

BACKGROUND: Advanced epithelial ovarian cancer (OC) patients often present with malnutrition; however, the ideal nutritional evaluation tool is unclear. We aimed to evaluate the role of preoperative albumin, Prognostic Nutritional Index [PNI], neutrophil-to-lymphocyte ratio [NLR], and platelet-to-lymphocyte ratio [PLR] as independent predictors of severe postoperative complications and 90-day mortality in OC patients who underwent primary cytoreductive surgery to identify the ideal tool. METHODS: OC patients who underwent surgery at Mayo Clinic (2003-2018) were included; biomarkers were retrospectively retrieved and established cut-offs were utilized. Outcomes included severe complications (Accordion grade ≥ 3) and 90-day mortality. Univariate and multivariable logistic regression models were performed. Biomarkers were evaluated in separate models adjusted for age and American Society of Anesthesiologists (ASA) score for 90-day mortality, and adjusted for age, ASA score, stage, and surgical complexity for severe complications. RESULTS: Albumin <3.5 g/dL, PNI < 45, NLR > 6 and PLR ≥ 200 were univariately associated with 90-day mortality (all p < 0.05) in 627 patients that met inclusion criteria. Each marker remained significant in adjusted models with albumin having the highest OR: 6.04 [95% CI:2.80-13.03] and AUC (0.83). Univariately, PNI <45, NLR >6, and PLR ≥200 were significant predictors of severe complications(all p < 0.05), however failed to reach significance in adjusted models. Albumin was not associated with severe complications. CONCLUSION: All biomarkers were associated with 90-day mortality in adjusted models, with albumin being the easiest predictor to attain clinically; none with severe complications. Future research should focus less on methods of nutritional assessment and more on strategies to improve nutrition during OC tumor-directed therapy.

Valgus stress knee radiographs accurately anticipate the bone resection in medial unicompartmental knee arthroplasty: Protocol validation using an image-based robotic system.

PURPOSE: The objective of this study was to describe a planning method for medial unicompartmental knee arthroplasty (UKA) implantation using preoperative stress radiographs to measure the thickness of tibial and femoral bone resections and to validate this method with data from an image-based robotic surgery system. Having such method for preoperative planning would be of interest for surgeons performing UKA in order to anticipate optimal bone resection on both tibia and femoral sides. METHODS: A new planning method for medial UKA based on valgus stress knee radiographs validated it with an image-based robotic surgery system (Restoris MCK, MAKO®, Stryker Corporation) was proposed. This retrospective study involved radiographic measurements of 76 patients who underwent image-based robotic medial UKA between April 2022 and February 2023. Preoperative anteroposterior stress radiographs of the knee were used to simulate UKA implantation. The UKA technique was based on Cartier's angle and aimed at restoring the joint line. The total dimension measured was 14 mm (8 mm for minimal tibial component and polyethylene insert + 4 mm for femoral component + 2 mm for safety laxity). Bone resections were measured in the preoperative valgus stress radiographs and then against the intraoperative bone resection data provided by the robotic system. Inter- and intra-observer reliability was assessed using 25 measurements. RESULTS: The mean planned tibial resection measured in the radiographs was 4.3 ± 0.4 [2.9-5.8], while the mean robotic resection was 4.2 ± 0.5 [2.7-5.8] (mean difference = 0.15 mm, 95% confidence interval [CI] [-0.27 to 0.57]). There was a strong correlation between these two values (Pearson's rank R = 0.79, p < 0.001). Intra- and inter-observer reliability were also very strong (Pearson's rank R = 0.91, p < 0.001, and Pearson's rank R = 0.82, p < 0.001, respectively). The mean planned femoral bone resection measured in the radiographs was 2.7 ± 0.7 mm [1-4.5], while the mean robotic resection was 2.5 ± 0.9 [1-5] (mean difference = 0.21 mm, 95% CI [-0.66 to 1.08]). There was a strong correlation between these two values (Pearson's rank R = 0.82, p < 0.001). Intra- and inter-observer reliability were also strong (Pearson's rank R = 0.88, p < 0.001, and Pearson's rank R = 0.84, p < 0.001, respectively). CONCLUSION: This study describes and validates with robotic information a simple and reproducible preoperative planning method to determine femoral and tibial bone resection for medial UKA implantation using antero-posterior valgus stress knee radiographs, leaving a medial safety laxity of 2 mm. It represents a very valuable contribution to the understanding of UKA principles, which can serve to extend its indications and increase reproducibility of the surgical technique. LEVEL OF EVIDENCE: III. Retrospective cohort study.

The Different Pathways of Epicardial Adipose Tissue across the Heart Failure Phenotypes: From Pathophysiology to Therapeutic Target.

Epicardial adipose tissue (EAT) is an endocrine and paracrine organ constituted by a layer of adipose tissue directly located between the myocardium and visceral pericardium. Under physiological conditions, EAT exerts protective effects of brown-like fat characteristics, metabolizing excess fatty acids, and secreting anti-inflammatory and anti-fibrotic cytokines. In certain pathological conditions, EAT acquires a proatherogenic transcriptional profile resulting in increased synthesis of biologically active adipocytokines with proinflammatory properties, promoting oxidative stress, and finally causing endothelial damage. The role of EAT in heart failure (HF) has been mainly limited to HF with preserved ejection fraction (HFpEF) and related to the HFpEF obese phenotype. In HFpEF, EAT seems to acquire a proinflammatory profile and higher EAT values have been related to worse outcomes. Less data are available about the role of EAT in HF with reduced ejection fraction (HFrEF). Conversely, in HFrEF, EAT seems to play a nutritive role and lower values may correspond to the expression of a catabolic, adverse phenotype. As of now, there is evidence that the beneficial systemic cardiovascular effects of sodium-glucose cotransporter-2 receptors-inhibitors (SGLT2-i) might be partially mediated by inducing favorable modifications on EAT. As such, EAT may represent a promising target organ for the development of new drugs to improve cardiovascular prognosis. Thus, an approach based on detailed phenotyping of cardiac structural alterations and distinctive biomolecular pathways may change the current scenario, leading towards a precision medicine model with specific therapeutic targets considering different individual profiles. The aim of this review is to summarize the current knowledge about the biomolecular pathway of EAT in HF across the whole spectrum of ejection fraction, and to describe the potential of EAT as a therapeutic target in HF.

Bösch osteotomy for hallux valgus correction: results at a mean 10-year follow-up.

INTRODUCTION: Bösch osteotomy (BO), which is a first metatarsal subcapital osteotomy stabilised with a K-wire, is a surgical option to correct hallux valgus (HV). The aim of this study was to assess the long-term clinical and radiographic results in a cohort of patients treated at our institution with such osteotomy. METHODS: In this retrospective monocentric single-surgeon cohort study, we included 58 HVs (46 patients) who underwent HV correction by BO and were followed at a minimum of 7 years. The range of motion (ROM), the American Orthopaedic Foot and Ankle Society's Forefoot scale (AOFAS-FS) and the Visual Analogic Scale (VAS) for pain were recorded. On weightbearing radiographs, the Hallux Valgus Angle (HVA), Intermetatarsal Angle (IMA), the Distal Metatarsal Articular Angle (DMAA), and the Lateral Sesamoid Position (LSP) were measured and compared with pre-operative values. The complication rate and first metatarsophalangeal joint stiffness were also assessed. RESULTS: At a mean follow-up of 10 ± 2 (7-17) years, mean ± standard deviation AOFAS-FS and VAS were 89 ± 11 (67-93) and 2.1 ± 2.8 (0-7) points, respectively. In 42 (72%) cases there was no limitation in the choice of footwears. Radiographically, we found a significant improvement in the HVA (from 33.9° ± 6.7 to 18.8° ± 5.6, p < 0.001), in the IMA (14.2° ± 3.1 to 9.4° ± 2.7, p < 0.001), in the DMAA (from 30.3° ± 6.8 to 11.5° ± 5.1, p < 0.001) and in LSP (median value from 3 to 1, p < 0.001). In 36 (62%) cases the ROM was greater than 75° while in 22 (38%) it ranged between 30° and 75°. Minor complications occurred in six (10%) cases, which did not require any further surgery at the longest follow-up. CONCLUSION: Bösch technique provided satisfactory clinical and radiographic outcomes in the treatment of hallux valgus which persisted at a mean 10-year follow-up. The complication rate did not differ from more recent techniques described in literature. LEVEL OF EVIDENCE: Level IV, retrospective cohort study.

Tissue-specific geometry and chemistry of modern and fossilized melanosomes reveal internal anatomy of extinct vertebrates.

Recent discoveries of nonintegumentary melanosomes in extant and fossil amphibians offer potential insights into the physiological functions of melanin not directly related to color production, but the phylogenetic distribution and evolutionary history of these internal melanosomes has not been characterized systematically. Here, we present a holistic method to discriminate among melanized tissues by analyzing the anatomical distribution, morphology, and chemistry of melanosomes in various tissues in a phylogenetically broad sample of extant and fossil vertebrates. Our results show that internal melanosomes in all extant vertebrates analyzed have tissue-specific geometries and elemental signatures. Similar distinct populations of preserved melanosomes in phylogenetically diverse vertebrate fossils often map onto specific anatomical features. This approach also reveals the presence of various melanosome-rich internal tissues in fossils, providing a mechanism for the interpretation of the internal anatomy of ancient vertebrates. Collectively, these data indicate that vertebrate melanins share fundamental physiological roles in homeostasis via the scavenging and sequestering of metals and suggest that intimate links between melanin and metal metabolism in vertebrates have deep evolutionary origins.

Influence of a High-Impact Multidimensional Rehabilitation Program on the Gut Microbiota of Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is a neurodegenerative inflammatory condition mediated by autoreactive immune processes. Due to its potential to influence host immunity and gut-brain communication, the gut microbiota has been suggested to be involved in the onset and progression of MS. To date, there is no definitive cure for MS, and rehabilitation programs are of the utmost importance, especially in the later stages. However, only a few people generally participate due to poor support, knowledge, and motivation, and no information is available on gut microbiota changes. Herein we evaluated the potential of a brief high-impact multidimensional rehabilitation program (B-HIPE) in a leisure environment to affect the gut microbiota, mitigate MS symptoms and improve quality of life. B-HIPE resulted in modulation of the MS-typical dysbiosis, with reduced levels of pathobionts and the replenishment of beneficial short-chain fatty acid producers. This partial recovery of a eubiotic profile could help counteract the inflammatory tone typically observed in MS, as supported by reduced circulating lipopolysaccharide levels and decreased populations of pro-inflammatory lymphocytes. Improved physical performance and fatigue relief were also found. Our findings pave the way for integrating clinical practice with holistic approaches to mitigate MS symptoms and improve patients' quality of life.

Sexual and reproductive health in adolescents: validation of the questionnaire SexContraKnow instrument in Italian.

BACKGROUND: Adolescents have an inadequate level of health literacy, particularly regarding sexual and reproductive health and the use of birth control methods. This contributes to a high percentage of unintentional pregnancies and sexual behaviors that endanger the entire population. AIM: The purpose of this study is to validate the questionnaire, Sexcontraknow Instrument, in Italian, in order to evaluate the health literacy of adolescents, aged 14 to 19, regarding sexual and reproductive health, particularly on the use of contraceptive methods. METHODS: This is a quantitative research study that aims to validate a knowledge tool on sexual and reproductive health in the adolescent population. RESULTS: The Sexcontraknow Instrument questionnaire has been translated according to the process indicated by the EORTC Quality of Life Group validation criteria. The linguistic validation of the questionnaire in Italian was carried out using the forward-backward translation method. The content validity process was carried out by a group of 9 experts in the area of sexual education addressed to the study population, such as: doctors, midwives, gynecologists, teachers and health assistants. The face validity process, however, was carried out with a sample of convenience made up of 12 students aged 14 to 19 years, homogeneous in the gender. CONCLUSIONS: The SexContraKnow Instrument questionnaire has been transalated in Italiana and face and content validity has been performed. NURSING IMPLICATIONS: Having a tool that help evaluate the knowledge of young people, aids the nurse in preparing and making up for shortcomings through proper education, reducing the negative effects of poor literacy.

Genital Pain and Sexual Functioning: Effects on Sexual Experience, Psychological Health, and Quality of Life.

BACKGROUND: Genital pain (GP) is a common symptom in women of reproductive age. The prevalence of GP is difficult to gauge as it has been underreported by both patients and clinicians and neglected in clinical studies despite wide recognition of the adverse effects to women's health. AIM: The purpose of the present study was 3-fold: (i) to explore the self-reported presence and perception of GP and its association with sexual functioning, sexual distress, emotions, psychopathology, and quality of life (QoL); (ii) to explore if, controlling for the pain effect, women with Female Sexual Function Index (FSFI) scores indicating sexual dysfunction also reported worse outcomes regarding sexual distress, emotions, psychological health, and QoL than GP women with higher FSFI scores; and (iii) to evaluate the effects of GP duration, comparing women with GP with shorter (<6 months) duration of symptoms with women with longer (≥6 months) duration of symptom of GP on sexual functioning, distress, emotions, psychopathology and QoL. METHODS: A total of 1,034 women (age ranges between 18 and 40 years) from the Italian general population completed a web survey on sexual health. OUTCOMES: 6 self-report questionnaires exploring different biopsychosocial factors were assessed: the FSFI, the Female Sexual Distress Scale, the Positive and Negative Affect Schedule, the Short Form McGill Pain Questionnaire adapted for GP, the Short Form 36, and the Symptom Check List-90-Revised. RESULTS: Women who reported GP (n = 319) indicated generally lower sexual function than women without GP (n = 648; P = .036). They reported a higher level of sexual distress (P < .001), more negative emotions related to sexual experiences (P = .001), lower scores in all QoL domains (P < .001), and higher levels of psychopathological symptoms (P < .001). Controlling for pain effects, women whose FSFI scores indicated sexual dysfunction (n = 150) reported higher rates of sexual distress than women whose FSFI scores indicated normal sexual function (n = 169; P < .001). The scores also indicated fewer positive (P < .001) and more negative emotions (P < .001) related to sexuality, lower QoL (P < .001) and significantly higher psychological burden (P < .001). Moreover, women experiencing GP for ≥6 months reported significantly lower means on the FSFI total score (P < .05; especially in the desire, satisfaction, and pain domains), distress (P < .001), and emotions (P < .05) than women experiencing GP duration <6 months. No significant differences were found on the QoL and the psychopathological symptoms. CLINICAL IMPLICATIONS: GP is significantly pervasive, but a high percentage of sexual problems and related emotional suffering is overlooked. Raising awareness about this issue is critical, both among clinicians and the general public. STRENGTHS & LIMITATIONS: The present study highlighted important characteristics of GP from a community sample; the results indicate problems related to pain experiences and their repercussions on sexual, psychological, affective health, and QoL. Major limitations are related to the use of self-report measures via a web-based study. CONCLUSION: The results provide evidence of a lack of awareness regarding pain experiences as they relate to sexual functioning in women; clinicians would be advised to more fully investigate sexual functioning and psychosocial variables associated with GP during routine consultation beginning with the first onset of the symptoms. Nimbi FM, Rossi V, Tripodi F, et al. Genital Pain and Sexual Functioning: Effects on Sexual Experience, Psychological Health, and Quality of Life. J Sex Med 2020; 17:771-783.

Dose-response relationship of active commuting to work: Results of the GISMO study.

The positive health benefits of regular exercise, particularly regarding cardiovascular risk and diseases, are well recognized and scientifically evident. However, a sedentary lifestyle is one of the most important cardiovascular risk factors that are still insufficiently addressed. Leisure-time active commuting like walking and biking is an ideal way to improve exercise behavior in the general population. The purpose of this substudy of the GISMO study was to assess dose-response relations in all commuters and the three subgroups of commuters (physically active by bicycle and/or walking, physically active by using public transportation (PT), and the controls using their own vehicles). As such, a positive dose-response relationship could be confirmed in all physically active commuters compared to the control group. Whether the commuters cycled, walked, or traveled by PT -the more the physical exercise they performed (measured in metabolic equivalent [MET]-hours), the larger their gain in physical fitness (measured in gained or "Delta" Watt during a maximal exercise test), and their physical fitness at the end of the study was P = .016 and P = .003, respectively. Health-related quality of life correlated in two out of eight subdomains of the SF-36 questionnaire with MET-hours achieved during the study period (General Health and Physical Functioning). No clearly significant dose-response could be observed regarding HDL(high-density lipoprotein)-cholesterol or body composition. Our results indicate a dose-response pattern of healthy commuting in exercise capacity and health-related quality of life to increase doses of physically active commuting.

Effects of active commuting on cardiovascular risk factors: GISMO-a randomized controlled feasibility study.

A sedentary lifestyle is a major modifiable risk factor for many chronic diseases. Lifestyle modification in order to increase exercise capacity is key in the prevention and rehabilitation of chronic diseases. This could be achieved by active commute. The aim of this study was to assess the effects of daily active commuting on physical activity (PA) and exercise capacity. Seventy-three healthy hospital employees (age: 46 ± 9 years, 38% male), with a predominantly passive way of commuting, were randomly assigned to two parallel groups, a control group (CG, N = 22) or an intervention group (IG, N = 51), which was further split into public transportation/active commuting (IG-PT, N = 25) and cycling (IG-C, N = 26). Both intervention groups were asked to reach 150 min/wk of moderate- to vigorous-intensity exercise during their commute for 1 year. CG maintained a passive commuting mode. All participants underwent assessment of anthropometry, risk factor stratification, and exercise capacity by a medical doctor at the Institute of Sports Medicine, Prevention and Rehabilitation. Weekly physical activity, using the International Physical Activity Questionnaire and commuting behavior, using an online diary, were used to assess physical activity. At the end of the study, the change in exercise capacity did significantly differ between IG and CG (P = .003, ES = 0.82). Actively covered distances through commuting significantly differed between groups (walking P = .026; cycling P < .001). Therefore, active commuting improves exercise capacity and can be recommended to the working population to increase exercise capacity.

Motivational Salience Modulates Early Visual Cortex Responses across Task Sets.

Motivationally relevant stimuli benefit from strengthened sensory processing. It is unclear, however, if motivational value of positive and negative valence has similar or dissociable effects on early visual processing. Moreover, whether these perceptual effects are task-specific, stimulus-specific, or more generally feature-based is unknown. In this study, we compared the effects of positive and negative motivational value on early sensory processing using ERPs. We tested the extent to which these effects could generalize to new task contexts and to stimuli sharing common features with the motivationally significant ones. At the behavioral level, stimuli paired with positive incentives were learned faster than stimuli paired with neutral or negative outcomes. The ERP results showed that monetary loss elicited higher neural activity in V1 (at the C1 level) compared with reward, whereas the latter influenced postperceptual processing stages (P300). Importantly, the early loss-related effect generalized to new contexts and to new stimuli with common features, whereas the later reward effects did not spill over to the new context. These results suggest that acquired negative motivational salience can influence early sensory processing by means of plastic changes in feature-based processing in V1.

Night-to-night variability of obstructive sleep apnea.

One night of a sleep study is the standard for diagnosis and exclusion of obstructive sleep apnea. Single testing requires high sensitivity of the test method and a stable disease of interest to warrant a low rate of false-negative tests. Obstructive sleep apnea is diagnosed and graded by conventional thresholds of apneas and hypopneas per hour of sleep, and treatment is usually initiated in the presence of symptoms. The aim of this study was to assess night-to-night variability of obstructive sleep apnea to reassess the current practice. Seventy-seven patients previously diagnosed with obstructive sleep apnea, randomised to continuous positive airway pressure withdrawal within four trials, performed nightly pulse-oximetry over 2 weeks while off continuous positive airway pressure. The main outcome of interest was the coefficient of variation of the oxygen desaturation index marking night-to-night variability in obstructive sleep apnea. Obstructive sleep apnea was categorised according to conventional thresholds using oxygen desaturation index (no obstructive sleep apnea: <5 per h; mild: 5-15 per h; moderate: 15-30 per h; and severe: >30 per h). High night-to-night variability of obstructive sleep apnea was evidenced by a coefficient of variation of oxygen desaturation index of 31.1% (SD 16.5). Differences in oxygen desaturation index of >10 per h between nights were found in 84.4% and shifts in obstructive sleep apnea severity category in 77.9% of patients. The probability of missing moderate obstructive sleep apnea was up to 60%. Variability was higher in less severe obstructive sleep apnea. Obstructive sleep apnea shows a considerable night-to-night variability. Single-night diagnostic sleep studies are prone to miscategorise obstructive sleep apnea if arbitrary thresholds are used. Thus, treatment decisions should be based less on the conventional derivatives from sleep studies, especially in patients with less severe obstructive sleep apnea. CLINICAL TRIAL REGISTRATION: www.controlled-trials.com (ISRCTN 93153804, ISRCTN 73047833) and www.clinicaltrials.gov (NCT01332175 & NCT02050425).

Effect of OSA on hypoxic and inflammatory markers during CPAP withdrawal: Further evidence from three randomized control trials.

BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea (OSA) is associated with cardiovascular disease. Intermittent hypoxia, endothelial dysfunction and adipose tissue-mediated inflammation have all been linked to cardiovascular disease in OSA. We therefore explored the effect of OSA on relevant associated blood markers: adrenomedullin (ADM), endocan, endothelin-1 (ET-1), resistin and vascular endothelial growth factor (VEGF). METHODS: Patients with OSA, established on and compliant with continuous positive airways pressure (CPAP) therapy for >1 year were included from three randomized controlled trials, conducted at two centres. Patients were randomized to either continued therapeutic CPAP or sham CPAP (CPAP withdrawal) for 2 weeks. Blood markers were measured at baseline and at 14 days and the treatment effect between sham CPAP and therapeutic CPAP was analysed. RESULTS: A total of 109 patients were studied (therapeutic CPAP n = 54, sham CPAP n = 55). Sham CPAP was associated with a return of OSA (between-group difference in oxygen desaturation index (ODI) 36.0/h, 95% CI 29.9-42.2, P < 0.001). Sham CPAP was associated with a reduction in ADM levels at 14 days (-26.0 pg/mL, 95% CI -47.8 to -4.3, P = 0.02), compared to therapeutic CPAP. Return of OSA was not associated with changes in endocan, ET-1, resistin or VEGF. CONCLUSION: Whilst CPAP withdrawal was associated with return of OSA, it was associated with an unexpected significant reduction in the vasodilator ADM and not with expected increases in hypoxia-induced markers, markers of endothelial function or resistin. We propose that the vascular effects occurring in OSA may be brought about by other mechanisms, perhaps partly through a reduction in ADM.

Chronic intestinal pseudo-obstruction in a child harboring a founder Hirschsprung RET mutation.

Chronic intestinal pseudo obstruction (CIPO) is a rare clinical entity characterized by symptoms and signs of intestinal obstruction without either recognizable anatomical abnormalities or intestinal aganglionosis. A Chinese female infant presented to our institution with a clinical diagnosis of CIPO. Aganglionosis was ruled out by full thickness colonic and ileal biopsies and by rectal suction biopsies. Unexpectedly, direct sequencing and PCR amplification of RET proto-oncogene from peripheral blood extracted DNA identified a RET R114H mutation. This mutation has already been reported as strongly associated with Asian patients affected by Hirschsprung's disease (HSCR) and is considered a founder mutation in Asia. The same mutation has never been reported in patients with CIPO, so far. These findings support the role of RET in the development of the enteric nervous system but underline the importance of other genetic or environmental factors contributing to the gastrointestinal phenotype of the disease. Somehow, this RET R114H mutation proved to have a role in the etiology of both CIPO and HSCR and could contribute to a more diffuse imbalance of gut dysmotility. © 2016 Wiley Periodicals, Inc.

Long-term outcome and need of re-operation in gastro-esophageal reflux surgery in children.

BACKGROUND: Fundoplication is considered a mainstay in the treatment of gastro-esophageal reflux. However, the literature reports significant recurrences and limited data on long-term outcome. AIMS: To evaluate our long-term outcomes of antireflux surgery in children and to assess the results of redo surgery. METHODS: We retrospectively analyzed all patients who underwent Nissen fundoplication in 8 consecutive years. Reiterative surgery was indicated only in case of symptoms and anatomical alterations. A follow-up study was carried out to analyzed outcome and patients' Visick score assessed parents' perspective. RESULTS: Overall 162 children were included for 179 procedures in total. Median age at first intervention was 43 months. Comorbidities were 119 (73 %), particularly neurological impairments (73 %). Redo surgery is equal to 14 % (25/179). Comorbidities were risk factors to Nissen failure (p = 0.04), especially children suffering neurological impairment with seizures (p = 0.034). Follow-up datasets were obtained for 111/162 = 69 % (median time: 51 months). Parents' perspectives were excellent or good in 85 %. CONCLUSIONS: A significant positive impact of redo Nissen intervention on the patient's outcome was highlighted; antireflux surgery is useful and advantageous in children and their caregivers. Children with neurological impairment affected by seizures represent significant risk factors.

Patterns of Care and Clinical Outcomes of First-Line Trastuzumab-Based Therapy in HER2-Positive Metastatic Breast Cancer Patients Relapsing After (Neo)Adjuvant Trastuzumab: An Italian Multicenter Retrospective Cohort Study.

BACKGROUND: We evaluated the patterns of care and clinical outcomes of metastatic breast cancer patients treated with first-line trastuzumab-based therapy after previous (neo)adjuvant trastuzumab. MATERIALS AND METHODS: A total of 416 consecutive, HER2-positive metastatic breast cancer patients who had received first-line trastuzumab-based therapy were identified at 14 Italian centers. A total of 113 patients had presented with de novo stage IV disease and were analyzed separately. Dichotomous clinical outcomes were analyzed using logistic regression and time-to-event outcomes using Cox proportional hazards models. RESULTS: In the 202 trastuzumab-naïve patients and 101 patients with previous trastuzumab exposure, we observed the following outcomes, respectively: overall response rate, 69.9% versus 61.3% (adjusted odds ratio [OR], 0.62; p = .131), clinical benefit rate, 79.1% versus 72.5% (adjusted OR, 0.73; p = .370), median progression-free survival (PFS), 16.1 months versus 12.0 months (adjusted hazards ratio [HR], 1.33; p = .045), and median overall survival (OS), 52.2 months versus 48.2 months (adjusted HR, 1.18; p = .404). Patients with a trastuzumab-free interval (TFI) <6 months, visceral involvement, and hormone receptor-negative disease showed a worse OS compared with patients with a TFI of ≥6 months (29.5 vs. 48.3 months; p = .331), nonvisceral involvement (48.0 vs. 60.3 months; p = .270), and hormone receptor-positive disease (39.8 vs. 58.6 months; p = .003), respectively. CONCLUSION: Despite the inferior median PFS, trastuzumab-based therapy was an effective first-line treatment for patients relapsing after (neo)adjuvant trastuzumab. Previous trastuzumab exposure and the respective TFI, type of first site of disease relapse, and hormone receptor status should be considered in the choice of the best first-line treatment option for HER2-positive metastatic breast cancer patients.

Natural interfaces and virtual environments for the acquisition of street crossing and path following skills in adults with Autism Spectrum Disorders: a feasibility study.

BACKGROUND: Lack of social skills and/or a reduced ability to determine when to use them are common symptoms of Autism Spectrum Disorder (ASD). Here we examine whether an integrated approach based on virtual environments and natural interfaces is effective in teaching safety skills in adults with ASD. We specifically focus on pedestrian skills, namely street crossing with or without traffic lights, and following road signs. METHODS: Seven adults with ASD explored a virtual environment (VE) representing a city (buildings, sidewalks, streets, squares), which was continuously displayed on a wide screen. A markerless motion capture device recorded the subjects' movements, which were translated into control commands for the VE according to a predefined vocabulary of gestures. The treatment protocol consisted of ten 45-minutes sessions (1 session/week). During a familiarization phase, the participants practiced the vocabulary of gestures. In a subsequent training phase, participants had to follow road signs (to either a police station or a pharmacy) and to cross streets with and without traffic lights. We assessed the performance in both street crossing (number and type of errors) and navigation (walking speed, path length and ability to turn without stopping). To assess their understanding of the practiced skill, before and after treatment subjects had to answer a test questionnaire. To assess transfer of the learned skill to real-life situations, another specific questionnaire was separately administered to both parents/legal guardians and the subjects' personal caregivers. RESULTS: One subject did not complete the familiarization phase because of problems with depth perception. The six subjects who completed the protocol easily learned the simple body gestures required to interact with the VE. Over sessions they significantly improved their navigation performance, but did not significantly reduce the errors made in street crossing. In the test questionnaire they exhibited no significant reduction in the number of errors. However, both parents and caregivers reported a significant improvement in the subjects' street crossing performance. Their answers were also highly consistent, thus pointing at a significant transfer to real-life behaviors. CONCLUSIONS: Rehabilitation of adults with ASD mainly focuses on educational interventions that have an impact in their quality of life, which includes safety skills. Our results confirm that interaction with VEs may be effective in facilitating the acquisition of these skills.

Electrical neuroimaging reveals content-specific effects of threat in primary visual cortex and fronto-parietal attentional networks.

Whereas effects of anticipatory anxiety on attention are usually assumed to remain largely undifferentiated, discrepant findings in the literature suggest that, depending on its content and causes, different modulatory effects on attention control and early sensory processing may arise. Using electrical neuroimaging and psychophysiology in a cross-over design, we tested the hypothesis that different types of anticipatory anxiety (bodily vs. psychological), transiently induced in healthy participants, had dissociable effects on brain systems regulating attention control. Attention control corresponded to the ability to maintain efficient goal-directed processing (indexed by the P300 ERP component and by activations in the attentional networks), as well as the ability to filter out irrelevant stimuli in early sensory cortex (C1 component, indexing attentional gating in V1). Results showed that while psychosocial threat, very much like perceptual load, primarily led to a stronger gating in V1, bodily threat resulted in impaired goal-directed processing within the fronto-parietal attentional network, as well as decreased filtering in V1. These results suggest that anticipatory anxiety is multifaceted, exerting different effects on attention control and early visual processing depending on its sub-type.

Feeling happy enhances early spatial encoding of peripheral information automatically: electrophysiological time-course and neural sources.

Previous research has shown that positive mood may broaden attention, although it remains unclear whether this effect has a perceptual or a postperceptual locus. In this study, we addressed this question using high-density event-related potential methods. We randomly assigned participants to a positive or a neutral mood condition. Then they performed a demanding oddball task at fixation (primary task ensuring fixation) and a localization task of peripheral stimuli shown at three positions in the upper visual field (secondary task) concurrently. While positive mood did not influence behavioral performance for the primary task, it did facilitate stimulus localization on the secondary task. At the electrophysiological level, we found that the amplitude of the C1 component (reflecting an early retinotopic encoding of the stimulus in V1) was enhanced in the positive, as compared with the neutral, mood group. Importantly, this effect appeared to be largely automatic, because it occurred regardless of the task relevance of the peripheral stimulus and prior to top-down gain control effects seen at the level of the subsequent P1 component. This early effect was also observed irrespective of a change of the target-related P300 component (primary task) by positive mood. These results suggest that positive mood can automatically boost the spatial encoding of peripheral stimuli early on following stimulus onset. This effect can eventually underlie the broadening of spatial attention, which has been associated with this specific mood state.